SC-Track: a robust cell-tracking algorithm for generating accurate single-cell lineages from diverse cell segmentations.

Computational analysis of fluorescent timelapse microscopy images at the single-cell level is a powerful approach to study cellular changes that dictate important cell fate decisions. Core to this approach is the need to generate reliable cell segmentations and classifications necessary for accurate quantitative analysis. Deep learning-based convolutional neural networks (CNNs) have emerged as a promising solution to these challenges. However, current CNNs are prone to produce noisy cell segmentations and classifications, which is a significant barrier to constructing accurate single-cell lineages. To address this, we developed a novel algorithm called Single Cell Track (SC-Track), which employs a hierarchical probabilistic cache cascade model based on biological observations of cell division and movement dynamics. Our results show that SC-Track performs better than a panel of publicly available cell trackers on a diverse set of cell segmentation types. This cell-tracking performance was achieved without any parameter adjustments, making SC-Track an excellent generalized algorithm that can maintain robust cell-tracking performance in varying cell segmentation qualities, cell morphological appearances and imaging conditions. Furthermore, SC-Track is equipped with a cell class correction function to improve the accuracy of cell classifications in multiclass cell segmentation time series. These features together make SC-Track a robust cell-tracking algorithm that works well with noisy cell instance segmentation and classification predictions from CNNs to generate accurate single-cell lineages and classifications.

A multicenter, randomized, double-blinded, placebo-controlled, phase â ¢ study evaluating the efficacy and safety of Xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Xeligekimab is a fully human monoclonal antibody that selectively neutralizes IL-17A and had shown potential efficacy in preliminary trials. OBJECTIVE: To evaluate the efficacy and safety of Xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200 mg Xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by extending the treatment schedule to GR1501 every 4 weeks for further 40 weeks. Efficacy was assessed by evaluating the Physician's Global Assessment (PGA) 0/1 and Psoriasis Area and Severity Index (PASI) 75/90/100 improvement. The safety profile was also evaluated. RESULTS: At week 12, The PASI 75/90/100 were achieved in 90.7%/74.4%/30.2%% patients in GR1501 group compared with 8.6%/1.4%/0% patients in placebo group, respectively. The PGA 0/1 were achieved in 74.4% patients of GR1501 group and 3.6% patients in placebo group, respectively. The PASI 75 and PGA 0/1 maintained until week 52. No unexpected adverse events were observed. CONCLUSION: Xeligekimab showed high efficacy and is well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.

The Typical Nail Lichen Planus Severity Index: An Outcome Instrument for Typical Nail Lichen Planus.

INTRODUCTION: Despite numerous treatment options for nail lichen planus (NLP), a validated method for measuring the severity of NLP and therapeutic response in clinical trials is absent. The aim of the study was to develop and validate a measurement instrument, Typical Nail Lichen Planus Severity Index (tNLPSI), for typical NLP that could be used in clinical trials. METHODS: A total of 48 patients pathologically confirmed with typical NLP were enrolled in this study. Five dermatologists were trained to use the tNLPSI activity scale and the Physician's Global Assessment (PGA) scale to score samples independently to estimate inter-rater and intra-rater reliability across two sessions. In addition, tNLPSI activity scores were compared with PGA scores to assess the construct validity. RESULTS: The tNLPSI activity scale had excellent internal consistency and inter-rater reliability (Cronbach's alpha 0.990; ICC = 0.954; 95% CI = 0.930-0.971), and the correlations between the different graders' scores indicate good consistency (rp = 0.934-0.968). In addition, the tNLPSI activity scale demonstrated high intra-rater reliability (ICC = 0.996; 95% CI = 0.993-0.998), showing good reproducibility. And tNLPSI activity scores and PGA scores showed good construct validity (Spearman's rho = 0.941 and Spearman's rho = 0.903-0.935, respectively; p < 0.01). CONCLUSION: The tNLPSI activity scale was demonstrated to be consistent, reliable, reproducible, and feasible, making it a potential valuable tool for evaluating the treatment response in typical NLP clinical trials.

Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion.

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

Identification and validation of a novel prognosis model based on m5C-related long non-coding RNAs in colorectal cancer.

