bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular approaches to deploy singlet oxygen in a Leishmania model as an unassailable biocide for disease mitigation and vector control
Authors: Chang Kwang Poo , Reynolds Joseph M. , Ng Dennis K. P. , Tu Yun-Hung , Fan Chia-Kwung , Shiao Shin-Hong
Published: May 2024

Singlet oxygen (1O2) is a potent biocide potentially deployable for integrated control of tropical diseases and their insect vectors. This very short-lived free radical is highly destructive of cellular molecules when generated intracellularly. Most organisms, including parasites and vectors, are defenseless against 1O2 except for plants, which produce it abundantly during photosynthesis, hence, the acquisition of specific mechanisms for its detoxification. In the presence of O2 under physiological conditions, certain dyes or photosensitizers (PS), e.g., porphyrins and phthalocyanines (PC), are excitable by light to produce biocidal 1O2. Its half-life is in the order of microseconds, necessitating its intracellular generation in order to harness its biocidal activity most effectively. This is achievable by loading cells with PS for excitation with light to produce 1O2in situ. One example to achieve this is the genetic engineering of Leishmania to complement its inherent defects in porphyrin biosynthesis, resulting in cytosolic accumulation of abundant PS in the form of uroporphyrin 1 (URO). Another example is the chemical engineering of PC for hydrophilicity, thereby facilitating the endocytosis of such PS by cells. Leishmania loaded with cytosolic URO and endosomal PC are inactivated by the 1O2 produced via light-activation of these PS in the two different cell compartments. The inactivated Leishmania are nonviable, but have their natural vaccines and adjuvants well-preserved for prophylactic vaccination against experimental leishmaniasis. 1O2-inactivated Leishmania is potentially useful to serve as a platform for the safe and effective delivery of transgenically add-on vaccines against malignant and viral diseases in experimental models. Hydrophilic and cationic PC were also shown experimentally to act as a new type of dim light-activable insecticides, i.e., their mosquito larvicidal activities with <µM LD50 values. Similar results are expected by studying PC in additional laboratory insect models. A significant advantage has long been attributed to this type of insecticide, i.e., their aversion to a selection of genetic variants for resistance. An additional advantage of PC is their excitability to produce insecticidal 1O2 with deep-penetrating red or infrared light invisible to most insects, thereby potentially increasing the range and scope of targetable insect vectors.
Bacterial etiologies, antimicrobial susceptibility pattern and associated factors among patients suspected sterile body site infections at Debre Markos Comprehensive Specialized Hospital, Northwest Ethiopia
Authors: Admas Dires , Demeke Gebreselassie , Adugna Adane , Esmael Ahmed
Published: May 2024

Background

Sterile body locations are usually associated with clinical urgency and life-threatening illnesses, and they are typically contaminated with diverse bacterial etiologies. If the bacteria acquire resistance to antimicrobial drugs, the public health crisis will only worsen. In developing countries, drug-resistant bacteria are common because of poor surveillance, diagnostic capacity, and control measures. Early diagnosis, and assessing the drug resistance and factors associated with infection are important to combat the drug resistance and treatment. This study aimed to assess the bacterial etiologies, antimicrobial susceptibility pattern, and possible associated factors among patients suspected of sterile body sites.

Methods

A hospital-based cross-sectional study was conducted from June 2022 to August 2022 at Debre Markos Comprehensive Specialized Hospital in Amhara regional state, Ethiopia. One hundred seven study participants were selected using consecutive convenient sampling techniques. A structured questionnaire was used to collect socio-demographic and clinical data. Gram stain was done for a preliminary report and inoculated into blood agar, MacConkey agar, and chocolate agar and incubated aerobically and micro aerobically at 37°C for 24 h. Antimicrobial susceptibility testing was done by the modified Kirby Bauer’s disk diffusion method. Data were analyzed using bivariate and multivariate logistic regression was used. A p-value less than 0.05 is considered as statistically significant.

Results

The overall magnitude of sterile body site infection among study participants was 7.5% (14/187). The majority of the isolates were Gram-negative bacteria with the predominant species Enterobacter cloacae accounting for 28.57% (4/14). Among isolates 78.57%(11/14) of them were multidrug-resistant isolates. Being inpatient, co-morbidity, and alcohol consumption were significantly associated with sterile body site infection.

Conclusion

In our study, Gram-negative bacteria were the predominant bacteria that infects sterile body fluid. The prevalence of multi-drug resistance bacteria isolates was significantly high. Therefore, before prescribing an empirical treatment, a medical professional should identify the bacterial etiology of sterile body fluids and the susceptibility of microbes to the drug.
Online groups show how technology supports healthcare needs for patients and families: an illustrative model for COPD facebook groups
Authors: Boyce LeAnn , Prybutok Gayle , Prybutok Victor
Published: May 2024

Introduction:

This study examines how online technologies can support patients and their families address specific medical needs by creating an integrated theoretical framework based on the Health Belief Model, Social Exchange Theory, and Technology Acceptance Model.

Methods:

We obtained a total of 264 responses from an online survey posted in several COPD Facebook groups. After data preprocessing, we were left with 155 responses that met our inclusion criteria. Using the Partial Least Squares-Structural Equation Model (PLS-SEM), we evaluate how individuals in Chronic Obstructive Pulmonary Disease (COPD) Facebook groups seek information.

