bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electromyostimulation With Blood Flow Restriction for Patellofemoral Pain Syndrome in Active Duty Military Personnel: A Randomized Controlled Trial
Authors: Talbot Laura A , Webb Lee , Morrell Christopher , Enochs Kayla , Hillner Jesse , Fagan Mathias , Metter E Jeffrey 
Published: February 2023

ABSTRACT

Introduction
The high prevalence of patellofemoral pain in military service members results in strength loss, pain, and functional limitations during required physical performance tasks. Knee pain is often the limiting factor during high-intensity exercise for strengthening and functional improvement, thus limiting certain therapies. Blood flow restriction (BFR) improves muscle strength when combined with resistance or aerobic exercise and may serve as a possible alternative to high-intensity training during recovery. In our previous work, we showed that Neuromuscular electrical stimulation (NMES) improves pain, strength, and function in patellofemoral pain syndrome (PFPS), which led us to ask whether the addition of BFR to NMES would result in further improvements. This randomized controlled trial compared knee and hip muscle strength, pain, and physical performance of service members with PFPS who received BFR-NMES (80% limb occlusion pressure [LOP]) or BFR-NMES set at 20 mmHg (active control/sham) over 9 weeks.

Methods
This randomized controlled trial randomly assigned 84 service members with PFPS to one of the two intervention groups. In-clinic BFR-NMES was performed two times per week, while at-home NMES with exercise and at-home exercise alone were performed on alternating days and omitted on in-clinic days. The outcome measures included strength testing of knee extensor/flexor and hip posterolateral stabilizers, 30-second chair stand, forward step-down, timed stair climb, and 6-minute walk.

Results
Improvement was observed in knee extensor (treated limb, P &lt; .001) and hip strength (treated hip, P = .007) but not flexor over 9 weeks of treatment; however, there was no difference between high BFR (80% LOP) and BFR-sham. Physical performance and pain measures showed similar improvements over time with no differences between groups. In analyzing the relationship between the number of BFR-NMES sessions and the primary outcomes, we found significant relationships with improvements in treated knee extensor strength (0.87 kg/session, P &lt; .0001), treated hip strength (0.23 kg/session, P = .04), and pain (−0.11/session, P &lt; .0001). A similar set of relationships was observed for the time of NMES usage for treated knee extensor strength (0.02/min, P &lt; .0001) and pain (−0.002/min, P = .002).

Conclusion
NMES strength training offers moderate improvements in strength, pain, and performance; however, BFR did not provide an additive effect to NMES plus exercise. Improvements were positively related to the number of BFR-NMES treatments and NMES usage.
Evolution of Spatial and Temporalcis-Regulatory Divergence in Sticklebacks
Authors: Mack Katya L , Square Tyler A , Zhao Bin , Miller Craig T , Fraser Hunter B 
Published: February 2023

AbstractCis-regulatory changes are thought to play a major role in adaptation. Threespine sticklebacks have repeatedly colonized freshwater habitats in the Northern Hemisphere, where they have evolved a suite of phenotypes that distinguish them from marine populations, including changes in physiology, behavior, and morphology. To understand the role of gene regulatory evolution in adaptive divergence, here we investigate cis-regulatory changes in gene expression between marine and freshwater ecotypes through allele-specific expression (ASE) in F1 hybrids. Surveying seven ecologically relevant tissues, including three sampled across two developmental stages, we identified cis-regulatory divergence affecting a third of genes, nearly half of which were tissue-specific. Next, we compared allele-specific expression in dental tissues at two timepoints to characterize cis-regulatory changes during development between marine and freshwater fish. Applying a genome-wide test for selection on cis-regulatory changes, we find evidence for lineage-specific selection on several processes between ecotypes, including the Wnt signaling pathway in dental tissues. Finally, we show that genes with ASE, particularly those that are tissue-specific, are strongly enriched in genomic regions of repeated marine-freshwater divergence, supporting an important role for these cis-regulatory differences in parallel adaptive evolution of sticklebacks to freshwater habitats. Altogether, our results provide insight into the cis-regulatory landscape of divergence between stickleback ecotypes across tissues and during development, and support a fundamental role for tissue-specific cis-regulatory changes in rapid adaptation to new environments.
Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components
Authors: Ugur Enes , de la Porte Alexandra , Qin Weihua , Bultmann Sebastian , Ivanova Alina , Drukker Micha , Mann Matthias , Wierer Michael , Leonhardt Heinrich 
Published: February 2023

