bluuebunny/crossref_metadata_2025 huggingface dataset:
ExPert ConsEnsus on the management of Advanced clear-cell RenaL celL carcinoma: INDIAn Perspective (PEARL-INDIA)
Authors: Sahoo Tarini Prasad , Desai Chirag , Agarwal Shyam , Rauthan Amit , Dhabhar Boman , Biswas Ghanshyam , Batra Sandeep , Saha Rajat , Philip Arun , Agarwal Vijay , Dattatreya Palanki Satya , Mohapatra PN , Deshmukh Chetan , Bhagat Sagar , Patil Saiprasad , Barkate Hanmant
Published: August 2023

In advanced Renal Cell Carcinoma (aRCC), systemic therapy is the mainstay of treatment, with no or little role for surgery in these patients. Tyrosine kinase inhibitors (TKIs) and immune-oncological (IOs) therapies, either alone or in combination, are recommended in these patients depending on patient and tumour factors. The sequencing of therapies is critical in RCC because the choice of subsequent line therapy is heavily dependent on the response and duration of the previous treatment. There are additional barriers to RCC treatment in India. Immunotherapy is the cornerstone of treatment in ccRCC, but it is prohibitively expensive and not always reimbursed, effectively putting it out of reach for the vast majority of eligible patients in India. Furthermore, in advanced RCC (particularly the clear cell variety), Indian oncologists consider the disease burden of the patients, which is particularly dependent on the quantum of the disease load, clinical symptoms, and performance status of the patient, before deciding on treatment. There are no India-specific guidelines for clear cell RCC (ccRCC) treatment or the positioning and sequencing of molecules in the management of advanced ccRCC that take these country-specific issues into account. The current consensus article provides expert recommendations and treatment algorithms based on existing clinical evidence, which will be useful to specialists managing advanced ccRCC.
Socioeconomic differences in tobacco outlet presence, density, and proximity in four cities in the Netherlands
Authors: van Deelen Tessa R.D. , Veldhuizen Els M. , van den Putte Bas , Kunst Anton E. , Kuipers Mirte A.G.
Published: August 2023

Background

Previous studies found that tobacco outlets were unevenly distributed by area socioeconomic status (SES). However, evidence from continental Europe is limited. This study aims to assess differences in tobacco outlet presence, density and proximity by area SES in the Netherlands.

Methods

All tobacco outlets in four Dutch cities (Amsterdam, and medium-sized cities Eindhoven, Haarlem, and Zwolle) were mapped between September 2019 and June 2020. We estimated associations between average property value of neighbourhoods (as an indicator of SES, grouped into quintiles) and (1) tobacco outlet presence in the neighbourhood (yes/no), (2) density (per km2), and (3) proximity to the closest outlet (in meters), using logistic and linear regression models.

Results

46% of neighbourhoods contained at least one tobacco outlet. Tobacco outlets were mostly situated in city centres, but the distribution of tobacco outlets varied per city due to differences in urban structures and functions. In the medium-sized cities, each quintile higher neighbourhood-SES was associated with lower tobacco outlet presence (OR:0.71, 95%CI:0.59;0.85), lower density (B:-1.20 outlets/km2, 95%CI:-2.20;-0.20) and less proximity (B:40.2 m, 95%CI 36.58;43.83). Associations were the other way around for Amsterdam (OR:1.22, 95%CI:1.05;1.40, B:3.50, 95%CI:0.81;6.20, and B:-18.45, 95%CI:-20.41;-16.49, respectively). Results were similar for most types of tobacco outlets.

Conclusion

In medium-sized cities in the Netherlands, tobacco outlets were more often located in low-SES neighbourhoods than high-SES. Amsterdam presented a reverse pattern, possibly due to its unique urban structure. We discuss how licensing might contribute to reducing tobacco outlets in low-SES neighbourhoods.
The effectiveness of theory-based smoking cessation interventions in patients with chronic obstructive pulmonary disease: a meta-analysis
Authors: Han Mengjing , Fu Yingping , Ji Quanyue , Deng Xiaoli , Fang Xuewen
Published: August 2023

Background

Smoking cessation can effectively reduce the risk of death, alleviate respiratory symptoms, and decrease the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). Effective smoking cessation strategies are crucial for the prevention and treatment of COPD. Currently, clinical interventions based on theoretical frameworks are being increasingly used to help patients quit smoking and have shown promising results. However, theory-guided smoking cessation interventions have not been systematically evaluated or meta-analyzed for their effectiveness in COPD patients. To improve smoking cessation rates, this study sought to examine the effects of theory-based smoking cessation interventions on COPD patients.

Methods

We adhered to the PRISMA guidelines for our systematic review and meta-analysis. The Cochrane Library, Web of Science, PubMed, Embase, Wanfang, CNKI, VIP Information Services Platform, and China Biomedical Literature Service System were searched from the establishment of the database to April 20, 2023. The study quality was assessed using the Cochrane Collaboration's risk assessment tool for bias. The revman5.4 software was used for meta-analysis. The I2 test was used for the heterogeneity test, the random effect model and fixed effect model were used for meta-analysis, and sensitivity analysis was performed by excluding individual studies.

