bluuebunny/crossref_metadata_2025 huggingface dataset:
Global DNA methylation and telomere length as markers of accelerated aging in people living with HIV and non-alcoholic fatty liver disease
Authors: Moreno Elena , Martínez-Sanz Javier , Martín-Mateos Rosa , Díaz-Álvarez Jorge , Serrano-Villar Sergio , Burgos-Santamaría Diego , Luna Laura , Vivancos María Jesús , Moreno-Zamora Ana , Pérez-Elías María Jesús , Moreno Santiago , Dronda Fernando , Montes María Luisa , Sánchez-Conde Matilde
Published: September 2023

Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system aging. In this prospective cohort study, we describe a straightforward methodology for quantifying biomarkers of aging, such as DNA methylation and telomere length, in PLWH and in the context of another relevant condition, such as MAFLD. Fifty-seven samples in total, thirty-eight from PLWH and nineteen from non-PLWH participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). Global DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. Our results show an increased association of these biomarkers in PLWH regardless of their MAFLD status. Thus, we propose including the quantification of these age-related factors in studies of comorbidities. This will allow a better understanding of the effect of comorbidities of HIV infection and MAFLD and prevent their effects in these populations in the future.
Genome-wide identification of the longan R2R3-MYB gene family and its role in primary and lateral root
Authors: Lv Xinmin , Tian Shichang , Huang Shilian , Wei Junbin , Han Dongmei , Li Jianguang , Guo Dongliang , Zhou Yan
Published: September 2023

R2R3-MYB is an important transcription factor family that regulates plant growth and development. Root development directly affects the absorption of water and nutrients by plants. Therefore, to understand the regulatory role of R2R3-MYB transcription factor family in root development of longan, this study identified the R2R3-MYB gene family members at the genome-wide level, and analyzed their phylogenetic characteristics, physical and chemical properties, gene structure, chromosome location and tissue expression. The analysis identified 124 R2R3-MYB family members in the longan genome. Phylogenetic analysis divided these members into 22 subfamilies, and the members of the unified subfamily had similar motifs and gene structures. The result of qRT-PCR showed that expression levels of DlMYB33, DlMYB34, DlMYB59, and DlMYB77 were significantly higher in main roots than in lateral as opposed to those of DlMYB35, DlMYB69, DlMYB70, and DlMYB83, which were significantly lower. SapBase database prediction and miRNAs sequencing results showed that 34 longan miRNAs could cleave R2R3-MYB, including 17 novel miRNAs unique to longan. The qRT-PCR and subcellular localization experiments of DlMYB92 and DlMYB98 showed that DlMYB92 is a key factor that regulates transcription in the nucleus and participates in the regulation of longan lateral root development. Longan also has a conserved miRNA-MYB-lateral root development regulation mechanism. This study provides a reference for further research on the transcriptional regulation of the miRNA-R2R3-MYB module in the root development of longan.
Mealtime interactions between nursing home staff and residents with dementia: a behavioral analysis of Language characteristics
Authors: Liu Wen , Jao Ying-Ling , Paudel Anju , Yoon Si On
Published: September 2023

Background

Quality staff-resident communication is crucial to promote outcomes in nursing home residents with dementia requiring assistance during mealtimes. Better understanding of staff-resident language characteristics in mealtime interactions help promote effective communication, yet evidence is limited. This study aimed to examine factors associated with language characteristics in staff-resident mealtime interactions.

Methods

This was a secondary analysis of 160 mealtime videos involving 36 nursing staff and 27 residents with moderately severe to severe dementia in 9 nursing homes. Mixed-effects models was used to examine the relationships between factors and language characteristics in staff-resident mealtime interactions. The independent variables were speaker (resident vs. staff), utterance quality (negative vs. positive), intervention (pre- vs. post-communication intervention), and resident dementia stage and comorbidities. The dependent variables were expression length (number of words in each utterance) and addressing partner by name (whether staff or resident named their partner in each utterance). All models included staff, resident, and staff-resident dyad as random effects.

Results

Staff (utterance n = 2990, 99.1% positive, mean = 4.3 words per utterance) predominated conversations and had more positive, longer utterances than residents (utterance n = 890, 86.7% positive, mean = 2.6 words per utterance). As residents progressed from moderately severe to severe dementia, both residents and staff produced shorter utterances (z=-2.66, p = .009). Staff (18%) named residents more often than residents (2.0%; z = 8.14, p < .0001) and when assisting residents with more severe dementia (z = 2.65, p = .008).

