High Transformation Rate Research Articles

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients.

This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological transformation in Chinese patients. 104 SLE patients with biopsy-proven LN class II were included and divided into proteinuria group (proteinuria ≥ 0.4g/24h, with or without microscopic hematuria) and hematuria group (microscopic hematuria with proteinuria < 0.4g/24h).Patients were treated with glucocorticoid alone (GC monotherapy) or GC in combination with other immunosuppressant (combination therapy). The rates of remission, relapse, histological transformation, end-stage renal disease (ESRD), adverse events, and risk factors related to the outcomes were analyzed. During the median follow-up of 77.5 (IQR 58-116.5) months, all the 104 patients achieved remission. Relapse occurred in 69 cases (66.3%), of which 37 were of renal relapse (35.6%). Histological transformation was found in 14 of the 16 (87.5%) cases who received repeated renal biopsy after renal relapse. At the end of follow-up, 3 (2.9%) patients developed ESRD. There were no significant differences in the rates of relapse, histological transformation, adverse events and in the time from remission to relapse between the proteinuria group and the hematuria group. In contrast, the cumulative relapse rate in the GC monotherapy group was much higher than that in the combination group (P < 0.01). Adverse events occurred in 55 (57.3%) patients during follow-up. Patients with LN class II have high rates of relapse and renal histological transformation and need optimal maintenance therapy. • The rates of relapse and histological transformation are high in patients with LN class II. • Patients with LN class II are suggested to receive combination therapy and consider repeat renal biopsy after renal relapse.

Induction Surface Hardening: a review

One of the methods of surface hardening the majority extensively used surface hardening procedure which can be used in many metals in their entirety in today’s applications. Induction coil is concentrated to the localized area where the necessary piece is hardened of the material. A high inductance coil is used to heat the surface of steel into the austenitic region. High heat transformation rates result in instant quenching by oil, resulting in a steep temperature gradient. This method necessitates external quenching because it induces phase conversion from austenite to martensite. This review paper ensures an overview of the principles of induction surface hardening, as well as some of its advantages over traditional hardening techniques. The results of experiments and computational approaches reported by different researchers are discussed.

Selection of transgenic citrus plants based on glyphosate tolerance conferred by a citrus 5-enolpyruvylshikimate-3-phosphate synthase variant.

We have defined the conditions for citrus transformations using glyphosate as selection agent. This protocol results in high transformation rate and low incidence of chimeric shoots. Glyphosate, the most widely used herbicide in the world, specifically inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), an essential enzyme of the shikimate pathway. Various laboratory-generated or naturally evolved glyphosate-resistant EPSPS variants have been used to produce glyphosate-tolerant transgenic crops, enabling highly effective weed control in agriculture. In this study, we explored the potential of using a citrus EPSPS variant that mimics the previously reported Eleusine indica glyphosate-resistant TIPS (T102I + P106S) mutant for selection of transgenic citrus plants in the presence of glyphosate. We found that glyphosate did not suppress bud formation on 'Duncan' grapefruit seedling explants, but inhibited non-transgenic bud outgrowth to produce shoots in a concentration-dependent manner. At certain concentrations, glyphosate had dramatic effect on the transformation rate and the percentage of non-chimeric transgenic shoots in this newly developed selection system. Specifically, at 0, 10, 20, and 50 μM of glyphosate, the citrus TIPS EPSPS-based selection resulted in transformation rates of 4.02, 5.04, 14.46, and 40.78%, respectively, and 6.41, 23.96, 42.94, and 40.17% of non-chimeric transgenic shoots, respectively. These results indicate that the citrus TIPS EPSPS-glyphosate selection system is highly efficient and can be used as an alternative to antibiotic-based selection methods in citrus genetic transformation. Furthermore, the selection conditions defined in this study are expected to greatly facilitate the production of genetically modified, market-friendly citrus plants, such as cisgenic and intragenic plants.

A Scoping Review on Gaps in the Diagnostic Criteria for Proliferative Verrucous Leukoplakia: A Conceptual Proposal and Diagnostic Evidence-Based Criteria.

Simple SummaryProliferative verrucous leukoplakia is considered as an oral potentially malignant disorder that presents the highest tendency to recurrence and malignant transformation, alt-hough published diagnostic criteria are inconsistent. A precise evidence-based diagnosis is im-portant to differentiate this lesion from others on the oral mucosa with less tendency for cancer progression, and thus establish specific management protocols aimed at the early diagnosis of oral cancer. In this scoping review the published conceptual and diagnostic criteria for prolifera-tive verrucous leukoplakia were comprehensively analyzed, and a conceptual proposal for fu-ture diagnosis is proposed based on current evidence.Proliferative verrucous leukoplakia (PVL) is considered as an oral potentially malignant disorder (OPMD) that presents with a high tendency to recurrence after treatment and has the highest malignant transformation ratio among all OPMD (50%). Evidence-based publications have indicated that the malignant evolution reported is significantly related to the inconsistent diagnostic criteria used in primary-level studies; so, it has been hypothesized that the risk of oral cancer for this disease could even be underestimated. This is important because PVL requires specific management protocols, evidence-based, aimed at the early diagnosis of cancer developing in these lesions. We present a scoping review—a novel approach to mapping the available literature on a given topic to provide an overview of the available research evidence and to highlight possible gaps in the evidence—especially related in our study to the diagnostic aspects of PVL, and to issue a conceptual proposal and diagnostic criteria for PVL. We conclude that PVL is a white, multifocal and progressive lesion with a high malignant transformation rate which is diagnosed mainly around the age of 60 years without any specific histological characterization. We also advise a personal reflection on the level of certainty with which the clinician makes the diagnosis of a particular case of PVL.

Clinical, Pathologic Characteristics and Survival Of Adult Patients With Essential Thrombocythemia: Experience In a Reference Center In Mexico

IntroductionEssential thrombocythemia (ET) is a myeloproliferative neoplasm, characterized by sustained thrombocytosis (≥450 x 109/L), vasomotor symptoms and thrombotic / hemorrhagic complications. Treatment and prognosis relies on risk stratification, based on age and thrombosis history. Survival is similar to that of general population, however there is a low risk of transformation to myelofibrosis (MF) and acute myeloid leukemia (AML). ObjectiveTo describe demographic, clinical and hystopathologic characteristics, as well as general outcome of patients with ET treated at INCMNSZ. MethodsDescriptive and retrospective study of patients with ET, diagnosed from January 2000 to December 2012 and reclassified according to WHO 2008 criteria. General data and overall survival were calculated using SPSS v17.0. ResultsForty-nine patients with ET were included, with a median age of 56 years, 65.3% were female. At diagnosis, 98% had an ECOG of 0 to 1, and 42.9% had three or more comorbidities. Table 1 shows laboratory parameters at diagnosis. Forty-nine percent and 16.3% were classified as having high risk according to Tefferi and IPSET classifications respectively. In 60.4% of biopsies, reticulin was not reported; in positive cases, grade 1 fibrosis was the most frequent in 20.8%. Karyotype was normal in 53.1%, and it was possible to determine JAK2 V617F mutation only in 16.4%, reported as positive in 8.2%. Thrombotic events were present in 16.3%, 50% of which were venous. Secondary Von Willebrand syndrome was documented in 10.2%. Hydroxyurea and acetylsalicylic acid were the most used drugs, 91.8% and 89.8% respectively, among others. Of patients who received treatment, 42.9% and 38.8% had partial and complete responses, respectively. Histological transformation was documented in 14.3%, 8.17% to MF and 6.12% to AML, at a median of 7.8 years from diagnosis. At last follow-up, 79.6% were alive, with median overall survival not reached, and 8.2% had died, mainly because of progression of MF/AML.Table 1Laboratory parameters at diagnosis (median)Hemoglobin14.1 g/dLWBC8,600 /uLPlatelets1,043,000 (535,000 – 2,580,000) / uLFerritin57.35 ng/mLVitaminB12713 pg/mLErythrocytesedimentationrate5 mm/hC-reactiveprotein0.15 mg/LProthrombintime / INR11.2” / 1.1Partialthromboplastintime33.4” Discussion and conclusionsIn this cohort thrombosis incidence is similar to international reports (11-25%), and the high rate of transformation to MF and AML perhaps is influenced by the diagnostic criteria used in the early 2000 (PVSG criteria vs WHO criteria). Concerning mutational status of JAK2 V617, the incidence is low and strong conclusions can not be made in this matter because of the retrospective sense of the study and the availability of the test in our center. In conclusion, these results emphasize the importance of adhering to strict clinical and histopatological criteria to diagnose patients with ET, establish the risk and identify those who do not require cytoreductive treatment, in order to reduce the risk of long term complications. Disclosures:No relevant conflicts of interest to declare.

Malignant transformation of Oral submucous fibrosis to Oral Squamous cell carcinoma : A case report

Oral submucous fibrosis (OSMF) is a potentially malignant disorder with high rate of malignant transformation. Oral epithelium being thin and atrophic becomes more vulnerable to attack of carcinogens. Malignant transformation in OSMF usually occurs gradually over a long period of time. Here, we report a case of oral submucous fibrosis turning into malignancy in a 27-year-old male patient.

Effects of CSF3R mutations on Myeloid Differentiation and Proliferation of Hematopoietic Cells of Congenital Neutropenia Patients

Over the last 25 years, with the clinical approval of recombinant human granulocyte colony-stimulating factor (rhG-CSF) remarkable progress has been achieved in the therapy of severe congenital neutropenia (CN). Nevertheless, CN patients have a high rate of transformation to myelodysplasia (MDS) or acute myeloid leukemia (AML). This risk is especially high in the group of patients who harbor acquired G-CSFR mutations, suggesting that these mutations are involved in the leukemogenesis. Deep sequencing of the intracellular part of G-CSFR allowed us to identify a subset of CN patients with a high mutant allele frequency (MAF) of G-CSFR mutations in the granulocytic compartment. We performed CSF3R mutation analysis of myeloid colonies from colony forming unit (CFU) assay of BM and CD34+ samples of 3 ELANE -CN patients, in which the percentage of granulocytes with G-CSFR mutation varied between 22.6% and 81%. Average number of sequenced colonies per CFU sample was 18. Intriguingly, we found that only cell clones with WT G-CSFR were grown in CFU assay. We hypothesized that lack of G-CSFR mutant clones in CFU assay is due to abnormal signaling downstream of truncated G-CSFR. To compare myeloid differentiation of G-CSFR mutant and WT G-CSFR hematopoietic cells, we generated ELANE -CN patient-derived induced pluripotent stem cells (CN-iPSCs) and performed CRISPR/Cas9 genome editing of CSF3R . Using 2 different sgRNAs specific for the intracellular region of G-CSFR, we introduced nucleotide indels at amino acid positions 740 and 735 (NP_000751.1) in CN-iPSCs. Subsequently, homozygous and heterozygous CN-iPSCs clones with truncated distal part of cytoplasmic domain of G-CSF receptor and subsequent loss of 3 out of 4 conserved tyrosine residues were generated.We compared myeloid differentiation of healthy donor iPSCs (HD-iPSCs), CN-iPSCs and CN-iPSCs with heterozygous and homozygous truncated G-CSF receptor (G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs, respectively). Absolute cell count during myeloid differentiation (18-32 day) of HD-iPSCs, G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs didn't differ significantly (p>0.05). In contrast, absolute cell count was found to be elevated from day 25 to day 32 of differentiation when G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs hematopoietic progenitors were compared with CN-iPSCs-derived hematopoietic cells (p<0.05). FACS analysis of CN-iPSCs derived hematopoietic progenitors with and without truncated G-CSF receptor using a panel of hematopoietic markers (KDR, CD34, CD235a, CD41a, CD45 and CD33) showed no difference in percentage of early progenitors (CD34+/KDR+), E/MK precursors (CD41a+CD235a+/ CD45-), CD34+/CD45+ and CD34+/CD43+ cells. Intriguingly, we observed increase in percentage of CD34+/CD43+ (p<0.01), CD33+/CD45+ (p<0.05) and CD41a+CD235a+/ CD45- (p<0.05) cells at day 14 of myeloid differentiation of G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs versus HD-iPSc. As expected, relative number CD14+ and CD16+ cells were not changed upon myeloid differentiation of hematopoietic progenitors with mutant G-CSFR but relative levels of CD15+ and CD15+/CD16+ were negatively affected by homozygous and heterozygous G-CSFR mutations. Next, CFU assay of hematopoietic progenitors derived from G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs produced markedly less colonies than HD- and CN-iPSCs derived hematopoietic cells. Cell morphology analysis also confirmed the reduced number of mature granulocytes seen after myeloid differentiation of G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs. Finally, reprogramming of BM cells from CN patients into iPSCs followed by mutation analysis of single cell derived iPSCs clones allowed us to identify iPSCs with naturally acquired G-CSFR mutations. Preliminary results revealed reduced myeloid differentiation of these cells, which is in line with data generated from G-CSFR*HET CN-iPSCs and G-CSFR*HOM CN-iPSCs.Using a combination of patient CN-iPSCs and CRISPR/Cas9 gene editing we were able to recapitulate main features of G-CSFR mutant versus G-CSFR WT CN cells - defective neutrophil differentiation and increased proliferation of human hematopoietic progenitors. Since virtually all studies of truncated G-CSFR receptor signaling have been performed in murine cytokine-responsive myeloid cell lines, our approach is more suitable to explore human aberrant G-CSF receptor signaling in depth. DisclosuresNo relevant conflicts of interest to declare.

