bluuebunny/crossref_metadata_2025 huggingface dataset:
A highly efficient protocol for isolation of protoplast from China, Assam and Cambod types of tea plants [Camellia sinensis (L.) O. Kuntze]
Authors: Kumar Abhishek , Rawat Nikhil , Thakur Shweta , Joshi Rohit , Pandey Shiv Shanker
Published: December 2023

Background

Tea is the most popular beverage worldwide second only to water. Its demand is tremendously rising due to increased awareness of its medicinal importance. The quality and uses of tea depend on the tea-types which are mainly three types including China, Assam and Cambod type having distinct compositions of secondary metabolites. Huge variation in secondary metabolites in different tea-types and cultivars limited the successful application of various approaches used for its trait improvement. The efficiency of a protocol for isolation of protoplast is specific to the types and cultivars of tea plants. The existing tea protoplast-isolation protocols [which were optimized for tea-types (China and Assam type) and Chinese cultivars grown in China] were found ineffective on types/cultivars grown in India due to type/cultivar variability. Therefore, optimization of protoplast-isolation protocol is essential for tea-types/cultivars grown in India, as it is the second largest producer of tea and the largest producer of black tea. Here, efforts were made to develop an efficient protoplast-isolation protocol from all major types of tea (China, Assam and Cambod types) grown in India and also from three types of tender leaves obtained from field-grown, hydroponically-grown and tissue culture-grown tea plants.

Results

Developed protoplast-isolation protocol was effective for different types of leaf tissue obtained from the tender leaves of field-grown, hydroponically-grown and tissue culture-grown tea plants. Moreover, optimized protocol effectively worked on all three types of tea including China, Assam and Cambod types cultivated in India. The digestion of leaves with 3% cellulase R-10, 0.6% macerozyme, 1% hemicellulase and 4% polyvinylpyrrolidone for 12 h at 28ºC yielded approximately 3.8–4.6 × 107 protoplasts per gram fresh tissue and 80–95% viability in selected tea cultivars, and tissue culture plant material was found most appropriate for protoplast isolation.

Conclusions

In conclusion, we reported an efficient protocol for isolation of protoplasts from tender tea leaves of all major tea-types (China, Assam and Cambod) grown in India. Moreover, the protocol is also effective for tender-leaf tissue of field-grown, hydroponically-grown and tissue culture-grown tea plants. The findings are expected to contribute to the genetic improvement of tea traits widely.
Administration of adipose-derived mesenchymal stem cell conditioned medium improves ovarian function in polycystic ovary syndrome rats: involvement of epigenetic modifiers system
Authors: Shafiei Golnaz , Saheli Mona , Ganjalikhan-hakemi Sepideh , Haghpanah Tahereh , Nematollahi-mahani Seyed Noureddin
Published: December 2023

Background

Polycystic ovary syndrome (PCOS) is a widespread heterogeneous disease that is in association with genetic, epigenetic, endocrine and environmental factors. Adipose-derived mesenchymal stem cell (ASC) and ASC-conditioned medium (ASC-CM) have shown promising abilities in tissue regeneration. In the present study, we aimed to investigate the effects of ASC and ASC-CM on epigenetic regulators, steroidal function and folliculogenesis in the letrozole-induced PCOS rats.

Results

Based on the measurement of the oral glucose tolerance test and physical parameters including body weight, estrus cycle pattern as well as ovary dimensions, PCOS-induced rats in sham and control (CTRL) groups showed signs of reproductive dysfunctions such as lack of regular estrus cyclicity, metabolic disorders such as increased ovary dimension, body weight and blood glucose level alteration which were improved especially by ASC-CM administration.
Effects of a multilevel intervention of resistance training with or without beta-hydroxy-beta-methylbutyrate in medical ICU patients during entire hospitalisation: a four-arm multicentre randomised controlled trial
Authors: Wu Ting-Ting , Chen Qiao-Ling , Lin Xiu-Xia , Xu Mei-Lian , Chen Xue-Xian , Luo Chen-Juan , Zhuang Yao-Ning , Wei Yue-Qing , Wu Jing-Bing , Xiong Jing , Chen Li-Li , Li Hong
Published: December 2023

Background

Intensive care unit-acquired weakness (ICU-AW) is a prevalent and severe issue among ICU patients. Resistance training and beta-hydroxy-beta-methylbutyrate (HMB) intervention have demonstrated the potential to enhance muscle function in patients with sarcopenia and in older adults. The purpose of this study was to determine whether resistance training and/or HMB administration would improve physical function, muscle strength, and quality of life in medical ICU patients.

Methods

In this multicentre, four-arm, single-blind randomised control trial, a total of 112 adult patients with internal medical diagnoses admitted to the ICU were enrolled. These participants were then randomly assigned to one of four treatment groups: the resistance training group received protocol-based multilevel resistance exercise, the HMB group received 3 g/day of HMBCa, combination group and control groups received standard care, from the ICU to the general ward until discharge. The primary outcomes assessed at discharge included six-minute walking distance (6MWD) and short physical performance battery (SPPB). Secondary outcomes measured included muscle mass, MRC score, grip strength, and health reports quality of life at different time points. Data analysis was performed using a generalised linear mixed model, adhering to the principles of intention-to-treat analysis.

