bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement activation drives antibody-mediated transfusion-related acute lung injury via macrophage trafficking and formation of NETs
Authors: van der Velden Saskia , van Osch Thijs L. J. , Seghier Amina , Bentlage Arthur E. H. , Mok Juk Yee , Geerdes Dionne M. , van Esch Wim J. E. , Pouw Richard B. , Brouwer Mieke C. , Jongerius Ilse , de Haas Masja , Porcelijn Leendert , van der Schoot C. Ellen , Vidarsson Gestur , Kapur Rick 
Published: October 2023

Abstract
Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and, to date, is without available therapies. Here, we investigated the role of the complement system in TRALI. Murine anti–major histocompatibility complex class I antibodies were used in TRALI mouse models, in combination with analyses of plasma samples from patients with TRALI. We found that in vitro complement activation was related to in vivo antibody-mediated TRALI induction, which was correlated with increased macrophage trafficking from the lungs to the blood in a fragment crystallizable region (Fc)-dependent manner and that this was dependent on C5. Human immunoglobulin G 1 variants of the murine TRALI-inducing antibody 34-1-2S, either unable to activate complement and/or bind to Fcγ receptors (FcγRs), revealed an essential role for the complement system, but not for FcγRs, in the onset of 34-1-2S–mediated TRALI in mice. In addition, we found high levels of complement activation in the plasma of patients with TRALI (n = 53), which correlated with elevated neutrophil extracellular trap (NET) markers. In vitro we found that NETs could be formed in a murine, 2-hit model, mimicking TRALI with lipopolysaccharide and C5a stimulation. Collectively, this reveals a critical role of Fc-mediated complement activation in TRALI, with a direct relation to macrophage trafficking from the lungs to the blood and an association with NET formation, suggesting that targeting the complement system may be an attractive therapeutic approach for combating TRALI.
Early complete response as a validated surrogate marker in extranodal marginal zone lymphoma systemic therapy
Authors: Bommier Côme , Zucca Emanuele , Chevret Sylvie , Conconi Annarita , Nowakowski Grzegorz , Maurer Matthew J. , Cerhan James R. , Thieblemont Catherine , Lambert Jérôme 
Published: October 2023

Abstract
Extranodal marginal zone lymphoma (EMZL) has a very indolent course, and the validation of surrogate markers could accelerate novel therapies. Although prognostic markers do exist, no surrogate markers have been validated in EMZL. We hypothesized that time to complete response within 24 months (TTCR24) and complete response (CR) at 24 months (CR24) could be valid surrogate markers of progression-free survival (PFS). The International Extranodal Lymphoma Study Group 19 phase 3 trial showed the advantage of double therapy (rituximab + chlorambucil) over single therapy (rituximab or chlorambucil) on PFS. We used 2 recently published single-trial approaches to assess whether TTCR24 and CR24 were good surrogate markers of 8-year PFS (8y-PFS). Among the 401 patients, 264 (66%) reached a CR in the first 24 months, of which 222 (84%) remained in CR at month 24. The cumulative incidence of CR over time was significantly higher in patients under double therapy (hazard ratio, 1.75; P &lt; .001). The double therapy arm was associated with a higher CR24 rate, a shorter TTCR24, and a longer 8y-PFS. The estimated proportion of treatment effect on 8y-PFS explained by TTCR24 was 95% (95% confidence interval [CI], 0.27-1.87). CR24 was also a strong surrogate marker because it mediated 90% (95% CI, 0.51-2.22) of the treatment effect on PFS and its natural indirect effect was significant throughout the follow-up. We found that TTCR24 predicted 95% and that CR24 mediated 90% of the treatment effect on long-term PFS. Therefore, TTCR24 and CR24 could be used in clinical trials as informative and valid early indicators of treatment effect on PFS. This trial was registered at www.clinicaltrials.gov as #NCT00210353.
Targeting and internalizing PEGylated nanodrugs to enhance the therapeutic efficacy of hematologic malignancies by anti-PEG bispecific antibody (mPEG × CD20)
Authors: Chen Huei-Jen , Cheng Yi-An , Chen Yu-Tung , Li Chia-Ching , Huang Bo-Cheng , Hong Shih-Ting , Chen I.-Ju , Ho Kai-Wen , Chen Chiao-Yun , Chen Fang-Ming , Wang Jaw-Yuan , Roffler Steve R. , Cheng Tian-Lu , Wu Tung-Ho 
Published: October 2023

