julilili42/papers huggingface dataset:
Evaluation of a newly designed deep learning-based algorithm for automated assessment of scapholunate distance in wrist radiography as a surrogate parameter for scapholunate ligament rupture and the correlation with arthroscopy
2023-09-20

Abstract Purpose Not diagnosed or mistreated scapholunate ligament (SL) tears represent a frequent cause of degenerative wrist arthritis. A newly developed deep learning (DL)-based automated assessment of the SL distance on radiographs may support clinicians in initial image interpretation. Materials and Methods A pre-trained DL algorithm was specifically fine-tuned on static and dynamic dorsopalmar wrist radiography (training data set n = 201) for the automated assessment of the SL distance. Afterwards the DL algorithm was evaluated (evaluation data set n = 364 patients with n = 1604 radiographs) and correlated with results of an experienced human reader and with arthroscopic findings. Results The evaluation data set comprised arthroscopically diagnosed SL insufficiency according to Geissler’s stages 0–4 (56.5%, 2.5%, 5.5%, 7.5%, 28.0%). Diagnostic accuracy of the DL algorithm on dorsopalmar radiography regarding SL integrity was close to that of the human reader (e.g. differentiation of Geissler’s stages ≤ 2 versus &gt; 2 with a sensitivity of 74% and a specificity of 78% compared to 77% and 80%) with a correlation coefficient of 0.81 ( P &lt; 0.01). Conclusion A DL algorithm like this might become a valuable tool supporting clinicians’ initial decision making on radiography regarding SL integrity and consequential triage for further patient management.
The Arabidopsis U1 snRNP regulates mRNA 3’-end processing
2023-09-20

ABSTRACT The removal of introns by the spliceosome is a key gene regulatory mechanism in eukaryotes, with the U1 snRNP subunit of the spliceosome playing a crucial role in the early stages of splicing. Studies in metazoans show that the U1 snRNP also conducts splicing-independent functions, but the lack of genetic tools and knowledge about U1 snRNP-associated proteins have limited the study of such splicing-independent functions in plants. Here, we describe an RNA-centric approach that identified more than 200 proteins associated with the Arabidopsis U1 snRNP, among them mRNA cleavage and polyadenylation factors. The loss of U1 core components is linked to premature cleavage and polyadenylation within gene bodies and alternative polyadenylation site selection in 3’-UTRs. Overall, our work provides a comprehensive view of U1 snRNP interactors and reveals novel functions in regulating mRNA 3’-end processing in Arabidopsis, thus establishing the groundwork for a better understanding of non-canonical functions of plant U1 snRNPs.
Dissimilar Laser Beam Welding of Titanium to Stainless Steel Using Pure Niobium as Filler Material in Lap Joint Configuration
2023-09-20

In the present investigation, commercially pure titanium is welded to AISI 316L stainless steel by intermixing niobium as filler material in a lap joint configuration. For this purpose, a pulsed Nd:YAG laser with various pulse durations and pulse peak powers is employed to obtain different mixing conditions for the materials. It will be demonstrated that, despite the implementation of the filler material, the weld seams are characterized by a high affinity for cracking, which in turn can be attributed to the formation of hard intermetallic compounds. Nevertheless, utilization of optimized process parameters can yield crack-free specimens in a reproducible manner through equable intermixing of otherwise critical alloy elements. Lap-shear forces of up to 140 N can be achieved with a single weld seam measuring 2.5 mm in length. By increasing the joint area with four adjacent weld seams, maximum loads up to 320 N are attained, thus exceeding the yield strength of the applied stainless steel. Considering the biocompatibility of the niobium filler material used, this work provides the foundation for this dissimilar material combination to be implemented in future medical technology applications.
A conserved cell-pole determinant organizes proper polar flagellum formation
2023-09-20

Abstract The coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus , Pseudomonas putida , and Shewanella putrefaciens , and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.
Evolutionary dynamics of proteinaceous MAMPs reveals intrabacterial antagonism of plant immune perception
2023-09-20