BACKGROUND: The prognosis of tumor patients can be assessed by measuring the levels of lncRNAs (long non-coding RNAs), which play a role in controlling the methylation of the RNA. Prognosis in individuals with colorectal adenocarcinoma (CRC) is strongly linked to lncRNA expression, making it imperative to find lncRNAs that are associated with RNA methylation with strong prognostic value. METHODS: In this study, by analyzing TCGA dataset, we were able to develop a risk model for lncRNAs that are associated with m5C with prognostic significance by employing LASSO regression and univariate Cox proportional analysis. There were a number of methods employed to ensure the model was accurate, including multivariate and univariate Cox regression analysis, Kaplan analysis, and receiver operating characteristic curve analysis. The principal component analysis, GSEA and GSVA analysis were used for risk model analysis. The CIBERSORT instrument and the TIMER database were used to evaluate the link between the immune cells that infiltrate tumors and the risk model. In vitro experiments were also performed to validate the predicted m5C-related significant lncRNAs. RESULTS: The m5c regulators were differentially expressed in colorectal cancer and normal tissue. Based on the screening criteria and LASSO regression, 11 m5c-related lncRNAs were identified for developing the prognostic risk model. Multivariate and univariate Cox regression analysis showed the risk score is a crucial prognostic factor in CRC patients. The 1-year, 3-year, and 5-year AUC curves showed the risk score was higher than those identified for other clinicopathological characteristics. A nomogram using the risk score as a quantitative tool was developed for predicting patients' outcomes in clinical settings. In addition, the risk profile of m5C-associated lncRNAs can discriminate between tumor immune cells' characteristics in CRC. Mutation patterns and chemotherapy were analyzed between high- and low- risk groups of CRC patients. Moreover, TNFRSF10A-AS1 was chosen for the in vitro verification of the m5C-connected lncRNA to demonstrate impressive effects on the proliferation, migration and invasion of CRC cells. CONCLUSION: A risk model including the prognostic value of 11 m5C-associated lncRNAs proves to be a useful prognostic tool for CRC and improves the care of patients suffering from CRC based on these findings.

Prophylactic Central Neck Dissection Based on Preoperative Imaging and Intraoperative Surgeon's Palpation Versus Total Thyroidectomy Alone for Papillary Thyroid Cancer.

INTRODUCTION: To compare the overall morbidity and recurrence of papillary thyroid cancer (PTC) after total thyroidectomy (TT) with or without prophylactic central compartment neck dissection (CCND) in cases of both preoperative and intraoperative nonsuspicious central lymph nodes (CLNs). METHODS: A total of 570 PTC patients who harbored no preoperative and intraoperative suspicious CLNs at two institutions were enrolled. They were randomly assigned to TT alone or TT with prophylactic CCND (pCCND) after intraoperative assessment of CLNs during the surgery. Lymph nodes that were hard or large enough to be palpated were regarded as suspicious metastatic lymph nodes during the surgery. The characteristics, postoperative complications, and locoregional recurrence of the two groups were recorded and compared. RESULTS: With a median follow-up of 5 y, the rates of lymph node recurrence in the TT alone and TT with pCCND groups were similar (7.3% versus 4.6%, P = 0.247), but there were significantly higher rates of overall morbidity (6.6% versus 19.1%, P < 0.001) when pCCND was performed. CONCLUSIONS: pCCND is not recommended for patients with clinically node-negative PTC preoperatively and intraoperatively because of the high complication rate and lack of benefit of reducing recurrence.

Efficacy and Safety of AbobotulinumtoxinA for the Treatment of Glabellar Lines in Chinese Patients: A Pivotal, Phase 3, Randomized, Double-Blind and Open-Label Phase Study.

