bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model
Authors: Liu Qian , Liu Jun , Guo Minmei , Sung Tzu-Cheng , Wang Ting , Yu Tao , Tian Zeyu , Fan Guoping , Wu Wencan , Higuchi Akon
Published: December 2023

Background

Retinal degeneration (RD) is a group of disorders on irreversible vision loss. Multiple types of stem cells were used in clinical trials for RD treatment. However, it remains unknown what kinds of stem cells are most effective for the treatment. Therefore, we investigated the subretinal transplantation of several types of stem cells, human adipose-derived stem cells (hADSCs), amniotic fluid stem cells (hAFSCs), bone marrow stem cells (hBMSCs), dental pulp stem cells (hDPSCs), induced pluripotent stem cell (hiPSC), and hiPSC-derived retinal pigment epithelium (RPE) cells for protection effects, paracrine effects and treatment efficiency in an RD disease model rats.

Methods

The generation and characterization of these stem cells and hiPSC-derived RPE cells were performed before transplantation. The stem cells or hiPSC-derived RPE cell suspension labelled with CellTracker Green to detect transplanted cells were delivered into the subretinal space of 3-week-old RCS rats. The control group received subretinal PBS injection or non-injection. A series of detections including fundus photography, optomotor response (OMR) evaluations, light–dark box testing, electroretinography (ERG), and hematoxylin and eosin (HE) staining of retinal sections were conducted after subretinal injection of the cells.

Results

Each stem cell, hiPSC-derived RPE cell or PBS (blank experiment) was successfully transplanted into at least six RCS rats subretinally. Compared with the control rats, RCS rats subjected to subretinal transplantation of any stem cells except hiPSCs showed higher ERG waves (p < 0.05) and quantitative OMR (qOMR) index values (hADSCs: 1.166, hAFSCs: 1.249, hBMSCs: 1.098, hDPSCs: 1.238, hiPSCs: 1.208, hiPSC-RPE cells: 1.294, non-injection: 1.03, PBS: 1.06), which indicated better visual function, at 4 weeks post-injection. However, only rats that received hiPSC-derived RPE cells maintained their visual function at 8 weeks post-injection (p < 0.05). The outer nuclear layer thickness observed in histological sections after HE staining showed the same pattern as the ERG and qOMR results.

Conclusions

Compared to hiPSC-derived RPE cells, adult and fetal stem cells yielded improvements in visual function for up to 4 weeks post-injection; this outcome was mainly based on the paracrine effects of several types of growth factors secreted by the stem cells. Patients with RD will benefit from the stem cell therapy.
IL20RB signaling enhances stemness and chemotherapy resistance in pancreatic cancer
Authors: Li Xiao-hui , Huang Gui-zhong , Xu Zi-lan , Zhao Chong-yu , Dong Xiao-yuan , Cui Bo-kang , Lin Xiao-jun
Published: December 2023

Objective

Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness.

Materials and Methods

Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored.

Results

IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects.

Conclusion

Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.

Graphical abstract
IL-17A promotes the progression of Alzheimer’s disease in APP/PS1 mice
Authors: Cao Min , Liu Jing , Zhang Xiaomin , Wang Yaqi , Hou Yuli , Song Qiao , Cui Yuting , Zhao Yue , Wang Peichang
Published: December 2023

Background

Alzheimer’s disease (AD), which is the most common cause of dementia in elderly individuals, is a progressive neurodegenerative disorder. Neuroinflammation, which is an immune response that is activated by glial cells in the central nervous system, plays an important role in neurodegenerative diseases. Many studies have shown that interleukin-17A (IL-17A) plays an important role in AD, but research on the pathological effects of IL-17A on AD is limited.

Methods

We report the effect of IL-17A on AD progression in APPswe/PS1dE9 (APP/PS1) mice, which are the most widely used AD model mice. The BV2 cell line, which is a microglial cell line derived from C57/BL6 mice, was used to establish a cell model to verify the role of IL-17A in neuroinflammation at the cellular level. The HT22 hippocampal neuronal cell line was used to investigate the relationship between IL-17A and Aβ deposition.

Results

In this research, we found that IL-17A promotes the progression of AD in the APP/PS1 mouse model. The role of IL-17A in neuroinflammation is related to tumour necrosis factor (TNF)-α. Circulating IL-17A stimulates the secretion of TNF-α by microglia through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signalling pathway, thus exacerbating neuroinflammation. In addition, intraperitoneal injection of IL-17A antibody (IL17Ab) significantly improved the cognitive function of APP/PS1 mice.

Conclusions

IL-17A increased TNF-α levels in the brain and exacerbated neuroinflammation through the TLR4/NF-κB signalling pathway and microglial activation in APP/PS1 mice. Moreover, IL-17A promoted the progression of AD by enhancing neuroinflammation, inhibiting microglial phagocytosis, and promoting the deposition of β-amyloid 42 in AD model mice.
Effect of perceived stigma on work and social roles among individuals with mental health disorders in Saudi Arabia: findings from a national survey
Authors: AlFattani Areej , Bilal Lisa , Saad Sami Y. , Naseem Mohammad Talal , Hyder Sanaa , Alhabib Abdulhamid , Alsubaie Abdullah , Altwaijri Yasmin
Published: December 2023

Background

It is known worldwide that stigma towards mental illness exists. Studies on stigma perceived by patients with mental illness have shown decreased quality of life and a negative impact on work, school and social life. The aim of this study was to estimate the prevalence of perceived stigma among respondents who had been diagnosed with a mental illness during the past 12 months, its association with socio-demographic variables and its effect on work and social roles limitations among Saudis.

Methods

The Saudi National Mental Health Survey (SNMHS) data were used for the analysis. The SNMHS is a nationally representative survey that was conducted using face-to -face interviews with Saudi individuals (age 15–65) in their households. Respondents were diagnosed (N = 639) with mental disorders based on a well-validated questionnaire—the Composite International Diagnostic Interview (CIDI) 3.0. Two dimensions from CIDI assessed perceived stigma: embarrassment and perceived discrimination.

Results

The prevalence of perceived stigma was 27.8% among mentally ill respondents. Stigma was lower among respondents who didn’t seek any type of treatment than those who sought treatment OR = 0.28 (95% CI 0.084–0.935, P = 0.03). Respondents who reported perceived stigma had more work role limitations (OR = 1.1 95% CI 1.01–0.10 P 0.006) and social limitations (OR = 1.3 95% CI 0.99–1.62 P 0.05) than respondents who didn’t report stigma.

Conclusion

Perceived stigma is experienced by mentally ill individuals and it negatively affects their work and social roles. Awareness programs to remove stigma and educate the public are needed to be established by policymakers and healthcare providers in Saudi Arabia.
Application accuracy of a frameless optical neuronavigation system as a guide for craniotomies in dogs
Authors: Gutmann Sarah , Heiderhoff Miriam , Möbius Robert , Siegel Tanja , Flegel Thomas
Published: December 2023

Background

Optical neuronavigation systems using infrared light to create a virtual reality image of the brain allow the surgeon to track instruments in real time. Due to the high vulnerability of the brain, neurosurgical interventions must be performed with a high precision. The aim of the experimental cadaveric study was to determine the application accuracy of a frameless optical neuronavigation system as guide for craniotomies by determining the target point deviation of predefined target points at the skull surface in the area of access to the cerebrum, cerebellum and the pituitary fossa. On each of the five canine cadaver heads ten target points were marked in a preoperative computed tomography (CT) scan. These target points were found on the cadaver skulls using the optical neuronavigation system. Then a small drill hole (1.5 mm) was drilled at these points. Subsequently, another CT scan was made. Both CT data sets were fused into the neuronavigation software, and the actual target point coordinates were identified. The target point deviation was determined as the difference between the planned and drilled target point coordinates. The calculated deviation was compared between two observers.

Results

The analysis of the target point accuracies of all dogs in both observers taken together showed a median target point deviation of 1.57 mm (range: 0.42 to 5.14 mm). No significant differences were found between the observers or the different areas of target regions.

Conclusion

The application accuracy of the described system is similar to the accuracy of other optical neuronavigation systems previously described in veterinary medicine, in which mean values of 1.79 to 4.3 mm and median target point deviations of 0.79 to 3.53 mm were determined.
Challenges and opportunities to computationally deconvolve heterogeneous tissue with varying cell sizes using single-cell RNA-sequencing datasets
Authors: Maden Sean K. , Kwon Sang Ho , Huuki-Myers Louise A. , Collado-Torres Leonardo , Hicks Stephanie C. , Maynard Kristen R.
Published: December 2023

Deconvolution of cell mixtures in “bulk” transcriptomic samples from homogenate human tissue is important for understanding disease pathologies. However, several experimental and computational challenges impede transcriptomics-based deconvolution approaches using single-cell/nucleus RNA-seq reference atlases. Cells from the brain and blood have substantially different sizes, total mRNA, and transcriptional activities, and existing approaches may quantify total mRNA instead of cell type proportions. Further, standards are lacking for the use of cell reference atlases and integrative analyses of single-cell and spatial transcriptomics data. We discuss how to approach these key challenges with orthogonal “gold standard” datasets for evaluating deconvolution methods.
Hybrid interpolative mappings for solving fractional Navier–Stokes and functional differential equations
Authors: Hammad Hasanen A. , Aydi Hassen , Kattan Doha A.
Published: December 2023

The purpose of this study is to establish fixed-point results for new interpolative contraction mappings in the setting of Busemann space involving a convex hull. To illustrate our findings, we also offer helpful and compelling examples. Finally, the theoretical results are applied to study the existence of solutions to fractional Navier–Stokes and fractional-functional differential equations as applications.
CHKB-AS1 enhances proliferation and resistance to NVP-BEZ235 of renal cancer cells via regulating the phosphorylation of MAP4 and PI3K/AKT/mTOR signaling
Authors: Chen Xinglin , Zhang Tongtong , Ren Xiaohan , Wei Yuang , Zhang Xu , Zang Xinyue , Ju Xiran , Qin Chao , Xu Dongliang
Published: December 2023

Targeted therapy is pivotal in renal carcinoma treatment, and the dual-inhibitor NVP-BEZ235 has emerged as a promising candidate in preliminary studies. Its effectiveness against renal carcinoma and the mechanisms underlying potential resistance, however, warrant further exploration. This study aims to elucidate these aspects, enhancing our understanding of NVP-BEZ235's future clinical utility. To investigate resistance mechanisms, renal cancer cell lines were exposed to progressively increasing concentrations of NVP-BEZ235, leading to the development of stable resistance. These resistant cells underwent extensive RNA-sequencing analysis. We implemented gene interference techniques using plasmid vectors and lentivirus and conducted regular IC50 assessments. To pinpoint the role of LncRNAs, we utilized FISH and immunofluorescence staining assays, supplemented by RNA pull-down and RIP assays to delineate interactions between LncRNA and its RNA-binding protein (RBP). Further, Western blotting and qRT-PCR were employed to examine alterations in signaling pathways, with an animal model providing additional validation. Our results show a marked increase in the IC50 of NVP-BEZ235 in resistant cell lines compared to their parental counterparts. A significant revelation was the role of LncRNA-CHKB-AS1 in mediating drug resistance. We observed dysregulated expression of CHKB-AS1 in both clinical samples of clear cell renal cell carcinoma (ccRCC) and cell lines. In vivo experiments further substantiated our findings, showing that CHKB-AS1 overexpression significantly enhanced tumor growth and resistance to NVP-BEZ235 in a subcutaneous tumorigenesis model, as evidenced by increased tumor volume and weight, whereas CHKB-AS1 knockdown led to a marked reduction in these parameters. Critically, CHKB-AS1 was identified to interact with MAP4, a key regulator in the phosphorylation of the PI3k/Akt/mTOR pathway. This interaction contributes to a diminished antitumor effect of NVP-BEZ235, highlighting the intricate mechanism through which CHKB-AS1 modulates drug resistance pathways, potentially impacting therapeutic strategies against renal carcinoma.
MRPL48 is a novel prognostic and predictive biomarker of hepatocellular carcinoma
Authors: Lin Yu-Xiang , Pan Jun-Yong , Feng Wen-Du , Huang Tian-Cong , Li Cheng-Zong
Published: December 2023

Background

Hepatocellular carcinoma (HCC) is one of the most prevalent forms of cancer and poses a threat to the health and survival of humans. Mitochondrial ribosomal protein L48 (MRPL48) belongs to the mitochondrial ribosomal protein family, which participates in energy production. Studies have shown that MRPL48 can predict osteosarcoma incidence and prognosis, as well as promotes colorectal cancer progression. However, the role of MRPL48 in HCC remains unknown.

Methods

TCGA, GEO, HCCDB, CPTAC, SMART, UALCAN, Kaplan–Meier plotter, cBioPortal, and MethSurv were performed for bioinformatics purposes. Quantitative RT-PCR, immunoblotting, and functional studies were conducted to validate the methodology in vitro.

Results

MRPL48 was greatly overexpressed in HCC tissues, compared with healthy tissue, which was subsequently demonstrated in vitro as well. The survival and regression analyses showed that MRPL48 expression is of significant clinical prognostic value in HCC. The ROC curve and nomogram analysis indicated that MRPL48 is a powerful predictor of HCC. MRPL48 methylation was adversely associated with the expression of MRPL48, and patients with a low level of methylation had poorer overall survival than those with a high level of methylation. GSEA showed that the expression of the MRPL48 was correlated with Resolution of Sister Chromatid Cohesion, Mitotic Prometaphase, Retinoblastoma Gene in Cancer, RHO Gtpases Activate Formins, Mitotic Metaphase and Anaphase, and Cell Cycle Checkpoints. An analysis of immune cell infiltration showed a significant association between MRPL48 and immune cell infiltration subsets, which impacted the survival of HCC patients. Additionally, MRPL48 knockdown reduced HCC cell proliferation, migration, and invasion in vitro.

Conclusions

We demonstrated that MRPL48 expression may be associated with HCC development and prognosis. These findings may open up new research directions and opportunities for the development of HCC treatments.
Emotional reactivity and prosocial behaviour in response to witnessing social exclusion in adolescents with eating disorders and healthy controls
Authors: Rowlands Katie , Simic Mima , Treasure Janet , Cardi Valentina
Published: December 2023

Background

Prosocial behaviour can promote positive social interactions and it is a key skill in adolescence. People with emotional problems or psychiatric disorders, such as people with eating disorders might have impairments in prosocial behaviour, due to broader documented difficulties in underlying processes (e.g., mentalizing).

Methods

The aim of this study was to examine prosocial behaviour in adolescents with eating disorders compared to healthy controls, using a computerised behavioural task. Adolescents (N = 123) including patients with eating disorders (n = 61) and healthy adolescents (n = 62) played a four-player computerised Prosocial Cyberball Game with three pre-programmed avatar players. During the task, participants witnessed the exclusion of one of the players, and subsequently had the opportunity to compensate for this by throwing the ball more often to the excluded player. Throughout the game, participants rated the level of negative emotion in themselves and in the excluded player.

Results

Patients made significantly fewer ball tosses towards the excluded player during the compensation round compared to healthy controls (large effect size). Patients reported a significantly smaller increase in negative emotion after witnessing the exclusion and a significantly smaller decrease in negative emotion following the compensation round (large effect sizes). Patients also estimated a smaller decrease in negative emotion in the excluded player following the compensation round (medium effect size). There were no significant associations between these outcomes and eating disorder psychopathology in patients.

Conclusions

Compared to healthy adolescents, adolescent patients with eating disorders demonstrated less prosocial compensatory behaviour towards a computerised victim of social exclusion. In addition, they reported flatter negative emotion in themselves in response to witnessing and compensating for exclusion, and in the excluded player following compensation. If these findings are replicated, interventions to target these difficulties might contribute to improvements in social functioning in this patient group.
Tough gel adhesive is an effective method for meniscal repair in a bovine cadaveric study
Authors: Mazy David , Chung‐Tze‐Cheong Christopher , Ma Zhenwei , Huo Ran , Lamer Stephanie , Li Jianyu , Nault Marie‐Lyne
Published: December 2023

Purpose

To test tough gel adhesives to repair meniscus tears under relevant loading conditions and determine if they have adequate biomechanical properties to repair meniscus tears in a bovine cadaveric study.

Methods

Cyclic compression tests on 24 dissected bovine knees were performed. The tough gel adhesive was used either as an adhesive patch or as a coating bonded onto commercially available surgical sutures. Forty‐eight menisci were tested in this study; 24 complete radial tears and 24 bucket‐handle tears. After preconditioning, the specimens underwent 100 cycles of compression, (800 N/0.5 Hz) on an Instron© machine and the size of the gaps measured. One third of the menisci were repaired with pristine sutures, one third with adhesive patches, and one third with sutures coated in adhesive gel. The size of the gaps was compared after 100 and 500 cycles of compression.

Results

The mean gap measured at the tear site without treatment was 6.46 mm (± 1.41 mm) for radial tears and 1.92 mm (± 0.65 mm) for bucket‐handle tears. After treatment and 500 cycles of compression, the mean gap was 1.63 mm (± 1.41 mm) for pristine sutures, 1.50 mm (± 1.16 mm) for adhesive sutures and 2.06 mm (± 1.53 mm) for adhesive gel patches. There was no significant difference between treatments regardless of the type of tear. Also, the gaps for radial tears increased significantly with the number of compression cycles applied (p > 0.001).

Conclusion

From a biomechanical standpoint, the tough adhesive gel patch is as effective as suturing. In addition, it would allow the repair of non‐suturable tears and thus broaden the indications for meniscus repair.

Level of evidence

Controlled laboratory study.
Effect of lateral hinge fractures for bone union and clinical outcomes following opening‐wedge distal tibial tubercle osteotomy in comparison with opening‐wedge high tibial osteotomy
Authors: Otsuki Shuhei , Ikeda Kuniaki , Ishitani Takashi , Okamoto Yoshinori , Wakama Hitoshi , Neo Masashi
Published: December 2023

Purpose

Although the effects of lateral hinge fractures (LHF) on bone union and clinical outcomes after opening‐wedge high tibial osteotomy (OWHTO) have been established, the effects of LHF after opening‐wedge distal tibial tubercle osteotomy (OWDTO) are unclear. We hypothesised that LHF after OWDTO would be associated with delayed bone union and result in poorer clinical outcomes than expected for LHF after OWHTO.

Methods

This study enrolled 100 patients, with 50 OWDTO patients (18 men; mean age, 63.2 years) and 50 OWHTO patients compared based on the propensity score matched analysis. The effect of LHF on bone union was compared between the groups. Clinical outcomes were assessed using the Lysholm score and the Knee Injury and Osteoarthritis Outcome Score (KOOS) at the mean follow‐up of 28 months.

Results

There was no between‐group difference in the incidence rate of LHF. However, the rate of bone union at the anterior flange in the presence of an LHF was significantly lower in the OWDTO (26%) than in the OWHTO (80%) 3 months postoperatively (p < 0.05), but no difference was observed 12 months postoperatively. The Lysholm score was significantly lower for patients with LHF following OWDTO than for OWDTO patients without LHF or OWHTO patients with/without LHF 3 and 12 months postoperatively (p < 0.001); Lysholm score and KOOS were not different at the final follow‐up.

Conclusions

LHF after OWDTO was associated with delayed bone union and poor clinical outcomes until 12 months. This information can guide decisions regarding the indications and the management of patients after OWDTO.

Level of evidence

IV
Comparing reflection levels between facilitator-led and student-led debriefing in simulation training for paramedic students
Authors: Christiansen Carl Robert , Andersen Jeanette Viggen , Dieckmann Peter
Published: December 2023

Background

Simulation in healthcare attempts to create relevant representations of patient encounters. It provides experiential learning, bridging typical classroom activities and clinical practice. This study aims to investigate whether the principle of Peer-Assisted Learning can be used in simulation by letting simulation-experienced paramedic students prepare, deliver, and debrief their own simulations, with minimal faculty assistance. This could be a way to support student learning by being involved in teaching, and it might at the same time optimise the cost-effectiveness of simulation-based training.

Methods

This observational non-inferiority study compared reflection levels between facilitator-led and student-led simulation and debriefing, between scenario types, and compared the number of turns in which students are involved in both settings. Third-year Bachelor in Paramedic Science students’ debriefings were filmed and transcribed. The degree of reflection in students’ statements was rated according to a modified version of Fleck’s analytical framework of reflection levels, assigning scores from lowest (R0 description) to highest (R4 critical reflection). Facilitator-led and student-led debriefings were compared using chi-square tests. Scenarios were also analysed according to type (paediatric emergencies and complex assessments) regardless of who led the simulation.

Results

Ten facilitator-led and 12 student-led debriefings were analysed. Students gave 682 (49%) contributions in the facilitator-led debriefings, and 702 (51%) contributions in student-led debriefings. Comparison of reflection levels between facilitator-led and student-led debriefings was respectively: R0-level 32.7% vs 33.8%, R1-level 44.0% vs 44.3%, R2-level 14.7% vs 17.1%, R3-level 0.1% vs 1.3%, and R4-level 0.1% vs 0.1%. There were no statistically significant differences in reflection levels between facilitator-led and student-led debriefings (p = 0.178). Comparing the reflection levels between the scenarios on “paediatric emergencies” and “complex assessments”, the results were respectively: R0-level 35.4% vs. 31.7%-level, R1-level 45.3% vs. 43.3%-level, R2-level 13.4% vs. 17.8%, R3-level 0.5% vs. 0.9%, and R4-level 0.0% vs. 0.3%. These differences were statistically significant (p = 0.010). No significant differences in engagement were found between debriefings led by a student or a facilitator, when measuring the number of turns in the conversations.

Conclusions

Facilitator-led and student-led debriefings resulted in equivalent reflection levels amongst students. Student-led simulation is potentially a cost-effective supplement to regular simulation within a healthcare degree program. Since complex scenarios provided higher reflection levels than paediatric, scenario design might influence reflection levels.
Variation in cartilage T2 and T2* mapping of the wrist: a comparison between 3- and 7-T MRI
Authors: Heiss Rafael , Weber Marc-André , Balbach Eva L. , Hinsen Maximilian , Geissler Frederik , Nagel Armin M. , Ladd Mark E. , Arkudas Andreas , Horch Raymund E. , Gall Christine , Uder Michael , Roemer Frank W.
Published: December 2023

Background

To analyze regional variations in T2 and T2* relaxation times in wrist joint cartilage and the triangular fibrocartilage complex (TFCC) at 3 and 7 T and to compare values between field strengths.

Methods

Twenty-five healthy controls and 25 patients with chronic wrist pain were examined at 3 and 7 T on the same day using T2- and T2*-weighted sequences. Six different regions of interest (ROIs) were evaluated for cartilage and 3 ROIs were evaluated at the TFCC based on manual segmentation. Paired t-tests were used to compare T2 and T2* values between field strengths and between different ROIs. Spearman’s rank correlation was calculated to assess correlations between T2 and T2* time values at 3 and 7 T.

Results

T2 and T2* time values of the cartilage differed significantly between 3 and 7 T for all ROIs (p ≤ 0.045), with one exception: at the distal lunate, no significant differences in T2 values were observed between field strengths. T2* values differed significantly between 3 and 7 T for all ROIs of the TFCC (p ≤ 0.001). Spearman’s rank correlation between 3 and 7 T ranged from 0.03 to 0.62 for T2 values and from 0.01 to 0.48 for T2* values. T2 and T2* values for cartilage varied across anatomic locations in healthy controls at both 3 and 7 T.

Conclusion

Quantitative results of T2 and T2* mapping at the wrist differ between field strengths, with poor correlation between 3 and 7 T. Local variations in cartilage T2 and T2* values are observed in healthy individuals.

Relevance statement

T2 and T2* mapping are feasible for compositional imaging of the TFCC and the cartilage at the wrist at both 3 and 7 T, but the clinical interpretation remains challenging due to differences between field strengths and variations between anatomic locations.

Key points

•Field strength and anatomic locations influence T2 and T2* values at the wrist.

•T2 and T2* values have a poor correlation between 3 and 7 T.

•Local reference values are needed for each anatomic location for reliable interpretation.

Graphical Abstract
A comparative study of stretch-and-flow voice therapy versus Smith accent method in rehabilitation of hyperfunctional dysphonia: a randomized controlled trial
Authors: Mohamed Dalia Maged , Shoeib Rasha Mohamed , Elfiky Yomna Hassan , ElNeshwey Hedia Muhey
Published: December 2023

Background

This work aims to compare between stretch-and-flow voice therapy and Smith accent method of voice therapy in treatment of hyperfunctional dysphonia in order to assess the benefit of using this new technique in its management. A randomized controlled trial was conducted at the Unit of Phoniatrics, Otorhinolaryngology Department, in the period from November 2020 to February 2023. A sample of 60 patients with hyperfunctional dysphonia was randomly divided into two groups; each group consisted of 30 patients: “group A” who received stretch-and-flow voice therapy (SnF) and “group B” who received Smith accent (SA) method of voice therapy. Assessment included auditory perceptual assessment (APA) using modified GRBAS scale and Arabic-voice handicap index (Arabic-VHI).

Results

The study revealed significant improvement in grade of dysphonia, voice quality, and Arabic-VHI post-therapy for both groups. There was a significant improvement regarding voice pitch in SnF group only and in loudness of voice in SA group only.

Conclusion

SnF can be considered as an alternative approach for treating hyperfunctional dysphonia, offering a shorter duration, and potentially being a simpler alternative for patients who struggle with the more intricate rhythms of the Smith Aaccent voice therapy method.
Waiting in Petro-Time
Authors: Davis Heather
Published: December 2023

To describe the multiple, colliding temporalities of climate change I put forward the concept of petro-time. Petro-time asserts that time itself has been compressed through millennia to become fossil fuels, and then burned, resulting in climate chaos. In this essay, I take up one aspect of petro-time, the feeling of waiting. I articulate this feeling of waiting through the opera Sun & Sea (Marina) by Rugilė Barzdžiukaitė, Vaiva Grainytė, and Lina Lapelytė, which explores the affective dimensions of climate change for those of us with the wealth and privilege that, so far, mostly shelters us from its worst effects. But climate change is always there, on the horizon, looming. This reality sits at the back of the brain, emerging in moments of relaxation as a “nagging malaise,” depicted in the opera through “insidiously pleasant melodies.” The tension that many of us experience in relation to climate change, where it cannot be sustained as the crisis that it is, instead blends into a background anxiety. I argue that waiting (for adequate policies, for climate relief) is felt differentially across the globe but that it also might provide a pause to recommit to climate solutions that don’t repeat the injustices of the past.
The Economy in Mind
Authors: Douglas Richard McNeill
Published: December 2023

This article applies thematic analysis to the discourse of the environmental countermovement, focusing primarily on the mutually referencing contributions of Julian Simon, Friedrich von Hayek, and Ronald Reagan. Utilizing a close reading of these texts, it aims to describe how the subscribers to this discourse picture the human relationship with the natural world, and how this in turn enables them to believe that the market can overcome environmental limits indefinitely. This analysis brings to the fore a belief apparently underlying their faith in unending growth: that humankind is able to progressively convert nature into economic reality, whose essence is the limitless quality of the human mind.
Metabolic Strata, Corporeal Sediment
Authors: Marston Andrea
Published: December 2023

This article explores the uneven geosocial traces created by transcontinental and corporeal circulations of tin ore, metallic tin, and tin cans from the mid-nineteenth to mid-twentieth centuries. Although tin has no essential relationship to human life, I argue that the extraction, circulation, and consumption of tin have nevertheless contributed to the production of metabolic unevenness across continental space. Since the early industrial era, tin has been used primarily for food preservation, in which capacity it has nutritionally supported the metabolic processes (and labor power) of workers, settlers, and soldiers, among others. Tin canning technologies relied, in turn, on the relentless labor of tin miners, whose own metabolic processes were interrupted by the accumulation of mineral dust in their lungs. These histories have been archived as geosocial strata as both discarded tin cans and pulmonary fibrosis. Drawing insights from geophilosophy and both Marxian and toxicological approaches to metabolism, this article reflects on how inhuman forces and substances subtend not only life but also its disparate energies and exposures.
Liquidity and Liquefaction
Authors: Zee Jerry
Published: December 2023

This article considers the collision of earthly and monetary phase shifts. It situates itself in Richmond, British Columbia, a seam where multiple and disparate processes of landing collaborate in the ongoing transformation and modulation of the earth’s surface. It poses a Chinese-funded construction boom on an island in western Canada as a geological formation, a physical outcropping at the collision of nineteenth-century Chinese terraforming labor and twenty-first-century flyaway Asian wealth. These collisions articulate fault lines in transpacific tectonic and geopolitical relations, even as the fluid dynamics of wealth and islands of impounded silt evince multiple figurations of Asian-ness. Through the juxtaposition of two permutations of land, economics, and racial formation across multiple centuries in the Fraser River Delta, I offer a notion of orogeny, the geological process of mountain building and crustal deformation, to attend to the earthmoving dynamisms of rivers, wealth, and Asian racialization.
Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes
Authors: Sanchez Sebastian , Wendt Linder , Hayakawa Minako , Chen Ching-Jen , Sheehan Jason P. , Kim Louis J. , Abecassis Isaac Josh , Levitt Michael R. , Meyer R. Michael , Guniganti Ridhima , Kansagra Akash P. , Lanzino Giuseppe , Giordan Enrico , Brinjikji Waleed , Bulters Diederik O. , Durnford Andrew , Fox W. Christopher , Smith Jessica , Polifka Adam J. , Gross Bradley , Amin-Hanjani Sepideh , Alaraj Ali , Kwasnicki Amanda , Starke Robert M. , Chen Stephanie H. , van Dijk J. Marc C. , Potgieser Adriaan R. E. , Satomi Junichiro , Tada Yoshiteru , Phelps Ryan , Abla Adib , Winkler Ethan , Du Rose , Rosalind Lai Pui Man , Ortega-Gutierrez Santiago , Zipfel Gregory J. , Derdeyn Colin , Samaniego Edgar A.
Published: December 2023

BACKGROUND AND OBJECTIVES:

Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs.

METHODS:

Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed.

RESULTS:

A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09)

CONCLUSION:

Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.
Spliceosome component PHD finger 5A is essential for early B lymphopoiesis
Authors: Zhang Rui , Wang Daoqin , Ruan Gui-Xin , Wang Ruisi , Li Yuxing , Chen Wenjing , Huang Hengjun , Wang Jing , Meng Limin , Zhu Zhijian , Lei Dengfeng , Xu Shengli , Ou Xijun
Published: December 2023

The spliceosome, a multi-megadalton ribonucleoprotein complex, is essential for pre-mRNA splicing in the nucleus and ensuring genomic stability. Its precise and dynamic assembly is pivotal for its function. Spliceosome malfunctions can lead to developmental abnormalities and potentially contribute to tumorigenesis. The specific role of the spliceosome in B cell development is poorly understood. Here, we reveal that the spliceosomal U2 snRNP component PHD finger protein 5A (Phf5a) is vital for early B cell development. Loss of Phf5a results in pronounced defects in B cell development, causing an arrest at the transition from pre-pro-B to early pro-B cell stage in the bone marrow of mutant mice. Phf5a-deficient B cells exhibit impaired immunoglobulin heavy (IgH) chain expression due to defective V-to-DJ gene rearrangement. Mechanistically, our findings suggest that Phf5a facilitates IgH gene rearrangement by regulating the activity of recombination-activating gene endonuclease and influencing chromatin interactions at the Igh locus.
Incentive-centered design of money-free mechanisms
Authors: Γκατζέλης Βασίλειος
Published: December 2023

Αυτή η διατριβή προσφέρει ένα βήμα προς την καλύτερη κατανόηση μεθόδων σχεδιασμού δίκαιων και αποτελεσματικών συστημάτων κατανομής πόρων μεταξύ πολλαπλών πρακτόρων, φέρνοντας τα κίνητρα των πρακτόρων αυτών στο επίκεντρο της διαδικασίας σχεδιασμού. Καθώς η ποιότητα αυτών των συστημάτων εξαρτάται σε μεγάλο βαθμό από τους τρόπους με τους οποίους οι συμμετέχοντες αλληλεπιδρούν μεταξύ τους και με το σύστημα, ένα εσφαλμένα σχεδιασμένο σύνολο κινήτρων μπορεί να οδηγήσει σε μεγάλη αναποτελεσματικότητα. Η εστίαση αυτής της εργασίας είναι στα προβλήματα που προκύπτουν όταν απαγορεύεται η χρήση νομισματικών ανταλλαγών μεταξύ του συστήματος και των συμμετεχόντων. Αυτός είναι ένας κοινός περιορισμός που περιπλέκει σε μεγάλο βαθμό το έργο του σχεδιαστή. Ωστόσο, παρέχουμε μια σειρά θετικών αποτελεσμάτων με τη μορφή μηχανισμών που μεγιστοποιούν την αποτελεσματικότητα ή τη δικαιοσύνη παρά την πιθανώς ιδιοτελή συμπεριφορά των συμμετεχόντων παραγόντων. Το πρώτο μέρος αυτής της εργασίας είναι μια συνεισφορά στη βιβλιογραφία του σχεδιασμού προσεγγιστικών μηχανισμών χωρίς χρήματα. Δεδομένου ενός συνόλου πόρων, στόχος μας είναι να σχεδιάσουμε έναν μηχανισμό που τους κατανέμει μεταξύ των πρακτόρων. Η κύρια περιπλοκή εδώ οφείλεται στο γεγονός ότι οι προτιμήσεις των πρακτόρων έναντι διαφορετικών κατανομών ενδέχεται να μην είναι γνωστές στο σύστημα. Επομένως, ο μηχανισμός πρέπει να σχεδιαστεί με τέτοιο τρόπο ώστε να είναι προς το συμφέρον του κάθε πράκτορα να αναφέρει την αλήθεια σχετικά με τις προτιμήσεις του. Δεδομένου ότι δεν μπορούν να χρησιμοποιηθούν χρηματικές ανταμοιβές και ποινές για να αποκαλυφθεί η αλήθεια, είναι απαραίτητη μια πολύ πιο λεπτή ρύθμιση της κατανομής των πόρων. Το δεύτερο μέρος αυτής της εργασίας αφορά το σχεδιασμό μηχανισμών κατανομής πόρων χωρίς χρήματα για κατανεμημένα συστήματα πολλών πρακτόρων. Καθώς ο κόσμος γίνεται όλο και πιο διασυνδεδεμένος, τέτοια συστήματα χρησιμοποιούν όλο και περισσότερους πόρους που είναι γεωγραφικά διασκορπισμένοι· Για να μπορούν να κλιμακωθούν αυτά τα συστήματα, οι μηχανισμοί πρέπει να είναι αποκεντρωμένοι. Δηλαδή, οι αποφάσεις κατανομής για οποιονδήποτε δεδομένο πόρο δεν πρέπει να προϋποθέτουν κεντρική πληροφόρηση σχετικά με τους διαθέσιμους πόρους ή σχετικά με τους πράκτορες που συμμετέχουν στο σύστημα. Στη διατριβή αυτή πετυχαίνουμε αυτόν τον περιορισμό χρησιμοποιώντας κατανεμημένους μηχανισμούς συντονισμού: απλές πολιτικές κατανομής πόρων, καθεμία από τις οποίες ελέγχει μόνο έναν από τους πόρους και χρησιμοποιεί μόνο τοπικές πληροφορίες σχετικά με την κατάσταση του συστήματος.
Μελέτη του ρόλου της σουμοϋλίωσης στη ρύθμιση και λειτουργία της πρωτεΐνης EXOSC10 κατά την υποξία
Authors: Φιλιπποπούλου Χρύσα
Published: December 2023

Η σουμοϋλίωση είναι μια δυναμική μετα-μεταφραστική τροποποίηση κατά την οποία πραγματοποιείται ομοιοπολική σύζευξη των πρωτεϊνών SUMO (Small Ubiquitin-like Modifier) στις πρωτεΐνες-στόχους. Μελέτες των τελευταίων ετών δείχνουν πως η σουμοϋλίωση παίζει σημαντικό ρόλο στην προσαρμογή και επιβίωση των κυττάρων σε συνθήκες στρες όπως η χαμηλή συγκέντρωση οξυγόνου (υποξία). Ειδικότερα, η σουμοϋλίωση επηρεάζει τους κύριους μεταγραφικούς παράγοντες και ρυθμιστές του μονοπατιού της υποξίας HIFs (Hypoxia Inducible Factors) άμεσα (μέσω ομοιοπολικής τροποποίησης) ή έμμεσα επηρεάζοντας τη δράση πρωτεϊνών που σχετίζονται με τη ρύθμιση τους. Πειράματα ανοσοκατακρήμνισης και φασματοσκοπίας μάζας έδειξαν πως η υποξία (1% Ο2) προκαλεί την αποσουμοϋλίωση της πρωτεΐνης EXOSC10. H ΕXOSC10 είναι μια καταλυτική υπομονάδα του πολύ-πρωτεϊνικού συμπλόκου του RNA εξωσώματος, με δράση στην επεξεργασία και την αποικοδόμηση διαφόρων RNA. Η παρούσα διδακτορική διατριβή εστιάστηκε στη μελέτη της σουμοϋλίωσης της EXOSC10 όσον αφορά πρώτον στην πλήρη αποσαφήνιση της επίδρασης της υποξίας στον μηχανισμό σουμοϋλίωσης της και δεύτερον στη διερεύνηση του βιολογικού ρόλου της σουμοϋλίωσης στην λειτουργία της EXOSC10 και της σημασίας της για την κυτταρική απόκριση στην υποξία. Συγκεκριμένα, δείχθηκε πως η σουμοϋλίωση της EXOSC10 μειώνεται αισθητά από τις πρώτες κιόλας ώρες επώασης στην υποξία με έναν μηχανισμό στον οποίο δεν εμπλέκονται άμεσα οι HIF. Ενδιαφέρον παρουσίασε το γεγονός πως στο ίδιο χρονικό πλαίσιο παρατηρήθηκε μετακίνηση της EXOSC10 από τον πυρηνίσκο προς το πυρηνόπλασμα, υποδεικνύοντας πως οι δυο διαδικασίες σχετίζονται. Πειράματα αποσιώπησης γνωστών ενζύμων του μηχανισμού σουμοϋλίωσης αποκάλυψαν πως η USP36 είναι απαραίτητη για την σουμοϋλίωση της EXOSC10, ενώ η SENP3 συμμετέχει στην απομάκρυνση της SUMO από αυτή. Οι τρεις αυτές πρωτεΐνες βρίσκονται σε κοινό σύμπλοκο στον πυρηνίσκο. Βρέθηκε πως η υποξία οδηγεί στην μετακίνηση της EXOSC10 στο πυρηνόπλασμα και την επακόλουθη κατάργηση της αλληλεπίδρασης της με την USP36, γεγονός που εξηγεί την παρατηρούμενη αποσουμοϋλίωση. Όσον αφορά στο δεύτερο ερευνητικό ερώτημα σχετικά με την διερεύνηση του βιολογικού ρόλου της σουμοϋλίωσης στην λειτουργία της EXOSC10 στο πλαίσιο της κυτταρικής απόκρισης στην υποξία, με πειράματα αλληλούχησης του ολικού RNA καρκινικών κυττάρων HeLa σε συνθήκες νορμοξίας και υποξίας ή σε κυτταρικές σειρές που εκφράζουν την αγρίου τύπου EXOSC10 ή την μη σουμοϋλιωμένη μορφή της (Κ583R), έδειξαν την διαφορική ρύθμιση των επιπέδων έκφρασης μιας ομάδας RNA που αποτελούν και στόχους της υποξίας. Συνολικά, η παρούσα διδακτορική διατριβή αποκαλύπτει την δυναμική ρύθμιση της σουμοϋλίωσης και του ενδοκυτταρικού εντοπισμού της εξωριβονουκλεάσης EXOSC10 από την υποξία, διεργασίες που οδηγούν στη ρύθμιση του μηχανισμού αποικοδόμησης mRNA στόχων της υποξίας, διευκολύνοντας την προσαρμογή των κυττάρων στις νέες συνθήκες οξυγόνου.
Invisibility in global health: A case for disturbing bioethical frameworks
Authors: Alenichev Arsenii , Suwalowska Halina , Faure Marlyn C. , Ng Shu Hui , Modlin Chelsea , Ambrogi Ilana , Shaffer Jonathan D. , Parker Michael , Kingori Patricia
Published: December 2023

In recent years, the global health community has increasingly reported the problem of ‘invisibility’: aspects of health and wellbeing, particularly amongst the world’s most marginalized and impoverished people, that are systematically overlooked and ignored by people and institutions in relative positions of power. It is unclear how to realistically manage global health invisibility within bioethics and other social science disciplines and move forward. In this letter, we reflect on several case studies of invisibility experienced by people in Brazil, Malaysia, West Africa and other transnational contexts. Highlighting the complex nature of invisibility and its interconnectedness with social, political and economic issues and trends, we argue that while local and targeted interventions might provide relief and comfort locally, they will not be able to solve the underlying causes of invisibility. Building from the shared lessons of case study presentations at an Oxford-Johns Hopkins Global Infectious Disease Ethics Collaborative (GLIDE), we argue that in dealing with an intersectional issue such as invisibility, twenty-first century global health bioethics could pursue a more ‘disturbing’ framework, challenging the narrow comforting solutions which take as a given the sociomaterial inequalities of the status quo. We highlight that comforting and disturbing bioethical frameworks should not be considered as opposing sides, but as two approaches working in tandem in order to achieve the internationally set global health milestones of providing better health and wellbeing for everyone. Insights from sociology, anthropology, postcolonial studies, history, feminist studies and other styles of critical reasoning have long been disturbing to grand narratives of people and their conditions. To rediscover the ethos of the WHO Alma Ata Declaration—a vision of “health for all by the year 2000”—these thinking tools will be necessary aids in developing cooperation and support beyond the narrow market logic that dominates the landscape of contemporary global health.