Agrobacterium-Mediated Transformation of pMDC140 Plasmid Containing the Wheatwin2 Gene into the Tadong Rice Genome

Blast disease resulting from Magnaporthe oryzae fungal infection reduces annual rice yield by up to 30% globally. The wheatwin2 (wwin2) is a pathogenesis-related (PR) gene that encodes for a PR-4 protein with chitinase properties that is capable of degrading chitin, a major constituent of certain fungal cell walls. However, the potential for wwin2 to contribute to M. oryzae resistance in rice is unclear. This study reports the construction of a pMDC140 vector carrying the wwin2 gene and its Agrobacterium-mediated transformation into the Tadong rice genome. In brief, the wwin2 gene was synthesized and integrated into a pMDC140 vector using Gateway cloning technology and was transformed into the Tadong rice genome. Our results show a promising high transformation rate, with more than 90% of the transformed rice calli expressing β-glucuronidase (GUS), the reporter gene marker. The expression of the wwin2 gene in transformed rice calli was further confirmed using quantitative real-time polymerase chain reaction. In conclusion, a pMDC140-wwin2 vector was constructed, which had a high transformation rate and could consistently induce expression of the GUS and wwin2 genes in Tadong rice. Data of this study is beneficial for subsequent in vitro and M. oryzae-infected field experiments to confirm the defense mechanism of the wwin2 gene towards blast disease in rice.

Deciphering the transformation mechanism of substituted polycyclic aromatic hydrocarbons on Al(III)-montmorillonite: An experimental and density functional theory study

The researches on transformation of polycyclic aromatic hydrocarbons (PAHs) on clay minerals modified by metal ions have received increasing attention. However, the transformation of PAHs with electron-withdrawing or electron-donating substitutional groups on clay minerals is not well understood currently. In this study, the degradation of anthracene (ANT) with different substituents (including -CH3, -CHO, -Br, -OMe, and -NO2) on Al(III)-montmorillonite (MMT) was investigated in the dark. The results showed that aromatic compounds were degraded with the rate constants (kobs) of 0.004–0.141 d−1. Moreover, ANT with electron-donating substituents (e.g., -CH3, -OMe) had a higher transformation rate than that with electron-withdrawing substituents (e.g., -Br, -NO2). The reactive oxygen species (ROS) quenching experiments indicated that ROS played a significant role in the transformation of ANT and ANT derivatives. Density functional theory (DFT) calculations revealed that the reactivity of single substituted PAHs was highly correlated with their ionization potential (IP), the energy of highest occupied molecular orbital (EHOMO), the energy of lowest unoccupied molecular orbital (ELUMO), and electronegativity (ζ), while independent of hardness (η). This study provides novel insights into predicting the reactivity of PAHs derivatives, and lays a fundamental basis for better understanding the fate of substituted PAHs in soils.

Damage development during the strain induced phase transformation of austenitic stainless steels at low temperatures

The strain-induced martensitic transformation greatly affects the plastic behavior of the metastable austenitic stainless steels. The martensitic transformation continuously changes the initially homogeneous material into a strongly heterogeneous bi-phase one. In addition to the hardening behavior, this phenomenon would influence the damage growth and load-carrying capacity of the material during the plastic deformation. In this study, plastic behavior of the material AISI 304 including the hardening and damage growth, has been examined at low temperature; where a high rate of martensitic transformation affects the microstructure strongly. Experimental analysis and microscopic observations have been performed for evaluating the martensite content and damage growth. In addition, based on the continuum damage mechanics, a simplified damage evolution model has been proposed to capture the effect of phase transformation on the damage growth rate explicitly. The results show that the damage initiates with a considerable rate in early stages of transformation, however at higher levels of transformation, damage growth rate decreases until a sudden fracture. The presented model properly predicts the observed damage behavior.

