bluuebunny/crossref_metadata_2025 huggingface dataset:
Short stature related to Growth Hormone Insensitivity (GHI) in childhood
Authors: Mastromauro Concetta , Giannini Cosimo , Chiarelli Francesco
Published: March 2023

Linear growth during childhood is the result of the synergic contribution of different factors. The best growth determinant system during each period of life is represented by the growth hormone–insulin-like growth factor axis (GH–IGF), even if several other factors are involved in normal growth. Within the broad spectrum of growth disorders, an increased importance has been placed on growth hormone insensitivity (GHI). GHI was reported for the first time by Laron as a syndrome characterized by short stature due to GH receptor (GHR) mutation. To date, it is recognized that GHI represents a wide diagnostic category, including a broad spectrum of defects. The peculiar characteristic of GHI is the low IGF-1 levels associated with normal or elevated GH levels and the lack of IGF-1 response after GH administration. Recombinant IGF-1 preparations may be used in the treatment of these patients.
Significance of pyroptosis-related gene in the diagnosis and classification of rheumatoid arthritis
Authors: Li Jian , Cui Yongfeng , Jin Xin , Ruan Hongfeng , He Dongan , Che Xiaoqian , Gao Jiawei , Zhang Haiming , Guo Jiandong , Zhang Jinxi
Published: March 2023

Background

Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, is often characterized by persistent morning stiffness, joint pain, and swelling. Early diagnosis and timely treatment of RA can effectively delay the progression of the condition and significantly reduce the incidence of disability. In the study, we explored the function of pyroptosis-related genes (PRGs) in the diagnosis and classification of rheumatoid arthritis based on Gene Expression Omnibus (GEO) datasets.

Method

We downloaded the GSE93272 dataset from the GEO database, which contains 35 healthy controls and 67 RA patients. Firstly, the GSE93272 was normalized by the R software “limma” package. Then, we screened PRGs by SVM-RFE, LASSO, and RF algorithms. To further investigate the prevalence of RA, we established a nomogram model. Besides, we grouped gene expression profiles into two clusters and explored their relationship with infiltrating immune cells. Finally, we analyzed the relationship between the two clusters and the cytokines.

Result

CHMP3, TP53, AIM2, NLRP1, and PLCG1 were identified as PRGs. The nomogram model revealed that decision-making based on established model might be beneficial for RA patients, and the predictive power of the nomogram model was significant. In addition, we identified two different pyroptosis patterns (pyroptosis clusters A and B) based on the 5 PRGs. We found that eosinophil, gamma delta T cell, macrophage, natural killer cell, regulatory T cell, type 17 T helper cell, and type 2 T helper cell were significant high expressed in cluster B. And, we identified gene clusters A and B based on 56 differentially expressed genes (DEGs) between pyroptosis cluster A and B. And we calculated the pyroptosis score for each sample to quantify the different patterns. The patients in pyroptosis cluster B or gene cluster B had higher pyroptosis scores than those in pyroptosis cluster A or gene cluster A.

Conclusion

In summary, PRGs play vital roles in the development and occurrence of RA. Our findings might provide novel views for the immunotherapy strategies with RA.
Spatio-temporal patterns of an invasive species Mimosa bimucronata (DC.) Kuntze under different climate scenarios in China
Authors: Xie Chunping , Li Meng , Jim C. Y. , Liu Dawei
Published: March 2023

Invasive alien plants pose a serious threat to native ecosystems and their biodiversity. To control their spread and damage, it is critical to clarify the potential distribution patterns of the invaders at the regional scale and their response to climate change. Mimosa bimucronata (DC.) Kuntze, a shrub extremely tolerant of stressful habitat conditions, is used as firewood and hedgerow in the tropics. Since its introduction to China in the 1950s, it has established a sustainable population and become an aggressive invasive species. Due to serious ecological threats in South China, it has been listed as a Key Management Invasive Alien Species. To understand its invasibility in China, two species distribution models (SDMs), BIOCLIM and DOMAIN, were employed to evaluate the main environmental factors regulating its geographical distribution under the current climate and a future climate change scenario with double CO2 concentration. We found an extensive spread of current suitability habitats in South China, concentrated mainly in the tropical-subtropical provinces of Guangdong, Guangxi, Hainan, and Fujian. The complex interplay of local bioclimatic factors shaped the species distribution. Under the current climate, the predicted range was somewhat larger than the current one. Under the climate change scenario, suitable habitats for Mimosa bimucronata would remain similar to the current one. However, its invasiveness in the current biogeographical range would be more serious. The suitability habitats would expand and shift to the Southeastern coastal and Northern parts of South China under future climate change. We suggest adopting early monitoring and eradication measures in potential invasion areas and practical measures to contain its spread. The results could provide a conceptual basis to formulate prevention and control strategies to improve future containment of its invasion.
Impact of the COVID-19 pandemic on the mental health of transgender persons in India: Findings from an exploratory qualitative study
Authors: Raghuram Harikeerthan , Parakh Sana , Chidambaranathan Supraja , Tugnawat Deepak , Pillai Venu , Singh Sanjana , Singh Satendra , Shaikh Aqsa , Bhan Anant
Published: March 2023

Introduction

Transgender persons in India, who are one of the most vulnerable groups, were particularly impacted by the COVID-19 pandemic. Increased risk of COVID-19, challenges with continuing livelihood, uncertainty, and anxiety around the pandemic over pre-existing social discrimination and exclusion pose risk of a mental health impact as well. To investigate this further, this component of a larger study on experiences in healthcare of transgender persons in India during COVID-19 and looks into the question “How did the COVID-19 pandemic impact the mental health of transgender persons in India”.

Methods

22 In-depth interviews (IDI) and 6 focus group discussions (FGD) were conducted virtually and in-person with persons self-identifying as transgender or belonging to ethnocultural transgender communities from different parts of India. Community based participatory research approach was used by ensuring representation from the community in the research team and through a series of consultative workshops. Purposive sampling with snowballing was used. The IDIs and FGDs were recorded, transcribed verbatim and analyzed using an inductive thematic analysis.

Results

Mental health of transgender persons were affected in the following ways. Firstly, COVID-19, its associated fear and suffering combined with pre-existing inaccessibility of healthcare and reduced access to mental health care affected their mental health. Secondly, unique social support needs of transgender persons were disrupted by pandemic linked restrictions. Thirdly, pre-existing vulnerabilities such as precarious employment and underlying stigma were exacerbated. Finally, gender dysphoria was a key mediating factor in the impact of COVID-19 on mental health with a negative and positive impact.

Conclusions

The study reiterates the need to make systemic changes to make mental healthcare and general healthcare services trans-inclusive while also recognizing the essential nature of gender affirmative services and the need to continue them even during emergencies and disaster situations. While this brings out how public health emergencies can exacerbate vulnerabilities, it also shows how the lived mental health experience of transgender person is intricately linked to the way work, travel and housing is structured in our society and therefore points to the structural nature of the linkage between mental health and gender.
PlGF/FLT-1 deficiency leads to reduced STAT3-C/EBPβ signaling and aberrant polarization in decidual macrophages during early spontaneous abortion
Authors: Chang Ruiqi , Dai Jingcong , Wang Li , Liu Hao , Jiang Huanhuan , Liu Xiaoyu , Jiang Linying , He Fan , Hu Lina
Published: March 2023

Introduction

Dysregulated macrophage polarization (excessive M1-like or limited M2-like macrophages) in the early decidua contributes to allogeneic fetal rejection and thus early spontaneous abortion. However, the modulators of M1/M2 balance at the early maternal-fetal interface remain mostly unknown.

Methods

First-trimester decidual tissues were collected from normal pregnant women undergoing elective pregnancy terminations and patients with spontaneous abortion. We measured the expression of placental growth factor (PlGF) and Fms-like-tyrosine-kinase receptor 1 (FLT-1), and characterized the profiles of macrophages in decidua. Notably, we investigated the effect of recombinant human PlGF (rhPlGF) on decidual macrophages (dMφs) from normal pregnancy and revealed the underlying mechanisms both in vitro and in vivo.

Results

The downregulated expression of PlGF/ FLT-1 may result in spontaneous abortion by inducing the M1-like deviation of macrophages in human early decidua. Moreover, the CBA/J×DBA/2 abortion-prone mice displayed a lower FLT-1 expression in uterine macrophages than did CBA/J×BALB/c control pregnant mice. In in vitro models, rhPlGF treatment was found to drive the M2-like polarization of dMφs via the STAT3/CEBPB signaling pathway. These findings were further supported by a higher embryo resorption rate and uterine macrophage dysfunction in Pgf knockout mice, in addition to the reduced STAT3 transcription and C/EBPβ expression in uterine macrophages.

Discussion

PlGF plays a key role in early pregnancy maintenance by skewing dMφs toward an M2-like phenotype via the FLT-1-STAT3-C/EBPβ signaling pathway. Excitingly, our results highlight a rationale that PlGF is a promising target to prevent early spontaneous abortion.
The role of NOD-like receptors in innate immunity
Authors: Almeida-da-Silva Cássio Luiz Coutinho , Savio Luiz Eduardo Baggio , Coutinho-Silva Robson , Ojcius David M.
Published: March 2023

The innate immune system in vertebrates and invertebrates relies on conserved receptors and ligands, and pathways that can rapidly initiate the host response against microbial infection and other sources of stress and danger. Research into the family of NOD-like receptors (NLRs) has blossomed over the past two decades, with much being learned about the ligands and conditions that stimulate the NLRs and the outcomes of NLR activation in cells and animals. The NLRs play key roles in diverse functions, ranging from transcription of MHC molecules to initiation of inflammation. Some NLRs are activated directly by their ligands, while other ligands may have indirect effects on the NLRs. New findings in coming years will undoubtedly shed more light on molecular details involved in NLR activation, as well as the physiological and immunological outcomes of NLR ligation.
An indicator-based approach to assess sustainability of port-cities and marine management in the Global South
Authors: Ogara Dinah A. E. , Morishita Joji , Davies Peter J. , Mbui Maina , Gamoyo Majambo , Njoroge Nashon , Chann Isaac Otieno , Igesa Benson Senelwa , Ochieng Stephen Odhiambo
Published: March 2023

