High Median Nerve Paralysis:Is the Hand of Benediction or Preacher's Hand A Correct Sign?

High median nerve injuries are commonly presented in textbooks as adopting the typical posture of hand of benediction or preacher’s hand. This study aimed to show that the hand of benediction or preacher’s hand is incorrectly associated with a high median nerve paralysis. METHODS: A retrospective review of four cases with a high median nerve injury is presented. Diagnosis of a high median nerve injury was performed by means of intraoperative findings, electrodiagnostic studies, or ultrasound imaging. None of the patients presented in this study had a hand of benediction on physical examination despite the presence of a high median nerve lesion. RESULTS: All four patients with high median nerve injuries showed a similar hand posture when attempting to make a fist. Firstly, the index finger still flexed at the metacarpophalangeal joint because of the ulnar innervated interossei muscles. Secondly the thumb is completely abducted at the carpometocarpal joint and extended at the interphalangeal joint. Lastly, middle finger flexion is possible due to dual innervation of its flexor digitorum profundus by the ulnar nerve as well as due to the quadriga phenomenon. CONCLUSIONS: The clinical appearance of a high median nerve palsy is different from the classical hand of benediction or preacher’s hand posture pointing finger. We have shown that this incorrect association can result in delayed referral of patients with high median nerve injuries

Simple and robust calibration procedure for k-linearization and dispersion compensation in optical coherence tomography

In Fourier-domain optical coherence tomography (FD-OCT), proper signal sampling and dispersion compensation are essential steps to achieve optimal axial resolution. These calibration steps can be performed through numerical signal processing, but require calibration information about the system that may require lengthy and complex measurement protocols. We report a highly robust calibration procedure that can simultaneously determine correction vectors for nonlinear wavenumber sampling and dispersion compensation. The proposed method requires only two simple mirror measurements and no prior knowledge about the system's illumination source or detection scheme. This method applies to both spectral domain and swept-source OCT systems. Furthermore, it may be implemented as a low-cost fail-safe to validate the proper function of calibration hardware such as k-clocks. We demonstrate the method's simple implementation, effectiveness, and robustness on both types of OCT systems

Comparison of the King’s and MiToS staging systems for ALS

Objective: To investigate and compare two ALS staging systems, King’s clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). Methods: Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman’s rank correlation. Results: For both systems, progressively higher stages occurred at progressively later proportions of the disease course, but the distribution differed between the two methods. King’s stage 3 corresponded to MiToS stage 1 most frequently, with earlier King’s stages 1 and 2 largely corresponding to MiToS stage 0 or 1. The Spearman correlation was 0.54. There was fair agreement between the two systems with kappa coefficient of 0.21. Conclusion: The distribution of timings shows that the two systems are complementary, with King’s staging showing greatest resolution in early to mid-disease corresponding to clinical or disease burden, and MiToS staging having higher resolution for late disease, corresponding to functional involvement. We therefore propose using both staging systems when describing ALS

The ReIMAGINE prostate cancer risk study protocol: A prospective cohort study in men with a suspicion of prostate cancer who are referred onto an MRI-based diagnostic pathway with donation of tissue, blood and urine for biomarker analyses

INTRODUCTION: The ReIMAGINE Consortium was conceived to develop risk-stratification models that might incorporate the full range of novel prostate cancer (PCa) diagnostics (both commercial and academic). METHODS: ReIMAGINE Risk is an ethics approved (19/LO/1128) multicentre, prospective, observational cohort study which will recruit 1000 treatment-naive men undergoing a multi-parametric MRI (mpMRI) due to an elevated PSA (≤20ng/ml) or abnormal prostate examination who subsequently had a suspicious mpMRI (score≥3, stage ≤T3bN0M0). Primary outcomes include the detection of ≥Gleason 7 PCa at baseline and time to clinical progression, metastasis and death. Baseline blood, urine, and biopsy cores for fresh prostate tissue samples (2 targeted and 1 non-targeted) will be biobanked for future analysis. High-resolution scanning of pathology whole-slide imaging and MRI-DICOM images will be collected. Consortium partners will be granted access to data and biobanks to develop and validate biomarkers using correlation to mpMRI, biopsy-based disease status and long-term clinical outcomes. RESULTS: Recruitment began in September 2019(n = 533). A first site opened in September 2019 (n = 296), a second in November 2019 (n = 210) and a third in December 2020 (n = 27). Acceptance to the study has been 65% and a mean of 36.5ml(SD+/-10.0), 12.9ml(SD+/-3.7) and 2.8ml(SD+/-0.7) urine, plasma and serum donated for research, respectively. There are currently 4 academic and 15 commercial partners spanning imaging (~9 radiomics, artificial intelligence/machine learning), fluidic (~3 blood-based and ~2urine-based) and tissue-based (~1) biomarkers. CONCLUSION: The consortium will develop, or adjust, risk models for PCa, and provide a platform for evaluating the role of novel diagnostics in the era of pre-biopsy MRI and targeted biopsy

CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses

The Arabidopsis ABA-Activated Kinase OST1 Phosphorylates the bZIP Transcription Factor ABF3 and Creates a 14-3-3 Binding Site Involved in Its Turnover

indicates that members of the Snf1-Related Kinases 2 family (SnRK2) are essential in mediating various stress-adaptive responses. Recent reports have indeed shown that one particular member, OPEN STOMATA (OST)1, whose kinase activity is stimulated by the stress hormone abscisic acid (ABA), is a direct target of negative regulation by the core ABA co-receptor complex composed of PYR/PYL/RCAR and clade A Protein Phosphatase 2C (PP2C) proteins. and that phospho-T451 is important for stabilization of ABF3. on T451 to create a 14-3-3 binding motif. In a wider physiological context, we propose that the long term responses to ABA that require sustained gene expression is, in part, mediated by the stabilization of ABFs driven by ABA-activated SnRK2s

X-chromosome and kidney function:evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research.</p

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology