bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Body Mass Index (BMI) with Diet, Physical Activity, and Lifestyle among Undergraduate Dental Students in a Private Dental College in Bangladesh
Authors: Rafique Taslima , Molla Golam Morshed , Ahamed Asma
Published: October 2024

Background: Obesity can lead to severe health problems and elevate the risk of diseases such as hypertension, dyslipidemia and diabetes due to metabolic changes. Undergraduate dental students often struggle to maintain a healthy lifestyle and eating habits due to academic pressures. BMI, a standard obesity measure, is simple to calculate and assess nutritional status, helping to identify and prevent obesity-related diseases in at-risk individuals. Method: A cross-sectional study was performed among 253 students of Sapporo Dental College, a private dental college in Uttara, Dhaka, Bangladesh, to reveal the prevalence of overweight and obesity according to BMI and its association with dietary habits, physical activities, and lifestyles among them. Data was collected using a self-written, anonymous, semi-structured questionnaire using the convenient sampling technique between July 2023 and September 2023. Result: Among the 253 participants, females (n = 190, 75.10%) are more than males (n = 63, 25%). The prevalence of normal weight, underweight, overweight, and obesity among the participants was 132 (37.93%), 31 (8.91%), 56 (16.09%), and 129 (37.07%), respectively, based on BMI. 84% of obese students were taken 1 meal from outside per day (p values < 0.05). 52% obese students did not engage in any form of physical activity on a weekly basis (p value 0.03). 55.5% obese students slept for < 6 hours every night (p-value 0.04). Conclusion: Early modifications of lifestyle improve health. Annual screenings help to prevent obesity. Fitness and diet programs can reduce dental students' chronic disease risk. Study participants are future physicians. Thus, dental students should be physically active and aware of their eating and sleep habits to reduce obesity, which might influence patients' outlooks.
Update Dent. Coll. j: 2024; 14(2):15-20
Towards optimised paediatric palliative care
Authors:   , van Teunenbroek Kim Cecile
Published: October 2024

Too often children with life-threatening and life-limiting conditions and their families fail to receive adequate and consistent paediatric palliative care that meets their physical, psychological, social, and spiritual needs. The aim of this dissertation was to further improve the quality of paediatric palliative care and thereby the quality of life of children aged 0 to 18 years with life-threatening and life-limiting conditions and their families by developing the revised Dutch clinical practice guideline for paediatric palliative care.

Health care providers expressed a need for more guidance on essential elements of paediatric palliative care based on the most recent evidence from scientific literature. This led to the revision of the first Dutch Paediatric palliative care guideline in 2013. The revised clinical practice guideline for paediatric palliative care was developed according to a standardized methodology that ensured trustworthiness. By using this methodology, we provided a large set of recommendations for essential components of paediatric palliative care including symptom treatment, advance care planning, shared decision-making, and psychosocial care including preloss and bereavement care. The recommendations were based upon evidence from scientific literature, clinical expertise and patient and family values.

The insights and the findings of this dissertation open opportunities to further optimise the guideline and paediatric palliative care research. We elaborated on several opportunities such as the use of automated tools to improve the efficacy and quality in guideline development, broaden scope of the guideline for paediatric palliative care in the future, address identified knowledge gaps in paediatric palliative care, and facilitate further implementation of the guideline. These opportunities can facilitate the further optimisation of paediatric palliative care in the Netherlands but can also be used to improve paediatric palliative care worldwide.
Evaluating the role of pericoronary adipose tissue on coronary artery disease: insights from CCTA on risk assessment, vascular stenosis, and plaque characteristics
Authors: Wang Jingyue , Zhang Huicong , Wang Zihao , Liu Wenyun , Cao Dianbo , Tong Qian
Published: October 2024

Introduction

Pericoronary adipose tissue (PCAT) plays a significant role in the occurrence and progression of coronary artery disease (CAD). This study investigates the relationship between PCAT and CAD, focusing on the occurrence of the disease, the severity of vascular narrowing, and the characteristics of arterial plaques.

Methods

We analyzed a cohort of 152 individuals with CAD and 55 individuals with non-coronary artery disease (N-CAD). Participants underwent both coronary computed tomography angiography (CCTA) and digital subtraction angiography (DSA). Utilizing United Imaging software for artificial intelligence delineation, we measured the fat attenuation index (FAI) and volume of PCAT in the left anterior descending (LAD), left circumflex (LCX), and right coronary arteries (RCA).

Results

Our findings demonstrate that while CCTA is effective in diagnosing CAD compared to DSA, its diagnostic power for individual coronary arteries remains limited. Further analysis revealed that the FAI of the RCA and the overall PCAT volume independently influenced CAD (OR: 1.057, 95% CI: 1.002 to 1.116; OR: 0.967, 95% CI: 0.936 to 0.999). FAI showed a significant independent effect on RCA stenosis (OR: 1.041, 95% CI: 1.003 to 1.081), while the fat volume of the LAD had a significant independent effect on LAD stenosis (OR: 0.884, 95% CI: 0.809 to 0.965). A higher FAI and a lower fat volume were significantly correlated with more severe vascular stenosis percentages in all three arteries (p < 0.05), except for the fat volume and stenosis of the LCX. Moreover, we found the significant differences in the fat volume of the LCX between different plaque types (H = 8.869, p = 0.012), with calcified plaques consistently exhibiting the lowest fat volume across all three arteries. Finally, the likelihood ratio test confirmed that incorporating the PCAT fat volume parameter of LAD significantly improved the diagnostic ability of CCTA for both CAD (p = 0.01543) and LAD stenosis (p = 0.001585).