Results

Resistance training and combination treatment groups exhibited significant increases in SPPB scores (3.848 and 2.832 points, respectively) compared to the control group and substantial improvements in 6WMD (99.768 and 88.577 m, respectively) (all with P < 0.01). However, no significant changes were observed in the HMB group. Muscle strength, as indicated by MRC and grip strength tests conducted at both ICU and hospital discharge, showed statistically significant improvements in the resistance training and combination groups (P < 0.05). Nevertheless, no significant differences were found between the treatment groups and usual care in terms of 60-day mortality, prevalence of ICU-AW, muscle mass, quality of life, or other functional aspects.

Conclusions

Resistance training with or without beta-hydroxy-beta-methylbutyrate during the entire hospitalisation intervention improves physical function and muscle strength in medical ICU patients, but muscle mass, quality of life, and 60-day mortality were unaffected.

Trial registration

ChiCTR2200057685 was registered on March 15th, 2022.
To adopt or adapt an existing neonatal core outcome set in Kenya: a study protocol
Authors: Karumbi Jamlick , Gathara David , Young Bridget , Williamson Paula
Published: December 2023

Background

Development and use of core outcome set(s) (COS) in research can reduce research wastage by ensuring that a minimum set of outcomes are always reported on. Neonatal morbidity and mortality are a big burden in low- and middle-income countries (LMICs). Research is continuously being undertaken to reduce this burden. Currently, there is no COS for neonatal research in LMICs but there exists one for neonatal research in high-income countries (HICs).

Objectives

To determine outcomes that are useful for neonatal care in Kenya to inform whether an existing COS should be adopted or adapted. To assess the feasibility of a routine data collection system to collect data of the agreed-on COS.

Methods

A review of existing literature on neonatal research in LMICs followed by a qualitative study of key stakeholders in neonatal care. To explore whether to adapt or adopt, in two hospitals, two focus group discussions with 6–8 parents/caregivers will be undertaken (one each in two hospitals). Key informant interviews will also be conducted with 6 health care providers in each of the hospitals. At the policy-making level, we will conduct 10 key informant interviews. Qualitative data will be analyzed thematically. A consensus meeting will be undertaken with key stakeholders, who will be presented with an overview of the COS developed for HICs, key findings from the literature, and the qualitative study to determine context-appropriate COS. The agreed-on outcomes will be counterchecked against the case records in the two hospitals. The feasibility of collecting the outcomes on a routine electronic research database, the Clinical Information Network that collects standardized data at admission and discharge, will be explored. The congruence (or not) of the outcomes will be documented and be used to enrich the discussion and provide a snapshot of the feasibility of the health information system to collect routine data on the COS.

Conclusions

A COS for use in neonatal care in Kenya will help enhance outcome measurements and reporting not just in research but also in routine practice. This will enhance the comparability of interventions in trials and routine settings leading to reduced research wastage and likely improved quality of care. Additionally, the methodology used for this work can be adopted in other settings as a means of adopting or adapting an existing COS.
Pre-hospital pulse glucocorticoid therapy in patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention: a randomized controlled trial (PULSE-MI)
Authors: Madsen Jasmine Melissa , Obling Laust Emil Roelsgaard , Rytoft Laura , Folke Fredrik , Hassager Christian , Andersen Lars Bredevang , Vejlstrup Niels , Bang Lia Evi , Engstrøm Thomas , Lønborg Jacob Thomsen
Published: December 2023

Background

Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI.

Methods

This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark, will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 h duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) 3 months after STEMI. Secondary outcomes comprise key CMR efficacy parameters, clinical endpoints at 3 months, the peak of cardiac biomarkers, and safety.

Discussion

We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation and thus reduces final infarct size in patients with STEMI treated with primary PCI.

Trial registration

EU-CT number: 2022–500762-10–00; Submitted May 5, 2022. ClinicalTrials.gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022.
The dual pro-inflammatory and bone-protective role of calcitonin gene-related peptide alpha in age-related osteoarthritis
Authors: Hildebrandt Alexander , Dietrich Tamara , Weber Jérôme , Günderoth Mara Meyer , Zhou Sijia , Fleckenstein Florian N. , Jiang Shan , Winkler Tobias , Duda Georg N. , Tsitsilonis Serafeim , Keller Johannes , Maleitzke Tazio
Published: December 2023

Background

The vasoactive neuropeptide calcitonin gene-related peptide alpha (αCGRP) enhances nociception in primary knee osteoarthritis (OA) and has been shown to disrupt cartilage and joint integrity in experimental rheumatoid arthritis (RA). Little is known about how αCGRP may alter articular structures in primary OA. We investigated whether αCGRP modulates local inflammation and concomitant cartilage and bone changes in a murine model of age-dependent OA.

Methods

Sixteen- to 18-month-old αCGRP-deficient mice (αCGRP−/−aged) were compared to, first, age-matched wild type (WTaged) and, second, young 4- to 5-month-old non-OA αCGRP-deficient (αCGRP−/−CTRL) and non-OA WT animals (WTCTRL). αCGRP levels were measured in serum. Knee and hip joint inflammation, cartilage degradation, and bone alterations were assessed by histology (OARSI histopathological grading score), gene expression analysis, and µ-computed tomography.

