bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote sampling of biomarkers of inflammation with linked patient generated health data in patients with rheumatic and musculoskeletal diseases: an Ecological Momentary Assessment feasibility study
Authors: Druce Katie L. , Gibson David S. , McEleney Kevin , Yimer Belay B. , Meleck Stephanie , James Ben , Hellman Bruce , Dixon William G. , McBeth John
Published: August 2022

Background

People with rheumatic diseases experience troublesome fluctuations in fatigue. Debated causes include pain, mood and inflammation. To determine the relationships between these potential causes, serial assessments are required but are methodologically challenging. This mobile health (mHealth) study explored the viability of using a smartphone app to collect patient-reported symptoms with contemporaneous Dried Blood Spot Sampling (DBSS) for inflammation.

Methods

Over 30 days, thirty-eight participants (12 RA, 13 OA, and 13 FM) used uMotif, a smartphone app, to report fatigue, pain and mood, on 5-point ordinal scales, twice daily. Daily DBSS, from which C-reactive Protein (CRP) values were extracted, were completed on days 1–7, 14 and 30. Participant engagement was determined based on frequency of data entry and ability to calculate within- and between-day symptom changes. DBSS feasibility and engagement was determined based on the proportion of samples returned and usable for extraction, and the number of days between which between-day changes in CRP which could be calculated (days 1–7).

Results

Fatigue was reported at least once on 1085/1140 days (95.2%). Approximately 65% of within- and between-day fatigue changes could be calculated. Rates were similar for pain and mood. A total of 287/342 (83.9%) DBSS, were returned, and all samples were viable for CRP extraction. Fatigue, pain and mood varied considerably, but clinically meaningful (≥ 5 mg/L) CRP changes were uncommon.

Conclusions

Embedding DBSS in mHealth studies will enable researchers to obtain serial symptom assessments with matched biological samples. This provides exciting opportunities to address hitherto unanswerable questions, such as elucidating the mechanisms of fatigue fluctuations.
Inhibitory effect of ficin on Candida albicans biofilm formation and pre-formed biofilms
Authors: Yu Jiantao , Wang Fan , Shen Yan , Yu Fangzheng , Qiu Lili , Zhang Lingjun , Chen Yanhan , Yuan Qing , Zhang Huan , Sun Yan , Zhang Keke
Published: August 2022

Background

To investigate the effect of ficin, a type of proteases, on Candida albicans (C. albicans) biofilm, including forming and pre-formed biofilms.

Methods

Crystal violet tests together with colony forming unit (CFU) counts were used to detect fungal biofilm biomass. Live/dead staining of biofilms observed by confocal laser scanning microscopy was used to monitor fungal activity. Finally, gene expression of C. albicans within biofilms was assessed by qRT-PCR.

Results

According to our results, biofilm biomass was dramatically reduced by ficin in both biofilm formation and pre-formed biofilms, as revealed by the crystal violet assay and CFU count (p < 0.05). Fungal activity in biofilm formation and pre-formed biofilms was not significantly influenced by ficin according to live/dead staining. Fungal polymorphism and biofilm associated gene expression were influenced by ficin, especially in groups with prominent antibiofilm effects.

Conclusions

In summary, ficin effectively inhibited C. albicans biofilm formation and detached its preformed biofilm, and it might be used to treat C. albicans biofilm associated problems.
Psychological distress and resilience in patients with advanced cancer during the Covid-19 pandemic: the mediating role of spirituality
Authors: Mihic-Gongora Luka , Jiménez-Fonseca Paula , Hernandez Raquel , Gil-Raga Mireia , Pacheco-Barcia Vilma , Manzano-Fernández Aránzazu , Hernando-Polo Susana , Antoñanzas-Basa Mónica , Corral María J. , Valero-Arbizu María , Calderon Caterina
Published: August 2022

Background

The purpose of this study was to investigate the sociodemographic factors related to psychological distress, spirituality, and resilience, and to examine the mediating role of spirituality with respect to psychological distress and resilience in patients with advanced, unresectable cancer during the Covid-19 pandemic.

Methods

A prospective, cross-sectional design was adopted. Data were collected from 636 participants with advanced cancer at 15 tertiary hospitals in Spain between February 2019 and December 2021. Participants completed self-report measures: Brief Resilient Coping Scale (BRCS), Brief Symptom Inventory (BSI-18), and Spiritual well-being (FACIT-Sp). Hierarchical linear regression models were used to explore the mediating role of spirituality.

Results

Spirituality was significantly different according to the person’s age and marital status. Psychological distress accounted for 12% of the variance in resilience (β = − 0.32, p < 0.001) and spirituality, another 15% (β =0.48, p < 0.001). Spirituality acted as a partial mediator in the relationship between psychological distress and resilience in individuals with advanced cancer.

