Modulation of Multisensory Nociceptive Neurons In Monkey Cortical Area 7b.

Wide range thermoreceptive neurons (WRT-EN) in monkey cortical area 7b that encoded innocuous and nocuous cutaneous thermal and threatening visuosensory stimulation with high fidelity were studied to identify their multisensory integrative response properties. Emphasis was given to characterizing the spatial and temporal effects of threatening visuosensory input on the thermal stimulus-response properties of these multisensory nociceptive neurons. Threatening visuosensory stimulation was most efficacious in modulating thermal evoked responses when presented as a downward ("looming"), spatially congruent, approaching and closely proximal target in relation to the somatosensory receptive field. Both temporal alignment and misalignment of spatially aligned threatening visual and thermal stimulation significantly increased mean discharge frequencies above those evoked by thermal stimulation alone, particularly at near noxious (43°C) and mildly noxious (45°C) temperatures. The enhanced multisensory discharge frequencies were equivalent to the discharge frequency evoked by overtly noxious thermal stimulation alone at 47°C (monkey pain tolerance threshold). A significant increase in behavioral mean escape frequency with shorter escape latency was evoked by multisensory stimulation at near noxious temperature (43°C ) which was equivalent to that evoked by noxious stimulation alone (47°C).The remarkable concordance of elevating both neural discharge and escape frequency from a non-nociceptive and pre-pain level by near noxious thermal stimulation to a nociceptive and pain level by multisensory visual and near noxious thermal stimulation and integration is an elegantly designed defensive neural mechanism that in effect lowers both nociceptive response and pain thresholds to preemptively engage nocifensive behavior and consequently, avert impending and actual injurious noxious thermal stimulation.

Aligning the domains in cross domain model inversion attack.

Model Inversion Attack reconstructs confidential training dataset from a target deep learning model. Most of the existing methods assume the adversary has an auxiliary dataset that has similar distribution with the private dataset. However, this assumption does not always hold in real-world scenarios. Since the private dataset is unknown, the domain divergence between the auxiliary dataset and the private dataset is inevitable. In this paper, we use Cross Domain Model Inversion Attack to represent the distribution divergence scenario in MIA. With the distribution divergence between the private images and auxiliary images, the distribution between the feature vectors of the private images and those of the auxiliary images is also different. Moreover, the outputted prediction vectors of the auxiliary images are also misclassified. The inversion attack is thus hard to be performed. We perform both the feature vector inversion task and prediction vector inversion task in this cross domain setting. For feature vector inversion, Domain Alignment MIA (DA-MIA) is proposed. While performing the reconstruction task, DA-MIA aligns the feature vectors of auxiliary images with the feature vectors of private images in an adversarial manner to mitigate the domain divergence between them. Thus, semantically meaningful images can be reconstructed. For prediction vector inversion, we further introduce an auxiliary classifier and propose Domain Alignment MIA with Auxiliary Classifier (DA-MIA-AC). The auxiliary classifier is pretrained by the auxiliary dataset and fine-tuned during the adversarial training stage. Thus, the misclassification problem caused by domain divergence can be solved, and the images can be reconstructed correctly. Various experiments are performed to show the advancement of our methods, the results show that DA-MIA can improve the SSIM score of the reconstructed images for up to 191%, DA-MIA-AC can increase the classification accuracy score of the reconstructed images from 9.18% to 81.32% in Cross Domain Model Inversion Attack.

Alignment of lyotropic liquid crystals using magnetic nanoparticles improves ionic transport through built-in peptide ion channels.

