Inhibition of TBL1 cleavage alleviates doxorubicin-induced cardiomyocytes death by regulating the Wnt/ß-catenin signal pathway.

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy (DCM) and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity, and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signaling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSIONS: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.

Environmental Factors Associated with Risk of Crohn's Disease Development in the CCC-GEM Project.

BACKGROUND AND AIMS: To date, it is unclear how environmental factors influence Crohn's Disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4,289 healthy first-degree relatives (FDRs) of CD patients from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio(LMR); gut inflammation via fecal calprotectin(FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5-15 (HR=0.62; 95% CI=0.40-0.96; P = .034), and living with a large family size in the first year of life (HR=0.43; 95% CI=0.21-0.85; P = .016) were associated with decreased CD risk; whereas having a bird at the time of recruitment (HR=2.78; CI=1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity; while bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.

Quantitative Analysis of the Effect of Stereotactic Radiosurgery for Postoperative Residual Cervical Dumbbell Tumors: A Multicenter Retrospective Cohort Study.

OBJECTIVE: Stereotactic radiosurgery (SRS) has been performed for spinal tumors. However, the quantitative effect of SRS on postoperative residual cervical dumbbell tumors remains unknown. This study aimed to quantitatively evaluate the efficacy of SRS for treating postoperative residual cervical dumbbell tumors. METHODS: We retrospectively reviewed cases of postoperative residual cervical dumbbell tumors from 1995 to 2020 in 2 tertiary institutions. Residual tumors underwent SRS (SRS group) or were observed with clinical and magnetic resonance imaging (MRI) follow-up (observation group). Tumor regrowth rates were compared between the SRS and observation groups. Additionally, risk factors for tumor regrowth were analyzed. RESULTS: A total of 28 cervical dumbbell tumors were incompletely resected. Eight patients were in the SRS group, and 20 in the observation group. The mean regrowth rate was not significantly lower (p = 0.784) in the SRS group (0.18 ± 0.29 mm/mo) than in the observation group (0.33 ± 0.40 mm/mo). In the multivariable Cox regression analysis, SRS was not a significant variable (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.18-1.79; p = 0.336). CONCLUSION: SRS did not significantly decrease the tumor regrowth rate in our study. We believe that achieving maximal resection during the initial operation is more important than postoperative adjuvant SRS.

Discovery of N-(1-(2-hydroxyethyl)quinolin-2-one)-N'-(1-phenyl-1H-pyrazol-5-yl)methyl) urea as Mode-Selective TRPV1 antagonist.

To discover mode-selective TRPV1 antagonists as thermoneutral drug candidates, the previous potent antagonist benzopyridone 2 was optimized based on the pharmacophore A- and C-regions. The structure activity relationship was investigated systematically by modifying the A-region by incorporating a polar side chain on the pyridone and then by changing the C-region with a variety of substituted pyridine and pyrazole moieties. The 3-t-butyl and 3-(1-methylcyclopropyl) pyrazole C-region analogs provided high potency as well as mode-selectivity. Among them, 51 and 54 displayed potent and capsaicin-selective antagonism with IC50 = 2.85 and 3.27 nM to capsaicin activation and 28.5 and 31.5 % inhibition at 3 µM concentration toward proton activation, respectively. The molecular modeling study of 51 with our homology model indicated that the hydroxyethyl side chain in the A-region interacted with Arg557 and Glu570, the urea B-region engaged in hydrogen bonding with Tyr511 and Thr550, respectively, and the pyrazole C-region made two hydrophobic interactions with the receptor. Optimization of antagonist 2, which has full antagonism for activators of all modes, lead to mode-selective antagonists 51 and 54. These observations will provide insight into the future development of clinical TRPV1 antagonists without target-based side effects.

Exploring the link between pediatric headaches and environmental noise exposure.

BACKGROUND: Headaches are the most common neurologic symptoms in the pediatric population. Most primary headache in children and adolescents focuses on associated factors, including noise. Auditory discomfort is related to recognizing the pain. We aimed to analyze the headache profile of pediatric populations and the connection between noise exposure and head pain in children and adolescents. METHODS: We reviewed retrospectively medical records of the pediatric population with headaches in Gyeongsang National University Changwon Hospital from January 2022 to April 2023. Personal headache profiling from self-questionnaires and environmental noise data from the National Noise Information System (NNIS) were used to analyze each variable, and chi-square tests and linear regression models by SAS were used to analyze the statistical correlation. RESULTS: Of the 224 participants, 125 were clinically diagnosed with headaches. Of the 104 pubertal subjects, 56.7% were diagnosed with headaches, compared to 60% in the prepubertal group. Both daytime and nighttime noise was significantly higher in the diagnosed headache group than in the non-diagnosed group. Headache duration increased by daytime and nighttime noise with statistical significance in age-adjusted models. CONCLUSION: We found that noise exposure is correlated to headaches in children and adolescents. Daytime and nighttime environmental noise exposure was significantly associated with the duration of headaches through our data. Therefore, we assume that noise exposure is vitally relevant to prolonged headaches in the pediatric population. Further research is needed to improve our data.

Chiral recognition and discrimination studies of tyrosine enantiomers on (-)-18-crown-6-tetracarboxylic acid as a chiral selector by nuclear magnetic resonance spectroscopy and docking simulations.

Considering the substantial significance of chiral biomolecules, such as amino acids, in our daily routines, we performed chiral recognition and discrimination of tyrosine (Tyr) enantiomers on (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid [(-)-18-C-6-TA] as crown-ether type chiral selector (CS) by nuclear magnetic resonance (NMR) spectroscopy and docking simulations. In this study, successful discrimination of the enantiomers of Tyr was achieved, as evidenced by the proton chemical shift differences (ΔΔδ) of Tyr enantiomers observed in the 1 H NMR spectra with (-)-18-C-6-TA CS. We compared the results of these two techniques with the findings obtained from high performance liquid chromatography (HPLC) investigations. In both NMR and HPLC experimental and docking simulation studies, a stronger interaction between the L-Tyr enantiomer with (-)-18-C-6-TA CS than the D-Tyr was consistently observed. Also, the binding energy differences (ΔΔEL-D ) found in simulation data that correspond to enantioselectivity aligned well with the NMR experimental result.

Development of a novel prediction model for differential diagnosis between spinal myxopapillary ependymoma and schwannoma.

Spinal myxopapillary ependymoma (MPE) and schwannoma represent clinically distinct intradural extramedullary tumors, albeit with shared and overlapping magnetic resonance imaging (MRI) characteristics. We aimed to identify significant MRI features that can differentiate between MPE and schwannoma and develop a novel prediction model using these features. In this study, 77 patients with MPE (n = 24) or schwannoma (n = 53) who underwent preoperative MRI and surgical removal between January 2012 and December 2022 were included. MRI features, including intratumoral T2 dark signals, subarachnoid hemorrhage (SAH), leptomeningeal seeding, and enhancement patterns, were analyzed. Logistic regression analysis was conducted to distinguish between MPE and schwannomas based on MRI parameters, and a prediction model was developed using significant MRI parameters. The model was validated internally using a stratified tenfold cross-validation. The area under the curve (AUC) was calculated based on the receiver operating characteristic curve analysis. MPEs had a significantly larger mean size (p = 0.0035), higher frequency of intratumoral T2 dark signals (p = 0.0021), associated SAH (p = 0.0377), and leptomeningeal seeding (p = 0.0377). Focal and diffuse heterogeneous enhancement patterns were significantly more common in MPEs (p = 0.0049 and 0.0038, respectively). Multivariable analyses showed that intratumoral T2 dark signal (p = 0.0439) and focal (p = 0.0029) and diffuse enhancement patterns (p = 0.0398) were independent factors. The prediction model showed an AUC of 0.9204 (95% CI 0.8532-0.9876) and the average AUC for internal validation was 0.9210 (95% CI 0.9160-0.9270). MRI provides useful data for differentiating spinal MPEs from schwannomas. The prediction model developed based on the MRI features demonstrated excellent discriminatory performance.

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes.

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Characterizing and controlling infrared phonon anomaly of bilayer graphene in optical-electrical force nanoscopy.

We, for the first time, report the nanoscopic imaging study of anomalous infrared (IR) phonon enhancement of bilayer graphene, originated from the charge imbalance between the top and bottom layers, resulting in the enhancement of E1u mode of bilayer graphene near 0.2 eV. We modified the multifrequency atomic force microscope platform to combine photo-induced force microscope with electrostatic/Kelvin probe force microscope constituting a novel hybrid nanoscale optical-electrical force imaging system. This enables to observe a correlation between the IR response, doping level, and topographic information of the graphene layers. Through the nanoscale spectroscopic image measurements, we demonstrate that the charge imbalance at the graphene interface can be controlled by chemical (doping effect via Redox mechanism) and mechanical (triboelectric effect by the doped cantilever) approaches. Moreover, we can also diagnosis the subsurface cracks on the stacked few-layer graphene at nanoscale, by monitoring the strain-induced IR phonon shift. Our approach provides new insights into the development of graphene-based electronic and photonic devices and their potential applications.