Conclusion

The quantification of PCAT has potential application value in the comprehensive assessment of CAD. It is recommended that cardiology and radiology departments consider incorporating PCAT into the assessment criteria for patients suspected of having CAD.
Evolution and sustainability analysis of global tungsten trade pattern from the perspective of industry chain
Authors: Xi Xian , Zhong Weiqiong , Zheng Huiling
Published: October 2024

Tungsten is an irreplaceable primary material and strategic resource for national economic development and modern national defense security. The endowment of tungsten ore resources in various countries is different; we should not only focus on the availability of tungsten ore itself but also the sustainability of its entire process from upstream supply to downstream industry demand. Analyzing the evolution of the supply and demand patterns of tungsten ore trade from the perspective of the industrial chain, identifying the key supply and demand subjects, and exploring the influencing factors of trade has become an important research topic. Therefore, we construct global tungsten trade networks based on the industrial chain, analyze its overall characteristics, explore critical trade supply and demand entities, and identify China’s trade position. We got some meaningful results: (1) The global tungsten trade networks have prominent power-law distribution characteristics. The trend of trade globalization is evident, but the dominance is still in the hands of a few developed countries or developing countries with developed manufacturing industries. (2) In different parts of the tungsten industry chain, the impact of resource endowment, industrial technology level, and geographical location on the country’s trade role is different. (3) China’s position in the global tungsten resource industry chain and value chain is constantly improving, but there is still a risk of high-end technology being “stuck.” This provides some suggestions for the systematic understanding of the evolution of the trade pattern of the tungsten industry chain and how countries occupy a dominant position in the game of tungsten resources.
Digital vs. conventional instructor-led midwifery training in Benue State, Nigeria: a randomized non-inferiority trial
Authors: Ujoh Fanan , Dzunic-Wachilonga Anja , Noor Rafat , Gusa Victoria , Ape-aii Roseline , Ohene Isaac , Bola Rajan , Christilaw Jan , Hodgins Stephen , Lett Ronald
Published: October 2024

Background

Many health education institutions in African countries such as Nigeria face increasing enrolment of students but lack an adequate number of instructors to train them. If digital learning can be demonstrated effective in augmenting knowledge and skills, this approach could help fill this gap and improve education efficiency. A needs assessment in two Nigerian midwifery schools confirmed that digital learning would be feasible and welcomed. In this study, the Midwifery Active Digitization Empowerment Initiative (MADE-I) program was tested to determine if digital delivery of the Fundamental Interventions, Referral and Safe Transfer (FIRST) course is at least equally effective for training midwifery students compared to conventional small-group delivery.

Methods

A non-inferiority randomized controlled trial design was used, enrolling 130 s-year students from 2 midwifery schools in Benue State, Nigeria. Students were randomly assigned into six cohorts. Each cohort received half of the course on a Learning Management Platform on their mobile phones, the other half through standard small-group teaching. Students’ knowledge, thinking, and technical skills were assessed using a pre-test, post-test, Objective Structured Clinical Exam (OSCE), and daily modular quizzes. The data was analyzed using the difference-in-difference method.

Results

The study revealed that post-intervention student knowledge and thinking skills did not significantly differ between digital learning (75.26%) and small-group learning arms of the trial (75.02%, p = 0.404). Student knowledge improved significantly compared to the pre-test in both groups (by 25.03 points in the digital arm, 26.39, in small-group). Some differences were observed between digital and small-group learning in disaggregated analysis by specific module and midwifery school. Although there was a trend toward small-group learning of technical skills being more effective than digital learning, no significant differences between groups were observed in the post-intervention OSCE. Students in both groups learned equally well regardless of age, gender, and midwifery school entrance exam score.

Conclusion

Digital learning is as effective as small-group learning, for midwifery trainees, in augmenting knowledge, thinking, and technical skills addressed in the FIRST course, and have lighter human resource requirements, an important consideration especially in LMIC. However, similar assessments would be needed to assess effectiveness for other digitally delivered clinical education programs.
Roles of NR1I3 and NR1H4 polymorphisms in the susceptibility to antituberculosis drug-induced liver injury in China: a case‒control study
Authors: Xu Xiaoyan , Chen Ruina , Lu Lihuan , Cheng Jingru , He Xiaomin , Pan Hongqiu , Zhang Meiling , Yi Honggang , Tang Shaowen
Published: October 2024

Objective

The pathogenesis of antituberculosis drug-induced liver injury (AT-DILI) remains largely unknown. The current investigation aimed to determine the genetic contribution of the nuclear receptor subfamily 1 Group I member 3 (NR1I3) and nuclear receptor subfamily 1 Group H member 4 (NR1H4) genes to the risk of AT-DILI in the Chinese population.

Methods

A 1:4 matched case‒control study was conducted, and five single nucleotide polymorphisms (SNPs) in the NR1I3 and NR1H4 genes were detected and assessed. Utilizing a multivariate conditional logistic regression model, the effects of haplotype and genotype on the risk of AT-DILI were examined. Extended subgroup analysis was carried out based on sex. The distribution of the peak value of serum liver enzymes also compared among different genotypes.

