bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of different social groups’ level of knowledge about malaria in a multicultural Amazonian cross-border context
Authors: Gaillet Mélanie , Musset Lise , Cropet Claire , Djossou Félix , Mallard Adeline , Odonne Guillaume , Davy Damien , Douine Maylis , Epelboin Loic , Lazrek Yassamine , Mathieu Luana , Nacher Mathieu , Mosnier Emilie
Published: August 2023

Background

A steady decline in the number of cases of malaria was observed in the 2000s in French Guiana. This enabled regional health policies to shift their public health goal from control to elimination. To include inhabitants in this strategy, the main objective of this study was to describe knowledge about malaria, and related attitudes and practices in persons living in the French Guiana border.

Methods

We conducted a survey in people over 15 years old living in the twelve neighbourhoods of Saint-Georges de l’Oyapock with the highest malaria incidence. It comprised a 147-item questionnaire which collected data on socio-demographic characteristics and included a Knowledge Attitude and Practices survey on malaria. Knowledge-related data were studied using exploratory statistical methods to derive summary variables. A binary variable assessing level of knowledge was proposed and then assessed using exploratory approaches.

Results

The mean age of the 844 participants was 37.2 years [15.8], the male/female sex ratio was 0.8. In terms of nationality, 485 (57.5%) participants were Brazilian and 352 (41.7%) French. One third (305, 36.1%) spoke Brazilian Portuguese as their native language, 295 (34.9%) the Amerindian language Palikur, 36 (4.3%) French. The symptoms of malaria and prevention means were poorly known by 213 (25.2%) and 378 (44.8%) respondents, respectively. A quarter (206, 24.4%) did not know that malaria can be fatal. Overall, 251 people (29.7%) had an overall poor level of knowledge about malaria. Being under 25 years old, living in a native Amerindian neighbourhood, having an Amerindian mother tongue language, having risk behaviours related to gold mining were significantly associated with a poor level of knowledge.

Conclusions

This study is the first to describe the poor level of knowledge about malaria in populations living in the malaria endemic border area along the Oyapock river in French Guiana. Results will allow to reinforce, to diversify and to culturally adapt prevention messages and health promotion to increase their effectiveness with a view to quickly reaching the goal of malaria elimination through empowerment.
Obstructive sleep apnea: a follow-up program in its relation to temporomandibular joint disorder, sleep bruxism and orofacial pain
Authors: Ning Ruoyu , Chen Junjie , Lu Yanqin , Guo Jing
Published: August 2023

Objective

To evaluate the correlation between obstructive sleep apnea (OSA) and temporomandibular joint (TMJ) morphology, tooth wear condition, orofacial pain through a follow-up program.

Materials and methods

Seventy one OSA patients were divided into three groups according to their (apnea hypopnea index) AHI: mild group (n = 23), moderate group (n = 24), and severe group (n = 24). All patients had OSA therapies around six months after confirm the diagnosis of OSA. The tooth wear score and orofacial pain condition of all patients were recorded via clinical examination. Cone beam computed tomography (CBCT) images were also taken when confirm the diagnosis of OSA (T0), 6 months after the diagnosis (T1), and 6 months after the OSA treatment (T2). Parameters indicating the condylar morphology and joint space were evaluated. The differences of clinical symptoms and TMJ conditions amongT0, T1andT2time point were detected in the three groups respectively. The changes inT1-T0andT2-T1of all descriptions among three groups were also compared.The correlations between AHI and clinical symptoms were detected with Spearman correlation analysis.

Results

In mild group, there was no difference in all clinical symptoms and TMJ morphology among the three time points. Both in moderate and severe group, the condylar volume, superficial area, wear score, visual analogue scales (VAS), and R value (indicating condyle position) displayed significant differences among the three time points (P < 0.05). FromT0toT1, mild group displayed fewer decreases in the condylar volume and superficial area and fewer increases in wear score than that in moderate and severe group (P < 0.05). FromT1toT2,there was a greatest reduction in severe group for R value, and significant difference in the description of VAS and R value were found among the three groups. AHI was negatively correlated condylar volume and condylar superficial area, and was positively correlated with tooth wear score and VAS (P < 0.05).

Conclusion

Moderate to severe OSA will aggravate orofacial pain and tooth wear, affect TMJ volume and superficial area, even change the location of condyles. Appropriate OSA therapies may be effective ways to alleviate these adverse effects in long-term.
The effect of nanobased irrigants on the root canal dentin microhardness: an ex-vivo study
Authors: Sahebi Safoora , Mofidi Hossein , Abbaszadegan Abbas , Gholami Ahmad , Eskandari Fateme
Published: August 2023

Background

Given the favorable antimicrobial properties of zinc oxide (ZnONPs), standard silver (AgNPs), and imidazolium-based silver (Im-AgNPs) nanoparticles, this study aimed to evaluate their influence on the microhardness of root canal dentin.

Methods

In this experimental study, 40 mandibular premolars were decoronated at the cementoenamel junction and longitudinally sectioned into halves to create 80 specimens. They were randomly allocated to 5 groups (n = 16) and irrigated with ZnONPs, AgNPs, Im-AgNPs, NaOCl, or normal saline (as the negative control) for 15 min. The Vickers Hardness Number (VHN) was measured on each root canal third before and after being soaked in irrigants. Statistical analysis was performed using paired t-test, one-way ANOVA, and post hoc Tukey’s test (α = 0.05).

