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CONCLUSIONS The difference in methylation levels of CTRP1 promoter may be involved in the development process of KD, and may be a potential predictive marker for the occurrence of CAAs. Recently, the (GGC)n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy. Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by specific patterns of gray and white matter damage and cognitive/behavioral manifestations. The cerebellum has also been implicated in the pathophysiology of AD. Because the cerebellum is known to have strong functional connectivity (FC) with associative cerebral cortex regions, it is possible to hypothesize that it is incorporated into intrinsic FC networks relevant to cognitive manifestation of AD. In the present study, the cerebellar dentate nucleus, the largest cerebellar nucleus and the major output channel to the cerebral cortex, was chosen as the region of interest to test potential cerebellocerebral FC alterations and correlations with patients' memory impairment in a group of patients with AD. Compared to controls, patients with AD showed an increase in FC between the dentate nucleus and regions of the lateral temporal lobe. This study demonstrates that lower memory performances in AD may be related to altered FC within specific cerebellocortical functional modules, thus suggesting the cerebellar contribution to AD pathophysiology and typical memory dysfunctions. Plasma biomarkers are promising prognostic tools in individuals with subjective cognitive decline (SCD). We aimed to investigate the relationships of baseline plasma amyloid beta (Aβ)42/Aβ40 and total Tau (tTau) with rate of cognitive decline, in comparison to relationships of baseline cerebrospinal fluid (CSF) Aβ42, tTau, and phosphorylated tau181 (pTau181) with rate of cognitive decline. We included 241 subjects with SCD (age = 61 ± 9, 40% female, Mini-Mental State Examination = 28 ± 2) with follow-up (average 2 ± 2 years, median visits 3 [range 1-11]) for re-evaluation of neuropsychological test performance (attention, memory, language, and executive functioning domains). Using age, gender and education-adjusted linear mixed models, we found that lower plasma Aβ42/Aβ40 was associated with steeper rate of decline on tests for attention, memory, and executive functioning, but not language. Lower CSF Aβ42 was associated with steeper decline on tests covering all domains. Associations for plasma amyloid and cognitive decline mirror those of CSF amyloid. Plasma tTau was not associated with rate of cognitive decline, whereas CSF tTau and pTau181 were on multiple tests covering all domains. Multidrug-resistant (MDR) Acinetobacter baumannii is a critical threat to global health. The type strain ATCC 19606 has been widely used in studying the virulence, pathogenesis and mechanisms of antimicrobial resistance in A. baumannii. However, the lack of a complete genome sequence is a hindrance towards detailed bioinformatic studies. Here we report the generation of a complete genome for ATCC 19606 using PacBio sequencing. ATCC 19606 genome consists of a 3,980,848-bp chromosome and a 9,450-bp plasmid pMAC, and harbours a chromosomal dihydropteroate synthase gene sul2 conferring resistance to sulphonamides and a plasmid-borne ohr gene conferring resistance to peroxides. The genome also contains 69 virulence genes involved in surface adherence, biofilm formation, extracellular phospholipase, iron uptake, immune evasion and quorum sensing. Insertion sequences ISCR2 and ISAba11 are embedded in a 36.1-Kb genomic island, suggesting an IS-mediated large-scale DNA recombination. Furthermore, a genome-scale metabolic model (GSMM) iATCC19606v2 was constructed using the complete genome annotation. The model iATCC19606v2 incorporated a periplasmic compartment, 1,422 metabolites, 2,114 reactions and 1,009 genes, and a set of protein crowding constraints taking into account enzyme abundance limitation. The prediction of bacterial growth on 190 carbon and 95 nitrogen sources achieved a high accuracy of 85.6% compared to Biolog experiment results. Based upon two transposon mutant libraries of AB5075 and ATCC 17978, the predictions of essential genes reached the accuracy of 87.6% and 82.1%, respectively. Together, the complete genome sequence and high-quality GSMM iATCC19606v2 provide valuable tools for antimicrobial systems pharmacological investigations on A. baumannii. PURPOSE To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRα) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRα-positive, platinum-resistant ovarian cancer. METHODS Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FRα positivity by immunochemistry and prior bevacizumab exposure was permitted. Adverse events, tumor response, and progression-free survival (PFS) were determined. RESULTS Sixty-six patients, with a median of 3 prior lines of therapy (range, 1-8), received the combination of mirvetuximab soravtansine and bevacizumab at full dosing during the escalation and expansion stages of the study. Adverse events were generally mild-to-moderate (≤grade 2) with diarrhea, blurred vision, nausea, and fatigue being the most common treatment-related toxicities. Six cases of pneumonitis (9%; all grade 1 or 2), an adverse event