Results

224 AT-DILI cases and 896 controls were included in this study. No significant difference was observed in genotypes or haplotypes frequencies between AT-DILI cases and controls. However, comparisons of liver function indicators revealed significant differences in the peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) among patients with different genotypes of NR1H4 rs56163822 (GG vs. GT vs. TT, 27.1 U/L vs. 26.0 U/L vs. 23.0 U/L, p = 0.020; 34.0 U/L vs. 31.0 U/L vs. 30.6 U/L, p = 0.008; 15.5 μmol/L vs. 15.0 μmol/L vs. 13.7 μmol/L, p = 0.029, respectively), as well as in the peak values of ALT and AST among male patients with different genotypes of NR1H4 rs56163822 (29.0 U/L vs. 26.9 U/L vs. 22.6 U/L, p = 0.002; 34.0 U/L vs. 32.0 U/L vs. 30.5 U/L, p = 0.019, respectively).

Conclusion

Based on this 1:4 individual-matched case‒control study, the SNP rs56163822 in the NR1H4 gene may be linked to the susceptibility to AT-DILI in Chinese patients receiving anti-TB treatment. Further studies in larger varied populations are needed to validate our findings.
Continuous debridement combined with short-term posaconazole therapy for cutaneous mucormycosis caused by Rhizopus oryzae infection secondary to acute myeloid leukemia: a case report
Authors: Wang Fengming , Li Jv , Xie Yilian , Ye Jiayuan
Published: October 2024

Cutaneous mucormycosis is a rare fungal infection marked by skin abscesses, swelling, necrosis, dry ulcers, and eschars. Though less fatal compared to other mucormycosis forms, delayed diagnosis and treatment in immunocompromised patients can cause the infection to spread to vital organs, becoming life-threatening. We report a case of lower extremity cutaneous mucormycosis secondary to acute myeloid leukemia, successfully managed with sustained surgical debridement and short-term oral posaconazole. This case highlights the effectiveness of surgical debridement and the potential for short-course antifungal therapy in managing cutaneous mucormycosis.
Non-invasive assessment of intracranial pressure through the eyes: current developments, limitations, and future directions
Authors: Bastani Viarsagh Solmaz , Agar Ashish , Lawlor Mitchell , Fraser Clare , Golzan Mojtaba
Published: October 2024

Detecting and monitoring elevated intracranial pressure (ICP) is crucial in managing various neurologic and neuro-ophthalmic conditions, where early detection is essential to prevent complications such as seizures and stroke. Although traditional methods such as lumbar puncture, intraparenchymal and intraventricular cannulation, and external ventricular drainage are effective, they are invasive and carry risks of infection and brain hemorrhage. This has prompted the development of non-invasive techniques. Given that direct, non-invasive access to the brain is limited, a significant portion of research has focused on utilizing the eyes, which uniquely provide direct access to their internal structure and offer a cost-effective tool for non-invasive ICP assessment. This review explores the existing non-invasive ocular techniques for assessing chronically elevated ICP. Additionally, to provide a comprehensive perspective on the current landscape, invasive techniques are also examined. The discussion extends to the limitations inherent to each technique and the prospective pathways for future advancements in the field.
The association between dietary consumption habits and psoriasis: a two-sample Mendelian randomization study
Authors: Minghui Lu , Changyong Gao , Runtian Zhang , Jianhong Li , Lingling Yuan , Xi Chen
Published: October 2024

Background

Psoriasis is a chronic inflammatory skin disease characterized primarily by erythema and scales, having a wide-ranging impact globally. Previous studies have suggested that dietary consumption habits may influence psoriasis. The objective of this study was to determine the causal relationship between dietary consumption habits and psoriasis using the Mendelian Randomization (MR) approach.

Methods

SNP data for 29 dietary consumption habits and psoriasis were obtained from the GWAS catalog database and the FinnGen database, respectively. The Mendelian Randomization analysis was performed using R software, with the 29 dietary consumption habits as the exposure factors and psoriasis as the outcome. Three MR analysis methods—Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), and MR-Egger regression—were employed to study the causal relationship between dietary consumption habits and psoriasis.

Results

The IVW analysis indicated an OR (95%CI) of 0.065 (0.008–0.555), p = 0.012, demonstrating a negative correlation between the consumption of dried fruit and psoriasis.

Conclusion

Among the 29 dietary consumption habits analyzed, the intake of dried fruits is a protective factor against psoriasis. Therefore, it is clinically advisable to appropriately increase the intake of dried fruits among patients with psoriasis, serving as a nutritional therapy method in conjunction with pharmacological treatment.
Case report: Acute liver failure during deferasirox therapy and the potential role of pharmacogenetics
Authors: García-Fariña Belén , Rink Lydia , Santarini Virginia , Westkemper Marco , Dohna-Schwake Christian , Möhlendick Birte
Published: October 2024

Background and aims

A number of case reports have documented the occurrence of acute hepatic and renal toxicity during treatment with deferasirox (DFX). The precise mechanisms underlying these adverse events remain unclear, with the time to toxicity varying considerably between patients—some experiencing it within weeks of treatment initiation, while others after several years. Recent studies have underscored the association of pharmacogenetic variants in genes responsible for the metabolism and clearance of DFX (ABCC2, ABCG2, and UGT1A1) in the development of toxicity. We present the case of an 8-year-old patient with beta thalassemia major who developed acute hepatic failure years after the initiation of DFX therapy. After ruling out the most likely causes, we performed a pharmacogenetic analysis, which suggested a possible link between the patient’s genotype and the development of toxicity.