Facet-Dependent Passivation for Efficient Perovskite Solar Cells.

Understanding the interplay between the surface structure and the passivation materials and their effects associated with surface structure modification is of fundamental importance; however, it remains an unsolved problem in the perovskite passivation field. Here, we report a surface passivation principle for efficient perovskite solar cells via a facet-dependent passivation phenomenon. The passivation process selectively occurs on facets, which is observed with various post-treatment materials with different functionality, and the atomic arrangements of the facets determine the alignments of the passivation layers. The profound understanding of facet-dependent passivation leads to the finding of 2-amidinopyridine hydroiodide as the material for a uniform and effective passivation on both (100) and (111) facets. Consequently, we achieved perovskite solar cells with an efficiency of 25.10% and enhanced stability. The concept of facet-dependent passivation can provide an important clue on unidentified passivation principles for perovskite materials and a novel means to enhance the performance and stability of perovskite-based devices.

Exploring chemical space for lead identification by propagating on chemical similarity network.

Motivation: Lead identification is a fundamental step to prioritize candidate compounds for downstream drug discovery process. Machine learning (ML) and deep learning (DL) approaches are widely used to identify lead compounds using both chemical property and experimental information. However, ML or DL methods rarely consider compound similarity information directly since ML and DL models use abstract representation of molecules for model construction. Alternatively, data mining approaches are also used to explore chemical space with drug candidates by screening undesirable compounds. A major challenge for data mining approaches is to develop efficient data mining methods that search large chemical space for desirable lead compounds with low false positive rate. Results: In this work, we developed a network propagation (NP) based data mining method for lead identification that performs search on an ensemble of chemical similarity networks. We compiled 14 fingerprint-based similarity networks. Given a target protein of interest, we use a deep learning-based drug target interaction model to narrow down compound candidates and then we use network propagation to prioritize drug candidates that are highly correlated with drug activity score such as IC50. In an extensive experiment with BindingDB, we showed that our approach successfully discovered intentionally unlabeled compounds for given targets. To further demonstrate the prediction power of our approach, we identified 24 candidate leads for CLK1. Two out of five synthesizable candidates were experimentally validated in binding assays. In conclusion, our framework can be very useful for lead identification from very large compound databases such as ZINC.

Surgical treatment of spondylolisthesis by oblique lumbar interbody fusion and transpedicular screw fixation: Comparison between conventional double position versus navigation-assisted single lateral position.

BACKGROUND AND OBJECTIVES: Oblique lumbar interbody fusion (OLIF) procedures involve anterior insertion of interbody cage in lateral position. Following OLIF, insertion of pedicle screws and rod system is performed in a prone position (OLIF-con). The location of the cage is important for restoration of lumbar lordosis and indirect decompression. However, inserting the cage at the desired location is difficult without reduction of spondylolisthesis, and reduction after insertion of interbody cage may limit the amount of reduction. Recent introduction of spinal navigation enabled both surgical procedures in one lateral position (OLIF-one). Therefore, reduction of spondylolisthesis can be performed prior to insertion of interbody cage. The objective of this study was to compare the reduction of spondylolisthesis and the placement of cage between OLIF-one and OLIF-con. METHODS: We retrospectively reviewed 72 consecutive patients with spondylolisthesis for this study; 30 patients underwent OLIF-one and 42 underwent OLIF-con. Spinal navigation system was used for OLIF-one. In OLIF-one, the interbody cage was inserted after reducing spondylolisthesis, whereas in OLIF-con, the cage was inserted before reduction. The following parameters were measured on X-rays: pre- and postoperative spondylolisthesis slippage, reduction degree, and the location of the cage in the disc space. RESULTS: Both groups showed significant improvement in back and leg pains (p < .05). Transient motor or sensory changes occurred in three patients after OLIF-con and in two patients after OLIF-one. Pre- and postoperative slips were 26.3±7.7% and 6.6±6.2% in OLIF-one, and 23.1±7.0% and 7.4±5.8% in OLIF-con. The reduction of slippage was 74.4±6.3% after OLIF-one and 65.4±5.7% after OLIF-con, with a significant difference between the two groups (p = .04). The cage was located at 34.2±8.9% after OLIF-one and at 42.8±10.3% after OLIF-con, with a significant difference between the two groups (p = .004). CONCLUSION: Switching the sequence of surgical procedures with OLIF-one facilitated both the reduction of spondylolisthesis and the placement of the cage at the desired location.