BACKGROUND: Various botulinumtoxinA formulations are approved for glabellar lines treatment worldwide, including abobotulinumtoxinA (Dysport®). OBJECTIVES: Assess abobotulinumtoxinA superiority versus placebo and non-inferiority versus active comparator (onabotulinumtoxinA; Botox®), for the treatment of Chinese patients with moderate/severe glabellar lines. METHODS: Phase 3, randomized study (NCT02450526) comprising a double-blind (cycle 1) phase and an open-label (cycles 2-5) phase. Patients received abobotulinumtoxinA 50 units or matching placebo (5:1), active comparator (onabotulinumtoxinA 20 units) or matching placebo (5:1). In cycles 2-5, eligible patients were retreated with abobotulinumtoxinA only. Responders had glabellar lines of none/mild severity. PRIMARY ENDPOINT: responder rates at cycle 1, day 29 at maximum frown with abobotulinumtoxinA versus placebo (for superiority; by investigator's live assessment [ILA] and subject's self-assessment [SSA]), and versus active comparator (for non-inferiority; by ILA). Treatment-emergent adverse events were recorded. RESULTS: Overall, 520 patients were randomized. Superiority and non-inferiority, respectively, were demonstrated for abobotulinumtoxinA versus placebo (ILA, SSA; both p < 0.0001) and abobotulinumtoxinA versus active comparator. AbobotulinumtoxinA efficacy was maintained over open-label cycles; median time to onset of efficacy was 2.0 days. After 6 months, 17% of patients treated with abobotulinumtoxinA remained responders. AbobotulinumtoxinA was well-tolerated. Safety results were in line with the known profile of abobotulinumtoxinA; adverse events rate decreased with repeated treatment. CONCLUSIONS: After a single injection, abobotulinumtoxinA demonstrated superiority versus placebo and non-inferiority versus onabotulinumtoxinA for the treatment of moderate-to-severe glabellar lines in Chinese patients. Multiple injections of abobotulinumtoxinA demonstrated efficacy and safety in the treatment of glabellar lines in Chinese patients. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Botulinum toxin injections can be used to smooth frown lines that appear between the eyebrows (known as glabellar lines) in patients who have moderate or severe frown lines. This study looked at how injections of a botulinum toxin (abobotulinumtoxinA [aboBoNT-A]) could help with smoothing frown lines in patients from China compared with an injection of another botulinum toxin called onabotulinumtoxinA (onaBoNT-A) or placebo (saltwater, no treatment). The study included 520 patients from China, 18­65 years old, who had moderate or severe frown lines. All patients received a first injection of either aboBoNT-A, onaBoNT-A, or saltwater, and were studied for 12 weeks. After the first injection, patients could receive up to four more injections of aboBoNT-A, given at 12-week intervals, if their frown lines became moderate or severe again. Most patients (92%) had not previously received any botulinum toxin injections. The results showed that single and repeat injections of aboBoNT-A helped to smooth moderate and severe frown lines. The researchers found that after a single injection, aboBoNT-A was superior to no treatment and was similar to onaBoNT-A. Patients recorded a response to aboBoNT-A after 2 days and the response lasted for 6 months in 17% of patients. The effect on frown lines was maintained after repeat injections and aboBoNT-A was well tolerated by patients. These results suggest that aboBoNT-A is a suitable treatment for smoothing frown lines in patients from China with moderate to severe frown lines.

Clinical efficacy of flap transplantation combined with vacuum sealing drainage and methylprednisolone and cyclosporine in the treatment of pyoderma gangrenosum.

This study was aimed to evaluate the clinical efficacy of flap transplantation combined with vacuum sealing drainage and methylprednisolone and cyclosporine in the treatment of ulcer wound of patients with pyoderma gangrenosum (PG). From August 2014 to February 2022, 30 patients with pyoderma gangrenosum ulcer wounds were selected as the research objects and randomly divided into the observation group (n = 12) and the control group (n = 18) in this retrospective study. The patients in observation group were treated with VSD combined with flap transplantation and immunosuppressive agent treatment, while the control group was treated with normal dressing change combined with hormone and cyclosporine. The ulcer wound healing time and dressing change times were compared between the two groups. All the 30 cases of two groups healed after corresponding treatment. The wound healing time of ulcer in the observation group was 35-40 days, with an average healing time of (35.83 ± 1.95) days, and the wound healing time of the control group was 60-200 days, with an average healing time of (44.14 ± 9.67) days. The healing time of observation groups was significantly shorter than that in the control group (t = 4.652, P < .05). The frequency of dressing change in the observation group was seven-eight times, with an average of (7.17 ± 0.39) times, and the frequency of dressing change in the control group was 75-86 times, with an average of (79.22 ± 3.62) times. The difference between the two groups was significant (t = 6.214, P < .05). The treatment of VSD combined with flap transplantation and immunosuppressive agent treatment promote ulcer wound healing of pyoderma gangrenosum.

Single-cell and WGCNA uncover a prognostic model and potential oncogenes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Single-cell transcriptome sequencing (scRNA-seq) can provide accurate gene expression data for individual cells. In this study, a new prognostic model was constructed by scRNA-seq and bulk transcriptome sequencing (bulk RNA-seq) data of CRC samples to develop a new understanding of CRC. METHODS: CRC scRNA-seq data were downloaded from the GSE161277 database, and CRC bulk RNA-seq data were downloaded from the TCGA and GSE17537 databases. The cells were clustered by the FindNeighbors and FindClusters functions in scRNA-seq data. CIBERSORTx was applied to detect the abundance of cell clusters in the bulk RNA-seq expression matrix. WGCNA was performed with the expression profiles to construct the gene coexpression networks of TCGA-CRC. Next, we used a tenfold cross test to construct the model and a nomogram to assess the independence of the model for clinical application. Finally, we examined the expression of the unreported model genes by qPCR and immunohistochemistry. A clone formation assay and orthotopic colorectal tumour model were applied to detect the regulatory roles of unreported model genes. RESULTS: A total of 43,851 cells were included after quality control, and 20 cell clusters were classified by the FindCluster () function. We found that the abundances of C1, C2, C4, C5, C15, C16 and C19 were high and the abundances of C7, C10, C11, C13, C14 and C17 were low in CRC tumour tissues. Meanwhile, the results of survival analysis showed that high abundances of C4, C11 and C13 and low abundances of C5 and C14 were associated with better survival. The WGCNA results showed that the red module was most related to the tumour and the C14 cluster, which contains 615 genes. Lasso Cox regression analysis revealed 8 genes (PBXIP1, MPMZ, SCARA3, INA, ILK, MPP2, L1CAM and FLNA), which were chosen to construct a risk model. In the model, the risk score features had the greatest impact on survival prediction, indicating that the 8-gene risk model can better predict prognosis. qPCR and immunohistochemistry analysis showed that the expression levels of MPZ, SCARA3, MPP2 and PBXIP1 were high in CRC tissues. The functional experiment results indicated that MPZ, SCARA3, MPP2 and PBXIP1 could promote the colony formation ability of CRC cells in vitro and tumorigenicity in vivo. CONCLUSIONS: We constructed a risk model to predict the prognosis of CRC patients based on scRNA-seq and bulk RNA-seq data, which could be used for clinical application. We also identified 4 previously unreported model genes (MPZ, SCARA3, MPP2 and PBXIP1) as novel oncogenes in CRC. These results suggest that this model could potentially be used to evaluate the prognostic risk and provide potential therapeutic targets for CRC patients.

Silencing of Rab23 by siRNA inhibits ultraviolet B-induced melanogenesis via downregulation of PKA/CREB/MITF.

Recent investigations have shown that the Rab family of GTPases is associated with all aspects of melanogenesis. However, the effect of Rab23, which localizes to the plasma membrane and regulates the endocytic pathway within eukaryotic cells, in melanogenesis has not been reported. To understand the role of Rab23 in UVB-induced melanogenesis, we evaluated changes in the level of melanin, activity of tyrosinase and levels of melanogenesis-related proteins such as microphthalmia transcription factor and tyrosinase-related protein-1 (TRP-1) and the melanosome transport-related protein complex Rab27a-melanophilin-myosin Va after the downregulation of Rab23 in B16F10 and SK-MEL-2 cells with or without UVB irradiation. Our results showed that downregulating Rab23 reduced the melanin level and tyrosinase activity and inhibited the expression of proteins involved in UVB-induced melanogenesis. Rab23 colocalized with mature melanosomes marked with TRP-1. Furthermore, downregulating Rab23 induced the abnormal accumulation of melanosomes around the nucleus. We demonstrated that the downregulation of Rab23 inhibited melanin synthesis and melanosome transport by decreasing the PKA/CREB/MITF pathway, which is the key regulator of UVB-induced melanogenesis.

CD8+ mycosis fungoides with ichthyosiform clinical presentation and angiocentric feature.

Mycosis fungoides (MF) is characterized by epidermotropic atypical lymphocytes infiltrate with α/ß T-helper memory immunophenotype (ßF1+, CD3+, CD4+, CD45Ro+, and CD8-). Angiocentricity is always associated with aggressive behavior or poor outcome in primary or secondary cutaneous lymphomas. Rare cases of angiocentric MF with a T-cytotoxic immunophenotype (CD3+, CD4-, CD8+, TIA-1+) have been described. Here, we report a 27-year-old man diagnosed with MF, clinically presenting with ichthyosiform lesions on his trunk and limbs. Biopsy demonstrated a CD3+ and CD8+ atypical lymphocytic infiltrate with marked epidermotropism and angiocentricity. Awareness of this rare MF variant with unusual clinicopathological characteristics is important to avoid misdiagnosis.

Vaccine-induced erythrodermic psoriasis in a child successfully treated with secukinumab: A case report and brief literature review.

We report a case of a 7-year-old male patient with vaccine-induced erythrodermic psoriasis (EP) complicated by pulmonary infection, hypoproteinemia, and liver dysfunction successfully treated with secukinumab in combination with symptomatic and supportive therapy. The patient presented with diffuse flushing on the head, face, trunk, and limbs, which were covered with chaff-like white scales in the rash-affected area, with no blisters, pustules, and no apparent abnormalities in the palms, soles, nails, and joints. Histopathology analysis revealed hyperkeratosis, focal parakeratosis, thinning or effacement of the granular layer, psoriasiform hyperplasia of the epidermis, neutrophilic microabscess formation in the upper part of the epidermis, edema of the dermal papilla, dilation of blood vessels, and lymphocyte infiltration. The patient was eventually diagnosed with EP. At weeks 0, 1, and 2, the patient received a subcutaneous injection of 150 mg secukinumab (three injections). Fluticasone propionate ointment, taccathitol ointment, yellow vaseline, and other drugs were also given topically. Following 2 weeks of treatment, the child's skin lesions resolved significantly with only slight pigmentation remaining and the Psoriasis Area and Severity Index (PASI) score decreased from 37.5 to 7.5 (PASI 75). Thereafter, 150 mg secukinumab was injected every 4 weeks until the last dose at 18 weeks (four more injections). After 18 weeks, the child's lesion resolved entirely (PASI 100), and no adverse effects were reported.

Recurrent Laryngeal Nerve with Loss of Signal During Monitored Thyroidectomy: Percentage Reduction in Sum of the Amplitude of Left and Right Channel.

PURPOSE: The prognostication for the injured recurrent laryngeal nerve (RLN) with incomplete loss of signal (LOS) and its function outcome have not been well unified. A warning criterion was proposed to predict RLN injury during monitored thyroidectomy. METHODS: A retrospective review of prospectively collected data from consecutive 357 patients with 560 nerves at risk was conducted. Vocal cords mobility with laryngoscope was performed preoperatively, on the second day, and once a month postoperatively until complete recovery. Different cutoff values of the percentage reduction in sum of the amplitude of left and right channel at the end of the surgery, for postoperative vocal cord paralysis (VCP) prediction were compared. RESULTS: Percentage reduction in sum of the amplitude of left and right channel at the end of operation ranged from 30.2 to 63.6% in 27 nerves with incomplete LOS (absolute amplitude value of final R2 > 100 µV with reduction > 50% of R1). Seven (1.25%) nerves experienced transient postoperative VCP, in which one nerve with postoperative VCP showed no amplitude reduction. The positive predictive value of VCP for the sum amplitude reduction exceeding 30, 40, 50, and 60% was 22.2, 40, 85.7, and 100%, respectively. Accuracy was 96.1, 98.2, 99.6, 99.4%, respectively. CONCLUSION: Percentage reduction in sum of the amplitude of left and right channel is a meaningful method to improve the accuracy of VCP prediction. When the sum amplitude reduction ≥ 50%, surgeons should consider the possibility of postoperative VCP and correct some surgical maneuvers.

Dosage optimization of voriconazole in children with haematological malignancies based on population pharmacokinetics.

WHAT IS KNOWN AND OBJECTIVES: Voriconazole has a complex pharmacokinetic profile and exhibits different pharmacokinetic characteristics in adults and children. Nevertheless, few studies have been conducted on the population pharmacokinetics (PPK) of voriconazole in children with haematological malignancies. This study aims to build a PPK model and propose a suitable voriconazole treatment scheme for children with haematological malignancies. METHODS: We retrospectively collected 146 samples from 67 children aged from 1.08 to 17.92 years. The PPK model was established using nonlinear mixed effects modelling (NONMEM). Dosage simulations were conducted on the basis of the final model's covariates. RESULTS AND DISCUSSION: Data were fully characterized by a one-compartment model with first-order absorption and elimination. The weight (WT), CYP2C19 phenotype, and Albumin (ALB) were notable covariates for clearance (CL). The typical values of CL, the volume of distribution (V), and oral bioavailability (F) were 2.29 L/h, 76 L, and 0.902, respectively. The proposed doses for different CYP2C19 genotypes were presented in this ranking: EM (extensive metabolizer) > IM (intermediate metabolizer) > PM (poor metabolizer). Furthermore, higher dosages for light WT patients were recommended while lower ALB levels required lower doses. The probability of achieving the target (PTA) for the recommended doses ranged from 72.2% to 99%. WHAT IS NEW AND CONCLUSION: We successfully built a voriconazole PPK model for children with hematologic malignancies. Dosing regimens were developed for different patients based on the final model, which could enhance the rational use of voriconazole in children with haematological malignancies.

A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma.

BACKGROUND: Numerous studies have implicated autophagy in the pathogenesis of thyroid carcinoma. This investigation aimed to establish an autophagy-related gene model and nomogram that can help predict the overall survival (OS) of patients with differentiated thyroid carcinoma (DTHCA). METHODS: Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. We also downloaded autophagy-related genes (ARGs) from the Gene Set Enrichment Analysis website and the Human Autophagy Database. First, we assigned patients into training and testing groups. R software was applied to identify differentially expressed ARGs for further construction of a protein-protein interaction (PPI) network for gene functional analyses. A risk score-based prognostic risk model was subsequently developed using univariate Cox regression and LASSO-penalized Cox regression analyses. The model's performance was verified using Kaplan-Meier (KM) survival analysis and ROC curve. Finally, a nomogram was constructed for clinical application in evaluating the patients with DTHCA. Finally, a 7-gene prognostic risk model was developed based on gene set enrichment analysis. RESULTS: Overall, we identified 54 differentially expressed ARGs in patients with DTHCA. A new gene risk model based on 7-ARGs (CDKN2A, FGF7, CTSB, HAP1, DAPK2, DNAJB1, and ITPR1) was developed in the training group and validated in the testing group. The predictive accuracy of the model was reflected by the area under the ROC curve (AUC) values. Univariate and multivariate Cox regression analysis indicated that the model could independently predict the prognosis of patients with THCA. The constrained nomogram derived from the risk score and age also showed high prediction accuracy. CONCLUSIONS: Here, we developed a 7-ARG prognostic risk model and nomogram for differentiated thyroid carcinoma patients that can guide clinical decisions and individualized therapy.

Utilization of intraoperative neuromonitoring during the Woodward procedure for treatment of Sprengel deformity.

BACKGROUND: Brachial plexus injury (BPI) leading to palsy of the upper extremities is the most serious complication of the Woodward procedure for treatment of Sprengel deformity. Intraoperative neuromonitoring (IONM) is widely used for detecting emerging spinal cord or peripheral nerve injury during spinal and shoulder surgery. However, to date, its utilization in pediatric patients with Sprengel deformity is limited. Furthermore, it remains unclear whether IONM can help prevent BPI during surgery. The purpose of the current study was to assess the feasibility and effectiveness of IONM for early identification and prevention of nerve injury during the Woodward procedure. METHODS: We retrospectively reviewed the records of patients who underwent the Woodward procedure for Sprengel deformity at our institution between January 2017 and January 2020. IONM, including somatosensory evoked potentials (SEP) and motor evoked potentials (MEPs), was performed in all patients. Detailed IONM data were collected and analyzed. Preoperative and postoperative cosmetic appearance (according to the Cavendish classification), shoulder joint abduction function, and radiologic evaluation of the scapula were reviewed. Surgical complications were recorded. RESULTS: Forty-six patients (19 girls, 27 boys) were included (mean age, 5.1 ± 2.1 years). Both SEP and MEP (amplitude of the abductor pollicis) were successfully performed (100%). MEP alerts occurred in 3 patients (6.5%). After scapula position adjustment, signals recovered in 2 patients and remained unchanged in 1 patient-this patient exhibited postoperative motor deficits that resolved completely by 4 months recovery. The SEP amplitudes decreased in all 3 patients but did not reach the warning criteria. Forty patients were classified as grade III and 6 as grade IV in the Cavendish classification, whereas 35 patients were classified as grade II and 11 as grade III in the Rigault scale. The preoperative Cavendish grade was III (III, IV) and the postoperative Cavendish grade was I (I, II) (χ2 = 88.098, P < .001). The preoperative Rigault grade was II (II, III) and the postoperative Rigault grade was I (I, II) (χ2 = 62.133, P < .001). The mean arc of shoulder joint abduction improved from 99° ± 8° to 167° ± 7° (t = -45.871, P < .001) after surgery. Except for temporary motor deficits detected in 1 patient, no other postoperative complications were observed through the time of final follow-up. CONCLUSION: IONM during the Woodward procedure for Sprengel deformity is feasible and effective in detecting intraoperative neurologic changes and may be effective in preventing BPI associated with surgery.

Plasma-Sprayed (Bi2O3)0.705 (Er2O3)0.245 (WO3)0.05 Electrolyte for Intermediate-Temperature Solid Oxide Fuel Cells (IT-SOFCs).

Stabilized bismuth oxide material with fluorite structure (δ-Bi2O3) has been studied as a promising electrolyte material for intermediate temperature solid oxide fuel cells (IT-SOFCs) due to its high oxygen ion conductivity in mediate temperature. Especially, the ternary system Bi2O3-Er2O3-WO3 is widely concerned for its high ionic conductivity and thermal stability. In this study, regarding its low melting point, the possibility to deposit dense Bi2O3-Er2O3-WO3 ((Bi2O3)0.705 (Er2O3)0.245 (WO3)0.05, EWSB) electrolyte by plasma spraying was examined. It was confirmed that the sintered EWSB bulk presents a high ion conductivity of 0.34 S cm-1 at 750 °C and excellent stability that indicates no structure transformation and conductivity degradation after annealing at 600 °C for 1000 h. The phase structure and cross-sectional microstructure of plasma-sprayed EWSB were characterized by XRD and SEM. Results showed that the as-plasma-sprayed EWSB presents a dense microstructure with well bonded lamellae. The XRD showed the formation of EWSB with δ-phase and a trace of ß-phase, while the ß-phase disappeared after annealing at 750 °C for 10 h. The deposited EWSB electrolyte presented the excellent ionic conductivity of 0.26 S cm-1 at 750 °C which can be directly applied to SOFC at intermediate temperature.

Recent Research Advances in Plasma Spraying of Bulk-Like Dense Metal Coatings with Metallurgically Bonded Lamellae.

Although thermal spray metallic coatings have been widely used for materials protection from wear, corrosion and oxidation, its porous feature limits the full utilization of materials potential. Moreover, the oxidation inherent to thermal spraying in the ambient atmosphere is detrimental to interlamellar bonding formation, which further degrades the performance of thermal spray metal coatings. How to tape out the full potential of spray materials in the form of the coating is a still great challenge to thermal spray coating technology. Facing such challenge, recent efforts have been made to deposit dense metallic coatings with sufficiently bonded lamellae by oxide-free molten droplets through atmospheric plasma spraying. In this paper, the strategies for depositing bulk-like metal coatings will be reviewed. The formation of the bulk-like coating through post-spray treatments is briefly reviewed including post-spray heat treatment and laser remelting following the brief introduction to the features of thermal spray metallic coatings. The effect of the substrate preheating temperature on the splat formation and subsequently the adhesion formation was examined to reveal the dominant limitation of resultant oxide scale. Then, the role of the deposition temperature on the formation of bulk-like metal deposits with neglecting the effect of oxidation during spraying by vacuum plasma spraying practices is shortly presented. The recent progress on the new strategies to develop spread-fusing bonding mechanism and in-situ in-flight deoxidizing mechanism through developing ultra-hot metallic droplets will be introduced. The thermodynamics and kinetics requirements for the in-situ in-flight deoxidizing through deoxidizer elements adding to alloy spray powders for achieving oxide-free molten droplets in the ambient atmosphere are examined. The conditions to develop the spread-fusing mechanism during the spreading of impacting molten metal droplet for metallurgical bonding are presented. It is obvious from this review paper that the realization of two mechanisms depends on both the spray materials design and heating control of in-flight particles. Through the generation of ultra-hot droplets by plasma spraying to achieve oxide-free molten droplets, strategically it will be possible to deposit bulk-like dense metallic coating through spread-fusing of splat surfaces with limited post-spray oxidation. Such strategies will tape out the full potential of coating materials and open up the new application fields for plasma spraying.

Structural, Genetic, and Serological Elucidation of Streptococcus pneumoniae Serogroup 24 Serotypes: Discovery of a New Serotype, 24C, with a Variable Capsule Structure.

Pneumococcal capsules are important in pneumococcal pathogenesis and vaccine development. Although conjugate vaccines have brought about a significant reduction in invasive pneumococcal disease (IPD) caused by vaccine serotypes, the relative serotype prevalence has shifted with the dramatic emergence of serotype 24F in some countries. Here, we describe 14 isolates (13 IPD and 1 non-IPD) expressing a new capsule type, 24C, which resembles 24F but has a novel serological profile. We also describe the antigenic, biochemical, and genetic basis of 24F and 24C and the related serotypes 24A and 24B. Structural studies show that 24B, 24C, and 24F have identical polysaccharide backbones [ß-Ribf-(1→4)-α-Rhap-(1→3)-ß-GlcpNAc-(1→4)-ß-Rhap-(1→4)-ß-Glcp] but with different side chains, as follows: 24F has arabinitol-phosphate and 24B has ribitol-phosphate. 24C has a mixture of 24F and 24B repeating units, with the ratio of ribitol to arabinitol being strain dependent. In contrast, the 24A capsule has a backbone without ß-Ribf but with arabinitol-phosphate and phosphocholine side chains. These structures indicate that factor-sera 24d and 24e recognize arabinitol and ribitol, respectively, which explains the serology of serogroup 24, including those of 24C. The structures can be genetically described by the bispecificity of wcxG, which is capable of transferring arabinitol or ribitol when arabinitol is limiting. Arabinitol is likely not produced in 24B but is produced in reduced amounts in 24C due to various mutations in abpA or abpB genes. Our findings demonstrate how pneumococci modulate their capsule structure and immunologic properties with small genetic changes, thereby evading host immune responses. Our findings also suggest a potential for new capsule types within serogroup 24.

Initial Dosage Optimization of Tacrolimus in Pediatric Patients With Thalassemia Major Undergoing Hematopoietic Stem Cell Transplantation Based on Population Pharmacokinetics.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for hematological disorders. Tacrolimus is widely used after HSCT, but it has highly interindividual variable pharmacokinetics. Population pharmacokinetics (PPK) researches of tacrolimus in children with ß-thalassemia major (ß-TM) undergoing HSCT are insufficient. OBJECTIVE: To establish a PPK model of tacrolimus in children with ß-TM and optimize initial dosing regimen for achieving target concentration of 5 to 15 ng/mL. METHODS: Data on patients aged <18 years were retrospectively collected from January 2017 to December 2018. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed-effects modeling. RESULTS: A data set of 55 patients with 332 concentrations was included. A 2-compartment model could best describe the pharmacokinetics of tacrolimus. The body surface area and gender were significant covariates in the final model. The typical value of clearance, the distribution volume of the central room, the distribution volume of the peripheral room, and the intercompartmental clearance were 5.05L/h, 4.33L, 155L, and 6.22L/h, respectively. The optimal initial dosing regimen of 0.03, 0.04, 0.05, 0.06, and 0.10 mg/kg were appropriate for female children with a weight (WT) of 50 to 10 kg. The regimen of 0.04, 0.05, 0.06, 0.07, and 0.12 mg/kg is suitable for male children with a WT of 50 to 10 kg. The probability of target attainment (PTA) of each regimen reached 91%. CONCLUSION AND RELEVANCE: A stable PPK model of tacrolimus was established. The proposed dosage regimen reached a good PTA, which could provide a reference for tacrolimus therapy.