DAESTB: inferring associations of small molecule-miRNA via a scalable tree boosting model based on deep autoencoder.

MicroRNAs (miRNAs) are closely related to a variety of human diseases, not only regulating gene expression, but also having an important role in human life activities and being viable targets of small molecule drugs for disease treatment. Current computational techniques to predict the potential associations between small molecule and miRNA are not that accurate. Here, we proposed a new computational method based on a deep autoencoder and a scalable tree boosting model (DAESTB), to predict associations between small molecule and miRNA. First, we constructed a high-dimensional feature matrix by integrating small molecule-small molecule similarity, miRNA-miRNA similarity and known small molecule-miRNA associations. Second, we reduced feature dimensionality on the integrated matrix using a deep autoencoder to obtain the potential feature representation of each small molecule-miRNA pair. Finally, a scalable tree boosting model is used to predict small molecule and miRNA potential associations. The experiments on two datasets demonstrated the superiority of DAESTB over various state-of-the-art methods. DAESTB achieved the best AUC value. Furthermore, in three case studies, a large number of predicted associations by DAESTB are confirmed with the public accessed literature. We envision that DAESTB could serve as a useful biological model for predicting potential small molecule-miRNA associations.

Quantitative DNA Methylation Analysis and Epigenotype-Phenotype Correlations in Taiwanese Patients with Silver-Russell Syndrome.

Background: Silver-Russell syndrome (SRS; OMIM #180860) is a clinically and genetically heterogeneous imprinting disorder characterized by prenatal and postnatal growth failure. The aim of this study was to identify the epigenotype-phenotype correlations in these patients using quantitative DNA methylation analysis. Methods: One hundred and eighty-three subjects clinically suspected of having SRS were referred for diagnostic testing by the methylation profiling of H19-associated imprinting center (IC) 1 and imprinted PEG1/MEST regions using methylation-specific high-resolution melting analysis and methylation quantification with the MassARRAY assay. Correlations between quantitative DNA methylation status and clinical manifestations of the subjects according to the Netchine-Harbison (N-H) clinical scoring system for SRS were analyzed. Results: Among the 183 subjects, 90 had a clinical diagnosis of SRS [N-H score ≥ 4 (maximum = 6)] and 93 had an SRS score < 4. Molecular lesions were detected in 41% (37/90) of the subjects with a clinical diagnosis of SRS, compared with 3% (3/93) of those with an N-H score < 4. The IC1 methylation level was negatively correlated with the N-H score. The molecular diagnosis rate was positively correlated with the N-H score. Thirty-one subjects had IC1 hypomethylation (IC1 methylation level <35% by the MassARRAY assay), seven had maternal uniparental disomy 7, and two had pathogenic copy number variants. Among the 90 subjects with an N-H score ≥ 4, the IC1 methylation level was significantly different between those with or without some clinical SRS features, including birth length ≤ 10th centile, relative macrocephaly at birth, normal cognitive development, body asymmetry, clinodactyly of the fifth finger, and genital abnormalities. Conclusions: This study confirmed the suitability of the N-H clinical scoring system as clinical diagnostic criteria for SRS. Quantitative DNA methylation analysis using the MassARRAY assay can improve the detection of epigenotype-phenotype correlations, further promoting better genetic counseling and multidisciplinary management for these patients.

First 100 total hip arthroplasties performed by a young surgeon using the direct anterior approach: learning curve and complications.

INTRODUCTION: Most of the reported discussions about the learning curve for the direct anterior approach (DAA) in total hip arthroplasty (THA) have been by experienced surgeons. The study's aim was to describe the learning curve, short-term outcomes, complications, and adaptations to the DAA used in the first 100 THA cases experienced by a young surgeon who had received DAA training for trauma surgeries. MATERIALS AND METHODS: This retrospective study summarizes the first 100 consecutive cases experienced by a young surgeon who performed the unilateral DAA for THA between 2019 and 2021. Cumulative sum (CUSUM) analysis was performed to evaluate the learning curve on the basis of operative time and overall complications. The demographics data, short-term outcomes, and complications of the first 50 and second 50 cases were compared. RESULTS: The CUSUM curve declined after 49 and 55 cases, measured by operative time and overall complications, respectively. The median operative time (104 vs. 80 min) and intraoperative fluoroscopic time (38 vs. 12 s) increased significantly in the first 50 cases compared with the times in the second 50 cases. Complications tended to occur in the first 50 cases (12% vs. 6%), and the overall rate was 9%. Major complications all occurred in the first 50 cases, with a rate of 4%. Only one case, which involved a complicated periprosthetic fracture around the stem that extended to the tip, required the intervention of a senior surgeon. CONCLUSIONS: Even after receiving training on the DAA for trauma surgeries, the young surgeon experienced a steep learning curve and more complications in the first 50 cases. The DAA for THA is a technically demanding procedure and may require guidance from an experienced surgeon to manage unexpected complications.

