bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective autophagy in cancer: mechanisms, therapeutic implications, and future perspectives
Authors: Liu Jiaxi , Wu Yongya , Meng Sha , Xu Ping , Li Shutong , Li Yong , Hu Xiuying , Ouyang Liang , Wang Guan
Published: January 2024

Eukaryotic cells engage in autophagy, an internal process of self-degradation through lysosomes. Autophagy can be classified as selective or non-selective depending on the way it chooses to degrade substrates. During the process of selective autophagy, damaged and/or redundant organelles like mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes, and lipid droplets are selectively recycled. Specific cargo is delivered to autophagosomes by specific receptors, isolated and engulfed. Selective autophagy dysfunction is closely linked with cancers, neurodegenerative diseases, metabolic disorders, heart failure, etc. Through reviewing latest research, this review summarized molecular markers and important signaling pathways for selective autophagy, and its significant role in cancers. Moreover, we conducted a comprehensive analysis of small-molecule compounds targeting selective autophagy for their potential application in anti-tumor therapy, elucidating the underlying mechanisms involved. This review aims to supply important scientific references and development directions for the biological mechanisms and drug discovery of anti-tumor targeting selective autophagy in the future.
Anti-hyperalgesic and anti-inflammatory effects of 4R-tobacco cembranoid in a mouse model of inflammatory pain
Authors: Rivera-García Luis G. , Francis-Malavé Adela M. , Castillo Zachary W. , Uong Calvin D. , Wilson Torri D. , Ferchmin P. A. , Eterovic Vesna , Burton Michael D. , Carrasquillo Yarimar
Published: January 2024

4R is a tobacco cembranoid that binds to and modulates cholinergic receptors and exhibits neuroprotective and anti-inflammatory activity. Given the established function of the cholinergic system in pain and inflammation, we propose that 4R is also analgesic. Here, we tested the hypothesis that systemic 4R treatment decreases pain-related behaviors and peripheral inflammation via modulation of the alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) in a mouse model of inflammatory pain. We elicited inflammation by injecting Complete Freund’s Adjuvant (CFA) into the hind paw of male and female mice. We then assessed inflammation-induced hypersensitivity to cold, heat, and tactile stimulation using the Acetone, Hargreaves, and von Frey tests, respectively, before and at different time points (2.5 h – 8d) after a single systemic 4R (or vehicle) administration. We evaluated the contribution of α7 nAChRs 4R-mediated analgesia by pre-treating mice with a selective antagonist of α7 nAChRs followed by 4R (or vehicle) administration prior to behavioral tests. We assessed CFA-induced paw edema and inflammation by measuring paw thickness and quantifying immune cell infiltration in the injected hind paw using hematoxylin and eosin staining. Lastly, we performed immunohistochemical and flow cytometric analyses of paw skin in α7 nAChR-cre::Ai9 mice to measure the expression of α7 nAChRs on immune subsets. Our experiments show that systemic administration of 4R decreases inflammation-induced peripheral hypersensitivity in male and female mice and inflammation-induced paw edema in male but not female mice. Notably, 4R-mediated analgesia and anti-inflammatory effects lasted up to 8d after a single systemic administration on day 1. Pretreatment with an α7 nAChR-selective antagonist prevented 4R-mediated analgesia and anti-inflammatory effects, demonstrating that 4R effects are via modulation of α7 nAChRs. We further show that a subset of immune cells in the hind paw expresses α7 nAChRs. However, the number of α7 nAChR-expressing immune cells is unaltered by CFA or 4R treatment, suggesting that 4R effects are independent of α7 nAChR-expressing immune cells. Together, our findings identify a novel function of the 4R tobacco cembranoid as an analgesic agent in both male and female mice that reduces peripheral inflammation in a sex-dependent manner, further supporting the pharmacological targeting of the cholinergic system for pain treatment.
How quality of life is measured in studies of nutritional intervention: a systematic review
Authors: Pemau Raquel Clapés , González-Palacios Patricia , Kerr Kirk W.
Published: January 2024

Background

Nutrition care can positively affect multiple aspects of patient’s health; outcomes are commonly evaluated on the basis of their impact on a patient’s (i) illness-specific conditions and (ii) health-related quality of life (HRQoL). Our systematic review examined how HRQoL was measured in studies of nutritional interventions. To help future researchers select appropriate Quality of Life Questionnaires (QoLQ), we identified commonly-used instruments and their uses across populations in different regions, of different ages, and with different diseases.

Methods

We searched EMCare, EMBASE, and Medline databases for studies that had HRQoL and nutrition intervention terms in the title, the abstract, or the MeSH term classifications “quality of life” and any of “nutrition therapy”, “diet therapy”, or “dietary supplements” and identified 1,113 studies for possible inclusion.We then reviewed titles, abstracts, and full texts to identify studies for final inclusion.

Results

Our review of titles, abstracts, and full texts resulted in the inclusion of 116 relevant studies in our final analysis. Our review identified 14 general and 25 disease-specific QoLQ. The most-used general QoLQ were the Short-Form 36-Item Health Survey (SF-36) in 27 studies and EuroQol 5-Dimension, (EQ-5D) in 26 studies. The European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC-QLQ), a cancer-specific QoLQ, was the most frequently used disease-specific QoLQ (28 studies). Disease-specific QoLQ were also identified for nutrition-related diseases such as diabetes, obesity, and dysphagia. Sixteen studies used multiple QoLQ, of which eight studies included both general and disease-specific measures of HRQoL. The most studied diseases were cancer (36 studies) and malnutrition (24 studies). There were few studies focused on specific age-group populations, with only 38 studies (33%) focused on adults 65 years and older and only 4 studies focused on pediatric patients. Regional variation in QoLQ use was observed, with EQ-5D used more frequently in Europe and SF-36 more commonly used in North America.

Conclusions

Use of QoLQ to measure HRQoL is well established in the literature; both general and disease-specific instruments are now available for use. We advise further studies to examine potential benefits of using both general and disease-specific QoLQ to better understand the impact of nutritional interventions on HRQoL.
Malignant myoepithelioma of the external auditory canal — a rare case report with literature review and clinical importance of foramen of Huschke
Authors: Mateášiková Zuzana , Salzman Richard , Michálek Jaroslav
Published: January 2024

Background

A malignant myoepithelioma is a rare tumor, mostly arising from the salivary glands. Myoepitheliomas of the ear have rarely been reported. The manuscript reports myoepithelial carcinoma of the external auditory canal (EAC) spreading to the infratemporal fossa. A clinician must be aware of anatomical variation of the bony EAC wall, such as the foramen of Huschke. This rare defect may be a pathway for spreading pathologies between these two anatomical regions.

Case report

We present a case of osteoma-like stenosis of the EAC, which turned out to be an extremely rare malignant tumor. The preoperative MRI and PET/CT revealed that two parts of the tumor communicated through a defect in the antero-inferior portion of the bony ear canal. No distant metastases were detected. Subsequently, the tumor was resected from the ear canal and the infratemporal fossa en bloc. Perioperatively the defect in the EAC wall was suspected of the foramen of Huschke. After the surgery, the older scans of the patient from the past showed no presence of a congenital EAC wall defect. Therefore, the authors concluded that the tumor aggressively grew through the bone due to its biological nature.

Conclusion

Malignant myoepithelioma of the external auditory canal is an extremely rare condition and could be misdiagnosed as other benign lesions. In cases of suspicious lesions, it is advisable to do a probatory biopsy from the EAC. Surgery is the treatment of choice in malignant myoepitheliomas, and regular follow-ups are essential to monitor for recurrence or metastatic disease. Any mass located at the antero-inferior portion of the EAC wall warrants close evaluation due to its potential for expansion from the EAC.
Comparison of three-dimensional imaging of the nose using three different 3D-photography systems: an observational study
Authors: Ritschl Lucas M. , Classen Carolina , Kilbertus Paul , Eufinger Julia , Storck Katharina , Fichter Andreas M. , Wolff Klaus-Dietrich , Grill Florian D.
Published: January 2024

Background

New 3D technologies for superficial soft tissue changes, especially in plastic and reconstructive surgical procedures, can improve the planning and documentation of facial surgeries. The purpose of this study was to compare and determine the applicability and feasibility of three different 3D-photography systems in clinical practice imaging the nose.

Methods

A total of 16 healthy non-operated noses were included in this prospective study. A plaster model of each nose was produced, digitized, and converted to a .stl mesh (= ground truth model). Three-dimensional images of each nose were then taken using Artec Space Spider (gold standard), Planmeca ProFace®, and the Bellus3D Dental Pro application. All resulting .stl files were aligned to the ground truth model using MeshLab software, and the root mean square error (RMSE), mean surface distance (MSD), and Hausdorff distance (HD) were calculated.

Results

The Artec Space Spider 3D-photography system showed significantly better results compared to the two other systems in regard to RMSE, MSD, and HD (eachp < 0.001). There was no significant difference between Planmeca ProFace® and Bellus3D Dental Pro in terms of RMSE, MSD, and HD. Overall, all three camera systems showed a clinically acceptable deviation to the reference model (range: -1.23–1.57 mm).

Conclusions

The three evaluated 3D-photography systems were suitable for nose imaging in the clinical routine. While Artec Space Spider showed the highest accuracy, the Bellus3D Dental Pro app may be the most feasible option for everyday clinical use due to its portability, ease of use, and low cost. This study presents three different systems, allowing readers to extrapolate to other systems when planning to introduce 3D photography in the clinical routine.
Ganoderma lucidum polysaccharide ameliorates cholesterol gallstone formation by modulating cholesterol and bile acid metabolism in an FXR-dependent manner
Authors: Huang Dan , Shen Shuang , Zhuang Qian , Ye Xin , Qian Yueqin , Dong Zhixia , Wan Xinjian
Published: January 2024

Background

Cholesterol gallstone (CG) disease is a worldwide common disease characterized by cholesterol supersaturation in gallbladder bile. Ganoderma lucidum polysaccharide (GLP) has been shown to possess various beneficial effects against metabolic disorders. However, the role and underlying mechanism of GLP in CG formation are still unknown. This study aimed to determine the role of GLP in ameliorating lithogenic diet (LD)-induced CG formation.