Results

Im-AgNPs and ZnONPs irrigants improved the microhardness of root dentin, whereas, AgNPs and NaOCl decreased it. ZnONPs yielded the highest VHN at the coronal third (P˂0.001), while the Im-AgNPs provided the highest VHN at the middle and apical thirds (P˂0.001). The AgNPs group showed the lowest VHN at the apical third.

Conclusions

The irrigants containing Im-AgNPs and ZnONPs significantly enhanced the root dentin microhardness. However, the use of AgNPs resulted in decreased microhardness.
Effects of thickness and polishing treatment on the translucency and opalescence of six dental CAD-CAM monolithic restorative materials: an in vitro study
Authors: Wu Zhengda , Tian Jiehua , Wei Donghao , Zhang Yifan , Lin Ye , Di Ping
Published: August 2023

Background

Computer-aided design and computer-aided manufacturing (CAD-CAM) materials for prosthetic is gaining popularity in dentistry. However, limited information exists regarding the impact of thickness and roughening treatment on the optical properties of contemporary CAD-CAM restorative materials. This study aimed to quantitatively evaluate the translucency and opalescence of six dental CAD-CAM materials in response to different thicknesses and roughening treatments.

Methods

Six dental CAD-CAM materials, lithium disilicate glass–ceramic (IPS e.max CAD, LS), polymer-infiltrated ceramic (VITA Enamic, VE), resin-nano ceramic glass–ceramic (LAVA Ultimate, LU), polymethyl methacrylate (Telio CAD, TE), and two zirconia reinforced lithium silicate (VITA Suprinity, VS, and Celtra Duo, CD), in shade A2 were prepared as 12 × 12mm2 specimens of four thicknesses (0.5mm, 1.0mm, 1.5mm, and 2.0mm) (N = 240, n = 10). After three different treatments (polished, roughened by SiC P800-grit, and SiC P300-grit), the translucency parameter (TP00) and opalescence parameter (OP) were measured with a spectrophotometer (VITA Easyshade V). The surface roughness was analyzed with a shape measurement laser microscope. The data were analyzed using a MANOVA, post hoc Tukey–Kramer test, the t test, and regression analysis (α = .05).

Results

The TP00 and OP were significantly influenced by material type, thickness and roughening treatment (P < .05). TP00 showed a continues decline with increasing thicknesses, while the variations of OP were material-dependent. TP00 ranged from 37.80 (LS in 0.5mm) to 5.66 (VS in 2.0mm), and OP ranged from 5.66 (LU in 0.5mm) to 9.55 (VS in 0.5mm). The variations in TP00 of all materials between adjacent thicknesses ranged from 2.10 to 15.29, exceeding the acceptable translucency threshold except for LU. Quadratic and logarithmic regression curves exhibited the best fit for TP00 among the materials. Compared to polished specimens, rougher specimens exhibited lower TP00 and higher OP in all materials except for LS (P < 0.05). Roughening with P300-grit decreased TP00 and OP by an average of 2.59 and 0.43 for 0.5mm specimens, and 1.26 and 0.25 for 2.0mm specimens, respectively.

Conclusions

Variations in translucency caused by thickness and roughening treatment were perceptible and may be clinically unacceptable. Careful consideration should be given to the selection of CAD-CAM materials based on their distinct optical properties.
Drug landscape in patients receiving general outpatient palliative care in Germany: results from a retrospective analysis of 10,464 patients
Authors: Loosen Sven H. , Schwartz Jacqueline , Grewe Steven , Krieg Sarah , Krieg Andreas , Luedde Tom , Batzler Yann-Nicolas , Kostev Karel , Neukirchen Martin , Roderburg Christoph
Published: August 2023

Background

According to § 27 and § 87 1b of the German Social Code, Book V, general outpatient palliative care (GOPC) aims to promote, maintain, and improve the quality of life and self-determination of seriously ill people. It should enable them to live in dignity until death in their preferred environment. Instead of a curative approach GOPC treatment focuses on the multiprofessional objective of alleviating symptoms and suffering on a case-by-case basis using medication or other measures, as well as the management of an individual treatment plan. The aim of this study was therefore to investigate to what extent medication differs from 12 months prior GOPC treatment within 12 months following GOPC treatment.

Methods

A retrospective database cross sectional study based on the IQVIA Disease Analyzer (DA) was performed, including adult patients with cancer diagnosis and at least one documentation of palliative support between January 1st, 2018 and December 31st, 2021, in 805 general practices (GP).

Results

The results of this study show, that in the context of general general outpatient palliative care, there is a significant increase in the prescription of opioids (18.3% vs. 37.7%), sedatives (7.8% vs. 16.2%) and antiemetics (5.3% vs. 9.7%), as well as a significant reduction in other medications such as statins (21.4% vs. 11.5%), proton pump inhibitors (PPI) (41.2% vs. 35.3%), or antihypertensives (57.5% vs. 46.6%).

