bluuebunny/crossref_metadata_2025 huggingface dataset:
Physiologically based pharmacokinetic modelling to predict potential drug–drug interactions of dersimelagon (MT‐7117)
Authors: Ogasawara Akihito , Kojima Koki , Murata Yukiko , Shimizu Hidetoshi
Published: October 2024

Aims

Dersimelagon is a novel, investigational, orally administered, selective agonist of the melanocortin‐1 receptor that has demonstrated efficacy at increasing symptom‐free light exposure and an acceptable safety profile in patients with protoporphyria. A phase 1 drug–drug interaction (DDI) study demonstrated that dersimelagon 300 mg has the potential for clinically relevant DDIs with drugs that are substrates for breast cancer resistance protein, such as atorvastatin and rosuvastatin. This study uses physiologically based pharmacokinetic (PBPK) modelling to further investigate the DDI effects at lower doses of dersimelagon with substrate drugs.

Methods

The data from in silico, in vitro and in vivo studies were used to construct a PBPK model for dersimelagon to assess the DDI potential between dersimelagon and substrate drugs for cytochrome P450 3A, P‐glycoprotein, organic anion transporting polypeptide 1B1/1B3, organic anion transporter 3 and breast cancer resistance protein, including atorvastatin and rosuvastatin.

Results

The systemic exposure of atorvastatin based on the maximum plasma concentration and area under the plasma concentration–time curve was predicted to increase 1.21‐fold and 1.25‐fold, respectively, if coadministered with dersimelagon 100 mg, and 1.42‐fold and 1.45‐fold with dersimelagon 200 mg. The systemic exposure of rosuvastatin followed trends similar to atorvastatin (1.67‐fold and 1.34‐fold increase in maximum plasma concentration and area under the plasma concentration–time curve, respectively, with dersimelagon 100 mg, and 2.40‐fold and 1.69‐fold with dersimelagon 200 mg).

Conclusion

Overall, PBPK modelling results indicate that the simulated changes in plasma exposure of atorvastatin and rosuvastatin following coadministration with dersimelagon 100 or 200 mg are not clinically significant, but caution and appropriate clinical monitoring should be recommended.
Prediction of refraction error after toric lens implantation with biometric input data uncertainties and power labelling tolerances
Authors: Langenbucher Achim , Szentmáry Nóra , Cayless Alan , Cooke David , Hoffmann Peter , Wendelstein Jascha
Published: October 2024

Background

The purpose of this study was to simulate the impact of biometric measure uncertainties, lens equivalent and toric power labelling tolerances and axis alignment errors on the refractive outcome after cataract surgery with toric lens implantation.

Methods

In this retrospective non‐randomised cross sectional Monte‐Carlo simulation study we evaluated a dataset containing 7458 LenStar 900 preoperative biometric measurements. The biometric uncertainties from literature, lens power labelling according to ISO 11979, and axis alignment tolerances of a modern toric lens (Hoya Vivinex) were taken to be normally distributed and used in a Monte‐Carlo simulation with 100 000 samples per eye. The target variable was the defocus equivalent (DEQ) derived using the Castrop (DEQC) and the Haigis (DEQH) formulae.

Results

Mean/median / 90% quantile DEQC was 0.22/0.21/0.36 D and DEQH was 0.20/0.19/0.32 D. Ignoring the variation in lens power labelling and toric axis alignment the respective DEQC was 0.20/0.19/0.32 D and DEQH was 0.18/0.17/0.29 D. DEQC and DEQH increased with shorter eyes, steeper corneas, equivalent lens power and highly with toric lens power.

Conclusions

According to our simulation results, uncertainties in biometric measures, lens power labelling tolerances, and axis alignment errors are responsible for a significant part of the refraction prediction error after cataract surgery with toric lens implantation. Additional labelling of the exact equivalent and toric power on the lens package could be a step to improve postoperative results.
Prevention and management of intra‐operative complications in maxillary sinus augmentation: A review
Authors: Valentini Pascal , Stacchi Claudio
Published: October 2024

Maxillary sinus floor elevation is usually performed in two different ways: the lateral approach involves the creation of a bony window on the maxillary sinus lateral wall, providing direct access to the sinus cavity for membrane elevation and subsequent graft placement, and the transcrestal approach is considered less invasive. The aim of this article is to describe, based on the literature, how to anticipate, avoid, and manage the intraoperative complications that can occur with both approaches. For both approaches, the most common complication is the sinus membrane perforation. For the lateral approach, an average frequency ranging from 15.7% to 23.1% is reported, but because of the better visibility, their management will be easier compared to the transcrestal approach. Mean perforation rate reported for the transcrestal approach is lower (3.1%–6.4%), but it should be noted that a significant number of perforations cannot be detected and managed given the blind nature of this technique. Anatomical parameters such as sinus width and buccal wall thickness may be a risk factor for one approach and not the other. As it is impossible to assess the resistance of the Schneiderian membrane, the transcrestal approach is more likely to lead to infectious complications in the event of perforation. Others, such as the risk of vascular damage, are encountered only with the lateral approach, which can be prevented easily by dissecting the alveolo‐antral artery. For both approaches, prevention is essential and consists in analyzing the anatomy, mastering the surgical technique, and collaborating with the ENT to manage the essentially infectious consequences of intraoperative complications.
Children's Selective Teaching and Informing: A Meta‐Analysis
Authors: Qiu Fanxiao Wani , Park Joanna , Vite Amanda , Patall Erika , Moll Henrike
Published: October 2024

Empirical studies on selective teaching and informing indicate that children may vary what they teach depending on whom they are teaching, taking into account how helpful the information is for a given audience. The current meta‐analysis quantifies the effect of selective informing and teaching in 2–7‐year‐olds by examining the relationship between the helpfulness of the information and the frequency of information transmission. Through a systematic search that yielded 1483 results, 28 studies (104 effect sizes, N = 2716) met the inclusion criteria. Using robust variance estimation, we found a medium average effect, Hedges’ g = 0.578, 95% CI (0.331, 0.825), suggesting that children selectively share information based on its perceived helpfulness to the listener. Moderator analyses revealed that age and communicative context were significant factors. Children were more informative in their communication when asked to teach compared to other, nonpedagogical prompts. This finding supports and extends natural pedagogy theory—young children not only interpret pedagogical information differently than information acquired through other means, but they are more selective in their informing when teaching. Additionally, we observed a key developmental progression at age 4. Four‐ to 7‐year‐olds, but not 2–3‐year‐olds, selectively shared information that was most helpful for a given learner. This coincides with the development of false‐belief understanding, which undergoes significant development at around age 4. Taken together, the present synthesis suggests that young children actively engage in selective social learning from both sides, that of beneficiaries and benefactors of valuable information.
Assessment of Left Ventricular Functional Impairment in Patients With Chronic Kidney Disease Using Three‐Dimensional Speckle Tracking Imaging
Authors: Gao Xue , Xiao Weiwei , Ji Liqin , Li Houyu , Zou Anlingzi , Zhang Xinru , Miao Zhuomeng , Yang Siyuan , Yu Shaomei
Published: October 2024

Background

Chronic kidney disease (CKD) is strongly linked to the incidence and mortality of cardiovascular diseases (CVDs), with left ventricular myocardial damage being the most prevalent. This study aimed to assess left ventricle (LV) dysfunction using three‐dimensional speckle tracking imaging (3D‐STI) in CKD patients.

Methods

A total of 110 CKD patients and 55 healthy volunteers underwent echocardiography. CKD patients were divided into CKD1 group and CKD2 group based on the estimated glomerular filtration rate (eGFR). Assessing cardiac function via two‐dimensional speckle tracking echocardiography (2D‐STE) and three‐dimensional speckle tracking echocardiography (3D‐STE) parameters, with strain presented in absolute terms. Collecting and comparing clinical and echocardiographic parameters from three groups, assessing 3D‐STI's value in evaluating LV functional impairment in CKD patients via correlation and receiver operating characteristic (ROC) curve analyses, and identifying risk factors for CKD progression to end‐stage renal disease (ESRD) through univariate and multivariate analyses.

Results

In CKD2 group, 2D‐left ventricular ejection fraction (LVEF), 3D‐LVEF, 2D left ventricular global longitudinal strain (2D‐LVGLS), 3D‐LVGLS, and 3D‐left ventricular global circumferential peak strain (LVGCS) significantly worsen compared to the control and CKD1 groups, with statistically significant distinctions between the latter two (all p < 0.05). The absolute value of 3D‐LVGLS shows a robust correlation with N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and serum creatinine (Scr) (r = −0.598, −0.649, both p < 0.001). ROC curve analysis indicates higher diagnostic efficacy of 3D‐LVGLS and 3D‐LVGCS for LV systolic function than 2D‐LVGLS. Univariate and multivariate analyses reveal an independent association of 3D‐LVGLS with the progression to ESRD in CKD.

Conclusion

3D‐LVGLS and 3D‐LVGCS effectively detect LV dysfunction in CKD patients. Specifically, 3D‐LVGLS demonstrates a robust correlation with NT‐proBNP and Scr and is independently linked to CKD progressing to ESRD.
Tetralogy of Fallot With Absent Pulmonary Valve Syndrome: The Experience of a Tertiary Care Center in a Developing Country
Authors: Farhat Aziz , Charanek Sujud , Zareef Rana , El‐Rassi Issam , Bitar Fadi , Arabi Mariam
Published: October 2024

Background

Tetralogy of Fallot with an absent pulmonary valve is a very rare variant of tetralogy. It is characterized by absent valve tissue, severe pulmonary regurgitation, and secondary aneurysmal dilatation of the pulmonary arteries.

Aim

In this study, we aim to investigate the clinical presentations, management strategies, and outcomes of patients with tetralogy of Fallot and absent pulmonary valve.

Methodology

We retrospectively reviewed the charts of all patients who presented to the American University of Beirut Medical Center between January 2010 and December 2020 and who were diagnosed with this anomaly.

