bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vestibular Schwannoma Management: Patient Perspectives and Health Literacy
Authors: Casazza Julia A. , Yancey Kristen L. , Hunter Jacob B. 
Published: April 2024

Objective:
To assess medical decision-making, reasons for attrition, and health literacy among vestibular schwannoma (VS) patients last seen in clinic more than 2 years ago.

Study Design:
Survey.

Setting:
Tertiary skull base center.

Patients:
Adults with sporadic VS last evaluated more than 2 years ago.

Methods:
Survey including Brief Health Literacy Screen (BHLS), a validated 3-question measure of health literacy, and open-ended questions on care; retrospective chart review.

Main Outcome Measures:
BHLS score, patient reasons for attrition.

Results:
Of 1011 patients contacted, 205 (20.3%) patients responded and met all criteria for analysis. At initial evaluation, mean patient age was 50.6 ± 12.8 years, roughly half (51.4%) were female, and the majority (80.2%) identified as White. At the time of the survey, 48 (23%) continued to observe their tumor. The remaining 160 (76.9%) patients previously underwent treatment (surgery and/or radiation). Of those treated, 34 (21.3%) underwent intervention elsewhere. Symptoms since the last patient visit did not differ between observed and treated patients. About 94.7% of the cohort displayed high health literacy (BHLS > 9), though rates of inadequate health literacy were higher among observed patients (12.5% versus 3.1% in those treated). The most common reasons for opting not to follow-up included counseling issues, personal decisions, and social/life stressors (including the COVID-19 pandemic).

Conclusions:
Despite being a highly health-literate cohort, patients cited multiple reasons for attrition. Regardless of whether they were observed or treated, patients described follow-up visits as burdensome and perceived them to be of minimal benefit.
Visual performance of optical films utilizing Spatio-Temporal Optical Phase technology
Authors: Fedtke Cathleen , Tilia Daniel , Ehrmann Klaus , Diec Jennie , Lahav-Yacouel Karen , Falk Darrin , Bakaraju Ravi C. 
Published: April 2024

SIGNIFICANCE
Spatio-Temporal Optical Phase technology utilizes film pairs containing optical elements applied to standard single-vision spectacle lenses. This technology provides a dynamic optical cue that may have efficacy in reducing the rate of myopia progression, but the visual performance of this technology is unknown.

PURPOSE
This study aimed to assess the visual performance of film pairs containing optical elements (tests) and a film pair with no optical elements (control).

METHODS
In this randomized, single-masked, bilateral wear study, 42 participants aged 18 to 40 years wore four test designs (E, F-1, G, and F-2) and the control. Subjective data (subjective ratings [1 to 10 scale]: clarity of vision [far-away, intermediate, near] and vision [at night, while walking, overall satisfaction], and willingness to purchase [yes/no response]) were collected after 3 days. Visual acuity (VA)–based measures (monocular high/low-contrast VA [6 m], contrast sensitivity [6 m], and binocular high-contrast VA [6 m and 40 cm]) were collected at dispensing. Visual acuity–based measures were also collected while wearing spectacles with no film. Analyses were performed using linear mixed models and the χ
2 test. Significance was set at 5%.

RESULTS
The control performed better than any test for all subjective ratings (mean differences, 1.6 to 3.1 units: p<0.001), willingness to purchase (p<0.001), and designs F-1 and F-2 for binocular high-contrast VA at 40 cm (p=0.001 and p=0.01, respectively). Clarity of vision was significantly worse with F-2 compared with F-1 and G (p<0.001 and p=0.02, respectively). There were no differences between tests for any other subjective rating (p>0.1), willingness to purchase (p=0.11), or any VA-based measure (p>0.08). There were no differences between control and spectacles with no film for any VA-based measure (p>0.08).

CONCLUSIONS
All four test film pairs reduced visual performance compared with control to a degree comparable with other myopia management devices. There was no difference in visual performance between three of the four test film pairs.
Infantile nystagmus syndrome: An observational, retrospective, multicenter study
Authors: Fossataro Claudia , Pafundi Pia Clara , Mattei Roberta , Cima Valentina , De Rossi Francesca , Savino Gustavo 
Published: April 2024

SIGNIFICANCE
This multicenter study assessed clinical and psychological aspects of infantile nystagmus syndrome (INS) focusing on its management and nonsurgical treatment.