Conclusions

Our results support the role of GOPC as an important element in improving pharmacological symptom control and deprescription to improve quality of life of patients at the end of their life.
Network pharmacology prediction and experimental verification of Rhubarb-Peach Kernel promoting apoptosis in endometriosis
Authors: Liao Zi , Lei Ya , Peng Li , Fu Xianyun , Wang Wei , Yang Dan
Published: August 2023

Background

“Rhubarb-Peach Kernel” herb pair (RP) one of the most frequently used drug pairs, has been used in traditional medicine in China to treat inflammation and diseases associated with pain. Although it is widely used clinically and has a remarkable curative effect, the mechanism of RP treatment for endometriosis (EMs) remains unclear due to its complicated components. The aim of this study was to investigate the anti-endometriosis effect of RP, with emphasis on apoptosis via network pharmacology prediction, molecular docking and experimental verification.

Methods

The related ingredients and targets of RP in treating EMs were screened out using Traditional Chinese Medicine Systems Pharmacology (TCMSP), Tool for Molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM), and GeneCards database. The data of the protein–protein interaction (PPI) network was obtained by the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) Database. The Metascape database was adopt for Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. After that, the molecular docking of the main active ingredients and apoptosis targets was performed. Finally, the pro-apoptotic effect of RP was verified in hEM15a cells.

Results

A total of 32 RP compounds were collected. Forty-two matching targets were picked out as the correlative targets of RP in treating EMs. Among these, 18 hub targets including P53, CASP3 were recognized by the PPI network. KEGG enrichment analysis discovered that the regulation of apoptosis was one of the potential mechanisms of RP against EMs. Anthraquinone compounds, flavonoids, and triterpenes in RP were identified as crucial active ingredients, involved in the pro-apoptotic effect, which were confirmed subsequently by molecular docking. Additionally, it was verified that RP treatment promoted apoptosis and inhibited the proliferation of EMs cells (assessed by MTT and Flow cytometry). Moreover, the induction of apoptosis in treated EMs cells may be due to the regulation of apoptosis-related protein expression, including P53, BAX, and CASP3.

Conclusions

The results of our study demonstrated that RP may exert its therapeutic effects on EMs through the potential mechanism of promoting apoptosis. Anthraquinones, flavonoids and triterpenoids are the possible pro-apoptotic components in RP.
Health care and harm reduction provider perspectives on treating older adults who use non-medical opioids: a qualitative study set in Chicago
Authors: Mason Maryann , Post Lori Ann , Aggarwal Rahul
Published: August 2023

Background

Opioid overdose death rates are increasing for adults aged 55 and older, with especially high rates in large urban areas. In parallel, admissions to treatment programs for older adults using illicit substances are increasing as well. Despite these trends, there is a lack of information about older adults who use non-medical opioids (NMO) and even less knowledge about their health and service encounters. Conducted in Chicago, Illinois, this qualitative study explores the perspectives of health care and harm reduction service providers who work with older adults using non-medical opioids.

Methods

The study used snowball sampling to locate participants with expertise in working with older adults who use non-medical opioids. In total, we conducted 26 semi-structured interviews from September 2021-August 2022. We explored questions regarding participants’ perceptions of older adult opioid use patterns, comorbidities, and involvement in harm reduction outreach and opioid use disorder treatment.

Results

Many of the providers we interviewed consider older adults who use NMO as a distinct population that employ unique use behaviors with the intent to protect them from opioid overdose. However, these same unique behaviors may potentiate their risk for overdose in today’s climate. Providers report initial encounters that are not care seeking for opioid use and primarily oriented around health conditions. Older adults who use non-medical opioids are seen as complex patients due to the need to diagnostically untangle symptoms of substance use from co-morbidities and conditions associated with aging.

Treatment for this population is also viewed as complicated due to the interactions between aging, comorbidities, and substance use. Providers also noted that older adults who use NMO have use behaviors that make them less visible to outreach and treatment service providers, potentially putting them at increased risk for overdose and health conditions associated with opioid use.

Conclusions

Findings from this study are intended to inform future research on care provision for older adults who use non-medical opioids and may be especially applicable to large urban reas with histories of opioid use dating back to earlier drug epidemics of the 1970s, 1980s, and 1990s.
Examining the absorption of post-internship medical officers into the public sector at county-level in devolved Kenya: a qualitative case study
Authors: Zhao Yingxi , Mbuthia Daniel , Munywoki Joshua , Gathara David , Nicodemo Catia , Nzinga Jacinta , English Mike
Published: August 2023

Background

After Kenya’s decentralization and constitutional changes in 2013, 47 devolved county governments are responsible for workforce planning and recruitment including for doctors/medical officers (MO). Data from the Ministry of Health suggested that less than half of these MOs are being absorbed by the public sector between 2015 and 2018. We aimed to examine how post-internship MOs are absorbed into the public sector at the county-level, as part of a broader project focusing on Kenya’s human resources for health.

Methods

We employed a qualitative case study design informed by a simplified health labour market framework. Data included interviews with 30 MOs who finished their internship after 2018, 10 consultants who have supervised MOs, and 51 county/sub-county-level managers who are involved in MOs’ planning and recruitment. A thematic analysis approach was used to examine recruitment processes, outcomes as well as perceived demand and supply.

