FGF9 is required for Purkinje cell development and function in the cerebellum.

Fibroblast growth factor 9 (FGF9) is a member of the fibroblast growth factor family, which is widely expressed in the central nervous system (CNS). It has been reported that deletion of FGF9 leads to defects in cerebellum development, including Purkinje cell defect. However, it is not clear how FGF9 regulating cerebellar development remains to be determined. Our results showed that in addition to disrupt Bergmann fiber scaffold formation and granule neuron migration, deletion of neuronal FGF9 led to ataxia defects. It affected development and function of Purkinje cells, and also changed the action potential threshold and excitation frequency. Mechanistically, depletion of FGF9 significantly changed neurotransmitter contents in Purkinje cells and led to preferential increase in inflammation, even downregulation in ERK signaling. Together, the data demonstrate that neuronal FGF9 is required for the development and function of Purkinje cells in the cerebellum. Insufficient FGF9 during cerebellum development will cause ataxia defects.

Efficacy and safety of high-intensity focused ultrasound combined with suction curettage for the treatment of caesarean scar pregnancy: a systematic review and single-arm meta-analysis.

PURPOSE: Caesarean scar pregnancy (CSP) presents a significant clinical challenge owing to the associated risks of uterine scar rupture, severe haemorrhage and adverse maternal outcomes. This study aimed to assess the safety and efficacy of combining high-intensity focused ultrasound (HIFU) with suction curettage for treating CSP. METHODS: We conducted a comprehensive search in four databases, namely PubMed, Web of Science, Embase and Cochrane Library, to identify published studies evaluating the use of HIFU combined with suction curettage to treat CSP. Intraoperative blood loss, treatment success rate, and reproductive results were the primary outcomes assessed. RESULTS: A total of 18 studies involving 1251 patients with CSP, all of whom received preoperative HIFU therapy were included. The average hospital stay was 6.22 days, the intraoperative blood loss was 26.29 ml and the incidence of adverse events was 15.60%, including abdominal or lower limb pain, fever, vaginal bleeding, haematuria and vomiting. Furthermore, post-treatment follow-up showed that serum ß-human chorionic gonadotropin levels were rapidly normalized (average of 25.48 days) and menstruation returned (average of 33.03 days). The treatment had a remarkable success rate of 97.60% and a subsequent pregnancy rate of 68.70%. CONCLUSION: While the combination of HIFU and suction-curettage may induce common adverse effects such as lower abdominal or limb pain, these reactions typically do not necessitate therapeutic intervention. Additionally, the size of the gestational sac is a determinant of the procedure's success. In conclusion, HIFU combined with suction curettage demonstrates promising clinical efficacy, safety and favourable reproductive outcomes in managing CSP.

Perioperative, function, and positive surgical margin in extraperitoneal versus transperitoneal single port robot-assisted radical prostatectomy: a systematic review and meta-analysis.

BACKGROUND: Extraperitoneal and transperitoneal approaches are two common modalities in single-port (SP) robot-assisted radical prostatectomy (RARP), but differences in safety and efficacy between the two remain controversial. This study aimed to compare the perioperative, function, and positive surgical margin of extraperitoneal with transperitoneal approaches SP-RARP. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, this study is registered with PROSPERO (CRD 42023409667). We systematically searched databases including PubMed, Embase, Web of Science, and Cochrane Library to identify relevant studies published up to February 2023. Stata 15.1 software was used to analyze and calculate the risk ratio (RR) and weighted mean difference (WMD). RESULTS: A total of five studies, including 833 participants, were included in this study. The SP-TPRP group is superior to the SP-EPRP group in intraoperative blood loss (WMD: - 43.92, 95% CI - 69.81, - 18.04; p = 0.001), the incidence of postoperative Clavien-Dindo grade II and above complications (RR: 0.55, 95% CI - 0.31, 0.99; p = 0.04), and postoperative continence recovery (RR: 1.23, 95% CI 1.05, 1.45; p = 0.04). Conversely, the hospitalization stays (WMD: 7.88, 95% confidence interval: 0.65, 15.1; p = 0.03) for the SP-EPRP group was shorter than that of the SP-TPRP group. However, there was no significant difference in operation time, postoperative pain score, total incidence of postoperative complications, and positive surgical margin (PSM) rates between the two groups (p > 0.05). CONCLUSIONS: This study demonstrates that both extraperitoneal and extraperitoneal SP-RARP approaches are safe and effective. SP-TPRP is superior to SP-EPRP in postoperative blood loss, the incidence of postoperative Clavien-Dindo grade II and above complications, and postoperative continence recovery, but it is accompanied by longer hospital stays.