Conclusions

Staff-resident communication was primarily positive, staff-initiated, and resident-oriented. Utterance quality and dementia stage were associated with staff-resident language characteristics. Staff play a critical role in mealtime care communication and should continue to initiate resident-oriented interactions using simple, short expressions to accommodate resident declining language abilities, particularly those with severe dementia. Staff should practice addressing residents by their names more frequently to promote individualized, targeted, person-centered mealtime care. Future work may further examine staff-resident language characteristics at other levels of language using more diverse samples.
A survey of Australian women’s digital media usage in pregnancy and labour and birth
Authors: Hussain Ilyana Mohamed , Hartney Nicki , Sweet Linda
Published: September 2023

Background

Given the rapid growth of digital media resources, it is worth exploring childbearing women’s use of digital media to address their information needs. The aim of this study was to explore the use of digital media during pregnancy and birth in the local population of Western Victorian women in Melbourne, Australia.

Methods

A descriptive exploratory approach was used. An online survey consisted of both quantitative and qualitative questions to identify and measure digital media use in pregnancy and the birthing period. Descriptive statistics and Pearson Chi-square test were used to analyse the quantitative data, while content analysis was used to analyse the qualitative data.

Results

Digital media has become an integral part of the experience in pregnancy with increasing growth of digital media in labour. The most used medium for digital media use was pregnancy applications, followed by websites, social media, YouTube, podcasts, online discussion forums and lastly, labour applications. Information seeking was the main reason for using digital media, and two main themes emerged from the qualitative data; ‘connection with others for social support and reassurance’ and ‘information seeking and providing to assist decision making and providing reassurance’.

Conclusion

This study highlights the need for future midwifery practice to include digital media sources in antenatal education and care. There is a need for healthcare institutions to improve digital media technology to meet the needs of women. This is crucial as digital media is constantly evolving, and as healthcare providers, we need to integrate digital media with healthcare services.
Predictive effects of platelet-to-lymphocyte ratio on neonatal thrombocytopenia in primary immune thrombocytopenic mothers: a retrospective cohort study
Authors: Qionghui Huang , Chaomei Zeng , Jie Liu , Jiong Qin
Published: September 2023

Background

Primary immune thrombocytopenia (ITP) can increase the risk of neonatal thrombocytopenia (NT). This study aimed to investigate the key factors for predicting the risk of NT.

Methods

Data were retrospectively collected from all pregnant women with ITP from 2015 to 2021. Newborns were divided into two groups according to the presence or absence of NT. The parameters between the two groups were then compared. Next, the correlation between maternal platelet-to-lymphocyte ratio (PLR) and neonatal platelet count was analyzed by logistic regression and generalized additive model. Additionally, the relationships among the platelet counts of siblings were also determined.

Results

A total of 147 maternal cases were included. NT was observed in 46 (31.72%) neonates. A history of previous children with NT appeared to have predictive value for NT (OR 16.484, 95% CI 2.212–122.858, P < 0.001), as the nadir gestational platelet (OR 0.958, 95% CI 0.93–0.988, P < 0.001). Correlation analysis of platelet count on postnatal day 1 and the nadir platelet count in 36 sibling neonates showed a positive correlation (r=0.684, P<0.001; r=0.900, P<0.05). PLR was divided into 3 groups via tertiles, and the incidence of NT was dramatically higher in the group with lower PLR during the second and third trimesters than in the other two groups (48.5% vs 33.3% vs 22%, P<0.05; 50% vs 21.3% vs 26.7%, P<0.001). Moreover, the risk of NT was markedly higher in the first trimester (PLR < 78.51; OR 0.975, 95% CI 0.951–0.999, P<0.05) and the second trimester (PLR < 20.41; OR, 0.899, 95% CI 0.820–0.985, P<0.05) compared to the third trimester.

Conclusion

Our findings suggest that a history of previous children with NT is a significant factor for predicting NT in subsequent pregnancies. PLR in the first, second and third trimesters can also be used as a reference to predict NT risk.
Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox®) and focused ultrasound
Authors: Spiers Laura , Gray Michael , Lyon Paul , Sivakumar Shivan , Bekkali Noor , Scott Shaun , Collins Linda , Carlisle Robert , Wu Feng , Middleton Mark , Coussios Constantin
Published: September 2023

Background

The dense stroma of pancreatic ductal adenocarcinomas is a major barrier to drug delivery. To increase the local drug diffusion gradient, high doses of chemotherapeutic agent doxorubicin can be released from thermally-sensitive liposomes (ThermoDox®) using ultrasound-mediated hyperthermia at the tumour target. PanDox is designed as a Phase 1 single centre study to investigate enhancing drug delivery to adult patients with non-operable pancreatic ductal adenocarcinomas. The study compares a single cycle of either conventional doxorubicin alone or ThermoDox® with focused ultrasound-induced hyperthermia for targeted drug release.

Methods

Adults with non-resectable pancreatic ductal adenocarcinoma are allocated to receive a single cycle of either doxorubicin alone (Arm A) or ThermoDox® with focused ultrasound-induced hyperthermia (Arm B), based on patient- and tumour-specific safety conditions. Participants in Arm B will undergo a general anaesthetic and pre-heating of the tumour by extra-corporal focused ultrasound (FUS). Rather than employing invasive thermometry, ultrasound parameters are derived from a patient-specific treatment planning model to reach the 41 °C target temperature for drug release. ThermoDox® is then concurrently infused with further ultrasound exposure. Tumour biopsies at the targeted site from all patients are analysed post-treatment using high performance liquid chromatography to quantify doxorubicin delivered to the tumour. The primary endpoint is defined as a statistically significant enhancement in concentration of total intra-tumoural doxorubicin, comparing samples from patients receiving liposomal drug with FUS to free drug alone. Participants are followed for 21 days post-treatment to assess secondary endpoints, including radiological assessment to measure changes in tumour activity by Positron Emission Tomography Response Criteria in Solid Tumours (PERCIST) criteria, adverse events and patient-reported symptoms.

Discussion

This early phase study builds on previous work targeting tumours in the liver to investigate whether enhancement of chemotherapy delivery using ultrasound-mediated hyperthermia can be translated to the stroma-dense environment of pancreatic ductal adenocarcinoma. If successful, it could herald a new approach towards managing these difficult-to-treat tumours.

Trial registration

ClinicalTrials.gov Identifier: NCT04852367. Registered 21st April 2022.

EudraCT number: 2019–003950-10 (Registered 2019)

Iras Project ID: 272253 (Registered 2019)

Ethics Number: 20/EE/0284.
Evaluation of sympathetic skin response for early diagnosis and follow-up of diabetic peripheral neuropathy in children
Authors: Jin Mei , Liu Jing , Liu Kang , Zhao Ziwei , Sun Suzhen
Published: September 2023

Background

The morbidity of type 1 diabetes mellitus (T1DM) in children is increasing and diabetic peripheral neuropathy (DPN) is one of the main microvascular complications of T1DM. The aim of this study was to explore sympathetic skin response (SSR) characteristics in children with T1DM and analyze the value of early diagnosis and follow-up in T1DM complicated with DPN.

Methods

Our prospective study enrolling 85 participants diagnosed with T1DM and 30 healthy controls (HCs) in the Children’s Hospital of Hebei Province from 2017 to 2020. Compared the outcomes of SSR and nerve conduction study (NCS) in T1DM, and evaluated the variations in SSR and NCS of different durations, as well as changes after six months of therapy.

Results

SSR latency of T1DM group showed statistical difference as compared to HCs (p < 0.05). The SSR test was more sensitive than the NCS test in the early diagnosis of T1DM with DPN (p < 0.05). The abnormal rates of SSR and NCS in long duration of disease were higher than those in short duration of disease (p < 0.05). Among 65 participants with diabetic neuropathy, the onset latencies of SSR were shortened and the NCS were improved after treatment (p < 0.05).

Conclusions

SSR could provide the accurate early diagnosis and follow-up of pediatric diabetic peripheral neuropathy.
Educational interventions targeting pregnant women to optimise the use of caesarean section: What are the essential elements? A qualitative comparative analysis
Authors: Zahroh Rana Islamiah , Sutcliffe Katy , Kneale Dylan , Vazquez Corona Martha , Betrán Ana Pilar , Opiyo Newton , Homer Caroline S. E. , Bohren Meghan A.
Published: September 2023

Background

Caesarean section (CS) rates are increasing globally, posing risks to women and babies. To reduce CS, educational interventions targeting pregnant women have been implemented globally, however, their effectiveness is varied. To optimise benefits of these interventions, it is important to understand which intervention components influence success. In this study, we aimed to identify essential intervention components that lead to successful implementation of interventions focusing on pregnant women to optimise CS use.

Methods

We re-analysed existing systematic reviews that were used to develop and update WHO guidelines on non-clinical interventions to optimise CS. To identify if certain combinations of intervention components (e.g., how the intervention was delivered, and contextual characteristics) are associated with successful implementation, we conducted a Qualitative Comparative Analysis (QCA). We defined successful interventions as interventions that were able to reduce CS rates. We included 36 papers, comprising 17 CS intervention studies and an additional 19 sibling studies (e.g., secondary analyses, process evaluations) reporting on these interventions to identify intervention components. We conducted QCA in six stages: 1) Identifying conditions and calibrating the data; 2) Constructing truth tables, 3) Checking quality of truth tables; 4) Identifying parsimonious configurations through Boolean minimization; 5) Checking quality of the solution; 6) Interpretation of solutions. We used existing published qualitative evidence synthesis to develop potential theories driving intervention success.

Results

We found successful interventions were those that leveraged social or peer support through group-based intervention delivery, provided communication materials to women, encouraged emotional support by partner or family participation, and gave women opportunities to interact with health providers. Unsuccessful interventions were characterised by the absence of at least two of these components.

