bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological mechanisms of carvacrol against hepatocellular carcinoma by network pharmacology and molecular docking
Authors: Liu Lu , Yu Ping , Zhao Zhongwei , Yang Hongyuan , Yu Risheng
Published: February 2025

Background

Preclinical studies have demonstrated that carvacrol possesses various biological and pharmacological properties, including anti-hepatocellular carcinoma (HCC) effects. However, the molecular basis of its therapeutic action on HCC remains unclear.

Objective

The aim of this study was to investigate and further validate the multi-target therapeutic mechanism of carvacrol against HCC.

Methods

The chemical structure of carvacrol was obtained from the PubChem database, and its potential targets were identified using SwissTargetPrediction, HERB, and BATMAN-TCM. HCC-specific genes were screened from the TCGA-LIHC cohort. The therapeutic targets of carvacrol against HCC were determined through the intersection of these datasets. Subsequently, a multivariate Cox regression prognostic model was established. Molecular docking was performed to analyze the interactions between carvacrol and its therapeutic targets. Additionally, molecular dynamics simulations were conducted to validate the molecular docking results using Discovery Studio 2019 software.

Results

A total of 223 carvacrol targets and 882 HCC-specific genes were identified. Fifteen therapeutic targets of carvacrol against HCC were obtained, including CA2, AR, ALB, AURKA, ALPL, EPHX2, BCHE, IL1RN, AGRN, CRP, DMGDH, APOA1, SOX9, HPX, and CHKA. The prognostic model accurately and independently predicted survival outcomes. AGRN and AURKA were significantly associated with HCC overall survival. Molecular docking and molecular dynamics simulations demonstrated that carvacrol exhibited strong potential for stable binding to the therapeutic targets AGRN and AURKA.

Conclusion

Our findings elucidate the multi-target mechanism of action of carvacrol against HCC, providing a foundation for future research on its application in HCC management.
Optimization of multiple outputs of electric arc spray coating parameters for EN AW 7020-T6
Authors: Yurdgülü Halil Ibrahim , Sadeler Recep , Koç Barış
Published: February 2025

Electric arc spray coating (EASC) is a method used to protect aluminum materials from corrosion, but there is no optimization in the literature using Al99.99 coating wire for EN AW 7020 alloy. The presented study aims to optimize the EASC process parameters (voltage, amperage, spray distance, and number of passes) for EN AW 7020-T6 aluminum samples. The experimental design of selected factors was made with Taguchi L9(34) orthogonal array and the aftermath of optimum values for coating were obtained with the TOPSIS multicriteria decision-making method. Output parameters respectively; pull-off strengths of coating were determined in compliance with the ASTM D4541 standard, the coating thicknesses were measured with a 3D profilometer, and the porosity values for cross-section were analyzed by optical microscope according to ASTM E2109 standard. After determining the optimum parameters, the substrates were coated and the crystallographic analysis of the coated samples was performed by XRD technique and electrochemical corrosion potential values were determined by galvanostat/potentiostat device in 3.5% NaCl solution. In exfoliation corrosion (EXCO) tests performed according to ASTM G34-1 standard, EXCO damage was detected on the surfaces of uncoated samples and graded as EA. In the EXCO tests with coated samples, no corrosion damages were observed on the coatings and they were rated with an N grade. The Al99.99 coating significantly improved the EXCO resistance of EN AW 7020-T6, reducing the corrosion rate by almost 100%. EXCO tests with uncoated and coated samples proved that the Al99.99 coating acts as a barrier to protect the substrate. Optimized Al99.99 coating offers a promising solution to improve the corrosion resistance of EN AW 7020-T6 aluminum alloys and extend their service life in harsh environments.
Evaluation of material and environmental price through material recycling of waste collected at the University of Seoul
Authors: An Tae Hwi , Lee Chan Young , Kim Ye Eun , An Se Yeon , Yang Ga Eun , Lim Doyeon , Jeon Gihyun , Seo Myung Won
Published: February 2025

In this study, we evaluated the material and environmental benefits of recycling materials collected at the University of Seoul. The waste composition was analyzed by sampling using the coning and quartering methods at the campus recycling center. The material cost was determined by comparing the prices of raw materials and recycled materials, while the environmental cost was calculated by estimating potential greenhouse gas emissions by incineration and multiplying this by the carbon price. It was analyzed that recycling rather than incineration can reduce greenhouse gas emissions up to 2.8 tCO2eq per tonne of waste. As a result, approximately 250 t of household waste is generated annually at the University of Seoul, with approximately 16% consisting of recyclable materials such as plastic and paper. Based on the carbon price of the Republic of Korea, the potential savings were around 608,000 USD/year. Using the current EU carbon price, the savings increased to 647,000 USD/year, and based on the 2030 target carbon price, the savings amounted to 677,000 USD/year. It represents that recycling not only minimizes natural resource depletion but also mitigates greenhouse gas emissions and results in significant economic cost savings. This research investigates specific methods for calculating monetary values to incentivize recycling and presents practical applications.
Empowering impaired learners: Technological advancements in higher education
Authors: Sharma Shruti , Dureja Simran , Saini Dhavni , Jose Ryan , Pant Riddhima , Singh Ashutosh
Published: February 2025

Background

Sensory impairments, such as visual impairment, deafblindness, deaf or hard of hearing (DHH), muteness, and Sensory Processing Disorder, present significant challenges for students in higher education. These challenges include difficulties in accessing information, participating in discussions, and adapting to academic environments.

