bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved autophagy and diverse cell wall composition: unifying features of vascular tissues in evolutionarily distinct plants
Authors: Michalak Kornel M , Wojciechowska Natalia , Marzec-Schmidt Katarzyna , Bagniewska-Zadworna Agnieszka 
Published: February 2024

Abstract

Background and Aims
The formation of multifunctional vascular tissues represents a significant advancement in plant evolution. Differentiation of conductive cells is specific, involving two main pathways, namely protoplast clearance and cell wall modification. In xylogenesis, autophagy is a crucial process for complete protoplast elimination in tracheary elements, whose cell wall also undergoes strong changes. Knowledge pertaining to living sieve elements, which lose most of their protoplast during phloemogenesis, remains limited. We hypothesized that autophagy plays a crucial role, not only in complete cytoplasmic clearance in xylem but also in partial degradation in phloem. Cell wall elaborations of mature sieve elements are not so extensive. These analyses performed on evolutionarily diverse model species potentially make it possible to understand phloemogenesis to an equal extent to xylogenesis.

Methods
We investigated the distribution of ATG8 protein, which is an autophagy marker, and cell wall components in the roots of ferns, gymnosperms and angiosperms (monocots, dicot herbaceous plants and trees). Furthermore, we conducted a bioinformatic analysis of complete data on ATG8 isoforms for Ceratopteris richardii.

Key Results
The presence of ATG8 protein was confirmed in both tracheary elements and sieve elements; however, the composition of cell wall components varied considerably among vascular tissues in the selected plants. Arabinogalactan proteins and β-1,4-galactan were detected in the roots of all studied species, suggesting their potential importance in phloem formation or function. In contrast, no evolutionary pattern was observed for xyloglucan, arabinan or homogalacturonan.

Conclusions
Our findings indicate that the involvement of autophagy in plants is universal during the development of tracheary elements that are dead at maturity and sieve elements that remain alive. Given the conserved nature of autophagy and its function in protoplast degradation for uninterrupted flow, autophagy might have played a vital role in the development of increasingly complex biological organizations, including the formation of vascular tissues. However, different cell wall compositions of xylem and phloem in different species might indicate diverse functionality and potential for substance transport, which is crucial in plant evolution.
507 - Dupilumab demonstrates greater improvement in disease activity than standard-of-care H1-antihistamines in CSU
Authors: Beck Lisa A , Casale Thomas B , Mortensen Eric , Laws Elizabeth , Thomas Ryan B , Chuang Chien-Chia 
Published: February 2024

Abstract

IntroductionChronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by wheals and/or angioedema recurring for &gt;6 weeks. Cumulative distribution function (CDF) curves compare cumulative probabilities of response between treatments across responder definition spectrums.

Methods
LIBERTY-CSU CUPID Study A (NCT04180488) was a randomized, placebo-controlled, phase 3 trial of dupilumab treatment for 24 weeks in patients with CSU remaining symptomatic despite standard-of-care (SOC) H1-antihistamines. Patients were randomized to receive add-on dupilumab (dupilumab/SOC) or placebo (placebo/SOC) subcutaneously every 2 weeks. CDF curves were plotted for the distribution of possible within-patient response for Urticaria Activity Score over 7 days (UAS7), Itch Severity Score over 7 days (ISS7), and Hives Severity Score over 7 days (HSS7) for dupilumab/SOC and placebo/SOC arms.

Results
In CDF analysis at Week 24, more patients experienced UAS7, ISS7, and HSS7 improvements with dupilumab/SOC than placebo/SOC; 74.2% vs 50.0% of patients (dupilumab/SOC vs placebo/SOC) achieved ≥11-point reductions (minimal important difference [MID] threshold) in UAS7. Similarly, 78.8% vs 51.7% of patients (dupilumab/SOC vs placebo/SOC) reached ≥5-point reductions (MID threshold) in ISS7 and HSS7. The responder proportion was ≥20% greater for dupilumab/SOC vs placebo/SOC for response thresholds of 9.5- to 22-point reductions for UAS7, 4.5- to 11-point reductions for ISS7, and 5- to 11-point reductions for HSS7.

Conclusion
Irrespective of within-patient responder thresholds, greater proportions of patients experienced improvement in UAS7, ISS7, and HSS7 with dupilumab/SOC vs placebo/SOC at Week 24. Overall safety was consistent with the known dupilumab safety profile.
541 - Real-world effectiveness of dupilumab in adult and adolescent patients with atopic dermatitis: 3-year data from the PROSE registry
Authors: Simpson Eric L , Lockshin Ben , Lee Lara Wine , Shao Liyang , Ozarslan Bengisu , Korotzer Andrew 
Published: February 2024

Abstract

Background
Dupilumab has shown efficacy in the treatment of atopic dermatitis (AD) in clinical trials, but there is a need for long-term data on patients starting dupilumab treatment for atopic dermatitis in a real-world setting.

Methods
PROSE (NCT03428646) is an ongoing 5-year, prospective, observational study of patients aged ≥12 years who initiated commercially available dupilumab treatment for AD per country-specific prescribing information. Patients received a loading dose of dupilumab at baseline, without restrictions on post-baseline dosing changes or concomitant medication and were encouraged to stay in the study if they discontinued dupilumab. Data presented are descriptive, from a 3-year interim analysis.

Results
857 patients were enrolled. In these patients, mean (SD) age was 40.1 (17.9) years, AD duration 17.4 (16.2) years, and dupilumab treatment duration 23.1 (13.7) months (M). Mean (SE) baseline EASI total score was 16.2 (0.4), Pruritus Numerical Rating Scale (NRS) 7.1(0.1), Dermatology Life Quality Index (DLQI) 13.3 (0.3), and skin pain NRS 5.4 (0.1). 189 (22.1%) patients had withdrawn by data cut-off; the most common reasons for discontinuation were withdrawal of consent in 76 patients and loss to follow-up in 30. Mean (SE) EASI total score was 5.6 (0.4) at 3M, 2.9 (0.2) at 12M, 2.7 (0.4) at 24M, and 1.7 (0.3) at 36M. Mean (SE) change from baseline in Peak Pruritus NRS was −3.5 (0.2) at 3M, −4.2 (0.2) at 12M, −4.7 (0.2) at 24M, and −5.1 (0.3) at 36M. Mean (SE) change from baseline in DLQI was −7.4 (0.3) at 3M, −8.3 (0.7) at 12M, −9.2 (0.9) at 24M, and −8.8 (1.5) at 36M. Mean (SE) change from baseline in skin pain NRS was −3.3 (0.3) at 3M, −3.8 (0.2) at 12M, −4.0 (0.3) at 24M, and −4.6 (0.3) at 36M. Safety findings were consistent with the previously described safety profile of dupilumab.

Conclusion
In this interim analysis of the PROSE registry, sustained disease control was observed in patients with moderate-to-­severe AD for up to 3 years after initiating dupilumab treatment.
Magnetically guided surgery after primary systemic therapy for breast cancer: implications for enhanced axillary mapping
Authors: Pantiora Eirini , Eriksson Staffan , Wärnberg Fredrik , Karakatsanis Andreas 
Published: February 2024

Abstract

Background
Superparamagnetic iron nanoparticles perform comparably to radioisotope ± blue dye for sentinel lymph node detection in breast cancer, even when injected up to 8 weeks before surgery. Using superparamagnetic iron nanoparticles for sentinel lymph node detection after primary systemic therapy, and the maximum time frame of superparamagnetic iron nanoparticle administration have not been investigated.

Methods
This cohort study included cN0/1-to-ycN0 patients undergoing sentinel lymph node detection or targeted axillary dissection. All patients received superparamagnetic iron nanoparticles either before primary systemic therapy or before surgery, and radioisotope on the day of surgery.

Results
For 113 patients analysed, superparamagnetic iron nanoparticles were injected a median of 3 (range 0–248) days before surgery, with a 97.4% detection rate compared with 91.2% for radioisotope (P = 0.057). Concordance for radioisotope was 97.1% and this was not affected by timing of superparamagnetic iron nanoparticle injection (Kendall’s tau 0.027; P = 0.746). The median sentinel lymph node yield was 3 (interquartile range (i.q.r.) 2–3) for superparamagnetic iron nanoparticles and 2 (i.q.r. 2–3) for radioisotope (P &lt; 0.001). In targeted axillary dissection, detection was 100% for superparamagnetic iron nanoparticles and 81.8% for radioisotope (P = 0.124). The index node was magnetic in 93.9% and radioactive in 66.7% (P = 0.007), an outcome that was not affected by any factors. For patients with metastases, superparamagnetic iron nanoparticle detection was 100% and radioisotope-based detection was 84.2% (P = 0.083), with superparamagnetic iron nanoparticles detecting more metastatic sentinel lymph nodes (median of 1 (i.q.r. 1–2) for superparamagnetic iron nanoparticles compared with a median of 1 (i.q.r. 0–1) for radioisotope; P = 0.005).

