bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased roll tilt thresholds are associated with subclinical postural instability in asymptomatic adults aged 21 to 84 years
Authors: Wagner Andrew R. , Kobel Megan J. , Merfeld Daniel M.
Published: August 2023

Background

Balance assessments that intentionally alter the reliability of visual and proprioceptive feedback (e.g., standing on foam with eyes closed) have become a standard approach for identifying vestibular mediated balance dysfunction in older adults. However, such assessments cannot discern which specific element of the vestibular system (e.g., semicircular canal, otolith, or combined canal-otolith) underlies the observed age-related changes in balance performance. The present study was designed to determine the associations between specific sources of vestibular noise and quantitative measures of quiet stance postural control measured during standard “vestibular” balance conditions.

Methods

A group of 52 asymptomatic adults (53.21 ± 19.7, 21 to 84 years) without a history of vestibular or neurologic disorders volunteered for this study. We measured a battery of five vestibular perceptual thresholds that assay vestibular noise with predominant contributions from the vertical canals, lateral canals, utricles, saccules, and the centrally integrated canal-otolith signal. In addition, participants completed two standard balance assessments that were each designed to prioritize the use of vestibular cues for quiet stance postural control—eyes closed on foam (Condition 4 of the Modified Romberg Balance Test) and eyes closed, on a sway referenced support surface (Condition 5 of the Sensory Organization Test).

Results

In age adjusted models, we found strong positive associations between roll tilt vestibular thresholds, a measure of noise in the centrally integrated canal-otolith signal, and the root mean square distance (RMSD) of the anteroposterior and mediolateral center of pressure (CoP) captured during eyes closed stance on a sway referenced support surface. The strength of the association between roll tilt thresholds and the RMSD of the CoP was between 3-times and 30-times larger than the association between postural sway and each of the other vestibular thresholds measured.

Conclusion

We posit that noise in the centrally estimated canal-otolith “tilt” signal may be the primary driver of the subclinical postural instability experienced by older adults during the “vestibular” conditions of balance assessments. Additional testing in adults with clinical balance impairment are needed to identify if roll tilt thresholds may also serve as a surrogate metric by which to detect vestibular mediated balance dysfunction and/or fall risk.
Effect of apparatus characteristics on anxiety-like behavior in young adult and old mice of both sexes assessed by the elevated plus maze assay
Authors: Gaspar Lauren , Bartman Sydney , Coppotelli Giuseppe , Ross Jaime M.
Published: August 2023

Incidence of anxiety-like disorders in humans has been shown to decrease with aging; however, it is still under debate whether there are similarities in mice, which would support the use of mouse models in understanding the neuronal network changes that regulate anxiety-like behavior in aging. One of the most common tests used to assess anxiety-like behavior in laboratory animals is the elevated plus maze (EPM). Although several variables, such as room brightness and width of the maze arms, have been shown to influence the spontaneous animal behavior during the EPM test, none of these variables have ever been evaluated in aging to understand their possible differential effect on younger and older mice. We therefore decided to investigate the effect of apparatus construction on young adult and old mice of both sexes on EPM test performance. Our results show that distance traveled during the test is the variable that is most affected by apparatus characteristics independent of age and sex. We also found that apparatus construction was key in demonstrating that old mice spent more time and had relatively more entries in the open arms as compared to young mice, suggesting a decrease in anxiety-like behavior with age. Taken together, our data demonstrate that EPM apparatus characteristics dramatically affect test outcome with a wider arm apparatus being more effective in revealing age-dependent changes in anxiety-like behavior, thus, suggesting the use of a wider arm EPM when conducting aging studies in mice.
Train-your-brain program to reduce depression, anxiety, and stress in stroke survivors: a pilot community-based cognitive intervention study
Authors: Tham Xiang Cong , Phua Vanessa Jing Xin , Ho Evelyn Kit Yee , Yan Tingting , Chen Nicole Yun Ching , Zuo Lijun , Thompson Claire L. , Dong Yanhong
Published: August 2023

Introduction

Stroke is a major cause of death and disability worldwide, and it often results in depression, anxiety, stress, and cognitive impairment in survivors. There is a lack of community-based cognitive interventions for stroke survivors. This pilot single trial aimed to assess the feasibility, acceptability, and perceived effectiveness of a community-based cognitive intervention program called Train-Your-Brain (TYB) for stroke survivors and caregivers. The study focused on improvements in emotional and psychological well-being, as well as cognitive functioning.

Methods

A quasi-experimental design was used in this study. A total of 48 participants were recruited and assessed using Depression, Anxiety, Stress Scale – 21 items (DASS-21), Montreal Cognitive Assessment (MoCA) and Symbol Digits Modality Test (SDMT) before and after the intervention. The TYB program consisted of nine sessions and was conducted via the Zoom software application. Participants provided feedback on the program, highlighting areas for improvement.

Results

Twenty-seven stroke survivors and 21 caregivers completed the program. Participants expressed high satisfaction with the TYB program but recommended avoiding assessments in December and customizing the program for stroke survivors and caregivers. Stroke survivors showed significant improvements in depression and stress scores, while caregivers experienced no significant improvements after the program. While there was a slight improvement in stroke survivors’ cognitive scores after the program, it was not statistically significant. Caregivers, however, experienced a significant decline in cognitive scores.

Discussion

The TYB program provided group support and validation, resulting in improved mood and reduced stress among stroke survivors. Cultural collectivism played a significant role in fostering group cohesion. However, the program’s limited focus on caregivers and timing of assessments during the December holidays may have affected the outcomes. The TYB program demonstrated feasibility and potential effectiveness in alleviating psychological distress and enhancing cognitive function among stroke survivors. Future research should explore long-term effects, larger sample sizes, and non-English-speaking populations to enhance generalizability. Tailored interventions for caregivers are necessary.
Treatable brain network biomarkers in children in coma using task and resting-state functional MRI: a case series
Authors: Boerwinkle Varina L. , Sussman Bethany L. , Broman-Fulks Jordan , Garzon-Cediel Emilio , Gillette Kirsten , Reuther William R. , Scher Mark S.
Published: August 2023

The withdrawal of life-sustaining therapies is frequently considered for pediatric patients with severe acute brain injuries who are admitted to the intensive care unit. However, it is worth noting that some children with a resultant poor neurological status may ultimately survive and achieve a positive neurological outcome. Evidence suggests that adults with hidden consciousness may have a more favorable prognosis compared to those without it. Currently, no treatable network disorders have been identified in cases of severe acute brain injury, aside from seizures detectable through an electroencephalogram (EEG) and neurostimulation via amantadine. In this report, we present three cases in which multimodal brain network evaluation played a helpful role in patient care. This evaluation encompassed various assessments such as continuous video EEG, visual-evoked potentials, somatosensory-evoked potentials, auditory brainstem-evoked responses, resting-state functional MRI (rs-fMRI), and passive-based and command-based task-based fMRI. It is worth noting that the latter three evaluations are unique as they have not yet been established as part of the standard care protocol for assessing acute brain injuries in children with suppressed consciousness. The first patient underwent serial fMRIs after experiencing a coma induced by trauma. Subsequently, the patient displayed improvement following the administration of antiseizure medication to address abnormal signals. In the second case, a multimodal brain network evaluation uncovered covert consciousness, a previously undetected condition in a pediatric patient with acute brain injury. In both patients, this discovery potentially influenced decisions concerning the withdrawal of life support. Finally, the third patient serves as a comparative control case, demonstrating the absence of detectable networks. Notably, this patient underwent the first fMRI prior to experiencing brain death as a pediatric patient. Consequently, this case series illustrates the clinical feasibility of employing multimodal brain network evaluation in pediatric patients. This approach holds potential for clinical interventions and may significantly enhance prognostic capabilities beyond what can be achieved through standard testing methods alone.
Is transcranial direct current stimulation (tDCS) effective to improve cognition and functionality after severe traumatic brain injury? A perspective article and hypothesis
Authors: Cordeiro Bárbara Naeme de Lima , Kuster Elizângela , Thibaut Aurore , Rodrigues Nascimento Lucas , Gonçalves Jessica Vaz , Arêas Guilherme Peixoto Tinoco , Paiva Wellingson Silva , Arêas Fernando Zanela da Silva
Published: August 2023

Severe traumatic brain injury (sTBI) is an important cause of disability and mortality and affects people of all ages. Current scientific evidence indicates that motor dysfunction and cognitive impairment are the main limiting factors in patients with sTBI. Transcranial direct current stimulation (tDCS) seems to be a good therapeutic option, but when it comes to patients with sTBI, the results are inconclusive, and some protocols have not yet been tested. In addition, there is still a lack of information on tDCS-related physiological mechanisms, especially during the acute phase. In the present study, based on current evidence on tDCS mechanisms of action, we hypothesized that performing tDCS sessions in individuals with sTBI, especially in the acute and subacute phases, together with conventional therapy sessions, could improve cognition and motor function in this population. This hypothesis presents a new possibility for treating sTBI, seeking to elucidate the extent to which early tDCS may affect long-term clinical outcomes.
3T vs. 7T fMRI: capturing early human memory consolidation after motor task utilizing the observed higher functional specificity of 7T
Authors: Kreitz Silke , Mennecke Angelika , Konerth Laura , Rösch Julie , Nagel Armin M. , Laun Frederik B. , Uder Michael , Dörfler Arnd , Hess Andreas
Published: August 2023

Objective

Functional magnetic resonance imaging (fMRI) visualizes brain structures at increasingly higher resolution and better signal-to-noise ratio (SNR) as field strength increases. Yet, mapping the blood oxygen level dependent (BOLD) response to distinct neuronal processes continues to be challenging. Here, we investigated the characteristics of 7 T-fMRI compared to 3 T-fMRI in the human brain beyond the effect of increased SNR and verified the benefits of 7 T-fMRI in the detection of tiny, highly specific modulations of functional connectivity in the resting state following a motor task.

Methods

18 healthy volunteers underwent two resting state and a stimulus driven measurement using a finger tapping motor task at 3 and 7 T, respectively. The SNR for each field strength was adjusted by targeted voxel size variation to minimize the effect of SNR on the field strength specific outcome. Spatial and temporal characteristics of resting state ICA, network graphs, and motor task related activated areas were compared. Finally, a graph theoretical approach was used to detect resting state modulation subsequent to a simple motor task.

Results

Spatial extensions of resting state ICA and motor task related activated areas were consistent between field strengths, but temporal characteristics varied, indicating that 7 T achieved a higher functional specificity of the BOLD response than 3 T-fMRI. Following the motor task, only 7 T-fMRI enabled the detection of highly specific connectivity modulations representing an “offline replay” of previous motor activation. Modulated connections of the motor cortex were directly linked to brain regions associated with memory consolidation.

Conclusion

These findings reveal how memory processing is initiated even after simple motor tasks, and that it begins earlier than previously shown. Thus, the superior capability of 7 T-fMRI to detect subtle functional dynamics promises to improve diagnostics and therapeutic assessment of neurological diseases.
DYT-TOR1A dystonia: an update on pathogenesis and treatment
Authors: Fan Yuhang , Si Zhibo , Wang Linlin , Zhang Lei
Published: August 2023

DYT-TOR1A dystonia is a neurological disorder characterized by involuntary muscle contractions and abnormal movements. It is a severe genetic form of dystonia caused by mutations in the TOR1A gene. TorsinA is a member of the AAA + family of adenosine triphosphatases (ATPases) involved in a variety of cellular functions, including protein folding, lipid metabolism, cytoskeletal organization, and nucleocytoskeletal coupling. Almost all patients with TOR1A-related dystonia harbor the same mutation, an in-frame GAG deletion (ΔGAG) in the last of its 5 exons. This recurrent variant results in the deletion of one of two tandem glutamic acid residues (i.e., E302/303) in a protein named torsinA [torsinA(△E)]. Although the mutation is hereditary, not all carriers will develop DYT-TOR1A dystonia, indicating the involvement of other factors in the disease process. The current understanding of the pathophysiology of DYT-TOR1A dystonia involves multiple factors, including abnormal protein folding, signaling between neurons and glial cells, and dysfunction of the protein quality control system. As there are currently no curative treatments for DYT-TOR1A dystonia, progress in research provides insight into its pathogenesis, leading to potential therapeutic and preventative strategies. This review summarizes the latest research advances in the pathogenesis, diagnosis, and treatment of DYT-TOR1A dystonia.
Peripheral metabolic alterations associated with pathological manifestations of Parkinson’s disease in gut-brain axis-based mouse model
Authors: Huh Eugene , Choi Jin Gyu , Lee Mee Youn , Kim Jin Hee , Choi Yujin , Ju In Gyoung , Eo Hyeyoon , Park Myoung Gyu , Kim Dong-Hyun , Park Hi-Joon , Lee Choong Hwan , Oh Myung Sook
Published: August 2023

Introduction

Parkinson’s disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis (P. mirabilis)-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis.

Methods

We performed gas chromatography–mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis-induced disease progression and pathology.

Results and discussion

Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis-induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis-mediated pathology of brain neurodegeneration.
Low myelin-related values in the fornix and thalamus of 7 Tesla MRI of major depressive disorder patients
Authors: Shim Jeong-Min , Cho Seo-Eun , Kang Chang-Ki , Kang Seung-Gul
Published: August 2023

Introduction

Abnormalities in myelin are believed to be one of the important causes of major depressive disorder, and it is becoming important to more accurately quantify myelin inin vivomagnetic resonance imaging of major depressive disorder patients. We aimed to investigate the difference in myelin concentration in the white matter and subcortical areas using new quantitative myelin-related maps of high-resolution 7 Tesla (7 T) magnetic resonance imaging between patients with major depressive disorder and healthy controls.

Methods

Myelin-related comparisons of the white matter and nearby subcortical regions were conducted between healthy controls (n= 36) and patients with major depressive disorder (n= 34). Smoothed quantitative ratio (sq-Ratio) myelin-related maps were created using the multi-echo magnetization-prepared two rapid gradient echoes (ME-MP2RAGE) sequence of the T1 and T2* images of 7 T magnetic resonance imaging. Differences in the myelin-related values of the regions of interest between the two groups were analyzed using a two-sample t-test, and multiple comparison corrections were performed using the false discovery rate.

Results

The average sq-Ratio myelin-related values were 2.62% higher in the white matter and 2.26% higher in the subcortical regions of the healthy controls group than in the major depressive disorder group. In the group analysis of the healthy control and major depressive disorder groups, the sq-Ratio myelin-related values were significantly different in the fornix area of the white matter (false discovery rate-correctedp= 0.012). In addition, significant differences were observed in both the left (false discovery rate-correctedp= 0.04) and right thalamus (false discovery rate-correctedp= 0.040) among the subcortical regions.

Discussion

The average sq-ratio myelin-related value and sq-ratio myelin-related values in the fornix of the white matter and both thalami were higher in the healthy controls group than in the major depressive disorder group. We look forward to replicating our findings in other populations using larger sample sizes.
Synaptic alterations and neuronal firing in human epileptic neocortical excitatory networks
Authors: Bod Réka , Tóth Kinga , Essam Nour , Tóth Estilla Zsófia , Erõss Loránd , Entz László , Bagó Attila G. , Fabó Dániel , Ulbert István , Wittner Lucia
Published: August 2023

Epilepsy is a prevalent neurological condition, with underlying neuronal mechanisms involving hyperexcitability and hypersynchrony. Imbalance between excitatory and inhibitory circuits, as well as histological reorganization are relatively well-documented in animal models or even in the human hippocampus, but less is known about human neocortical epileptic activity. Our knowledge about changes in the excitatory signaling is especially scarce, compared to that about the inhibitory cell population. This study investigated the firing properties of single neurons in the human neocortex in vitro, during pharmacological blockade of glutamate receptors, and additionally evaluated anatomical changes in the excitatory circuit in tissue samples from epileptic and non-epileptic patients. Both epileptic and non-epileptic tissues exhibited spontaneous population activity (SPA), NMDA receptor antagonization reduced SPA recurrence only in epileptic tissue, whereas further blockade of AMPA/kainate receptors reversibly abolished SPA emergence regardless of epilepsy. Firing rates did not significantly change in excitatory principal cells and inhibitory interneurons during pharmacological experiments. Granular layer (L4) neurons showed an increased firing rate in epileptic compared to non-epileptic tissue. The burstiness of neurons remained unchanged, except for that of inhibitory cells in epileptic recordings, which decreased during blockade of glutamate receptors. Crosscorrelograms computed from single neuron discharge revealed both mono- and polysynaptic connections, particularly involving intrinsically bursting principal cells. Histological investigations found similar densities of SMI-32-immunopositive long-range projecting pyramidal cells in both groups, and shorter excitatory synaptic active zones with a higher proportion of perforated synapses in the epileptic group. These findings provide insights into epileptic modifications from the perspective of the excitatory system and highlight discrete alterations in firing patterns and synaptic structure. Our data suggest that NMDA-dependent glutamatergic signaling, as well as the excitatory synaptic machinery are perturbed in epilepsy, which might contribute to epileptic activity in the human neocortex.
Glioblastoma survival is associated with distinct proteomic alteration signatures post chemoirradiation in a large-scale proteomic panel
Authors: Krauze Andra Valentina , Sierk Michael , Nguyen Trinh , Chen Qingrong , Yan Chunhua , Hu Ying , Jiang William , Tasci Erdal , Zgela Theresa Cooley , Sproull Mary , Mackey Megan , Shankavaram Uma , Meerzaman Daoud , Camphausen Kevin
Published: August 2023

Background

Glioblastomas (GBM) are rapidly progressive, nearly uniformly fatal brain tumors. Proteomic analysis represents an opportunity for noninvasive GBM classification and biological understanding of treatment response.

Purpose

We analyzed differential proteomic expression pre vs. post completion of concurrent chemoirradiation (CRT) in patient serum samples to explore proteomic alterations and classify GBM by integrating clinical and proteomic parameters.

Materials and methods

82 patients with GBM were clinically annotated and serum samples obtained pre- and post-CRT. Serum samples were then screened using the aptamer-based SOMAScan® proteomic assay. Significant traits from uni- and multivariate Cox models for overall survival (OS) were designated independent prognostic factors and principal component analysis (PCA) was carried out. Differential expression of protein signals was calculated using paired t-tests, with KOBAS used to identify associated KEGG pathways. GSEA pre-ranked analysis was employed on the overall list of differentially expressed proteins (DEPs) against the MSigDB Hallmark, GO Biological Process, and Reactome databases with weighted gene correlation network analysis (WGCNA) and Enrichr used to validate pathway hits internally.

Results

3 clinical clusters of patients with differential survival were identified. 458 significantly DEPs pre- vs. post-treatment, 316 upregulated, 142 downregulated emerged including several pathways relevant to cancer metabolism and progression. The worst survival group (median OS 13.2 months) was associated with DEPs affiliated with proliferative pathways and distinct oppositional response (including RT) as compared to better-performing groups (intermediate, median OS 22.4 months; highest, median OS 28.7 months). Opposite signaling patterns across multiple analyses in several pathways (notably fatty acid metabolism, TNFα via NF-κB, Myc target V1 signaling, UV response, unfolded protein response, peroxisome, and interferon response) were distinct between clinical survival groups and supported by WGCNA. 9 proteins were statistically signficant for OS with 1 (CEACAM16) supported by KM.

Conclusion

Distinct proteomic alterations with hallmarks of cancer, including progression, resistance, stemness, and invasion, were identified in serum samples obtained from GBM patients pre vs. post CRT and corresponded with clinical survival. The proteome can potentially be employed for glioma classification and biological interrogation of cancer pathways.
Prostate-specific membrane antigen-based imaging for stereotactic irradiation of low-volume progressive prostate cancer: a single-center experience
Authors: Varga Linda , Besenyi Zsuzsanna , Paczona Viktor R. , Farkas István , Urbán Szabolcs , Sipka Gábor , Pávics László , Varga Zoltan , Fodor Emese , Hideghéty Katalin , Olah Judit , Bajory Zoltán , Maráz Anikó
Published: August 2023

Introduction

Prostate-specific membrane antigen (PSMA) is a transmembrane protein that may be expressed on the surface of prostate cancer (PC) cells. It enables a more sensitive and specific diagnosis PC, compared to conventional anatomical imaging.