Results

A total of 11 RCTs involving 3,830 patients were included in the meta-analysis. Results showed that theory-based smoking cessation interventions improved smoking cessation rates, quality of life, and lung function in COPD patients compared to conventional nursing. However, these interventions did not significantly affect the level of nicotine dependence in patients.

Conclusion

Theory-based smoking cessation intervention as a non-pharmacologically assisted smoking cessation strategy has a positive impact on motivating COPD patients to quit smoking and improving their lung function and quality of life.

Trial registration

PROSPERO registration Number: CRD42023434357.
Treatment of type II symptomatic ulnar styloid nonunions with reinsertion of the triangular fibrocartilage complex
Authors: Yu Xiaofei , Yu Yadong , Zhang Xu , Li Jia , Zhou Tong , Chen Huan
Published: August 2023

Purpose

The purpose of this retrospective study was to introduce an alternative technique for the treatment of type II symptomatic ulnar styloid nonunion by the reinsertion of the triangular fibrocartilage complex and the ulnar collateral ligament.

Methods

Between March 2009 and May 2017, 45 patients (34 males and 11 females) suffering from the nonunion of type II ulnar styloid fractures all underwent the subperiosteal resection of the avulsed fragments and the reinsertion of the TFCC and ulnar collateral ligament. Outcome assessments included the ranges of motion of the wrist, grip strength, pain, and Mayo wrist score. The preoperative and postoperative parameters were compared. A P-value less than 0.05 was considered to be statistically significant.

Result

The mean follow-up period was 21.66 ± 7.93 months (range, 12 to 26 months). At the final follow-up, the mean preoperative flexion and extension were 79.32 ± 4.52° and 74.40 ± 4.36° respectively. The mean preoperative pain score, grip strength, and Mayo wrist score were 32.48 ± 4.00; 23.88 ± 8.38 kg, and 77.72 ± 8.31 respectively. The mean postoperative flexion and extension of the wrist were 80.56 ± 6.32° and 75.43 ± 3.12° respectively. The mean postoperative pain score, grip strength, and Mayo wrist score were 12.41 ± 3.27, 26.31 ± 8.30 kg, and 90.71 ± 7.97 respectively. There were significant differences in pain, grip strength, and Mayo wrist score (P < 0.05), but no significant differences concerning the range of motion of the wrist.

Conclusion

In the treatment of the nonunion of type II ulnar styloid fractures, the resection of the avulsed fragments followed by the reinsertion of the TFCC and the ulnar collateral ligament with an anchor was a reliable alternative technique, bringing the satisfactory function of the wrist.
The anterior transmuscular intrapelvic approach for the treatment of acetabular fractures—a new anterior surgical strategy
Authors: Lippross Sebastian , Wehrenpfennig Clara , Wedel Thilo , Seekamp Andreas , Osmonov Daniar , Moradi Babak , Fitschen-Oestern Stefanie , Finn Joerg , Klueter Tim , Kurz Bodo , Alkatout Ibrahim
Published: August 2023

The anterior ilioinguinal and the posterior Kocher-Langenbeck approach have long been the standard surgical approaches to the acetabulum. The last decade has witnessed the development of so-called intrapelvic approaches for anterior pathologies because they provide better exposure of the quadrilateral plate. Currently, the modified Stoppa approach and the pararectus approach are frequently used by surgeons for the treatment of acetabular fractures. We investigated an even more direct access to the entire anterior column and the quadrilateral plate via the abdominal wall muscles, between the incisions for the ilioinguinal and the pararectus approach.

After intensive study of anatomic specimens, a cadaver dissection was performed prior to clinical application. The approach was then used in 20 patients who were assessed retrospectively.

Postoperative CT scans showed that, according to the Matta scoring system, the quality of fracture reduction was “anatomical” (≤ 1 mm) in 12 (60%), “imperfect” (2–3 mm) in four (20%), and “poor” (> 3 mm) in four (20%) patients. Numerous minor complications were observed; the majority of these had resolved at the time of discharge.

In conclusion, the anterior transmuscular intrapelvic approach (ATI) is a safe and effective alternative to the ilioinguinal and pararectal approaches, and may be regarded as an evolutionary advancement of traditional procedures.
Management of dental care of patients on immunosuppressive drugs for chronic immune-related inflammatory diseases: a survey of French dentists’ practices
Authors: Bourgoin Alice , Agossa Kevimy , Seror Raphaele , Fumery Mathurin , Radoi Loredana , Gosset Marjolaine
Published: August 2023

Objectives

The aim of the study was to provide an overview of the practices of French general dentists (GDs) and specialists (SDs) concerning the management of patients with inflammatory bowel diseases (IBDs), rheumatic inflammatory diseases (IRDs), and vasculitis on biologic disease-modifying antirheumatic drugs (bDMARDs), conventional DMARDs, or immunosuppressants (ISs).

Materials and methods

An online national cross-sectional survey with 53 questions was developed by a multidisciplinary team including rheumatologists, gastroenterologists and dentists based on their clinical experience. It was refined following a test with nine dentists in private practice and in hospital before being disseminated to the members of French scientific societies and colleges of dentistry teachers over 3 months. Responses of general dentists versus specialists were compared with respect to their experience in managing patients with IRDs or IBDs, knowledge/training, type of invasive procedure performed, management of medical treatment, perioperative oral-care protocols, and frequency of postoperative complications after invasive dental care procedures.