Results

WTaged mice exhibited elevated αCGRP serum levels compared to young WTCTRL animals. Marked signs of OA-induced cartilage destruction were seen in WTaged animals, while αCGRP−/−aged mice were mostly protected from this effect. Age-dependent OA was accompanied by an increased gene expression of pro-inflammatory Tnfa, Il1b, and Il6 and catabolic Mmp13, Adamts5, Ctsk, Tnfs11 (Rankl), and Cxcl12/Cxcr4 in WTaged but not in αCGRP−/−aged mice. αCGRP-deficiency however further aggravated subchondral bone sclerosis of the medial tibial plateau and accelerated bone loss in the epi- and metaphyseal trabecular tibial bone in age-dependent OA.

Conclusions

Similar to its function in experimental RA, αCGRP exerts a dual pro-inflammatory and bone-protective function in murine primary OA. Although anti-CGRP treatment was previously not successful in reducing pain in OA clinically, these data underline a crucial pathophysiological role of αCGRP in age-related OA.
Transcriptome-wide map of N6-methyladenosine (m6A) profiling in coronary artery disease (CAD) with clopidogrel resistance
Authors: Yu Ruoyan , Yu Qinglin , Li Zhenwei , Li Jiyi , Yang Jin , Hu Yingchu , Zheng Nan , Li Xiaojin , Song Yudie , Li Jiahui , Chen Xiaomin , Du Weiping , Su Jia
Published: December 2023

Background

Clopidogrel resistance profoundly increases the risk of major cardiovascular events in coronary artery disease (CAD) patients. Here, we comprehensively analyse global m6A modification alterations in clopidogrel-resistant (CR) and non-CR patients.

Methods

After RNA isolation, the RNA transcriptome expression (lncRNA, circRNA, and mRNA) was analysed via RNA-seq, and m6A peaks were identified by MeRIP-seq. The altered m6A methylation sites on mRNAs, lncRNAs, and circRNAs were identified, and then, GO and KEGG pathway analyses were performed. Through joint analysis with RNA-seq and MeRIP-seq data, differentially expressed mRNAs harbouring differentially methylated sites were identified. The changes in m6A regulator levels and the abundance of differentially methylated sites were measured by RT-PCR. The identification of m6A-modified RNAs was verified by m6A-IP-qPCR.

Results

The expression of 2919 hypermethylated and 2519 hypomethylated mRNAs, 192 hypermethylated and 391 hypomethylated lncRNAs, and 375 hypermethylated and 546 hypomethylated circRNAs was shown to be altered in CR patients. The m6A peaks related to CR indicated lower mark density at the CDS region. Functional enrichment analysis revealed that inflammatory pathways and insulin signalling pathways might be involved in the pathological processes underlying CR. The expression of mRNAs (ST5, KDM6B, GLB1L2, and LSM14B), lncRNAs (MSTRG.13776.1 and ENST00000627981.1), and circRNAs (hsa_circ_0070675_CBC1, hsa-circRNA13011-5_CBC1, and hsa-circRNA6406-3_CBC1) was upregulated in CR patients, while the expression of mRNAs (RPS16 and CREG1), lncRNAs (MSTRG.9215.1), and circRNAs (hsa_circ_0082972_CBC1) was downregulated in CR patients. Moreover, m6A regulators (FTO, YTHDF3, and WTAP) were also differentially expressed. An additional combined analysis of gene expression and m6A peaks revealed that the expression of mRNAs (such as ST5, LYPD2, and RPS16 mRNAs) was significantly altered in the CR patients.

Conclusion

The expression of m6A regulators, the RNA transcriptome, and the m6A landscape was altered in CR patients. These findings reveal epitranscriptomic regulation in CR patients, which might be novel therapeutic targets in future.
Mitochondrial DNA copy number variation across three generations: a possible biomarker for assessing perinatal outcomes
Authors: Fukunaga Hisanori , Ikeda Atsuko
Published: December 2023

Background

Mitochondria have their own circular multi-copy genome (mtDNA), and abnormalities in the copy number are implicated in mitochondrial dysfunction, which contributes to a variety of aging-related pathologies. However, not much is known about the genetic correlation of mtDNA copy number across multiple generations and its physiological significance.

Methods

We measured the mtDNA copy number in cord blood or peripheral blood from 149 three-generation families, specifically the newborns, parents, and grandparents, of 149 families, totaling 1041 individuals. All of the biological specimens and information were provided by the Tohoku Medical Megabank Project in Japan. We also analyzed their maternal factors during pregnancy and neonatal outcomes.

Results

While the maternal peripheral blood mtDNA copy number was lower than that of other adult family members, it was negatively correlated with cord blood mtDNA copy number in male infants. Also, cord blood mtDNA copy numbers were negatively correlated with perinatal outcomes, such as gestation age, birth weight, and umbilical cord length, for both male and female neonates. Furthermore, the mtDNA copy number in the infants born to mothers who took folic acid supplements during pregnancy would be lower than in the infants born to mothers who did not take them.