Conclusion
Injection before primary systemic therapy is feasible and does not affect concordance with radioisotope. Superparamagnetic iron nanoparticles perform comparably to radioisotope, but detect more sentinel lymph nodes and have a higher rate of detection of metastatic sentinel lymph nodes.
Is surgical risk of aortic arch aneurysm repair underestimated? A novel perspective based on 30-day versus 1-year mortality
Authors: Rajesh Kavya , Levine Dov , Murana Giacomo , Castagnini Sabrina , Bianco Edoardo , Childress Patra , Zhao Yanling , Kurlansky Paul , Pacini Davide , Takayama Hiroo 
Published: February 2024

Abstract

OBJECTIVES
The decision to undergo aortic aneurysm repair balances the risk of operation with the risk of aortic complications. The surgical risk is typically represented by perioperative mortality, while the aneurysmal risk relates to the 1-year risk of aortic events. We investigate the difference in 30-day and 1-year mortality after total arch replacement for aortic aneurysm.

METHODS
This was an international two-centre study of 456 patients who underwent total aortic arch replacement for aneurysm between 2006 and 2020. Our primary end-point of interest was 1-year mortality. Our secondary analysis determined which variables were associated with 1-year mortality.

RESULTS
The median age of patients was 65.4 years (interquartile range 55.1–71.1) and 118 (25.9%) were female. Concomitantly, 91 (20.0%) patients had either an aortic root replacement or aortic valve procedure. There was a drop in 1-year (81%, 95% confidence interval (CI) 78–85%) survival probability compared to 30-day (92%, 95% CI 90–95%) survival probability. Risk hazards regression showed the greatest risk of mortality in the first 4 months after discharge. Stroke [hazard ratio (HR) 2.54, 95% CI (1.16–5.58)], renal failure [HR 3.59 (1.78–7.25)], respiratory failure [HR 3.65 (1.79–7.42)] and reoperation for bleeding [HR 2.97 (1.36–6.46)] were associated with 1-year mortality in patients who survived 30 days.

CONCLUSIONS
There is an increase in mortality up to 1 year after aortic arch replacement. This increase is prominent in the first 4 months and is associated with postoperative complications, implying the influence of surgical insult. Mortality beyond the short term may be considered in assessing surgical risk in patients who are undergoing total arch replacement.
Deglycosylated RBD produced in Pichia pastoris as a low-cost sera COVID-19 diagnosis tool and a vaccine candidate
Authors: Idrovo-Hidalgo Tommy , Pignataro María F , Bredeston Luis M , Elias Fernanda , Herrera María G , Pavan María F , Foscaldi Sabrina , Suireszcz Mayra , Fernández Natalia B , Wetzler Diana E , Paván Carlos H , Craig Patricio O , Roman Ernesto A , Ruberto Lucas A M , Noseda Diego G , Ibañez Lorena I , Czibener Cecilia ,   Argentinian AntiCovid Consortium, Blaustein M , Bredeston L , Craig P O , D’Alessio C , Elías F , Fernandez N B , Gudesblat G , Herrera M G , Ibañez L I , Idrovo-Hidalgo T , Nadra A D , Noseda D G , Pavan C , Pignataro M F , Roman E , Ruberto L , Rubinstein N , Santos J , Wetzler D , Zelada A , Ugalde Juan E , Nadra Alejandro D , Santos Javier , D’Alessio Cecilia 
Published: February 2024