Results:

This study examines the relationship between demographic variables, psychological attributes (including emotional support and self-worth), perceived disease severity, benefits and barriers, and the perceived utility and ease of internet use in the information-seeking behavior of COPD patients on Facebook.

Discussion:

The findings underscore the importance of ease of internet use and intuitive platform design as a critical determinant that positively affects user engagement and fosters active participation among online participants. These findings offer critical insights into how online communities help patients and families obtain broad support and enhance the adoption and acceptance of emerging healthcare technologies. This also shows the advantages that online platforms offer individuals managing chronic diseases. Given these insights, we urge healthcare providers to recognize the beneficial effects of online health communities on patient well-being and health outcomes. This understanding is essential for healthcare professionals seeking to enhance patient care, aiming to improve the quality of life for individuals with chronic diseases in an increasingly digital landscape.
The role of small RNAs in resistant melon cultivar against Phelipanche aegyptiaca parasitization
Authors: Mao Jian-Cai , Yan Miao , Li Jun-Hua , Yang Jun-Yan , Wang Hao-Jie
Published: May 2024

Bidirectional trans-kingdom RNA silencing, a pivotal factor in plant-pathogen interactions, remains less explored in plant host-parasite dynamics. Here, using small RNA sequencing in melon root systems, we investigated microRNA (miRNA) expression variation in resistant and susceptible cultivars pre-and post-infection by the parasitic plant, broomrape. This approach revealed 979 known miRNAs and 110 novel miRNAs across 110 families. When comparing susceptible (F0) and resistant (R0) melon lines with broomrape infection (F25 and R25), 39 significantly differentially expressed miRNAs were observed in F25 vs. F0, 35 in R25 vs. R0, and 5 in R25 vs. F25. Notably, two miRNAs consistently exhibited differential expression across all comparisons, targeting genes linked to plant disease resistance. This suggests their pivotal role in melon’s defense against broomrape. The target genes of these miRNAs were confirmed via degradome sequencing and validated by qRT-PCR, ensuring reliable sequencing outcomes. GO and KEGG analyses shed light on the molecular functions and pathways of these differential miRNAs. Furthermore, our study unveiled four trans-kingdom miRNAs, forming a foundation for exploring melon’s resistance to broomrape.
Multikinase inhibitors modulate non-constitutive proteasome expression in colorectal cancer cells
Authors: Burov Alexander , Grigorieva Ekaterina , Lebedev Timofey , Vedernikova Valeria , Popenko Vladimir , Astakhova Tatiana , Leonova Olga , Spirin Pavel , Prassolov Vladimir , Karpov Vadim , Morozov Alexey
Published: May 2024

Introduction: Proteasomes are multi-subunit protein complexes responsible for protein degradation in cells. Immunoproteasomes and intermediate proteasomes (together non-constitutive proteasomes) are specific forms of proteasomes frequently associated with immune response, antigen presentation, inflammation and stress. Expression of non-constitutive proteasome subunits has a prognostic value in several types of cancer. Thus, factors that modulate non-constitutive proteasome expression in tumors are of particular interest. Multikinase inhibitors (MKIs) demonstrate promising results in treatment of cancer. At the same time, their immunomodulatory properties and effects on non-constitutive proteasome expression in colorectal cancer cells are poorly investigated.

Methods: Proteasome subunit expression in colorectal cancer was evaluated by bioinformatic analysis of available datasets. Two colorectal cancer cell lines, expressing fluorescent non-constitutive proteasomes were treated with multikinase inhibitors: regorafenib and sorafenib. The proteasome subunit expression was assessed by real-time PCR, Western blotting and flow cytometry. The proteasome activity was studied using proteasome activity-based probe and fluorescent substrates. Intracellular proteasome localization was revealed by confocal microscopy. Reactive oxygen species levels following treatment were determined in cells. Combined effect of proteasome inhibition and treatment with MKIs on viability of cells was estimated.

Results: Expression of non-constitutive proteasomes is increased in BRAF-mutant colorectal tumors. Regorafenib and sorafenib stimulated the activity and synthesis of non-constitutive proteasomes in examined cell lines. MKIs induced oxidative stress and redistribution of proteasomes within cells. Sorafenib stimulated formation of cytoplasmic aggregates, containing proteolyticaly active non-constitutive proteasomes, while regorafenib had no such effect. MKIs caused no synergistic action when were combined with the proteasome inhibitor.

Discussion: Obtained results indicate that MKIs might affect the crosstalk between cancer cells and immune cells via modulation of intracellular proteasome pool. Observed phenomenon should be considered when MKI-based therapy is applied.
Alzheimer’s disease manifests abnormal sphingolipid metabolism
Authors: Uranbileg Baasanjav , Isago Hideaki , Sakai Eri , Kubota Masayuki , Saito Yuko , Kurano Makoto
Published: May 2024

Introduction

Alzheimer’s disease (AD) is associated with disturbed metabolism, prompting investigations into specific metabolic pathways that may contribute to its pathogenesis and pathology. Sphingolipids have garnered attention due to their known physiological impact on various diseases.

Methods

We conducted comprehensive profiling of sphingolipids to understand their possible role in AD. Sphingolipid levels were measured in AD brains, Cerad score B brains, and controls, as well as in induced pluripotent stem (iPS) cells (AD, PS, and control), using liquid chromatography mass spectrometry.