Conclusions

Both psychological distress and spirituality played a role in resilience in cases of advanced cancer. Spirituality can help promote subjective well-being and increased resilience in these subjects.
Developing and evaluating an instrument to assess perceptions of an entry-level physician associate doctoral degree
Authors: Jun Hyun-Jin , Gordes Karen  L. , Fleming Shani , Kulo Violet , Cawley James F. , Kayingo Gerald
Published: August 2022

Background

Most health professions in the United States have adopted clinical or practice doctorates, sparking an ongoing debate on whether physician assistants/associates (PAs) should transition from a master’s to a doctorate as the terminal degree for the profession. Although more studies are anticipated, there is no validated instrument assessing perceptions of various stakeholders regarding an entry-level PA doctoral degree. The objective of this study was to develop and evaluate a novel self-report measure to assess perceptions of an entry-level PA doctoral degree.

Methods

A multifaceted, mixed-methods approach was adopted. Based on a comprehensive literature review of the doctoral transition experiences in other health professions, an initial version ofperceptions of an entry-level terminal PA doctoral degree scale(PEDDS) was generated. This scale was pilot tested with a group of PA faculty, students, and clinicians. Then, a cross-sectional survey consisting of 67 items was conducted with a national random sample of practicing PAs and PA students. Additionally, semi-structured interviews were conducted to ensure the validity of PEDDS. A principal component analysis (PCA) was conducted to reduce the number of items and reveal the underlying structure of PEDDS.

Results

The PCA confirmed 10 factors of PEDDS consisting of 53 items as the best-fit factor structure with adequate internal consistency of subscales. Those factors include a) expected positive impact on the PA profession, b) expected impact on prerequisites, (c) expected impact on the student preparedness as PA faculty and educators, (d) expected impact on the student preparedness as clinicians, (e) expected impact on accreditation and certification, (f) expected impact on curriculum, (g) expected impact on PA educators, (h) expected positive impact on diversity, (i) expected negative impact on the PA profession, and (j) expected impact on the student competency.

Conclusions

The present study highlights the need to develop valid and reliable measurements to assess perceptions regarding the transition to the entry-level doctorate across health professions. This study could be used to guide further discussion of the entry-level doctorates for PAs and other health professions by bridging the gap of existing literature related to valid, reliable, and standardized measures on this topic.
Increasing physician participation as subjects in scientific and quality improvement research
Authors: Hysong Sylvia J. , McGuire Amy L.
Published: August 2022

Background

The twenty-first century has witnessed an exponential increase in healthcare quality research. As such activities become more prevalent, physicians are increasingly needed to participate as subjects in research and quality improvement (QI) projects. This raises an important ethical question: how should physicians be remunerated for participating as research and/or QI subjects?

Financial versus non-monetary incentives for participation

Research suggests participation in research and QI is often driven by conditional altruism, the idea that although initial interest in enrolling in research is altruistic or prosocial, decisions to actually perform study tasks are cost–benefit driven. Thus, the three models commonly employed to appropriately compensate participants (in-kind compensation such as travel reimbursement, paying market rates for the subject’s time, and paying market rates for the activity asked of the participant) are a poor fit when the participant is a clinician, largely due to the asymmetry between cost and benefit or value to the participant. Non-monetary alternatives such as protected time for participation, continuing education or maintenance of certification credit, or professional development materials, can provide viable avenues for reducing this asymmetry.

Conclusion

Research and QI are integral to the betterment of medicine and healthcare. To increase physician participation in these activities as the subject of study, new models are needed that clarify the physician’s role in research and QI as a subject. Non-monetary approaches are recommended to successfully and ethically encourage research and QI participation, and thus incorporate these activities as a normal part of the ethical clinician’s and successful learning healthcare system’s world view.
Human-centered design of clinical decision support for management of hypertension with chronic kidney disease
Authors: Garabedian Pamela M. , Gannon Michael P. , Aaron Skye , Wu Edward , Burns Zoe , Samal Lipika
Published: August 2022

Background

Primary care providers face challenges in recognizing and controlling hypertension in patients with chronic kidney disease (CKD). Clinical decision support (CDS) has the potential to aid clinicians in identifying patients who could benefit from medication changes. This study designed an alert to control hypertension in CKD patients using an iterative human-centered design process.

Methods

In this study, we present a human-centered design process employing multiple methods for gathering user requirements and feedback on design and usability. Initially, we conducted contextual inquiry sessions to gather user requirements for the CDS. This was followed by group design sessions and one-on-one formative think-aloud sessions to validate requirements, obtain feedback on the design and layout, uncover usability issues, and validate changes.

Results

This study included 20 participants. The contextual inquiry produced 10 user requirements which influenced the initial alert design. The group design sessions revealed issues related to several themes, including recommendations and clinical content that did not match providers' expectations and extraneous information on the alerts that did not provide value. Findings from the individual think-aloud sessions revealed that participants disagreed with some recommended clinical actions, requested additional information, and had concerns about the placement in their workflow. Following each step, iterative changes were made to the alert content and design.

Discussion

This study showed that participation from users throughout the design process can lead to a better understanding of user requirements and optimal design, even within the constraints of an EHR alerting system. While raising awareness of design needs, it also revealed concerns related to workflow, understandability, and relevance.