Results

We found that Kenya has a large mismatch between supply and demand for MOs. An increasing number of medical schools are offering training in medicine while the demand for MOs in the county-level public sector has not been increasing at the same pace due to fiscal resource constraints and preference for other workforce cadres. The local Department of Health put in requests and participate in interviews but do not lead the recruitment process and respondents suggested that it can be subject to political interference and corruption. The imbalance of supply and demand is leading to unemployment, underemployment and migration of post-internship MOs with further impacts on MOs’ wages and contract conditions, especially in the private sector.

Conclusion

The mismatched supply and demand of MO accompanied by problematic recruitment processes led to many MOs not being absorbed by the public sector and subsequent unemployment and underemployment. Although Kenya has ambitious workforce norms, it may need to take a more pragmatic approach and initiate constructive policy dialogue with stakeholders spanning the education, public and private health sectors to better align MO training, recruitment and management.
Rhinovirus infection induces secretion of endothelin-1 from airway epithelial cells in both in vitro and in vivo models
Authors: Dy Alane Blythe C. , Girkin Jason , Marrocco Antonella , Collison Adam , Mwase Chimwemwe , O’Sullivan Michael J. , Phung Thien-Khoi N. , Mattes Joerg , Koziol-White Cynthia , Gern James E. , Bochkov Yury A. , Bartlett Nathan W. , Park Jin-Ah
Published: August 2023

Background

Rhinovirus (RV) infection of airway epithelial cells triggers asthma exacerbations, during which airway smooth muscle (ASM) excessively contracts. Due to ASM contraction, airway epithelial cells become mechanically compressed. We previously reported that compressed human bronchial epithelial (HBE) cells are a source of endothelin-1 (ET-1) that causes ASM contraction. Here, we hypothesized that epithelial sensing of RV by TLR3 and epithelial compression induce ET-1 secretion through a TGF-β receptor (TGFβR)-dependent mechanism.

Methods

To test this, we used primary HBE cells well-differentiated in air–liquid interface culture and two mouse models (ovalbumin and house dust mite) of allergic airway disease (AAD). HBE cells were infected with RV-A16, treated with a TLR3 agonist (poly(I:C)), or exposed to compression. Thereafter, EDN1 (ET-1 protein-encoding gene) mRNA expression and secreted ET-1 protein were measured. We examined the role of TGFβR in ET-1 secretion using either a pharmacologic inhibitor of TGFβR or recombinant TGF-β1 protein. In the AAD mouse models, allergen-sensitized and allergen-challenged mice were subsequently infected with RV. We then measured ET-1 in bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR) following methacholine challenge.

Results

Our data reveal that RV infection induced EDN1 expression and ET-1 secretion in HBE cells, potentially mediated by TLR3. TGFβR activation was partially required for ET-1 secretion, which was induced by RV, poly(I:C), or compression. TGFβR activation alone was sufficient to increase ET-1 secretion. In AAD mouse models, RV induced ET-1 secretion in BALF, which positively correlated with AHR.

Conclusions

Our data provide evidence that RV infection increased epithelial-cell ET-1 secretion through a TGFβR-dependent mechanism, which contributes to bronchoconstriction during RV-induced asthma exacerbations.
Expanding the genetic toolbox of Rhodotorula toruloides by identification and validation of six novel promoters induced or repressed under nitrogen starvation
Authors: Brink Daniel P. , Mierke Friederike , Norbeck Joakim , Siewers Verena , Andlid Thomas
Published: August 2023

Background

The non-conventional yeast Rhodotorula toruloides is an emerging host organism in biotechnology by merit of its natural capacity to accumulate high levels of carotenoids and intracellular storage lipids from a variety of carbon sources. While the number of genetic engineering strategies that employ R. toruloides is increasing, the lack of genetic tools available for modification of this yeast is still limiting strain development. For instance, several strong, constitutive R. toruloides promoters have been characterized, but to date, only five inducible promoters have been identified. Although nitrogen-limited cultivation conditions are commonly used to induce lipid accumulation in this yeast, no promoters regulated by nitrogen starvation have been described for R. toruloides.

Results

In this study, we used a combination of genomics and transcriptomics methods to identify novel R. toruloides promoter sequences that are either inducible or repressible by nitrogen starvation. RNA sequencing was used to assess gene expression in the recently isolated strain R. toruloides BOT-A2 during exponential growth and during nitrogen starvation, when cultivated with either glucose or xylose as the carbon source. The genome of BOT-A2 was sequenced using a combination of long- and short-read sequencing and annotated with support of the RNAseq data. Differential expression analysis was used to identify genes with a |log2 fold change|≥ 2 when comparing their expression during nitrogen depletion to that during exponential growth. The promoter regions from 16 of these genes were evaluated for their ability to drive the expression of a fluorescent reporter gene. Three promoters that were clearly upregulated under nitrogen starvation and three that were downregulated were selected and further characterized. One promoter, derived from gene RTBOTA2_003877, was found to function like an on–off switch, as it was only upregulated under full nitrogen depletion and downregulated in the presence of the nitrogen source.