Conclusions

This data-driven study offers the most comprehensive view to date on the genetic and physiological significance of mtDNA copy number in cord blood or peripheral blood taken from three generations, totaling more than 1000 individuals. Our findings indicate that mtDNA copy number would be one of the transgenerational biomarkers for assessing perinatal outcomes, as well as that appropriate medical interventions could improve the outcomes via quantitative changes in mtDNA.
A novel patient-derived meningioma spheroid model as a tool to study and treat epithelial-to-mesenchymal transition (EMT) in meningiomas
Authors: van de Weijer Laurien L. , Ercolano Emanuela , Zhang Ting , Shah Maryam , Banton Matthew C. , Na Juri , Adams Claire L. , Hilton David , Kurian Kathreena M. , Hanemann C. Oliver
Published: December 2023

Meningiomas are the most common intracranial brain tumours. These tumours are heterogeneous and encompass a wide spectrum of clinical aggressivity. Treatment options are limited to surgery and radiotherapy and have a risk of post-operative morbidities and radiation neurotoxicity, reflecting the need for new therapies. Three-dimensional (3D) patient-derived cell culture models have been shown to closely recapitulate in vivo tumour biology, including microenvironmental interactions and have emerged as a robust tool for drug development. Here, we established a novel easy-to-use 3D patient-derived meningioma spheroid model using a scaffold-free approach. Patient-derived meningioma spheroids were characterised and compared to patient tissues and traditional monolayer cultures by histology, genomics, and transcriptomics studies. Patient-derived meningioma spheroids closely recapitulated morphological and molecular features of matched patient tissues, including patient histology, genomic alterations, and components of the immune microenvironment, such as a CD68 + and CD163 + positive macrophage cell population. Comprehensive transcriptomic profiling revealed an increase in epithelial-to-mesenchymal transition (EMT) in meningioma spheroids compared to traditional monolayer cultures, confirming this model as a tool to elucidate EMT in meningioma. Therefore, as proof of concept study, we developed a treatment strategy to target EMT in meningioma. We found that combination therapy using the MER tyrosine kinase (MERTK) inhibitor UNC2025 and the histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) effectively decreased meningioma spheroid viability and proliferation. Furthermore, we demonstrated this combination therapy significantly increased the expression of the epithelial marker E-cadherin and had a repressive effect on WHO grade 2-derived spheroid invasion, which is suggestive of a partial reversal of EMT in meningioma spheroids.
Maritime silk road heritage: quantitative typological analysis of qing dynasty export porcelain bowls from Guangzhou from the perspective of social factors
Authors: Ao Jinghui , Li Weicong , Ji Shanshan , Chen Simin
Published: December 2023

The formation of decorative patterns on export porcelain has risen to the research dimension of cross-regional culture. The interplay between social elements and the formal evolution of export porcelain bowls from the Qing Dynasty in Guangzhou remains nebulous. This study elucidates these underlying cultural dynamics through the lenses of utility and societal implications, thus addressing how societal components contribute to the molding of tangible cultural heritage. Key findings include: (1) A dominance of the ring-foot design in the bases of Qing Dynasty export bowls; (2) The diameter and height of the Qing Dynasty export bowls show relatively concentrated characteristics, reflecting a systemic production trend and relative consistency in form; (3) Some of the Qing Dynasty bowls exceed the parameter range of typical tableware, reflecting the adaptability and innovation of production mechanisms in responding to special market demands. The morphological evolution of the Qing Dynasty export bowls is a true reflection of the interweaving of multiple factors such as comfort design and aesthetic preferences, while the uniformity in shape is a comprehensive reflection of meeting market demands and advances in production technology. This study extends the research dimension to the interaction between standardized production techniques and socio-cultural demands.
Cost-benefit Analysis and Financial Viability of Household Biogas Plant Investment in South Ethiopia
Authors: Geddafa Tale , Melka Yoseph , Sime Getachew
Published: December 2023

This study investigates the cost–benefit analysis and financial viability of biogas plant investment in South Ethiopia. A multi-stage sampling technique was employed to select sample households. A total of 105 adopter households were selected for household survey using a purposive sampling technique. All the households adopting biogas technology were considered. Besides, a biogas plant with 6 m3 and 8 m3 sizes were selected because they were the most commonly used size in the study area. Data were collected from the household survey, key informant interviews, focus group discussion and market price assessment. The installation cost took the largest share of the total cost of construction and was one of the main constraints that hindered adoption. The findings of the study indicate that the production of biogas increased household income by reducing the costs incurred for buying firewood, kerosene and chemical fertilizers. Relatively, lower plant size was more profitable than larger plant size. Installation under the subsidy scheme was more financially viable at 10% discount rate than its counterparts. Subsidy is important to enhance biogas plant investment, particularly for larger biogas plant sizes. Nevertheless, both plant sizes, installed without subsidy, had smaller NPV values and UDBP greater than 1 year, making this scenario financially less viable. Installation of low cost plants could more attract the engagement of a large number of rural households with low economic capacity. However, both plant sizes (6 m3 and 8 m3) are financially viable and profitable at 10% discount rate. Moreover, the profitability of biogas investment is highly sensitive to variation in discount rates, level of expenditure savings and input prices.
Predicting future global temperature and greenhouse gas emissions via LSTM model
Authors: Hamdan Ahmad , Al-Salaymeh Ahmed , AlHamad Issah M. , Ikemba Samuel , Ewim Daniel Raphael Ejike
Published: December 2023