Result

In total, 105 practitioners fully completed the survey (participation rate 11.1%). SDs more frequently performed invasive surgical procedures and were more aware of the recommendations of learned societies than GDs. They encountered more post-operative complications for patients on bDMARDs. For both SDs and GDs, most patients were managed without stopping treatment and pre- and postoperative antibiotics were prescribed to more than 75% of patients. When medical treatment was stopped, the decision was made by the prescribing physician.

Conclusion

Complications were reported more frequently by SDs when highly invasive procedures were performed on patients under active drug therapy. Certain common procedures, such as scaling and root planing, appear to be safe, regardless of treatment management. However, adapted guidelines for the practice of dentistry are needed to standardize the management of patients on bDMARDS, conventional DMARDs, or ISs.

Clinical relevance

French dentists perform a wide range of oral procedures on patients on bDMARDS, conventional DMARDs, or ISs under antibiotic coverage and antiseptic mouthwashes. SDs reported more postoperative complications after extensive invasive procedures for patients under active drug therapy, despite their greater knowledge of recommendations on how to manage such patients.
Laparoscopic transabdominal preperitoneal repair for female patients with groin hernias
Authors: Lin Ronggui , Lin Xianchao , Yang Yuanyuan , Wang Congfei , Fang Haizong , Chen Yanchang , Huang Heguang , Lu Fengchun
Published: August 2023

Background

Laparoscopic transabdominal preperitoneal repair (TAPP) was recommended for female patients with groin hernias. Whereas, only a few studies focused on whether and how to preserve the round ligament of the uterus in TAPP.

Methods

Clinical data of 159 female patients with 181 groin hernias who underwent TAPP at a single institution in China from January 2016 to June 2022 were retrospectively reviewed and collected.

Results

All the patients underwent the operation smoothly without conversion. Division of the round ligament was performed for 33 hernias. Preservation of the round ligament was adopted for 148 hernias, 51 with the “keyhole” technique, 86 with the “longitudinal incision of peritoneum” method, and 11 with total dissection of the round ligament. The mean operative time was 55.6 ± 8.7 min for unilateral TAPP and 99.1 ± 15.8 min for bilateral TAPP. The mean estimated blood loss was 7.1 ± 4.5 mL. The postoperative complications included 6 (3.3%) cases of seroma, 1 (0.5%) case of hematoma, and 3 (1.6%) cases of mild chronic pain. The incidences of chronic pelvic pain and genital prolapse seemed to be higher in the division group than in the preservation groups (6.1% vs. 0.6% and 3.0% vs. 0%, separately). However, no statistical difference was observed (p > 0.05).

Conclusions

TAPP is feasible and effective for female patients with groin hernias, especially in preserving the round ligament of the uterus.
Digital education for health professionals in India: a scoping review of the research
Authors: Jensen Lasse X , Buhl Alexandra , Hussain Suhaib , Karan Anup , Konradsen Flemming , Bearman Margaret
Published: August 2023

Background

The World Health Organization (WHO) predicts a global shortfall of 18 million health workers by 2030, particularly in low- and middle-income countries like India. The country faces challenges such as inadequate numbers of health professionals, poor quality of personnel, and outdated teaching styles. Digital education may address some of these issues, but there is limited research on what approaches work best in the Indian context. This paper conducts a scoping review of published empirical research related to digital health professions education in India to understand strengths, weaknesses, gaps, and future research opportunities.

Methods

We searched four databases using a three-element search string with terms related to digital education, health professions, and India. Data was extracted from 36 included studies that reported on empirical research into digital educational innovations in the formal health professions education system of India. Data were analysed thematically.

Results

Most study rationales related to challenges facing the Indian health care system, rather than a wish to better understand phenomena related to teaching and learning. Similarly, most studies can be described as general evaluations of digital educational innovations, rather than educational research per se. They mostly explored questions related to student perception and intervention effectiveness, typically in the form of quantitative analysis of survey data or pre- and post-test results.

Conclusions

The analysis revealed valuable insights into India-specific needs and challenges. The Indian health professions education system's size and unique challenges present opportunities for more nuanced, context-specific investigations and contributions to the wider digital education field. This, however, would require a broadening of methodological approaches, in particular rigorous qualitative designs, and a focus on addressing research-worthy educational phenomena.
The protocol of DECO-MOM: a clinical trial testing the effectiveness of a mobile application for an environmental health intervention among pregnant women
Authors: Kim Hyun Kyoung
Published: August 2023

Background

Environmental toxins are particularly harmful to pregnant women and their fetuses due to the long-term effects of these toxins on children after birth. Environmental health behaviors can prevent and protect mothers and their babies’ environmental health.

