The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis.

Background: Recently, anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunotherapy offers promising results for advanced biliary tract cancer (BTC). However, patients show highly heterogeneous responses to treatment, and predictive biomarkers are lacking. We performed a systematic review and meta-analysis to assess the potential of PD-L1 expression as a biomarker for treatment response and survival in patients with BTC undergoing anti-PD-1/PD-L1 therapy. Methods: We conducted a comprehensive systematic literature search through June 2023, utilizing the PubMed, EMBASE, and Cochrane Library databases. The outcomes of interest included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) according to PD-L1 expression. Subgroup analyses and meta-regression were performed to identify possible sources of heterogeneity. Results: A total of 30 studies was included in the final analysis. Pooled analysis showed no significant differences in ORR (odds ratio [OR], 1.56; 95% confidence intervals [CIs], 0.94-2.56) and DCR (OR, 1.84; 95% CIs, 0.88-3.82) between PD-L1 (+) and PD-L1 (-) patients. In contrast, survival analysis showed improved PFS (hazard ratio [HR], 0.54, 95% CIs, 0.41-0.71) and OS (HR, 0.58; 95% CI, 0.47-0.72) among PD-L1 (+) patients compared to PD-L1 (-) patients. Sensitivity analysis excluding retrospective studies showed no significant differences with the primary results. Furthermore, meta-regression demonstrated that drug target (PD-1 vs. PD-L1), presence of additional intervention (monotherapy vs. combination therapy), and PD-L1 cut-off level (1% vs. ≥5%) significantly affected the predictive value of PD-L1 expression. Conclusion: PD-L1 expression might be a helpful biomarker for predicting PFS and OS in patients with BTC undergoing anti-PD-1/PD-L1 therapy. The predictive value of PD-L1 expression can be significantly influenced by diagnostic or treatment variables. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023434114.

Mitochondrial dysfunction precedes hippocampal IL-1ß transcription and cognitive impairments after low-dose lipopolysaccharide injection in aged mice.

Acute cognitive impairments termed delirium often occur after inflammatory insults in elderly patients. While previous preclinical studies suggest mitochondria as a target for reducing neuroinflammation and cognitive impairments after LPS injection, fewer studies have evaluated the effects of a low-grade systemic inflammation in the aged brain. Thus, to identify the significance of mitochondrial dysfunction after a clinically relevant systemic inflammatory stimulus, we injected old-aged mice (18-20 months) with low-dose lipopolysaccharide (LPS, 0.04 mg/kg). LPS injection reduced mitochondrial respiration in the hippocampus 24 h after injection (respiratory control ratio [RCR], state3u/state4o; control = 2.82 ± 0.19, LPS = 2.57 ± 0.08). However, gene expression of the pro-inflammatory cytokine IL-1ß was increased (RT-PCR, control = 1.00 ± 0.30; LPS = 2.01 ± 0.67) at a more delayed time point, 48 h after LPS injection. Such changes were associated with cognitive impairments in the Barnes maze and fear chamber tests. Notably, young mice were unaffected by low-dose LPS, suggesting that mitochondrial dysfunction precedes neuroinflammation and cognitive decline in elderly patients following a low-grade systemic insult. Our findings highlight mitochondria as a potential therapeutic target for reducing delirium in elderly patients.

Comparative study between biliary covered self-expandable metal stent and conventional endoscopic bile drainage treatment in endoscopic retrograde cholangiopancreatography-related Stapfer type II retroperitoneal perforations.