Results

A total of 300 cases of tetralogy of Fallot were identified, of which 18 patients had absent pulmonary valves. They were followed up for an average of 8.2 years. Prenatal diagnoses were made in four patients, while 13 patients were identified in the neonatal period, with an average age of 4.5 days. Genetic testing confirmed DiGeorge syndrome in one patient. Five patients underwent surgical intervention in the neonatal period, while the remaining patients were operated on during their early childhood. While overall there were no surgical mortalities nor any need for reinterventions, a variety of morbidities were encountered.

Conclusion

This study provides an overview of this rare anomaly and its management in a developing country.
c‐Met inhibitor upregulates E‐cadherin, which is lost in portal vein tumor thrombus of hepatocellular carcinoma
Authors: Abe Satoru , Inagaki Yoshinori , Kokudo Takashi , Miyata Akinori , Nishioka Yujiro , Ichida Akihiko , Kaneko Junichi , Akamatsu Nobuhisa , Kawaguchi Yoshikuni , Hasegawa Kiyoshi
Published: October 2024

Aim

Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) is an essential therapeutic and prognostic factor. E‐cadherin plays a crucial role in adhesive properties and intercellular interaction in various cancer tissues, including HCC, but the expression profile and functional contribution of E‐cadherin in PVTT remain unknown. This study aimed to analyze the expression of E‐cadherin in the main tumor tissue and PVTT tissue of HCC, and evaluate the functional roles of E‐cadherin in PVTT formation.

Methods

A retrospective analysis was performed using the medical records of patients who underwent liver resection for HCC with PVTT, analyzing tissue specimens from 1995 to 2016. E‐cadherin expression is evaluated using immunohistochemistry and western blot. The study also uses a c‐Met inhibitor to explore its impact on E‐cadherin expression in vitro and in vivo using cell lines and a tumor xenograft mouse model.

Results

The results revealed a reduced E‐cadherin expression in PVTT tissue than in the main tumor tissue. The inhibition of c‐Met activation, frequently detected in HCC, upregulated E‐cadherin expression in HCC cell lines. Furthermore, treatment with c‐Met inhibitors induced changes in epithelial morphology, and inhibited migration and invasion of HCC cell lines.

Conclusions

This study demonstrates the downregulation of E‐cadherin in PVTT, and underscores the potential of c‐Met inhibition in upregulating E‐cadherin and inhibiting metastatic behavior. Understanding the significance of E‐cadherin and c‐Met in HCC progression provides a foundation for future clinical investigations into the therapeutic effects of c‐Met inhibitors on PVTT in HCC patients.
Teaching of magnification in the undergraduate curriculum: A position statement from the British Endodontic Society Teachers of Endodontology Group
Authors: McLean W. , Qualtrough A. J. E.
Published: October 2024

This position statement on undergraduate teaching on the use of magnification in endodontics represents the consensus of the British Endodontic Society Teachers of Endodontology Group. Current clinical and scientific evidence, as well as the expertise of the committee, has been used to develop this statement. The contributors to this position statement consider, as a minimum requirement, the use of dental loupes in non‐surgical endodontics at undergraduate level. It is recommended that the use of dental loupes should be integrated into endodontic clinical skills training and the performance of endodontic treatment in the undergraduate curriculum.
Genotypes and phenotypes of capillary malformation–arteriovenous malformation: characterization and correlation analysis
Authors: Chen Yuxi , Liu Hongyuan , Zhou Jingwei , Yang Xi , Jia Hechen , Ma Gang , Sun Bin , Chen Hongrui , Jin Yunbo , Hua Chen , Lin Xiaoxi
Published: October 2024

Background

Capillary malformation–arteriovenous malformation (CM‐AVM) is a rare genetic disorder characterized by multiple small capillary malformations (CMs) and arteriovenous malformations (AVMs), which has been linked with pathogenic variants in RASA1 and EPHB4. However, more data are needed to explore the phenotypic characteristics and the association between genotypes and clinical phenotypes.

Objectives

Our aim was to investigate the phenotypic and genetic characteristics of CM‐AVM in East Asians, identify potential unique phenotypes, and conduct genotype–phenotype association analyses.

Methods

This is a single‐center study prospectively collecting CM‐AVM patients' clinical data, with genetic data from blood or tissue samples.

Results

A total of 59 patients were enrolled. Thirty‐two individuals had a leading CM greater than Schobinger stage II. The trigeminal nerve branches and greater auricular, transverse cervical, and lesser occipital nerves' somatosensory innervation zones divided head and neck CMs into six zones: V1, V2, V3, GA, TC, and LO zones. GA, TC, and LO zones had a positive correlation with one another but a negative correlation with V2 zone involvement. The RASA1 and EPHB4 pathogenic variants were detected in 41 out of 59, which showed two types of variant allele frequency (VAF) distributions. VAF above 30% made RASA1 pathogenic variants more susceptible to multifocal CMs than those below 30%.

Conclusions

Leading CMs in the head and neck exhibit two segmentation patterns, anterior and lateral, which may differ in ear involvement and progression. Germline RASA1 pathogenic variants increased multifocal CM risk more than the somatic variants.
Barriers and Facilitators to Mental Health Service Integration: A Scoping Review
Authors: Searby Adam , Burr Dianna , Carolin Renae , Hutchinson Alison
Published: October 2024

Mental health service integration currently has no consensus definition and exists in a variety of settings, including primary care, addiction treatment and chronic disease management, and mental health nurses have often experienced efforts at service integration with varying degrees of success. The intent of mental health service integration is to enable collaboration between mental health services and other healthcare providers to improve service access and the care provided to individuals with mental health issues or mental illness. This scoping review aimed to explore service integration between mental health services and with a specific focus on those evaluated in peer‐reviewed, primary literature, to determine facilitators and barriers to service integration. Using the Arksey and O'Malley's framework for scoping reviews, we located 3148 studies, with screening narrowing final papers for inclusion to 18. Facilitators to service integration included clinician education, adequate resourcing and an interdisciplinary approach, while barriers included staff factors such as a reluctance to work with individuals with mental illness, consumer level barriers such as poor mental health literacy, ‘territorialism’ among staff and organisational climate. Research indicates that service integration is an effective means to detect and treat mental health issues in settings that do not traditionally provide mental health care, lowering the costs of providing healthcare and providing improved care for mental health needs; however, there are several barriers to be addressed to achieve full implementation of integration models.
Development and Psychometric Evaluation of the Sexual Life Quality Evaluation Tool for Patients With Coronary Heart Disease
Authors: Zhang Fengpei , Li Yachai , Shi Zhili , Fan Yingying , Wang Aiping
Published: October 2024

Purpose

Patients with coronary heart disease (CHD) will have a series of sexual problems, and their sexual life quality can be affected. However, a standardised evaluation tool for patients with CHD was lacking. Therefore, this study aimed to develop a sexual life quality questionnaire for patients with CHD and to evaluate its psychometric properties.

Methods

Based on previous phenomenological studies, literature analysis and group discussion, questionnaire items were formed. After two rounds of expert consultation and pre‐survey, the questionnaire items were modified. Items were screened by item analysis. Exploratory factor analysis and confirmatory factor analysis were used to explore and confirm the structure of the questionnaire. Content validity and criterion validity were evaluated using the expert consultation and correlation analysis, respectively. The questionnaire reliability was evaluated using internal consistency, split half reliability, and test‐retest reliability.

Results

The sexual life quality questionnaire of patients with CHD was developed, which included two versions: male version and female version. The male version of the questionnaire contains 3 dimensions and 20 items, while the female version contains 3 dimensions and 17 items. After reliability and validity test, the two versions of the questionnaire have good reliability and validity.

Conclusions

In this study, the sexual life quality questionnaire of patients with CHD was developed and its psychometric properties were confirmed, which can be used to evaluate the sexual life quality of patients with CHD.

Implications for Clinical Practice

The development of a sexual life quality evaluation tool for patients with coronary heart disease to provide objective and quantitative tools for clinical staff to evaluate patients' sexual life status.

Patient Contribution

Patients were invited to participate in a questionnaire survey for this study.
The relationships between unmet social needs, oral health measures, and dental service utilization in a pediatric population
Authors: Riley Alison , Dolce Millie , Peng Jin , Casamassimo Paul , Amini Homa
Published: October 2024

Objectives

Social Determinants of Health (SDoH) have been linked to health, including oral health and oral health behaviors. Objectives of this retrospective records review were to evaluate the relationships between self‐reported unmet social needs and (1) oral health measures and (2) dental service utilization in a pediatric population at a hospital‐based dental clinic.

Methods

Children 2–5 years of age whose families had completed a SDoH survey and who had an encounter with one United States (U.S.) urban children's hospital dental clinic within 6 months (± 3 months) of the survey date were included. A chart review was performed, and information was collected about the child's (1) oral health (e.g., plaque level, presence of caries) and (2) dental service utilization (e.g., no‐show rates, number of dental surgeries). The data of patients with one or more parental/caretaker‐reported unmet social needs were compared with that of patients with no unmet social needs.

Results

Inclusion criteria were met by 2646 children. Those with unmet social needs had significantly higher no‐show rates at scheduled appointments than those without unmet social needs (p‐value <0.001). Patients who identified as African/Black were more likely to report unmet social needs. There was no statistically significant difference in oral health measures of patients with or without unmet social needs.

Conclusions

Children in this population demonstrated varying associations between unmet social needs, health measures, and health behaviors, suggesting a likely complicated association between unmet social needs and health.
Artificial intelligence methods used in various aquaculture applications: A systematic literature review
Authors: Aung Thurein , Abdul Razak Rafiza , Rahiman Bin Md Nor Adibi
Published: October 2024