&lt;p&gt;This submission contains Extended Figures, an&nbsp;HTML database,&nbsp;and raw experimental data from &quot;&lt;strong&gt;Evolutionary dynamics of proteinaceous MAMPs reveals intrabacterial antagonism of plant immune perception&quot; &lt;/strong&gt;by Stevens et al. See file description for more information. Preprint DOI:&nbsp;https://doi.org/10.1101/2023.09.21.558511&lt;/p&gt;
Seeing the future of progressive glasses: a new perceptual approach to spectacle lens design
2023-09-20

The eye’s natural aging influences our ability to focus on close objects. Without optical correction, all adults will suffer from blurry close vision starting in their 40s. In effect, different optical corrections are necessary for near and far vision. Current state-of-the-art glasses offer a gradual change of correction across the field of view for any distance—using Progressive Addition Lenses (PALs). However, an inevitable side effect of PALs is geometric distortion, which causes the swim effect, a phenomenon of unstable perception of the environment leading to discomfort for many wearers. Unfortunately, little is known about the relationship between lens distortions and their perceptual effects, that is, between the complex physical distortions on the one hand and their subjective severity on the other.We show that perceived distortion can be measured as a psychophysical scaling function using a VR experiment with accurately simulated PAL distortions. Despite the multi-dimensional space of physical distortions, the measured perception is well represented as a 1D scaling function; distortions are perceived less with negative far correction, suggesting an advantage for short-sighted people.Beyond that, our results successfully demonstrate that psychophysical scaling with ordinal embedding methods can investigate complex perceptual phenomena like lens distortions that affect geometry, stereo, and motion perception. Our approach provides a new perspective on lens design based on modeling visual processing that could be applied beyond distortions. We anticipate that future PAL designs could be improved using our method to minimize subjectively discomforting distortions rather than merely optimizing physical parameters.
Diagnostic genome sequencing improves diagnostic yield: a prospective single-centre study in 1000 patients with inherited eye diseases
2023-09-21

Purpose Genome sequencing (GS) is expected to reduce the diagnostic gap in rare disease genetics. We aimed to evaluate a scalable framework for genome-based analyses ‘beyond the exome’ in regular care of patients with inherited retinal degeneration (IRD) or inherited optic neuropathy (ION). Methods PCR-free short-read GS was performed on 1000 consecutive probands with IRD/ION in routine diagnostics. Complementary whole-blood RNA-sequencing (RNA-seq) was done in a subset of 74 patients. An open-source bioinformatics analysis pipeline was optimised for structural variant (SV) calling and combined RNA/DNA variation interpretation. Results A definite genetic diagnosis was established in 57.4% of cases. For another 16.7%, variants of uncertain significance were identified in known IRD/ION genes, while the underlying genetic cause remained unresolved in 25.9%. SVs or alterations in non-coding genomic regions made up for 12.7% of the observed variants. The RNA-seq studies supported the classification of two unclear variants. Conclusion GS is feasible in clinical practice and reliably identifies causal variants in a substantial proportion of individuals. GS extends the diagnostic yield to rare non-coding variants and enables precise determination of SVs. The added diagnostic value of RNA-seq is limited by low expression levels of the major IRD disease genes in blood.
Solid pseudopapillary neoplasms of the pancreas in childhood and adolescence—an analysis of the German Registry for Rare Pediatric Tumors (STEP)
2023-09-21

Abstract Solid pseudopapillary neoplasms (SPNs) are the most common entity among pediatric pancreatic tumors. Still, these are rare tumors with an annual incidence of 0.1–0.2/1,000,000, and little is known about their optimal treatment. This analysis aimed to increase knowledge about the occurrence and treatment strategies of SPN in childhood. Data regarding diagnostics, treatment, and outcome of children aged 0–18 years with SPN recorded in the German Registry for Rare Pediatric Tumors (STEP) were analyzed. Thirty-eight patients were identified with a median age of 14.5 years at diagnosis (range: 8–18) and a female preponderance (81.6%). The most frequent location of the tumor was the pancreatic tail. In histopathological and immunohistochemical examination, pseudopapillary, solid, and cystic lesions as well as expression of beta-catenin, progesterone receptors, and cyclin D1 were the most common findings. All patients underwent surgical resection. Most patients underwent open resection, predominantly tail resection for tumors in the tail region and pylorus-preserving pancreaticoduodenectomy for tumors in the head region. The main postoperative sequela was exogenous pancreatic insufficiency (23.7%), especially with SPN in the pancreatic head. No recurrence occurred during follow-up, although two patients underwent resection with microscopic residue. Conclusion : SPN of the pancreas in childhood are low-grade malignancies with usually favorable treatment outcomes. However, therapy can lead to relevant long-term sequelae. To prevent recurrence, complete surgical resection is recommended, sparing as much healthy pancreatic tissue as possible. Interdisciplinary collaboration between specialists is essential to optimize treatment. Molecular genetic analysis of these tumors could improve understanding of their genesis. What is Known: • Solid pseudopapillary neoplasms (SPNs) of the pancreas are very rare tumors in childhood. • Little is known about tumorigenesis, and there are no specific guidelines for treatment and follow-up in pediatric patients. What is New: • Characteristics, treatment, and outcome were comprehensively assessed in a large cohort of pediatric patients with SPN. • We propose recommendations for diagnosis, treatment, and follow-up of children with SPN, based on our analysis and considering published experience.
Natural variation of immune epitopes reveals intrabacterial antagonism
2023-09-21

Abstract Plants and animals detect biomolecules termed Microbe-Associated Molecular Patterns (MAMPs) and induce immunity. Agricultural production is severely impacted by pathogens which can be controlled by transferring immune receptors. However, most studies use a single MAMP epitope and the impact of diverse multi-copy MAMPs on immune induction is unknown. Here we characterized the epitope landscape from five proteinaceous MAMPs across 4,228 plant-associated bacterial genomes. Despite the diversity sampled, natural variation was constrained and experimentally testable. Immune perception in both Arabidopsis and tomato depended on both epitope sequence and copy number variation. For example, Elongation Factor Tu is predominantly single copy and 92% of its epitopes are immunogenic. Conversely, 99.9% of bacterial genomes contain multiple Cold Shock Proteins and 46% carry a non-immunogenic form. We uncovered a new mechanism for immune evasion, intrabacterial antagonism, where a non-immunogenic Cold Shock Protein blocks perception of immunogenic forms encoded in the same genome. These data will lay the foundation for immune receptor deployment and engineering based on natural variation. Significance Statement Plants recognize pathogens as non-self using innate immune receptors. Receptors on the cell surface can recognize amino acid epitopes present in pathogen proteins. Despite many papers investigating receptor signaling, the vast majority use a single epitope. Here, we analyzed the natural variation across five different epitopes and experimentally characterized their perception in plants. We highlight the importance of analyzing all epitope copies within a pathogen genome. Through genetic and biochemical analyses, we revealed a mechanism for immune evasion, intrabacterial antagonism, where a non-immunogenic epitope blocks perception of immunogenic forms encoded in a single genome. These data can directly inform disease control strategies by enabling prediction of receptor utility and deployment for current and emerging pathogens.
Surgical Therapy of Congenital Nevi in the First Year of Life—Psychological Impact on Parents
2023-09-21

