bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and numerical studies of laminar natural convection heat transfer from an isothermally heated narrow flat plate oriented at different angles of rotation
Authors: Alhendal Yousuf , Kalendar Abdulrahim
Published: June 2024

The laminar natural convection heat transfer from isothermally heated narrow flat plates oriented at different angles of rotation is experimentally and numerically studied. The heated flat plate is narrow, i.e., has a relatively small width, w, to length, l, ratio, and is embedded in a plane adiabatic surface within which the heated plate can be oriented at different angles of rotation. The three-dimensional governing equations for geometrical assessment were solved numerically in terms of non-dimensional variables using finite volume-based solution. Model results for the average Nusselt number were obtained for a relatively wide range of non-dimensional variables included the Rayleigh number ranging from 1×103 ≤ Ra ≤ 1×108, non-dimensional plate width ranging from 0.15 ≤ W ≤ 1, and angle of rotation ranging from 0° ≤ α ≤ 90°. On the other hand, experimental results for the average Nusselt number were obtained for a narrower range of non-dimensional variables included the Rayleigh number ranged from 5.98×103 ≤ Ra ≤ 1.18×105, the angle of rotation ranged from 0° ≤ α ≤ 90°, and the non-dimensional plate width was fixed at 0.4. Additionally, a Prandtl number of 0.7 was used, which is the value for air in some of the applications that initiated this study. The model results are validated against present experimental results and existing correlations. The effects of these non-dimensional variables on the average and local Nusselt numbers for the heated flat plate were investigated. It was found that in some situations the non-dimensional variables have a significant effect on heat transfer rate from the heated flat plate. Correlations to calculate the average Nusselt number for the heated flat plate were developed.
Predictive Modeling of Gestational Weight Gain: A Machine Learning Multiclass Classification Study
Authors: Victor Audêncio , Santos Hellen Geremias dos , Silva Gabriel Ferreira dos Santos , Filho Fabiano Barcellos , Cobre Alexandre de Fátima , Luzia Liania A. , Rondó Patrícia H.C. , Filho Alexandre Dias  Porto Chiavegatto
Published: June 2024

Background
Gestational weight gain (GWG) is a critical factor influencing maternal and fetal health. Excessive or insufficient GWG can lead to various complications, including gestational diabetes, hypertension, cesarean deliver, low birth weight, and preterm birth. This study aims to develop and evaluate machine learning models to predict GWG categories (below, within, or above recommended guidelines)
Methods
We analyzed data from the Araraquara Cohort, Brazil comprising 1557 pregnant women with a gestational age of 19 weeks or less. Predictors included socioeconomic, demographic, lifestyle, morbidity, and anthropometric factors. Five machine learning algorithms (Random Forest, LightGBM, AdaBoost, CatBoost, and XGBoost) were employed for model development. The models were trained and evaluated using a multiclass classification approach. Model performance was assessed using metrics such as area under the ROC curve (AUC-ROC), F1 score and Matthews correlation coefficient (MCC).
Results
The outcome were categorized as follows: GWG within recommendations (28.7%), GWG below (32.5%), and GWG above recommendations (38.7%). The LightGBM model presented the best overall performance with an AUC-ROC of 0.79 for predicting GWG within recommendations, 0.756 for GWG below recommendations, and 0.624 for GWG above recommendations. The Random Forest model also performed well, achieving an AUC-ROC of 0.774 for GWG within recommendations, 0.732 for GWG below recommendations, and 0.593 for GWG above recommendations. The most importante were predictors of GWG were pre-gestational BMI, maternal age, glycemic profile, hemoglobin levels, and arm circumference.
Conclusion
Machine learning models can effectively predict GWG categories, providing a valuable tool for early identification of at-risk pregnancies. This approach can enhance personalized prenatal care and interventions to promote optimal pregnancy outcomes.
Malignant spinal cord compression pathway: A new step toward standard of care for a critical oncological finding
Authors: Aldakheel Abdulrahman , Al-Rajhi Nasser , Alshabanah Mohammed , Alwhaid Mohammed , Julaidan Bedour , Alsamari Faisal , Aldehaim Mohammed
Published: June 2024

Background: Malignant cord compression syndrome (MCCS) must be addressed clinically using whole-spine magnetic resonance imaging in suspected patients and managed accordingly. Establishing a Malignant spinal cord compression pathway is crucial for addressing these patients sequentially with an immediate management plan. Here, we reported the outcomes of a Malignant spinal cord compression pathway and compared the results with those before its implementation.
Methods: This is a prospective observational study where data collection was performed for patients with activated cord compression pathway between July 2021 and October 2022. Collected data was including demographics of patients, presenting symptoms, time of recorded clinical pathway activation and subsequent events including final management plan. Retrospective data collection was done for 52 patients whom were treated from the period between 2018-2019. Non-parametric test was used to compare medians for both groups.
Results: In total, 170 patients were included, and 52 of them were treated based on positive magnetic resonance imaging (MRI) findings of Malignant spinal cord compression pathway between 2018 and 2019. Moreover, 118 patients were identified during the implementation of the cord compression pathway in 2020–2022. Three main targeted intervals were calculated in hours using medians and means: interval 1, time from cord compression suspicion to MRI; interval 2, MRI completion to MRI report; and interval 3, cord compression suspicion to intervention. In 2018–2019, medians of these three intervals were 9.5, 12, and 110 h, and in 2020–2022, they substantially decreased to 6, 3, and 24 h, respectively. An independent nonparametric test was performed to compare the medians, and statistically significant results were obtained for intervals between MRI completion and MRI report (p = 0.001) as well as between cord compression suspicion and intervention (p = 0.001).
Conclusions: The use of the malignant spinal cord compression pathway effectively shortens the time needed for identifying patients at risk, reduces the time to report critical findings, and significantly shortens the interval between identification and treatment. In our study, clinical pathway reduced time needed to identify, diagnose and manage such disease.
A Model to Protect Disaster Recovery Centers from Cyber Threats with Multi-Layered Network Security Architecture
Authors: Yilmaz Aykut , Gunes Ali
Published: June 2024