HYPOTHESIS: We hypothesize that simultaneous incorporation of ion channel peptides (in this case, potassium channel as a model) and hydrophobic magnetite Fe3O4 nanoparticles (hFe3O4NPs) within lipidic hexagonal mesophases, and aligning them using an external magnetic field can significantly enhance ion transport through lipid membranes. EXPERIMENTS: In this study, we successfully characterized the incorporation of gramicidin membrane ion channels and hFe3O4NPs in the lipidic hexagonal structure using SAXS and cryo-TEM methods. Additionally, we thoroughly investigated the conductive characteristics of freestanding films of lipidic hexagonal mesophases, both with and without gramicidin potassium channels, utilizing a range of electrochemical techniques, including impedance spectroscopy, normal pulse voltammetry, and chronoamperometry. FINDINGS: Our research reveals a state-of-the-art breakthrough in enhancing ion transport in lyotropic liquid crystals as matrices for integral proteins and peptides. We demonstrate the remarkable efficacy of membranes composed of hexagonal lipid mesophases embedded with K+ transporting peptides. This enhancement is achieved through doping with hFe3O4NPs and exposure to a magnetic field. We investigate the intricate interplay between the conductive properties of the lipidic hexagonal structure, hFe3O4NPs, gramicidin incorporation, and the influence of Ca2+ on K+ channels. Furthermore, our study unveils a new direction in ion channel studies and biomimetic membrane investigations, presenting a versatile model for biomimetic membranes with unprecedented ion transport capabilities under an appropriately oriented magnetic field. These findings hold promise for advancing membrane technology and various biotechnological and biomedical applications of membrane proteins.

Mutation Screening of Dictyostelium Restriction Enzyme-Mediated Integration (REMI) Libraries.

Identifying the mechanisms of action of existing and novel drugs is essential for the development of new compounds for therapeutic and commercial use. Here we provide a technique to identify these mechanisms through isolating mutant cell lines that show resistance to drug-induced phenotypes using Dictyostelium discoideum REMI libraries. This approach provides a robust and rapid chemical-genetic screening technique that enables an unbiased approach to identify proteins and molecular pathways that control drug sensitivity. Mutations that result in drug resistance often occur in target proteins thus identifying the specific protein targets for drugs and bioactive natural products. Following the identification of a list of putative molecular targets user selected compound targets can be analyzed to confirm and validate direct inhibitory effects.

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus.

Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.

Duplications and retrogenes are numerous and widespread in modern canine genomic assemblies.

Recent years have seen a dramatic increase in the number of canine genome assemblies available. Duplications are an important source of evolutionary novelty and are also prone to misassembly. We explored the duplication content of nine canine genome assemblies using both genome self-alignment and read-depth approaches. We find that 8.58% of the genome is duplicated in the canFam4 assembly, derived from the German Shepherd Dog Mischka, including 90.15% of unplaced contigs. Highlighting the continued difficulty in properly assembling duplications, less than half of read-depth and assembly alignment duplications overlap, but the mCanLor1.2 Greenland wolf assembly shows greater concordance. Further study shows the presence of multiple segments that have alignments to four or more duplicate copies. These high-recurrence duplications correspond to gene retrocopies. We identified 3,892 candidate retrocopies from 1,316 parental genes in the canFam4 assembly and find that approximately 8.82% of duplicated base pairs involve a retrocopy, confirming this mechanism as a major driver of gene duplication in canines. Similar patterns are found across eight other recent canine genome assemblies, with metrics supporting a greater quality of the PacBio HiFi mCanLor1.2 assembly. Comparison between the wolf and other canine assemblies found that 92% of retrocopy insertions are shared between assemblies. By calculating the number of generations since genome divergence, we estimate that new retrocopy insertions appear, on average, in 1 out of 3,514 births. Our analyses illustrate the impact of retrogene formation on canine genomes and highlight the variable representation of duplicated sequences among recently completed canine assemblies.

Congenital Fibrosis of Extraocular Muscles: A Retrospective Study of 76 Patients.

