bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expansion strategies for umbilical cord blood haematopoietic stem cells in vitro
Authors: Ren Yan , Cui Yanni , Tan Yanhong , Xu Zhifang , Wang Hongwei 
Published: October 2023

AbstractHaematopoietic stem cell transplantation (HSCT) is considered an effective treatment for some haematopoietic malignancies, haematopoietic failure and immunodeficiency. Compared with bone marrow and mobilized peripheral blood, cord blood has the advantages of easy access, being harmless to donors and low requirement for HLA matching. In addition, umbilical cord blood transplantation (UCBT) has achieved remarkable clinical success in the past 30 years due to the low recurrence rate of malignancies treated by UCBT, mild degree of chronic graft‐versus‐host disease (GVHD) and good quality of life for patients after transplantation. However, the number of cells in a single cord blood is too small for rapid bone marrow implantation. We summarize the various factors involved that need to be considered in the expansion of haematopoietic stem cells (HSCs) in vitro, which all avoid complex operations, such as vector construction and virus transfection. We also found it necessary to identify a new molecule as the carrier of HSCs cultured in vitro, which not only would provide a three‐dimensional structure conducive to the self‐renewal of HSCs but also prevent their differentiation.
Effect of Unsteady Fan-Intake Interaction on Short Intake Design
Authors: Boscagli Luca , MacManus David , Christie Robert , Sheaf Chris 
Published: October 2023

Abstract
The next generation of ultrahigh bypass ratio civil aero-engines promises notable engine cycle benefits. However, these benefits can be significantly eroded by a possible increase in nacelle weight and drag due to the typical larger fan diameters. More compact nacelles, with shorter intakes, may be required to enable a net reduction in aero-engine fuel burn. The aim of this paper is to assess the influence of the design style of short intakes on the unsteady interaction under crosswind conditions between fan and intake, with a focus on the separation onset and characteristics of the boundary layer within the intake. Three intake designs were assessed, and a hierarchical computational fluid dynamics (CFD) approach was used to determine and quantify primary aerodynamic interactions between the fan and the intake design. Similar to previous findings for a specific intake configuration, both intake flow unsteadiness and the unsteady upstream perturbations from the fan have a detrimental effect on the separation onset for the range of intake designs. The separation of the boundary layer within the intake was shock driven for the three different design styles. The simulations also quantified the unsteady intake flows with an emphasis on the spectral characteristics and engine-order signatures of the flow distortion. Overall, this work showed that is beneficial for the intake boundary layer to delay the diffusion closer to the fan and reduce the preshock Mach number to mitigate the adverse unsteady interaction between the fan and the shock.
The Efficacy of Cryotherapy on Decreasing Swelling: A Critically Appraised Topic
Authors: Ziner Rachel A. , Mansell Jamie L. , Russ Anne C. , Tierney Ryan T. 
Published: October 2023

Context: Swelling is a major consequence of musculoskeletal conditions and can be a barrier to healing. Cryotherapy has been reported to decrease swelling. How effective is cryotherapy in reducing swelling during rehabilitation? Methods: PubMed was searched in June 2022 using the Boolean phrases: Swelling OR edema AND cryotherapy OR ice, Swelling AND injury AND cryotherapy. Included articles were published during or after 2017, consisted of one or more cryotherapy interventions, and listed swelling as an outcome measure. The PEDro scale was used to assess study validity. Swelling was measured by the figure-of-eight method (in centimeters). Means, SDs, and 95% confidence interval (CI) were calculated. Results: Three articles were screened. Stasinopoulos et al. received a score of 9/10; Sari et al. and Tittley et al. received a score of 10/10. Tittley et al. reported a decrease in swelling from 52.7 (SD = 0.8; 95% CI [52.35, 53.05]) to 52.0 (SD = 0.8; 95% CI [51.65, 52.35]). Stasinopoulos et al. reported decreases from 62.62 (SD = 0.34; 95% CI [62.51, 62.80]) to 61.10 (SD = 0.30; 95% CI [60.98, 61.24]). Sari et al. also found minimal change in swelling from pre- to posttreatment, 38.7 (SD = 2.6; 95% CI [37.83, 39.57]) to 38.2 (SD = 2.4; 95% CI [37.40, 39.00]). Conclusion: There is consistent evidence indicating that cryotherapy applied during rehabilitation does not decrease swelling in a patient with a musculoskeletal condition.
Distinct motifs in the E protein are required for SARS-CoV-2 virus particle formation and lysosomal deacidification in host cells
Authors: Miura Koya , Suzuki Youichi , Ishida Kotaro , Arakawa Masashi , Wu Hong , Fujioka Yoshihiko , Emi Akino , Maeda Koki , Hamajima Ryusei , Nakano Takashi , Tenno Takeshi , Hiroaki Hidekazu , Morita Eiji 
Published: October 2023