Disaster Recovery Centers (DRC) systems are critical infrastructures for business continuity, cyber-attacks can cause valuable corporate and personal data to be seized by cyber attackers. This, in return, results in material and moral damages to institutions, individuals and states. In this study, a modern cyber network security architecture was developed to prevent attack vectors managed by cyber attackers from the internet to DRC systems. EVE-NG, Nessus, OpenVAS, Kali, Parrot, MITRE ATT&CK Enterprise, NIST v2 professional applications and framework systems, which are used and accessible worldwide, were used. A comprehensive application was conducted with ninety-nine real world systems and fourteen different virtual networks in the simulation environment. The simulation was conducted in three phases: the first phase involved attacks aimed at partially or completely disrupting internet access, while the second and third phases involved attacks aimed at rendering the application service servers (DMZ) and local network servers unavailable to the internet. As a result of attacks using various techniques on this network, attempts were made to damage target servers and devices. At the time of the attack, the network traffic between the attacker and the target device was examined using Wireshark and Forti Analyzer software.
Perceived Structural Empowerment, Resilience, and Intent to Stay among Midwives and Registered Nurses in Saudi Arabia: a convergent parallel mixed methods study.
Authors: Al-Otaibi Areej , Aboshaiqah Ahmad , Aburshaid Fatimah , AlKhunaizi Anwar , AlAbdalhai Sarah
Published: June 2024

Background
The retention of midwives and registered nurses in Obstetrics and Gynecology department/unit (OB/GYN) is not just a matter of organizational effectiveness and financial wellness. It's a crucial aspect of ensuring quality healthcare delivery. This study delves into the factors that influence retention, with a particular focus on structural empowerment and resilience.
Methods
The study adopted a convergent parallel mixed methods approach. The study was divided into two phases. Phase one was a cross-sectional quantitative study utilizing a convenience sample of 200 midwives and nurses in OB/GYN departments to discuss the level of structurally empowered, resilient, and committed to staying in the organization and to examine their perceptions of structural empowerment and resilience are good predictors of their decision to remain with the organization, Phase two was a qualitative study; a semi-structured, open-ended interview was adopted. Eighteen nurses and midwives purposely selected as the target population were invited to participate in individual interviews and interview the Obstetrics and Gynecology department/unit participants towards their perception of the phenomenon under study. The data collection took place at three major hospitals in Saudi Arabia, commenced at the beginning of January 2023, and continued until the end of February 2023.
Results
The study results revealed that structural empowerment and resilience were statistically significant predictors of the intent to stay in the organization (F = 35.216, p < 0.001), with 26.3% variation, the structural empowerment is higher predictor (β = 0.486) to intent to stay if compared to resilience (β = 0.215). Five major themes emerged from the narratives of the nurses and midwives: the nurturing of the physical and physiological, the developing the psychological, the managing Financial, the restructuring of the organization, and the enriching of the professional and occupational.
Conclusion
The study's findings have significant implications for healthcare organizations. They highlight the importance of cultivating a culture of empowerment and resilience, which can serve as a powerful tool to encourage registered nurses and midwives to remain in their organization. This insight empowers healthcare administrators, human resource managers, and professionals in the field of obstetrics and gynecology to take proactive steps toward improving retention rates.
Human centred design of Luminear, a digital wellbeing program for adults with hearing loss
Authors: Laird Emma C. , Barr Caitlin M. , Williams Zoe , Bryant Christina A
Published: June 2024

Purpose: This study uses a human-centred design (HCD) approach to co-create an accessible and personalised web-based intervention to address the psychosocial impacts of adults living with hearing loss.
Methods: Employing a HCD methodology, this project adapted a paper-based hearing wellbeing program into a web-based program incorporating iterative feedback from co-designers including adults with lived experience of hearing loss. The co-design team consisted of three researchers, five designers, and nine adults with lived experience of hearing loss. Further consultation was provided by a seven-member research steering committee.
Results: The HCD process led to development of Luminear, a digital hearing wellbeing program, that successfully integrated feedback from a diverse co-design team, leading to significant improvements in content accessibility, user engagement, and system usability. Iterative testing phases included low- and high-fidelity prototyping, culminating in a minimum viable product.
Conclusion: Future research will focus on conducting a feasibility study to prepare for efficacy testing in a randomised controlled trial. The HCD process underscores the importance of involving multidisciplinary teams and end-users in the design process to ensure that digital health interventions are both effective and user centred.
Prevalence and Level of Stress among Final-year Students at a Health Science Institute in Bangladesh
Authors: Alam Md. Jonaied , Pratik Mahmudul Islam Khan , Khan Abid Hasan , Islam Muhammad Shahidul , Hossain Muhammad Millat
Published: June 2024

