bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of recombinant human epidermal growth factor on radiation dermatitis in rectal and anal cancer patients: a self-controlled study
Authors: Liu Shuai , Wang Yun-Long , Shi Shu-Ting , Zeng Guang-Dong , Song Yi-Wen , Zhang Xiao-Dong , Zheng Jian , Fan Xin-Juan , Liu Yan-Ping
Published: November 2022

Background

Our previous study reported that recombinant human epidermal growth factor (rhEGF)-triggered EGFR internalization promoted radioresistance. Here, we aimed to evaluate the effect of rhEGF on the skin protection of rectal and anal cancer patients receiving radiotherapy.

Methods

One hundred and ninety-three rectal and anal cancer patients who received radiotherapy were prospectively enrolled from January 2019 to December 2020. To perform self-controlled study, the left and right pelvic skin area (separated by midline) were randomly assigned to the rhEGF and control side. The association between radiation dermatitis and factors including rhEGF, the dose of radiotherapy and tumor distance from anal edge were analyzed.

Results

Among 193 enrolled patients, 41 patients (21.2%) did not develop radiation dermatitis, and 152 patients (78.8%) suffered radiation dermatitis on at least one side of pelvic skin at the end of radiotherapy. For the effect on radiation dermatitis grade, rhEGF had improved effect on 6 (4.0%) patients, detrimental effect on 2 (1.3%) patients, and no effect on 144 (94.7%) patients. Whereas for the effect on radiation dermatitis area, rhEGF showed improved effect on the radiation dermatitis area of 46 (30.2%) patients, detrimental effect on 15 (9.9%) patients, and no effect on 91 (59.9%) patients. The radiation dermatitis area of rhEGF side was significantly smaller than that of control side (P = 0.0007).

Conclusions

rhEGF is a skin protective reagent for rectal and anal cancer patients receiving radiotherapy.

Trial registration

Chinese Clinical Trial Registry identifier: ChiCTR1900020842; Date of registration: 20/01/2019.
Prevalence of thyroid nodules and characteristics of thyroid ultrasound in children with goiter: a single center experience
Authors: Al Juraibah Fahad , Al Noaim Khalid , AlDbas Abdulaziz , AlMuallimi Ahmed , AlOtaibi Omar , AlShareef Mozon , AlSuhibani Alanoud , AlZaharani Ahmed , AlDubayee Mohammed , Babiker Amir
Published: November 2022

Background

Goiter is a common presenting sign of various thyroid diseases in children. Thyroid nodules are clinically and/or radiologically significant findings due to their high malignancy rate. The ultrasound (US) characteristics of pediatric patients with goiter are rarely reported in literature; thus, the purpose of this study is to assess the characteristics of thyroid US and the prevalence of thyroid nodules in pediatric patients with goiter.

Methods

A retrospective review of children and adolescents under the age of 18 (2015–2020) referred for neck ultrasound due to goiter in clinical examination.

Results

A total of 262 patients were included with a mean age of 13.77 ± 3.7 years. Thyroid antibodies were positive in 119/262 (45.4%) patients. Thyroid US reported to be abnormal in 210/262 (80%) patients. Thyroid nodule were found in 33.6% (n = 88/262) of patients with goiter and in 41.9% (n = 88/210) of patients with abnormal thyroid US result. Patients with positive antibodies had more of heterogeneity and hypervascularity of the gland on thyroid US (P < 0.001). On the other hand, thyroid nodules were more likely to be presented in patients with negative thyroid antibodies (P = 0.025). The heterogeneity within the thyroid positive group was significantly correlated with increasing TPOAb (P < 0.001) and TSH levels (P < 0.028). Heterogeneity on US had a positive predictive value (P = 0.041), while hypervascularity had low prediction for thyroid nodules (P = 0.022). Age, gender, family history of thyroid diseases, antibodies status and echogenicity in US did not show any significant associations with thyroid nodules. Papillary thyroid carcinoma was diagnosed in six patients and one of these patients was positive for thyroid antibodies.

Conclusion

Thyroid nodules are quite common in our population. Thyroid nodules were significantly associated with heterogeneity in US. Although, no clinical or biochemical factors could predict the presence of thyroid nodules on thyroid US in our cohort, the absence of thyroid antibodies should lower the threshold for performing thyroid US.
Lost in explanation: internal conflicts in the discourse of ADHD psychoeducation
Authors: van Langen Myrte J. M. , Szőke Rebeka , Rijkelijkhuizen Dominique N. J. , Durston Sarah , van Hulst Branko M.
Published: November 2022

Background

Psychiatric classifications are understood in many different ways. For children with ADHD and their parents, psychoeducation is an important source of information for shaping their understanding. Moreover, psychoeducation is often taken by children and parents to represent how their story is understood by the therapist. As a result, the way psychoeducation is formulated may affect the therapeutic alliance, one of the most robust mediators of treatment outcome. In addition, psychoeducation may indirectly influence the way we understand psychological differences as a society.

Methods

To better understand how the classification ADHD is given meaning through psychoeducation, we analyzed 41 written psychoeducational materials from four different countries; the USA, UK, Netherlands and Hungary.

