bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Impact of Including Gust and Flutter Constraints on the Design of Flying Wing Aircraft
Authors: Deslich Joshua , McHugh Kevin 
Published: June 2024

Abstract
Flying Wing Aircraft, while theoretically performant, suffer from a multitude of design challenges. These challenges include controllability and aeroelastic stability, among others. This paper introduces some early aeroelastic and control considerations into the conceptual/preliminary level design process and evaluates the impact these considerations have on the shape and weight of the design. Using the Equivalent Static Load method, gust responses from aeroelastic analyses are integrated into NASTRAN Solution 200, enabling the design of a wing structure sized with gust loads. Additionally, flutter constraints and maneuver trim conditions are implemented to determine aeroelastic stability and controllability. These NASTRAN-based optimizations are implemented as sub-optimizations in a Sequential Linear Programming algorithm, allowing for variations in the planform of the vehicle. Results indicate that the Equivalent Static Load method performs well and matches dynamic results. Optimization results indicate that the inclusion of the flutter constraint increases the weight of the vehicle, consistent with literature trends. Notably the inclusion of the gust response in addition to the flutter constraint drastically increases the weight of the vehicle as the aircraft must increase torsional stiffness via additional structural material to support the gust loads.
WrapToR Truss Joints: Path Planning for Three Dimensionally Wound Joint Structures With Manufacturing Constraints
Authors: Zhao Mengzhou , Macquart Terence , Woods Benjamin K. S. 
Published: June 2024

Abstract
Wrapped Tow Reinforced (WrapToR) truss structures are a unique class of truss beams fabricated from composite materials via a modified filament winding technique. While past studies have highlighted their weight advantages over traditional tubular composites, there’s growing attention towards their integration into Hierarchical Space Frames (HSFs), facilitating greater geometric flexibility for diverse applications. Central to this idea is the need for an efficient joining technology. This study introduces a concept employing a 3D version of the WrapToR winding method to generate optimal lattice joint designs. As designing winding paths for intricate joints involving varying numbers of trusses and angles is challenging, this paper presents a path planning algorithm underpinned by graph theory and manufacturing constraints. Primary considerations include tow continuity, geometric limitations, and issues arising from filament overlap and interference in 3D space. The proposed method involves identifying edges and nodes, prioritising them based on a dominance algorithm to minimise interference, and subdividing the problem into manageable sub-graphs. These are tackled using an adjusted graph theory technique, with the global solution being a combination of these sub-graphs, which can be wound in turn. To validate the methodology, specimens of 3-truss and 4-truss joints were path=planned and fabricated, underscoring the viability of the proposed approach.
Guarding the walls: the multifaceted roles of Bce modules in cell envelope stress sensing and antimicrobial resistance
Authors: George Natasha L. , Bennett Ellen C. , Orlando Benjamin J. 
Published: June 2024

ABSTRACT

Bacteria have developed diverse strategies for defending their cell envelopes from external threats. In Firmicutes, one widespread strategy is to use Bce modules—membrane protein complexes that unite a peptide-detoxifying ABC transporter with a stress response coordinating two-component system. These modules provide specific, front-line defense for a wide variety of antimicrobial peptides and small molecule antibiotics as well as coordinate responses for heat, acid, and oxidative stress. Because of these abilities, Bce modules play important roles in virulence and the development of antibiotic resistance in a variety of pathogens, including
Staphylococcus
,
Streptococcus
, and
Enterococcus
species. Despite their importance, Bce modules are still poorly understood, with scattered functional data in only a small number of species. In this review, we will discuss Bce module structure in light of recent cryo-electron microscopy structures of the
B. subtilis
BceABRS module and explore the common threads and variations-on-a-theme in Bce module mechanisms across species. We also highlight the many remaining questions about Bce module function. Understanding these multifunctional membrane complexes will enhance our understanding of bacterial stress sensing and may point toward new therapeutic targets for highly resistant pathogens.
Deficiency in
Ever2
does not increase susceptibility of mice to pathogenesis by the mouse papillomavirus, MmuPV1
Authors: Torres Alexandra D. , King Renee E. , Uberoi Aayushi , Buehler Darya , Yoshida Satoshi , Ward-Shaw Ella , Lambert Paul F. 
Published: June 2024

