bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between coffee-related factors and cortical and hippocampal structure: a triangulation of evidence approach and Mendelian randomization research
Authors: Luo Zining , Xiong Lijun , Xu Xinyu , Sun Meng , Mu Yingfei , Chen Hongjie , Liu Zhenglong , Luo Zhiyong , Wang Jianli , Liu Ying
Published: May 2024

Objective

Existing studies have reported sustained changes in the cortical structure of rats due to coffee-related factors, which are speculated to occur in the human body. However, there is a lack of research on this topic. Additionally, previous observational studies have found the impact of diseases on cortical structure and the potential therapeutic effects of coffee on these diseases. Our aim was to study the causal effects of coffee-related factors on the human brain using SNPs (single nucleotide polymorphisms). We will connect these discovered causal effects to the impact of diseases on the brain. Through triangulating evidence, we will reveal the potential active areas of coffee in preventing diseases.

Methods

We utilized GWAS data from multiple cohorts and their databases, selecting instrumental variables for genetic prediction of coffee intake and plasma levels of caffeine and its direct metabolites. We applied these instrumental variables to individual data on cortical thickness and surface area, as well as hippocampal volume, from the ENIGMA and CHARGE consortium for Mendelian randomization analysis (MR). Triangular evidence was obtained by integrating existing evidence through a specified retrieval strategy, calculating the overlap between coffee's effects on brain regions and disease-related brain regions to identify potential regions of action.

Results

The MR analysis yielded 93 positive results for 9 exposures, among which theobromine, a metabolite in the caffeine pathway, was found to be associated with increased hippocampal volume. For cortical structure, theobromine in the caffeine pathway was associated with a decrease in total surface area, while theobromine and caffeine in the pathway were associated with an increase in total thickness. The overlap rate of triangular evidence showed no difference in both overall and subgroup analyses, indicating a high overlap between the effects of coffee on brain regions and disease.

Conclusions

From predicted outcomes from causal effects, coffee intake-related factors may have lasting effects on cortical structure. Additionally, theobromine and theophylline have the greatest impact on certain brain gyri, rather than caffeine. Triangulation evidence indicates that disease and coffee intake-related factors act on the same cortical regions, suggesting the presence of potential shared or antagonistic pathways.
Current status and research progress of minimally invasive treatment of glioma
Authors: Wu Hao , Zhou Feng , Gao Wenwen , Chen Peng , Wei Yao , Wang Fenglu , Zhao Haikang
Published: May 2024

Glioma has a high malignant degree and poor prognosis, which seriously affects the prognosis of patients. Traditional treatment methods mainly include craniotomy tumor resection, postoperative radiotherapy and chemotherapy. Although above methods have achieved remarkable curative effect, they still have certain limitations and adverse reactions. With the introduction of the concept of minimally invasive surgery and its clinical application as well as the development and progress of imaging technology, minimally invasive treatment of glioma has become a research hotspot in the field of neuromedicine, including photothermal treatment, photodynamic therapy, laser-induced thermal theraphy and TT-Fields of tumor. These therapeutic methods possess the advantages of precision, minimally invasive, quick recovery and significant curative effect, and have been widely used in clinical practice. The purpose of this review is to introduce the progress of minimally invasive treatment of glioma in recent years and the achievements and prospects for the future.
Mechanisms and management of CAR T toxicity
Authors: Ferreri Christopher J. , Bhutani Manisha
Published: May 2024

Chimeric antigen receptor (CAR) T cell therapies have dramatically improved treatment outcomes for patients with relapsed or refractory B-cell acute lymphoblastic leukemia, large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and multiple myeloma. Despite unprecedented efficacy, treatment with CAR T cell therapies can cause a multitude of adverse effects which require monitoring and management at specialized centers and contribute to morbidity and non-relapse mortality. Such toxicities include cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, neurotoxicity distinct from ICANS, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome, and immune effector cell-associated hematotoxicity that can lead to prolonged cytopenias and infectious complications. This review will discuss the current understanding of the underlying pathophysiologic mechanisms and provide guidelines for the grading and management of such toxicities.
Interaction between intestinal flora and gastric cancer in tumor microenvironment
Authors: Yang Mingjin
Published: May 2024

Gastric Cancer (GC) is a prevalent malignancy globally and is the third leading cause of cancer-related deaths. Recent researches focused on the correlation between intestinal flora and GC. Studies indicate that bacteria can influence the development of gastrointestinal tumors by releasing bacterial extracellular vesicles (BEVs). The Tumor microenvironment (TME) plays an important role in tumor survival, with the interaction between intestinal flora, BEVs, and TME directly impacting tumor progression. Moreover, recent studies have demonstrated that intestinal microflora and BEVs can modify TME to enhance the effectiveness of antitumor drugs. This review article provides an overview and comparison of the biological targets through which the intestinal microbiome regulates TME, laying the groundwork for potential applications in tumor diagnosis, treatment, and prognosis.
The role of living donor liver transplantation in treating intrahepatic cholangiocarcinoma
Authors: Andraus Wellington , Ochoa Gabriela , de Martino Rodrigo Bronze , Pinheiro Rafael Soares Nunes , Santos Vinicius Rocha , Lopes Liliana Ducatti , Arantes Júnior Rubens Macedo , Waisberg Daniel Reis , Santana Alexandre Chagas , Tustumi Francisco , D’Albuquerque Luiz Augusto Carneiro
Published: May 2024

Introduction

Intrahepatic cholangiocarcinoma (iCC) is the liver’s second most common neoplasm. Until now, surgery is the only curative option, but only 35% of the cases are considered resectable at the diagnosis, with a post-resection survival of around 30%. Advancements in surgical techniques and perioperative care related to liver transplantation (LT) have facilitated the expansion of indications for hepatic neoplasms.

