bluuebunny/crossref_metadata_2025 huggingface dataset:
A gaming app developed for vestibular rehabilitation improves the accuracy of performance and engagement with exercises
Authors: D’Silva Linda J. , Phongsavath Tarah , Partington Kelly , Pickle Nathan T. , Marschner Katherine , Zehnbauer Timothy P. , Rossi Michael , Skop Karen , Roos Paulien E.
Published: November 2023

Introduction

Vestibular hypofunction is associated with dizziness, imbalance, and blurred vision with head movement. Vestibular rehabilitation is the gold standard recommendation to decrease symptoms and improve postural stability. The Clinical Practice Guidelines for vestibular hypofunction suggest home exercises 3–5 times daily, but patient adherence is a problem, with compliance rates often below 50%.

Methods

An app was developed to increase engagement with home exercises by providing exercises as games. This study compared the accuracy of exercise performance in a one-time session using the app versus no-app and gathered participant feedback on using the app for vestibulo-ocular reflex (VOR) and balance exercises. The app was tested with 40 adults (20 women), mean age of 67 ± 5.7 years, with symptomatic unilateral or bilateral vestibular hypofunction. Participants completed VOR exercises in pitch and yaw planes, weight-shift, and single-leg balance exercises using an inertial motion unit to move the character on the tablet screen. Participants were randomly assigned to begin the exercises with or without the app.

Results

Results show that during VOR exercises, participants achieved the prescribed frequency of head motion for the yaw plane (p ≤ 0.001) and reduced variability of head movement frequency in both the yaw (p ≤ 0.001) and pitch plane (p ≤ 0.001) in the app compared to the no-app condition. During weight-shifting exercises, a larger range of body motion was noted in the anteroposterior and mediolateral directions in the app compared to the no-app condition (p < 0.05). During single-leg balance exercises, pelvic motion was lower in the app versus no-app condition (p = 0.02). Participants modified their exercise performance and corrected their mistakes to a greater extent when they used the app during the VOR exercises. Participants agreed that they felt motivated while playing the games (97%) and felt motivated by the trophies (92%). They agreed that the app would help them perform the exercises at home (95%), improve their rehab performance (95%) and that it was fun to do the exercises using the app (93%).

Discussion

The results of this study show that technology that is interactive and provides feedback can be used to increase accuracy and engagement with exercises.
Microperimetric evaluation and predictive factors of visual recovery after successful inverted internal limiting membrane-flap technique for macular hole in high myopic eyes
Authors: Sborgia Alessandra , Boscia Giacomo , Niro Alfredo , Landini Luca , Pastore Valentina , Albano Valeria , Piepoli Marina , Donghia Rossella , Dore Stefano , Viggiano Pasquale , Buonamassa Rosa , Di Pardo Camilla , Molfetta Teresa ,   Eye Clinic Research Group, Coassin Marco , Dell’Omo Roberto , Boscia Francesco , Alessio Giovanni , Sborgia Giancarlo
Published: November 2023

Introduction

Inverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis.

Methods

A retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables.

Results

Overall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up (p < 0.001). Over 6 months, overall sensitivity measurements improved (RS, p = 0.001; CRS, p < 0.0001; MD, p = 0.03), and the BCEA decreased in dimension, although not significantly (p ≥ 0.05). The mixed model revealed a significantly better effect of inverted ILM-flap combined with cataract surgery on BCVA and CRS in phakic eyes than inverted ILM-flap alone in pseudophakic ones. The regression model revealed a relationship of 6-month BCVA with pre-operative BCVA (β = 0.60, p = 0.02) and RS (β = −0.03, p = 0.01).

Conclusion

The inverted ILM-flap technique significantly improved visual acuity and retinal sensitivity after the hMMH closure, particularly when combined with cataract extraction. Pre-operative visual acuity and retinal sensitivity at central 12° may predict post-surgical visual acuity.
Targeting cellular senescence in senile osteoporosis: therapeutic potential of traditional Chinese medicine
Authors: Zhang Yingyi , Yu Xinfeng , Zhou Chengcong , Fu Keqi , Luo Huan , Wu Chengliang
Published: November 2023

Senile osteoporosis (SOP) is a prevalent manifestation of age-related bone disorders, resulting from the dysregulation between osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption, coupled with the escalating burden of cellular senescence. Traditional Chinese medicine (TCM) herbs, renowned for their remarkable attributes encompassing excellent tolerability, low toxicity, heightened efficacy, and minimal adverse reactions, have gained considerable traction in OP treatment. Emerging evidence substantiates the therapeutic benefits of various TCM formulations and their active constituents, including Zuogui wan, Fructus Ligustri Lucidi, and Resveratrol, in targeting cellular senescence to address SOP. However, a comprehensive review focusing on the therapeutic efficacy of TCM against SOP, with a particular emphasis on senescence, is currently lacking. In this review, we illuminate the pivotal involvement of cellular senescence in SOP and present a comprehensive exploration of TCM formulations and their active ingredients derived from TCM, delineating their potential in SOP treatment through their anti-senescence properties. Notably, we highlight their profound effects on distinct aging models that simulate SOP and various senescence characteristics. Finally, we provide a forward-looking discussion on utilizing TCM as a strategy for targeting cellular senescence and advancing SOP treatment. Our objective is to contribute to the unveiling of safer and more efficacious therapeutic agents for managing SOP.
C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis
Authors: Ponticelli Claudio , Calatroni Marta , Moroni Gabriella
Published: November 2023

Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are types of membranoproliferative glomerulonephritis classified as C3 glomerulopathies. These conditions are characterized by an increased number of intraglomerular cells and diffuse thickening of the glomerular capillary walls, along with the deposition of C3 and minimal or absent immunoglobulin deposits. The underlying cause of both DDD and C3Gn is an abnormal activation of the alternative complement pathway, which can result from acquired or genetic alteration. In acquired forms of DDD and C3GN, the dysregulation of the alternative pathway is commonly induced by the presence of C3 nephritic factors (C3NeFs), which are autoantibodies that stabilize C3 convertase. Both DDD and C3GN can affect individuals of any age, but DDD is primarily diagnosed in children, whereas C3GN tends to be diagnosed at a significantly higher age. The presenting features of these diseases are variable and may include proteinuria, hematuria, hypertension, or kidney failure. A common finding in these diseases is low serum C3 levels with normal serum C4 levels. Chronic deterioration of renal function is commonly observed in DDD and C3GN, often leading to end-stage renal disease (ESRD), especially in DDD. Kidney transplantation outcomes in patients with these conditions are characterized by histological recurrence, which may contribute to higher rates of allograft failure.
Discordant patterns between nitrogen-cycling functional traits and taxa in distant coastal sediments reveal important community assembly mechanisms
Authors: Song Wen , Li Hongjun , Zhou Yuqi , Liu Xia , Li Yueyue , Wang Mengqi , Li Dan-dan , Tu Qichao
Published: November 2023

A central question in microbial ecology is how immense microbes are assembled in changing natural environments while executing critical ecosystem functions. Over the past decade, effort has been made to unravel the contribution of stochasticity and determinism to the compositional of microbial communities. However, most studies focus on microbial taxa, ignoring the importance of functional traits. By employing shotgun metagenomic sequencing and state-of-the-art bioinformatics approaches, this study comprehensively investigated the microbially mediated nitrogen (N) cycling processes in two geographically distant coastal locations. Both shotgun and 16S rRNA gene amplicon sequencing demonstrated significantly differed taxonomic compositions between the two sites. The relative abundance of major microbial phyla, such as Pseudomonadota, Thaumarchaeota, and Bacteroidota, significantly differed. In contrast, high homogeneity was observed for N-cycling functional traits. Statistical analyses suggested that N-cycling taxonomic groups were more related to geographic distance, whereas microbial functional traits were more influenced by environmental factors. Multiple community assembly models demonstrated that determinism strongly governed the microbial N-cycling functional traits, whereas their carrying taxonomic groups were highly stochastic. Such discordant patterns between N-cycling functional traits and taxa demonstrated an important mechanism in microbial ecology in which essential ecosystem functions are stably maintained despite geographic distance and stochastic community assembly.
Lipidomic chemotaxonomy aligned with phylogeny of Halobacteria
Authors: Yao Wenyong , Zhang Wan , He Wei , Xiao Wenjie , Chen Yufei , Zhu Yuanqing , Zheng Fengfeng , Zhang Chuanlun
Published: November 2023

Archaea play an important role in global biogeochemical cycles and are considered ancestral to eukaryotes. The unique lipid composition of archaea, characterized by isoprenoid alkyl chains and ether linkage to glycerol-1-phosphate, offers valuable insights into archaeal phylogeny and evolution. However, comprehensive studies focusing on archaeal lipidomes, especially at the intact polar lipid level, are currently limited. Here, we built an in-house library of archaeal lipids by using high-performance liquid chromatography coupled with mass-spectrometry, which was integrated with bioinformatics and molecular network analyses. Seven halobacterial strains, representing three distinct orders, were cultured under identical conditions to investigate their lipidomes. A total of 162 features were identified, corresponding to 107 lipids that could be assigned to different strains. Clustering analyses of both core lipids and total lipids matched the phylogeny of Halobacteria at the order level. Notably, lipids such as triglycosyl diether-phosphatidyl acid and bis-sulfate glycosyl lipids were specific to particular groups and could serve as diagnostic intact lipid biomarkers for Halobacteria. Furthermore, the analysis of network-coordinated features facilitated the linkage of unknown lipid compounds to phylogeny, which promotes a lipidome to phylogeny matchup among three Haloferax strains, thereby expanding the knowledge of the halobacterial lipidome. Our study provides a comprehensive view of the lipidomes of the seven strains of Halobacteria and highlights the potential of lipidomics for studying archaeal phylogeny.
Telomere maintenance in African trypanosomes
Authors: Li Bibo
Published: November 2023