Conclusion

The human-centered design framework using multiple methods for CDS development informed the creation of an alert to assist in the treatment and recognition of hypertension in patients with CKD.
Fuzzy constraint-based agent negotiation framework for doctor-patient shared decision-making
Authors: Lin Kaibiao , Liu Yong , Lu Ping , Yang Yimin , Fan Haiting , Hong Feiping
Published: August 2022

Background

The clinical practice of shared decision-making (SDM) has grown in importance. However, most studies on SDM practice concentrated on providing auxiliary knowledge from the third-party standpoint without consideration for the value preferences of doctors and patients. The essences of these methods are complete and manual negotiation, and the problems of high cost, time consumption, delayed response, and decision fatigue are serious.

Methods

In response to the above limitations, this article proposes a fuzzy constraint-directed agent-based negotiation and recommendation framework for bilateral and multi-issue preference negotiation in SDM (PN-SDM). Its purpose is to provide preference information and intellectualize PN-SDM to promote SDM practice. We modeled PN-SDM problems as distributed fuzzy constraint satisfaction problems and designed the doctor agent and patient agent to negotiate on behalf of the doctor and patient. The negotiation result was then transformed into treatment plans by the recommendation model. The proposed negotiation and recommendation models were introduced in detail by an instance.

Results

The proposed method with different strategies and negotiation pairs achieves good performance in terms of negotiation running time, negotiation rounds, and combined aggregated satisfaction value. Specifically, it can feasibly and effectively complete multiple rounds of PN-SDM in a few seconds and obtain higher satisfaction.

Conclusion

The experimental results indicate that the negotiation model can effectively simulate preference negotiation and relieve the pressure of increasing issues. The recommendation model can assist in decision-making and help to realize SDM. In addition, it can flexibly cope with various negotiation scenarios by using different negotiation strategies (e.g., collaborative, win–win, and competitive).
Implementation of a telemedicine, stroke evaluation service; a qualitative study
Authors: Kjelle Elin , Myklebust Aud Mette
Published: August 2022

Background

Acute ischemic stroke requires early medical imaging with a computed tomography (CT) scan and immediate thrombolysis treatment. In rural areas, the long distance to the nearest hospital reduce the patients’ probability of receiving medical assistance within the 4.5-h period. The aim of this study was to assess how the service was set-up, and how managers and personnel experience the organisation and value of a rural telemedicine, remote controlled CT stroke service.

Methods

Ten semi-structured individual interviews and one semi-structured focus group interview were conducted. The sample included 15 participants involved in the telemedicine service in Hallingdal, Norway. The interview guide consisted of questions on the service, experience of working with the service, value and quality, management, and challenges. Interviews were recorded and transcribed verbatim. Thematic content analysis was used to develop a narrative of the findings.

Results

Findings were categorised into three main categories; value of the service, organisation of the project, and from project to permanent service. Participants perceived the service to be valuable for patients and the local community. The service included task shifting from radiographers and junior doctors to the local paramedics. To enable long- term operation of the service the participants suggested management, coordination, and continuous training as important factors.

Conclusions

The service was perceived as valuable to the local community, providing a sense of healthcare security and equitability. Management’s involvement, flexibility, and coordination appears to be a key factor for successful implementation and long-term sustainability of the service.
Selenium and/or vitamin E upregulate the antioxidant gene expression and parameters in broilers
Authors: Elgendey Fatma , Al Wakeel Rasha A. , Hemeda Shabaan A. , Elshwash Aya Mohamed , Fadl Sabreen E. , Abdelazim Aaser M. , Alhujaily Muhanad , Khalifa Olla A.
Published: August 2022

Background

In contrast to free radicals, the first line of protection is assumed to be vitamin E and selenium. The present protocol was designed to assess the roles of vitamin E and/or a selenium-rich diet that affected the blood iron and copper concentrations, liver tissue antioxidant and lipid peroxidation, and gene expression linked to antioxidants in the liver tissue of broilers. The young birds were classified according to the dietary supplement into four groups; control, vitamin E (100 mg Vitamin/kg diet), selenium (0.3 mg sodium selenite/kg diet), and vitamin E pulse selenium (100 mg vitamin/kg diet with 0.3 mg sodium selenite/kg diet) group.

Results

The results of this experiment suggested that the addition of vitamin E with selenium in the broiler diet significantly increased (P ≤ 0.05) serum iron when compared with the other groups and serum copper when compared with the vitamin E group. Moreover, the supplements (vitamin E or vitamin E with selenium) positively affected the enzymatic activity of the antioxidant-related enzymes with decreased malondialdehyde (MDA),which represents lipid peroxidation in broiler liver tissue. Moreover, the two supplements significantly upregulated genes expression related to antioxidants.

Conclusion

Therefore, vitamin E and/or selenium can not only act as exogenous antioxidants to prevent oxidative damage by scavenging free radicals and superoxide, but also act as gene regulators, regulating the expression of endogenous antioxidant enzymes.
A first report on the efficacy of a single intra-articular administration of blood cell secretome, triamcinolone acetonide, and the combination of both in dogs with osteoarthritis
Authors: Alves J. C. , Santos A. , Jorge P. , Carreira L. Miguel
Published: August 2022

Background

Osteoarthritis represents a significant welfare problem for many dogs, with limited therapeutic options other than palliative pain control. To evaluate the effect of the intra-articular administration of blood cell secretome and triamcinolone, 15 dogs with bilateral hip osteoarthritis were randomly assigned to a blood cell secretome (BCSG,n = 5), triamcinolone (TG) or their combination group (BCS + TG,n = 5). BCSG received a single intra-articular administration of 3 ml of blood cell secretome, TG 0.5 ml of triamcinolone acetonide 40 mg/ml, and BCS + TG received the combined products. The volume to administrate was corrected to 3.5 ml with saline. On days 0, 8, 15, 30, 60, 90, 120, 150, and 180, a copy of the Canine Brief Pain Inventory (divided into pain interference score—PIS and Pain Severity Score—PSS), Liverpool Osteoarthritis in Dogs (LOAD), Hudson Visual Analogue Scale (HVAS), and Canine Orthopedic Index (COI, divided into function, gait, stiffness, and quality of life) was completed. Results were analyzed with the Kruskal–Wallis test and the Kaplan–Meier estimators were conducted and compared with the Log Rank test,p < 0.05.

Results

Animals in the sample had a mean age of 9.0 ± 2.9 years and a bodyweight of 28.8 ± 4.1 kg. Hips were classified as moderate (8) and severe (7) osteoarthritis. No differences were found between groups at T0 regarding considered evaluations. Significant differences were observed between groups in pain scores from + 8d- + 150d, with BCS + TG exhibiting better results. The same was observed for HVAS and LOAD, from + 8d- + 120d. Improvements were also observed in several dimensions of the COI. Kaplan–Meier estimators showed that BCS + TG produced longer periods with better results, followed by BCSG and TG.

Conclusion

The intra-articular administration of blood cell secretome improved the clinical signs and scores of several clinical metrology instruments in dogs with hip OA, particularly when combined with triamcinolone. Further studies are required.
Functional and structural characteristics of HLA-B*13:01-mediated specific T cells reaction in dapsone-induced drug hypersensitivity
Authors: Jiang Haiqin , Wang Chuang-Wei , Wang Zhaoxi , Dai Yufei , Zhu Yanping , Lee Yun-Shien , Cao Yang , Chung Wen-Hung , Ouyang Songying , Wang Hongsheng
Published: August 2022

Background

Severe cutaneous adverse drug reactions (SCARs) are a group of serious clinical conditions caused by immune reaction to certain drugs. The allelic variance of human leukocyte antigens of HLA-B*13:01 has been strongly associated with hypersensitivities induced by dapsone (DDS). T-cell receptor mediated activation of cytotoxic T lymphocytes (CTLs) has also been suggested to play an essential role in pathogenesis of SCARs. However, HLA-B*13:01-DDS-TCR immune synapse that plays role in drug-induced hypersensitivity syndrome (DIHS) associated T cells activation remains uncharacterized.

Methods

To investigate the molecular mechanisms for HLA-B*13:01 in the pathogenesis of Dapsone-induced drug hypersensitivity (DDS-DIHS), we performed crystallization and expanded drug-specific CTLs to analyze the pathological role of DDS-DIHS.

Results

Results showed the crystal structure of HLA-B*13:01-beta-2-microglobulin (β2M) complex at 1.5 Å resolution and performed mutation assays demonstrating that I118 or I119, and R121 of HLA-B*13:01 were the key residues that mediate the binding of DDS. Subsequent single-cell TCR and RNA sequencing indicated that TCRs composed of paired TRAV12-3/TRBV28 clonotype with shared CDR3 region specifically recognize HLA-B*13:01-DDS complex to trigger inflammatory cytokines associated with DDS-DIHS.

Conclusion

Our study identified the novel p-i-HLA/TCR as the model of interaction between HLA-B*13:01, DDS and the clonotype-specific TCR in DDS-DIHS.

Graphical Abstract
Upregulating carnitine palmitoyltransferase 1 attenuates hyperoxia-induced endothelial cell dysfunction and persistent lung injury
Authors: Chang Jason L. , Gong Jiannan , Rizal Salu , Peterson Abigail L. , Chang Julia , Yao Chenrui , Dennery Phyllis A. , Yao Hongwei
Published: August 2022

Background

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants that may cause long-term lung dysfunction. Accumulating evidence supports the vascular hypothesis of BPD, in which lung endothelial cell dysfunction drives this disease. We recently reported that endothelial carnitine palmitoyltransferase 1a (Cpt1a) is reduced by hyperoxia, and that endothelial cell-specific Cpt1a knockout mice are more susceptible to developing hyperoxia-induced injury than wild type mice. Whether Cpt1a upregulation attenuates hyperoxia-induced endothelial cell dysfunction and lung injury remains unknown. We hypothesized that upregulation of Cpt1a by baicalin or l-carnitine ameliorates hyperoxia-induced endothelial cell dysfunction and persistent lung injury.

Methods

Lung endothelial cells or newborn mice (< 12 h old) were treated with baicalin or l-carnitine after hyperoxia (50% and 95% O2) followed by air recovery.

Results

We found that incubation with l-carnitine (40 and 80 mg/L) and baicalin (22.5 and 45 mg/L) reduced hyperoxia-induced apoptosis, impaired cell migration and angiogenesis in cultured lung endothelial cells. This was associated with increased Cpt1a gene expression. In mice, neonatal hyperoxia caused persistent alveolar and vascular simplification in a concentration-dependent manner. Treatment with l-carnitine (150 and 300 mg/kg) and baicalin (50 and 100 mg/kg) attenuated neonatal hyperoxia-induced alveolar and vascular simplification in adult mice. These effects were diminished in endothelial cell-specific Cpt1a knockout mice.

