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1.
Nanotechnology ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38636473

RESUMO

Two-dimensional transition metal dichalcogenide (TMDC) semiconductors are emerging as strong contenders for electronic devices that can be used in highly radioactive environments such as outer space where conventional silicon-based devices exhibit nonideal characteristics for such applications. To address the radiation-induced interface effects of TMDC-based electronic devices, we studied high-energy proton beam irradiation effects on the electrical properties of field-effect transistors (FETs) made with tungsten diselenide (WSe2) channels and hexagonal boron-nitride (hBN)/SiO2 gate dielectrics. The electrical characteristics of WSe2 FETs were measured before and after the irradiation at various proton beam doses of 1013, 1014, and 1015 cm-2. In particular, we demonstrated the dependence of proton irradiation-induced effects on hBN layer thickness in Wse2 FETs. We observed that the hBN layer reduces the WSe2/dielectric interface effect which would shift the transfer curve of the FET toward the positive direction of the gate voltage. Also, this interface effect was significantly suppressed when a thicker hBN layer was used. This phenomenon can be explained by the fact that the physical separation of the WSe2 channel and SiO2 dielectric by the hBN interlayer prevents the interface effects originating from the irradiation-induced positive trapped charges in SiO2 reaching the interface. This work will help improve our understanding of the interface effect of high-energy irradiation on TMDC-based nanoelectronic devices. .

2.
Orthop J Sports Med ; 12(4): 23259671241237126, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38617889

RESUMO

Background: Malalignment has been suggested as a predisposing factor for the development of osteochondral lesions of the talus (OLTs). Purpose: To evaluate the clinical and radiographic outcomes of realignment surgery in patients with a large cystic OLT of the talar shoulder and concurrent malalignment of the foot and ankle. Study Design: Case series; Level of evidence, 4. Methods: The authors reviewed consecutive patients with large cystic OLTs (diameter, >10 mm) of the talar shoulder and concurrent malalignment of the foot and ankle who underwent realignment surgery between September 2013 and April 2021. The type of realignment procedure was determined based on patient symptoms and findings on plain radiographs and weightbearing computed tomography. Clinical improvement was assessed using pre- and postoperative Foot Function Index (FFI) scores and the visual analog scale (VAS) for pain. The OLT location was categorized according to Raikin zone, and the OLT area and volume were measured and compared pre- and postoperatively. The comparative analysis was performed using the Wilcoxon signed-rank test. Results: In total, 27 ankles in 27 patients (mean age, 34.4 ± 11.9 years) were included in the analysis. There were 25 patients with a medial lesion (zone 4 [n = 19], zone 7 [n = 5], and zone 1 [n = 1]), and 2 patients with a lateral lesion (zone 6). Despite OLT location, patients' symptoms varied; 15 (55.6%) patients reported both medial- and lateral-sided pain, 10 (37%) reported lateral-sided pain, and 2 (7%) reported medial-sided pain. Supramalleolar osteotomy was performed in 18 patients, while foot and hindfoot correction without supramalleolar osteotomy was performed in 9 patients. Postoperatively, both the median FFI (from 44.4 [interquartile range (IQR), 35.7-52.2] to 9.1 [IQR, 5.2-13.9]) and median VAS pain score (from 6 [IQR, 5-6] to 1 [IQR, 1-2]) improved significantly (P < .0001 for both), and the median lesion size (from 25.8 mm2 [IQR, 19.3-45.2 mm2] to 13.8 mm2 [IQR, 6.8-26.5 mm2]) and median volume (from 2226.8 mm3 [IQR, 1311-3104 mm3] to 1326.5 mm3 [IQR, 714-2100 mm3]) decreased significantly (P < .0001 for both). During the mean follow-up of 4.1 ± 2.1 years, no subsequent surgery for OLT was necessary. Conclusion: The results suggest that realignment procedures can improve the symptoms and radiographic profile of OLTs in patients with large cystic OLTs of the talar shoulder and malalignment of the foot and ankle.

