bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diosgenin prevents periodontitis by inhibiting inflammation and promoting osteogenic differentiation
Authors: Cong Shaohua , Peng Qian , Cao Liou , Yi Qingqing , Liu Yi , Li Linhui , Tong Qingchun , Liang Dongyu 
Published: August 2023

AbstractDiosgenin, an essential dietary steroidal sapogenin, possess multiple pharmacological activities. This study aimed to assess the effects of diosgenin on periodontitis and elucidate the mechanisms. Lipopolysaccharide (LPS)‐stimulated human periodontal ligament stem cells (hPDLCs) and a Porphyromonas gingivalis (P.g) plus ligation‐induced animal model were used for in vitro and in vivo studies, respectively. Inflammatory responses, nuclear factor κ‐B (NF‐κB) signaling and osteogenesis‐related markers were measured both in LPS‐stimulated hPDLSCs and in gingival tissue of periodontitis rats. Treatment with diosgenin significantly inhibited the production of tumor necrosis factor α (TNF‐α), interleukin (IL)‐1β, and interleukin (IL)‐6 and the activation of NF‐κB pathway in LPS‐stimulated hPDLSCs. Further, treatment with diosgenin enhanced the expression of osteoblast‐related genes and increased the osteogenic differentiation capacity. Further, activation NF‐κB pathway largely abolished the protective effects of diosgenin. Consistent with the in vitro studies, in vivo studies showed that administering diosgenin to periodontitis rats significantly lowered the levels of the TNF‐α, IL‐1β, and IL‐6 and the inflammatory transcription factor NF‐κB in gingival tissue. In addition, osteoblast‐related genes were promoted. Diosgenin attenuates periodontitis by adjusting NF‐κB signaling to inhibit inflammatory effects and promoting osteogenesis, suggesting diosgenin might be developed as a therapeutic strategy for treating periodontitis in the future.
Endotheliopathy of liver sinusoidal endothelial cells in liver disease
Authors: Kondo Reiichiro , Iwakiri Yasuko , Kage Masayoshi , Yano Hirohisa 
Published: August 2023

AbstractLiver is the largest solid organ in the abdominal cavity, with sinusoid occupying about half of its volume. Under liver disease, hemodynamics in the liver tissue dynamically change, resulting in injury to liver sinusoidal endothelial cells (LSECs). We discuss the injury of LSECs in liver diseases in this article. Generally, in noninflamed tissues, vascular endothelial cells maintain quiescence of circulating leukocytes, and unnecessary blood clotting is inhibited by multiple antithrombotic factors produced by the endothelial cells. In the setting of inflammation, injured endothelial cells lose these functions, defined as inflammatory endotheliopathy. In chronic hepatitis C, inflammatory endotheliopathy in LSECs contributes to platelet accumulation in the liver tissue, and the improvement of thrombocytopenia by splenectomy is attenuated in cases with severe hepatic inflammation. In COVID‐19, LSEC endotheliopathy induced by interleukin (IL)‐6 trans‐signaling promotes neutrophil accumulation and platelet microthrombosis in the liver sinusoids, resulting in liver injury. IL‐6 trans‐signaling promotes the expression of intercellular adhesion molecule‐1, chemokine (C‐X‐C motif) ligand (CXCL1), and CXCL2, which are the neutrophil chemotactic mediators, and P‐selectin, E‐selectin, and von Willebrand factor, which are involved in platelet adhesion to endothelial cells, in LSECs. Restoring LSECs function is important for ameliorating liver injury. Prevention of endotheliopathy is a potential therapeutic strategy in liver disease.
Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology
Authors: Kobayashi Go , Hayashi Tetsutaro , Sentani Kazuhiro , Uraoka Naohiro , Fukui Takafumi , Kido Aya , Katsuya Narutaka , Ishikawa Akira , Babasaki Takashi , Sekino Yohei , Nose Hiroyuki , Hinata Nobuyuki , Oue Naohide 
Published: August 2023