ABSTRACT
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is a major public health concern, but the mechanisms underlying its viral particle formation are not well understood. In this study, we established a system for producing virus-like particles (VLPs) by expressing four structural proteins that make up SARS-CoV-2 virus particles in cells and used a spike (S) protein fused with the HiBiT peptide as a marker for evaluating VLP production. Using this system, we confirmed that the E protein plays an important role in VLP release. Both the co-expression of VPS4A K173Q and ORF3A and treatment with bafilomycin A1 enhanced VLP release. These results suggest that VLPs are released in an endosomal sorting complex required for transport-independent manner and that lysosomal dysfunction is required for the efficient release of VLPs. Screening various E protein mutants revealed that the F56/Y57/Y59 amyloidization motif and the D72/L73/L74/V75 PDZ-binding motif (PBM) are critical for E protein function in VLP release. We also found that E protein expression led to an increase in the pH of lysosomes and that the N15 residue required for viroporin activity, the C40/C43 consensus sequence, or the K63 dibasic motif are required for its function. However, amyloidization or PBM mutations did not affect lysosomal deacidification, suggesting that the mechanisms of E protein activity during VLP formation and lysosomal deacidification are distinct. Overall, this study highlights the importance of the E protein in SARS-CoV-2 viral particle formation, and the results may be useful in the development of drugs that inhibit this process.

IMPORTANCE
Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has caused a global public health crisis. The E protein, a structural protein found in this virus particle, is also known to be a viroporin. As such, it forms oligomeric ion channels or pores in the host cell membrane. However, the relationship between these two functions is poorly understood. In this study, we showed that the roles of E protein in virus particle and viroporin formation are distinct. This study contributes to the development of drugs that inhibit SARS-CoV-2 virus particle formation. Additionally, we designed a highly sensitive and high-throughput virus-like particle detection system using the HiBiT tag, which is a useful tool for studying the release of SARS-CoV-2.
SARS-CoV-2 replicates in the human testis with slow kinetics and has no major deleterious effects
ex vivo
Authors: Mahé Dominique , Bourgeau Salomé , da Silva Janaina , Schlederer Julie , Satie Anne-Pascale , Kuassivi Nadège , Mathieu Romain , Guillou Yves-Marie , Le Tortorec Anna , Guivel-Benhassine Florence , Schwartz Olivier , Plotton Ingrid , Dejucq-Rainsford Nathalie 
Published: October 2023

ABSTRACT

SARS-CoV-2, the etiological agent of the ongoing Covid-19 pandemic, is a respiratory virus that infects several organs beyond the lungs. The alterations of semen parameters, testicular morphology, and testosteronemia reported in Covid-19 patients, along with the high expression of SARS-CoV-2 main receptor ACE2 in the testis, raise questions about the underlying mechanisms. Using a previously validated
ex vivo
model of human testis, we show that SARS-CoV-2 infects ACE2-positive Leydig and Sertoli cells. Slow virus replication kinetics were observed, with a peak of infection at day 6 post-infection and a decline of infectious virions at day 9. The infection had no major impact on testicular morphology or main hormonal functions, but some steroidogenic enzymes were decreased at day 9. While antiviral effectors were upregulated, there was no transcriptional induction of key pro-inflammatory cytokines. Altogether, these data indicate that SARS-CoV-2 replication in the human testis
ex vivo
is limited and suggest that testicular damages in infected individuals are unlikely to result from direct deleterious effects of SARS-CoV-2 on this organ.