Conclusions

Six new R. toruloides promoters that were either upregulated or downregulated under nitrogen-starvation were identified. These substantially contribute to the available promoters when engineering this organism and are foreseen to be particularly useful for future engineering strategies requiring specific regulation of target genes in accordance with nitrogen availability.
Next-generation nanomaterials: advancing ocular anti-inflammatory drug therapy
Authors: Wei Jing , Mu Jinyu , Tang Yong , Qin Dalian , Duan Junguo , Wu Anguo
Published: August 2023

Ophthalmic inflammatory diseases, including conjunctivitis, keratitis, uveitis, scleritis, and related conditions, pose considerable challenges to effective management and treatment. This review article investigates the potential of advanced nanomaterials in revolutionizing ocular anti-inflammatory drug interventions. By conducting an exhaustive analysis of recent advancements and assessing the potential benefits and limitations, this review aims to identify promising avenues for future research and clinical applications. The review commences with a detailed exploration of various nanomaterial categories, such as liposomes, dendrimers, nanoparticles (NPs), and hydrogels, emphasizing their unique properties and capabilities for accurate drug delivery. Subsequently, we explore the etiology and pathophysiology of ophthalmic inflammatory disorders, highlighting the urgent necessity for innovative therapeutic strategies and examining recent preclinical and clinical investigations employing nanomaterial-based drug delivery systems. We discuss the advantages of these cutting-edge systems, such as biocompatibility, bioavailability, controlled release, and targeted delivery, alongside potential challenges, which encompass immunogenicity, toxicity, and regulatory hurdles. Furthermore, we emphasize the significance of interdisciplinary collaborations among material scientists, pharmacologists, and clinicians in expediting the translation of these breakthroughs from laboratory environments to clinical practice. In summary, this review accentuates the remarkable potential of advanced nanomaterials in redefining ocular anti-inflammatory drug therapy. We fervently support continued research and development in this rapidly evolving field to overcome existing barriers and improve patient outcomes for ophthalmic inflammatory disorders.

Graphical Abstract
Targeting macrophage M1 polarization suppression through PCAF inhibition alleviates autoimmune arthritis via synergistic NF-κB and H3K9Ac blockade
Authors: Li Jinteng , Ye Feng , Xu Xiaojun , Xu Peitao , Wang Peng , Zheng Guan , Ye Guiwen , Yu Wenhui , Su Zepeng , Lin Jiajie , Che Yunshu , Liu Zhidong , Feng Pei , Cao Qian , Li Dateng , Xie Zhongyu , Wu Yanfeng , Shen Huiyong
Published: August 2023

Sustained inflammatory invasion leads to joint damage and progressive disability in several autoimmune rheumatic diseases. In recent decades, targeting M1 macrophage polarization has been suggested as a promising therapeutic strategy for autoimmune arthritis. P300/CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) that exhibits a strong positive relationship with the proinflammatory microenvironment. However, whether PCAF mediates M1 macrophage polarization remains poorly studied, and whether targeting PCAF can protect against autoimmune arthritis in vivo remains unclear. Commonly used drugs can cause serious side effects in patients because of their extensive and nonspecific distribution in the human body. One strategy for overcoming this challenge is to develop drug nanocarriers that target the drug to desirable regions and reduce the fraction of drug that reaches undesirable targets. In this study, we demonstrated that PCAF inhibition could effectively inhibit M1 polarization and alleviate arthritis in mice with collagen-induced arthritis (CIA) via synergistic NF-κB and H3K9Ac blockade. We further designed dextran sulfate (DS)-based nanoparticles (DSNPs) carrying garcinol (a PCAF inhibitor) to specifically target M1 macrophages in inflamed joints of the CIA mouse model via SR-A–SR-A ligand interactions. Compared to free garcinol, garcinol-loaded DSNPs selectively targeted M1 macrophages in inflamed joints and significantly improved therapeutic efficacy in vivo. In summary, our study indicates that targeted PCAF inhibition with nanoparticles might be a promising strategy for treating autoimmune arthritis via M1 macrophage polarization inhibition.
Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials
Authors: Shi Linlin , Li Danni , Tong Qianqian , Jia Guorong , Li Xiaohong , Zhang Lan , Han Qingqing , Li Rou , Zuo Changjing , Zhang Wei , Li Xiao
Published: August 2023

Background

The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin.

Results

SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism.

Conclusion

The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.

Graphical abstract
Ideal marker for targeted axillary dissection (IMTAD): a prospective multicentre trial
Authors: Žatecký Jan , Coufal Oldřich , Zapletal Ondřej , Kubala Otakar , Kepičová Markéta , Faridová Adéla , Rauš Karel , Gatěk Jiří , Kosáč Peter , Peteja Matúš
Published: August 2023

Background

Targeted axillary dissection (TAD) is an established method for axillary staging in patients with breast cancer after neoadjuvant chemotherapy (NAC). TAD consists of sentinel lymph node biopsy and initially pathological lymph node excision, which must be marked by a reliable marker before NAC.

Methods

The IMTAD study is a prospective multicentre trial comparing three localisation markers for lymph node localisation (clip + iodine seed, magnetic seed, carbon suspension) facilitating subsequent surgical excision in the form of TAD. The primary outcome was to prospectively compare the reliability, accuracy, and safety according to complication rate during marker implantation and detection and marker dislodgement.