Prediction of radiation pneumonia after radiotherapy for esophageal cancer using a unified fractional dosiomics combined model.

OBJECTIVE: This study aimed to construct an optimal model to predict radiation pneumonia (RP) after radiotherapy for esophageal cancer using unified fractional dosiomics and to investigate the improvements in the prediction efficiency of each model for RP. METHODS: The clinical data, DVH, pre-treatment CT, and dose distribution of 182 patients were retrospectively analyzed.The independent risk factors were screened using univariate and multivariate logistic regression. The mutual information (MI),least absolute shrinkage and selection operator (LASSO), and recursive feature elimination (RFE) methods were used to screen the omics features. The AUC values of ROC, calibration curves, and clinical decision curves were calculated to evaluate the efficacy and trends of each model. RESULTS: The AUC of dosiomics model were 0.783 and 0.760 in the training and test cohorts, higher than 0.585 and 0.579 in the training and test cohorts of the DVH model. The AUC value of the R + D combination was the highest, reaching 0.833. The combined R + D model had a better calibration degree than the other models (mean absolute error = 0.018) and better net benefit in clinical decision-making. CONCLUSIONS: The radiomics combined dosiomics model was the best combined model to predict RP after radiotherapy for esophageal cancer. The dosiomics model could cover the efficiency of the DVH model and significantly improve the efficiency of the combined model.In the future, we will include other centers for further verification. ADVANCES IN KNOWLEDGE: For the first time, this study used CT images combined dose distribution to predict the occurrence of radiation pneumonitis after radiotherapy for esophageal cancer.

Developing a CT-based radiomics nomogram for predicting post-acute pancreatitis diabetes mellitus incidence.

OBJECTIVE: The present study aimed to develop the utility of a nomogram based on clinical and radiomics as a tool for predicting post-acute pancreatitis diabetes mellitus (PPDM-A). METHODS: This retrospective investigation evaluated 244 patients with acute pancreatitis. Patients were randomized in a 7:3 ratio into training and validation cohorts. Radiomics feature selection was then achieved using the variance threshold, select best K, and least absolute shrinkage and selection operator methods. The area under the curve values, decision, and calibration curves have been used to determine the models' predictive value. RESULTS: The developed nomogram performed superior to the clinical model in the validation (0.815 vs 0.677, p = 0.016) and training cohorts (0.803 vs 0.683, p = 0.002). The calibration curves demonstrated that the expected and actual values were satisfactory. In contrast, decision curve analysis revealed a stronger relationship between the nomogram and net clinical value than with the distinct radiomics or clinical signature effects. CONCLUSION: In summary, the findings of this study demonstrated that establishing a predictive nomogram as a non-invasive technique may be useful in predicting the risk of PPDM-A. ADVANCES IN KNOWLEDGE: This is the first time to use a CT radiomics nomogram to predict PPDM-A. The nomogram is conducive to the personalized prediction of patients. It only needs to input the patient's information, and a simple addition operation can quantitatively obtain its risk. The resultant tool has the potential to provide new opportunities to treat or prevent PPDM-A more effectively.

Calling on Sponsorship: Analysis of Speaker Gender Representation at Hand Society Meetings.

BACKGROUND: The paucity of leadership diversity in surgical specialties is well documented. Unequal opportunities for participation at scientific meetings may impact future promotions within academic infrastructures. This study evaluated gender representation of surgeon speakers at hand surgery meetings. METHODS: Data were retrieved from the 2010 and 2020 meetings of the American Association for Hand Surgery (AAHS) and American Society for Surgery of the Hand (ASSH). Programs were evaluated for invited and peer-reviewed speakers excluding keynote speakers and poster presentations. Gender was determined from publicly available sources. Bibliometric data (Hirsch index) for invited speakers were analyzed. RESULTS: In 2010 at the AAHS ( n = 142) and ASSH meetings ( n = 180), female surgeons represented 4% of the invited speakers and in 2020 increased to 15% at AAHS ( n = 193) and 19% at ASSH ( n = 439). From 2010 to 2020, female surgeon invited speakers had a 3.75-fold increase at AAHS and 4.75-fold increase at ASSH. Representation of female surgeon peer-reviewed presenters at these meetings was similar (2010 AAHS, 26%; and 2010 ASSH, 22%; 2020 AAHS, 23%; 2020 ASSH, 22%). The academic rank of women speakers was significantly lower ( P < 0.001) than for male speakers. At the assistant professor level, the mean Hirsch index was significantly lower ( P < 0.05) for female invited speakers. CONCLUSIONS: Although there was a significant improvement in gender diversity in invited speakers at the 2020 meetings compared with 2010, female surgeons remain underrepresented. Gender diversity is lacking at national hand surgery meetings, and continued effort and sponsorship of speaker diversity is imperative to curate an inclusive hand society experience.

DNA-Compatible Diversification of Indole π-Activated Alcohols via a Direct Dehydrative Coupling Strategy.

Indole-based diversification is highly desired in the DNA-encoded chemical library construction. Herein, we present a general strategy for on-DNA synthesis of diverse C3-functionalized indole derivatives via indole π-activated alcohol formation followed by direct dehydrative coupling. Highly efficient bond linkages of C-C, C-N, and C-S were achieved to fuse building blocks that are widely commercially available. DNA-encoding compatibility of the method has been further demonstrated to pave an avenue for application in constructing indole-focused three-dimensional libraries.

Reversible Covalent Headpiece Enables Interconversion between Double- and Single-Stranded DNA-Encoded Chemical Libraries.

The use of a proper encoding methodology is one of the most important aspects when practicing DEL technology. A "headpiece"-based double-stranded DEL encoding method is currently the most widely used for productive DEL. However, the robustness of double-stranded DEL construction conflicts with the versatility presented by single-stranded DEL applications. We here report a novel encoding method, which is based on a "reversible covalent headpiece (RCHP)". The RCHP allows reversible interconversion between double- and single-stranded DNA formats, providing an avenue to robust synthesis and allowing for the applications in distinct setups. We have validated the versatility of this encoding method with encoded self-assembled chemical library and DNA-encoded dynamic library technology. Notably, based on the RCHP-settled library construction, a unique "ternary covalent complex" mediating ligand isolation methodology against non-immobilized targets was developed.

Upper Extremity Surgery in Tetraplegia and the Online Information Void.

Background: People with tetraplegia lack awareness of, and subsequently underutilize, reconstructive surgery to improve upper extremity function. This is a topic of international discussion. To bridge the information gap, proposed mandates encourage providers to discuss surgical options with all tetraplegic patients. Outside of the clinical setting, little is known about information available to patients and caregivers-particularly online. The purpose of this study is to evaluate online content for surgical options for improved upper extremity function for people with tetraplegia. Methods: A sample of online content was generated using common search engines and 2 categories of key words and phrases, general and specific. Articles on the first 2 search pages were evaluated for content and audience. Results: A total of 76 different search results appeared on the first 2 pages using 8 unique search phrases. Of articles generated from general phrases, only 5% mentioned tendon or nerve transfers in tetraplegia. When more specific key search phrases were used, the number of lay articles increased to 71%. Conclusions: Based on initial results, general online information on the management of tetraplegia largely excludes discussions of upper limb reconstruction and the well-known benefits. Unless patients, their caregivers, and nonsurgical health care providers have baseline knowledge of tendon and/or nerve transfers, they are unlikely to obtain de novo awareness of surgical options with self-initiated searches. Thus, the challenge and opportunity is to revise the online dialogue to include upper extremity surgery as a fundamental tenet of tetraplegia care.

Genome-wide analysis and characterization of Aux/IAA family genes related to fruit ripening in papaya (Carica papaya L.).

BACKGROUND: Auxin/indole-3-acetic acid (Aux/IAA) family genes encode short-lived nuclear proteins that mediate the responses of auxin-related genes and are involved in several plant developmental and growth processes. However, how Aux/IAA genes function in the fruit development and ripening of papaya (Carica papaya L.) is largely unknown. RESULTS: In this study, a comprehensive identification and a distinctive expression analysis of 18 C. papaya Aux/IAA (CpIAA) genes were performed using newly updated papaya reference genome data. The Aux/IAA gene family in papaya is slightly smaller than that in Arabidopsis, but all of the phylogenetic subfamilies are represented. Most of the CpIAA genes are responsive to various phytohormones and expressed in a tissues-specific manner. To understand the putative biological functions of the CpIAA genes involved in fruit development and ripening, quantitative real-time PCR was used to test the expression profiling of CpIAA genes at different stages. Furthermore, an IAA treatment significantly delayed the ripening process in papaya fruit at the early stages. The expression changes of CpIAA genes in ACC and 1-MCP treatments suggested a crosstalk between auxin and ethylene during the fruit ripening process of papaya. CONCLUSIONS: Our study provided comprehensive information on the Aux/IAA family in papaya, including gene structures, phylogenetic relationships and expression profiles. The involvement of CpIAA gene expression changes in fruit development and ripening gives us an opportunity to understand the roles of auxin signaling in the maturation of papaya reproductive organs.

Anticoagulation for Hypercoagulable Patients Associated with Complications after Large Cranioplasty Reconstruction.

BACKGROUND: Despite advancements in materials and techniques used for cranial reconstruction, complication rates following reconstructive cranioplasty remain significant. METHODS: In this study, the authors assessed the association of perioperative anticoagulation use and/or a hypercoagulable state with minor (i.e., not requiring surgical intervention) and major (i.e., surgical intervention required) complications after reconstructive cranioplasty for large skull defects. A retrospective cohort review of 108 consecutive cranioplasties performed between 2011 and 2014 was conducted. A multiple logistic regression analysis was performed to identify the adjusted association between the predictor variables and complications. RESULTS: Twenty-three primary (21.3 percent) and 85 secondary (78.7 percent) cranioplasties were performed on 94 patients with a median age of 50 years (interquartile range, 38 to 63 years). Median full-thickness calvarial defect size was 154 cm (interquartile range, 104 to 230 cm). Eleven minor (10.2 percent) and 18 major postoperative complications (16.7 percent) occurred in 26 cases (24.1 percent). Multiple logistic regression analysis revealed that coagulation status (i.e., perioperative use of anticoagulation therapy or hypercoagulable state) was statistically significant in predicting minor complications (OR, 7.8; 95 percent CI, 2.4 to 25.2; p = 0.001). Of note, the odds of a minor complication were an order of magnitude higher when both perioperative anticoagulation and a hypercoagulable state were present. CONCLUSION: To the authors' knowledge, this is the first study to document that the use of perioperative anticoagulant therapy for patients with thromboembolic conditions is a positive predictor of complications following cranioplasty reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Time Interval Reduction for Delayed Implant-Based Cranioplasty Reconstruction in the Setting of Previous Bone Flap Osteomyelitis.

BACKGROUND: Reinfections following implant-based cranioplasty, in the setting of previous bone flap osteomyelitis, are common and associated with significant morbidity. The timing of reconstruction following initial osteomyelitic bone flap removal remains controversial; most advocate for prolonged time intervals of approximately 6 to 12 months. Thus, the authors investigated their delayed cranioplasty outcomes following both early (between 90 and 179 days) and late (≥ 180 days) time intervals with custom craniofacial implants to determine whether timing affected outcomes and rates of reinfection. METHODS: An institutional review board-approved retrospective cohort review of 25 consecutive cranioplasties, from 2012 to 2014, was conducted. A nonparametric bivariate analysis compared variables and complications between the two different time interval groups, defined as early cranioplasty (between 90 and 179 days) and cranioplasty (≥ 180 days). RESULTS: No significant differences were found in primary and secondary outcomes in patients who underwent early versus late cranioplasty (p > 0.29). The overall reinfection rate was only 4 percent (one of 25), with the single reinfection occurring in the late group. Overall, the major complication rate was 8 percent (two of 25). Complete and subgroup analyses of specific complications yielded no significant differences between the early and late time intervals (p > 0.44). CONCLUSIONS: The results suggest that early cranioplasty is a viable treatment option for patients with previous bone flap osteomyelitis and subsequent removal. As such, a reduced time interval of 3 months--with equivalent outcomes and reinfection rates--represents a promising area for future study aiming to reduce the morbidity surrounding prolonged time intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Immediate Single-Stage Cranioplasty Following Calvarial Resection for Benign and Malignant Skull Neoplasms Using Customized Craniofacial Implants.

UNLABELLED: Craniectomy defects following resection of calvarial lesions are most often reconstructed using on-table manufacturing. With the advent of computer-aided design/manufacturing and customized craniofacial implants (CCIs), there seems to be more suited alternatives. In this study, the authors report their institutional experience and outcome using immediate, single-stage, CCI-based reconstruction for benign and malignant skull neoplasm defects. METHODS: A retrospective review of a prospectively maintained database of all implant cranioplasties performed between 2011 and 2014, by a single craniofacial surgeon at a tertiary academic medical institution was performed. Preoperative and postoperative computed tomography scans with 3D reconstruction were performed for the purpose of assessing adequate resection and reconstructive outcomes. Primary endpoints included length of surgery, predicted defect versus postoperative implant surface area, contour irregularities, and complications. RESULTS: Of the 108 patients with cranioplasty identified, 7 patients were found to undergo immediate CCI-based reconstruction for calvarial neoplasms; 4 patients (4/7, 57%) presented with malignant pathology. All defects were >5  cm2. As compared with their original size, all implants were modified intraoperatively between 0.2% and 40.8%, with a mean of 13.8%. With follow-up ranging between 1 and 16 months, there were no implant-related complications identified. The immediate and long-term aesthetic results, as well as patient satisfaction, were ideal. CONCLUSION: With this preliminary experience, the authors have successfully demonstrated that immediate customized implant reconstructive techniques, by way of intraoperative modification, are both safe and feasible for benign and malignant skull neoplasms. The authors believe that with wider acceptance of this multidisciplinary approach and increased surgeon familiarity, this technique will soon become the reconstructive standard of care.

Quantitative analysis of dual-purpose, patient-specific craniofacial implants for correction of temporal deformity.

BACKGROUND: The development of computer-assisted design, virtual modeling, and computed tomography has allowed precise customization of implants for patients who undergo neurosurgical or craniofacial surgery procedures. However, such techniques and implant designs have not adequately addressed temporal asymmetry due to postoperative bone resorption, temporalis muscle malposition/foreshortening, and/or temporal fat pad atrophy. OBJECTIVE: We hypothesized that an alteration in customized craniofacial implant (CCI) design with a strategic extension inferolaterally and excessive material bulking would provide simultaneous reconstruction of coexisting temporal skull defects and therefore reduce the effect of soft tissue deformities. METHODS: A single-surgeon, single-institution retrospective cohort study was performed to include 10 consecutive subjects who underwent cranioplasty reconstruction with modified implants during a 3-year period. Implants were placed with the use of our previously described pericranial-onlay technique. With the use of a computed tomography-based, computer-assisted design/manufacturing methodology, novel dual-purpose implants were designed to prevent and/or correct persistent temporal hollowing. The efficacy of the new CCI shape and design for cranial restoration of temporal symmetry was analyzed in both 2 and 3 dimensions. RESULTS: In 2-dimensional analyses, the modified implant provided enhanced lateral projection (21%; 1.06 cm(3)) in areas closest to the temporal arch. Three-dimensional volumetric analyses demonstrated that additional bulking totaled 24 ± 11 cm(3) (range, 9-43 cm), which essentially replaced 40 ± 13.7% (range, 26%-60%) of the absent temporal volume contributing to persistent temporal hollowing. CONCLUSION: Computer-designed, dual-purpose CCIs can be safely created with unprecedented shape to prevent and/or eradicate postoperative temporal deformity.