Method

This study is a comprehensive review of the global experience in living donor LT (LDLT) for treating iCC and describes our first case of LDLT for an unresectable iCC.

Results

While exploring LT for intrahepatic cholangiocarcinoma dates to the 1990s, the initial outcomes were discouraging, marked by poor survival and high recurrence rates. Nevertheless, contemporary perspectives underscore a reinvigorated emphasis on extending the frontiers of LT indications within the context of the “oncologic era.” The insights gleaned from examining explants, wherein incidental iCC was categorized as hepatocellular carcinoma in the preoperative period, have demonstrated comparable survival rates to small hepatocellular carcinoma. These findings substantiate the potential viability of LT as a curative alternative for iCC. Another investigated scenario pertains to “unresectable tumors with favorable biological behavior,” LT presents a theoretical advantage by providing free margins without the concern of a small future liver remnant. The constraint of organ shortage persists, particularly in nations with low donation rates. LDLT emerges as a viable and secure alternative for treating iCC.

Conclusion

LDLT is an excellent option for augmenting the graft pool, particularly in carefully selected patients.
The role of inflammation in central serous chorioretinopathy: From mechanisms to therapeutic prospects
Authors: Shen Xiao , Kong Fanhua , Wen Jing , Wang Xiao , Huang Chunlian
Published: May 2024

Central serous chorioretinopathy (CSC) is a leading cause of permanent vision loss, ranking fourth among macular diseases, trailing only age-related macular degeneration, diabetic retinopathy, and retinal vein obstruction. While mounting evidence implicates inflammation as a pivotal factor in the onset and advancement of CSC, the specific pathophysiological process and molecular mechanisms underlying inflammation remain incompletely understood. A complex network of cytokines, chemokines, and adhesion molecules interplay to trigger inflammatory and pathological cascades, highlighting the need for a comprehensive comprehension of the inflammation-related mechanisms behind CSC progression. In this piece, we examine the existing comprehension of CSC’s pathology and pathogenesis. Additionally, we present an overview of the mechanisms underlying the onset and progression of CSC inflammation, followed by a thorough analysis and discussion of the potential of targeted inflammatory intervention for both preventing and treating CSC.
Nimbidiol protects from renal injury by alleviating redox imbalance in diabetic mice
Authors: Juin Subir Kumar , Pushpakumar Sathnur , Sen Utpal
Published: May 2024

Introduction

Chronic hyperglycemia-induced oxidative stress plays a crucial role in the development of diabetic nephropathy (DN). Moreover, adverse extracellular matrix (ECM) accumulation elevates renal resistive index leading to progressive worsening of the pathology in DN. Nimbidiol is an alpha-glucosidase inhibitor, isolated from the medicinal plant, ‘neem’ (Azadirachta indica) and reported as a promising anti-diabetic compound. Previously, a myriad of studies demonstrated an anti-oxidative property of a broad-spectrum neem-extracts in various diseases including diabetes. Our recent study has shown that Nimbidiol protects diabetic mice from fibrotic renal dysfunction in part by mitigating adverse ECM accumulation. However, the precise mechanism remains poorly understood.

Methods

The present study aimed to investigate whether Nimbidiol ameliorates renal injury by reducing oxidative stress in type-1 diabetes. To test the hypothesis, wild-type (C57BL/6J) and diabetic Akita (C57BL/6‐Ins2Akita/J) mice aged 10–14 weeks were used to treat with saline or Nimbidiol (400 μg kg−1 day−1) for 8 weeks.

Results

Diabetic mice showed elevated blood pressure, increased renal resistive index, and decreased renal vasculature compared to wild-type control. In diabetic kidney, reactive oxygen species and the expression levels of 4HNE, p22phox, Nox4, and ROMO1 were increased while GSH: GSSG, and the expression levels of SOD-1, SOD-2, and catalase were decreased. Further, eNOS, ACE2, Sirt1 and IL-10 were found to be downregulated while iNOS and IL-17 were upregulated in diabetic kidney. The changes were accompanied by elevated expression of the renal injury markers viz., lipocalin-2 and KIM-1 in diabetic kidney. Moreover, an upregulation of p-NF-κB and a downregulation of IkBα were observed in diabetic kidney compared to the control. Nimbidiol ameliorated these pathological changes in diabetic mice.

Conclusion

Altogether, the data of our study suggest that oxidative stress largely contributes to the diabetic renal injury, and Nimbidiol mitigates redox imbalance and thereby protects kidney in part by inhibiting NF-κB signaling pathway in type-1 diabetes.
Meta-analysis of the effects of CYP3A5*3 gene polymorphisms on tacrolimus blood concentration and effectiveness in Chinese patients with membranous nephropathy
Authors: Dai Xiaona , Yuan Fang , Chai Lan
Published: May 2024

Objective

The study aimed to systematically evaluate the relationship between CYP3A5*3 gene polymorphisms and the blood concentration and effectiveness of tacrolimus (TAC) in patients with membranous nephropathy (MN).

Methods

PubMed, Cochrane Library, Embase, Web of Science, China Biomedical, China National Knowledge Infrastructure, Wanfang, Vipshop, ReadShow, Clinical Trials Registry, and other databases were searched. Studies on the relationship between CYP3A5*3 gene polymorphism and TAC blood concentration in MN patients were collected, and meta-analysis was performed using Stata 16 software.

Results

A total of eight publications were included in the study, including 498 MN patients. CYP3A5*3 gene polymorphisms are associated with tacrolimus blood levels in patients with MN. The results of the relationship between CYP3A5*3 genotype polymorphisms and tacrolimus blood trough concentrations of the AA + AG genotype were lower than those of the GG genotype at ≤1 month [WMD = −2.08, 95% CI (−2.57, −1.59), p < 0.001] and 1–6 months [WMD = −0.63, 95% CI (−0.98, −0.27), p < 0.001]; however, they were not statistically significant at ≥6 months (p = 0.211). Furthermore, the subgroup analysis revealed that the dose-adjusted concentration of tacrolimus (C0/D) of the AA + AG genotype was lower than that of the GG genotype at ≤1 month [SMD = −1.93, 95% CI (−2.79, −1.08), p < 0.001], 1–6 months [SMD = −2.25, 95% CI (−2.71, −1.79), p < 0.001], and ≥6 months [SMD = −2.36, 95% CI (−2.86, −1.86), p < 0.001]. In addition, there was no statistically significant difference in effectiveness between the two groups at 3, 6, and 12 months of TAC administration (p > 0.05).

Conclusion

Serum TAC concentrations in MN patients were correlated with CYP3A5*3 genotype polymorphisms. Detection of the CYP3A5*3 genotype before the administration of TAC may provide some clinical value for optimizing the treatment of MN patients.

Systematic Review Registration:

https://inplasy.com/, identifier [INPLASY202430083].
Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study
Authors: Chen Siyuan , Li Tao , Yang Wenyu , Wang Ting , Qin Yuhui , Du Zhijuan , Li Yanan , Cui Pengfei , Hu Yi , Liu Zhefeng
Published: May 2024

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.
TRPC absence induces pro-inflammatory macrophage polarization to promote obesity and exacerbate colorectal cancer
Authors: Lin Yanting , Gao Rui , Jing Dongquan , Liu Yiming , Da Huijuan , Birnbaumer Lutz , Yang Yong , Gao Xinghua , Gao Zhenhua , Cao Qiuhua
Published: May 2024

During the past half-century, although numerous interventions for obesity have arisen, the condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wild-type counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the well-established connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention.
Comparative study of urea-15N fate in pure bamboo and bamboo-broadleaf mixed forests
Authors: Wu Yiyuan , Dong Wenyuan , Zhong Huan , Duan Jixia , Li Weidong , Pu Chan , Li Xin , Xie Zexuan
Published: May 2024

Objectives

Bamboo is a globally significant plant with ecological, environmental, and economic bene-fits. Choosing suitable native tree species for mixed planting in bamboo forests is an effective measure for achieving both ecological and economic benefits of bamboo forests. However, little is currently known about the impact of bamboo forests on nitrogen cycling and utilization efficiency after mixing with other tree species. Therefore, our study aims to compare the nitrogen cycling in pure bamboo forests with that in mixed forests.

Methods

Through field experiments, we investigated pure Qiongzhuea tumidinoda forests and Q. tumidinoda-Phellodendron chinense mixed forests, and utilized 15N tracing technology to explore the fertilization effects and fate of urea-15N in different forest stands.

Results

The results demonstrated the following: 1) in both forest stands, bamboo culms account for the highest biomass percentage (42.99%-51.86%), while the leaves exhibited the highest nitrogen concentration and total nitrogen uptake (39.25%-44.52%/29.51%-33.21%, respectively) Additionally, the average nitrogen uptake rate of one-year-old bamboo is higher (0.25 mg kg-1 a-1) compared to other age groups. 2) the urea-15N absorption in mixed forests (1066.51–1141.61 g ha-1, including 949.65–1000.07 g ha-1 for bamboo and 116.86–141.54 g ha-1 for trees) was significantly higher than that in pure forests (663.93–727.62 g ha-1, P<0.05). Additionally, the 15N recovery efficiency of culms, branches, leaves, stumps, and stump roots in mixed forests was significantly higher than that in pure forests, with increases of 43.14%, 69.09%, 36.84%, 51.63%, 69.18%, 34.60%, and 26.89%, respectively. 3) the recovery efficiency of urea-15N in mixed forests (45.81%, comprising 40.43% for bamboo and 5.38% for trees) and the residual urea-15N recovery rate in the 0–60 cm soil layer (23.46%) are significantly higher compared to those in pure forests (28.61%/18.89%). This could be attributed to the nitrogen losses in mixed forests (30.73%, including losses from ammonia volatilization, runoff, leaching, and nitrification-denitrification) being significantly lower than those in pure forests (52.50%).