Objective

This review aims to explore advancements in assistive technology that support sensory-impaired individuals in higher education and identify existing gaps in accessibility, usability, and educator preparedness, aligning with (UNSDG) (United Nations Sustainable Development Goals) 4’s goal of inclusive lifelong education by 2030.

Methods

We conducted a systematic literature review of 68 studies focussing on technological solutions such as assistive devices, adaptive learning platforms, and communication tools designed to enhance accessibility and inclusion in academic settings.

Results

While various assistive technologies have improved access, disparities in resource availability across institutions persist. Many educators lack adequate training to effectively integrate these technologies, and infrastructure limitations further hinder their use.

Conclusions

The findings underscore the need for further research to address accessibility gaps and improve educator training. By enhancing the adoption of assistive technologies, higher education institutions can create more inclusive learning environments, ensuring equal opportunities for all students, regardless of sensory impairments.
A Rare Lesion of Soft Tissue Malakoplakia Mimicking Neoplasm in the Thigh
Authors: Arwikar Asawari , Shetty Divya , Sharan Anita
Published: February 2025

Malakoplakia, a rare acquired histiocytic inflammatory disease. It is an incidental finding on histopathology examination, as it does not have definite clinical manifestations. It typically affects the genitourinary tract but can also involve various anatomical sites. We present malakoplakia involving the left thigh, a rare extragenital manifestation. A 42-year-old male patient presented with insidious left thigh swelling, which gradually increased in size over a year, without associated pain or systemic symptoms. Imaging and fine needle aspiration cytology prompted a suspicion of malignancy. Wide resection was performed, and histopathological examination revealed characteristic features of malakoplakia, including Michaelis-Gutmann bodies and histiocytic infiltrates. Immunohistochemistry confirmed the histiocytic origin of the cells. Despite the absence of microbiological correlation, the patient remained asymptomatic with no recurrence at one-year follow-up. Malakoplakia poses diagnostic challenges due to its non-specific clinical and radiological features. Comprehensive histopathological evaluation is essential for accurate diagnosis, particularly in atypical locations. Our report underscores the importance of considering malakoplakia in the differential diagnosis of soft tissue masses, highlighting the need for further research to elucidate its pathogenesis and optimize management strategies.
Retained foreign body in radial artery: Endovascular retrieval and salvage of a hemodialysis arteriovenous fistula
Authors: Choon Kwang Adrian Chia , Hsien Tsung Tay
Published: February 2025

A foreign body was inadvertently retained in the patient’s radial artery during a previous endovascular procedure, leading to early recurrent thrombosis of his hemodialysis arteriovenous fistula. Through the strategic use of ultrasound, a through-and-through wire, as well as sequential balloon inflation to “push” the foreign body, it was successfully retrieved endovascularly, leading to effective salvage of the patient’s hemodialysis access.
Feasibility and Safety of bedside placement of tunneled dialysis catheters: A systematic review and meta-analysis of prevalence
Authors: Bsat Ayman , Hojeij Moussa , Hafez Bassel , Nabhani Sami , Bahmad Marwan , Kotob Yasmine , Nassereldine Rakan
Published: February 2025

Tunneled dialysis catheters (TDCs) are typically the vascular access of choice for critically ill patients in need of urgent dialysis for prolonged periods of time. The standard of practice is to insert these catheters under fluoroscopic guidance to ensure proper catheter placement in the cavo-atrial junction or right atrium. However, there is increasing interest in bedside placement of TDCs without fluoroscopic guidance in patients deemed too critically ill to be transported to the fluoroscopy suite or operating room. Our aim was to systematically review the literature on bedside placement of TDCs and to calculate the pooled prevalence rates of technical success, favorable clinical outcomes, and overall complications. We searched PubMed and Google Scholar for articles on bedside insertion of TDCs without setting a specific timeframe. We stratified the articles based on the risk of publication bias. Data on technical success, favorable clinical outcomes and complications were collected. A total of 22 articles were included, comprising 1546 TDCs inserted at bedside. The technical success rate was found to be 97.2% [95% CI: 94.6 – 98.9%; I2 = 77.5%]; LFK index = −0.72 and favorable clinical outcome was reported in 97.6% [95% CI: 94.5–99.5%; I2 = 84.8%]; LFK index = −1.62. The pooled prevalence of complications was found to be 6.98% [95% CI: 3.12 – 12.1%; I2 = 87.8%]; LFK index = 0.95, most of which were mechanical in nature. Our findings suggest that bedside placement of TDCs is a technically feasible procedure with high favorable clinical outcomes and comparable complication rates to the conventional method of TDC insertion under fluoroscopic guidance. Several non-fluoroscopic techniques have also been suggested to confirm the proper positioning of the catheter in the right atrium. These findings may challenge the gold standard of utilizing fluoroscopic guidance for TDCs.
Role of renal vascular coordinator on access flow dysfunction: A quality improvement initiative on improving patency rate
Authors: Lim Zhi Ting Mary , Kong May Ching Cathrine , Chung Cheen Chai , Yan Lun Allen Liu
Published: February 2025

