Review of MR spectroscopy analysis and artificial intelligence applications for the detection of cerebral inflammation and neurotoxicity in Alzheimer's disease.

INTRODUCTION: Magnetic resonance spectroscopy (MRS) has an emerging role as a neuroimaging tool for the detection of biomarkers of Alzheimer's disease (AD). To date, MRS has been established as one of the diagnostic tools for various diseases such as breast cancer and fatty liver, as well as brain tumours. However, its utility in neurodegenerative diseases is still in the experimental stages. The potential role of the modality has not been fully explored, as there is diverse information regarding the aberrations in the brain metabolites caused by normal ageing versus neurodegenerative disorders. MATERIALS AND METHODS: A literature search was carried out to gather eligible studies from the following widely sourced electronic databases such as Scopus, PubMed and Google Scholar using the combination of the following keywords: AD, MRS, brain metabolites, deep learning (DL), machine learning (ML) and artificial intelligence (AI); having the aim of taking the readers through the advancements in the usage of MRS analysis and related AI applications for the detection of AD. RESULTS: We elaborate on the MRS data acquisition, processing, analysis, and interpretation techniques. Recommendation is made for MRS parameters that can obtain the best quality spectrum for fingerprinting the brain metabolomics composition in AD. Furthermore, we summarise ML and DL techniques that have been utilised to estimate the uncertainty in the machine-predicted metabolite content, as well as streamline the process of displaying results of metabolites derangement that occurs as part of ageing. CONCLUSION: MRS has a role as a non-invasive tool for the detection of brain metabolite biomarkers that indicate brain metabolic health, which can be integral in the management of AD.

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11).

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.

Airway Epithelial Cells Drive Airway Smooth Muscle Cell Phenotype Switching to the Proliferative and Pro-inflammatory Phenotype.

The increased mass of airway smooth muscle (ASM) in the airways of asthmatic patients may contribute to the pathology of this disease by increasing the capacity for airway narrowing. Evidence for the airway epithelium as a participant in ASM remodeling is accruing. To investigate mechanisms by which airway epithelial cells induce ASM cell (ASMC) proliferation, we have employed a co-culture model to explore markers of ASMC proliferative phenotype. Co-culture with epithelial cells led to incorporation of bromodeoxyuridine into ASMCs, indicating augmented proliferation and an associated increase in mRNA of the pro-proliferative co-transcription factor Elk1. Although the mitogen heparin-binding epidermal growth factor (HB-EGF) was augmented in the co-culture supernatant, the ASMC epidermal growth factor receptor (EGFR), an effector of HB-EGF induced proliferation, did not mediate epithelial-induced proliferation. The co-culture increased the expression of ASMC mRNA for the pro-inflammatory cytokines IL-6 and IL-8 as well as the pro-proliferative microRNA miR-210. The transcriptional repressor Max-binding protein (Mnt), a putative target of miR-210, was transcriptionally repressed in co-cultured ASMCs. Together, these data indicate that the airway epithelium-induced proliferative phenotype of ASMCs is not driven by EGFR signaling, but rather may be dependent on miR210 targeting of tumor suppressor Mnt.

Guideline No. 408: management of gestational trophoblastic diseases

This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. Women of reproductive age with gestational trophoblastic diseases. Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care.

Irisin promotes odontogenic differentiation and angiogenic potential in human dental pulp cells.

AIM: To determine whether irisin, a newly discovered myokine that links exercise-induced and metabolic homeostasis, is able to promote odontogenic differentiation and angiogenesis in human dental pulp cells (HDPCs). METHODOLOGY: Cell viability in the presence of irisin was measured. Real-time PCR and Western blot analysis were performed to evaluate the expression levels of irisin, odontogenic and angiogenic markers. The involvement of mitogen-activated protein kinase (MAPK) and the protein kinase B (Akt) signalling pathway was evaluated by Western blot. To evaluate mineralization nodule formation, alkaline phosphatase (ALP) staining and alizarin red S staining were performed. Scratch wound assays were performed to evaluate the effects of irisin on cell migration. The data were analysed using one-way analysis of variance (anova) followed by Tukey post hoc test and Student's t-test. Statistical significance was considered at P < 0.05. RESULTS: Irisin significantly promoted odontogenic differentiation as evidenced by formation of mineralized nodules, induction of ALP activity and upregulation of odontogenic and angiogenic markers (P < 0.05). Scratch wound assays revealed that irisin significantly increased migration of HDPCs (P < 0.05). Phosphorylation of both MAPK and Akt was increased by irisin. MAPK and Akt inhibitors inhibited mineralization, cell migration and the increased expression of odontogenic and angiogenic markers. CONCLUSIONS: Irisin promoted odontogenic differentiation and mineralization and has the potential for angiogenesis through activation of the MAPK and Akt signalling pathways in HDPCs.