Results

We identified five patterns of how the materials construct the discourse on ADHD. Notably, tension between biomedical and psychosocial perspectives resulted in conflictwithina single thematic stance on ADHD as opposed to a conflictbetweenparties with a different vision on ADHD. There were only few differences between countries in the way they constructed the discourse in the materials.

Conclusions

These conflicts cause confusion, misrepresentation and decontextualization of ADHD. Ultimately, for those diagnosed with ADHD and their parents, conflicting information in psychoeducation materials may hamper their ability to understand themselves in the context of their difficulties.
Hepatitis B, C and human immunodeficiency virus knowledge among the general greek population: results from the Hprolipsis nationwide survey
Authors: Kaskafetou Sylvia , Karakosta Argiro , Sypsa Vana , Kalpourtzi Natasa , Gavana Magda , Vantarakis Apostolos , Rachiotis George , Chlouverakis Grigoris , Trypsianis Grigoris , Voulgari Paraskevi V. , Alamanos Yannis , Papatheodoridis George , Touloumi Giota ,   on behalf of the Hprolipsis study group, Terzidis Agis , Antypas Tzanetos , Psara Christina , Rozenberg Theofilos , Kantzanou Maria
Published: November 2022

Background

Although several studies on hepatitis B (HBV), C (HCV) and human immunodeficiency virus (HIV) infection have been conducted in Greece, little is known on the knowledge level of the Greek population towards these three infections. Our aim was to assess the knowledge level of the adult Greek general population about the HBV, HCV and HIV.

Methods

Data were derived from the first general population health survey, Hprolipsis. The sample was selected by multistage stratified random sampling. A standardized questionnaire was administered by trained interviewers during home visits. A knowledge score was constructed based on responses to 17 per infection selected items and categorized in three levels; high (12–17 correct replies) medium (6–11) and low (0–5). Among 8,341 eligible individuals, 6,006 were recruited (response rate: 72%) and 5,878 adults (≥ 18 years) were included in the analysis. The statistical analysis accounted for the study design.

Results

Only 30.4%, 21.6%, and 29.6% of the participants had a high overall knowledge level of HBV, HCV and HIV, respectively. These low percentages were mainly attributed to the high levels of misconception about transmission modes (65.9%, 67.2%, and 67.9%, respectively). Results showed that increasing age and living out of the big metropolitan cities were associated with decreased odds of having higher knowledge. Female gender, higher education level, higher monthly family income, higher medical risk score, history of testing and being born in Greece or Cyprus, were associated with increased odds of having higher knowledge.

Conclusions

There are significant knowledge gaps in the Greek general population regarding modes of transmission, preventive measures and treatment availability for HBV, HCV and HIV. There is an urgent need for large scale but also localized awareness activities targeted to less privileged populations, to fill the gaps in knowledge and increase population engagement in preventive measures.
Constructing and validating an Occupational Mechanical Job Exposure Index based on five Norwegian nationwide Surveys of Living Conditions on work environment
Authors: Hermansen Åsmund , Dahl Espen
Published: November 2022

Background

The overall aim of this study was to examine essential aspects of reliability and validity of a constructed Occupational Mechanical Job Exposure Index for use in analyses of Norwegian register data. 

Methods

We utilized data from the Norwegian nationwide Survey of Living Conditions on work environment in 2006, 2009, 2013, 2016 and 2019. Occupations were classified on a 4-digit level based on the Norwegian version of the International Standard Classification of Occupations (ISCO-88). We constructed a 4-digit correspondence table between the occupational codes used in the 2006 and 2009 surveys (STYRK-98) and the codes used in 2013, 2016 and 2019 (STYRK-08). The mechanical exposures were collected by Statistics Norway using telephone interviews. As for reliability, we examined the agreement between the individual- and the occupational-based mechanical exposures using Cohen’s kappa, sensitivity and specificity measures. Construct, concurrent and predictive validity pertaining to the Occupational Mechanical Job Exposure Index were analysed using both survey data and nationwide register data.

Results

The analysis shows a fair-to-moderate overlap between occupational-based mechanical exposures and the individually reported exposures. Construct validity of the Occupational Mechanical Job Exposure Index, as estimated by a confirmatory factor analysis using the occupational-based mechanical exposures, showed that the 8 exposures formed one underlying factor. When assessing the concurrent value of the Occupational Mechanical Job Exposure Index to the index based on the individual reported exposures, the occupational mechanical index showed lower and reproducible associations with lower back pain for both men and women. For long-term sick leave, the occupational mechanical index showed higher and reproducible associations for both genders. As for predictive validity, the register data analysis shows that the occupational mechanical index was associated with disability and a higher number of long-term sickness benefits periods for both men and women. For men the index also predicted higher mortality.

Conclusion

Our tests of reliability and validity of the Occupational Mechanical Job Exposure Index indicate that the index overall has acceptable statistical properties and will be useful in analyses of Norwegian register data where individual information on these types of exposures is missing.
Catastrophic failure of a titanium locking plate in a proximal humeral fracture: case report and literature review
Authors: Lian Yan-Shiang , Huang Chang-Hung , Chuang Min-Yao
Published: November 2022

Background

Angular stable locking plates have shown good clinical results in treating proximal humeral fractures, but complications are not uncommon. This study reported a rare case of catastrophic failure of a titanium locking plate. A retrieval analysis of the implants was performed using an optic microscope and a scanning electron microscope.

