bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory landscape enrichment analysis (RLEA): a computational toolkit for non-coding variant enrichment and cell type prioritization
Authors: Rosean Samuel , Sosa Eric A. , O’Shea Dónal , Raj Srilakshmi M. , Seoighe Cathal , Greally John M.
Published: May 2024

Background

As genomic studies continue to implicate non-coding sequences in disease, testing the roles of these variants requires insights into the cell type(s) in which they are likely to be mediating their effects. Prior methods for associating non-coding variants with cell types have involved approaches using linkage disequilibrium or ontological associations, incurring significant processing requirements. GaiaAssociation is a freely available, open-source software that enables thousands of genomic loci implicated in a phenotype to be tested for enrichment at regulatory loci of multiple cell types in minutes, permitting insights into the cell type(s) mediating the studied phenotype.

Results

In this work, we present Regulatory Landscape Enrichment Analysis (RLEA) by GaiaAssociation and demonstrate its capability to test the enrichment of 12,133 variants across the cis-regulatory regions of 44 cell types. This analysis was completed in 134.0 ± 2.3 s, highlighting the efficient processing provided by GaiaAssociation. The intuitive interface requires only four inputs, offers a collection of customizable functions, and visualizes variant enrichment in cell-type regulatory regions through a heatmap matrix. GaiaAssociation is available on PyPi for download as a command line tool or Python package and the source code can also be installed from GitHub at https://github.com/GreallyLab/gaiaAssociation.

Conclusions

GaiaAssociation is a novel package that provides an intuitive and efficient resource to understand the enrichment of non-coding variants across the cis-regulatory regions of different cells, empowering studies seeking to identify disease-mediating cell types.
Elucidating the callus-to-shoot-forming mechanism in Capsicum annuum ‘Dempsey’ through comparative transcriptome analyses
Authors: Han Sang-Yun , Park So Young , Won Kang-Hee , Park Sung-il , Park Jae-Hyeong , Shim Donghwan , Hwang Inhwan , Jeong Dong-Hoon , Kim Hyeran
Published: May 2024

Background

The formation of shoots plays a pivotal role in plant organogenesis and productivity. Despite its significance, the underlying molecular mechanism of de novo regeneration has not been extensively elucidated in Capsicum annuum ‘Dempsey’, a bell pepper cultivar. To address this, we performed a comparative transcriptome analysis focusing on the differential expression in C. annuum ‘Dempsey’ shoot, callus, and leaf tissue. We further investigated phytohormone-related biological processes and their interacting genes in the C. annuum ‘Dempsey’ transcriptome based on comparative transcriptomic analysis across five species.

Results

We provided a comprehensive view of the gene networks regulating shoot formation on the callus, revealing a strong involvement of hypoxia responses and oxidative stress. Our comparative transcriptome analysis revealed a significant conservation in the increase of gene expression patterns related to auxin and defense mechanisms in both callus and shoot tissues. Consequently, hypoxia response and defense mechanism emerged as critical regulators in callus and shoot formation in C. annuum ‘Dempsey’. Current transcriptome data also indicated a substantial decline in gene expression linked to photosynthesis within regenerative tissues, implying a deactivation of the regulatory system governing photosynthesis in C. annuum ‘Dempsey’.

Conclusion

Coupled with defense mechanisms, we thus considered spatial redistribution of auxin to play a critical role in the shoot morphogenesis via primordia outgrowth. Our findings shed light on shoot formation mechanisms in C. annuum ‘Dempsey’ explants, important information for regeneration programs, and have broader implications for precise molecular breeding in recalcitrant crops.
Indirect calorimetry directed feeding and cycling in the older ICU population: a pilot randomised controlled trial
Authors: Elizabeth Ng Shu Hui , Yanni Tan , May Leong Siaw , Fen Tiong Hui , Janice Li Xuanhui , Peijun Kwan , Pheng Ong Sze , Jie Toh Shi , Will Loh Ne Hooi
Published: May 2024

Background

Older critically ill patients experience rapid muscle loss during stay in an intensive care unit (ICU) due to physiological stress and increased catabolism. This may lead to increased ICU length of stay, delayed weaning from ventilation and persistent functional limitations. We hypothesized that with optimal nutrition and early physical therapy acting in synergism, we can reduce muscle mass loss and improve functional outcomes.

