bluuebunny/crossref_metadata_2025 huggingface dataset:
Current knowledge of the immune reconstitution inflammatory syndrome in Whipple disease: a review
Authors: Song Xiangyi , Duan Ruifeng , Duan Liwei , Wei Lijuan
Published: October 2023

Immune reconstitution inflammatory syndrome (IRIS) is characterized by exaggerated and dysregulated inflammatory responses that occur as a result of reconstitution of adaptive or innate immunity. A wide range of microorganisms have been found to be associated with IRIS, such as human immunodeficiency virus (HIV), Mycobacterium and actinobacteria. Whipple disease (WD) is an infectious disorder caused by the Gram-positive bacterium Tropheryma whipplei (T. whipplei) and IRIS also serves as a complication during its treament. Although many of these pathological mechanisms are shared with related inflammatory disorders, IRIS in WD exhibits distinct features and is poorly described in the medical literature. Novel investigations of the intestinal mucosal immune system have provided new insights into the pathogenesis of IRIS, elucidating the interplay between systemic and local immune responses. These insights may be used to identify monitoring tools for disease prevention and to develop treatment strategies. Therefore, this review synthesizes these new concepts in WD IRIS to approach the feasibility of manipulating host immunity and immune reconstitution of inflammatory syndromes from a newer, more comprehensive perspective and study hypothetical options for the management of WD IRIS.
Causal atlas between inflammatory bowel disease and mental disorders: a bi-directional 2-sample Mendelian randomization study
Authors: Yang Xiaorong , Yang Lejin , Zhang Tongchao , Zhang Hong , Chen Hui , Zuo Xiuli
Published: October 2023

Background

The brain-gut axis link has attracted increasing attention, with observational studies suggesting that the relationship between common mental disorders and inflammatory bowel disease (IBD) may run in both directions. However, so far, it is not clear whether there is causality and in which direction.

Methods

We conducted a bidirectional 2-sample Mendelian randomization study to investigate the relationship between IBD, including Crohn’s disease (CD) and ulcerative colitis (UC), and mental disorders, using summary-level GWAS data. The main analysis was the inverse variance weighted method. IBD (including CD and UC), and nine mental disorders were used as both exposures and outcomes.

Results

We found that UC could significantly lead to obsessive-compulsive disorder, attention deficit hyperactivity disorder, and autism spectrum disorder, with odds ratio (OR) of 1.245 (95% confidence intervals [CI]: 1.069-1.450; P=0.008), 1.050 (95%CI: 1.023-1.077; P=2.42×10-4), and 1.041 (95%CI: 1.015-1.068; P=0.002) respectively. In addition, we found that bipolar disorder and schizophrenia could increase the odds of IBD, with OR values of 1.138 (95%CI: 1.084-1.194; P=1.9×10-7), and 1.115 (95%CI: 1.071-1.161; P=1.12×10-7), respectively. Our results also indicate that obsessive-compulsive disorder could lead to IBD, especially for UC, with OR values of 1.091 (95%CI: 1.024-1.162; P=0.009), and 1.124 (95%CI: 1.041-1.214; P=0.004), respectively.

Conclusions

Our findings indicate that the brain-gut axis involves the association between IBD, especially UC, and some mental disorders, which guides the targeted prevention, management, and mechanism exploration of these diseases.
Research progress of single-cell sequencing in tuberculosis
Authors: Pan Jiahui , Chang Zecheng , Zhang Xinyue , Dong Qinzhou , Zhao He , Shi Jingwei , Wang Guoqing
Published: October 2023

Tuberculosis is a major infectious disease caused by Mycobacterium tuberculosis infection. The pathogenesis and immune mechanism of tuberculosis are not clear, and it is urgent to find new drugs, diagnosis, and treatment targets. A useful tool in the quest to reveal the enigmas related to Mycobacterium tuberculosis infection and disease is the single-cell sequencing technique. By clarifying cell heterogeneity, identifying pathogenic cell groups, and finding key gene targets, the map at the single cell level enables people to better understand the cell diversity of complex organisms and the immune state of hosts during infection. Here, we briefly reviewed the development of single-cell sequencing, and emphasized the different applications and limitations of various technologies. Single-cell sequencing has been widely used in the study of the pathogenesis and immune response of tuberculosis. We review these works summarizing the most influential findings. Combined with the multi-molecular level and multi-dimensional analysis, we aim to deeply understand the blank and potential future development of the research on Mycobacterium tuberculosis infection using single-cell sequencing technology.
Microbiome variability in invasive coral (Tubastraea aurea) in response to diverse environmental stressors
Authors: Girija Gowri Krishna , Tseng Li-Chun , Chen Yu-Ling , Meng Pei-Jie , Hwang Jiang-Shiou , Ho Ying-Ning
Published: October 2023