Case presentation

A 69-year-old male reported a right proximal humeral fracture at the surgical neck and was treated by open reduction and internal fixation with a locking plate system. Ninety-six days after surgery, the patient came to clinic for acute local pain over the shoulder without any trauma. The radiographs showed a complete breakage of the implant accompanying displaced fracture. Revision surgery was performed to restabilize the fracture with a longer locking plate. The follow-up radiographs at 9 months showed complete union of the bone fracture.

Conclusions

From the retrieval analysis, repetitive torsion loads on the vulnerable area of the implant are assumed to cause this catastrophic event. It is recommended that adequate activity restriction, such as reaching, be undertaken to avoid this rare complication. Current study also provides contributive information for the modification of plate design and pre-operative planning for device configuration to improve the success rate of locking plate fixation.
The rs35874116 single nucleotide polymorphism increases sweet intake and the risk of severe early childhood caries: a case–control study
Authors: Liang Yan , Yao Junyu , Qiu Rongmin , Chen Aihua , Huang Hua , Lin Huancai , Yu Lixia
Published: November 2022

Background

Dental caries is one of the most prevalent chronic diseases worldwide among children. The rs35874116 single nucleotide polymorphism (SNP) in the sweet receptor gene TAS1R2 has been associated with dental caries at a high risk in permanent teeth among school children and adults. To date, little is known about the association of this SNP with sweet intake and caries risk in the primary school children.

Methods

Total of 236 children were included, namely 118 subjects in the non-caries (NC) group and severe early childhood caries (S-ECC) group, respectively. Oral mucosa cells were collected from all the selected children, and the full length of exon 3 in TAS1R2 was sequenced to analyse rs35874116 polymorphism. A questionnaire was used to collect information about socio-demographic information, frequency of sweet intake and oral hygiene habits. Multiple logistic regression models were applied to assess the relationship of rs35874116 polymorphism with frequency of sweet intake and S-ECC among the five-year-old children.

Results

Children with the TT genotype of rs35874116 had a higher frequency of sweet intake than CT/CC carriers (51.3% vs. 32.7%; x2 = 5.436, p = 0.020), and S-ECC individuals were more likely to be TT genotype carriers than NC individuals (53.5% vs. 46.5%; x2 = 4.353, p = 0.037). Multiple logistic regression analyses showed that the TT genotype of rs35874116 was not only significantly related to the frequency of sweet intake (OR = 2.25, 95% CI = 1.14–4.44) but also significantly associated with S-ECC (OR = 2.11, 95% CI = 1.01 ~ 4.42).

Conclusions

The rs35874116 polymorphism might increase sweet intake and the risk of S-ECC among five-year-old children in Nanning, China.
RETRACTED ARTICLE: Polyphenols from Conyza dioscoridis (L.) ameliorate Alzheimer’s disease- like alterations through multi-targeting activities in two animal models
Authors: Gomaa Adel A. , Farghaly Hanan S. M. , Makboul Rania M. , Hussien Abeer M. , Nicola Mariam A.
Published: November 2022

Background

Recent investigations suggested that anticancer agents may inhibit the progression of Alzheimer's disease (AD) pathology. Conyza dioscoridis (L.) was demonstrated to have anticancer, antioxidant, anti-inflammatory and antidiabetic effects. This study was carried out to investigate the efficacy of polyphenols from Conyza dioscoridis (L.) extract (PCDE) on AD.

Methods

Impacts of 3 doses of PCDE and donepezil, a reference drug, on the features of Alzheimer's disease in two animal models were investigated.

Results

PCDE ameliorated the memory and learning impairment shown in rats following a single dose of scopolamine (scopolamine model) or 17 weeks of high-fat/high-fructose(HF/Hfr) diet coupled with a single dose of streptozotocin, (25 mg/kg) (T2D model). They reduced significantly the high hippocampal cholinesterase activity in the two models of rats. Administration of PCDE for 8 weeks in the T2D model showed a significant reduction in hippocampal GSK-3β, caspase-3 activity and increase in the inhibited glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). A significant reduction of HOMA-insulin resistance and serum hypercholesterolemia was observed. The Tau hyperphosphorylation and Aβ 1–42 generation in the hippocampal of T2D rats were significantly decreased by PCDE. Modulation of the oxidative stress markers, (rise in GH and SOD; decrease in MDA levels) and a significant reduction of TNF-α and IL-1β in the hippocampus of T2D rats treated by PCDE extract were important findings in this study. The highest dose tested was 4% of the highest safe dose.