Ports and neighbouring cities function as connectors between land and water and have long accommodated a substantial flow of goods and services. Port cities in the Western Indian Ocean (WIO) region and the Global South (GS) are rapidly and inevitably expanding as the demand for global trade increases. However, this expansion has numerous impacts on the surrounding marine ecosystem and the socio-economic livelihoods of local communities. We propose a framework to evaluate the sustainability of port cities in the WIO region and more broadly for cities in the GS. Through an exploratory approach, a systematic literature review (SLR) was undertaken to identify existing themes on port city and marine ecosystem sustainability indicator frameworks. The results revealed a strong bias towards sustainability publications designed for port cities in Global North. The approach developed from this study focuses on the socio-economic and environmental attributes relevant to ports in the WIO region and for GS countries. This draws from the Drivers, Pressures, States, Impacts and Responses (DPSIR) framework and includes 78 indicators. The indicators are designed to identify and report on the complex land and sea interdependencies of port cities. To test the validity of these indicators their interdependencies were examined through a Causal Network (CN) structure which identified 12 priority DPSIR CN. These were also mapped to the UNSDGs enabling the wider applicability and transferability of the framework. The resulting framework enables port cities in emerging economies to establish robust sustainable reporting systems and provides a framework that offers a unique lens for evaluating interactions embedded in the land and sea continuum.
Phase variations of the summer and winter seasons in the Bohai Sea during the last four decades
Authors: Yuan Chengyi , Kuang Xiaodi , Xu Jingbo , Li Ruopeng , Wang Chen
Published: March 2023

In most coastal oceans, the impacts of global warming on season duration and timing of seasonal transitions remain unknown. To mirror the reality of the ongoing climate change, the summer and winter seasons are redefined using the local water temperature thresholds in the Bohai Sea. Then the phase variations of these seasons are quantified using the duration and transition timing indices, including the duration (DUR), onset (ONS), and withdrawal (WIT) indices derived from the OSTIA SST dataset at a very high resolution (0.05°). During the last four decades (1982–2019), secular trends of summer indices extracted by the ensemble empirical mode decomposition (EEMD) method reveal that the summer DUR has an accumulated increase of about 17 days (4.5 days decade-1), which is primarily induced by the phase advance of the summer ONS by about 16 days (4.2 days decade-1). Spatial features of the duration and timing indices demonstrate that the lengthening of summer DUR and the phase advance of summer ONS have significantly enhanced in the shallow regions, due to the limited thermal inertia and the shorter period of the ocean’s memory. In contrast, the secular trend of winter DUR exhibits an accumulated shortening of about 18 days (4.8 days decade-1), which is induced by a moderately delayed winter ONS of 6 days (1.6 days decade-1) and a significantly advanced winter WIT of 12 days (3.2 days decade-1). The potential linkage between the phase variations in the oceanic seasonal cycle and those of the atmospheric forcing was investigated by analyzing both the interannual variability and the secular trend. Over the analysis period, the secular trend of an earlier summer ONS is related to a total reduction of cloud cover by 30% of its climatological mean and an increase of incoming solar radiation of 10 W m-2 month-1 in the late spring. Thus, our results highlight the influence of cloud cover in addition to wind speed on the temporal variations of season transition timing.
Application of magnetic analyzers for detecting carburization of pyrolysis furnace tubes
Authors: Du Chenyang , Liu Chang , Li Xiaowei , Liu Baolin , Lu Jianyu , Tan Xinli , Song Ce
Published: March 2023

Ethylene pyrolysis furnace is a key equipment in the ethylene production industry with the pyrolysis furnace tube being the core component of the system. The tube operates at high temperature (950°C–1,100°C) and hydrocarbon medium for a long time, and the Cr35Ni45Nb centrifugal casting alloy material is often chosen as the material of the tube. Due to its harsh working conditions, its common failure issues include carburization, high-temperature creep cracking, thermal shock and thermal fatigue, overheating, creep expansion, bending, etc. Among them, carburization is the main cause of furnace tube failure. In this work, based on the characteristics of HP series (ASTM HP grade) furnace tube material, which is transformed from paramagnetic material to ferromagnetic material following carburization, the cracking furnace tube with different carburization layer thickness has been prepared, and the coercivity of furnace tube with different thickness of carburization layer is tested by magnetic analyzer. The relationship curve between carburization layer thickness and coercivity is subsequently studied to find a means to test the carburization layer thickness in engineering. By fitting the experimental data, the fitting rate reached 97%, which in turn verified the validity and accuracy of the method.
Numerical realization of a semi-active virtual acoustic black hole effect
Authors: Soleimanian Sina , Petrone Giuseppe , Franco Francesco , De Rosa Sergio , Kołakowski Przemysław
Published: March 2023