Conclusion

We identified four key essential intervention components which can lead to successful interventions targeting women to reduce CS. These four components are 1) group-based delivery, 2) provision of IEC materials, 3) partner or family member involvement, and 4) opportunity for women to interact with health providers. Maternal health services and hospitals aiming to better prepare women for vaginal birth and reduce CS can consider including the identified components to optimise health and well-being benefits for the woman and baby.
Clustering of health risk behaviors among school-going adolescents in Mymensingh district, Bangladesh
Authors: Kundu Lakshmi Rani , Al Masud Abdullah , Islam Zohurul , Hossain Jamil
Published: September 2023

Background

Adolescents frequently engage in risky behaviors that negatively influence their health and pose a serious public health concern. This study aimed to examine the clustering pattern of health risk behaviors among school-going adolescents in Bangladesh.

Methods

A cross-sectional study was conducted from 15 April to 27 June 2022 among 412 school-going adolescents in Mymensingh district of Bangladesh through a convenience sampling technique. Data were collected via face-to-face interviews using a modified Global School-Based Student Health Survey (GSHS) 2021 questionnaire. Cluster membership was identified using the k-means clustering algorithm. The chi-square test was adopted to explore the association between sociodemographic variables and each cluster membership. The ordinal logistic regression model was employed to examine the predictors associated with cluster membership.

Results

Most of the respondents were female (55.3%) and belonged to the 16-19 years (74.5%) age group. Three behavioral clusters were identified, including Cluster 1: Low-risk taker (50.2%), Cluster 2: Moderate risk taker (39.6%), and Cluster 3: High-risk taker (10.2%). Influential factors of high-risk behavior among adolescents were significantly associated with their age (p = 0.03), father’s education who were illiterate (p = 0.02), monthly family income >30000 BDT (p = 0.04), parent’s those were understanding their child’s problems in most of the time (p = 0.001).

Conclusions

The study found that high-risk behaviors are significantly higher among late adolescents, those whose fathers are illiterate, whose monthly income is higher, those whose parents or guardians never realize their child's complications and worries, and those whose parents or guardians never recognize what they did in their leisure time. These findings will help to develop intervention programs, policies, strategies, and curricula in school by the experts following the necessity to adopt the adolescent toward healthy behavior and help to reduce the prevalence of health risk behavior.
Patient and social factors related to nebulizer use in COPD patients at the transition of care: a qualitative study
Authors: Foster Amanda A. , Stoll Jennifer , Daly Christopher J. , Clark Collin M. , Sethi Sanjay , Jacobs David M.
Published: September 2023

Background

Transition from hospital to home is a vulnerable period for patients with COPD exacerbations, with a high risk for readmission and mortality. Twenty percent of patients with an initial hospitalization for a COPD exacerbation are readmitted to a hospital within 30 days, costing the health care system over $15 billion annually. While nebulizer therapy directed at some high-risk COPD patients may improve the transition from hospital to home, patient and social factors are likely to contribute to difficulties with their use. Current literature describing the COPD patient’s experience with utilizing nebulizer therapy, particularly during care transitions, is limited. Therefore, the objective of this study was to explore underlying COPD patient and social factors contributing to practical difficulties with nebulizer use at the care transition from hospital to home.

Methods

This was a qualitative study conducted between September 2020 and June 2022. Patients were included if they were ≥ 40 years old, had a current diagnosis of COPD, had an inpatient admission at a hospital, and were discharged directly to home with nebulizer therapy. Semi-structured, one-on-one interviews with patients were conducted covering a broad range of patient and social factors and their relationships with nebulizer use and readmission. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using a mixed inductive and deductive approach.

Results

Twenty-one interviews were conducted, and subjects had a mean age of 64 ± 8.4 years, 62% were female, and 76% were White. The predominant interview themes were health care system interactions and medication management. The interviews highlighted that discharge counseling methods and depth of counseling from hospitals were inconsistent and were not always patient-friendly. They also suggested that patients could appropriately identify, set up, and utilize their nebulizer treatment without difficulties, but additional patient education is required for nebulizer clean up and maintenance.

Conclusions

Our interviews suggest that there is room for improvement within the health care system for providing consistent, effective discharge counseling. Also, COPD patients discharged from a hospital on nebulizer therapy can access and understand their treatment but require additional education for nebulizer clean up and maintenance.
PEDF inhibits LPS-induced acute lung injury in rats and promotes lung epithelial cell survival by upregulating PPAR-γ
Authors: Xu Lei , Chen Yifei , Feng Shoujie , Liu Zeyan , Ye Ying , Zhou Ranran , Liu Lijun
Published: September 2023

Background

The progression of acute lung injury (ALI) involves numerous pathological factors and complex mechanisms, and cause the destruction of epithelial and endothelial barriers. Pigment epithelium-derived factor (PEDF) is an angiogenesis inhibitor and a potential anti-inflammatory factor. The purpose of this study was to investigate the effect of PEDF on lipopolysaccharide (LPS)-induced ALI in rats.