Conclusion

Our study suggests that PCDE is multi-targeting agent with multiple beneficial activities in combating features of AD. This study may provide a novel therapeutic strategy for AD treatment that warrants clinical studies.
Spanish adaptation of the quality in psychiatric care-outpatient (QPC-OP) instrument community mental health patients’ version: psychometric properties and factor structure
Authors: Tomás-Jiménez Manuel , Roldán-Merino Juan Francisco , Sanchez-Balcells Sara , Schröder Agneta , Lundqvist Lars-Olov , Puig-Llobet Montserrat , Moreno-Poyato Antonio R. , Domínguez del Campo Marta , Lluch-Canut Maria Teresa
Published: November 2022

Background

Health systems in the field of mental health are strongly committed to community models that allow patients to be attended in their own environment. This helps them to maintain their family and social ties while trying to avoid costly hospital admissions. The patients’ perspective is a key component in the assessment of the quality of psychiatric care and can even determine their adherence to the devices where they are treated. However, there are few instruments with adequate psychometric properties for the evaluation of the quality of psychiatric care in community mental health. The Quality in Psychiatric Care – Outpatient (QPC-OP) instrument has adequate psychometric properties to assess the quality of psychiatric care from the patients’ perspective. The aim of this study was to adapt and validate the Spanish version of the QPC-OP instrument.

Methods

A translation and back-translation of the instrument was carried out. To examine its psychometric properties, the instrument was administered to 200 patients attending various community mental health services. To assess test-retest reliability, the instrument was readministered after 7-14 days (n = 98).

Results

The Confirmatory Factor Analysis revealed a structure of 8 factors identical to the original version, with an adequate model fit. The internal consistency coefficient (Cronbach’s alpha) was 0.951. The intraclass correlation coefficient was 0.764 (95% IC: 0.649 – 0.842), and higher than 0.70 in 5 of the 8 factors. Additionally, an EFA was performed and revealed that the instrument could behave in a unifactorial or four factor manner in the sample analyzed.

Conclusions

Results show that the Spanish version of the QPC-OP instrument is valid and reliable for the assessment of quality of psychiatric care in the community setting.
Second opinion opportunity declined: patient typology and experiences regarding the decision-making process preceding elective surgeries in Germany
Authors: May Susann , Bruch Dunja , Muehlensiepen Felix , Prediger Barbara , Pieper Dawid , Ronckers Cecile , von Peter Sebastian , Neugebauer Edmund
Published: November 2022

Background

To address the problem of overuse of elective surgery and to support patients in their decision-making process, a Second Opinion Directive was introduced in Germany, which enables patients with statutory health insurance to obtain a second opinion for certain surgical indications. The study aims to identify, based on the experiences of patients who have undergone elective surgery, the role of seeking a second opinion in reaching their decision.

Methods

Sixty-two patients who had undergone an elective surgery (hysterectomy, tonsillectomy, shoulder arthroscopy) were recruited using purposive sampling and interviewed during October to December 2020. The transcribed interviews were analysed using a framework analysis to create a typology from the patient’s perspective.

Results

The time spent by patients in making the decision to undergo surgery varies between individuals, and is influenced by factors such as the type of physician-patient relationship, individual patient aspects, prior experiences in the health care system, as well as information needs. Within the framework of the analysis, we were able to identify three patterns of patient types based on the three different time-points or phases when decisions were typically made, with one type being divided into two subtypes: Type 1a: Quick decision making, Type 1b: Overwhelmed quick decision making, Type 2: Time to consider, Type 3: Struggling with the decision.

Conclusions

Patients who followed a recommendation for elective surgery appreciate having the possibility to seek a second opinion. However, various factors influenced their opting for a second opinion during the decision-making process. Patients have differing information needs, such that a one-size-fits-all second opinion service may not fit adequately for all patients.
Reliability and validity of the Veterans Administration Mobility Screening and Solutions Tool
Authors: Melillo Christine , Rugs Deborah , Toyinbo Peter , Barrett Blake , Chavez Margeaux , Cowan Linda , Wyatt Susan , Arnold Margaret , Hilton Pauline , Martin Marie , Earwood Jill , Sullivan Sheila Cox
Published: November 2022

Objectives

The Veterans Administration (VA) Mobility Screening and Solutions Tool (VA MSST) was developed to screen a patient’s safe mobility level ‘in the moment’ and provide clinical decision support related to the use of safe patient handling and mobility (SPHM) equipment. This evidence-based flowchart tool is a common language tool that enables any healthcare worker at any time to accurately measure and communicate patient mobility and transfer equipment needs across disciplines and settings.

Methods

The VA MSST has four levels and differentiates between the need for powered and non-powered equipment depending on the patient’s independence. Subject matter experts wrote scenarios for interrater reliability and validity testing. The initial VA MSST draft iteration was reviewed by 163 VA staff (mostly physical therapists and occupational therapists) amongst simulation scenarios and provided content validity, and additional insight and suggestions. Revisions were made to create the final VA MSST which was evaluated by over 200 healthcare workers from varied disciplines (including medical doctors, advanced practice registered nurses, registered nurses, licensed practical nurses, certified nursing assistants, occupational therapists, physical therapists, speech therapists, radiology and ultrasound technicians, etc.). An instruction video and eighteen scenario videos were embedded in an online survey. The survey intended to demonstrate the interrater reliability and validity (concurrent and construct) of the VA MSST. Over 500 VA staff (raters) received a survey invitation via email.