Noise mitigation by means of the acoustic black hole (ABH) effect is a well-known engineering solution. However, the conventional method of applying ABH effect which requires modification of the structure geometry has various limitations which encourage the research of virtual ABH concept. In this study, the effect of ABH was applied through introducing virtual stiffness by a shunt circuit. According to the force-voltage electric analogy, stiffness has an inverse relationship with capacitance. So that the ABH effect can be virtually realized by following a power law profile using an array of independent capacitive shunts. The concept is studied through finite element simulation developing a macro code in ANSYS Parametric Design Language (APDL). To evaluate the influence of capacitance profile on the acoustic radiated power, parametric studies are conducted. Based on the results of the parametric studies, the capacitance profile is tuned for minimum radiated power. It is revealed that the virtual acoustic black hole (ABH) effect can offer 10.29%, 6.37%, and 7.47% reduction in the radiated power from the first to the last targeted mode, respectively. The virtual ABH effect introduced in this study can be used for semi-active structural noise isolation without any weight or manufacturing penalty.
The impact of analgesic on EMG and other biosignals in a postoperative setting
Authors: Gruss Sascha , Schmid Matthias , Walter Steffen , Schick Benedikt , Holler Lena , Barth Eberhard
Published: March 2023

Background

In the clinical context, the assessment of pain in patients with inadequate communication skills is standardly performed externally by trained medical staff. Automated pain recognition (APR) could make a significant contribution here. Hereby, pain responses are captured using mainly video cams and biosignal sensors. Primary, the automated monitoring of pain during the onset of analgesic sedation has the highest relevance in intensive care medicine. In this context, facial electromyography (EMG) represents an alternative to recording facial expressions via video in terms of data security. In the present study, specific physiological signals were analyzed to determine, whether a distinction can be made between pre-and post-analgesic administration in a postoperative setting. Explicitly, the significance of the facial EMG regarding the operationalization of the effect of analgesia was tested.

Methods

N = 38 patients scheduled for surgical intervention where prospectively recruited. After the procedure the patients were transferred to intermediate care. Biosignals were recorded and all doses of analgesic sedations were carefully documented until they were transferred back to the general ward.

Results

Almost every biosignal feature is able to distinguish significantly between ‘before’ and ‘after’ pain medication. We found the highest effect sizes (r = 0.56) for the facial EMG.

Conclusion

The results of the present study, findings from research based on the BioVid and X-ITE pain datasets, staff and patient acceptance indicate that it would now be appropriate to develop an APR prototype.
Experiences of obstetric nurses and midwives receiving a perinatal bereavement care training programme: A qualitative study
Authors: Qian Jialu , Chen Shuyi , Jevitt Cecilia , Sun Shiwen , Wang Man , Yu Xiaoyan
Published: March 2023

Aim

To explore obstetric nurses and midwifery professionals’ experiences with the Perinatal Bereavement Care Training Programme (PBCTP) after implementation.

Design

A qualitative descriptive design was used.

Method

This qualitative study was conducted at a tertiary level maternity hospital in China. The PBCTP was implemented at Women’s Hospital School of Medicine, Zhejiang University from March to May 2022. A total of 127 nurses and 44 midwives were invited to participate in the training. Obstetric nurses and midwives studied a 5-module training programme comprised of eight online theoretical courses and submitted a reflective journal after each session. Semi-structured interviews were conducted with 12 obstetric nurses and four midwives from May to July 2022 as a post-intervention evaluation. Thematic analysis was used in data analysis.

Findings

A total of 16 participants in this study ranged in age from 23 to 40 years [mean age (SD), 30 (4) years]. Six main themes within participants’ experiences of PBCTP intervention were identified: participants’ aims of undertaking the training; personal growth and practice changes after training; the most valuable training content; suggestions for training improvement; directions for practice improvement; influencing factors of practice optimization.

Conclusion

Nursing and midwifery professionals described the PBCTP as satisfying their learning and skills enhancement needs and supporting positive changes in their care providing for bereaved families. The optimized training programme should be widely applied in the future. More efforts from the hospitals, managers, obstetric nurses, and midwives are needed to jointly contribute to forming a uniform care pathway and promoting a supportive perinatal bereavement care practice.
A first case of successful using of ibrutinib in treating paraneoplastic pemphigus related bronchiolitis obliterans concurrent with CLL
Authors: Chen Can , Xu Ying , Yu Jingdi , Qian Shenxian , Xie Yaping
Published: March 2023

Paraneoplastic pemphigus (PNP) is a rare life-threatening disease which always associated with an underlying neoplasm. Tumor-related PNP most commonly precedes the detection of a hematological malignancy, with some cases seen during disease remission following cytotoxic drug therapy or radiotherapy. The lung is the most frequently-involved site in PNP, second only to the eyes, and involvement is seen in 59.2% to 92.8% of PNP cases. Bronchiolitis obliterans (BO) is the end stage of respiratory involvement and is regarded as life-threatening. The key point in treatment of PNP is to control the associated underlying hematologic neoplasia. High-dose systemic corticosteroids combined with other immunosuppressants are considered the first line of treatment. Other therapies that have shown beneficial effects include plasmapheresis, intravenous immunogloblin (IVIG), and more recently, daclizumab, alemtuzumab, and rituximab. There is no effective treatment for BO with PNP, and suppression of the cellular immune response may be necessary. Patients with PNP-BO associated with lymphoma mostly die within approximately 1 year. Herein, we reported a patient who diagnosed with PNP-BO concurrent with chronic lymphocytic leukemia. He was successful treated with ibrutinib and had achieved the longest survival which suggested that ibrutinib may be the best treatment choice for such patient.
Changes of gut microbiota and tricarboxylic acid metabolites may be helpful in early diagnosis of necrotizing enterocolitis: A pilot study
Authors: Du Ting-Ting , Liu Xiao-Chen , He Yu , Gao Xiong , Liu Zhen-Zhen , Wang Zheng-Li , Li Lu-Quan
Published: March 2023

Purpose

We aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations.

Methods

Thirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data.

Results

There was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively.

Conclusion

Decreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.
Syk inhibitors protect against microglia-mediated neuronal loss in culture
Authors: Birkle Timothy J. Y. , Brown Guy C.
Published: March 2023

Microglia are brain macrophages and play beneficial and/or detrimental roles in many brain pathologies because of their inflammatory and phagocytic activity. Microglial inflammation and phagocytosis are thought to be regulated by spleen tyrosine kinase (Syk), which is activated by multiple microglial receptors, including TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), implicated in neurodegeneration. Here, we have tested whether Syk inhibitors can prevent microglia-dependent neurodegeneration induced by lipopolysaccharide (LPS) in primary neuron-glia cultures. We found that the Syk inhibitors BAY61-3606 and P505-15 (at 1 and 10 μM, respectively) completely prevented the neuronal loss induced by LPS, which was microglia-dependent. Syk inhibition also prevented the spontaneous loss of neurons from older neuron-glia cultures. In the absence of LPS, Syk inhibition depleted microglia from the cultures and induced some microglial death. However, in the presence of LPS, Syk inhibition had relatively little effect on microglial density (reduced by 0–30%) and opposing effects on the release of two pro-inflammatory cytokines (IL-6 decreased by about 45%, TNFα increased by 80%). Syk inhibition also had no effect on the morphological transition of microglia exposed to LPS. On the other hand, inhibition of Syk reduced microglial phagocytosis of beads, synapses and neurons. Thus, Syk inhibition in this model is most likely neuroprotective by reducing microglial phagocytosis, however, the reduced microglial density and IL-6 release may also contribute. This work adds to increasing evidence that Syk is a key regulator of the microglial contribution to neurodegenerative disease and suggests that Syk inhibitors may be used to prevent excessive microglial phagocytosis of synapses and neurons.
Phenotypic correlates of serum neurofilament light chain levels in amyotrophic lateral sclerosis
Authors: Verde Federico , Milone Ilaria , Colombo Eleonora , Maranzano Alessio , Solca Federica , Torre Silvia , Doretti Alberto , Gentile Francesco , Manini Arianna , Bonetti Ruggero , Peverelli Silvia , Messina Stefano , Maderna Luca , Morelli Claudia , Poletti Barbara , Ratti Antonia , Silani Vincenzo , Ticozzi Nicola
Published: March 2023

Objective

To investigate the relationship between serum levels of the neuroaxonal degeneration biomarker neurofilament light chain (NFL) and phenotype in ALS.

Materials and methods

Serum NFL (sNFL) concentration was quantified in 209 ALS patients and 46 neurologically healthy controls (NHCs).

Results

sNFL was clearly increased in ALS patients and discriminated them from NHCs with AUC = 0.9694. Among ALS patients, females had higher sNFL levels, especially in case of bulbar onset. sNFL was more increased in phenotypes with both upper (UMN) and lower motor neuron (LMN) signs, and particularly in those with UMN predominance, compared to LMN forms. At the same time, primary lateral sclerosis (PLS) had significantly lower levels compared to UMN-predominant ALS (AUC = 0.7667). sNFL correlated negatively with disease duration at sampling and ALSFRS-R score, positively with disease progression rate, differed among King’s stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn UMN Score, LMN score, MRC composite score, active spinal denervation score). On the contrary, sNFL was not associated with cognitive deficits nor with respiratory parameters. Notably, we found a negative correlation between sNFL and estimated glomerular filtration rate (eGFR).