Methods/Design

This study presents a protocol for a double-blinded randomized controlled trial to examine the effect of a mobile application named “DECO-MOM” (Deep ECOlogy-MOM) for pregnant women. This application contains content related to environmental perceptions and behaviors according to the revised protection motivation theory. The mobile intervention will be implemented for 4 weeks for 40 pregnant women with a gestational age in the first trimester. As the control group, 40 pregnant women will be recruited at public healthcare centers in Chuncheon and Gongju in South Korea. The hypothesis is that the experimental group will have higher scores for environmental perceptions and behaviors than the control group. An online survey administered before and after the intervention will contain outcome parameters including depression, stress, quality of life, e-learning satisfaction, environmental perceptions, and environmental behaviors.

Discussion

This study will elaborate a guide for an intervention to enhance the effects of the mobile application on strengthening environmental health perceptions, behaviors, e-learning satisfaction, and quality of life and curtailing depression and stress among pregnant women.

Trial registration

Trial registration Number: KCT0007725, Registered September 22, 2022. Prospectively registered.
Factors influencing parent-child relationships in chinese nurses: a cross-sectional study
Authors: Huang Lei , Huang Xia , Wang Jingjun , Zhang Fengjian , Fei Yang , Tang Jie , Wang Ya
Published: August 2023

Background

With the development of the social economy, the effective coordination of the conflict between work and family has become an urgent problem for most parents. Such conflicts are especially acute in the families of nurses with children. Therefore, a timely understanding of the status quo of the parent-child relationship and associated risk factors among nurses will assist in improving their family harmony and the healthy growth of their children.

Methods

A total of 350 nurses with children at a general tertiary hospital in Sichuan Province, China, were interviewed using a structured questionnaire between June 23 and July 9, 2022. The results were analyzed by multiple linear regression using the stepwise method.

Results

The results showed that the parent-child relationship received a middle-level mean score of 77.74 (SD = 10.77). The factors that influenced the parent-child relationship among nurses included the parents’ character type (β = 0.143, P = 0.002), feeling tired due to dealing with patients (β=-0.150, P = 0.002), the nurse-patient relationship (β = 0.137, P = 0.004), the age of older children (β=-0.153, P = 0.001), number of children (β=-0.093, P = 0.041), sleep quality (β = 0.116, P = 0.014), and family adaptability (β = 0.308, P = 0.000); these factors accounted for 31.3% of the variance in parent-child relationships among nurses.

Conclusion

The findings of this study will help policy makers and nursing managers to better understand parent-child relationships in Chinese nurses. The results highlighted the importance of the creation of a family-oriented work environment while paying more attention to the parent-child relationships of nurses who are introverted and have more or older children. After busy workdays, nurses should also be encouraged to participate more in family decision-making and strategic parent-child interactions to avoid negative effects on children caused by work-related emotional exhaustion, physical and mental fatigue, and other reasons. The development of good parent-child relationships may help maintain both their and their children’s mental health while enhancing their enthusiasm for work and their professional identity.
Quality of care during rural care transitions: a qualitative study on structural conditions
Authors: Winqvist Idun , Näppä Ulla , Häggström Marie
Published: August 2023

Background

Registered nurses are critical for the delivery of high-quality healthcare during care transitions from hospital to home. Older co-morbid patients are most vulnerable during these transitions. A growing population of older adults with a higher prevalence of diseases implies increased demands on healthcare and its quality, which is affected by the environment where healthcare is provided. One can draw inferences on the quality of care when classified into structure, process, and outcome. This study explored registered nurses’ perspectives on structural conditions that promote or hinder good quality care during transitions from hospital to home healthcare in rural areas.

Methods

We conducted a reflexive thematic analysis of interviews with 21 registered nurses experienced in care transitions from hospital to home healthcare in a rural area of Sweden. We based the theoretically driven analysis on Donabedian’s definition of structures regarding the quality of care.

Results

The structural conditions were represented by three themes; (I) “Distances and inaccessibility” explains physical matters such as geographical (in)accessibility, bed (un)availability and electronic aids. (II) “Competence of the actors” explains continuity, knowledge and collaboration among the individuals involved. (III) “Levels of organizational governance” explains laws, expectations, values, and agreements regarding care transitions. All themes involved promoting and hindering factors, mutually influencing aspects of the others.

Conclusions

Care actors, educators, managers, and decision-makers need to understand how structures in the physical, social and symbolic environment interactively affect the quality of care during care transitions since understanding this is a prerequisite for improvements. These aspects must be considered to optimize conditions for high-quality care transitions from hospital to rural home healthcare and implemented continuously to improve transitions within the respective organization and inter-organizationally. According to this study, these aspects are critical in a rural context due to structural care quality influencers such as geographical challenges, difficulties in finding competent staff members, development of technical devices, and access to the Internet.
Women’s experience of the health information process involving a digital information tool before commencing radiation therapy for breast cancer: a deductive interview study
Authors: Grynne Annika , Wångdahl Josefin , Fristedt Sofi , Smith Frida , Browall Maria
Published: August 2023

Background

Individuals undergoing radiation therapy for breast cancer frequently request information before, throughout and after the treatment as a means to reduce distress. Nevertheless, the provision of information to meet individuals needs from their level of health literacy is often overlooked. Thus, individuals information needs are often unmet, leading to reports of discontent. Internet and digital information technology has significantly augmented the available information and changed the way in which persons accesses and comprehends information. As health information is no longer explicitly obtained from healthcare professionals, it is essential to examine the sequences of the health information process in general, and in relation to health literacy. This paper reports on qualitative interviews, targeting women diagnosed with breast cancer who were given access to a health information technology tool, Digi-Do, before commencing radiation therapy, during, and after treatment.