AbstractThe establishment of cellular identity is driven by transcriptional and epigenetic regulators of the chromatin proteome - the chromatome. Comprehensive analyses of the chromatome composition and dynamics can therefore greatly improve our understanding of gene regulatory mechanisms. Here, we developed an accurate mass spectrometry (MS)-based proteomic method called Chromatin Aggregation Capture (ChAC) followed by Data-Independent Acquisition (DIA) and analyzed chromatome reorganizations during major phases of pluripotency. This enabled us to generate a comprehensive atlas of proteomes, chromatomes, and chromatin affinities for the ground, formative and primed pluripotency states, and to pinpoint the specific binding and rearrangement of regulatory components. These comprehensive datasets combined with extensive analyses identified phase-specific factors like QSER1 and JADE1/2/3 and provide a detailed foundation for an in-depth understanding of mechanisms that govern the phased progression of pluripotency. The technical advances reported here can be readily applied to other models in development and disease.
Flanking strand separation activity of RecA nucleoprotein filaments in DNA strand exchange reactions
Authors: Yu Fangzhi , Zhang Dapeng , Zhao Chubin , Zhao Qiang , Jiang Guibin , Wang Hailin 
Published: February 2023

AbstractThe recombinase RecA/Rad51 ATPase family proteins catalyze paramount DNA strand exchange reactions that are critically involved in maintaining genome integrity. However, it remains unclear how DNA strand exchange proceeds when encountering RecA-free defects in recombinase nucleoprotein filaments. Herein, by designing a series of unique substrates (e.g. truncated or conjugated incoming single-stranded DNA, and extended donor double-stranded DNA) and developing a two-color alternating excitation-modified single-molecule real-time fluorescence imaging assay, we resolve the two key steps (donor strand separation and new base-pair formation) that are usually inseparable during the reaction, revealing a novel long-range flanking strand separation activity of synaptic RecA nucleoprotein filaments. We further evaluate the kinetics and free energetics of strand exchange reactions mediated by various substrates, and elucidate the mechanism of flanking strand separation. Based on these findings, we propose a potential fundamental molecular model involved in flanking strand separation, which provides new insights into strand exchange mechanism and homologous recombination.
Umberto Eco
Authors: Pacchioni Federico , Kelly Sawyer 
Published: February 2023

Umberto Eco (b. 1932–d. 2016) was an Italian author and theorist whose contributions to the academic and creative zeitgeists ripple into inter- and multidisciplinary fields including, but not limited to, semiotics, linguistics, communication theory, narrative theory, politics, pop culture, history, and aesthetic theory. Best known for his groundbreaking work surrounding the relationships between language, texts, authors, and audiences, Eco’s theoretical work has prompted a reckoning of modern discourses surrounding interpretation and the rights of readers and authors respectively. Eco’s discursive style is characterized by its emphasis on intertextual ideation—the conceptualization of history, culture, theory, and language as sedimentary accumulations, the combination of which may yield increased and deepened insight into each discipline both separately, and as a coalesced unit. A champion of expressive forms, Eco demolished the false binary between “high” and “low” art forms, recognizing mass media and pop culture as compelling, rich areas of academic pursuit. In this way, Eco’s theoretical and fictional work may also be conceptualized as efforts to demystify and expand the ivory tower frequently associated with the academic and artistic spheres. His works posit the notion that interpretative validity cannot be singularly conferred by virtue of a source’s academic or artistic ethos, but rather both creation and interpretation of work constitutes a living dialogic process wherein meaning is negotiated through complex semiotic communicative systems. As an author, Eco single-handedly crafts a literary world that is as entrancing as it is mysterious. Traversing the boundaries of genre, perspective, reality, fiction, and history, Eco’s literary works are in many ways embodied narrative manifestos of the way Eco views reality—as a kaleidoscopic (and at times, contradictory) ontological mosaic. A totalizing bibliographic account of Eco’s contributions and academia’s responses is nearly impossible. However, the following resources below present several different avenues through which to begin to engage with both his theoretical and creative work. Included below are Eco’s own most notable writings in English translation, as well as a selection of English-language scholarly sources that reflect and respond to Eco. Ultimately, although encapsulating Eco in textual form is in many ways unattainable, these bibliographic entries hope to offer a semblance of a map for (to borrow Joseph Consoli’s metaphor) navigating Eco’s labyrinth.
Paul Gauguin
Authors: Perelman Allison 
Published: February 2023