This work is executed to predict the variation in global temperature and greenhouse gas (GHG) emissions resulting from climate change and global warming, taking into consideration the natural climate cycle. A mathematical model was developed using a Recurrent Neural Network (RNN) with Long–Short-Term Memory (LSTM) model. Data sets of global temperature were collected from 800,000 BC to 1950 AD from the National Oceanic and Atmospheric Administration (NOAA). Furthermore, another data set was obtained from The National Aeronautics and Space Administration (NASA) climate website. This contained records from 1880 to 2019 of global temperature and carbon dioxide levels. Curve fitting techniques, employing Sin, Exponential, and Fourier Series functions, were utilized to reconstruct both NOAA and NASA data sets, unifying them on a consistent time scale and expanding data size by representing the same information over smaller periods. The fitting quality, assessed using the R-squared measure, ensured a thorough process enhancing the model's accuracy and providing a more precise representation of historical climate data. Subsequently, the time-series data were converted into a supervised format for effective use with the LSTM model for prediction purposes. Augmented by the Mean Squared Error (MSE) as the analyzed loss function, normalization techniques, and refined data representation from curve fitting the LSTM model revealed a sharp increase in global temperature, reaching a temperature rise of 4.8 °C by 2100. Moreover, carbon dioxide concentrations will continue to boom, attaining a value of 713 ppm in 2100. In addition, the findings indicated that the RNN algorithm (LSTM model) provided higher accuracy and reliable forecasting results as the prediction outputs were closer to the international climate models and were found to be in good agreement. This study contributes valuable insights into the trajectory of global temperature and GHG emissions, emphasizing the potential of LSTM models in climate prediction.
Transcranial direct current stimulation as treatment for major depression in a home treatment setting (HomeDC trial): study protocol and methodology of a double-blind, placebo-controlled pilot study
Authors: Kumpf Ulrike , Ezim Harry , Stadler Matthias , Burkhardt Gerrit , Palm Ulrich , Dechantsreiter Esther , Padberg Frank
Published: December 2023

Introduction

Transcranial direct current stimulation (tDCS) of prefrontal cortex regions has been reported to exert therapeutic effects in patients with major depressive disorder (MDD). Due to its beneficial safety profile, its easy mode of application, and its cost-effectiveness, tDCS has recently been proposed for treatment at home. This would offer new chances for regionally widespread and long-term application. However, tDCS at home must meet the new methodological challenges of handling and adherence. At the same time, data from randomized controlled trials (RCT) investigating this mode of application are still lacking. In this pilot RCT, we therefore investigate the feasibility, safety, and effectiveness of a new antidepressant tDCS application set-up.

Methods and analysis

The HomeDC trial will be conducted as a double-blind, placebo-controlled, parallel-group design trial. Thirty-two study participants with MDD will be randomly assigned to active or sham tDCS groups. Participants will self-administer prefrontal tDCS for 6 weeks. Active tDCS will be conducted with anode over F3, cathode over F4, for 5 sessions/week, with a duration of 30 min/day, and 2 mA stimulation intensity. Sham tDCS, conversely, follows an identical protocol in regard to electrode montage and timing, but with no electric stimulation between the ramp-in and ramp-out periods. Both conditions will be administered either as a monotherapy or an adjunctive treatment to a stable dose of antidepressant medication. Adjunctive magnetic resonance imaging (MRI) and electric field (E-field) modelling will be conducted at baseline. Primary outcome is feasibility based on successfully completed stimulations and drop-out rates. The intervention is considered feasible when 20 out of 30 sessions have been fully conducted by at least 75% of the participants. Effectiveness and safety will be assessed as secondary outcomes.

Discussion

In the HomeDC trial, the technical requirements for a placebo-controlled tDCS study in a home-based treatment setting have been established. The trial addresses the crucial points of the home-based tDCS treatment approach: uniform electrode positioning, frequent monitoring of stimulation parameters, adherence, and ensuring an appropriate home treatment environment. This study will further identify constraints and drawbacks of this novel mode of treatment.

Trial registration

www.ClinicalTrials.gov. Trial registration number: NCT05172505. Registration date: 12/13/2021.
An audit of the use of CT pituitary scans to exclude a pituitary macroadenoma
Authors: Douglas Lisa , Caldwell James , Bolland Mark
Published: December 2023

Background

Pituitary imaging is often required to exclude an adenoma suspected clinically or biochemically. Although magnetic resonance (MR) is the gold standard, computerised tomography (CT) is faster, cheaper and induces less claustrophobia. Our audit at Auckland City Hospital, New Zealand, investigated whether the use of CT of the pituitary as the first line imaging to assess for a pituitary macroadenoma reduces the need for MR.