BACKGROUND: Perforation is one of the most serious complications of endoscopic retrograde cholangiopancreatography (ERCP). Conventional nonsurgical endoscopic treatments including intravenous antibiotic administration and plastic endoscopic biliary drainage are generally approved for the treatment of ERCP-related Stapfer type II perforation (perivaterian type). Biliary covered metal stent placement has recently been reported to have favorable outcomes in ERCP-related Stapfer type II perforations. We aimed to compare the outcomes of conventional endoscopic bile drainage and biliary covered self-expandable metal stent (SEMS) insertion in patients with Stapfer type II perforation. METHODS: Medical records of patients who underwent ERCP at Kyungpook National University Hospital in Daegu from 2011 to 2022 were retrospectively reviewed. RESULTS: A total of 8,402 ERCP procedures were performed in our hospital. Sixty-six ERCP-related perforations (0.78%) were identified. Among them, 37 patients (56.1%) who had Stapfer type II perforations were enrolled. Thirteen and twenty-four patients received biliary covered SEMS insertion and conventional endoscopic bile drainage treatments, respectively. No significant differences were observed in the clinical success rate (92.3% vs. 91.7%, p = 1.000), hospital stay (9.46 ± 5.97 vs. 13.9 ± 13.2 days, p = 0.258), and post-ERCP-related fasting time (5.4 ± 3.4 vs 4.3 ± 3.0 days, p = 0.305). Complications including bleeding, post-ERCP pancreatitis, fever, and death were not significantly different between the two groups. The conventional endoscopic bile drainage group took less time for ERCP than the SEMS group (11.5 ± 5.2 vs. 18.5 ± 11.2 min, p = 0.013). CONCLUSIONS: Compared with the conventional endoscopic bile drainage treatment method, biliary covered SEMS did not improve patient outcomes in ERCP-related Stapfer type II perforations.

Dynamic three-dimensional structures of a metal-organic framework captured with femtosecond serial crystallography.

Crystalline systems consisting of small-molecule building blocks have emerged as promising materials with diverse applications. It is of great importance to characterize not only their static structures but also the conversion of their structures in response to external stimuli. Femtosecond time-resolved crystallography has the potential to probe the real-time dynamics of structural transitions, but, thus far, this has not been realized for chemical reactions in non-biological crystals. In this study, we applied time-resolved serial femtosecond crystallography (TR-SFX), a powerful technique for visualizing protein structural dynamics, to a metal-organic framework, consisting of Fe porphyrins and hexazirconium nodes, and elucidated its structural dynamics. The time-resolved electron density maps derived from the TR-SFX data unveil trifurcating structural pathways: coherent oscillatory movements of Zr and Fe atoms, a transient structure with the Fe porphyrins and Zr6 nodes undergoing doming and disordering movements, respectively, and a vibrationally hot structure with isotropic structural disorder. These findings demonstrate the feasibility of using TR-SFX to study chemical systems.

Accuracy of generative deep learning model for macular anatomy prediction from optical coherence tomography images in macular hole surgery.

This study aims to propose a generative deep learning model (GDLM) based on a variational autoencoder that predicts macular optical coherence tomography (OCT) images following full-thickness macular hole (FTMH) surgery and evaluate its clinical accuracy. Preoperative and 6-month postoperative swept-source OCT data were collected from 150 patients with successfully closed FTMH using 6 × 6 mm2 macular volume scan datasets. Randomly selected and augmented 120,000 training and 5000 validation pairs of OCT images were used to train the GDLM. We assessed the accuracy and F1 score of concordance for neurosensory retinal areas, performed Bland-Altman analysis of foveolar height (FH) and mean foveal thickness (MFT), and predicted postoperative external limiting membrane (ELM) and ellipsoid zone (EZ) restoration accuracy between artificial intelligence (AI)-OCT and ground truth (GT)-OCT images. Accuracy and F1 scores were 94.7% and 0.891, respectively. Average FH (228.2 vs. 233.4 µm, P = 0.587) and MFT (271.4 vs. 273.3 µm, P = 0.819) were similar between AI- and GT-OCT images, within 30.0% differences of 95% limits of agreement. ELM and EZ recovery prediction accuracy was 88.0% and 92.0%, respectively. The proposed GDLM accurately predicted macular OCT images following FTMH surgery, aiding patient and surgeon understanding of postoperative macular features.

Lacticaseibacillus pabuli sp. nov., isolated from fermented cattle feed.

Strain BSF-3MT is a Gram-stain-positive, non-flagellated, facultative anaerobic and rod-shaped bacterium that was isolated from fermented feed collected at a cattle farm in the Daejeon region of the Republic of Korea. It was studied using polyphasic taxonomic methods. Using 16S rRNA gene sequences and the resulting phylogenetic tree, the strain was primarily identified as a member of the genus Lacticaseibacillus. Strain BSF-3MT contained a chromosome of 2.5 Mbp and a plasmid of 33.4 kbp. The G+C content of genomic DNA was 51.3 mol%. Strain BSF-3MT had the highest ortho-average nucleotide identity value of 73.7 % with Lacticaseibacillus songhuajiangensis 7-19T, its closest relative in the phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree based on up-to-date bacterial core genes. Based on the results of a polyphasic taxonomic study, strain BSF-3MT represents a novel species in the genus Lacticaseibacillus, for which the name Lacticaseibacillus pabuli sp. nov. is proposed. The type strain is BSF-3MT (=KACC 23028T=NBRC 116014T).