IMPORTANCE
SARS-CoV-2 is a new virus responsible for the Covid-19 pandemic. Although SARS-CoV-2 primarily affects the lungs, other organs are infected. Alterations of testosteronemia and spermatozoa motility in infected men have raised questions about testicular infection, along with high level in the testis of ACE2, the main receptor used by SARS-CoV-2 to enter host cells. Using an organotypic culture of human testis, we found that SARS-CoV-2 replicated with slow kinetics in the testis. The virus first targeted testosterone-producing Leydig cells and then germ-cell nursing Sertoli cells. After a peak followed by the upregulation of antiviral effectors, viral replication in the testis decreased and did not induce any major damage to the tissue. Altogether, our data show that SARS-CoV-2 replicates in the human testis to a limited extent and suggest that testicular damages in infected patients are more likely to result from systemic infection and inflammation than from viral replication in the testis.
Structural basis for the hydrolytic activity of the transpeptidase-like protein DpaA to detach Braun’s lipoprotein from peptidoglycan
Authors: Wang Hsiu-Jung , Hernández-Rocamora Víctor M. , Kuo Chiao-I , Hsieh Kan-Yen , Lee Szu-Hui , Ho Meng-Ru , Tu Zhijay , Vollmer Waldemar , Chang Chung-I 
Published: October 2023

ABSTRACT

The peptidoglycan layer is a defining characteristic of bacterial cells, providing them with structural support and osmotic protection. In
Escherichia coli
, this layer is linked to the outer membrane via the abundant membrane-anchored protein Lpp, known as Braun’s lipoprotein, with LD-transpeptidases LdtA, LdtB, and LdtC catalyzing the attachment. However, one distinctive member of the YkuD-type transpeptidase family, LdtF (recently renamed DpaA), carries out the opposite reaction of detaching Lpp from the peptidoglycan layer. In this study, we report the crystal structure of DpaA, which reveals the enzyme’s ability to cleave, rather than form, the Lpp-peptidoglycan linkage. Assays with purified peptidoglycan-Lpp as the substrate and chemically synthesized compounds suggest that DpaA’s shallow L-shaped active site can only accommodate and cleave the peptidoglycan-Lpp cross-link with a constrained conformation. This study provides insights into how homologous Ldt enzymes can perform opposing chemical reactions.

IMPORTANCE
Cross-linking reaction of Braun's lipoprotein (Lpp) to peptidoglycan (PG) is catalyzed by some members of the YkuD family of transpeptidases. However, the exact opposite reaction of cleaving the Lpp-PG cross-link is performed by DpaA, which is also a YkuD-like protein. In this work, we determined the crystal structure of DpaA to provide the molecular rationale for the ability of the transpeptidase-like protein to cleave, rather than form, the Lpp-PG linkage. Our findings also revealed the structural features that distinguish the different functional types of the YkuD family enzymes from one another.
Improved detection of infection with SARS-CoV-2 Omicron variants of concern in healthcare workers by a second-generation rapid antigen test
Authors: Wettengel Jochen M. , Strehle Katharina , von Lucke Catharina , Roggendorf Hedwig , Jeske Samuel D. , Christa Catharina , Zelger Otto , Haller Bernhard , Protzer Ulrike , Knolle Percy A. 
Published: October 2023

ABSTRACT

The continuous genetic evolution of SARS-CoV-2 resulting in the immune escape variant of concern (VoC) Omicron poses a challenge to rapid and accurate diagnosis of infection, especially in high-risk groups such as healthcare workers. We performed a clinical study to determine the diagnostic accuracy and robustness of a second-generation rapid antigen test compared to a first-generation rapid antigen test with an RT-qPCR-based assay as gold standard, for early detection of infections with SARS-CoV-2 Omicron VoC. A total of 428 healthcare workers with COVID-19-associated symptoms or during routine testing participated in the study and completed a questionnaire on infection-associated symptoms, previous SARS-CoV-2 infections, and vaccination status. All participants performed a second- and first-generation rapid antigen test on the day of presentation and repeated the test 2 days later, and a diagnostic SARS-CoV-2 RT-qPCR assay was performed. qPCR-confirmed SARS-CoV-2 infections (
n
= 104) with Omicron VoC (BA.2, BA.4, BA.5) were detected by the first-generation rapid antigen test with a sensitivity of 83.7% (95% CI 75.12%–90.18%), whereas the second-generation rapid antigen test performed with a sensitivity of 89.4% (95% CI 81.9%–94.6%). Increased sensitivity of the second-generation rapid antigen test led to earlier detection of SARS-CoV-2 infection, while lower test sensitivity of the first-generation rapid antigen test was compensated by repeated testing 2 days later. Moreover, direct
in vitro
comparison revealed a lower limit of detection for the second-generation rapid antigen test for isolates of currently circulating Omicron sub-lineages BA.5.2, BQ.1, and XBB.1.

IMPORTANCE
The results from this study demonstrate the usefulness of a second-generation rapid antigen test for early detection of infection with the SARS-CoV-2 Omicron variant of concern (VoC) and reveal a higher sensitivity to detect immune escape Omicron VoCs compared to a first-generation rapid antigen test (89.4% vs 83.7%) in the high-risk group of healthcare workers.
Molecular characterization and pathogenicity evaluation of enterovirus G isolated from diarrheic piglets
Authors: Ibrahim Yassein M. , Zhang Wenli , Wang Xinrong , Werid Gebremeskel Mamu , Fu Lizhi , Yu Haidong , Wang Yue 
Published: October 2023

ABSTRACT

Four enterovirus G (EV-G) strains were isolated from diarrheic piglets that were negative for common swine enteric viruses. The spherical enterovirus particles of roughly 30-nm diameter were observed under transmission electron microscopy by using plaque-purified enterovirus. The complete genome sequence analysis revealed that each of four enteroviruses contained a papain-like cysteine protease (PLCP) gene between the 2C and 3A junction regions of the viral genome. This insertion encoded a predicted protease similar to the PLCP of porcine torovirus. The phylogenetic analysis based on complete genome with and without
PLCP
gene revealed that the four isolated EV-G strains were grouped together with global enterovirus G1-PLCP strains, and more closely related to EV-G/PLCP strains previously detected in China, Japan, and Korea (90.3%–92.2% similarities based on nucleotides). The cell susceptibility test demonstrated that the isolated EV-G could infect and replicate in cell lines from various host species. Furthermore, pathogenicity evaluation showed that the isolated EV-Gs induced mild diarrhea, pyrexia, and reduced body weight in infected piglets. The epidemiological investigation revealed a high prevalence of EV-G in swine herds. Together, our findings demonstrate that the isolated EV-G is pathogenic in piglets and may be advantageous in providing more trustworthy data on the evolution and pathological properties of EV-G.