The Indo-Pacific native azooxanthellate Tubastraea (Scleractinia) has been identified as an invasive marine species with substantial environmental, economic, and social implications worldwide. Despite their exceptional invasive capacity, our understanding of the role of their symbiotic microbiota in host resilience, as well as their response to ambient environmental conditions, remains limited. In this study, we analyzed the symbiotic bacterial communities found in the tissue and mucus of Tubastraea aurea from different habitats along the northeastern coast of Taiwan. These habitats included two extreme sites (a hydrothermal vent [HV] and a copper mining [CM] site) and two normal environments (inlet of a nuclear power plant [NPP] and a habitat adjacent to a conservation zone [CZ]). We employed full-length 16S rRNA sequencing (~1.5 kilobases) to determine coral-associated microbiome responses to local environments. Results showed significant variations in bacterial communities between corals from extreme and normal habitats. Chemoheterotrophic Endozoicomonas bacteria dominated the tissue samples from the HV and CM sites, whereas phototrophic Synechococcus cyanobacteria dominated the NPP and CZ sites. Hydrographic parameters such as pH, salinity, biological oxygen demand, turbidity, and concentration of heavy metals (e.g., Cu and Fe) increased at the HV and CM sites compared with those at the NPP and CZ sites. This difference created more stressful conditions at the HV and CM sites. The microbial assemblages associated with T. aurea exhibited a prevalence of diverse symbiotic bacteria that could potentially contribute to the host’s ability to adapt and survive in challenging ecological conditions. Therefore, these advantageous microorganisms, along with the host’s physiological mechanisms of dispersion, range expansion, and invasiveness, may enhance the resilience and ability of T. aurea to thrive in extreme environments.
Emerging technologies for advancing microalgal photosynthesis and metabolism toward sustainable production
Authors: Hu Jingyan , Meng Weizhao , Su Yixi , Qian Cheng , Fu Weiqi
Published: October 2023

Microalgae are unicellular photosynthetic microorganisms that play a vital role in primary production and have diverse applications in various industries. They have high photosynthetic and metabolic capacities and can produce a variety of valuable metabolites, such as lipids, carbohydrates, pigments, and proteins. However, practical applications of microalgae are limited to high-value products due to the high production costs. Algal biotechnology faces challenges such as low energy utilization efficiency and product yield that are currently inadequate to fulfill commercial production. To overcome these challenges, emerging technologies have shown promise to achieve higher production efficiency, including molecular manipulation of photosynthetic efficiency and metabolic activities. Here, we provided an overview of the importance, diversity, and photosynthesis of microalgae, as well as strategies for enhancing their photosynthetic efficiency. We discussed various approaches for improving microalgal photosynthesis, including strain selection and optimization, rational genetic modification, and innovative technologies such as spectral recomposition of light, nanomaterials, advanced cultivation systems, and symbiotic systems. Additionally, we summarized metabolic engineering strategies that focus on optimizing the synthesis of value-added metabolites, such as pigments, long-chain polyunsaturated fatty acids, starch, proteins, and hydrogen in microalgae. By concentrating on improving photosynthetic efficiency and the synthesis of bioactive metabolites, this review provided valuable insights into enhancing microalgae production yields. Overcoming limitations in microalgae production costs can lead to broader applications in various industries. Furthermore, we highlight the potential of these strategies in increasing the efficiency of microalgae as a sustainable source for high-value products.
Alternative mitigating solutions based on inorganic nanoparticles for the preservation of cultural heritage
Authors: Corbu Viorica Maria , Dumbravă Andreea Ştefania , Marinescu Liliana , Motelica Ludmila , Chircov Cristina , Surdu Adrian Vasile , Gheorghe-Barbu Irina , Pecete Ionuţ , Balotescu Irina , Popa Marcela , Marinas Ioana Cristina , Ianovici Nicoleta , Ciobanu Daniela-Georgiana , Dițu Lia Mara , Ficai Denisa , Oprea Ovidiu Cristian , Ficai Anton , Eugenia Șesan Tatiana , Chifiriuc Mariana Carmen
Published: October 2023

Introduction: Biodeterioration is a big challenge for the preservation of cultural heritage objects and for the community’s safety, fostering the search for novel methods effective in removing microbial biofilms and subsequent biodeterioration. In this context, nanoparticles (NPs) are considered an interesting alternative, based on their unique physico-chemical and biological properties.

Methods: The present study aimed to evaluate the antimicrobial efficiency of Ag, Au, Cu, and ZnO NPs against a significant number of filamentous fungi and bacterial strains isolated from wooden and stone cultural heritage objects from different Romanian regions, as well as from museum collections, with the final goal to establish their potential to develop novel preservation strategies, which have high efficiency and low ecotoxicity.

Results: Six types of nanoparticles (NPs) based on Ag, Au, Cu, and ZnO were synthesized and characterized for their physico-chemical properties, ecotoxicity, and efficacy against 75 filamentous fungi and 17 bacterial strains isolated from wooden and stone cultural heritage objects (15th–19th century). The results showed that all synthetized NPs are homogeneous, demonstrating a good stabilizing coating, and have spherical or triangular shapes, with sizes between 9 and 25 nm. The highest antifungal efficiency has been recorded for Ag NPs, followed by Cu NPs and ZnO NPs, with the most susceptible strains being Aspergillus montevidensis, Penicillium commune, Penicillium corylophilum, Bacillus megaterium, and B. cereus. The Cu NPs and ZnO NPs decreased the capacity of microbial strains to adhere to the inert substratum. The influence of the tested NPs against enzyme/organic acid production varied depending on the NP types and by species.