Long-term Follow-up of Complicated Crown Fracture With Fragment Reattachment: Two Case Reports.

Two cases of complicated crown fracture of the maxillary incisors were restored using the fragment reattachment technique. Root canal treatment was performed, and the fractured fragment was bonded to the tooth structure using a dentin adhesive system and a flowable composite resin, followed by the insertion of a fiber post using dual-cured resin cement. Reattached fragments have shown reliable prognosis without inflammatory signs around bonded junctions after long-term follow-up.

Detection of bovine coronavirus in nasal swab of non-captive wild water deer, Korea.

Bovine coronavirus (BCoV) is a causative agent of respiratory and enteric diseases in cattle and calves. BCoV infection was also evident in captive wild ruminants. Recently, water deer are recognized as the most common wildlife to approach farmhouses and livestock barns in Korea. Therefore, we investigated 77 nasal swab samples from non-captive wild water deer (Hydropotes inermis) between November 2016 and September 2017 and identified three samples positive for coronavirus, indicating potential for respiratory shedding. The full genomic sequences of the water deer coronavirus were closely related to BCoV (>98%). Therefore, effective biosecurity system in bovine farms would be necessary to prevent contact between farm ruminants and free-ranging wild water deer.

Lysyl oxidase-mediated VEGF-induced differentiation and angiogenesis in human dental pulp cells.

AIM: To investigate the effects of recombinant human vascular endothelial growth factor (rhVEGF) on odontoblastic differentiation, in vitro angiogenesis, and expression and activity of lysyl oxidase (LOX) in human dental pulp cells (HDPCs), compared with rhFGF-2. To identify the underlying molecular mechanisms, the study focused on whether LOX was responsible for the actions of rhVEGF. METHODOLOGY: Recombinant human vascular endothelial growth factor (rhVEGF) was constructed using the pBAD-HisA plasmid in Escherichia coli. HDPCs were treated with 1-50 µg mL-1 rhVEGF for 14 days. Alkaline phosphatase (ALP) activity was measured, and the formation of calcified nodules was assessed using alizarin red staining after the induction of odontogenic differentiation of HDPCs. The expression level of the odontogenic differentiation markers was detected by reverse transcription polymerase chain reaction. Signal pathways were assessed by Western blot and immunocytochemistry. The data were analysed by anova with Bonferroni's test (α = 0.05). RESULTS: Recombinant human vascular endothelial growth factor significantly increased cell growth (P < 0.05), ALP activity (P < 0.05) and mineralization nodule formation and upregulated the mRNA expression levels of the osteogenic/odontogenic markers that were lower with rhFGF-2. rhVEGF significantly increased amine oxidase activity (P < 0.05) and upregulated LOX and LOXL mRNA expression in HDPCs. Additionally, rhVEGF dose-dependently upregulated angiogenic gene mRNAs and capillary tube formation to a greater degree than rhFGF-2. Inhibition of LOX using ß-aminopropionitrile (BAPN) and LOX or LOXL gene silencing by RNA interference attenuated rhVEGF-induced growth, ALP activity, mineralization, the expression of marker mRNAs and in vitro angiogenesis. Furthermore, treatment with rhVEGF resulted in phosphorylation of Akt, ERK, JNK and p38, and activation of NF-κB, which was inhibited by LOX or LOXL silencing and BAPN. CONCLUSION: Recombinant human vascular endothelial growth factor promoted cell growth, odontogenic potential and in vitro angiogenesis via modulation of LOX expression. These results support the concept that rhVEGF may offer therapeutic benefits in regenerative endodontics.

Quantum-mechanical analysis of effect of alloying elements on ε-martensite start temperature of steels.

With regard to the transformation mechanism of austenitic high manganese steel, the prediction of the ε-martensite start temperature is a critical consideration in alloy design. Evaluation of the ε-martensite start temperature makes it possible to predict the microstructure and to understand the phase transformation occurring during deformation. Here we use the quantum mechanical calculation of random alloys to understand the physics for ε-martensitic transformation in steels. We could find the linear relationship between the measured ε-martensite start temperatures and the crystal structure stability for various compositions. We also could estimate the effect of several alloying elements. It is expected that the effect of decreasing the temperatures for the same amount of alloying elements addition will be larger moving farther from Group VIII. By creating a free-energy model that reflects the temperature effect, we were able to calculate the average driving force required for the ε-martensitic transformations.

Anterolateral femoral bowing and loss of thigh muscle are associated with occurrence of atypical femoral fracture: Effect of failed tension band mechanism in mid-thigh.