Results

Raters (N = 230) from multiple disciplines and healthcare settings independently screened patient mobility status for each of 18 scenarios using the VA MSST. The raters were diverse in their age and years of experience. The estimated interrater reliability (IRR) for VA MSST was excellent and statistically significant with an estimated Krippendorff’s alpha (ICC (C, k)) of 0.998 [95% CI: 0.996–0.999]. Eighty-two percent of raters reported that overall VA MSST instructions were clear or very clear and understandable. VA MSST ratings made by technicians and nursing assistants group correlated strongly (r = 0.99, p < 0.001) with the ‘gold standard’ (experienced physical therapists), suggesting a high concurrent validity of the tool. The VA MSST significantly discriminated between the different levels of patient mobility required for safe mobilization as intended (each difference, p < 0.0001); this suggests a good construct validity.

Conclusions

The VA MSST is an evidence-based flowchart screening and decision support tool that demonstrates excellent interrater reliability across disciplines and settings. VA MSST has strong face and content validity, as well as good concurrent and construct validity.
High-yield production of protopanaxadiol from sugarcane molasses by metabolically engineered Saccharomyces cerevisiae
Authors: Zhu Yuan , Li Jianxiu , Peng Longyun , Meng Lijun , Diao Mengxue , Jiang Shuiyuan , Li Jianbin , Xie Nengzhong
Published: November 2022

Background

Ginsenosides are Panax plant-derived triterpenoid with wide applications in cardiovascular protection and immunity-boosting. However, the saponins content of Panax plants is fairly low, making it time-consuming and unsustainable by direct extraction. Protopanaxadiol (PPD) is a common precursor of dammarane-type saponins, and its sufficient supply is necessary for the efficient synthesis of ginsenoside.

Results

In this study, a combinational strategy was used for the construction of an efficient yeast cell factory for PPD production. Firstly, a PPD-producing strain was successfully constructed by modular engineering in Saccharomyces cerevisiae BY4742 at the multi-copy sites. Then, the INO2 gene, encoding a transcriptional activator of the phospholipid biosynthesis, was fine-tuned to promote the endoplasmic reticulum (ER) proliferation and improve the catalytic efficiency of ER-localized enzymes. To increase the metabolic flux of PPD, dynamic control, based on a carbon-source regulated promoter PHXT1, was introduced to repress the competition of sterols. Furthermore, the global transcription factor UPC2-1 was introduced to sterol homeostasis and up-regulate the MVA pathway, and the resulting strain BY-V achieved a PPD production of 78.13 ± 0.38 mg/g DCW (563.60 ± 1.65 mg/L). Finally, sugarcane molasses was used as an inexpensive substrate for the first time in PPD synthesis. The PPD titers reached 1.55 ± 0.02 and 15.88 ± 0.65 g/L in shake flasks and a 5-L bioreactor, respectively. To the best of our knowledge, these results were new records on PPD production.

Conclusion

The high-level of PPD production in this study and the successful comprehensive utilization of low-cost carbon source -sugarcane molassesindicate that the constructed yeast cell factory is an excellent candidate strain for the production of high-value-added PPD and its derivativeswith great industrial potential.

Graphical Abstract
Engineering Cupriavidus necator H16 for enhanced lithoautotrophic poly(3-hydroxybutyrate) production from CO2
Authors: Kim Soyoung , Jang Yong Jae , Gong Gyeongtaek , Lee Sun-Mi , Um Youngsoon , Kim Kyoung Heon , Ko Ja Kyong
Published: November 2022

Background

A representative hydrogen-oxidizing bacterium Cupriavidus necator H16 has attracted much attention as hosts to recycle carbon dioxide (CO2) into a biodegradable polymer, poly(R)-3-hydroxybutyrate (PHB). Although C. necator H16 has been used as a model PHB producer, the PHB production rate from CO2 is still too low for commercialization.

Results

Here, we engineer the carbon fixation metabolism to improve CO2 utilization and increase PHB production. We explore the possibilities to enhance the lithoautotrophic cell growth and PHB production by introducing additional copies of transcriptional regulators involved in Calvin Benson Bassham (CBB) cycle. Both cbbR and regA-overexpressing strains showed the positive phenotypes for 11% increased biomass accumulation and 28% increased PHB production. The transcriptional changes of key genes involved in CO2—fixing metabolism and PHB production were investigated.

Conclusions

The global transcriptional regulator RegA plays an important role in the regulation of carbon fixation and shows the possibility to improve autotrophic cell growth and PHB accumulation by increasing its expression level. This work represents another step forward in better understanding and improving the lithoautotrophic PHB production by C. necator H16.
Induction mechanism of cigarette smoke components (CSCs) on dyslipidemia and hepatic steatosis in rats
Authors: Ge Jian , Xu Wei-jia , Chen Hai-feng , Dong Zong-hua , Liu Wei , Nian Fu-zhao , Liu Jun
Published: November 2022

Objective

The purpose of this study was to explore the effect of cigarette smoke component (CSC) exposure on serum lipid levels in rats and the underlying molecular mechanism.