Conclusion

These findings suggest that compared to pure bamboo forests, bamboo in mixed forests exhibits higher nitrogen recovery efficiency, particularly with one-year-old bamboo playing a crucial role.
Essential role of ABA signaling and related transcription factors in phenolic acid and lignin synthesis during muskmelon wound healing
Authors: Wang Qihui , Liu Ning , Yang Ruirui , Zhang Xuejiao , Wang Ying , Li Yongcai , Prusky Dov , Bi Yang , Han Ye
Published: May 2024

Abscisic acid (ABA) is a key phytohormone involved in wound healing in fruits and vegetables, while fluridone (FLD) is its synthetic inhibitor. However, it is unknown whether ABA signaling and downstream transcription factors are involved in the synthesis of phenolic acids and lignin monomers in muskmelon wounds, and the underlying mechanisms. In our study, exogenous ABA promoted endogenous ABA synthesis by increasing the levels of β-carotenoid and zeaxanthin, activating 9-cis-epoxycarotenoid dioxygenase (NCED) and zeaxanthin epoxidase (ZEP), facilitated ABA signaling by increasing the expression levels of protein phosphatases type 2C (CmPP2C) and ABA-responsive element binding factors (CmABF), upregulated the expression levels of CmMYB1 and CmWRKY1, and ABA induced phenylpropanoid metabolism by activating phenylalanine ammonia-lyase (PAL), 4-coenzyme A ligase (4CL), and cinnamyl alcohol dehydrogenase (CAD), which further increased the synthesis of phenolic acids and lignin monomers in muskmelon wounds during healing. Taken together, exogenous ABA induced phenylpropanoid metabolism and increased the synthesis of phenolic acid and lignin monomer in muskmelon wounds during healing, and may be involved in endogenous ABA synthesis and signaling and related transcription factors.
The inverted-U model of employee happiness: examining overdose happiness in context of personal characteristics, job-relationship dependency, benign stress, and various theories
Authors: Kalfaoğlu Serap
Published: May 2024

In recent years, the management literature has begun to deal with individual and organizational results after happiness rather than the pursuit of happiness in business life and finally reaching happiness. After the fact that everything in an overdose is harmful, it has become the subject of even more research with paradoxical results that happiness that evokes positive emotions is not as innocent as it seems. In this study, which aims to reveal the harmful effects of overdose of employee happiness, the reasons for the manager’s fear - or anxiety - about the happiness of his employees are interpreted. The Inverted-U Model of Employee Happiness (IUMEH) has been developed and individual work outputs have been evaluated in three areas that (1) support happiness, (2) reflect balanced happiness, and (3) turn negative with an overdose of happiness intoxication. It has been suggested that IUMEH, which is thought to contribute to the literature as it is the first descriptive model to emerge, should be supported by applied studies, and it has been reminded that the curvilinear aspect of the model may include differences in terms of culture, type and characteristics of job, private, public or non-profit enterprises, generations of managers and the level of managers (front-line, middle level and senior level etc.).
Knowledge, attitudes, and practices among patients with anemia towards disease management
Authors: Yao Binlian , Xu Min , Cheng Fang , Peng Min , Mao Xiaopei
Published: May 2024

Objective

This study aimed to assess the knowledge, attitudes and practices among anemia patients toward disease management.

Methods

This web-based cross-sectional study was conducted between September and December 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine). A self-designed questionnaire was developed to collect demographic information of anemia patients, and assess their knowledge, attitudes and practices (KAP) toward disease management.

Results

A total of 396 valid questionnaires were collected. The mean age of the participants was 57.44 ± 16.80 years, and 52.02% were female. The mean knowledge, attitudes, and practices scores were 11.47 ± 1.73 (possible range: 0–14), 27.32 ± 2.96 (possible range: 7–35), and 40.49 ± 6.06 (possible range: 10–50), respectively. Multivariate analysis showed that bachelor’s degree or above was independently associated with sufficient knowledge (OR = 2.372, 95%CI: 1.160–4.853, p = 0.018). Knowledge (OR = 1.350, 95%CI: 1.166–1.563, p < 0.001) and hemoglobin within 60-90 g/L (OR = 1.782, 95%CI: 1.090–2.912, p = 0.021) were independently associated with positive attitudes. Moreover, attitudes (OR = 1.618, 95%CI: 1.454–1.799, p < 0.001) and diagnosis ≥1 year (OR = 1.949, 95%CI: 1.171–3.243, p = 0.010) were independently associated with proactive practices. The path analysis demonstrated that knowledge was directly and positively correlated with attitudes (β = 0.484, 95% CI: 0.363–0.647, p = 0.008), and attitudes was directly and positively correlated with practices (β = 1.195, 95% CI: 1.062–1.332, p = 0.007). Moreover, knowledge was indirectly and positively correlated with practice (β = 0.579, 95% CI: 0.434–0.805, p = 0.004).