Methods

Mice were fed either a normal chow diet, a LD, or LD supplemented with GLP. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of genes involved in cholesterol and bile acid (BA) metabolism. The BA concentrations in the ileum were quantified by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The microbiota in cecal contents were characterized using 16S ribosomal RNA (16S rRNA) gene sequencing.

Results

GLP effectively alleviated CG formation induced by LD. Specifically, GLP reduced the total cholesterol (TC) levels, increased the total BA levels, and decreased the cholesterol saturation index (CSI) in gallbladder bile. The protective effect of GLP was attributed to the inhibition of farnesoid X receptor (FXR) signaling, increased hepatic BA synthesis and decreased hepatic cholesterol synthesis and secretion. GLP also altered the BA composition in the ileum, reducing FXR-agonistic BAs and increasing FXR-antagonistic BAs, which may contribute to the inhibition of intestinal FXR signaling. Additionally, GLP improved dysbiosis of the intestinal flora and reduced the serum levels of hydrogen sulfide (H2S), a bacterial metabolite that can induce hepatic FXR, thereby inhibiting hepatic FXR signaling. Moreover, the protective effect of GLP against CG formation could be reversed by both the global and gut-restricted FXR agonists.

Conclusions

Taken together, GLP ameliorates CG formation by regulating cholesterol and BA metabolism in an FXR-dependent manner. Our study demonstrates that GLP may be a potential strategy for the prevention against CG disease.
Effect of immersive virtual reality-based cognitive remediation in patients with mood or psychosis spectrum disorders: study protocol for a randomized, controlled, double-blinded trial
Authors: Jespersen Andreas E. , Lumbye Anders , Vinberg Maj , Glenthøj Louise , Nordentoft Merete , Wæhrens Eva E. , Knudsen Gitte M. , Makransky Guido , Miskowiak Kamilla W.
Published: January 2024

Background

Cognitive impairments are prevalent across mood disorders and psychosis spectrum disorders, but there is a lack of real-life-like cognitive training programmes. Fully immersive virtual reality has the potential to ensure motivating and engaging cognitive training directly relevant to patients’ daily lives. We will examine the effect of a 4-week, intensive virtual reality-based cognitive remediation programme involving daily life challenges on cognition and daily life functioning in patients with mood disorders or psychosis spectrum disorders and explore the neuronal underpinnings of potential treatment efficacy.

Methods

The trial has a randomized, controlled, double-blinded, parallel-group design. We will include 66 symptomatically stable outpatients with mood disorders or psychosis spectrum disorders aged 18–55 years with objective and subjective cognitive impairment. Assessments encompassing a virtual reality test of daily life cognitive skills, neuropsychological testing, measures of daily life functioning, symptom ratings, questionnaires on subjective cognitive complaints, and quality of life are carried out at baseline, after the end of 4 weeks of treatment and at a 3-month follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and at the end of treatment. The primary outcome is a broad cognitive composite score comprising five subtasks on a novel ecologically valid virtual reality test of daily life cognitive functions. Two complete data sets for 54 patients will provide a power of 80% to detect a clinically relevant between-group difference in the primary outcome. Behavioural data will be analysed using linear mixed models in SPSS, while MRI data will be analysed with the FMRIB Expert Analysis Tool (FEAT). Treatment-related changes in neural activity from baseline to end of treatment will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest.

Discussion

The results will provide insight into whether virtual reality-based cognitive remediation has beneficial effects on cognition and functioning in symptomatically stable patients with mood disorders or psychosis spectrum disorders, which can aid future treatment development.

Trial registration

ClinicalTrials.gov NCT06038955. Registered on September 15, 2023.
Utilising electrodermal activity sensor signals to quantify nociceptive response during movement activities
Authors: Hamilton Rebecca I. , Garcia Ashly Alava , Bowd Jake , Hamilton David , Mason Deborah , Elliott Mark , Holt Cathy
Published: January 2024

Objective

With an increasingly ageing population and osteoarthritis prevalence, the quantification of nociceptive signals responsible for painful movements and individual responses could lead to better treatment and monitoring solutions. Changes in electrodermal activity (EDA) can be detected via changes in skin conductance (SC) and measured using finger electrodes on a wearable sensor, providing objective information for increased physiological stress response.

Results

To provide EDA response preliminary data, this was recorded with healthy volunteers on an array of activities while receiving a noxious stimulus. This provides a defined scenario that can be utilised as protocol feasibility testing. Raw signal extraction, processing and statistical analysis was performed using mean SC values on all participant data. The application of the stimuli resulted in a significant average increase (p < 0.05) in mean SC in four out of five activities with significant gender differences (p < 0.05) in SC and self-reported pain scores and large effect sizes. Though EDA parameters are a promising tool for nociceptive response indicators, limitations including motion artifact sensitivities and lack of previous movement-based EDA published data result in restricted analysis understanding. Refined processing pipelines with signal decomposition tools could be utilised in a protocol that quantifies nociceptive response clinically meaningfully.
Challenges in the diagnosis and management of a ruptured heterotopic gestation following ultrasound-guided embryo transfer in low resource settings: a case report
Authors: Oyeh Ernest , Ofori Samuel , Hiadzi Edem K. , Sefogah Promise E.
Published: January 2024

Background

Heterotopic pregnancies are increasing in incidence with the advent of rising prevalence of in vitro fertilization and embryo transfer (IVF-ET) globally. Although rare, this condition is a serious potentially life-threatening gynaecological complication.