Methods

A qualitative research design, inspired by the integrated health literacy model, was chosen to enable critical reflection by the participating women. Semi-structured interviews were conducted with 15 women with access to a digital information tool, named Digi-Do, in addition to receiving standard information (oral and written) before commencing radiation therapy, during, and after treatment. A deductive thematic analysis process was conducted.

Results

The results demonstrate how knowledge, competence, and motivation influence women’s experience of the health information process. Three main themes were found: Meeting interactive and personal needs by engaging with health information; Critical recognition of sources of information; and Capability to communicate comprehended health information. The findings reflect the women’s experience of the four competencies: to access, understand, appraise, and apply, essential elements of the health information process.

Conclusions

We can conclude that there is a need for tailored digital information tools, such as the Digi-Do, to enable iterative access and use of reliable health information before, during and after the radiation therapy process. The Digi-Do can be seen as a valuable complement to the interpersonal communication with health care professionals, facilitating a better understanding, and enabling iterative access and use of reliable health information before, during and after the radiotherapy treatment. This enhances a sense of preparedness before treatment starts.
An application of the density standard and scaled–pixel–counting protocol to assess the radiodensity of equine incisor teeth affected by resorption and hypercementosis: preliminary advancement in dental radiography
Authors: Górski Kamil , Borowska Marta , Turek Bernard , Pawlikowski Marek , Jankowski Krzysztof , Bereznowski Andrzej , Polkowska Izabela , Domino Małgorzata
Published: August 2023

Background

Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) syndrome is a dental disease where the radiographic signs may be quantified using radiographic texture features. This study aimed to implement the scaled–pixel–counting protocol to quantify and compare the image structure of teeth and the density standard in order to improve the identification of the radiographic signs of tooth resorption and hypercementosis using the EOTRH syndrome model.

Methods and results

A detailed examination of the oral cavity was performed in 80 horses and maxillary incisor teeth were evaluated radiographically, including an assessment of the density standard. On each of the radiographs, pixel brightness (PB) was extracted for each of the ten steps of the density standard (S1–S10). Then, each evaluated incisor tooth was assigned to one of 0–3 EOTRH grade–related groups and annotated using region of interest (ROI). For each ROI, the number of pixels (NP) from each range was calculated. The linear relation between an original X–ray beam attenuation and PB was confirmed for the density standard. The NP values increased with the number of steps of the density standard as well as with EOTRH degrees. Similar accuracy of the EOTRH grade differentiation was noted for data pairs EOTRH 0–3 and EOTRH 0–1, allowing for the differentiation of both late and early radiographic signs of EOTRH.

Conclusion

The scaled–pixel–counting protocol based on the use of density standard has been successfully implemented for the differentiation of radiographic signs of EOTRH degrees.
Circulating tumour DNA alterations: emerging biomarker in head and neck squamous cell carcinoma
Authors: Huang Xiaomin , Duijf Pascal H. G. , Sriram Sharath , Perera Ganganath , Vasani Sarju , Kenny Lizbeth , Leo Paul , Punyadeera Chamindie
Published: August 2023

Head and Neck cancers (HNC) are a heterogeneous group of upper aero-digestive tract cancer and account for 931,922 new cases and 467,125 deaths worldwide. About 90% of these cancers are of squamous cell origin (HNSCC). HNSCC is associated with excessive tobacco and alcohol consumption and infection with oncogenic viruses. Genotyping tumour tissue to guide clinical decision-making is becoming common practice in modern oncology, but in the management of patients with HNSCC, cytopathology or histopathology of tumour tissue remains the mainstream for diagnosis and treatment planning. Due to tumour heterogeneity and the lack of access to tumour due to its anatomical location, alternative methods to evaluate tumour activities are urgently needed. Liquid biopsy approaches can overcome issues such as tumour heterogeneity, which is associated with the analysis of small tissue biopsy. In addition, liquid biopsy offers repeat biopsy sampling, even for patients with tumours with access limitations. Liquid biopsy refers to biomarkers found in body fluids, traditionally blood, that can be sampled to provide clinically valuable information on both the patient and their underlying malignancy. To date, the majority of liquid biopsy research has focused on blood-based biomarkers, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and circulating microRNA. In this review, we will focus on ctDNA as a biomarker in HNSCC because of its robustness, its presence in many body fluids, adaptability to existing clinical laboratory-based technology platforms, and ease of collection and transportation. We will discuss mechanisms of ctDNA release into circulation, technological advances in the analysis of ctDNA, ctDNA as a biomarker in HNSCC management, and some of the challenges associated with translating ctDNA into clinical and future perspectives. ctDNA provides a minimally invasive method for HNSCC prognosis and disease surveillance and will pave the way in the future for personalized medicine, thereby significantly improving outcomes and reducing healthcare costs.
Use of the mCherry fluorescent protein to optimize the expression of class I lanthipeptides in Escherichia coli
Authors: Van Zyl Winschau F , Van Staden Anton D. , Dicks Leon M T. , Trindade Marla
Published: August 2023

Background

Lanthipeptides are a rapidly expanding family of ribosomally synthesized and post-translationally modified natural compounds with diverse biological functions. Lanthipeptide structural and biosynthetic genes can readily be identified in genomic datasets, which provides a substantial repository for unique peptides with a wide range of potentially novel bioactivities. To realize this potential efficiently optimized heterologous production systems are required. However, only a few class I lanthipeptides have been successfully expressed using Escherichia coli as heterologous producer. This may be attributed to difficulties experienced in the co-expression of structural genes and multiple processing genes as well as complex optimization experiments.