Methods

We investigated the usefulness of CT pituitary imaging in the exclusion of pituitary macroadenoma between 2012 and 2020. A re-audit was then undertaken for a period of one year between March 2021 and March 2022 to assess outcomes once a departmental policy change was implemented. At Auckland City Hospital, 32 patients across eight years were eligible for this analysis, of which 31 had data available. In our re-audit, 29 patients were eligible for this analysis. We collected data on patient demographics, relevant hormone levels, indication for imaging and imaging results and subsequent management.

Results

After CT pituitary imaging, 28/31 (90%) of patients did not require further imaging because the clinical question had been addressed. One year after routine initial CT pituitary imaging was implemented by the Auckland City Hospital Endocrinology Department, 29 CT pituitary scans were performed to exclude a pituitary macroadenoma. Of these patients one required further imaging due to the finding of an expanded pituitary sella but not a pituitary macroadenoma.

Conclusion

CT pituitary imaging to exclude a pituitary macroadenoma is a useful test that may reduce the need for MR pituitary scans.

Trial registration

Not applicable. This was an audit as defined by the New Zealand National Ethics Advisory Committee guidelines. Please see ‘Declarations’ section.
£25 and a biscuit: Women’s Health Research and Public Engagement in the UK
Authors: Perry Alison Gabrielle , Mullins Edward
Published: December 2023

It is over a  year since the Department of Health launched the Women’s Health Strategy for England and included the rally cry of “women’s voices”. However, methods and modes of the inclusion of women in their own health and health research still fall short. Patient and public engagement and involvement (PPIE) in women’s health research is considered a hallmark of a moral, ethical, and democratic society. Despite the call for the inclusion of “women’s voices” and “women’s stories”, approaches to PPIE often remain tokenistic and don’t address issues of representation, equality, and diversity or respond to wider racial inequalities in health. This past August marked the 103rd birthday of the late Henrietta Lacks who died of cervical cancer. Clones of her cells (HeLa cells) obtained without consent, continue to be used in laboratories around the world and serves as an ongoing reminder of dynamics and power in health research relationships with the public today. Historically, women have been mistreated and excluded from research and the reality that Black women in the UK remain 3.7 times more likely to die in childbirth makes the effectiveness of our research pathways critical (MBRRACE-UK, https://www.npeu.ox.ac.uk/mbrrace-uk). PPIE holds much potential to contribute to the improvement of shortcomings in maternity and women’s health, but not without deeper understanding of the ways in which engagement intrinsically, works. This article raises criticism of the current quality of engagement in women’s health research and calls for a redesign of our frameworks and the need to explore new configurations of the relationship between women’s health, research, and people.
Implementation of community physiotherapy in primary care: one-year results of an on-call physiotherapy service
Authors: Paci Matteo , Bianchi Lapo , Buonandi Elisa , Rosiello Laura , Moretti Sandra
Published: December 2023

Background

Primary health care systems have a key role in meeting health needs of community, including function. The aim of this paper is to describe the population involved in the Community Physiotherapist project and their health outcomes over a one-year period.

Methods

The Community Physiotherapist is an on-call service which requires a request by general practitioners or medical specialists. Reason for prescription, waiting time for service delivery, diagnostic categories, provided intervention, number of interventions and outcomes were recorded for everyone included in the project. Possible differences in characteristics between individuals referred by medical specialists and general practitioners were also investigated.

Results

From January to December 2022, 409 individuals were referred to the Community Physiotherapist pathway. Functional goals were achieved in 79.5% of interventions, without reported adverse events. In most cases physiotherapists provided counselling or caregiver training and 3.3% of individuals needed a full rehabilitation program. The groups of individuals referred by the two types of prescribers showed no significant differences, apart, as expected, from their median age.

Conclusions

The introduction of the Community Physiotherapist model within the primary care setting allows to provide appropriate, effective and safe interventions. Sharing the project among all the health professionals helped to support its appropriateness and effectiveness. Results also indicate that a new organizational model, such as the Community Physiotherapist, will take a long time to be implemented.
14,15-Dihydroxyeicosatrienoic acid, a soluble epoxide hydrolase metabolite in blood, is a predictor of anthracycline-induced cardiotoxicity – a hypothesis generating study
Authors: dos Santos Julia Matzenbacher , Joiakim Aby , Putt David A. , Scherrer-Crosbie Marielle , Kim Hyesook
Published: December 2023

Background

Early identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted treatment to reduce cardiac dysfunction. Rats treated with doxorubicin (DOX), a chemotherapeutic agent, have increased cardiac expression of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), a bioactive lipid implicated in hypertension and coronary artery disease. However, the utility of 14,15-DHET as plasma biomarkers was not defined. The aim of this study is to investigate if levels of 14,15-DHET are an early blood biomarker to predict the subsequent occurrence of cardiotoxicity in cancer patients after chemotherapy.

Methods

H9c2 rat cardiomyocytes were treated with DOX (1 μM) for 2 h and levels of 14,15-DHET in cell media was quantified at 2, 6 or 24 h in media after DOX treatment. Similarly, female Sprague–Dawley rats were treated with DOX for two weeks and levels of 14,15-DHET was assessed in plasma at 48 h and 2 weeks after DOX treatment. Changes in brain natriuretic peptide (BNP) mRNA, an early cardiac hypertrophy process, were determined in the H9c2 cells and rat cardiac tissue. Results were confirmed in human subjects by assessment of levels of 14,15-DHET in plasma of breast cancer patients before and after DOX treatment and left ventricular ejection fraction (LVEF), a clinical marker of cardiotoxicity.