Paul Gauguin (b. 1848–d. 1903) is perhaps equally well known for his life story as for his art. Born in Paris, he spent most of the first six years of his life in Peru until his family returned to their native France. As a young man, Gauguin sailed internationally in the Merchant Marines before becoming an assistant to a stockbroker in Paris. In the 1870s, his interest in art collecting led to meeting several prominent avant-garde artists, including the Impressionist Camille Pissarro. Soon Gauguin was not only buying art, but he was also practicing painting and sculpture in his spare time. By the early 1880s, he was pursuing a fulltime career as an artist. Gauguin worked in a broad range of media, such as painting, wood carving, ceramics, drawing, and printmaking, in addition to his written manuscripts. He was one of the most radically experimental artists of his time, and his oeuvre reflects the breadth of his material interests and international inspirations. Known for his extensive travels, he lived and worked not only in Paris but also the French regions of Brittany and Provence as well as Denmark, Martinique, Tahiti, and the Marquesas Islands. In 1891, Gauguin left Paris for Tahiti, in search of new subject matter for his art and to cement his reputation as a primitivist. After a brief return to France, where his Polynesian-inspired paintings, sculptures, and prints shocked and confounded audiences, he traveled back to Tahiti. He remained there for six years before moving to the Marquesas Islands, where he lived the last two years of his life. Gauguin is best known for his paintings of Polynesian subjects, particularly female figures. Found in museums around the world, his canvases are often characterized by bright colors, flat application of paint, and a style that emphasized subjective feeling and fantastical imagery over naturalistic representation. Although he began his career with the Impressionists, he is also associated with styles and art movements of Cloisonnism, Symbolism, and Primitivism. Posthumously, he has also been categorized as a Post-Impressionist along with Vincent van Gogh, with whom he had a productive yet combative collaboration. The conflation between Gauguin’s life and art can be traced back to the artist himself. He was a savvy promoter of his own work and created a self-mythology in which he embraced a dual persona as both cerebral avant-gardist and uncivilized savage. During his lifetime, he recognized the value of controversy and defiant aesthetic and political stances in his efforts to promote his career. Gauguin remains a controversial figure, however, largely due to his sexual relationships with girls and young women; his participation in French imperialist and colonialist endeavors overseas; and his utilization of motifs, myths, and figures from other, often marginalized, cultures. With the rise of gender, race, and postcolonial theory in recent decades, scholars around the world continue to grapple with the artist, his work, and his lasting cultural impact.
What is the Source of Infections Causing Invasive NontyphoidalSalmonellaDisease?
Authors: Chirwa Esmeda B , Dale Helen , Gordon Melita A , Ashton Philip M 
Published: February 2023

AbstractInvasive nontyphoidal Salmonella (iNTS) disease is a clinical condition distinct from Salmonella gastroenteritis. With an overall case-fatality rate of 14.5%, iNTS remains a major cause of morbidity and mortality, particularly in sub-Saharan Africa. However, the sources of infections that lead to cases of iNTS remain unclear. Broadly, there are 2 hypotheses as to the source of infections: (i) transmission from a zoonotic reservoir, similar to other nontyphoidal salmonelloses; or (ii) person-to-person transmission. Here we review several recent studies that have asked, “What is the source of infections causing invasive nontyphoidal Salmonella disease?” Two studies reported isolates in the stool of household members of iNTS cases that were very closely related (&lt;3 single-nucleotide polymorphisms) to the iNTS case isolates; this is consistent with the hypothesis of person-to-person transmission, but infection from a common source (eg, a foodstuff) cannot be excluded. On the other hand, thorough investigations of the domestic environment of iNTS cases and the food pathway found only a single iNTS-associated Salmonella Enteritidis isolate. Therefore, we recommend that future studies test the hypothesis that iNTS is transmitted between people within the domestic environment. Further studies of food and water pathways are also warranted.
On the Epistemic Significance of Perceptual Structure
Authors: Alford-Duguid Dominic 
Published: February 2023

Abstract
Our awareness of the boundedness of the spatial sensory field—a paradigmatic structural feature of visual experience—possesses a distinctive epistemic role. Properly understood, this result undermines a widely assumed picture of how visual experience permits us to learn about the world. This paper defends an alternative picture in which visual experience provides at least two kinds of non-inferential justification for beliefs about the external world. Accommodating this justification in turn requires recognising a new way for visual experience to encode information about the world. Reflection upon the epistemic contribution of sensory experience's structural features thus forces us to revise our understanding of how perception, cognition, and the world fit together.
Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production
Authors: Cantoni Eleonora , Merelli Ivan , Stefanoni Davide , Tomelleri Alessandro , Campochiaro Corrado , Giordano Vito , Panigada Maddalena , Baldissera Elena M , Merlo Pich Laura , Natoli Valentina , Ziogas Athanasios , Domínguez-Andrés Jorge , De Luca Giacomo , Mazza Davide , Zambrano Samuel , Gnani Daniela , Ferrarini Marina , Ferrero Elisabetta , Agresti Alessandra , Vergani Barbara , Leone Biagio Eugenio , Cenci Simone , Ravelli Angelo , Matucci-Cerinic Marco , D’Alessandro Angelo , Joosten Leo A B , Dagna Lorenzo , Netea Mihai G , Molteni Raffaella , Cavalli Giulio 
Published: February 2023

Abstract

Objective
Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production.

