bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-lasting neutralizing antibodies and T cell response after the third dose of mRNA anti-SARS-CoV-2 vaccine in multiple sclerosis
Authors: Maglione Alessandro , Francese Rachele , Arduino Irene , Rosso Rachele , Matta Manuela , Rolla Simona , Lembo David , Clerico Marinella
Published: June 2023

Background and objectives

Long lasting immune response to anti-SARS-CoV-2 vaccination in people with Multiple Sclerosis (pwMS) is still largely unexplored. Our study aimed at evaluating the persistence of the elicited amount of neutralizing antibodies (Ab), their activity and T cell response after three doses of anti-SARS-CoV-2 vaccine in pwMS.

Methods

We performed a prospective observational study in pwMS undergoing SARS-CoV-2 mRNA vaccinations. Anti-Region Binding Domain (anti-RBD) of the spike (S) protein immunoglobulin G (IgG) titers were measured by ELISA. The neutralization efficacy of collected sera was measured by SARS-CoV-2 pseudovirion-based neutralization assay. The frequency of Spike-specific IFNγ-producing CD4+ and CD8+ T cells was measured by stimulating Peripheral Blood Mononuclear Cells (PBMCs) with a pool of peptides covering the complete protein coding sequence of the SARS-CoV-2 S.

Results

Blood samples from 70 pwMS (11 untreated pwMS, 11 under dimethyl fumarate, 9 under interferon-γ, 6 under alemtuzumab, 8 under cladribine, 12 under fingolimod and 13 under ocrelizumab) and 24 healthy donors were collected before and up to six months after three vaccine doses. Overall, anti-SARS-CoV-2 mRNA vaccine elicited comparable levels of anti-RBD IgGs, neutralizing activity and anti-S T cell response both in untreated, treated pwMS and HD that last six months after vaccination. An exception was represented by ocrelizumab-treated pwMS that showed reduced levels of IgGs (p<0.0001) and a neutralizing activity under the limit of detection (p<0.001) compared to untreated pwMS. Considering the occurrence of a SARS-CoV-2 infection after vaccination, the Ab neutralizing efficacy (p=0.04), as well as CD4+ (p=0.016) and CD8+ (p=0.04) S-specific T cells, increased in treated COVID+ pwMS compared to uninfected treated pwMS at 6 months after vaccination.

Discussion

Our follow-up provides a detailed evaluation of Ab, especially in terms of neutralizing activity, and T cell responses after anti-SARS-CoV-2 vaccination in MS context, over time, considering a wide number of therapies, and eventually breakthrough infection. Altogether, our observations highlight the vaccine response data to current protocols in pwMS and underline the necessity to carefully follow-up anti-CD20- treated patients for higher risk of breakthrough infections. Our study may provide useful information to refine future vaccination strategies in pwMS.
Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials
Authors: Luo Chengxin , Huang Xiangtao , Wei Ling , Wu Guixian , Huang Yarui , Ding Yaqun , Huang Zhen , Chen Jieping , Li Xi , Zou Yunding , Xu Shuangnian
Published: June 2023

Objective

Steroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens.

Methods

Literature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method.

Results

Eight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01–1.32, P = 0.04), especially in patients with severe (grade III–IV or grade C–D) aGVHD (RR = 1.26, 95% CI = 1.04–1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05–1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy.

Conclusions

Adding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.
Small-scale fisheries catch and fishing effort in the Socotra Archipelago (Yemen) between 1950 and 2019
Authors: Derrick Brittany , Burns Keanna , Zhu Audrey , Andreoli Vania , Zeller Dirk , Pauly Daniel
Published: June 2023

The Socotra Archipelago (Yemen), a group of four islands off the north-eastern tip of Africa in the western Indian Ocean, has a population that relies heavily on small-scale fishing for livelihoods and food security. However, the reporting of fisheries catches by Yemen has consistently been incomplete, with artisanal (small-scale, commercial) catches underreported and small-scale non-commercial subsistence and recreational catches not reported at all. Here, we reconstruct the total small-scale catches and fishing effort from the waters of the Socotra Archipelago for 1950 to 2019, and derive catch-per-unit-effort (CPUE) estimates for these fisheries. The catch officially reported by the Food and Agriculture Organization on behalf of Yemen that was assumed taken from the archipelago is thought to be around 20% of the total reconstructed catch for the archipelago. The reconstructed small-scale catch increased from ~1,500 t in 1950 to an all-time peak of 12,000 t in 2000 before declining to 3,300 t by 2014. Thereafter, catches increased again slightly to just over 3,700 t·year-1 by 2019. Artisanal catches accounted for around 70% of total small-scale catches prior to 2010, but made up only around 46% by 2019. Conversely, subsistence catches increased from ~1,000 t in 2010 to ~2,000 t in 2019, and accounted for 54% of total catches by 2019. Small-scale fishing effort increased by over 1000% since 1950 and reached over 11 million kWdays by 2019. The CPUE derived for small-scale fisheries declined by 78% since 1950, from 1.4 kg·kWday-1 to 0.3 kg·kWday-1 in 2019, with most of the decline occurring after 2000. Our findings suggest resource overexploitation, and may assist efforts to more sustainably manage the Socotra Archipelago’s fish stocks. Small-scale fisheries support food and nutrient security of the local population, not least during political and humanitarian crises such as in Yemen.
A promising alternative: examining TVS tellurite glass for gamma radiation shielding applications
Authors: Uosif M. A. M. , Issa Shams A. M. , Ene Antoaneta , Mostafa A. M. A. , Atta Ali , Badawi Ali , El Agammy E. F. , Zakaly Hesham M. H.
Published: June 2023

Radiation shielding is crucial in many types of medical, industrial, and nuclear facilities due to the widespread usage of radioactive isotopes. In this research, we examine the impact of tellurite 65TeO2–(35-x)V2O5-xSm2O3 glasses, where x ranges from 0.1 to 5 mol%, for its nuclear security and radiation shielding versus gamma attenuation capabilities. For gamma, the effect that the systematic replacement of Sm2O3 with V2O5 has on the shielding qualities was dissected in great depth. In addition, comparative research was carried out using the most recent borate glasses and the typical shielding materials considered the industry standard. In this study, we utilized the FLUKA algorithm and the FLAIR graphical interface to calculate the attenuation coefficients of glass compositions in the 65TeO2–(35-x)V2O5-xSm2O3system. The gamma energies of 0.356, 0.662, 1.332, and 2.614 MeV, commonly used in gamma shielding investigations, were selected as the radiation source. A comparison between the simulation results by FLUKA and theoretical calculations for mass attenuation coefficients demonstrated excellent agreement, confirming the reliability and accuracy of the FLUKA simulation method. The findings of the current research point to the fact that the TVS5 sample has the highest GMAC and lowest GHVL and GMFP, among other glasses. This points to the possibility that the TVS5 sample might be used in radiation shielding activities, which would result in increased nuclear safety.
Analysis and research on the constant-rate penetration mechanism of the seabed cone penetration test system
Authors: Ren Ziqiang , Chen Jiawang , Guo Jin , Liu Bijin , Hu Xiaohui , Zhou Hang , Liu Houhong , Gao Feng
Published: June 2023

The seabed Cone Penetration Test (CPT) system is a common method for investigating offshore soil. This paper focuses on a new subsea CPT method for assessing physical and mechanical properties of marine sediments. The new method enables automatic docking and dismantling of the probe rods underwater. The constant-rate penetration mechanism is the basis and core component of the seabed CPT, allowing the probe rod and cone to penetrate the seafloor sediment. Double hydraulic cylinders are used to meet the high penetration force requirements. To maintain a constant penetration rate of 20 ± 5 mm/s, the model identification of the electro-hydraulic servo system is performed using Simcenter AMESim and MATLAB software, and the relevant transfer function is obtained using the PID method. Based on this transfer function, the sliding mode variable structure controller of the electro-hydraulic servo system is designed to regulate the constant penetration rate of the hydraulic cylinder against varying penetration resistance. In-situ measurements were operated using the new seabed CPT rig in Zhoushan Island. The simulation and testing results confirm that the sliding mode variable structure controller is suitable for controlling the system during actual operation.
Effectiveness and safety of Levofloxacin containing regimen in the treatment of Isoniazid mono-resistant pulmonary Tuberculosis: a systematic review
Authors: Inbaraj Leeberk Raja , Shewade Hemant Deepak , Daniel Jefferson , Srinivasalu Vignes Anand , Paul Jabez , Satish S. , Kirubakaran Richard , Padmapriyadarsini Chandrasekaran
Published: June 2023

Background

We aimed to determine the effectiveness and safety of the Levofloxacin-containing regimen that the World Health Organization is currently recommending for the treatment of Isoniazid mono-resistant pulmonary Tuberculosis.

Methods

Our eligible criteria for the studies to be included were; randomized controlled trials or cohort studies that focused on adults with Isoniazid mono-resistant tuberculosis (HrTB) and treated with a Levofloxacin-containing regimen along with first-line anti-tubercular drugs; they should have had a control group treated with first-line without Levofloxacin; should have reported treatment success rate, mortality, recurrence, progression to multidrug-resistant Tuberculosis. We performed the search in MEDLINE, EMBASE, Epistemonikos, Google Scholar, and Clinical trials registry. Two authors independently screened the titles/abstracts and full texts that were retained after the initial screening, and a third author resolved disagreements.

Results

Our search found 4,813 records after excluding duplicates. We excluded 4,768 records after screening the titles and abstracts, retaining 44 records. Subsequently, 36 articles were excluded after the full-text screening, and eight appeared to have partially fulfilled the inclusion criteria. We contacted the respective authors, and none responded positively. Hence, no articles were included in the meta-analysis.

Conclusion

We found no “quality” evidence currently on the effectiveness and safety of Levofloxacin in treating HrTB.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022290333, identifier: CRD42022290333.
Effectiveness of coordinated care to reduce the risk of prolonged disability among patients suffering from subacute or recurrent acute low back pain in primary care: protocol of the CO.LOMB cluster-randomized, controlled study
Authors: Ramond-Roquin Aline , Bègue Cyril , Vizzini Jonathan , Chhor Sidonie , Bouchez Tiphanie , Parot-Schinkel Elsa , Loiez Anthéa , Petit Audrey , Ghali Maria , Peurois Matthieu , Bouton Céline
Published: June 2023

Background

Low back pain (LBP) is a common musculoskeletal condition and, globally, a leading cause of years lived with disability. It leads to reduced social participation, impaired quality of life, and direct and indirect costs due to work incapacity. A coordinated approach focusing on psychosocial risk factors, active reeducation, and the early use of tools to maintain employment, may be effective for improving prognosis of patients with LBP. Primary care professionals and multidisciplinary teams, who see patients in the early stages of LBP may be in the best position to implement such a coordinated approach. We designed this study to assess a coordinated multi-faceted strategy in primary care for patients with subacute or recurrent acute LBP.

Methods

The CO.LOMB study was designed as a multicentric, cluster-randomized, controlled study. Patients aged 18–60 years, with subacute or recurrent acute LBP are eligible. Patients also need to be employed (but can be on sick leave) with access to occupational health services. The clusters of GPs will be randomized (1:1) to either the Coordinated-care group or the Usual-care group. Patients will be assigned the group allocated to their GP. The healthcare professionals (GPs and associated physiotherapists) allocated to the Coordinated-care group will perform a 2-session study training. The following interventions are planned in the Coordinated-care group: exploration and management of psychosocial factors, active reeducation with a physiotherapist, the implementing of tools to maintain employment, and a reinforced cooperation between primary healthcare professionals. The primary objective is to assess the benefit of coordinated primary care to reduce disability in LBP patients at 12 months after enrollment: measure using the validated French version of the Roland Morris Disability Questionnaire. Secondary objectives include the evaluation of pain, work status, and quality of life at various time points. The study plans to enroll 500 patients in 20 GP clusters. Patients will be followed up for 12months.

Discussion

This study will evaluate the benefit of a coordinated multi-faceted strategy in primary care for patients with LBP. Notably whether this approach will alleviate the associated disability, attenuate pain, and promote the maintenance or return to work.

Clinical Trial Registration

NCT04826757.
Case report: Sudden onset optic neuritis shortly after SARS-CoV-2 vaccination in an allogeneic hematopoietic stem cell transplant recipient with chronic graft-vs.-host disease
Authors: Chu Chiang , Jiang Shin-Kuang , Shao Yi-Ching , Yeh Su-Peng
Published: June 2023

Hematopoietic stem cell transplantation (HSCT) recipients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have a high mortality rate. The American Society of Transplantation and Cellular Therapy (ASTCT) and the European Society for Blood and Marrow Transplantation (EBMT) recommend vaccination for these vulnerable populations. However, emerging data suggested that vaccination might elicit immunological adverse events, including an exacerbation of graft-vs.-host disease (GVHD). Herein, we report a case of severe optic neuritis developed shortly after AstraZeneca COVID-19 vaccination in an allogeneic HSCT recipient with underlying chronic GVHD. The patient had a headache 5 days after vaccination, and the disease progressed rapidly to complete blindness 17 days after the vaccination. The diagnosis of optic neuritis was well-confirmed by the presence of an anti-myelin oligodendrocyte glycoprotein antibody and the typical features of MRI image and Ophthalmoscopy. Other differential diagnoses, such as infection or leukemia relapse in the central nervous system (CNS), were carefully excluded. A timely high-dose corticosteroid was administered, and her visual acuity improved rapidly. She returned to her baseline status 1 month later. With more than 1 year of follow-up, no optic neuritis or leukemia relapse was observed. In summary, allogeneic transplant recipients can develop severe optic neuritis after vaccination. Optic neuritis can be an exacerbation of GVHD or rarely a sporadic adverse event of vaccination. Furthermore, our experience indicates that a prompt diagnosis and early steroid treatment are vital for a good recovery.
Modified underwater endoscopic mucosal resection for intermediate-sized sessile colorectal polyps
Authors: Kim Dong Hyun , Park Seon-Young , You Hye-Su , Jung Yong-Wook , Joo Young-Eun , Myung Dae-Seong , Kim Hyun-Soo , Kim Nah Ihm , Kim Seong-Jung , Ju Jae Kyun
Published: June 2023

Introduction

Underwater endoscopic mucosal resection (UEMR) is effective for treating intermediate-sized colorectal polyps. However, it is sometimes difficult to obtain visibility in underwater conditions.

Methods

This prospective, observational, single-center study included consecutive patients with intermediate-sized (10–20 mm) sessile colorectal polyps. Modified UEMR method was used to initially snare the lesion without injection or water infusion. Thereafter, water was infused until the lesion was submerged, then it was resected using electrocautery. We also evaluated the rates of complete resection and procedure-related complications.

Results

Forty-two patients with 47 polyps were enrolled in the study. The median procedure time and fluid infusion were 71 s (42–607) and 50 mL (30–130), respectively. The rates of R0 resection and en bloc resection were 80.9 and 97.9%, respectively, with 100% technical success. R0 resection was observed in 42.9% of polyps sized ≥15 mm and 87.5% sized <15 mm (p < 0.01). Muscle entrapment was found in 71.4% of patients with polyps sized ≥15 mm and 10% <15 mm (p < 0.01). Immediate bleeding occurred in 12.8% of cases and was controlled using a snare tip or hemostatic forceps. Snare-tip ablation and hemostatic forceps ablation were performed in 27.7 and 6.4% of patients, respectively. No delayed bleeding, perforation, or any other complications were reported.

Conclusion

Modified UEMR can be used in cases in which securing visibility or performing the existing UEMR is challenging. Careful treatment is required when removing polyps >15 mm in size.
Novel parasitic chytrids infecting snow algae in an alpine snow ecosystem in Japan
Authors: Nakanishi Hiroaki , Seto Kensuke , Takeuchi Nozomu , Kagami Maiko
Published: June 2023

Introduction

Microbial communities are important components of glacier and snowpack ecosystems that influence biogeochemical cycles and snow/ice melt. Recent environmental DNA surveys have revealed that chytrids dominate the fungal communities in polar and alpine snowpacks. These could be parasitic chytrids that infect snow algae as observed microscopically. However, the diversity and phylogenetic position of parasitic chytrids has not been identified due to difficulties in establishing their culture and subsequent DNA sequencing. In this study, we aimed to identify the phylogenetic positions of chytrids infecting the snow algae, Chloromonas spp., bloomed on snowpacks in Japan.

Methods

By linking a microscopically picked single fungal sporangium on a snow algal cell to a subsequent sequence of ribosomal marker genes, we identified three novel lineages with distinct morphologies.

Results

All the three lineages belonged to Mesochytriales, located within “Snow Clade 1”, a novel clade consisting of uncultured chytrids from snow-covered environments worldwide. Additionally, putative resting spores of chytrids attached to snow algal cells were observed.

Discussion

This suggests that chytrids may survive as resting stage in soil after snowmelt. Our study highlights the potential importance of parasitic chytrids that infect snow algal communities.
Molecular and biochemical investigations of the anti-fatigue effects of tea polyphenols and fruit extracts of Lycium ruthenicum Murr. on mice with exercise-induced fatigue
Authors: Bi Yingxin , Liu Xianjun , Liu Yue , Wang Mengyuan , Shan Yaming , Yin Yuhe , Meng Xianglong , Sun Fengjie , Li Hao , Li Zhandong
Published: June 2023

Background: The molecular mechanisms regulating the therapeutic effects of plant-based ingredients on the exercise-induced fatigue (EIF) remain unclear. The therapeutic effects of both tea polyphenols (TP) and fruit extracts of Lycium ruthenicum (LR) on mouse model of EIF were investigated.

Methods: The variations in the fatigue-related biochemical factors, i.e., lactate dehydrogenase (LDH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), and interleukin-6 (IL-6), in mouse models of EIF treated with TP and LR were determined. The microRNAs involved in the therapeutic effects of TP and LR on the treatment of mice with EIF were identified using the next-generation sequencing technology.

Results: Our results revealed that both TP and LR showed evident anti-inflammatory effect and reduced oxidative stress. In comparison with the control groups, the contents of LDH, TNF-α, IL-6, IL-1β, and IL-2 were significantly decreased and the contents of SOD were significantly increased in the experimental groups treated with either TP or LR. A total of 23 microRNAs (21 upregulated and 2 downregulated) identified for the first time by the high-throughput RNA sequencing were involved in the molecular response to EIF in mice treated with TP and LR. The regulatory functions of these microRNAs in the pathogenesis of EIF in mice were further explored based on Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses with a total of over 20,000–30,000 target genes annotated and 44 metabolic pathways enriched in the experimental groups based on GO and KEGG databases, respectively.

Conclusion: Our study revealed the therapeutic effects of TP and LR and identified the microRNAs involved in the molecular mechanisms regulating the EIF in mice, providing strong experimental evidence to support further agricultural development of LR as well as the investigations and applications of TP and LR in the treatment of EIF in humans, including the professional athletes.
Visual cortical LFP in relation to the hippocampal theta rhythm in track running rats
Authors: Kennedy Jack P. , Zhou Yuchen , Qin Yu , Lovett Sarah D. , Cooper Tara , Sheremet Alex , Burke Sara N. , Maurer Andrew P.
Published: June 2023

Theta oscillations in the primary visual cortex (VC) have been observed during running tasks, but the mechanism behind their generation is not well understood. Some studies have suggested that theta in the VC is locally generated, while others have proposed that it is volume conducted from the hippocampus. The present study aimed to investigate the relationship between hippocampal and VC LFP dynamics. Analysis of power spectral density revealed that LFP in the VC was similar to that in the hippocampus, but with lower overall magnitude. As running velocity increased, both the power and frequency of theta and its harmonics increased in the VC, similarly to what is observed in the hippocampus. Current source density analysis triggered to theta did not identify distinct current sources and sinks in the VC, supporting the idea that theta in the VC is conducted from the adjacent hippocampus. Phase coupling between theta, its harmonics, and gamma is a notable feature in the hippocampus, particularly in the lacunosum moleculare. While some evidence of coupling between theta and its harmonics in the VC was found, bicoherence estimates did not reveal significant phase coupling between theta and gamma. Similar results were seen in the cross-region bicoherence analysis, where theta showed strong coupling with its harmonics with increasing velocity. Thus, theta oscillations observed in the VC during running tasks are likely due to volume conduction from the hippocampus.
A review of auditory processing and cognitive change during normal ageing, and the implications for setting hearing aids for older adults
Authors: Windle Richard , Dillon Harvey , Heinrich Antje
Published: June 2023

Throughout our adult lives there is a decline in peripheral hearing, auditory processing and elements of cognition that support listening ability. Audiometry provides no information about the status of auditory processing and cognition, and older adults often struggle with complex listening situations, such as speech in noise perception, even if their peripheral hearing appears normal. Hearing aids can address some aspects of peripheral hearing impairment and improve signal-to-noise ratios. However, they cannot directly enhance central processes and may introduce distortion to sound that might act to undermine listening ability. This review paper highlights the need to consider the distortion introduced by hearing aids, specifically when considering normally-ageing older adults. We focus on patients with age-related hearing loss because they represent the vast majority of the population attending audiology clinics. We believe that it is important to recognize that the combination of peripheral and central, auditory and cognitive decline make older adults some of the most complex patients seen in audiology services, so they should not be treated as “standard” despite the high prevalence of age-related hearing loss. We argue that a primary concern should be to avoid hearing aid settings that introduce distortion to speech envelope cues, which is not a new concept. The primary cause of distortion is the speed and range of change to hearing aid amplification (i.e., compression). We argue that slow-acting compression should be considered as a default for some users and that other advanced features should be reconsidered as they may also introduce distortion that some users may not be able to tolerate. We discuss how this can be incorporated into a pragmatic approach to hearing aid fitting that does not require increased loading on audiology services.
Patterns of gray and white matter functional networks involvement in glioblastoma patients: indirect mapping from clinical MRI scans
Authors: Sansone Giulio , Pini Lorenzo , Salvalaggio Alessandro , Gaiola Matteo , Volpin Francesco , Baro Valentina , Padovan Marta , Anglani Mariagiulia , Facchini Silvia , Chioffi Franco , Zagonel Vittorina , D’Avella Domenico , Denaro Luca , Lombardi Giuseppe , Corbetta Maurizio
Published: June 2023

Background

Resting-state functional-MRI studies identified several cortical gray matter functional networks (GMNs) and white matter functional networks (WMNs) with precise anatomical localization. Here, we aimed at describing the relationships between brain’s functional topological organization and glioblastoma (GBM) location. Furthermore, we assessed whether GBM distribution across these networks was associated with overall survival (OS).

Materials and methods

We included patients with histopathological diagnosis of IDH-wildtype GBM, presurgical MRI and survival data. For each patient, we recorded clinical-prognostic variables. GBM core and edema were segmented and normalized to a standard space. Pre-existing functional connectivity-based atlases were used to define network parcellations: 17 GMNs and 12 WMNs were considered in particular. We computed the percentage of lesion overlap with GMNs and WMNs, both for core and edema. Differences between overlap percentages were assessed through descriptive statistics, ANOVA, post-hoc tests, Pearson’s correlation tests and canonical correlations. Multiple linear and non-linear regression tests were employed to explore relationships with OS.

Results

99 patients were included (70 males, mean age 62  years). The most involved GMNs included ventral somatomotor, salient ventral attention and default-mode networks; the most involved WMNs were ventral frontoparietal tracts, deep frontal white matter, and superior longitudinal fasciculus system. Superior longitudinal fasciculus system and dorsal frontoparietal tracts were significantly more included in the edema (p < 0.001). 5 main patterns of GBM core distribution across functional networks were found, while edema localization was less classifiable. ANOVA showed significant differences between mean overlap percentages, separately for GMNs and WMNs (p-values<0.0001). Core-N12 overlap predicts higher OS, although its inclusion does not increase the explained OS variance.

Discussion and conclusion

Both GBM core and edema preferentially overlap with specific GMNs and WMNs, especially associative networks, and GBM core follows five main distribution patterns. Some inter-related GMNs and WMNs were co-lesioned by GBM, suggesting that GBM distribution is not independent of the brain’s structural and functional organization. Although the involvement of ventral frontoparietal tracts (N12) seems to have some role in predicting survival, network-topology information is overall scarcely informative about OS. fMRI-based approaches may more effectively demonstrate the effects of GBM on brain networks and survival.
KCNQ2 channels regulate the population activity of neonatal GABAergic neurons ex vivo
Authors: Hou Bowen , Santaniello Sabato , Tzingounis Anastasios V.
Published: June 2023

Over the last decade KCNQ2 channels have arisen as fundamental and indispensable regulators of neonatal brain excitability, with KCNQ2 loss-of-function pathogenic variants being increasingly identified in patients with developmental and epileptic encephalopathy. However, the mechanisms by which KCNQ2 loss-of-function variants lead to network dysfunction are not fully known. An important remaining knowledge gap is whether loss of KCNQ2 function alters GABAergic interneuron activity early in development. To address this question, we applied mesoscale calcium imaging ex vivo in postnatal day 4–7 mice lacking KCNQ2 channels in interneurons (Vgat-ires-cre;Kcnq2f/f;GCamp5). In the presence of elevated extracellular potassium concentrations, ablation of KCNQ2 channels from GABAergic cells increased the interneuron population activity in the hippocampal formation and regions of the neocortex. We found that this increased population activity depends on fast synaptic transmission, with excitatory transmission promoting the activity and GABAergic transmission curtailing it. Together, our data show that loss of function of KCNQ2 channels from interneurons increases the network excitability of the immature GABAergic circuits, revealing a new function of KCNQ2 channels in interneuron physiology in the developing brain.
Enhanced lower-limb motor imagery by kinesthetic illusion
Authors: Wang Weizhen , Shi Bin , Wang Dong , Wang Jing , Liu Gang
Published: June 2023

Brain-computer interface (BCI) based on lower-limb motor imagery (LMI) enables hemiplegic patients to stand and walk independently. However, LMI ability is usually poor for BCI-illiterate (e.g., some stroke patients), limiting BCI performance. This study proposed a novel LMI-BCI paradigm with kinesthetic illusion(KI) induced by vibratory stimulation on Achilles tendon to enhance LMI ability. Sixteen healthy subjects were recruited to carry out two research contents: (1) To verify the feasibility of induced KI by vibrating Achilles tendon and analyze the EEG features produced by KI, research 1 compared the subjective feeling and brain activity of participants during rest task with and without vibratory stimulation (V-rest, rest). (2) Research 2 compared the LMI-BCI performance with and without KI (KI-LMI, no-LMI) to explore whether KI enhances LMI ability. The analysis methods of both experiments included classification accuracy (V-rest vs. rest, no-LMI vs. rest, KI-LMI vs. rest, KI-LMI vs. V-rest), time-domain features, oral questionnaire, statistic analysis and brain functional connectivity analysis. Research 1 verified that induced KI by vibrating Achilles tendon might be feasible, and provided a theoretical basis for applying KI to LMI-BCI paradigm, evidenced by oral questionnaire (Q1) and the independent effect of vibratory stimulation during rest task. The results of research 2 that KI enhanced mesial cortex activation and induced more intensive EEG features, evidenced by ERD power, topographical distribution, oral questionnaire (Q2 and Q3), and brain functional connectivity map. Additionally, the KI increased the offline accuracy of no-LMI/rest task by 6.88 to 82.19% (p < 0.001). The simulated online accuracy was also improved for most subjects (average accuracy for all subjects: 77.23% > 75.31%, and average F1_score for all subjects: 76.4% > 74.3%). The LMI-BCI paradigm of this study provides a novel approach to enhance LMI ability and accelerates the practical applications of the LMI-BCI system.
Tumor-infiltrating lymphocytes provides recent survival information for early-stage HER2-low-positive breast cancer: a large cohort retrospective study
Authors: Sun Teng , Wang Tong , Li Xiangjun , Wang Haibo , Mao Yan
Published: June 2023

Purpose

It has been reported that breast cancer (BC) with low expression of human epidermal growth factor receptor 2 (HER2) might be a distinct subtype of BC. However, the prognostic effect of low HER2 expression on BC patients remains controversial. We aim to conduct this single-institution retrospective analysis to assess HER2-low-positive BC outcomes in Chinese women and the prognostic role of TILs in HER2-low-positive early-stage BC.

Method

We retrospectively enrolled 1,763 BC patients treated in a single institution from 2017 to 2018. TILs are regarded as continuous variables and are divided into low TILs (≤10%) and high TILs (>10%) for statistical analysis. Univariate and multivariable Cox proportional hazards regression models were used to test the associations between TILs and disease-free survival (DFS) with adjustment for clinicopathologic characteristics.

Result

High TIL levels (>10%) were associated with tumor size (>2 cm, p = 0.042), age at diagnosis (p = 0.005), Ki-67 index (>25%; p <0.001), HR (hormone receptor) status (positive, p <0.001), advanced pathological stage (p = 0.043), subtype (p <0.001), and HER2 status (p <0.001). The Kaplan−Meier analysis indicated that no significant difference in DFS (p = 0.83) could be found between HER2-positive, HER2-low-positive, and HER2-0 BC. The DFS of HER2-low-positive BC and HER2-nonamplified BC with high levels of TILs was statistically better than that of patients with low levels of TILs (p = 0.015; p = 0.047). In HER2-low-positive BC patients with high TIL levels (>10%), DFS was significantly improved in both the univariate (HR = 0.44, 95% CI 0.22–0.87, P = 0.018) and multivariate (HR = 0.47, 95% CI 0.23–0.95, P = 0.035) Cox models. For further subgroup analysis, HR (+)/HER2-low-positive BC with high TIL (>10%) levels was associated with improved DFS in both the univariate (HR = 0.41, 95% CI 0.19–0.90, P = 0.025) and multivariate (HR = 0.42, 95% CI 0.19–0.93, P = 0.032) Cox models. The HR (−)/HER2-0 BC with high TIL (>10%) level was not statistically significant in the univariate Cox model, but it was statistically significant in the multivariate (HR = 0.16, 95% CI 0.28–0.96, P = 0.045) Cox model.

Conclusion

Among early-stage BC, no significant survival difference could be found between the HER2-positive, HER2-low-positive, and HER2-0 cohorts. High levels of TILs were significantly associated with improved DFS in HER2-low-positive patients, especially in the HR (+)/HER2-low-positive subtype.
Pancreatic stellate cells in pancreatic cancer: as potential targets for future therapy
Authors: Wang Zhengfeng , He Ru , Dong Shi , Zhou Wence
Published: June 2023

Pancreatic cancer is a strongly malignant gastrointestinal carcinoma characterized by late detection, high mortality rates, poor patient prognosis and lack of effective treatments. Consequently, there is an urgent need to identify novel therapeutic strategies for this disease. Pancreatic stellate cells, which constitute a significant component of the mesenchymal cellular layer within the pancreatic tumor microenvironment, play a pivotal role in modulating this environment through their interactions with pancreatic cancer cells. This paper reviews the mechanisms by which pancreatic stellate cells inhibit antitumor immune responses and promote cancer progression. We also discuss preclinical studies focusing on these cells, with the goal of providing some theoretical references for the development of new therapeutic approaches for pancreatic cancer.
Emerging trends and research foci in autophagy of pancreatic cancer: a bibliometric and visualized study
Authors: Fan Linlin , Wei Zhiyong , Liu Lili , Qi Xiaojie , Yu Hong
Published: June 2023

Objective

The purpose of this study was to analyze the trends by year, country, institution, journal, reference and keyword in publications on the autophagy of pancreatic cancer (PC) and to predict future research hotspots.

Methods

The Web of Science Core Collection was used to search for publications. The contributions of various countries/regions, institutes, authors, identified research hotspots, and promising future trends were analyzed using the VOSviewer1.6.16 and CiteSpace6.6.R2 programs. We also summarized autophagy relevant clinical trials of PC.

Results

A total of 1293 papers on the autophagy of PC published between 2013 and 2023 were included in the study. The average number of citations per article was 33.76. The China had the most publications, followed by USA, and a total of 50 influential articles were identified through co-citation analysis. Clustering analysis revealed clusters of keywords: metabolic reprogramming and ER stress, mTOR-mediated apoptosis, extracellular trap as the most concerned clusters. The co-occurrence cluster analysis showed pancreatic stellate cell, autophagy-dependent ferroptosis, autophagy-related pathway, metabolic rewiring, on-coding RNA as the highly concerned research topics in recently.

Conclusion

The number of publications and research interest have generally increased over the past few years. The China and USA have made prominent contributions to the study of the autophagy of PC. The current research hotspots mainly focus not only on the related modulation, metabolic reprogramming, ferroptosis of tumor cells themselves, but also on tumor microenvironments such as autophagy associated pancreatic stellate cells and new treatments targeting autophagy.
Development of a smartphone virtual reality game to support the radiation therapy of children and adolescents in proton centers
Authors: Schenck Leonardo , Bäumer Christian , Ross Björn , Schäfer Gabriele , Stember Nicole , Thomas Heike , Stieglitz Stefan , Timmermann Beate
Published: June 2023

Introduction

For most patients, cancer therapy with radiation is a new experience coming with many unknown challenges. This can be stressful, particularly for children and adolescents. With the aim of reducing this stress and anxiety, a virtual-reality (VR) game, which can be used by patients prior to treatment, was developed and evaluated in a proton therapy center.

Methods

The specifications were derived from literature and from interviews with medical staff and patients. The gantry including the sound of its moving components and the sound of the interlock and safety system were identified as the main features relevant for preparation of a radiation course. Potential implementation difficulties were identified in a literature study and regarded in the design. Within the VR game, patients could interact with modeled equipment of the treatment room and hear the reportedly stress-inducing sounds in a stress-free environment prior to the treatment. The VR game was evaluated in a second series of interviews with patients.

Results and Discussion

This exploratory study demonstrated the specification, implementation and safe application of a VR game dedicated to young proton therapy patients. Initial anecdotal evidence suggested that the VR gaming experience was well received and found to be helpful when preparing young patients for radiation therapy.
How does external reference pricing work in developing countries: evidence from Iran
Authors: Babaie Fatemeh , Motevalli Mohammad Hossein , Mehralian Gholamhossein , Peiravian Farzad , Yousefi Nazila
Published: June 2023

Introduction: Governments apply different pricing policies to ensure public accessibility, availability, and affordability of medicines. In this way, external reference pricing (ERP) because of its easy implementation is used widely across countries. However, ERP is completely path dependent, and it would both bring pros and cons, related to its implementing strategy which makes understanding of its impact in different countries challenging. In this study, we examine the performance of the ERP approach in Iran as a pricing tool.

Method: We conducted a cross-sectional descriptive study. Although Iran officially uses a reference country basket for ERP, in this study, we use different reference countries based on socioeconomic comparability, access to their price data, medicine pricing approaches, and pharmaceutical expenditure to examine the effect of reference countries as well as the method performance. Then, an empirical study was applied to a list of selected samples of medicines in the Iranian market to compare their price with our new reference countries. Then, we discuss the performance of ERP process based on the real prices in the Iranian pharmaceutical market.

Result: The prices of 57 medicines, which contain about 69.2% of the imported Iran pharma market in value, were compared with their prices in selected reference countries. It was found that 49.1% of prices were more expensive in at least one of the reference countries, and in 21% of products, the average price in Iran was higher than the average price in reference countries.

Conclusion: Achieving efficient and fair pricing of pharmaceuticals between and within countries is still a complex conceptual and policy problem that ERP in short term can handle. ERP cannot be considered a perfect tool for pricing alone, although its effectiveness is acceptable. It is expected that using other pricing methods alongside the ERP will improve patients’ access to medicines. In Iran, we use value base pricing as the main pricing method for every new molecule. Then, we use other methods such as ERP as a complementary method.
Tislelizumab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of advanced non-small cell lung cancer: systematic review and indirect comparison of randomized trials
Authors: Guo Yimeng , Jia Junting , Hao Zhiying , Yang Jing
Published: June 2023

Purpose: Pembrolizumab and tislelizumab have demonstrated significant clinical benefits in first-line treatment for advanced NSCLC. However, no head-to-head clinical trial has ever compared the optimal choice. Therefore, we conducted an indirect comparison to explore the optimal choice for advanced NSCLC combined with chemotherapy.

Methods: We conducted a systematic review of randomized trials; the clinical outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). Indirect comparisons between tislelizumab and pembrolizumab were conducted with the Bucher method.

Results: Data were abstracted from 6 randomized trials involving more than 2,000 participants. Direct meta-analysis showed that both treatment regimens improved clinical outcomes compared with chemotherapy alone (PFS: hazard ratio (HR)tis+chemo/chemo 0.55, 95% CI 0.45–0.67; HRpem+chemo/chemo 0.53, 95% CI 0.47–0.60; ORR: relative risk (RR)tis+chemo/chemo 1.50, 95% CI 1.32–1.71; RRpem+chemo/chemo 1.89, 95% CI 1.44–2.48). Regarding safety outcomes, tislelizumab and pembrolizumab have a higher risk in the incidence of grade 3 or higher AEs (RRtis+chemo/chemo 1.12, 95% CI 1.03–1.21; RRpem+chemo/chemo 1.13, 95% CI 1.03–1.24). The indirect comparison showed that there was no significant difference between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy in terms of PFS (HR: 1.04, 95% CI 0.82–1.31), ORR (RR: 0.79, 95% CI 0.59–1.07), the incidence of grade 3 or higher AEs (RR 0.99, 95% CI 0.87–1.12), and AEs leading to death (RR 0.70, 95% CI 0.23–2.09). In progression-free survival subgroup analysis, the results demonstrate no significant differences in PFS by PD-L1 TPS expression level, age, liver metastasis status, and smoking status between tislelizumab plus chemotherapy and pembrolizumab plus chemotherapy.

Conclusion: The efficacy and safety of tislelizumab combination chemotherapy were not substantially different from pembrolizumab combination chemotherapy.
Pharmacological effects and mechanisms of paeonol on antitumor and prevention of side effects of cancer therapy
Authors: Chang Xindi , Feng Xiaoteng , Du Min , Li Sijin , Wang Jiarou , Wang Yiru , Liu Ping
Published: June 2023

Cancer represents one of the leading causes of mortality worldwide. Conventional clinical treatments include radiation therapy, chemotherapy, immunotherapy, and targeted therapy. However, these treatments have inherent limitations, such as multidrug resistance and the induction of short- and long-term multiple organ damage, ultimately leading to a significant decrease in cancer survivors’ quality of life and life expectancy. Paeonol, a nature active compound derived from the root bark of the medicinal plant Paeonia suffruticosa, exhibits various pharmacological activities. Extensive research has demonstrated that paeonol exhibits substantial anticancer effects in various cancer, both in vitro and in vivo. Its underlying mechanisms involve the induction of apoptosis, the inhibition of cell proliferation, invasion and migration, angiogenesis, cell cycle arrest, autophagy, regulating tumor immunity and enhanced radiosensitivity, as well as the modulation of multiple signaling pathways, such as the PI3K/AKT and NF-κB signaling pathways. Additionally, paeonol can prevent adverse effects on the heart, liver, and kidneys induced by anticancer therapy. Despite numerous studies exploring paeonol’s therapeutic potential in cancer, no specific reviews have been conducted. Therefore, this review provides a systematic summary and analysis of paeonol’s anticancer effects, prevention of side effects, and the underlying mechanisms involved. This review aims to establish a theoretical basis for the adjunctive strategy of paeonol in cancer treatment, ultimately improving the survival rate and enhancing the quality of life for cancer patients.