Case presentation

We present the case of a 36-year-old Ghanaian woman who conceived following IVF and presented two weeks after confirmation of intrauterine gestation with sudden onset lower abdominal pain. A diagnosis of ruptured heterotopic pregnancy was made, laparotomy and salpingectomy was done followed with further management of the intrauterine gestation.

Conclusion

To the best of our knowledge, this is the first reported case of heterotopic pregnancy in Ghana. A high index of suspicion for heterotopic pregnancy is required even in the presence of a confirmed intrauterine gestation following IVF-ET.
A new reverse Mulholland’s inequality with one partial sum in the kernel
Authors: Huang Xianyong , Luo Ricai , Yang Bicheng , Huang Xingshou
Published: January 2024

By means of the techniques of real analysis, applying some basic inequalities and formulas, a new reverse Mulholland’s inequality with one partial sum in the kernel is given. We obtain the equivalent conditions of the parameters related to the best value in the new inequality. As applications, we reduce to the equivalent forms and a few inequalities for particular parameters.
Predictive modeling for acute kidney injury after percutaneous coronary intervention in patients with acute coronary syndrome: a machine learning approach
Authors: Behnoush Amir Hossein , Shariatnia M. Moein , Khalaji Amirmohammad , Asadi Mahsa , Yaghoobi Alireza , Rezaee Malihe , Soleimani Hamidreza , Sheikhy Ali , Aein Afsaneh , Yadangi Somayeh , Jenab Yaser , Masoudkabir Farzad , Mehrani Mehdi , Iskander Mina , Hosseini Kaveh
Published: January 2024

Background

Acute kidney injury (AKI) is one of the preventable complications of percutaneous coronary intervention (PCI). This study aimed to develop machine learning (ML) models to predict AKI after PCI in patients with acute coronary syndrome (ACS).

Methods

This study was conducted at Tehran Heart Center from 2015 to 2020. Several variables were used to design five ML models: Naïve Bayes (NB), Logistic Regression (LR), CatBoost (CB), Multi-layer Perception (MLP), and Random Forest (RF). Feature importance was evaluated with the RF model, CB model, and LR coefficients while SHAP beeswarm plots based on the CB model were also used for deriving the importance of variables in the population using pre-procedural variables and all variables. Sensitivity, specificity, and the area under the receiver operating characteristics curve (ROC-AUC) were used as the evaluation measures.

Results

A total of 4592 patients were included, and 646 (14.1%) experienced AKI. The train data consisted of 3672 and the test data included 920 cases. The patient population had a mean age of 65.6 ± 11.2 years and 73.1% male predominance. Notably, left ventricular ejection fraction (LVEF) and fasting plasma glucose (FPG) had the highest feature importance when training the RF model on only pre-procedural features. SHAP plots for all features demonstrated LVEF and age as the top features. With pre-procedural variables only, CB had the highest AUC for the prediction of AKI (AUC 0.755, 95% CI 0.713 to 0.797), while RF had the highest sensitivity (75.9%) and MLP had the highest specificity (64.35%). However, when considering pre-procedural, procedural, and post-procedural features, RF outperformed other models (AUC: 0.775). In this analysis, CB achieved the highest sensitivity (82.95%) and NB had the highest specificity (82.93%).

Conclusion

Our analyses showed that ML models can predict AKI with acceptable performance. This has potential clinical utility for assessing the individualized risk of AKI in ACS patients undergoing PCI. Additionally, the identified features in the models may aid in mitigating these risk factors.

Graphical Abstract
METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control
Authors: Zhao Pan , Xia Lin , Chen Dan , Xu Wei , Guo Huanping , Xu Yinying , Yan Bingbing , Wu Xiao , Li Yuxia , Zhang Yunfang , Zhang Xi
Published: January 2024

Background

RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined.

Methods

METTL1/WDR4 expression levels were quantified using qRT-PCR, western blot analysis on AML clinical samples, and bioinformatics analysis on publicly available AML datasets. CCK-8 assays and cell count assays were performed to determine cell proliferation. Flow cytometry assays were conducted to assess cell cycle and apoptosis rates. Multiple techniques were used for mechanism studies in vitro assays, such as northern blotting, liquid chromatography-coupled mass spectrometry (LC–MS/MS), tRNA stability analysis, transcriptome sequencing, small non-coding RNA sequencing, quantitative proteomics, and protein synthesis measurements.

Results

METTL1/WDR4 are significantly elevated in AML patients and associated with poor prognosis. METTL1 knockdown resulted in reduced cell proliferation and increased apoptosis in AML cells. Mechanically, METTL1 knockdown leads to significant decrease of m7G modification abundance on tRNA, which further destabilizes tRNAs and facilitates the biogenesis of tsRNAs in AML cells. In addition, profiling of nascent proteins revealed that METTL1 knockdown and transfection of total tRNAs that were isolated from METTL1 knockdown AML cells decreased global translation efficiency in AML cells.