Results

AD brains exhibited higher levels of sphingosine (Sph), total ceramide 1-phosphate (Cer1P), and total ceramide (Cer) compared to control and Cerad-B brains. Deoxy-ceramide (Deoxy-Cer) was elevated in Cerad-B and AD brains compared to controls, with increased sphingomyelin (SM) levels exclusively in Cerad-B brains. Analysis of cell lysates revealed elevated dihydroceramide (dhSph), total Cer1P, and total SM in AD and PS cells versus controls. Multivariate analysis highlighted the relevance of Sph, Cer, Cer1P, and SM in AD pathology. Machine learning identified Sph, Cer, and Cer1P as key contributors to AD.

Discussion

Our findings suggest the potential importance of Sph, Cer1P, Cer, and SM in the context of AD pathology. This underscores the significance of sphingolipid metabolism in understanding and potentially targeting mechanisms underlying AD.
Hybrid knowledge transfer for MARL based on action advising and experience sharing
Authors: Liu Feng , Li Dongqi , Gao Jian
Published: May 2024

Multiagent Reinforcement Learning (MARL) has been well adopted due to its exceptional ability to solve multiagent decision-making problems. To further enhance learning efficiency, knowledge transfer algorithms have been developed, among which experience-sharing-based and action-advising-based transfer strategies share the mainstream. However, it is notable that, although there exist many successful applications of both strategies, they are not flawless. For the long-developed action-advising-based methods (namely KT-AA, short for knowledge transfer based on action advising), their data efficiency and scalability are not satisfactory. As for the newly proposed experience-sharing-based knowledge transfer methods (KT-ES), although the shortcomings of KT-AA have been partially overcome, they are incompetent to correct specific bad decisions in the later learning stage. To leverage the superiority of both KT-AA and KT-ES, this study proposes KT-Hybrid, a hybrid knowledge transfer approach. In the early learning phase, KT-ES methods are employed, expecting better data efficiency from KT-ES to enhance the policy to a basic level as soon as possible. Later, we focus on correcting specific errors made by the basic policy, trying to use KT-AA methods to further improve the performance. Simulations demonstrate that the proposed KT-Hybrid outperforms well-received action-advising- and experience-sharing-based methods.
Learning capabilities to resolve tilt-translation ambiguity in goldfish
Authors: Tadokoro Shin , Shinji Yusuke , Yamanaka Toshimi , Hirata Yutaka
Published: May 2024

Introduction

Spatial orientation refers to the perception of relative location and self-motion in space. The accurate formation of spatial orientation is essential for animals to survive and interact safely with their environment. The formation of spatial orientation involves the integration of sensory inputs from the vestibular, visual, and proprioceptive systems. Vestibular organs function as specialized head motion sensors, providing information regarding angular velocity and linear acceleration via the semicircular canals and otoliths, respectively. However, because forces arising from the linear acceleration (translation) and inclination relative to the gravitational axis (tilt) are equivalent, they are indistinguishable by accelerometers, including otoliths. This is commonly referred to as the tilt - translation ambiguity, which can occasionally lead to the misinterpretation of translation as a tilt. The major theoretical frameworks addressing this issue have proposed that the interpretation of tilt versus translation may be contingent on an animal’s previous experiences of motion. However, empirical confirmation of this hypothesis is lacking.

Methods

In this study, we conducted a behavioral experiment using goldfish to investigate how an animal’s motion experience influences its interpretation of tilt vs. translation. We examined a reflexive eye movement called the vestibulo-ocular reflex (VOR), which compensatory-rotates the eyes in response to head motion and is known to reflect an animal’s three-dimensional head motion estimate.

Results

We demonstrated that the VORs of naïve goldfish do not differentiate between translation and tilt at 0.5 Hz. However, following prolonged visual-translation training, which provided appropriate visual stimulation in conjunction with translational head motion, the VORs were capable of distinguishing between the two types of head motion within 3 h. These results were replicated using the Kalman filter model of spatial orientation, which incorporated the variable variance of process noise corresponding to the accumulated motion experience.

Discussion

Based on these experimental and computational findings, we discuss the neural mechanism underlying the resolution of tilt-translation ambiguity within a context analogous to, yet distinct from, previous cross-axis VOR adaptations.
Transdiagnostic considerations are critical to understanding childhood neurodevelopmental disorders
Authors: Hoza Betsy , Shoulberg Erin K.
Published: May 2024

Growing dissatisfaction with the current categorical diagnostic systems has led to a movement toward transdiagnostic dimensional approaches to assessment of childhood mental health disorders. We argue that a transdiagnostic approach is especially important and appropriate when screening for neurodevelopmental disorders during early childhood. In the early childhood years, symptoms often appear in the form of developmental delays that could portend a variety of different disorders. Early intervention at this point is critical, even though a final endpoint disorder is not yet apparent. Intervening early has the potential to grow the area of weakness, possibly correcting or at least ameliorating these delays. Early intervention requires a multidisciplinary approach integrating efforts across settings and providers that monitor the development of young children. We argue here that young children’s language ability is central to the development of social cognition, and a prerequisite for adequate social functioning. Social deficits are defining features of a subset of neurodevelopmental disorders such as autism spectrum disorder and social (pragmatic) communication disorder. Critically, impairment in social functioning is common in additional neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD), learning disorders, and even motor disorders. For this reason, we argue that, at the earliest sign of a possible neurodevelopmental disorder, children should be screened for language deficits prior to initiating a focused assessment for a specific type of neurodevelopmental disorder such as ADHD. Any detected language deficits should be considered in the design and implementation of the assessment, as well as the ultimate intervention plan.
Same principle, but different computations in representing time and space
Authors: Sima Sepehr , Sanayei Mehdi
Published: May 2024

