bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care
Authors: Marcus Rebecca , C Pike , Gill K. , Smith P. , Rouhani S. , Mendelsohn A. , Mendel E. , Lince-Deroche N. , Naidoo K. , Ahmed N. , Stirrup O. , Roseleur J. , Leuner R. , Meyer-Rath G. , Bekker L. G. 
Published: October 2023

Abstract
Background
Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town.

Methods
YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability.

Results
Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%).
Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire.

Conclusion
Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.
Metabolic flux analysis of coenzyme Q10 synthesized by Rhodobacter sphaeroides under the influence of different pH regulators
Authors: Xiao Yujun , Zheng Yi , Zhou Yong , Yu Chaofan , Ye Ting-E 
Published: October 2023

AbstractCoenzyme Q10 (CoQ10) is crucial for human beings, especially in the fields of biology and medicine. The aim of this experiment was to investigate the conditions for increasing CoQ10 production. At present, microbial fermentation is the main production method of CoQ10, and the production process of microbial CoQ10 metabolism control fermentation is very critical. Metabolic flux is one of the most important determinants of cell physiology in metabolic engineering. Metabolic flux analysis (MFA) is used to estimate the intracellular flux in metabolic networks. In this experiment, Rhodobacter sphaeroides was used as the research object to analyze the effects of aqueous ammonia (NH3·H2O) and calcium carbonate (CaCO3) on the metabolic flux of CoQ10. When CaCO3 was used to adjust the pH, the yield of CoQ10 was 274.43 mg·L−1 (8.71 mg·g−1 DCW), which was higher than that of NH3·H2O adjustment. The results indicated that when CaCO3 was used to adjust pH, more glucose-6-phosphate (G6P) entered the pentose phosphate (HMP) pathway and produced more NADPH, which enhanced the synthesis of CoQ10. At the chorismic acid node, more metabolic fluxes were involved in the synthesis of p-hydroxybenzoic acid (pHBA; the synthetic precursor of CoQ10), enhancing the anabolic flow of CoQ10. In addition, Ca2+ produced by the reaction of CaCO3 with organic acids promotes the synthesis of CoQ10. In summary, the use of CaCO3 adjustment is more favorable for the synthesis of CoQ10 by R. sphaeroides than NH3·H2O adjustment. The migration of metabolic flux caused by the perturbation of culture conditions was analyzed to compare the changes in the distribution of intracellular metabolic fluxes for the synthesis of CoQ10. Thus, the main nodes of the metabolic network were identified as G6P and chorismic acid. This provides a theoretical basis for the modification of genes related to the CoQ10 synthesis pathway.
The transcription factor GCN4 contributes to maintaining intracellular amino acid contents under nitrogen-limiting conditions in the mushroom Ganoderma lucidum
Authors: Lian Lingdan , Qiao Jinjin , Guo Xiaoyu , Xing Zhenzhen , Ren Ang , Zhao Mingwen , Zhu Jing 
Published: October 2023

Abstract
Background
Edible mushrooms are delicious in flavour and rich in high-quality protein and amino acids required by humans. A transcription factor, general control nonderepressible 4 (GCN4), can regulate the expression of genes involved in amino acid metabolism in yeast and mammals. A previous study revealed that GCN4 plays a pivotal role in nitrogen utilization and growth in Ganoderma lucidum. However, its regulation is nearly unknown in mushrooms.

Results
In this study, we found that the amino acid contents reached 120.51 mg per gram of mycelia in the WT strain under 60 mM asparagine (Asn) conditions, but decreased by 62.96% under 3 mM Asn conditions. Second, silencing of gcn4 resulted in a 54.2% decrease in amino acid contents under 60 mM Asn, especially for the essential and monosodium glutamate-like flavour amino acids. However, these effects were more pronounced under 3 mM Asn. Third, silencing of gcn4 markedly inhibited the expression of amino acid biosynthesis and transport genes. In addition, GCN4 enhanced the tricarboxylic acid cycle (TCA) and glycolytic pathway and inhibited the activity of target of rapamycin complex 1 (TORC1), thus being beneficial for maintaining amino acid homeostasis.

Conclusion
This study confirmed that GCN4 contributes to maintaining the amino acid contents in mushrooms under low concentrations of nitrogen. In conclusion, our study provides a research basis for GCN4 to regulate amino acid synthesis and improve the nutrient contents of edible mushrooms.
Why do transgender individuals experience discrimination in healthcare and thereby limited access to healthcare? An interview study exploring the perspective of German transgender individuals
Authors: Skuban-Eiseler Tobias , Orzechowski Marcin , Steger Florian 
Published: October 2023

Abstract
Background
Transgender individuals experience limited access to healthcare. This results not least from experiences of discrimination to which they are exposed in the health system. These contribute to transgender individuals having poorer health than cis individuals, i.e. individuals whose sex assigned at birth is in line with their gender identity. It is an ethical duty to take effective measures to minimize inequalities in medical care. At best, such measures should also be assessed as appropriate from the perspective of those affected in order to be accepted and thus effective. It is therefore important to know whether measures touch on the subjectively assumed reasons for experiences of discrimination. Hence, to be able to take appropriate measures, it is important to identify the reasons that transgender individuals see as causal for their experiences of discrimination in healthcare.

Methods
We conducted semi-structured interviews with 14 German transgender individuals and asked them about their own experiences of discrimination in healthcare and their assumptions on the reasons for discrimination. We analyzed the responses using the method of structured qualitative content analysis.

Results
13 transgender individuals reported experiences of discrimination in healthcare. These emanated from different professional groups and took place in trans-specific as well as general medical settings. We were able to identify a total of 12 reasons that transgender individuals see as causal for their experiences of discrimination: (1) internalized trans-hostility and “protection” of cis individuals, (2) lack of knowledge/uncertainties regarding transition, (3) “protection” of a binary worldview, (4) binary worldview in medicine, (5) structural deficits, (6) asymmetric interactions with specialists, (7) current political debate, (8) view of transgender individuals as a “burden for society”, (9) objectification, (10) homophobia, (11) misogyny/androcentrism and (12) discrimination as reaction to discrimination.

Conclusions
German transgender individuals have a very differentiated picture regarding their subjective reasons for experiencing discrimination in healthcare. Overall, disrespect regarding gender identity and a confrontation with foreignness seems to be seen as the decisive factor. Thus, it is not enough to focus only on measures that aim to remedy the information deficit on the part of medical providers. Measures must be taken that can create a granting and respectful attitude towards transgender individuals.
Short-term exposure sequences and anxiety symptoms: a time series clustering of smartphone-based mobility trajectories
Authors: Lan Yuliang , Helbich Marco 
Published: October 2023

Abstract
Background
Short-term environmental exposures, including green space, air pollution, and noise, have been suggested to affect health. However, the evidence is limited to aggregated exposure estimates which do not allow the capture of daily spatiotemporal exposure sequences. We aimed to (1) determine individuals’ sequential exposure patterns along their daily mobility paths and (2) examine whether and to what extent these exposure patterns were associated with anxiety symptoms.

Methods
We cross-sectionally tracked 141 participants aged 18–65 using their global positioning system (GPS) enabled smartphones for up to 7 days in the Netherlands. We estimated their location-dependent exposures for green space, fine particulate matter, and noise along their moving trajectories at 10-min intervals. The resulting time-resolved exposure sequences were then partitioned using multivariate time series clustering with dynamic time warping as the similarity measure. Respondents’ anxiety symptoms were assessed with the Generalized Anxiety Disorders-7 questionnaire. We fitted linear regressions to assess the associations between sequential exposure patterns and anxiety symptoms.

Results
We found four distinctive daily sequential exposure patterns across the participants. Exposure patterns differed in terms of exposure levels and daily variations. Regression results revealed that participants with a “moderately health-threatening” exposure pattern were significantly associated with fewer anxiety symptoms than participants with a “strongly health-threatening” exposure pattern.

Conclusions
Our findings support that environmental exposures’ daily sequence and short-term magnitudes may be associated with mental health. We urge more time-resolved mobility-based assessments in future analyses of environmental health effects in daily life.
Infrared laser therapy decreases systemic oxidative stress and inflammation in hypercholesterolemic mice with periodontitis
Authors: Ribeiro Isadora Martins , de Souza Barroso Maria Eduarda , Kampke Edgar Hell , Braga Larissa Trarbach Figueiredo , Campagnaro Bianca Prandi , Meyrelles Silvana dos Santos 
Published: October 2023

Abstract
Background
Near-infrared irradiation photobiomodulation (NIR-PBM) has been successfully used in periodontal treatment as an adjuvant tool to locally improve cell function and regeneration. Although the relationship between periodontitis and systemic disease constitutes an important aspect of periodontal clinical research, the systemic effects of NIR-PBM in periodontitis are not well known. In this study, we aimed to investigate the effects of NIR-PBM on systemic oxidative stress and inflammation in an apolipoprotein E (ApoE) knockout mouse model of periodontal disease (PD).

Methods
We evaluated alveolar bone loss by measuring the distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC), reactive oxygen species (ROS) production in blood cells, inflammatory activity, plasma cholesterol levels, and lipid peroxidation levels in three experimental groups: (1) ApoEC, control group without intervention; (2) ApoEP, first molar ligation-induced periodontitis for 4 weeks; and (3) ApoEP + PBM, exposed to 808 nm continuous wave, ø ~ 3 mm2, 100 mW, 60 s of NIR-PBM for 7 consecutive days after 4 weeks of periodontitis. At the end of the experimental protocols, ApoEP mice presented significantly increased alveolar bone loss, ROS production, inflammatory activity, plasma cholesterol, and lipid peroxidation levels compared to the ApoEC group (P < 0.05). NIR-PBM for 7 days in the ApoEP + PBM mice significantly decreased systemic ROS production, inflammatory response, plasma cholesterol, and lipid peroxidation levels, similar to those found in the ApoEC group (P > 0.05). However, it was not capable of preventing alveolar bone loss (P > 0.05 compared to ApoEP mice).