Background The birth of a child with a congenital melanocytic nevus (CMN) can lead to distress in the parents. Surgical treatment of CMN can begin in infancy. Objectives To provide insight into the perspective of parents of children with CMN regarding their experienced psychological burden and motivation to undergo surgery as well as their satisfaction. Methods Retrospective analysis of patient data of infants (&lt; 1 year of age), who were surgically treated by power stretching for CMN using subcutaneous infiltration anesthesia (SIA) from 01/01/2020 to 08/31/2021. To evaluate the parent’s motivation and psychological burden during the surgical treatment of their child, a questionnaire was designed to interview them in a standardized telephone-based interview. Results Out of 45 interviewed parents, 62.2% indicated “severe” or “very severe” distress at the time of their child’s birth. Distress was mostly reduced by information about diagnosis and treatment (n = 34) and treatment-progress (n = 27). Stigmatization was experienced by 35.6% of parents. 84,5% of parents were highly satisfied with early initiation of surgical therapy. 69% felt “very satisfied” or “satisfied” with the outcome of surgery. Motivation for surgical therapy was concern about malignant transformation of the, possible stigmatization of the child due to the nevus, while most of the parents (73.3%) mentioned both. Conclusions Surgical treatment of CMN by power stretching in SIA in infancy is associated with high levels of satisfaction among the children’s parents. Early initiation of surgical therapy and education about the diagnosis can reduce the psychological burden of the parents and can prevent psychosocial problems in affected children.
Foxes in Retrospect—Unraveling Human-Fox Relationships through Fox Tooth Ornaments in the Swabian Jura
2023-09-21

Personal ornaments play an important role in our understanding of human cultural and behavioral change during the Upper Paleolithic, providing insights into intangible aspects of human cultural behavior. Some ornament forms are better studied than others, and fox tooth ornaments, despite their frequent occurrence and broad spatiotemporal span, are relatively under-addressed. Here we present the first comprehensive study of 40 perforated fox teeth recovered from four cave sites in southwestern Germany. This region’s rich record of symbolic representations, as well as evidence of long-standing human–fox relationships, make the Swabian Jura an ideal case study for investigations of fox tooth ornaments. By applying a holistic approach, including geometric morphometrics and traceology coupled with experimental archaeology, we show that fox teeth were mostly perforated by bifacial scraping and grooving and were worn as ornaments. We discuss the role of foxes within human socio-symbolic and paleoenvironmental systems during the Upper Paleolithic of the Swabian Jura, and we contextualize our results within the broader context of sites across Europe during the Upper Paleolithic. The data we provide are in line with general trends observed across the continent and offer insight into the role of foxes during the Upper Paleolithic, especially regarding human subsistence, cultural expression, and ornament production.
Daratumumab, Bortezomib, and Dexamethasone for Treatment of Patients with Relapsed or Refractory Multiple Myeloma and Severe Renal Impairment: Results from the Phase 2 GMMG-DANTE Trial
2023-09-21

Renal function impairment (RI) is a common complication in multiple myeloma (MM). However, limited data exist on the safety and efficacy of anti-MM regimens in patients with severe RI, as these patients are frequently excluded from clinical trials. This investigator-initiated multicentric phase II GMMG-DANTE trial evaluated daratumumab, bortezomib, and dexamethasone (DVd) in relapsed or refractory (r/r) MM patients with severe RI. r/rMM patients with ≥1 prior treatment line and a GFR &lt;30 mL/min/1.73 m2 or undergoing hemodialysis were eligible and received eight cycles of DVd followed by daratumumab maintenance. The trial closed prematurely after 22/36 planned patients. The primary endpoint was overall response rate (ORR). Median age of patients was 70 (range 55–89) years, with a median GFR of 20.1 mL/min/1.73 m2 (interquartile range, 9.4–27.3 mL/min/1.73 m2), and eight patients under hemodialysis. Median number of prior lines was two (range 1–10). The trial was successful, albeit with premature termination, as it met its primary endpoint, with an ORR of 67% (14/21). The rates of partial response, very good partial response, and complete response were 29%, 29%, and 10%, respectively (n = 6, 6, and 2). Fourteen patients (67%) achieved renal response. After median follow-up of 28 months, median progression-free survival was 10.4 months; median overall survival was not reached. Higher-grade toxicity was mainly hematologic, and non-hematologic toxicities ≥Grade 3 were mostly infections (24%). The prospective GMMG-DANTE trial investigating DVd exclusively in r/rMM patients with severe RI showed efficacy and safety to be comparable to data from patients without RI.
Mosquito-Borne Arboviruses Occurrence and Distribution in the Last Three Decades in Central Africa: A Systematic Literature Review
2023-09-21