Citrus Cell Suspension Culture Establishment, Maintenance, Efficient Transformation and Regeneration to Complete Transgenic Plant.

Agrobacterium-mediated transformation of epicotyl segment has been used in Citrus transgenic studies. The approach suffers, however, from limitations such as occasionally seed unavailability, the low transformation efficiency of juvenile tissues and the high frequency of chimeric plants. Therefore, a suspension cell culture system was established and used to generate transgenic plants in this study to overcome the shortcomings. The embryonic calli were successfully developed from undeveloped ovules of the three cultivars used in this study, “Sweet orange”-Egyptian cultivar (Citrus sinensis), “Shatangju” (Citrus reticulata) and “W. Murcott” (Citrus reticulata), on three different solid media. Effects of media, genotypes and ages of ovules on the induction of embryonic calli were also investigated. The result showed that the ovules’ age interferes with the callus production more significantly than media and genotypes. The 8 to 10 week-old ovules were found to be the best materials. A cell suspension culture system was established in an H+H liquid medium. Transgenic plants were obtained from Agrobacterium-mediated transformation of cell suspension as long as eight weeks subculture intervals. A high transformation rate (~35%) was achieved by using our systems, confirming BASTA selection and later on by PCR confirmation. The results demonstrated that transformation of cell suspension should be more useful for the generation of non-chimeric transgenic Citrus plants. It was also shown that our cell suspension culture procedure was efficient in maintaining the vigor and regeneration potential of the cells.

The interplay of hypoxia and autophagy in epithelium-derived ameloblastoma cell survival: a pilot study

Objectives Ameloblastoma is the most clinically significant benign odontogenic tumor of the jaws. Ameloblastomas have a locally aggressive growth pattern and a high rate of malignant transformation. The etiopathogenesis of ameloblastoma is still unknown, and there is still a paucity of information on the factors regulating the locally aggressive growth characteristics of ameloblastoma. Hypoxia and autophagy are 2 mechanistic processes associated with tumor behavior as several tumor cells induce a hypoxic microenvironment to survive. Epithelium-derived ameloblastoma cells (EPAMCs) demonstrate enhanced basal autophagy, but the roles of hypoxia and autophagy in EPAMC survival and ameloblastoma recurrence are still unknown. To understand ameloblastoma pathogenicity and behavior, the goals of this study were to assess differential expression of ameloblastoma-specific and autophagy markers in primary and recurrent ameloblastoma and to assess the roles of hypoxia and autophagy in EPAMC survival. Our hypotheses were that ameloblastoma expresses markers similar to odontogenic epithelial tissue and hypoxia induces oxidative stress and activates autophagy in EPAMCs, favoring their survival and recurrence. Methods Primary and recurrent ameloblastoma tissues from 2 patients were immunostained with pan-cytokeratin, vimentin, and SQSTM1/p62 to assess the expression levels of ameloblastoma and autophagic markers. Additionally, EPAMCs were subjected to severe hypoxia (0.1% O2) and then allowed to recover for 24 hours in order to define responsiveness to hypoxia based on expression levels of hypoxic (hypoxia-inducible factor [HIF]-1α), survival (phosphorylated extracellular signal-regulated kinase 1/2), and autophagic (Beclin1, phosphorylated 40S ribosomal protein S6 [pS6], SQSTM1/p62, LC3A/B) markers as detected by Western blotting. Previously characterized human odontoma-derived cells (HODCs) served as control odontogenic cells. All experiments were performed in at least triplicates. Data were analyzed as fold change relative to normoxia and expressed as mean ± standard deviation. A paired t test comparison of means was done to compare the expression of autophagy proteins when cells were under normoxia to protein expression under hypoxia and recovery conditions. The Welch 2-sample t test was used to compare fold changes from normoxia in EPAMCs and HODCs with each other. P values were adjusted for multiple comparisons using the Benjamini-Hochberg procedure. Results Both primary and recurrent tissue samples stained positive for pan-cytokeratin in the cytoplasm of the ameloblastoma islands. Vimentin and SQSTM1/p62 were undetectable in all samples, but the connective tissue stained positive for vimentin. Relative to normoxia, HIF-1α and SQSTM1/p62 expression was increased when the EPAMCs were reoxygenated (P = .056). pS6 levels were decreased in EPAMCs in both hypoxia (P = .005) and recovery (P = .005) compared with basal levels. Hypoxia, however, did not induce any significant changes among the remainder of the hypoxic, survival, and autophagic markers; no statistically significant difference was observed between the EPAMCs and HODCs. Conclusions The results of this pilot study provide insight into the pathogenicity of ameloblastoma and the possible behavior of EPAMCs when subjected to hypoxia. Our observation of vimentin expression alongside the pan-cytokeratin pattern is consistent with an epithelial origin of both primary and recurrent ameloblastoma. In EPAMCs, canonical autophagy tended to increase with hypoxia and did not recover when cells were reoxygenated, as evident by the increased HIF-1α and SQSTM1/p62 and the reduced levels of pS6 24 hours following hypoxia. This supports EPAMCs re-establishing basal autophagy after severe hypoxia and that recurrence of ameloblastoma may be related to autophagy.

Improved in planta genetic transformation efficiency in bitter gourd (Momordica charantia L.)

Production of transformed bitter gourd plants through in vitro regeneration is a laborious practice, which may also result in somaclonal variations. Thereby, in the current study, we have established a less tedious in planta protocol for more efficient genetic transformation of bitter gourd var. NBGH-470 (Apurva) using the seed as a target material. Bitter gourd seeds were transformed by Agrobacterium tumefaciens strain LBA4404 bearing the pCAMBIA1301 binary vector, and the transformed plants were selected against hygromycin B. The putatively transformed bitter gourd (To) plants were examined by GUS assay. Two parameters, including vacuum infiltration and sonication improving the in planta transformation, have been investigated in the present work. Amongst several time durations examined, the highest transformation rate (37%) was achieved upon subjecting the pre-cultured bitter gourd seeds to sonication for 15 min, followed by vacuum infiltration for 6 min in LBA4404 culture suspension. The transformed bitter gourd (T1) plants were selected against hygromycin B, and the transgene integration was evaluated by polymerase chain reaction (PCR), Southern hybridization, and reverse transcriptase PCR (RT-PCR). The developed protocol in the current study is suitable to genetically engineer the bitter gourd plants with disease and pest-resistant traits.

Malignant transformation of oral potentially malignant disorders in Taiwan: An observational nationwide population database study.

Oral cancer is one of the leading causes of cancer death, which are mostly preceded by oral potentially malignant disorders (OPMDs). Taiwanese government launched a free oral cancer screening program. The aim of this study was to analyze the malignant transformation rate of OPMDs.This study was based on national-wide oral screening databases. 3,362,232 people were enrolled. Patients clinically diagnosed with leukoplakia, erythroplakia, oral submucosal fibrosis (OSF), oral verrucous hyperplasia (OVH), and oral lichen planus (OLP), from 2010 to 2013, were identified. We followed up OPMD patients in cancer registry databases to analyze the malignant transformation rate.The malignant transformation rates from the highest to the lowest were: OVH > OSF > erythroplakia > OLP > leukoplakia. The malignant transformation rate was 24.55, 12.76, 9.75, 4.23, and 0.60 per 1000 person-years in the OVH, OSF, erythroplakia, leukoplakia, and comparison cohort. The hazard ratio was 8.19 times higher in the OPMD group compared with comparison cohort group, after age and habit adjustment. Female patients with OPMDs had a high risk of malignant transformation.Nationwide screening is very important for early diagnosis. OVH had the highest malignant transformation possibility. Female OPMD patients are a rare but have a relatively high malignant transformation rate.

Clinicopathologic factors associated with malignant transformation of oral leukoplakias: a retrospective cohort study