Methods

In vivo, pathological and injury related factors examination were performed on rat lung to investigate the effect of PEDF on ALI. In vitro, the effect of PEDF on inflammatory injury and apoptosis of lung epithelial type II RLE-6TN cell was evaluated, and the expression of inflammatory factors and related pathway proteins and PPAR-γ (in the presence or absence of PPAR-γ inhibitors) were analyzed.

Results

In vivo results showed that PEDF inhibited the inflammatory factor expression (TNF-α, IL-6 and IL-1β) and progression of ALI and reduced lung cell apoptosis in rats. In vitro results showed that PEDF could effectively inhibit LPS-stimulated inflammatory damage and apoptosis of RLE-6TN cells. PEDF inhibited the RLE-6TN cell injury by enhancing the expression of PPAR-γ.

Conclusions

PEDF is an anti-inflammatory factor, which can inhibit apoptosis of lung epithelial cells by upregulating the expression of PPAR-γ and reducing LPS-induced ALI in rats.
Ae index is an independent predictor of kidney stone recurrence in overweight and obese patients
Authors: Xia Kaiguo , Xu Yuexian , Qi Qiao , Pan Jiashan , Yao Rui , Huang Qingfeng , Hao Zongyao
Published: September 2023

Background

Finding some convenient and economical indicators to initially screen overweight and obese patients at high risk of kidney stone recurrence can help them prevent stone recurrence with lower medical cost. The purpose of this article is to determine the clinical value of Ae index (Apo B × 1000/eGFR) as an independent predictor for kidney stone recurrence in overweight and obese populations.

Methods

We queried the electronic medical records of patients with kidney stone operated at our hospital from March 2016 to March 2022, and selected BMI ≥ 25 kg/m2 as the study population and divided the patients into stone recurrence group and non-recurrence group. Relevant parameters of routine blood and biochemical test, glycated serum protein (GSP), and history of hypertension and hyperglycemia were collected. Then the Chi-square test, independent samples t-test or Wilcoxon rank-sum test were used to calculate the differences between the two groups of data. Next, we performed univariate and multivariate logistic regression analysis to screen out the most significant variables Apo B and eGFR, and then we calculated the Ae index using the formula Apo B × 1000/eGFR, and analyzed the relationship between Ae index and kidney stone recurrence.

Results

Univariate analysis found that Apo B (OR:8.376,95%CI:3.093–22.680), Creatinine (OR:1.012,95%CI:1.003–1.021), Cystatin C(OR:2.747,95%CI:1.369–5.508), LDL-C (OR:1.588,95%CI:1.182–2.134), TC (OR:1.543,95%CI:1.198–1.988) were positively associated, eGFR (OR:0.980,95%CI:0.970–0.991) was negatively associated with kidney stone recurrence. And multivariate logistic regression analysis suggested that Apo B (OR:11.028, 95%CI:3.917–31.047) and eGFR (OR:0.976, 95%CI:0.965–0.988) were the most significant factors. Then we calculated Ae index and analyzed it, the sensitivity was 74.26% and the specificity was 60.00%, higher than either individual variable. Its smoothed curve revealed a non-linear relationship between them with the inflection point of 9.16. And the OR on the left side of the inflection point was 1.574 (95% CI: 1.228–2.018), whereas the OR on the right side of the inflection point was 1.088 (95% CI: 1.007–1.177).

Conclusions

Ae index is an easily calculated and obtained index that has some predictive value for kidney stone recurrence in overweight and obese patients, which is of interest.
Tolerability of endometriosis medical treatment: a comparison between combined hormonal contraceptives and progestins
Authors: da Costa Pinheiro Denise Joffily Pereira , Pereira Ana Maria Gomes , Antonini Marcelo , Maria Albuquerque Salgado Isabella , Dias Alexandre Torchio , Lopes Reginaldo Guedes Coelho
Published: September 2023

Endometriosis is a chronic inflammatory disease that occurs in women of reproductive age. Much of the treatment involves hormone therapy that suppresses the proliferation of endometriosis lesions.

Objective To compare discontinuation rates of pharmacological treatment with estrogen-progestins and progestins medications. The secondary objective is to evaluate the main side effects of these drugs in patients with endometriosis.

Methods This retrospective study analyzed data from 330 patients who attended the Hospital of the State Public Servant of São Paulo from August 1999 to September 2020 and received pharmacological treatment for endometriosis. The data were obtained by review of the files of medical appointments with specialized staff.

Results The median treatment time was 18 months, ranging from 1 to 168 months, and 177 patients interrupted the proposed treatment. The combined contraceptives with estrogens and progestins were significantly linked to treatment interruption, with a relative risk of 1,99 (p = 0,005). The most important side effects that resulted in treatment interruption were pain persistence (p = 0,043), weight gain (p = 0,017) and spotting (p < 0,001).
Exploring individual character traits and behaviours of clinical academic allied health professionals: a qualitative study
Authors: King Elizabeth , Cordrey Terry , Gustafson Owen
Published: September 2023

Background

Clinical academic allied health professionals can positively impact patient care, organisational performance, and local research culture. Despite a previous national drive to increase these roles, they remain low in number with no clear strategy for growth. Reported barriers to this growth cite organisational and economic factors with little recognition of the challenges posed to individuals. There is a lack of research to help allied health professionals understand the personal challenges of clinical academic training and practice. The aim of this study is to explore the character traits and behaviours of clinical academic allied health professionals to understand the individual attributes and strategies taken to pursue a career in this field.