This research article presents a systematic literature review on the current state‐of‐the‐art artificial intelligence (AI) methodologies used in aquaculture applications. As the demand for seafood continues to grow, the aquaculture industry faces numerous challenges, including disease management, feeding optimization, water quality monitoring, and extraction of aquaculture area. To address these challenges effectively and sustainably, AI techniques have been increasingly applied in aquaculture systems over recent years. This review aims to analyze various AI methodologies utilized within different aspects of aquacultural practices. By examining existing studies and identifying trends and gaps in research areas related to AI integration into aquaculture practices, this paper provides valuable insights for further advancements. The purpose was to synthesize current knowledge on application and its challenges in implementing AI technologies within the commercial aquaculture industry. Specifically, the review is to identify and analyze peer‐reviewed studies reporting on applications of AI technologies in aquaculture industry, to classify and summarize the key findings from the selected studies in aquaculture operations through AI, and to evaluate and discuss any challenges reported regarding the implementation and adoption of AI solutions in commercial aquaculture. The overall goal was to comprehensively assess these via a systematic literature review process. Challenges of AI technologies and methods were identified in the research literature for applying AI to optimize commercial aquaculture practices and production. An exhaustive search of a scholarly database from Scopus, was performed and papers published in English between 2020 and 2024 were considered for inclusion. After a rigorous screening process involving over 116 studies, 57 highly relevant works were identified and analyzed according to key themes involving demonstrated AI applications, employed methodologies and challenges that are expected when applying such methods. The findings revealed that AI‐driven tools such as computer vision, machine learning, and predictive modeling hold much potential for enhancing sustainability, efficiency, and productivity within aquaculture operations through applications like disease monitoring, environmental management, and production optimization. However, the review also uncovered substantial challenges that will continue limiting widespread adoption, including restricted access to representative data, prohibitive expenses, technical complexities, lack of social acceptance, and data privacy and security concerns. This comprehensive synthesis of the current evidence available provides an empirical foundation upon which further progress can be built by identifying priority areas requiring additional research efforts to fully address challenges on the responsible integration of suitable solutions for the commercial aquaculture industry globally.
The Enteric Bacterium Enterococcus faecalis Elongates and Incorporates Exogenous Short and Medium Chain Fatty Acids Into Membrane Lipids
Authors: Zou Qi , Dong Huijuan , Cronan John E.
Published: October 2024

Enterococcus faecalis incorporates and elongates exogeneous short‐ and medium‐chain fatty acids to chains sufficiently long to enter membrane phospholipid synthesis. The acids are activated by the E. faecalis fatty acid kinase (FakAB) system and converted to acyl‐ACP species that can enter the fatty acid synthesis cycle to become elongated. Following elongation the acyl chains are incorporated into phospholipid by the PlsY and PlsC acyltranferases. This process has little effect on de novo fatty acid synthesis in the case of short‐chain acids, but a greater effect with medium‐chain acids. Incorporation of exogenous short‐chain fatty acids in E. faecalis was greatly increased by overexpression of either AcpA, the acyl carrier protein of fatty acid synthesis, or the phosphate acyl transferase PlsX. The PlsX of Lactococcus lactis was markedly superior to the E. faecalis PlsX in incorporation of short‐chain but not long‐chain acids. These manipulations also allowed unsaturated fatty acids of lengths too short for direct transfer to the phospholipid synthesis pathway to be elongated and support growth of E. faecalis unsaturated fatty acid auxotrophic strains. Short‐ and medium‐chain fatty acids can be abundant in the human gastrointestinal tract and their elongation by E. faecalis would conserve energy and carbon by relieving the requirement for total de novo synthesis of phospholipid acyl chains.
Changes in choroidal thickness and blood flow in response to form deprivation‐induced myopia and repeated low‐level red‐light therapy in Guinea pigs
Authors: Xiang Aiqun , He Hong , Li Anzhen , Meng Xuyun , Luo Yanting , Luo Yuhan , Wang Xingxing , Yang Junming , Chen Xiaolian , Zhong Xingwu
Published: October 2024

Purpose

To evaluate ocular refractive development, choroidal thickness (ChT) and changes in choroidal blood flow in form‐deprived myopia (FDM) Guinea pigs treated with repeated low‐level red‐light (RLRL) therapy.

Methods

Twenty‐eight 3‐week‐old male tricolour Guinea pigs were randomised into three groups: normal controls (NC, n = 10), form‐deprived (FD, n = 10) and red light treated with form‐deprivation (RLFD, n = 8). Interocular refraction and axial length (AL) changes were monitored. Optical coherence tomography angiography (OCTA) measured choroidal thickness, vessel area density, vessel skeleton density and blood flow signal intensity (flux) in the choriocapillaris and medium–large vessel layers. The experimental intervention lasted 3 weeks.

Results

At week 3, the FD group had higher myopia and longer axial length than the NC group (all p < 0.001). The RLFD group had higher hyperopia and shorter axial length than the FD group (all p < 0.001). At week 1, the NC group had a thicker choroidal thickness than the FD group (p < 0.05). At weeks 2 and 3, the RLFD group had a thicker choroidal thickness than the FD group (p = 0.002, p < 0.001, respectively). Additionally, the NC group had higher vessel area density, vessel skeleton density and flux in the choriocapillaris layer than the FD group at the three follow‐up time points (all p < 0.05). At week 3, the vessel skeleton density and flux were higher in the RLFD group than in the FD group (all p < 0.05). Correlation analysis results showed that weekly changes in refraction and choroidal thickness were negatively correlated with changes in axial length (all p < 0.05). Choroidal thickness changes were positively correlated with alterations in the vessel area density, vessel skeleton density and flux in the choriocapillaris layer, as well as vessel skeleton density and flux changes in the medium–large vessel layers (all p < 0.05).

