bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-energy amplitude-modulated radiofrequency electromagnetic fields as a systemic treatment for cancer: Review and proposed mechanisms of action
Authors: Tuszynski Jack A. , Costa Frederico
Published: September 2022

Exposure to Low-Energy Amplitude-Modulated Radiofrequency Electromagnetic Fields (LEAMRFEMF) represents a new treatment option for patients with advanced hepatocellular carcinoma (AHCC). We focus on two medical devices that modulate the amplitude of a 27.12 MHz carrier wave to generate envelope waves in the low Hz to kHz range. Each provides systemic exposure to LEAMRFEMF via an intrabuccal antenna. This technology differs from so-called Tumour Treating Fields because it uses different frequency ranges, uses electromagnetic rather than electric fields, and delivers energy systemically rather than locally. The AutemDev also deploys patient-specific frequencies. LEAMRFEMF devices use 100-fold less power than mobile phones and have no thermal effects on tissue. Tumour type-specific or patient-specific treatment frequencies can be derived by measuring haemodynamic changes induced by exposure to LEAMRFEMF. These specific frequencies inhibited growth of human cancer cell lines in vitro and in mouse xenograft models. In uncontrolled prospective clinical trials in patients with AHCC, minorities of patients experienced complete or partial tumour responses. Pooled comparisons showed enhanced overall survival in treated patients compared to historical controls. Mild transient somnolence was the only notable treatment-related adverse event. We hypothesize that intracellular oscillations of charged macromolecules and ion flows couple resonantly with LEAMRFEMF. This resonant coupling appears to disrupt cell division and subcellular trafficking of mitochondria. We provide an estimate of the contribution of the electromagnetic effects to the overall energy balance of an exposed cell by calculating the power delivered to the cell, and the energy dissipated through the cell due to EMF induction of ionic flows along microtubules. We then compare this with total cellular metabolic energy production and conclude that energy delivered by LEAMRFEMF may provide a beneficial shift in cancer cell metabolism away from aberrant glycolysis. Further clinical research may confirm that LEAMRFEMF has therapeutic value in AHCC.
Antimicrobial activity of bovine lactoferrin against Gardnerella species clinical isolates
Authors: Pino Alessandra , Mazza Tommaso , Matthews Maura-Ann H. , Castellana Stefano , Caggia Cinzia , Randazzo Cinzia L. , Gelbfish Gary A.
Published: September 2022

Gardnerella species play a key role in the development and recurrence of Bacterial Vaginosis (BV), a common imbalance of the vaginal microbiota. Because of the high rates of BV recurrence reported after treatment with standard of care antibiotics, as well as the emergence of antibiotic-resistant BV, the development of alternative treatment approaches is needed. Bovine lactoferrin, a well studied iron-binding glycoprotein with selective antimicrobial activity, may ameliorate vaginal dysbiosis either alone or in combination with antibiotics. The present study evaluated the antimicrobial resistance/susceptibility profile of seventy-one presumptive G. vaginalis clinical isolates to metronidazole and clindamycin. In addition, the in vitro antimicrobial activity of Metrodora Therapeutics bovine Lactoferrin (MTbLF) against the tested clinical isolates, both alone and in combination with metronidazole and clindamycin, was in depth evaluated using defined-iron culture conditions. All 71 presumptive G. vaginalis clinical isolates exhibited resistance to metronidazole, with MIC values greater than 256 μg/ml. Different susceptibility profiles were detected for clindamycin. In detail, the vast majority of the tested strains (45%), exhibiting MIC lower than 2 μg/ml, were considered sensitive; 18 strains (25%) with MIC higher or equal to 8 μg/ml, were classified as resistant, whereas the remaining 21 (30%) were classified as intermediate. MTbLF was tested in culture medium at different concentrations (32, 16, 8, 4, 2, 1, and 0.5 mg/ml) showing ability to inhibit the growth of the tested presumptive G. vaginalis clinical isolates, including those metronidazole-resistant, in a dose-dependent and not in a strain-dependent manner. MTbLF, at concentrations ranging from 32 to 8 mg/ml, exerted a statistically different antimicrobial activity compared with lower concentrations (4, 2, 1, and 0.5 mg/ml). A synergistic effect between MTbLF (8 and 4 mg/ml) and clindamycin was revealed for all the tested strains. When tested in the absence of other sources of iron, MTbLF did not support the growth of the tested presumptive G. vaginalis clinical isolates. Bovine lactoferrin may be a potential candidate to treat Gardnerella species infection.
Microorganisms present in artisanal fermented food from South America
Authors: Jimenez Maria Eugenia , O’Donovan Ciara M. , Ullivarri Miguel Fernandez de , Cotter Paul D.
Published: September 2022