Results

Here, an optimized modular plasmid system is presented for the complete biosynthesis for each of the class I lanthipeptides nisin and clausin, in E. coli. Genes encoding precursor lanthipeptides were fused to the gene encoding the mCherry red fluorescent protein and co-expressed along with the required synthetases from the respective operons. Antimicrobially active nisin and clausin were proteolytically liberated from the expressed mCherry fusions. The mCherry-NisA expression system combined with in vivo fluorescence monitoring was used to elucidate the effect of culture media composition, promoter arrangement, and culture conditions including choice of growth media and inducer agents on the heterologous expression of the class I lanthipeptides. To evaluate the promiscuity of the clausin biosynthetic enzymes, the optimized clausin expression system was used for the heterologous expression of epidermin.

Conclusion

We succeeded in developing novel mCherry-fusion based plug and play heterologous expression systems to produce two different subgroups of class I lanthipeptides. Fully modified Pre-NisA, Pre-ClausA and Pre-EpiA fused to the mCherry fluorescence gene was purified from the Gram-negative host E. coli BL21 (DE3). Our study demonstrates the potential of using in vivo fluorescence as a platform to evaluate the expression of mCherry-fused lanthipeptides in E. coli. This allowed a substantial reduction in optimization time, since expression could be monitored in real-time, without the need for extensive and laborious purification steps or the use of in vitro activity assays. The optimized heterologous expression systems developed in this study may be employed in future studies for the scalable expression of novel NisA derivatives, or novel genome mined derivatives of ClausA and other class I lanthipeptides in E. coli.
Association of fine particulate matter and its constituents with hypertension: the modifying effect of dietary patterns
Authors: Huang Kun , Yu Dongmei , Fang Hongyun , Ju Lahong , Piao Wei , Guo Qiya , Xu Xiaoli , Wei Xiaoqi , Yang Yuxiang , Zhao Liyun
Published: August 2023

Background

Studies have shown that nutritional supplements could reduce the adverse effects induced by air pollution. However, whether dietary patterns can modify the association of long-term exposure to fine particulate matter (PM2.5) and its constituents with hypertension defined by the 2017 ACC/AHA guideline has not been evaluated.

Methods

We included 47,501 Chinese adults from a nationwide cross-sectional study. PM2.5 and five constituents were estimated by satellite-based random forest models. Dietary approaches to stop hypertension (DASH) and alternative Mediterranean diet (AMED) scores were calculated for each participant. Interactions between dietary patterns and air pollution were examined by adding a multiplicative interaction term to logistic models.

Results

Long-term exposure to PM2.5 and its constituents was associated with an increased risk of hypertension and stage 1–2 hypertension. The DASH and AMED scores significantly modified these associations, as individuals with higher scores had a significantly lower risk of air pollution-related hypertension and stage 1–2 hypertension (P-interaction < 0.05), except for interaction between PM2.5, sulfate, nitrate, ammonium, and AMED score on stage 1 hypertension. For each IQR increase in PM2.5, participants with the lowest DASH and AMED quintiles had hypertension risk with ORs (95%CI) of 1.20 (1.10, 1.30) and 1.19 (1.09, 1.29), whereas those with the highest DASH and AMED quintiles had lower risks with 0.98 (0.91, 1.05) and 1.04 (0.97, 1.11). The stratified analysis found modification effect was more prominent in the < 65 years age group. Consuming more fresh vegetables, fruits, whole grains, and dairy would reduce the risk of hypertension caused by PM2.5 and its constituents.

Conclusions

Dietary patterns rich in antioxidants can reduce long-term exposure to PM2.5 and its constituents-induced hypertension defined by the 2017 ACC/AHA guideline, especially in young and middle-aged individuals. Compared to the Mediterranean diet, the DASH diet offers superior dietary guidance to prevent stage 1 hypertension caused by air pollution.
Translation and evaluation of the HeartQoL in patients with coronary heart disease in Iceland
Authors: Svavarsdóttir Margrét Hrönn , Ingadottir Brynja , Oldridge Neil , Årestedt Kristofer
Published: August 2023

Background

Health-related quality of life (HRQoL) reflects an individual’s own perception of their symptom burden, functional limitations, prognosis, overall health and changes associated with treatment. The HeartQoL is a validated heart disease-specific questionnaire with a physical and an emotional subscale that is used internationally to assess HRQoL in patients with coronary heart disease (CHD). The aim of this study was to translate and evaluate the psychometric properties of the HeartQoL in patients with CHD in Iceland.