Conclusions

Upregulating Cpt1a by baicalin or l-carnitine ameliorates hyperoxia-induced lung endothelial cell dysfunction, and persistent alveolar and vascular simplification. These findings provide potential therapeutic avenues for using l-carnitine and baicalin as Cpt1a upregulators to prevent persistent lung injury in premature infants with BPD.
Ethanol yield improvement in Saccharomyces cerevisiae GPD2 Delta FPS1 Delta ADH2 Delta DLD3 Delta mutant and molecular mechanism exploration based on the metabolic flux and transcriptomics approaches
Authors: Yang Peizhou , Jiang Shuying , Lu Shuhua , Jiang Suwei , Jiang Shaotong , Deng Yanhong , Lu Jiuling , Wang Hu , Zhou Yong
Published: August 2022

Background

Saccharomyces cerevisiae generally consumes glucose to produce ethanol accompanied by the main by-products of glycerol, acetic acid, and lactic acid. The minimization of the formation of by-products in S. cerevisiae was an effective way to improve the economic viability of the bioethanol industry. In this study, S. cerevisiae GPD2, FPS1, ADH2, and DLD3 genes were knocked out by the Clustered Regularly Interspaced Short Palindromic Repeats Cas9 (CRISPR-Cas9) approach. The mechanism of gene deletion affecting ethanol metabolism was further elucidated based on metabolic flux and transcriptomics approaches.

Results

The engineered S. cerevisiae with gene deletion of GPD2, FPS1, ADH2, and DLD3 was constructed by the CRISPR-Cas9 approach. The ethanol content of engineered S. cerevisiae GPD2 Delta FPS1 Delta ADH2 Delta DLD3 Delta increased by 18.58% with the decrease of glycerol, acetic acid, and lactic acid contents by 22.32, 8.87, and 16.82%, respectively. The metabolic flux analysis indicated that the carbon flux rethanol in engineered strain increased from 60.969 to 63.379. The sequencing-based RNA-Seq transcriptomics represented 472 differential expression genes (DEGs) were identified in engineered S. cerevisiae, in which 195 and 277 genes were significantly up-regulated and down-regulated, respectively. The enriched pathways of up-regulated genes were mainly involved in the energy metabolism of carbohydrates, while the down-regulated genes were mainly enriched in acid metabolic pathways.

Conclusions

The yield of ethanol in engineered S. cerevisiae increased with the decrease of the by-products including glycerol, acetic acid, and lactic acid. The deletion of genes GPD2, FPS1, ADH2, and DLD3 resulted in the redirection of carbon flux.
Cheese whey supports high riboflavin synthesis by the engineered strains of the flavinogenic yeast Candida famata
Authors: Ruchala Justyna , Andreieva Yuliia A. , Tsyrulnyk Andriy O. , Sobchuk Svitlana M. , Najdecka Alicja , Wen Liu , Kang Yingqian , Dmytruk Olena V. , Dmytruk Kostyantyn V. , Fedorovych Dariya V. , Sibirny Andriy A.
Published: August 2022

Background

Riboflavin is a precursor of FMN and FAD which act as coenzymes of numerous enzymes. Riboflavin is an important biotechnological commodity with annual market sales exceeding nine billion US dollars. It is used primarily as a component of feed premixes, a food colorant, a component of multivitamin mixtures and medicines. Currently, industrial riboflavin production uses the bacterium, Bacillus subtilis, and the filamentous fungus, Ashbya gossypii, and utilizes glucose and/or oils as carbon substrates.

Results

We studied riboflavin biosynthesis in the flavinogenic yeast Candida famata that is a genetically stable riboflavin overproducer. Here it was found that the wild type C. famata is characterized by robust growth on lactose and cheese whey and the engineered strains also overproduce riboflavin on whey. The riboflavin synthesis on whey was close to that obtained on glucose. To further enhance riboflavin production on whey, the gene of the transcription activator SEF1 was expressed under control of the lactose-induced promoter of the native β-galactosidase gene LAC4. These transformants produced elevated amounts of riboflavin on lactose and especially on whey. The strain with additional overexpression of gene RIB6 involved in conversion of ribulose-5-phosphate to riboflavin precursor had the highest titer of accumulated riboflavin in flasks during cultivation on whey. Activation of riboflavin synthesis was also obtained after overexpression of the GND1 gene that is involved in the synthesis of the riboflavin precursor ribulose-5-phosphate. The best engineered strains accumulated 2.5 g of riboflavin/L on whey supplemented only with (NH4)2SO4 during batch cultivation in bioreactor with high yield (more than 300 mg/g dry cell weight). The use of concentrated whey inhibited growth of wild-type and engineered strains of C. famata, so the mutants tolerant to concentrated whey were isolated.