Abstract
Background
PEGylated nanoparticles (PEG-NPs) are not effective for hematologic malignancies as they lack the enhanced permeability and retention effect (EPR effect). Tumor-targeted PEG-NPs can systemically track lymphoma and actively internalize into cancer cells to enhance therapeutic efficacy. We generated an anti-PEG bispecific antibody (BsAb; mPEG × CD20) which was able to simultaneously bind to methoxy PEG on liposomes and CD20 to form multivalent αCD20-armed liposomes. This αCD20-armed liposome was able to crosslink CD20 on lymphoma cells to enhance cellular internalization and the anti-cancer efficacy of the liposomes to lymphoma. We generated mPEG × CD20 and used this bispecific antibody to modify PEGylated liposomal doxorubicin (PLD) through a one-step formulation.

Results
αCD20-armed PLD (αCD20/PLD) specifically targeted CD20+ Raji cells and enhanced PLD internalization 56-fold after 24 h. αCD20/PLD also increased cytotoxicity to Raji cells by 15.2-fold in comparison with PLD and control mPEG × DNS-modified PLD (αDNS/PLD). mPEG × CD20 significantly enhanced the tumor accumulation 2.8-fold in comparison with mPEG × DNS-conjugated PEGylated liposomal DiD in Raji tumors. Moreover, αCD20/PLD had significantly greater therapeutic efficacy as compared to αDNS/PLD (P < 0.0001) and PLD(P < 0.0001), and αCD20/PLD-treated mice had a 90% survival rate at 100-day post-treatment.

Conclusions
Modification of mPEG × CD20 can confer PLD with CD20 specificity to enhance the internalization and the anti-cancer efficacy of PEG-NPs. This therapeutic strategy can conveniently be used to modify various PEG-NPs with anti-PEG BsAb to overcome the lack of EPR effect of hematologic malignancies and improve therapeutic efficacy.
Emerging roles for diguanylate cyclase during the evolution of soma in dictyostelia
Authors: Kawabe Yoshinori , Du Qingyou , Narita Takaaki B. , Bell Craig , Schilde Christina , Kin Koryu , Schaap Pauline 
Published: October 2023

Abstract
Background
Cyclic di-guanylate (c-di-GMP), synthesized by diguanylate cyclase, is a major second messenger in prokaryotes, where it triggers biofilm formation. The dictyostelid social amoebas acquired diguanylate cyclase (dgcA) by horizontal gene transfer. Dictyostelium discoideum (Ddis) in taxon group 4 uses c-di-GMP as a secreted signal to induce differentiation of stalk cells, the ancestral somatic cell type that supports the propagating spores. We here investigated how this role for c-di-GMP evolved in Dictyostelia by exploring dgcA function in the group 2 species Polysphondylium pallidum (Ppal) and in Polysphondylium violaceum (Pvio), which resides in a small sister clade to group 4.

Results
Similar to Ddis, dgcA is upregulated after aggregation in Ppal and Pvio and predominantly expressed in the anterior region and stalks of emerging fruiting bodies. DgcA null mutants in Ppal and Pvio made fruiting bodies with very long and thin stalks and only few spores and showed delayed aggregation and larger aggregates, respectively. Ddis dgcAˉ cells cannot form stalks at all, but showed no aggregation defects. The long, thin stalks of Ppal and Pvio dgcAˉ mutants were also observed in acaAˉ mutants in these species. AcaA encodes adenylate cyclase A, which mediates the effects of c-di-GMP on stalk induction in Ddis. Other factors that promote stalk formation in Ddis are DIF-1, produced by the polyketide synthase StlB, low ammonia, facilitated by the ammonia transporter AmtC, and high oxygen, detected by the oxygen sensor PhyA (prolyl 4-hydroxylase). We deleted the single stlB, amtC and phyA genes in Pvio wild-type and dgcAˉ cells. Neither of these interventions affected stalk formation in Pvio wild-type and not or very mildly exacerbated the long thin stalk phenotype of Pvio dgcAˉ cells.