Methods

Sanger sequencing was performed for the most extensively studied single nucleotide polymorphisms (SNPs) studied associated with changes in transporter/enzyme function: ABCC2 rs717620 (c.-24C>T), rs2273697 (c.1249G>A), rs8187710 (c.4544G>A), rs369192412 (g.99781071delG); ABCG2 rs2231142 (c.421C>A); UGT1A1 *6 rs4148323 (c.211G>A), *28 rs3064744 (g.233760235TA[8]), *36 rs3064744 (g.233760235TA[6]) and *37 rs3064744 (g.233760235TA[9]).

Results

The patient is heterozygous for two ABCC2 variants, namely rs717620 (c.-24C>T) and rs2273697 (c.1249G>A). These variants have the potential to cause a reduction in transporter function, which could in turn result in decreased drug clearance and increased toxicity.

Discussion

The precise mechanism by which toxicity developed in this case remains unclear and is likely multifactorial. However, it is probable that the presence of SNPs in the gene ABCC2 played a substantial role. Our findings align with those of previously published reports of remarkably similar cases, where patients also exhibited genetic variants in the gene ABCC2.
De novo design of mIDH1 inhibitors by integrating deep learning and molecular modeling
Authors: Sun Dingkang , Xu Lulu , Tong Mengfan , Wei Zhao , Zhang Weitong , Liang Jialong , Liu Xueying , Wang Yuwei
Published: October 2024

Background

Mutations in the IDH1 gene have been shown to be an important driver in the development of acute myeloid leukemia, gliomas and certain solid tumors, which is a promising target for cancer therapy.

Methods

Bidirectional recurrent neural network (BRNN) and scaffold hopping methods were used to generate new compounds, which were evaluated by principal components analysis, quantitative estimate of drug-likeness, synthetic accessibility analysis and molecular docking. ADME prediction, molecular docking and molecular dynamics simulations were used to screen candidate compounds and assess their binding affinity and binding stability with mutant IDH1 (mIDH1).

Results

BRNN and scaffold hopping methods generated 3890 and 3680 new compounds, respectively. The molecules generated by the BRNN performed better in terms of molecular diversity, druggability, synthetic accessibility and docking score. From the 3890 compounds generated by the BRNN model, 10 structurally diverse drug candidates with great docking score were preserved. Molecular dynamics simulations showed that the RMSD of the four systems, M1, M2, M3 and M6, remained stable, with local flexibility and compactness similar to the positive drug. The binding free energy results indicated that compound M1 exhibited the best binding properties in all energy aspects and was the best candidate molecule among the 10 compounds.

Conclusion

In present study, compounds M1, M2, M3 and M6 generated by BRNN exhibited optimal binding properties. This study is the first attempt to use deep learning to design mIDH1 inhibitors, which provides theoretical guidance for the design of mIDH1 inhibitors.
Could an evaluative conditioning intervention ameliorate paranoid beliefs? Self-reported and neurophysiological evidence from a brief intervention focused on improving self-esteem
Authors: Trucharte Almudena , Carmen Valiente , Pacios Javier , Bruña Ricardo , Espinosa Regina , Peinado Vanesa , Pascual Teodoro , Martinez Anton P. , Maestu Fernando , Bentall Richard P.
Published: October 2024

Introduction

Much research on the treatment of paranoia has involved cognitive-behavioural interventions that address explicit social cognition processes. However, much of human cognition is preverbal or implicit, raising the possibility that such social judgements are implicated in paranoia. One type of implicit social cognition that has been investigated concerning paranoia is implicit self-esteem with some evidence that it may be possible to change implicit self-esteem using techniques based on conditioning theory. Therefore, the primary purpose of this research is to further evaluate the potential of this approach. At the same time, as a secondary purpose, we introduce a novel way of measuring social cognition that, we argue, has utility for investigating the psychological processes involved in paranoia.

Method

We conducted two proof-of-concept studies of a novel brief intervention based on evaluative conditioning, targeting implicit cognition. The first study was conducted with a large non-clinical sample, while the second study included a small series of psychotic patients. As part of our proof-of-concept evaluation of the potential of evaluative conditioning, we attempted to probe for neurophysiological changes following the intervention using magnetoencephalography in an exploratory way in the clinical sample.

Results

Our results revealed that both non-clinical and clinical participants in the experimental group showed a significant change in how they evaluated themselves in the social cognition task, which could be related to the perception of social information in a less threatening way. In addition, clinical participants in the experimental group showed changes in brain activity during the social cognition task, particularly in regions involved in emotional reactivity and mentalization processes.