ABSTRACT

Epidermodysplasia verruciformis (EV) is a rare genetic skin disorder that is characterized by the development of papillomavirus-induced skin lesions that can progress to squamous cell carcinoma (SCC). Certain high-risk, cutaneous β-genus human papillomaviruses (β-HPVs), in particular HPV5 and HPV8, are associated with inducing EV in individuals who have a homozygous mutation in one of three genes tied to this disease:
EVER1
,
EVER2
, or
CIB1. EVER1
and
EVER2
are also known as
TMC6
and
TMC8,
respectively. Little is known about the biochemical activities of
EVER
gene products or their roles in facilitating EV in conjunction with β-HPV infection. To investigate the potential effect of
EVER
genes on papillomavirus infection, we pursued
in vivo
infection studies by infecting
Ever2
-null mice with mouse papillomavirus (MmuPV1). MmuPV1 shares characteristics with β-HPVs including similar genome organization, shared molecular activities of their early, E6 and E7, oncoproteins, the lack of a viral E5 gene, and the capacity to cause skin lesions that can progress to SCC. MmuPV1 infections were conducted both in the presence and absence of UVB irradiation, which is known to increase the risk of MmuPV1-induced pathogenesis. Infection with MmuPV1 induced skin lesions in both wild-type and
Ever2
-null mice with and without UVB. Many lesions in both genotypes progressed to malignancy, and the disease severity did not differ between
Ever2
-null and wild-type mice. However, somewhat surprisingly, lesion growth and viral transcription was decreased, and lesion regression was increased in
Ever2
-null mice compared with wild-type mice. These studies demonstrate that
Ever2
-null mice infected with MmuPV1 do not exhibit the same phenotype as human EV patients infected with β-HPVs.

IMPORTANCE

Humans with homozygous mutations in the
EVER2
gene develop epidermodysplasia verruciformis (EV), a disease characterized by predisposition to persistent β-genus human papillomavirus (β-HPV) skin infections, which can progress to skin cancer. To investigate how EVER2 confers protection from papillomaviruses, we infected the skin of homozygous
Ever2
-null mice with mouse papillomavirus MmuPV1. Like in humans with EV, infected
Ever2
-null mice developed skin lesions that could progress to cancer. Unlike in humans with EV, lesions in these
Ever2
-null mice grew more slowly and regressed more frequently than in wild-type mice. MmuPV1 transcription was higher in wild-type mice than in
Ever2
-null mice, indicating that mouse EVER2 does not confer protection from papillomaviruses. These findings suggest that there are functional differences between MmuPV1 and β-HPVs and/or between mouse and human EVER2.
A food color-based colorimetric assay for
Cryptococcus neoformans
laccase activity
Authors: Sanchez Ramirez Lia , Dragotakes Quigly , Casadevall Arturo 
Published: June 2024

ABSTRACT

Cryptococcus neoformans
is a fungal pathogen that causes cryptococcosis primarily in immunocompromised patients, such as those with HIV/AIDS. One survival mechanism of
C. neoformans
during infection is melanin production, which catalyzed by laccase and protects fungal cells against immune attack. Hence, the comparative assessment of laccase activity is useful for characterizing cryptococcal strains. We serendipitously observed that culturing
C. neoformans
with food coloring resulted in degradation of some dyes with phenolic structures. Consequently, we investigated the color changes for the food dyes metabolized by
C. neoformans
laccase and by using this effect explored the development of a colorimetric assay to measure laccase activity. We developed several versions of a food dye-based colorimetric laccase assay that can be used to compare the relative laccase activities between different
C. neoformans
strains. We found that phenolic color degradation was glucose-dependent, which may reflect changes in the reduction properties of the media. Our food color-based colorimetric assay has several advantages, including lower cost, irreversibility, and not requiring constant monitoring , over the commonly used 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay for determining laccase activity. This method has potential applications to bioremediation of water pollutants in addition to its use in determining laccase virulence factor expression.

IMPORTANCE

Cryptococcus neoformans
is present in the environment, and while infection is common, disease occurs mostly in immunocompromised individuals.
C. neoformans
infection in the lungs results in symptoms like pneumonia, and consequently, cryptococcal meningitis occurs if the fungal infection spreads to the brain. The laccase enzyme catalyzes the melanization reaction that serves as a virulence factor for
C. neoformans
. Developing a simple and less costly assay to determine the laccase activity in
C. neoformans
strains can be useful for a variety of procedures ranging from studying the relative virulence of cryptococci to environmental pollution studies.
EasyNAT Malaria: a simple, rapid method to detect
Plasmodium
species using cross-priming amplification technology
Authors: Dong Liu , Xu Qianqian , Shen Linjie , Cao Ruoshui , Deng Xuan , Chen Jian , Jiang Haoqin , Guan Ming 
Published: June 2024

ABSTRACT

Malaria infection remains a serious threat to human health worldwide. Rapid and accurate detection technology is crucial for preventing malaria transmission and minimizing damage. We aimed to establish and validate a new rapid molecular detection method for malaria, called EasyNAT Malaria Assay, targeting
Plasmodium vivax
,
Plasmodium falciparum
,
Plasmodium ovale
, and
Plasmodium malariae
. The analytical performance of EasyNAT Malaria Assay was determined using positive materials. We identified 42 clinical samples as malaria positive and 95 negative samples. Each sample was examined by four methods: light microscopy, rapid diagnostic test, EasyNAT Malaria Assay, and digital PCR. Diagnostic accuracy and clinical performance were evaluated. The limit of detection (LOD)
95%
of EasyNAT Malaria was consistently 40 parasites/mL. It specifically amplified
Plasmodium
and performed with reliable repeatability and reproducibility. In 137 clinical samples, EasyNAT Malaria detected four more positive samples than microscopic examination and two more positive samples than rapid diagnostic test (RDT). One clinical sample was positive only under digital PCR. However, no significant differences statistically in sensitivity or specificity were observed. Compared with microscopy, the total, positive, and negative concordance rates of EasyNAT were 97.08%, 100%, and 95.79%, respectively. Enhanced diagnostic accuracy of EasyNAT Malaria in patients who had taken anti-malarial medication before their clinical appointment was observed. The EasyNAT Malaria Assay has good detection efficiency for clinical samples, presents a promising molecular detection tool in clinical practice, and is particularly suitable for rapid screening of high-risk populations in the emergency room.

IMPORTANCE
This study established and validated EasyNAT Malaria Assay as a promising molecular detection tool for malaria screening of high-risk populations in clinical practice. This novel isothermal amplification method may effectively facilitate the rapid diagnosis of malaria and prevent its transmission.
Risk factors for curable sexually transmitted infections among youth: findings from the STICH population survey in Zimbabwe
Authors: Martin Kevin , Dauya Ethel , Simms Victoria , Bandason Tsitsi , Azizi Steven , Machiha Anna , Shamu Tinei , Musiyandaka Primrose , Mwaturura Tinashe , Francis Suzanna C , Mackworth-Young Constance R S , Busza Joanna , Mavodza Constancia , Tembo Mandi , Hayes Richard J , Kranzer Katharina , Ferrand Rashida A , Dziva Chikwari Chido 
Published: June 2024

ObjectivesYouth are at high risk of sexually transmitted infections (STIs) in Africa. We aimed to determine the risk factors for curable STIs in youth in Zimbabwe.MethodsA population-based survey was conducted among randomly selected 18–24 year-olds in 16 communities across two provinces in Zimbabwe to ascertain outcomes for a cluster randomised trial investigating the impact of community-based STI screening for youth on population prevalence of STIs. Participants underwent an interviewer-administered questionnaire, HIV testing and screening forChlamydia trachomatis(CT),Neisseria gonorrhoeae(NG) andTrichomonas vaginalis(TV). Risk factors for curable STIs were explored through multivariable logistic regression.ResultsOf the 5601 participants, 62.5% (n=3500) were female, and the median age was 20 (IQR 19–22) years. HIV prevalence was 6.3% (351/5556), and 55.4% (1939/3501) reported condomless sex at last intercourse. Only 7.2% (401/5599) reported STI symptoms, but CT/NG/TV prevalence was 19.8% (1107/5601). On multivariable analysis, factors associated with STI diagnosis included being aged 21–24 years (adjusted OR (aOR) 1.37, 95% CI 1.17 to 1.61); female sex (aOR 2.11, 95% CI 1.76 to 2.53); being unemployed/informally employed (compared with in education/formal employment) (aOR 1.35, 95% CI 1.13 to 1.61); increasing number of sexual partners in the preceding 12 months (one partner: aOR 2.23, 95% CI 1.73 to 2.88; two partners: aOR 2.39, 95% CI 1.69 to 3.39); living with HIV (aOR 1.44, 95% CI 1.07 to 1.94); and previous attempted suicide (aOR 1.58, 95% CI 1.08 to 2.32).ConclusionsThe prevalence of STIs among youth in Zimbabwe is high, particularly among those with HIV. In addition to moving away from syndromic STI management and strengthening implementation of existing prevention tools, there is a need for a more holistic focus on broader risk factors such as mental health and employment opportunities, and of integration of HIV and STI programming.Trial registration numberISRCTN15013425,NCT03719521.
Serratus anterior plane block improves pain and incentive spirometry volumes in trauma patients with multiple rib fractures: a prospective cohort study
Authors: Sadauskas Victor , Fofana Mariame , Brunson Dalton , Choi Jeff , Spain David , Quinn James V , Duanmu Youyou 
Published: June 2024

BackgroundRib fractures are common injuries associated with considerable morbidity, long-term disability, and mortality. Early, adequate analgesia is important to mitigate complications such as pneumonia and respiratory failure. Regional anesthesia has been proposed for rib fracture pain control due to its superior side effect profile compared with systemic analgesia. Our objective was to evaluate the effect of emergency physician-performed, ultrasound-guided serratus anterior plane block (SAPB) on pain and respiratory function in emergency department patients with multiple acute rib fractures.MethodsThis was a prospective observational cohort study of adult patients at a level 1 trauma center who had two or more acute unilateral rib fractures. Eligible patients received a SAPB if an emergency physician trained in the procedure was available at the time of diagnosis. Primary outcomes were the absolute change in pain scores and percent change in expected incentive spirometry volumes from baseline to 3 hours after rib fracture diagnosis.Results38 patients met eligibility criteria, 15 received the SAPB and 23 did not. The SAPB group had a greater decrease in pain scores at 3 hours (−3.7 vs. −0.9; p=0.003) compared with the non-SAPB group. The SAPB group also had an 11% (CI 1.5% to 17%) increase in percent expected spirometry volumes at 3 hours which was significantly better than the non-SAPB group, which had a −3% (CI −9.1% to 2.7%) decrease (p=0.008).ConclusionPatients with rib fractures who received SAPB as part of a multimodal pain control strategy had a greater improvement in pain and respiratory function compared with those who did not. Larger trials are indicated to assess the generalizability of these initial findings.
Multiple targets, germline BRCA1 mutation and HRD in a lung cancer patient: Molecular considerations and treatment decision-making
Authors: Perrone Fabiana , Facchinetti Francesco , Pellegrino Benedetta , Minari Roberta , Gnetti Letizia , Azzoni Cinzia , Bottarelli Lorena , Campanini Nicoletta , Grau-Bejar Juan Francisco , Mingozzi Anna , Cognigni Valeria , Tiseo Marcello 
Published: June 2024

Introduction: Several biomarkers are currently available to address targeted treatments in cancer patients, with lung malignancies representing one of the best examples. Case description: We report the case of a patient affected by advanced non-small cell lung cancer with an uncommon histology and a complex biology. The use of a large next-generation sequencing (NGS) NGS panel allowed us to identify an extremely rare BRAF mutation (V600Q), a MET amplification, a high tumor mutational burden, a germline pathogenetic BRCA1 mutation and a homologous recombination deficiency through RAD51 assay. The treatment decision was driven by the abundance of molecular information. Conclusions: This case highlights that an attentive and critical evaluation of molecular reports is key for the tailoring of treatment algorithms at the patient-level scale.
Single-Cell Molecular Profiling of Head and Neck Squamous Cell Carcinoma Reveals Five Dysregulated Signaling Pathways Associated With Circulating Tumor Cells
Authors: Stucky Andres , Viet Chi T. , Aouizerat Bradley E. , Ye Yi , Doan Coleen , Mundluru Tarun , Sedhiazadeh Parish , Sinha Uttam K. , Chen Xuelian , Zhang Xi , Li Shengwen Calvin , Cai Jin , Zhong Jiang F. 
Published: June 2024

Objectives To determine the dysregulated signaling pathways of head and neck squamous cell carcinoma associated with circulating tumor cells (CTCs) via single-cell molecular characterization. Introduction Head and neck squamous cell carcinoma (HNSCC) has a significant global burden and is a disease with poor survival. Despite trials exploring new treatment modalities to improve disease control rates, the 5 year survival rate remains low at only 60%. Most cancer malignancies are reported to progress to a fatal phase due to the metastatic activity derived from treatment-resistant cancer cells, regarded as one of the most significant obstacles to develope effective cancer treatment options. However, the molecular profiles of cancer cells have not been thoroughly studied. Methods Here, we examined in-situ HNSCC tumors and pairwisely followed up with the downstream circulating tumor cells (CTCs)-based on the surrogate biomarkers to detect metastasis that is established in other cancers – not yet being fully adopted in HNSCC treatment algorithms. Results Specifically, we revealed metastatic HNSCC patients have complex CTCs that could be defined through gene expression and mutational gene profiling derived from completed single-cell RNASeq (scRNASeq) that served to confirm molecular pathways inherent in these CTCs. To enhance the reliability of our findings, we cross-validated those molecular profiles with results from previously published studies. Conclusion Thus, we identified 5 dysregulated signaling pathways in CTCs to derive HNSCC biomarker panels for screening HNSCC in situ tumors.
Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment
Authors: Gervaso Lorenzo , Ciardiello Davide , Gregato Giuliana , Guidi Lorenzo , Valenza Carmine , Ascione Liliana , Boldrini Laura , Frassoni Samuele , Cella Chiara Alessandra , Spada Francesca , Funicelli Luigi , De Roberto Giuseppe , Petz Wanda , Borin Simona , Gerardi Marianna Alessandra , Bottiglieri Luca , Tamayo Darina , Bertani Emilio , Fumagalli Romario Uberto , Bagnardi Vincenzo , Curigliano Giuseppe , Bertolini Francesco , Fazio Nicola , Zampino Maria Giulia 
Published: June 2024

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy. Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes. Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery. Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS). Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10–1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02–1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63–8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35–4.06, p = 0.79). Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.