Conclusion
A 7-day treatment with NIR-PBM effectively reduces systemic oxidative stress and inflammatory parameters in hypercholesterolemic mice with PD. However, more studies with longer evaluation times are needed to confirm the systemic effects of locally applied NIR-PBM on PD associated with hypercholesterolemia.
Macrophage targeted iron oxide nanodecoys augment innate immunological and drug killings for more effective Mycobacterium Tuberculosis clearance
Authors: Shen Ling , Liao Kangsheng , Yang Enzhuo , Yang Fen , Lin Wensen , Wang Jiajun , Fan Shuhao , Huang Xueqin , Chen Lingming , Shen Hongbo , Jin Hua , Ruan Yongdui , Liu Xing , Zeng Gucheng , Xu Jun-Fa , Pi Jiang 
Published: October 2023

AbstractTuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is still one of the top killers worldwide among infectious diseases. The escape of Mtb from immunological clearance and the low targeting effects of anti-TB drugs remain the substantial challenges for TB control. Iron is particularly required for Mtb growth but also toxic for Mtb in high dosages, which makes iron an ideal toxic decoy for the ‘iron-tropic’ Mtb. Here, a macrophage-targeted iron oxide nanoparticles (IONPs)-derived IONPs-PAA-PEG-MAN nanodecoy is designed to augment innate immunological and drug killings against intracellular Mtb. IONPs-PAA-PEG-MAN nanodecoy exhibits preferential uptake in macrophages to significantly increase drug uptake with sustained high drug contents in host cells. Moreover, it can serve as a specific nanodecoy for the ‘iron-tropic’ Mtb to realize the localization of Mtb contained phagosomes surrounding the drug encapsulated nanodecoys and co-localization of Mtb with the drug encapsulated nanodecoys in lysosomes, where the incorporated rifampicin (Rif) can be readily released under acidic lysosomal condition for enhanced Mtb killing. This drug encapsulated nanodecoy can also polarize Mtb infected macrophages into anti-mycobacterial M1 phenotype and enhance M1 macrophage associated pro-inflammatory cytokine (TNF-α) production to trigger innate immunological responses against Mtb. Collectively, Rif@IONPs-PAA-PEG-MAN nanodecoy can synergistically enhance the killing efficiency of intracellular Mtb in in vitro macrophages and ex vivo monocyte-derived macrophages, and also significantly reduce the mycobacterial burdens in the lung of infected mice with alleviated pathology. These results indicate that Rif@IONPs-PAA-PEG-MAN nanodecoy may have a potential for the development of more effective therapeutic strategy against TB by manipulating augmented innate immunity and drug killings.
Graphic Abstract
A potential paradigm in CRISPR/Cas systems delivery: at the crossroad of microalgal gene editing and algal-mediated nanoparticles
Authors: Feng Shuying , Xie Xin , Liu Junjie , Li Aifang , Wang Qianqian , Guo Dandan , Li Shuxuan , Li Yalan , Wang Zilong , Guo Tao , Zhou Jin , Tang Doris Ying Ying , Show Pau Loke 
Published: October 2023

AbstractMicroalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae.Graphical Abstract
Implementation of policy and management interventions to improve health and care workforce capacity to address the COVID-19 pandemic response: a systematic review
Authors: Cavalcante de Oliveira Ana Paula , Galante Mariana Lopes , Maia Leila Senna , Craveiro Isabel , da Silva Alessandra Pereira , Fronteira Ines , Chança Raphael , Cometto Giorgio , Ferrinho Paulo , Dal Poz Mario 
Published: October 2023

Abstract
Background
The COVID-19 pandemic highlighted pre-existing weaknesses in health and care systems and services and shortages of health and care workers (HCWs). As a result, policymakers needed to adopt measures to improve the health and care workforce (HCWF) capacity. This review aims to identify countries’ range of policies and management interventions implemented to improve HCWs’ capacity to address the COVID-19 pandemic response, synthesize their evidence on effectiveness, and identify gaps in the evidence.

Methods
The literature was searched in PubMed, Embase, Scopus, LILACS–BVS, WHO’s COVID-19 Research Database and the ILO, OECD and HSRM websites for literature and documents published between January 2020 and March 2022. Eligibility criteria were HCWs as participants and policy and management interventions aiming to improve HCWF capacity to address the COVID-19 pandemic response. Risk of bias was assessed with Joanna Briggs Institute (JBI) Critical Appraisal Tools (CAT) and certainty of the evidence in presented outcomes with GRADE.