Results

One hundred eighty-nine patients were included in the study—in 135 patients clip + iodine seed was used, in 30 patients magnetic seed and in 24 patients carbon suspension. The complication rate during the marker implantation and detection were not statistically significant between individual markers (p = 0.263; p = 0.117). Marker dislodgement was reported in 4 patients with clip + iodine seed localisation (3.0%), dislodgement did not occur in other localisation methods (p = 0.999). The false-negativity of sentinel lymph node (SLN) was observed in 8 patients, the false-negativity of targeted lymph nodes (TLN) wasn´t observed at all, the false-negativity rate (FNR) from the subcohort of ypN + patients for SLN is 9.6% and for TLN 0.0%.

Conclusion

The IMTAD study indicated, that clip + iodine seed, magnetic seed and carbon suspension are statistically comparable in terms of complications during marker implantation and detection and marker dislodgement proving their safety, accuracy, and reliability in TAD. The study confirmed, that the FNR of the TLN was lower than the FNR of the SLN proving that the TLN is a better marker for axillary lymph node status after NAC.

Trial registration

NCT04580251. Name of registry: Clinicaltrials.gov. Date of registration: 8.10.2020.
sEMG-controlled forearm bracelet and serious game-based rehabilitation for training manual dexterity in people with multiple sclerosis: a randomised controlled trial
Authors: Marcos-Antón Selena , Jardón-Huete Alberto , Oña-Simbaña Edwin Daniel , Blázquez-Fernández Aitor , Martínez-Rolando Lidia , Cano-de-la-Cuerda Roberto
Published: August 2023

Background

Muscle strength and dexterity impairments are common among patients with multiple sclerosis (MS) producing limitations in activities of daily living related to the upper limb (UL). This study aimed to evaluate the effectiveness of serious games specifically developed for the MYO Armband® capture sensor in improving forearm and wrist mobility, UL muscle strength, dexterity, fatigue, functionality, quality of life, satisfaction, adverse effects and compliance.

Methods

A double-blinded (allocation concealment was performed by a blinded investigator and by blinding for assessors) randomised controlled trial was conducted. The sample was randomised into two groups: an experimental group that received treatment based on UL serious games designed by the research team and controlled by the MYO Armband® gesture capture sensor, along with conventional rehabilitation and a control group that received the same conventional rehabilitation for the UL. Both groups received two 60-min sessions per week over an eight-week period. Wrist range of motion (goniometry), grip muscle strength (Jamar® dynamometer), coordination and gross UL dexterity (Box and Block Test), fatigue (Fatigue Severity Scale), functionality (ABILHAND), quality of life (Multiple Sclerosis Impact Scale-29), adverse effects (Simulator Sickness Questionnaire, SSQ), perceived workload (NASA-Task load index), satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8), Satisfaction with Technology Scale, System Usability Scale (SUS) and QUEST 2.0) and compliance (attendance) were assessed in both groups pre-treatment, post-treatment and during a follow-up period of 2 weeks without receiving any treatment.

Results

Significant differences were observed in the experimental group compared to the control group in the assessment of forearm supination (p = .004) and grip strength (p = .004). Adverse effects were minimal (SSQ: 7/100 points) and perceived workload was low (NASA-Task Load Index: 25/100 points) in the experimental group. The MYO Armband® technology proved to be useful for the participants (SUS: 80.66/100) and the satisfaction scales received high scores (QUEST 2.0: 59.4/70 points; Satisfaction with Technology: 84.36/100 points). There were significant differences between the groups in terms of attendance percentage (p = .029).

Conclusions

An experimental protocol using MYO Armband®-based serious games designed for UL rehabilitation showed improvements in active wrist range of motion and handgrip strength in patients with MS, with high satisfaction, minimal adverse effects and workload and excellent compliance.

Trial registration number: This randomised controlled trial has been registered at ClinicalTrials.gov Identifier: NCT04171908.
The value of deep neural networks in the pathological classification of thyroid tumors
Authors: Deng Chengwen , Li Dan , Feng Ming , Han Dongyan , Huang Qingqing
Published: August 2023

Background

To explore the distinguishing diagnostic value and clinical application potential of deep neural networks (DNN) for pathological images of thyroid tumors.

Methods

A total of 799 pathological thyroid images of 559 patients with thyroid tumors were retrospectively analyzed. The pathological types included papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), follicular thyroid carcinoma (FTC), adenomatous goiter, adenoma, and normal thyroid gland. The dataset was divided into a training set and a test set. Resnet50, Resnext50, EfficientNet, and Densenet121 were trained using the training set data and tested with the test set data to determine the diagnostic efficiency of different pathology types and to further analyze the causes of misdiagnosis.

Results

The recall, precision, negative predictive value (NPV), accuracy, specificity, and F1 scores of the four models ranged from 33.33% to 100.00%. The area under curve (AUC) ranged from 0.822 to 0.994, and the Kappa coefficient ranged from 0.7508 to 0.7713. However, the performance of diagnosing FTC, adenoma, and adenomatous goiter was slightly inferior to other types of pathological tissues.

