bluuebunny/crossref_metadata_2025 huggingface dataset:
Specialist palliative care until the very end of life - reports of family caregivers and the multiprofessional team
Authors: Ullrich Anneke , Goldbach Sven , Hollburg Wiebke , Wagener Bettina , Rommel Annette , Müller Marten , Kirsch Denise , Kopplin-Foertsch Katrin , Schulz Holger , Bokemeyer Carsten , Oechsle Karin
Published: October 2023

Background

Specialist palliative care (SPC) includes care for incurably ill patients and their family caregivers at home or on a palliative care ward until the very end of life. However, in the last days of life, patients can rarely express their needs and little is known about SPC outcomes as reported by multiprofessional SPC teams and family caregivers.

Methods

Using the Palliative Care Outcome Scale (POS; Score 0–40), proxy assessments of SPC outcomes in the patient’s last 3 days of life were performed by SPC teams and primary family caregivers of three home care and three inpatient services. Additional questions were asked about problems solved ‘particularly well’ or ‘inadequately’ (last 7 days), which were content analyzed and quantified.

Results

Proxy assessments by SPC teams were available in 142 patients (of whom 51% had died at home). Family caregiver assessments exist for a subgroup of 60 of these patients. SPC teams (POS total score: mean 13.8, SD 6.3) reported SPC outcomes slightly better than family caregivers (mean 16.7, SD 6.8). The POS items consistently rated as least affected (= 0) by both, SPC teams and family caregivers, were ‘not wasted time’ (team 99%/family caregivers 87%), ‘information’ (84%/47%) and ‘support’ (53%/31%). Items rated as most affected (= 4) were ‘patient anxiety’ (31%/51%), ‘life not worthwhile’ (26%/35%) and ‘no self-worth’ (19%/30%). Both groups indicated more problems solved ‘particularly well’ than ‘inadequately’; the latter concerned mainly clinically well-known challenges during end-of-life care and family caregiver care.

Conclusions

This study shows the range and type of symptoms and other concerns reported in the patient’s last days. Starting points for further improvements in family caregiver care and psychosocial and spiritual issues were identified.
Impact of a simulation-based education approach for health sciences: demo, debrief, and do
Authors: Orsega-Smith Elizabeth , Leonard Tara , Ruggiero Laurie , Amato Nicolette , O’Hara Jamie
Published: October 2023

Background

Skill-based practice (e.g., communication skills) is important for individuals to incorporate into students' learning and can be challenging in large classes. Simulation-based education (SBE) is a method where students can learn and practice skills in a safe environment to use in real world settings with assistance of peer coaching. The COVID-19 pandemic presented challenges to providing students with sufficient SBE. The purpose of this paper is to: a.) describe a SBE approach for health coaching referred to as “Demo, Debrief, and Do” (DDD), b.) discuss how this approach became important in COVID-19 classroom experiences, c.) describe the impact of DDD activity on students in a health sciences curriculum. DDD is a collaborative activity where graduate health coaching students demonstrate coaching skills, debrief their demonstration, and support undergraduate students to demonstrate (or do) their own coaching skills in a small virtual online setting.

Methods

Qualitative feedback from 121 undergraduate students enrolled in 3 sections of a behavior change strategies course and quantitative surveys to examine their confidence in applying the skills and overall satisfaction with DDD were gathered.

Results

The overall average confidence level following the lab was 31.7 (0–35). The average satisfaction level following the lab was 23.3 (0–25 range). The most common highlight of this DDD experience described was observing the coaching demonstration (i.e., demo), followed by the feedback (i.e., debrief), and the practice (i.e., do).

Conclusion

The (DDD) simulation approach fulfilled an educational need during the COVID 19 pandemic and filled a gap in offering SBE opportunities for both graduate and undergraduate students while learning effective client-communication skills health coaching delivery.
How will the Covid-19 pandemic shape the future of primary care undergraduate teaching? Understanding modifications and developments deployed by UK academic units of primary care, and their implications for the future
Authors: Harrison Michael , Hall Lauren , Alberti Hugh
Published: October 2023

Background

Primary care has been under-represented in its contribution to the academic literature base on Covid-19 developments. We sought to understand how teaching and learning was modified and developed by primary care academic leaders to support the continuation of primary care-orientated learning during the Covid-19 pandemic; and explore how these changes may shape future educational delivery in primary care.