Resource analysis and modifications of quantum computing with noisy qubits for elliptic curve discrete logarithms.

We estimate the number of physical qubits and execution time by decomposing an implementation of Shor's algorithm for elliptic curve discrete logarithms into universal gate units at the logical level when surface codes are used. We herein also present modified quantum circuits for elliptic curve discrete logarithms and compare our results with those of the original quantum circuit implementations at the physical level. Through the analysis, we show that the use of more logical qubits in quantum algorithms does not always lead to the use of more physical qubits. We assumed using rotated surface code and logical qubits with all-to-all connectivity. The number of physical qubits and execution time are expressed in terms of bit length, physical gate error rate, and probability of algorithm failure. In addition, we compare our results with the number of physical qubits and execution time of Shor's factoring algorithm to assess the risk of attack by quantum computers in RSA and elliptic curve cryptography.

Effects of a Combination of Polynucleotide and Hyaluronic Acid for Treating Osteoarthritis.

Knee osteoarthritis (OA), an age-related degenerative disease characterized by severe pain and disability, is treated using polynucleotides (PNs) and hyaluronic acid (HA). The intra-articular (IA) injection of HA has been studied extensively in both animal models and in humans; however, the efficacy and mechanisms of action remain unclear. In addition, there has been a paucity of research regarding the use of PN alone or in combination with HA in OA. To investigate the effect of the combined injection of PN and HA in vivo, pathological and behavioral changes were assessed in an OA model. Anterior cruciate ligament transection and medial meniscectomy were performed in Sprague-Dawley rats to create the OA animal model. The locomotor activity improved following PNHA injection, while the OARSI grade improved in the medial tibia and femur. In mild OA, TNFα levels decreased histologically in the PN, HA, and PNHA groups but only the PNHA group showed behavioral improvement in terms of distance. In conclusion, PNHA exhibited anti-inflammatory effects during OA progression and improved locomotor activity regardless of the OARSI grade.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

Successful Management of Refractory Kimura Disease with CVP Chemotherapy: A Case Report.

BACKGROUND Kimura disease is a rare, chronic inflammatory disorder typically presenting as a painless mass in the head or neck and associated with elevated serum immunoglobulin E and blood and tissue eosinophilia. Generally benign, its management is not well-defined, but corticosteroids are a common initial treatment. We detail a case of refractory Kimura disease successfully managed with CVP (Cyclophosphamide, Vincristine, Prednisone) chemotherapy and no recurrence during 6 rounds of treatment. CASE REPORT A 64-year-old woman, previously diagnosed with Kimura disease, returned to the hospital with upper eyelid ptosis. Upon examination, a solid mass was palpable in her left upper eyelid. Peripheral blood tests confirmed elevated IgE levels at 356.0 IU/ml. An excisional biopsy showed infiltration of lymphocytes and eosinophils, consistent with Kimura disease. Despite undergoing corticosteroid treatment, surgical debulking, radiation, and immunosuppressant therapy, her condition worsened. Concerns were raised due to imaging features suggestive of lymphoma, although no malignancy was evident in subsequent biopsies. It was decided to manage the disease using CVP chemotherapy, leading to significant symptom improvement. There have been no recurrences during the 12-month follow-up period. CONCLUSIONS Kimura disease is typically benign and responsive to treatment, but it often recurs and can progress. When symptoms are not controlled with conventional treatments, including corticosteroids, immunosuppressants, radiation, and surgical debulking, chemotherapy may be a reasonable option even when no definite signs of malignancy is identified. Further research is needed to explore the utility of CHOP and CVP in managing uncontrolled Kimura disease.

Capturing the generation and structural transformations of molecular ions.

Molecular ions are ubiquitous and play pivotal roles1-3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4-6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9-11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED)12-14, used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP+ cation remains for a substantial duration of 3.6 ps in aptly named 'dark states' that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations15 and ab initio calculations16, reveal that the cation subsequently decays to iso-DBP+, an unusual intermediate with a four-membered ring containing a loosely bound17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure19. We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry.

Brevibacillus ruminantium sp. nov., isolated from cow faeces.