Arboviruses represents a real public health problem globally and in the Central African subregion in particular that represents a high risk zone for the emergence and re-emergence of arboviruses outbreaks. Furthermore, an updated review on the current arboviruses burden and associated mosquito vectors is lacking for this region. To contribute in filling this knowledge gap, the current study was designed with following objectives: (i) to systematically review data on the occurrence and distribution of arboviruses and mosquito fauna and (ii) to identify potential spillover mosquito species in Central African region in the last 30 years. Web search enabled the documentation of 2454 articles from different online databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and The Quality of Reporting of Meta-analyses (QUORUM) steps for a systematic review enabled the selection of 164 articles that fulfilled our selection criteria. Of the six arboviruses (Dengue Virus (DENV), Chikungunya Virus (CHIKV), Yellow Fever Virus (YFV), Zika Virus (ZIKV), Rift Valley Fever Virus (RVFV), and West Nile Virus (WNV)) of public health concern studied, the most frequently reported were Chikungunya and Dengue. The entomological records showed &amp;gt;248 species of mosquitoes and regrouped under 15 genera with Anopheles (n= 100 species), Culex (n= 56 species) and Aedes (n=52 species) having high species diversity. Three genera were rarely represented with only one species and included: Orthopodomyia, Lutzia, and Verrallina, but individuals of the genera Toxorhinchites and Finlayas were not identified upto the species level. We found that two Aedes species (Ae. aegypti and Ae. albopictus) colonised the same microhabitat and were involved in major epidemics of the six medically important arboviruses and other less frequently identified mosquito-genera consisted of competent species and were associated with outbreaks of medical and zoonotic arboviruses. The present study reveals high species richness of competent mosquito-vectors that could lead to the spillover of medically important arboviruses in the region. Although epidemiological studies were found, they were not regularly documented and this also applies to vector competence and transmission studies. Future studies will consider unpublished information in dissertations, technical reports from different countries to enable it more consistent. A regional project entitled: Ecology of Arboviruses (EcoVir) is underway in three countries (Gabon, Benin and Cote d’Ivoire) to generate a more comprehensive epidemiological and entomological data on this topic.
Where’s the Critique? On the Dearth of Critical Theory in German Communication Research
2023-09-21

While the influence of critical theory – connected to the Frankfurt School – has been profound, its legacy is almost non-existent in the field of communication research in Germany. In order to address this counterintuitive state of affairs, we first sketch the historical context that led to the dearth of critical in the German field. We then give a brief overview of the current institutionalization of the field and connect it to the founding of the Network for Critical Communications Research (abbreviated: KriKoWi) that aims to (re-) introduce critical theories (that is the critical theory of the Frankfurt School but also other critical approaches). Last but not least, we sketch our understanding of critique which ought to help scholars using different methodological and theoretical approaches to work together. We hope that similar initiatives in other parts of the world might find our endeavours inspiring and join them.
Antibacterial marinopyrroles and pseudilins act as protonophores
2023-09-21

Elucidating the mechanism of action (MoA) of antibacterial natural products is crucial to evaluating their potential as novel antibiotics. The marinopyrroles, pentachloropseudilin, and pentabromopseudilin are densely halogenated, hybrid pyrrole-phenol natural products with potent activity against Gram-positive bacterial pathogens like Staphylococcus aureus. However, the exact way in which they exert this antibacterial activity has not been established. In this study, we explore their structure-activity relationship, determine their spatial location in bacterial cells, and investigate their MoA. We show that the natural products share a common MoA based on membrane depolarization and dissipation of the proton motive force (PMF) that is essential for cell viability. The compounds show potent protonophore activity, but do not appear to destroy the integrity of the cytoplasmic membrane via the formation of larger pores or interfere with the stability of the peptidoglycan sacculus. Thus, our current model for the antibacterial MoA of marinopyrrole, pentachloropseudilin, and pentabromopseudilin stipulates that the acidic compounds insert into the membrane and transport protons inside the cell. This MoA may explain many of the deleterious biological effects in mammalian cells, plants, phytoplankton, viruses, and protozoans that have been reported for these compounds.