Conclusion: The obtained results are promising for the development of efficient and economical alternative solutions for heritage preservation, showing high antimicrobial activity against the prevalent fungal and bacterial strains involved in the biodeterioration of Romanian heritage objects.
Evaluating lightweight gear transmission error: a novel nonlinear finite element approach using direct constraint contact algorithm
Authors: Masmoudi Wael , Wojtowicki Jean-Luc , Petrone Giuseppe , Franco Francesco , De Rosa Sergio
Published: October 2023

With the growing demand for lightweight gear transmission systems, composite materials have emerged as a promising solution due to their high specific properties. However, the complexity of designing gear pairs with composite materials necessitates the development of reliable numerical procedures. This study presents a robust numerical approach using a flexible multibody method through the MSC MARC solver to accurately estimate static transmission error (STE) in lightweight gears, considering the nonlinear behavior caused by gear contact. The Finite Element (FE) model uses the Multi-Point Constraint equations (MPCs) to ensure the non-penetration condition considering a node-to-surface contact detection. The proposed method is compared against commercial software for standard gear pair cases, demonstrating its effectiveness in addressing complex structures based on composite materials. The numerical procedure is further applied to analyze hybrid metal-composite gear pairs and compared to a holed one. The results provide insights into the time evolution and harmonic components of STE, highlighting the advantages of hybrid gears in terms of reduced vibrations and noise for the same mass reduction compared to holed gears. Additionally, ply arrangements resulting in quasi-isotropic properties of the composite disc are compared to unidirectional laminates to highlight the fiber orientation effect on the STE results.
Application of a flipped classroom teaching model based on micro-videos in the standardized training of dermatological residents in China
Authors: Li Yang , Tang Xian-fa , Cheng Hui
Published: October 2023

Objective

To explore the effects of a micro-video-based flipped classroom teaching model on the standardized training of dermatological residents in China.

Methods

A total of 78 residents who had received standardized training at the Department of Dermatology of the First Affiliated Hospital of Anhui Medical University were selected and randomly divided into an experimental group (39 residents) and a control group (39 residents). The experimental group received micro-video-based flipped classroom teaching, whereas the control group received traditional lecture-based classroom teaching. Scores relating to theoretical knowledge of dermatology, clinical practice skills, and the results of a questionnaire survey were used to evaluate the teaching effects.

Results

The average score of the experimental group in the theoretical knowledge test (88.56 ± 5.80) was significantly higher than that of the control group (81.90 ± 7.45). Similarly, the average score of the experimental group in the clinical practice skills test (85.44 ± 5.97) was also significantly higher than that of the control group (78.46 ± 5.94). The results of the questionnaire survey showed that the experimental group exhibited significant improvements in learning interest, mastery of teaching content, communication skills, expression skills, clinical practice skills, autonomous learning, clinical thinking, clinical application, and team cooperation.

Conclusion

Flipped classroom teaching based on micro-videos helped to improve the teaching effects of theoretical knowledge, clinical practice skills, and residents’ comprehensive ability during dermatological residents’ standardized training.
A thermostable organic solvent-tolerant lipase from Brevibacillus sp.: production and integrated downstream processing using an alcohol-salt-based aqueous two-phase system
Authors: Leykun Senaite , Johansson Eva , Vetukuri Ramesh Raju , Ceresino Elaine Berger , Gessesse Amare
Published: October 2023

Lipases are used for the synthesis of different compounds in the chemical, pharmaceutical, and food industries. Most of the reactions are carried out in non-aqueous media and often at elevated temperature, requiring the use of organic solvent-tolerant thermostable lipases. However, most known lipases are not stable in the presence of organic solvents and at elevated temperature. In this study, an organic solvent-tolerant thermostable lipase was obtained from Brevibacillus sp. SHI-160, a moderate thermophile isolated from a hot spring in the East African Rift Valley. The enzyme was optimally active at 65°C and retained over 90% of its activity after 1 h of incubation at 70°C. High lipase activity was measured in the pH range of 6.5 to 9.0 with an optimum pH of 8.5. The enzyme was stable in the presence of both polar and non-polar organic solvents. The stability of the enzyme in the presence of polar organic solvents allowed the development of an efficient downstream processing using an alcohol-salt-based aqueous two-phase system (ATPS). Thus, in the presence of 2% salt, over 98% of the enzyme partitioned to the alcohol phase. The ATPS-recovered enzyme was directly immobilized on a solid support through adsorption and successfully used to catalyze a transesterification reaction between paranitrophenyl palmitate and short-chain alcohols in non-aqueous media. This shows the potential of lipase SHI-160 to catalyze reactions in non-aqueous media for the synthesis of valuable compounds. The integrated approach developed for enzyme production and cheap and efficient downstream processing using ATPS could allow a significant reduction in enzyme production costs. The results also show the potential of extreme environments in the East African Rift Valley as sources of valuable microbial genetic resources for the isolation of novel lipases and other industrially important enzymes.
Phylogenetic distribution of malonate semialdehyde decarboxylase (MSAD) genes among strains within the genus Mycobacterium: evidence of MSAD gene loss in the evolution of pathogenic mycobacteria
Authors: Lee Duhyung , Kim Dong Hyun , Seo Hyejun , Choi Seaone , Kim Bum-Joon
Published: October 2023

Despite the great diversity of malonate semialdehyde decarboxylases (MSADs), one of five subgroups of the tautomerase superfamily (TSF) found throughout the biosphere, their distribution among strains within the genus Mycobacterium remains unknown. In this study, we sought to investigate the phylogenetic distribution of MSAD genes of mycobacterial species via genome analysis of 192 different reference Mycobacterium species or subspecies retrieved from NCBI databases. We found that in a total of 87 of 192 strains (45.3%), MSAD-1 and MSAD-2 were distributed in an exclusive manner among Mycobacterium species except for 12 strains, including Mycobacterium chelonae members, with both in their genome. Of note, Mycobacterium strains better adapted to the host and of high virulence potential, such as the Mycobacterium tuberculosis complex, Mycobacterium leprae, Mycobacterium marinum, Mycobacterium ulcerans, and Mycobacterium avium subsp. paratuberculosis, had no orthologs of MSAD in their genome, suggesting MSAD loss during species differentiation in pathogenic slow-growing Mycobacterium. To investigate the MSAD distribution among strains of M. avium subspecies, the genome sequences of a total of 255 reference strains from the four subspecies of M. avium (43 of subspecies avium, 162 of subspecies hominissuis, 49 of subspecies paratuberculosis, and 1 of subspecies silvaticum) were further analyzed. We found that only 121 of 255 strains (47.4%) had MSADs in their genome, with none of the 49 M. avium subsp. paratuberculosis strains having MSAD genes. Even in 13 of 121 M. avium strains with the MSAD-1 gene in their genome, deletion mutations in the 98th codon causing premature termination of MSAD were found, further highlighting the occurrence of MSAD pseudogenization during species or subspecies differentiation of M. avium. In conclusion, our data indicated that there are two distinct types of MSADs, MSAD-1 and MSAD-2, among strains in the Mycobacterium genus, but more than half of the strains, including pathogenic mycobacteria, M. tuberculosis and M. leprae, have no orthologs in their genome, suggesting MSAD loss during host adaptation of pathogenic mycobacteria. In the future, the role of two distinct MSADs, MSAD-1 and MSAD-2, in mycobacterial pathogenesis or evolution should be investigated.
The chemistry of gut microbiome-derived lipopolysaccharides impacts on the occurrence of food allergy in the pediatric age
Authors: Di Lorenzo Flaviana , Paparo Lorella , Pisapia Laura , Oglio Franca , Pither Molly Dorothy , Cirella Roberta , Nocerino Rita , Carucci Laura , Silipo Alba , de Filippis Francesca , Ercolini Danilo , Molinaro Antonio , Berni Canani Roberto
Published: October 2023

Introduction: Food allergy (FA) in children is a major health concern. A better definition of the pathogenesis of the disease could facilitate effective preventive and therapeutic measures. Gut microbiome alterations could modulate the occurrence of FA, although the mechanisms involved in this phenomenon are poorly characterized. Gut bacteria release signaling byproducts from their cell wall, such as lipopolysaccharides (LPSs), which can act locally and systemically, modulating the immune system function.

Methods: In the current study gut microbiome-derived LPS isolated from fecal samples of FA and healthy children was chemically characterized providing insights into the carbohydrate and lipid composition as well as into the LPS macromolecular nature. In addition, by means of a chemical/MALDI-TOF MS and MS/MS approach we elucidated the gut microbiome-derived lipid A mass spectral profile directly on fecal samples. Finally, we evaluated the pro-allergic and pro-tolerogenic potential of these fecal LPS and lipid A by harnessing peripheral blood mononuclear cells from healthy donors.

Results: By analyzing fecal samples, we have identified different gut microbiome-derived LPS chemical features comparing FA children and healthy controls. We also have provided evidence on a different immunoregulatory action elicited by LPS on peripheral blood mononuclear cells collected from healthy donors suggesting that LPS from healthy individuals could be able to protect against the occurrence of FA, while LPS from children affected by FA could promote the allergic response.

Discussion: Altogether these data highlight the relevance of gut microbiome-derived LPSs as potential biomarkers for FA and as a target of intervention to limit the disease burden.
Sex-specific relationship between non-alcoholic fatty liver disease and amyloid-β in cognitively unimpaired individuals
Authors: Kang Sung Hoon , Yoo Heejin , Cheon Bo Kyoung , Kim Jun Pyo , Jang Hyemin , Kim Hee Jin , Kang Mira , Oh Kyungmi , Koh Seong-Beom , Na Duk L. , Chang Yoosoo , Seo Sang Won
Published: October 2023

Background

Non-alcoholic fatty liver disease (NAFLD) is known to be associated with a high risk of clinically diagnosed Alzheimer’s disease (AD). Additionally, the prevalence of NAFLD and AD is higher in elderly females than in males. However, a sex-specific association between NAFLD and amyloid-beta (Aβ) deposition remains unclear. Therefore, we investigated the sex-specific relationship between NAFLD and Aβ deposition in a large-sized cohort of cognitively unimpaired (CU) individuals.

Methods

We enrolled 673 (410 [60.9%] females and 263 [39.1%] males) CU individuals aged ≥45 years who underwent Aβ positron emission tomography (PET). The presence of NAFLD, assessed using the hepatic steatosis index, and the severity of NAFLD, assessed using the Fibrosis-4 index, were considered predictors. Aβ deposition on PET was considered as an outcome.

Results

Females had a higher frequency of NAFLD than males (48 and 23.2%, p < 0.001). Among females, the presence of NAFLD (β = 0.216, p < 0.001) was predictive of increased Aβ deposition, whereas among males, the presence of NAFLD (β = 0.191, p = 0.064) was not associated with Aβ deposition. Among females, the presence of NAFLD with low (β = 0.254, p = 0.039), intermediate (β = 0.201, p = 0.006), and high fibrosis (β = 0.257, p = 0.027) was predictive of increased Aβ deposition. Aβ deposition also increased as the severity of NAFLD increased in females (p for trend = 0.001).

Conclusion

We highlight the marked influence of NAFLD and its severity on the risk of Aβ deposition in relation to sex. Furthermore, our findings suggest that sex-specific strategies regarding the management of NAFLD are necessary for the prevention of Aβ deposition.
Computational assessment of visual coding across mouse brain areas and behavioural states
Authors: Xie Yizhou , Sadeh Sadra
Published: October 2023

Introduction

Our brain is bombarded by a diverse range of visual stimuli, which are converted into corresponding neuronal responses and processed throughout the visual system. The neural activity patterns that result from these external stimuli vary depending on the object or scene being observed, but they also change as a result of internal or behavioural states. This raises the question of to what extent it is possible to predict the presented visual stimuli from neural activity across behavioural states, and how this varies in different brain regions.

Methods

To address this question, we assessed the computational capacity of decoders to extract visual information in awake behaving mice, by analysing publicly available standardised datasets from the Allen Brain Institute. We evaluated how natural movie frames can be distinguished based on the activity of units recorded in distinct brain regions and under different behavioural states. This analysis revealed the spectrum of visual information present in different brain regions in response to binary and multiclass classification tasks.

Results

Visual cortical areas showed highest classification accuracies, followed by thalamic and midbrain regions, with hippocampal regions showing close to chance accuracy. In addition, we found that behavioural variability led to a decrease in decoding accuracy, whereby large behavioural changes between train and test sessions reduced the classification performance of the decoders. A generalised linear model analysis suggested that this deterioration in classification might be due to an independent modulation of neural activity by stimulus and behaviour. Finally, we reconstructed the natural movie frames from optimal linear classifiers, and observed a strong similarity between reconstructed and actual movie frames. However, the similarity was significantly higher when the decoders were trained and tested on sessions with similar behavioural states.

Conclusion

Our analysis provides a systematic assessment of visual coding in the mouse brain, and sheds light on the spectrum of visual information present across brain areas and behavioural states.
Biallelic pathogenic variants in POLR3D alter tRNA transcription and cause a hypomyelinating leukodystrophy: A case report
Authors: Macintosh Julia , Perrier Stefanie , Pinard Maxime , Tran Luan T. , Guerrero Kether , Prasad Chitra , Prasad Asuri N. , Pastinen Tomi , Thiffault Isabelle , Coulombe Benoit , Bernard Geneviève
Published: October 2023

RNA polymerase III-related leukodystrophy (POLR3-related leukodystrophy) is a rare, genetically determined hypomyelinating disease arising from biallelic pathogenic variants in genes encoding subunits of RNA polymerase III (Pol III). Here, we describe the first reported case of POLR3-related leukodystrophy caused by biallelic pathogenic variants in POLR3D, encoding the RPC4 subunit of Pol III. The individual, a female, demonstrated delays in walking and expressive and receptive language as a child and later cognitively plateaued. Additional neurological features included cerebellar signs (e.g., dysarthria, ataxia, and intention tremor) and dysphagia, while non-neurological features included hypodontia, hypogonadotropic hypogonadism, and dysmorphic facial features. Her MRI was notable for diffuse hypomyelination with myelin preservation of early myelinating structures, characteristic of POLR3-related leukodystrophy. Exome sequencing revealed the biallelic variants in POLR3D, a missense variant (c.541C > T, p.P181S) and an intronic splice site variant (c.656-6G > A, p.?). Functional studies of the patient’s fibroblasts demonstrated significantly decreased RNA-level expression of POLR3D, along with reduced expression of other Pol III subunit genes. Notably, Pol III transcription was also shown to be aberrant, with a significant decrease in 7SK RNA and several distinct tRNA genes analyzed. Affinity purification coupled to mass spectrometry of the POLR3D p.P181S variant showed normal assembly of Pol III subunits yet altered interaction of Pol III with the PAQosome chaperone complex, indicating the missense variant is likely to alter complex maturation. This work identifies biallelic pathogenic variants in POLR3D as a novel genetic cause of POLR3-related leukodystrophy, expanding the molecular spectrum associated with this disease, and proposes altered tRNA homeostasis as a factor in the underlying biology of this hypomyelinating disorder.
Hearing loss, depression, and cognition in younger and older adult CI candidates
Authors: Huber Maria , Reuter Lisa , Weitgasser Lennart , Pletzer Belinda , Rösch Sebastian , Illg Angelika
Published: October 2023

Background and Aim

Hearing loss in old age is associated with cognitive decline and with depression. Our study aimed to investigate the relationship between hearing loss, cognitive decline, and secondary depressive symptoms in a sample of younger and older cochlear implant candidates with profound to severe hearing loss.

Methods

This study is part of a larger cohort study designated to provide information on baseline data before CI. Sixty-one cochlear implant candidates with hearing loss from adulthood onwards (>18 years) were enrolled in this study. All had symmetrical sensorineural hearing loss in both ears (four-frequency hearing threshold difference of no more than 20 dB, PTA). Individuals with primary affective disorders, psychosis, below-average intelligence, poor German language skills, visual impairment, and a medical diagnosis with potential impact on cognition (e.g., neurodegenerative diseases,) were excluded. Four-frequency hearing thresholds (dB, PTA, better ear) were collected. Using the Abbreviated Profile of Hearing Aid Benefit, we assessed subjective hearing in noise. Clinical and subclinical depressive symptoms were assessed with the Beck Depression Inventory (BDI II). Cognitive status was assessed with a neurocognitive test battery.

Results

Our findings revealed a significant negative association between subjective hearing in noise (APHAB subscale “Background Noise”) and BDII. However, we did not observe any link between hearing thresholds, depression, and cognition. Additionally, no differences emerged between younger (25–54 years) and older subjects (55–75 years). Unexpectedly, further unplanned analyses unveiled correlations between subjective hearing in quiet environments (APHAB) and cognitive performance [phonemic fluency (Regensburg Word Fluency), cognitive flexibility (TMTB), and nonverbal episodic memory (Nonverbal Learning Test), as well as subjective hearing of aversive/loud sounds (APHAB)], cognitive performance [semantic word fluency (RWT), and inhibition (Go/Nogo) and depression]. Duration of hearing loss and speech recognition at quiet (Freiburg Monosyllables) were not related to depression and cognitive performance.

Conclusion

Impact of hearing loss on mood and cognition appears to be independent, suggesting a relationship with distinct aspects of hearing loss. These results underscore the importance of considering not only conventional audiometric measures like hearing thresholds but also variables related to hearing abilities during verbal communication in everyday life, both in quiet and noisy settings.
The shared genetic risk factors between Tourette syndrome and obsessive-compulsive disorder
Authors: Khoodoruth Mohamed Adil Shah , Ahammad Foysal , Khan Yasser Saeed , Mohammad Farhan
Published: October 2023

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) are two neuropsychiatric disorders that frequently co-occur. Previous evidence suggests a shared genetic diathesis underlying the comorbidity of TS and OCD. This review aims to comprehensively summarize the current literature on the genetic factors linked with TS and its comorbidities, with a focus on OCD. Family studies, linkage analysis, cytogenetic studies, and genome-wide association studies (GWAS) have played a pivotal role in identifying common and rare genetic variants connected with TS and OCD. Although the genetic framework of TS and OCD is complex and multifactorial, several susceptibility loci and candidate genes have been identified that might play a crucial role in the pathogenesis of both disorders. Additionally, post-infectious environmental elements have also been proposed to contribute to the development of TS-OCD, although the dynamics between genetic and environmental factors is not yet fully understood. International collaborations and studies with well-defined phenotypes will be crucial in the future to further elucidate the genetic basis of TS and OCD and to develop targeted therapeutic strategies for individuals suffering from these debilitating conditions.
Thermosensory thalamus: parallel processing across model organisms
Authors: Leva Tobias M. , Whitmire Clarissa J.
Published: October 2023

The thalamus acts as an interface between the periphery and the cortex, with nearly every sensory modality processing information in the thalamocortical circuit. Despite well-established thalamic nuclei for visual, auditory, and tactile modalities, the key thalamic nuclei responsible for innocuous thermosensation remains under debate. Thermosensory information is first transduced by thermoreceptors located in the skin and then processed in the spinal cord. Temperature information is then transmitted to the brain through multiple spinal projection pathways including the spinothalamic tract and the spinoparabrachial tract. While there are fundamental studies of thermal transduction via thermosensitive channels in primary sensory afferents, thermal representation in the spinal projection neurons, and encoding of temperature in the primary cortical targets, comparatively little is known about the intermediate stage of processing in the thalamus. Multiple thalamic nuclei have been implicated in thermal encoding, each with a corresponding cortical target, but without a consensus on the role of each pathway. Here, we review a combination of anatomy, physiology, and behavioral studies across multiple animal models to characterize the thalamic representation of temperature in two proposed thermosensory information streams.
The value of ultrasound measurement of muscle thickness at different sites and shear wave elastography in Parkinson’s disease with sarcopenia: a pilot study
Authors: Chen Minglei , Liu Xiaofang , Liu Qiuwan , Ding Changwei , Zhao Ping , Zhang Yingchun , Mao Chengjie , Liu Chunfeng
Published: October 2023

Background

Patients with Parkinson’s disease (PD) and sarcopenia often exhibit resilience, frailty, disability, and depression, highlighting the complex and interrelated nature of these conditions.