An aerobic, Gram-stain-positive, rod-shaped, endospore-forming bacterial strain, designated BB3-R1T, was isolated from cow faeces sampled in Daejeon, Republic of Korea. Growth was observed at 25-45 °C (optimum, 35-40 °C) and pH 7.0-9.0 (optimum, pH 8.0), with up to 3 % (w/v) NaCl (optimum, 0 % NaCl). blast analysis of 16S rRNA gene sequences revealed the highest sequence similarity of strain BB3-R1T to Brevibacillus borstelensis NRRL NRS-818T (98.8 %) followed by Brevibacillus panacihumi JCM 15085T (97.5 %). According to 16S rRNA gene and whole-genome based phylogenetic trees, strain BB3-R1T clustered with Brevibacillus composti FJAT-54423T and B. borstelensis NRRL NRS-818T. OrthoANI and dDDH values of strain BB3-R1T with the closely related strains were lower than 77.5 and 26.8 %, respectively. The major menaquinones and polar lipids of the strain were MK-7 and phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, respectively. The major fatty acids (>10 %) were C14 : 0 iso, C15 : 0 iso, C15 : 0 anteiso and C16 : 1 ω7c alcohol. The cell-wall peptidoglycan contained cross-linked meso-diaminopimelic acid (type A1 gamma). The phenotypic, chemotaxonomic and genotypic data obtained in this study showed that the strain represents a novel species of the genus Brevibacillus, for which the name Brevibacillus ruminantium sp. nov. (type strain BB3-R1T=KACC 22663T=NBRC 115962T) is proposed.

Whole-genome sequence of the Halobacillus naozhouensis type strain KACC 21980.

We present the whole-genome sequence of Halobacillus naozhouensis Korean Agricultural Culture Collection (KACC) 21980T, isolated from China by Chen et al.. The genome of Halobacillus naozhouensis KACC 21980T comprises a circular chromosome (4.2 Mb) and one plasmid (17 kb). It includes a total of 4,168 predicted coding genes.

Halobacillus salinarum sp. nov., Halobacillus shinanisalinarum sp. nov. and Halobacillus amylolyticus sp. nov., isolated from saltern soil.

Three bacterial strains, designated SSBR10-3T, SSTM10-2T and SSHM10-5T, were isolated from saltern soil sampled in Jeollanam-do, Republic of Korea. Cells were aerobic, Gram-stain-positive, flagellated and rod-shaped. The strains grew optimally at 28°C and at pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strains SSBR10-3T, SSTM10-2T and SSHM10-5T were placed within the genus Halobacillus, showing the highest similarity to Halobacillus alkaliphilus FP5T (98.6 %), 'Halobacillus ihumii' Marseille-Q1234T (98.5 %) and Halobacillus locisalis MSS-155T (98.6 %), respectively. The genomic similarity values between strains SSBR10-3T, SSTM10-2T and SSHM10-5T and their related species were 17.6-22.6 % for digital DNA-DNA hybridization (dDDH) and 69.6-78.5 % for orthologous average nucleotide identity (OrthoANI), which were lower than the thresholds recommended for species delineation. The dDDH and OrthoANI values among the three strains were below 38.3 and 89.4 %, respectively. Besides the differences in genomic features, strains SSBR10-3T, SSTM10-2T and SSHM10-5T were distinct from each other and from members of the genus in terms of phenotypic traits related to substrate assimilation. The cell-wall peptidoglycan contained meso-diaminopimelic acid, the major fatty acids were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0, and the predominant menaquinone was MK-7 for all three strains. Diphosphatidylglycerol, phosphatidylglycerol and an unidentified phospholipid were present in their polar lipid profiles. Based on a polyphasic approach incorporating genomic data, strains SSBR10-3T, SSTM10-2T and SSHM10-5T represent novel species, for which the names Halobacillus salinarum sp. nov. (SSBR10-3T=DSM 114353T=KACC 21935T=NBRC 115504T), Halobacillus shinanisalinarum sp. nov. (SSTM10-2T=DSM 114354T=KACC 21936T=NBRC 115505T) and Halobacillus amylolyticus sp. nov. (SSHM10-5T=DSM 114355T= KACC 21937T=NBRC 115506T) are proposed.

Gracilibacillus salinarum sp. nov. and Gracilibacillus caseinilyticus sp. nov., halotolerant bacteria isolated from a saltern environment.