AbstractβIII‐Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high‐grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki‐67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer‐related molecules, TUBB3 was an independent predictor of progression‐free survival and high‐grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high‐grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.
Identifying different ‘types’ of participants in the Chilean student movement: A latent transition analysis of collective action intentions, social class and movement identification
Authors: Álvarez Belén , Jetten Jolanda , Selvanathan Hema Preya , González Roberto , Carvacho Héctor 
Published: August 2023

AbstractAround the world, we witness not only growing levels of economic inequality but also the rise of protests whereby people from different social classes are demanding a more equal society. Our research uses a person‐centered approach to examine subgroups of participants in a social movement against inequality on the basis of their social class, intention to participate in conventional and/or radical collective actions, and social identification with the movement. We used longitudinal data from the Chilean student movement (two time points; total N = 1226) to conduct latent profile and latent transition analysis. We identified four profiles of participants: (1) inactive supporters (mostly from the upper class), (2) low radicals (mostly from the middle class), (3) moderate radicals (mostly from the middle class), and (4) high radicals (mostly from the middle class). The four profiles were generally stable over the one‐year period. We further found that group efficacy and a “nothing to lose” mindset predicted the profile membership of participants. Group efficacy also predicted transitions of participants between different profiles. Our findings highlight the key role that the middle class plays in diverse forms of collective action.
Entheogens: Psychedelic religion in the United States, part one
Authors: Stoddard Brad 
Published: August 2023

AbstractScholars across the academic spectrum have written about the renewed interest in psychedelics that is commonly called the Psychedelic Renaissance (PR). Psychedelic religion is a major component of the PR, as psychedelic churches are growing exponentially and as people who consume and who research psychedelics routinely contend that these substances induce or occasion religious, spiritual, or mystical experiences. Scholars have noticed the growing association of psychoactive substances and religiosity, and they have addressed this association from a variety of academic fields, methods, and methodologies. This article explores the historiography of associations of psychoactive substances and religiosity in the United States from the 1800s to the 1980s.
Toward an integrated analysis of social movements and new religious movements research
Authors: Moon Minyoung 
Published: August 2023

AbstractDespite calls from researchers for intersectional studies between religion and social movements over the past few decades, scholars have not engaged in fruitful conversation about integrating the two disciplines. This article aims to facilitate such discussion by examining the topic of new religious movements (NRMs). I first review the existing literature on NRMs and discuss why NRM research has been neglected in social movement studies. Then, I explore a few research areas where both NRM studies and social movement research could intersect and benefit from a synthetic approach. Specifically, I suggest that social movement studies could advance through the examination of some relatively ignored subjects of research, such as persistent participation and disengagement, by drawing on empirical cases of NRMs. I also propose ways in which the application of social movement theories would enhance our understanding of different aspects of NRMs, such as their leadership and coalition practices. In making these arguments, I refer to one of the prominent, long‐term NRMs, the Unification Church or Movement, to help illustrate my ideas.
Tick-Tock Goes the Biological Clock: Challenges Facing Elite Scandinavian Mother-Athletes
Authors: Bergström Max , Sæther Stig Arve , Solli Guro Strøm , McGawley Kerry 
Published: August 2023

Challenges facing mother-athletes (MAs) have aroused research and media attention in recent years, with an increasing number of sportswomen attempting to successfully combine pregnancy and motherhood with an elite athletic career. The aims of this study were to explore how MA-specific challenges manifest in elite cross-country skiing in Scandinavia and to better understand how female athletes balance their priorities as they initiate, maintain, and/or discontinue their role as a MA. Qualitative data were collected through semistructured interviews with 13 female cross-country skiers from Norway and Sweden. Thematic analyses revealed four MA-specific challenges facing the athletes: (a) Biological clock versus peak performance, (b) Maintaining fitness versus training safely, (c) Receiving support versus facing deselection, and (d) Balancing competing MA demands. Many of the athletes felt pressured into prioritizing either motherhood or athletic excellence, particularly in their early to mid-30s when the window of opportunity for building a family was considered limited. Further, maintaining fitness and training safely during pregnancy were perceived as a challenge, as was balancing the MA role after childbirth. In many cases, athletes felt uncertain about whether they would receive support from their team or federation. Moreover, there were expectations of incompatibility surrounding the MA role. More research and educational efforts to promote MA-specific knowledge, as well as developing structured processes and providing policies to support female athletes, are identified as vital future steps. These measures may prolong athletic careers and enhance well-being for elite female athletes.
New insight into flavivirus maturation from structure/function studies of the yellow fever virus envelope protein complex
Authors: Crampon E. , Covernton E. , Vaney M. C. , Dellarole M. , Sommer S. , Sharma A. , Haouz A. , England P. , Lepault J. , Duquerroy S. , Rey F. A. , Barba-Spaeth G. 
Published: August 2023

ABSTRACT
Flavivirus particle maturation, a process essential for virus infectivity, has been mostly studied using dengue virus. In infected cells, immature icosahedral virions bud into the endoplasmic reticulum. Budding is induced by lateral contacts between heterodimers of transmembrane glycoproteins prM and E. During exocytosis through the trans-Golgi network (TGN), the acidic environment triggers a major particle reorganization in which E forms head-to-tail dimers and furin cleaves prM into globular pr and transmembrane M proteins. pr remains bound to E at acidic pH and blocks its fusogenic activity, but at neutral pH, its affinity for E drops and pr is shed from the particle in the extracellular environment, leaving a virion activated for fusion at low pH. We report here that recombinant yellow fever virus (YFV) pr retains high affinity for soluble E (sE) at neutral pH—significantly shifting the current paradigm. The X-ray structure of the YFV pr/sE complex shows essentially the same pattern of interactions reported for dengue virus, while the X-ray structure of YFV sE at neutral pH shows the same canonical head-to-tail sE dimer. pr binding to the sE dimer is precluded by the E “150-loop,” indicating it must adopt a different conformation in the E dimers on virions at acidic pH for pr binding. We had previously reported a similar local reorganization of the E 150-loop at acidic pH for the tick-borne encephalitis virus, with the important difference that pr stabilized a soluble sE head-to-tail dimer, which is not the case for YFV.

IMPORTANCE
All enveloped viruses enter cells by fusing their envelope with a target cell membrane while avoiding premature fusion with membranes of the producer cell—the latter being particularly important for viruses that bud at internal membranes. Flaviviruses bud in the endoplasmic reticulum, are transported through the TGN to reach the external milieu, and enter other cells via receptor-mediated endocytosis. The trigger for membrane fusion is the acidic environment of early endosomes, which has a similar pH to the TGN of the producer cell. The viral particles therefore become activated to react to mildly acidic pH only after their release into the neutral pH extracellular environment. Our study shows that for yellow fever virus (YFV), the mechanism of activation involves actively knocking out the fusion brake (protein pr) through a localized conformational change of the envelope protein upon exposure to the neutral pH external environment. Our study has important implications for understanding the molecular mechanism of flavivirus fusion activation in general and points to an alternative way of interfering with this process as an antiviral treatment.
The
Campylobacter concisus
BisA protein plays a dual role: oxide-dependent anaerobic respiration and periplasmic methionine sulfoxide repair
Authors: Benoit Stéphane L. , Maier Robert J. 
Published: August 2023

ABSTRACT

Campylobacter concisus
, an emerging pathogen found throughout the human oral-gastrointestinal tract, is able to grow under microaerobic or anaerobic conditions; in the latter case, N- or S-oxides could be used as terminal electron acceptors (TEAs). Analysis of 23 genome sequences revealed the presence of multiple (at least two and up to five) genes encoding for putative periplasmic N- or S-oxide reductases (N/SORs), all of which are predicted to harbor a molybdopterin (or tungstopterin)-
bis
guanine dinucleotide (Mo/W-
bis
PGD) cofactor. Various N- or S-oxides, including nicotinamide N-oxide, trimethylamine N-oxide , biotin sulfoxide, dimethyl sulfoxide, and methionine sulfoxide (MetO), significantly increased anaerobic growth in two
C. concisus
intestinal strains (13826 and 51562) but not in the
C. concisus
oral (type) strain 33237. A collection of mutants was generated to determine each N/SOR substrate specificity. Surprisingly, we found that disruption of a single gene, annotated as “
bisA
” (present in strains
Cc
13826 and
Cc
51562 but not in
Cc
33237), abolished all N-/S-oxide-supported respiration. Furthermore, Δ
bisA
mutants showed increased sensitivity to oxidative stress and displayed cell envelope abnormalities, suggesting BisA plays a role in protein MetO repair. Indeed, purified recombinant
Cc
BisA was able to successfully repair MetO residues on a commercial protein (β-casein), as shown by mass spectrometry. Our results suggest that BisA plays a dual role in
C. concisus
, by allowing the pathogen to use N-/S-oxides as TEAs and by repairing periplasmic protein-bound MetO residues, therefore essentially being a periplasmic methionine sulfoxide reductase (Msr). This is the first report of a Mo/W-
bis
PGD-containing Msr enzyme in a pathogen.

IMPORTANCE

Campylobacter concisus
is an excellent model organism to study respiration diversity, including anaerobic respiration of physiologically relevant N-/S-oxides compounds, such as biotin sulfoxide, dimethyl sulfoxide, methionine sulfoxide (MetO), nicotinamide N-oxide, and trimethylamine N-oxide. All
C. concisus
strains harbor at least two, often three, and up to five genes encoding for putative periplasmic Mo/W-bisPGD-containing N-/S-oxide reductases. The respective role (substrate specificity) of each enzyme was studied using a mutagenesis approach. One of the N/SOR enzymes, annotated as "BisA", was found to be essential for anaerobic respiration of both N- and S-oxides. Additional phenotypes associated with disruption of the
bisA
gene included increased sensitivity toward oxidative stress and elongated cell morphology. Furthermore, a biochemical approach confirmed that BisA can repair protein-bound MetO residues. Hence, we propose that BisA plays a role as a periplasmic methionine sulfoxide reductase. This is the first report of a Mo/W-bisPGD-enzyme supporting both N- or S-oxide respiration and protein-bound MetO repair in a pathogen.
How and why snakebite became a global health priority: a policy analysis
Authors: Bhaumik Soumyadeep , Zwi Anthony B , Norton Robyn , Jagnoor Jagnoor 
Published: August 2023

BackgroundSnakebite was added to the WHO neglected tropical disease (NTD) list in 2017, followed by a World Health Assembly resolution in 2018, and an explicit global target being set to reduce the burden in 2019. We aimed to understand how and why snakebite became a global health priority.MethodsWe conducted a policy case study, using in-depth interviews, and documents (peer-reviewed and grey literature) as data sources. We drew on Shiffmanet al’s framework on global health network to guide the analysis.ResultsWe conducted 20 interviews and examined 91 documents. The prioritisation of snakebite occurred in four phases: pre-crescendo, crescendo, de-crescendo and re-crescendo. The core snakebite network consisted of academics, which expanded during the re-crescendo phase to include civil society organisations and state actors. The involvement of diverse stakeholders led to better understanding of WHO processes. The use of intersecting and layered issue framing, framing solutions around snake antivenoms, in a background of cross-cultural fascination and fear of snakes enabled prioritisation in the re-crescendo phase. Ebbs and flows in legitimacy of the network and reluctant acceptance of snakebite within the NTD community are challenges.ConclusionOur analyses imply a fragile placement of snakebite in the global agenda. We identify two challenges, which needs to be overcome. The study highlights the need to review the WHO criteria for classifying diseases as NTD. We propose that future prioritisation analysis should consider identifying temporal patterns, as well as integrating legitimacy dimensions, as in our study.
Patient and family contributions to improve the diagnostic process through the OurDX electronic health record tool: a mixed method analysis
Authors: Bell Sigall K , Harcourt Kendall , Dong Joe , DesRoches Catherine , Hart Nicholas J , Liu Stephen K , Ngo Long , Thomas Eric J , Bourgeois Fabienne C. 
Published: August 2023