Conclusion

Anemia patients have sufficient knowledge, negative attitudes, but proactive practices toward the toward disease management Comprehensive training programs are needed to improve anemia patients practices in this area.
Digital competence using the example of executives in residential care facilities in Germany—a comparison
Authors: Liebl Stefanie , Tischendorf Tim , Hummel Michel , Günther Lydia , Schaal Tom
Published: May 2024

Background

Change and progress through digitalisation is also becoming increasingly important in the field of professional care and the associated increasing demands on the skills of nursing staff. The European Union considers digital skills to be one of the eight key competences for lifelong learning. At present, few reliable statements can be made about the status of digital skills in professional nursing care in Germany. The aim of this study was to map the current status of digital competences of executives in full inpatient care facilities in Germany and to identify possible differences to reference values of academics.

Methodology

This survey is based on a Germany-wide cross-sectional survey in full inpatient care facilities (N = 8,727). The survey instrument Digital Competences Framework (DigComp 2.2) according to the European Union's reference framework was used as the basis for recording the digital competence characteristics. The statistical analysis was descriptive and inferential (t-test, two-sided, p < 0.05).

Results

Out of 15 items across five dimensions, significant differences for nine items can be determined. The competence levels of the participating managers from the full inpatient care facilities were lower compared to the reference sample.

Discussion

In order to be able to counter the skills discrepancy shown by the study in the future, it is of central importance to deepen knowledge and skills in the area of digitalisation in the care context.
Realistic 3D human saccades generated by a 6-DOF biomimetic robotic eye under optimal control
Authors: Van Opstal A. John , Javanmard Alitappeh Reza , John Akhil , Bernardino Alexandre
Published: May 2024

We recently developed a biomimetic robotic eye with six independent tendons, each controlled by their own rotatory motor, and with insertions on the eye ball that faithfully mimic the biomechanics of the human eye. We constructed an accurate physical computational model of this system, and learned to control its nonlinear dynamics by optimising a cost that penalised saccade inaccuracy, movement duration, and total energy expenditure of the motors. To speed up the calculations, the physical simulator was approximated by a recurrent neural network (NARX). We showed that the system can produce realistic eye movements that closely resemble human saccades in all directions: their nonlinear main-sequence dynamics (amplitude-peak eye velocity and duration relationships), cross-coupling of the horizontal and vertical movement components leading to approximately straight saccade trajectories, and the 3D kinematics that restrict 3D eye orientations to a plane (Listing’s law). Interestingly, the control algorithm had organised the motors into appropriate agonist-antagonist muscle pairs, and the motor signals for the eye resembled the well-known pulse-step characteristics that have been reported for monkey motoneuronal activity. We here fully analyse the eye-movement properties produced by the computational model across the entire oculomotor range and the underlying control signals. We argue that our system may shed new light on the neural control signals and their couplings within the final neural pathways of the primate oculomotor system, and that an optimal control principle may account for a wide variety of oculomotor behaviours. The generated data are publicly available at https://data.ru.nl/collections/di/dcn/DSC_626870_0003_600.
Controlling the fold: proprioceptive feedback in a soft origami robot
Authors: Hanson Nathaniel , Mensah Immanuel Ampomah , Roberts Sonia F. , Healey Jessica , Wu Celina , Dorsey Kristen L.
Published: May 2024

We demonstrate proprioceptive feedback control of a one degree of freedom soft, pneumatically actuated origami robot and an assembly of two robots into a two degree of freedom system. The base unit of the robot is a 41 mm long, 3-D printed Kresling-inspired structure with six sets of sidewall folds and one degree of freedom. Pneumatic actuation, provided by negative fluidic pressure, causes the robot to contract. Capacitive sensors patterned onto the robot provide position estimation and serve as input to a feedback controller. Using a finite element approach, the electrode shapes are optimized for sensitivity at larger (more obtuse) fold angles to improve control across the actuation range. We demonstrate stable position control through discrete-time proportional-integral-derivative (PID) control on a single unit Kresling robot via a series of static set points to 17 mm, dynamic set point stepping, and sinusoidal signal following, with error under 3 mm up to 10 mm contraction. We also demonstrate a two-unit Kresling robot with two degree of freedom extension and rotation control, which has error of 1.7 mm and 6.1°. This work contributes optimized capacitive electrode design and the demonstration of closed-loop feedback position control without visual tracking as an input. This approach to capacitance sensing and modeling constitutes a major step towards proprioceptive state estimation and feedback control in soft origami robotics.
Rett syndrome: a review of clinical manifestations and therapeutic approaches
Authors: Bricker Katelyn , Vaughn Bradley V.
Published: May 2024