Methods

Male SPF-grade SD rats were randomly divided into a control group and a CSC exposure group, with the CSC group being exposed to CSC for 6 weeks. RT–PCR and Western blotting methods were used to detect lipid metabolism gene expression in rats, and 16S RNA gene sequencing was used to detect the gut microbiota in the rat cecum. Rat serum exosomes were prepared and identified, and the interaction of exosomal miR-291a-3p and miR-126a-5p with AMPK and CYP7A1 was detected by a dual luciferase reporter gene assay (DLRG).

Results

Serum indicators, including cholesterol levels and trimethylamine oxide (TMAO) content, were significantly affected in the CSC exposure group compared with the control group (P < 0.05), and the expression levels of adenylate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and HMG-CoA reductase (HMG-CoAR) genes were significantly increased (P < 0.05) in the liver, while the expression level of cholesterol 7α-hydroxylase (CYP7A1) was markedly decreased (P < 0.01). 16S rRNA gene sequencing of the gut microbiota in the rat cecum showed that the abundance of Firmicutes in the CSC group increased significantly at the phylum level, while the abundances of Bacteroidota and Spirochaetota were reduced significantly (P < 0.01). The relative abundance of Romboutsia, Turicibacter, and Clostridium sensu stricto increased significantly (P < 0.01), and the relative abundance of Prevotella, Muribaculaceae_norank, Lachnospiraceae NK4A136 group, Roseburia, Treponema, and Ruminococcus significantly decreased (P < 0.01) at the genus level. In addition, the exosome miR-291a-3p and miR-126a-5p levels were markedly regulated by CSC exposure (P < 0.01). The interactions of miR-291a-3p and miR-126a-5p with AMPK and CYP7A1 mRNA were also validated by the DLRG method.

Conclusions

In summary, the rat dyslipidemia induced by CSC exposure may be related to the interference of gut microbiota structure and interaction of miRNAs from serum exosomes with target mRNAs, which further regulated AMPK-ACC/CYP7A1 signaling in rats.
Serpin-loaded extracellular vesicles promote tissue repair in a mouse model of impaired wound healing
Authors: Park Dong Jun , Duggan Erika , Ho Kayla , Dorschner Robert A. , Dobke Marek , Nolan John P. , Eliceiri Brian P.
Published: November 2022

Chronic metabolic diseases such as diabetes are characterized by delayed wound healing and a dysregulation of the inflammatory phase of wound repair. Our study focuses on changes in the payload of extracellular vesicles (EVs) communicating between immune cells and stromal cells in the wound bed, which regulate the rate of wound closure. Adoptive transfer of EVs from genetically defined mouse models are used here to demonstrate a functional and molecular basis for differences in the pro-reparative biological activity of diabetic (db/db) vs. wildtype EVs in wound healing. We identify several members of the Serpin family of serine protease inhibitors that are absent in db/db EVs, then we overexpress Serpin A1, F2 and G1 in EVs to evaluate their effect on wound healing in db/db mice. Serpins have an important role in regulating levels of elastase, plasmin and complement factors that coordinate immune cell signaling in full thickness wounds in a diabetic model. Here, we establish a novel therapeutic approach by engineering the payload of EVs based on proteomic analysis. Serpin-loaded EVs were used to rescue the Serpin deficiency identified by proteomics and promote wound healing in db/db mice, as well as evaluated how EVs affected extracellular matrix remodeling and the resolution of tissue injury. Therefore, we propose that the identification of EV payloads that are downregulated in diabetic wounds can be systematically analyzed for their functional activity and potential as a therapeutic, based on whether their re-expression in engineered EVs restores normal kinetics of tissue repair in chronic wounds.

Graphical Abstract
SOX21-AS1 activated by STAT6 promotes pancreatic cancer progression via up-regulation of SOX21
Authors: Yu Dandan , Zhao Zhigang , Wang Li , Qiao Shishi , Yang Zhen , Wen Qiang , Zhu Guanghui
Published: November 2022

Background

Pancreatic cancer (PC) is a highly malignant tumor which threatens human’s health. Long non-coding RNAs (lncRNAs) are implicated in many cancers, including PC, but their mechanisms in PC have not yet been entirely clarified. We focused on revealing the potential function of lncRNA SOX21-AS1 in PC.

Methods

Functional assays assessed SOX21-AS1 function on PC progression. Bioinformatics analysis, along with mechanism assays were taken to unmask the regulatory mechanism SOX21-AS1 may exert in PC cells.

Results

SOX21-AS1 possessed a high expression level in PC cells. SOX21-AS1 absence suppressed PC cell proliferation, migration, stemness and epithelial-mesenchymal transition (EMT) while elevated cell apoptosis. SOX21-AS1 positively regulated its nearby gene SRY-box transcription factor 21 (SOX21) at post-transcriptional level. Through mechanism assays, we uncovered that SOX21-AS1 sponged SOX21-AS1 to elevate SOX21 mRNA and recruited ubiquitin-specific peptidase 10 (USP10) to deubiquitinate and stabilize SOX21 protein. Moreover, signal transducer and activator of transcription 6 (STAT6) could transcriptionally activate SOX21-AS1 and SOX21 expression.