A renal vascular coordinator (RVC) is a single point-of-contact allied health professional in the early detection and timely intervention of flow dysfunction. In Khoo Teck Puat Hospital (KTPH), RVC performs access ultrasonography assessment and assists in reviewing direct referrals about dysfunctional arteriovenous fistula (AVF)/arteriovenous graft (AVG) from community dialysis centres and plans for appointments with interventional nephrologists and vascular surgeons. We conducted a prospective study from April 2020 to December 2022 to evaluate the appointment-to-intervention time (AIT) and patency rate (PR) of vascular access interventions. Secondary outcome was the percentage of vascular access loss. Ninety-three patients were referred to the RVC and were offered thrombectomy or angioplasty. Twenty-seven patients were excluded from the analysis (did not require intervention (9), admitted without RVC assessment (13), defaulted (4), or bypassed an RVC appointment to their first intervention (1)). The median time from referral to their first RVC visit was 4 (3–6) days. The median AIT for the RVC group was 6 (3–11) days (21.5% within 48 h). The median AIT for the non-RVC group was 6 (2.3–12.8) days (25.5% within 48 h, p = 1.0). The 6-month and 12-month post-intervention PR was 71% and 61.3%, respectively. Fifty-one of the remaining ninety-three patients had previous procedures done to their AVF before April 2020 without RVC involvement. The 6-month and 12-month post-intervention PR was 51% ( p < 0.016) and 15.7% ( p < 0.00001), respectively. The percentage of vascular access loss was similar in both RVC and non-RVC groups (4.3% vs 2%, p = 0.44). With the addition of RVC, vascular access outcome is improved with longer PR for up to 12 months, with no difference in AIT and number of vascular access losses.
A method for reconstruction of structural health monitoring data using WGANGP with U-net generator
Authors: Zhu Yi-Kai , Wan Hua-Ping , Todd Michael D
Published: February 2025

Data loss issue often occurs in structural health monitoring (SHM), which can undermine the reliability of structural condition diagnosis and prognosis. Neural networks are commonly employed for reconstruction of missing SHM data by modeling the correlation between intact and missing signals. The existing neural network methods use deeper architectures to capture complex data correlations. As network depth increases, the ability to preserve both low- and high-level features diminishes, and network training becomes challenging, which reduces data reconstruction accuracy. This study proposes a data reconstruction method that utilizes a Wasserstein generative adversarial network containing a gradient penalty term with a U-net generator. Multiple improvements are made to the generative adversarial network to enhance the reconstruction performance. First, the U-net is used as a generator, and the signal features at low and high levels are preserved based on the skip-connection technique. The U-net is pre-set with multiple layers to enhance the reconstruction accuracy. Second, a mean square error (MSE) term is added to the loss function. The MSE coefficient is proposed to balance adversarial training and reconstruction feature learning. Third, the Wasserstein distance is introduced to replace the cross-entropy loss function of traditional generative adversarial networks, avoiding gradient vanishing and exploding. The reconstruction performance of the proposed method is evaluated on a computational bridge model and Canton Tower, and the influence of reconstruction parameters on the accuracy of reconstruction results is discussed in detail. The reconstructed data by the proposed method closely matches the original data in both the time domain and frequency domain. The time–frequency characteristics of the acceleration data can be accurately reconstructed, demonstrating the effectiveness of the reconstructed signals in data analysis. By comparing with typical neural network methods, it is found that the proposed method has higher reconstruction accuracy.
Robot-Assisted Thoracoscopic Surgery Can Be Safely Performed in Patients With Obesity from the Early Stages of Implementation
Authors: Tao Hiroyuki , Waki Shohei , Yoshikawa Mao , Kubo Yujiro , Mizutani Hisao
Published: February 2025

Objective:

This study aimed to compare the perioperative outcomes of robot-assisted thoracoscopic surgery (RATS) and conventional video-assisted thoracoscopic surgery (VATS) for lung cancer in patients with obesity.

Methods:

Anatomical pulmonary lobectomy or segmentectomy performed at a single institution from April 2018 to September 2023 in patients with obesity (body mass index ≥25 kg/m2) were statistically compared in terms of perioperative clinical factors including operative time, blood loss, chest tube duration, pain score, intraoperative events, and early postoperative complications between RATS and VATS.

Results:

In all, 89 patients were evaluated; 43 underwent RATS and 46 underwent VATS. All RATS procedures were performed using the da Vinci Xi system. Patient characteristics were comparable between the 2 groups. The operative time, blood loss, number of dissected lymph nodes, intraoperative events, and conversion rate to open thoracotomy were similar between the 2 groups. The frequencies of postoperative complications and chest tube placement duration between the groups were also similar. The median pain scores were slightly higher in the RATS group on postoperative day 1 but were equivalent between the 2 groups on postoperative day 7. The RATS group had a shorter postoperative hospital stay than the VATS group ( P < 0.01).

Conclusions:

A surgical team proficient in conventional VATS can safely introduce RATS in patients with obesity and lung cancer with equivalent perioperative outcomes.
Extremely preterm infant with double aortic arch presenting with severe tracheal obstruction and devastating esophageal hemorrhage
Authors: Kanamori Ryosuke , Nomura Tomoaki , Hirose Akira , Ito Hiroki , Yamoto Masaya , Mitsushita Norie , Nakano Reiji
Published: February 2025

Background: Double aortic arch is the most constrictive type of vascular ring, completely encircling the trachea and esophagus, and can cause severe respiratory failure, dysphagia, or devastating esophageal hemorrhage. Although surgical repair is usually recommended shortly after diagnosis, surgery in extremely preterm infants presents significant challenges. The optimal timing of surgery and the management of complications that arise while awaiting surgery are not well understood.

Case presentation: We report the case of an Asian female infant weighing 509 g at 24 + 5 weeks of gestation with a double aortic arch. Initially managed conservatively to allow for growth, the patient developed progressive tracheal granulation and recurrent, life-threatening esophageal hemorrhage. Gastrostomy and division of the vascular ring were successfully performed on days 65 and 66 (postmenstrual age 33 weeks; weight 1126 g), and tracheal granulation was managed conservatively. Despite mild respiratory symptoms persisting, the patient survived until discharge without any recurrence of esophageal bleeding.

Conclusion: The management of double aortic arch in extremely preterm infants is particularly challenging. In this case, surgical repair was successfully performed at a weight of 1126 g without lethal postoperative complications. Early gastrostomy before the surgical repair of the double aortic arch may be advantageous in preventing devastating esophageal hemorrhage, especially in patients with severe tracheal narrowing indicative of a tight vascular ring and significant esophageal compression.
Atypical presentation of a common condition
Authors: Pereira Mariana Oliveira , Pereira Rita Lages , Carvalho Fábia , Pinheiro Liliana , Neiva Filipa
Published: February 2025

Cow’s milk protein allergy (CMPA) presents a wide range of clinical manifestations. Although gastrointestinal symptoms are common, they are not always present. In this report, we present two cases of infants with atypical CMPA presentations. Case 1 involves a male newborn who was admitted with polyarthritis and a target-shaped rash, while case 2 features a female newborn who presented with soft swelling of extremities. Both infants had recently started using infant formula, which raised CMPA’s suspicion. An extensively hydrolyzed formula (eHF) was introduced, resulting in the resolution of symptoms, with positive specific IgE measurements supporting the diagnosis. Further, in case 2, she underwent an oral provocation test that confirmed the diagnosis. These cases underscore the clinical variability of CMPA, which can present diagnostic challenges. While specific IgE measurements can offer valuable supporting information, a clinical diagnosis remains indispensable. Awareness of the diverse presentations and a thorough patient history are critical for accurate diagnosis and the prevention of unnecessary treatments.
Head, Hands, Knees and Ankles, Knees and Ankles: Injury Profiles of Women and Girls Playing Community Australian Football
Authors: Cowan Sallie M. , Patterson Brooke E. , King Matthew G. , Girdwood Mick A. , Mosler Andrea B. , Donaldson Alex , Culvenor Adam G. , Bruder Andrea M. , Haberfield Melissa J. , Makdissi Michael , Barton Christian J. , Roughead Eliza , Lampard Sarah , Chilman Karina , Bonello Christian , Birch Elizabeth , Frost Joshua , McGhee Deirdre E. , Crossley Kay M.
Published: February 2025

Background:

Women’s participation in all football codes (including Australian Football [AF]) is increasing rapidly. To guide injury prevention strategies, the authors aimed to describe the current and lifetime prevalence of significant musculoskeletal injuries and concussions for women and girls playing community AF.

Hypothesis:

Women will have high rates of injury associated with playing AF.

Study Design:

Cross-sectional survey.

Level of Evidence:

Level 3.

Methods:

Participants were Victorian community AF players from 165 participating teams (<16 years, <18 years, senior women’s). Demographics, injury prevalence, and health outcomes are reported descriptively. To explore relationships between sociodemographic factors and anterior cruciate ligament (ACL) injury history, the authors fitted univariate logistic regression models. Independent variables were age, body mass index, number of career AF games, sport experience, location (metropolitan/regional), and socio-economic index.

Results:

A total of 2435 players (95% of players enrolled in the trial), aged 24 ± 7 years completed the survey. One-quarter (n = 619, 25%) reported a current injury, and half (n = 1238, 51%) reported a previous significant injury. The most common injury sites were knee (n = 160 26% current, n = 403 33% previous), ankle (n = 130 21% current, n = 427 35% previous), and hand/fingers (n = 100 16% current, n = 317 26% previous). Self-reported previous ACL injury (n = 139, 6%) and concussion (n = 1335, 55%) were also prevalent. Increasing age (odds ratio [OR], 1.07; 95% CI, 1.05-1.09) and more career games (OR, 2.22; 95% CI, 1.24-3.97) were associated with ACL injury history.

Conclusion:

Women and girls playing community AF reported high rates of significant injury. Injury prevention programs should target the most prevalent injury sites: head (concussion), ankle, knee, and hand/fingers.

Clinical Relevance:

These findings highlight high injury rates for women playing AF and will be invaluable in shaping injury prevention strategies.
Habitual Caffeine Consumption and Training Status Affect the Ergogenicity of Acute Caffeine Intake on Exercise Performance
Authors: Khodadadi Davar , Azimi Farhad , Eghbal Moghanlou Abdorreza , Gursoy Recep , Demirli Abdullah , Jalali Parham , Behdari Reza , Seyedheydari Maryam
Published: February 2025

Background:

Acute caffeine ingestion can improve exercise performance. Interplay between caffeine habituation and training status on the performance-enhancing effect of caffeine is unknown.

Hypothesis:

Habitual caffeine consumption and training status affect the ergogenicity of pre-exercise caffeine intake on exercise performance.

Study Design:

Double-blind, placebo-controlled, counterbalanced experimental design.

Level of Evidence:

Level 3.