Methods

A semi-structured interview study design was used to collect data from aspiring and established clinical academic allied health professionals. Participants were recruited voluntarily through social media advertisement (aspiring) and purposively through direct email invitation (established). Participants were asked about their experience of pursuing a clinical academic career. The interviews were conducted virtually using Zoom and were audio recorded. The data were transcribed verbatim prior to reflexive thematic analysis. Informed consent was gained prior to data collection and the study was approved by the university’s research ethics committee.

Results

Twenty participants from six allied health professions were interviewed. We developed five themes: risk and reward, don’t wait to be invited, shifting motivations, research is a team sport, and staying the course. Clinical academic allied health professionals demonstrated traits including inquisitiveness, intuition, motivation, and resilience. The source of their motivation was rooted in improving clinical services, conducting research, and personal achievement.

Conclusion

Clinical academic allied health professionals describe personal traits of high inquisitiveness, opportunism, motivation, and determination in pursuing their career ambitions. The tolerance of rejection, failure, and risk was considered important and viewed as an essential source for learning and professional development. Future research should concentrate on ways to reduce the over-reliance on individual strength of character to succeed in this field and explore programmes to increase the preparedness and support for clinical academics from these professions.
Modeled small airways lung deposition of two fixed-dose triple therapy combinations assessed with in silico functional respiratory imaging
Authors: Usmani Omar , Li Grace , De Backer Jan , Sadafi Hosein , Wu Libo , Marshall Jonathan
Published: September 2023

Background

Small airways disease plays a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and is a major cause of obstruction; therefore, it is a critical pharmacotherapy target. This study evaluated lung deposition of two inhaled corticosteroid (ICS)/long-acting β2-agonist/long-acting muscarinic antagonist single-inhaler triple therapies using in silico functional respiratory imaging (FRI). Deposition was assessed using real-world inhalation profiles simulating everyday use where optimal inhalation may be compromised.

Methods

Three-dimensional airway models were produced from 20 patients with moderate-to-very severe COPD. Total, central, and regional small airways deposition as a percentage of delivered dose of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 160/7.2/5 µg per actuation and fluticasone furoate/umeclidinium/vilanterol (FF/UM/VI) 100/62.5/25 µg were evaluated using in silico FRI based on in vitro aerodynamic particle size distributions of each device. Simulations were performed using multiple inhalation profiles of varying durations and flow rates representing patterns suited for a pressurized metered-dose inhaler or dry-powder inhaler (four for BGF, two for FF/UM/VI, with one common profile). For the common profile, deposition for BGF versus FF/UM/VI was compared post-hoc using paired t-tests.

Results

Across inhalation profiles, mean total lung deposition was consistently higher with BGF (47.0–54.1%) versus FF/UM/VI (20.8–22.7%) and for each treatment component, with greater deposition for BGF also seen in the central large airways. Mean regional small airways deposition was also greater across inhalation profiles with BGF (16.9–23.6%) versus FF/UM/VI (6.8–8.7%) and for each treatment component. For the common profile, total, central, and regional small airways deposition were significantly greater for BGF versus FF/UM/VI (nominal p < 0.001), overall and for treatment components; notably, regional small airways deposition of the ICS components was approximately five-fold greater with budesonide versus fluticasone furoate (16.1% vs. 3.3%).

Conclusions

BGF was associated with greater total, central, and small airways deposition for all components versus FF/UM/VI. Importantly, using an identical inhalation profile, there was an approximately five-fold difference in small airways deposition for the ICS components, with only a small percentage of the ICS from FF/UM/VI reaching the small airways. Further research is needed to understand if the enhanced delivery of BGF translates to clinical benefits.