Results

Levels of 14,15-DHET in cell media and rat plasma increased ~ 3-fold and was accompanied with increase in BNP mRNA in H9c2 cells and rat cardiac tissue after DOX treatment. In matched plasma samples from breast cancer patients, levels of 14,15-DHET were increased in patients that developed cardiotoxicity at 3 months before occurrence of LVEF decrease.

Conclusions

Together, these results indicate that levels of 14,15-DHET are elevated prior to major changes in cardiac structure and function after exposure to anthracyclines. Increased levels of 14,15-DHET in plasma may be an important clinical biomarker for early detection of anthracycline-induced cardiotoxicity in cancer patients.
Connective tissue involvement in an m.10191 T > C carrier with Leigh-like syndrome
Authors: Finsterer Josef , Newstead Shaundra M.
Published: December 2023

Background

Connective tissue involvement in a mitochondrial disorder has been only rarely reported.

Case presentation

A 32-year-old female with Leigh-like syndrome extending into adulthood due to the mtDNA variant m.10191 T > C developed various connective tissue abnormalities, which manifested as hyperlaxity of joints, decreased clivo-axial angle, subluxations of various joints, scoliosis, hyperextensibility of skin (stretchy skin), easy tearing, papyraceous scarring, frequent petechiae, very easy bruising, impaired wound healing, blood pooling in feet, and tiny veins. She received symptomatic treatment and physiotherapy, which provided some sort of relief.

Conclusions

The phenotypic spectrum of the m.10191 T > C variant is broader than previously anticipated.
Sphericity index for bedside diagnosis of acute myocarditis
Authors: AbdelMassih Antoine , El-Saiedi Sonia , Hendawy Rana , Esmail Reem , AbdelHameed Manal , Sobeih Alaa , Kharabish Ahmed , Diab Nourine , Gaber Hanya , El-Husseiny Nadine , Agha Hala M.
Published: December 2023

Background

Differentiating acute myocarditis (AMY) from dilated cardiomyopathy (DCM) in a patient presenting with acute heart failure and poor systolic function is of utmost importance to initiate timely anti-inflammatory treatment in AMY. Using cardiac magnetic resonance (CMR) or endomyocardial biopsies (EMB) as gold standards might be limited due to the likelihood of hemodynamic compromise. Eccentric myocardial remodeling as measured by sphericity index (SPI) might be useful in differentiating AMY from DCM, due to the progressive increase in transverse LV diameter in DCM. The primary outcome parameter of our study was to test the diagnostic accuracy of SPI in the differentiation of AMY from DCM, while the secondary outcome parameter was to compare the diagnostic accuracy of SPI to troponin I in the same context. For this purpose, we conducted a retrospective study involving a chart review of the files of sixty patients admitted with acute heart failure due to hypokinetic left ventricle in our hospital. Patients were divided after CMR imaging into two groups: group 1 with AMY (n = 30) and group 2 with DCM (n = 30). Demographic and clinical characteristics of the patients, including heart rate, need for mechanical ventilation, use of milrinone, epinephrine and norepinephrine, troponin I, and 2D-derived sphericity index, were collected from patients’ files.

Results

Patients with AMY had a higher need for mechanical ventilation inopressors and vasopressors; 73% of AMY patients required mechanical ventilation and epinephrine use, compared to less than 50% of DCM patients. Troponin I elevation was more marked in AMY compared to DCM patients (0.25 ± 0.04 vs. 0.21 ± 0.03, respectively). SPI was significantly higher in DCM compared to AMY cases, denoting a spherical configuration of the myocardium acquired due to progressive remodeling, because of the chronicity of the pathology. ROC analysis revealed that an SPI ≤ 0.38 was 100% sensitive in differentiating DCM from AMY, compared to a 53% sensitivity with the commonly used troponin I.

Conclusion

AMY diagnosis can be achieved by the assessment of sphericity index rather than troponin I. The bedside nature and noninvasiveness of SPI should reshape the practice in this context. SPI assessment can be part of point-of-care echocardiography, taught to emergency room (ER) physicians and intensivists.
Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?
Authors: Fisher Alessandra D , Ristori Jiska , Romani Alessia , Cassioli Emanuele , Mazzoli Francesca , Cocchetti Carlotta , Pierdominici Marina , Marconi Matteo , Ricca Valdo , Maggi Mario , Vignozzi Linda , Castellini Giovanni
Published: December 2023

Context

The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated.

Objective

The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time.

Methods

This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2.

Results

The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist–hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns.