Background Congenital fibrosis of the extraocular muscles (CFEOM) is a non-progressive sporadic or familial disease characterized by abnormal innervation of the extraocular muscles. This study aims to evaluate the types of diseases, management steps, and surgical outcomes. Methodology A total of 76 patients diagnosed with CFEOM between 2000 and 2022 were evaluated retrospectively. Patients were divided into CFEOM 1, 2, or 3 based on clinical findings. Preoperative and postoperative ocular deviations, as well as abnormal head positions (AHPs), of the patients were evaluated. Excellent outcomes for the head position were defined as less than 5°, good as less than 10°, and poor as greater than 10°. Excellent alignment for strabismus was considered to be less than 10 prism diopters (PD), good as less than 20 PD, and poor as greater than 20 PD. Results The average age at the first surgery in our clinic was 11.6 (1-51) years. The mean follow-up was 28.6 ± 7.4 months (range = 4-56 months). Type 1 disease was detected in 48 (63.2%) patients, type 2 disease in eight (10.5%), and type 3 disease in 20 (26.3%) patients. Of the 49 patients with AHP, 20 achieved excellent outcomes, 17 had good outcomes, and the remaining had poor outcomes. Ocular alignment in the primary position following the latest surgery was excellent in 30 patients, good in 26 patients, and poor in 20 patients. Conclusions No single best surgical method can be universally applied to every patient diagnosed with CFEOM. Patients must be evaluated individually and carefully, and the appropriate surgical procedure must be chosen. In this way, satisfactory gaze alignment and improvement of the AHP can be achieved.

Evaluation of distal tibia slope in pilon fractures after surgical fixation.

INTRODUCTION: Alteration of sagittal alignment during fracture fixation directly impacts ankle motion in dorsiflexion and plantarflexion. Previously research measured the anterior distal tibia angle (ADTA) in a normal healthy population. The null hypothesis for this study is that ADTA is restored to normal range following unstable pilon fractures. The aim of this study is to identify the range of the ADTA in distal tibia fractures after surgical fixation, compared to a previously published normal population. MATERIAL AND METHODS: A retrospective review of operative distal tibia fractures (AO/OTA classification 43A and 43C - 43B were excluded due to lower likelihood of fracture changing the ADTA) was performed. ADTA on lateral radiograph was measured as the angle relative to the tibia shaft. RESULTS: 100 patients with post-operative radiographs that met inclusion criteria were analyzed. The average ADTA was 6.9° (⌠=4.62°) with a maximum slope of 19.2° (i.e. anterior orientation) and a minimum of -3.3° (i.e. posterior orientation). The uninjured population had an average ADTA of 6.0° (range -2.0°-14°, ⌠=3.0°). CONCLUSION: This analysis shows the average distal tibia sagittal alignment in the post-surgical group is similar to a normal, uninjured population. Large alterations in ADTA would directly impact the ankle in the plane of motion (i.e. negative ADTA would decrease ankle dorsiflexion). Considering ADTA as an objective intra-operative parameter optimizes sagittal plane alignment.

Influence of different standing positions on anatomical parameters of coronal whole-leg weight-bearing radiographs in preoperative planning for high tibial osteotomy.

Purpose: The purpose of this study was to assess the differences in lower limb global alignment and anatomical parameters of coronal whole-leg radiographs, which were generally used in preoperative planning for high tibial osteotomy (HTO), according to different weight-bearing standing positions. Methods: Between April 2021 and December 2022, 176 patients (60 males and 116 females) were investigated. Full-weight-bearing coronal whole-leg radiographs were obtained with the patella centred on the femoral condyle. Patients were divided by Kellgren-Lawrence grade (KL-0, KL-I, KL-II and KL-III) and assessed in two standing positions: legs closed and legs spread. Patients with flexion contractures or those unable to stand with full weight bearing were excluded. The mechanical distal femoral angle, medial proximal tibial angle (MPTA), femorotibial angle, joint line convergence angle, percentage weight-bearing line (%WBL) and hip-knee-ankle angle (HKAA) were measured. The Student's t test was used to compare the two standing positions. A p value < 0.05 indicated a statistically significant difference. Results: The MPTAs of legs closed standing and legs spread standing were 84.9 ± 2.6° and 85.1 ± 2.4° in KL-0, 84.7 ± 2.0° and 84.9 ± 2.1° in KL-I and 85.0 ± 2.43° and 85.4 ± 2.4° in KL-II, respectively. There were statistically significant differences in the MPTA between the two standing positions in KL-0, KL-I and KL-II. In contrast, the %WBL and HKAA did not change regardless of the standing position. In the KL-III group, no statistical significance was observed for any of the anatomical parameters. Conclusion: Several anatomical parameters were changed between the legs closed standing and the legs spread standing positions. It was suggested that the standing position should be taken into consideration in the planning for HTO. Level of Evidence: Level IV, Case series with no comparison group.