Time and space are two intertwined contexts that frame our cognition of the world and have shared mechanisms. A well-known theory on this case is “A Theory of Magnitude (ATOM)” which states that the perception of these two domains shares common mechanisms. However, evidence regarding shared computations of time and space is intermixed. To investigate this issue, we asked human subjects to reproduce time and distance intervals with saccadic eye movements in similarly designed tasks. We applied an observer model to both modalities and found underlying differences in the processing of time and space. While time and space computations are both probabilistic, adding priors to space perception minimally improved model performance, as opposed to time perception which was consistently better explained by Bayesian computations. We also showed that while both measurement and motor variability were smaller in distance than time reproduction, only the motor variability was correlated between them, as both tasks used saccadic eye movements for response. Our results suggest that time and space perception abide by the same algorithm but have different computational properties.
The role of small extracellular vesicles and microRNA as their cargo in the spinal cord injury pathophysiology and therapy
Authors: Sintakova Kristyna , Romanyuk Nataliya
Published: May 2024

Spinal cord injury (SCI) is a devastating condition with a complex pathology that affects a significant portion of the population and causes long-term consequences. After primary injury, an inflammatory cascade of secondary injury occurs, followed by neuronal cell death and glial scar formation. Together with the limited regenerative capacity of the central nervous system, these are the main reasons for the poor prognosis after SCI. Despite recent advances, there is still no effective treatment. Promising therapeutic approaches include stem cells transplantation, which has demonstrated neuroprotective and immunomodulatory effects in SCI. This positive effect is thought to be mediated by small extracellular vesicles (sEVs); membrane-bound nanovesicles involved in intercellular communication through transport of functional proteins and RNA molecules. In this review, we summarize the current knowledge about sEVs and microRNA as their cargo as one of the most promising therapeutic approaches for the treatment of SCI. We provide a comprehensive overview of their role in SCI pathophysiology, neuroprotective potential and therapeutic effect.
PCB169 exposure aggravated the development of non-alcoholic fatty liver in high-fat diet-induced male C57BL/6 mice
Authors: Wei Yunli , Zhou Guangxian , Lv Guangzhou , Wei Wan , Shera Lunguelizabeth , Lin Hongying , Chen Jinjun , Kang Danju
Published: May 2024

Polychlorinated biphenyls (PCBs) are lipophilic environmental toxicants. Epidemiological studies have established a link between PCBs and both metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Multiple studies have reported that exposure to both PCB156 and PCB126 among the 12 dioxin-like PCBs leads to the development of NAFLD. However, studies to elucidate whether PCB169 induces the development of NAFLD by constructing in vivo models have not been reported. Therefore, we evaluated the effects of exposure to PCB169 (5 mg/kg-bw) on hepatic lipid metabolism in C57BL/6 mice from control diet and high-fat diet cohorts. The results showed that PCB169 exposure reduced body weight and intraperitoneal fat mass in mice on the control diet, but the liver lipid levels were significantly increased, exacerbating NAFLD in mice on a high-fat diet. Through transcriptomics studies, it was found that PCB169 exposure induced significant up-regulation of Pparγ, Fasn, and Aacs genes involved in hepatic lipogenesis, as well as remarkable up-regulation of Hmgcr, Lss, and Sqle genes involved in cholesterol synthesis. Additionally, there was notable down-regulation of Pparα and Cpt1 genes involved in lipid β-oxidation, leading to abnormal lipid accumulation in the liver. In addition, we found that PCB169 exposure significantly activated the Arachidonic acid metabolism, PPAR signaling pathway, Metabolism of xenobiotics by cytochrome P450, and Retinol metabolism pathways, and so on. Our study suggests that PCB169 can modify gene expression related to lipid metabolism, augument lipid accumulation in the liver, and further contribute to the development of NAFLD, thereby revealing the detrimental effects associated with PCB exposure on animal growth and metabolism.
Comparative analysis of the image quality and diagnostic performance of the zooming technique with diffusion-weighted imaging using different b-values for thyroid papillary carcinomas and benign nodules
Authors: Jiang Liling , Chen Jiao , Tan Yong , Wu Jian , Zhang Junbin , Liu Daihong , Zhang Jiuquan
Published: May 2024

Objective

To compare image quality and diagnostic performance using different b-values for the zooming technique with diffusion-weighted imaging (ZOOMit-DWI) in thyroid nodules

Materials and methods

A total of 51 benign thyroid nodules and 50 thyroid papillary carcinomas were included. ZOOMit-DWI was performed with b-values of 0, 500, 1000, 1500 and 2000 s/mm2. The sharpness was evaluated as subjective index. The signal intensity ratio (SIR), signal-to-noise ratio (SNR) and apparent diffusion coefficient (ADC) were measured as objective indices. Pairwise comparisons were performed among the different b-value groups using the Friedman test. A receiver operating characteristic curve of the ADC value was used to evaluate diagnostic performance. The DeLong test was used to compare diagnostic effectiveness among the different b-value groups

