bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological significance of C-reactive protein, the ancient acute phase functionary
Authors: Bhattacharya Shelley , Munshi Chayan
Published: October 2023

C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca2+. The attention regarding the origin of CRP and its multifunctionality has gripped researchers for several decades. The reason can be traced to the integrated evolution of CRP in the animal kingdom. CRP has been unequivocally listed as a key indicator of infectious and inflammatory diseases including autoimmune diseases. The first occurrence of CRP in the evolutionary ladder appeared in arthropods followed by molluscs and much later in the chordates. The biological significance of CRP has been established in the animal kingdom starting from invertebrates. Interestingly, the site of synthesis of CRP is mainly the liver in vertebrates, while in invertebrates it is located in diverse tissues. CRP is a multifunctional player in the scenario of innate immunity. CRP acts as an opsonin in the area of complement activation and phagocytosis. Interestingly, CRP upregulates and downregulates both cytokine production and chemotaxis. Considering various studies of CRP in humans and non-human animals, it has been logically proposed that CRP plays a common role in animals. CRP also interacts with Fcγ receptors and triggers the inflammatory response of macrophages. CRP in other animals such as primates, fish, echinoderms, arthropods, and molluscs has also been studied in some detail which establishes the evolutionary significance of CRP. In mammals, the increase in CRP levels is an induced response to inflammation or trauma; interestingly, in arthropods and molluscs, CRP is constitutively expressed and represents a major component of their hemolymph. Investigations into the primary structure of CRP from various species revealed the overall relatedness between vertebrate and invertebrate CRP. Invertebrates lack an acquired immune response; they are therefore dependent on the multifunctional role of CRP leading to the evolutionary success of the invertebrate phyla.
Influence of age and fitness level on immune responses of T and NK cells in healthy physically active subjects after strenuous aerobic exercise: a cross-sectional study
Authors: Almeida-Neto Paulo Francisco de , Gonçalves Ciro Alexandre Mercês , Wilde Phelipe , Jaggers Jason R. , Júnior Geraldo Barroso Cavalcanti , de Farias Sales Valéria Soraya , Medeiros Radamés Maciel Vitor , Dantas Paulo Moreira Silva , Cabral Breno Guilherme de Araújo Tinôco
Published: October 2023

Aim

The aim of this study is to analyze whether immune responses after strenuous exercise are influenced by chronological age and fitness level in physically active healthy men.

Methods

Cross-sectional study with a sample of 32 physically active men. Participants were divided into two groups based on chronological age (younger: age 21.8 ± 1.8 vs. older: age 34.6 ± 8.3) and subsequently regrouped and divided based on fitness level (More conditioned: excellent and superior VO2max vs. Less conditioned: VO2max: weak, regular and good). Fitness was classified according to VO2max levels obtained by a treadmill test using a gas analyzer. Before and immediately after the ergospirometry test, blood samples were collected for evaluation of immunological markers: leukocytes, neutrophils, lymphocytes and subpopulations.

Results

Chronological age had a moderate effect on CD3+CD4+ lymphocyte count (effect size: 0.204) and CD4/CD8 ratio (effect size: 0.278), favoring older subjects. The level of physical fitness had no significant effect on the analyzed immunological markers.

Conclusions

Immune responses observed immediately after strenuous exercise may be more dependent on chronological age than on fitness level in healthy, physically active men.
Hepatic stellate cell-intrinsic role of SOCS1 in controlling hepatic fibrogenic response and the pro-inflammatory macrophage compartment during liver fibrosis
Authors: Kandhi Rajani , Yeganeh Mehdi , Yoshimura Akihiko , Menendez Alfredo , Ramanathan Sheela , Ilangumaran Subburaj
Published: October 2023

Introduction

Hepatic stellate cells (HSC) become activated, differentiate to myofibroblasts and produce extracellular fibrillar matrix during liver fibrosis. The hepatic fibrogenic response is orchestrated by reciprocal interactions between HSCs and macrophages and their secreted products. SOCS1 can regulate several cytokines and growth factors implicated in liver fibrosis. Here we investigated the role of SOCS1 in regulating HSC activation.

Methods

Mice lacking SOCS1 in HSCs (Socs1ΔHSC) were generated by crossing Socs1fl/fl and LratCre mice. Liver fibrosis was induced by carbon tetrachloride and evaluated by Sirius red staining, hydroxyproline content and immunostaining of myofibroblasts. Gene expression of pro-fibrogenic factors, cytokines, growth factors and chemokines were quantified by RT-qPCR. The phenotype and the numbers of intrahepatic leukocyte subsets were studied by flow cytometry. The impact of fibrosis on the development of diethyl nitrosamine-induced hepatocellular carcinoma was evaluated.

Results

Socs1ΔHSC mice developed more severe liver fibrosis than control Socs1fl/fl mice that was characterized by increased collagen deposition and myofibroblast differentiation. Socs1ΔHSC mice showed a significant increase in the expression of smooth muscle actin, collagens, matrix metalloproteases, cytokines, growth factors and chemokines in the liver following fibrosis induction. The fibrotic livers of Socs1ΔHSC mice displayed heightened inflammatory cell infiltration with increased proportion and numbers of Ly6ChiCCR2+ pro-inflammatory macrophages. This macrophage population contained elevated numbers of CCR2+CX3CR1+ cells, suggesting impaired transition towards restorative macrophages. Fibrosis induction following exposure to diethyl nitrosamine resulted in more numerous and larger liver tumor nodules in Socs1ΔHSC mice than in Socs1fl/fl mice.

Discussion

Our findings indicate that (i) SOCS1 expression in HSCs is a critical to control liver fibrosis and development of hepatocaellular carcinoma, and (ii) attenuation of HSC activation by SOCS1 regulates pro-inflammatory macrophage recruitment and differentiation during liver fibrosis.
Mechanism of regulating macrophages/osteoclasts in attenuating wear particle-induced aseptic osteolysis
Authors: Yin Zhaoyang , Gong Ge , Liu Xinhui , Yin Jian
Published: October 2023

Joint replacement surgery is the most effective treatment for end-stage arthritis. Aseptic loosening caused by periprosthetic osteolysis is a common complication after joint replacement. Inflammation induced by wear particles derived from prosthetic biomaterials is a major cause of osteolysis. We emphasize that bone marrow-derived macrophages and their fusion-derived osteoclasts play a key role in this pathological process. Researchers have developed multiple intervention approaches to regulate macrophage/osteoclast activation. Aiming at wear particle-induced periprosthetic aseptic osteolysis, this review separately discusses the molecular mechanism of regulation of ROS formation and inflammatory response through intervention of macrophage/osteoclast RANKL-MAPKs-NF-κB pathway. These molecular mechanisms regulate osteoclast activation in different ways, but they are not isolated from each other. There is also a lot of crosstalk among the different mechanisms. In addition, other bone and joint diseases related to osteoclast activation are also briefly introduced. Therefore, we discuss these new findings in the context of existing work with a view to developing new strategies for wear particle-associated osteolysis based on the regulation of macrophages/osteoclasts.
Spatial and temporal distribution of fish egg communities in the adjacent waters of Daya Bay nuclear power plant and their relationship with environmental factors
Authors: Tan Zhen , Wu Fengxia , Rao Yiyong , Pan Chuanhao , Hou Gang , Huang Honghui
Published: October 2023

The thermal discharge of Daya Bay Nuclear Power Plant has a certain impact on the ecological environment of the adjacent waters. In order to understand and evaluate changes in the fish egg community structure in the adjacent waters of Daya Bay Nuclear Power Plant and their relationship with environmental factors, four surveys were conducted to investigate fish eggs in January (winter), March (spring), August (summer) and November (autumn) of 2020. A total of 100,985 fish eggs were collected and 17 taxa were identified, belonging to five orders, 14 families and 17 genera. Among them, Perciformes and Clupeiformes were the main contributing taxa to fish egg species and abundance in the waters adjacent to Daya Bay Nuclear Power Plant. The number of fish egg species ranged from high to low was summer, spring, autumn and winter; the average abundance ranged from high to low was spring, summer, winter and autumn. The results showed that except in winter, the average abundance of fish eggs was greater in northeast area than in southwest area. The Shannon-Weiner species diversity index (H’), Pielou evenness index (J’) and Margalef richness index (d) were significantly different between seasons, but none were significantly different between areas. The results of NMDS analysis showed that there were significant differences in fish egg communities between seasons. Surface seawater temperature the average abundance of fish eggs was positively correlated in the results of all four seasons. Although the entrainment effect of nuclear power plant water intake and thermal pollution of partial waters owing to thermal discharge can cause some loss of fish eggs, fish resources can still be effectively maintained.
Effects of immersive virtual reality on sensory overload in a random sample of critically ill patients
Authors: Naef Aileen C. , Gerber Stephan M. , Single Michael , Müri René M. , Haenggi Matthias , Jakob Stephan M. , Jeitziner Marie-Madlen , Nef Tobias
Published: October 2023

Background

Sensory overload and sensory deprivation have both been associated with negative health outcomes in critically ill patients. While there is a lack of any clear treatment or prevention strategies, immersive virtual reality is a promising tool for addressing such problems, but which has not been repetitively tested in random samples. Therefore, this study aimed to determine how critically ill patients react to repeated sessions of immersive virtual reality.