Methods

Patients ≥ 18 years (n = 396; mean age 64.4 ± 8.8 years; 79.6% male) admitted with CHD were recruited from two hospitals in Iceland and completed the Icelandic versions of the HeartQoL, Short-Form 12v2 Health Survey (SF-12v2), and Hospital Anxiety and Depression Scale (HADS). A subsample of 47 patients completed the HeartQoL 14 days later. Confirmatory factor analysis for ordinal data was used to evaluate the measurement model with a physical and an emotional subscale. Convergent and divergent validity, internal consistency, and test-retest reliability were evaluated.

Results

Overall, the hypothesized two-factor structure of the Icelandic version of the HeartQoL was supported. However, problems with cross-loadings and correlated error variances were identified. Convergent and divergent validity were supported in correlational analyses between HeartQoL, SF-12v2, and HADS. Internal consistency reliability, measured by ordinal alpha, was good for the physical (α = 0.96) and emotional (α = 0.90) subscale. According to intraclass correlations (ICC), acceptable test-retest reliability was demonstrated (ICC = 0.79–0.86).

Conclusion

With the two-factor structure confirmed, the Icelandic HeartQoL demonstrated satisfactory psychometric properties in the sample of patients with CHD. Users of the instrument can use the original scoring.
SARS-CoV-2-associated organs failure and inflammation: a focus on the role of cellular and viral microRNAs
Authors: Rasizadeh Reyhaneh , Aghbash Parisa Shiri , Nahand Javid Sadri , Entezari-Maleki Taher , Baghi Hossein Bannazadeh
Published: August 2023

SARS-CoV-2 has been responsible for the recent pandemic all over the world, which has caused many complications. One of the hallmarks of SARS-CoV-2 infection is an induced immune dysregulation, in some cases resulting in cytokine storm syndrome, acute respiratory distress syndrome and many organs such as lungs, brain, and heart that are affected during the SARS-CoV-2 infection. Several physiological parameters are altered as a result of infection and cytokine storm. Among them, microRNAs (miRNAs) might reflect this poor condition since they play a significant role in immune cellular performance including inflammatory responses. Both host and viral-encoded miRNAs are crucial for the successful infection of SARS-CoV-2. For instance, dysregulation of miRNAs that modulate multiple genes expressed in COVID-19 patients with comorbidities (e.g., type 2 diabetes, and cerebrovascular disorders) could affect the severity of the disease. Therefore, altered expression levels of circulating miRNAs might be helpful to diagnose this illness and forecast whether a COVID-19 patient could develop a severe state of the disease. Moreover, a number of miRNAs could inhibit the expression of proteins, such as ACE2, TMPRSS2, spike, and Nsp12, involved in the life cycle of SARS-CoV-2. Accordingly, miRNAs represent potential biomarkers and therapeutic targets for this devastating viral disease. In the current study, we investigated modifications in miRNA expression and their influence on COVID-19 disease recovery, which may be employed as a therapy strategy to minimize COVID-19-related disorders.
Targeted mRNA demethylation in Arabidopsis using plant m6A editor
Authors: Fang Ruiqiu , Chen Xiaolong , Shen Jie , Wang Bin
Published: August 2023

Background

N6-methyladenosine (m6A) is an important epigenetic modification involved in RNA stability and translation regulation. Manipulating the expression of RNA m6A methyltransferases or demethylases makes it difficult to study the effect of specific RNA methylation.

Results

In this study, we report the development of Plant m6A Editors (PMEs) using dLwaCas13a (from L. wadei) and human m6A demethylase ALKBH5 catalytic domain. PMEs specifically demethylates m6A of targeted mRNAs (WUS, STM, FT, SPL3 and SPL9) to increase mRNAs stability. In addition, we discovered that a double ribozyme system can significantly improve the efficiency of RNA editing.

Conclusion

PMEs specifically demethylates m6A of targeted mRNAs to increase mRNAs stability, suggesting that this engineered tool is instrumental for biotechnological applications.
CircECE1 promotes osteosarcoma progression through regulating RAB3D by sponging miR-588
Authors: Liang Zhizhong , Shi Yuxia , Guan Zhe
Published: August 2023

Background

Circular RNAs (circRNAs) have been confirmed to be involved in cancer pathogenesis. However, the underlying mechanism of circRNA endothelin converting enzyme 1 (circECE1) in osteosarcoma (OS) development is still not understood.

Methods

The expression levels of circECE1, microRNA-588 (miR-588) and RAB3D, member RAS oncogene family (RAB3D) were gauged by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. OS cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and 5-ethynyl-2’-deoxyuridine (EdU) assay. OS cell apoptosis rate and metastasis were identified by flow cytometry and transwell assay. Dual-luciferase reporter analysis and RNA immunoprecipitation (RIP) assay were performed to confirm the interactions among circECE1, miR-588 and RAB3D. Xenograft tumor models were established to explore circECE1 function in vivo. Immunohistochemistry (IHC) assay was applied to analyze RAB3D level after circECE1 knockdown.