Artisanal fermented products (foods and beverages) are produced in an artisanal way in many countries around the world. The main purpose of fermentation is to preserve the food, improve its safety, increase the nutritional and health-promoting value and add specific flavours. In South America, there is a great variety of fermented food produced in an artisanal way. Different raw materials are used such as potatoes, sweet potato, cassava, maize, rice, milk (cow, ewe, goat) and meat (beef, goat, lamb, llama and guanaco). Some of these fermented foods are typical of the region and are part of the culture of native communities, e.g.tocosh,masa agria,puba flour,charqui,chicha,champuandcauimamong others (indigenous foods). However, other fermented foods produced in South America introduced by mainly European immigration, such as cheeses and dry sausages, and they are also produced in many different parts of the world. In this work, the microbial composition of the different artisanal fermented products produced in South America is reviewed, taking into consideration the associated raw materials, fermentation conditions and methodologies used for their production.
Pesticide thiram exposure alters the gut microbial diversity of chickens
Authors: Wu Zhiwen , Su Rongsheng
Published: September 2022

Thiram is a major dithiocarbamate pesticide commonly found in polluted field crops, feed, and rivers. Environmental thiram exposure has been demonstrated to cause angiogenesis and osteogenesis disorders in chickens, but information regarding thiram influences on gut microbiota, apoptosis, and autophagy in chickens has been insufficient. Here, we explored the effect of thiram exposure on gut microbiota, apoptosis, and autophagy of chickens. Results demonstrated that thiram exposure impaired the morphology and structure of intestinal and liver tissues. Moreover, thiram exposure also triggered liver apoptosis and autophagy. The gut microbiota in chickens exposed to thiram exhibited a significant decline in alpha diversity, accompanied by significant shifts in taxonomic compositions. Bacterial taxonomic analysis indicated that thiram exposure causes a significant reduction in the levels of eight genera, as well as a significant increase in the levels of two phyla and 10 genera. Among decreased bacterial genera, seven genera even cannot be observed in the thiram-induced chickens. In summary, this study demonstrated that thiram exposure not only dramatically altered the gut microbial diversity and composition but also induced liver apoptosis and autophagy in chickens. Importantly, this study also conveyed a key message that the dysbiosis of gut microbiota may be one of the major pathways for thiram to exert its toxic effects.
The shortcut of mycobacterial interspersed repetitive unit-variable number tandem repeat typing for Mycobacterium tuberculosis differentiation
Authors: Hadifar Shima , Kargarpour Kamakoli Mansour , Eybpoosh Sana , Nakhaeizadeh Mehran , Kargarpour Kamakoli Mohammad Ali , Ebrahimifard Nasim , Fateh Abolfazl , Siadat Seyed Davar , Vaziri Farzam
Published: September 2022

The 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) genotyping has been used as an international standard method for Mycobacterium tuberculosis (Mtb) genotyping. However, different optimized VNTR loci sets for improving the discrimination of specific Mtb genotypes have been proposed. In this regard, we investigated the efficacy of accumulation of the percentage differences (APDs) compared with the least absolute shrinkage and selection operator (LASSO) regression strategy to identify a customized genotype-specific VNTR loci set which provides a resolution comparable to 24-loci MIRU-VNTR in divergent Mtb populations. We utilized Spoligotyping and 24-loci MIRU-VNTR typing for genotyping 306 Mtb isolates. The APD and LASSO regression approaches were used to identify a customized VNTR set in our studied isolates. Besides, the Hunter-Gaston discriminatory index (HGDI), sensitivity, and specificity of each selected loci set were calculated based on both strategies. The selected loci based on LASSO regression compared with APD-based loci showed a better discriminatory power for identifying all studied genotypes except for T genotype, which APD-based loci showed promising discriminative power. Our findings suggested the LASSO regression rather than the APD approach is more effective in the determination of possible discriminative VNTR loci set to precise discrimination of our studied Mtb population and may be beneficial to be used in finding reduced number loci sets in other Mtb genotypes or sublineages. Moreover, we proposed customized genotype-specific MIRU-VNTR loci sets based on the LASSO regression and APD approaches for precise Mtb strains identification. As the proposed VNTR sets offered a comparable discriminatory power to the standard 24 MIRU-VNTR loci set could be promising alternatives to the standard genotyping for using in resource-limited settings.
Detection of Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphoid B, and Shigella dysentery in live Bacillus licheniformis products using propidium monoazide-real-time-quantitative polymerase chain reaction
Authors: Zheng Xiaoling , Wang Yinhuan , Gong WanZi , Cai Qianru , Li Jue , Wu Jiequn
Published: September 2022

To eliminate the influences of excipients and interference of dead bacterial DNA on the detection of Escherichia coli, Pseudomonas aeruginosa, Salmonella paratyphoid B, and Shigella dysentery in live Bacillus licheniformis capsules, a polymerase chain reaction (PCR) method with high sensitivity and specificity was established. By combining bromide with propidium monoazide (PMA) -real-time quantitative PCR (qPCR) with microporous membrane filtration, excipients were removed, the filtrate was collected, and the bacteria were enriched using the centrifugal method. The optimal PMA working concentration, dark incubation time, and exposure time were determined. Specific E. coli, P. aeruginosa, S. paratyphoid B, and S. dysentery primers were selected to design different probes and a multiplex qPCR reaction system was established. The PMA-qPCR method was verified using different concentrations of dead and live bacteria. This method is efficient and accurate and can be widely applied to the detection of aforementioned pathogenic bacterial strains in live Bacillus licheniformis products.
Microbiome analysis reveals the effects of black soldier fly oil on gut microbiota in pigeon
Authors: Liu Suzhen , Luo Houqiang , Wang Meng , Wang Qingyan , Duan Longchuan , Han Qingsong , Sun Siwei , Wei Caixia , Jin Junjie
Published: September 2022