Abstract
During the COVID-19 outbreak, numerous tools including protein-based vaccines have been developed. The methylotrophic yeast Pichia pastoris (synonymous to Komagataella phaffii) is an eukaryotic cost-effective and scalable system for recombinant protein production, with the advantages of an efficient secretion system and the protein folding assistance of the secretory pathway of eukaryotic cells. In a previous work, we compared the expression of SARS-CoV-2 Spike Receptor Binding Domain in P. pastoris with that in human cells. Although the size and glycosylation pattern was different between them, their protein structural and conformational features were indistinguishable. Nevertheless, since high mannose glycan extensions in proteins expressed by yeast may be the cause of a nonspecific immune recognition, we deglycosylated RBD in native conditions. This resulted in a highly pure, homogenous, properly folded and monomeric stable protein. This was confirmed by circular dichroism and tryptophan fluorescence spectra and by SEC-HPLC, which were similar to those of RBD proteins produced in yeast or human cells. Deglycosylated RBD was obtained at high yields in a single step, and it was efficient in distinguishing between SARS-CoV-2-negative and positive sera from patients. Moreover, when the deglycosylated variant was used as an immunogen, it elicited a humoral immune response ten times greater than the glycosylated form, producing antibodies with enhanced neutralizing power and eliciting a more robust cellular response. The proposed approach may be used to produce at a low cost, many antigens that require glycosylation to fold and express, but do not require glycans for recognition purposes.
Barriers to seeking tobacco cessation services: a qualitative assessment of university students’ needs in Qatar
Authors: Al-Jindi Lama , Al-Sulaiman Naema , Al-Jayyousi Ghadir Fakhri 
Published: February 2024

Abstract
The prevalence of tobacco use in the Middle East is alarmingly high, especially among university students; most users initiate tobacco use during adolescence and young adulthood. Evidence-based cessation services can be beneficial when quitting tobacco use; however, these services are underutilized. This study aimed to explore the barriers preventing university students in Qatar from seeking tobacco cessation services. Semi-structured interviews were conducted with 20 Qatar University students who are current or former tobacco users (n = 18/2); most current cigarette smokers were also waterpipe users. The interviews were transcribed verbatim, coded, and analyzed using thematic analysis. The major barriers to seeking tobacco cessation services included misconceptions regarding nicotine addiction, negative perceptions of the cessation services’ effectiveness, self-efficacy regarding the ability to quit without seeking cessation services, concerns and preferences regarding practitioners’ characteristics at clinics, masculine culture that discourages men from seeking cessation help, social stigma around women who use tobacco in Arab culture, and a lack of time to visit cessation clinics. Our findings address gaps in the literature regarding the individual and sociocultural barriers to seeking tobacco cessation among youth in Qatar. A better understanding of these barriers can facilitate successful promotion of tobacco cessation services and enhance cessation-seeking behaviors.
Changing Clinical Epidemiology of Plasmodium vivax Malaria as Transmission Decreases: Population-Based Prospective Panel Survey in the Brazilian Amazon
Authors: Fontoura Pablo S , Macedo Evelyn G , Calil Priscila R , Corder Rodrigo M , Rodrigues Priscila T , Tonini Juliana , Esquivel Fabiana D , Ladeia Winni A , Fernandes Anderson R J , Johansen Igor C , Silva Marcos F , Fernandes Amanda O S , Ladeia-Andrade Simone , Castro Marcia C , Ferreira Marcelo U 
Published: February 2024

Abstract

Background
Malarial infections are often missed by microscopy, and most parasite carriers are asymptomatic in low-endemicity settings. Whether parasite detectability and its ability to elicit symptoms change as transmission declines remains unclear.

Methods
We performed a prospective panel survey with repeated measurements on the same participants over 12 months to investigate whether Plasmodium vivax detectability by microscopy and risk of symptoms upon infection varied during a community-wide larviciding intervention in the Amazon basin of Brazil that markedly reduced vector density. We screened 1096 to 1400 residents in the intervention site for malaria by microscopy and quantitative TaqMan assays at baseline and twice during intervention.

Results
We found that more P vivax infections than expected from their parasite densities measured by TaqMan assays were missed by microscopy as transmission decreased. At lower transmission, study participants appeared to tolerate higher P vivax loads without developing symptoms. We hypothesize that changes in the ratio between circulating parasites and those that accumulate in the bone marrow and spleen, by avoiding peripheral blood microscopy detection, account for decreased parasite detectability and lower risk of symptoms under low transmission.

Conclusions
P vivax infections are more likely to be subpatent and remain asymptomatic as malaria transmission decreases.
Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine
Authors: Hu Xintao , Karthigeyan Krithika P , Herbek Savannah , Valencia Sarah M , Jenks Jennifer A , Webster Helen , Miller Itzayana G , Connors Megan , Pollara Justin , Andy Caroline , Gerber Linda M , Walter Emmanuel B , Edwards Kathryn M , Bernstein David I , Hou Jacob , Koch Matthew , Panther Lori , Carfi Andrea , Wu Kai , Permar Sallie R 
Published: February 2024

Abstract

Background
MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure.

Methods
A messenger RNA (mRNA)–based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients.

Results
mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses.

Conclusions
Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine.

Clinical Trials Registration
NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59).
Nuclear Factor κB Signaling Deficiency in CD11c-Expressing Phagocytes Mediates Early Inflammatory Responses and Enhances Mycobacterium tuberculosis Control
Authors: Chauhan Kuldeep S , Dunlap Micah D , Akter Sadia , Gupta Ananya , Ahmed Mushtaq , Rosa Bruce A , Dela Peña Noreen B , Mitreva Makedonka , Khader Shabaana A 
Published: February 2024

Abstract
Early innate immune responses play an important role in determining the protective outcome of Mycobacterium tuberculosis (Mtb) infection. Nuclear factor κB (NF-κB) signaling in immune cells regulates the expression of key downstream effector molecules that mount early antimycobacterial responses. Using conditional knockout mice, we studied the effect of abrogation of NF-κB signaling in different myeloid cell types and its impact on Mtb infection. Our results show that the absence of IKK2-mediated signaling in all myeloid cells resulted in increased susceptibility to Mtb infection. In contrast, the absence of IKK2-mediated signaling in CD11c+ myeloid cells induced early proinflammatory cytokine responses, enhanced the recruitment of myeloid cells, and mediated early resistance to Mtb. Abrogation of IKK2 in MRP8-expressing neutrophils did not affect disease pathology or Mtb control. Thus, we describe an early immunoregulatory role for NF-κB signaling in CD11c-expressing phagocytes and a later protective role for NF-κB in LysM-expressing cells during Mtb infection.
“High Politics” and Everyday Practices at the Border: Emerging Communities of Practice in the High North
Authors: Græger Nina 
Published: February 2024

Abstract
Using the concept of communities of practice, the article explores how boundary-crossing practices on borders vulnerable to states' “high politics” have developed overtime, leading to the formation of communities of doers bound by shared interests in learning and performing shared practices. Existing research on how diplomats, civilian and military staff in the European Union and the North Atlantic Treaty Organization (NATO) has shown how shared professional identities that cut across organizational, cultural and national boundaries has led to the emergence of communities of practice though everyday informal interaction. This article examines the emergence of long-term everyday border-crossing practices between Norway and Russia in the High North region and the extent to which they have been contested or continued in situations of tension or conflict between the West and Russia, and especially following the Russian invasion of Ukraine in 2022. Studying how these communities of doers engage in shared repertoires and practices that transcend and blur, rather than challenge the border may also shed new light onhow we understand the relationship between international politics and local politics. Arguably, the social dynamics of such boundary-work have also contributed to confidence-building and low tension, also beyond the border on which it takes place.
The Perceived Fit Between Music and Movement: A Multisensory Account of Dance as a Novel Feature Type
Authors: Olsson Tyler 
Published: February 2024

Abstract
Whether you are a sophisticated critic or an untrained spectator, when it comes to our experience of dance, we are generally able to appreciate the way a dancer’s bodily movements fit the music. Our experience of dance thus lends itself to a range of crossmodal judgments, that is, our perception of dance enables us to make claims that purport to be about how bodily movements which can be visually seen fit together with aspects of the music which can be heard or felt. But we are not determined to perceive every case of fit unproblematically. That it is possible one may fail to initially perceive a fit that others claim ought to be viewable suggests that there is a normative dimension to this phenomenon. In this article, I argue that we can explain the source of this normativity with a multisensory account of dance. More specifically, I argue that dance is a novel feature type, a feature of perceptual experience that is essentially multimodal. The basic perception of dance, which grounds more sophisticated forms of judgment concerning crossmodal fit downstream, is the actualization of a unique multisensory capacity that non-inferentially tracks a real, fundamental connection between music and movement.