Two aerobic, Gram-stain-positive, spore-forming motile bacterial strains, designated SSPM10-3T and SSWR10-1T, were isolated from salterns in Jeollanam province of South Korea. Both strains were halotolerant and grew well in 5 % NaCl but not in 20 and 25% NaCl, respectively. Optimal growth was observed with 5 % NaCl, at 30 °C and at pH 7.0-8.0. On the basis of the results of phylogenetic analysis using 16S rRNA gene sequence, both the strains were placed within the genus Gracilibacillus with Gracilibacillus massiliensis (98.65 % similarity) as their nearest neighbour. Menaquinone-7 (MK-7) (97 %) was the major isoprenoid quinone in both strains and major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. Orthologous average nucleotide identity with usearch (OrthoANIu) and digital DNA-DNA hybridisation (dDDH) percentage comparison indicated that SSPM10-3T and SSWR10-1T exhibited highest similarity with G. massiliensis Awa-1T at 74.27 % and 21.0 and 74.23 % and 20.0 %, respectively. The DNA G+C contents of the strains were 39.1 % (SSPM10-3T) and 38.5 % (SSWR10-1T). Members of the genus Gracilibacillus, both strains were distinct from each other with respect to their ability to produce urease, ß-glucosidase, assimilation of inulin and methyl-α-d-glucopyranoside and degradation of casein. Compared with each other, ANI and d4 dDDH calculations were only 88.2 % and 36.3 %, well below the cut-off values for species delineation for each index. On the basis of their phenotypic, physiological, biochemical and phylogenetic characteristics,SSPM10-3T and SSWR10-1T represent distinct novel species for which names Gracilibacillus salinarum SSPM10-3T and Gracilibacillus caseinilyticus SSWR10-1T are proposed. The type strains are SSPM10-3T (=KACC 21933T =NBRC 115502T) and SSWR10-1T (=KACC 21934T =NBRC 115503T).

Decellularized human pancreatic extracellular matrix-based physiomimetic microenvironment for human islet culture.

A strategy that seeks to combine the biophysical properties of inert encapsulation materials like alginate with the biochemical niche provided by pancreatic extracellular matrix (ECM)-derived biomaterials, could provide a physiomimetic pancreatic microenvironment for maintaining long-term islet viability and function in culture. Herein, we have demonstrated that incorporating human pancreatic decellularized ECM within alginate microcapsules results in a significant increase in Glucose Stimulation Index (GSI) and total insulin secreted by encapsulated human islets, compared to free islets and islets encapsulated in only alginate. ECM supplementation also resulted in long-term (58 days) maintenance of GSI levels, similar to that observed in free islets at the first time point (day 5). At early time points in culture, ECM promoted gene expression changes through ECM- and cell adhesion-mediated pathways, while it demonstrated a mitochondria-protective effect in the long-term. STATEMENT OF SIGNIFICANCE: The islet isolation process can damage the islet extracellular matrix, resulting in loss of viability and function. We have recently developed a detergent-free, DI-water based method for decellularization of human pancreas to produce a potent solubilized ECM. This ECM was added to alginate for microencapsulation of human islets, which resulted in significantly higher stimulation index and total insulin production, compared to only alginate capsules and free islets, over long-term culture. Using ECM to preserve islet health and function can improve transplantation outcomes, as well as provide novel materials and platforms for studying islet biology in microfluidic, organ-on-a-chip, bioreactor and 3D bioprinted systems.

Five novel Hymenobacter species isolated from air: Hymenobacter cellulosilyticus sp. nov., Hymenobacter cellulosivorans sp. nov., Hymenobacter aerilatus sp. nov., Hymenobacter sublimis sp. nov. and Hymenobacter volaticus sp. nov.