The gut microbiota plays a vital roles in poultry physiology, immunity and metabolism. Black soldier fly oil is known to have a positive effect on the gut microbiota. However, the specific effect of black soldier fly oil on the composition and structure of the gut microbiota of the pigeon is unknown. In this experiment, 16S rDNA high-throughput sequencing was performed to study the effect of different doses of black soldier fly oil on the changes of pigeon intestinal microbes. Results indicated that the different doses of black soldier fly oil had no effect on the gut microbial diversity of the pigeon. Although the dominant phyla (Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria) and genus (uncultured_bacterium_f_Lachnospiraceae and Desulfovibrio) in control group and experimental group with different doses were the same, the abundances of some beneficial bacteria (Megasphaera, Intestinimonas, Prevotella_9, Lachnospiraceae_UCG-001, Faecalibacterium, Coprococcus_2, Parabacteroides, Megasphaera, Leuconostoc, Prevotellaceae_UCG-001, Lactococcus, Ruminococcaceae_UCG-014, and Coprococcus_2) increased significantly as the concentration of black soldier fly oil increased. Taken together, this study indicated that black soldier fly oil supplementation could improve gut microbial composition and structure by increasing the proportions of beneficial bacteria. Notably, this is the first report on the effects of black soldier fly oil on the gut microbiota of pigeon, which contribute to understanding the positive effects of black soldier fly oil from the gut microbial perspective.
Metabolomics in Otorhinolaryngology
Authors: Noto Antonio , Piras Cristina , Atzori Luigi , Mussap Michele , Albera Andrea , Albera Roberto , Casani Augusto Pietro , Capobianco Silvia , Fanos Vassilios
Published: September 2022

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the “omics” sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all “omics.” Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere’s disease. In conclusion, metabolomics study indicates a “fil rouge” that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine.
Primary progressive aphasia and motor neuron disease: A review
Authors: Aiello Edoardo Nicolò , Feroldi Sarah , De Luca Giulia , Guidotti Lucilla , Arrigoni Eleonora , Appollonio Ildebrando , Solca Federica , Carelli Laura , Poletti Barbara , Verde Federico , Silani Vincenzo , Ticozzi Nicola
Published: September 2022

Background

This study aims at reviewing, within the framework of motor neuron disease-frontotemporal degeneration (MND-FTD)-spectrum disorders, evidence on the co-occurrence between primary progressive aphasia (PPA) and MND in order to profile such a complex at pathological, genetic and clinical levels.

Methods

This review was pre-registered (osf.io/ds8m4) and performed in accordance with the 2020 PRISMA guidelines. Case reports/series and group studies were included if addressing (1) progressive non-fluent aphasia (PNFA) or semantic dementia (SD) with MND or (2) MND patients with co-morbid PNFA/SD.

Results

Out of 546 initial records, 56 studies were included. As to case reports/series (N = 35), which included 61 PPA-MND patients, the following findings yielded: (1) PNFA is more frequent than SD in PPA-MND; (2) in PPA-MND, the most prevalent motor phenotypes are amyotrophic lateral sclerosis and predominant-upper MND, with bulbar involvement being ubiquitous; (3) extrapyramidal features are moderately frequent in PPA-MND; (4) PPA-MND patients usually display frontotemporal, left-greater-than-right involvement; (5) TDP-43-B is the typical pathological substrate of PPA-MND; (6) TBK1 mutations represent the most frequent genetic risk factors for PPA-MND.

As to group studies, including 121 patients, proportional meta-analytic procedures revealed that: (1) the lifetime prevalence of MND in PPA is 6%; (2) PPA occurs in 19% of patients with co-morbid MND and FTD; (3) MND is more frequent in PNFA (10%) than in SD patients (3%).

Discussion

Insights herewith delivered into the clinical, neuropathological and genetic features of PPA-MND patients prompt further investigations aimed at improving clinical practice within the MND-FTD spectrum.
Age-related differences in the transient and steady state responses to different visual stimuli
Authors: Zhang Xin , Jiang Yi , Hou Wensheng , Jiang Ning
Published: September 2022

Objective

Brain-computer interface (BCI) has great potential in geriatric applications. However, most BCI studies in the literature used data from young population, and dedicated studies investigating the feasibility of BCIs among senior population are scarce. The current study, we analyzed the age-related differences in the transient electroencephalogram (EEG) response used in visual BCIs, i.e., visual evoked potential (VEP)/motion onset VEP (mVEP), and steady state-response, SSVEP/SSMVEP, between the younger group (age ranges from 22 to 30) and senior group (age ranges from 60 to 75).