Conclusions

Taken together, our study demonstrates the important role of METTL1/WDR4 in AML leukaemogenesis, which provides a promising target candidate for AML therapy.
Using a longitudinal network structure to subgroup depressive symptoms among adolescents
Authors: Liang Sugai , Huang Zejun , Wang Yiquan , Wu Yue , Chen Zhiyu , Zhang Yamin , Guo Wanjun , Zhao Zhenqing , Ford Sabrina D. , Palaniyappan Lena , Li Tao
Published: January 2024

Background

Network modeling has been proposed as an effective approach to examine complex associations among antecedents, mediators and symptoms. This study aimed to investigate whether the severity of depressive symptoms affects the multivariate relationships among symptoms and mediating factors over a 2-year longitudinal follow-up.

Methods

We recruited a school-based cohort of 1480 primary and secondary school students over four semesters from January 2020 to December 2021. The participants (n = 1145) were assessed at four time points (ages 10–13 years old at baseline). Based on a cut-off score of 5 on the 9-item Patient Health Questionnaire at each time point, the participants were categorized into the non-depressive symptom (NDS) and depressive symptom (DS) groups. We conducted network analysis to investigate the symptom-to-symptom influences in these two groups over time.

Results

The global network metrics did not differ statistically between the NDS and DS groups at four time points. However, network connection strength varied with symptom severity. The edge weights between learning anxiety and social anxiety were prominently in the NDS group over time. The central factors for NDS and DS were oversensitivity and impulsivity (3 out of 4 time points), respectively. Moreover, both node strength and closeness were stable over time in both groups.

Conclusions

Our study suggests that interrelationships among symptoms and contributing factors are generally stable in adolescents, but a higher severity of depressive symptoms may lead to increased stability in these relationships.
In-vitro evaluation of Indigofera heterantha extracts for antibacterial, antifungal and anthelmintic activities
Authors: Bhat Showkat Ahmad , Zargar Mohammed Iqbal , Wani Shahid Ud Din , Mohiuddin Ishfaq , Masoodi Mubashir Hussain , Shakeel Faiyaz , Ali Mohammad , Mehdi Seema
Published: January 2024

Background

Multidrug-resistant bacterial strains cause several serious infections that can be fatal, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae (often referred to as ESKAPE pathogens). Since ancient times, several indigenous medical systems in India have utilized diverse medicinal plants (approximately 80,000 species) as conventional treatments for a variety of illnesses. A member of the Fabaceae family, also referred to as “Himalayan indigo,” Indigofera heterantha Wall, is well known for its therapeutic properties.

Methods

The present study investigated the antibacterial, antifungal and antihelmintic properties of the roots, bark, leaves, and flowers of I. heterantha from the Kashmir Himalayas. The effectiveness of the extracts against bacteria, fungi, and earthworms. Three of the tested organisms for bacteria were ESKAPE pathogens, as they are responsible for creating fatal bacterial infections. The antifungal potency of I. heterantha aqueous and methanolic extracts was evaluated using the Agar Well Diffusion Assay. The antihelmintic activity was carried out on an adult Pheretima posthuma Indian earth worm, which shares physiological and anatomical similarities with human intestinal roundworm parasites.

Results

The methanolic extracts of root and bark have shown prominent activity against all bacterial strains, whereas aqueous extracts of flower, root, and leaves have shown promising activity against Staphylococcus aureus. The aqueous extract demonstrated good activity against S. cerevisiae at a concentration of 200 mg/ml with a zone of inhibition of 16 mm, while the methanolic extract displayed comparable activity against the fungal strains. The remaining two strains, P. crysogenum and A. fumigatus, were only moderately active in response to the extracts. All the extracts have shown anthelmintic activity except aqueous flower.

Conclusion

These results will pave the way for the bioassay-guided isolation of bioactive constituents that may act as hits for further development as potential antibacterial agents against drug-resistant microbial and helminthic infections.
Recommendations for initial diabetic retinopathy screening of diabetic patients using large language model-based artificial intelligence in real-life case scenarios
Authors: Gopalakrishnan Nikhil , Joshi Aishwarya , Chhablani Jay , Yadav Naresh Kumar , Reddy Nikitha Gurram , Rani Padmaja Kumari , Pulipaka Ram Snehith , Shetty Rohit , Sinha Shivani , Prabhu Vishma , Venkatesh Ramesh
Published: January 2024

Purpose

To study the role of artificial intelligence (AI) to identify key risk factors for diabetic retinopathy (DR) screening and develop recommendations based on clinician and large language model (LLM) based AI platform opinions for newly detected diabetes mellitus (DM) cases.

Methods

Five clinicians and three AI applications were given 20 AI-generated hypothetical case scenarios to assess DR screening timing. We calculated inter-rater agreements between clinicians, AI-platforms, and the “majority clinician response” (defined as the maximum number of identical responses provided by the clinicians) and “majority AI-platform” (defined as the maximum number of identical responses among the 3 distinct AI). Scoring was used to identify risk factors of different severity. Three, two, and one points were given to risk factors requiring screening immediately, within a year, and within five years, respectively. After calculating a cumulative screening score, categories were assigned.

Results

Clinicians, AI platforms, and the “majority clinician response” and “majority AI response” had fair inter-rater reliability (k value: 0.21–0.40). Uncontrolled DM and systemic co-morbidities required immediate screening, while family history of DM and a co-existing pregnancy required screening within a year. The absence of these risk factors required screening within 5 years of DM diagnosis. Screening scores in this study were between 0 and 10. Cases with screening scores of 0–2 needed screening within 5 years, 3–5 within 1 year, and 6–12 immediately.