Background
Health science institutes can contribute to stress among final-year students, potentially leading to negative academic and professional outcomes, as psychological disorders like anxiety and depression are often underdiagnosed and untreated.
Methods
A prospective cross-sectional study involving 134 final-year students at Bangladesh Health Professions Institute (BHPI), in Bangladesh assessed stress using the Academic Stress Scale (ASS-40). Data was collected through face-to-face interviews and analyzed using SPSS software 25.0. Both descriptive and inferential statistics were used to analyse the data which was retrieved from the participants.
Results
In this study, 31.40% of 134 participants were in a normal state, while 68.60% were in a stressful state. The highest level of stress was fear of failure, followed by personal inadequacy. Addressable stress areas included teacher-pupil relationship/teaching method. A negligible association (p > 0.05) was found between age of the participants and level of stress of the participants.
Conclusion
This implies that the educational system, means of teaching, teaching materials, system of materials, teachers as well as the services provided by the institutions cannot provide a conducive environment for effective learning as well as creating a secure future for the students as long as they are able to cope with the academic pressure. A student's educational career is being nipped in the bud due to the weak system of our education and institutional system.
Successful modified combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique with semicircular seromuscular layer incision for gastric gastrointestinal stromal tumors near the cardia: a case report and video demonstration
Authors: Hara Hitoshi , Shimizu Seito , Muto Yasuhide , Kido Tomoki , Miyata Ryohei , Tokuda Moe , Takahashi Kyuichiro , Maesono Tomohiro , Ajihara Takahiro , Yagi Aki , Naritomi Takuma , Itabashi Michio
Published: June 2024

Background:
Laparoscopic and endoscopic cooperative surgery (LECS) combines laparoscopic gastric resection and endoscopic techniques for local resection of gastric tumors, such as gastrointestinal stromal tumors (GIST), with minimal surgical margins. We describe a case that underwent a modified combination of laparoscopic and endoscopic approaches to neoplasia with a non-exposure technique (CLEAN-NET) approach, which is an LECS with a semi-circular seromuscular layer incision around the tumor to preserve the mucosal continuity, which acts as a barrier to avoid intraoperative tumor dissemination.
Case presentation:
A 43-year-old woman was referred to our hospital because of a gastric submucosal tumor near the cardia that was detected on medical examination. The patient was diagnosed with gastric GIST based on the results of endoscopic ultrasound-guided fine-needle aspiration. Modified CLEAN-NET was performed with a semicircular incision of the seromuscular layer on the opposite side of the cardia, making the surgical procedure simple and minimizing partial resection of the gastric wall, including the tumor, while preserving the cardia.
The operative time was 147 min, the preoperative blood loss volume was 3 mL, and the postoperative hospital stay duration was 9 days. The resected specimen revealed a minimal resection of the gastric wall, including the tumor. The cardia and gastric nerves were preserved, and the postoperative food intake was good.
Conclusions:
The modified CLEAN-NET with semicircular seromuscular layer dissection is a simple and reliable surgical procedure for GIST near the cardia.
Analysis of Risk Factors for Postoperative Deep Vein Thrombosis in Traumatic Spinal Fracture Complicated with Spinal Cord Injury
Authors: Yang Diao , Chen Shiwen , Zhuo Can , Chen Haidan
Published: June 2024

The purpose of this study is to investigate the risk factors for postoperative DVT in patients with traumatic spinal fractures complicated with Spinal Cord Injury(SCI). We conducted a retrospective analysis of 110 patients with traumatic spinal fractures and SCI admitted to our hospital from March 2021 to April 2024. DVT was diagnosed usingr ultrasound.Patient history, general data, surgical data, laboratory tests, and thromboelastogram (TEG) results were collected. The patients were divided into a DVT group and a non-DVT group according to the results of color ultrasound one week after surgery. The risk factors and diagnostic value were analyzed using binary logistic regression and receiver operating characteristic (ROC) curves in both univariate and multivariate analyses. The incidence of postoperative DVT was 52.7% (58 / 110). Seven patients (6.4%) had proximal thrombus, and 51 patients had distal thrombus (46.4%). Multivariate and ROC analysis results showed that D-dimer, lower extremity, duration of bed, and MA values were independent risk factors for DVT in SCI, with D-dimer having the highest diagnostic value (AUC = 0.883). The AUC values for lower extremity, duration of bed, and MA were 0.731, 0.750, and 0.625. In conclusion, Postoperative D-dimer>5.065mg/l, lower extremity< 3, duration of bed, and MA value are independent risk factors for postoperative DVT in SCI patients, D-dimer having the highest diagnostic value.
Effect of genistein supplementation on microenvironment regulation of breast tumors in obese mice
Authors: Jin Shengzi , Zheng Yingce , Li Ding , Liu Xingyao , Zhu Tingting , Wang Shuang , Liu Zhonghua , Liu Yun
Published: June 2024

Obesity is an important risk factor for breast cancer in women before and after menopause. Adipocytes, key mediators in the tumor microenvironment, play a pivotal role in linking obesity with cancer. However, the potential of dietary components in modulating this link remains underexplored. Genistein, a soy-derived isoflavone, has shown promise in reducing breast cancer risk, attenuating obesity-associated inflammation, and improving insulin resistance. Yet, there are no reports examining whether genistein has the ability to reduce the breast tumor development effects of obesity. In this study, we constructed a mammary tumor model on ovariectomized obese mice and examined the effects of genistein on body condition and tumor growth. Meanwhile, the effects of genistein on tumor microenvironment were examined by experimental observation of peritumoral adipocytes and macrophages. In addition, we further investigated the effect of genistein on adipocyte and breast cancer cell crosstalk in co-culture experiments. Our findings indicate that dietary genistein significantly alleviates obesity, systemic inflammation, and metabolic disorders induced by a high-fat diet in ovariectomized mice. Notably, it also inhibits tumor growth in vivo. Genistein's impact extends to the tumor microenvironment, where it reduces the production of cancer-associated adipocytes (CAAs) and the recruitment of M2d subtype macrophages. In vitro, genistein mitigates the transition of adipocytes into CAAs and curbs inflammatory factors by activating PPAR-γ and degrading nuclear NF-κB. Furthermore, it impedes the acquisition of invasive capabilities and epithelial-mesenchymal transition in breast cancer cells under CAA-induced inflammation, disrupting the Wnt3a/β-catenin pathway. Intriguingly, the PPAR-γ inhibitor T0070907 counteracted genistein's effects in the co-culture system, underscoring the specificity of its action. Our study suggests that genistein could mitigate the adverse effects of obesity on breast cancer by modulating tumor microenvironment. And these findings provide theoretical support for confirming that genistein can be used as a dietary component in the adjuvant treatment of obese breast cancer patients.
Prevalence of Burnout among Healthcare Workers during the COVID-19 Pandemic: A Systematic Literature Review
Authors: Jan Beebee Zeba Mahetaab Mubarak , Keenoo Bibi Sumera
Published: June 2024

Background
Burnout among healthcare workers has been a significant issue exacerbated by the COVID-19 pandemic. This review aims to synthesise the existing literature on the prevalence, signs, symptoms, and risk factors of burnout among healthcare workers during the pandemic.
Methods
This systematic review follows the PRISMA guidelines. We searched the Web of Science and Scopus for relevant studies published between January 2020 and December 2022. Inclusion criteria were studies reporting burnout prevalence among healthcare workers during the COVID-19 pandemic. All healthcare workers were above 18years old and consent was obtained. Data were extracted and analysed using a structured framework.
Results
The review included 50 studies, with a total sample size of 30,000 healthcare workers. Prevalence of burnout varied significantly across regions, with the highest rates reported in Saudi Arabia (75%) and Kuwait (76.9%). Common symptoms included emotional exhaustion, depersonalisation, and reduced personal accomplishment. Key risk factors identified were high work demands, lack of personal protective equipment (PPE), and prolonged working hours.
Conclusion
The COVID-19 pandemic has significantly impacted the mental health of healthcare workers, leading to high burnout rates. Tailored interventions are needed to address this issue and support healthcare workers during global health emergencies
Binge eating as an emotional response to the Covid-19 pandemic: A sequential mediation model via the impact of events and social anxiety
Authors: Bianchi Dora , Tata Daniele Di , Norcia Anna Di , Pompili Sara , Fatta Laura Maria , Laghi Fiorenzo
Published: June 2024

Background
The long-lasting consequences of the COVID-19 pandemic on the psychological well-being of young people have become an emerging research topic, which still raises several questions for post-pandemic interventions at the individual and community levels. This research investigated the relationship between COVID-19 pandemic life events and the occurrence of binge eating behaviors in emerging adults, hypothesizing indirect effects of the emotional impact of pandemic events and social anxiety.
Methods
Data collection was conducted in November and December 2021 in Italy, involving 286 emerging adults aged 18 to 30 years (Mage = 20.20; SDage = 2.43; 69.6% women) who completed an online anonymous survey. Participants reported the pandemic-related stressors experienced in the last year (i.e., adverse life events; the number of days in quarantine), the long-lasting emotional impact of these experiences in the previous week (i.e., intrusive thoughts; avoidance of thoughts), social anxiety symptoms, and frequency of binge eating episodes. A serial mediation model was tested in line with the research hypotheses.
Results
Both the number of days in quarantine and the pandemic adverse life events in the last year were significantly and positively related to binge eating via the sequential indirect effects of (1) intrusive thoughts and (2) social anxiety.
Conclusion
Our findings provide support for the long-lasting effects of pandemic events and quarantine on youths’ mental health, with cascade effects on intrusive symptoms, social anxiety, and binge eating, with interesting implications for research, practice, and public health policies.
Species diversity, population density and habitat association of large carnivores in Maze National Park, Ethiopia
Authors: Tolcha Abraham , Shibru Simon , Takele Serekebirehan , Dingamo Temesgen , Ayechw Belayneh
Published: June 2024