Methods

The visual stimulations, including flicker, checkerboard, and action observation (AO), were designed with a periodic frequency. Videos of several hand movement, including grasping, dorsiflexion, the thumb opposition, and pinch were utilized to generate the AO stimuli. Eighteen senior and eighteen younger participants were enrolled in the experiments. Spectral-temporal characteristics of induced EEG were compared. Three EEG algorithms, canonical correlation analysis (CCA), task-related component analysis (TRCA), and extended CCA, were utilized to test the performance of the respective BCI systems.

Results

In the transient response analysis, the motion checkerboard and AO stimuli were able to elicit prominent mVEP with a specific P1 peak and N2 valley, and the amplitudes of P1 elicited in the senior group were significantly higher than those in the younger group. In the steady-state analysis, SSVEP/SSMVEP could be clearly elicited in both groups. The CCA accuracies of SSVEPs/SSMVEPs in the senior group were slightly lower than those in the younger group in most cases. With extended CCA, the performance of both groups improved significantly. However, for AO targets, the improvement of the senior group (from 63.1 to 71.9%) was lower than that of the younger group (from 63.6 to 83.6%).

Conclusion

Compared with younger subjects, the amplitudes of P1 elicited by motion onset is significantly higher in the senior group, which might be a potential advantage for seniors if mVEP-based BCIs is used. This study also shows for the first time that AO-based BCI is feasible for the senior population. However, new algorithms for senior subjects, especially in identifying AO targets, are needed.
Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
Authors: González-Cubero Elsa , González-Fernández María Luisa , Rodríguez-Díaz María , Palomo-Irigoyen Marta , Woodhoo Ashwin , Villar-Suárez Vega
Published: September 2022

Background

Neuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM).

Methods

To this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy.

Results

Our data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins.

Conclusion

Findings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology.
Two modes of being together: The levels of intersubjectivity and human relatedness in neuroscience and psychoanalytic thinking
Authors: Williams Riccardo , Trentini Cristina
Published: September 2022

The notion of intersubjectivity has achieved a primary status in contemporary psychoanalytic debate, stimulating new theoretical proposals as well as controversies. This paper presents an overview of the main contributions on inter-subjectivity in the field of neurosciences. In humans as well as—probably—in other species, the ability for emotional resonance is guaranteed early in development. Based on this capacity, a primary sense of connectedness is established that can be defined inter-subjective in that it entails sharing affective states and intentions with caregivers. We propose to define such a form of inter-subjectivity ascontingent, since the infant’s early abilities for resonance do not imply the more generalized capacity to permanently conceive of the relationship outside the realm of current interactions and the infant-caregiver’s mutual correspondence of internal states. This form of connection, hence, results in a self-referential, bodily, and affectively codified, context- and time dependent, like-me experience of interactions. The gradual maturation of brain structures and processes as well as interactive experiences allow proper intersubjectivity exchanges, grounded on new intentional and representational capacities, to evolve. In this more mature form of intersubjectivity, the individual is allowed to conceive of her own psychic space both as distinct and as possibly connected with the other’s contents and experience, even in the absence of current behavioral indicators of such correspondence. This multi-layered model of intersubjectivity, which is embraced by current neuroscience research, seems to allow for new interpretations of psychoanalytic models of human relatedness based upon classic clinical observations.
Unveiling the knowledge domain and emerging trends of olfactory dysfunction with depression or anxiety: A bibliometrics study
Authors: Zhou Fangwei , Zhang Tian , Jin Ying , Ma Yifei , Li Yangsong , Zeng Mengting , Yu Guodong
Published: September 2022

Olfactory dysfunction (OD) accompanied by depression or anxiety is a very common clinical problem, and there has been a growing number of studies on OD with depression or anxiety in recent decades. This study performed bibliometric and visual analyses of the literature on OD with depression or anxiety to derive research trends and identify emerging research foci. Relevant publications were obtained from the Science Citation Index-Expanded and Social Sciences Citation Index in the Web of Science Core Collection databases (2002–2021). CiteSpace and VOSviewer were applied to identify and evaluate research foci and emerging trends in this research domain. The analyses found that the number of publications related to OD with depression or anxiety has increased significantly over the past 20 years, up from 15 in 2002 to 114 in 2022. The country that ranked highest in the number of articles and international cooperation was the United States. The top 10 most frequent keywords were “depression,” “olfaction,” “anxiety,” “dysfunction,” “olfactory bulbectomy,” “olfactory dysfunction,” “Parkinson’s disease,” “odor identification,” “brain,” and “disorders.” Analysis of keywords with the strongest citation bursts revealed that “oxidative stress” is an emerging research hotspot. A timeline chart of the cluster of co-cited references demonstrated that Parkinson’s disease was always a topic of interest in this area of research. This study conducted an objective, comprehensive, and systematic analysis of these publications, and identified the development of trends and hotspots in this research domain. It is hoped that this work will provide scholars, worldwide, with information to assist them in further research and the development of new therapies.
Epidemiological characteristics of hearing loss associated with noise temporal structure among manufacturing workers
Authors: Zhou Lifang , Ruan Xiaoying , Wang Tongshuai , Xie Hongwei , Hu Yong , Shi Zhihao , Xin Jiarui , Zhou Jiena , Xue Panqi , Wei Fang , Zhang Yixin , Zhang Meibian , Zou Hua
Published: September 2022