Aim

The integration of PSMA-based imaging in the personalized radiotherapy of PC patients and the evaluation of its impact on target volume definition if stereotactic body radiotherapy (SBRT) is planned for locally recurrent or oligometastatic disease.

Patients and methods

The data from 363 examinations were analyzed retrospectively. Inclusion criteria were histologically verified PC and clinical data suggesting local recurrence or distant metastasis. Whole-body 99mTc-PSMA-I&S single-photon emission computed tomography (SPECT)/CT or 18F-JK-PSMA-7 positron emission tomography/computer tomography (PET/CT) was carried out, and the evaluation of the scans and biological tumor volume contouring was performed at the Department of Nuclear Medicine. The target volume delineation on topometric CT (TCT) scan was performed at the Department of Oncotherapy. The comparison of the two volumes was performed by image fusion and registration.

Results

From 363 PSMA isotope-based examinations, 84 lesions of 64 patients were treated with SBRT. In 50 patients, 70 lesions were examined for intermodality comparison. The target volume defined by the PSMA density was significantly smaller than the tumor size defined by the TCT scan: GTVCT (gross tumor volume on the TCT), 27.58 ± 46.07 cm3; BTVPSMA (biological target volume on the PSMA-based examination), 16.14 ± 29.87 cm3. During geometrical analyses, the Dice similarity coefficient (DSC) was 0.56 ± 0.20 (0.07–0.85). Prostate-specific antigen (PSA) control was performed to evaluate the response: mean pre-radiotherapy (pre-RT) PSA was 16.98 ng/ml ( ± SD: 33.81), and post-RT PSA at 3 months after SBRT was 11.19 ng/ml ( ± SD: 32.85). Three-month post-therapy PSMA-based imaging was performed in 14 cases, in which we observed a decrease or cessation of isotope uptake. Conventional imaging control was performed in 42 cases (65.6% of all cases): 22 (52.4%) complete remissions, 14 (33.3%) partial remissions, four (9.5%) stable diseases, and two (4.8%) progressive diseases were described.

Conclusion

PSMA-based imaging is a promising diagnostic method for specifying the stage and detecting the low-volume progression. Our results suggest that PSMA-based hybrid imaging can influence treatment decisions and target volume delineation for SBRT.
Exploring the regulatory role of lncRNA in cancer immunity
Authors: Zhan Dan-ting , Xian Hong-chun
Published: August 2023

Imbalanced immune homeostasis in cancer microenvironment is a hallmark of cancer. Increasing evidence demonstrated that long non-coding RNAs (lncRNAs) have emerged as key regulatory molecules in directly blocking the cancer immunity cycle, apart from activating negative regulatory pathways for restraining tumor immunity. lncRNAs reshape the tumor microenvironment via the recruitment and activation of innate and adaptive lymphoid cells. In this review, we summarized the versatile mechanisms of lncRNAs implicated in cancer immunity cycle, including the inhibition of antitumor T cell activation, blockade of effector T cell recruitment, disruption of T cell homing, recruitment of immunosuppressive cells, and inducing an imbalance between antitumor effector cells (cytotoxic T lymphocytes, M1 macrophages, and T helper type 1 cells) versus immunosuppressive cells (M2 macrophages, T helper type 2 cells, myeloid derived suppressor cells, and regulatory T cells) that infiltrate in the tumor. As such, we would highlight the potential of lncRNAs as novel targets for immunotherapy.
Impact of supradiaphragmatic lymphadenectomy on the survival of patients in stage IVB ovarian cancer with thoracic lymph node metastasis
Authors: Park Soo Jin , Na Kwon Joong , Lee Maria , Park In Kyu , Chung Hyun Hoon , Kang Chang Hyun , Kim Jae-Weon , Park Noh Hyun , Kim Young-Tae , Song Yong Sang , Park Samina , Kim Hee Seung
Published: August 2023

Introduction

To evaluate the survival impact of supradiaphragmatic lymphadenectomy as part of debulking surgery in stage IVB ovarian cancer with thoracic lymph node metastasis (LNM).

Methods

We retrospectively enrolled patients diagnosed with stage IVB ovarian, fallopian or primary peritoneal cancer between 2010 and 2020, carrying cardiophrenic, parasternal, anterior mediastinal or supraclavicular lymph nodes ≥5 mm on axial chest computed tomography. All tumors were classified into the abdominal (abdominal tumors and cardiophrenic lymph nodes) and supradiaphragmatic (parasternal, anterior mediastinal or supraclavicular lymph nodes) categories depending on the area involved. Residual tumors were classified into <5 vs ≥5 mm in the abdominal and supradiaphragmatic areas. Based on the site of recurrence, they were divided into abdominal, supradiaphragmatic and other areas.

Results

A total of 120 patients underwent primary debulking surgery (PDS, n=68) and interval debulking surgery after neoadjuvant chemotherapy (IDS/NAC, n=53). Residual tumors in the supradiaphragmatic area ≥5 mm adversely affected progression-free survival (PFS) and overall survival (OS) with marginal significance after PDS despite the lack of effect on survival after IDS/NAC (adjusted hazard ratios [HRs], 6.478 and 6.370; 95% confidence intervals [CIs], 2.224-18.864 and 0.953-42.598). Further, the size of residual tumors in the abdominal area measuring ≥5 mm diminished OS after IDS/NAC (adjusted HR, 9.330; 95% CIs, 1.386-62.800).