Can convertible metal-backed glenoid components replace cemented polyethylene glenoid components in anatomical total shoulder arthroplasty?

BACKGROUND: Anatomical total shoulder arthroplasty (aTSA) has been used to manage degenerative diseases such as primary osteoarthritis. An increase in the use of this procedure has led to several developments in humeral and glenoid components to improve patient outcomes. This study aimed to compare clinical and radiological outcomes of the newly-introduced convertible metal-backed glenoid components with cemented polyethylene glenoid components in aTSA, and to determine whether the new component would be comparable to a conventional one for reducing the burden of future revision or conversion surgeries. METHODS: Medical records of fifty patients who underwent aTSA with at least two years of follow-up were retrospectively reviewed. Eighteen patients received convertible metal-backed glenoid components with vitamin E1-coated liner (MB group), while thirty-two patients received conventional cemented polyethylene glenoid components (PE group). Pre- and postoperative clinical and radiological outcomes (acromion-greater tuberosity angle [AGA] and humeral lateral offset [LO]) at final follow-up were assessed. Radiolucent lines (RLLs) and loosening around the humeral and glenoid components were also evaluated. RESULTS: Clinical outcomes improved after surgery in both groups (all p < 0.001). The arc of rotation measured by AGA improved postoperatively in both groups (all p < 0.001), and AGA and LO were not different according to the type of glenoid components (all p > 0.05). Overall complication rates including RLLs of PE and MB groups were 43.8% (14/32) and 16.7% (3/18), respectively (p = 0.031). Although the PE group had more RLLs than did the MB group (p < 0.05), related symptoms and/or glenoid implant loosening were not observed in both groups. Subscapularis failure occurred in two patients in the PE group and in one in the MB group. CONCLUSION: The convertible metal-backed glenoid implant with vitamin E1-coated liner may be a good alternative for considering the potential for an easier conversion to reverse total shoulder arthroplasty.

Probabilistic graphical modelling using Bayesian networks for predicting clinical outcome after posterior decompression in patients with degenerative cervical myelopathy.

BACKGROUND: Probabilistic graphical modelling (PGM) can be used to predict risk at the individual patient level and show multiple outcomes and exposures in a single model. OBJECTIVE: To develop PGM for the prediction of clinical outcome in patients with degenerative cervical myelopathy (DCM) after posterior decompression and to use PGM to identify causal predictors of the outcome. METHODS: We included data from 59 patients who had undergone cervical posterior decompression for DCM. The candidate predictive parameters were age, sex, body mass index, trauma history, symptom duration, preoperative and last Japanese Orthopaedic Association (JOA) scores, gait impairment, claudication, bladder dysfunction, Nurick grade, American Spinal Injury Association (ASIA) grade, smoking, diabetes mellitus, cardiopulmonary disorders, hypertension, stroke, Parkinson's disease, dementia, psychiatric disorders, arthritis, ossification of the posterior longitudinal ligament, cord signal change, postoperative kyphosis and the cord compression ratio. RESULTS: In regression analyses, preoperative JOA (PreJOA) score, presence of a psychiatric disorder, and ASIA grade were identified as significant factors associated with the last JOS score. Dementia, sex, PreJOA score and gait impairment were causal factors in the PGM. Sex, dementia and PreJOA score were direct causal factors related to the last follow-up JOA (LastJOA) score. Being female, having dementia, and having a low PreJOA score were significantly related to having a low LastJOA score. CONCLUSIONS: The causal predictors of surgical outcome for DCM were sex, dementia and PreJOA score. Therefore, PGM may be a useful personalized medicine tool for predicting the outcome of patients with DCM.

Sex, dementia and preoperative neurological status are causal factors contributing to the postoperative outcome of patients with degenerative cervical myelopathy.The Bayesian network (BN) structure may be useful for predicting the probability for clinical outcomes for each patient who undergoes posterior decompressive surgery.The BN structure may provide a useful model in the current era of personalized medicine.