Methods

This exploratory study was conducted in the mixed medical–surgical intermediate care unit of the University Hospital of Bern (Inselspital). Participants (N = 45; 20 women, 25 men; age = 57.73 ± 15.92 years) received two immersive virtual reality sessions via a head-mounted display and noise-canceling headphones within 24 h during their stay in the unit. Each session lasted 30-min and showed a 360-degree nature landscape. Physiological data were collected as part of the participants’ standard care, while environmental awareness, cybersickness, and general acceptance were assessed using a questionnaire designed by our team (1 = not at all, 10 = extremely).

Results

During both virtual reality sessions, there was a significant negative linear relationship found between the heart rate and stimulation duration [first session: r(43) = −0.78, p < 0.001; second session: r(38) = −0.81, p < 0.001] and between the blood pressure and stimulation duration [first session: r(39) = −0.78, p < 0.001; second session: r(30) = −0.78, p < 0.001]. The participants had a high comfort score [median (interquartile range {IQR}) = 8 (7, 10); mean = 8.06 ± 2.31], did not report being unwell [median (IQR) = 1 (1, 1); mean = 1.11 ± 0.62], and were not aware of their real-world surroundings [median (IQR) = 1 (1, 5); mean = 2.99 ± 3.22].

Conclusion

The subjectively reported decrease in environmental awareness as well as the decrease in the heart rate and blood pressure over time highlights the ability of immersive virtual reality to help critically ill patients overcome sensory overload and sensory deprivation. Immersive virtual reality can successfully and repetitively be provided to a randomly selected sample of critically ill patients over a prolonged duration.
Ecologically different earthworm species are the driving force of microbial hotspots influencing Pb uptake by the leafy vegetable Brassica campestris
Authors: Tibihenda Cevin , Zhong Hesen , Liu Kexue , Dai Jun , Lin Xiaoqin , Motelica-Heino Mikael , Hou Shuyu , Zhang Menghao , Lu Ying , Xiao Ling , Zhang Chi
Published: October 2023

Food chain contamination by soil lead (Pb), beginning with Pb uptake by leafy vegetables, is a threat to food safety and poses a potential risk to human health. This study highlights the importance of two ecologically different earthworm species (the anecic species Amynthas aspergillum and the epigeic species Eisenia fetida) as the driving force of microbial hotspots to enhance Pb accumulation in the leafy vegetable Brassica campestris at different Pb contamination levels (0, 100, 500, and 1,000 mg·kg−1). The fingerprints of phospholipid fatty acids (PLFAs) were employed to reveal the microbial mechanism of Pb accumulation involving earthworm–plant interaction, as PLFAs provide a general profile of soil microbial biomass and community structure. The results showed that Gram-positive (G+) bacteria dominated the microbial community. At 0 mg·kg−1 Pb, the presence of earthworms significantly reduced the total PLFAs. The maximum total of PLFAs was found at 100 mg·kg−1 Pb with E. fetida inoculation. A significant shift in the bacterial community was observed in the treatments with E. fetida inoculation at 500 and 1,000 mg·kg−1 Pb, where the G+/G− bacteria ratio was significantly decreased compared to no earthworm inoculation. Principal component analysis (PCA) showed that E. fetida had a greater effect on soil microbial hotspots than A. aspergillum, thus having a greater effect on the Pb uptake by B. campestris. Redundancy analysis (RDA) showed that soil microbial biomass and structure explained 43.0% (R2 = 0.53) of the total variation in Pb uptake by B. campestris, compared to 9.51% of microbial activity. G− bacteria explained 23.2% of the total variation in the Pb uptake by B. campestris, significantly higher than the other microbes. The Mantel test showed that microbial properties significantly influenced Pb uptake by B. campestris under the driving force of earthworms. E. fetida inoculation was favorable for the G− bacterial community, whereas A. aspergillum inoculation was favorable for the fungal community. Both microbial communities facilitated the entry of Pb into the vegetable food chain system. This study delivers novel evidence and meaningful insights into how earthworms prime the microbial mechanism of Pb uptake by leafy vegetables by influencing soil microbial biomass and community composition. Comprehensive metagenomics analysis can be employed in future studies to identify the microbial strains promoting Pb migration and develop effective strategies to mitigate Pb contamination in food chains.
The potentials and challenges of using fermentation to improve the sensory quality of plant-based meat analogs
Authors: Elhalis Hosam , See Xin Yi , Osen Raffael , Chin Xin Hui , Chow Yvonne
Published: October 2023

Despite the advancements made in improving the quality of plant-based meat substitutes, more work needs to be done to match the texture, appearance, and flavor of real meat. This review aims to cover the sensory quality constraints of plant-based meat analogs and provides fermentation as a sustainable approach to push these boundaries. Plant-based meat analogs have been observed to have weak and soft textural quality, poor mouth feel, an unstable color, and unpleasant and beany flavors in some cases, necessitating the search for efficient novel technologies. A wide range of microorganisms, including bacteria such as Lactobacillus acidophilus and Lactiplantibacillus plantarum, as well as fungi like Fusarium venenatum and Neurospora intermedia, have improved the product texture to mimic fibrous meat structures. Additionally, the chewiness and hardness of the resulting meat analogs have been further improved through the use of Bacillus subtilis. However, excessive fermentation may result in a decrease in the final product’s firmness and produce a slimy texture. Similarly, several microbial metabolites can mimic the color and flavor of meat, with some concerns. It appears that fermentation is a promising approach to modulating the sensory profiles of plant-derived meat ingredients without adverse consequences. In addition, the technology of starter cultures can be optimized and introduced as a new strategy to enhance the organoleptic properties of plant-based meat while still meeting the needs of an expanding and sustainable economy.
More than medications: a patient-centered assessment of Parkinson’s disease care needs during hospitalization
Authors: Shurer Jessica , Golden Shannon L. S. , Mihas Paul , Browner Nina
Published: October 2023

Background

Parkinson’s disease (PD) increases the risk of hospitalization and complications while in the hospital. Patient-centered care emphasizes active participation of patients in decision-making and has been found to improve satisfaction with care. Engaging in discussion and capturing hospitalization experience of a person with PD (PwP) and their family care partner (CP) is a critical step toward the development of quality improvement initiatives tailored to the unique hospitalization needs of PD population.

Objectives

This qualitative study aimed to identify the challenges and opportunities for PD patient-centered care in hospital setting.

Methods

Focus groups were held with PwPs and CPs to capture first-hand perspectives and generate consensus themes on PD care during hospitalization. A semi-structured guide for focus group discussions included questions about inpatient experiences and interactions with the health system and the clinical team. The data were analyzed using inductive thematic analysis.

Results

A total of 12 PwPs and 13 CPs participated in seven focus groups. Participants were 52% female and 28% non-white; 84% discussed unplanned hospitalizations. This paper focuses on two specific categories that emerged from the data analysis. The first category explored the impact of PD diagnosis on the hospital experience, specifically during planned and unplanned hospitalizations. The second category delves into the unique needs of PwPs and CPs during hospitalization, which included the importance of proper PD medication management, the need for improved hospital ambulation protocols, and the creation of disability informed hospital environment specific for PD.

Conclusion

PD diagnosis impacts the care experience, regardless of the reason for hospitalization. While provision of PD medications was a challenge during hospitalization, participants also desired flexibility in ambulation protocols and an environment that accommodated their disability. These findings highlight the importance of integrating the perspectives of PwPs and CPs when targeting patient-centered interventions to improve hospital experiences and outcomes.
An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes
Authors: Peng Yong , Yang Huan , Xue Ya-hui , Chen Quan , Jin Hong , Liu Shu , Yao Shun-yu , Du Miao-qiao
Published: October 2023

Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most prevalent carcinoma linked to SPSSDs, followed by lung cancer and lymphoma. Furthermore, classic SPS was the most common SPSSD subtype, followed by stiff limb syndrome and progressive encephalomyelitis with rigidity and myoclonus. GAD65 was the most common autoantigen in patients with cancer and SPSSDs, followed by amphiphysin and GlyR. Patients with cancer subtypes might have multiple SPSSD subtypes, and conversely, patients with SPSSD subtypes might have multiple carcinoma subtypes. The first aim of this review was to highlight the complex nature of the relationships among cancers, autoantigens, and SPSSDs as new information in this field continues to be generated globally. The adoption of an open-minded approach to updating information on new cancer subtypes, autoantigens, and SPSSDs is recommended to renew our database. The second aim of this review was to discuss SPS animal models, which will help us to understand the mechanisms underlying the pathogenesis of SPS. In future, elucidating the relationship among cancers, autoantigens, and SPSSDs is critical for the early prediction of cancer and discovery of new therapeutic modalities.
Transcranial Doppler during the first week after cardiac arrest and association with 6-month outcomes
Authors: Reichenbach Antje , Alteheld Lars , Henriksen Julia , Nakstad Espen Rostrup , Andersen Geir Øystein , Sunde Kjetil , Šaltytė Benth Jūratė , Lundqvist Christofer
Published: October 2023

Background

Early prediction of outcomes in comatose patients after out-of-hospital cardiac arrest is challenging. Prognostication tools include clinical examination, biomarkers, and neuroradiological and neurophysiological tests. We studied the association between transcranial Doppler (TCD) and the outcome.

Methods

This was a pre-defined sub-study of the prospective observational Norwegian Cardiorespiratory Arrest Study. Patients underwent standardized post-resuscitation care, including target temperature management (TTM) to 33°C for 24 h. TCD was performed at days 1, 3, and 5–7. The primary endpoint was cerebral performance category (CPC) at 6 months, dichotomized into good (CPC 1–2) and poor (CPC 3–5) outcomes. We used linear mixed modeling time-series analysis.