Conclusion

Supradiaphragmatic lymphadenectomy during PDS may improve survival in patients diagnosed with stage IVB ovarian cancer manifesting thoracic LNM. Further, suboptimal debulking surgery in the abdominal area may be associated with poor OS after IDS/NAC.

Trial registration

ClinicalTrials.gov (NCT05005650; https://clinicaltrials.gov/ct2/show/NCT05005650; first registration, 13/08/2021).

Research Registry (Research Registry UIN, researchregistry7366; https://www.researchregistry.com/browse-the-registry#home/?view_2_search=researchregistry7366&view_2_page=1).
Branched-chain amino acids catabolism and cancer progression: focus on therapeutic interventions
Authors: Xu Er , Ji Bangju , Jin Ketao , Chen Yefeng
Published: August 2023

Branched-chain amino acids (BCAAs), including valine, leucine, and isoleucine, are crucial amino acids with significant implications in tumorigenesis across various human malignancies. Studies have demonstrated that altered BCAA metabolism can influence tumor growth and progression. Increased levels of BCAAs have been associated with tumor growth inhibition, indicating their potential as anti-cancer agents. Conversely, a deficiency in BCAAs can promote tumor metastasis to different organs due to the disruptive effects of high BCAA concentrations on tumor cell migration and invasion. This disruption is associated with tumor cell adhesion, angiogenesis, metastasis, and invasion. Furthermore, BCAAs serve as nitrogen donors, contributing to synthesizing macromolecules such as proteins and nucleotides crucial for cancer cell growth. Consequently, BCAAs exhibit a dual role in cancer, and their effects on tumor growth or inhibition are contingent upon various conditions and concentrations. This review discusses these contrasting findings, providing valuable insights into BCAA-related therapeutic interventions and ultimately contributing to a better understanding of their potential role in cancer treatment.
Cell-in-cell: a potential biomarker of prognosis and a novel mechanism of drug resistance in cancer
Authors: Liu Xiaona , Yang Jun
Published: August 2023

The cell-in-cell (CIC) phenomenon has received increasing attention over recent years because of its wide existence in multiple cancer tissues. The mechanism of CIC formation is considerably complex as it involves interactions between two cells. Although the molecular mechanisms of CIC formation have been extensively investigated, the process of CIC formation remains ambiguous. Currently, CIC is classified into four subtypes based on different cell types and inducing factors, and the underlying mechanisms for each subtype are distinct. Here, we investigated the subtypes of CIC and their major mechanisms involved in cancer development. To determine the clinical significance of CIC, we reviewed several clinical studies on CIC and found that CIC could serve as a diagnostic and prognostic biomarker. The implications of CIC on the clinical management of cancers also remain largely unknown. To clarify this aspect, in the present review, we highlight the findings of recent investigations on the causal link between CIC and cancer treatment. We also indicate the existing issues that need to be resolved urgently to provide a potential direction for future research on CIC.
Case report: Preimplantation genetic testing for X-linked alport syndrome caused by variation in the COL4A5 gene
Authors: Liu Nengqing , Wen Xiaojun , Ou Zhanhui , Fang Xiaowu , Du Jing , Lin Xiufeng
Published: August 2023

X-Linked Alport Syndrome (XLAS) is an X-linked, dominant, hereditary nephropathy mainly caused by mutations in the COL4A5 gene, found on chromosome Xq22. In this study, we reported a pedigree with XLAS caused by a COL4A5 mutation. This family gave birth to a boy with XLAS who developed hematuria and proteinuria at the age of 1 year. We used next-generation sequencing (NGS) to identify mutations in the proband and his parents and confirmed the results using Sanger sequencing. This testing showed there was a single nucleotide missense variation, c.3659G>A (p.Gly1220Asp) (NM_033380.3), in the COL4A5 gene. To prevent the inheritance of the syndrome, we used eight embryos for trophoblast biopsy after assisted reproductive technology treatment, and whole genome amplification (WGA) was performed using multiple annealing and looping-based amplification cycles (MALBAC). Embryos were subjected to Preimplantation Genetic Testing (PGT) procedures, including Sanger sequencing, NGS-based single nucleotide polymorphism (SNP) haplotype linkage analysis, and chromosomal copy number variation (CNV) analysis. The results showed that three embryos (E1, E2, and E4) were free of CNV and genetic variation in the COL4A5 gene. Embryo E1 (4AA) was transferred after consideration of the embryo growth rate, morphology, and PGT results. Prenatal diagnosis in the second trimester showed that the fetus had a normal karyotype and did not carry the COL4A5 mutation (c.3659G>A). Ultimately, a healthy boy was born and did not carry the pathogenic COL4A5 mutation, which indicated that PGT prevented the intergenerational transmission of the causative mutation of XLAS.
Drought and heat stress mediated activation of lipid signaling in plants: a critical review
Authors: Sharma Parul , Lakra Nita , Goyal Alisha , Ahlawat Yogesh K. , Zaid Abbu , Siddique Kadambot H. M.
Published: August 2023