Methods

This was a prospective, single blinded randomized, controlled single-center pilot study to compare the lean muscle mass (measured at bilateral quadriceps femoris using ultrasound) of older ICU patients at 4 time points over 14 days between the control and intervention groups. The control group received standard weight-based empiric feeding and standard ICU physiotherapy. The intervention group received indirect calorimetry directed feeding adjusted daily and 60 min per day of cycle ergometry. 21 patients were recruited and randomized with 11 patients in the control arm and 10 patients in the intervention arm. Secondary outcome measures included ICU and hospital mortality, length of stay, functional assessments of mobility and assessment of strength.

Results

Median age was 64 in the control group and 66 in the intervention group. Median calories achieved was 24.5 kcal/kg per day in the control group and 23.3 kcal/kg per day in the intervention group. Cycle ergometry was applied to patients in the intervention group for a median of 60 min a day and a patient had a median of 8.5 sessions in 14 days. Muscle mass decreased by a median of 4.7cm2 in the right quadriceps femoris in the control group and 1.8cm2 in the intervention group (p = 0.19), while the left quadriceps femoris decreased by 1.9cm2 in the control group and 0.1cm2 in the intervention group (p = 0.51).

Conclusion

In this pilot study, we found a trend towards decrease muscle loss in bilateral quadriceps femoris with our combined interventions. However, it did not reach statistical significance likely due to small number of patients recruited in the study. However, we conclude that the intervention is feasible and potentially beneficial and may warrant a larger scale study to achieve statistical significance.

Trial Registration

This study was registered on Clinicaltrials.gov on 30th May 2018 with identifier NCT03540732.
Effect of lidocaine on intraoperative blood pressure variability in patients undergoing major vascular surgery
Authors: Gajniak Dariusz , Mendrala Konrad , König-Widuch Gabriela , Parzonka Szymon , Gierek Danuta , Krzych Łukasz J
Published: May 2024

Background

Dynamic fluctuations of arterial blood pressure known as blood pressure variability (BPV) may have short and long-term undesirable consequences. During surgical procedures blood pressure is usually measured in equal intervals allowing to assess its intraoperative variability, which significance for peri and post-operative period is still under debate. Lidocaine has positive cardiovascular effects, which may go beyond its antiarrhythmic activity. The aim of the study was to verify whether the use of intravenous lidocaine may affect intraoperative BPV in patients undergoing major vascular procedures.

Methods

We performed a post-hoc analysis of the data collected during the previous randomized clinical trial by Gajniak et al. In the original study patients undergoing elective abdominal aorta and/or iliac arteries open surgery were randomized into two groups to receive intravenous infusion of 1% lidocaine or placebo at the same infusion rate based on ideal body weight, in concomitance with general anesthesia. We analyzed systolic (SBP), diastolic (DBP) and mean arterial blood (MAP) pressure recorded in 5-minute intervals (from the first measurement before induction of general anaesthesia until the last after emergence from anaesthesia). Blood pressure variability was then calculated for SBP and MAP, and expressed as: standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and coefficient of hemodynamic stability (C10%), and compared between both groups.

Results

All calculated indexes were comparable between groups. In the lidocaine and placebo groups systolic blood pressure SD, CV, AVR and C10% were 20.17 vs. 19.28, 16.40 vs. 15.64, 14.74 vs. 14.08 and 0.45 vs. 0.45 respectively. No differences were observed regarding type of surgery, operating and anaesthetic time, administration of vasoactive agents and intravenous fluids, including blood products.

Conclusion

In high-risk vascular surgery performed under general anesthesia, lidocaine infusion had no effect on arterial blood pressure variability.

Trial registration

ClinicalTrials.gov; NCT04691726 post-hoc analysis; date of registration 31/12/2020.
Prospective measurement of the width of cerebrospinal fluid spaces by cranial ultrasound in neurologically healthy children aged 0–19 months
Authors: Fandak Jozef , Markart Stefan , Willems Erik P. , Wildermuth Simon , Frauenfelder Thomas , Fischer Tim , Dietrich Tobias J. , Waelti Stephan L.
Published: May 2024

Background

Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0–19 months and assess whether subdural fluid collections can be delineated.

Methods

Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US.

Results

This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1–599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected.

Conclusion

Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.
Microsurgical treatment of ophthalmic artery aneurysm, a case series of 55 patients with long-term follow-up
Authors: Rahmanian Abdolkarim , Mohammad Hosseini Ehsan , Sourani Arman , Jamali Mohammad , Saffarian Arash , Eghbal Keyvan , Taherpour Sanaz , Foroughi Mina
Published: May 2024

Background

Ophthalmic artery aneurysm (OAA) can be secured in endovascular or microsurgical approaches. Still there are controversies in technique selection and their long term outcomes.

Methods

All the patients with OAA were treated microsurgically and followed. Demographic data, neurological status, physical examination findings, angiographic data, operation details, and intraoperative and postoperative events were recorded and analyzed. P < 0.05 was considered significant.

Results

Among 55 patients, 38 were females (69.1%). Median preoperative glasgow coma scale (GCS), Fisher Grade, and Hunt and Hess(HH) scores were 15, 1 and 1, respectively. The most common neurologic manifestation was visual problems (n = 15). The most common anatomical projection was medial (43.6%) oriented lesions. 85.5% of them only had 1 ophthalmic aneurysm while multiple aneurysms were reported in 14.6%. In 52 patients temporary clip was used. in 21 patients (38.2%) intraoperative aneurysm rupture occurred. Larger aneurysm size and preoperative hydrocephalus were associated with higher rates of aneurysm rupture (P = 0.003 and 0.031). 28.5% of the patients with visual problems had clinical improvement in the postoperative period. The mean follow-up period was 5 years. Follow-up angiography showed a 100% obliteration rate with a 0.0% recurrence rate. Median values for follow-up glasgow outcome scale and modified Rankin scale were 5 and 0, respectively. favorable neurological outcomes were associated with better primary GCS and HH scores.

Conclusion

OAA microsurgery is an effective and safe procedure with significant improvement in both visual and neurological status. Low recurrence rate and excellent clinical recovery are the most important advantages of microsurgery in OAA treatment.
Ovarian response to controlled stimulation and its predictors in a limited-resource setting
Authors: Dermolo Munira , Ansa Meseret , Siferih Melkamu
Published: May 2024

Background

Infertility remains a serious health concern for Ethiopian women. Most of its treatment approaches entail controlled ovarian stimulation, the responses of which vary. However, there are no data on ovarian response to stimulation or its predictors in our situation. Thus, the current study aimed to assess the ovarian response to controlled stimulation and identify predictors.

Methods

A retrospective follow-up study was undertaken from April 1, 2021, to March 31, 2022, among patients who had first-cycle controlled ovarian stimulation at St.Paul’s Hospital Fertility Center in Addis Ababa, Ethiopia. Clinical data were extracted using a checklist. SPSS-26 for data analysis and Epidata-4.2 for data entry were employed. The binary logistic regression model was fitted. A p-value < 0.05 indicated a significant association. The ROC curve was used to determine cutoff values and identify accurate predictors.

Results

A total of 412 study participants were included in the final analysis. The patients had a mean age of 32.3 ± 5.1 years (range: 20 − 4). The good ovarian response rate was 67% (95% CI: 62.2–71.5). An anti-Mullerian hormone (AMH) concentration < 1.2ng/ml (AOR = 0.19, 95% CI (0.06–0.57)), an antral follicle count (AFC) < 5 (AOR = 0.16, 95% CI (0.05–0.56)), and an induction length < 10 days (AOR = 0.23, 95% CI (0.06–0.93)) were significantly associated with ovarian response. The prediction accuracies for the AFC and AMH concentrations were 0.844 and 0.719, respectively. The optimal cutoff point for prediction was 5.5 AFC, which had a sensitivity of 77.2% and a specificity of 72.8%. However, its positive and negative predictive values were 85.2% and 61.1%, respectively. For AMH, the optimal cutoff value was 0.71ng/mL, with a corresponding sensitivity and specificity of 65.2% and 66%. At this value, the positive and negative predictive values were 63.8% and 67.3%, respectively.

Conclusion

Only two-thirds of our patients achieved a good ovarian response. Induction duration, AMH concentration, and AFC were found to be predictors, with the AFC being the strongest predictor. Therefore, the AFC should be performed on all of our patients, and the AMH is selectively employed. Future research must verify the best cutoff points and investigate additional factors affecting ovarian response.
The impact of the Systematic Assessment for Resilience (SAR) framework on students’ resilience, anxiety, depression, burnout, and academic-related stress: a quasi-experimental study
Authors: Wadi Majed , Shorbagi Ali , Shorbagi Sarra , Taha Mohamed Hassan , Bahri Yusoff Muhamad Saiful
Published: May 2024

Background

Medical students face significant psychological stress, impacting their academic performance and well-being. The Systematic Assessment for Resilience (SAR) framework is designed to enhance resilience and mitigate stress among medical students, addressing the need for interventions within the assessment system in medical education. The aim of this study was to evaluate the implementation of SAR framework on medical students’ resilience, anxiety, depression, burnout, and academic stress.

Methods

This study employed a quasi-experimental design with pre- and post-testing. It involved the training of course coordinators in implementing the SAR framework and its integration into the daily learning activities. Fourth-year medical students were assessed before and after the intervention using standardized measures of resilience, anxiety, depression, burnout, and academic stress. Data were analyzed using quantitative methods and thematic analysis for qualitative feedback.

Results

Post-intervention, students demonstrated a significant increase in resilience scores (p < 0.001) and a notable decrease in measures of anxiety, depression, and academic stress (p < 0.001). The burnout types were also statistically different (p < 0.001) except client-related burnout (p > 0.05). Qualitative feedback of the course coordinators highlighted an improved learning environment, increased coping strategies, and a more supportive academic culture.

Conclusion

The SAR framework significantly contributes to enhancing medical students’ resilience and reducing psychological distress. Its implementation suggests a promising approach to fostering a supportive educational environment that not only addresses the psychological challenges faced by medical students but also enhances their academic performance and overall well-being. Further research is warranted to explore the long-term impacts of SAR across different medical education contexts.
Perceptions of undergraduate medical students on artificial intelligence in medicine: mixed-methods survey study from Palestine
Authors: Jebreen Kamel , Radwan Eqbal , Kammoun-Rebai Wafa , Alattar Etimad , Radwan Afnan , Safi Walaa , Radwan Walaa , Alajez Mohammed
Published: May 2024

Background

The current applications of artificial intelligence (AI) in medicine continue to attract the attention of medical students. This study aimed to identify undergraduate medical students’ attitudes toward AI in medicine, explore present AI-related training opportunities, investigate the need for AI inclusion in medical curricula, and determine preferred methods for teaching AI curricula.

Methods

This study uses a mixed-method cross-sectional design, including a quantitative study and a qualitative study, targeting Palestinian undergraduate medical students in the academic year 2022–2023. In the quantitative part, we recruited a convenience sample of undergraduate medical students from universities in Palestine from June 15, 2022, to May 30, 2023. We collected data by using an online, well-structured, and self-administered questionnaire with 49 items. In the qualitative part, 15 undergraduate medical students were interviewed by trained researchers. Descriptive statistics and an inductive content analysis approach were used to analyze quantitative and qualitative data, respectively.

Results

From a total of 371 invitations sent, 362 responses were received (response rate = 97.5%), and 349 were included in the analysis. The mean age of participants was 20.38 ± 1.97, with 40.11% (140) in their second year of medical school. Most participants (268, 76.79%) did not receive formal education on AI before or during medical study. About two-thirds of students strongly agreed or agreed that AI would become common in the future (67.9%, 237) and would revolutionize medical fields (68.7%, 240). Participants stated that they had not previously acquired training in the use of AI in medicine during formal medical education (260, 74.5%), confirming a dire need to include AI training in medical curricula (247, 70.8%). Most participants (264, 75.7%) think that learning opportunities for AI in medicine have not been adequate; therefore, it is very important to study more about employing AI in medicine (228, 65.3%). Male students (3.15 ± 0.87) had higher perception scores than female students (2.81 ± 0.86) (p < 0.001). The main themes that resulted from the qualitative analysis of the interview questions were an absence of AI learning opportunities, the necessity of including AI in medical curricula, optimism towards the future of AI in medicine, and expected challenges related to AI in medical fields.

Conclusion

Medical students lack access to educational opportunities for AI in medicine; therefore, AI should be included in formal medical curricula in Palestine.
Crisis leadership behaviors in healthcare: survey validation and influence on staff outcomes in primary care clinics during the COVID-19 pandemic
Authors: Yang Michelle , Evans Jenna M. , Singer Sara J. , Gutberg Jennifer , Porter Tracy H. , Grudniewicz Agnes
Published: May 2024

Background

The COVID-19 pandemic triggered an unprecedented transition from in-person to virtual delivery of primary health care services. Leaders were at the helm of the rapid changes required to make this happen, yet outcomes of leaders’ behaviours were largely unexplored. This study (1) develops and validates the Crisis Leadership and Staff Outcomes (CLSO) Survey and (2) investigates the leadership behaviours exhibited during the transition to virtual care and their influence on select staff outcomes in primary care.

Methods

We tested the CLSO Survey amongst leaders and staff from four Community Health Centres in Ontario, Canada. The CLSO Survey measures a range of crisis leadership behaviors, such as showing empathy and promoting learning and psychological safety, as well as perceived staff outcomes in four areas: innovation, teamwork, feedback, and commitment to change. We conducted an exploratory factor analysis to investigate factor structure and construct validity. We report on the scale’s internal consistency through Cronbach’s alpha, and associations between leadership scales and staff outcomes through odds ratios.

Results

There were 78 staff and 21 middle and senior leaders who completed the survey. A 4-factor model emerged, comprised of the leadership behaviors of (1) “task-oriented leadership” and (2) “person-oriented leadership”, and select staff outcomes of (3) “commitment to sustaining change” and (4) “performance self-evaluation”. Scales exhibited strong construct and internal validity. Task- and person-oriented leadership behaviours positively related to the two staff outcomes.

Conclusion

The CLSO Survey is a reliable measure of leadership behaviours and select staff outcomes. Our results suggest that crisis leadership is multifaceted and both person-oriented and task-oriented leadership behaviours are critical during a crisis to improve perceived staff performance and commitment to change.
Genomic insights into the cellular specialization of predation in raptorial protists
Authors: Li Zaihan , Chen Xiao , Zhao Fangqing , Miao Miao
Published: May 2024

Background

Predation is a fundamental mechanism for organisms to acquire energy, and various species have evolved diverse tools to enhance their hunting abilities. Among protozoan predators, raptorial Haptorian ciliates are particularly fascinating as they possess offensive extrusomes known as toxicysts, which are rapidly discharged upon prey contact. However, our understanding of the genetic processes and specific toxins involved in toxicyst formation and discharge is still limited.

Results

In this study, we investigated the predation strategies and subcellular structures of seven Haptoria ciliate species and obtained their genome sequences using single-cell sequencing technology. Comparative genomic analysis revealed distinct gene duplications related to membrane transport proteins and hydrolytic enzymes in Haptoria, which play a crucial role in the production and discharge of toxicysts. Transcriptomic analysis further confirmed the abundant expression of genes related to membrane transporters and cellular toxins in Haptoria compared to Trichostomatia. Notably, polyketide synthases (PKS) and l-amino acid oxidases (LAAO) were identified as potentially toxin genes that underwent extensive duplication events in Haptoria.

Conclusions

Our results shed light on the evolutionary and genomic adaptations of Haptorian ciliates for their predation strategies in evolution and provide insights into their toxic mechanisms.
Supplementation with selenium and coenzyme Q10 in an elderly Swedish population low in selenium — positive effects on thyroid hormones, cardiovascular mortality, and quality of life
Authors: Alehagen Urban , Alexander Jan , Aaseth Jan O. , Larsson Anders , Opstad Trine B.
Published: May 2024

Background

Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q10 on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL).

Methods

Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 µg/L, corresponding to an estimated intake of 35 µg/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses.

Results

In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q10 for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p < 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH > median and fT3 < median were associated with a decline in mental Hr-QoL measures vs. TSH < and fT3 > median in the placebo group during 4 years of follow-up, but this was wiped out in the active group.

Conclusions

Supplementation with selenium and coenzyme Q10 had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency.

Trial registration

This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.
Glucose competition between endothelial cells in the blood-spinal cord barrier and infiltrating regulatory T cells is linked to sleep restriction-induced hyperalgesia
Authors: Huang Yulin , Xu Rui , Liu Qi , Zhang Xiao , Mao Yanting , Yang Yan , Gu Xiaoping , Liu Yue , Ma Zhengliang
Published: May 2024

Background

Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously.

Methods

The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration.

Results

The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro.

Conclusions

Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.
Vaginal leiomyoma in a goat expressing the nuclear progesterone receptor (PGR): a case report
Authors: Trzebiatowski Lukas , Kowalewski Mariusz Pawel , Schmid Sarah , Skaar Kirstin , Müller Jana , Wehrend Axel
Published: May 2024

Background

The risk of developing tumorous diseases in the genital tract also increases with age in animals. One of the classified tumor types is genital leiomyoma. Presently, our understanding of the pathogenesis of this tumor in goats is, however, limited. This accounts also for the information regarding the presence of steroid hormone receptors and, thus, possible responsiveness to circulating steroids.

Case presentation

This study describes the case of a vaginal tumor in a seven-year-old Anglo-Nubian goat. The goat was presented due to blood mixed vaginal discharge. Per vaginal examination a singular pedunculated mass in the dorsum of the vagina measuring approximately 3 cm x 4 cm x 4 cm was revealed. After administering epidural anesthesia, the mass was removed electrothermally. There were no postoperative complications. The histopathological examination identified the mass as a leiomyoma. The immunohistochemical examination revealed the presence of the nuclear progesterone receptor (PGR) in the tumor tissue. One year after the surgery, during the follow-up examination, the goat was in good overall health, and the owners had not observed any recurrence of vaginal discharge.

Conclusions

When observing vaginal discharge in goats, it is important to consider the possibility of genital tract tumors. These tumors may express sex steroid receptors. In the future, it is worth considering the investigation of potential approaches for preventing tumorigenesis or treating the tumor, such as castration or the administration of antiprogestogens.
Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: a national cohort study
Authors: Cui Cancan , Liu Lin , Qi Yitian , Han Ning , Xu Haikun , Wang Zhijia , Shang Xinyun , Han Tianjiao , Zha Yining , Wei Xin , Wu Zhiyuan
Published: May 2024

Background

Both the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and systemic inflammation are predictors of cardiovascular diseases; however, little is known about the coexposures and relative contributions of TyG index and inflammation to cardiovascular diseases. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted longitudinal analyses to evaluate the joint and mutual associations of the TyG index and high-sensitivity C-reactive protein (hsCRP) with cardiovascular events in middle-aged and older Chinese population.

Methods

This study comprised 8 658 participants aged at least 45 years from the CHARLS 2011 who are free of cardiovascular diseases at baseline. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Cardiovascular events were defined as the presence of physician-diagnosed heart disease and/or stroke followed until 2018.We performed adjusted Cox proportional hazards regression and mediation analyses.

Results

The mean age of the participants was 58.6 ± 9.0 years, and 3988 (46.1%) were females. During a maximum follow-up of 7.0 years, 2606 (30.1%) people developed cardiovascular diseases, including 2012 (23.2%) cases of heart diseases and 848 (9.8%) cases of stroke. Compared with people with a lower TyG index (< 8.6 [median level]) and hsCRP < 1 mg/L, those concurrently with a higher TyG and hsCRP had the highest risk of overall cardiovascular disease (adjusted hazard ratio [aHR], 1.300; 95% CI 1.155–1.462), coronary heart disease (aHR, 1.294; 95% CI 1.130–1.481) and stroke (aHR, 1.333; 95% CI 1.093–1.628), which were predominant among those aged 70 years or below. High hsCRP significantly mediated 13.4% of the association between the TyG index and cardiovascular disease, while TyG simultaneously mediated 7.9% of the association between hsCRP and cardiovascular risk.

Conclusions

The findings highlight the coexposure effects and mutual mediation between the TyG index and hsCRP on cardiovascular diseases. Joint assessments of the TyG index and hsCRP should be underlined for the residual risk stratification and primary prevention of cardiovascular diseases, especially for middle-aged adults.
New insights into targeted therapy of glioblastoma using smart nanoparticles
Authors: Ghaznavi Habib , Afzalipour Reza , Khoei Samideh , Sargazi Saman , Shirvalilou Sakine , Sheervalilou Roghayeh
Published: May 2024

In recent times, the intersection of nanotechnology and biomedical research has given rise to nanobiomedicine, a captivating realm that holds immense promise for revolutionizing diagnostic and therapeutic approaches in the field of cancer. This innovative fusion of biology, medicine, and nanotechnology aims to create diagnostic and therapeutic agents with enhanced safety and efficacy, particularly in the realm of theranostics for various malignancies. Diverse inorganic, organic, and hybrid organic–inorganic nanoparticles, each possessing unique properties, have been introduced into this domain. This review seeks to highlight the latest strides in targeted glioblastoma therapy by focusing on the application of inorganic smart nanoparticles. Beyond exploring the general role of nanotechnology in medical applications, this review delves into groundbreaking strategies for glioblastoma treatment, showcasing the potential of smart nanoparticles through in vitro studies, in vivo investigations, and ongoing clinical trials.
Polymorphism rs2327430 in TCF21 predicts the risk and prognosis of gastric cancer by affecting the binding between TFAP2A and TCF21
Authors: Zhou Xinyi , Shen Kuan , Cao Shuqing , Li Pengyu , Xiao Jian , Dong Jiacheng , Cheng Quan , Hu Li , Xu Zekuan , Yang Li
Published: May 2024

Background

Single nuclear polymorphisms (SNPs) have been published to be correlated with multiple diseases. Transcription Factor 21 (TCF21) is a critical transcription factor involved in various types of cancers. However, the association of TCF21 genetic polymorphisms with gastric cancer (GC) susceptibility and prognosis remains unclear.

Methods

A case-control study comprising 890 patients diagnosed with GC and an equal number of cancer-free controls was conducted. After rigorous statistical analysis, molecular experiments were carried out to elucidate the functional significance of the SNPs in the context of GC.

Results

TCF21 rs2327430 (OR = 0.78,P = 0.026) provides protection against GC, while rs4896011 (OR = 1.39,P = 0.005) exhibit significant associations with GC risk. Furthermore, patients with the (TC + CC) genotype of rs2327430 demonstrate a relatively favorable prognosis (OR = 0.47,P = 0.012). Mechanistically, chromatin immunoprecipitation assay and luciferase reporter assay revealed that the C allele of rs2327430 disrupts the binding of Transcription Factor AP-2 Alpha (TFAP2A) to the promoter region of TCF21, resulting in increased expression of TCF21 and inhibition of malignant behaviors in GC cells.

Conclusion

Our findings highlight the significant role of TCF21 SNPs in both the risk and prognosis of GC and provide valuable insights into the underlying molecular mechanisms. Specifically, the disruptive effect of rs2327430 on TCF21 expression and its ability to modulate malignant cell behaviors suggest that rs2327430 may serve as a potential predictive marker for GC risk and prognosis.
circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)
Authors: Tang Yi-fang , Liu Zheng-hua , Zhang Lei-yi , Shi Sheng-hao , Xu Shun , Ma Jin-An , Hu Chun-Hong , Zou Fang-wen
Published: May 2024

Background

Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC.

Methods

Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis.

Results

The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance.

Conclusions

Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.

Graphical Abstract
Algorithm for detection and screening of familial hypercholesterolemia in Lithuanian population
Authors: Aliosaitiene Urte , Petrulioniene Zaneta , Rinkuniene Egidija , Mainelis Antanas , Brazdziuniene Egle , Smailyte Urte , Sileikiene Vaida , Laucevicius Aleksandras
Published: May 2024

Background

Familial hypercholesterolemia (FH) is one of the most common autosomal dominant diseases. FH causes a lifelong increase in low-density lipoprotein cholesterol (LDL-C) levels, which in turn leads to atherosclerotic cardiovascular disease. The incidence of FH is widely underestimated and undertreated, despite the availability and effectiveness of lipid-lowering therapy. Patients with FH have an increased cardiovascular risk; therefore, early diagnosis and treatment are vital. To address the burden of FH, several countries have implemented national FH screening programmes. The currently used method for FH detection in Lithuania is mainly based on opportunistic testing with subsequent cascade screening of index cases’ first-degree relatives.