Results

Of 139 TCD-examined patients, 81 (58%) had good outcomes. Peak systolic velocity in the middle cerebral artery (PSV) was low during TTM (Day 1) and elevated after rewarming (Day 3). Thereafter, it continued to rise in patients with poor, but normalized in patients with good, outcomes. At days 5–7, PSV was 1.0 m/s (95% CI 0.9; 1.0) in patients with good outcomes and 1.3 m/s (95% CI 1.1; 1.4) in patients with poor outcomes (p < 0.001)

Conclusion

Elevated PSV at days 5–7 indicated poor outcomes. Our findings suggest that serial TCD examinations during the first week after cardiorespiratory arrest may improve our understanding of serious brain injury.
Narrow band green light effects on headache, photophobia, sleep, and anxiety among migraine patients: an open-label study conducted online using daily headache diary
Authors: Lipton Richard B. , Melo-Carrillo Agustin , Severs Mark , Reed Michael , Ashina Sait , Houle Timothy , Burstein Rami
Published: October 2023

Background

Narrow band green light (NbGL) has been shown to relieve headache in small numbers of subjects but large-scale real-world assessments are lacking. The goal of this prospective, observational, open-label, real world study was to determine whether treatment with NbGL during the ictal phase of migraine, improves patients' perception of their headache, photophobia, anxiety and same-night sleep.

Methods

The study was conducted in purchasers of the NbGL Lamp in two phases. In Phase I purchasers of the Lamp completed a survey and were asked to participate in a 6-week diary study. In Phase 2 participants completed daily diaries for 6 weeks. Specifically, they were asked to use their judgement/impression/perception when choosing between headache-improved or headache-unimproved after using the NbGL during acute attacks. Diary outcomes of interest included rates of attacks improve in responders (≥50%), non-responders (<50%), super-responders (≥75%), and super non-responders (<30%).

Results

Of 3,875 purchasers of the Lamp for migraine, 698 (18%) agreed to participate, filled out a pre-study survey, and agreed to a 6-week daily headache diary. Complete data were provided by 181 (26%) participants. Using criteria above, 61, 39, 42, and 27% of participants were classified responder, non-responder, super-responder and super non-responder, respectively. Headache improved in 55% of all 3,232 attacks, in 82% of the 1,803 attacks treated by responders, and in 21% of the 1,429 attacks treated by non-responders. Photophobia improved in 53% of all attacks, 68% of the attacks in responders and in 35% of the attacks in non-responders. Anxiety improved in 34% of all attacks, 46% of the responders' attacks, and 18% of the non-responders' attacks. Sleep improved in 49% of all attacks, 59% of the responders' attacks, and 36% of the non-responders' attacks.

Conclusion

This open-label real world study suggests that 2 h of treatment with the lamp during migraine attacks is associated with relief of pain and photophobia, reduction in anxiety, and improved sleep. The absence of rigorous diagnosis and a blinded contemporaneous control group limits the rigor of this interpretation. Improvement in photophobia, anxiety and sleep among the responders may be secondary to the improvement in the headache itself.

Clinical trial registration

ClinicalTrial.gov (NCT04841083).
A novel untrained SSVEP-EEG feature enhancement method using canonical correlation analysis and underdamped second-order stochastic resonance
Authors: Chen Ruiquan , Xu Guanghua , Zhang Huanqing , Zhang Xun , Li Baoyu , Wang Jiahuan , Zhang Sicong
Published: October 2023

Objective

Compared with the light-flashing paradigm, the ring-shaped motion checkerboard patterns avoid uncomfortable flicker or brightness modulation, improving the practical interactivity of brain-computer interface (BCI) applications. However, due to fewer harmonic responses and more concentrated frequency energy elicited by the ring-shaped checkerboard patterns, the mainstream untrained algorithms such as canonical correlation analysis (CCA) and filter bank canonical correlation analysis (FBCCA) methods have poor recognition performance and low information transmission rate (ITR).

Methods

To address this issue, a novel untrained SSVEP-EEG feature enhancement method using CCA and underdamped second-order stochastic resonance (USSR) is proposed to extract electroencephalogram (EEG) features.

Results

In contrast to typical unsupervised dimensionality reduction methods such as common average reference (CAR), principal component analysis (PCA), multidimensional scaling (MDS), and locally linear embedding (LLE), CCA exhibits higher adaptability for SSVEP rhythm components.

Conclusion

This study recruits 42 subjects to evaluate the proposed method and experimental results show that the untrained method can achieve higher detection accuracy and robustness.

Significance

This untrained method provides the possibility of applying a nonlinear model from one-dimensional signals to multi-dimensional signals.
Mapping of the supplementary motor area using repetitive navigated transcranial magnetic stimulation
Authors: Kern Giulia , Kempter Miriam , Picht Thomas , Engelhardt Melina
Published: October 2023

Background

The supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse.

Objective

The aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities.

Methods

To this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21–67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task.

Results

Mean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p < 0.01). Bimanual finger tapping led to a significant increase in taps during stimulation (28.43taps) compared to unimanual tapping (p < 0.01). Compared to baseline, completion time for the NHPT increased significantly during stimulation (baseline: 13.6 s, stimulation: 16.4 s; p < 0.01). No differences between hemispheres were observed.

Conclusion

The current study validated and extended a rnTMS based protocol for the mapping of the SMA regarding motor function of upper and lower extremity. This protocol could be beneficial to better understand functional SMA organisation and improve preoperative planning in patients with SMA lesions.
Effect of methanol fixation on single-cell RNA sequencing of the murine dentate gyrus
Authors: Sánchez-Carbonell Marta , Jiménez Peinado Patricia , Bayer-Kaufmann Cathrin , Hennings Jean-Christopher , Hofmann Yvonne , Schmidt Silvio , Witte Otto W. , Urbach Anja
Published: October 2023

Single-cell RNA sequencing (scRNA-seq) provides a powerful tool to evaluate the transcriptomic landscape and heterogeneity of thousands of cells in parallel. However, complex study designs or the unavailability of in-house instruments require the temporal disconnection between sample preparation and library construction, raising the need for efficient sample preservation methods which are compatible with scRNA-seq downstream analysis. Several studies evaluated the effect of methanol fixation as preservation method, yet none of them deeply assessed its effect on adult primary dissociated brain tissue. Here, we evaluated its effect on murine dentate gyrus (DG) single cell suspensions and on subsequent scRNA-seq downstream analysis by performing SOrting and Robot-assisted Transcriptome SEQuencing (SORT-seq), a partially robotized version of the CEL-seq2 protocol. Our results show that MeOH fixation preserves RNA integrity and has no apparent effects on cDNA library construction. They also suggest that fixation protects from sorting-induced cell stress and increases the proportion of high-quality cells. Despite evidence of mRNA leakage in fixed cells, their relative gene expression levels correlate well with those of fresh cells and fixation does not significantly affect the variance of the dataset. Moreover, it allows the identification of all major DG cell populations, including neural precursors, granule neurons and different glial cell types, with a tendency to preserve more neurons that are underrepresented in fresh samples. Overall, our data show that MeOH fixation is suitable for preserving primary neural cells for subsequent single-cell RNA profiling, helping to overcome challenges arising from complex workflows, improve experimental flexibility and facilitate scientific collaboration.
[18F]NaF PET/CT imaging of response to single fraction SABR to bone metastases from breast cancer
Authors: Hardcastle Nicholas , Liu Yang , Siva Shankar , David Steven
Published: October 2023

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0–20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%–34% for non-tumour bone in each dose level.
Identification and validation of PCSK9 as a prognostic and immune-related influencing factor in tumorigenesis: a pan-cancer analysis
Authors: Sun Chao , Zhu Guoji , Shen Conghuan , Huang Shungen , Li Ruidong , Li Jianhua , Ma Zhenyu , Wang Zhengxin
Published: October 2023

Introduction

Proprotein convertase subtilisin/kexin-9 (PCSK9) has been primarily studied in the cardiovascular field however, its role in cancer pathophysiology remains incompletely defined. Recently, a pivotal role for PCSK9 in cancer immunotherapy was proposed based on the finding that PCSK9 inhibition was associated with enhancing the antigen presentation efficacy of target programmed cell death-1 (PD-1). Herein, we provide results of a comprehensive pan-cancer analysis of PCSK9 that assessed its prognostic and immunological functions in cancer.

Methods

Using a variety of available online cancer-related databases including TIMER, cBioPortal, and GEPIA, we identified the abnormal expression of PCSK9 and its potential clinical associations in diverse cancer types including liver, brain and lung. We also validated its role in progression-free survival (PFS) and immune infiltration in neuroblastoma.

Results

Overall, the pan-cancer survival analysis revealed an association between dysregulated PCSK9 and poor clinical outcomes in various cancer types. Specifically, PCSK9 was extensively genetically altered across most cancer types and was consistently found in different tumor types and substages when compared with adjacent normal tissues. Thus, aberrant DNA methylation may be responsible for PCSK9 expression in many cancer types. Focusing on liver hepatocellular carcinoma (LIHC), we found that PCSK9 expression correlated with clinicopathological characteristics following stratified prognostic analyses. PCSK9 expression was significantly associated with immune infiltrate since specific markers of CD8+ T cells, macrophage polarization, and exhausted T cells exhibited different PCSK9-related immune infiltration patterns in LIHC and lung squamous cell carcinoma. In addition, PCSK9 was connected with resistance of drugs such as erlotinib and docetaxel. Finally, we validated PCSK9 expression in clinical neuroblastoma samples and concluded that PCSK9 appeared to correlate with a poor PFS and natural killer cell infiltration in neuroblastoma patients.

Conclusion

PCSK9 could serve as a robust prognostic pan-cancer biomarker given its correlation with immune infiltrates in different cancer types, thus potentially highlighting a new direction for targeted clinical therapy of cancers.
Challenges associated with the identification of germline variants on myeloid malignancy genomic profiling—a Singaporean experience
Authors: Chin Hui-Lin , Lam Joyce Ching Mei , Christopher Dheepa , Michelle Poon Limei , Junrong Benedict Yan
Published: October 2023

Genomic profiling to identify myeloid-malignancy-related gene mutations is routinely performed for patients with suspected or definite myeloid malignancies. The most common specimen types in our experience are peripheral blood and bone marrow aspirates. Although primarily intended to identify somatic mutations, not infrequently, potentially clinically significant germline variants are also identified. Confirmation of the germline status of these variants is typically performed by hair follicle or skin fibroblast testing. If the germline variant is classified as a pathogenic or likely pathogenic variant and occurs in a gene known to be associated with a disease relevant to the patient’s phenotype (for example, the identification of a DDX41 pathogenic variant in an individual with acute myeloid leukemia), the management algorithm is typically quite straightforward. Challenging situations may occur such as when the germline variant is classified as a pathogenic or likely pathogenic variant and occurs in a gene not known to be associated with the patient’s phenotype/presenting complaint. We have encountered several such challenging cases in which potentially clinically significant germline variants were identified on the initial genomic profiling of peripheral blood or bone marrow aspirate. In this article, we present these cases and discuss the genetic counseling and management approaches.
Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer
Authors: Zhang Hongsheng , Mi Jintao , Xin Qi , Cao Weiwei , Song Chunjiao , Zhang Naidan , Yuan Chengliang
Published: October 2023

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.
Evaluation of IL-6, FoxP3 Treg lymphocytes, intestinal barrier biomarkers and the use of synbiotics in obese adolescents: a pilot study
Authors: Aziz Cylmara , Morales Armando , Pinto Walter , Fanchini Vanessa , Dell Aquila Luis , Sangaleti Carine , Elias Rosilene , Dalboni Maria
Published: October 2023

Aim

This prospective pilot study evaluated inflammatory and intestinal barrier biomarkers and the effects of a synbiotic in obese adolescents.

Methods

Eighteen obese and 20 eutrophic adolescents were evaluated for body composition using bioimpedance analysis (BIA), body mass index (BMI), IL-6 and lipopolysaccharide (LPS) serum levels, CD4 and FoxP3 Treg lymphocytes and monocytes. Synbiotic supplementation for 60 days was also evaluated for these parameters only in obese adolescents.

Results

We observed an increase in CD4 lymphocyte (18.0 ± 12.4 vs. 8.9 ± 7.5; p < 0.01), IL-6 (0.30 ± 0.06 vs. 0.20 ± 0.06; p = 0.02) and LPS (0.18 ± 0.15 vs. 0.08 ± 0.05; p < 0.01) levels in obese compared to eutrophic adolescents. After synbiotic supplementation, FoxP3 Treg lymphocytes increased (14.0 ± 6.7 vs. 9.9 ± 5.4; p = 0.02) in obese adolescents.

Conclusions

Obese adolescents presented a state of microinflammation and intestinal barrier breakdown, and synbiotic supplementation increased the expression of FoxP3 Treg lymphocytes, an anti-inflammatory regulator. Whether the increase in FoxP3 Treg lymphocytes may have an impact on inflammation and outcomes in obese adolescents deserves further evaluation.
TRPA1-dependent and -independent activation by commonly used preservatives
Authors: Mager Maximilian L. , Ciotu Cosmin I. , Gold-Binder Markus , Heber Stefan , Fischer Michael J. M.
Published: October 2023

Background and purpose: Addition of preservatives ensures microbial stability, especially in multidose containers of parenterally administered pharmaceuticals. These compounds can cause side effects, and particularly at the site of application, might elicit or facilitate pain. TRPA1 is a cation channel expressed in peripheral neurons which contributes to pain and inflammation and is sensitive to many irritants. The most commonly used preservatives, in particular with a focus on parenteral formulations, were investigated for their potential to activate TRPA1.

Experimental approach: Sixteen preservatives were screened for mediating calcium influx in human TRPA1-transfected HEK293t cells. Untransfected cells served as control, results were further validated in mouse sensory neurons. In addition, proinflammatory mediators serotonin, histamine and prostaglandin E2 were co-administered to probe a potential sensitisation of preservative-induced TRPA1 activation.

Key results: Butylparaben, propylparaben, ethylparaben, bronopol, methylparaben, phenylethyl alcohol and phenol induced a TRPA1-dependent calcium influx in transfected HEK293t cells at concentrations used for preservation. Other preservatives increased calcium within the used concentration ranges, but to a similar degree in untransfected controls. Serotonin, histamine, and prostaglandin enhanced TRPA1 activation of phenylethyl alcohol, bronopol, ethylparaben, propylparaben and butylparaben.

Conclusion and implications: Systematic screening of common preservatives applied for parenterally administered drugs resulted in identifying several preservatives with substantial TRPA1 channel activation. This activation was enhanced by the addition of proinflammatory meditators. This allows selecting a preservative without TRPA1 activation, particularly in case of pharmaceuticals that could act proinflammatory.
Lights should support circadian rhythms: evidence-based scientific consensus
Authors: Moore-Ede Martin , Blask David E. , Cain Sean W. , Heitmann Anneke , Nelson Randy J.
Published: October 2023

For over a hundred years, the lighting industry has primarily been driven by illumination aesthetics, energy efficiency and product cost with little consideration of the effects of light on health. The recent widespread replacement of traditional light sources by blue-enriched LED lights has heightened concerns about the disruption of the blue-sensitive human circadian system by these LED lights and their impact on the multiple health disorders linked to circadian disruption. Despite these health concerns, less than 0.5% of the lighting sold today modifies spectral content and intensity between day and night. We report that 248 scientists, with a total of 2,697 peer-reviewed publications on light and circadian clocks since 2008, reached consensus on 25 statements about the impact of light on circadian rhythms and health based on accumulated scientific evidence, including support for the widespread introduction of circadian lighting and warning labels on blue-enriched LED lights indicating they “maybe harmful if used at night”.
The dynamic changes of mango (Mangifera indica L.) epicuticular wax during fruit development and effect of epicuticular wax on Colletotrichum gloeosporioides invasion
Authors: Wu Jingbo , You Yuquan , Wu Xiao , Liu Feng , Li Guoping , Yin Hao , Gu Chao , Qi Kaijie , Wei Qing , Wang Songbiao , Yao Quansheng , Zhan Rulin , Zhang Shaoling
Published: October 2023

Mango fruits are susceptible to diseases, such as anthracnose, during fruit development, leading to yield reduction. Epicuticular wax is closely related to resistance of plants to pathogenic bacterial invasion. In this study, the effect of mango fruit epicuticular wax on the invasion of Colletotrichum gloeosporioides was investigated, followed by to understand the changes of wax chemical composition and crystal morphology during mango fruit development using GC-MS and SEM. Results showed that the epicuticular wax of mango fruits can prevent the invasion of C. gloeosporioides, and ‘Renong’ showed the strongest resistance to C. gloeosporioides. The wax content of four mango varieties first increased and then decreased from 40 days after full bloom (DAFB) to 120 DAFB. In addition, 95 compounds were detected in the epicuticular wax of the four mango varieties at five developmental periods, in which primary alcohols, terpenoids and esters were the main wax chemical composition. Furthermore, the surface wax structure of mango fruit changed dynamically during fruit development, and irregular platelet-like crystals were the main wax structure. The present study showed the changes of wax content, chemical composition and crystal morphology during mango fruit development, and the special terpenoids (squalene, farnesyl acetate and farnesol) and dense crystal structure in the epicuticular wax of ‘Renong’ fruit may be the main reason for its stronger resistance to C. gloeosporioides than other varieties. Therefore, these results provide a reference for the follow-up study of mango fruit epicuticular wax synthesis mechanism and breeding.
Genetic characterization of root architectural traits in barley (Hordeum vulgare L.) using SNP markers
Authors: Farooqi M. Q. U. , Moody David , Bai Guihua , Bernardo Amy , St. Amand Paul , Diggle Art J. , Rengel Zed
Published: October 2023

Increasing attention is paid to providing new tools to breeders for targeted breeding for specific root traits that are beneficial in low-fertility, drying soils; however, such information is not available for barley (Hordeum vulgare L.). A panel of 191 barley accessions (originating from Australia, Europe, and Africa) was phenotyped for 26 root and shoot traits using the semi-hydroponic system and genotyped using 21 062 high-quality single nucleotide polymorphism (SNP) markers generated by genotyping-by-sequencing (GBS). The population structure analysis of the barley panel identified six distinct groups. We detected 1199 significant (P<0.001) marker-trait associations (MTAs) with r2 values up to 0.41. The strongest MTAs were found for root diameter in the top 20 cm and the longest root length. Based on the physical locations of these MTAs in the barley reference genome, we identified 37 putative QTLs for the root traits, and three QTLs for shoot traits, with nine QTLs located in the same physical regions. The genomic region 640-653 Mb on chromosome 7H was significant for five root length-related traits, where 440 annotated genes were located. The putative QTLs for various root traits identified in this study may be useful for genetic improvement regarding the adaptation of new barley cultivars to suboptimal environments and abiotic stresses.