Conclusion

Based on the findings of this study, AI could play a critical role in DR screening of newly diagnosed DM patients by developing a novel DR screening score. Future studies would be required to validate the DR screening score before it could be used as a reference in real-life clinical situations.

Clinical trial registration

Not applicable.
Percutaneous full-endoscopic transforaminal discectomy versus open microdiscectomy in the treatment of lumbar disc herniation: randomized controlled trial
Authors: Kandeel Moustafa Mohamed , Yousef Magdy Gamal Abdel Kader , Saoud Abdelfattah Mohamed Fathy , Abu-Elghait Zakaria Hassan Ibrahim
Published: January 2024

Background

Lumbar disc herniation is one of the most common degenerative spine conditions. In our center, the standard surgical technique for treatment of lumbar disc herniation is open microdiscectomy. The full-endoscopic transforaminal discectomy is done for selective cases of lumbar disc herniation under local anesthesia, achieving good results. This study aims to compare the clinical outcomes, operative data, and complications of the treatment of lumbar disc herniation with “percutaneous full-endoscopic transforaminal discectomy” (TED) and the gold standard “open microdiscectomy" (MD). This was a randomized controlled trial that included 65 patients with lumbar disc herniation: 32 in the TED group and 33 in the MD group.

Results

There was no statistically significant difference between the two groups with regard to the visual analogue scale (VAS) for leg pain, the VAS for back pain, or the Oswestry Low Back Pain Disability Questionnaire (ODI) score at the end of the 1-year follow-up. The operative time in minutes was statistically shorter in the TED group, with a mean value of 50.38 (± 11.65) and 61.09 (± 12.32) in the MD group. The blood loss was 77.33 CC (± 23.14) in the TED group and 170 CC (± 56.06) in the MD group. The mean duration of hospital stay in days was statistically shorter in the TED group. Exposure to radiation in minutes was higher in the TED group: 1.09 (± 0.33) and 0.18 (± 0.08) in the TED group and MD group, respectively. There was no statistically significant difference in the rate of complications.

Conclusion

TED showed superiority over MD with regard to blood loss, operative time and shorter hospital stays, but with increased radiation exposure. There was no difference in clinical outcomes regarding VAS for leg and back pain and ODI score at 1 year follow-up with no significant difference in complications.
Soluble guanylate cyclase stimulators for heart failure: a network meta-analysis and subgroup analyses of reduced and preserved ejection fraction
Authors: Abuelazm Mohamed T. , Attia Abdelrahman , Abdelnabi Mohamed , Jafar Uzair , Almaadawy Omar , Elzeftawy Mohamed A. , Mahmoud Abdelrahman , Albakri Khaled , Abdelazeem Basel
Published: January 2024

Background

Soluble guanylate cyclase (sGC) stimulators have been investigated for heart failure (HF) in several randomized controlled trials (RCTs). However, its place in the management guidelines of either HFrEF or HfpEF is still inconclusive.

Methods

We conducted a network meta-analysis synthesizing RCTs investigating sGC for HF management, which were retrieved by systematically searching five databases until January 24th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) along with confidence interval (CI).

Results

Eight RCTs with a total of 7307 patients were included. Vericiguat 10 mg significantly reduced the composite cardiovascular (CVS) mortality and HF hospitalization in HF (RR: 0.88, 95% CI [0.79; 0.98]) and in HFrEF (RR: 0.87, 95% CI [0.78; 0.97]); however, it was not effective in HFpEF (RR: 0.69, 95% CI [0.15; 3.05]). Also, vericiguat 10 mg showed no difference compared to placebo regarding the incidence of all-cause mortality (RR: 0.96, 95% CI [0.84; 1.10]), any adverse events (AEs) (RR: 0.94, 95% CI [0.83; 1.07]), any serious AEs (RR: 0.91, 95% CI [0.81; 1.01]), and any AEs leading to drug discontinuation (RR: 1.14, 95% CI [0.92; 1.40]).

Conclusion

Vericiguat 10 mg was effective in reducing the composite CVS mortality and HF hospitalization, with an acceptable safety profile. This was only observed in HFrEF patients, but not in HFpEF patients. However, our data regarding other agents (riociguat and praliciguat) and HFpEF can be underpowered, warranting further RCTs to clarify vericiguat 10 mg place in HFrEF management guidelines and to investigate sGC stimulators for HFpEF in large-scale trials.
Characterization of resonant coupled inductor in a wireless power transfer system
Authors: Nebrida Alan P.
Published: January 2024