Carnivores help to maintain ecological balance by preying on herbivores and ensuring the survival of plants. However, large carnivores are experiencing continuous decline around the globe. This study was performed in the Maze National Park (MzNP), Ethiopia, for which no previous empirical data are available. We investigated the diversity, population density and habitat association from October 2020 to September 2022. Direct and indirect sampling methods were held using transect lines, call-up surveys and spoor tracking. The habitat differences for species abundance and seasonal effect were tested using the Chi-square. We hypothesized that the habitat quality and seasons affect the ecology of species. The lion (Panthera leo), leopard (Panthera pardus), cheetah (Acinonyx jubatus) and spotted hyena (Crocuta crocuta) were recorded. The savannah grassland comprised a high abundance (Wet: 46.43%, Dry: 49.58%). The grassland with scattered tree habitat showed high species diversity and evenness (Wet: H’=1.33, J = 0.96; Dry: H’=1.38, J = 0.995), while the riverine forest showed the least (Wet: H’=0.943, J = 0.859; Dry: H’=0.803, J = 0.731). The estimated population density was 0.3–0.33 Panthera leo/km2, 0.14-021 Panthera pardus/km2, 0.09–0.098 Acinonyx jubatus/km2, and 0.2–0.23 Crocuta crocuta/km2. One-way ANOVA was used to compare species abundance among habitats, and the difference was significant (Dry: F = 5.848, df = 3, p = 0.011; Wet: F = 3.903; df = 3, p = 0.037). Our findings suggest that the MzNP has the potential to comprise large carnivores in a good population stand. We recommend that high emphasis be given to habitats for their substantial contribution to supporting the species.
Effects of process parameters of fast EDM drilling on the recast layer
Authors: Xuecheng Xi , Chu Hao-Yu , Li Bin , Zhao Wan-Sheng
Published: June 2024

Fast EDM (electrical discharge machining) drilling is widely used in the machining of film cooling holes of aero-engine turbine blades. However, the EDM process will produce a recast layer, which will affect the surface performance of blades. Therefore, there is a need to explore the mechanism by which process parameters of fast EDM drilling can affect a recast layer. In this paper, the effects of process parameters on the recast layer thickness is studied in detail according to the electrical parameters (pulse-width-time (Ton), pulse-off-time (Toff), average current (Ip), capacitance (C), etc.), machine tool parameters (flushing pressure (P), tube electrode diameter (D), tool electrode rotation speed (n), etc.) of the high-speed electric spark small hole. According to the formation mechanism of the recast layer, the reasons for influences of different parameters on the recast layer are explored from a theoretical level, and the range of process parameters is selected according to actual machining conditions. Through the control variable method, the influence rules of various process parameter variables on the recast layer are explored one by one, and the variable parameter simulation is carried out by using a thermal-fluid coupling model, and the mathematical formulas of different process parameters affecting the recast layer are derived respectively. Combining the variable parameter simulation results and mathematical theory, the mechanism of different process parameters on the recast layer thickness is explored.
Amine Adsorbents Based on N-(2-Hydroxyethyl)ethylenediamine for Carbon Dioxide Capture from simulated biogas
Authors: Bi shumei , Yang haiyan , Gong yue , Yu miao , Zheng jiamin , Shen ruibo
Published: June 2024

N-(2-Hydroxyethyl)ethylenediamine (AEEA) was effectively loaded into a porous resin (ADS-17) using the impregnation method, resulting in the creation of a cost-effective solid amine adsorbent with a high CO2 adsorption capacity. The performance of this adsorbent was evaluated through dynamic adsorption studies, while its structure and morphology were analyzed using N2 adsorption-desorption isotherms and scanning electron microscopy (SEM). The effects of organic amine loading, adsorption temperature, and gas flow rate on its CO2 adsorption performance were thoroughly investigated. The study revealed that under specific conditions—particularly with 40% amine loading at an adsorption temperature of 25°C and a gas flow rate of 150 mL/min—the CO2 adsorption capacity of the adsorbent reached an impressive 149.36 mg/g. Furthermore, even after undergoing five cycles of regeneration, the adsorbent demonstrated good adsorption performance, indicating its stability and potential for practical application.
How to establish and sustain a disease register: Insights from a qualitative study of six registers in the UK
Authors: Stubbs Edmund , Exley Josephine , Wittenberg Raphael , Mays Nicholas
Published: June 2024