Lipids are a principal component of plasma membrane, acting as a protective barrier between the cell and its surroundings. Abiotic stresses such as drought and temperature induce various lipid-dependent signaling responses, and the membrane lipids respond differently to environmental challenges. Recent studies have revealed that lipids serve as signal mediators forreducing stress responses in plant cells and activating defense systems. Signaling lipids, such as phosphatidic acid, phosphoinositides, sphingolipids, lysophospholipids, oxylipins, and N-acylethanolamines, are generated in response to stress. Membrane lipids are essential for maintaining the lamellar stack of chloroplasts and stabilizing chloroplast membranes under stress. However, the effects of lipid signaling targets in plants are not fully understood. This review focuses on the synthesis of various signaling lipids and their roles in abiotic stress tolerance responses, providing an essential perspective for further investigation into the interactions between plant lipids and abiotic stress.
In vitro production of steroidal saponin, total phenols and antioxidant activity in callus suspension culture of Paris polyphylla Smith: an important Himalayan medicinal plant
Authors: Rawat Janhvi Mishra , Pandey Shweta , Rawat Balwant , Purohit Sumit , Anand Jigisha , Negi Arvind S. , Thakur Ajay , Mahmoud Mohamed H. , El-Gazzar Ahmed M. , El-Saber Batiha Gaber
Published: August 2023

Paris polyphylla Smith (Melanthiaceae) family, which is native to the Himalayan region, has received a lot of attention recently due to its extensive history of usage in traditional medicine. The production of steroidal saponin from callus suspension cultures of P. polyphylla was observed in the current study. The current study attempted to develop a P. polyphylla plant callus suspension culture through optimization of cultivation technique for callus suspension, quantification of total phenolic components and estimation of the extract’s antioxidant activity. A light-yellow callus was formed within six weeks of cultivating rhizomes on Murashige and Skoog (MS) media supplemented with Thidiazuron (TDZ). Furthermore, the effect of TDZ, Methyl Jasmonate (MeJA), and Yeast Extract (YE) on callus growth, steroidal saponin (dioscin and diosgenin), total phenolic content, total flavonoids, total tannin, and total antioxidant activity was also measured. The medium containing 0.5 μM TDZ depicted the maximum callus biomass (2.98 g fresh weight). Significantly high phenolic and tannin content was observed in the MS medium containing 50 μM MeJA, whereas, no significant increase was observed in total tannin production in any treatment. Three in vitro assays, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis (3-ethylbenzothiazoline- 6-sulfonic acid)) and FRAP (ferric ion reducing antioxidant potential) and FC (Folin-Ciocalteu), were used to assess antioxidant potential of callus. Maximum antioxidant analysis reported in 1.0 μM TDZ (6.89 mM AAE/100 g) containing medium followed by 50 μM MeJA (6.44 mM AAE/100 g). The HPLC analysis showed a high presence of dioscin and diosgenin (5.43% and 21.09%, respectively) compared to the wild sample (2.56% and 15.05%, respectively). According to the results, callus produced on media supplemented with 50 μM MeJA have significant phenolic contents and elevated antioxidant activity; nevertheless, callus growth was greater in the presence of 0.5 μM TDZ. The findings of the current study have commercial implications since greater biomass production will result in active phytochemicals that the pharmaceutical and nutraceutical sectors are in need desperately.
Open Dialogue in Spain: an initial survey of knowledge and perspectives
Authors: Parrabera-García Silvia , Oujo-Fernández Casilda , Lirola María-Jesús , Cangas Adolfo J. , Marfá-Vallverdú Jordi , Correa-Urquiza Martín , Garcia-Torrents Enric
Published: August 2023

In Spain, the introduction of the Open Dialogue framework is relatively recent. This study takes a closer look at Open Dialogue training, interest and research in this region. To this end, a survey has been conducted through a convenience sample of professionals, people with their own experiences in mental health, family members, relatives, university professors and students. The results showed that a significant number of participants had no training in OD, and their exposure to relevant literature and congress attendance was limited. Amongst the different profiles, professionals reported the highest level of training. These findings highlight the urgent need for further research and training initiatives to improve the understanding and application of the OD framework in Spain. Efforts should be directed towards broadening the knowledge base, increasing access to training programmes and fostering interest amongst different stakeholders. By addressing these gaps, the implementation and use of OD can be expanded to meet the growing demand and interest in this approach in the Spanish context.
Structure and factorial invariance of the Grit-Original scale and convergent validity of the network with job satisfaction and happiness
Authors: Ramos-Vera Cristian , Soza-Herrera Juan José , Quispe-Callo Gleni , Serpa-Barrientos Antonio , Calizaya-Milla Yaquelin E. , Saintila Jacksaint
Published: August 2023

Background

The concept of Grit refers to a person’s ability to maintain perseverance and passion in the pursuit of long-term objectives. However, research on the applicability of the Grit-Original scale (Grit-O) in the Latin American context is limited.

Objective

This instrumental design study aimed to analyze the structure of this scale and its factorial invariance in relation to gender, as well as to examine its convergent validity with job satisfaction and happiness.

Methods

A sample of 364 Peruvian workers that were selected through non-probabilistic convenience sampling in 2021.