Telomere maintenance is essential for genome integrity and chromosome stability in eukaryotic cells harboring linear chromosomes, as telomere forms a specialized structure to mask the natural chromosome ends from DNA damage repair machineries and to prevent nucleolytic degradation of the telomeric DNA. In Trypanosoma brucei and several other microbial pathogens, virulence genes involved in antigenic variation, a key pathogenesis mechanism essential for host immune evasion and long-term infections, are located at subtelomeres, and expression and switching of these major surface antigens are regulated by telomere proteins and the telomere structure. Therefore, understanding telomere maintenance mechanisms and how these pathogens achieve a balance between stability and plasticity at telomere/subtelomere will help develop better means to eradicate human diseases caused by these pathogens. Telomere replication faces several challenges, and the “end replication problem” is a key obstacle that can cause progressive telomere shortening in proliferating cells. To overcome this challenge, most eukaryotes use telomerase to extend the G-rich telomere strand. In addition, a number of telomere proteins use sophisticated mechanisms to coordinate the telomerase-mediated de novo telomere G-strand synthesis and the telomere C-strand fill-in, which has been extensively studied in mammalian cells. However, we recently discovered that trypanosomes lack many telomere proteins identified in its mammalian host that are critical for telomere end processing. Rather, T. brucei uses a unique DNA polymerase, PolIE that belongs to the DNA polymerase A family (E. coli DNA PolI family), to coordinate the telomere G- and C-strand syntheses. In this review, I will first briefly summarize current understanding of telomere end processing in mammals. Subsequently, I will describe PolIE-mediated coordination of telomere G- and C-strand synthesis in T. brucei and implication of this recent discovery.
Bio-inspired circular latent spaces to estimate objects' rotations
Authors: Plebe Alice , Da Lio Mauro
Published: November 2023

This paper proposes a neural network model that estimates the rotation angle of unknown objects from RGB images using an approach inspired by biological neural circuits. The proposed model embeds the understanding of rotational transformations into its architecture, in a way inspired by how rotation is represented in the ellipsoid body of Drosophila. To effectively capture the cyclic nature of rotation, the network's latent space is structured in a circular manner. The rotation operator acts as a shift in the circular latent space's units, establishing a direct correspondence between shifts in the latent space and angular rotations of the object in the world space. Our model accurately estimates the difference in rotation between two views of an object, even for categories of objects that it has never seen before. In addition, our model outperforms three state-of-the-art convolutional networks commonly used as the backbone for vision-based models in robotics.
Radiological markers of neurological manifestations of post-acute sequelae of SARS-CoV-2 infection: a mini-review
Authors: Cull Olivia , Al Qadi Lina , Stadler Josiane , Martin Mykella , El Helou Antonios , Wagner Jeffrey , Maillet Danica , Chamard-Witkowski Ludivine
Published: November 2023

The neurological impact of COVID-19 is a rising concern among medical professionals, as patients continue to experience symptoms long after their recovery. This condition, known as neurological post-acute sequelae of COVID-19 (Neuro-PASC), can last for more than 12 weeks and includes symptoms such as attention disorders, brain fog, fatigue, and memory loss. However, researchers and health professionals face significant challenges in understanding how COVID-19 affects the brain, limiting the development of effective prevention and treatment strategies. In this mini-review, we provide readers with up-to-date information on the imaging techniques currently available for measuring the neurological impact of post-SARS-CoV-2 infection. Our search of PubMed and Google Scholar databases yielded 38 articles on various brain imaging techniques, including structural MRI (magnetic resonance imaging), functional MRI, diffusion MRI, susceptibility-weighted imaging, SPECT (single-photon emission computed tomography) imaging, and PET (positron emission tomography) imaging. We also discuss the optimal usage, limitations, and potential benefits of these techniques. Our findings show that various cerebral imaging techniques have been evaluated to identify a reliable marker for Neuro-PASC. For instance, 18F-FDG-PET/CT and functional MRI have demonstrated hypometabolism in cerebral regions that are directly linked to patient symptoms. Structural MRI studies have revealed different findings, such as infarcts, white matter atrophy, and changes in gray matter volumes. One SPECT imaging study noted frontal lobe hypometabolism, while diffusion MRI showed increased diffusivity in the limbic and olfactory cortical systems. The sequence SWI showed abnormalities primarily in white matter near the gray-white matter junction. A study on 18F-amyloid PET/CT found amyloid lesions in frontal and anterior cingulate cortex areas, and a study on arterial spin labeling (ASL) found hypoperfusion primarily in the frontal lobe. While accessibility and cost limit the widespread use of 18F-FDG-PET/CT scans and functional MRI, they seem to be the most promising techniques. SPECT, SWI sequence, and 18F-amyloid PET/CT require further investigation. Nevertheless, imaging remains a reliable tool for diagnosing Neuro-PASC and monitoring recovery.
The importance of pyramidal tract integrity for cortical plasticity and related functionality in patients with multiple sclerosis
Authors: Balloff Carolin , Albrecht Philipp , Stucke Arved-Sebastian , Scala Lina , Novello Sveva , Hartmann Christian Johannes , Meuth Sven Günther , Schnitzler Alfons , Penner Iris-Katharina , Groiss Stefan Jun
Published: November 2023

Background

Cortical plasticity induced by quadripulse stimulation (QPS) has been shown to correlate with cognitive functions in patients with relapsing-remitting multiple sclerosis (RRMS) and to not be reduced compared to healthy controls (HCs).

Objective

This study aimed to compare the degree of QPS-induced plasticity between different subtypes of multiple sclerosis (MS) and HCs and to investigate the association of the degree of plasticity with motor and cognitive functions. We expected lower levels of plasticity in patients with progressive MS (PMS) but not RRMS compared to HCs. Furthermore, we expected to find positive correlations with cognitive and motor performance in patients with MS.

Methods

QPS-induced plasticity was compared between 34 patients with PMS, 30 patients with RRMS, and 30 HCs using linear mixed-effects models. The degree of QPS-induced cortical plasticity was correlated with various motor and cognitive outcomes.

Results

There were no differences regarding the degree of QPS-induced cortical plasticity between HCs and patients with RRMS (p = 0.86) and PMS (p = 0.18). However, we only found correlations between the level of induced plasticity and both motor and cognitive functions in patients with intact corticospinal tract integrity. Exploratory analysis revealed significantly reduced QPS-induced plasticity in patients with damage compared to intact corticospinal tract integrity (p < 0.001).

Conclusion

Our study supports the notion of pyramidal tract integrity being of more relevance for QPS-induced cortical plasticity in MS and related functional significance than the type of disease.
Prolonged course of brain edema and neurological recovery in a translational model of decompressive craniectomy after closed head injury in mice
Authors: Szczygielski Jacek , Hubertus Vanessa , Kruchten Eduard , Müller Andreas , Albrecht Lisa Franziska , Schwerdtfeger Karsten , Oertel Joachim
Published: November 2023

Background

The use of decompressive craniectomy in traumatic brain injury (TBI) remains a matter of debate. According to the DECRA trial, craniectomy may have a negative impact on functional outcome, while the RescueICP trial revealed a positive effect of surgical decompression, which is evolving over time. This ambivalence of craniectomy has not been studied extensively in controlled laboratory experiments.

Objective

The goal of the current study was to investigate the prolonged effects of decompressive craniectomy (both positive and negative) in an animal model.

Methods

Male mice were assigned to the following groups: sham, decompressive craniectomy, TBI and TBI followed by craniectomy. The analysis of functional outcome was performed at time points 3d, 7d, 14d and 28d post trauma according to the Neurological Severity Score and Beam Balance Score. At the same time points, magnetic resonance imaging was performed, and brain edema was analyzed.

Results

Animals subjected to both trauma and craniectomy presented the exacerbation of the neurological impairment that was apparent mostly in the early course (up to 7d) after injury. Decompressive craniectomy also caused a significant increase in brain edema volume (initially cytotoxic with a secondary shift to vasogenic edema and gliosis). Notably, delayed edema plus gliosis appeared also after decompression even without preceding trauma.

Conclusion

In prolonged outcomes, craniectomy applied after closed head injury in mice aggravates posttraumatic brain edema, leading to additional functional impairment. This effect is, however, transient. Treatment options that reduce brain swelling after decompression may accelerate neurological recovery and should be explored in future experiments.
Identification of novel SHANK2 variants in two Chinese families via exome and RNA sequencing
Authors: Wu Yong , Li Wenzhou , Tan Bo , Luo Sanchuan
Published: November 2023

Background

SHANK2 encodes a postsynaptic scaffolding protein involved in synapse formation, stabilization and homeostasis. Variations or microdeletions in the SHANK2 gene have been linked to a variety of neurodevelopmental disorders, including autism spectrum disorders (ASD) and mild to moderate intellectual disability (ID) in human. However, the number of reported cases with SHANK2 defects remains limited, with only 14 unrelated patients documented worldwide.

Methods

In this study, we investigated four patients from three families with ID. Whole-exome sequencing (WES) was performed to explore the genetic causes, while Sanger sequencing was used to confirm the identified variants. Furthermore, RNA sequencing and functional enrichment analysis were performed on patients with likely pathogenic variants to gain further insights into the molecular landscape associated with these variants.

