Type C1 Research Articles

Endothelial and neuronal engagement by AAV-BR1 gene therapy alleviates neurological symptoms and lipid deposition in a mouse model of Niemann-Pick type C2

BackgroundPatients with the genetic disorder Niemann-Pick type C2 disease (NP-C2) suffer from lysosomal accumulation of cholesterol causing both systemic and severe neurological symptoms. In a murine NP-C2 model, otherwise successful intravenous Niemann-Pick C2 protein (NPC2) replacement therapy fails to alleviate progressive neurodegeneration as infused NPC2 cannot cross the blood–brain barrier (BBB). Genetic modification of brain endothelial cells (BECs) is thought to enable secretion of recombinant proteins thereby overcoming the restrictions of the BBB. We hypothesized that an adeno-associated virus (AAV-BR1) encoding the Npc2 gene could cure neurological symptoms in Npc2−/− mice through transduction of BECs, and possibly neurons via viral passage across the BBB.MethodsSix weeks old Npc2−/− mice were intravenously injected with the AAV-BR1-NPC2 vector. Composite phenotype scores and behavioral tests were assessed for the following 6 weeks and visually documented. Post-mortem analyses included gene expression analyses, verification of neurodegeneration in Purkinje cells, determination of NPC2 transduction in the CNS, assessment of gliosis, quantification of gangliosides, and co-detection of cholesterol with NPC2 in degenerating neurons.ResultsTreatment with the AAV-BR1-NPC2 vector improved motor functions, reduced neocortical inflammation, and preserved Purkinje cells in most of the mice, referred to as high responders. The vector exerted tropism for BECs and neurons resulting in a widespread NPC2 distribution in the brain with a concomitant reduction of cholesterol in adjacent neurons, presumably not transduced by the vector. Mass spectrometry imaging revealed distinct lipid alterations in the brains of Npc2−/− mice, with increased GM2 and GM3 ganglioside accumulation in the cerebellum and hippocampus. AAV-BR1-NPC2 treatment partially normalized these ganglioside distributions in high responders, including restoration of lipid profiles towards those of Npc2+/+ controls.ConclusionThe data suggests cross-correcting gene therapy to the brain via delivery of NPC2 from BECs and neurons.

Short-term clinical efficacy of unilateral external fixator combined with percutaneous Kirschner wire fixation in the treatment of type C1 distal radius fractures in elderly patients

To investigate the short-term clinical effect of closed reduction single arm external fixator combined with percutaneous needle fixation in the treatment of C1 distal radius fracture in elderly patients. Between December 2022 and December 2023, a total of 60 elderly patients diagnosed with type C1 distal radius fractures were treated, comprising 9 males and 51 females. The age ranged from 65 to 84 years old, with an average of (72.69±8.14) years old. Among them, there were 18 cases on the left side and 42 cases on the right side. There were 55 cases of falling injury and 5 cases of traffic accident injury. According to the different surgical methods, the patients were divided into observation group and control group, with 30 cases in each group. The control group underwent manual reduction and unilateral external fixator fixation, consisting of 4 males and 26 females. The mean age was (72.54±8.67) years old. The body mass index (BMI) was (20.61±2.17) kg·m-2. There were 10 cases on the left side and 20 cases on the right side. Among them, there were 27 cases of falling injury and 3 cases of traffic accident injury. The observation group was treated with manual reduction and unilateral external fixator combined with percutaneous Kirschner wire fixation, including 5 males and 25 females. The mean age was (72.76±7.23) years old. BMI (20.82±2.03) kg·m-2. The left side was involved in 8 cases and the right side in 22 cases. There were 28 cases of falling injury and 2 cases of traffic accident injury. The changes in radial height, ulnar declination, palmar inclination angle parameters and patient-rated wrist evaluation (PRWE) were assessed on X-ray films before surgery, 2 days after surgery, and 12 weeks after surgery between the two groups. All surgical procedures were successfully completed in both groups without any significant complications. All patients were followed up for a duration from 12 to 20 weeks with an average of(14.50±2.78) weeks. The two groups exhibited significant differences in radial height, palmar inclination angle, and ulnar deviation angle at 2 days and 12 weeks post-operation (P<0.05). However, there was no statistically significant difference observed in radial height, palmar inclination, and ulnar deviation between the two groups at 2 days after the operation (P>0.05). There were significant differences in radial height, palmar inclination angle, and ulnar deviation between the two groups at 12 weeks after operation (P<0.05). At 2 days and 12 weeks after the operation, there were significant differences in PRWE scores of the two groups compared with preoperative scores(P<0.05). At 2 days after the operation, there was no significant difference in PRWE score between the two groups (P>0.05). The PRWE score showed a significant difference between the two groups at 12 weeks post-operation(P<0.05). The combination of closed reduction and unilateral external fixator, along with percutaneous pin fixation provides move stable fixation for type C1 distal radius fractures. Gradual removal of external fixator further facilitatse the recovery of wrist joint function.