Conclusion

Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed.
An Overview of Cannabidiol
Authors: Sideris Alexandra , Doan Lisa V.
Published: December 2023

Cannabidiol (CBD) is one of the most interesting constituents of cannabis, garnering significant attention in the medical community in recent years due to its proven benefit for reducing refractory seizures in pediatric patients. Recent legislative changes in the United States have made CBD readily available to the general public, with up to 14% of adults in the United States having tried it in 2019. CBD is used to manage a myriad of symptoms, including anxiety, pain, and sleep disturbances, although rigorous evidence for these indications is lacking. A significant advantage of CBD over the other more well-known cannabinoid delta-9-tetrahydroncannabinol (THC) is that CBD does not produce a “high.” As patients increasingly self-report its use to manage their medical conditions, and as the opioid epidemic continues to drive the quest for alternative pain management approaches, the aims of this narrative review are to provide a broad overview of the discovery, pharmacology, and molecular targets of CBD, its purported and approved neurologic indications, evidence for its analgesic potential, regulatory implications for patients and providers, and future research needs.
Low achromatic contrast sensitivity in birds: a common attribute shared by many phylogenetic orders
Authors: Blary Constance L. M. , Duriez Olivier , Bonadonna Francesco , Mitkus Mindaugas , Caro Samuel P. , Besnard Aurélien , Potier Simon
Published: December 2023

Vision is an important sensory modality in birds, which can outperform other vertebrates in some visual abilities. However, sensitivity to achromatic contrasts – the ability to discern luminance difference between two objects or an object and its background – has been shown to be lower in birds compared with other vertebrates. We conducted a comparative study to evaluate the achromatic contrast sensitivity of 32 bird species from 12 orders using the optocollic reflex technique. We then performed an analysis to test for potential variability in contrast sensitivity depending on the corneal diameter to the axial length ratio, a proxy of the retinal image brightness. To account for potential influences of evolutionary relatedness, we included phylogeny in our analyses. We found a low achromatic contrast sensitivity for all avian species studied compared with other vertebrates (except small mammals), with high variability between species. This variability is partly related to phylogeny but appears to be independent of image brightness.
Δημιουργικές αντιστάσεις και υποκείμενα μετά τη νεοφιλελεύθερη αναδιάρθρωση
Authors: Ζαφείρης Κωνσταντίνος
Published: December 2023

Η παρούσα διδακτορική διατριβή ασχολείται με τη μελέτη αυτοοργανωμένων χώρων που προέκυψαν σε πόλεις οι οποίες έχουν περάσει από επιθετικές νεοφιλελεύθερες αναδιαρθρώσεις μετά από μεγάλες οικονομικές κρίσεις. Η δημιουργικότητα ως αντίσταση και όχι ως μηχανισμός κερδοφορίας αποτελεί ένα ανοιχτό θεωρητικό ερώτημα στο σύνολο αυτής της έρευνας. Η κριτική γεωγραφία και ο ανοιχτός Μαρξισμός, μέσα από την επανανοηματοδότηση μίας αρνητικής διαλεκτικής, αποτέλεσαν τους βασικούς θεωρητικούς άξονες της έρευνας. Άλλος άξονας είναι οι σύγχρονες μετα- και αντι-αποικιακές προσεγγίσεις. Η έρευνα εστιάζει στις ακόλουθες πόλεις της λεγόμενης "ημιπεριφέρειας": την Πόλη του Μεξικού, το Μπουένος Άιρες και την Αθήνα. Τα τελευταία 30 χρόνια οι τρεις αυτές πόλεις βρέθηκαν αντιμέτωπες με πολιτικές διαχείρισης της οικονομικής κρίσης οι οποίες απέκτησαν εξορυκτικά -τόσο για τον χώρο όσο και για τα υποκείμενα- χαρακτηριστικά, μέσα από ένα μίγμα πολιτικών που οδήγησαν σε βάθεμα των κοινωνικών αντιθέσεων και μεγάλες οικονομικό-κοινωνικές αναδιαρθρώσεις. Η αντίσταση σ’ αυτήν την ακραία νεοφιλελεύθερη καθημερινότητα γίνεται μέσα από την αναζήτηση και δημιουργία απελευθερωμένων χώρων εντός των μεγαλουπόλεων. Αυτοί οι χώροι αντιστέκονται στις αυστηρές εποπτικές χρήσεις του χώρου, αλλά και στους τρόπους αξιοποίησης των πόρων μιας πόλης (οικονομικών, πολιτιστικών, κοινωνικών, συμβολικών). Μέσα απ’ αυτούς τους χώρους και αυτές τις πρακτικές επαναδιατυπώνεται η έννοια και το αίτημα για το δικαίωμα στην πόλη. Αυτό συμβαίνει μέσα από την δημιουργία διαφόρων δομών αυτοοργάνωσης, αλληλεγγύης και δημιουργίας που -πιάνοντας το νήμα των ιδιαίτερων κατά τόπους παραδόσεων ανταρσίας- διεκδικούν τον δικό τους χώρο εντός των πόλεων.Βασικό εργαλείο ανάπτυξης των τρόπων έρευνας αποτέλεσε μία προσπάθεια ένταξης μιας αντι-αποικιακής επιστημολογίας στους τρόπους έρευνας. Τελικά, η "συμμετοχική έρευνα-δράση" κάνει τα υποκείμενα μελέτης συν-συγγραφείς της συγκεκριμένης διατριβής.