Conclusions

Our data show that the waste of dairy industry is a promising substrate for riboflavin production by C. famata. Possibilities for using the engineered strains of C. famata to produce high-value commodity (riboflavin) from whey are discussed.
Potential of antibody–drug conjugates (ADCs) for cancer therapy
Authors: Marei Hany E. , Cenciarelli Carlo , Hasan Anwarul
Published: August 2022

The primary purpose of ADCs is to increase the efficacy of anticancer medications by minimizing systemic drug distribution and targeting specific cells. Antibody conjugates (ADCs) have changed the way cancer is treated. However, because only a tiny fraction of patients experienced long-term advantages, current cancer preclinical and clinical research has been focused on combination trials. The complex interaction of ADCs with the tumor and its microenvironment appear to be reliant on the efficacy of a certain ADC, all of which have significant therapeutic consequences. Several clinical trials in various tumor types are now underway to examine the potential ADC therapy, based on encouraging preclinical results. This review tackles the potential use of ADCs in cancer therapy, emphasizing the essential processes underlying their positive therapeutic impacts on solid and hematological malignancies. Additionally, opportunities are explored to understand the mechanisms of ADCs action, the mechanism of resistance against ADCs, and how to overcome potential resistance following ADCs administration. Recent clinical findings have aroused interest, leading to a large increase in the number of ADCs in clinical trials. The rationale behind ADCs, as well as their primary features and recent research breakthroughs, will be discussed. We then offer an approach for maximizing the potential value that ADCs can bring to cancer patients by highlighting key ideas and distinct strategies.
Non-invasive myocardial work index contributes to early identification of impaired left ventricular myocardial function in uremic patients with preserved left ventricular ejection fraction
Authors: Zhu Huizhen , Li Yanan , Cui Cunying , Huang Danqing , Liu Yuanyuan , Liu Ruijie , Zhao Qingqing , Wang Ying , Liu Lin
Published: August 2022

Background

Cardiac damage is the leading cause of death in uremic patients. This study aimed to evaluate the application of non-invasive myocardial work index (NIMWI) by echocardiography in assessing the left ventricular (LV) systolic function in uremic patients.

Methods

Twenty-six uremic patients and 27 age- and sex-matched healthy volunteers were enrolled in the study. Except for the conventional echocardiographic parameters, the LV myocardial work (MW) parameters including GWI (myocardial global work index), GCW (global constructive work), GWW (global wasted work), and GWE (global work efficiency) were calculated in study participants. Differences in MW parameters between the uremic and normal groups were compared by independent-sample t-test. Receiver operating characteristic (ROC) curves were constructed for MW parameters to detect abnormal LV systolic function in uremic patients.

Results

Compared with the normal group, GWW was significantly increased and GWE decreased in the uremic group (P < 0.05). Area under the curve (AUC) for GWE by the ROC analysis was 0.966. The best threshold, sensitivity and specificity values of GWE to detect abnormality of LV systolic function in uremic patients were 92.5%, 0.89 and 0.96, respectively.

Conclusions

NIMWI may be applied to assess the global MW of uremic patients. The presence of reduced GWE can help identify impaired left ventricular myocardial function in uremic patients with preserved LV ejection fraction with a high sensitivity and specificity.
Development of artesunate intelligent prodrug liposomes based on mitochondrial targeting strategy
Authors: Gu Liwei , Zhang Jiaxing , Liu Dandan , Chen Jiayun , Liu Shuzhi , Peng Qing , Tian Ya , Du Maobo , Zhang Junzhe , Xiao Wei , Shen Shuo , Wang Jigang
Published: August 2022

Breast cancer is the leading cause of cancer-related deaths in women and remains a formidable therapeutic challenge. Mitochondria participate in a myriad of essential cellular processes, such as metabolism, and are becoming an ideal target for cancer therapy. Artemisinin and its derivatives have demonstrated multiple activities in the context of various cancers. Mitochondrial autophagy(mitophagy) is one of the important anti-tumor mechanisms of artemisinin drugs. However, the lack of specific tumor targeting ability limits the anti-tumor efficacy of artemisinin drugs. In this study, a GSH-sensitive artesunate smart conjugate (TPP-SS-ATS) was synthesized and liposomes (TPP-SS-ATS-LS) that target tumor cells and mitochondria were further prepared. The advantages of TPP-SS-ATS-LS targeting to the breast tumor were verified by in vivo and in vitro evaluations. In our study, the cytotoxicity was obviously enhanced in vitro and tumor growth inhibition rate was increased from 37.7% to 56.4% at equivalent artesunate dosage in breast cancer orthotopic implanted mice. Meanwhile, mitochondrial dysfunction, suppression of ATP production and respiratory capacity were detected in breast cancer cells. We further discovered that TPP-SS-ATS-LS inhibited tumor cells proliferation through mitophagy by regulating PHB2 and PINK1 expression. These results provide new research strategies for the development of new artemisinin-based anti-tumor drugs.
Low-intensity pulsed ultrasound/nanomechanical force generators enhance osteogenesis of BMSCs through microfilaments and TRPM7
Authors: Yao Huan , Zhang Liang , Yan Shujin , He Yiman , Zhu Hui , Li Yasha , Wang Dong , Yang Ke
Published: August 2022

Background

Low-intensity pulsed ultrasound (LIPUS) has been reported to accelerate fracture healing, but the mechanism is unclear and its efficacy needs to be further optimized. Ultrasound in combination with functionalized microbubbles has been shown to induce local shear forces and controllable mechanical stress in cells, amplifying the mechanical effects of LIPUS. Nanoscale lipid bubbles (nanobubbles) have high stability and good biosafety. However, the effect of LIPUS combined with functionalized nanobubbles on osteogenesis has rarely been studied.