Methods:

Eighty physically inactive men were randomized into 1 of 4 groups: caffeine supplementation (CAF), caffeine supplementation + exercise training (CAFEXE), placebo (PLA), and placebo + exercise training (PLAEXE); high-intensity interval training and caffeine were administered for 9 and 8 weeks, respectively. Data were collected pre-test, mid-test, post-test, and delayed post-test, each including 2 experiment sessions (3 mg/kg caffeine or placebo), with an additional experiment session post-test (6 mg/kg caffeine). In each experiment session, 45-min after consuming a placebo or caffeine, a 3-km running test and a Wingate power test were performed.

Results:

Pre-exercise ingestion of 3 mg/kg caffeine improved 3-km running time and mean power output (MPO) in all groups at all stages ( P < 0.05); this effect was higher in trained than in untrained volunteers ( P < 0.05). Habitual caffeine consumption reduced the ergogenic effect of caffeine in both aerobic and anaerobic trials ( P < 0.05); 6 mg/kg caffeine enhanced this decrease only in CAFEXE ( P < 0.05). Short-term caffeine withdrawal augmented the reduced ergogenic effect of caffeine on 3-km running performance and MPO in CAF and CAFEXE ( P < 0.05).

Conclusion:

Habituation to caffeine and training status could partially influence the ergogenic effects of caffeine on exercise performance.

Clinical Relevance:

Regular caffeine consumption leads to some degree of tolerance and decreases its ergogenicity. A pre-exercise increase in caffeine dosage in trained people and short-term caffeine withdrawal in both trained and untrained people could compensate for the reduced caffeine ergogenicity in young men.
Impact of High-Intensity Interval Exercise With Elastic Bands Versus Continuous Moderate-Intensity Aerobic Exercise on Glycemic Control in People With Type 1 Diabetes
Authors: Martín-San Agustín Rodrigo , Cuerda Del Pino Alba , Laguna Sanz Alejandro José , Palanca Ana , Rossetti Paolo , Marco Romero Cynthia , Bondia Jorge , Ampudia-Blasco F. Javier
Published: February 2025

Background:

Engaging in physical exercise is recommended to enhance cardiovascular health and manage blood sugar levels in people with type 1 diabetes (T1D).

Hypothesis:

The impact of high-intensity interval exercise with elastic bands (EB-HIIE) versus continuous moderate-intensity aerobic exercise (CONT) on glycemic control is different in men with T1D.

Study Design:

Crossover study design.

Level of Evidence:

Level 3.

Methods:

Participants (39 men with T1D) underwent either an EB-HIIE or a CONT session in randomized order, with a separation of ≥72 hours to avoid carry-over effects. Changes in glucose values during exercise were measured simultaneously from venous blood (YSI) and interstitial fluid (Dexcom G6 glucose sensor). Subsequent 24-hour glucose was monitored using the glucose sensor.

Results:

Blood glucose was lower in CONT vs EB-HIIE ( P < .01). Post hoc analysis revealed clinically relevant differences during exercise (–35.1 mg/dl; P = .02), at its end (–49.5 mg/dl; P < .01), and at 10 and 20 minutes after completion (–51.2 mg/dl; P < .01 and −45.9 mg/dl; P < .01, respectively). Time-in-range 24 hours after exercise completion was significantly higher with EB-HIIE than with CONT (66.5% vs 59.3%), although both were significantly better than the previous 24 hours before exercise (50%).

Conclusion:

Results suggest that EB-HIIE is a safe training method for male adults with diabetes, resulting in euglycemia during and immediately after exercise and improving glucose outcomes in the subsequent 24 hours.

Clinical Relevance:

This study provides new evidence and practical information on how to implement safe physical activity in daily life of patients with diabetes. EB-HIIT exhibited lower hypoglycemia risk during exercise and better glycemic control in the subsequent 24 hours. In contrast, practicing CONT exercise is associated with higher risk of hypoglycemia. Healthcare providers should take this information into account when prescribing exercise.
Pharmacological management of chronic insomnia disorder in Singapore: Recommendations from an expert panel
Authors: Ho Roger , Lim Chau Sian , Tor Phern Chern , Ho Cyrus Su Hui , Pang Jason Wui Chi , Ng Beng Yeong
Published: February 2025

Background

Chronic insomnia disorder, a condition associated with frequent and persistent difficulty in initiating or maintaining sleep, is one of the most common reasons for patients consulting general practitioners and psychiatrists in Singapore.

Objectives

The landscape for managing chronic insomnia disorder is constantly changing but a clear, updated guidance for its management is lacking.

Methods

This guidance document provides guidance and recommendation for the diagnosis, assessment, and management of chronic insomnia disorder in Singapore based on a review of the current clinical practice guidelines and recent evidence including findings specific to Singapore.

Results and Conclusion

This document further summarises the properties and safety profiles of various pharmacological agents and provides guidance for their use across patient profiles. Lastly, this document provides recommendations from a panel of 5 clinicians with expertise in treating patients with sleep disorders.
Austere life-courses and foreclosed futures: A relational geographical approach to work, housing, and family across austerity Europe
Authors: del Río Santiago , Hall Sarah Marie , Ackerley Elizabeth , Fenton Laura
Published: February 2025