Results

In both the papillary carcinoma group (P = 0.670) and the benign nodule group (P = 0.185), the sharpness of nodules was similar between b-values of 1000 s/mm2and 1500 s/mm2. In the papillary carcinoma group, the SIRnodule was statistically higher in DWI images with a b-value of 1500 s/mm2than in DWI images with b-values of 500 s/mm2(P = 0.004), 1000 s/mm2(P = 0.002), and 2000 s/mm2(P = 0.003). When the b-values were 1500 s/mm2(P = 0.008) and 2000 s/mm2(P = 0.009), the SIRnodule significantly differed between the papillary carcinoma group and the benign nodule group. When b = 500 s/mm2, the ADC had an AUC of 0.888. When b = 1000 s/mm2, the ADC had an AUC of 0.881. When b = 1500 s/mm2, the ADC had an AUC of 0.896. When b = 2000 s/mm2, the ADC had an AUC of 0.871. The DeLong test showed comparable diagnostic effectiveness among the different b-value groups except for between b-values of 2000 s/mm2and 1500 s/mm2, with a b-value of 2000 s/mm2showing lower effectiveness

Conclusion

This study suggests that 1500 s/mm2may be a suitable b-value to differentiate benign and malignant thyroid nodules in ZOOMit-DWI images, which yielded better image quality
MRI radiomics captures early treatment response in patient-derived organoid endometrial cancer mouse models
Authors: Espedal Heidi , Fasmer Kristine E. , Berg Hege F. , Lyngstad Jenny M. , Schilling Tomke , Krakstad Camilla , Haldorsen Ingfrid S.
Published: May 2024

Background

Radiomics can capture microscale information in medical images beyond what is visible to the naked human eye. Using a clinically relevant mouse model for endometrial cancer, the objective of this study was to develop and validate a radiomic signature (RS) predicting response to standard chemotherapy.

Methods

Mice orthotopically implanted with a patient-derived grade 3 endometrioid endometrial cancer organoid model (O-PDX) were allocated to chemotherapy (combined paclitaxel/carboplatin, n=11) or saline/control (n=13). During tumor progression, the mice underwent weekly T2-weighted (T2w) magnetic resonance imaging (MRI). Segmentation of primary tumor volume (vMRI) allowed extraction of radiomic features from whole-volume tumor masks. A radiomic model for predicting treatment response was derived employing least absolute shrinkage and selection operator (LASSO) statistics at endpoint images in the orthotopic O-PDX (RS_O), and subsequently applied on the earlier study timepoints (RS_O at baseline, and week 1-3). For external validation, the radiomic model was tested in a separate T2w-MRI dataset on segmented whole-volume subcutaneous tumors (RS_S) from the same O-PDX model, imaged at three timepoints (baseline, day 3 and day 10/endpoint) after start of chemotherapy (n=8 tumors) or saline/control (n=8 tumors).

Results

The RS_O yielded rapidly increasing area under the receiver operating characteristic (ROC) curves (AUCs) for predicting treatment response from baseline until endpoint; AUC=0.38 (baseline); 0.80 (week 1), 0.85 (week 2), 0.96 (week 3) and 1.0 (endpoint). In comparison, vMRI yielded AUCs of 0.37 (baseline); 0.69 (w1); 0.83 (week 2); 0.92 (week 3) and 0.97 (endpoint). When tested in the external validation dataset, RS_S yielded high accuracy for predicting treatment response at day10/endpoint (AUC=0.85) and tended to yield higher AUC than vMRI (AUC=0.78, p=0.18). Neither RS_S nor vMRI predicted response at day 3 in the external validation set (AUC=0.56 for both).

Conclusions

We have developed and validated a radiomic signature that was able to capture chemotherapeutic treatment response both in an O-PDX and in a subcutaneous endometrial cancer mouse model. This study supports the promising role of preclinical imaging including radiomic tumor profiling to assess early treatment response in endometrial cancer models.
Extended dosing (12 cycles) vs conventional dosing (6 cycles) of adjuvant temozolomide in adults with newly diagnosed high-grade gliomas: a randomized, single-blind, two-arm, parallel-group controlled trial
Authors: Anvari Kazem , Seilanian Toussi Mehdi , Saghafi Mohammadreza , Javadinia Seyed Alireza , Saghafi Hamidreza , Welsh James S.
Published: May 2024

Purpose

Maximum safe surgical resection followed by adjuvant chemoradiation and temozolomide chemotherapy is the current standard of care in the management of newly diagnosed high grade glioma. However, there are controversies about the optimal number of adjuvant temozolomide cycles. This study aimed to compare the survival benefits of 12 cycles against 6 cycles of adjuvant temozolomide adults with newly diagnosed high grade gliomas.

Methods

Adult patients with newly diagnosed high grade gliomas, and a Karnofsky performance status>60%, were randomized to receive either 6 cycles or 12 cycles of adjuvant temozolomide. Patients were followed-up for assessment of overall survival (OS) and progression-free survival (PFS) by brain MRI every 3 months within the first year after treatment and then every six months.