Objective: This study aimed to investigate the epidemiological characteristics of occupational noise-induced hearing loss (NIHL) among manufacturing workers, and to provide evidence for diagnosing and preventing occupational hearing loss caused by complex noise, which is different from Gaussian noise in temporal structure.

Methods: One thousand and fifty manufacturing workers exposed to occupational noise were recruited in a cross-sectional survey. Exposure characteristics and epidemiological distribution of hearing loss and noise exposure metrics (noise energy and kurtosis) were investigated, and the relationship between noise exposure and hearing loss was analyzed. The effects of kurtosis on hearing threshold shift across different frequencies and on NIHL development with exposure duration and noise intensity were also investigated.

Results: Each type of work had specific noise exposure metrics. Noise intensity and kurtosis were independent parameters (r = −0.004, p = 0.885). The prevalence of NIHL and the hearing threshold level had a specific distribution in different types of work. Kurtosis deepened the hearing notch at high frequencies and accelerated the formation of early hearing loss. The effect of exposure duration and noise intensity on the prevalence of high-frequency NIHL (i.e., at 3, 4, 6, and 8 kHz) for manufacturing workers increased with kurtosis in workers with noise exposure duration of less than 10 years and with LAeq.8h between 80 and 90 dB(A). Male (OR = 1.557, 95%CI = 1.141–2.124), age (OR = 1.033, 95%CI = 1.014–1.052), exposure duration (OR = 1.072, 95%CI = 1.038–1.107), kurtosis (OR = 1.002, 95%CI = 1.001–1.003), and noise intensity (LAeq.8h; OR = 1.064, 95%CI = 1.044–1.084) were risk factors for high-frequency NIHL. The speech-frequency NIHL (i.e., at 0.5, 1, and 2 kHz) risk of workers exposed to manufacturing noise was related to age (OR = 1.071, 95%CI = 1.043–1.100). There were no statistically significant associations between speech-frequency NIHL and sex, noise exposure duration, kurtosis, and noise intensity (LAeq.8h).

Conclusion: The high-frequency NIHL prevalence among manufacturing workers is associated with sex, age, exposure duration, noise intensity, and temporal structure of noise, while the speech-frequency NIHL prevalence is associated with age. Kurtosis strengthens the association of noise exposure duration and noise intensity with high-frequency hearing loss. The influence of noise temporal structure should be considered in the diagnosis and early prevention of occupational hearing loss caused by complex noise.
Aflatoxin tests in herbal products and its quantification: Latest updates
Authors: Victor Jeyaraj Simon Vienoth , Loy Mei Jun , Goh Khang Wen , Lean Yen Loong , Chan Siok Yee , Ming Long Chiau
Published: September 2022

Aflatoxin is naturally occurring mycotoxins produced by fungi. The existence of aflatoxin in herbal medicines is a well-known issue. The detection of aflatoxin with good sensitivity and also that is reliable in complex matrices like herbs usually necessitates difficult processes and powerful detection instrument in preparation of sample. This study investigated the global occurrence of aflatoxin contamination herbal products. This article pivots on key breakthroughs in preparation of sample and its importance in analytical technology. Studies from published studies were screened to determine the general level of aflatoxin contamination. The countries involved were Malaysia, Indonesia, Kenya, Brazil, Nigeria, Thailand, South Africa, and Morocco. This review also includes recent studies on the development and application of screening assays such as lateral flow immunoassays, enzyme-linked immunosorbent assays, aptamer-based lateral flow assays, and cytometric bead arrays, as well as traditional chromatographic techniques for aflatoxin qualification or quantitation. The current study looks at aflatoxin contamination of key herbal drug raw material, which are frequently used in the production of numerous herbal pharmaceuticals. Contamination of aflatoxin might occur in herbal products if the ingredients such as medicinal herbs and plants that are used in manufacturing of herbal products are not dried thoroughly or stored inappropriately after preparation.
Differentiation between spinal multiple myeloma and metastases originated from lung using multi-view attention-guided network
Authors: Chen Kaili , Cao Jiashi , Zhang Xin , Wang Xiang , Zhao Xiangyu , Li Qingchu , Chen Song , Wang Peng , Liu Tielong , Du Juan , Liu Shiyuan , Zhang Lichi
Published: September 2022

Purpose

Multiple myeloma (MM) and metastasis originated are the two common malignancy diseases in the spine. They usually show similar imaging patterns and are highly demanded to differentiate for precision diagnosis and treatment planning. The objective of this study is therefore to construct a novel deep-learning-based method for effective differentiation of two diseases, with the comparative study of traditional radiomics analysis.

