bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility study of a game-based virtual reality intervention for functional prosthesis use training: A preclinical assessment
Authors: Mu Jing , Garcia-Rosas Ricardo , Mayer Raphael Maria , Meise Daniel , Lavranos Jim , Graf Mark , Tan Ying , Oetomo Denny , Choong Peter 
Published: November 2024

Objective:
This paper presents a preclinical feasibility study to investigate the efficacy of a game-based virtual reality (VR) intervention in the functional training of upper-limb prosthesis use.

Methods:
The study compared the skill of 2 able-bodied groups (intervention and control, 5 participants in each group) using a surface electromyography controlled self-experience prosthetic hand and wrist through the Box and Blocks Test (BBT). The Intervention Group followed the game-based VR intervention for 4 weeks and underwent real-life (RL) BBT assessments before and after the intervention using the self-experience prosthesis. The Control Group performed the RL BBT assessments 4 weeks apart with no VR intervention in between. As a follow-on study, the Control Group then underwent the VR intervention for further validation. The VR intervention consisted of 2 games designed to train the control and use of a surface electromyography–controlled prosthetic hand and an assessment (VR BBT). The VR intervention protocol included three 30-minute sessions per week over a period of 4 weeks.

Results:
A significantly larger improvement was shown in the BBT scores from the Intervention Group (mean 6.375) compared to the Control Group (1.5). The follow-on study further confirmed the result.

Conclusion:
The study demonstrated promising outcomes in the use of a game-based VR intervention for training functional prosthesis use, with participants showing significant improvements in prosthesis use skills measured with RL BBT. This motivates further development of VR interventions for prosthesis use training and their validation through clinical trials.
18F-FDG PET/CT Imaging of Cutaneous and Intramuscular Multiple Myeloma
Authors: Lippold Brandon , Jahromi Amin H. 
Published: November 2024

Abstract
Cutaneous manifestations of multiple myeloma are rare but, as with other extramedullary manifestations, carry a worse prognosis. We present the case of a 65-year-old man with immunoglobulin G κ multiple myeloma and prior autologous stem cell transplant. On subsequent therapy, he presented with multiple new cutaneous and subcutaneous left hip masses. Biopsy of these lesions revealed plasma cell neoplasm with anaplastic morphology, confirming progression of disease. He subsequently underwent radiation to these lesions with plans for chimeric antigen receptor T-cell therapy due to refractory disease.
Impact of Nonalcoholic Fatty Liver Disease on Weight Loss Outcomes After One Anastomosis Gastric Bypass
Authors: Athar Rahmatullah , Shahsavan Masoumeh , Shahabi Shahab , Pazouki Abdolreza , Husain Farah A. , Kermansaravi Mohammad 
Published: November 2024

Background:
Obesity-associated nonalcoholic fatty liver disease (NAFLD) is a significant cause of chronic liver disease. Our study sought to investigate preoperative NAFLD and the effect at 6 months and 2 years after surgery of one anastomosis gastric bypass (OAGB) and its development 6 months after surgery regarding weight loss outcomes.

Materials and Methods:
A retrospective cohort study was conducted on patients with severe obesity who underwent primary OAGB at Hazrat-e-Rasool Hospital between March 2020 and June 2021. Preoperative assessments included abdominal ultrasound (US) for NAFLD grading, weight, and biochemical blood tests. Follow-up examinations were performed at 10 days and 1, 3, 6, 9, 12, and 24 months postsurgery, with subsequent US examinations at the 6-month follow-up.

Results:
Two hundred thirty-one patients were included, with an average age of 40.3±10.5 years and a percentage of 78.4 women. Their mean weight and BMI were 131.2±26.8 and 48.8±8.5, respectively. Six-month grades of NAFLD showed that patients with grade 3 NAFLD had significantly lower TWL% compared with the lower grades. NAFLD grades improved in 72.3% of our patients, remained the same at 21.2%, and worsened at 6.5%. The 6-month TWL% was 28.4±4.3 in the no-change group, 28.4±5.3 for the improved group, and 25.2±14.6 in the worse group.

Conclusion:
The severity and progression of NAFLD can significantly impact weight loss outcomes post-OAGB, highlighting the importance of monitoring and managing NAFLD in patients undergoing bariatric surgery.
Quantitative MRI Measurements Capture Pancreatic Cancer and Stroma Reactions to New KRAS Inhibitor
Authors: Gupta Mamta , Choi Hoon , Kemp Samantha B , Furth Emma E , Pickup Stephen , Clendenin Cynthia , Orlen Margo , Rosen Mark , Liu Fang , Cao Quy , Stanger Ben Z. , Zhou Rong 
Published: November 2024

AbstractIn pancreatic ductal adenocarcinoma (PDAC), KRAS mutations drive both cancer cell growth and formation of a dense stroma. Small molecule KRAS inhibitors (KRASi) represent a breakthrough for PDAC treatment hence clinical tools that can assess early response, detect resistance and/or predict prolonged survival are desirable for management of patients undergoing KRASi therapy. We hypothesized that diffusion-weighted MRI (DWI) can detect cell death while dynamic contrast enhanced MRI (DCE) and magnetization transfer ratio (MTR) imaging are sensitive to tumor microenvironment changes, and these metrics shed insights into tumor size (standard care assessment) change induced by KRASi treatment. We tested this hypothesis in multiple preclinical PDAC models receiving MRTX1133, an investigational new drug specific for KRASG12Dmutation. Quantitative imaging markers corroborated by immunohistochemistry (IHC) revealed significant and profound changes related to cell death accompanied by changes in tumor cellularity, capillary perfusion /permeability and stromal matrix as early as 48h and day-7 after initiation of KRASi treatment, and greatly prolonged median survival over controls in a genetic engineered mouse model of PDAC (KPC). The MRI markers also captured distinct responses to KRASi therapy from PDAC tumors carrying KRASG12CversusKRASG12Dmutation. In tumors developed resistance to MRTX1133, the imaging markers exhibited a reversal from those of responding tumors. Our findings have established that multiparametric MRI provide biological insights including cell death, reduced cellularity and tumor microenvironment changes induced by KRASi treatment and set the stage for testing the utility of these clinically ready MRI methods in patients receiving KRASi therapy.Translational relevanceEmerging small molecule KRAS inhibitors (KRASi) represent a new class of therapy for PDAC. Clinical tools that can provide biological insights beyond tumor size change are desirable for management of patients under KRASi therapy. DWI and DCE are frequently applied MRI methods for assessing cancer treatment responses in clinical trials. Using multiple PDAC models, we examined whether DWI, DCE and MTR can enhance the standard care assessment (tumor size) to MRTX1133, a KARSi with investigational new drug (IND) status. Our data demonstrate the abilities of DWI, DCE and MTR derived imaging markers to detect the early (48h) cell death, pronounced stromal changes and development of resistance to KRASi. This study has high translational relevance by testing clinically ready MRI methods, an IND and a genetic engineered mouse model that recapitulates saline features of human PDAC.
Analysis of a hypomorphicmei-P26mutation reveals developmental control of CO patterning mechanisms
Authors: Berent Erica , Solomon Ally , Spencer Amanda P. , Bautista Oscar , Terry Joe , Ables Elizabeth T. , Crown Nicole 
Published: November 2024

AbstractFemale gametogenesis inDrosophilarequires both differentiation of germline stem cells and the unique cell cycle meiosis. Successful segregation of chromosomes into gametes during meiosis requires the formation of crossovers between homologous chromosomes. The frequency and distribution of crossovers is highly regulated at several levels, including formation of at least one obligate crossover per pair of homologs, crossover interference that keeps crossovers farther apart than expected by chance, and suppression of crossovers in and near the centromere. To achieve crossover patterning, a meiosis specific version of homologous recombination is used to repair programmed double-stranded breaks, and inDrosophila melanogaster, this recombination pathway requires the putative double Holliday junction resolvase MEI-9. Despite our understanding of crossover patterning mechanisms at the phenomenological level, how crossover patterning mechanisms are developmentally controlled in the context of germ cell differentiation is unknown. Here, we take advantage of a hypomorphic mutation inmei-P26,a gene previously associated with regulation of both germ cell mitoses and meiotic induction. We confirm thatmei-P261mutants show extended expression of mitotic cell cycle markers but rarely completely block differentiation, indicating that the mitotic cell cycle is mis-regulated. In this developmentally delayed context, we show thatmei-P261mutants enter meiosis and complete the earliest stages of prophase, including loading of synaptonemal complex proteins onto the centromere and initial loading onto the arms. Most nuclei do not progress past this to make full length synaptonemal complex, yet meiotic double-strand breaks are induced and crossovers form. However, while these crossovers require MEI-9 and exhibit crossover assurance, the centromere effect and interference are lost. We suggest a model where entry into zygotene of prophase is enough to commit pro-oocytes to using the meiotic homologous recombination machinery and thus ensuring crossover assurance, but that full length synaptonemal complex assembly is required for crossover interference.
Extraordinary physiology of polyphosphate-accumulatingBeggiatoamats suggests a key role for phosphate buffering in marine sediments
Authors: Iakovchuk Nadezhda , Fabian Jenny , Dellwig Olaf , Hassenrück Christiane , Schulz-Vogt Heide N. 
Published: November 2024

AbstractFilamentous sulfide-oxidizingBeggiatoaspp. are widespread in marine coastal environments and can achieve significant biomass because of their substantial size. Their ability to store phosphates in the polymerized form of polyphosphates makes them potentially key players in altering the phosphorus (P) cycle at the sediment-water interface. This study examined phosphate uptake and polyphosphate formation in a P starved culture of theBeggiatoasp. 35Flor strain. Remarkably, even after severe P starvation over five generations, the survival of the cultures was 46%, demonstrating considerable plasticity to different levels of phosphate availability. Under these P-depleted conditions, 23% of filaments still contained polyphosphates, underscoring its critical role in their metabolism. Upon reintroduction of phosphate to starved cultures, an extremely rapid phosphate uptake was observed within the first 10 minutes, with rates reaching up to 298 mmol P g-1protein d-1, which is significantly higher than values previously described in the literature for similar-sized organisms. The high phosphate uptake capacity ofBeggiatoaspp., estimated at 0.6 – 6 mmol m-2d-1for typical densities of filaments in coastal sediments, suggests that these bacteria may play an important role in buffering the phosphate flux in these environments. Thereby, they reduce primary production and subsequent oxygen consumption by other organisms, creating a negative feedback loop that helps maintain ecosystem stability.ImportanceSulfide-oxidizing bacteria of the genusBeggiatoaoccur ubiquitously in marine coastal sediments and have a large potential to influence phosphate fluxes at the sediment-water interface owing to their ability to accumulate polyphosphate and their large size. However, the extent to which these bacteria can contribute to phosphorus (P) sequestration or release remains poorly assessed. The importance of this study lies in demonstrating the unusual flexibility in adaptation of theBeggiatoasp. 35Flor strain to varying P availability, including extreme P starvation, and its capacity to rapidly uptake and store available phosphate in the form of polyphosphate. When considered at a global scale, these physiological traits could lead to P retention in shallow coastal waters, which, in turn, profoundly impacts ecological stability and ecosystem functioning.
Sequence-Dependent Liquid Crystalline Ordering of Gapped DNA
Authors: Kodikara Sineth G. , Gleeson James , Jakli Antal , Sprunt Samuel , Balci Hamza 
Published: November 2024

AbstractWe investigate the impact of poly-adenine (poly-A) sequences on the type and stability of liquid crystalline (LC) phases formed by concentrated solutions of gapped DNA (two duplex arms bridged by a flexible single strand) using synchrotron small angle X-ray scattering and polarizing optical microscopy. While samples with mixed sequence form layered (smectic) phases, poly-A samples demonstrate a columnar phase at lower temperatures (5-35 °C), not previously observed in GDNA samples, and a smectic-B phase of exceptional stability at higher temperatures (35-65 °C). We present a model that connects formation of these LC phases with the unique characteristics of poly-A sequences, which manifest in various biological contexts, including DNA condensation and nucleosome formation.
Unravelling the bottom-up and top-down control of a worldwide chestnut tree pest invader through integrative ecological genomics
Authors: Zitoun Jean-Loup , Rousseau Raphaël , Bertrand Joris , Toulza Eve , Rosalie Martin , Gourbière Sébastien 
Published: November 2024

AbstractBiological invasions have become a major threat to all agro-ecosystems. Estimating the bottom-up and top-down forces controlling the spread of invasive insects is a key challenge to lessen their burden on crops, forestry, and biodiversity. We combined ecological, metabarcoding and population genomics analyses with an integrative modelling of the invasion of a global insect pest to identify the impacts of its chestnut tree resource, natural enemies and biological control agent in Eastern Pyrenees. The host tree frequency and genomic variation associated with common resistance pathways had effects 4-10 times greater than the native hyperparasite community on the pest’s invasion potential (R0). The >90% field rates of hyperparasitism by the control agent and the associated 80% reduction in pest infestation are likely to be deceptive as our modelling consistently predicts their long-term coexistence with periodic re-emergences. Such a persistent ‘co-invasion’ scenario calls for a thorough assessment of the impact of these global pest and control agent on natural forest ecosystems.
FAK inhibition suppresses breast cancer progression via DNA methylation-mediated DAB2 gene reactivation
Authors: Murphy James M. , Jeong Kyuho , Ahn Eun-Young Erin , Lim Ssang-Taek Steve 
Published: November 2024

AbstractEpigenetic silencing of tumor suppressor genes is one of the main drivers of tumor progression. Without these tumor suppressors to reduce proliferation, tumor cells proliferate unchecked. Focal adhesion kinase (FAK) is a tyrosine kinase which is often upregulated in various tumors and promotes cell proliferation and migration. Recent studies have demonstrated that pharmacological or genetic FAK inhibition can reduce suppressive DNA methylation in vascular cells. Mechanistically, this is through nuclear FAK-mediated ubiquitination and proteasomal degradation of DNA methyltransferase 3A (DNMT3A). Treatment of breast cancer cell lines with FAK inhibitor (FAK-I) was able to reduce both FAK activity and DNMT3A protein expression. Further, global DNA methylation was reduced in breast cancer cell lines treated with FAK-I. This decrease in DNA methylation was correlated with decreased cell proliferation. We further showed that FAK-I reduced DNMT3A expression in breast cancer cells and that treatment with the proteasome inhibitor MG132 prevented loss of DNTM3A protein stability. To identify how FAK-I and DNMT3A loss could reduce breast cancer cell growth we compared RNA sequencing data from breast cancer cells treated with or without FAK-I or in shRNA DNMT3A knockdown. We have identified a potential tumor suppressor, DAB2, as being regulated by the nuclear FAK-DNMT3A axis. DAB2 is often downregulated in cancers and has been shown to play a vital role in switching TGFβ signaling from proliferative to apoptotic by altering TGFβRI binding partners. Immunoblotting and immunostaining indeed revealed that FAK-I and shDNMT3A could induce DAB2 protein expression. Further, FAK-I treatment showed efficacy in reducing tumor growth in vivo using the murine 4T1 tumor model. Immunostaining of 4T1 tumors showed FAK-I decreased DNMT3A, DNA methylation (5-methylcytosine, 5-mC), and increased DAB2 expression. Taken together, these data suggest that nuclear FAK-mediated regulation of DNMT3A can alter the epigenetic landscape and induce tumor suppressor gene expression.
Ascitic fluid protects against ferroptosis and enables the peritoneal spread of ovarian cancer
Authors: Setayeshpour Yasaman , Chen Ssu-Yu , Dayanidhi Divya L. , Lee Yunji , Federico Chiara , Aristizabal-Henao Juan J. , Wu Jianli , Lin Chao-Chieh , Mestre Alexander A. , Kiebish Michael A. , Berchuck Andrew , Hsu David S. , Huang Zhiqing , Murphy Susan K. , Chi Jen-Tsan 
Published: November 2024

AbstractOne of the most common sites of metastasis in ovarian cancer (OVCA) is the peritoneum. Often, this spread is accompanied by the accumulation of a fluid called ascites in the peritoneal cavity. Despite its common occurrence in metastatic OVCA patients, ascites and its influence on the peritoneal spread of OVCA are poorly understood. Interestingly, OVCA cells are vulnerable to ferroptosis, a type of cell death caused by lipid peroxidation. Hence, how these ferroptosis-sensitive OVCA cells persist in their spread to the peritoneum remains unknown. Here, we show that ascites robustly protects OVCA cells and patient-derived organoids against ferroptosis and enhances the peritoneal spread of OVCA cells in mice. Mechanistically, ascites downregulates the mitochondrial enzyme, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), which contributes to an increase in lipid droplets. Additionally, upon ferroptosis induction, ascites represses the upregulation of the transferrin receptor,TFRC, thereby decreasing cellular labile iron levels. Furthermore, we show that lipid-lowering fibrates reverse cellular changes induced by ascites, and they attenuate the peritoneal spread of OVCA cells in mice. Our findings implicate the importance of ascites in ferroptosis protection and the peritoneal spread of OVCA, and they suggest that targeting the ferroptosis protection by ascites may present a novel therapeutic approach to limit OVCA metastasis.
Th1 cells are critical tissue organizers of myeloid-rich perivascular activation niches
Authors: Bala Noor , McGurk Alexander , Carter Evan M. , Sidhu Ikjot , Niak Shruti , Leddon Scott A. , Fowell Deborah J. 
Published: November 2024

SUMMARYAggregating immune cells within perivascular niches (PVN) can regulate tissue immunity in infection, autoimmunity and cancer. How cells are assembled at PVNs and the activation signals imparted within remain unclear. Here, we integrate dynamic time-resolvedin vivoimaging with a novel spatially-resolved platform for microanatomical interrogation of transcriptome, immune phenotype and inflammatory mediators in skin PVNs. We uncover a complex positive-feedback loop within CXCL10+PVNs that regulates myeloid and Th1 cell positioning for exchange of critical signals for Th1 activation. Th1 cells spend ∼24h in the PVN, receiving initial peripheral activation signals, before redeploying to the inflamed dermal parenchyma. Niche-enriched, CCR2-dependent myeloid cells were critical for Th1 IFNγ-production. In turn, PVN instructional signals enabled Th1s to orchestrate PVN assembly by CXCR2-dependent intra-tissue myeloid cell aggregation. The results reveal a critical tissue organizing role for Th1s, gained rapidly on tissue entry, that could be exploited to boost regional immunity.HIGHLIGHTSPerivascular niche (PVN): myeloid hubs in inflamed mouse and healthy human skinTh1 cells enter, get activated, and leave the PVN within first 24h of tissue entryAntigen-specific signals in the PVN promote the tissue organizing functions of Th1sTh1 cells assemble the PVN via CXCR2-dependent myeloid cell aggregation
Leg immobilization and subsequent recovery resistance training affect skeletal muscle angiogenesis related markers in young healthy adults regardless of prior resistance training experience
Authors: McIntosh Mason C. , Michel J. Max , Godwin Joshua S. , Plotkin Daniel L. , Anglin Derick A. , Mattingly Madison L. , Agyin-Birikorang Anthony , Kontos Nicholas J. , Baweja Harsimran S. , Stock Matt S. , Mobley C. Brooks , Roberts Michael D. 
Published: November 2024

ABSTRACTWe recently reported that resistance trained (T, n=10) and untrained (UT, n=11) young adults experience vastus lateralis (VL) muscle atrophy following two weeks of disuse, and 8 weeks of recovery resistance training (RT) promotes VL hypertrophy in both participant cohorts. However, angiogenesis targets and muscle capillary number were not examined and currently no human studies that have sought to determine if disuse followed by recovery RT affects these outcomes. Thus, we examined whether disuse and/or recovery RT affected these outcomes. All participants underwent two weeks of left leg immobilization using locking leg braces and crutches followed by eight weeks (3d/week) of knee extensor focused progressive RT. VL biopsies were obtained at baseline (PRE), immediately after disuse (MID), and after RT (POST). Western blotting was used to assay angiogenesis markers and immunohistochemistry was performed in 16/21 participants to determine type I and II muscle fiber capillary number. Significant main effects of time (p<0.05) were observed for protein levels of VEGF (MID<POST), VEGFR2 (PRE&MID<POST), TSP-1 (PRE<POST), TIMP1 (MID<POST), phosphorylated/pan eNOS (Ser1177) (POST<PRE), and pan eNOS (PRE<POST). VEGFR2 exhibited a training status*time (p=0.018), but no differences existed between T and UT at any time point. A significant main effect of time was observed for type II fiber capillary number (PRE<POST), and type II fiber cross-sectional area (fCSA) increased from MID to POST (+25%, p<0.001) and PRE to POST (+20%, p=0.019). No significant correlations exist for percentage changes in type II fiber capillary number and type II fCSA from PRE-to-MID (r= 0.020), MID-to-POST (r= 0.392), or PRE-to-POST (r= −0.120) across all participants (p>0.100). Although disuse and recovery RT affect skeletal muscle angiogenesis-related protein targets, prior training history does not differentially affect these outcomes.NEW AND NOTEWORTHYThis is the first study to examine how limb immobilization and recovery resistance training affect molecular outcomes related to angiogenesis in younger adults with or without a prior training history. Regardless of resistance training history, the molecular responses are largely similar between participant cohorts and is suggestive of a reduced (pre-mid) and increased (mid-post) angiogenic response, with disuse and subsequent recovery resistance training.