Five Hymenobacter strains isolated from air samples collected from the Suwon and Jeju regions of the Republic of Korea were studied using polyphasic taxonomic methods. Using 16S rRNA gene sequences and the resulting phylogenetic tree, the strains were primarily identified as members of the genus Hymenobacter. Digital DNA-DNA hybridization values and average nucleotide identities values for species delineation (70 and 95-96 %, respectively) between the five strains and their nearest type strains indicated that each strain represented a novel species. All strains were aerobic, Gram-stain-negative, mesophilic, rod-shaped and catalase- and oxidase-positive, with red to pink coloured colonies. The genome sizes of the five strains varied from 4.8 to 7.1 Mb and their G+C contents were between 54.1 and 59.4 mol%. Based on their phenotypic, chemotaxonomic and genotypic characteristics, we propose to classify these isolates into five novel species within the genus Hymenobacter for which we propose the names, Hymenobacter cellulosilyticus sp. nov., Hymenobacter cellulosivorans sp. nov., Hymenobacter aerilatus sp. nov., Hymenobacter sublimis sp. nov. and Hymenobacter volaticus sp. nov., with strains 5116 S-3T (=KACC 21925T=JCM 35216T), 5116 S-27T (=KACC 21926T=JCM 35217T), 5413 J-13T (=KACC 21928T=JCM 35219T), 5516 S-25T (=KACC 21931T=JCM 35222T) and 5420 S-77T (=KACC 21932T=JCM 35223T) as the type strains, respectively.

Comparison Study between ERCP and PTBD for Recurrent Choledocholithiasis in Patients Following Gastrectomy.

The recurrence rate of choledocholithiasis in the general population has been reported to exceed 10%. The incidence of cholelithiasis was reported to be higher in patients following gastrectomy than that in the general population. However, there is no study for recurrent choledocholithiasis incidence in patients following gastrectomy. This study aimed to evaluate the recurrence rate of choledocholithiasis and identify risk factors for recurrent choledocholithiasis in patients following gastrectomy. A retrospective analysis was performed on patients with gastrectomy history who underwent choledocholithiasis removal in Kyungpook National University Hospital between January 2011 and December 2019. Choledocholithiases were treated by endoscopic retrograde cholangiopancreatography (ERCP) (n = 41) or percutaneous transhepatic biliary drainage (PTBD) (n = 90). The gastrectomy type was classified as subtotal gastrectomy with Billroth I (18.3%), Billroth II (45.0%), and total gastrectomy with Roux-en-Y (36.6%). During a median follow-up period of 31.5 (range, 6-105) months, choledocholithiasis recurrence was noted in 19 of 131 patients (14.5%). In subgroup analysis, the ERCP group (24.4%) had higher choledocholithiasis recurrence than the PTBD group (10.0%). Stone removal modality (ERCP), no use of balloon sphincteroplasty, and the presence of periampullary diverticulum were significant risk factors for recurrent choledocholithiasis. In multivariate analysis, ERCP (hazard ratio (HR), 3.597; 95% confidence interval (CI): 1.264-10.204) CBD stricture (HR, 3.823; 95% CI: 1.118-13.080) and no use of balloon sphincteroplasty (HR, 4.830; 95% CI: 1.669-13.889) were risk factors for recurrent choledocholithiasis following stone removal. The incidence of CBD stones in patients who underwent gastrectomy is similar to that of the general population. ERCP, CBD stricture, and no use of balloon sphincteroplasty are potential risk factors for recurrent CBD stones following gastrectomy. When we consider PTBD disadvantages, the ERCP procedure with active use of balloon sphincteroplasty is recommended to decrease recurrent CBD stones.

Crif1 deficiency in dopamine neurons triggers early-onset parkinsonism.

Mitochondrial dysfunction has been implicated in Parkinson's Disease (PD) progression; however, the mitochondrial factors underlying the development of PD symptoms remain unclear. One candidate is CR6-interacting factor1 (CRIF1), which controls translation and membrane insertion of 13 mitochondrial proteins involved in oxidative phosphorylation. Here, we found that CRIF1 mRNA and protein expression were significantly reduced in postmortem brains of elderly PD patients compared to normal controls. To evaluate the effect of Crif1 deficiency, we produced mice lacking the Crif1 gene in dopaminergic neurons (DAT-CRIF1-KO mice). From 5 weeks of age, DAT-CRIF1-KO mice began to show decreased dopamine production with progressive neuronal degeneration in the nigral area. At ~10 weeks of age, they developed PD-like behavioral deficits, including gait abnormalities, rigidity, and resting tremor. L-DOPA, a medication used to treat PD, ameliorated these defects at an early stage, although it was ineffective in older mice. Taken together, the observation that CRIF1 expression is reduced in human PD brains and deletion of CRIF1 in dopaminergic neurons leads to early-onset PD with stepwise PD progression support the conclusion that CRIF1-mediated mitochondrial function is important for the survival of dopaminergic neurons.