Methods

We retrospectively enrolled a total of 217 patients with 269 lesions, who were diagnosed with spinal MM (79 cases, 81 lesions) or spinal metastases originated from lung cancer (138 cases, 188 lesions) confirmed by postoperative pathology. Magnetic resonance imaging (MRI) sequences of all patients were collected and reviewed. A novel deep learning model of the Multi-view Attention-Guided Network (MAGN) was constructed based on contrast-enhanced T1WI (CET1) sequences. The constructed model extracts features from three views (sagittal, coronal and axial) and fused them for a more comprehensive differentiation analysis, and the attention guidance strategy is adopted for improving the classification performance, and increasing the interpretability of the method. The diagnostic efficiency among MAGN, radiomics model and the radiologist assessment were compared by the area under the receiver operating characteristic curve (AUC).

Results

Ablation studies were conducted to demonstrate the validity of multi-view fusion and attention guidance strategies: It has shown that the diagnostic model using multi-view fusion achieved higher diagnostic performance [ACC (0.79), AUC (0.77) and F1-score (0.67)] than those using single-view (sagittal, axial and coronal) images. Besides, MAGN incorporating attention guidance strategy further boosted performance as the ACC, AUC and F1-scores reached 0.81, 0.78 and 0.71, respectively. In addition, the MAGN outperforms the radiomics methods and radiologist assessment. The highest ACC, AUC and F1-score for the latter two methods were 0.71, 0.76 & 0.54, and 0.69, 0.71, & 0.65, respectively.

Conclusions

The proposed MAGN can achieve satisfactory performance in differentiating spinal MM between metastases originating from lung cancer, which also outperforms the radiomics method and radiologist assessment.
Immune-modulatory effect of human milk in reducing the risk of Kawasaki disease: A nationwide study in Korea
Authors: Na Jae Yoon , Cho Yongil , Lee Juncheol , Yang Seung , Kim Yong Joo
Published: September 2022

Background

Kawasaki disease (KD) is the most common acquired heart disease among children in developed countries, but the etiology is still unclear. There are several hypotheses regarding the outbreak of KD, including infection, genetics, and immunity. Since breastfeeding plays an essential role in the immune system's composition, investigating breastfeeding's effects on the occurrence of KD would be an excellent way to identify the etiology of KD.

Aim

To determine whether the incidence of KD decreases with breastfeeding.

Methods

This nationwide cohort study analyzed data from the National Health Insurance Service (NHIS) in South Korea and included 1,910,438 infants who underwent their first National Children's Health Examination (NCHE) between 2008 and 2014. Feeding types were collected using a questionnaire in NCHE. The NHIS data and NCHE data were merged and analyzed. First, we investigated the effect of breastfeeding on the development of KD at 1 year of age. Then, we surveyed the age at which no significant effect appeared by expanding the observation range yearly.

Results

The most prevalent feeding type in the study population was exclusive breastfeeding (41.5%). At 10–12 months of follow-up age, 3,854 (0.2%) infants were diagnosed with KD. Compared to the exclusive formula feeding group, the adjusted odds ratio (aOR) for KD was 0.84 [95% confidence interval (CI), 0.78–0.90] and 0.86 (95% CI, 0.79–0.94) in the exclusive and partial breastfeeding groups, respectively. At 22–24 months of age, aOR for KD was 0.94 (95% CI, 0.90–0.98) in the exclusive breastfeeding group and 0.98 (95% CI, 0.92–1.03) in the partial breastfeeding group. There was no difference in the risk between the groups at 34–36 months.

Conclusions

Using a large amount of national data on children aged <2 years, we proved that breastfeeding has a protective effect on the development of KD.
Interleukin-6 in blood and bronchoalveolar lavage fluid of hospitalized children with community-acquired pneumonia
Authors: Zhang Yun , Zheng Wenyu , Ning Haonan , Liu Jing , Li Fuhai , Ju Xiuli
Published: September 2022

Background

Host biomarkers and cytokines help in the prediction of disease severity in adults with community-acquired pneumonia (CAP). Accurate assessment of pathogens and disease severity is essential to clinical decision-making. There are few validated prognostic tools in blood and bronchoalveolar lavage for children with CAP to assist with proper decision and management.

Methods

We performed a retrospective study of 118 children under 18 years of age, hospitalized for CAP with bronchoalveolar lavage management within the first 2 days. The primary outcome was disease severity: mild (with no complications), moderate (with mild to moderate complications), and severe (with severe complications). Comparison and performance analysis of biomarkers and cytokines in the blood or bronchoalveolar lavage fluid (BALF) across different severity categories/different pathogens were performed.