Conclusions
The study reveals a novel role for c-di-GMP in aggregation, while the reduced spore number in Pvio and Ppal dgcAˉ is likely an indirect effect, due to depletion of the cell pool by the extended stalk formation. The results indicate that in addition to c-di-GMP, Dictyostelia ancestrally used an as yet unknown factor for induction of stalk formation. The activation of AcaA by c-di-GMP is likely conserved throughout Dictyostelia.
Synergistic antibacterial action of the iron complex and ampicillin against Staphylococcus aureus
Authors: Kosaristanova Ludmila , Rihacek Martin , Sucha Frantiska , Milosavljevic Vedran , Svec Pavel , Dorazilova Jana , Vojtova Lucy , Antal Peter , Kopel Pavel , Patocka Zdenek , Adam Vojtech , Zurek Ludek , Dolezelikova Kristyna 
Published: October 2023

Abstract
Objectives
Resistance to antibiotics among bacteria of clinical importance, including Staphylococcus aureus, is a serious problem worldwide and the search for alternatives is needed. Some metal complexes have antibacterial properties and when combined with antibiotics, they may increase bacterial sensitivity to antimicrobials. In this study, we synthesized the iron complex and tested it in combination with ampicillin (Fe16 + AMP) against S. aureus.

Methods
An iron complex (Fe16) was synthesized and characterized using spectroscopy methods. Confirmation of the synergistic effect between the iron complex (Fe16) and ampicillin (AMP) was performed using ζ–potential, infrared spectra and FICI index calculated from the minimum inhibitory concentration (MIC) from the checkerboard assay. Cytotoxic properties of combination Fe16 + AMP was evaluated on eukaryotic cell line. Impact of combination Fe16 + AMP on chosen genes of S. aureus were performed by Quantitative Real-Time PCR.

Results
The MIC of Fe16 + AMP was significantly lower than that of AMP and Fe16 alone. Furthermore, the infrared spectroscopy revealed the change in the ζ–potential of Fe16 + AMP. We demonstrated the ability of Fe16 + AMP to disrupt the bacterial membrane of S. aureus and that likely allowed for better absorption of AMP. In addition, the change in gene expression of bacterial efflux pumps at the sub-inhibitory concentration of AMP suggests an insufficient import of iron into the bacterial cell. At the same time, Fe16 + AMP did not have any cytotoxic effects on keratinocytes.

Conclusions
Combined Fe16 + AMP therapy demonstrated significant synergistic and antimicrobial effects against S. aureus. This study supports the potential of combination therapy and further research.
Digital measurement and clinical significance of proximal femur in the older people of Inner Mongolia population, China
Authors: Jiawei Li , Kai Zhang , Haiyan Wang , Chao Wu , Yunfeng Zhang , Liangjia Ding , Qinghua Liu , Canran Li , Feng Jin , Xiaohe Li 
Published: October 2023

Abstract
Objective
This study aimed to measure the parameters of the proximal femur in the older people of Inner Mongolia, China and understand the influence of age and gender so as to provide guidance for the design and improvement of prosthesis for total hip arthroplasty.

Methods
A total of 236 patients who underwent CT angiography of lower limbs in the Department of Imaging, Affiliated Hospital of Inner Mongolia Medical University of China were collected. They were divided into 4 groups according to age: < 60 (group A), 60–69 (group B), 70–79 (group C), and > 80 years (group D). Four anatomical parameters, including femoral head diameter (FHD), femoral neck-shaft angle (FNSA), femoral offset (FO), femoral neck anteversion (FNA), were measured by Mimics 21.0. Comparisons were made between age groups of the same gender and between genders in the same age group to analyze the correlation of the 4 parameters of proximal femur with age and gender. In addition, the results of this study were compared with previous studies.

Results
There were no significant differences in FHD and FO between age groups, indicating no correlation with age. FNSA and FNA were no significantly different between group C and group D in the same gender, whereas there were significant differences between other age groups and were negatively correlated with age. There were significant differences in FHD and FO between genders in the same age group, with the males being larger than the females. FNSA and FNA were no significant differences between genders in the same age group.

Conclusions
FNSA and FNA decrease with age. FHD and FO were larger in males than in females in all age groups. Age and gender should be considered in the design of prosthesis.
Effects of rasagiline combined with levodopa and benserazide hydrochloride on motor function and homocysteine and IGF-1 levels in elderly patients with Parkinson’s disease
Authors: Yang Yifan , Gao Feng , Gao Li , Miao Jiaodan 
Published: October 2023

Abstract
Background
During the course of their illness, people with Parkinson’s disease may see changes in their insulin-like growth factor (IGF-1) and serum homocysteine (Hcy) indices. In this study, patients with intermediate to severe Parkinson’s disease were examined for how Resagiline and levodopa and benserazide hydrochloride affected their motor performance, serum levels of homocysteine (Hcy), and insulin-like growth factor (IGF-1).