Objective

Despite the presence of clinical manifestations of muscle atrophy in both PD and sarcopenia, accurately discerning the coexistence of sarcopenia in PD patients remains a challenging task with significant implications for treatment strategies and prognostic assessments. This study aims to elucidate the specific ultrasonic diagnostic parameters associated with PD accompanied by sarcopenia through a comparative analysis of muscle ultrasound parameters in patients with PD, thereby presenting a novel approach for rapid identification of this condition.

Methods

A total of 110 participants were enrolled in this study, including patients with PD and control subjects. Demographic data, clinical characteristics, physical performance tests, appendicular skeletal muscle mass index (ASMI), bioelectrical impedance analysis and muscle ultrasound measurements were collected from all participants. The muscle ultrasound measurements encompassed assessments of muscle thickness, pennation angle and shear wave elastography at various anatomical sites.

Results

Parkinson’s disease patients exhibited decreased muscle strength and physical performance, and increased shear wave elastography value. In PD patients with sarcopenia, body circumference, including calf circumference, mid-arm circumference, Waist-to-Hip Ratio and body mass index (BMI) were all significantly decreased. Biceps brachii muscle thickness (MT) and gastrocnemius MT decreased in PD patients with sarcopenia and low ASMI. Binary logistic regression analysis revealed that male PD patients, BMI and gastrocnemius MT were predictive factors for ASMI in PD patients.

Conclusion

Biceps brachii MT and gastrocnemius MT are important indicators for distinguishing whether PD patients have sarcopenia. Male patients, low BMI and gastrocnemius MT were identified as valid predictors of low ASMI in PD patients. The findings of this study provide important insights into the use of muscle ultrasound in the diagnosis of PD with sarcopenia.
The TMEM106B T186S coding variant increases neurite arborization and synaptic density in primary hippocampal neurons
Authors: Nguyen Quynh , Wood Caleb A. , Kim Peter J. , Jankowsky Joanna L.
Published: October 2023

The lysosomal protein TMEM106B was identified as a risk modifier of multiple dementias including frontotemporal dementia and Alzheimer’s disease. The gene comes in two major haplotypes, one associated with disease risk, and by comparison, the other with resilience. Only one coding polymorphism distinguishes the two alleles, a threonine-to-serine substitution at residue 185 (186 in mouse), that is inherited in disequilibrium with multiple non-coding variants. Transcriptional studies suggest synaptic, neuronal, and cognitive preservation in human subjects with the protective haplotype, while murine in vitro studies reveal dramatic effects of TMEM106B deletion on neuronal development. Despite this foundation, the field has not yet resolved whether coding variant is biologically meaningful, and if so, whether it has any specific effect on neuronal phenotypes. Here we studied how loss of TMEM106B or expression of the lone coding variant in isolation affected transcriptional signatures in the mature brain and neuronal structure during development in primary neurons. Homozygous expression of the TMEM106B T186S variant in knock-in mice increased cortical expression of genes associated with excitatory synaptic function and axon outgrowth, and promoted neurite branching, dendritic spine density, and synaptic density in primary hippocampal neurons. In contrast, constitutive TMEM106B deletion affected transcriptional signatures of myelination without altering neuronal development in vitro. Our findings show that the T186S variant is functionally relevant and may contribute to disease resilience during neurodevelopment.
Analysis of some flavonoids for inhibitory mechanism against cancer target phosphatidylinositol 3-kinase (PI3K) using computational tool
Authors: Suhail Mohd , AlZahrani Wejdan M. , Shakil Shazi , Tarique Mohammad , Tabrez Shams , Zughaibi Torki A. , Rehan Mohd
Published: October 2023

Cancer has been one of the leading causes of mortality worldwide over the past few years. Some progress has been made in the development of more effective cancer therapeutics, resulting in improved survival rates. However, the desired outcome in the form of successful treatment is yet to be achieved. There is high demand for the development of innovative, inexpensive, and effective anticancer treatments using natural resources. Natural compounds have been increasingly discovered and used for cancer therapy owing to their high molecular diversity, novel biofunctionality, and minimal side effects. These compounds can be utilized as chemopreventive agents because they can efficiently inhibit cell growth, control cell cycle progression, and block several tumor-promoting signaling pathways. PI3K is an important upstream protein of the PI3K-Akt-mTOR pathway and a well-established cancer therapeutic target. This study aimed to explore the small molecules, natural flavonoids, viz. quercetin, luteolin, kaempferol, genistein, wogonin, daidzein, and flavopiridol for PI3Kγ kinase activity inhibition. In this study, the binding pose, interacting residues, molecular interactions, binding energies, and dissociation constants were investigated. Our results showed that these flavonoids bound well with PI3Kγ with adequate binding strength scores and binding energy ranging from (−8.19 to −8.97 Kcal/mol). Among the explored ligands, flavopiridol showed the highest binding energy of −8.97 Kcal/mol, dock score (−44.40), and dissociation constant term, pKd of 6.58 against PI3Kγ. Based on the above results, the stability of the most promising ligand, flavopiridol, against PI3Kγ was evaluated by molecular dynamics simulations for 200 ns, confirming the stable flavopiridol and PI3Kγ complex. Our study suggests that among the selected flavonoids specifically flavopiridol may act as potential inhibitors of PI3Kγ and could be a therapeutic alternative to inhibit the PI3Kγ pathway, providing new insights into rational drug discovery research for cancer therapy.
Radius additivity score: a novel combination index for tumour growth inhibition in fixed-dose xenograft studies
Authors: Melillo Nicola , Dickinson Jake , Tan Lu , Mistry Hitesh B. , Huber Heinrich J.
Published: October 2023