Results

Two novel variants in the SHANK2 gene: a heterozygous splicing substitution (NM_012309.5:c.2198-1G>A p.Pro734Glyfs*22) in Family 1, and a heterozygous nonsense variant [NM_012309.5:c.2310dupT p.(Lys771*)] in Family 2 were identified by WES and confirmed by Sanger sequencing. RNA sequencing and cohort analysis identified a total of 1,196 genes exhibiting aberrant expression in three patients. Functional enrichment analysis revealed the involvement of these genes in protein binding and synaptic functions.

Conclusion

We identified two novel loss of function variants that broadens the spectrum of SHANK2 variants. Furthermore, this study enhances our understanding of the molecular mechanisms underlying SHANK2-related disorders.
Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model
Authors: Garofalo Mariangela , Wieczorek Magdalena , Anders Ines , Staniszewska Monika , Lazniewski Michal , Prygiel Marta , Zasada Aleksandra Anna , Szczepińska Teresa , Plewczynski Dariusz , Salmaso Stefano , Caliceti Paolo , Cerullo Vincenzo , Alemany Ramon , Rinner Beate , Pancer Katarzyna , Kuryk Lukasz
Published: November 2023

Introduction

Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage of the malignancy. The aim of this study was to evaluate the anti-tumor efficacy of a novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with an anti-PD-1 monoclonal antibody.

Methods

The efficacy of the vector was confirmed in vitro in three mesothelioma cell lines – H226, Mero-82, and MSTO-211H, and subsequently the antineoplastic properties in combination with anti-PD-1 was evaluated in xenograft H226 mesothelioma BALB/c and humanized NSG mouse models.

Results and discussion

Anticancer efficacy was attributed to reduced tumour volume and increased infiltration of tumour infiltrating lymphocytes, including activated cytotoxic T-cells (GrB+CD8+). Additionally, a correlation between tumour volume and activated CD8+ tumour infiltrating lymphocytes was observed. These findings were confirmed by transcriptomic analysis carried out on resected human tumour tissue, which also revealed upregulation of CD83 and CRTAM, as well as several chemokines (CXCL3, CXCL9, CXCL11) in the tumour microenvironment. Furthermore, according to observations, the combinatorial therapy had the strongest effect on reducing mesothelin and MUC16 levels. Gene set enrichment analysis suggested that the combinatorial therapy induced changes to the expression of genes belonging to the “adaptive immune response” gene ontology category. Combinatorial therapy with oncolytic adenovirus with checkpoint inhibitors may improve anticancer efficacy and survival by targeted cancer cell destruction and triggering of immunogenic cell death. Obtained results support further assessment of the AdV5/3-D24-ICOSL-CD40L in combination with checkpoint inhibitors as a novel therapeutic perspective for mesothelioma treatment.
Pancreatic cancer outcome—local treatment with radiation using MRI-LINAC
Authors: Almog Galit , Pfeffer Raphael M. , Zalmanov Svetlana , Grinberg Vladislav , Lipsky Yoav , Chernomordikov Elena , Levin Daphne , Apter Sara , Arsenault Orit , Epstein Dan , Tamimi Qusai , Hod Keren , Limon Dror , Golan Talia , Ben-Aharon Irit , Lawrence Yaacov Richard , Ben-David Merav Akiva
Published: November 2023

Introduction

Stereotactic MR-guided on-table adaptive radiotherapy (SMART) allows the precise delivery of high-dose radiation to tumors in great proximity to radiation-sensitive organs. The aim of this study is to evaluate the toxicity and clinical outcome in locally advanced or recurrent pancreatic tumors, with or without prior irradiation, treated with SMART.

Methods

Patients were treated for pancreatic cancer (PC) using SMART technology to a prescribed dose of 50 Gy (BED10, 100 Gy) in five fractions, with daily on-table adaptation of treatment plan. Endpoints were acute and late toxicities, local control, local disease-free period, and overall survival.

Results

A total of 54 PC patients were treated between August 2019 and September 2022, with a median follow-up of 8.9 months from SMART. The median age was 70.4 (45.2–86.9) years. A total of 40 patients had upfront inoperable PC (55% were locally advanced and 45% metastatic), and 14 had local recurrence following prior pancreatectomy (six patients also had prior adjuvant RT). Of the patients, 87% received at least one chemotherapy regimen (Oxaliplatin based, 72.2%), and 25.9% received ≥2 regimens. Except from lower CA 19-9 serum level at the time of diagnosis and 6 weeks prior to SMART in previously operated patients, there were no significant differences in baseline parameters between prior pancreatectomy and the inoperable group. On-table adaptive replanning was performed for 100% of the fractions. No patient reported grade ≥2 acute GI toxicity. All previously irradiated patients reported only low-grade toxicities during RT. A total of 48 patients (88.9%) were available for evaluation. Complete local control was achieved in 21.7% (10 patients) for a median of 9 months (2.8–28.8); three had later local progression. Eight patients had regional or marginal recurrence. Six- and 12-month OS were 75.0% and 52.1%, respectively. Apart from mild diarrhea 1–3 months after SMART and general fatigue, there were no significant differences in toxicity and outcomes between post-pancreatectomy and inoperable groups.