Wireless power transfer (WPT) has garnered significant interest as a potentially transformative technology in the energy sector, as it presents a novel approach to powering and charging devices. The functionality of this technology is predicated upon the utilization of electromagnetic coupling to facilitate the wireless transmission of energy between two entities. Despite the considerable potential, wireless power transfer (WPT) faces significant obstacles that restrict its practical feasibility. One notable challenge that arises is the decrease in power transfer efficiency as the distance between the transmitter and receiver increases. Moreover, the wireless power transfer (WPT) technology is further limited by its reliance on accurate alignment between the transmitting source and the receiving device, thereby posing challenges for its practical implementation. The issues present substantial obstacles to the widespread commercialization of wireless power transfer (WPT). This study seeks to improve the efficacy of power transfer by optimizing the resonance frequency of the power transfer in response to the challenges. By systematically manipulating various parameters including coil dimensions, input voltage levels, and operational frequency, a novel approach is proposed to enhance the efficiency of power transfer. The study additionally offers valuable insights regarding the correlation between the distance separating the coils and the efficiency of power transfer. The findings of this study offer a thorough empirical analysis and are supported by a strong theoretical framework, resulting in a substantial coefficient of determination (R2 = 0.937118). This finding suggests that the linear regression model under consideration could account for approximately 93.7118 percent of the variability observed in the distance. The findings of this study establish a pathway toward enhanced and feasible wireless power technology, thereby establishing a robust basis for the prospective commercial implementation of wireless power transfer (WPT) systems.
Beyond State of the Art: Digital psychiatry is coming of age!
Authors: Riper H.
Published: January 2024

Digital interventions for common mental disorders are coming of age. The uptake of evidence-based self-guided and guided (a-synchronic in time) cognitive behavioural digital interventions for depression and anxiety in routine care is however low. Blended treatment formats appear an attractive alternative for routine care settings as these combine face-to-face sessions with digital ones in integrated treatment protocols. Yet little is known about the clinical and cost-effectiveness of blended CBT (bCBT). In this presentation I will touch upon the current state of the art of digital interventions for depression and anxiety disorders, including blended formats in routine care and I will go beyond that state by addressing new developments. I will illustrate these new developments by virtue of several studies (RCT’s) we conducted on the clinical and cost-effectiveness of blended CBT interventions (and their implementation) in routine care settings. A specific focus will be put on blending digital phenotyping in CBT treatment which includes mobile ecological momentary assessment tools and AI algorithms.

Conclusion

While digital mental health for depression and anxiety in routine care was boosted through the Covid-19 pandemic, the question remains whether the current knowledge base will leveraging digital mental health research and services to the next level. Implications for future research on blended treatments and clinical applications in routine care will be discussed.

Disclosure of Interest

None Declared
Microbiome-gut-brain axis in Nutritional Psychiatry
Authors: Schellekens H.
Published: January 2024

The last decade has seen an enormous expansion on our knowledge of the human gut microbiome and its importance for human physiology. The gastrointestinal inhabitants have taken centre stage as regulators of the bidirectional gut to brain communication. The gut microbiota is not only critical for metabolism, glucose homeostasis and body composition, but increasing evidence is demonstrating the significant effects of the gut microbiota on mood and mental wellbeing and its role in the development of affective disorders, such as anxiety and depression, and other neuropsychiatric conditions. Studies in the field of nutritional neuroscience and nutritional psychiatry are now increasingly including the gut microbiota as a key factor mediating the impact of diet on central nervous system function. Accumulating evidence from cell-based in vitro studies, animal models and preclinical intervention studies are linking the gut microbiota to the effects of diet on brain function, but the precise mechanism are still not fully understood and studies have had limited translation to human intervention studies. Overall, the increase in our understanding of interconnectedness of the gastrointestinal microbiota of human health and disease, has led to a strong focus on the development of microbiota-targeted strategies to influence all host physiological responses, including those that can modulate central nervous system function. In this talk, I will provide an overview of the most recent advances in the nutritional psychiatry–microbiome field, highlighting significant opportunities for future research.

Disclosure of Interest

None Declared
Cost-Effectiveness of eRAPID eHealth Intervention for Symptom Management During Chemotherapy
Authors: Dawkins Bryony , Absolom Kate , Hewison Jenny , Warrington Lorraine , Hudson Eleanor , Holch Patricia , Carter Robert , Gibson Andrea , Holmes Marie , Rogers Zoe , Dickinson Sarah , Morris Carolyn , Woroncow Barbara , Brown Julia , Hulme Claire , Velikova Galina
Published: January 2024

PURPOSE

A randomized controlled trial of online symptom monitoring during chemotherapy with electronic patient self-Reporting of Adverse-events: Patient Information and aDvice (eRAPID) system found improved symptom control and patient self-efficacy, without increasing hospital admissions and visits. The aim of this study was to evaluate the cost-effectiveness of the eRAPID eHealth intervention compared with usual care for patients receiving systemic treatment for colorectal, breast, or gynecologic cancers in the United Kingdom.

METHODS

An embedded economic evaluation was conducted alongside the trial evaluating the effectiveness of eRAPID from health care provider and societal perspectives. Costs and quality-adjusted life-years (QALYs) of patients were compared over 18 weeks of the trial. Incremental cost-effectiveness ratios (ICERs) were estimated and compared with the National Institute for Health and Care Excellence cost-effectiveness threshold. Uncertainty around the ICER was explored using nonparametric bootstrapping and sensitivity analyses. Follow-up data were collected 12-months after random assignment for a subset of the study sample to conduct exploratory analysis of potential longer-term effects.