Preliminary application of human-computer interaction CT imaging AI recognition and positioning technology in the treatment of type C1 distal radius fractures

To explore the accuracy of human-computer interaction software in identifying and locating type C1 distal radius fractures. Based on relevant inclusion and exclusion criteria, 14 cases of type C1 distal radius fractures between September 2023 and March 2024 were retrospectively analyzed, comprising 3 males and 11 females(aged from 27 to 82 years). The data were assigned randomized identifiers. A senior orthopedic physician reviewed the films and measured the ulnar deviation angle, radial height, palmar inclination angle, intra-articular step, and intra-articular gap for each case on the hospital's imaging system. Based on the reduction standard for distal radius fractures, cases were divided into reduction group and non-reduction group. Then, the data were sequentially imported into a human-computer interaction intelligent software, where a junior orthopedic physician analyzed the same radiological parameters, categorized cases, and measured fracture details. The categorization results from the software were consistent with manual classifications (6 reduction cases and 8 non-reduction cases). For non-reduction cases, the software performed further analyses, including bone segmentation and fracture recognition, generating 8 diagnostic reports containing fracture recognition information. For the 6 reduction cases, the senior and junior orthopedic physicians independently analyzed the data on the hospital's imaging system and the AI software, respectively. Bone segments requiring reduction were identified, verified by two senior physicians, and measured for displacement and rotation along the X (inward and outward), Z (front and back), and Y (up and down) axes. The AI software generated comprehensive diagnostic reports for these cases, which included all measurements and fracture recognition details. Both the manual and AI software methods consistently categorized the 14 cases into 6 reduction and 8 non-reduction groups, with identical data distributions. A paired sample t-test revealed no statistically significant differences (P>0.05) between the manual and software-based measurements for ulnar deviation angle, radial ulnar bone height, palmar inclination angle, intra-articular step, and joint space. In fracture recognition, the AI software correctly identified 10 C-type fractures and 4 B-type fractures. For the 6 reduction cases, a total of 24 bone fragments were analyzed across both methods. After verification, it was found that the bone fragments identified by the two methods were consistent. A paired sample t-tests revealed that the identified bone fragments and measured displacement and rotation angles along the X, Y, and Z axes were consistent between the two methods. No statistically significant differences(P>0.05) were found between manual and software measurements for these parameters. Human-computer interaction software employing AI technology demonstrated comparable accuracy to manual measurement in identifying and locating type C1 distal radius fractures on CT imaging.

Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer.

Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling. This process is dependent on cholesterol transport through Niemann-Pick disease type C1 (NPC1) and mediates homeostatic and Toll-like receptor (TLR)-induced maturation. Importantly, we identified the receptor tyrosine kinase AXL as a regulator of the NPC1-dependent construction of lipid nanodomains. Deleting AXL from cDCs enhances their maturation, thus improving anti-tumor immunity. Altogether, our study presents new insights into cholesterol mobilization as a fundamental basis for cDC maturation and highlights AXL as a therapeutic target for modulating cDCs.