Conclusion

SMART allows safe delivery of an ablative dose of radiotherapy, with minimal treatment-related toxicity, even in previously resected or irradiated patients. In this real-world cohort, local control with complete response was achieved by 20% of the patients. Further studies are needed to evaluate long-term outcome and late toxicity.
Case Report: Balancing immune responses – multiple sclerosis disease exacerbation under BRAF/MEK treatment for malignant melanoma
Authors: Pape Katrin , Protopapa Maria , Schraad Muriel , Steffen Falk , Zipp Frauke , Bittner Stefan
Published: November 2023

Background

Combination treatment with BRAF/MEK inhibitors favorably impact progression-free survival in malignant melanoma. However, it may cause paradoxical activation of the MAPK/ERK pathway in immune cells without BRAF mutation, which may lead to over activation of the immune system, especially in patients with pre-existing autoimmune conditions. In this case report, treatment of malignant melanoma with BRAF/MEK inhibitors was associated with radiological disease exacerbation of pre-existing multiple sclerosis (MS).

Case presentation

A 47-year-old patient with pre-existing MS was diagnosed with malignant melanoma in June 2020. Anti-tumor treatment was initiated with a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. In February 2022, the patient presented at our neurological clinic after routine MRI revealed exacerbation of radiological MS disease activity with ten new and gadolinium-enhancing lesions, and concomitant high levels of neurofilament light chain (NfL) in serum, a marker for axonal damage. In-depth analysis of immune cells in both peripheral blood and cerebrospinal fluid was performed by multi-color flow cytometry. After treatment with the B cell-depleting antibody ocrelizumab, MS disease stability was obtained and anti-tumor medication could be continued.

Conclusions

Immunomodulatory treatment in cancer patients is highly effective from an oncological point of view, but may be associated with autoimmune side effects. This is of special importance in patients with pre-existing autoimmune diseases, as reflected by our case of MS disease reactivation under treatment with BRAF/MEK inhibitors. In our case, sequential modulation of immune cell subsets by B cell depletion, associated with marked shifts in B and T cell subsets, allowed for stabilization of disease and continuation of anti-tumor treatment.
Tibetan mineral-herbal medicine Zuotai alleviates the depressive-like behaviors in chronic restraint-stressed mice while regulating stress hormone, inflammation and monoamine
Authors: Li Cen , Niu Cuiying , Bi Hongtao , Zhao Jing , Ivan Alvarez Jorge , Yuan Farong , Gai Xiangyun , Wei Lixin , Du Yuzhi , Qiao Yajun , Kebir Hania , Xiao Yuancan , Yang Hongxia
Published: November 2023

Introduction:Zuotaiis an ancient mineral-herbal mixture containing β-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicineRasasindura. However, one of the key problems faced byZuotaiis that its indications are ambiguous. Our previous study found thatZuotaiexhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation.

Methods:Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect ofZuotai. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress.

Results:It was observed thatZuotaiand β-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice.Zuotaiand β-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated withZuotai; however, there was no statistically significant difference. AlthoughZuotaiincreased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; andZuotaishowed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients.

Conclusion:Zuotaiexhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter.
Population pharmacokinetics of everolimus in patients with seizures associated with focal cortical dysplasia
Authors: Park Jinha , Kim Se Hee , Hahn Jongsung , Kang Hoon-Chul , Lee Sang-Guk , Kim Heung Dong , Chang Min Jung
Published: November 2023

Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type Ⅱ (FCD Ⅱ) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed.

Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States).

Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5–15 ng/mL.

Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg.
Sulfur signaling pathway in cardiovascular disease
Authors: Song Yunjia , Xu Zihang , Zhong Qing , Zhang Rong , Sun Xutao , Chen Guozhen
Published: November 2023

Hydrogen sulfide (H2S) and sulfur dioxide (SO2), recognized as endogenous sulfur-containing gas signaling molecules, were the third and fourth molecules to be identified subsequent to nitric oxide and carbon monoxide (CO), and exerted diverse biological effects on the cardiovascular system. However, the exact mechanisms underlying the actions of H2S and SO2 have remained elusive until now. Recently, novel post-translational modifications known as S-sulfhydration and S-sulfenylation, induced by H2S and SO2 respectively, have been proposed. These modifications involve the chemical alteration of specific cysteine residues in target proteins through S-sulfhydration and S-sulfenylation, respectively. H2S induced S-sulfhydrylation can have a significant impact on various cellular processes such as cell survival, apoptosis, cell proliferation, metabolism, mitochondrial function, endoplasmic reticulum stress, vasodilation, anti-inflammatory response and oxidative stress in the cardiovascular system. Alternatively, S-sulfenylation caused by SO2 serves primarily to maintain vascular homeostasis. Additional research is warranted to explore the physiological function of proteins with specific cysteine sites, despite the considerable advancements in comprehending the role of H2S-induced S-sulfhydration and SO2-induced S-sulfenylation in the cardiovascular system. The primary objective of this review is to present a comprehensive examination of the function and potential mechanism of S-sulfhydration and S-sulfenylation in the cardiovascular system. Proteins that undergo S-sulfhydration and S-sulfenylation may serve as promising targets for therapeutic intervention and drug development in the cardiovascular system. This could potentially expedite the future development and utilization of drugs related to H2S and SO2.
CPDD-CLMM: a comprehensive lightweight mobile-optimized network for composite plate defect detection
Authors: Wang Biao , Huang Yan , Yang Yongyue , Wang Yonghong , Li Hongli , Huang Bin , Chen Jianbin
Published: November 2023

Automatic defect-detection technology based on deep learning is increasingly used for distinguishing production quality by many industries. However, production lines are usually installed with lots of function modules, which make it difficult to integrate new modules. Common deep learning models run on PC platforms and require a big space with high cost, while ARM64 mobile platforms are much smaller with less cost and equivalent connectivity but also weaker performance. Considering these facts, ARM64 platforms with a fully optimized model are the best solution for adding a defect-detection function for existing production lines. This paper focused on a mobile-optimized model to achieve higher speed and equivalent precision on the ARM64 mobile platform for detection. First, the model structure is simplified by reducing the redundancy of feature maps to increase the network inference speed. Second, a convolutional block attention module is attached to compensate for the decrease in precision caused by structure simplification. Furthermore, a transfer learning method is adopted to improve training performance. Finally, the trained and compiled module is exported to the PyTorch Mobile format and deployed on the mobile platform application to execute its defect-detection function. The results show that the optimized network achieves a speed of 2.124 fps, 210.7% compared with that of You Only Look Once v5n, i.e., 1.008 fps, on the RK3399 ARM64 platform, and has an average mAP of 99.2%. The studied mobile-optimized model has better speed and equivalent precision and can be available on many different ARM64 platforms regardless of the processor manufacturer. It can satisfy the need for real-time defect detection and can be used in similar scenarios. In the future, more improvements could be made such as deploying on platforms with NPU support to achieve faster speed, exploring the relationships between dataset properties and transfer learning effects, even training and running the model directly on ARM64 platforms.
Assessment of the chemical and genetic variability among accessions of Cicerbita alpina (L.) Wallr., an alpine plant with anthelmintic properties
Authors: Martinidou Eftychia , Palmieri Luisa , Sordo Maddalena , Masuero Domenico , Ourda Maria , Delucchi Luca , Fusani Pietro , Tremml Veronika , Poulopoulou Ioanna , Gauly Matthias , Horgan Mark J. , Siewert Bianka , Stuppner Hermann , Martens Stefan
Published: November 2023

Cicerbita alpina(L.) Wallr, is a perennial alpine plant and a member of theAsteraceaefamily, typically found at altitudes above 1000 meters in the Italian Alps. Although previously utilized primarily as a local delicacy, recent studies have revealed strong antiparasitic activity throughin vitroexperiments. In Europe, numerous chemical drugs employed to combat nematodes — helminths that infest the digestive tract of livestock — are banned due to their environmental harm or show only reduced efficiency because of the development of resistance. Consequently, there is a growing demand for new alternative anthelmintic treatments in agricultural practices. Specialized metabolites found in the extracts ofC. alpinacould offer a sustainable and biological alternative to chemical drugs, specifically for nematode control. For this purpose, a unique germplasm collection originating from eight distinct natural populations in the Italian Alps was analyzed for its chemical diversity using state-of-the-art targeted LC-MS/MS spectrometry, including quantification based on multiple reaction monitoring. The predominant metabolites identified from the species were the caffeic acid derivatives chicoric acid, chlorogenic acid, and 3. 5-dicaffeoylquinic acid, the sesquiterpene lactone derivative 8-O-acetyl-15-ß-D-glucopyranosyl lactucin and the flavone glycosides, apigenin-7-O-glucoside and luteolin-7-O-glucoside, alongside their precursors apigenin and luteolin, respectively. Additionally, the genetic diversity of eighty individual plants within the germplasm collection was evaluated using ten DNA molecular markers (Simple Sequence Repeats), successfully transferred from two closely related species (Cichorium intybusandTanacetum parthenium). This investigation unveiled a significant range of genetic diversity within the examined populations, resulting in the establishment of three distinct genetic groups. The findings were further correlated with the original ecological environment and local climate conditions spanning a biennial period, indicating substantial variations among the different accessions and the intricate interplay between genetic background and environmental factors. These results could serve as a basis for future domestication of the species through plant breeding programs ensuring product quality, but also facilitating the cultivation ofC. alpinain more diverse geographic regions.
Assessing attentional bias to emotions in adolescent offenders and nonoffenders
Authors: Pino Mariana , Pardo Victor , Ruiz Ronald , González Gabriel , Parra Mario Alfredo
Published: November 2023

Emotional processing is a cognitive function essential for the interaction of humans with their environment and the development of adaptive behaviors. Adolescent offenders (AOs) express difficulty in cognitive processes linked to emotional processing, which is a response consistently observed during the endogenous (i.e., controlled) control of attention. Less remains understood of the extent to which such atypical responses extend beyond controlled attention and influence exogenous mechanisms (i.e., automatic). This study explores this hypothesis using the recently devised emotional Flanker paradigm. It recruited a group of 39 male AOs and 39 nonoffenders from Barranquilla, Colombia. Assessment consists of an emotional Flanker paradigm administered along with traditional neurocognitive and social cognition tasks. The AOs displayed the well-known attentional bias to threat and a relatively atypical response to emotional targets in which they detected emotions, particularly negative ones, faster than did nonoffenders. Frontal lobe functions account for these effects but not sociodemographic variables nor general cognitive abilities. The results are interpreted in light of evidence suggesting that youngsters with high levels of antisocial behaviors (e.g., callous–unemotional traits) present an enhanced orientation toward distressing stimuli, which is explained by lifelong experiences (e.g., histories of abuse). The findings suggest that environmental influences seemingly exist in the development of these traits, but additional research is required to elucidate the role of cognitive and environmental factors in the development of antisocial behavior.
A process to foster pathology-related effects of design primes – how orthopedic patients might benefit from design features that influence health behaviour intention
Authors: Rehn-Groenendijk Jonas , Schuster Kai , Müller Helena , Chrysikou Evangelia
Published: November 2023

A growing body of literature mainly in the context of consumer research indicates that the formal-aesthetic and conceptual design of objects can influence users’ thoughts, emotions and even behavioural patterns. While there is strong evidence regarding these effects on actual purchasing decisions, evidence on the effect of aesthetic design features (e.g., haptics, colour) on health-related mental concepts and intentions for health behaviour change is scarce. Based on insights from material and conceptual priming, this article illustrates the research-driven and evidence-based design process of two design primes and comprises pre-tests and an experiment in two settings on the effect of design on health behaviour focusing i.a. on intention for health behaviour change. In an evidence-based and research-driven process, two lecterns were designed to work as primes, i.e., to have a positive vs. negative influence on several mental constructs (sense of control, sense of coherence, resiliency, self-efficacy) and health-related intention. The lecterns differed mainly in terms of aesthetic appearance (e.g., material, colour, proportion, steadiness). They were tested in (a.) a university setting with students (n = 83) and (b.) a clinical setting with orthopaedic rehabilitation patients (n = 38). Participants were asked to perform an unrelated task (evaluation of an unrelated product) while standing at and using the lecterns. Overall, t-tests and Mann–Whitney-U tests show no significant differences but differing tendencies in a mentioning task. When asked to name health-promoting activities, in the clinical setting, participants using the “positive” prime (i.e., the steady lectern, n = 13) mentioned more sport-related aspects on average and a higher portion of sport-related aspects of their answers than participants using the “negative” prime (n = 11). In the university setting (positive: n = 36; negative n = 38), no such differences emerged. This finding gives reason to believe that the prime might be specifically effective in the clinical setting as it relates to physical activity being the most relevant topic of the patients’ pathology.
The Lithuanian version of the Burnout Assessment Tool (BAT-LT): psychometric characteristics of the primary and secondary symptoms scales
Authors: Lazauskaitė-Zabielskė Jurgita , Žiedelis Arūnas , Jakštienė Rita , Urbanavičiūtė Ieva , De Witte Hans
Published: November 2023

The Burnout Assessment Tool (BAT) is a new measure of burnout that was developed to address the shortcomings of existing burnout instruments. This study investigates the psychometric properties of the Lithuanian version of the Burnout Assessment Tool (BAT-LT). In total, 408 adult workers were surveyed (the mean age was 35.94 years; 68.6 per cent were female; 43.9 per cent held managerial positions). Participants came from different sectors of economic activity. The results showed that BAT-LT had good factorial validity, indicating that BAT-LT’s four subscales (exhaustion, cognitive impairment, emotional impairment, and mental distance) can be combined into a single burnout score. Moreover, Cronbach’s alpha values indicate good reliability for all six core and secondary burnout symptoms scales. Furthermore, the results confirmed that BAT-LT could be differentiated from job boredom, workaholism, work engagement and depression. Finally, measurement invariance across managerial status and the sector was observed. The results of this study provide solid evidence for BAT-LT’s reliability and factorial and construct validity.