Results

In this study, we report cyclic arginine-glycine-aspartic acid-modified nanobubbles (cRGD-NBs), with a particle size of ~ 500 nm, able to actively target bone marrow mesenchymal stem cells (BMSCs) via integrin receptors. cRGD-NBs can act as nanomechanical force generators on the cell membrane, and further enhance the BMSCs osteogenesis and bone formation promoted by LIPUS. The polymerization of actin microfilaments and the mechanosensitive transient receptor potential melastatin 7 (TRPM7) ion channel play important roles in BMSCs osteogenesis promoted by LIPUS/cRGD-NBs. Moreover, the mutual regulation of TRPM7 and actin microfilaments promote the effect of LIPUS/cRGD-NBs. The extracellular Ca2 + influx, controlled partly by TRPM7, could participated in the effect of LIPUS/cRGD-NBs on BMSCs.

Conclusions

The nanomechanical force generators cRGD-NBs could promote osteogenesis of BMSCs and bone formation induced by LIPUS, through regulation TRPM7, actin cytoskeleton, and intracellular calcium oscillations. This study provides new directions for optimizing the efficacy of LIPUS for fracture healing, and a theoretical basis for the further application and development of LIPUS in clinical practice.
MTUS1 is a promising diagnostic and prognostic biomarker for colorectal cancer
Authors: Cheng Lin-Yao , Huang Mao-sen , Zhong Hua-Ge , Ru Hai-Ming , Mo Si-Si , Wei Chun-Yin , Su Zi-Jie , Mo Xian-Wei , Yan Lin-Hai , Tang Wei-Zhong
Published: August 2022

Background

The morbidity and mortality of colorectal cancer (CRC) remain high, posing a serious threat to human life and health. The early diagnosis and prognostic evaluation of CRC are two major challenges in clinical practice. MTUS1 is considered a tumour suppressor and can play an important role in inhibiting cell proliferation, migration, and tumour growth. Moreover, the expression of MTUS1 is decreased in different human cancers, including CRC. However, the biological functions and molecular mechanisms of MTUS1 in CRC remain unclear.

Methods

In the present study, data from The Cancer Genome Atlas (TCGA) database were analysed using R statistical software (version 3.6.3.) to evaluate the expression of MTUS1 in tumour tissues and adjacent normal tissues using public databases such as the TIMER and Oncomine databases. Then, 38 clinical samples were collected, and qPCR was performed to verify MTUS1 expression. We also investigated the relationship between MTUS1 expression and clinicopathological characteristics and elucidated the diagnostic and prognostic value of MTUS1 in CRC. In addition, the correlation between MTUS1 expression and immune infiltration levels was identified using the TIMER and GEPIA databases. Furthermore, we constructed and analysed a PPI network and coexpression modules of MTUS1 to explore its molecular functions and mechanisms.

Results

CRC tissues exhibited lower levels of MTUS1 than normal tissues. The logistic regression analysis indicated that the expression of MTUS1 was associated with N stage, TNM stage, and neoplasm type. Moreover, CRC patients with low MTUS1 expression had poor overall survival (OS). Multivariate analysis revealed that the downregulation of MTUS1 was an independent prognostic factor and was correlated with poor OS in CRC patients. MTUS1 expression had good diagnostic value based on ROC analysis. Furthermore, we identified a group of potential MTUS1-interacting proteins and coexpressed genes. GO and KEGG enrichment analyses showed that MTUS1 was involved in multiple cancer-related signalling pathways. Moreover, the expression of MTUS1 was significantly related to the infiltration levels of multiple cells. Finally, MTUS1 expression was strongly correlated with various immune marker sets.

Conclusions

Our results indicated that MTUS1 is a promising biomarker for predicting the diagnosis and prognosis of CRC patients. MTUS1 can also become a new molecular target for tumour immunotherapy.
Tight gene co-expression in BCB positive cattle oocytes and their surrounding cumulus cells
Authors: Walker Bailey N. , Nix Jada , Wilson Chace , Marrella Mackenzie A. , Speckhart Savannah L. , Wooldridge Lydia , Yen Con-Ning , Bodmer Jocelyn S. , Kirkpatrick Laila T. , Moorey Sarah E. , Gerrard David E. , Ealy Alan D. , Biase Fernando H.
Published: August 2022

Background

Cytoplasmic and nuclear maturation of oocytes, as well as interaction with the surrounding cumulus cells, are important features relevant to the acquisition of developmental competence.

Methods

Here, we utilized Brilliant cresyl blue (BCB) to distinguish cattle oocytes with low activity of the enzyme Glucose-6-Phosphate Dehydrogenase, and thus separated fully grown (BCB positive) oocytes from those in the growing phase (BCB negative). We then analyzed the developmental potential of these oocytes, mitochondrial DNA (mtDNA) copy number in single oocytes, and investigated the transcriptome of single oocytes and their surrounding cumulus cells of BCB positive versus BCB negative oocytes.