IMPORTANCE

Enterovirus G is a species of positive-sense single-stranded RNA viruses associated with several mammalian diseases. The porcine enterovirus strains isolated here were chimeric viruses with the
PLCP
gene of porcine torovirus, which grouped together with global EV-G1 strains. The isolated EV-G strain could infect various cell types from different species, suggesting its potential cross-species infection risk. Animal experiment showed the pathogenic ability of the isolated EV-G to piglets. Additionally, the EV-Gs were widely distributed in the swine herds. Our findings suggest that EV-G may have evolved a novel mechanism for broad tropism, which has important implications for disease control and prevention.
Anti-topoisomerase 1 Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis
Authors: Ananyeva L. P. , Garzanova L. A. , Koneva O. A. , Starovoytova M. N. , Desinova O. V. , Ovsyannikova O. B. , Shayakhmetova R. U. , Cherkasova M. V. , Aleksankin A. P. , Nasonov E. L. 
Published: October 2023

Abstract
The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANAs) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSs) patients on rituximab (RTX) therapy. The prospective study included 88 patients (73 women) with a mean age of 47 (17–71) years. The mean disease duration was 5.9 ± 4.8 years. The mean follow-up period was more than 2 years (27 (12–42) months). We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r = 0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with patients negative for anti-Topo 1. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy, and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.
Culture, diversity and inclusion: a survey of British Hip Society members
Authors: Dayananda K , Gill K , Grove A , Parr J , Hook S , Howell J R , Maggs J 
Published: October 2023

AimTo explore the perceptions and experiences of members of the British Hip Society (BHS) as they relate to culture, diversity and inclusion in the professional sphere.MethodBHS members participated in an anonymised online survey in 2021. Quantitative and qualitative data were collected on demographics, professional experiences and perceptions of workplace culture. Members provided suggestions for improving working culture and supporting inclusivity.ResultsA 45% response rate (n=217) was achieved. Most respondents were male consultant surgeons, of white ethnicity. Almost a quarter of respondents reported experiencing barriers to career progression within the hip subspecialty. Experience of barriers was more common among women and those of non-white ethnicity. Several members experienced an elitist, exclusive culture in the BHS which is closed to outsiders. Thematic analysis of textual data revealed narratives which portray the perception of the society as a closed-door society, and described a clique culture in orthopaedics, and the pervasiveness of discrimination and banter.ConclusionWe found that barriers to inclusion and diversity exist within the professional society. Exploring the narratives around these has informed strategies to overcome them and has shaped future BHS initiatives. To ensure our patients receive the best possible surgical care, it is vital that those with the skills and expertise to deliver it, are supported by the Society and feel a sense of belonging and representation.
National examination of occupational hazards in emergency medical services
Authors: Powell Jonathan R , Cash Rebecca E , Kurth Jordan D , Gage Christopher B , Mercer Christopher B , Panchal Ashish R 
Published: October 2023

ObjectiveEmergency medical services (EMS) clinicians operate in environments that predispose them to occupational hazards. Our objective was to evaluate the frequency of occupational hazards and associations with mitigation strategies in a national dataset.MethodsWe performed a cross-sectional analysis of currently working, nationally certified civilian EMS clinicians aged 18–85 in the USA. After recertifying their National EMS Certification, respondents were invited to complete a survey with questions regarding demographics, work experience and occupational hazards. Three multivariable logistic regression models (OR, 95% CI) were used to describe associations between these hazards and demographics, work characteristics and mitigation strategies. Models were adjusted for age, sex, minority status, years of experience, EMS agency type, service type and EMS role.ResultsA total of 13 218 respondents met inclusion criteria (response rate=12%). A high percentage of EMS clinicians reported occupational injuries (27%), exposures (38%) and violence (64%) in the past 12 months. Odds of injury were lower with the presence of a lifting policy (0.73, 0.67–0.80), lift training (0.74, 0.67–0.81) and always using a powered stretcher (0.87, 0.78–0.97). Odds of exposure decreased with chemical, biological and nuclear exposure protection training (0.75, 0.69–0.80). Training in de-escalation techniques was associated with lower odds of experiencing violence (0.87, 0.79–0.96).ConclusionsOccupational hazards are commonly experienced among EMS clinicians. Common mitigation efforts are associated with lower odds of reporting these hazards. Mitigation strategies were not widespread and associated with lower odds of occupational hazards. These findings may present actionable items to reduce occupational hazards for EMS clinicians.