Background:
The advent of new chronic conditions such as long COVID-19 raises the question of whether and, if so, how best to establish new disease registers for such conditions. Prompted by the potential need for a long COVID-19 register, we examined experiences of existing UK disease registers to understand barriers and enablers to establishing and sustaining a register, and how these have changed over time.
Methods:
We undertook semi-structured interviews between November 2022 and April 2023 with individuals representing six disease registers that collect individual-level longitudinal data on people diagnosed with a chronic condition.
Results:
Registers examined were developed by a few individuals, usually clinicians, to gain a greater understanding of the disease. Patient voices were largely absent from initial agenda setting processes, but, over time, all registers sought to increase patient involvement.
Securing long-term funding was cited as the biggest challenge; due to limited funds, one of the registers examined no longer actively recruits patients. Charities devoted to the diseases in question were key funders, though most registers also sought commercial opportunities. Inclusion on the NIHR Clinical Research Network Portfolio was also considered a vital resource to support recruitment and follow-up of participants.
All registers have sought to minimise the primary data collected to reduce the burden on clinicians and patients, increasingly relying on linkage to other data sources. Several registers have developed consent procedures that enable participants to be contacted for additional data collection. In some cases, the initial patient consent and data sharing permissions obtained had limited the flexibility to adapt the register to changing data needs. Finally, there was a need to foster buy-in from the community of patients and clinicians who provide and/or use the data.
Conclusion:
We identified six key considerations when establishing a disease register: (1) include a diverse set of stakeholders; (2) involve patients at every stage; (3) collect a core data set for all participants; (4) ensure the data system is flexible and interoperable with the wider data landscape; (5) anticipate changing data needs over time; and (6) identify financial opportunities to sustain the register’s activities for the long term.
Spin freezing induced giant exchange bias in a doped Hund’s metal
Authors: Wu Tao , Li Shunjiao , Zhao Dan , Li Jian , Kang Baolei , Shan Min , Zhou Yanbing , Li Xuyang , Chen Xianhui
Published: June 2024

Exchange bias (EB) is a fundamental phenomenon in widespread information technologies. However, a comprehensive understanding of its microscopic origin remains a great challenge. One key issue in the debate is the role of frustration and disorder in the EB mechanism, which motivates the exploration of the EB effect in spin glass (SG) systems. Here, in the SG state of Cr-doped Hund’s metal CsFe2As2, we discover a giant EB effect with a maximum bias field of ~ 2 Tesla, which is almost two orders of magnitude larger than that of traditional alloy SGs. Our results indicate that the giant EB effect should originate from the exchange interactions at the natural boundaries between the tunable ferromagnetic-like (FM) regions around the Cr dopants and the SG matrix, via which the FM spins are strongly pinned by the frozen spins in the SG matrix. In addition, the temperature-dependent and cooling-field-dependent EB behaviors could be interpreted well by the SG model with frustrated FM/SG boundaries, which provides an intuitive and explicit understanding of the impact of glassy parameters on the EB effect. All these results suggest that Hund’s metal or other correlated metals are promising directions for exploring the EB effect in the SG state.
Classification rule for ten year MACE Risk in Primary Care Tarragona Older Adults with type2 Diabetes. A CHAID decision-tree analysis.
Authors: Ribas Domingo , Forcadell M José , Vila-Córcoles Angel , Diego Cinta , Ochoa-Gondar Olga , Lujan Francisco Martin , Satué Eva
Published: June 2024

Background
Cardiovascular disease is the leading cause of mortality among individuals with Type 2 Diabetes Mellitus (T2DM). This study developed a simple tool to predict the 10-year risk of major adverse cardiovascular events (MACE) in T2DM patients over 60 years within primary care.
Methods
A retrospective cohort study was conducted on patients with T2DM who were over 60 years old in Tarragona, spanning from 01/01/2009-31/12/2018. Primary outcome was MACE, which included acute myocardial infarction (AMI), stroke, and cardiovascular death, all of which were identified using ICD-9 diagnostic codes. Other variables were age, sex, comorbidities, risk factors, as well as clinical and laboratory parameters.
A Chi-Square Automatic Interaction Detector (CHAID) decision tree classification was utilized to assess the 10-year risk of developing a new MACE.
Results
5554 patients with T2DM were identified. Among the 4,666 with T2DM and without previous MACE, 779 patients went on to develop a new MACE.
The CHAID model categorizes individuals into three risk groups based on the primary predictor variable, which is age. For patients under the age of 71 with hypertension, having HDL-c levels less than 39 mg/dL increases the risk of developing a new MACE to 19.9%. Among individuals aged 71 to 75 years, having fasting glucose levels greater than 177 mg/dL elevates the risk to 27.2%.
Conclusion
Classification trees based on CHAID allow for the development of decision rules and simplify the stratification of cardiovascular risk in patients with T2DM, making it a valuable tool for risk assessment within a primary care setting.
A Reliable Routing Algorithm Based on Path Satisfaction in Energy Internet
Authors: Wei Xiangqian , Hu Haifeng , Yu Peng , Shi Lei , Liu Baoju , Sun Zejun
Published: June 2024

Energy Internet (EI) is the trend of smart grids evolution. Since there are large number of services with different performance requirements in the EI. To ensure its smooth operation, it is necessary to design reliable routing algorithms. However, the existing routing strategies in the IP layer place more emphasis on algorithm robustness but neglect resource use in the optical layer as well as characteristic of EI network structure. Actually, resources status of the optical layer affects the availability of the routing algorithm. In view of this, we propose a cross-layer reliable service routing approach, which comprehensively service characteristics in the application layer, link satisfaction and spectrum resources status in the optical layer. The final objective is to satisfy service QoS requirements and ensure services evenly distributed in the network. To reduce the computational complexity, a heuristic algorithm is designed. Extensive experiments are carried out, and the simulation results reflect that the proposed algorithm is superior to the existing algorithms according to the service blocking ratio(SBR) and service distribution fairness index.
Effects of glucocorticoid treatment and survival duration on symptom scores and biomarkers
Authors: Sackmann Valerie , Fransson Karin , Jakobsson Maria , Karlsson Marit , Nilsberth Camilla
Published: June 2024