Graphical Abstract
DSCC1 interacts with HSP90AB1 and promotes the progression of lung adenocarcinoma via regulating ER stress
Authors: Lin Xu , Liu Ye-han , Zhang Huan-qi , Wu Lin-wen , Li Qi , Deng Jun , Zhang Qingyi , Yang Yuhong , Zhang Chong , Li Yang-ling , Hu Jian
Published: September 2023

Lung cancer is a leading cause of cancer-related deaths, and the most common type is lung adenocarcinoma (LUAD). LUAD is frequently diagnosed in people who never smoked, patients are always diagnosed at advanced inoperable stages, and the prognosis is ultimately poor. Thus, there is an urgent need for the development of novel targeted therapeutics to suppress LUAD progression. In this study, we demonstrated that the expression of DNA replication and sister chromatid cohesion 1 (DSCC1) was higher in LUAD samples than normal tissues, and the overexpression of DSCC1 or its coexpressed genes were highly correlated with poor outcomes of LUAD patients, highlighting DSCC1 might be involved in LUAD progression. Furthermore, the expression of DSCC1 was positively correlated with multiple genetic mutations which drive cancer development, including TP53, TTN, CSMD, and etc. More importantly, DSCC1 could promote the cell proliferation, stemness, EMT, and metastatic potential of LUAD cells. In addition, DSCC1 interacted with HSP90AB1 and promoted the progression of LUAD via regulating ER stress. Meanwhile, DSCC1 expression negatively correlated with immune cell infiltration in lung cancer, and DSCC1 positively regulated the expression of PD-L1 in LUAD cells. Collectively, this study revealed that DSCC1 is a novel therapeutic target to treat LUAD and a biomarker for predicting the efficiency of PD-1/PD-L1 blockade treatment.
Design of percutaneous transluminal coronary angioplasty balloon catheters
Authors: Amstutz C. , Behr J. , Krebs S. , Haeberlin A. , Vogel R. , Zurbuchen A. , Burger J.
Published: September 2023

Background

Eight commercially available percutaneous transluminal coronary angioplasty (PTCA), including semi-compliant and non-compliant balloons, have been assessed in detail on their tip, balloon, shaft, RX-Port, and hypotube design. Important performance characteristics such as tip deformation, balloon elongation, and deflation rate have been quantified.

Methods

Five catheters of each model were evaluated during various tests. The robustness of the tips was evaluated through compression, measuring any occurrence of damage. The longitudinal growth of the balloons was recorded during inflation up to Rated Burst Pressure (RBP). The forces required to move the catheter forward and retract it into the guide catheter were measured in a simulated use test setup. The deflation behavior was studied by measuring extracted contrast media over time. Furthermore, balloon compliance and catheter dimensions were investigated.

Results

The outer dimensions of the catheter were found to be smallest at the hypotube (0.59–0.69 mm) and highest at the balloon, respectively, the crossing profile (0.9–1.2 mm). The tip diameter increased after compression by 1.7–22%. Cross-sections of the folded balloons revealed a tri- and two-fold, respectively. The measured balloon elongation ranged from 0.6 to 2.0 mm. After the inflation of the balloon, an increase in friction between the guide wire and the catheter was observed on four catheters. A maximum increase of 0.12 N to 1.07 N was found. Cross-sections of the RX-Port revealed a semicircular-shaped inflation lumen and a circular guide wire lumen. The measured deflation rate ranged from 0.004 to 0.013 µL/s, resulting in an estimated balloon deflation time of 10.2–28.1 s.

Conclusion

This study provides valuable insights into the design characteristics of RX PTCA balloon catheters, which can contribute to facilitating the development of improved catheter designs and enhancing clinical outcomes. Distinctions between SC and NC catheters, such as balloon performance and dimensions, are evident. It is important to note that no single catheter excels in all aspects, as each possesses unique strengths. Therefore, it is essential to consider individual intervention requirements when selecting a catheter.

The research also identifies specific catheter weaknesses, such as reduced wall thickness, fringes at the tip, and reduced performance characteristics.
Designing a microbial fermentation-functionalized alginate microsphere for targeted release of 5-ASA using nano dietary fiber carrier for inflammatory bowel disease treatment
Authors: Qiu Lei , Shen Renbin , Wei Lei , Xu Shujuan , Xia Wei , Hou Yan , Cui Jinxin , Qu Rong , Luo Jiale , Cao Jian , Yang Jie , Sun Jing , Ma Ronglin , Yu Qiang
Published: September 2023

Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.
Multi-functional conductive hydrogels based on heparin–polydopamine complex reduced graphene oxide for epidermal sensing and chronic wound healing
Authors: Dou Yiyong , Zhang Yuwei , Zhang Shuo , Ma Shuo , Zhang Hong
Published: September 2023