Conclusions

Repeated low‐level red‐light (RLRL) therapy retards FDM progression in Guinea pigs, potentially through increased choroidal blood flow in the choriocapillaris layer.
Intravenous lidocaine infusion therapy and intraoperative neurophysiological monitoring in adolescents undergoing idiopathic scoliosis correction: A retrospective study
Authors: Bates Rachel , Cave Fiona , West Nicholas , Bone Jeffrey N. , Hofmann Bradley , Miyanji Firoz , Lauder Gillian R.
Published: October 2024

Background

Posterior spinal instrumentation and fusion is an established surgical procedure for the correction of adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring is standard practice for this procedure. Anesthetic agents can have different, but significant, effects on neurophysiological monitoring outcomes.

Aim

To determine if intravenous lidocaine infusion therapy has an impact on the intraoperative neurophysiological monitoring during posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis.

Methods

Following ethical approval, we conducted a retrospective review of charts and the archived intraoperative neurophysiological data of adolescents undergoing posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring data included the amplitude of motor evoked potentials and the amplitude and latency of somatosensory evoked potentials. A cohort who received intraoperative lidocaine infusion were compared to those who did not.

Results

Eighty‐one patients were included in this analysis, who had surgery between February 4, 2016 and April 22, 2021: 39 had intraoperative intravenous lidocaine infusion and 42 did not. Based on hourly snapshot data, there was no evidence that lidocaine infusion had a detrimental effect on the measured change from baseline for MEP amplitudes in either lower (mean difference 41.9; 95% confidence interval −304.5 to 388.3; p = .182) or upper limbs (MD −279.0; 95% CI −562.5 to 4.4; p = .054). There was also no evidence of any effect on the measured change from baseline for SSEP amplitudes in either lower (MD 16.4; 95% CI −17.7 to 50.5; p = .345) or upper limbs (MD −2.4; 95% CI −14.5 to 9.8; p = .701). Finally, there was no evidence of a difference in time to first reportable neurophysiological event (hazard ratio 1.13; 95% CI 0.61 to 2.09; p = .680).

Conclusions

Data from these two cohorts provide preliminary evidence that intravenous lidocaine infusion has no negative impact on intraoperative neurophysiological monitoring during PSIF for adolescent idiopathic scoliosis.
Adult stakeholders' perspectives on supporting or undermining the mental health of sexual and gender minoritised adolescents
Authors: Samra Rajvinder , Lucassen Mathijs F. G. , Núñez‐García Alicia , Brown Katherine E. , Rimes Katharine A. , Wallace Louise M.
Published: October 2024

Objectives

To explore adult stakeholders' perspectives on what supports or undermines the mental health of sexual and gender minoritised adolescents (SGMA) in everyday life in order to better understand how to foster supportive psychosocial environments for SGMA.

Design

Descriptive qualitative study design, using framework analysis.

Methods

Semi‐structured interviews were conducted remotely with 16 UK‐based adult stakeholders which included parents of SGMA, health and social care professionals, community‐based professionals, and professionals who commission services related to adolescent health and well‐being.

Results

Nine themes were identified that represented barriers and enablers of fostering psychosocial environments that are supportive of SGMA mental health. Example barrier themes include SGMA ‘facing chronic and acute safety threats and stress’, ‘psychological responses to social connection losses and navigating alienation’, ‘digital exposure and online risk and vulnerability’ and ‘conflicting messages, resulting divisions and adult distancing’. Example enablers include ‘exploring, owning, and changing (personal) identities’, ‘advocating alongside adolescents whilst containing oneself as the adult in the situation’ and ‘personally fostering adolescents’ psychological safety and inclusion’.

Conclusions

Adult stakeholders report that SGMA are often exposed to environments hostile to key aspects of their identity which then by extension undermines their mental health. These experiences can threaten their sense of safety and evolving identity. Practitioners in particular should be aware of the stressors relating to SGMA identity and minoritisation experiences in order to develop the psychological safety and sense of inclusion needed for SGMA to trust in the relationship and the support offered.
Safety of Prior Propranolol Therapy for Infantile Hemangioma
Authors: Hasan Iraj , Zinn Zachary
Published: October 2024

Propranolol has been the primary treatment for infantile hemangioma (IH) since 2008. Prior studies have investigated the effects in late childhood of propranolol therapy given in infancy for IH, including neurocognitive dysfunction, sleep disorders, and hypoglycemia. However, few studies have determined the risk of these adverse effects later in life. Using the TrinetX database, we studied the risk of growth impairment, sleep disorders, learning disabilities, and diabetes mellitus in children aged 10–17 years who had received propranolol for IH in infancy. The maximum age of 17 years was chosen for the study, as propranolol was established as a treatment for IH in 2008. The results showed no statistically significant risk of growth impairment, sleep disorders, learning disabilities, or diabetes mellitus in IH patients treated with propranolol. These findings support existing evidence that propranolol therapy given in infancy for IH is not associated with long‐term adverse effects up to age 17 years in the studied patient population.
Pre‐procedural Topical Antisepsis in the Neonate: A Systematic Review Evaluating Risk Factors for Skin Injury
Authors: Mulinda Carly , Suhail Sana , Sutherland Bronwyn , Lauren Christine T. , Hunt Raegan D.
Published: October 2024

Background

Pre‐procedural antisepsis is a critical component of hospital‐acquired infection prevention in the neonatal intensive care unit (NICU). However, broadly utilized topical antiseptic agents pose an elevated risk of disruption to neonatal skin integrity, and evidence‐based guidelines are lacking. This systematic review of the literature sought to assess and characterize the predisposing risk factors for and types of neonatal skin injury from topical antiseptic agents.