Rett syndrome (RTT) is a severe X-linked dominant neurodevelopmental disorder predominantly affecting females and over 90% of these patients mutations linked to the methyl-CpG-binding protein 2 (MeCP2) gene. Although the syndrome is well noted for the classic repetitive hand motion with decline in speech, patients may have a wide range of cognitive and motor impairments. Typical comorbidities in RTT are characterized by poor growth, seizures, disrupted sleep, hyperventilation, breath holding spells, feeding difficulties, scoliosis, and behavioral issues. This paper aims to provide a brief overview of RTT, focusing on the clinical features of sleep and epilepsy, effects on childhood development, and available emerging treatment options. Sleep disturbances, epilepsy, and developmental regression can have profound effects on the quality of life in affected individuals. Current management strategies focus on a multidisciplinary approach to address symptoms and enhance overall wellbeing of individuals with RTT.
Rice straw incorporation and Azolla application improves agronomic nitrogen-use-efficiency and rice grain yields in paddy fields
Authors: Marzouk Said H. , Semoka Johnson M. , Amuri Nyambilila A. , Tindwa Hamisi J.
Published: May 2024

In paddy soils, excessive application of N fertilizer often results in substantial N losses due to low N utilization efficiency. However, this condition can be mitigated by enhancing soil organic carbon content. Two-year field experiment was carried out at Mkula Irrigation Scheme in Kilombero Valley, Tanzania with the aim of investigating the impact of Azolla, rice straw incorporation and reduced levels of nitrogen input from NPKS-containing fertilizers on N use efficiency, soil chemical properties and rice grain yield. Assuming that this technology will introduce a novel perspective to the research, shedding light on alternative and potentially more sustainable methods for nitrogen management in paddy soils, it will be particularly relevant in sub-Saharan Africa, where the annual cost of chemical fertilizers is expected to continue rising. The treatments involved absolute control, half dose N (50 kg N ha-1), full dose N (100 kg N ha-1), and combination of these N doses with PKS, dry Azolla (3.4 t ha-1) and rice straw (6.9 t ha-1) through omission approach. The soil of the experimental area was sandy clay loam in texture, very strongly acid (pH 4.8), normal electrical conductivity (0.06 dS m-1), low amounts of recorded organic carbon (1.35%), total nitrogen (0.33%), 0.68 mg kg−1 available P, exchangeable potassium (0.15 cmol(+) kg−1), calcium (0.19 mg kg−1) and sodium percentage (3.75%), with very low cation exchange capacity (1.6 cmol(+) kg−1). The results showed that combination of Azolla, rice straw +100 kg N ha-1 + 30 kg P ha-1 + 30 kg K ha-1 + 20 kg S ha-1 resulted in higher rice grain yield, nitrogen uptake and agronomic efficiency of N. Azolla, being an effective biofertilizer, significantly contributes to nitrogen fixation and soil enrichment. Interestingly, this study demonstrates that co-application of Azolla, rice straw, and 50% reduced N is effective for achieving high rice yields, minimizing over-dependence on chemical N fertilizer, sustainable agricultural development, and environmental conservation.
Taphonomy of biosignatures in carbonate nodules from the Mars-analog Qaidam Basin: constraints from microscopic, spectroscopic, and geochemical analyses
Authors: Chen Yan , Yin Zongjun , Lin Wei
Published: May 2024

Early diagenetic nodules with low permeable and weather-resistant structures are considered to be favorable for biosignature preservation. Numerous nodular structures forming in neutral-to-alkaline and saline diagenetic fluids were previously identified at Gale Crater on Mars, yet their astrobiological significance remains poorly understood. In the Mars-like western Qaidam Basin, China, there are a multitude of carbonate nodules which can be analogous to those found at Gale Crater on Mars in terms of their formation backgrounds and post-depositional processes. In this study, we combine microscopic, spectroscopic, and geochemical methods to characterize the biosignature preservation of the Qaidam nodules. Carbonaceous materials, including an organic annulus inferred to be a fossil spore or algal filament microfossil, are observed in the Qaidam nodules. The total organic carbon contents of the Qaidam nodules are slightly higher than those of the surrounding fluvio-lacustrine deposits, suggesting that early diagenesis of the Qaidam nodules might facilitate the rapid entombment of biomass within magnesium carbonate or aragonite matrixes before complete degradation. The carbonate matrix showing alternating micritic and sparry layers as well as enrichment of 13C could have a physicochemical origin though the possibilities of biomineralization and organomineralization cannot be entirely ruled out. The I-1350/1,600 distribution of carbonaceous materials implies the existence of carbon precursors of various subcellular components or coexisting organisms in pore waters. Organic carbon isotopes indicate the carbon fixation pathways such as the Calvin cycle or the Wood-Ljungdahl pathway utilized by organisms in pore waters. The findings of this study shed light into the taphonomy and detection of biosignatures in terrestrial playa nodules, with potential applications for biosignature exploration on Mars.
Onset and progression of postmortem histological changes in the central nervous system of RccHan™: WIST rats
Authors: Weber Klaus , Domènech Anna , Kegler Kristel , Kreutzer Robert , Mayoral Francisco José , Okazaki Yoshimasa , Ortega Paula , Polledo Laura , Razinger Tanja , Richard Olivia Kristina , Sanchez Raúl , Warfving Nils , Vallejo Raquel , de Miguel Ricardo
Published: May 2024

Death initiates a cascade of physiological and biochemical alterations in organs and tissues, resulting in microscopic changes that challenge the histopathological evaluation. Moreover, the brain is particularly susceptible to artifacts owing to its unique composition and its location within the cranial vault. The aim of this study was to compile and illustrate the microscopic changes in the central nervous system (CNS) of rats subjected to delayed postmortem fixation. It also scrutinizes the influence of exsanguination and cooling methods on the initiation and progression of these alterations. Twenty-four Wistar Han outbred rats (RccHan™: WIST) were sacrificed and stored either at room temperature (18–22°C) or under refrigeration (2–4°C). Necropsies were conducted at different time points postmortem (i.e., 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h, 36 h, 48 h, 7 days and 14 days). Brain sections underwent simultaneous digital evaluation by 14 pathologists until a consensus was reached on terminology, key findings, and intensity levels. Microscopic observations varied among cell types. Glial cells were similarly affected throughout the CNS and showed pericellular halo, chromatin condensation and nuclear shrinkage. Neurons showed two types of postmortem changes as most of them showed progressive shrinkage, cytoplasmic dissolution and karyorrhexis whereas others acquired a dark-neuron-like appearance. Neuronal changes showed marked differences among neuroanatomical locations. Additional postmortem changes encompassed: granulation and microcavitation in neuropil and white matter; retraction spaces; detachment of ependyma, choroid plexus, and leptomeninges. Severity of findings after 48 h at room temperature was higher than after seven days under refrigeration and similar to or slightly lower than after 14 days under refrigeration. No clear differences were observed related to the sex or weight of the animals or their exsanguination status. This work elucidates the onset and progression of autolytic changes in the brains of Wistar Han rats, offering insights to accurately identify and enhance the histopathological evaluation.
Underweight and Predictors Among Children Aged 6–59 Months in South Ethiopia
Authors: Toma Temesgen Mohammed , Andargie Kassahun Tamene , Alula Rahel Abera , Kebede Bahiru Mulatu , Temesgen Kidus , Guyo Tamirat Gezahegn
Published: May 2024

Objectives

Underweight remains the primary public health concern among under-five-year-old children in Ethiopia, despite numerous government-implemented nutrition-specific and sensitive interventions. Therefore, this study aimed to assess underweight and associated factors among children in South Ethiopia.

Methods

Between March and April 2021, 717 children in the South Ari district who were between the ages of 6 and 59 months participated in a cross-sectional study. To choose a sample of households containing a minimum of one child between the ages of 6 and 59 months, a multi-stage sampling procedure was used. Data were collected by interviewer-administered structured questionnaires from the mothers of the children. To determine the factors associated with being underweight, a binary logistic regression analysis was built. All variables with a p-value <0.25 in the bivariable analysis were entered into a multivariable logistic regression analysis. To assess the strength of the association, an adjusted odds ratio (AOR) with a 95% confidence interval was used. With a p-value below 0.05, statistical significance was declared.

Results

The prevalence of underweight was determined to be 29.7% (95% CI: 26.5%, 33.2%). Child age 6–23 months [adjusted odds ratio (AOR) = 0.28; 95% confidence interval (CI): 0.18, 0.44], food insecurity (AOR = 1.48; 95% CI: 1.04, 2.10), sub-optimal child dietary diversity (AOR = 1.44; 95% CI: 1.01, 2.03), birth interval <24 months (AOR = 2.49; 95% CI: 1.75, 3.54), and common childhood illness (AOR = 2.21; 95% CI: 1.52, 3.21) were associated with being underweight.

Conclusion

Underweight among children is predicted by household food insecurity, suboptimal dietary diversity, and common childhood illnesses, necessitating further efforts to improve food security and manage common illnesses.
A Primer for Utilizing Deep Learning and Abdominal MRI Imaging Features to Monitor Autosomal Dominant Polycystic Kidney Disease Progression
Authors: Zhu Chenglin , He Xinzi , Blumenfeld Jon D. , Hu Zhongxiu , Dev Hreedi , Sattar Usama , Bazojoo Vahid , Sharbatdaran Arman , Aspal Mohit , Romano Dominick , Teichman Kurt , Ng He Hui Yi , Wang Yin , Soto Figueroa Andrea , Weiss Erin , Prince Anna G. , Chevalier James M. , Shimonov Daniil , Moghadam Mina C. , Sabuncu Mert , Prince Martin R.
Published: May 2024

Abdominal imaging of autosomal dominant polycystic kidney disease (ADPKD) has historically focused on detecting complications such as cyst rupture, cyst infection, obstructing renal calculi, and pyelonephritis; discriminating complex cysts from renal cell carcinoma; and identifying sources of abdominal pain. Many imaging features of ADPKD are incompletely evaluated or not deemed to be clinically significant, and because of this, treatment options are limited. However, total kidney volume (TKV) measurement has become important for assessing the risk of disease progression (i.e., Mayo Imaging Classification) and predicting tolvaptan treatment’s efficacy. Deep learning for segmenting the kidneys has improved these measurements’ speed, accuracy, and reproducibility. Deep learning models can also segment other organs and tissues, extracting additional biomarkers to characterize the extent to which extrarenal manifestations complicate ADPKD. In this concept paper, we demonstrate how deep learning may be applied to measure the TKV and how it can be extended to measure additional features of this disease.
Iloperidone and Temozolomide Synergistically Inhibit Growth, Migration and Enhance Apoptosis in Glioblastoma Cells
Authors: Mubeen Sahar , Raza Iffat , Ujjan Badaruddin , Wasim Bushra , Khan Lubna , Naeem Nadia , Enam Syed Ather , Hanif Farina
Published: May 2024