Treatment of unstable pelvic fractures with double INFIX

BackgroundThis study investigated the clinical efficacy of Double INFIX for the treatment of unstable pelvic fractures.MethodsWe performed a retrospective analysis of 23 patients with unstable pelvic fractures treated using the Double INFIX minimally invasive technique. The cohort included five cases of Tile B1 type, eight cases of B2 type, six cases of B3 type, three cases of C1 type and one case of type C2. Pre- and postoperative evaluations included standardised pelvic serial films and three-dimensional CT scans. Key observational indicators were fracture reduction quality (assessed using Matta’s criteria), fracture healing, functional recovery (evaluated with the Majeed function assessment criteria), and incidence of complications.ResultsThe mean follow-up duration was 24.48 ± 1.78 months. The average fracture healing time was 4.00 ± 1.41 months, and the average time for removal of fixation was 7.43 ± 1.75 months. Repeat imaging at 12 months postoperatively using Matta’s criteria showed eight cases with excellent results (52.17%), 13 cases with good results (34.78%), three cases with fair results (13.04%), and no cases with poor results. The combined excellent and good rate was 86.96%, whereas the fair rate was 13.04%. The average Majeed hip joint function score at the final follow-up was 95.04 ± 1.72. Postoperative complications included meralgia paresthetica in two cases (8.7%) and sacrococcygeal discomfort in three patients when lying flat.ConclusionDouble INFIX is a minimally invasive treatment technique with adequate clinical efficacy for managing unstable pelvic fractures.

Discrepancy between radiography and magnetic resonance imaging in Japanese Investigation Committee classification type C osteonecrosis of the femoral head

PurposeThe Japanese Investigation Committee (JIC) classification for osteonecrosis of the femoral head (ONFH) is based on the necrotic area relative to the weight-bearing surface on anteroposterior (AP) radiographs or central coronal MRI. Discrepancies exist between these methods, potentially related to the AP necrosis area. This study evaluated these discrepancies and the extent of AP necrotic lesions.MethodsWe retrospectively reviewed 139 patients (188 hips) with nontraumatic ONFH, JIC type C1 or C2 on radiography, and collapse < 3 mm. Cases with and without discrepancies between radiography and MRI were designated as discrepancy and consistent groups, respectively. We assessed the proportion of patients in the discrepancy group and survival rates in both groups, with femoral head collapse > 3 mm as the endpoint. The cutoff value for AP necrotic regions on lateral radiographs identifying discrepancies was calculated using ROC curve analysis.ResultsThe discrepancy group comprised 28 hips (14.9%) vs. 160 hips in the consistent group. Five-year survival rates were 73.3% vs. 31.9% (P < 0.01), and AP necrotic region extent was 61.2 vs. 73.8 mm (P < 0.001) in discrepancy vs. consistent groups. The cutoff value for necrotic region extent revealing discrepancies was 66.9% (AUC 0.833, sensitivity 83.8%, specificity 82.4%).ConclusionPatients with AP necrotic regions < 66.9% were more likely to show discrepancies between radiography and MRI in type classification. This study can help improve accuracy in assessing ONFH severity and prognosis.

Biomechanical Evaluation of Clival Screw Fixation for Occipitocervical Instablity: A Finite Element Analysis.

The clivus is trapezoidal in shape with uneven bone structure, the optimal number and position of screws for clival fixation are not clear. Therefore, this study aims to explore the optimization clival screw fixation method for occipitocervical instability using finite element analysis. Seven finite element models were developed to evaluate biomechanical properties of clival screw fixation for treating occipitocervical stability, including (i) one clival screw fixation A1 and A2 models; (ii) two clival screws fixation B1 and B2 models; (iii) three clival screws fixation C1 and C2 models; (iv) four clival screws fixation D1 model. Loads of 1.5 Nm were applied to the model fRoM different directions to induce flexion, extension, lateral bending, and axial rotation movements. The regular triangle C1 type three clival screws fixation exhibited great stability, with RoM of 4.20° in flexion, 5.80° in extension, 0.85° in lateral bending, and 1.60° in axial rotation. The peak stress on the internal fixation devices were relatively low, with maximum screw stress of 194 MPa in flexion, 276 MPa in extension, 180 MPa in lateral bending, and 213 MPa in axial rotation; the maximum plate stress were 126, 554, 426, and 378 MPa, respectively. The areas with higher stress were mainly concentrated at the robust neck section of the plate. The triangular configuration of three clival screws fixation represented the optimized anterior occipitocervical fixation method through the clivus, offering superior biomechanical stability, lower stress on the devices and dispersed stress distribution in the occipitocervical region.

Cerebrospinal Fluid and Serum Neuron-Specific Enolase in Niemann-Pick Disease Type C1.

Niemann-Pick disease, type C1 (NPC1) is an ultra rare, autosomal recessive disorder characterized by impaired intracellular cholesterol trafficking. This study assessed neuron-specific enolase (NSE) as a biomarker for disease status and treatment response in individuals with NPC1. We also evaluated the concordance between serum and cerebrospinal fluid (CSF) NSE measurements. A total of 34 individuals with NPC1 were included in this analysis. Overall, 10 participants were used to compare concurrent samples of CSF and serum NSE. NSE levels were correlated with indexes of disease severity (Annual Severity Increment Score [ASIS] and age of neurological onset) and disease burden (NPC Neurological Severity Score [NSS]). NSE was elevated in CSF, but paired CSF/serum samples were not correlated (rs = -0.16, p = 0.64). Additionally, no significant correlations were observed between serum NSE levels and clinical measures of either disease burden or severity. CSF NSE values showed a significant positive association with the ASIS (rs = 0.37, p = 0.0291) but no association with age of neurological onset or NPC NSSs. Longitudinal analysis of nine participants showed a significant (p = 0.0317) decrease in CSF NSE levels after initiation of intrathecal 2-hydroxypropyl-β-cyclodextrin (IT HPβCD) therapy. This study suggests that CSF NSE may have some utility as a biomarker in NPC1 therapeutic trials.

Feline Adenovirus Isolate Shows Silent Nucleotide Alterations, Alternative Receptor/Coreceptor Binding, High Resistance to Disinfectants and Antiviral Drugs, as Well as Immunomodulation.

Adenovirus (AdV) infection has been rarely documented in cats and other felids. Partial sequences of the hexon and fiber genes of a Hungarian feline adenovirus isolate (FeAdV isolate) showed a close relationship to human AdV (HAdV) type C1. Further molecular and biological characterization is reported here. Whole-genome sequencing revealed two silent mutations in the genome of the FeAdV isolate compared to a HAdV-C1 reference strain (at positions 14,096 and 15,082). Competitive antibody binding to the Coxsackie-adenovirus receptor and αvβ3 and αvβ5 integrin coreceptors inhibited the binding of the FeAdV isolate in different cell lines, but residual infections suggested alternative entry routes. The FeAdV isolate was found to be more sensitive to heat, low pH and detergents, but more resistant to alkaline and free chlorine treatments, as well as to ribavirin, stavudine and cidofovir treatments, than other human AdV types. We observed a suppression of IL-10 and TGF-β1 production during the entire course of viral replication. This immunomodulation may restore intratumoral immunity; thus, the FeAdV isolate could serve as an alternative oncolytic vector. Collectively, our results support that the Hungarian FeAdV isolate is a variant of common HAdV-C1. The cohabitation of cats with humans might result in reverse zoonotic infection. Felids appear to be susceptible to persistent and productive adenovirus infection, but further studies are needed to better understand the clinical and epidemiological implications.

Dipyridamole Ameliorates Memory Impairment and Increases Hippocampal Calbindin Expression in Niemann Pick C1 Mice

ABSTRACTNiemann Pick type C1 (NPC1) is a rare, fatal disorder characterized by endosomal lipid accumulation that leads to damage of both peripheral organs and central nervous system (cerebellum and hippocampus are especially affected). Currently, miglustat is the only approved drug for NPC1, thus the identification of new treatments is mandatory. We have previously demonstrated that the drug dipyridamole (DIP), an enhancer of adenosine signaling, can reduce the pathological phenotype in patient‐derived fibroblasts. In this paper, we evaluated the in vivo effects of DIP in NPC1 mice. Male and female NPC1nih mice were treated with DIP 30 mg/kg i.p. from 28 to 64 days of age. Motor function was assessed by Erasmus Ladder test, hippocampal cognitive decline by Novel Object Recognition test and brain pathology by immunofluorescence and biochemical assays. Peripheral pathology was evaluated by analyzing lipid accumulation in spleen and liver (HP‐TLC). In NPC1, mice DIP rescued recognition memory and increased hippocampal expression of calbindin. On the contrary, the drug was unable to improve motor function, cerebellar pathology and lipid accumulation in spleen and liver. Our results demonstrated that DIP selectively ameliorates the cognitive impairment in NPC1 mice. This drug could thus represent a valuable therapeutic tool to be used in combination with other treatments in NPC1.