Methods
From June 2020 to December 2021, a total of 100+ cases of Parkinson’s patients over 60 years old in the middle and late stages of Parkinson’s were seen in the outpatient and inpatient departments of the Third People’s Hospital of Chengdu City and had a detailed observation record, and according to the inclusion criteria, the patients who met the criteria were randomly grouped into a clinical observation group and a control group. The subjects in the control group received only levodopa and benserazide hydrochloride treatment, while the observation group was treated with Resagiline in combination with the clinical control group. The total treatment observation period was 1 year for both groups, and the motor function and serum Hcy and IGF-1 indexes of both groups were compared after the end of treatment.

Results
We randomly and evenly grouped 64 patients who met the requirements of the inclusion criteria into a clinical observation group and a control group, each with 32 patients, from among 168 patients over 60 years of age with detailed observation records in the middle and late stages of Parkinson’s. After the 1-year observation period, we found that the total effective rate after treatment in the clinical observation group (93.75%) and significantly higher than that in the control group (68.75%) (P < 0.05); after 1 year of treatment, the UPDRS score decreased in both groups, and the observation group was significantly lower than the control group (P < 0.05); after treatment, serum Hcy decreased and IGF-1 increased in both groups, and the observation group was higher than the control group mean values (P < 0.05).

Conclusions
In patients with Parkinson’s disease who are in the middle and late stages of the disease, the administration of Resagiline combined with levodopa and benserazide hydrochloride can significantly lower the body’s serum Hcy level, significantly raise IGF-1 levels, and significantly improve motor function in patients with Parkinson’s disease. It can also have significant therapeutic effects.
Dynamic changes in macrophage morphology during the progression of choroidal neovascularization in a laser-induced choroidal neovascularization mouse model
Authors: Xu Nana , Sun Tao , Wang Yulan , Tong Xiaowei , Lu Shiheng , Yang Fan , Wang Jing , Bo Qiyu , Sun Junran , Sun Xiaodong 
Published: October 2023

Abstract
Background
Neovascular age-related macular degeneration (AMD) is responsible for the majority of severe vision loss cases and is mainly caused by choroidal neovascularization (CNV). This condition persists or recurs in a subset of patients and regresses after 5 or more years of anti-vascular endothelial growth factor (VEGF) treatment. The precise mechanisms of CNV continue to be elucidated. According to our previous studies, macrophages play a critical role in CNV. Herein, we aimed to determine the morphological changes in macrophages in CNV to help us understand the dynamic changes.

Methods
Mice were subjected to laser injury to induce CNV, and lesion expansion and macrophage transformation were examined by immunofluorescence and confocal analysis. Several strategies were used to verify the dynamic changes in macrophages. Immunofluorescence and confocal assays were performed on choroidal flat mounts to evaluate the morphology and phenotype of macrophages in different CNV phases, and the results were further verified by western blotting and RT–PCR.

Results
The location of infiltrated macrophages changed after laser injury in the CNV mouse model, and macrophage morphology also dynamically changed. Branching macrophages gradually shifted to become round with the progression of CNV, which was certified to be an M2 phenotypic shift.

Conclusions
Dynamic changes in macrophage morphology were observed during CNV formation, and the round-shaped M2 phenotype could promote neovascularization. In general, the changes in morphology we observed in this study can help us to understand the critical role of macrophages in CNV progression and exploit a potential treatment option for CNV indicated by a shift in macrophage polarity.
Social and emotional wellbeing of Aboriginal and Torres Strait Islander peoples in Aboriginal controlled social housing
Authors: Brown Alison , Haregu Tilahun , Gee Graham , Mensah Fiona , Waters Lea , Brown Stephanie J , Nicholson Jan M , Hegarty Kelsey , Smith Darren , D’Amico Sue , Ritte Rebecca , Paradies Yin , Armstrong Gregory 
Published: October 2023

Abstract
Background
Little is known about the wellbeing and aspirations of Aboriginal and Torres Strait Islander peoples living in social housing. Aboriginal and Torres Strait Islander peoples living in social housing face common social housing challenges of low income, higher incidence of mental health issues and poorer health along with specific challenges due to the impacts of colonisation and its ongoing manifestations in racism and inequity. A greater understanding of social and emotional wellbeing needs and aspirations is essential in informing the provision of appropriate support.