Methods

We adopted a qualitative approach, using semi-structured interviews of seven General Practice Heads of Teaching (GP HoTs) from UK medical schools. We used mixed deductive and inductive coding to analyse interview transcripts. Modifications and developments were coded to four a priori themes (clinical off-site; clinical on-site; synchronous remote; asynchronous remote). We concurrently used inductive coding to identify developments that did not readily fit into these categories. To understand how participants perceived the developments may shape primary care teaching in the future, we carried out an inductive thematic analysis.

Results

A range of modifications and developments were described. Examples of developments include: GP practices being provided with increased flexibility to support ongoing provision of clinical placements (on-site clinical), examples of initiatives enabling students to consult remotely from their homes (off-site clinical), transfer of face-to-face teaching to remote formats (synchronous remote) and development of new, interactive on-line teaching materials (asynchronous remote). One additional theme arose inductively: collaboration and co-operation.

For future implications, five themes arose: the evolution of flexible and hybrid clinical placement models; an increased role for telemedicine; increased networking and collaboration; increased active student involvement in patient care; and opportunities for community-based teaching afforded by the pandemic.

Conclusion

This study highlights how teaching was modified to support the continuation of primary care-based learning during the Covid-19 pandemic, and implications for the future. Collaboration and placement flexibility were notable features in the response. Participants perceived that flexible placement models containing a mixture of clinical on-site with remote synchronous and asynchronous teaching and learning activities, may persist into the post-Covid era. Further research is required to understand which developments become routinely embedded into primary care teaching in the post-Covid era and explain how and why this occurs.
Measuring group function in problem-based learning: development of a reflection tool
Authors: Li Athena , Mellon Matthew , Keuhl Amy , Sibbald Matthew
Published: October 2023

Background

Problem-based learning (PBL) is a pedagogy involving self-directed learning in small groups around case problems. Group function is important to PBL outcomes, but there is currently poor scaffolding around key self-reflective practices that necessarily precedes students’ and tutors’ attempts to improve group function. This study aims to create a structured, literature-based and stakeholder-informed tool to help anchor reflective practices on group function. This article reports on the development process and perceived utility of this tool.

Methods

Tool development unfolded in four steps: 1) a literature review was conducted to identify existent evaluation tools for group function in PBL, 2) literature findings informed the development of this new tool, 3) a group of PBL experts were consulted for engagement with and feedback of the tool, 4) four focus groups of stakeholders (medical students and tutors with lived PBL experiences) commented on the tool’s constructs, language, and perceived utility. The tool underwent two rounds of revisions, informed by the feedback from experts and stakeholders.

Results

Nineteen scales relating to group function assessment were identified in the literature, lending 18 constructs that mapped into four dimensions: Learning Climate, Facilitation and Process, Engagement and Interactivity, and Evaluation and Group Improvement. Feedback from experts informed the addition of missing items. Focus group discussions allowed further fine-tuning of the organization and language of the tool. The final tool contains 17 descriptive items under the four dimensions. Users are asked to rate each dimension holistically on a 7-point Likert scale and provide open comments.

Researchers, faculty, and students highlighted three functions the tool could perform: (1) create space, structure, and language for feedback processes, (2) act as a reference, resource, or memory aid, and (3) serve as a written record for longitudinal benchmarking. They commented that the tool may be particularly helpful for inexperienced and poor-functioning groups, and indicated some practical implementation considerations.

Conclusion

A four-dimension tool to assist group function reflection in PBL was produced. Its constructs were well supported by literature and experts. Faculty and student stakeholders acknowledged the utility of this tool in addressing an acknowledged gap in group function reflection in PBL.
Construction of a knowledge graph for breast cancer diagnosis based on Chinese electronic medical records: development and usability study
Authors: Li Xiaolong , Sun Shuifa , Tang Tinglong , Lu Ji , Zhang Lijuan , Yin Jie , Geng Qian , Wu Yirong
Published: October 2023

Background

Electronic medical records (EMRs) contain a wealth of information related to breast cancer diagnosis and treatment. Extracting relevant features from these medical records and constructing a knowledge graph can significantly contribute to an efficient data analysis and decision support system for breast cancer diagnosis.