Results

A total of 100 patients (6 cycles, 50; 12 cycles, 50) were entered. The rate of treatment completion in 6 cycles and 12 cycles groups were 91.3% and 55.1%, respectively. With a median follow-up of 26 months, the 12-, 24-, 36-, and 48-month OS rates in 6 cycles and 12 cycles groups were 81.3% vs 78.8%, 58.3% vs 49.8%, 47.6% vs 34.1%, and 47.6% vs 31.5%, respectively (p-value=.19). Median OS of 6 cycles and 12 cycles groups were 35 months (95% confidence interval (CI), 11.0 to 58.9) and 23 months (95%CI, 16.9 to 29.0). The 12-, 24-, 36-, and 48- month PFS rates in 6 cycles and 12 cycles groups were 70.8% vs 56.9%, 39.5% and 32.7%, 27.1% vs 28.8%, and 21.1% vs 28.8%, respectively (p=.88). The Median PFS of 6 cycles and 12 cycles groups was 18 months (95% CI, 14.8 to 21.1) and 16 (95% CI, 11.0 to 20.9) months.

Conclusion

Patients with newly diagnosed high grade gliomas treated with adjuvant temozolomide after maximum safe surgical resection and adjuvant chemoradiation do not benefit from extended adjuvant temozolomide beyond 6 cycles.

Trial registration

Prospectively registered with the Iranian Registry of Clinical Trials: IRCT20160706028815N3. Date registered: 18/03/14.
Long-term oral administration of Huaier granules improves survival outcomes in hepatocellular carcinoma patients within Milan criteria following microwave ablation: a propensity score matching and stabilized inverse probability weighting analysis
Authors: Xie Kailing , Ma Mingxiu , Xu Feng
Published: May 2024

Objective

This study aimed to elucidate the therapeutic effects of Huaier granules on hepatocellular carcinoma (HCC) within the Milan criteria in patients who underwent microwave ablation (MWA).

Materials and methods

A total of 228 patients were included, with 97 in the Huaier group and 131 in the control group. We evaluated progression-free survival (PFS), overall survival (OS), and extrahepatic metastasis survival (EMS) using Kaplan–Meier (KM) curves with a log-rank test. Propensity Score Matching (PSM) and Stabilized Inverse Probability of Treatment Weighting (IPTW) were performed to minimize selection and confounding biases.

Results

Following PSM, the 1-, 3-, and 5-year PFS rates in the Huaier and control groups were 83.5% vs 70.7%, 57.7% vs 42.6%, and 43.6% vs 31.9% (p = 0.030), respectively. The 1-, 3-, and 5-year OS rates were 98.9% vs 95.6%, 83.9% vs 72.3%, and 72.2% vs 53.7% (p = 0.023), respectively. The corresponding 1-, 3-, and 5-year EMS rates were 98.9% vs 93.4%, 91.7% vs 83.7%, and 91.7% vs 78.5% (p = 0.039), respectively. Stabilized IPTW analysis of KM curves yielded results similar to those of the PSM analysis. Additionally, administering Huaier granules for at least 6 months significantly improved PFS and OS.

Conclusion

Huaier granules can reduce the risk of recurrence and improve the OS of patients with HCC within the Milan criteria following MWA. Administering Huaier granules for over 6 months proved beneficial.
Analysis of professional competency awareness based on visible network graphs
Authors: Meng Shilin , Han Lidan , Mou Pengbing
Published: May 2024

Introduction: With the advancement of society and technology, the importance of professional competency has been increasingly emphasized. This study aims to provide an in-depth analysis of the Baidu search index for “professional competency” from July 3, 2017, to October 6, 2023, across 34 provincial-level administrative regions in China.

Methods: The study begins with a literature review to establish a theoretical framework. Subsequently, it delves into the fundamental concepts of complex networks, their parameters, and the principles of visible network graph algorithms. The application of system clustering and community detection algorithms is explored within this framework.

Results: The empirical analysis starts with a provincial-level examination, involving the construction of visible network graphs, the exploration of scale-free networks, and discussions on regional system clustering. Following this, a nationwide analysis is conducted, focusing on the construction of visible network graphs to visualize the awareness of professional competency and studying community structures.

Discussion: The findings provide insights into the awareness of professional competency across different regions. These insights are valuable for informing policy formulation and corporate decision-making, contributing to a deeper understanding of professional competency awareness and its implications.
Split-cavity tuning of a rectangular axion haloscope operating around 8.4 GHz
Authors: Golm Jessica , García-Barcelo Jose María , Arguedas Cuendis Sergio , Calatroni Sergio , Wuensch Walter , Dobrich Babette
Published: May 2024

The axion haloscope is the currently most sensitive method to probe the vanishingly small coupling of this prominent Dark Matter candidate to photons. To scan a sizeable axion Dark Matter parameter space, the cavities that make up the haloscope need to be tuned efficiently. In this article, we describe a novel technique to tune axion haloscopes around 8.4 GHz in a purely mechanical manner without the use of dielectrics. We achieve tuning by introducing a gap along the cavity geometry. A quality factor reduction of less than 20% is achieved experimentally for a tuning range of around 600 MHz at room temperature and at cryogenic temperatures for around 300 MHz. A larger tuning range would require an improved alignments mechanism. We present the results of a corresponding prototype and outline prospects to further develop this technique.
Connexins in epidermal health and diseases: insights into their mutations, implications, and therapeutic solutions
Authors: Yasarbas S. Suheda , Inal Ece , Yildirim M. Azra , Dubrac Sandrine , Lamartine Jérôme , Mese Gulistan
Published: May 2024