ortho-Methoxycarbonylethynylphenyl Thioglycosides (MCEPTs): Versatile Glycosyl Donors Enabled by Electron-Withdrawing Substituents and Catalyzed by Gold(I) or Cu(II) Complexes.

With easily accessible and operator-friendly reagents, shelf-stable ortho-methoxycarbonylethynylphenyl thioglycosides were efficiently prepared. Based on these MCEPT glycoside donors, a novel glycosylation protocol featuring mild and catalytic promotion conditions with Au(I) or Cu(II) complexes, expanded substrate scope encompassing challenging donors and acceptors and clinically used pharmaceuticals, and versatility in various strategies for highly efficient synthesis of glycosides has been established. The practicality of the MCEPT glycosylation protocol was fully exhibited by highly efficient and scalable synthesis of surface polysaccharide subunits of Acinetobacter baumannii via latent-active, reagent-controlled divergent orthogonal one-pot and orthogonal one-pot strategies. The underlying reaction mechanism was investigated systematically through control reactions, leading to the isolation and characterization of the vital catalyst species in MCEPT glycosylation, the benzothiophen-3-yl-gold(I) complex. Based on the results obtained both from control reactions and from studies leading to the glycosylation protocol establishment, an operative mechanism was proposed and the effect of the vital catalyst species reactivity on the results of metal-catalyzed alkyne-containing donor-involved glycosylation was disclosed. Moreover, the mechanism for C-glycosylation side product formation from ortho-(substituted)ethynylphenyl thioglycoside donors with electron-donating substituents was also illuminated.

22q11.2 Deletion Syndrome in Taiwan: Clinical Presentation and Immune System Status of Patients.

Background: 22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome exhibiting significant clinical phenotype variability. This study aimed to investigate the clinical features, immune profiles, and cognitive abilities of 22q11.2DS patients receiving treatment at MacKay Memorial Hospital in Taipei, Taiwan. Methods: This is a cross-sectional analysis between January 2001 and December 2022. We recruited 27 patients with 22q11.2DS using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (aCGH). Our evaluation included patient history, physical examination, laboratory analysis, and cardiac and cognitive assessment. Results: We included 27 patients with 22q11.2DS, 7 (25.9%) of whom were female. The median age of the patients was 17.9 yr. Ninety-three percent of the patients exhibited the characteristic facial features associated with the syndrome. A family history of 22q11.2DS was found in 11.1% of the patients. Furthermore, 74.1% of the patients had a congenital heart defect, the most common of which was tetralogy of Fallot (40.7%). Hypocalcemia was observed in 40.7% of the patients. A low T-cell count was observed in 66.7% of the patients, whereas 18.5% had low immunoglobulin levels. Cognitive assessments revealed that four out of six evaluated patients (66.7%) had an intellectual disability, as evidenced by intellectual quotient scores less than 70. The remaining two patients (33.3%) had a borderline intellectual function. Conclusion: Tetralogy of Fallot, hypocalcemia, immunologic defects, and cognitive impairment were common among our patients. To address the potential multisystem involvement, we recommend that all affected individuals undergo a comprehensive evaluation by a multidisciplinary care team.

Epithelioid dedifferentiated liposarcoma: A clinicopathological and molecular study of 6 cases.