Methods

An approach was proposed to develop a workflow for effectively extracting breast cancer-related features from Chinese breast cancer mammography reports and constructing a knowledge graph for breast cancer diagnosis. Firstly, the concept layer of the knowledge graph for breast cancer diagnosis was constructed based on breast cancer diagnosis and treatment guidelines, along with insights from clinical experts. .Next, a BiLSTM-Highway-CRF model was designed to extract the mammography features, which formed the data layer of the knowledge graph. Finally, the knowledge graph was constructed by combining the concept layer and the data layer in a Neo4j graph data platform, and then applied in visualization analysis, semantic query and computer assisted diagnosis.

Results

Mammographic features were extracted from a total of 1171 mammography examination reports. The overall extraction performance of the model achieved an accuracy rate of 97.16%, a recall rate of 98.06%, and a F1 score of 97.61%. Additionally, 47,660 relationships between entities were identified based on the four different types of relationships defined in the concept layer. The knowledge graph for breast cancer diagnosis was constructed after inputting mammographic features and relationships into the Neo4j graph data platform. The model was assessed from the concept layer, data layer, and application layer perspectives, and showed promising results.

Conclusions

The proposed workflow is applicable for constructing knowledge graphs for breast cancer diagnosis based on Chinese EMRs. This study serves as a reference for the rapid design, construction, and application of knowledge graphs for diagnosis and treatment of other diseases. Furthermore, it offers a potential solution to address the issues of limited data sharing and format inconsistencies present in Chinese EMR data.
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

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

Coenzyme 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

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

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

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

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

Tuberculosis (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

Microalgae 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

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

Background

Extracellular 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.

Methods

To 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.

Results

Stiff 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.

Conclusions

Our 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

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.
Paeoniflorin shows chondroprotective effects under IL-1β stress by regulating circ-PREX1/miR-140-3p/WNT5B axis
Authors: Wu Lan’e , Tang Runke , Xiong Weibiao , Song Shuhua , Guo Qian , Zhang Qingqing
Published: October 2023

Background

Osteoarthritis (OA) is a chronic and degenerative bone and joint disease, and paeoniflorin shows anti-arthritis role in OA. This study planned to investigate the mechanism related to chondroprotective role of paeoniflorin in OA.

Methods

Real-time quantitative PCR and western blotting were performed to measure expression levels of circ-PREX1, microRNA (miR)-140-3p, Wingless-type MMTV integration site family, member 5B (WNT5B), B cell lymphoma (Bcl)-2, and Bcl-2 Associated X Protein (Bax). MTT assay, EdU assay, flow cytometry and enzyme-linked immunosorbent assay evaluated cell viability, proliferation, apoptosis and inflammatory response, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay identified the relationship among circ-PREX1, miR-140-3p, and WNT5B.

Results

IL-1β highly induced apoptosis rate, Bax expression and TNF-α product, accompanied with decreased cell viability, cell proliferation and IL-10 secretion, whereas these effects were partially reversed after paeoniflorin pretreatment. Expression of circ-PREX1 was upregulated and miR-140-3p was downregulated in cartilage tissues of patients with knee OA (KOA) and IL-1β-induced human chondrocytes (C28/I2). Circ-PREX1 overexpression and miR-140-3p silencing attenuated the suppressive effect of paeoniflorin in IL-1β-induced C28/I2 cells. Furthermore, miR-140-3p was negatively regulated by circ-PREX1. WNT5B was a downstream target of miR-140-3p and could be modulated by the circ-PREX1/miR-140-3p pathway in IL-1β-induced C28/I2 cells.

Conclusion

Paeoniflorin might protect human chondrocytes from IL-1β-induced inflammatory injury via circ-PREX1-miR-140-3p-WNT5B pathway, suggesting a potential preventative agent and a novel target for the treatment of KOA.
Acute cardiac tamponade following thoracoscopic lobectomy: a case report and literatures review
Authors: Chen Wei , Shen Yi , Yuan Yang , Zheng Qiangqiang , Zhou Yunfeng
Published: October 2023

Thoracoscopic lobectomy is a common surgical procedure for the treatment of lung cancer. With the continuous development of surgical techniques and medical devices, complications after thoracoscopic lobectomy are less and less, and cardiac tamponade is even rarer. This case is a 62-year-old woman who underwent thoracoscopic left upper lobectomy for a left upper lobe nodule. The patient developed acute cardiac tamponade on postoperative day 2, and symptoms resolved after pericardiocentesis. However, 20 h later, the patient underwent emergency surgery for re-developed acute cardiac tamponade, which was found to be a coronary tear. A review of the literature suggested that cardiac tamponade is more common in left lung surgery than right lung surgery. Pericardiocentesis can resolve initial acute cardiac tamponade, but pericardiotomy may be urgently needed after recurrence.
Case report of non-tracheal intubation—an alternative for postpneumonectomy patients undergoing contralateral pulmonary resection
Authors: Deng Jingdan , Zeng Zhiwen , Zhang Zizheng
Published: October 2023

Background

Surgery on the contralateral or other lungs after pneumonectomy on one side is highly challenging and complex. It is critical to creating conditions for fluent surgical maneuvers while ensuring adequate ventilation for a patient during such an operation in the same chest cavity that appears incompatible.

Case presentation

We have reported herein the case of a patient who, following a left pneumonectomy, underwent a right upper pulmonary nodule wedge resection via video-assisted thoracoscopic surgery without requiring endotracheal intubation. We managed ventilation with a laryngeal mask airway under general anesthesia combined with a thoracic epidural block. The diseased lobe collapsed well for the surgical procedure during VATS without hypoxia, after which the resection was safely performed.

Conclusions

Non-tracheal intubation anesthesia can be a potentially attractive alternative for patients undergoing contralateral pulmonary resection after pneumonectomy.
Total arch replacement for an aortic arch aneurysm with cold agglutinin disease after rituximab and plasmapheresis
Authors: Mitsuishi Atsuyuki , Miura Yujiro , Saeki Kyosuke , Nomura Yoshinori , Yoshifumi Katsumata , Yoshida Keisuke
Published: October 2023

Background

Cold agglutinin disease can lead to significant complications, especially for patients undergoing arch repair requiring hypothermic circulatory arrest. Rituximab and plasmapheresis are treatments for cold agglutinin disease. However, its use in patients with Stanford type A dissection has not been reported. Therefore, after consultation with hematologists, we used rituximab and plasmapheresis before mild hypothermic aortic arch surgery to maintain the body temperature above the thermal altitude.

Case presentation

This report describes an 86-year-old male patient with acute type A aortic dissection who received outpatient treatment for rheumatoid arthritis and a 55-mm thoracic aortic aneurysm. The patient was scheduled to undergo urgent surgery for a type A intramural hematoma and progressive aortic aneurysm; however, laboratory test results indicated blood clotting and cold agglutinin. Consequently, urgent surgery was rescheduled. After consulting with hematologists, rituximab was initiated 3 months before surgery, and plasmapheresis was performed 2 days before surgery for cold agglutinin disease. Under mild hypothermia conditions, total arch replacement using the frozen elephant trunk technique was performed while maintaining cerebral and lower body perfusion. The postoperative course was uneventful. On postoperative day 42, the patient was discharged without any neurological deficits.

Conclusions

This case involving total arch replacement with mild hypothermia for an aortic arch aneurysm with cold agglutinin disease after rituximab treatment and plasmapheresis resulted in a successful outcome.
Implementing digital mental health interventions at scale: one-year evaluation of a national digital CBT service in Ireland
Authors: Harty Siobhán , Enrique Angel , Akkol-Solakoglu Selin , Adegoke Adedeji , Farrell Hannah , Connon Graham , Ward Fiona , Kennedy Conor , Chambers Derek , Richards Derek
Published: October 2023

Background

In recent years, exponential growth in digital innovations and internet access has provided opportunities to deliver health services at a much greater scale than previously possible. Evidence-based technology-enabled interventions can provide cost-effective, accessible, and resource-efficient solutions for addressing mental health issues. This study evaluated the first year of a supported digital cognitive behavioral therapy (CBT) service provided by the national health service in Ireland, which has been accessible to individuals who receive a referral from one of five referring groups: General Practitioners, Primary Care Psychology, Counselling Primary Care, Community Mental Health, and Jigsaw (a nationwide youth mental health service).