Discussion

Our results are encouraging, suggesting that implicit cognition is manipulable, that such manipulation affects underlying neurophysiological mechanisms, and that there may be an impact on paranoid symptoms. However, much more work is required to determine whether this approach can produce meaningful clinical change and be delivered in routine clinical settings. Finally, it is important to note that we are not claiming the clinical effectiveness of our intervention, which is in a very early stage of development. Our goal here is to demonstrate clinical possibilities that warrant further investigation
Dual-Arm Space Robot On-Orbit Operation of Auxiliary Docking Prescribed Performance Impedance Control
Authors: Liu Dongbo , Chen Li
Published: October 2024

The impedance control of a dual-arm space robot in orbit auxiliary docking operation is studied. First, for the closed-chain hybrid system formed by the dual-arm space robot after capture operation, the dynamic equation of position uncontrolled and attitude controlled is established. The second-order linear impedance model and second-order approximate environment model are established for the problem of simultaneous output force/pose control of the end of the manipulator. Then, aiming at the transient performance control requirements of the dual-arm space robot auxiliary docking operation in orbit, a sliding mode controller with equivalent replacement of tracking errors is designed by introducing Prescribed Performance Control (PPC) theory. Next, Radial Basis Function Neural Networks (RBFNN) are used to accurately compensate for the modeling uncertainties of the system. Finally, the stability of the system is verified by Lyapunov stability determination. The simulation results show that the attitude control accuracy is better than 0.5°, the position control accuracy is better than 10−3 m, and the output force control accuracy is better than 0.5 N when it reaches 30 N. It also indicated that the proposed control algorithm can limit the transient performance of the controlled system within the preset range and achieve high-precision force/pose control, which ensures a more stable on-orbit auxiliary docking operation of the dual-arm space robot.
Research on the Inner Surface Discharge of the Insulation Sheath of Electric Locomotive Cable Terminals
Authors: Zou Huanqing , Yin Yufeng , Chen Juan , Zhang Shun , Tian Fuqiang
Published: October 2024

Adding an insulating sheath to the exposed metal part of the outer insulation of a roof cable terminal can extend the creepage distance of the leakage current and significantly reduce the probability of pollution flashover on the outer insulation of the equipment. However, during the actual operation of the locomotive, the inner surface of the insulating sheath is discharged, resulting in cable insulation breakdown, the mechanism of which is unclear. This paper establishes a cable terminal–sheath electric field simulation model and studies the interface air gap, the interface with wet pollution, and the distribution of damp pollution on the outer surface and other factors on the electric field distribution of the cable terminal–sheath structure and the interface discharge, revealing the mechanism of discharge on the inner surface of the cable terminal’s insulation sheath. A voltage of 25 kV rms is applied, and the simulation results show that when the outer surface of the cable terminal is clean and there are air gaps and wet dirt on the inner surface, the maximum distortion electric field at the inner surface is 0.8 × 105~3.4 × 105 V/m, and the value of the electric field at this time is not enough to cause a partial discharge; when there is a uniform layer of wet dirt on the outer surface of the cable terminal, the electric field on the inner surface averages 1.5 × 105 V/m, which is about 275% higher than the average electric field when the outer surface is clean; when there is wetting or an air gap on the inner surface at the same time, the maximum aberration electric field on the inner surface is 1.8 × 105~1.9 × 106 V/m. The wetting on the outer surface of the cable terminal strengthens the non-uniformity degree of the distribution of the electric field, and when there is wetting and an air gap on the inner surface, the over-voltage on the cable terminal inevitably leads to a discharge phenomenon in the air gap. This provides a theoretical basis for optimizing the insulation sheath structure to solve the discharge problem.
Managing Crohn’s Disease Postoperative Recurrence Beyond Prophylaxis: A Comprehensive Review with Meta-Analysis
Authors: Olteanu Andrei Ovidiu , Klimko Artsiom , Tieranu Eugen Nicolae , Bota Andreea Daniela , Preda Carmen Monica , Tieranu Ioana , Pavel Christopher , Pahomeanu Mihai Radu , Toma Cristian Valentin , Saftoiu Adrian , Ionescu Elena Mirela , Tieranu Cristian George
Published: October 2024

Background and Aims: Postoperative recurrence in Crohn’s disease remains a significant clinical challenge, with high recurrence rates despite advancements in medical therapy. This study aims to evaluate the efficacy of various treatments for managing postoperative recurrence following ileocolonic resection in Crohn’s disease. Methods: A comprehensive search of PubMed, Cochrane, and Scopus databases was performed to identify studies reporting on the therapeutic management of postoperative recurrence in Crohn’s disease. Studies encompassing patients with an endoscopic Rutgeerts score of at least I2 were included. Results: Ustekinumab showed promise, achieving significant endoscopic and clinical success in difficult-to-treat patients. Anti-TNF agents demonstrated superior endoscopic and clinical remission rates compared to mesalamine and azathioprine. Retreatment with anti-TNF therapy remained effective even after preoperative failure. Thalidomide showed efficacy in refractory Crohn’s disease, but carries significant toxicity risks, necessitating careful patient selection and monitoring. Combination therapies and non-pharmacologic strategies like enteral nutrition offer additional options, though patient compliance remains challenging. Conclusions: Personalized treatment plans based on individual risk factors and biomarkers are crucial. Infliximab is recommended as the first-line treatment, with ustekinumab and vedolizumab as alternatives in case of anti-TNF failure or intolerance. Early intervention, patient education, and ongoing evaluation are essential for optimizing long-term outcomes in managing postoperative recurrence in Crohn’s disease.
Metamaterial Sensing of Cyanobacteria Using THz Thermal Curve Analysis
Authors: Jeong Tae Hee , Jun Seung Won , Ahn Yeong Hwan
Published: October 2024