Methods
Monocytes from GCA patients and from age- and sex-matched healthy donors were subjected to polyfunctional studies, including cytokine production assays at baseline and following stimulation, intracellular metabolomics, chromatin immunoprecipitation-qPCR, and combined ATAC/RNA sequencing. Immunometabolic activation (i.e. glycolysis) was assessed in inflamed vessels of GCA patients with FDG-PET and immunohistochemistry (IHC), and the role of this pathway in sustaining cytokine production was confirmed with selective pharmacologic inhibition in GCA monocytes.

Results
GCA monocytes exhibited hallmark molecular features of TI. Specifically, these included enhanced IL-6 production upon stimulation, typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis) and epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation. Immunometabolic changes of TI (i.e. glycolysis) were a feature of myelomonocytic cells in GCA lesions and were required for enhanced cytokine production.

Conclusions
Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.
Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species‐mediated activation of placental GCN2/eIF2α pathway
Authors: Lin Shuai , Ye Meng‐Ying , Fu Qian‐Yun , Pan Chao‐Lin , Liu Ya‐Jie , Zheng Li‐Ming , Hong Qiang , Chen Yuan‐Hua 
Published: February 2023

AbstractEpidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown‐rump length, and increased the incidence of FGR in a dose‐dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down‐regulating the protein but not the mRNA level of placental 11β‐Hydroxysteroid dehydrogenase‐2 (11β‐HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA‐induced down‐regulation of 11β‐HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA‐induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down‐regulation of 11β‐HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA‐induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS‐mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis‐induced placental dysfunction and subsequent FGR.
Use of Pediatric Outcomes Data Collection Instrument to Evaluate Functional Outcomes in Multiple Hereditary Exostoses
Authors: Sundin Palmeira de Oliveira Nathalia , Rocha Dias da Silva Marcela , Bedeschi Rego de Mattos Camila 
Published: February 2023

Background:
The Pediatric Outcomes Data Collection Instrument (PODCI) is a validated quality-of-life questionnaire with 6 domains designed to provide a standardized method of measuring outcomes in pediatric musculoskeletal conditions. To our knowledge there are no reports on its use in children with multiple hereditary exostosis (MHE).

Questions/Purposes:
Most published studies on MHE patients have described the efficacy of specific surgical techniques or the specification of deformities. Little is known about the general health status of pediatric patients, the severity of pain, loss of function, and how MHE influences the activities of daily life. We aim to assess the functional levels of MHE pediatric patients with PODCI questionnaire.

Patients and Methods:
As a cross-sectional study, we prospectively administered PODCI to 34 pediatric patients diagnosed with MHE and their families. The score distributions were compared with values published earlier for children and adolescents without musculoskeletal disorders using the Student and Welch t tests. Parents and adolescents’ reports were compared using Wilcoxon signed rank test. Physical examination and PODCI score relation were evaluated by Spearman test.

Results:
Children with MHE have significantly lower scores (P<0,05) in comparison with unaffected children in all domains using the Student and Welch t test. Parents score differs from children score with statistically relevance in pain and comfort domain (P<0,5). The Spearman test showed a negative correlation between physical examination and PODCI score with statistical significance.

Conclusions:
These results point towards PODCI’s capacity in evaluating functional outcomes of pediatric patients with MHE.

Level of Evidence:
Diagnostic Study, Level III.
Ambient fine particulate matter and cardiopulmonary health risks in China
Authors: Li Tiantian , Zhang Yi , Jiang Ning , Du Hang , Chen Chen , Wang Jiaonan , Li Qiutong , Feng Da , Shi Xiaoming 
Published: February 2023

Abstract
In China, the level of ambient fine particulate matter (PM2.5) pollution far exceeds the air quality standards recommended by the World Health Organization. Moreover, the health effects of PM2.5 exposure have become a major public health issue. More than half of PM2.5-related excess deaths are caused by cardiopulmonary disease, which has become a major health risk associated with PM2.5 pollution. In this review, we discussed the latest epidemiological advances relating to the health effects of PM2.5 on cardiopulmonary diseases in China, including studies relating to the effects of PM2.5 on mortality, morbidity, and risk factors for cardiovascular and respiratory diseases. These data provided important evidence to highlight the cardiopulmonary risk associated with PM2.5 across the world. In the future, further studies need to be carried out to investigate the specific relationship between the constituents and sources of PM2.5 and cardiopulmonary disease. These studies provided scientific evidence for precise reduction measurement of pollution sources and public health risks. It is also necessary to identify effective biomarkers and elucidate the biological mechanisms and pathways involved; this may help us to take steps to reduce PM2.5 pollution and reduce the incidence of cardiopulmonary disease.