This article seeks to advance geographical understandings of the impact of austerity on young adults in Europe and particularly on their social, relational, and temporal sense of the future. We adopt a life-course perspective to theorise personal, generational, institutional, and social change in relation to one another. Firstly, we progress relational life-course perspectives in human geography to illustrate how place-based experiences of austerity shape lived experiences, temporalities, and normative ideas surrounding life transitions. We introduce the concept of ‘foreclosed futures’ to re-examine conceptualisations of young adults’ eroding material conditions as a postponement of adulthood. We argue that the enduring impact of austerity contests the theorisation of young adults’ experiences of precarity as a transient elongation of youth. Expanding upon non-teleological life-course perspectives, we show that while austere institutions have foreclosed stable futures, the paths to precarity are myriad and rooted in geographically varied forms of austerity. Secondly, in examining how austere institutions shape young people's work, housing, and family biographies, we argue that, rather than leading to de-institutionalisation, austerity marks a process of life-course re-institutionalisation or ‘familialisation of the life-course’. To conclude, this article proposes a series of prompts for future international empirical research on austere life-courses and foreclosed futures.
School counsellor perspectives: Training to lead and implement trauma-informed practices
Authors: Brown Meegan
Published: February 2025

Research has identified the significance of trauma-informed practices in schools to support students, families and communities impacted by trauma. And it is school counsellors who are widely recognised as having the expertise to lead and implement these trauma-informed practices. It is imperative, then, for school counsellors to undergo comprehensive preparation programmes to fulfil this vital role, and that these preparation programmes be evaluated in terms of effectiveness. The small body of research into school counsellor preparation for trauma-informed practice comes largely from the US and indicates US school counsellors did not feel their preparation programmes prepared them to implement trauma-informed practices. The Australian study of 36 school counsellors in an online survey, also established an inadequacy for these school counsellors to either support students impacted by trauma or lead and implement trauma-informed practices in schools, notably schools that take a behaviourist approach to behaviour management. Clearly, a new holistic approach to school counsellor education, the School-Based Family Counselling meta-model must be available for all school counsellors to skilfully and confidently use trauma-informed practices with the people in the schools, families and communities they serve.
SNAP and/or WIC Participation and Diet Quality in Mother-Child Dyads living in Greater Boston after Pandemic: A Mixed-Method Study
Authors: Vinitchagoon Thanit , Zhang Fang Fang , Fauth Rebecca C. , Hennessy Erin , Maafs Ana G. , Browning Emma M. , Economos Christina D.
Published: February 2025

Introduction/Objectives:

Since the COVID-19 pandemic, few studies have examined how participation in Supplemental Nutrition Assistance Program (SNAP) and/or Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) impacts diet quality in families with young children. This study aims to explore the association between SNAP and/or WIC participation and diet quality in mother-child dyads in Greater Boston, MA.

Methods:

A mixed-method approach involving cross-sectional surveys and in-depth interviews were utilized. Participants included 69 mother-child dyads for quantitative and 18 mothers for qualitative data collection. Analysis of covariance using generalized linear models was employed to compare differences in Healthy Eating Index-2015 (HEI-2015) scores based on SNAP and/or WIC participation, and thematic analysis was used for coding themes.

Results:

Mothers who participated in SNAP and/or WIC were more from lower socioeconomic backgrounds. After adjusting for age, race/ethnicity, and education, no significant differences in diet quality were found for both mothers and their children. However, qualitative results showed that mothers prioritized their children’s nutrition, used benefits to buy fruits and vegetables, and experienced stress that impacted their own diet quality.

Conclusions:

Since the pandemic, SNAP and WIC appeared to support families experiencing socioeconomic disadvantage (e.g., lower income and educational attainment) to improve diet quality, particularly through increased access to fruits and vegetables. However, these programs have not fully eliminated persistent disparities in diet quality, which seems to continue even the pandemic’s immediate effects have subsided.
Changing Our Mental and Emotional Trajectory (COMET): The Feasibility and Acceptability of a Rural Community-Based Strategy to Prevent Mental and Emotional Health Problems
Authors: Zittleman Linda , Felzien Maret , Curcija Kristen , Bennett Christopher , Bennett Kaitlyn , Carrica Joseph , Sutter Christin , Sherrill Ashley , Westfall John M
Published: February 2025

Introduction:

People in rural regions frequently lack resources for mental health support. Changing Our Mental and Emotional Trajectory (COMET) is a universal, community-based program designed to address mental and emotional health issues early and prevent crises. COMET Community Training is a short, interactive training that teaches people how to initiate a supportive and potentially emotional conversation using the simple, 7-item COMET Conversational Gravity Assist. This article describes and reports on the feasibility and acceptability of COMET and its Community Training.

Methods:

COMET was developed using a participatory research approach by community members and health professionals living in a rural region and their research partners. COMET Community Trainings were conducted over a 22-month period. Surveys were administered to attendees before and after training to describe attendees’ characteristics, view on content, and impact on intention to use COMET components. Field notes were completed by trainers to document the date and number of attendees.

Results:

Over 700 people attended 60 Community Trainings. Questionnaires were completed by 644 trainees before and 580 after training. Of pre-survey respondents, 25% worked in education and 15% in farming/ranching. Post-survey respondents were 62% female, and 32% were between age 18 and 36. High levels of training satisfaction were reported. Average likelihood of using items in the COMET conversational guide increased significantly from pre to post training. On a scale of 1 to 10, nearly 80% of respondents rated their likelihood of using COMET in the next 3 months a 7 or higher.