Revisiting En Bloc Resection Versus Piecemeal Resection for the Treatment of Giant Cell Tumor of the Spine.

OBJECTIVE: Surgery for spinal giant cell tumors (GCTs) is challenging because these tumors often exhibit a poor clinical course owing to their locally aggressive features. This study aimed to investigate the prognostic factors of GCT recurrence in the spine by focusing on surgical factors. METHODS: We retrospectively reviewed patients who underwent surgery for spinal GCTs between January 2005 and December 2016. Using the Kaplan-Meier method, surgical variables were evaluated for disease-free survival (DFS). Since tumor violation may occur at the pedicle during en bloc resection of the spine, it was further analyzed as a separate variable. Multivariate Cox proportional hazard regression analysis was performed for other clinical and radiographic variables. A total of 28 patients (male:female = 8:20) were included. The mean follow-up period was 90.5 months (range, 15-184 months). RESULTS: Among the 28 patients, gross total resection (GTR) was the most important factor for DFS (P = 0.001). Any form of tumor violation was also correlated with DFS (P = 0.049); however, use of en bloc resection technique did not show a significant DFS gain compared to piecemeal resection (P = 0.218). In the patient group that achieved GTR, the mode of resection was not a significant factor for DFS (P = 0.959). In the multivariate analysis, the extent of resection was the only significant variable that affected DFS (P = 0.016). CONCLUSIONS: Conflicting results on tumor violation from univariate and multivariate analyses suggest that GTR without tumor violation should be the treatment goal for spinal GCTs. However, when tumor violation is unavoidable, it would be important to prioritize GTR over adhering to en bloc resection.

Gut Microbiome Composition Is Associated With Future Onset of Crohn's Disease in Healthy First-Degree Relatives.

BACKGROUND & AIMS: The cause of Crohn's disease (CD) is unknown, but the current hypothesis is that microbial or environmental factors induce gut inflammation in genetically susceptible individuals, leading to chronic intestinal inflammation. Case-control studies of patients with CD have cataloged alterations in the gut microbiome composition; however, these studies fail to distinguish whether the altered gut microbiome composition is associated with initiation of CD or is the result of inflammation or drug treatment. METHODS: In this prospective cohort study, 3483 healthy first-degree relatives (FDRs) of patients with CD were recruited to identify the gut microbiome composition that precedes the onset of CD and to what extent this composition predicts the risk of developing CD. We applied a machine learning approach to the analysis of the gut microbiome composition (based on 16S ribosomal RNA sequencing) to define a microbial signature that associates with future development of CD. The performance of the model was assessed in an independent validation cohort. RESULTS: In the validation cohort, the microbiome risk score (MRS) model yielded a hazard ratio of 2.24 (95% confidence interval, 1.03-4.84; P = .04), using the median of the MRS from the discovery cohort as the threshold. The MRS demonstrated a temporal validity by capturing individuals that developed CD up to 5 years before disease onset (area under the curve > 0.65). The 5 most important taxa contributing to the MRS included Ruminococcus torques, Blautia, Colidextribacter, an uncultured genus-level group from Oscillospiraceae, and Roseburia. CONCLUSION: This study is the first to demonstrate that gut microbiome composition is associated with future onset of CD and suggests that gut microbiome is a contributor in the pathogenesis of CD.

Impact on Spine Surgery during the First Two Years of COVID-19 Pandemic: A Nationwide Study in South Korea.

Since December 2019, the novel coronavirus (COVID-19) has infected people worldwide. Owing to its rapid spread, elective surgeries, including spine surgery, have been re-scheduled. We analyzed nationwide data to investigate changes in the volume of spine surgery during the first two years of the pandemic. Nationwide data from January 2016 to December 2021 were obtained. We compared the total number of patients who underwent spine surgery and related medical expenses before and during the COVID-19 pandemic. In February and September, the number of patients was significantly smaller compared to January and August, respectively. Despite the pandemic, the proportion of patients undergoing spine surgery for degenerative diseases in 2021 was the highest. In contrast, the proportions of patients undergoing spine surgery for tumors showed a continuous decrease from 2019 to 2021. Although the number of spine surgeries performed at tertiary hospitals was lowest in 2020, it was not significantly smaller than that in 2019.The number of patients who underwent spine surgery in March 2020, during the first outbreak, decreased compared to the previous month, which differed from the trend observed in the pre-COVID-19 period. However, as the pandemic continues, the impact of COVID-19 on spine surgery has become less evident.