Conclusion

The DNN model achieved satisfactory results in the task of classifying thyroid tumors by learning thyroid pathology images. These results indicate the potential of the DNN model for the efficient diagnosis of thyroid tumor histopathology.
Role of the DEAD-box RNA helicase DDX5 (p68) in cancer DNA repair, immune suppression, cancer metabolic control, virus infection promotion, and human microbiome (microbiota) negative influence
Authors: Li Fengzhi , Ling Xiang , Chakraborty Sayan , Fountzilas Christos , Wang Jianmin , Jamroze Anmbreen , Liu Xiaozhuo , Kalinski Pawel , Tang Dean G.
Published: August 2023

There is increasing evidence indicating the significant role of DDX5 (also called p68), acting as a master regulator and a potential biomarker and target, in tumorigenesis, proliferation, metastasis and treatment resistance for cancer therapy. However, DDX5 has also been reported to act as an oncosuppressor. These seemingly contradictory observations can be reconciled by DDX5’s role in DNA repair. This is because cancer cell apoptosis and malignant transformation can represent the two possible outcomes of a single process regulated by DDX5, reflecting different intensity of DNA damage. Thus, targeting DDX5 could potentially shift cancer cells from a growth-arrested state (necessary for DNA repair) to apoptosis and cell killing. In addition to the increasingly recognized role of DDX5 in global genome stability surveillance and DNA damage repair, DDX5 has been implicated in multiple oncogenic signaling pathways. DDX5 appears to utilize distinct signaling cascades via interactions with unique proteins in different types of tissues/cells to elicit opposing roles (e.g., smooth muscle cells versus cancer cells). Such unique features make DDX5 an intriguing therapeutic target for the treatment of human cancers, with limited low toxicity to normal tissues. In this review, we discuss the multifaceted functions of DDX5 in DNA repair in cancer, immune suppression, oncogenic metabolic rewiring, virus infection promotion, and negative impact on the human microbiome (microbiota). We also provide new data showing that FL118, a molecular glue DDX5 degrader, selectively works against current treatment-resistant prostate cancer organoids/cells. Altogether, current studies demonstrate that DDX5 may represent a unique oncotarget for effectively conquering cancer with minimal toxicity to normal tissues.
Becoming a podiatrist: an exploration of the practices and processes which underpin the acquisition of a professional identity
Authors: Tobbell Jane , Roberts Peter
Published: August 2023

Background

Undergraduate podiatry degrees are designed to enable students to become professional podiatrists. To be successful students must manage academic and practical activity to ultimately acquire a professional identity. Little is known about the practices and processes which underpin the acquisition of a professional podiatry identity. It is the aim of this paper to begin to address this absence of knowledge. Community of Practice theory, arguably the dominant contemporary learning theory, represents identity shift as an interaction of imagination, engagement and alignment which enables students to successfully participate in higher education, and ultimately, the professional context. This success is underpinned through assisting students to develop an enabling identity in their learning and doing.

Methods

Here we present findings that emerged from a yearlong ethnography in a successful higher education podiatry department. The project followed students and staff in the classroom and the clinic and explored their experiences through interviews.

Results

The findings suggest that the journey to professional identity is facilitated through meaningful learning relationships between staff and students and clarity around professional practices. Here we discuss how those relationships form and enable undergraduates to become podiatrists.

Conclusions

Our findings offer a model for the transition from student to professional and highlight the importance of relationship and experience in becoming a podiatrist. There is a paucity of research around not only podiatry but also other allied health professions around this topic and given the increasing emphasis around employability skills in HE, more research in a range of contexts is needed.
Clinical trial protocol for P-NeLoP: a randomized controlled trial comparing the feasibility and outcomes of robot-assisted partial nephrectomy with low insufflation pressure using AirSeal versus standard insufflation pressure (UroCCR no. 85 study)
Authors: Margue Gaelle , Bigot Pierre , Ingels Alexandre , Roupret Morgan , Waeckel Thibaut , Long Jean-Alexandre , Pignot Géraldine , Bensalah Karim , Lang Hervé , Olivier Jonathan , Bruyere Franck , Durand Matthieu , Beauval Jean-Baptiste , Mallet Richard , Parier Bastien , De La Taille Alexandre , Bernhard Jean-Christophe
Published: August 2023

Robot-assisted partial nephrectomy (RAPN) is the standard of care for small, localized kidney tumors. This surgery is conducted within a short hospital stay and can even be performed as outpatient surgery in selected patients. In order to allow early rehabilitation of patients, an optimal control of postoperative pain is necessary. High-pressure pneumoperitoneum during surgery seems to be the source of significant pain during the first hours postoperatively. Our study is a prospective, randomized, multicenter, controlled study which aims to compare post-operative pain at 24 h between patients undergoing RAPN at low insufflation pressure (7 mmHg) and those operated on at standard pressure (12 mmHg) using the AirSeal system.

This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT05404685).
Sustainable chromatographic quantitation of multi-antihypertensive medications: application on diverse combinations containing hydrochlorothiazide along with LC–MS/MS profiling of potential impurities: greenness and whiteness evaluation
Authors: Marzouk Hoda M. , El-Hanboushy Sara , Obaydo Reem H. , Fayez Yasmin M. , Abdelkawy Mohamed , Lotfy Hayam M.
Published: August 2023

Cardiovascular disorders are among the leading causes of death worldwide, especially hypertension, a silent killer syndrome requiring multiple drug therapy for appropriate management. Hydrochlorothiazide is an extensively utilized thiazide diuretic that combines with several antihypertensive drugs for effective treatment of hypertension. In this study, sustainable, innovative and accurate high performance liquid chromatographic methods with diode array and tandem mass detectors (HPLC–DAD and LC–MS/MS) were developed, optimized and validated for the concurrent determination of Hydrochlorothiazide (HCT) along with five antihypertensive drugs, namely; Valsartan (VAL), Amlodipine besylate (AML), Atenolol (ATN), Amiloride hydrochloride (AMI), and Candesartan cilextil (CAN) in their diverse pharmaceutical dosage forms and in the presence of Chlorothiazide (CT) and Salamide (DSA) as HCT officially identified impurities. The HPLC–DAD separation was achieved utilizing Inertsil ODS-3 C18 column (250 × 4.6 mm, 5 μm) attached with photodiode array detection at 225.0 nm. Gradient elution was performed utilizing a mixture of solvent A (20.0 mM potassium dihydrogen phosphate, pH 3.0 ± 0.2, adjusted with phosphoric acid) and solvent B (acetonitrile) at ambient temperature. Linearity ranges were 0.1–100.0 µg/mL for HCT, VAL, AML and CAN, 0.05 –100.0 µg/mL for both ATN and AMI and 0.05–8.0 µg/mL for both CT and DSA. Additionally, this work describes the use of liquid chromatography–electrospray–tandem mass spectrometry for the accurate detection and quantification of the impurities; CT and DSA in the negative mode utilizing triple quadrupole mass spectrometry. The linearity ranges for those impurities were 1.0–200.0 ng/mL and 5.0–200.0 ng/mL for CT and DSA, respectively. Developed methods’ validation was achieved in accordance with International Conference on Harmonization (ICH) guidelines. Upon applying liquid chromatographic techniques for the drug analysis, a green and sustainable assessment have to be handled due to the consumption of energy and many solvents. Through the use of the HEXAGON, Analytical Greenness (AGREE) and White Analytical Chemistry (WAC) tools, greenness and sustainability have been statistically assessed. The optimized HPLC–DAD and LC–MS/MS methods were fast, accurate, precise, and sensitive, and consequently could be applied for conventional analysis and quality control of the proposed drugs in their miscellaneous dosage forms for the purpose of reducing laboratory wastes, time of the analysis time, effort, and cost.

Graphical Abstract
Whole genome sequencing and the lignocellulose degradation potential of Bacillus subtilis RLI2019 isolated from the intestine of termites
Authors: Liu Gongwei , Zhang Ke , Gong Hanxuan , Yang Kaiyao , Wang Xiaoyu , Zhou Guangchen , Cui Wenyuan , Chen Yulin , Yang Yuxin
Published: August 2023

Background

Lignocellulosic biomass is the most abundant and renewable terrestrial raw material for conversion into bioproducts and biofuels. However, the low utilization efficiency of lignocellulose causes environmental pollution and resource waste, which limits the large-scale application of bioconversion. The degradation of lignocellulose by microorganisms is an efficient and cost-effective way to overcome the challenge of utilizing plant biomass resources. This work aimed to screen valuable cellulolytic bacteria, explore its molecular mechanism from genomic insights, and investigate the ability of the strain to biodegrade wheat straw.

Results

Bacillus subtilis (B. subtilis) RLI2019 was isolated from the intestine of Reticulitermes labralis. The strain showed comprehensive enzyme activities related to lignocellulose degradation, which were estimated as 4.06, 1.97, 4.12, 0.74, and 17.61 U/mL for endoglucanase, β-glucosidase, PASC enzyme, filter paper enzyme, and xylanase, respectively. Whole genome sequencing was performed to better understand the genetic mechanism of cellulose degradation. The genome size of B. subtilis RLI2019 was 4,195,306 bp with an average GC content of 43.54%, and the sequence characteristics illustrated an extremely high probability (99.41%) as a probiotic. The genome contained 4,381 protein coding genes with an average GC content of 44.20%, of which 145 genes were classified into six carbohydrate-active enzyme (CAZyme) families and 57 subfamilies. Eight cellulose metabolism enzyme-related genes and nine hemicellulose metabolism enzyme-related genes were annotated by the CAZyme database. The starch and sucrose metabolic pathway (ko00500) was the most enriched with 46 genes in carbohydrate metabolism. B. subtilis RLI2019 was co-cultured with wheat straw for 7 days of fermentation, the contents of neutral detergent fiber, acid detergent fiber, hemicellulose, and lignin were significantly reduced by 5.8%, 10.3%, 1.0%, and 4.7%, respectively. Moreover, the wheat straw substrate exhibited 664.9 μg/mL of reducing sugars, 1.22 U/mL and 6.68 U/mL of endoglucanase and xylanase activities, respectively. Furthermore, the fiber structures were effectively disrupted, and the cellulose crystallinity was significantly reduced from 40.2% to 36.9%.

Conclusions

The complex diversity of CAZyme composition mainly contributed to the strong cellulolytic attribute of B. subtilis RLI2019. These findings suggest that B. subtilis RLI2019 has favorable potential for biodegradation applications, thus it can be regarded as a promising candidate bacterium for lignocellulosic biomass degradation.