Conclusions:

COMET Community Training is a feasible program that effectively reaches a range of community members and improves the likelihood that they will initiate conversations when concerned about someone else’s mental health. Results lay the groundwork for COMET as an intervention that promotes mental and emotional well-being to address inequality in mental health for people living in rural communities.
Differential antibody response to EBV proteome following EBVST immunotherapy in EBV-associated lymphomas
Authors: Sarathkumara Yomani D , Van Bibber Nathan W , Liu Zhiwei , Heslop Helen E , Rouce Rayne H. , Coghill Anna Elizabeth , Rooney Cliona M , Proietti Carla , Doolan Denise L
Published: February 2025

Epstein-Barr virus (EBV) is associated with a diverse range of lymphomas. EBV-specific T-cell (EBVST) infusions have shown promise in safety and clinical effectiveness in treating EBV-associated lymphomas; however, not all patients respond to T-cell immunotherapies. To identify EBV-antigen specific antibody responses associated with clinical outcomes, we comprehensively characterized the antibody responses to the complete EBV proteome using a custom protein microarray in 56 EBV-associated lymphoma patients who received EBVST infusions enrolled in Phase I clinical trials. Responders (non-progressors) and non-responders (progressors) had distinct antibody profiles against EBV. Twenty-five IgG antibodies were significantly elevated in higher levels in non-responders compared to responders at 3 months post-EBVST infusion. Ten of these remained significant after adjustment for sex, age, and cancer type, including LMP2A (four variants), BGRF1/BDRF1 (two variants), LMP1, BKRF2, BKRF4, and BALF5. Random forest analysis identified these 10-IgG antibodies as key predictors of clinical response. Paired analyses using blood samples collected at both pre-infusion and 3 months post-EBVST infusion indicated an increase in the mean antibody level for six other anti-EBV antibodies (IgG: BGLF2, LF1, BGLF3; IgA: BGLF3, BALF2, BBLF2/3) in non-responders. Overall, our findings suggest that these EBV-directed antibodies as potential serological markers for predicting clinical responses to EBVST infusions and as therapeutic targets for immunotherapy in EBV-positive lymphomas. NCT01555892 - Cytotoxic T-Lymphocytes for EBV-positive Lymphoma, GRALE NCT02973113 - Nivolumab With Epstein Barr Virus Specific T Cells (EBVSTS), Relapsed/Refractory EBV Positive Lymphoma (PREVALE) NCT02287311 - Most Closely Matched 3rd Party Rapidly Generated LMP, BARF1 And EBNA1 Specific CTL, EBV-Positive Lymphoma (MABEL)
Allogeneic Off-the-Shelf CAR T-Cell Therapy for Relapsed or Refractory B-Cell Malignancies
Authors: Shahid Sanam , Prockop Susan E. , Flynn Georgia C , Mauguen Audrey , White Charlie , Bieler Jennifer , McAvoy Devin , Hosszu Kinga , Cancio Maria I. , Jakubowski Ann A. , Scaradavou Andromachi , Boelens Jaap Jan , Sauter Craig S , Perales Miguel-Angel , Giralt Sergio A. , Taylor Clare , Chaudhari Jagrutiben , Wang Xiuyan , Rivière Isabelle , Sadelain Michel , Brentjens Renier J. , Kernan Nancy A , O'Reilly Richard J , Curran Kevin J.
Published: February 2025

Despite clinical benefit with the use of CAR T-cells, the need to manufacture patient-specific products severely limits the clinical utility of this therapy. To overcome this barrier, we developed an allogeneic, "off-the-shelf" CAR T-cell product using Epstein-Barr virus (EBV)-specific T cells (EBV-VSTs) genetically modified with a CD19-specific CAR (19-28z). Patients with relapsed/refractory (R/R) B-cell malignancies (n=16) were stratified into 3 treatment cohorts: cohort 1 (n=8; disease recurrence after allogeneic or autologous hematopoietic cell transplant (HCT)), cohort 2 (n=6; consolidative therapy after autologous HCT), or cohort 3 (n=2; consolidative therapy after allogeneic HCT) (NCT01430390). The primary objective of this trial was to determine safety of multiple CAR EBV-VST infusions. Most patients (n=12/16; 75%) received multiple doses (overall median 2.5; range 1-3) with 3x106 T-cells/kg determined to be the optimal dose enabling multiple treatments per manufactured cell line. Severe cytokine release syndrome or neurotoxicity did not occur post-infusion, and no dose limiting toxicity was observed in the trial. Median follow-up was 48 months (range 4-135 months) with 4 deaths due to disease progression. Overall survival of all patients was 81% (95% confidence interval: 64-100%) at 12 months and 75% (57-100%) at 36 months. Post-infusion expansion and persistence were limited, and CAR EBV-VSTs demonstrated a unique T-cell phenotype as compared to autologous 19-28z CAR T-cells. Our study demonstrates the feasibility and safety of an allogeneic, "off-the-shelf" CAR EBV-VST product with favorable outcomes for patients with R/R B-cell malignancies when targeting the CD19 antigen.
Impact of exercise training on cognitive function in patients with COPD: a systematic review and meta-analysis of randomised controlled trials
Authors: Ding Kexin , Song Feiyun , Sun Wen , Sun Mingyun , Xia Rui
Published: February 2025

Objective

The aim of this study was to describe the characteristics of exercise therapies in randomised controlled trials (RCTs) targeted at improving cognitive function and to assess their efficacy in COPD.