Interpretation

We confirm that ALS is characterized by increased sNFL levels, whose main determinant is the rate of degeneration of both UMNs and LMNs. sNFL is a biomarker of only motor, not of extra-motor, disease. The negative correlation with kidney function might reflect varying renal clearance of the molecule and deserves further investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.
Soluble TNF mediates amyloid-independent, diet-induced alterations to immune and neuronal functions in an Alzheimer’s disease mouse model
Authors: MacPherson Kathryn P. , Eidson Lori N. , Houser Madelyn C. , Weiss Blaine E. , Gollihue Jenna L. , Herrick Mary K. , de Sousa Rodrigues Maria Elizabeth , Sniffen Lindsey , Weekman Erica M. , Hamilton Adam M. , Kelly Sean D. , Oliver Danielle L. , Yang Yuan , Chang Jianjun , Sampson Timothy R. , Norris Christopher M. , Tansey Malú Gámez
Published: March 2023

Introduction: Increasing evidence indicates that neurodegenerative diseases, including Alzheimer’s disease (AD), are a product of gene-by-environment interplay. The immune system is a major contributor mediating these interactions. Signaling between peripheral immune cells and those within the microvasculature and meninges of the central nervous system (CNS), at the blood-brain barrier, and in the gut likely plays an important role in AD. The cytokine tumor necrosis factor (TNF) is elevated in AD patients, regulates brain and gut barrier permeability, and is produced by central and peripheral immune cells. Our group previously reported that soluble TNF (sTNF) modulates cytokine and chemokine cascades that regulate peripheral immune cell traffic to the brain in young 5xFAD female mice, and in separate studies that a diet high in fat and sugar (HFHS) dysregulates signaling pathways that trigger sTNF-dependent immune and metabolic responses that can result in metabolic syndrome, which is a risk factor for AD. We hypothesized that sTNF is a key mediator of peripheral immune cell contributions to gene-by-environment interactions to AD-like pathology, metabolic dysfunction, and diet-induced gut dysbiosis.

Methods: Female 5xFAD mice were subjected to HFHS diet for 2 months and then given XPro1595 to inhibit sTNF for the last month or saline vehicle. We quantified immune cell profiles by multi-color flow cytometry on cells isolated from brain and blood; metabolic, immune, and inflammatory mRNA and protein marker biochemical and immunhistological analyses, gut microbiome, and electrophysiology in brain slices were also performed.

Results: Here, we show that selective inhibition of sTNF signaling via the biologic XPro1595 modulates the effects of an HFHS diet in 5xFAD mice on peripheral and central immune profiles including CNS-associated CD8+ T cells, the composition of gut microbiota, and long-term potentiation deficits.

Discussion: Obesogenic diet induces immune and neuronal dysfunction in 5xFAD mice and sTNF inhibition mitigates its effects. A clinical trial in subjects at risk for AD due to genetic predisposition and underlying inflammation associated with peripheral inflammatory co-morbidities will be needed to investigate the extent to which these findings translate to the clinic.
Measuring brain potentials of imagination linked to physiological needs and motivational states
Authors: Proverbio A. M. , Pischedda F.
Published: March 2023

Introduction

While EEG signals reflecting motor and perceptual imagery are effectively used in brain computer interface (BCI) contexts, little is known about possible indices of motivational states. In the present study, electrophysiological markers of imagined motivational states, such as craves and desires were investigated.

Methods

Event-related potentials (ERPs) were recorded in 31 participants during perception and imagery elicited by the presentation of 360 pictograms. Twelve micro-categories of needs, subdivided into four macro-categories, were considered as most relevant for a possible BCI usage, namely: primary visceral needs (e.g., hunger, linked to desire of food); somatosensory thermal and pain sensations (e.g., cold, linked to desire of warm), affective states (e.g., fear: linked to desire of reassurance) and secondary needs (e.g., desire to exercise or listen to music). Anterior N400 and centroparietal late positive potential (LPP) were measured and statistically analyzed.

Results

N400 and LPP were differentially sensitive to the various volition stats, depending on their sensory, emotional and motivational poignancy. N400 was larger to imagined positive appetitive states (e.g., play, cheerfulness) than negative ones (sadness or fear). In addition, N400 was of greater amplitude during imagery of thermal and nociceptive sensations than other motivational or visceral states. Source reconstruction of electromagnetic dipoles showed the activation of sensorimotor areas and cerebellum for movement imagery, and of auditory and superior frontal areas for music imagery.

Discussion

Overall, ERPs were smaller and more anteriorly distributed during imagery than perception, but showed some similarity in terms of lateralization, distribution, and category response, thus indicating some overlap in neural processing, as also demonstrated by correlation analyses. In general, anterior frontal N400 provided clear markers of subjects’ physiological needs and motivational states, especially cold, pain, and fear (but also sadness, the urgency to move, etc.), than can signal life-threatening conditions. It is concluded that ERP markers might potentially allow the reconstruction of mental representations related to various motivational states through BCI systems.
Facial feedback effect on the sense of body ownership during the rubber hand illusion
Authors: Kaneno Yoshitaka , Ashida Hiroshi
Published: March 2023