Patients with cancer experience several severe symptoms that can affect quality of life. The present study investigated how symptoms evolve during the disease and how biomarkers in the blood change during the course of the disease. The effects of glucocorticoid treatment on symptoms and biomarkers were also studied. Forty-eight patients who died within 3 months of inclusion were compared to 62 patients who survived more than 3 months after inclusion. In addition, analysis was performed by comparing the 61 patients who received glucocorticoid treatment to the 49 patients who did not. Symptom scores were assessed by the EORTC QLQ-C15-PAL questionnaire, and CRP, procalcitonin, LDH, albumin and cytokines were measured in the blood. Patients at the end-stage of the disease scored higher on the physical functioning, appetite and dyspnea scores. CRP, procalcitonin, LDH and the cytokines IL-1RA, IL-6, IL-7, IL-8, IL-10, IL-17A, IP10 and TNF-RII were increased, whereas albumin was significantly decreased. The glucocorticoid-treated group displayed higher (worse) symptom scores for physical functioning. In addition, the levels of several cytokines (IL-1RA, IL-10, and TNF-RII) and LDH were significantly greater in the glucocorticoid-treated group. Patients at the end stage of the disease experience more debilitating symptoms, which can be explained by greater inflammatory activity. Patients receiving glucocorticoid treatment also reported higher symptom scores associated with higher levels of biomarkers in the blood. Further studies are required to clarify whether these results are because patients on glucocorticoid treatment are more affected by the tumor or if there may be another explanation.
Identification key genes involved in lignin and flavonoid accumulation during Tilia tuan seed maturation
Authors: Liu Lei , Long Cui , Hao Xuri , Zhang Rui , Li Chenqi , Song Yuepeng
Published: June 2024

Tilia tuan Szyszyl. (T. tuan) is a timber tree species with important ecological and commercial value. However, its highly lignified pericarp results in a low seed germination rate and a long dormancy period. In addition, it is unknown whether there is an interaction between the biosynthesis of flavonoids and lignin as products of the phenylpropanoid pathway during seed development. To explore the molecular regulatory mechanism of lignin and flavonoid biosynthesis, T. tuan seeds were harvested at five stages (30, 60, 90, 120, and 150 days after pollination) for lignin and flavonoid analyses. The results showed that lignin accumulated rapidly in the early and middle stages (S1, S3, and S4), and rapid accumulation of flavonoids during the early and late stages (S1 and S5). High-throughput RNA sequencing analysis of developing seeds identified 50,553 transcripts., including 223 phenylpropanoid biosynthetic pathway genes involved in lignin accumulation grouped into three clusters, and 106 flavonoid biosynthetic pathway genes (FBPGs) grouped into two clusters. Subsequent WGCNA and time-ordered gene co-expression network (TO-GCN) analysis revealed that 24 TFs (e.g., TtARF2and TtWRKY15) were involved in lignin and flavonoid biosynthesis regulation. The transcriptome data were validated by qRT-PCR to analyze the expression profiles of key enzyme-coding genes. This study revealed that there existed a competitive relationship between the flavonoid biosynthesis pathway and the lignin biosynthesis pathway, both of which are downstream pathways of phenylpropane that provide a foundation for the further exploration of molecular mechanisms underlying lignin and flavonoid accumulation in T. tuanseeds.
Accuracy of RENOVO Predictions on Genetic Variants Reclassified Over Time
Authors: Bonetti Emanuele , Tini Giulia , Mazzarella Luca
Published: June 2024

Background
Interpreting the clinical consequences of genetic variants is the central problem in modern clinical genomics, for both hereditary diseases and oncology. However, clinical validation lags behind the pace of discovery, leading to distressing uncertainty for patients, physicians and researchers. This “interpretation gap” changes over time as evidence accumulates, and variants initially deemed of uncertain (VUS) significance may be subsequently reclassified in pathogenic/benign. We previously developed RENOVO, a random forest-based tool able to predict variant pathogenicity based on publicly available information, and tested on variants that have changed their classification status over time. Here, we comprehensively evaluated the accuracy of RENOVO predictions on variants that have been reclassified over the last four years.
Methods
we retrieved 16 retrospective instances of the ClinVar database, every 3 months since March 2020 to March 2024, and analyzed time trends of variant classifications. We identified variants that changed their status over time and compared RENOVO predictions generated in 2020 with the actual reclassifications.
Results
VUS have become the dominant class in ClinVar (44.97% vs 9.75% (likely) pathogenic and 40,33% (likely) benign). The rate of VUS/CIP reclassification is linear and slow compared to the rate of VUS/CIP reporting, exponential and currently ~ 30x faster, creating a growing divide between what can be sequenced vs what can be interpreted. Out of 10,196 VUS/CIP variants in January 2020 that have undergone a clinically meaningful reclassification to march 2024, RENOVO correctly classified 82.6% in 2020. In addition, RENOVO correctly identified the majority of the few variants that switched clinically meaningful classes (e.g., from benign to pathogenic and vice versa). We highlight variant classes and clinically relevant genes for which RENOVO provides particularly accurate estimates. In particularly, genes characterized by dominant prevalence of high- or low-impact mutations (e.g., POLE, NOTCH1, FANCM etc.). Suboptimal RENOVO predictions mostly concern genes validated through dedicated consortia (e.g., BRCA1/2), in which RENOVO would anyway have a limited impact.
Conclusions
Time trend analysis demonstrates that the current model of variant interpretation cannot keep up with variant discovery. Machine learning-based tools like RENOVO confirm high accuracy that can aid in clinical practice and research.
Early-life tobacco exposure is causally implicated in aberrant RAG-mediated recombination in childhood acute lymphoblastic leukemia
Authors: Liu Tanxin , Xu Keren , Pardeshi Anmol , Myint Swe Swe , Kang Alice , Morimoto Libby , Lieber Michael , Wiemels Joseph , Kogan Scott , Metayer Catherine , de Smith Adam J.
Published: June 2024