Results

The BCB positive oocytes were twice as likely to produce a blastocyst in vitro compared to BCB- oocytes (P < 0.01). We determined that BCB negative oocytes have 1.3-fold more mtDNA copies than BCB positive oocytes (P = 0.004). There was no differential transcript abundance of genes expressed in oocytes, however, 172 genes were identified in cumulus cells with differential transcript abundance (FDR < 0.05) based on the BCB staining of their oocyte. Co-expression analysis between oocytes and their surrounding cumulus cells revealed a subset of genes whose co-expression in BCB positive oocytes (n = 75) and their surrounding cumulus cells (n = 108) compose a unique profile of the cumulus-oocyte complex.

Conclusions

If oocytes transition from BCB negative to BCB positive, there is a greater likelihood of producing a blastocyst, and a reduction of mtDNA copies, but there is no systematic variation of transcript abundance. Cumulus cells present changes in transcript abundance, which reflects in a dynamic co-expression between the oocyte and cumulus cells.
A qualitative study on patient-centered care and perceptions of nurses regarding primary healthcare facilities in Nigeria
Authors: Lateef Monsurat Adepeju , Mhlongo Euphemia Mbali
Published: August 2022

Background

Patient-centered care (PCC) approach has continued to gain recognition globally as the key to providing quality healthcare. However, this concept is not fully integrated into the management of primary health care (PHC) in existing nursing practice due to numerous challenges. Among these challenges is the perception of nursing on PCC in the Primary Health Care system. This study seeks to present the results of qualitative research performed at various selected PHC centres on nurses’ perceptions in PCC practice. This study aim was to explore the perception of nurses on PCC.

Methods

A qualitative action research approach was adopted. The study involved 30 local government PHC centres located in Osun State Southwest of the federal republic of Nigeria. Data was collected through a semi-structured interview guide questions. Thereafter, data analysis was performed using thematic analysis and NVivo 12 software to generate themes, subthemes, and codes.

Results

PCC perceptions of nurses that was revealed in our findings were categorised into positive and negative themes. The negative themes include: poor approach by the nurses and lack of enforcement agency. The positive themes that emerged include: outcome driven healthcare, valued care provider, communication to sharpen care and driven healthcare service.

Conclusion

There is need for continuous training, and upgrading of nurses in line with global recommended standards of providing quality healthcare service delivery to the people. Therefore, the federal and state governments and local government council through the Nursing and Midwifery Council body should regulate, supervise, monitor and enforce the use and implementation of PCC in the PHC healthcare system.
α2-fraction and haptoglobin as biomarkers for disease activity in oligo- and polyarticular juvenile idiopathic arthritis
Authors: Zeller Ludwig , Tyrrell Pascal N. , Wang Stella , Fischer Nadine , Haas Johannes-Peter , Hügle Boris
Published: August 2022

Objectives

Unlike in adult rheumatology, for most forms of juvenile idiopathic arthritis (JIA) no reliable biomarkers currently exist to assess joint and disease activity. However, electrophoresis is frequently found changed in active juvenile arthritis. The objective of this study was to evaluate the α2-fraction of serum electrophoresis and its main components as biomarkers for JIA, categories extended/persistent oligoarthritis and seronegative polyarthritis, in comparison with the conventionally used erythrocyte sedimentation rate and C-reactive protein.

Methods

Serum samples and clinical data from 181 patients with JIA were collected. Serum electrophoresis and α2-fraction and its components were determined using standard methods. Relationship between calculated α2-fraction of serum electrophoresis (CA2F) and its components, acute-phase parameters and cJADAS27 was assessed using Pearson’s correlation coefficient and linear regression modelling, adjusting for confounding effects. Results were confirmed in a second cohort with 223 serum samples from 37 patients, using a mixed model to account for repeated measures.

Results

Compared to ESR and CRP, CA2F showed higher correlation to cJADAS27, in particular for persistent oligoarthritis. Of the three components of the α2-fraction, haptoglobin showed the highest correlation to cJADAS27. Regression analysis demonstrated higher ability to predict cJADAS27 for CA2F, and especially for haptoglobin as a component thereof, than for CRP and ESR.

Conclusion

Compared to conventional methods, α2-fraction of serum electrophoresis and specifically, haptoglobin show higher correlations with disease activity in common subtypes of JIA, representing excellent candidates as biomarkers for disease activity. Further studies are necessary to determine diagnostic value and correlations in other subtypes.
Humoral and cellular immune response to mRNA SARS-CoV-2 BNT162b2 vaccine in adolescents with rheumatic diseases
Authors: Udaondo Clara , Cámara Carmen , Miguel Berenguel Laura , Alcobendas Rueda Rosa , Muñoz Gómez Celia , Millán Longo Claudia , Díaz – Delgado Blanca , Falces-Romero Iker , Díaz Almirón Mariana , Ochando Jordi , Méndez – Echevarría Ana , Remesal Camba Agustín , Calvo Cristina
Published: August 2022

Background

Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question.

Objective

To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group.

Methods

Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins.

Results

There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination.

Conclusions

We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.