Methods

A systematic search of Medline Ovid, Embase, Web of Science, CINAHL, and Cochrane Library was conducted, including academic literature providing data on neonatal skin injuries related to topical antisepsis in the NICU.

Results

A total of 19 articles (99 patients) met the inclusion criteria. Of the available data, most reported skin injuries were described in extremely preterm (98.1%) and very low birth weight (98.4%) infants. The majority of reported adverse cutaneous events were attributed to chlorhexidine preparations (74.8%), followed by octenidine (18.2%), povidone‐iodine (6.1%), and isopropyl alcohol (2.0%). Erythema (40.1%), skin breakdown (23.4%), and chemical burns (17.5%) were the skin reactions reported most frequently, followed by skin irritation (8.3%), and skin necrosis (2.8%).

Conclusions

Our findings indicate that both extremely preterm and very low birth weight infants are particularly susceptible to skin toxicities from pre‐procedural antiseptic preparations. These data underscore the need for future research to support the development of guidelines which minimize iatrogenic cutaneous injuries in the neonatal population, specifically for the care of infants under 2 months of age, for whom current recommendations are lacking due to a paucity of data.
The SME R&D intensity and product innovation relationship: the mediating role of quality management in the context of a developing country
Authors: Omari Dacosta , Scott Stephanie A. , Tóth Zsófia , Tsinopoulos Christos
Published: October 2024

SMEs engage in product innovation despite their inherent resource constraints, lack of financial slack, and the under‐development of competitively viable strategic configurations around the globe. While progress has been made in identifying the antecedents and capabilities attributed to successful innovation outcomes and the performance of these firms, there remain disparate and often paradoxical observations on the factors that affect SME innovation performance across geographies (i.e. developed vs developing countries) and operational contexts (R&D intensity and quality management practices). This study collected data from 241 resource‐constrained small and medium‐sized enterprises (SMEs) in a developing country (Ghana) to contribute to this debate. The results of structural equation modeling show that quality management mediates the relationship between R&D intensity and product innovation. The results also reveal the effects of knowledge integration and financial slack on the relationship between R&D intensity and product innovation, with a high level of knowledge integration enhancing the effect but a high financial slack hinders it. This study sheds light on a broader range of contextual and financial variables when seeking contingencies of SME product innovation performance within theory and practice.
Impact of textural layers in soils on irrigation infiltration processes in an oasis farmland, northwestern China
Authors: Hong Zhou , Zhao Wenzhi , Sun Chenpeng
Published: October 2024

The Hexi Corridor Oasis in China is an important agricultural area supported by extensive irrigation. The sandy soil in the area exhibits textural layering, which has marked effects on its properties. Textural layered soils play an important role in distributing and regulating water regimes in irrigated fields. However, little is known about the textural layering‐dependent variability in soil water infiltration characteristics following irrigation and the potential effects on soil hydrology and water regimes in these soils. The objective of this study was to determine water infiltration processes and their influencing factors for six soil profile types in an oasis farmland. Six in situ constant‐head infiltration measurements (with three replications in each of six sites) were conducted with a single‐ring infiltrometer in different soil texture configurations, and Hydrus‐2D model was applied to evaluate soil water distribution. The results showed that the wetting front depth for all treatments was in the following order: ST‐1 > ST‐5 > ST‐6 > ST‐3 > ST‐2 > ST‐4; the stable infiltration rate ranged from 1.2 to 3.3 cm/min during the investigation period in all treatments. The presence of a finer‐textured soil layer decreased water infiltration rates through the profiles, and the thickness and burial depth of textured layers had obvious effects on infiltration, compared with homogeneous sand profiles. Presence of a medium‐textured layer affected the infiltration characteristics and soil water spatial variability; driven by increased field capacity and the wilting point, hydraulic conductivity was correlated with soil variables that were related to soil structure, such as wilting point and field capacity, and less so with variables that were related to soil texture, such as the clay fractions (p < 0.001). These results suggested that textural layering altered the soil structure and caused heterogeneous infiltration of water, with implications for the distribution of irrigation water and prevention of deep percolation in this oasis farmland. The result of this study offers a new analysis of ponded single‐ring water infiltrometer data that the soil water infiltration is also influenced by the type of textural layered than just the irrigation system, which supports crop irrigation management in study area and other regions with similar soil regimes.
Advancements in genetic analysis: Insights from a case study and review of next‐generation sequencing techniques for veterinary oncology applications
Authors: Harris R. Adam , Nolan Jillian , Ammons Dylan , Beeson Samantha , Thamm Douglas , Avery Anne
Published: October 2024