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, yet few environmental risk factors have been identified. We previously found an association between early-life tobacco smoke exposure and frequency of somatic deletions of 8 leukemia driver genes among childhood ALL patients in the California Childhood Leukemia Study. To expand analysis genome-wide and examine potential mechanisms, we conducted tumor whole-genome sequencing in 35 ALL patients, including 18 with high prenatal tobacco exposure and 17 with low exposure as determined by established epigenetic biomarkers. High tobacco exposure patients had significantly more structural variants (P < .001) and deletions (P = .001) genome-wide than low exposure patients. Investigation of off-target RAG recombination revealed that 41% of deletions in the high tobacco exposure patients were putatively RAG-mediated (full RAG motif identified at one or both breakpoints) compared with only 21% in the low exposure group (P = .001). In a multilevel model, deletions in high tobacco exposure patients were 2.44-fold (95% CI:1.13–5.38) more likely to be putatively RAG-mediated than deletions in low exposure patients. No point mutational signatures were associated with prenatal tobacco exposure. Our findings suggest that early-life tobacco smoke exposure may promote leukemogenesis by driving development of somatic deletions in pre-leukemic lymphocytes via off-target RAG recombination.
Elicitation of callus cultures of the medicinally important plant Embelia ribes Burm f. using biotic and abiotic elicitors for enhanced production of embelin
Authors: Kamble Vidya V. , Rather Shabir A. , Razaq Mohsin , Phukela Banisha , Gaikwad Nikhil B.
Published: June 2024

The berries of Embelia ribes Burm f. are a rich source of embelin, a compound known for its anthelmintic, antidiabetic, and anticancer activity. Due to over-exploitation, the natural habitat of Embelia ribes is now considered vulnerable. Traditional propagation methods are insufficient to meet current demands, necessitating alternative production methods. This study was designed to explore in vitro culture as a viable alternative for the production of embelin. While numerous studies have focused on extracting embelin from callus cultures, there is a lack of research on enhancing the embelin content in both organogenic and embryogenic callus cultures. The objective of this study was to enhance embelin production in callus cultures by using both biotic and abiotic elicitors. Additionally, efforts were made to optimize rapid in vitro shoot induction. We achieved the best response rate for the induction of organogenic and embryogenic calli using MS basal medium supplemented with TDZ. Among the various elicitors tested, chitosan at 200 mg/L was the most effective, yielding the highest embelin content, at 6.44% in embryogenic calli and 5.72% in organogenic calli. Subsequent subculturing enabled successful differentiation of callus cultures into shoot buds on MS medium supplemented with a combination of BAP (6-benzylaminopurine) and IAA (indole-3-acetic acid) at concentrations of 2.0 mg/l and 0.1 mg/l, respectively. An effective protocol has been developed for obtaining the highest embelin content from embryogenic and organogenic callus cultures, coupled with a high frequency of shoot multiplication. The protocol can be instrumental for large-scale embelin production, ex-situ conservation, sustainable utilization, and industrial applications.
Unveiling Optimal Molecular Features for hERG Insights with Automatic Machine Learning
Authors: Xu Congying , Xu Youjun , Hu Ziang , Pei Jianfeng
Published: June 2024

We have developed MaxQsaring, a novel universal framework integrating molecular descriptors, fingerprints, and deep-learning pretrained representations, to predict the properties of compounds. Applied to a case study of hERG (human Ether-à-go-go-Related Gene) blockage prediction, MaxQsaring achieved state-of-the-art performance on two external challenging datasets through automatic optimal feature combinations, and successfully identified top 10 important interpretable features that could be used to model a high-accuracy decision tree. The models’ predictions could well align with empirical hERG optimization strategies, demonstrating their interpretability for practical utilities. Deep-learning-pretrained representations can moderately improve the performance of the models, but contribute less to improve models’ generalizability for compounds with novel scaffolds. MaxQsaring excelled in the Therapeutics Data Commons benchmark, ranking first in 19 out of 22 tasks, showcasing its potential for universal accurate compound property prediction to facilitate high success rate of early drug discovery, which is still a formidable challenge.