The epidermis, the outermost layer of the skin, serves as a protective barrier against external factors. Epidermal differentiation, a tightly regulated process essential for epidermal homeostasis, epidermal barrier formation and skin integrity maintenance, is orchestrated by several players, including signaling molecules, calcium gradient and junctional complexes such as gap junctions (GJs). GJ proteins, known as connexins facilitate cell-to-cell communication between adjacent keratinocytes. Connexins can function as either hemichannels or GJs, depending on their interaction with other connexons from neighboring keratinocytes. These channels enable the transport of metabolites, cAMP, microRNAs, and ions, including Ca2+, across cell membranes. At least ten distinct connexins are expressed within the epidermis and mutations in at least five of them has been linked to various skin disorders. Connexin mutations may cause aberrant channel activity by altering their synthesis, their gating properties, their intracellular trafficking, and the assembly of hemichannels and GJ channels. In addition to mutations, connexin expression is dysregulated in other skin conditions including psoriasis, chronic wound and skin cancers, indicating the crucial role of connexins in skin homeostasis. Current treatment options for conditions with mutant or altered connexins are limited and primarily focus on symptom management. Several therapeutics, including non-peptide chemicals, antibodies, mimetic peptides and allele-specific small interfering RNAs are promising in treating connexin-related skin disorders. Since connexins play crucial roles in maintaining epidermal homeostasis as shown with linkage to a range of skin disorders and cancer, further investigations are warranted to decipher the molecular and cellular alterations within cells due to mutations or altered expression, leading to abnormal proliferation and differentiation. This would also help characterize the roles of each isoform in skin homeostasis, in addition to the development of innovative therapeutic interventions. This review highlights the critical functions of connexins in the epidermis and the association between connexins and skin disorders, and discusses potential therapeutic options.
Characterization of arbuscular mycorrhizal fungal species associating with Zea mays
Authors: Maússe-Sitoe Sílvia , Dames Joanna
Published: May 2024

Taxonomic identification of arbuscular mycorrhizal (AM) fungal spores extracted directly from the field is sometimes difficult because spores are often degraded or parasitized by other organisms. Single-spore inoculation of a suitable host plant allows for establishing monosporic cultures of AM fungi. This study aimed to propagate AM fungal spores isolated from maize soil using single spores for morphological characterization. First, trap cultures were established to trigger the sporulation of AM fungal species. Second, trap cultures were established with individual morphotypes by picking up only one spore under a dissecting microscope and transferring it to a small triangle of sterilized filter paper, which was then carefully inoculated below a root from germinated sorghum seeds in each pot and covered with a sterile substrate. All pots were placed in sunbags and maintained in a plant growth room for 120 days. Spores obtained from single spore trap cultures from each treatment, maize after oats (MO), maize after maize (MM), maize after peas (MP), and maize after soybean (MS), were extracted using the sieving method. Healthy spores were selected for morphological analysis. Direct PCR was conducted by crushing spores in RNAlater and applying three sets of primer pairs: ITS1 × ITS4, NS31 × AML2, and SSUmcf and LSUmBr. Nucleotide sequences obtained from Sanger sequencing were aligned on MEGA X. The phylogenetic tree showed that the closest neighbors of the propagated AM fungal species belonged to the genera Claroideoglomus, Funneliformis, Gigaspora, Paraglomus, and Rhizophagus. The morphological characteristics were compared to the descriptive features of described species posted on the INVAM website, and they included Acaulospora cavernata, Diversispora spurca, Funneliformis geosporus, Funneliformis mosseae, Gigaspora clarus, Gigaspora margarita, Glomus macrosporum, Paraglomus occultum, and Rhizophagus intraradices. These findings can provide a great contribution to crop productivity and sustainable management of the agricultural ecosystem. Also, the isolate analyzed could be grouped into efficient promoters of growth and mycorrhization of maize independent of their geographical location.
The effect of music therapy on language communication and social skills in children with autism spectrum disorder: a systematic review and meta-analysis
Authors: Shi Zijuan , Wang Si , Chen Maoqing , Hu Aimin , Long Qingwen , Lee Yujun
Published: May 2024

Background

Studies have shown that music therapy can be used as a therapeutic aid for clinical disorders. To evaluate the effects of music therapy (MT) on language communication and social skills in children with autism spectrum disorder (ASD), a meta-analysis was performed on eligible studies in this field.

Methods

A systematic search was conducted in eight databases: PubMed, Embase, Web of Science, Cochrane Library databases, the China National Knowledge Infrastructure (CNKI), Wanfang Data, the Chinese Biomedical Literature (CBM) Database, and the VIP Chinese Science and Technology Periodicals Database. The standard mean difference (SMD) values were used to evaluate outcomes, and the pooled proportions and SMD with their 95% confidence intervals (CIs) were also calculated.

Results

Eighteen randomized controlled trial (RCT) studies were included, with a total of 1,457 children with ASD. This meta-analysis revealed that music therapy improved their language communication [SMD = −1.20; 95%CI –1.45, −0.94; χ2 (17) = 84.17, I2 = 80%, p < 0.001] and social skills [SMD = −1. 13; 95%CI –1.49, −0.78; χ2 (17) = 162.53, I2 = 90%, p < 0.001]. In addition, behavior [SMD = −1.92; 94%CI –2.56, −1.28; χ2 (13) = 235.08, I2 = 95%, p < 0.001], sensory perception [SMD = −1.62; 95%CI –2.17, −1.08; χ2 (16) = 303.80, I2 = 95%, p < 0.001], self-help [SMD = −2. 14; 95%CI –3.17, −1.10; χ2 (6) = 173.07, I2 = 97%, p < 0.001] were all improved.