of special interest, were observed. The confirmed objective response rate (ORR) was 39%, including 5 complete responses and 21 partial responses, and the median PFS was 6.9 months. The combination was particularly active in the subset of patients (n = 16) who were bevacizumab-naïve, less heavily pretreated (1-2 prior lines), and whose tumors exhibited medium/high FRα expression (ORR, 56% with a median duration of response of 12 months; PFS, 9.9 months). CONCLUSION The combination of mirvetuximab soravtansine with bevacizumab is well tolerated in patients with platinum-resistant, recurrent ovarian cancer. The encouraging efficacy measures compare favorably to reported outcomes for bevacizumab combined with standard chemotherapy in similar patient populations. OBJECTIVE Characterize change in rates of minimally invasive (MIS) radical hysterectomy after presentation of the LACC trial. METHODS Longitudinal analysis of data from Vizient® database for surgically treated patients with invasive cervical cancer from April 2017-March 2019. Covariates studied included patient demographic and obesity categories, dates of LACC trial presentation and publication, and hospital characteristics. RESULTS 2102 cervical cancer patients had surgery at 201 hospitals. Most were age 31-50 (51.2%), White (64.8%), and had public (49.2%) health insurance. Annual rates of MIS fell from 51.9% to 27.1% after the LACC trial presentation (RR 0.52, 95% CI 0.47, 0.58; p less then 0.0001). Adjusting for within hospital correlation, the odds of MIS dropped by 13% per month (OR = 0.872 per month, 95% CI 0.852, 0.891; p less then 0.001), without further change in rates of MIS after the peer-review publication (OR = 1.033 per month, 95% CI 0.897, 1.189; p = 0.65). Rates of MIS declined across all demographics (RR = 0.32-0.65; p less then 0.01), except in morbidly obese women (RR = 0.90; p = 0.60). Applying mixed effects model, rates of MIS fell by 3% per month in morbidly obese women versus 18% per month if body mass index less then 40 kg/m2. NCCN member hospitals and hospitals with gynecologic oncology fellowship training programs significantly reduced rates of MIS radical hysterectomy faster, but not earlier, than other hospitals. CONCLUSIONS Rates of MIS radical hysterectomy fell dramatically and pervasively after the LACC trial presentation, despite ongoing substantive controversy. Practice pattern changes were not significant in morbidly obese women. Studies of endodontic outcomes suggest that fracture of the tooth after endodontic therapy may be a greater problem than endodontic reinfection. Immediate full coverage with or without a post and core is the best way to prevent fracture. Unfortunately, in many population areas, due predominantly to cost, this restoration is often delayed, leading to fracture of the tooth. Reviews of several in vitro studies suggest that a composite restoration reinforced with glass fibers, particularly with fiberglass posts laid horizontally in a buccolingual direction, significantly increased the resistance to fracture. This case report describes in detail the placement of horizontal posts in an endodontically treated molar to reinforce the coronal structure. In the discussion, we outlined the agreement of most of the authors on the increase in fracture resistance and the lack of consensus on what constitutes a catastrophic fracture. INTRODUCTION An accurate diagnosis is required for the appropriate management of endodontic conditions. It is unknown whether the specific descriptive terminology used in diagnosis influences treatment decision making. The aim of this study was to determine whether treatment choices made by dentists are influenced by the diagnostic terminology used. METHODS One hundred ninety-four dentists in Australia were recruited through the Australian Dental Association to complete an online survey regarding 14 endodontic cases. Respondents selected treatment options based on a given diagnosis and radiograph. Data were analyzed using SPSS software (Version 26; IBM Corp, Armonk, NY) and the exact McNemar test to determine if there was a difference between treatment choices for matched diagnoses with different terminology. RESULTS More dentists chose to manage irreversible pulpitis operatively when the descriptive term chronic was used compared with asymptomatic (93.3% vs 59.8%, χ12 = 57.69, P less then .005). This trend was repeated when using chronic or asymptomatic to describe apical periodontitis (96.9% vs 89.7%, exact P = .004) and apical abscesses (99.0% vs 83.5%, χ12 = 104.125, P less then .005). The differences between acute and symptomatic were less dramatic but still presented significant differences in treatment choices for an apical abscess described as "primary acute" or "secondary acute" compared with "symptomatic" (82.0% and 96.4% vs 93.3%, P less then .05). CONCLUSIONS Descriptive terminology, specifically the terms acute and chronic as opposed to symptomatic and asymptomatic, used in the diagnosis of endodontic conditions did influence whether clinicians chose operative management or nonoperative management. Lipopolysaccharides nmr Further research is warranted to determine the extent of this influence among dentists.
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