The effect of combination therapies in many cancers has often been shown to be superior to that of monotherapies. This success is commonly attributed to drug synergies. Combinations of two (or more) drugs in xenograft tumor growth inhibition (TGI) studies are typically designed at fixed doses for each compound. The available methods for assessing synergy in such study designs are based on combination indices (CI) and model-based analyses. The former methods are suitable for screening exercises but are difficult to verify in in vivo studies, while the latter incorporate drug synergy in semi-mechanistic frameworks describing disease progression and drug action but are unsuitable for screening. In the current study, we proposed the empirical radius additivity (Rad-add) score, a novel CI for synergy detection in fixed-dose xenograft TGI combination studies. The Rad-add score approximates model-based analysis performed using the semi-mechanistic constant-radius growth TGI model. The Rad-add score was compared with response additivity, defined as the addition of the two response values, and the bliss independence model in combination studies derived from the Novartis PDX dataset. The results showed that the bliss independence and response additivity models predicted synergistic interactions with high and low probabilities, respectively. The Rad-add score predicted synergistic probabilities that appeared to be between those predicted with response additivity and the Bliss model. We believe that the Rad-add score is particularly suitable for assessing synergy in the context of xenograft combination TGI studies, as it combines the advantages of CI approaches suitable for screening exercises with those of semi-mechanistic TGI models based on a mechanistic understanding of tumor growth.
Safety of sodium-glucose transporter 2 (SGLT-2) inhibitors in patients with type 2 diabetes: a meta-analysis of cohort studies
Authors: Li Chun Xing , Liu Tian Tian , Zhang Qian , Xie Qing , Geng Xu Hua , Man Chun Xia , Li Jia Yi , Mao Xin Ying , Qiao Yue , Liu Hua
Published: October 2023

Aims: This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies.

Methods: A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated.

Results: A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07–1.38, p = 0.003) and GTI (HR: 2.72, 95% CI: 2.48–2.98, p < 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92–1.23, p = 0.42), UTI (HR: 0.99, 95% CI: 0.89–1.10, p = 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94–1.04, p = 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04–1.36, p = 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease.

Conclusion: SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.
Evaluation of anti-inflammatory and immunomodulatory potential of Lawsone (2-hydroxy-1,4-naphthoquinone) using pre-clinical rodent model of rheumatoid arthritis
Authors: Sattar Sara , Shabbir Arham , Shahzad Muhammad , Akhtar Tasleem , Anjum Syed Muneeb , Bourhia Mohammed , Nafidi Hiba-Allah , Bin Jardan Yousef A. , Dauelbait Musaab , Mobashar Aisha
Published: October 2023

Background: Lawsone (2-hydroxy-1,4-naphthoquinone) is naturally present in Lawsonia Inermis and flowers of Eicchornia crassipes. This study assessed the anti-arthritic potential of Lawsone, using FCA-induced Sprague-Dawley rats.

Methods: Arthritic progress was analyzed through a macroscopic scoring scale, measurement of paw edema, and histopathological changes. Effects of Lawsone on mRNA expression levels of inflammatory markers were examined using the reverse transcription PCR technique. ELISA technique was used to evaluate the PGE2 levels. Moreover, levels of biochemical and hematological parameters were also analyzed.

Results: The research elucidated that Lawsone showed an inhibitory potential towards arthritic progress and ameliorated the paw edema. The histopathological analysis also validated the inhibition in arthritic development. Treatment with Lawosne reduced the expression levels of inflammatory markers in rats i.e., VEGF, TNF-α, MMP-2, MMP-3, NF-κB, IL-1β, and IL-6. PGE2 levels (all p < 0.001) were also found reduced in treatment groups. Lab investigations showed improved results of hematological and hepatic parameters in the treated groups as compared to the positive control. This study found no hepatotoxic or nephrotoxic effects of Lawsone in the test doses.

Conclusion: Lawsone possesses an anti-arthritic property which could be ascribed to its immunomodulatory and anti-inflammatory effects.
Quantum commutation relationship for photonic orbital angular momentum
Authors: Saito Shinichi
Published: October 2023

Orbital Angular Momentum (OAM) of photons are ubiquitously used for numerous applications. However, there is a fundamental question whether photonic OAM operators satisfy standard quantum mechanical commutation relationship or not; this also poses a serious concern on the interpretation of an optical vortex as a fundamental quantum degree of freedom. Here, we examined canonical angular momentum operators defined in cylindrical coordinates, and applied them to Laguerre-Gauss (LG) modes in a graded index (GRIN) fibre. We confirmed the validity of commutation relationship for the LG modes and found that ladder operators also work properly with the increment or the decrement in units of the Dirac constant (ℏ). With those operators, we calculated the quantum-mechanical expectation value of the magnitude of angular momentum, which includes contributions from both intrinsic and extrinsic OAM. The obtained results suggest that OAM characterised by the LG modes exhibits a well-defined quantum degree of freedom.