PURPOSE
This study aimed to assess clinical features, management, relationship life, and psychological impact in a group of patients with nystagmus onset in pediatric age.

METHODS
This observational study included patients diagnosed with INS referred to two Italian centers from January 1, 2017, to December 31, 2020. Ophthalmologic and orthoptic features and impact of visual function on quality of life, according to nystagmus-specific nystagmus quality of life questionnaire, were analyzed within the overall sample and in any of INS subgroups.

RESULTS
Forty-three patients were included; 65.1% of them had idiopathic INS (IINS), and 34.9% had INS associated with ocular diseases (INSOD). The median age was 15.4 years (interquartile range [IQR], 10.4 to 17.3 years), significantly different between groups (median, 15.8 years among those with IINS vs. 12.3 years among those with INSOD; p<0.001). In the INSOD subgroup, strabismus was significantly more prevalent (93.3 vs. 57.1%; p=0.017). Binocular distance best-corrected visual acuity in primary position was significantly higher in the IINS subsample (p<0.001). Such behavior was further confirmed at anomalous head position evaluation (p<0.001). At near best-corrected visual acuity assessment, differences between groups were more remarkable in primary position (p<0.001) than in anomalous head position. Contrast sensitivity showed significantly higher values in the IINS subgroup (p<0.001). The nystagmus quality of life questionnaire disclosed a significantly lower score in IINS as compared with INSOD (median total score, 90.5 [IQR, 84 to 97] vs. 94 [IQR, 83.0 to 96.5]; p<0.001).

CONCLUSIONS
The IINS group showed significantly better ophthalmologic and orthoptic outcomes than the INSOD group. The psychological and quality-of-life impact was instead significantly greater in the IINS group. To the best of our knowledge, this is the first multicenter study investigating the clinical features of IIN and comparing the two main subgroups, IINS and INSOD.
Reshaped functional connectivity gradients in acute ischemic stroke
Authors: Koba Cemal , Falcó-Roget Joan , Crimi Alessandro 
Published: April 2024

ABSTRACTIschemic brain stroke disrupts blood flow, leading to functional and structural changes associated with behavioral deficits. Importantly, despite this disruption occurring in localized regions, the resulting changes in the functional organization are both high-dimensional and widespread across the human cortex. However, the mechanisms with which these global patterns emerge and the subsequent behavioral deficits they entail, remain largely unexplored. Functional connectivity gradients provide consistent, reproducible, and robust low-dimensional representations of brain function that can be explored to reduce brain heterogeneity to a handful of axes along which brain function is organized. Here, we investigated how stroke disrupts this canonical gradient space by aligning each patient to a control-averaged gradient embedding and computing the distances to the “correct” positions to quantify functional deviations and their contribution to behavioral deficits. Importantly, we explicitly corrected these gradients for stroke-induced hemodynamic lags to further study their contribution. We found that lag correction enhanced the functional connectivity gradients most prominently in the second gradient, on which visual and somatomotor function is concentrated. Additionally, we identified significant functional deviations primarily within somatomotor, visual, and ventral attention networks, correlating with behavioral impairments. We studied the hemispheric asymmetries of these deviations finding that intact hemispheres preserve comparable patterns of asymmetry while damaged ones presented important changes. Lastly, right-sided lesions displayed more localized functional deviations than their contralateral lesions. Overall, we provide evidence that 1) correcting for hemodynamic lags improves gradient accuracy, as indicated by increased percentages of explained variance, and 2) behavioral impairments and hemispheric asymmetries result from a repositioning of region-based connectivity profiles in a low-dimensional, interpretable space. This suggests that large-scale brain function alterations manifest in slight, predictable movements largely confined to the visual-somatomotor axis.
In situcell condensation-based cartilage tissue engineering via immediately implantable high-density stem cell core and rapidly degradable shell microgels
Authors: Lee Sang Jin , Jeon Oju , Lee Yu Bin , Alt Daniel S. , Ding Aixiang , Tang Rui , Alsberg Eben 
Published: April 2024

AbstractFormation of chondromimetic human mesenchymal stem cells (hMSCs) condensations typically requiredin vitroculture in defined environments. In addition, extendedin vitroculture in differentiation media over several weeks is usually necessary prior to implantation, which is costly, time consuming and delays clinical treatment. Here, this study reports on immediately implantable core/shell microgels with a high-density hMSC-laden core and rapidly degradable hydrogel shell. The hMSCs in the core formed cell condensates within 12 hours and the oxidized and methacrylated alginate (OMA) hydrogel shells were completely degraded within 3 days, enabling spontaneous and precipitous fusion of adjacent condensed aggregates. By delivering transforming growth factor-β1 (TGF-β1) within the core, the fused condensates were chondrogenically differentiated and formed cartilage microtissues. Importantly, these hMSC-laden core/shell microgels, fabricated without anyin vitroculture, were subcutaneously implanted into mice and shown to form cartilage tissue via cellular condensations in the core after 3 weeks. This innovative approach to form cell condensationsin situwithoutin vitroculture that can fuse together with each other and with host tissue and be matured into new tissue with incorporated bioactive signals, allows for immediate implantation and may be a platform strategy for cartilage regeneration and other tissue engineering applications.
Different molecular recognition by three domains of the full-length GRB2 to SOS1 proline-rich motifs and EGFR phosphorylated sites
Authors: Tateno Keita , Ando Takami , Tabata Maako , Sugasawa Haruka , Hayashi Toshifumi , Sayeesh PM , Inomata Kohsuke , Mikawa Tsutomu , Ito Yutaka , Ikeya Teppei 
Published: April 2024

AbstractThe adaptor protein human GRB2 plays crucial roles in mediating signal transduction from cell membrane receptors to RAS and its downstream proteins by recruiting SOS1. Recent studies have revealed that GRB2 also serves as a scaffold for liquid-liquid phase separation (LLPS) with SOS1 and transmembrane receptors, which is thought to regulate the magnitude of cell signalling pathways. In this study, we employed solution NMR spectroscopy to investigate the interactions of the full-length GRB2 with proline-rich motifs (PRMs) derived from ten potential GRB2-binding sites in SOS1, as well as a peptide from a phosphorylation site of EGFR. Our findings indicate that the binding affinity of the two SH3 domains of GRB2 for PRMs differs by a factor of ten to twenty, with the N-terminal SH3 domain (NSH3) exhibiting a markedly higher affinity. The interactions of PRMs with the SH3 domains affected not only the regions surrounding the PRM binding sites on the SH3 domains but also the linker area connecting the three domains and parts of the SH2 domain. Analysis of the interaction between the phosphorylated EGFR binding site and the SH2 domain revealed chemical shift perturbations in regions distal from the known binding site of SH2. Moreover, we observed that the inter-domain interactions of the two SH3 domains with the SH2 domain of GRB2 are asymmetric. These findings suggest that the local binding of PRMs and phosphorylated EGFR to GRB2 impacts the overall structure of the GRB2 molecule, including domain orientation and dimerisation, which may contribute to LLPS formation.
Antithrombotic Efficacy and Bleeding Risks of Vaccine-Induced Immune Thrombotic Thrombocytopenia Treatments
Authors: Leung H.H.L. , Ahmadi Z. , Casey J. , Ratnasingam S. , McKenzie S.E. , Perdomo J.S. , Chong B.H. 
Published: April 2024

AbstractCurrent guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend non-heparin anticoagulants and intravenous immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to a lack of comparative clinical trials or animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies due to their ability to disrupt VITT IgG-PF4 binding. Here, we examined the effects of various anticoagulants (including unfractionated (UF) heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3, in relation to VITT pathophysiology. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, and thrombosis. Danaparoid, at therapeutic doses, was the sole anticoagulant that reduced VITT IgG-PF4 binding, verified by purified anti-PF4 specific VITT IgG. Low-dose UF heparin (< 2U/mL) augmented VITT IgG binding to PF4 on platelets. While danaparoid and high-dose UF heparin (10 U/mL) inhibited platelet activation, none of the anticoagulants significantly affected thrombocytopenia in our VITT animal model, and all prolonged bleeding time. IVIg and all anticoagulants, except UF heparin, protected VITT mice from thrombosis. Direct FcγRIIa receptor inhibition with IV.3 antibody proved the most effective approach for managing both thrombosis and thrombocytopenia in VITT. Our results underscore the necessity of animal model investigations to inform patient treatment strategies. This study provides compelling evidence for developing FcγRIIa receptor blockers to treat VITT and other FcγRIIa-related thrombotic inflammatory disorders.Key pointsNon-heparin anticoagulants and IVIg reduce thrombosisin vivoby varying degrees whereas heparin exacerbates thrombosis.Direct blocking of FcγRIIa receptor is the most effective strategy to treating both thrombosis and thrombocytopenia in VITT.
Organ specificity and commonality of epigenetic aging in low- and high-running capacity rats
Authors: Kawamura Takuji , Kerepesi Csaba , Torma Ferenc , Bori Zoltan , Zhou Lei , Bakonyi Peter , Kolonics Attila , Balogh Laszlo , Higuchi Mitsuru , Koch Lauren Gerard , Britton Steven Loyal , Koltai Erika , Radak Zsolt 
Published: April 2024

AbstractBackgroundEpigenetic drift, which are gradual age-related changes in DNA methylation patterns, plays a significant role in aging and age-related diseases. However, the relationship between exercise, epigenetics, and aging and the molecular mechanisms underlying their interactions are poorly understood. The aim of this study was to investigate the relationship between cardiorespiratory fitness (CRF), epigenetic aging, and promoter methylation of individual genes across multiple organs in selectively bred low- and high-capacity runner (LCR and HCR) aged rats.MethodsIn this study, we performed reduced representation bisulfite sequencing (RRBS) on LCR and HCR aged rats, focusing on the hippocampus, heart, soleus muscle, and large intestine samples. We calculated various epigenetic indicators, including rat epigenetic clocks, global mean DNA methylation (GMM), mean methylation entropy (MME), and gene-specific promoter methylation.ResultsEpigenetic clocks, trained on available rat blood-derived RRBS data did not reflect differences in CRF between LCR and HCR rats across all four organs. However, we observed organ specific differences in GMM and MME between LCR and HCR rats. The direction of these differences was the opposite compared to the age-related changes in the rat blood suggesting that a high CRF may mitigate age-related epigenetic changes in an organ-specific manner. Notably the soleus muscle, exhibited the most pronounced differences in promoter methylation due to CRF. We also identified seven genes whose promoter methylation was consistently influenced by CRF in all four organs. Moreover, we found that age acceleration of the soleus muscle was significantly higher compared to the heart and the hippocampus, and significantly lower compared to the large intestine. Finally, we found that the age acceleration was not consistent across organs.ConclusionsOur data suggest that CRF associates with epigenetic aging in an organ-specific manner and regulates the promoter methylation of individual genes in an organ-specific and organ-common manner. Our findings provide important insights into the biology of aging and emphasize the need to validate rejuvenation strategies in the context of the organ-specific nature of epigenetic aging.
More the merrier? Influence of Mango Orchards on the Composition of the Reptile Communities of the Lateritic Plateaus, Maharashtra, India
Authors: Amberkar Prathamesh , Mungikar Rahul 
Published: April 2024

ABSTRACTChange in land use patterns affects a landscape by changing the composition of local flora and fauna. The lateritic plateaus in Konkan are one such example of this rapid land use change. The area between the West coast and the Northern-Western Ghats of India, the Konkan region is characterized by these plateaus. Although these plateaus are rich in endemic flora and fauna, they are considered as wastelands due to lack of woody vegetation and thus, are subjected to various land uses. Mango cultivation in this region has become a major source of income since it’s known for its Alphonso variety of mangoes. Hence, over the last few decades, many plateaus have been converted into mango orchards. However, how the conversion of plateaus to mango orchards have effected species composition of different groups of organisms remains unclear. In the present study, we sampled the lateritic plateaus and plateaus converted into mango orchards in Ratnagiri, Maharashtra, to investigate the response of the reptile communities. We observed more species heterogeneity in the orchards compared to the plateaus. Since, the orchards offered more diverse microhabitats for species to occupy. Moreover, it appeared that there was a species turnover when the plateaus were converted into orchards. The generalist and widespread species such as agamids and skinks and very few specialist species were comparatively more abundant in the orchards. On a contrary, the plateaus without orchards harboured more specialist species likeHemidactylus albofasciatus,Echis carinatusandOphisops jerdoniicompared to the generalist species.
Metabolic Reprogramming Driven by Ant2 -Targeting Augments T-Cell Function and Anti-Tumor Immunity
Authors: Yosef Omri , Cohen-Daniel Leonor , Shamriz Oded , Bar-On Zahala , Saragovi Amijai , Abramovich Ifat , Agranovich Bella , Lutz Veronika , Tam Joseph , Permyakova Anna , Gottlieb Eyal , Huber Magdalena , Berger Michael 
Published: April 2024

AbstractT-cell activation requires a substantial increase in NAD+production, often exceeding the capacity of oxidative phosphorylation (OXPHOS). To investigate how T cells adapt to this metabolic challenge, we generated T cell-specific ADP/ATP translocase-2 knockout (Ant2−/−) mice. Loss of Ant2, a crucial protein mediating ADP/ATP exchange between mitochondria and cytoplasm, induces OXPHOS restriction by limiting ATP synthase activity, impeding NAD+regeneration. Interestingly, Ant2−/−naïve T cells exhibited enhanced activation, proliferation, and effector functions compared to wild-type controls. Metabolic profiling revealed that these cells adopt an activated-like metabolic program with increased mitobiogenesis and anabolism. Pharmacological inhibition of ANT in wild-type T cells recapitulated the Ant2−/−phenotype, and improved adoptive cell therapy of cancer. Our findings suggest that Ant2-deficient T cells bypass the typical metabolic reprogramming required for activation, leading to enhanced T-cell function. These results highlight the critical role of mitochondrial metabolism in regulating T-cell fate and underscore the therapeutic potential of targeting ANT for immune modulation.
Bilateral cellular flows display asymmetry prior to left-right organizer formation in amniote gastrulation
Authors: Asai Rieko , Sinha Shubham , Prakash Vivek N. , Mikawa Takashi 
Published: April 2024

AbstractA bilateral body plan is predominant throughout the animal kingdom. Bilaterality of amniote embryos becomes recognizable as midline morphogenesis begins at gastrulation, bisecting an embryonic field into the left and right sides, and left-right asymmetry patterning follows. While a series of laterality genes expressed after the left-right compartmentalization has been extensively studied, the laterality patterning prior to and at the initiation of midline morphogenesis has remained unclear. Here, through a biophysical quantification in a high spatial and temporal resolution, applied to a chick model system, we show that a large-scale bilateral counter-rotating cellular flow, termed as ‘polonaise movements’, display left-right asymmetries in early gastrulation. This cell movement starts prior to the formation of the primitive streak (the earliest midline structure) and the subsequent appearance of Hensen’s node (the left-right organizer). The cellular flow speed and vorticity unravel the location and timing of the left-right asymmetries. The bilateral flows displayed a Right dominance after six hours since the start of cell movements. Mitotic arrest that diminishes primitive streak formation resulted in changes in the bilateral flow pattern, but the Right dominance persisted. Our data indicate that the left-right asymmetry in amniote gastrula becomes detectable earlier than suggested by current models, which assume that the asymmetric regulation of the laterality signals at the node leads to the left-right patterning. More broadly, our results suggest that physical processes can play an unexpected but significant role in influencing left-right laterality during embryonic development.Significance StatementBilaterians are defined by a bilaterally symmetrical body plan. Vertebrates exhibit external bilateral symmetry but display left-right (LR) asymmetry in their internal organs. Amniote embryos switch the patterning of internal organs from bilateral symmetry to LR-asymmetry. Using chick embryos as a model system, here we examined the initiation of LR symmetry breaking. Our biophysical approaches to quantify cellular flows inferred that LR symmetry breaking occurs before the formation of Hensen’s node, a LR organizer, which serves as a signaling center for LR patterning-gene programs. Our work demonstrates that quantitative biophysical parameters can help unravel the initiation of LR symmetry breaking, suggesting an involvement of physical mechanisms in this critical biological patterning process.