The sense of body ownership, a feeling that one’s body belongs to the self, is an essential aspect of self-consciousness. Studies have focused on emotions and bodily states that could influence multisensory integration for the sense of body ownership. Based on the Facial Feedback Hypothesis, the purpose of this study was to examine whether displaying specific facial expressions affects the rubber hand illusion. We hypothesized that the expression of a smiling face changes the emotional experience and facilitates the formation of a sense of body ownership. In the experiment, participants (n = 30) were asked to hold a wooden chopstick in their mouths to simulate smile, neutral, and disgusted facial expressions during the induction of the rubber hand illusion. The results did not support the hypothesis, showing that proprioceptive drift (an index of illusory experience) was enhanced when the subjects displayed a disgusted facial expression, while the subjective reports of the illusion were not affected. These results, together with the previous studies regarding the effect of positive emotions, suggest that bodily affective information, regardless of its valence, facilitates multisensory integration and could influence the conscious representation of the bodily self.
Novel methods for elucidating modality importance in multimodal electrophysiology classifiers
Authors: Ellis Charles A. , Sendi Mohammad S. E. , Zhang Rongen , Carbajal Darwin A. , Wang May D. , Miller Robyn L. , Calhoun Vince D.
Published: March 2023

Introduction

Multimodal classification is increasingly common in electrophysiology studies. Many studies use deep learning classifiers with raw time-series data, which makes explainability difficult, and has resulted in relatively few studies applying explainability methods. This is concerning because explainability is vital to the development and implementation of clinical classifiers. As such, new multimodal explainability methods are needed.

Methods

In this study, we train a convolutional neural network for automated sleep stage classification with electroencephalogram (EEG), electrooculogram, and electromyogram data. We then present a global explainability approach that is uniquely adapted for electrophysiology analysis and compare it to an existing approach. We present the first two local multimodal explainability approaches. We look for subject-level differences in the local explanations that are obscured by global methods and look for relationships between the explanations and clinical and demographic variables in a novel analysis.

Results

We find a high level of agreement between methods. We find that EEG is globally the most important modality for most sleep stages and that subject-level differences in importance arise in local explanations that are not captured in global explanations. We further show that sex, followed by medication and age, had significant effects upon the patterns learned by the classifier.

Discussion

Our novel methods enhance explainability for the growing field of multimodal electrophysiology classification, provide avenues for the advancement of personalized medicine, yield unique insights into the effects of demographic and clinical variables upon classifiers, and help pave the way for the implementation of multimodal electrophysiology clinical classifiers.
Cerebral cortical hemodynamic metrics to aid in assessing pain levels? A pilot study of functional near-infrared spectroscopy
Authors: Du Jiahao , Shi Ping , Fang Fanfu , Yu Hongliu
Published: March 2023

Introduction

Establishing an accurate way to quantify pain is one of the most formidable tasks in neuroscience and medical practice. Functional near-infrared spectroscopy (fNIRS) can be utilized to detect the brain’s reaction to pain. The study sought to assess the neural mechanisms of the wrist-ankle acupuncture transcutaneous electrical nerve stimulation analgesic bracelet (E-WAA) in providing pain relief and altering cerebral blood volume dynamics, and to ascertain the reliability of cortical activation patterns as a means of objectively measuring pain.

Methods

The participants (mean age 36.6 ± 7.2 years) with the cervical-shoulder syndrome (CSS) underwent pain testing prior to, 1 min following, and 30 min after the left point Jianyu treatment. The E-WAA was used to administer an electrical stimulation therapy that lasted for 5 min. A 24-channel fNIRS system was utilized to monitor brain oxyhemoglobin (HbO) levels, and changes in HbO concentrations, cortical activation areas, and subjective pain assessment scales were documented.

Results

We discovered that HbO concentrations in the prefrontal cortex significantly increased when CSS patients were exposed to painful stimuli at the cerebral cortex level. The second pain test saw a considerable decrease in the average HbO change amount in the prefrontal cortex when E-WAA was applied, which in turn led to a reduction in the amount of activation and the size of the activated area in the cortex.

Discussion

This study revealed that the frontal polar (FP) and dorsolateral prefrontal cortex (DLPFC) were linked to the analgesic modulation activated by the E-WAA.
7,8-dihydroxyflavone enhances long-term spatial memory and alters brain volume in wildtype mice
Authors: Rawlings-Mortimer Florence , Lazari Alberto , Tisca Cristiana , Tachrount Mohamed , Martins-Bach Aurea B. , Miller Karla L. , Lerch Jason P. , Johansen-Berg Heidi
Published: March 2023

Introduction: 7,8-dihydroxyflavone (7,8-DHF) is a low molecular weight compound that can cross the blood brain barrier and has been implicated in numerous functions and behaviours. It is thought to have neuroprotective capability and has been shown to alleviate symptoms in a wide range of diseases.

Methods: 7,8-DHF was administered systemically to wildtype mice during Morris water maze training. Long-term spatial memory was assessed 28 days later. Ex-vivo T2-weighted (T2w) imaging was undertaken on a subset of these mice to assess brain-wide changes in volume.

Results: We found that systemic 7,8-DHF administration during the training period enhanced spatial memory 28 days later. Volumetric changes were observed in numerous brain regions associated with a broad range of functions including cognition, sensory, and motor processing.

Discussion: Our findings give the first whole brain overview of long-term anatomical changes following 7,8-DHF administration providing valuable information for assessing and understanding the widespread effects this drug has been shown to have in behaviour and disease.
Serum lipid biomarkers and inflammatory cytokines associated with onset and clinical status of patients with early knee osteoarthritis
Authors: Herrero-Manley Luz , Alabajos-Cea Ana , Suso-Martí Luis , Cuenca-Martínez Ferran , Calatayud Joaquín , Casaña José , Viosca-Herrero Enrique , Vázquez-Arce Isabel , Ferrer-Sargues Francisco José , Blanco-Díaz María
Published: March 2023

Introduction

Osteoarthritis (OA) is a common joint condition and one of the greatest causes of disability worldwide. The role of serum lipid and inflammatory biomarkers in the origin and development of the disease is not clear, although it could have important implications for diagnosis and treatment. The primary aim of this study was to evaluate differences of serum lipid and inflammatory biomarkers with knee EOA in comparison with matched controls, in order to determine the role of these factors in the origin of EOA.

Methods

For this proposal, a cross-sectional study with a non-randomized sample was performed. 48 subjects with early osteoarthritis (EOA) and 48 matched controls were selected and serum lipid levels (total cholesterol, LDL, HDL) and inflammatory biomarkers C-reactive protein (CRP), uric acid (UA) were analyzed. In addition, clinical (pain, disability) and functional (gait speed, sit-to-stand) variables were measured to establish their relationship to serum lipid levels and inflammatory biomarkers.

Results

Patients with EOA showed higher levels of total cholesterol LDL, UA, and CRP. Higher levels of total cholesterol, LDL and CRP were correlated with higher levels of pain intensity and higher disability (p < 0.05). In addition, UA and CRP were inversely correlated with gait speed and sit-to-stand tests (r = −0.038 to −0.5, p < 0.05).

Conclusion

These results highlight the relevance of metabolic and proinflammatory aspects in the early stages of knee OA and could be key to developing early diagnoses to prevent the onset and development of the disease.
A distress thermometer with a cutoff score of ≥ 6 is the optimal point to identify highly distressed patients with advanced cancer stages in resource-limited countries without palliative care services
Authors: Abu-Odah Hammoda , Molassiotis Alex , Liu Justina Yat Wa
Published: March 2023

Purpose

Although the distress thermometer (DT) scale has been widely validated and used in different cancer types and settings, an optimal cutoff score of DT is not defined to screen advanced cancer patients. The study aimed to define the optimal DT’s cutoff score among advanced cancer patients in resource-limited countries without palliative care services and to assess the prevalence and factors associated with psychological distress among this population.

Methods

A secondary analysis was performed. Three hundred seventy-nine patients were recruited from Palestine. Participants completed the DT and the Hospital Anxiety and Depression Scale (HADS). Receiver operating characteristic analysis (ROC) was used to define the optimal cutoff score for the DT against HADS-Total ≥15. Multiple logistic regression was utilized for identifying the factors associated with psychological distress of the DT.

Results

A DT cutoff score ≥ 6 correctly identified 74% of HADS distress cases and 77% of HADS non-distress cases, with a positive predictive value (PPV) and negative predictive value (NPV) of 97% and 18%, respectively. The prevalence of distress was found to be 70.7%, and the major sources of distress were related to physical (n = 373; 98.4%) and emotional problems (n = 359; 94.7%). Patients with colon (OR = 0.44, 95% CI: 0.31 – 0.62) and lymphoid cancers (OR = 0.41, 95% CI: 0.26 – 0.64) were less likely to have psychological distress than patients with other types of cancer, whereas patients with lung (OR = 1.80, 95% CI: 1.20 – 2.70) and bone cancers (OR = 1.75, 95% CI: 1.14 – 2.68) were more likely to experience it.

Conclusion

A cutoff DT score of 6 appeared acceptable and effective for screening distress in patients with advanced cancer stages. Palestinian patients exhibited a high level of distress, and the high prevalence supports the argument of using a DT within the standard delivery of cancer care to identify highly distressed patients. These highly distressed patients should then be involved in a psychological intervention programme.
A 6-month-old girl with mesenteric teratoma: A Case report and literature review
Authors: Jin Yuyan , Zhang Yanan , Chen Yongwei , Huang Jinshi
Published: March 2023

An otherwise healthy 4-month-old girl presented to the community health service center because her abdomen was distended. Over the next 2 months, the girl's abdomen gradually became more distended. Her examination was notable for abdominal distention with a large, mobile, non-tender abdominal mass. Abdominal ultrasound images and subsequently obtained CT images showed a large, circumscribed cystic and solid mass. This led to the presumptive diagnosis of teratoma of the mesentery. The mass was completely resected during a laparotomy. The pathology, along with the surgical findings and imaging, led to the final diagnosis.