RESULTS

Patients in the eRAPID group had the highest QALY gain and lowest costs over 18 weeks. Although differences were small and not statistically significant, eRAPID had a 55%-58% probability of being more cost-effective than usual care. Patient out-of-pocket costs were lower in the eRAPID group, indicating eRAPID may help patients access support needed within the National Health Service. Exploratory 12-months analysis showed small differences in costs and QALYs, with higher QALY gains in the eRAPID group but also higher costs. Exploratory subgroup analysis by disease status indicated that the eRAPID intervention was cost-effective for patients with early-stage cancers but not for patients with metastatic disease.

CONCLUSION

Despite small differences in QALYs and costs, the analyses show potential cost-effectiveness of online symptom monitoring, when added to usual care, particularly during adjuvant systemic treatment for early-stage cancers.
Virtual Bioequivalence Assessment of Ritlecitinib Capsules with Incorporation of Observed Clinical Variability Using a Physiologically Based Pharmacokinetic Model
Authors: Saadeddin Anas , Purohit Vivek , Huh Yeamin , Wong Mei , Maulny Aurelia , Dowty Martin E. , Sagawa Kazuko
Published: January 2024

Ritlecitinib, an orally available Janus kinase 3 and tyrosine kinase inhibitor being developed for the treatment of alopecia areata (AA), is highly soluble across the physiological pH range at the therapeutic dose. As such, it is expected to dissolve rapidly in any in vitro dissolution conditions. However, in vitro dissolution data showed slower dissolution for 100-mg capsules, used for the clinical bioequivalence (BE) study, compared with proposed commercial 50-mg capsules. Hence, a biowaiver for the lower 50-mg strength using comparable multimedia dissolution based on the f2 similarity factor was not possible. The in vivo relevance of this observed in vitro dissolution profile was evaluated with a physiologically based pharmacokinetic (PBPK) model. This report describes the development, verification, and application of the ritlecitinib PBPK model to translate observed in vitro dissolution data to an in vivo PK profile for ritlecitinib capsule formulations. Virtual BE (VBE) trials were conducted using the Simcyp VBE module, including the model-predicted within-subject variability or intra-subject coefficient of variation (ICV). The results showed the predicted ICV was predicted to be smaller than observed clinical ICV, resulting in a more optimistic BE risk assessment. Additional VBE assessment was conducted by incorporating clinically observed ICV. The VBE trial results including clinically observed ICV demonstrated that proposed commercial 50-mg capsules vs clinical 100-mg capsules were bioequivalent, with > 90% probability of success. This study demonstrates a PBPK model–based biowaiver for a clinical BE study while introducing a novel method to integrate clinically observed ICV into VBE trials with PBPK models. Trial registration: NCT02309827, NCT02684760, NCT04004663, NCT04390776, NCT05040295, NCT05128058.

Graphical Abstract
Humanin Treatment Protects Against Venetoclax-Induced Bone Growth Retardation in Ex Vivo Cultured Rat Bones
Authors: Velentza Lilly , Wickström Malin , Kogner Per , Ohlsson Claes , Zaman Farasat , Sävendahl Lars
Published: January 2024

Context

Recent preclinical studies reported that the BCL-2 inhibitor venetoclax can impair bone growth. A strategy to prevent such a side effect of this promising anticancer drug is highly desired. Earlier in vitro and in vivo studies suggested that the mitochondrial peptide humanin has the potential to prevent drug-induced growth impairment.

Objective

We hypothesized that co-treatment with the humanin analog HNG may prevent venetoclax-induced bone growth impairment.

Methods

Ex vivo studies were performed in fetal rat metatarsal bones and human growth plate samples cultured for 12 and 2 days, respectively, while in vivo studies were performed in young neuroblastoma mice being treated daily for 14 days. The treatment groups included venetoclax, HNG, venetoclax plus HNG, or vehicle. Bone growth was continuously monitored and at the end point, histomorphometric and immunohistochemical analyses were performed in fixed tissues.

Results

Venetoclax suppressed metatarsal bone growth and when combined with HNG, bone growth was rescued and all histological parameters affected by venetoclax monotherapy were normalized. Mechanistic studies showed that HNG downregulated the pro-apoptotic proteins Bax and p53 in cultured metatarsals and human growth plate tissues, respectively. The study in a neuroblastoma mouse model confirmed a growth-suppressive effect of venetoclax treatment. In this short-term in vivo study, no significant bone growth-rescuing effect could be verified when testing HNG at a single dose. We conclude that humanin dose-dependently protects ex vivo cultured metatarsal bones from venetoclax-induced bone growth impairment by restoring the growth plate microstructure.
Children of the Sexual Politics of Abortion and Transition
Authors: Gill-Peterson Jules
Published: January 2024

This article elucidates the connection between anti-trans and anti-abortion political movements, looking closely at laws banning gender-affirming care in the wake of the Supreme Court's Dobbs v. Jackson decision in 2022. In particular, the article claims, “anti-abortion and anti-trans political successes are floated by a moral crisis over a fantasized, imperiled child.”
“Criminalization is the Antithesis of Care”
Authors: Haley Sarah , Ritchie Andrea J. , Thuma Emily L.
Published: January 2024

In this contribution to GLQ's Q2, the authors discuss the long histories of gender violence, anti-Blackness, and criminalization and the strategies and resources of abolition feminism for responding to the Supreme Court's Dobbs v. Jackson decision in 2022.