Results

Analysis of 118 CAP cases revealed significant differences in the BALF levels of IL-6 (p= 0.000), CRP (p= 0.001), and ESR (p= 0.004) across different severity categories, while BALF IL-6 level was indicated as the best indicator to discriminate mild from moderate-to-severe cases with highest AUC (0.847, 95% CI: 0.748–0.946), fair sensitivity (0.839), and specificity (0.450), and severe from non-severe cases with highest AUC (0.847), sensitivity (0.917), and specificity (0.725). ALL biomarkers and cytokines exhibited no significant differences across different pathogen categories (p> 0.05), while BALF IL-6 (p= 0.000), blood ANC (p= 0.028), and ESR (p= 0.024) levels were obviously different in comparison to single Mycoplasma pneumoniae (MP)-, bacteria-, or virus-positive group vs. non-group. Blood CRP (r= 0.683,p= 0.000) and ESR (r= 0.512,p= 0.000) levels revealed significant correlation with the hospitalization course (HC). Among all the BALF cytokines, only BALF IL-6 showed a significant difference (p= 0.004,p< 0.01) across different severity categories, with good performance for predicting CAP severity in hospitalized children (AUC = 0.875,P= 0.004). Blood IL-6 and BALF IL-6 levels showed no significant correlation; in addition, BALF IL6 was better at predicting CAP severity in hospitalized children (AUC = 0.851,p= 0.011,p< 0.05) compared to blood IL-6.

Conclusion

BALF IL-6 and blood CRP levels, and ESR may have the ability for discriminating disease severity in hospitalized children with CAP, whereas WBC count and ANC have limited ability. No biomarkers or cytokines seemed to have the ability to predict the pathogen category, while BALF IL-6, blood ANC, and ESR may assist in the diagnosis of single MP, bacteria, and virus infections, respectively.
Identification of molecular patterns and diagnostic biomarkers in juvenile idiopathic arthritis based on the gene expression of m6A regulators
Authors: Zhang Shibo , Qin Jing , Zhao Yuechao , Wang Jian , Tian Zhiliang
Published: September 2022

The role of N6-methyladenosine modification in immunity is increasingly being appreciated. However, the landscape of m6A regulators in juvenile idiopathic arthritis (JIA) is poorly understood. Thus, this study explored the impact of m6A modification and related lncRNAs in JIA immune microenvironment. Fourteen m6A regulators and eight lncRNAs were identified as potential diagnostic biomarkers for JIA. Two diagnostic models for JIA were also constructed. The putative molecular regulatory mechanism of FTO-mediated m6A modification in JIA was hypothesized. Three distinct m6A patterns mediated by 26 m6A regulators and three diverse lncRNA clusters mediated by 405 lncRNAs were thoroughly investigated. They exhibited dramatically diverse immune microenvironments and expression of HLA genes. The identification of two separate subtypes of enthesitis-related arthritis implies that our work may aid in the establishment of a more precise categorization system for JIA. m6A modification-related genes were obtained, and their underlying biological functions were explored. The m6Ascore system developed for individual JIA patients may be utilized to evaluate the immunological state or molecular pattern, thereby offering therapy recommendations. In short, through the investigation of the m6A regulators in JIA, the current work may contribute to our knowledge of the pathophysiology of JIA.
Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistance via regulating GLUT4 translocation in diabetic mice
Authors: Ye Zimengwei , Ma Jinkun , Liu Yage , Xu Bingrui , Dai Xuan , Fu Min , Tian Tian , Sui Xin , Mo Fangfang , Gao Sihua , Zhao Dandan , Zhang Dongwei
Published: September 2022

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.
Remdesivir in treating hospitalized patients with COVID-19: A renewed review of clinical trials
Authors: Wu Zhenchao , Han Zhifei , Liu Beibei , Shen Ning
Published: September 2022

Since December 2019, COVID-19 has spread across the world almost through 2.5 years. As of 16 June 2022, the cumulative number of confirmed cases of COVID-19 worldwide has reached 542.62 million, and the death toll has risen to 6.33 million. With the increasing number of deaths, it is urgent to find effective treatment drugs. Remdesivir, an investigational broad-spectrum antiviral drug produced by Gilead has been shown to inhibit SARS-CoV-2, in vitro and in vivo. This review is aimed to analyze the feasibility of remdesivir in COVID-19 and put forward the shortcomings of present clinical studies. We systematically searched PubMed and Web of Science up until 24 May 2022, using several specific terms such as “remdesivir” or “GS-5734” and “COVID-19” or “SARS-CoV-2” and retrieved basic researches and clinical studies of remdesivir in COVID-19. In this review, we summarized and reviewed the mechanism of remdesivir in SARS-COV-2, clinical trials of using remdesivir in COVID-19, analyzed the efficacy and safety of remdesivir, and judged whether the drug was effective for the treatment of COVID-19. In different clinical trials, remdesivir showed a mixed result in the treatment of COVID-19. It seemed that remdesivir shortened the time to recovery and had an acceptable safety profile. However, more clinical trials are needed to test the efficacy and safety of remdesivir.
Success of social inequality measures in predicting critical or failure points in some models of physical systems
Authors: Ghosh Asim , Biswas Soumyajyoti , Chakrabarti Bikas K.
Published: September 2022