Results

In OS, circECE1 expression was higher than that in normal chondroma tissues. High levels of circECE1 were positively linked to OS cell viability, proliferation, migration and invasion, and negatively linked to OS cell apoptosis rate. It was found that circECE1 was a miR-588 sponge, and miR-588 inhibitor abrogated the influence of si-circECE1 on OS cells. MiR-588 targeted RAB3D to further regulate the pathological process of OS. Moreover, silencing circECE1 blocked OS tumor growth in vivo.

Conclusion

We elucidated the function of a novel circECE1/miR-588/RAB3D axis in OS progression.
Macrophage-organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance
Authors: Jiang Shengwei , Deng Tingwei , Cheng Huan , Liu Weihan , Shi Dan , Yuan Jiahui , He Zhiwei , Wang Weiwei , Chen Boning , Ma Li , Zhang Xianbin , Gong Peng
Published: August 2023

Background

Gemcitabine resistance (GR) is a significant clinical challenge in pancreatic adenocarcinoma (PAAD) treatment. Macrophages in the tumor immune-microenvironment are closely related to GR. Uncovering the macrophage-induced GR mechanism could help devise a novel strategy to improve gemcitabine treatment outcomes in PAAD. Therefore, preclinical models accurately replicating patient tumor properties are essential for cancer research and drug development. Patient-derived organoids (PDOs) represent a promising in vitro model for investigating tumor targets, accelerating drug development, and enabling personalized treatment strategies to improve patient outcomes.

Methods

To investigate the effects of macrophage stimulation on GR, co-cultures were set up using PDOs from three PAAD patients with macrophages. To identify signaling factors between macrophages and pancreatic cancer cells (PCCs), a 97-target cytokine array and the TCGA-GTEx database were utilized. The analysis revealed CCL5 and AREG as potential candidates. The role of CCL5 in inducing GR was further investigated using clinical data and tumor sections obtained from 48 PAAD patients over three years, inhibitors, and short hairpin RNA (shRNA). Furthermore, single-cell sequencing data from the GEO database were analyzed to explore the crosstalk between PCCs and macrophages. To overcome GR, inhibitors targeting the macrophage-CCL5-Sp1-AREG feedback loop were evaluated in cell lines, PDOs, and orthotopic mouse models of pancreatic carcinoma.

Results

The macrophage-CCL5-Sp1-AREG feedback loop between macrophages and PCCs is responsible for GR. Macrophage-derived CCL5 activates the CCR5/AKT/Sp1/CD44 axis to confer stemness and chemoresistance to PCCs. PCC-derived AREG promotes CCL5 secretion in macrophages through the Hippo-YAP pathway. By targeting the feedback loop, mithramycin improves the outcome of gemcitabine treatment in PAAD. The results from the PDO model were corroborated with cell lines, mouse models, and clinical data.

Conclusions

Our study highlights that the PDO model is a superior choice for preclinical research and precision medicine. The macrophage-CCL5-Sp1-AREG feedback loop confers stemness to PCCs to facilitate gemcitabine resistance by activating the CCR5/AKT/SP1/CD44 pathway. The combination of gemcitabine and mithramycin shows potential as a therapeutic strategy for treating PAAD in cell lines, PDOs, and mouse models.
Fibronectin fragments generated by pancreatic trypsin act as endogenous inhibitors of pancreatic tumor growth
Authors: Resovi Andrea , Persichitti Perla , Brunelli Laura , Minoli Lucia , Borsotti Patrizia , Garattini Giulia , Tironi Matteo , Dugnani Erica , Redegalli Miriam , De Simone Giulia , Pastorelli Roberta , Bani Maria Rosa , Piemonti Lorenzo , Mosher Deane F. , Giavazzi Raffaella , Taraboletti Giulia , Belotti Dorina
Published: August 2023

Background

The pancreatic microenvironment has a defensive role against cancer but it can acquire tumor-promoting properties triggered by multiple mechanisms including alterations in the equilibrium between proteases and their inhibitors. The identification of proteolytic events, targets and pathways would set the basis for the design of new therapeutic approaches.

Methods and results

Here we demonstrate that spheroids isolated from human and murine healthy pancreas and co-transplanted orthotopically with pancreatic ductal adenocarcinoma (PDAC) in mouse pancreas inhibited tumor growth. The effect was mediated by trypsin-generated fibronectin (FN) fragments released by pancreatic spheroids. Tumor inhibition was observed also in a model of acute pancreatitis associated with trypsin activation. Mass spectrometry proteomic analysis of fragments and mAb against different FN epitopes identified the FN type III domain as responsible for the activity. By inhibiting integrin α5β1, FAK and FGFR1 signaling, the fragments induced tumor cell detachment and reduced cell proliferation. Consistent with the mutual relationship between the two pathways, FGF2 restored both FGFR1 and FAK signaling and promoted PDAC cell adhesion and proliferation. FAK and FGFR inhibitors additively inhibited PDAC growth in vitro and in orthotopic in vivo models.

Conclusions

This study identifies a novel role for pancreatic trypsin and fibronectin cleavage as a mechanism of protection against cancer by the pancreatic microenvironment. The finding of a FAK-FGFR cross-talk in PDAC support the combination of FAK and FGFR inhibitors for PDAC treatment to emulate the protective effect of the normal pancreas against cancer.