Acute myeloid leukemia (AML) poses significant challenges in veterinary medicine, with limited treatment options and poor survival rates. While substantial progress has been made in characterizing human AML, translating these advancements to veterinary practice has been hindered by limited molecular understanding and diagnostic tools. The case study presented illustrates the application of whole genome sequencing in diagnosing AML in a dog, showcasing its potential in veterinary oncology. Our approach facilitated comprehensive genomic analysis, identifying mutations in genes that may be associated with AML pathogenesis in dogs, such as KRAS, IKZF1, and RUNX1. However, without supportive evidence of its clinical utility (eg, association with response to treatment or prognosis), the information is limited to exploration. This article reviews the comparative features of canine AML with human AML and discusses strategies to shrink the knowledge gap between human and veterinary medicine with cost‐effective next‐generation sequencing (NGS) techniques. By utilizing these approaches, the unique and shared molecular features with human AML can be identified, aiding in molecular classification and therapeutic development for both species. Despite the promise of NGS, challenges exist in implementing it into routine veterinary diagnostics. Cost considerations, turnaround times, and the need for robust bioinformatics pipelines and quality control measures must be addressed. Most importantly, analytical and clinical validation processes are essential to ensure the reliability and clinical utility of NGS‐based assays. Overall, integrating NGS technologies into veterinary oncology holds great potential for advancing our understanding of AML and improving disease stratification, in hopes of improving clinical outcomes.
Ultrasonographic assessment of equine metacarpal cartilage thickness is more accurate than computed tomographic arthrography
Authors: Hoey Seamus , Fogarty Ursula , McAllister Hester , Puggioni Antonella , Cloak Brian , Richard Hélène , Skelly Cliona , Laverty Sheila
Published: October 2024

Articular cartilage can be directly imaged using ultrasonography. The fetlock is a common site of osteochondrosis, with the sagittal ridge of the third metacarpal bone most commonly affected. In osteochondrosis, cartilage thickening may be an initial finding. This postmortem study investigated the ability of ultrasonography to accurately measure the dorsodistal articular cartilage of the third metacarpal bone in young horses, compared to computed tomographic arthrography (CTA) and histological measurements. A total of 33 metacarpophalangeal joints from 18 horses between the ages of 12 days and 10 months old were imaged ultrasonographically and with CTA and sectioned and measured using histology. Imaging measurements were made by two observers. Despite overall weak agreement between ultrasonography and histology, the best agreement was at the distal aspect of the sagittal ridge of the third metacarpal bone. Interobserver agreement at this site was also moderate. CTA showed poor agreement overall with histology. Cartilage thickness decreased with age on ultrasonography, CTA, and histology. In conclusion, ultrasonography is a more accurate imaging modality than CTA in the assessment of cartilage in young horses.
The synaptic vesicle cluster as a controller of pre‐ and postsynaptic structure and function
Authors: Reshetniak Sofiia , Bogaciu Cristian A. , Bonn Stefan , Brose Nils , Cooper Benjamin H. , D'Este Elisa , Fauth Michael , Fernández‐Busnadiego Rubén , Fiosins Maksims , Fischer André , Georgiev Svilen V. , Jakobs Stefan , Klumpp Stefan , Köster Sarah , Lange Felix , Lipstein Noa , Macarrón‐Palacios Victor , Milovanovic Dragomir , Moser Tobias , Müller Marcus , Opazo Felipe , Outeiro Tiago F. , Pape Constantin , Priesemann Viola , Rehling Peter , Salditt Tim , Schlüter Oliver , Simeth Nadja , Steinem Claudia , Tchumatchenko Tatjana , Tetzlaff Christian , Tirard Marilyn , Urlaub Henning , Wichmann Carolin , Wolf Fred , Rizzoli Silvio O.
Published: October 2024

The synaptic vesicle cluster (SVC) is an essential component of chemical synapses, which provides neurotransmitter‐loaded vesicles during synaptic activity, at the same time as also controlling the local concentrations of numerous exo‐ and endocytosis cofactors. In addition, the SVC hosts molecules that participate in other aspects of synaptic function, from cytoskeletal components to adhesion proteins, and affects the location and function of organelles such as mitochondria and the endoplasmic reticulum. We argue here that these features extend the functional involvement of the SVC in synapse formation, signalling and plasticity, as well as synapse stabilization and metabolism. We also propose that changes in the size of the SVC coalesce with changes in the postsynaptic compartment, supporting the interplay between pre‐ and postsynaptic dynamics. Thereby, the SVC could be seen as an ‘all‐in‐one’ regulator of synaptic structure and function, which should be investigated in more detail, to reveal molecular mechanisms that control synaptic function and heterogeneity.

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Biogenesis and reformation of synaptic vesicles
Authors: Bolz Svenja , Haucke Volker
Published: October 2024

Communication within the nervous system relies on the calcium‐triggered release of neurotransmitter molecules by exocytosis of synaptic vesicles (SVs) at defined active zone release sites. While decades of research have provided detailed insight into the molecular machinery for SV fusion, much less is known about the mechanisms that form functional SVs during the development of synapses and that control local SV reformation following exocytosis in the mature nervous system. Here we review the current state of knowledge in the field, focusing on the pathways implicated in the formation and axonal transport of SV precursor organelles and the mechanisms involved in the local reformation of SVs within nerve terminals in mature neurons. We discuss open questions and outline perspectives for future research.

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