Conclusion

Music therapy has a positive effect on the improvement of symptoms in children with ASD.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/.
The relationship between perceived social support and rumination among parents of children with autism: moderating effect of the degree of intervention received by children
Authors: Xu Li , Song Li , Xiong Zhiheng , Chen Jiejia
Published: May 2024

Objective

As the number of children diagnosed with autism rises year by year, the issue of nurturing this particular group becomes increasingly salient. Parents of autistic children, as the nearest and most reliable caregivers for their children, shoulder immense psychological strain and accountability. They are compelled to confront an array of daily life challenges presented by their children, as well as endure multiple pressures such as societal scrutiny and financial burdens. Consequently, the mental health status of the parents is of utmost significance.

Methods

In this study, questionnaire survey combined with literature analysis were applied. The rumination thinking scale and the social support scale were used to investigate the relationship between social support perceived by parents of autistic children and rumination. Meanwhile, the moderating effects of intervention on children with autism were also explored. It hopes that our research would provide a basis for alleviating psychological stress and improving the mental health levels of the parents. A total of 303 parents of children with autism were collected (including 160 females and 143 males). Corresponding data analyses were conducted using SPSS 26.0.

Results

Parents of autistic children generally exhibited high levels of rumination, with significant gender differences. At the same time, the perceived social support by the parents significantly influenced their level of rumination. It showed that the higher the social support received by parents, the lower the level of rumination. More importantly, the extent of intervention received by the children had a regulating effect on rumination of their parents.

Conclusion

The personalized psychological support programs should be developed based on the actual situation of parents, to better manage the challenges presented by raising a child with autism. Our findings would provide important theoretical underpinnings and practical guidance for psychological intervention efforts aimed at families of autistic children. Moreover, these findings offer novel insights for future research, with the potential to advance the field of mental health studies concerning parents of children with autism.
Reducing the risk of suicidal behaviors in medical graduate students: exploration of student-supervisor relationship and subjective family socioeconomic status
Authors: Wu Yan , Qu Zheng , Tang Wanjie , Zheng Yunhao , Xiong Xin , Ye Zheng , Li Zhenlin
Published: May 2024

Objective

This study aimed to investigate the association between the risk of suicidal behaviors and student-supervisor relationships and subjective family socioeconomic status (SFSS) in medical graduate students, and to propose preventive strategies to reduce the suicidal risk among medical graduate students.

Materials and methods

A total of 1,310 validated questionnaires were collected from medical graduate students, which included demographic information, study programs, the Suicidal Behaviors Questionnaire-Revised (SBQ-R) questionnaire, the Leader-Member Exchange 7 (LMX-7) questionnaire, and SFSS by MacArthur Scale. Multiple regression analysis was employed to examine the associations between variables and adjust for confounders. A moderation analysis, containing simple slope analysis and Johnson-Neyman interval plots were used to analyze the moderating effect of the SFSS in the association of SBQ-R and LMX-7 scores.

Results

A total of 88 participants (6.7%) were at risk of suicidal behaviors. In the high-quality student-supervisor relationship group (LMX-7 score ≥ 25), SFSS was significantly higher than in the low- and moderate-quality relationship group (p=0.002). The median SBQ-R score and proportion of suicide risk was significantly lower (p<0.001) in the high-quality student-supervisor relationship group. Multiple regression analysis indicated LMX-7 scores (β=-0.098, 95% CI [-0.118, -0.077], p<0.001) and SFSS (β=-0.073, 95% CI [-0.127, -0.019], p=0.008) were significantly negatively associated with SBQ-R, whereas the interaction term of SFSS with LMX-7 (β=0.018, 95% CI [0.007, 0.029], p=0.001) showed a significant positive association with SBQ-R. The Johnson-Neyman interval showed a significant association between LMX-7 and SBQ-R scores only when SFSS was less than 7.82 (p<0.05).

Conclusion

The risk of suicidal behaviors was associated with student-supervisor relationships and SFSS among medical graduate students. Poor relationships with supervisor were associated with an elevated risk of suicidality, and SFSS moderated this association. Educators should pay increased attention to the suicidal risk of medical graduate students with poor supervisor relationships, especially those from families with low SFSS, and provide timely preventive strategies.
The effect of forest-based health and wellness on the stress-relieve of middle-aged people
Authors: Quan Wei , Yu Shaona , Huang Qi , Ying Miaomiao
Published: May 2024

In order to explore the impact of experience in forest-based health and wellness (FHW) on the stress of middle-aged people, 12 participants aged 35–39 were selected to conduct a 3-day/2-night study on FHW experience in Wencheng, Wenzhou. Huawei bracelets were used to monitor participants’ movement, pulse and blood pressure and their mood state was measured before and after the health care experience using the Profile of Mood States (POMS) scale. After the FHW experience, the lowest value of bracelet stress appeared on the second day of the experience for men and women. The total mood disturbance (TMD) decreased by 38.8 points on average, which significantly improved the positive mood and relieved the stress. The decompression effect of the FHW experience showed some variability among individuals. Furthermore, there were gender differences in alleviation of fatigue and puzzlement, which was greater for females than males.