In this study, we perform thermal curve analyses based on terahertz (THz) metamaterials for the label-free sensing of cyanobacteria. In the presence of bacterial films, significant frequency shifts occur at the metamaterial resonance, but these shifts become saturated at a certain thickness owing to the limited sensing volume of the metamaterial. The saturation value was used to determine the dielectric constants of various cyanobacteria, which are crucial for dielectric sensing. For label-free identification, we performed thermal curve analysis of THz metamaterials coated with cyanobacteria. The resonant frequency of the cyanobacteria-coated metasensor changed with temperature. The differential thermal curves (DTC) obtained from temperature-dependent resonance exhibited peaks unique to individual cyanobacteria, which helped identify individual species. Interestingly, despite being classified as Gram negative, cyanobacteria exhibit DTC profiles similar to those of Gram-positive bacteria, likely due to their unique extracellular structures. DTC analysis can reveal unique characteristics of various cyanobacteria that are not easily accessible by conventional approaches.
Panobinostat Synergizes with Chemotherapeutic Agents and Improves Efficacy of Standard-of-Care Chemotherapy Combinations in Ewing Sarcoma Cells
Authors: Smith Kaitlyn H. , Trovillion Erin M. , Sholler Chloe , Gandra Divya , McKinney Kimberly Q. , Mulama David , Dykema Karl J. , Nagulapally Abhinav B. , Oesterheld Javier , Saulnier Sholler Giselle L.
Published: October 2024

Background: The survival rate of patients with Ewing sarcoma (EWS) has seen very little improvement over the past several decades and remains dismal for those with recurrent or metastatic disease. HDAC2, ALK, JAK1, and CDK4 were identified as potential targets using RNA sequencing performed on EWS patient tumors with the bioinformatic analysis of gene expression. Methods/Results: The pan-HDAC inhibitor Panobinostat was cytotoxic to all the Ewing sarcoma cell lines tested. Mechanistically, Panobinostat decreases the expression of proteins involved in the cell cycle, including Cyclin D1 and phospho-Rb, and DNA damage repair, including CHK1. Further, Panobinostat induces a G1 cell cycle arrest. The combination of Panobinostat with Doxorubicin or Etoposide, both of which are used as standard of care in upfront treatment, leads to a synergistic effect in EWS cells. The combination of Panobinostat and Doxorubicin induces an accumulation of DNA damage, a decrease in the expression of DNA damage repair proteins CHK1 and CHK2, and an increase in caspase 3 cleavage. The addition of Panobinostat to standard-of-care chemotherapy combinations significantly reduces cell viability compared to that of chemotherapy alone. Conclusions: Overall, our data indicate that HDAC2 is overexpressed in many EWS tumor samples and HDAC inhibition is effective in targeting EWS cells, alone and in combination with standard-of-care chemotherapy agents. This work suggests that the addition of an HDAC inhibitor to upfront treatment may improve response.
A Comprehensive Review of TRPS1 as a Diagnostic Immunohistochemical Marker for Primary Breast Carcinoma: Latest Insights and Diagnostic Pitfalls
Authors: Georgescu Antonia-Carmen , Georgescu Tiberiu-Augustin , Duca-Barbu Simona-Alina , Pop Lucian Gheorghe , Toader Daniela Oana , Suciu Nicolae , Cretoiu Dragos
Published: October 2024

Background/Objectives: Immunohistochemical expression of TRPS1 (trichorhinophalangeal syndrome type 1) protein is usually used by pathologists to confirm breast origin for triple-negative breast cancers (TNBC) or metastatic carcinomas of unknown primary. However, recent studies have reported TRPS1 expression in a variety of non-breast lesions. This review aims to provide a comprehensive evaluation of TRPS1 expression across various tumor types, highlighting both its diagnostic utility and potential pitfalls that may arise in clinical practice. Methods: A thorough search of the PubMed database on TRPS1 immunoexpression in tumor pathology was conducted. While the gene itself has been known for several decades, most studies regarding its use in immunohistochemistry emerged in the late 2010s. Particular emphasis was placed on case reports and cohort studies that examined the implications of TRPS1 expression in non-breast tissues, as well as variations in the results between commercially available TRPS1 clones, which may influence the staining intensity and specificity. Results: TRPS1 demonstrated a strong diagnostic utility in identifying primary breast lesions, particularly in TNBC cases. However, its expression in a growing number of non-breast cancers, such as lung adenocarcinoma, prostate adenocarcinoma, urothelial carcinoma, ovarian high-grade serous carcinoma, and endometrial adenocarcinoma, as well as up to 96% of synovial sarcomas with SS18-SSX fusion, emphasizes the need for caution when interpreting TRPS1 positivity and suggests a multi-marker approach in order to increase the diagnostic accuracy. Conclusions: While TRPS1 remains a highly sensible immunohistochemical marker for confirming breast primary lesions, pathologists should be aware of its low specificity and incorporate complementary diagnostic methods in order to ensure accurate clinical management. Further research should focus on elucidating the molecular pathways regulating TRPS1 expression in various tumor types, which may better define its clinical utility.
Evaluation of Selected MRI Parameters in the Differentiation of Mucinous Ovarian Carcinomas and Metastatic Ovarian Tumors
Authors: Halaburda-Rola Marta , Grabowska-Derlatka Laretta , Kraj Leszek , Stec Rafal , Derlatka Pawel
Published: October 2024