Methods

A retrospective, observational study examining data from the service between April 2021 to April 2022 was conducted. Descriptive statistics on referrals, account activations, user demographics, program usage, and user satisfaction were extracted, and pre-to-post clinical outcomes for depression measured by the Patient Health Questionnaire-9 and for anxiety measured by the Generalised Anxiety Disorder-7 were analysed using linear mixed effect models.

Results

There were 5,298 referrals and 3,236 (61%) account activations within the year. Most users were female (72.9%) and aged between 18 and 44 years (75.4%). The CBT programs were associated with significant reductions in both depression (β = 3.34, 95% CI [3.03, 3.65], p < 0.001) and anxiety (β = 3.64, 95% CI [3.36, 3.93], p < 0.001), with large effect sizes (Cohen’s d > 0.8). Time spent using the programs was also found to be a predictor of the variability in these clinical outcomes (p < 0.001), and accounting for this resulted in significantly better model fits (p < 0.001). User satisfaction ratings were also very high, exceeding 94%.

Conclusions

Efforts to improve the representation of male and older adult users are warranted. However, overall, the results demonstrate how digital CBT can be provided at scale and lead to symptom reductions with large effect sizes for patients seeking help for depression and anxiety. The findings substantiate the continued use and expansion of this service in Ireland and the more widespread implementation of similar services in other international public healthcare settings.
Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms
Authors: Sigurjonsdottir Gudbjörg , De Marchi Tommaso , Ehinger Anna , Hartman Johan , Bosch Ana , Staaf Johan , Killander Fredrika , Niméus Emma
Published: October 2023

Background

Immunohistochemical (IHC) PD-L1 expression is commonly employed as predictive biomarker for checkpoint inhibitors in triple-negative breast cancer (TNBC). However, IHC evaluation methods are non-uniform and further studies are needed to optimize clinical utility.

Methods

We compared the concordance, prognostic value and gene expression between PD-L1 IHC expression by SP142 immune cell (IC) score and 22C3 combined positive score (CPS; companion IHC diagnostic assays for atezolizumab and pembrolizumab, respectively) in a population-based cohort of 232 early-stage TNBC patients.

Results

The expression rates of PD-L1 for SP142 IC ≥ 1%, 22C3 CPS ≥ 10, 22C3 CPS ≥ 1 and 22C3 IC ≥ 1% were 50.9%, 27.2%, 53.9% and 41.8%, respectively. The analytical concordance (kappa values) between SP142 IC+ and these three different 22C3 scorings were 73.7% (0.48, weak agreement), 81.5% (0.63) and 86.6% (0.73), respectively. The SP142 assay was better at identifying 22C3 positive tumors than the 22C3 assay was at detecting SP142 positive tumors. PD-L1 (CD274) gene expression (mRNA) showed a strong positive association with all two-categorical IHC scorings of the PD-L1 expression, irrespective of antibody and cut-off (Spearman Rho ranged from 0.59 to 0.62; all p-values < 0.001). PD-L1 IHC positivity and abundance of tumor infiltrating lymphocytes were of positive prognostic value in univariable regression analyses in patients treated with (neo)adjuvant chemotherapy, where it was strongest for 22C3 CPS ≥ 10 and distant relapse-free interval (HR = 0.18, p = 0.019). However, PD-L1 status was not independently prognostic when adjusting for abundance of tumor infiltrating lymphocytes in multivariable analyses.

Conclusion

Our findings support that the SP142 and 22C3 IHC assays, with their respective clinically applied scoring algorithms, are not analytically equivalent where they identify partially non-overlapping subpopulations of TNBC patients and cannot be substituted with one another regarding PD-L1 detection.

Trial registration The Swedish Cancerome Analysis Network - Breast (SCAN-B) study, retrospectively registered 2nd Dec 2014 at ClinicalTrials.gov; ID NCT02306096.