Methods

We conducted a comprehensive search of eight databases, namely PubMed, Web of Science, Embase, Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang and Weipu, covering the period from database construction to 23 April 2024. Our search specifically targeted RCTs studying the effects of exercise on cognitive functioning in COPD patients. Trials consisted of one or more exercise training interventions along with at least one cognitive outcome study. Two reviewers independently reviewed papers, extracted data and evaluated the research literature's quality using the Cochrane risk-of-bias assessment tool RoB 2.0 and the modified Jadad scale. Meta-analysis of Montreal Cognitive Assessment (MoCA) scores in the groups with and without exercise intervention was performed and subgroup analyses were undertaken to identify potential causes of heterogeneity.

Results

We included a total of nine studies that included 578 COPD patients (69% male). Each study demonstrated that patients improved significantly in at least one cognitive component following training. All current research focuses on attention, executive function, motor ability, mental capacity, verbal fluency, visuoconstructive abilities and memory. The results revealed that exercise significantly improved MoCA scores in COPD patients (standardised mean difference (SMD) 0.576 (95% CI 0.054–1.097); p=0.029). A subgroup analysis of the duration of each intervention revealed that exercise training with an intervention duration of >30 min significantly improved overall cognitive performance in COPD patients (SMD 0.499 (95% CI −0.165–1.163); p=0.000, I2=0.0%). A subgroup analysis of varied intervention durations revealed that 4 weeks of exercise training significantly improved overall cognitive performance in COPD patients (SMD 0.202 (95% CI −0.238–0.641); p=0.000, I2=0.0%). In addition, just one study had a year-long follow-up period.

Conclusion

Participation in exercise training, whether aerobic exercise alone or in combination with resistance or muscular strength, healthy qigong, dance or breathing exercises, can improve cognitive performance to varying degrees in people with COPD. Nonetheless, the findings should be regarded with caution due to the limitations of the included studies.
Nitidine chloride inhibits the progression of hepatocellular carcinoma by suppressing IGF2BP3 and modulates metabolic pathways in an m6A-dependent manner
Authors: Xiong Dan-dan , Chen Zhen-dong , Li Jian-di , Deng Yu-long , He Rong-quan , Huang Zhi-guang , An San-qi , Dang Yi-wu , Chen Gang
Published: February 2025

Background

Hepatocellular carcinoma (HCC) stands as a major health concern due to its significant morbidity and mortality. Among potential botanical therapeutics, nitidine chloride (NC) has garnered attention for its potential anti-HCC properties. However, the underlying mechanisms, especially the possible involvement of the m6A pathway, remain to be elucidated.

Methods

HCC cell and zebrafish xenograft models were utilized to validate the anti-HCC effects of NC. RNA-seq and MeRIP-seq analyses were performed to explore the potential targets and mechanisms of NC against HCC. The target effect of NC on IGF2BP3 was verified through RT-qPCR, WB, molecular docking, molecular dynamics (MD) simulation, surface plasmon resonance (SPR), and CCK8 off-target assays. Downstream target genes were confirmed using RNA stability assays.

Results

In this study, utilizing HCC cell and zebrafish xenograft models, we validated NC’s ability to inhibit the growth, metastasis, and angiogenesis of HCC. Subsequently, employing RNA sequencing, RT-qPCR, WB, molecular docking, MD simulation, SPR, and CCK8 off-target assays, we pinpointed IGF2BP3 as a direct target of NC. IGF2BP3 is highly expressed in HCC, and IGF2BP3 knockdown significantly inhibited the proliferation, migration and invasion of HCC cells. Further MeRIP-seq and RIP-seq revealed 197 genes interacting with IGF2BP3, downregulated at mRNA and m6A levels after NC treatment, primarily associated with multiple metabolism-related pathways. Through intersection analysis, we pinpointed 30 potential metabolic target genes regulated by NC through IGF2BP3. Based on the expression of these genes, the metabolic scores for each HCC patient were calculated. Our findings suggest that patients with high metabolic scores have poorer prognoses, and the metabolic score serves as an independent prognostic factor. Finally, RNA stability experiments confirmed CKB, RRM2, NME1, PKM, and UXS1 as specific metabolic target genes affected by NC/IGF2BP3, displaying reduced RNA half-life post IGF2BP3 downregulation.

Conclusion

Our study suggest that NC may exert its anti-HCC effects by downregulating IGF2BP3, inhibiting the m6A modification levels of metabolic-related genes, thereby reducing their stability and expression. Such insights provide a new direction in the study of NC’s anti-HCC mechanisms and offer novel perspectives for the treatment of HCC patients, focusing on both metabolic levels and m6A modification levels.
ROITP: Road Obstacle-Involved Trajectory Planner for Autonomous Trucks
Authors: Qin Yechen , Huang Yiwei , Yu Wenhao , Wang Hong
Published: February 2025

Autonomous trucks have the potential to enhance both safety and convenience in intelligent transportation. However, their maximum speed and ability to navigate a variety of driving conditions, particularly uneven roads, are limited by a high center of gravity, which increases the risk of rollover. Road bulges, sinkholes, and unexpected debris all present additional challenges for autonomous trucks' operational design, which current perception and decision-making algorithms often overlook. To mitigate rollover risks and improve adaptability to damaged roads, this paper presents a novel Road Obstacle-Involved Trajectory Planner (ROITP). The planner categorizes road obstacles using a learning-based algorithm. A discrete optimization algorithm selects a multi-objective optimal trajectory while taking into account constraints and objective functions derived from truck dynamics. Validation across various scenarios on a hardware-in-loop platform demonstrates that the proposed planner is effective and feasible for real-time implementation.