BackgroundAccurate and timely diagnosis relies on sharing perspectives among team members and avoiding information asymmetries. Patients/Families hold unique diagnostic process (DxP) information, including knowledge of diagnostic safety blindspots—information that patients/families know, but may be invisible to clinicians. To improve information sharing, we co-developed with patients/families an online tool called ‘Our Diagnosis (OurDX)’. We aimed to characterise patient/family contributions in OurDX and how they differed between individuals with and without diagnostic concerns.MethodWe implemented OurDX in two academic organisations serving patients/families living with chronic conditions in three subspecialty clinics and one primary care clinic. Prior to each visit, patients/families were invited to contribute visit priorities, recent histories and potential diagnostic concerns. Responses were available in the electronic health record and could be incorporated by clinicians into visit notes. We randomly sampled OurDX reports with and without diagnostic concerns for chart review and used inductive and deductive qualitative analysis to assess patient/family contributions.Results7075 (39%) OurDX reports were submitted at 18 129 paediatric subspecialty clinic visits and 460 (65%) reports were submitted among 706 eligible adult primary care visits. Qualitative analysis of OurDX reports in the chart review sample (n=450) revealed that participants contributed DxP information across 10 categories, most commonly: clinical symptoms/medical history (82%), tests/referrals (54%) and diagnosis/next steps (51%). Participants with diagnostic concerns were more likely to contribute information on DxP risks including access barriers, recent visits for the same problem, problems with tests/referrals or care coordination and communication breakdowns, some of which may represent diagnostic blindspots.ConclusionPartnering with patients and families living with chronic conditions through OurDX may help clinicians gain a broader perspective of the DxP, including unique information to coproduce diagnostic safety.
T-cell receptor beta variable gene polymorphism predicts immune-related adverse events during checkpoint blockade immunotherapy
Authors: Stephen Bettzy , Hajjar Joud , Sarda Shrutii , Duose Dzifa Yawa , Conroy Jeffrey M , Morrison Carl , Alshawa Anas , Xu Mingxuan , Zarifa Abdulrazzak , Patel Sapna P , Yuan Ying , Kwiatkowski Evan , Wang Linghua , Rodon Ahnert Jordi , Fu Siqing , Meric-Bernstam Funda , Lowman Geoffrey M , Looney Timothy , Naing Aung 
Published: August 2023

BackgroundImmune checkpoint inhibitors have revolutionized cancer treatment. However, they are associated with a unique spectrum of side effects, called immune-related adverse events (irAEs), which can cause significant morbidity and quickly progress to severe or life-threatening events if not treated promptly. Identifying predictive biomarkers for irAEs before immunotherapy initiation is therefore a critical area of research. Polymorphisms within the T-cell receptor beta (TCRB) variable (TRBV) gene have been implicated in autoimmune disease and may be mechanistically linked to irAEs. However, the repetitive nature of the TCRB locus and incomplete genome assembly has hampered the evaluation of TRBV polymorphisms in the past.Patients and methodsWe used a novel method for long-amplicon next generation sequencing of rearranged TCRB chains from peripheral blood total RNA to evaluate the link between TRBV polymorphisms and irAEs in patients treated with immunotherapy for cancer. We employed multiplex PCR to create amplicons spanning the three beta chain complementarity-determining regions (CDR) regions to enable detection of polymorphism within the germline-encoded framework and CDR1 and CDR2 regions in addition to CDR3 profiling. Resultant amplicons were sequenced via the Ion Torrent and TRBV allele profiles constructed for each individual was correlated with irAE annotations to identify haplotypes associated with severe irAEs (≥ grade 3).ResultsOur study included 81 patients who had irAEs when treated with immunotherapy for cancer. By using principal component analysis of the 81 TRBV allele profiles followed by k-means clustering, we identified six major TRBV haplotypes. Strikingly, we found that one-third of this cohort possessed a TRBV allele haplotype that appeared to be protective against severe irAEs.ConclusionThe data suggest that long-amplicon TCRB repertoire sequencing can potentially identify TRBV haplotype groups that correlate with the risk of severe irAEs. Germline-encoded TRBV polymorphisms may serve as a predictive biomarker of severe irAEs.