Flexible hydrogel sensors have expanded the applications of electronic devices due to their suitable mechanical properties and excellent biocompatibility. However, conventionally synthesized reduced graphene oxide (rGO) encounters limitations in reduction degree and dispersion, restricting the conductivity of graphene hydrogels and impeding the development of high-sensitivity flexible sensors. Moreover, hydrogels are susceptible to inflammation and bacterial infections, jeopardizing sensor stability over time. Thus, the challenge persists in designing conductive hydrogels that encompass high sensitivity, antibacterial efficacy, and anti-oxidative capabilities. In this study, GO was modified and reduced via a heparin-polydopamine (Hep-PDA) complex, yielding well-reduced and uniformly dispersed Hep-PDA-rGO nanosheets. Consequently, a hydrogel utilizing Hep-PDA-rGO was synthesized, showcasing commendable conductivity (3.63 S/m) and sensor performance, effectively applied in real-time motion monitoring. Notably, the hydrogel’s attributes extend to facilitating chronic diabetic wound healing. It maintained a suitable inflammatory environment credited to its potent antibacterial and antioxidative properties, while its inherent conductivity promoted angiogenesis. The multifunctional nature of this hydrogel highlight its potential not only as an epidermal sensor but also as a promising dressing candidate for chronic wound treatment.
DNA methylation regulator-mediated modification patterns and risk of intracranial aneurysm: a multi-omics and epigenome-wide association study integrating machine learning, Mendelian randomization, eQTL and mQTL data
Authors: Maimaiti Aierpati , Turhon Mirzat , Abulaiti Aimitaji , Dilixiati Yilidanna , Zhang Fujunhui , Axieer Aximujiang , Kadeer Kaheerman , Zhang Yisen , Maimaitili Aisha , Yang Xinjian
Published: September 2023

Background

Intracranial aneurysms (IAs) pose a significant and intricate challenge. Elucidating the interplay between DNA methylation and IA pathogenesis is paramount to identify potential biomarkers and therapeutic interventions.

Methods

We employed a comprehensive bioinformatics investigation of DNA methylation in IA, utilizing a transcriptomics-based methodology that encompassed 100 machine learning algorithms, genome-wide association studies (GWAS), Mendelian randomization (MR), and summary-data-based Mendelian randomization (SMR). Our sophisticated analytical strategy allowed for a systematic assessment of differentially methylated genes and their implications on the onset, progression, and rupture of IA.

Results

We identified DNA methylation-related genes (MRGs) and associated molecular pathways, and the MR and SMR analyses provided evidence for potential causal links between the observed DNA methylation events and IA predisposition.

Conclusion

These insights not only augment our understanding of the molecular underpinnings of IA but also underscore potential novel biomarkers and therapeutic avenues. Although our study faces inherent limitations and hurdles, it represents a groundbreaking initiative in deciphering the intricate relationship between genetic, epigenetic, and environmental factors implicated in IA pathogenesis.

Graphical Abstract
Multi-omics analysis reveals attenuation of cellular stress by empagliflozin in high glucose-treated human cardiomyocytes
Authors: Scisciola Lucia , Chianese Ugo , Caponigro Vicky , Basilicata Manuela Giovanna , Salviati Emanuela , Altucci Lucia , Campiglia Pietro , Paolisso Giuseppe , Barbieri Michelangela , Benedetti Rosaria , Sommella Eduardo
Published: September 2023

Background

Sodium–glucose cotransporter 2 (SGLT2) inhibitors constitute the gold standard treatment for type 2 diabetes mellitus (T2DM). Among them, empagliflozin (EMPA) has shown beneficial effects against heart failure. Because cardiovascular diseases (mainly diabetic cardiomyopathy) are the leading cause of death in diabetic patients, the use of EMPA could be, simultaneously, cardioprotective and antidiabetic, reducing the risk of death from cardiovascular causes and decreasing the risk of hospitalization for heart failure in T2DM patients. Interestingly, recent studies have shown that EMPA has positive benefits for people with and without diabetes. This finding broadens the scope of EMPA function beyond glucose regulation alone to include a more intricate metabolic process that is, in part, still unknown. Similarly, this significantly increases the number of people with heart diseases who may be eligible for EMPA treatment.

Methods

This study aimed to clarify the metabolic effect of EMPA on the human myocardial cell model by using orthogonal metabolomics, lipidomics, and proteomics approaches. The untargeted and multivariate analysis mimicked the fasting blood sugar level of T2DM patients (hyperglycemia: HG) and in the average blood sugar range (normal glucose: NG), with and without the addition of EMPA.

Results

Results highlighted that EMPA was able to modulate and partially restore the levels of multiple metabolites associated with cellular stress, which were dysregulated in the HG conditions, such as nicotinamide mononucleotide, glucose-6-phosphate, lactic acid, FA 22:6 as well as nucleotide sugars and purine/pyrimidines. Additionally, EMPA regulated the levels of several lipid sub-classes, in particular dihydroceramide and triacylglycerols, which tend to accumulate in HG conditions resulting in lipotoxicity. Finally, EMPA counteracted the dysregulation of endoplasmic reticulum-derived proteins involved in cellular stress management.

Conclusions

These results could suggest an effect of EMPA on different metabolic routes, tending to rescue cardiomyocyte metabolic status towards a healthy phenotype.

Graphical Abstract
Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets
Authors: Jin Zhuangzhuang , Zhang He , Bai Lunhao , Yue Lingyu , Zhang Weiming , Liang Jiajian , Chang Bohan , Yang Yue , Hu Zhehan , Chen Liang , Guo Chuanji
Published: September 2023

Background

The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients.

Methods

The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium.

Results

JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level.

Conclusions

The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis.