bluuebunny/crossref_metadata_2025_split huggingface dataset:
1145. Meningococcal B Immunization for Adolescents in the Presence of Added Gonorrhea Protection: A Public Health Impact Modelling Study in the United States
Authors: Kocaata Zeki , Bhor Menaka , Sohn Woo-Yun , Meszaros Kinga 
Published: November 2023

Abstract

Background
Several observational studies showed the added gonorrhea protection of outer membrane vesicle (OMV)-containing meningococcal B (MenB) vaccines, raising hopes for achieving WHO gonorrhea control targets. With evolving meningococcal vaccine recommendations in the United States (US), a key policy consideration can be the optimal age for adolescent MenB immunization considering added gonorrhea protection. This study assessed the additional gonorrhea public health impact that could be achieved in the two major existing meningococcal vaccination platforms at 11 and 16-18 years of age in the US.

Methods
A single cohort Markov model was built to simulate primary and recurrent gonorrhea infections (Figure 1). Vaccine effectiveness was assumed to follow recent observational evidence in the US (40% [95% Confidence Interval: 23%, 53%]) post two-doses. Based on clinical evidence on the OMV antigen decay of the 4CMenB vaccine, protection was assumed to wane exponentially over 72 months. The impact was assessed based on (i) uptake rates for completed immunization series (20% to 90%) and (ii) two age groups to mimic the existing MenACWY and MenB vaccination recommendation features for adolescents: 11 vs 17-year-old as a proxy for 16-18-year vaccine recommendation.

Results
Substantial reductions in gonorrhea prevalence were observed for the cohort following vaccination at age 17 years, ranging from 3.0% [Credibility Interval (CrI): 1.7%, 4.0%] to 13.5% [CrI: 7.8%, 18.0%] for low (20%) to high (90%) uptake scenarios. The reductions in prevalence were substantially lower for vaccination at 11 years of age, ranging from 0.6% [CrI: 0.3%, 0.8%] to 2.7% [CrI: 1.5%, 3.5%] for the same uptake scenarios (Figure 2). Scenario analyses on shorter durations of protection confirmed the directionality of the results (Table 1).

Conclusion
Even with low coverage and without considering disease transmission, an OMV-containing MenB vaccine recommendation for older adolescents could result in significantly higher gonorrhea public health impact compared to younger adolescents. Dual effects for MenB and gonorrhea could be considered when recommending vaccines based on age of vaccination.

Disclosures
Zeki Kocaata, PhD, GSK: Stocks/Bonds Menaka Bhor, PhD, GSK: Stocks/Bonds Woo-Yun Sohn, MD, GSK: Stocks/Bonds Kinga Meszaros, MBA, GSK: Employee|GSK: Stocks/Bonds
1157. Immune Persistence and Booster Response of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) 5 Years After Primary Vaccination of Adults ≥59 Years of Age
Authors: Robertson Corwin A , Galarza Katherine , Jacqmein Jeffry , Selmani Alexandre , Oster Philipp 
Published: November 2023

Abstract

Background
MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It is approved for use in persons aged ≥2 years in the US and persons aged ≥1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. The second stage of a 2-stage study of MenACYW-TT, reported herein, evaluated immune persistence among older adults who received primary vaccination with either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT five years earlier at age ≥ 56 years. The immunogenicity and safety of a MenACYW-TT booster dose given to this population were also evaluated.

Methods
This was a Phase 3, 2-stage, randomized, open-label, multi-center study (NCT04142242) of adults aged ≥59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune persistence and response were assessed with a serum bactericidal assay using human complement (hSBA). Safety data were collected for up to 30 days after booster vaccination. All analyses were descriptive.

Results
Of the initial study population (N=471), 70 adults participated in Stage II of the study. At 5 years post-primary vaccination, seroprotection (hSBA ≥ 1:8) rates (SPRs) and hSBA geometric mean titers (GMTs) declined in both MenACYW-TT- and MPSV4-primed subjects, with SPRs and hSBA GMTs for serogroups A, C, W, and Y trending higher in MenACYW-TT- vs MPSV4-primed subjects (Table 1). Thirty days after booster vaccination, hSBA GMTs and SPRs increased from pre-booster for all serogroups and were, along with seroresponse rates, higher in MenACYW-TT-primed subjects compared to MPSV4-primed subjects (Table 2). Rates of AEs following booster vaccination were similar regardless of priming vaccine. No safety concerns were identified.

Conclusion
Five years after primary vaccination, immune persistence tended to be greater for MenACYW-TT vs MPSV4. A MenACYW-TT booster was well tolerated and immunogenic in adults ≥ 61 years, when administered 5 years after primary vaccination with either MPSV4 or MenACYW-TT.

Disclosures
Corwin A. Robertson, MD, MPH, FACP, Sanofi: Sanofi employee|Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Katherine Galarza, MD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Alexandre Selmani, PhD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Philipp Oster, MD, Sanofi: Sanofi employee
A divergent tumor overexpressed gene domain and oligomerization contribute to SPIRAL2 function in stabilizing microtubule minus ends
Authors: Fan Yuanwei , Bilkey Natasha , Bolhuis Derek L , Slep Kevin C , Dixit Ram 
Published: November 2023

Abstract
The acentrosomal cortical microtubules (MTs) of higher plants dynamically assemble into specific array patterns that determine the axis of cell expansion. Recently, the Arabidopsis (Arabidopsis thaliana) SPIRAL2 (SPR2) protein was shown to regulate cortical MT length and light-induced array reorientation by stabilizing MT minus ends. SPR2 autonomously localizes to both the MT lattice and MT minus ends, where it decreases the minus end depolymerization rate. However, the structural determinants that contribute to the ability of SPR2 to target and stabilize MT minus ends remain unknown. Here, we present the crystal structure of the SPR2 N-terminal domain, which reveals a unique tumor overexpressed gene (TOG) domain architecture with 7 HEAT repeats. We demonstrate that a coiled-coil domain mediates the multimerization of SPR2, which provides avidity for MT binding, and is essential to bind soluble tubulin. In addition, we found that an SPR2 construct spanning the TOG domain, basic region, and coiled-coil domain targets and stabilizes MT minus ends similar to full-length SPR2 in plants. These results reveal how a TOG domain, which is typically found in microtubule plus-end regulators, has been appropriated in plants to regulate MT minus ends.
Partnership approaches in policing: An analysis of different types of partnerships and how they work to reduce crime and disorder
Authors: Mazerolle Lorraine 
Published: November 2023

Abstract
Partnerships in policing are commonplace approaches to reduce crime and disorder problems across most parts of the world. Police forge partnerships with businesses, government agencies, and communities to co-produce public safety, usually cooperatively but sometimes using coercion. The co-production approach to crime control permeates all levels of law enforcement from tackling complex corporate crimes to reducing the flow of drugs to street-level markets. In this paper, I draw from the Global Policing Database (GPD) and the final stage of the search and screening from a systematic review of third-party policing (TPP) interventions to analyse 29 unique TPP interventions in 36 studies described across 45 documents. Each of the 29 unique TPP interventions depicts different types of partnerships and how they work to reduce crime and disorder. Partnerships are grouped along two continuums: the number and complexity of partners involved and the level and type of engagement. Some partnerships in policing are extremely complex involving multiple agencies, whereas others are dyadic. The type of engagement between partners also varies: some partnerships are collaborative, guided by memorandums of understanding, and motivated by mutual need for crime control solutions. Other partnerships are more coercive and dictated through legislated mandates and forceful measures. In this paper, I examine the range of partnerships evident within the review and offer insights into how those partnerships work to tackle different types of problems.
Metrology supporting the European regulation for radiation protection
Authors: Alves João G , Caldeira Margarida C , Röttger Annette , Khanbabaee Behnam , Adam-Guillermin Christelle , Siiskonen Teemu , Živanović Miloš , Šabeta Amra , Glavič-Cindro Denis 
Published: November 2023

Abstract
The European Association of National Metrology Institutes (EURAMET) within its research programme European Metrology Programme for Innovation and Research (EMPIR) funded project EMPIR 19NET03 supportBSS that contributes to the establishment of a European Metrology Network (EMN) for Radiation Protection (RP). The EMN-RP was established in September 2021 with the intent to work as a meeting point for the metrology community and all stakeholders in the field of ionising radiation regulation, thus providing quality assurance for measurements in each of the exposure situations contemplated in the European Legislation. Within project EMPIR 19NET03, work package 3 aims at the preparation of a Strategic Research Agenda (SRA) by identifying the metrology needs to support the European legislation and regulation in Radiation Protection and of two Roadmaps for metrology services, one under the European Council Directive 2013/59/EURATOM and the other under the EURATOM Treaty. Following a Gaps Workshop held in September 2020 and a second internal workshop that took place in April 2022, a questionnaire was prepared for distribution to the stakeholders, e.g. RP platforms and authorities, academia, industry, among other, together with an accompanying paper. In this paper, the authors present the state of the art of European legislation in RP, address the importance of metrology, the practices and activities that need metrology to meet the requirements set in the regulations, emphasise the need for quality assured measurements in all fields, highlight the stakeholders contributions in their specific area and show their vision of the EMN-RP.
The Characteristics of Respiratory Bocavirus Infection in Acutely Sick Children Admitted to a Tertiary Hospital in Jordan
Authors: AL-Iede Montaha , Ezar Daniel , Armouty Layan , Abdoh Momen , Karmi Munia , Sarhan Lena , AL-Zayadneh Eans , Daher Amirah , Alqutawneh Basim , Toubasi Ahmad A. 
Published: November 2023

Objective:
The clinical manifestations of human bocavirus infections are diverse, ranging from mild common cold to severe lower respiratory tract infections. Bocaviruses have frequently been codetected with other respiratory viruses. We aimed to estimate the burden of bocavirus and multiple viral infections and to investigate the risk factors associated with these infections.

Methods:
This study was a retrospective chart review of admitted patients. The medical records of the included children were searched, and data on demographics, clinical presentation, imaging, laboratory and nasopharyngeal swab results were collected.

Results:
A total of 157 patients were included. Most of the patients were males (62.1%) and under 6 months of age (52%). The 3 most common symptoms presented in the patients were cough (81.8%), rhinorrhea (58.6%) and fever (55.8%). Bocavirus DNA was detected in 12.66% of the patients, while 22.30% had multiple viruses. Age distribution was significantly different between bocavirus and nonbocavirus groups, with a lower proportion of bocavirus infection in all age groups (P = 0.032). The radiograph patterns significantly differed between the 2 study groups, with a lower number of patients in the bocavirus group having normal radiographs (P = 0.007). Patients infected with multiple viruses had more severe respiratory distress symptoms and diarrhea than those infected with only 1 virus.

Conclusions:
The prevalence of multiple viruses and bocavirus respiratory infections is significant. This study can guide physicians toward the clinical presentation and characteristics of children with respiratory bocavirus and multiple viral infections and propose future studies conducted in this regard.
Emergence of a Technology-Dependent Phenotype of Pediatric Sepsis in a Large Children’s Hospital
Authors: Aldewereld Zachary , Horvat Christopher , Carcillo Joseph A. , Clermont Gilles 
Published: November 2023

Abstract

Objective
To investigate whether pediatric sepsis phenotypes are stable in time.

Methods
Retrospective cohort study examining children with suspected sepsis admitted to a PICU at a large free-standing children’s hospital during two distinct periods: 2010-2014 (Early Cohort) and 2018-2020 (Late Cohort). K-means consensus clustering was used to derive types separately in the cohorts. Variables included ensured representation of all organ systems.

Results
1,091 subjects were in the Early Cohort and 737 subjects in the Late Cohort. Clustering analysis yielded 4 phenotypes in the Early Cohort and 5 in the Late Cohort. Four types were in both: Type A (34% of Early Cohort, 25% of Late Cohort), mild sepsis, with minimal organ dysfunction and low mortality; Type B (25%, 22%), primary respiratory failure; Type C (25%, 18%), liver dysfunction, coagulopathy, and higher measures of systemic inflammation; Type D (16%, 17%), severe multiorgan dysfunction, with high degrees of cardiorespiratory support, renal dysfunction, and highest mortality. Type E was only detected in the Late Cohort (19%) and was notable for respiratory failure less severe than B or D, mild hypothermia, and high proportion of diagnoses and technologic dependence associated with medical complexity. Despite low mortality, this type had the longest PICU length of stay.

Conclusions
This single center study identified 4 pediatric sepsis phenotypes in an earlier epoch but 5 in a later epoch, with the new type having a large proportion of characteristics associated with medical complexity, particularly technology dependence. Personalized sepsis therapies need to account for this expanding patient population.
Early Blood Lactate as a Biomarker for Cardiovascular Collapse in Experimental Sepsis
Authors: Calente Thander Jacson Nunes , Albino Lucas Braga , de Oliveira Junior Garcia , Delfrate Gabrielle , Sordi Regina , Santos Fábio André , Fernandes Daniel 
Published: November 2023

ABSTRACTCecal ligation and puncture (CLP) is the gold standard model for studying septic shock which is characterized by hypotension and hyporeactivity to vasoconstrictors. However, approximately 30% of CLP animals do not exhibit cardiovascular changes, requiring more replicates due to the high variability of the model. Therefore, biomarkers enabling the early prediction of cardiovascular collapse in sepsis would greatly benefit sepsis nonclinical studies, refining experimental models and improving clinical translation. Thus, this study aimed to test whether the early increase in lactate levels could predict hypotension and hyporesponsiveness to vasoconstrictors in a rat model of sepsis. Male and female Wistar rats were subjected to CLP or sham procedure. Tail blood lactate was measured 6, 12 and 24 hours after surgery. Then, inflammatory, biochemical, and hemodynamic parameters were evaluated. Rats subjected to CLP developed hypotension, hyporesponsiveness to vasoconstrictors, an intense inflammatory process, and increased plasma markers of organ dysfunction. By employing ROC curve analysis, we have established that a lactate value of 2.45 mmol/L can accurately discriminate between a rat exhibiting a normal vasoconstrictive response and a vasoplegic rat with 84% accuracy (AUC: 0.84, CI: 0.67-1.00). The sensitivity, which is the ability to identify the true positive rats, was 75% (CI: 41 – 95), and the true negative rate was 81% (CI: 57 – 93). Therefore, early measurement of lactate levels in sepsis could serve as a valuable biomarker for distinguishing vasoplegic rats from those exhibiting normal vasoconstrictive responses.
CircESPL1 silencing protects against lipopolysaccharide-induced lung fibroblast dysfunction partly by targeting the miR-146b-3p/TRAF1 axis in pneumonia
Authors: Tian Yubo , Wang Yi , Wang Zhen 
Published: November 2023

Abstract

Background
Neonatal pneumonia is a common disease in the neonatal period with high mortality. The present work concentrated on the role and mechanism of circular RNA (circRNA) extra spindle pole bodies like 1, separase (circESPL1) in lipopolysaccharide (LPS)-induced dysfunction of lung fibroblasts.

Methods
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to analyze RNA and protein expression, respectively. Cell viability, proliferation, apoptosis, and inflammation were assessed by Cell Counting Kit-8 (CCK8) assay, 5-Ethynyl-2’-deoxyuridine (EdU) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), respectively. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the intermolecular interactions among circESPL1, miR-146b-3p and TRAF1.

Results
CircESPL1 expression was up-regulated in the serum samples of pneumonia patients and LPS-induced lung fibroblasts. CircESPL1 silencing protected lung fibroblasts against LPS-induced dysfunction. CircESPL1 bound to microRNA-146b-3p (miR-146b-3p) in lung fibroblasts. CircESPL1 knockdown-mediated protective effects on LPS-induced lung fibroblasts were largely reversed by the silence of miR-146b-3p. miR-146b-3p directly interacted with the 3’ untranslated region (3’UTR) of TNF receptor associated factor 1 (TRAF1), and TRAF1 expression was regulated by the circESPL1/miR-146b-3p axis in lung fibroblasts. TRAF1 overexpression largely reversed miR-146b-3p accumulation-mediated protective effects on LPS-induced lung fibroblasts.

Conclusion
CircESPL1 knockdown protected lung fibroblasts from LPS-induced injury partly by targeting the miR-146b-3p/TRAF1 axis.
Coagulopathy Parameters Predictive of Outcomes in Sepsis-induced Acute Respiratory Distress Syndrome: A Sub-Analysis of the Two Prospective Multicenter Cohort Studies
Authors: Matsuoka Tadashi , Fujishima Seitaro , Sasaki Junchi , Gando Satoshi , Saitoh Daizoh , Kushimoto Shigeki , Ogura Hiroshi , Abe Toshikazu , Shiraishi Atsushi , Mayumi Toshihiko , Kotani Joji , Takeyama Naoshi , Tsuruta Ryosuke , Takuma Kiyotsugu , Yamashita Norio , Shiraishi Shin-ichiro , Ikeda Hiroto , Shiino Yasukazu , Tarui Takehiko , Nakada Taka-aki , Hifumi Toru , Otomo Yasuhiro , Okamoto Kohji , Sakamoto Yuichiro , Hagiwara Akiyoshi , Masuno Tomohiko , Ueyama Masashi , Fujimi Satoshi , Yamakawa Kazuma , Umemura Yutaka ,   on behalf of the JAAM Focused Outcomes Research on Emergency Care for Acute respiratory distress syndrome, Sepsis and Trauma (FORECAST) Group and Sepsis Prognostication in Intensive Care unit and Emergency room (SPICE) Group
Published: November 2023

AbstractBackgroundAlthough coagulopathy is often observed in acute respiratory distress syndrome (ARDS), its clinical impact remains poorly understood.ObjectivesThis study aimed to clarify the coagulopathy parameters that are clinically applicable for prognostication and to determine anticoagulant indications in sepsis-induced ARDS.MethodThis study enrolled patients with sepsis-derived ARDS from two nationwide multicenter, prospective observational studies. We explored coagulopathy parameters that could predict outcomes in the FORECAST cohort, and the defined coagulopathy criteria were validated in the SPICE-ICU cohort. The correlation between anticoagulant use and outcomes was also evaluated.ResultsA total of 181 patients with sepsis-derived ARDS in the FORECAST study and 61 patients in the SPICE-ICU study were included. In a preliminary study, we found the set of PT-INR ≥1.4 and platelets ≤12 × 104/μL, Thrombocytopenia and Elongated Prothrombin time, TEP, coagulopathy as the best coagulopathy parameters, and used for further analysis, of which odds ratio of TEP coagulopathy for in-hospital mortality adjusted for confounding was 3.84 (95% CI, 1.66–8.87; p = 0.005). In the validation cohort, the adjusted odds ratio for in-hospital mortality was 32.99 (95% CI, 2.60–418.72; p = 0.002). Although patients without TEP coagulopathy showed significant improvements in oxygenation over the first 4 days, patients with TEP coagulopathy showed no significant improvement (ΔPaO2/FiO2ratio, 24 ± 20 vs. 90 ± 9; p = 0.026). Furthermore, anticoagulant use was significantly correlated with mortality and oxygenation recovery in patients with TEP coagulopathy but not in patients without TEP coagulopathy.ConclusionTEP coagulopathy is closely associated with better outcomes and responses to anticoagulant therapy in sepsis-induced ARDS, and our coagulopathy criteria may be clinically useful.Trial registrationFORECAST study: UMIN-CTR ID: UMIN000019742. Registration date: November 11th, 2015.SPICE-ICU study: UMIN-CTR ID: UMIN000027258. Registration date: May 6th, 2017.
Soluble guanylate cyclase (sGC) stimulators in heart failure with preserved ejection fraction: a systematic review and meta-analysis
Authors: Zhao Yang , Zang Bin , Wang Qian 
Published: November 2023

Abstract

Aims
We conducted a systemic review and meta-analysis to evaluate the therapeutic efficacy and safety of soluble guanylate cyclase(sGC) stimulators in patients with heart failure with preserved ejection fraction(HFpEF).

Methods
We systematically searched PubMed, EMBASE and Cochrane Library databases for original randomized controlled trials comparing sGC stimulators with placebo in HFpEF patients. A random-effects model was applied to evaluate the mortality, quality of life and drug-related adverse events. This meta-analysis is registered in PROSPERO under the number CRD42023457382.

Results
We included five studies involving 1600 HFpEF patients. Comprehensively, the combined risk ratio (RR) for mortality was not significant(RR(95% CI) = 1.44 (0.71-2.91), p = 0.31). Furthermore, there were no statistically significant differences in the Kansas City Cardiomyopathy Questionnaire (KCCQ) results, including the Clinical Summary Score(CSS) (WMD (95% CI) =0.32( -7.38-8.02), p = 0.94) and the Overall Summary Score(OSS) (WMD (95% CI) = -0.87( -8.87-7.14), P = 0.83). Similarly, there was no significant improvement in the 6-minute walk distance(6MWD) (WMD(95% CI) = -6.22(-18.56-6.12), p = 0.32). Additionally, drug-related adverse events were more common in patients treated with sGC stimulators(RR(95%CI) = 1.63,(1.25-2.14), p < 0.05).

Conclusions
Oral sGC stimulators do not significantly improve mortality outcomes, functional capacity and quality of life in HFpEF patients but are associated with increased drug-related adverse events. Therefore, we should consider using sGC stimulators in HFpEF patients carefully.