3.
Foot Ankle Int ; : 10711007241238209, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504500

RESUMO

BACKGROUND: Although operative treatment of the flexible progressive collapsing foot deformity (PCFD) remains controversial, correction of residual forefoot varus and stabilization of the medial column are important components of reconstruction. A peroneus brevis (PB) to peroneus longus (PL) tendon transfer has been proposed to address these deformities. The aim of our study was to determine the effect of an isolated PB-to-PL transfer on medial column kinematics and plantar pressures in a simulated PCFD (sPCFD) cadaveric model. METHODS: The stance phase of level walking was simulated in 10 midtibia cadaveric specimens using a validated 6-degree of freedom robot. Bone motions and plantar pressure were collected in 3 conditions: intact, sPCFD, and after PB-to-PL transfer. The PB-to-PL transfer was performed by transecting the PB and advancing the proximal stump 1 cm into the PL. Outcome measures included the change in joint rotation of the talonavicular, first naviculocuneiform, and first tarsometatarsal joints between conditions. Plantar pressure outcome measures included the maximum force, peak pressure under the first metatarsal, and the lateral-to-medial forefoot average pressure ratio. RESULTS: Compared to the sPCFD condition, the PB-to-PL transfer resulted in significant increases in talonavicular plantarflexion and adduction of 68% and 72%, respectively, during simulated late stance phase. Talonavicular eversion also decreased in simulated late stance by 53%. Relative to the sPCFD condition, the PB-to-PL transfer also resulted in a 17% increase (P = .045) in maximum force and a 45-kPa increase (P = .038) in peak pressure under the first metatarsal, along with a medial shift in forefoot pressure. CONCLUSION: The results from this cadaver-based simulation suggest that the addition of a PB-to-PL transfer as part of the surgical management of the flexible PCFD may aid in correction of deformity and increase the plantarflexion force under the first metatarsal. CLINICAL RELEVANCE: This study provides biomechanical evidence to support the addition of a PB-to-PL tendon transfer in the surgical treatment of flexible PCFD.

4.
JBMR Plus ; 8(2): ziad014, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505527

RESUMO

Bone homeostasis is maintained by tightly coordinated activities of bone-forming osteoblasts and bone-resorbing osteoclasts. In the present report, the role of Mer tyrosine kinase (MerTK) in bone metabolism was investigated. The expression of MerTK decreased upon BMP2 stimulation of osteoblast precursors. The femurs of Mertk-deficient mice showed significantly increased bone volume with concomitant increase of bone formation and reduction in bone resorption. These bone phenotypes were attributed to the increased osteoblast differentiation and mineralization accounted by the enhanced ß-catenin and Smad signaling in the absence of MerTK in osteoblast precursors. Although the Mertk-deficient bone marrow macrophages were predisposed to enhanced osteoclast differentiation via augmented Ca2+-NFATc1 signaling, the dramatic increase of Tnfsf11b/Tnfsf11 (Opg/Rankl) ratio in Mertk knockout bones and osteoblast precursors corroborated the reduction of osteoclastogenesis in Mertk deficiency. In ligature-induced periodontitis and ovariectomy models, the bone resorption was significantly attenuated in Mertk-deficient mice compared with wild-type control. Taken together, these data indicate novel role of MerTK in bone metabolism and suggest a potential strategy targeting MerTK in treating bone-lytic diseases including periodontitis and osteoporosis.

5.
Sci Rep ; 14(1): 7178, 2024 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531959

RESUMO

Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar-alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar-alveolar hyperplasia progression, although bronchiolar-alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.


Assuntos
Carcinoma , Lesão Pulmonar , Neoplasias Pulmonares , Ratos , Animais , Seguimentos , Carcinógenos , Hiperplasia , Guanidinas , Carcinogênese
6.
BMC Med ; 22(1): 141, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532472

RESUMO

BACKGROUND: Previous studies have shown that lifestyle/environmental factors could accelerate the development of age-related hearing loss (ARHL). However, there has not yet been a study investigating the joint association among genetics, lifestyle/environmental factors, and adherence to healthy lifestyle for risk of ARHL. We aimed to assess the association between ARHL genetic variants, lifestyle/environmental factors, and adherence to healthy lifestyle as pertains to risk of ARHL. METHODS: This case-control study included 376,464 European individuals aged 40 to 69 years, enrolled between 2006 and 2010 in the UK Biobank (UKBB). As a replication set, we also included a total of 26,523 individuals considered of European ancestry and 9834 individuals considered of African-American ancestry through the Penn Medicine Biobank (PMBB). The polygenic risk score (PRS) for ARHL was derived from a sensorineural hearing loss genome-wide association study from the FinnGen Consortium and categorized as low, intermediate, high, and very high. We selected lifestyle/environmental factors that have been previously studied in association with hearing loss. A composite healthy lifestyle score was determined using seven selected lifestyle behaviors and one environmental factor. RESULTS: Of the 376,464 participants, 87,066 (23.1%) cases belonged to the ARHL group, and 289,398 (76.9%) individuals comprised the control group in the UKBB. A very high PRS for ARHL had a 49% higher risk of ARHL than those with low PRS (adjusted OR, 1.49; 95% CI, 1.36-1.62; P < .001), which was replicated in the PMBB cohort. A very poor lifestyle was also associated with risk of ARHL (adjusted OR, 3.03; 95% CI, 2.75-3.35; P < .001). These risk factors showed joint effects with the risk of ARHL. Conversely, adherence to healthy lifestyle in relation to hearing mostly attenuated the risk of ARHL even in individuals with very high PRS (adjusted OR, 0.21; 95% CI, 0.09-0.52; P < .001). CONCLUSIONS: Our findings of this study demonstrated a significant joint association between genetic and lifestyle factors regarding ARHL. In addition, our analysis suggested that lifestyle adherence in individuals with high genetic risk could reduce the risk of ARHL.


Assuntos
Estudo de Associação Genômica Ampla , Presbiacusia , Humanos , Estudos de Casos e Controles , Fatores de Risco , Presbiacusia/genética , Estilo de Vida Saudável , Predisposição Genética para Doença
7.
Patterns (N Y) ; 5(3): 100929, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38487802

RESUMO

We described a challenge named "DRAC - Diabetic Retinopathy Analysis Challenge" in conjunction with the 25th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2022). Within this challenge, we provided the DRAC datset, an ultra-wide optical coherence tomography angiography (UW-OCTA) dataset (1,103 images), addressing three primary clinical tasks: diabetic retinopathy (DR) lesion segmentation, image quality assessment, and DR grading. The scientific community responded positively to the challenge, with 11, 12, and 13 teams submitting different solutions for these three tasks, respectively. This paper presents a concise summary and analysis of the top-performing solutions and results across all challenge tasks. These solutions could provide practical guidance for developing accurate classification and segmentation models for image quality assessment and DR diagnosis using UW-OCTA images, potentially improving the diagnostic capabilities of healthcare professionals. The dataset has been released to support the development of computer-aided diagnostic systems for DR evaluation.

8.
Foot Ankle Int ; : 10711007241230554, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482821

RESUMO

BACKGROUND: Although intraoperative ankle motion serves as a foundational reference for anticipated motion after surgery and guides the addition of procedures to enhance ankle motion in total ankle arthroplasty (TAA), the relationship between intraoperative and postoperative ankle motion remains unclear. This study aimed to investigate the discrepancy between intraoperative and postoperative ankle range of motion (ROM) following TAAs using the anterior-approach, fixed-bearing systems. METHODS: This study retrospectively reviewed 67 patients (67 ankles) who underwent primary TAA at a single institution. Three different types of anterior-approach, fixed-bearing TAA systems were included. Intraoperative fluoroscopy was used to document the maximal dorsiflexion and plantar flexion at the end of the case. Standardized weightbearing maximum dorsiflexion and plantar flexion sagittal radiographs were obtained pre- and postoperatively, following a previously described method. The motion between 3 different time points (preoperative, intraoperative, and postoperative [mean 11.4 months]) was compared using pairwise t tests, and their differences were quantified. RESULTS: The mean total tibiotalar ROM was 38.1 degrees (SD 7.8) intraoperatively, and the postoperative total tibiotalar ROM was 24.2 degrees (SD 9.7) (P < .001), indicating that a mean of 65.3% (SD 26.7) of the intraoperative motion was maintained postoperatively. Intraoperative dorsiflexion (mean 11.6 [SD 4.5] degrees) showed no evidence of difference from postoperative dorsiflexion (mean 11.4 [SD 5.8] degrees, P > .99), indicating that a median of 95.6% (interquartile range: 66.2-112) of the intraoperative maximum dorsiflexion was maintained postoperatively. However, there was a significant difference between intraoperative plantarflexion (mean 26.4 [SD 6.3]) and postoperative plantarflexion (12.8 [SD 6.9] degrees, P < .001), indicating a mean 50.6% (SD 29.6) of intraoperative motion maintained in the postoperative assessment. There was an improvement of 2.5 degrees in the total tibiotalar ROM following TAA with statistical significance (P < .043). CONCLUSION: This study revealed a significant difference between intraoperative ankle ROM and ankle ROM approximately 1 year after anterior-approach, fixed-bearing TAA, mainly due to plantarflexion motion restriction. Minimal difference in dorsiflexion suggests the importance of achieving the desired postoperative dorsiflexion motion during the surgery using the best possible adjunct procedures. LEVEL OF EVIDENCE: Level IV, case series.

9.
Foot Ankle Int ; : 10711007241231230, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38445609

RESUMO

BACKGROUND: Establishing a surgical plan for ankle deformities necessitates a comprehensive understanding of the deforming forces involved, and the morphology of the ankle deformity plays an important role as well. Valgus tibiotalar tilt development has mostly been described in patients with a low medial longitudinal arch, as seen in progressive collapsing foot deformity (PCFD). However, some valgus ankles demonstrate no radiographic evidence of a collapsed medial arch. This study aims to investigate whether there are differences in the radiographic morphology of valgus ankle deformities between patients with and without a low medial longitudinal arch to explore if they have different etiologies. METHODS: We retrospectively reviewed patients who underwent surgical treatment for asymmetric valgus ankle deformity at our institution between 2017 and 2021. Patients with a valgus tibiotalar tilt (TT) greater than 4 degrees and Meary angle greater than 30 degrees (mean: 38.9) were included in the PCFD group (n = 29). The non-PCFD group (n = 24) with TT greater than 4 degrees and Meary angle less than 4 degrees (mean: 0.3) was also established. In the weightbearing ankle anteroposterior view, the TT and medial distal tibial angle were measured. Additionally, to assess the mediolateral position of the talus, the talar center migration (TCM) and lateral talar dome-plafond distance (LTD-P) ratio in the coronal plane were measured. In weightbearing computed tomography (WBCT), the degree of axial plane talocalcaneal subluxation and the prevalence of sinus tarsi bony impingement were assessed. Intergroup comparison was conducted. RESULTS: Both groups demonstrated a similar degree of TT, with a mean of 11.6 degrees in the PCFD group and 13.7 degrees in the non-PCFD group (P = .2330). However, the PCFD group showed a significantly greater TCM and LTD-P ratio compared with those of the non-PCFD group (P < .0001), indicating that PCFD patients have a more medially translated talus in ankle anteroposterior radiographs. WBCT showed that the PCFD group on average had 18 degrees greater axial plane talocalcaneal subluxation (P < .0001) and 52% higher prevalence of sinus tarsi bony impingement (P = .0002) compared with the non-PCFD group. CONCLUSION: This study suggests that valgus ankles may exhibit different radiographic morphologies depending on the status of the longitudinal arch. Valgus ankles in PCFD patients tend to have a more medially translated talus. This finding may suggest the presence of different deforming forces between the 2 groups and may indicate the need for different treatment strategies to address talar tilt. LEVEL OF EVIDENCE: Level III, case-control.

10.
J Bone Joint Surg Am ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470951

RESUMO

BACKGROUND: Reduced hindfoot eversion motion has been proposed as a cause of increased lateral foot pressure following lateral column lengthening (LCL) for progressive collapsing foot deformity (PCFD). A subjective intraoperative assessment of passive eversion has been suggested to help evaluate correction; however, it is unclear how passive eversion correlates with objective measurements of foot stiffness. Our objectives were to quantify the relationship between the maximum passive eversion in hindfoot joints following LCL with plantar pressure during stance and to determine the influence of wedge size on these outcomes. METHODS: Ten cadaveric specimens extending from the mid-tibia distally were tested on a 6-degrees-of-freedom robot to simulate the stance phase of level walking. Five conditions were tested: intact, simulated PCFD, and 3 LCL wedge conditions (4, 6, and 8 mm). Outcomes included the lateral-to-medial forefoot plantar pressure (LM) ratio during stance and the maximum passive eversion measured in the hindfoot joints. Simple linear regressions were performed to evaluate relationships between outcomes and wedge sizes. RESULTS: A strong negative relationship was found between passive subtalar eversion and the LM ratio during stance (r[38] = -0.46; p = 0.0007), but not between passive talonavicular eversion and the LM ratio (r[38] = -0.02; p = 0.37). Wedge size was strongly related to subtalar eversion (r[38] = -0.77; p < 0.0001), talonavicular eversion (r[38] = -0.55; p = 0.0003), and the LM ratio (r[38] = 0.70; p < 0.0001). Increased wedge size resulted in average decreases in subtalar and talonavicular eversion of 1.0° (95% confidence interval [CI]: 0.8° to 1.3°) and 1.2° (95% CI: 0.6° to 1.6°), respectively. Increased wedge size also increased the LM ratio by 0.38 (95% CI: 0.25 to 0.50), indicating a lateral shift in plantar pressure. CONCLUSIONS: Decreased hindfoot eversion following LCL was related to increased lateral plantar pressure during stance. Increasing wedge size correlated with decreasing passive hindfoot eversion and increasing lateral plantar pressure, suggesting that intraoperative preservation of eversion motion may be important for preventing excessive lateral loading. CLINICAL RELEVANCE: To avoid overcorrection or undercorrection of the deformity, hindfoot eversion assessment in addition to radiographic evaluation may be important for optimizing the amount of lengthening to achieve successful LCL.

11.
Psychiatry Res ; 333: 115753, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335777

RESUMO

Creativity is known to be heritable and exhibits familial aggregation with psychiatric disorders; however, the complex nature of their relationship has not been well-established. In the present study, we demonstrate that using an expanded and validated machine learning (ML)-based phenotyping of occupational creativity (OC) can allow us to further understand the trait of creativity, which was previously difficult to define and study. We conducted the largest genome-wide association study (GWAS) on OC with 241,736 participants from the UK Biobank and identified 25 lead variants that have not yet been reported and three candidate causal genes that were previously associated with educational attainment and psychiatric disorders. We found extensive genetic overlap between OC and psychiatric disorders with mixed effect direction through various post-GWAS analyses, including the bivariate causal mixture model. In addition, we discovered a strongly genetic correlation between our original GWAS and the GWAS adjusted for education years (rg = 0.95). Our GWAS analysis via ML-based phenotyping contributes to the understanding of the genetic architecture of creativity, which may inform genetic discovery and genetic prediction in human cognition and psychiatric disorders.


Assuntos
Estudo de Associação Genômica Ampla , Transtornos Mentais , Humanos , Predisposição Genética para Doença , Transtornos Mentais/genética , Cognição , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
12.
J Assoc Res Otolaryngol ; 25(2): 167-177, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38361011

RESUMO

One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.


Assuntos
Doenças Vestibulares , Vestíbulo do Labirinto , Animais , Reflexo Vestíbulo-Ocular , Peixe-Zebra
13.
J Transl Med ; 22(1): 154, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355577

RESUMO

BACKGROUND: Tumor cells of diffuse-type gastric cancer (DGC) are discohesive and infiltrate into the stroma as single cells or small subgroups, so the stroma significantly impacts DGC progression. Cancer-associated fibroblasts (CAFs) are major components of the tumor stroma. Here, we identified CAF-specific secreted molecules and investigated the mechanism underlying CAF-induced DGC progression. METHODS: We conducted transcriptome analysis for paired normal fibroblast (NF)-CAF isolated from DGC patient tissues and proteomics for conditioned media (CM) of fibroblasts. The effects of fibroblasts on cancer cells were examined by transwell migration and soft agar assays, western blotting, and in vivo. We confirmed the effect of blocking tubulointerstitial nephritis antigen-like 1 (TINAGL1) in CAFs using siRNA or shRNA. We evaluated the expression of TINAGL1 protein in frozen tissues of DGC and paired normal stomach and mRNA in formalin-fixed, paraffin-embedded (FFPE) tissue using RNA in-situ hybridization (RNA-ISH). RESULTS: CAFs more highly expressed TINAGL1 than NFs. The co-culture of CAFs increased migration and tumorigenesis of DGC. Moreover, CAFs enhanced the phosphorylation of focal adhesion kinase (FAK) and mesenchymal marker expression in DGC cells. In an animal study, DGC tumors co-injected with CAFs showed aggressive phenotypes, including lymph node metastasis. However, increased phosphorylation of FAK and migration were reduced by blocking TINAGL1 in CAFs. In the tissues of DGC patients, TINAGL1 was higher in cancer than paired normal tissues and detected with collagen type I alpha 1 chain (COL1A1) in the same spot. Furthermore, high TINAGL1 expression was significantly correlated with poor prognosis in several public databases and our patient cohort diagnosed with DGC. CONCLUSIONS: These results indicate that TINAGL1 secreted by CAFs induces phosphorylation of FAK in DGC cells and promotes tumor progression. Thus, targeting TINAGL1 in CAFs can be a novel therapeutic strategy for DGC.


Assuntos
Fibroblastos Associados a Câncer , Nefrite Intersticial , Neoplasias Gástricas , Animais , Humanos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Fibroblastos/metabolismo , Integrina beta1/genética , Integrina beta1/metabolismo , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , RNA Interferente Pequeno/metabolismo , Neoplasias Gástricas/patologia , Microambiente Tumoral
14.
medRxiv ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38405768

RESUMO

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 22 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, YWHAE, DPH1, GSDMB, MED24, THRA, EEF1A2, and KCNQ2 in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance and transferability of BD polygenic risk scores across ancestrally diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI).

15.
Phys Rev Lett ; 132(3): 036702, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38307068

RESUMO

Altermagnetism is a newly identified fundamental class of magnetism with vanishing net magnetization and time-reversal symmetry broken electronic structure. Probing the unusual electronic structure with nonrelativistic spin splitting would be a direct experimental verification of an altermagnetic phase. By combining high-quality film growth and in situ angle-resolved photoemission spectroscopy, we report the electronic structure of an altermagnetic candidate, α-MnTe. Temperature-dependent study reveals the lifting of Kramers degeneracy accompanied by a magnetic phase transition at T_{N}=267 K with spin splitting of up to 370 meV, providing direct spectroscopic evidence for altermagnetism in MnTe.

16.
Foot Ankle Clin ; 29(1): 111-122, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309796

RESUMO

Gutter impingement is one of the most common causes of subsequent surgery after total ankle arthroplasty (TAA). Although gutter debridement has been reported to resolve preoperative symptoms early on, persistent pain after surgery, recurrence, and poor functional outcome scores have been described in patients who have undergone reoperation for gutter debridement. The cause of gutter impingement after TAA is multifactorial, and a better understanding of its causes and optimal surgical techniques for intervention is needed.


Assuntos
Tornozelo , Artroplastia de Substituição do Tornozelo , Humanos , Reoperação , Tornozelo/cirurgia , Estudos Retrospectivos , Artroplastia de Substituição do Tornozelo/efeitos adversos , Artroplastia de Substituição do Tornozelo/métodos , Articulação do Tornozelo/cirurgia , Resultado do Tratamento
17.
Nat Hum Behav ; 8(3): 562-575, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38182883

RESUMO

Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.


Assuntos
Sucesso Acadêmico , População do Leste Asiático , Humanos , Estudo de Associação Genômica Ampla , Escolaridade , Herança Multifatorial/genética
18.
Foot Ankle Int ; 45(3): 252-260, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38281125

RESUMO

BACKGROUND: Flatfoot deformity is believed to play a role in hallux valgus development and recurrence. While symptomatic flatfoot deformity can be treated with separate procedures at the time of hallux valgus correction, the question remains whether the patient undergoing correction of a symptomatic hallux valgus deformity should have their asymptomatic flatfoot concurrently addressed. We aimed to investigate whether the presence of asymptomatic flatfoot influences patient-reported and radiographic outcomes of the minimally invasive chevron and Akin bunionectomy. METHODS: A total of 104 patients were included in this study. Forty-two asymptomatic patients met the radiographic criteria for flatfoot while 62 had a normal arch. Patient-reported outcomes were evaluated and compared between the two groups using validated PROMIS measures preoperatively and at a minimum one-year postoperatively. Radiographic outcomes including hallux valgus angle (HVA), intermetatarsal angle (IMA), Meary's angle, calcaneal pitch (CP), and talonavicular coverage angle (TNCA) were measured and compared preoperatively and minimum six-months postoperatively. RESULTS: Both groups demonstrated similar preoperative and postoperative PROMIS scores with significant improvements in physical function, pain interference, pain intensity, and global physical health. Preoperatively, HVA was similar between both groups, however the flatfoot group showed a greater IMA, Meary's angle, TNCA, and lower CP. Postoperatively, HVA and IMA were similar between groups, although patients in the flatfoot group retained a significantly greater Meary's angle, TNCA, and lower CP. Both groups showed significant improvements in HVA, IMA, and TNCA. CONCLUSION: Our study indicates that the minimally invasive chevron and Akin bunionectomy leads to improved clinical and radiographic hallux valgus outcomes without adversely impacting radiographic flatfoot parameters. Therefore, the MIS bunionectomy may be an effective option for hallux valgus correction in patients with mild, asymptomatic flatfoot. LEVEL OF EVIDENCE: Level III, retrospective cohort.


Assuntos
Joanete , Pé Chato , Hallux Valgus , Humanos , Estudos Retrospectivos , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Pé Chato/diagnóstico por imagem , Pé Chato/cirurgia , Osteotomia/métodos , Radiografia , Resultado do Tratamento
19.
Water Res ; 251: 121125, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38218073

RESUMO

This research introduces a comprehensive methodology to enhance hyperspectral image data (HSD) utility, specifically focusing on the three-dimensional (3-D) augmentation of Chlorophyll-a (Chl-a). This study comprises three significant steps: (1) the augmentation of limited field water quality data in terms of time interval and number of variables using neural network models, (2) the generation of 3-D data using numerical models, and (3) the extension of the hyperspectral image data into 3-D data using machine learning models. In the first phase, Multilayer Perceptron (MLP) models were developed to train water quality interactions and successfully generated high-frequency water quality data by adjusting biased measurements and predicting detailed water quality variables. In the second phase, high-frequency data generated by MLP models were applied to develop two numerical models. These numerical models successfully generated 3-D data, thereby demonstrating the effectiveness of integrating numerical modeling with neural networks. In the final phase, ten machine learning models were trained to generate 3-D Chl-a data from HSD. Notably, the Gaussian Process Regression model exhibited superior performance, effectively estimating 3-D Chl-a data with robust accuracy, as evidenced by an R-square value of 0.99. The findings align with theories of algal bloom dynamics, further validating the effectiveness of the approach. This study demonstrated the successful integrated development for HSD extension using machine learning models, numerical models, and original HSD, highlighting the potential of such integrated methodologies in advancing water quality monitoring and estimation. Notably, the approach leverages readily accessible data, allowing for the swift generation of results and bypassing time-consuming data collection processes. This research marks a significant step towards more robust, comprehensive water quality monitoring and prediction, thereby facilitating better management of aquatic ecosystems.


Assuntos
Ecossistema , Qualidade da Água , Clorofila A , Aprendizado de Máquina , Redes Neurais de Computação , Monitoramento Ambiental/métodos
20.
Sci Rep ; 14(1): 942, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200085

RESUMO

This study measured and analyzed chronological changes in temporomandibular joint space volume by compartment following transoral vertical ramus osteotomy (TOVRO) using reconstructed 3-dimensional (3D) images of patients with mandibular prognathism. It included 70 joints of 35 patients who underwent TOVRO between January 2018 and December 2021. Computed tomography (CT) or cone-beam CT (CBCT) was performed before surgery (T0) and at 3 days (T1), 6 months (T2), and 12 months postoperatively (T3). These scans were then analyzed using 3D software. The volumes of the overall (Vjs), anterior (Vajs), posterior (Vpjs), medial (Vmjs), and lateral (Vljs) joint spaces were calculated at each time point. A linear mixed model and repeated-measures covariance pattern with unstructured covariance were used to evaluate significant changes in joint space volume over time. Vjs significantly increased to 134.54 ± 34.28 mm3 at T3 compared to T0 (p < 0.001). Vpjas and Vljs increased by 130.72 ± 10.07 mm3 and 109.98 ± 7.52 mm3 at T3 compared to T0, respectively (p < 0.001). However, no significant difference was observed between T0 and T2 in Vajs and Vmjs (p = 0.9999). The observed volume increases in Vpjs and Vljs appeared to contribute to the overall Vjs increase.


Assuntos
Má Oclusão Classe III de Angle , Prognatismo , Humanos , Seguimentos , Osteotomia Sagital do Ramo Mandibular , Prognatismo/diagnóstico por imagem , Prognatismo/cirurgia , Articulação Temporomandibular/diagnóstico por imagem , Polímeros
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