In this study, we present six cases of epithelioid dedifferentiated liposarcoma to further characterize its clinical and pathological features. The patients are all adult men with age at presentation ranging from 46 to 64 years (median 58.5 years). The patients presented with nonspecific symptoms of retroperitoneal mass, intermittent dull pain or discomfort. None of the patients had any prior history of a primary tumor. Radiological examinations revealed the presence of ill-demarcated heterogenous mass located in the deep soft tissue, including retroperitoneum (4 cases), pelvis and trunk (1 case each). Grossly, they appeared as solid tumors with focal areas of necrosis being presented in 2 cases. Histologically, all tumors were characterized by sheets of epithelioid cells that displayed marked cellular atypia and brisk mitotic activity. Variable portion of atypical lipomatous tumor/well-differentiated liposarcoma was present in 3 cases. By immunohistochemistry, the high-grade epithelioid component in all 6 cases showed strong and diffuse nuclear staining of MDM2, CDK4 and P16, with partial expression of AE1/AE3 in 3 cases. Fluorescence in situ hybridization analysis revealed high-level amplification of MDM2 in all 6 cases, with co-amplification of CDK4 in 3 cases. Follow up information showed that two patients died of the disease within one year despite multidisciplinary treatment. Due to the striking epithelioid appearance, this rare variant of dedifferentiated liposarcoma may be confused with undifferentiated epithelioid sarcoma, poorly differentiated carcinoma, mesothelioma or other malignancies with epithelioid phenotype. The study presented herein further highlights the aggressive clinical behavior of this unique tumor type. For patients with advanced disease, CDK4 inhibitor may provide an optional targeted treatment.

Cisplatin triggers oxidative stress, apoptosis and pro-inflammatory responses by inhibiting the SIRT1-mediated Nrf2 pathway in chondrocytes.

Although the height of the proliferating layer that was suppressed in the growth plate has been recognized as an adverse effect of cisplatin in pediatric cancer survivors, the detailed pathological mechanism has not been elucidated. Sirtuin-1 (SIRT1) has been reported as an essential modulator of cartilage homeostasis, but its role in cisplatin-induced damage of chondrocytes remains unclear. In this study, we examined how cisplatin affected the expression of SIRT1 and cell viability. Next, we showed downregulation of SIRT1 after cisplatin treatment resulted in suppression of Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), leading to inhibition of Nrf2 nuclear translocation and subsequently decreased Heme oxygenase-1(HO-1) and NAD(P)H Quinone Dehydrogenase 1(NQO-1) expression. Blockage of the SIRT1/ PGC-1α axis not only increased oxidative stress with lower antioxidant SOD and GSH, but also contributed to mitochondrial dysfunction evidenced by the collapse of membrane potential and repression of mitochondrial DNA copy number and ATP. We also found that Cisplatin up-regulated the p38 phosphorylation, pro-inflammatory events and matrix metalloproteinases (MMPs) in chondrocytes through the SIRT1-modulated antioxidant manner. Collectively, our findings suggest that preservation of SIRT1 in chondrocytes may be a potential target to ameliorate growth plate dysfunction for cisplatin-receiving pediatric cancer survivors.

Prespinal Versus Conventional Hemicontralateral C7 Nerve Transfer in the Treatment of Total Brachial Plexus Roots Avulsion Injuries: A Retrospective Study With a Minimum Follow-Up Period of 4 Years.

PURPOSE: Contralateral C7 (CC7)-to-median nerve transfer has been commonly used to restore hand function in brachial plexus injury. To shorten the nerve graft, the prespinal route was described and achieved direct coaptation when combined with humeral shortening osteotomy. The limb was positioned at 0° shoulder abduction and neutral head position. Given our concern about donor-site morbidity when harvesting the whole CC7 nerve and tension across the neurorrhaphy site after mobilization, we aimed to describe our modified prespinal route and compare its outcomes and complications with the conventional hemi-CC7 transfer. METHODS: From 2004 to 2014, 39 patients with preganglionic total brachial plexus root avulsion injuries, with a minimum of 4 years of follow-up, were included. Overall, 20 and 19 patients underwent the conventional hemi-CC7-to-median nerve and hemi-CC7-to-lower trunk (LT) transfer through the modified prespinal route, respectively. The modified prespinal route was combined with bilateral clavicle shortening osteotomy to achieve direct coaptation to the LT at 45° shoulder abduction. RESULTS: The modified prespinal route showed the median period to achieve ≥M3 hand grip assessed in clinical follow-up was shorter (26.5 months vs 45.5 months), and a higher proportion of patients achieved ≥M3 hand grip recovery (63% vs 30%). One patient experienced symptomatic phrenic nerve injury; however, the hemidiaphragm fully recovered after 6 months. The long-term donor-site complication rate was 2.6%, including one sensory abnormality, and no permanent donor-site weakness after hemi-CC7 harvesting was observed. CONCLUSIONS: The modified prespinal route combined with clavicle osteotomy allowed direct coaptation to the LT and did not require head immobilization. It may allow a higher proportion of patients to achieve ≥M3 hand grip more quickly than conventional hemi-CC7 transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Use of Silicone Tubes as Antiadhesion Devices in a Modified Two-Stage Flexor Tendon Reconstruction in Zone II: A Retrospective Study.