Statistical physicists and social scientists both extensively study some characteristic features of the unequal distributions of energy, cluster, or avalanche sizes and of income, wealth, etc., among the particles (or sites) and population, respectively. While physicists concentrate on the self-similar (fractal) structure (and the characteristic exponents) of the largest (percolating) cluster or avalanche, social scientists study the inequality indices such as Gini and Kolkata, given by the non-linearity of the Lorenz function representing the cumulative fraction of the wealth possessed by different fractions of the population. Here, using results from earlier publications and some new numerical and analytical results, we reviewed how the above-mentioned social inequality indices, when extracted from the unequal distributions of energy (in kinetic exchange models), cluster sizes (in percolation models), or avalanche sizes (in self-organized critical or fiber bundle models) can help in a major way in providing precursor signals for an approaching critical point or imminent failure point. Extensive numerical and some analytical results have been discussed.
Upregulation of P2X3 receptors in primary afferent pathways involves in colon-to-bladder cross-sensitization in rats
Authors: Dong XingYou , Yang Yang , Luo Shengjun , Deng Xiaohong , Tang Wei
Published: September 2022

Background: Clinical investigation indicates a high level of co-morbidity between bladder overactivity and irritable bowel syndrome. The cross-sensitization of afferent pathways has been demonstrated to be the main reason for the cross-organ sensitization, but the underlying mechanism is unclear.

Methods: A single dose of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) was applied to induce the colitis rat models by intracolonic administration. All rats were randomly divided into three groups: control, TNBS-3-day, and TNBS-7-day groups. Western blot and immunofluorescent staining were performed to detect the expression of the P2X3 receptor. The spontaneous contractions of the detrusor strip were measured to evaluate the detrusor contractility function. The micturition function was measured by a cystometry experiment. The intercontractile interval (ICI) and maximum bladder pressure (BP) were recorded.

Results: The distal colon from colitis showed serious tissue damage or chronic inflammation after TNBS instillation (p < 0.01). However, there were no detectable histological changes in bladder among groups (p > 0.05). TNBS-induced colitis significantly increased P2X3 receptor expression on the myenteric and submucosal plexus of the distal colon and urothelium of the bladder, especially at day 3 post-TNBS (p < 0.05). Meanwhile, the expression of the P2X3 receptor on DRG neurons was increased in TNBS-induced colitis (p < 0.01). The detrusor strip of rats exhibited detrusor overactivity after days 3 and 7 of TNBS administration (p < 0.01), but inhibition of the P2X3 receptor had no effect (p > 0.05). Moreover, the rats with colitis exhibited the micturition pattern of bladder overactivity, manifested by decreased ICI and increased maximum BP (p < 0.05). Interestingly, inhibition of the P2X3 receptor by intrathecal injection of A-317491 alleviated bladder overactivity evoked by TNBS-induced colitis (p < 0.05).

Conclusion: The upregulation of the P2X3 receptor in an afferent pathway involved in bladder overactivity evoked by TNBS-induced colonic inflammation, suggesting that the P2X3 receptor antagonist may be an available and novel strategy for the control of bladder overactivity.
Engineering the N-glycosylation pathway of Nicotiana tabacum for molecular pharming using CRISPR/Cas9
Authors: Göritzer Kathrin , Grandits Melanie , Grünwald-Gruber Clemens , Figl Rudolf , Mercx Sébastien , Navarre Catherine , Ma Julian K-C. , Teh Audrey Y-H.
Published: September 2022

Molecular pharming in plants offers exciting possibilities to address global access to modern biologics. However, differences in the N-glycosylation pathway including the presence of β(1,2)-xylose and core α(1,3)-fucose can affect activity, potency and immunogenicity of plant-derived proteins. Successful glycoengineering approaches toward human-like structures with no changes in plant phenotype, growth, or recombinant protein expression levels have been reported for Arabidopsis thaliana and Nicotiana benthamiana. Such engineering of N-glycosylation would also be desirable for Nicotiana tabacum, which remains the crop of choice for recombinant protein pharmaceuticals required at massive scale and for manufacturing technology transfer to less developed countries. Here, we generated N. tabacum cv. SR-1 β(1,2)-xylosyltransferase (XylT) and α(1,3)-fucosyltransferase (FucT) knockout lines using CRISPR/Cas9 multiplex genome editing, targeting three conserved regions of the four FucT and two XylT genes. These two enzymes are responsible for generating non-human N-glycan structures. We confirmed full functional knockout of transformants by immunoblotting of total soluble protein by antibodies recognizing β(1,2)-xylose and core α(1,3)-fucose, mass spectrometry analysis of recombinantly produced VRC01, a broadly neutralizing anti-HIV-1 hIgG1 antibody, and Sanger sequencing of targeted regions of the putative transformants. These data represent an important step toward establishing Nicotiana tabacum as a biologics platform for Global Health.