Glioblastoma (GBM) is a fatal astrocytic glioma with poor prognosis and treatment resistance. Repurposing potential FDA-approved drugs like anti-psychotics can address the concerns in a timely and cost-effective manner. Epidemiological studies have shown that patients with schizophrenic using anti-psychotics have a low incidence of GBM. Therefore, we aimed to investigate the therapeutic potential of atypical anti-psychotic Iloperidone (ILO) alone and in combination with Temozolomide (TMZ) against GBM. The study assessed the growth inhibitory effect of ILO, TMZ, and their combination (ILO + TMZ) on U-87MG and T-98G cell lines using an MTT assay. The drug interaction coefficient (CDI) was determined, and doses with synergistic effects were used for subsequent experiments, including migratory, invasion, and TUNEL assays. The expressions of DRD2, β-catenin, Dvl2, Twist, and Slug were assessed by RTq-PCR, whereas the β-catenin protein expression was also determined by immunocytochemistry. ILO (p < 0.05) and TMZ (p < 0.01) significantly inhibited the growth of U-87MG cells at all tested doses. The combination of 60 µM of both drugs showed synergistic activity with CDI < 1. The inhibition of migration and apoptosis was more pronounced in the case of combination treatment (p < 0.001). Inhibition of the invading cells was also found to be significant in ILO- and combination-treated groups (p < 0.001). ILO and combination treatment also significantly downregulated the expression of DRD2, while TMZ upregulated the expression (p < 0.001). The expressions of β-catenin (p < 0.001), Dvl2 (p < 0.001), Twist (p < 0.001), and Slug (p < 0.001) were also significantly downregulated in all treatment groups as compared to the vehicle control. The data suggest that ILO possesses strong growth inhibitory activity, possibly due to its effect on DRD2 and β-catenin expression and has the potential to be repurposed against GBM.
Is There a Connection between Hyperhomocysteinemia and the Cardiometabolic Syndrome?
Authors: Tarcau Bogdan Mihai , Negru Andra , Ghitea Timea Claudia , Marian Eleonora
Published: May 2024

This study investigates the distribution of hyperhomocysteinemia and cardiovascular metabolic syndrome (SM) among participants, shedding light on their prevalence and co-occurrence within the study cohort. Through an analysis of demographic characteristics and health parameters, including age, gender, and body mass index (BMI), alongside nutritional data, correlations between these factors and health risks are explored. Results reveal a notable prevalence of hyperhomocysteinemia, with 45.3% of participants exhibiting this condition. Furthermore, 31.4% of the cohort does not present hyperhomocysteinemia or SM, while 23.3% shows SM without hyperhomocysteinemia. The study underscores gender-specific dietary recommendations due to significant variations in nutrient intake patterns. Additionally, inverse correlations between health risks like obesity, hypertension, and hypercholesterolemia and nutrient requirements highlight the need for tailored dietary interventions. Age-related changes in nutrient needs and the positive correlation between physical activity levels and certain nutrient demands further emphasize the importance of personalized dietary strategies. Variations in nutrient intake by gender, inverse correlations with health risks, and age-related changes underscore the need for tailored dietary strategies. These findings provide valuable insights for healthcare professionals in developing targeted nutritional interventions to mitigate disease risk and promote overall health and well-being.
Enhancing the Efficiency of a Cybersecurity Operations Center Using Biomimetic Algorithms Empowered by Deep Q-Learning
Authors: Olivares Rodrigo , Salinas Omar , Ravelo Camilo , Soto Ricardo , Crawford Broderick
Published: May 2024

In the complex and dynamic landscape of cyber threats, organizations require sophisticated strategies for managing Cybersecurity Operations Centers and deploying Security Information and Event Management systems. Our study enhances these strategies by integrating the precision of well-known biomimetic optimization algorithms—namely Particle Swarm Optimization, the Bat Algorithm, the Gray Wolf Optimizer, and the Orca Predator Algorithm—with the adaptability of Deep Q-Learning, a reinforcement learning technique that leverages deep neural networks to teach algorithms optimal actions through trial and error in complex environments. This hybrid methodology targets the efficient allocation and deployment of network intrusion detection sensors while balancing cost-effectiveness with essential network security imperatives. Comprehensive computational tests show that versions enhanced with Deep Q-Learning significantly outperform their native counterparts, especially in complex infrastructures. These results highlight the efficacy of integrating metaheuristics with reinforcement learning to tackle complex optimization challenges, underscoring Deep Q-Learning’s potential to boost cybersecurity measures in rapidly evolving threat environments.