Methods

A total of 428 patients were included in this study. Patients with suspected FH are referred to a lipidology center for thorough evaluation. Patients who met the criteria for probable or definite FH according to the Dutch Lipid Clinic Network (DLCN) scoring system and/or had LDL-C > = 6.5 mmol/l were subjected to genetic testing. Laboratory and instrumental tests, vascular marker data of early atherosclerosis, and consultations by other specialists, such as radiologists and ophthalmologists, were also recorded.

Results

A total of 127/428 (30%) patients were genetically tested. FH-related mutations were found in 38.6% (n = 49/127) of the patients. Coronary artery disease (CAD) was diagnosed in 13% (n = 57/428) of the included patients, whereas premature CAD was found in 47/428 (11%) patients. CAD was diagnosed in 19% (n = 9/49) of patients with FH-related mutations, and this diagnosis was premature for all of them.

Conclusions

Most patients in this study were classified as probable or possible FH without difference of age and sex. The median age of FH diagnosis was 47 years with significantly older females than males, which refers to the strong interface of this study with the LitHir programme. CAD and premature CAD were more common among patients with probable and definite FH, as well as those with an FH-causing mutation. The algorithm described in this study is the first attempt in Lithuania to implement a specific tool which allows to maximise FH detection rates, establish an accurate diagnosis of FH, excluding secondary causes of dyslipidaemia, and to select patients for cascade screening initiation more precisely.
Predictors for temporary stomas non-closure among non-metastatic rectal cancer patients undergoing curative resection: a retrospective analysis
Authors: Hsu Chia-Chien , Tsai Wen-Sy , Tsai Tzong-yun , You Jeng-Fu , Yeh Chien-Yuh , Hsieh Pao-Shiu , Tang Reiping , Huang Shu-Huan
Published: May 2024

Background

The primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection.

Methods

Consecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed.

Results

Out of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001).

Conclusion

Prognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.
Coping strategies, resilience and quality of life: reaction to the COVID-19 pandemic among Romanian physicians
Authors: Crișan Cătălina Angela , Pop Răzvan , Stretea Roland , Milhem Zaki , Forray Alina-Ioana
Published: May 2024

Background

The COVID-19 pandemic has presented multiple psychological challenges for healthcare workers, such as anxiety, depression, burnout, and substance use disorders. In this research, we investigate the different ways Romanian physicians dealt with the difficult period of the COVID-19 pandemic. We also analyze how positive and negative stress-reducing strategies, as well as demographic variables, affect their psychological resilience and quality of life. Our goal is to provide a comprehensive overview of how physicians coped with the unprecedented global health challenges.

Methods

We carried out a national cross-sectional study of 265 physicians in Romania between January 2021 and January 2022 using a web-based questionnaire. The study employed a web-based questionnaire to assess coping mechanisms using the COPE inventory, resilience through the Connor-Davidson Resilience Scale 25 (CD-RISC 25), and quality of life via the WHOQOL-BREF scale. The COPE inventory, consisting of 60 items across 15 subscales, categorizes coping strategies into problem-focused, emotion-focused, and dysfunctional types, with each item rated on a 4-point scale. The CD-RISC 25 measures resilience on a 5-point Likert scale, with total scores ranging from 0 to 100. WHOQOL-BREF assesses quality of life through 26 items in 4 domains: physical, mental, social relations, and environmental, scored from 1 to 5 and converted to a 0–100 scale for domain scores. Univariate and multivariate linear regression models were employed to discern the intricate relationships between coping strategies, resilience levels, quality of life dimensions, and pertinent demographic factors.

Results

The average CD-RISC score among participants was 66.2. The mean scores for the values for the QOL subscales were 64.0 for physical well-being, 61.7 for psychological well-being, 61.2 for social relationships, and 64.7 for environment. Individuals tend to use problem-focused and emotion-focused coping more than dysfunctional mechanisms, according to the COPE inventory. Problem-focused and emotion-focused coping are positively correlated with resilience, while dysfunctional coping is negatively correlated. Resilience is significantly influenced by gender and professional status, with males and senior specialists reporting higher levels while younger physicians and residents reporting lower levels.

Conclusions

Our data points to specific protective characteristics and some detrimental factors on physicians' resilience and quality of life during the pandemic.