On Lusztig’s Character Formula for Chevalley Groups of Type Al

For a Chevalley group G over an algebraically closed field K of characteristic p&gt;0 with the irreducible root system R, Lusztig’s character formula expresses the formal character of a simple G-module by the formal characters of the Weyl modules and the values of the Kazhdan–Lusztig polynomials at 1. It is known that, for a sufficiently large characteristic p of the field K, Lusztig’s character formula holds. The known lower bound of the characteristic p is much larger than the Coxeter number h of the root system R. Observations show that for simple modules with restricted highest weights of small Chevalley groups such as those of types A1,A2, A3,B2, B3, and C3, Lusztig’s character formula holds for all p≥h. For large Chevalley groups, no other examples are known. In this paper, for G of type Al, we give some series of simple modules for which Lusztig’s character formula holds for all p≥h. Using this result, we compute the cohomology of G with coefficients in these simple modules. To prove the results, Jantzen’s filtration properties for Weyl modules and the properties of Kazhdan–Lusztig polynomials are used.

Comparison of the stability of dual INFIX and INFIX combined with sacroiliac screw fixation for C1 type pelvic fractures

To evaluate the biomechanical stability of dual anterior subcutaneous internal fixation (INFIX) in pelvic C1 fractures by finite element analysis, and to compare it with INFIX combined with sacroiliac screws to determine whether it is sufficient to replace the combined fixation of anterior and posterior rings. The pelvic CT data of a 43-year-old female volunteer were imported into the computer and the normal pelvic model and pelvic C1 fractures model were constructed using Mimics, Workbench and other software. The latter was fixed with dual INFIX and INFIX combined with sacroiliac screws, respectively. First, the effectiveness of the normal pelvic model in anatomical landmarks, stress conduction and displacement distribution was verified. Then, a vertical downward load of 500 N was applied to the two internal fixation models to simulate the standing and sitting positions of the human body, and the displacement of the anterior and posterior ring fractures ends, the stress of the internal fixation and the stress of the nail channel in the bone were collected. The model passed the validity verification. The maximum displacement of the anterior and posterior ring fractures in the standing dual INFIX group were 0.861 mm and 4.128 mm, respectively, which were both smaller than the 0.152 mm and 0.293 mm in the combined fixation group. The displacement of the posterior ring fractures in the sitting dual INFIX group was 3.757 mm, which was larger than the 0.560 mm in the combined fixation group, while the maximum displacement of the anterior ring fractures was 0.221 mm, which was not much different from the 0.194 mm in the combined fixation group. The maximum stress of internal fixation in the standing dual INFIX group was greater than that in the combined fixation group, while the opposite was true in the sitting position. The maximum stress of each internal fixation was lower than the yield strength of titanium alloy 790 MPa. The maximum stress of the nail channel in the standing and sitting daul INFIX groups was lower than that in the combined fixation group, and the stress of all nail channels was lower than the strength limit of bone 290 to 540 MPa. The stability of dual INFIX fixation in anterior and posterior ring fractures is generally inferior to that of INFIX combined with sacroiliac screw fixation. Although simple dual INFIX fixation can share part of the load for the posterior ring, the posterior ring will still have a large displacement, so the fixation of the posterior ring is very important. In addition, the fixation strength and stability of dual INFIX in the anterior ring are better than INFIX. When INFIX cannot provide sufficient strength to stabilize the anterior ring fractures, dual INFIX will be a good choice.

Inhibition of NPC1 suppresses cell proliferation and β-catenin signaling activation of liver cancer.

Niemann-Pick Type C1 (NPC1) plays a significant role in the development of liver diseases and liver cancer. Our objective was to investigate the involvement of NPC1 in regulating liver cancer development. We observed that high levels of NPC1 expression in tumor tissues from patients with liver cancer were associated with a poor prognosis. Through in vitro experiments, we found that inhibiting NPC1 expression reduced the proliferation, invasion, and migration of liver cancer cells, while also inducing apoptosis in these cells. Additionally, the inhibition of NPC1 led to decreased activation of Wnt/β-catenin signaling. In vivo studies further supported our findings by demonstrating that the suppression of liver cancer cell growth was effectively achieved through the inhibition of NPC1. Overall, our results strongly indicate that the inhibition of NPC1 suppresses liver cancer cell proliferation. Targeting NPC1 is a promising potential therapeutic strategy for liver cancer.

Experimental study of fractures of the posterior pelvic ring C1.1 using LC-II screws and internal fixation by plate

IntroductionTo compare the biomechanical outcomes of C1.1 posterior pelvic ring fractures treated with different numbers of LC-II screws and plate internal fixation.Materials and methodsNine adult preserved pelvic specimens were used. After being measured by bone densitometry, the specimens were randomly divided into 3 groups of 3 pelvic specimens each. The C1.1 pelvic fractures were generated by iliac osteotomies and anterior pelvic ring osteotomies. The fractures were fixed and randomly divided into three groups: (1) one LC-II screw, (2) two LC-II screws, and (3) two reconstruction plates. The anterior pelvic rings were all fixed with pubic branch screws. A biomechanical testing machine loaded all specimens vertically, recording the displacement and ultimate load of the specimens to quantify the stiffness.ResultsWhen loads up to 1000 N were applied, the displacement of the iliac bone was close between the one LC-II screw and the two LC-II screw group specimens; (P > 0.05); when loads such as 1000 N, 1200 N and 1400 N were applied, there was no significant difference in displacement between the plate fixation group and the two LC-II screw fixation group (P > 0.05), both of which were superior to the one LC-II screw fixation group (P < 0.05). There was no significant difference in compressive stiffness between the two LC-II screw fixation groups and the plate fixation group (P > 0.05), and both were superior to the one LC-II screw fixation group (P < 0.05) the ultimate load of both the two LC-II screws and the steel plate is greater than that of one LC-II screw (1.74 times the ultimate load of one LC-II screw for the two LC-II screws and 1.83 times the ultimate load of one LC-II screw for the steel plate).ConclusionFor posterior pelvic ring fractures of type C1.1, placement of two LC-II screws provides comparable posterior pelvic ring stability compared to reconstructed plates. At loads below 1000 N, one LC-II screw fixation and two LC-II screws were comparable in restoring posterior pelvic ring stability.

Severe multiple injuries in a 15-year-old boy with pelvic fracture complete anterior dislocation of the sacroiliac joint and rupture of the internal and external iliac arteries: A case report of a rare injury.

Anterior dislocation of the sacroiliac joint combined with pelvic fractures is relatively rare in clinical practice. It is often associated with hemodynamic instability and severe injuries to other regions, resulting in a complex condition, prolonged treatment duration, and high rates of mortality and disability. However, there are few reports in the literature describing the diagnosis and treatment of anterior dislocation of the sacroiliac joint. In this case, the patient sustained a pelvic fracture with anterior sacroiliac joint dislocation and rupture of both the internal and external iliac arteries following a motor vehicle accident, making it an even rarer and more challenging case to treat. Reporting such cases can enhance the understanding of the diagnosis and treatment of anterior sacroiliac joint dislocation with rupture of the iliac arteries and provide valuable references for similar cases. The patient was riding an electric bicycle and was hit by a small truck, resulting in a pelvic fracture, anterior dislocation of the sacroiliac joint, and rupture of the internal and external iliac arteries. The patient was diagnosed with open pelvic fracture (type C1.2), left complete anterior dislocation of the sacroiliac joint, left acetabular fracture, left internal and external iliac arteriovenous rupture. emergency room resuscitation, intensive care unit resuscitation, 6 surgeries and perioperative management. He has been discharged from the hospital for more than 1 year and was rechecked every month after discharge, the fracture has healed, there is no obvious pain and discomfort in and around the wound, he has been fitted with a prosthesis, and he is doing the walking function exercise. Pelvic fracture with anterior sacroiliac dislocation is clinically rare and critical, and is associated with large vessel rupture, severe organ damage, and high mortality and disability rates. Rapid restoration of pelvic stability and hemodynamic stability is the key to treatment. Rapid transfer to a tertiary trauma center, rapid examination through the green channel to clarify the diagnosis, close intensive care, and reasonable multidisciplinary teamwork for surgical intervention are all valuable experiences that we have concluded.

Radiographic features and subtypes of congenital thumb duplication type C3 according to Wu et al. and their potential implications for surgical management: new classification and preliminary results

BackgroundWu et al. introduced a modified radiographic system that allows classification of all forms of CTD with excellent interobserver and intraobserver reliability. No study to date has evaluated the radiographic characteristics of Wu et al. type C3 CTD with osseous attachment at the level of the metacarpal.ObjectiveThis study aimed to evaluate the radiographic features of type C3 CTD according to the system of Wu et al., to describe the different anatomical subtypes of the duplication, and to propose a categorization approach to distinguish diverse surgical strategies based on the radiographic anatomy of this specific subtype of duplication.MethodsWe performed a retrospective analysis of 215 patients (221 thumbs) diagnosed with Wu et al. type C3 CTD at our Institution between 2015 and 2021. We evaluated all CTDs by examining the alignment of the interphalangeal (IP) and metacarpophalangeal (MP) joints and by assessing the presence of abnormal hypertrophic epiphysis of the primary thumb on posteroanterior (PA) radiographs. The proposed classification system has four types: Type I with good alignment of both MP and IP joints, Type II with ulnar deviation of the MP joint, Type III with radial deviation in the MP joint and Type IV with abnormal hypertrophic epiphysis of the distal phalanx of the main thumb with ulnar deviation of the IP joint with or without ulnar deviation of the MP joint.ResultsThere were 140 male and 75 female patients with CTD (221 thumbs). There were 65 left, 144 right and 6 bilateral forms. The right-to-left, male-to-female and unilateral-to-bilateral ratios were 2.2:1, 1.9:1 and 35.8:1 respectively. The mean age at surgery was 22.3 ± 11.8 months (range, 8–80). The proposed classification system allowed the classification of all CTDs (n = 221). Specifically, 53 fingers were classified as Type I (24%), 136 as Type II (61.5%), 21 as Type III (9.5%), and 11 as Type IV (5%).ConclusionThe proposed system is based on radiographic pathoanatomy and complements that of Wu et al. by identifying four distinct subtypes of deformity. It has the potential to improve inter-professional communication and guide surgery in patients with Wu et al. type C3 CTD. However, our results are preliminary and further research is needed to validate them.Level of evidenceIII.

Response of Types of Cuttings and IBA Concentration from First Sprout to Highest Sprouting and Rooting in Crossandra (Crossandra infundibuliformis L.)

The present investigation was conducted under Konkan Agro-climatic conditions at College of Horticulture, Dr. Balasaheb Sawant Konkan Krishi Vidyapeeth, Dapoli, Dist. Ratnagiri (India) during the kharif season (2023-2024). The experiment was laid out in Factorial Randomized Block Design (FRBD) with twelve treatment combinations and three replications. Present investigation found that in types of stem cuttings treatment C1 :Softwood cuttings was found best with respect to minimum days to first sprout, days to highest sprouting , maximum number of new sprouts/cuttings, girth of sprout, length of new sprout, number of leaves, leaf area, survival(%), fresh weight of shoot, dry weight of shoot, absolute growth rate, relative growth rate, number of roots, length of longest root, fresh weight of root, dry weight of root, shoot to root ratio. In different IBA concentration treatment H4 : IBA@2000ppm was found best with respect to minimum days to first sprout, days to highest sprouting , maximum number of new sprouts/cuttings, girth of sprout, length of new sprout, number of leaves, leaf area, survival(%), fresh weight of shoot, dry weight of shoot, absolute growth rate, relative growth rate, number of roots, length of longest root, fresh weight of root, dry weight of root. In interaction effect treatment C1H4 (Softwood cuttings treated with IBA@2000 ppm) is found to be most effective among all other treatment combinations in terms of most of the parameters such as Sprouting percentage, Number of new sprouts/cuttings, Length of sprout/cuttings, Girth of new sprout, Number of leaves/cuttings, Leaf area, Survival percentage, Fresh weight of shoot, Relative Growth Rate, Fresh weight to dry weight of shoot ratio, Number of roots.

Decision tree insights analytics (DTIA) tool: an analytic framework to identify insights from large data records across fields of science

Abstract Supervised machine learning (SML) techniques have been developed since the 1960s. Most of their applications were oriented towards developing models capable of predicting numerical values or categorical output based on a set of input variables (input features). Recently, SML models’ interpretability and explainability were extensively studied to have confidence in the models’ decisions. In this work, we propose a new deployment method named Decision Tree Insights Analytics (DTIA) that shifts the purpose of using decision tree classification from having a model capable of differentiating the different categorical outputs based on the input features to systematically finding the associations between inputs and outputs. DTIA can reveal interesting areas in the feature space, leading to the development of research questions and the discovery of new associations that might have been overlooked earlier. We applied the method to three case studies: (1) nuclear reactor accident propagation, (2) single-cell RNA sequencing of Niemann-Pick disease type C1 in mice, and (3) bulk RNA sequencing for breast cancer staging in humans. The developed method provided insights into the first two. On the other hand, it showed some of the method’s limitations in the third case study. Finally, we presented how the DTIA’s insights are more agreeable with the abstract information gain calculations and provide more in-depth information that can help derive more profound physical meaning compared to the random forest’s feature importance attribute and K-means clustering for feature ranking.

Immune-related glycosylation genes based classification predicts prognosis and therapy options of osteosarcoma

Osteosarcoma is the most common primary bone malignancy, with a very poor prognosis. Aberrant glycosylation is close involvement in osteosarcoma. Accordingly, this study aimed at investigating the role of glycosylation genes in the prognosis and therapy options of osteosarcoma. The microenvironment of osteosarcoma was assessed using estimate algorithm. A total of 20 immune-related glycosylation genes (IRGGs) was identified using Pearson correlation analysis. Accordingly, osteosarcoma patients were divided into C1 and C2 type using consensus clustering. Multiple algorithms (Xcell, MCP-counter, ssGSEA, epic, quantiseq), cancer immune cycle analysis, and GSVA were applied to estimate the immune, molecule and metabolism characteristics of osteosarcoma, indicating that C1 type was featured with high immune infiltration, high glycosylation, enriched MEK signaling, and good prognosis, while C2 type was characterized by more metastasis, enriched immunotherapy-positive gene signatures, high tumor mutation burden, and poor prognosis. Results from TIDE algorithm and immunotherapy datasets suggested the C2 type’s preference of immune checkpoint inhibitors (ICIs), while data of GDSC, CMap analysis and cell experiments indicated that C1 type was sensitivity to MEK inhibitor PD0325901. In addition, univariate Cox and Lasso analysis was combined to establish an IRGGs’ risk score containing 6 genes (B3GNT8, FUT7, GAL3ST4, GALNT14, HS3ST2, and MFNG). The data of DCA and ROC indicated its well prediction of prognosis in osteosarcoma. Finally, cellular location analysis showed that the 6 genes not only distributed in tumor cells but also in immune cells. In summary, the classification and risk score based on IRGGs effectively predicted the prognosis and therapy options of osteosarcoma. Further studies on IRGGs may contribute to the understanding of cancer immunity in osteosarcoma.

Tissue-Engineered Bone Regeneration for Medium-to-Large Osteonecrosis of the Femoral Head in the Weight-Bearing Portion: An Observational Study.

Stem cell therapy for the treatment of osteonecrosis of the femoral head (ONFH) showed promising outcomes. However, ONFH with a large lesion in the weight-bearing portion is a poor prognostic factor and still challenging issue to be solved. We aimed to evaluate the effect of tissue-engineered bone regeneration for this challenging condition to preserve the femoral head. A total of 7 patients (9 hips) with ONFH who received osteoblasts expanded ex vivo from bone marrow-derived mesenchymal stem cells (BMdMSCs) and calcium metaphosphate (CMP) as scaffolds from March 2002 to March 2004 were retrospectively reviewed. The median age was 27.0 years (interquartile range [IQR], 23.0-34.0 years), and the median follow-up period was 20.0 years (IQR, 11.0-20.0 years). After culture and expansion of stem cells, we performed core decompression with BMdMSC implantation at a median number of 10.1 ×107 (IQR, 9.9-10.9 ×107). To evaluate radiographic outcomes, the Association Research Circulation Osseous (ARCO) classifications, the Japanese Investigation Committee (JIC) classification, and modified Kerboul combined necrotic angle (mKCNA) were evaluated preoperatively and during follow-up. Clinical outcomes were evaluated by a visual analog scale (VAS) and Harris Hip Score (HHS). The preoperative stage of ONFH was ARCO 2 in 5 hips and ARCO 3a in 4 hips. The ARCO staging was maintained in 3 hips of ARCO 2 and 4 hips of ARCO 3a. Two hips of ARCO 2 with radiographic progression underwent total hip arthroplasty. According to mKCNA, 2 hips showed medium lesions, and 7 hips showed large lesions. The size of necrotic lesion was decreased in 4 hips (2 were ARCO 2 and 2 were ARCO 3a). There were no significant changes in JIC classification in all hips (type C1: 3 hips and type C2: 6 hips) (p = 0.655). Clinically, there were no significant changes in the VAS and HHS between preoperative and last follow-up (p = 0.072 and p = 0.635, respectively). Tissue engineering technique using osteoblasts expanded ex vivo from BMdMSC and CMP showed promising outcomes for the treatment of pre-collapsed and early-collapsed stage ONFH with medium-to-large size, mainly located in weight-bearing areas.