Methods
Surveys of social and emotional wellbeing (SEWB) were completed by 95 Aboriginal people aged 16 years and older living in Aboriginal Housing Victoria social housing in 2021. The survey addressed a range of domains reflecting social and emotional wellbeing, as defined by Aboriginal and Torres Strait Islander peoples.

Results
Most respondents demonstrated a strong sense of identity and connection to family however 26% reported having 6 or more health conditions. Ill health and disability were reported to be employment barriers for almost a third of people (32%). Improving health and wellbeing (78%) was the most cited aspiration. Experiences of racism and ill health influenced engagement with organisations and correspondingly education and employment.

Conclusion
Strong connections to identity, family and culture in Aboriginal peoples living in social housing coexist along with disrupted connections to mind, body and community. Culturally safe and appropriate pathways to community services and facilities can enhance these connections. Research aimed at evaluating the impact of strengths-based interventions that focus on existing strong connections will be important in understanding whether this approach is effective in improving SEWB in this population.

Trial Registration
: This trial was retrospectively registered with the ISRCTN Register on the 12/7/21 with the study ID:ISRCTN33665735.
Factors impacting HIV testing among young sexually active women migrant workers in Vietnamese industrial zones
Authors: Ha Toan , Shi Hui , Givens David , Nguyen Trang , Nguyen Nam 
Published: October 2023

Abstract
Background
Young migrant workers living in low- and middle-income countries often experience barriers and inadequate access to HIV prevention and treatment services. This study examines the prevalence of HIV testing, associated factors, and reasons for obtaining and not obtaining HIV testing among young sexually active women migrant workers in an industrial zone in Hanoi, Vietnam.

Methods
A cross-sectional study was conducted among 512 sexually active young women migrant workers (aged 18 to 29) working in the Thang Long industrial zone in Hanoi, Vietnam. Data was collected via a face-to-face interview from January 2020 to June 2021. Multivariable logistic regression analysis was used to explore factors associated with ever-testing for HIV among sexually active participants.

Results
The study found a low level of HIV testing and high rates of unprotected sex. Among those who reported being sexually active, only 23.7% of participants (n = 126) reported having ever been tested for HIV. Among those who reported never having tested for HIV, 38.2% reported not using condoms during their most recent sexual encounter. Factors associated with engaging in HIV testing included being older (25–29 years), having greater knowledge about HIV, past use of sexual and reproductive health and HIV services, and familiarity with HIV testing locations.

Conclusions
Overall, a low level of HIV testing, high rates of unprotected sex, and low perceived risks regarding HIV among the study participants point to a need to implement targeted HIV interventions that can improve both safe sex practices and perceptions of and knowledge about risky sexual behaviors. Such interventions should use insights from this study to address factors facilitating HIV testing among industrial zones’ women migrant workers.
Barriers and facilitators to palliative care for patients with non-curable cancer in Colombia: perspectives of allied health and social care professionals
Authors: Mendieta Cindy V. , de Vries Esther , Gomez-Neva Maria Elizabeth , Muñoz-Escudero Angela Maria , Calvache Jose Andrés , McConnell Tracey 
Published: October 2023

Abstract
Background
Palliative care aims to improve the quality of life of people with life-limiting illness and their families by addressing physical, psychological, social and spiritual suffering. Allied Health and Social Care Professionals (AHSCP) are key to delivering comprehensive, high quality palliative care. In recent years, Colombia has developed changes in the legal, and regulatory framework for access to palliative care but barriers and facilitators to palliative care for patients with non-curable cancer have not been explored from the perspective of AHSCP.

Method
This study aims to address this knowledge gap in two cities in Colombia: one in a medium-sized city in a rural area (Popayan) and one in a highly urbanized area (Bogota). Two focus groups with AHSCP were conducted using the World Cafe method, and a subsequent thematic analysis was performed to establish the main barriers and facilitators.

Results
A wide range of 18 AHSCPs attended the two World Cafe groups in Popayan and Bogota. As a result of this iterative process, we established five thematic areas: (i) Humanizing care, (ii) Normalizing palliative care: referral at the time of diagnosis, (iii) Misunderstandings related to palliative care, (iv) Barriers within the health system, and (v) Geographic barriers.

Conclusion
This study provided the perspectives of AHSCPs in Colombia in relation to barriers and facilitators in the framework of comprehensive palliative care attention. Participants identified misconceptions about palliative care, which are explained by the lack of inclusion of this area in the educational programs of health professionals and AHSCPs, along with the limited supply and access to palliative care, especially in rural areas.