Conclusions

SOX21-AS1 aggravated the malignant development of PC, which might provide the utility value for PC treatment.
Irradiation-induced exosomal HMGB1 to confer radioresistance via the PI3K/AKT/FOXO3A signaling pathway in ESCC
Authors: Du Xingyu , Zhang Xueyuan , Dong Jing , Zou Naiyi , Guo Dong , Yao Weinan , Wang Xiaobin , Li Shuguang , Song Chunyang , Yan Ke , Shen Wenbin , Zhu Shuchai
Published: November 2022

Background

Radioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells.

Methods

Plasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group.

Results

The expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX.

Conclusion

These findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.
A review of user needs to drive the development of lower limb prostheses
Authors: Manz Sabina , Valette Romain , Damonte Federica , Avanci Gaudio Lucas , Gonzalez-Vargas Jose , Sartori Massimo , Dosen Strahinja , Rietman Johan
Published: November 2022

Background

The development of bionic legs has seen substantial improvements in the past years but people with lower-limb amputation still suffer from impairments in mobility (e.g., altered balance and gait control) due to significant limitations of the contemporary prostheses. Approaching the problem from a human-centered perspective by focusing on user-specific needs can allow identifying critical improvements that can increase the quality of life. While there are several reviews of user needs regarding upper limb prostheses, a comprehensive summary of such needs for those affected by lower limb loss does not exist.

Methods

We have conducted a systematic review of the literature to extract important needs of the users of lower-limb prostheses. The review included 56 articles in which a need (desire, wish) was reported explicitly by the recruited people with lower limb amputation (N = 8149).

Results

An exhaustive list of user needs was collected and subdivided into functional, psychological, cognitive, ergonomics, and other domain. Where appropriate, we have also briefly discussed the developments in prosthetic devices that are related to or could have an impact on those needs. In summary, the users would like to lead an independent life and reintegrate into society by coming back to work and participating in social and leisure activities. Efficient, versatile, and stable gait, but also support to other activities (e.g., sit to stand), contribute to safety and confidence, while appearance and comfort are important for the body image. However, the relation between specific needs, objective measures of performance, and overall satisfaction and quality of life is still an open question.

Conclusions

Identifying user needs is a critical step for the development of new generation lower limb prostheses that aim to improve the quality of life of their users. However, this is not a simple task, as the needs interact with each other and depend on multiple factors (e.g., mobility level, age, gender), while evolving in time with the use of the device. Hence, novel assessment methods are required that can evaluate the impact of the system from a holistic perspective, capturing objective outcomes but also overall user experience and satisfaction in the relevant environment (daily life).
Three-dimensional microenvironment regulates gene expression, function, and tight junction dynamics of iPSC-derived blood–brain barrier microvessels
Authors: Linville Raleigh M. , Sklar Matthew B. , Grifno Gabrielle N. , Nerenberg Renée F. , Zhou Justin , Ye Robert , DeStefano Jackson G. , Guo Zhaobin , Jha Ria , Jamieson John J. , Zhao Nan , Searson Peter C.
Published: November 2022

The blood–brain barrier (BBB) plays a pivotal role in brain health and disease. In the BBB, brain microvascular endothelial cells (BMECs) are connected by tight junctions which regulate paracellular transport, and express specialized transporter systems which regulate transcellular transport. However, existing in vitro models of the BBB display variable accuracy across a wide range of characteristics including gene/protein expression and barrier function. Here, we use an isogenic family of fluorescently-labeled iPSC-derived BMEC-like cells (iBMECs) and brain pericyte-like cells (iPCs) within two-dimensional confluent monolayers (2D) and three-dimensional (3D) tissue-engineered microvessels to explore how 3D microenvironment regulates gene expression and function of the in vitro BBB. We show that 3D microenvironment (shear stress, cell-ECM interactions, and cylindrical geometry) increases BBB phenotype and endothelial identity, and alters angiogenic and cytokine responses in synergy with pericyte co-culture. Tissue-engineered microvessels incorporating junction-labeled iBMECs enable study of the real-time dynamics of tight junctions during homeostasis and in response to physical and chemical perturbations.
Calcaneal osteotomy due to insertional calcaneal tendinopathy: preoperative planning
Authors: Mazura Matej , Goldman Tomas , Stanislav Popelka , Kachlik David , Hromadka Rastislav
Published: November 2022

Purpose

Dorsal closing wedge calcaneal osteotomy (DCWCO) is indicated in patients with insertional tendinopathy of the calcaneal (Achilles) tendon. The Chauveaus-Liet’s (CL) angle is represented by the difference between the angle of verticalization (α) and morphological angle (β) of the calcaneus (CL angle = α − β). The purpose of the study was to assess whether the DCWCO affects the Chauveaus-Liet’s angle.