PURPOSE: This study aimed to assess the outcome of a modified two-stage flexor tendon reconstruction using silicone tubes as antiadhesion devices while performing simultaneous tendon grafting. METHODS: From April 2008 to October 2019, 16 patients (21 fingers) with zone II flexor tendon injuries, who sustained failed tendon repair or neglected tendon laceration, were treated by a modified two-stage flexor tendon reconstruction. The first stage of treatment comprised flexor tendon reconstruction with interposition of silicone tubes to minimize fibrosis and adhesion around the tendon graft; the second stage of treatment comprised silicone tube removal under local anesthesia. RESULTS: The patient median age was 38 (range, 22-65) years. After a median follow-up period of 14 (range, 12-84) months, the median total active motion (TAM) of fingers was 220° (range, 150-250°). Excellent and good TAM ratings were identified in 71.4%, 76.2%, and 76.2% according to the Strickland, modified Strickland, and American Society for Surgery of the Hand (ASSH) evaluation systems, respectively. At follow-up, complications included superficial infections in two fingers of one patient whose silicone tube was removed 4 weeks postoperatively. The most common complication was a flexion deformity of the proximal interphalangeal joint (four fingers) and/or distal interphalangeal joint (nine fingers). The rate of failed reconstruction was higher in patients with preoperative stiffness and infection. CONCLUSIONS: Silicone tubes are suitable antiadhesion devices, and the modified two-stage flexor tendon reconstruction technique is an alternative procedure with a shorter rehabilitation period for complicated flexor tendon injury, compared with current popular reconstructions. Preoperative stiffness and postoperative infection may compromise the final clinical outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Does an Internal Joint Stabilizer and Standardized Protocol Prevent Recurrent Instability in Complex Persistent Elbow Instability?

BACKGROUND: The treatment of complex persistent elbow instability after trauma is challenging. Previous studies on treatments have reported varied surgical techniques, which makes it difficult to establish a therapeutic algorithm. Furthermore, the surgical procedures may not sufficiently restore elbow stability, even with an additional device, and a noted high rate of arthritis progression.While a recently developed internal joint stabilizer effectively treats elbow instability, its clinical application for complex persistent elbow instability is limited and the standardized protocol is not well described. Additionally, we want to know whether the arthritis progression will cause a negative impact on the functional outcomes of complex persistent elbow instability. QUESTIONS/PURPOSES: (1) Does treatment of complex persistent elbow instability with a hinged internal joint stabilizer and a standardized protocol prevent recurrent instability and other complications? (2) What are the pre- to postoperative improvements in pain, disability, elbow performance, and ROM? (3) Is the development of post-traumatic arthritis associated with worse pain, disability, elbow performance, and ROM? METHODS: Between September 2014 and October 2019, we treated 22 patients for persistent dislocation or subluxation after initial treatment of traumatic elbow fracture-dislocations. Of those, we considered patients who were at least 20 years of age, with an interval of 6 weeks or more between the injury (initial treatment) and the index reconstructive procedure, which had been performed at our institute, as potentially eligible. During that time, we used an internal joint stabilizer with a standardized protocol for posttraumatic complex persistent elbow instability. We performed total elbow replacements in patients older than 50 years who had advanced elbow arthritis. Based on that, 82% (18 of 22) of patients were eligible; 14% (3 of 22) were excluded because total elbow replacements was undertaken, and another 5% (1 of 22) were lost before the minimum study follow-up of 1 year (median 24 months [range 12 to 63]), leaving 64% (14 of 22) for analysis in this retrospective study. We treated 14 patients (14 elbows) with posttraumatic complex persistent elbow instability with an internal joint stabilizer and a standardized protocol that comprised debridement arthroplasty with ulnar neurolysis, restoration of bony and ligamentous (reattachment) structures, application of an internal joint stabilizer, and early rehabilitation. There were eight men and six women in this study, with a median (range) age of 44 years (21 to 68). The initial elbow fracture-dislocation injury pattern was a terrible triad injury in seven patients, a posterolateral rotatory injury in four patients, and a posterior Monteggia fracture in three patients. Preoperative and follow-up radiographs were reviewed for evidence of recurrent instability and arthritis. Complications such as wound infection, seroma, neurovascular injury, and hardware complications were ascertained through chart review. Preoperative and postoperative VAS score for pain, DASH, and Mayo Elbow Performance Scores (MEPS) were collected and compared. Furthermore, extension-flexion and supination-pronation arcs were collected by chart review. We divided the patients into two groups according to whether or not they developed posttraumatic arthritis. We then presented the differences between pain, disability, elbow performance, and ROM. The hinged internal joint stabilizer was removed using another open procedure under general anesthesia 6 to 8 weeks after surgery. RESULTS: There were no recurrent instability during and after device removal. Seven patients developed complications, including wound infection, seroma, neurovascular injury, hardware complications, and heterotopic ossification. Two patients had complications related to internal joint stabilizers and three had complications linked to radial head prostheses. Median (range) preoperative to postoperative changes included decreased pain (VAS 5 [2 to 9] to 0 [0 to 3], difference of medians -5; p < 0.001), decreased disability (DASH 41 [16 to 66] to 7 [0 to 46], difference of medians -34; p < 0.001), improved function (MEPS 60 [25 to 70] to 95 [65 to 100], difference of medians 35; p < 0.001), improved extension-flexion arc (40° [10° to 70°] to 113° [75° to 140°], difference of medians 73°; p < 0.001), and supination-pronation arc (78° [30° to 165°] to 148° [70° to 175°], difference of medians 70°; p < 0.001). Between patients with and without development of post-traumatic arthritis, there were no differences in postoperative pain (VAS 0 [0 to 3] to 0 [0 to 1], difference of medians 0; p = 0.17), disability (DASH 7 [0 to 46] to 7 [0 to 18], difference of medians 0; p = 0.40), function (MEPS 80 [65 to 100] to 95 [75 to 100], difference of medians 15; p = 0.79), extension-flexion arc (105° [75° to 140°] to 115° [80° to 125°], difference of medians 10°; p = 0.40), and supination-pronation arc (155° [125° to 175°] to 135° [70° to 160°], difference of medians -20°; p < 0.18). CONCLUSION: In this small, retrospective study, we found that an internal joint stabilizer with a standardized treatment protocol could maintain concentric reduction while allowing early functional motion, and that it could improve clinical outcomes for patients with complex persistent elbow instability. However, patients must be counseled that the complications related to the radial head prostheses may occur, and that the benefits of early motion must compensate for an additional removal procedure and the risk of seroma formation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Effects of Kinesio taping on forearm supination/pronation performance fatigability.

BACKGROUND: Repetitive exertion in supination/pronation could increase the risk of forearm diseases due to fatigue. Kinesio taping (KT) is a physical therapy technique that decreases muscle tone and musculoskeletal disorders (MSDs) risk. Many assumptions about taping have been made and several studies have considered the taping applications; however, the effect of KT on strength and fatigue of the forearm supination/pronation remains unclear. The purpose of this study was to evaluate the effect of KT on forearm performance fatigability. METHODS: A screwing test was constructed to measure the forearm force loss and screwing efficiency during repetitive supination/pronation. Data from 18 healthy adults who underwent both KT and no taping (NT) sessions were used to investigate the forearm strength change in terms of grip force (GF), driving torque (DT), and push force (PF). The maximal isometric forces before and after the screwing test and force decreasing rate (efficiency) during screwing were evaluated to assess the performance fatigability in KT and NT conditions. RESULTS: A statistically significant force loss (FL) in maximal isometric GF (p = 0.039) and maximal isometric DT (p = 0.044); however, no significant difference was observed in maximal isometric PF (p = 0.426) between NT and KT. KT provides greater screwing efficiency than NT. CONCLUSIONS: KT could not improve FL in the maximal muscle strength of the forearm in healthy subjects. KT on the forearm was associated with a lesser decline in DT efficiency than NT, implying that KT could decrease the loss rate of muscle strength and delay the development of fatigue; however, the KT did not yield improvements in PF while performing screwing tasks.

Using External Joint Stabilizer - Elbow (EJS-E) for treating elbow instability-biomechanical assessment and clinical outcomes.

BACKGROUND: This study aimed to evaluate the outcome of using an External Joint Stabilizer - Elbow (EJS-E) for persistent elbow instability based on biomechanical experiments and analysis of clinical results. METHODS: An EJS-E was used in 17 elbow instability patients. The median follow-up was 26 months (range, 12-42 months). We evaluated the flexion-extension and pronation-supination movement arcs, visual analog scale (VAS) score, Mayo Elbow Performance Score (MEPS), Broberg and Morrey classification system, and occurrence of complications in these patients. Moreover, construct stiffness and maximum strength tests were performed to evaluate the strength of the fixation techniques. RESULTS: The final median range of the extension-to-flexion and pronation-to-supination arc of the elbow was 135° (range, 110°-150°) and 165° (range, 125°-180°), respectively. The VAS pain scores were > 3 in two patients. The median MEPS was 90 (range, 80-100 points). Five patients showed signs of grade I post-traumatic osteoarthritis according to the Broberg and Morrey radiographic classification system, while grade II changes were observed in three patients. Complications included axis pin loosening with pin-tract infection in two patients, transient ulnar nerve symptoms in two patients, heterotopic ossification in two patients, and suture anchors infection in one patient. Based on the biomechanical testing results, the EJS-E exhibited higher stiffness and resisting force in varus loading. It was 0.5 (N/mm) stiffer and 1.8 (N·m) stronger than the internal joint stabilizer (IJS) by difference of medians (p < 0.05). CONCLUSIONS: Biomechanical and clinical outcomes show that EJS-E via the posterior approach can restore mobility and stability in all patients, thus serving as a valuable alternative option for the treatment of persistent instability of the elbow.

Galectin-3 facilitates inflammation and apoptosis in chondrocytes through upregulation of the TLR-4-mediated oxidative stress pathway in TC28a2 human chondrocyte cells.

Osteoarthritis (OA) is a common degenerative joint disease. The pathological changes of chondrocytes involve oxidative stress, the pro-inflammatory response, and pro-apoptotic events. Galectin-3 (Gal-3) is a 35 kDa protein with a special chimeric structure. Gal-3 participates in the progression of many diseases, such as cancer metastasis and heart failure. A previous study demonstrated that Gal-3 expression in human cartilage with OA is increased. However, the role of Gal-3 in chondrocyte dysfunction in joints is still unclear. In this study, we applied Gal-3 (5-20 µg/ml) to TC28a2 human chondrocyte cells for 24 h to induce chondrocyte dysfunction. We found that Gal-3 upregulated TLR-4 and MyD88 expression and NADPH oxidase, thereby increasing intracellular ROS in the chondrocytes. Gal-3 increased phosphorylated MEK1/2 and ERK levels, and promoted NF-κB activity. This activation of NF-κB was reduced by silencing TLR-4 and NOX-2. In addition, Gal-3 caused apoptosis of chondrocytes through the mitochondrial-dependent pathway via the TLR-4/NADPH oxidase/MAPK axis. Our study proves the pathogenic role of Gal-3 in Gal-3-induced chondrocyte dysfunction and injuries.

Arthroscopic resection of recurrent wrist ganglions - A retrospective study of 17 patients.

BACKGROUND: Arthroscopic resection has become a favorable alternative for wrist ganglions. However, for recurrent wrist ganglions, arthroscopic resection is relatively contraindicated. The purpose of this study was to evaluate the clinical outcomes of arthroscopic resection for recurrent wrist ganglions and to identify their safety and efficacy. METHODS: From June 2011 to February 2017, 17 patients with recurrent wrist ganglion were treated with arthroscopic resection. We evaluated the visual analog scale, modified Mayo wrist score, and Disabilities of Arm, Shoulder and Hand Outcome Measure preoperatively and at the final follow-up. Patients were questioned for pain reduction, pain during pushups, and any difficulty in returning to work. Recurrence and complications were also assessed at each follow-up visit. RESULTS: We enrolled 17 patients and median follow-up was 58 months. The reduction in pain was significant. Only 2 of the 17 patients had residual pain after arthroscopic resection. One female patient showed recurrences 3 years later. Although 2 cases of stiffness were noted after the operation, no significant complication was present 3 months postoperatively. Most patients had good recovery and could resume work; however, 2 patients reported fair recovery. CONCLUSION: The results of this study confirmed that arthroscopic excision could be an effective and safe treatment for recurrent ganglions; therefore, should not be contraindicated for treating recurrent wrist ganglions. Nevertheless, further prospective studies with larger patient numbers are needed to establish a stronger evidence for arthroscopic resection of recurrent wrist ganglions.

Updated Confirmatory Diagnosis for Mucopolysaccharidoses in Taiwanese Infants and the Application of Gene Variants.

Mucopolysaccharidosis (MPS) is a lysosomal storage disease caused by genetic defects that result in deficiency of one specific enzyme activity, consequently impairing the stepwise degradation of glycosaminoglycans (GAGs). Except for MPS II, the other types of MPS have autosomal recessive inheritance in which two copies of an abnormal allele must be present in order for the disease to develop. In this study, we present the status of variant alleles and biochemistry results found in infants suspected of having MPS I, II, IVA, and VI. A total of 324 suspected infants, including 12 for MPS I, 223 for MPS II, 72 for MPS IVA, and 17 for MPS VI, who were referred for MPS confirmation from newborn screening centers in Taiwan, were enrolled. In all of these infants, one specific enzyme activity in dried blood spot filter paper was lower than the cut-off value in the first blood sample, as well asin a second follow-up sample. The confirmatory methods used in this study included Sanger sequencing, next-generation sequencing, leukocyte enzyme fluorometric assay, and GAG-derived disaccharides in urine using tandem mass spectrometry assays. The results showed that five, nine, and six infants had MPS I, II, and IVA, respectively, and all of them were asymptomatic. Thus, a laboratory diagnosis is extremely important to confirm the diagnosis of MPS. The other infants with identified nucleotide variations and reductions in leukocyte enzyme activities were categorized as being highly suspected cases requiring long-term and intensive follow-up examinations. In summary, the final confirmation of MPS depends on the most powerful biomarkers found in urine, i.e., the quantification of GAG-derived disaccharides including dermatan sulfate, heparan sulfate, and keratan sulfate, and analysis of genetic variants can help predict outcomes and guide treatment.

[Clinical study of modified Yiyi Baijiang Decoction on psoriasis vulgaris due to dampness-heat accumulation].

The present study observed the clinical effect of modified Yiyi Baijiang Decoction on psoriasis vulgaris and explored its influence on growth factors and inflammatory factors in the serum and skin tissues. A total of 130 patients were randomly divided into control group and experimental group, with 65 cases in each group. The patients in the control group received Acitretin Capsules and Calcipotriol Ointment, and those in the experimental group received modified Yiyi Baijiang Decoction combined with external application for four weeks. The psoriasis area and severity index(PASI), blood vessel count in the superficial dermis(SDBVC), skin thickness(STK), and traditional Chinese medicine(TCM) symptoms were observed before and after treatment. The growth factors [epidermal growth factor(EGF), endothelial cell-specific molecule-1(ESM-1), fibroblast growth factor-23(FGF-23), and transforming growth factor-ß1(TGF-ß1)] and inflammatory factors [nuclear factor-κB(NF-κB), prealbumin(PA), CC chemokine ligand 20(CCL20), and procalcitonin(PCT)] in the serum and skin tissues were detected. The total effective rate was 98.5% in the experimental group, higher than that 83.1% in the control group(P<0.05). Compared with the control group after treatment, the experimental group showed decreased PASI, SDBVC, STK, TCM symptoms, ESM-1, FGF-23, TGF-ß1, NF-κB, CCL20, and PCT(P<0.05), and increased EGF and PA(P<0.05). The incidence of adverse events was 1.5% in the experimental group, lower than that 21.5% in the control group(P<0.05). The results showed that modified Yiyi Baijiang Decoction could effectively relieve skin lesions in patients with psoriasis vulgaris and improve the growth factors and inflammatory factors in the serum and skin lesions, with high safety.

The coordination of OsbZIP72 and OsMYBS2 with reverse roles regulates the transcription of OsPsbS1 in rice.

Nonphotochemical quenching (NPQ), an intricate photoprotective process, plays fundamental roles in maintaining plant fitness. The PsbS protein is essential for the rapid induction of NPQ, and acts in a dose-dependent manner in leaves. However, little information is known on the transcriptional control of PsbS in land plants. Here we demonstrated that the expression of OsPsbS1 is directly upregulated by OsbZIP72 while repressed by OsMYBS2 in rice. We identified a new cis-element GACAGGTG in japonica OsPsbS1 promoter, to which OsbZIP72 could strongly bind and activate the expression of OsPsbS1. The new cis-element CTAATC confers specific binding for OsMYBS2 in japonica OsPsbS1 promoter. OsbZIP72 can be activated by SAPK1, and acts depending on the abscisic acid (ABA) signalling pathway. GF14A protein affects the repression activity of OsMYBS2 by regulating its nucleocytoplasmic shuttling, and Ser53 is necessary for OsMYBS2 to be retained in the cytoplasm. The inducibility of OsPsbS1 transcription under high light conditions in OsbZIP72 knockout lines was greatly impaired, while the repression of OsPsbS1 transcription under a low light environment in OsMYBS2 knockout lines was significantly alleviated. These results reveal cross-talk among NPQ processes, the ABA signalling pathway and abiotic stress signalling. The elaborate mechanisms may help enhance photoprotection and improve photosynthesis in rice.

Involvement of activin a receptor type 1 (ACVR1) in the pathogenesis of primary focal hyperhidrosis.

The pathogenesis of primary focal hyperhidrosis (PFH) is still not clear. PFH is thought to be a genetic disease. Whether activin A receptor type 1 (ACVR1) is involved in the pathogenesis of PFH is unknown. In this study, the expression of ACVR1 in sweat glands of patients with PAH was detected by western blot and immunofluorescence. The primary sweat gland cells obtained from primary axillary hyperhidrosis (PAH) patients were transfected with acvr1 vector. Cell proliferation, apoptosis and cell cycling of gland cells were measured after transfection with acvr1 vector. The mRNA and protein expression of aquaporin 5 (AQP5) and Na:K:2Cl Cotransporter 1 (NKCC1/SLC12A2) were detected. Our data showed that ACVR1 expression in axillary sweat gland tissue of PAH patients was significantly higher than that of normal control group. The function of ACVR1 was further investigated in the gland cells obtained from PAH patients. Compared with NC group, ACVR1 overexpression significantly promoted the proliferation of sweat gland cells and inhibited the apoptosis of sweat gland cells. Meanwhile, ACVR1 overexpression significantly reduced the percentage of cells in G0/G1 and G2/M phases, and increased the percentage of cells in S phase. In addition, ACVR1 overexpression significantly promoted the expression of AQP5 and NKCC1 at both mRNA and protein levels. Together, ACVR1 expression is related to PFH and ACVR1 overexpression can promote the proliferation of sweat gland cells and inhibit apoptosis by promoting the expression of AQP5 and NKCC1.

Testing for Severe Acute Respiratory Syndrome-Coronavirus 2: Challenges in Getting Good Specimens, Choosing the Right Test, and Interpreting the Results.

OBJECTIVES: We explore ways to reduce errors in laboratory diagnosis of severe acute respiratory syndrome-coronavirus 2 infection by considering preanalytic, analytic, and postanalytic sources. To address preanalytic challenges, we first consider alternative anatomic sites for specimen collection, then discuss self-collection, alternative sampling devices, and transport media. Strengths and limitations of various analytic test systems are considered in the context of postanalytic challenges associated with making test results meaningful, specifically considering the complex relationship between "positive" test results and reproduction and shedding of intact virus. Finally, we provide recommendations regarding healthcare worker surveillance and release of patients with coronavirus disease 2019 from isolation. DATA SOURCES: Material was derived from a Webinar available to the public, manufacturer's websites, U.S. Food and Drug Administration, and Centers for Disease Control and Prevention websites and from both peer-reviewed papers identified by PubMed search and nonpeer-reviewed papers posted on Biorxiv and Medrxiv. Unpublished data came from the Washington State Department of Health. STUDY SELECTION: We included studies that compared diagnostic performance strategies without introducing bias due to use of an imperfect gold standard. Case series and case reports were included as necessary to illuminate the significance of results. DATA EXTRACTION: Data were extracted manually. DATA SYNTHESIS: Sensitivity, specificity, and CIs were computed from article data using a composite reference standard. Nucleic acid-based tests were assumed to perform at 100% specificity. CONCLUSIONS: Although sputum and bronchoalveolar lavage samples provide the highest diagnostic sensitivity for severe acute respiratory syndrome-coronavirus 2, nasopharyngeal, mid turbinate, and nasal specimens are suitable in most cases and require less use of personal protective equipment. When desired sampling materials are unavailable, alternatives may be substituted with no loss of performance. Both reverse transcriptase polymerase chain reaction tests and rapid nucleic acid-based tests offer good performance in most circumstances. Testing is not required to release most patients from isolation.

Reagent-Controlled Divergent Synthesis of C-Glycosides.

By turning on or switching off the directing effect of the C3-OH-located o-diphenylphosphanylbenzoyl (o-DPPB) group in glycals, a reagent-controlled protocol for divergent and regio- and stereoselective syntheses of C-glycosides has been established. In particular, the silence of the directing effect of o-DPPB was achieved by the introduction of a ZnCl2 additive, which is operationally simple and efficient. The flexibility of the novel protocol was exhibited not only by the easy access of both α- and ß-C-glycosides but also by the versatility of the obtained formal Ferrier rearrangement products, which can be easily derivatized to various C-glycoside analogues owing to the embedded multifunctionalities.