Stem Alignment With the Tapered Wedge Cementless Stem "Accolade II" Does Not Affect Bone Mineral Density Over 5 Years After Total Hip Arthroplasty.

Background: This study aimed to investigate the relationship between 3-dimensional (3D) alignment and postoperative bone mineral density (BMD) changes with Accolade II tapered wedge stems, which have a different proximal shape from other tapered wedge stems, up to 5 years after primary total hip arthroplasty. Methods: We retrospectively analyzed the hips of 89 patients who underwent total hip arthroplasty using the second-generation proximally coated cementless stem (Accolade II; Stryker Orthopedics, Mahwah, NJ) at our institution from 2014 to 2018 over a 5-year follow-up. We evaluated the relationship between stem alignment, measured using 3D-templating software, and BMD changes in the 7 Gruen zones and compared the data with those from a former study using other short taper-wedge stems. Results: BMDs in zones 1 and 7 continued to decrease gradually every year after surgery, and BMD in zone 7 showed the largest decrease (21%) from baseline over 5 years. No correlation was found between stem alignment (varus/valgus, flexion/extension, and anteversion/retroversion) and changes in BMD in each zone over 5 years. Conclusions: Our data showed no correlation between 3D stem alignment and changes in BMD in each Gruen zone over 5 years. This suggests that the Accolade II stem may fit better into any shape of the proximal medullary canal because of its unique characteristics.

Longitudinal impact of multi-segment spinal fixation surgery on mobility status and clinical outcomes in adult spinal deformity: a multicenter retrospective study.

PURPOSE: To investigate changes in postoperative mobility status in patients with ASD, and the determining factors that influence these changes and their impact on clinical outcomes, including the rate of home discharge and long-term mobility. METHODS: A total of 299 patients with ASD who underwent multi-segment posterior spinal fusion were registered in a multi-center database were investigated. Patient mobility status was assessed using walking aids and classified into five levels (1: independent, 2: cane, 3: walker, 4: assisted, and 5: wheelchair) preoperatively, at discharge, and after 2 years. We determined improvements or declines in the patient's mobility based on changes in the classification levels. The analysis focused on the factors contributing to the deterioration of postoperative mobility. RESULTS: Two years postoperatively, 87% of patients maintained or improved mobility. However, 27% showed decreased mobility status at discharge, associated with a lower rate of home discharge (49% vs. 80% in the maintained mobility group) and limited improvement in mobility status (35% vs. 5%) after 2 years. Notably, postoperative increases in thoracic kyphosis (7.0 ± 12.1 vs. 2.0 ± 12.4°, p = 0.002) and lower lumbar lordosis (4.2 ± 13.1 vs. 1.8 ± 12.6°, p = 0.050) were substantial factors in mobility decline. CONCLUSION: Postoperative mobility often temporarily decreases but generally improves after 2 years. However, an overcorrection in sagittal alignment, evidenced by increased TK, could detrimentally affect patients' mobility status. Transient mobility decline associated with overcorrection may require further rehabilitation or hospitalization. Further studies are required to determine the biomechanical effects of surgical correction on mobility.

Examining the influence of body fat distribution on standing balance and functional performance in overweight female patients with degenerative lumbar disease.

Introduction: Degenerative lumbar disease (DLD) is a prevalent disorder that predominantly affects the elderly population, especially female. Extensive research has demonstrated that overweight individuals (categorized by body fat distribution) have a higher susceptibility to developing DLD and an increased risk of falling. However, there is limited research available on the standing balance and functional performance of overweight females with DLD. Aims: To determine the impact of body fat distribution on standing balance and functional performance in overweight females with DLD. Methods: This cross-sectional study evaluated thirty females with DLD were categorized into three types of body fat distribution based on body mass index (BMI) and waist-hip ratio, specifically as android-type, gynoid-type, and normal weight groups. In addition, a control group of ten age-matched females with normal weight was recruited. The Visual Analogue Scale, Roland Morris Disability Questionnaire, Cobb angle (Determined using x-ray), and body composition (Determined using the InBody S10), were conducted only on the DLD groups. All participants were assessed standing balance in the anteroposterior and mediolateral directions. The functional assessments included timed-up-and-go and 5-times-sit-to-stand tests. Results: There were 10 people in each group. Android-type (Age = 65.00 ± 6.34 years; BMI = 26.87 ± 2.05 kg/m2), Gynoid-type (Age = 65.60 ± 4.99 years; BMI = 26.60 ± 1.75 kg/m2), Normal weight (Age = 65.70 ± 5.92 years; BMI = 22.35 ± 1.26 kg/m2), and Control (Age = 65.00 ± 5.23 years; BMI = 22.60 ± 1.12 kg/m2). The android-type group had higher body fat, visceral fat, and lower muscle mass (p < 0.05), along with an increased Cobb angle (p < 0.05). They showed greater ellipse area, total excursion, and mean distance in the anteroposterior direction (p < 0.05). During the functional performance assessments, the android-type group had longer durations in both the 5-times-sit-to-stand and timed-up-and-go tasks (p < 0.05). Conclusion: Our study found that android-type overweight individuals showed postural instability, reduced functional performance, and insufficient lower limb muscle strength and mass. These findings might help physical therapists in planning interventions, as they imply that patients with DLD may require specific types of standing balance training and lower extremities muscle-strengthening based on their body fat distribution. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05375201.

Blending Self-Assembled Monolayers for Enhanced Band Alignment and Improved Morphology in p-i-n Perovskite Photodetectors.

Perovskite photodetectors, devices that convert light to electricity, require good extraction and low noise levels to maximize the signal-to-noise ratio. Self-assembling monolayers (SAMs) have been shown to be effective hole transport materials thanks to their atomic layer thickness, transparency, and energetic alignment with the valence band of the perovskite. While efforts are being made to reduce noise levels via the active layer, little has been done to reduce noise via SAM interfacial engineering. Herein, we report hybrid perovskite photodetectors with high detectivity by blending two different SAMs (2-PACz and Me-4PACz). We find that with a 1:1 2-PACz:Me-4PACz ratio (by weight), the devices achieved a low noise of 1 × 10-13 A Hz-1/2, a high responsivity of 0.41 A W-1 at 710 nm, and a specific detectivity of 6.4 × 1011 Jones at 710 nm at -0.5 V, outperforming its two counterparts. In addition to the improved noise levels in these devices, impedance spectroscopy revealed that higher recombination lifetimes of 0.85 µs were achieved for the 1:1 2-PACz:Me-4PACz-based photodetectors, confirming their low defect density.

Increased prevalence of valgus constitutional alignment subtypes in a South African arthritic population group using the coronal plane alignment of the knee (CPAK) classification.

BACKGROUND: Knee alignment philosophies and patient specific models to improve patient reported outcomes are gaining increasing attention. The coronal plane alignment of the knee (CPAK) classification describes nine knee phenotypes and then proposes surgical alignment strategies to achieve constitutional alignment. The CPAK classification has been validated in Australian, European, Asian and North American population groups. To date no African data has been analyzed using CPAK. METHODS: A total of 344 arthritic patients (608 knees) with appropriate long leg radiographs were classified based on the CPAK type. Measurements included mechanical hip-knee-angle(mHKA), medial proximal tibial angle (mMPTA) and lateral distal femoral angle (mLDFA) and the derived calculations of joint line obliquity (JLO) and arithmetic hip-knee-angle (aHKA). RESULTS: The sample population was 77.9% (n = 268) female with a mean age of 68.4 ± 9.2 years. The most common CPAK types in order were type 3 (n = 174; 28.6%), type 2 (n = 155; 25.5%), type 1 (n = 94; 15.5%) and type 6 (n = 80; 13.2%). The most common limb alignment types were valgus (CPAK types 3,6,9; 41.8%). CONCLUSION: This study, which investigated arthritic patients from a single institution in South Africa, shows a divergence of CPAK phenotypic knee patterns relative to other international studies, with much higher proportions of valgus phenotypes (3 and 6). This regional difference should be further investigated in other South African and African population samples and used to adapt the surgical strategies employed by local surgeons.

Sociability across Eastern-Western cultures: Is it the same underlying construct?

In this study, we examined cross-cultural differences in sociability, a core personality facet of the higher order extraversion trait, which has been reported at lower levels in Eastern versus Western cultures several decades ago. Up until now, however, East-West cultural comparisons on the Western-defined construct of sociability have been limited, despite the extensive research published on extraversion indicating that this personality dimension is globally relevant across cultures. Following current practices, we first assessed for measurement invariance (MI) on the Cheek and Buss sociability scale between Chinese (n = 816, 47.2% male, M = 18.51 years, SD = 1.26 years) and Canadian (n = 995, 30.8% male, M = 19.62 years, SD = 1.25 years) young adult samples to ensure any comparisons would be valid and meaningful. Results from a multigroup confirmatory factor analysis (exact invariance) showed that there was measurement non-invariance at the scalar level in the sociability construct across country and country by sex, and the newer alignment method (approximate invariance) confirmed these results, suggesting that mean level comparisons of sociability were biased and noninformative. Our findings indicated that although a few of the higher-level personality dimensions such as extraversion are considered universal, the facets underlying their meaning, like sociability, are not as clearly delineated between cultures. Alongside the present-day pursuit of understanding personality across cultures through an indigenous measurement lens in tandem with the notion of universality, researchers should also consider narrowing their focus onto lower-level facets, each of which is likely to be uniquely embedded into a cultural context.

Mechanically aligned total knee arthroplasty does not yield uniform outcomes across all coronal plane alignment of the knee (CPAK) phenotypes.

PURPOSE: Patient dissatisfaction rates following total knee arthroplasty (TKA) reported in the literature reach 20%. The optimal coronal alignment is still under debate. The aim of this retrospective study was to compare clinical outcomes in different coronal plane alignment of the knee (CPAK) phenotypes undergoing mechanically aligned (MA) TKA. The hypothesis was that knees with preoperative varus arithmetic hip-knee-ankle angle (aHKA) would achieve inferior clinical outcomes after surgery compared to other aHKA categories. Additionally, another objective was to assess CPAK phenotypes distribution in the study population. METHODS: A retrospective selection was made of 180 patients who underwent MA TKA from April 2021 to December 2022, with a 1-year follow-up. Coronal knee alignment was classified according to the CPAK classification. Clinical outcome evaluations were measured using the Knee Society Score (KSS), Oxford Knee Score (OKS), Short Form Survey 12 and Forgotten Joint Score (FJS). Differences in clinical outcomes were considered statistically significant with a p value <0 .05. RESULTS: Patients with varus aHKA achieved significantly inferior outcomes at final follow-up compared to other aHKA categories in KSS pt. 1 (79.7 ± 17.2 vs. 85.6 ± 14.7; p = 0.028), OKS (39.2 ± 9.2 vs. 42.2 ± 7.2; p = 0.019) and FJS (75.4 ± 31.0 vs. 87.4 ± 22.9; p =0 .003). The most common aHKA category was the varus category (39%). The most common CPAK phenotypes were apex distal Types I (23.9%), II (22.8%) and III (13.3%). CONCLUSION: MA TKA does not yield uniform outcomes across all CPAK phenotypes. Varus aHKA category shows significantly inferior results at final follow-up. The most prevalent CPAK categories are varus aHKA and apex distal JLO, with phenotypes I, II and III being the most common. However, their gender distribution varies significantly. LEVEL OF EVIDENCE: Level IV.

Femorotibial angle scan-rescan reproducibility: A high-precision calculation on a large cohort.

PURPOSE: Femorotibial angle (FTA) is a convenient measure of coronal knee alignment that can be extracted from a short knee radiograph, avoiding the additional radiation exposure and specialist equipment required for full-leg radiographs. While intra- and inter-reader reproducibility from the same image has been reported, the full scan-rescan reproducibility across images, as calculated in this study, has not. METHODS: In this study, 4589 FTA measurement pairs from 2586 subjects acquired a year apart were used to estimate FTA scan-rescan reproducibility using data from the Osteoarthritis Initiative. Subjects with radiographic progression of osteoarthritis or other conditions that may cause a change in coronal knee alignment were excluded. Measurement pairs were analysed using paired-samples  t $t$ tests to detect differences and compared to symptomatic changes in Western Ontario and McMaster Universities Arthritis Index scores for joint pain, stiffness and physical function to detect correlations. RESULTS: The 95% limit of agreement and the paired-samples correlation were calculated with high precision to be [-1.76°, +1.78°] and 0.938, considerably worse than the corresponding figures for intra- and inter-reader reproducibility, without relation to symptomatic or radiographic changes in knee condition. This error will weakly attenuate R 2 ${R}^{2}$ and r $r$ values from their true values in correlative studies involving FTA. The realistic maximum value for R 2 ${R}^{2}$ is 87% and for Pearson's r $r$ is 93%. CONCLUSION: The scan-rescan reproducibility in FTA is almost double the intra- and inter-reader reliability from a single scan. At almost ±2° accuracy, FTA is inappropriate for surgical use, but it is sufficiently reproducible to produce good correlations in studies predicting disease incidence and progression. LEVEL OF EVIDENCE: Level II, retrospective study.

Dual Hole Transport Layers Heterojunction and Band Alignment Engineered Mo:BiVO4 Photoanodes for Efficient Water Splitting.

BiVO4-based photoanode is one of the most promising photoanodes for photoelectrocatalytic water splitting. However, the serious problem of interface charge recombination limits its further development. Here, a Mo:BiVO4/NiOx/CPF-TCzB/NiCoBi photoanode is constructed with double hole transport layer and an energy level gradient to achieve an effective photo-generated holes extraction and accumulation at the surface electrocatalyst. The conjugated polycarbazole framework CPF-TCzB is used as hole transport layer to eliminate the charge recombination center between Mo:BiVO4 and NiCoBi electrocatalyst and realize the extraction and storage of photo-generated hole; NiOx nanoparticles are further inserted between Mo:BiVO4 and CPF-TCzB to form a gradient energy level, eliminating the energy level barrier and optimizing band alignment. As a result, Mo:BiVO4/NiOx/CPF-TCzB/NiCoBi achieves a much higher photocurrent densities of 3.14 mA cm-2 than that of Mo:BiVO4 (0.42 mA cm-2) at 0.6 V versus RHE. This work provides an specific way to adjust the band structure of BiVO4-based photoanodes and realize efficient hole extraction and storage for PEC water splitting.

A comparative cohort study of surgical approaches for adult spinal deformity at a minimum 2-year follow-up.

STUDY DESIGN: This study was a retrospective multi-center comparative cohort study. MATERIALS AND METHODS: A retrospective institutional database of operative adult spinal deformity patients was utilized. All fusions > 5 vertebral levels and including the sacrum/pelvis were eligible for inclusion. Revisions, 3 column osteotomies, and patients with < 2-year clinical follow-up were excluded. Patients were separated into 3 groups based on surgical approach: 1) posterior spinal fusion without interbody (PSF), 2) PSF with interbody (PSF-IB), and 3) anteroposterior (AP) fusion (anterior lumbar interbody fusion or lateral lumbar interbody fusion with posterior screw fixation). Intraoperative, radiographic, and clinical outcomes, as well as complications, were compared between groups with ANOVA and χ2 tests. RESULTS: One-hundred and thirty-eight patients were included for study (PSF, n = 37; PSF-IB, n = 44; AP, n = 57). Intraoperatively, estimated blood loss was similar between groups (p = 0.171). However, the AP group had longer operative times (547.5 min) compared to PSF (385.1) and PSF-IB (370.7) (p < 0.001). Additionally, fusion length was shorter in PSF-IB (11.4) compared to AP (13.6) and PSF (12.9) (p = 0.004). There were no differences between the groups in terms of change in alignment from preoperative to 2 years postoperative. There were no differences in clinical outcomes. While postoperative complications were largely similar between groups, operative complications were higher in the AP group (31.6%) compared to the PSF (5.4%) and PSF-IB (9.1) groups (p < 0.001). CONCLUSION: While there were differences in intraoperative outcomes (operative time and fusion length), there were no differences in postoperative clinical or radiographic outcomes. AP fusion was associated with a higher rate of operative complications.

Unveiling the evolution of policies for enhancing protein structure predictions: A comprehensive analysis.

Predicting protein structure is both fascinating and formidable, playing a crucial role in structure-based drug discovery and unraveling diseases with elusive origins. The Critical Assessment of Protein Structure Prediction (CASP) serves as a biannual battleground where global scientists converge to untangle the intricate relationships within amino acid chains. Two primary methods, Template-Based Modeling (TBM) and Template-Free (TF) strategies, dominate protein structure prediction. The trend has shifted towards Template-Free predictions due to their broader sequence coverage with fewer templates. The predictive process can be broadly classified into contact map, binned-distance, and real-valued distance predictions, each with distinctive strengths and limitations manifested through tailored loss functions. We have also introduced revolutionary end-to-end, and all-atom diffusion-based techniques that have transformed protein structure predictions. Recent advancements in deep learning techniques have significantly improved prediction accuracy, although the effectiveness is contingent upon the quality of input features derived from natural bio-physiochemical attributes and Multiple Sequence Alignments (MSA). Hence, the generation of high-quality MSA data holds paramount importance in harnessing informative input features for enhanced prediction outcomes. Remarkable successes have been achieved in protein structure prediction accuracy, however not enough for what structural knowledge was intended to, which implies need for development in some other aspects of the predictions. In this regard, scientists have opened other frontiers for protein structural prediction. The utilization of subsampling in multiple sequence alignment (MSA) and protein language modeling appears to be particularly promising in enhancing the accuracy and efficiency of predictions, ultimately aiding in drug discovery efforts. The exploration of predicting protein complex structure also opens up exciting opportunities to deepen our knowledge of molecular interactions and design therapeutics that are more effective. In this article, we have discussed the vicissitudes that the scientists have gone through to improve prediction accuracy, and examined the effective policies in predicting from different aspects, including the construction of high quality MSA, providing informative input features, and progresses in deep learning approaches. We have also briefly touched upon transitioning from predicting single-chain protein structures to predicting protein complex structures. Our findings point towards promoting open research environments to support the objectives of protein structure prediction.