Methods

The study included 12 patients indicated to DCWCO. Three directions of close wedge osteotomy were designed for each patient—horizontal, vertical and in the middle type of osteotomy and a virtual osteotomy was created in each of them in the ABAQUS system in cooperation with Czech Technical University. The most used directions of osteotomy according to the available literature were used. We evaluated α and β angles before and after osteotomy, changes of the length plantar aponeurosis and the elevation of distal insertional point of the calcaneal tendon. The changes of grades, median and standard deviation were observed.

Results

The change of the alfa angle was dependent on the direction of the osteotomy and the change of the beta angle was affected by the size of the osteotomy. The greatest elevation of the distal insertional point of the calcaneal tendon occurred in the horizontal type of the osteotomy.

Conclusion

Our study shows that the more we want to reduce the tension in the calcaneal tendon, the more we have to perform an osteotomy horizontally. This study could serve as a preoperative guide for osteotomy planning.
Deciphering the impact of genetic variation on human polyadenylation using APARENT2
Authors: Linder Johannes , Koplik Samantha E. , Kundaje Anshul , Seelig Georg
Published: November 2022

Background

3′-end processing by cleavage and polyadenylation is an important and finely tuned regulatory process during mRNA maturation. Numerous genetic variants are known to cause or contribute to human disorders by disrupting the cis-regulatory code of polyadenylation signals. Yet, due to the complexity of this code, variant interpretation remains challenging.

Results

We introduce a residual neural network model,APARENT2, that can infer 3′-cleavage and polyadenylation from DNA sequence more accurately than any previous model. This model generalizes to the case of alternative polyadenylation (APA) for a variable number of polyadenylation signals. We demonstrate APARENT2’s performance on several variant datasets, including functional reporter data and human 3′ aQTLs from GTEx. We apply neural network interpretation methods to gain insights into disrupted or protective higher-order features of polyadenylation. We fine-tune APARENT2 on human tissue-resolved transcriptomic data to elucidate tissue-specific variant effects. By combining APARENT2 with models of mRNA stability, we extend aQTL effect size predictions to the entire 3′ untranslated region. Finally, we perform in silico saturation mutagenesis of all human polyadenylation signals and compare the predicted effects of$${>}43$$>43million variants against gnomAD. While loss-of-function variants were generally selected against, we also find specific clinical conditions linked to gain-of-function mutations. For example, we detect an association between gain-of-function mutations in the 3′-end and autism spectrum disorder. To experimentally validate APARENT2’s predictions, we assayed clinically relevant variants in multiple cell lines, including microglia-derived cells.

Conclusions

A sequence-to-function model based on deep residual learning enables accurate functional interpretation of genetic variants in polyadenylation signals and, when coupled with large human variation databases, elucidates the link between functional 3′-end mutations and human health.
The clinical value and cost-effectiveness of treatments for patients with coronary artery disease
Authors: Weiting Huang , Yaoxian Alwin Zhang , Keong Yeo Khung , Lam Shao Wei , How Lau Yee , Sahlén Anders Olof , Pourghaderi Ahmadreza , Che Matthew , Terrance Chua Siang Jin , Graves Nicholas
Published: November 2022

Background

The clinical value and cost-effectiveness of invasive treatments for patients with coronary artery disease is unclear. Invasive treatments such as coronary artery bypass grafting and percutaneous coronary intervention are frequently used as a starting treatment, yet they are much more costly than optimal medical therapy. While patients may transition into other treatments over time, the choices of starting treatments are likely important determinants of costs and health outcomes. The aim is to predict by how much costs and health outcomes will change from a decision to use different starting treatments for patients with coronary artery disease in an Asian setting.

Methods

A cost-effectiveness study using a Markov model informed by data from Singapore General Hospital was done. All patients with initial presentations of stable coronary disease and no acute coronary syndromes who received medical treatments and interventional therapies were included. We compare existing practice, where the starting treatment can be medical therapy or stent percutaneous coronary interventions or coronary artery bypass grafting, with alternate starting treatment strategies.

Results

When compared to ‘existing practice’ a policy of starting 14% of patients with coronary artery bypass grafting and 86% with optimal medical therapy showed savings of $1,743 per patient and 0.23 additional quality adjusted life years. A change to policy nationwide would save $10 million and generate 1,380 quality adjusted life years.

Conclusions

Increasing coronary artery bypass grafting and use of medical therapy in the setting of coronary artery disease is likely to saves costs and improve health outcomes. A definitive study to address the question we investigate would be very difficult to undertake and so using existing data to model the expected outcomes is a useful tool. There are likely to be large and complex barriers to the implementation of any policy change based on the findings of this study.
Parameter estimation and tracking algorithm for resolvable group targets based on GLMB filter and RLS algorithm
Authors: Liu Weifeng , Zhao Zhi , Liu Qiliang , Peng Zhangming
Published: November 2022

Current resolvable group targets tracking algorithms can only track a small number of group targets assuming the standard deviation vectors (SDVs) are known. Based on generalized labeled multi-Bernoulli filter, this paper first proposes a serial tracking algorithm, in order to save the computational cost of filter tracking large-batch and multi-structure group targets. Then, the least squares and the k-means algorithms are used to jointly estimate the SDVs and the group target states. The experimental simulation results verify the effectiveness of the proposed methods.