Introduction: Analysis of selected MRI parameters in initial MRI for the characterization of ovarian masses enables differentiation between mucinous ovarian carcinoma and metastatic ovarian tumors. Material and Methods: A prospective analysis of contrast-enhanced MRI of patients with suspected ovarian masses diagnosed in ultrasound and CT examination. Morphological criteria, such as the size of lesion, bilateral location, presence of “mille-feuille sign”, so-called Seidman criteria, as well as the diffusion weighted imaging and dynamic contrast enhancement of each lesion, were evaluated. Patients were allocated into two groups; the first group contained patients with mucinous ovarian cancer, and the second group contained patients with metastatic ovarian tumors. Results: A total of 35 patients were enrolled into the study. Median age was 49 in the first group and 59 in the second group of patients (p = 0.04). In the first group, all patients (100%) had unilateral lesions, and in the second group, 94% had bilateral tumors (p < 0.000001). In the first group, a tumor size equal or greater than 10 cm was present in 80% of patients, and the same was true for 21% of patients in the second group. The mille-feuille sign was present in 30% of patients from the first group and in 64% of patients from the second group. In the first group of patients, TTP was 410 and Perf.Max Enhancement was 141; in the second group, they were, respectively, 154 and 167 (p = 0.0001 and p = 0.5). Median ADC values in the first group were significantly higher in the first group than in the second group (p < 0.01). Conclusions: Significant differences in TTP and ADC values as well as in Seidman criteria enable reliable differentiation between the analyzed groups of tumors.
The Immunomodulatory Mechanisms of BTK Inhibition in CLL and Beyond
Authors: Jiang Qu , Peng Yayi , Herling Carmen Diana , Herling Marco
Published: October 2024

Bruton’s tyrosine kinase (BTK), a cytoplasmic tyrosine kinase, plays a pivotal role in B cell biology and function. As an essential component of the B cell receptor (BCR) signaling pathway, BTK is expressed not only in B cells but also in myeloid cells, including monocytes/macrophages, dendritic cells, neutrophils, and mast cells. BTK inhibitors (BTKis) have revolutionized the treatment of chronic lymphocytic leukemia (CLL) and other B cell malignancies. Besides their well-characterized role in inhibiting BCR signaling, BTKis also exert significant immunological influences outside the tumor cell that extend their therapeutic potential and impact on the immune system in different ways. This work elucidates the immunomodulatory mechanisms associated with BTK inhibition, focusing on CLL and other clinical contexts. We discuss how BTK inhibition affects various immune cells, including B cells, T cells, and macrophages. The effects of BTKis on the profiles of cytokines, also fundamental parts of the tumor microenvironment (TME), are summarized here as well. This review also appraises the implications of these immunomodulatory actions in the management of autoimmune diseases and infections. Summarizing the dual role of BTK inhibition in modulating malignant lymphocyte and immune cell functions, this paper highlights the broader potential clinical use of compounds targeting BTK.
3D-Q-FISH/Telomere/TRF2 Nanotechnology Identifies a Progressively Disturbed Telomere/Shelterin/Lamin AC Complex as the Common Pathogenic, Molecular/Spatial Denominator of Classical Hodgkin Lymphoma
Authors: Knecht Hans , Petrogiannis-Haliotis Tina , Louis Sherif , Mai Sabine
Published: October 2024

The bi- or multinucleated Reed–Sternberg cell (RS) is the diagnostic cornerstone of Epstein–Barr Virus (EBV)-positive and EBV-negative classical Hodgkin lymphoma (cHL). cHL is a germinal center (GC)-derived B-cell disease. Hodgkin cells (H) are the mononuclear precursors of RS. An experimental model has to fulfill three conditions to qualify as common pathogenic denominator: (i) to be of GC-derived B-cell origin, (ii) to be EBV-negative to avoid EBV latency III expression and (iii) to support permanent EBV-encoded oncogenic latent membrane protein (LMP1) expression upon induction. These conditions are unified in the EBV-, diffuse large B-Cell lymphoma (DLBCL) cell line BJAB-tTA-LMP1. 3D reconstructive nanotechnology revealed spatial, quantitative and qualitative disturbance of telomere/shelterin interactions in mononuclear H-like cells, with further progression during transition to RS-like cells, including progressive complexity of the karyotype with every mitotic cycle, due to BBF (breakage/bridge/fusion) events. The findings of this model were confirmed in diagnostic patient samples and correlate with clinical outcomes. Moreover, in vitro, significant disturbance of the lamin AC/telomere interaction progressively occurred. In summary, our research over the past three decades identified cHL as the first lymphoid malignancy driven by a disturbed telomere/shelterin/lamin AC interaction, generating the diagnostic RS. Our findings may act as trailblazer for tailored therapies in refractory cHL.
The Otoacoustic Emissions in the Universal Neonatal Hearing Screening: An Update on the European Data (2004 to 2024)
Authors: Hatzopoulos Stavros , Cardinali Ludovica , Skarżyński Piotr Henryk , Zimatore Giovanna
Published: October 2024

Background: The reported data on European universal neonatal hearing screening (UNHS) practices tend to be scarce, despite the fact that the European Union project, EUScreen, collected unofficial data from 38 collaborating European institutions. The objectives of this systematic review were as follows: (a) to identify the most recent (in a 20-year span) literature information about UNHS programs in Europe and (b) to provide data on the procedures used to assess the population, the intervention policies, and on the estimated prevalence of congenital hearing loss with emphasis on the bilateral hearing loss cases. Methods: Queries were conducted via the Pubmed, Scopus and Google Scholar databases for the time period of 2004–2024. The Mesh terms used were “OAE”, “Universal Neonatal Hearing Screening”, “congenital hearing loss” and “well babies”. Only research articles and review papers of European origin were considered good candidates. The standard English language filter was not used, in order to identify information from non-English-speaking scientific communities and groups. Results: Very few data and reports were identified in the literature search. Eleven manuscripts were identified corresponding to eight UNHS programs. Except in Poland, most of the data refer to regional and not national programs. The screening coverage estimates of all programs exceed 90%; infants were mostly assessed by a three-stage protocol (TEOAE + TEOAE + AABR), followed by a clinical ABR test. The average prevalence (i.e., from well babies AND NICU infants) of bilateral hearing loss ranged from 0.5 to 20.94 per 1000 (Zurich sample). Infants presenting unilateral or bilateral hearing losses were first rehabilitated by hearing aids and consequently (>15 mo) by cochlear implants. Conclusions: Even though UNHS programs are well-established clinical practices in the European States, the amount of information in the literature about these programs is surprising low. The existing data in the timespan 2004–2024 corroborate the international UNHS data in terms of coverage and bilateral hearing loss prevalence, but there is a strong need to supplement the existing information with the latest developments, especially in the area of hearing loss rehabilitation.
Next-Generation Block Ciphers: Achieving Superior Memory Efficiency and Cryptographic Robustness for IoT Devices
Authors: Aziz Saadia , Shoukat Ijaz Ali , Iftikhar Mohsin , Murtaza Mohsin , Alenezi Abdulmajeed M. , Lee Cheng-Chi , Taj Imran
Published: October 2024

Traditional cryptographic methods often need complex designs that require substantial memory and battery power, rendering them unsuitable for small handheld devices. As the prevalence of these devices continues to rise, there is a pressing need to develop smart, memory-efficient cryptographic protocols that provide both high speed and robust security. Current solutions, primarily dependent on dynamic permutations, fall short in terms of encryption and decryption speeds, the cryptographic strength, and the memory efficiency. Consequently, the evolution of lightweight cryptographic algorithms incorporating randomised substitution properties is imperative to meet the stringent security demands of handheld devices effectively. In this paper, we present an advanced design of lightweight block ciphers that enhances traditional dynamic permutations with innovative randomised substitutions. This design utilises straightforward randomized encryption methods such as XOR, nibble swap, count ones, and left shift. The cryptographic robustness of our proposed block cipher has been rigorously tested through several standardised statistical tests, as recommended by the National Institute of Standards and Technology (NIST). These evaluations confirm that our algorithm maintains strong cryptographic properties with randomised substitutions and outperforms existing models in several key aspects. Moreover, comparative assessments reveal that our algorithm achieves a throughput of 853.31 Kbps while consuming only 1510 bytes of memory and demonstrating over 60% avalanche properties, significantly outperforming other solutions in terms of CPU utilisation and memory consumption. These results underscore the efficacy of our approach in fulfilling the advanced security requirements of modern handheld devices.
Thirty Years of Research on Ecosystem Services: The Socio-Economic Role of Forest Visits and Foraging in Enhancing Human Well-Being
Authors: Riedl Marcel , Němec Martin , Jarský Vilém
Published: October 2024

This paper examines the socio-economic significance of forest visits and the collection of forest berries and mushrooms (FBMs) in the Czech Republic, emphasising their role in enhancing human well-being and contributing to regional economies. Over a 30-year period, data were collected on the quantities and economic values of FBMs, alongside the intensity of forest visits by the Czech population. This study incorporates a detailed analysis of time series data on FBM collection, exploring trends and fluctuations in the harvested quantities and their economic value. A Lorenz curve analysis reveals significant disparities in the distribution of economic benefits, with a small segment of the population accounting for the majority of the FBM-derived value. Additionally, the research investigates the impact of forest visitation on well-being at the regional level, highlighting the relationship between forest access, visitation intensity, and public health benefits. This study also examines visitors’ expectations, motivations, and perceptions regarding an ideal forest for visitation, providing recommendations for effective marketing strategies. Furthermore, the study explores the contribution of FBMs to net income across different regions, demonstrating substantial regional variation in their economic importance. Notably, the analysis shows that the value of FBMs represents approximately 37% of the net income generated by traditional forestry activities, underscoring its significant economic potential. The findings emphasise the potential of territorial marketing strategies to enhance well-being, particularly in economically disadvantaged regions, and advocate for sustainable forest management practices to protect these valuable resources and ensure equitable access to the benefits provided by forest ecosystems.