BACKGROUND: The purpose of this study was to characterize anterolateral bowing of the femur using X-rays and muscular atrophy in the mid-thigh using computed tomography (CT) in patients with atypical femoral fractures (AFFs). We then compared the results with those of an intertrochanteric fracture to understand whether these measures act as causative factors of AFFs. METHODS: From January 2009 to December 2015, 37 patients with complete AFF and 12 patients with incomplete AFF were enrolled in this study. Lateral femoral bowing, anterior femoral bowing, cross-sectional area (CSA), and attenuation coefficient of thigh muscles in the AFF group are measured and compare with those in the intertrochanteric fracture group. RESULTS: Lateral and anterior femoral bowing in the AFF group were significantly higher than those in the intertrochanteric fracture group. The level of fracture was found to be significantly associated with lateral and anterior femoral bowing (r = 0.569, r2 = 0.324, p < 0.001; r = -0.530, r2 = 0.281, p < 0.001, respectively). Total CSA and CSA of anterior and medial compartments were significantly lower in the AFF group (p < 0.05). The attenuation coefficient of the total thigh muscle and all three compartments in the AFF group were significantly lower than those in the intertrochanteric fracture group (p < 0.05). CONCLUSIONS: This study demonstrated that anterolateral femoral bowing and loss of thigh muscle were highly associated with the occurrence of AFFs.

Predictors of general discomfort, limitations in activities of daily living and intention of a second donation in unrelated hematopoietic stem cell donation.

We performed a retrospective study of 1868 consecutive unrelated donors to predict the risk factors related to general discomfort, limitations in activities of daily living (ADLs) and intention of a second donation in hematopoietic stem cell (HSC) donation. General discomfort and limitations in ADLs were assessed by numerical measurement (scores of 0-10) and donor's intention of a second donation by yes or no reply. The post-donation questionnaires were completed within 48 h after HSC collection and at 1 week, 4 weeks, and 4 months thereafter. Predictors of general discomfort included female sex (P<0.0001), bone marrow (BM) collection (P<0.0001) or PBSC collection through a central line (CL; P=0.0349), 2-day collection (P=0.0150) and negative or undetermined intention of a second donation on day 1 (P<0.0001). Predictors of limitations in ADLs included age group of 30-39 years (P=0.0046), female sex (P<0.0001), BM collection (P<0.0001) or PBSC collection through a CL (P<0.0001) and negative or undetermined intention of a second donation on day 1 (P<0.0001). The only predictor of positive intention of a second donation was male sex (P=0.0007). Age, sex and collection method and period should be considered risk factors when unrelated HSC donation is performed.

Clinical Effectiveness of Different Polishing Systems and Self-Etch Adhesives in Class V Composite Resin Restorations: Two-Year Randomized Controlled Clinical Trial.

The aim of this randomized controlled clinical trial was to compare the clinical effectiveness of different polishing systems and self-etch adhesives in class V composite resin restorations. A total of 164 noncarious cervical lesions (NCCLs) from 35 patients were randomly allocated to one of four experimental groups, each of which used a combination of polishing systems and adhesives. The two polishing systems used were Sof-Lex XT (Sof), a multistep abrasive disc, and Enhance/Pogo (EP), a simplified abrasive-impregnated rubber instrument. The adhesive systems were Clearfil SE bond (CS), a two-step self-etch adhesive, and Xeno V (XE), a one-step self-etch adhesive. All NCCLs were restored with light-cured microhybrid resin composites (Z250). Restorations were evaluated at baseline and at 6, 12, 18, and 24 months by two blinded independent examiners using modified FDI criteria. The Fisher exact test and generalized estimating equation analysis considering repeated measurements were performed to compare the outcomes between the polishing systems and adhesives. Three restorations were dislodged: two in CS/Sof and one in CS/EP. None of the restorations required any repair or retreatment except those showing retention loss. Sof was superior to EP with regard to surface luster, staining, and marginal adaptation (p<0.05). CS and XE did not show differences in any criteria (p>0.05). Sof is clinically superior to EP for polishing performance in class V composite resin restoration. XE demonstrates clinically equivalent bonding performance to CS.

Properties of Dye-Sensitized Solar Cells Using Carbon Nanowall Counter Electrodes.

This research investigates plasma-treated and metal-coated carbon nanowalls (CNWs) for use as counter electrodes of dye-sensitized solar cells (DSSCs). The CNWs were synthesized on a fluorine-tin-oxide (FTO) glass substrate using the microwave plasma-enhanced chemical vapor deposition (PECVD) system with methane (CH4) gas. The post-plasma treatment was performed on the CNWs with hydrogen (H2) plasma using PECVD, and the CNWs were sputter-coated with metal films using the RF magnetron sputtering system with a four-inch tungsten (W) target. Then the post-plasma-treated and metal-coated CNWs were used as counter electrodes for the fabrication of the DSSCs. Field-emission scanning electron microscopy (FE-SEM) was performed to obtain cross-sectional and planar images of the grown CNWs. The energy conversion efficiencies of the DSSCs manufactured using the post-plasma-treated and metal-layer-coated CNWs as the counter electrodes were measured.

Surface Engineering of Nanostructured Titanium Implants with Bioactive Ions.

Surface nanofeatures and bioactive ion chemical modification are centrally important in current titanium (Ti) oral implants for enhancing osseointegration. However, it is unclear whether the addition of bioactive ions definitively enhances the osteogenic capacity of a nanostructured Ti implant. We systematically investigated the osteogenesis process of human multipotent adipose stem cells triggered by bioactive ions in the nanostructured Ti implant surface. Here, we report that bioactive ion surface modification (calcium [Ca] or strontium [Sr]) and resultant ion release significantly increase osteogenic activity of the nanofeatured Ti surface. We for the first time demonstrate that ion modification actively induces focal adhesion development and expression of critical adhesion­related genes (vinculin, talin, and RHOA) of human multipotent adipose stem cells, resulting in enhanced osteogenic differentiation on the nanofeatured Ti surface. It is also suggested that fibronectin adsorption may have only a weak effect on early cellular events of mesenchymal stem cells (MSCs) at least in the case of the nanostructured Ti implant surface incorporating Sr. Moreover, results indicate that Sr overrides the effect of Ca and other important surface factors (i.e., surface area and wettability) in the osteogenesis function of various MSCs (derived from human adipose, bone marrow, and murine bone marrow). In addition, surface engineering of nanostructured Ti implants using Sr ions is expected to exert additional beneficial effects on implant bone healing through the proper balancing of the allocation of MSCs between adipogenesis and osteogenesis. This work provides insight into the future surface design of Ti dental implants using surface bioactive ion chemistry and nanotopography.

Artefacts at a glance: differentiating features of artefactual stenosis from true stenosis at the genu of the petrous internal carotid artery on TOF MRA.

AIM: To investigate the distinguishing features of artefactual stenosis from true stenosis at the genu of the petrous internal carotid artery (ICA) on time of flight (TOF) magnetic resonance angiography (MRA). MATERIALS AND METHODS: Both TOF MRA and digital subtraction angiography (DSA) were performed in 65 patients with 74 vessels who demonstrated artefactual stenosis in 43 patients with 50 vessels and true stenosis in 22 patients with 24 vessels. The following findings of the signal loss were compared between the two groups: (1) margin, (2) darkness, (3) the presence of bilaterality, (4) the presence of tandem arterial stenosis, (5) the location of the epicentre, and (6) length. RESULTS: In five out of the six evaluated items, statistically significant differences were present between the two groups (p<0.00 in all five items). Artefactual stenosis more frequently showed signal loss with ill-defined margins (47/50), less darkness compared to the background darkness (46/50), the absence of tandem arterial stenosis (35/50), epicentre at the genu (34/50), and shorter length (2.57 ± 0.68 mm). No significant difference was noted in the presence of bilaterality of signal loss between the two groups (p=0.706). CONCLUSION: Several MRA features can be useful for suggesting artefactual stenosis rather than true stenosis at the genu of the petrous ICA on TOF MRA.

Resection of a physeal bar with complete transverse osteotomy at the metaphysis and Ilizarov external fixation.

The traditional techniques involving an oblique tunnel or triangular wedge resection to approach a central or mixed-type physeal bar are hindered by poor visualisation of the bar. This may be overcome by a complete transverse osteotomy at the metaphysis near the growth plate or a direct vertical approach to the bar. Ilizarov external fixation using small wires allows firm fixation of the short physis-bearing fragment, and can also correct an associated angular deformity and permit limb lengthening. We accurately approached and successfully excised ten central- or mixed-type bars; six in the distal femur, two in the proximal tibia and two in the distal tibia, without damaging the uninvolved physis, and corrected the associated angular deformity and leg-length discrepancy. Callus formation was slightly delayed because of periosteal elevation and stretching during resection of the bar. The resultant resection of the bar was satisfactory in seven patients and fair in three as assessed using a by a modified Williamson-Staheli classification.

Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.

Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.

Splinted Porcelain Laminate Veneers With a Natural Tooth Pontic: A Provisional Approach for Conservative and Esthetic Treatment of a Challenging Case.

Esthetic rehabilitation of discolored anterior teeth is always a great challenge, especially in the presence of pathology. Fortunately, conservative management in the esthetic zone has become more feasible in compromised cases because of the development of restorative materials and advances in dental adhesives. This report presents a complicated case of a patient with tetracycline-related discoloration, multiple root resorption, and a periapical lesion. Treatment was conservative and used a natural tooth pontic and splinted porcelain laminate veneers.