Results
The searches retrieved 3378 documents. A total of 69 were included, but only 8 presented outcomes of interventions implemented. Most of the selected documents described at least one intervention implemented by countries at the organizational environment level to increase the flexibility and capacity of the HCWF to respond to the pandemic, followed by interventions to attract and retain HCWs in safe and decent working environments. There was a lack of studies addressing social protection, human resources for health information systems, and regarding the role of community health workers and other community-based providers. Regarding the risk of bias, most of documents were rated as medium or high quality (JBI’s CAT), while the evidence presented for the outcomes of interventions was classified as mostly low-certainty evidence (GRADE).

Conclusions
Countries have implemented various interventions, some innovative, in response to the pandemic, and others had their processes started earlier and accelerated by the pandemic. The evidence regarding the impact and efficacy of the strategies used by countries during the pandemic still requires further research.
Matrix stiffness induces Drp1-mediated mitochondrial fission through Piezo1 mechanotransduction in human intervertebral disc degeneration
Authors: Ke Wencan , Wang Bingjin , Liao Zhiwei , Song Yu , Li Gaocai , Ma Liang , Wang Kun , Li Shuai , Hua Wenbin , Yang Cao 
Published: October 2023

AbstractBackgroundExtracellular matrix stiffness is emerging as a crucial mechanical cue that drives the progression of various diseases, such as cancer, fibrosis, and inflammation. The matrix stiffness of the nucleus pulposus (NP) tissues increase gradually during intervertebral disc degeneration (IDD), while the mechanism through which NP cells sense and react to matrix stiffness remains unclear. In addition, mitochondrial dynamics play a key role in various cellular functions. An in-depth investigation of the pathogenesis of IDD can provide new insights for the development of effective therapies. In this study, we aim to investigate the effects of matrix stiffness on mitochondrial dynamics in IDD.MethodsTo build the gradient stiffness model, NP cells were cultured on polystyrene plates with different stiffness. Western blot analysis, and immunofluorescence staining were used to detect the expression of mitochondrial dynamics-related proteins. Flow cytometry was used to detect the mitochondrial membrane potential and intracellular Ca2+levels. Apoptosis related proteins, ROS level, and TUNEL staining were performed to assess the effect of substrate stiffness on NP cells.ResultsStiff substrate increased phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 by activating extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which promoted mitochondrial fission and apoptosis in NP cells. Furthermore, Piezo1 activation was involved in the regulation of the post-translational modifications of Drp1 and mitochondrial fission caused by matrix stiffness. Inhibition of Piezo1 and ERK1/2 can effectively reduce stiffness-induced ROS elevation and apoptosis in NP cells.ConclusionsOur results revealed that stiff substrate causes Piezo1 activation and Ca2+influx, results in ERK1/2 activation and phosphorylation of Drp1 at S616, and finally leads to mitochondrial fission and apoptosis in NP cells. These findings reveal a new mechanism of mechanotransduction in NP cells, providing novel insights into the development of therapies for treating IDD.
The efficacy and safety of direct superior approach (DSA) for total hip arthroplasty: a systematic review and meta-analysis
Authors: Zhang Zhuangzhuang , Zhang Fukang , Yang Xin , Fan Hua , Cheng Qinghao , Guo Hongzhang 
Published: October 2023

Abstract
Objective
To systematically evaluate the clinical safety and efficacy of the direct superior approach and the conventional surgical approach.

Date sources
From PubMed, Embase, the Cochrane Library, and China Knowledge Network up to January 30, 2023.

Main results
A total of 7 case series involving 4306 patients undergoing total hip arthroplasty were included, including 679 patients with direct superior approach. All outcome measures: Oxford Hip Score [MD = 0.30, 95% CI (− 0.87, 1.47), P = 0.62], Hip Harris Score [MD = − 0.18, 95% CI (− 0.86, 0.49), P = 0.59], intraoperative blood loss [MD = − 54.14, 95% CI (− 102.75,-5.52), P = 0.03], transfusion rate [MD = 0.49, 95% CI (0.29, 0.83), P = 0.008], Limb Length Differences [MD = − 0.21, 95% CI (0.02, 0.39), P = 0.03], Length of Stay [MD = − 0.61, 95% CI (− 0.69, − 0.52), P < 0.00001].

Conclusions
The DSA was superior to conventional access in terms of incision length, bleeding, postoperative transfusion rate, and early postoperative HHS. In addition, our study found that because the DSA has less tissue damage, it has the potential advantages of accelerating patient recovery after surgery, shortening hospitalization time, and reducing patient economic pressure, which can significantly improve patient quality of life and satisfaction.