Results

The results of the confirmatory factor analysis showed that the two-dimensional structure of 12 items presented adequate goodness-of-fit indices. Additionally, the instrument is invariant between men and women. Likewise, the convergent relationship between the Grit scale, job satisfaction, and happiness variables was confirmed, which supports the validity of the instrument in the study context.

Conclusion

The findings of the study confirm that the GRIT-O is a measure with adequate psychometric properties in the Peruvian context.
Parental stress in families of children with special educational needs: a systematic review
Authors: Cheng Andrew W. Y. , Lai Cynthia Y. Y.
Published: August 2023

Background

This systematic review aimed to identify the risk factors and protective factors for parental stress in families with children with special educational needs. Studies have indicated that the wellbeing of families is related to the physical, psychological, and social conditions of the children, as well as the family functioning, stress coping strategies, and social and professional support of their parents. The parents of children with special educational needs experience high levels of parental stress. Identifying the associated risk factors and protective factors may shed light on the provision of interventions to promote the mental wellbeing of these parents.

Methods

Boolean operators were used to search multiple online databases, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied in this systematic review. Data were extracted into categories of population, age, region, the child's diagnosis, the stress-measuring instrument, and the risk factors and protective factors.

Results

Twenty-six studies, including 5,169 parents and 3,726 children, were reviewed. The following four major risk factors and protective factors were found to be associated with parental stress: the sex of the parents, diagnosis-related coping issues, socioeconomic characteristics, and social isolation of the parents.

Conclusions

This systematic review identified four significant risk factors and protective factors related to social support from couples, family members, and social circles. Various agencies may provide financial and manpower assistance and professional support and services to improve the parents' knowledge and coping skills, as well as affectional support, early screening, and continuous assessment of the parents' progress. Social policies and interventions offering continuous and diagnosis-related support to the parents of children with special educational needs are highly recommended.
A multifactorial framework of psychobehavioral determinants of coping behaviors: an online survey at the early stage of the COVID-19 pandemic
Authors: Ding Yi , Ishibashi Ryo , Abe Tsuneyuki , Honda Akio , Sugiura Motoaki
Published: August 2023

Coronavirus disease 2019 dramatically changed people’s behavior because of the need to adhere to infection prevention and to overcome general adversity resulting from the implementation of infection prevention measures. However, coping behavior has not been fully distinguished from risk perception, and a comprehensive picture of demographic, risk-perception, and psychobehavioral factors that influence the major coping-behavior factors remain to be elucidated. In this study, we recruited 2,885 Japanese participants. Major coping-behavior and risk-perception factors were identified via exploratory factor analysis of 50 candidate items. Then, we conducted a hierarchical multiple regression analysis to investigate factors associated with each coping-behavior factor. We identified four types of coping behavior [CB1 (mask-wearing), CB2 (information-seeking), CB3 (resistance to social stagnation), and CB4 (infection-prevention)] and three risk-perception factors [RP1 (shortages of daily necessities), RP2 (medical concerns), and RP3 (socioeconomic concerns)]. CB1 was positively associated with female sex and etiquette. CB2 was positively related to RP1 and RP3. CB3 was positively related to RP1 and leadership, and negatively associated with etiquette. CB4 was positively associated with female sex, etiquette, and active well-being. This parsimonious model may help to elucidate essential social dynamics and provide a theoretical framework for coping behavior during a pandemic.
CIAO: a living experiment in interdisciplinary large-scale collaboration facilitated by the Adverse Outcome Pathway framework
Authors: Carusi Annamaria , Filipovska Julija , Wittwehr Clemens , Clerbaux Laure-Alix
Published: August 2023

Introduction

The CIAO project was launched in Spring 2020 to address the need to make sense of the numerous and disparate data available on COVID-19 pathogenesis. Based on a crowdsourcing model of large-scale collaboration, the project has exploited the Adverse Outcome Pathway (AOP) knowledge management framework built to support chemical risk assessment driven by mechanistic understanding of the biological perturbations at the different organizational levels. Hence the AOPs might have real potential to integrate data produced through different approaches and from different disciplines as experienced in the context of COVID-19. In this study, we aim to address the effectiveness of the AOP framework (i) in supporting an interdisciplinary collaboration for a viral disease and (ii) in working as the conceptual mediator of a crowdsourcing model of collaboration.

Methods

We used a survey disseminated among the CIAO participants, a workshop open to all interested CIAO contributors, a series of interviews with some participants and a self-reflection on the processes.

Results

The project has supported genuine interdisciplinarity with exchange of knowledge. The framework provided a common reference point for discussion and collaboration. The diagram used in the AOPs assisted with making explicit what are the different perspectives brought to the knowledge about the pathways. The AOP-Wiki showed up many aspects about its usability for those not already in the world of AOPs. Meanwhile their use in CIAO highlighted needed adaptations. Introduction of new Wiki elements for modulating factors was potentially the most disruptive one. Regarding how well AOPs support a crowdsourcing model of large-scale collaboration, the CIAO project showed that this is successful when there is a strong central organizational impetus and when clarity about the terms of the collaboration is brought as early as possible.

Discussion

Extrapolate the successful CIAO approach and related processes to other areas of science where the AOP could foster interdisciplinary and systematic organization of the knowledge is an exciting perspective.