It is clinically challenging to identify oral leukoplakias that have a high risk of undergoing malignant transformation. The aim of this retrospective study was to elucidate the associations between malignant transformation of oral leukoplakias and various clinicopathologic factors. Patients with a diagnosis of clinical oral leukoplakia, verified through histopathologic examination and with access to digital images of the lesion, were retrospectively included for the period 2003–2013. Using the clinical images, all lesions were re-evaluated regarding diagnosis and clinical subtype. Of the 234 included patients, with a median follow-up of 9 years, 27 (11.5%) developed oral squamous cell carcinoma. Among the clinicopathologic factors investigated, non-homogeneous oral leukoplakia (OL), OL with dysplasia, and OL localized to the tongue showed statistically significant increased rates of malignant transformation in the multivariate Cox regression analysis. Non-homogeneous OL showed a 15.2-times higher transformation rate than homogenous OL (P<0.001). Dysplastic leukoplakias developed into carcinomas 2.4-times more often than did non-dysplastic leukoplakias (P=0.048). OL located on the tongue showed a 2.8-times higher malignant transformation rate than OLs at other oral locations (P=0.018), when other locations were combined into one group. Non-homogeneous OL, OL with dysplasia, and OL localized to the tongue have higher transformation rates.

Regulation of Collagen Synthesis in Tobacco/Pan-Masala Induced Oral Sub-Mucosal Fibrosis and Diagnostic Approach - Review Article

&lt;p&gt;&lt;strong&gt;Introduction :&lt;/strong&gt; oral submucosal fibrosis (OSMF) is related to juxta epithelial inflammatory response followed by a fibroelastic change of the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa, causing trismus and inability to eat.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Methods and Materials:&lt;/strong&gt; The suitability standards for studies were: Research Articles that studied the metabolic activities in oral submucous fibrosis mainly caused by some carcinogenic substances or chemicals which may present in tobacco, alcohol, cigarettes, pan-masala etc Reference list of selected articles and reviews on the topic also were searched. studies were extracted, A total of 90-100 studies were extracted, using the keywords oral submucous fibrosis, oral potentially malignant lesion and diagnosis, collagen synthesis etc.,&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;cancer risk among these patients, periodic biopsies of suspicious regions of the oral mucosa are essential for the early detection and management of high?risk oral premalignant lesions and prevention of cancer.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Conclusion&lt;/strong&gt;: OSMF is hardly recognized and is poorly understood across the globe. significant improvement in management, nor reduction in its high malignant transformation rate. Better integration of medical and dental services, especially in developing countries, may reduce patients’ suffering and improve their life quality.&lt;/p&gt;

Comparative Study of Stress and Strain Partitioning Behaviors in Medium Manganese and Transformation-Induced Plasticity-Aided Bainitic Ferrite Steels

The origins of the superior work hardening capability of medium manganese (M-Mn) and conventional transformation-induced plasticity-aided bainitic ferrite (TBF) steels of similar tensile strength and elongation are comparatively investigated via synchrotron X-ray diffraction measurements. The M-Mn steel undergoes preferential plastic deformation in austenite; its superior work hardening capability and associated uniform elongation are attributed to the high rates of martensitic transformation and dislocation accumulation per strain in the retained austenite. By contrast, the excellent work hardening behavior and uniform elongation of the TBF steel are attributed to the sustained transformability until the occurrence of a large strain and significant stress partitioning between the face-centered cubic (FCC) and body-centered cubic (BCC) phases due to the high austenite phase stability and high resistance to slip deformation of austenite.

Management of Histologically Proven Oral Submucous Fibrosis with Intralesional Steroids and Hyaluronidase- A Report of Two Cases

Oral Submucous Fibrosis (OSMF) is a chronic debilitating disease characterised by progressive fibrosis. The disease is predominantly seen in South East Asia and mainly attributed to areca nut chewing habit. The classical presentation includes generalised blanching with palpable fibrotic bands in the oral mucosa. Patients experience severe burning sensation, trismus and difficulty in gustatory functions, thus resulting in compromised nutritional status. The OSMF has been grouped under Oral Potentially Malignant Disorders (OPMD) and has high rates of malignant transformation. Although randomised controlled trials on different treatment modalities have been conducted, currently there is no effective medical management. This paper highlights two cases of OSMF presenting with severe burning sensation and trismus, who underwent incisional biopsy for histopathological confirmation and to rule out dysplasia. Both the patients were treated with dexamethasone and hyaluronidase, biweekly for four weeks. Post-treatment there was significant improvement in the clinical symptoms, thus providing the patients with better quality of life.

Інноваційний розвиток в умовах комплементарності.

The peculiarities of innovative development in the interaction of economic and social components of the external and internal environment are studied on the basis of a complementary approach, namely the relationship between economic efficiency and social justice, their negative and positive impact on the quality of life and socio-economic development opportunities. As for complementary development, the idea of justice, which currently is an important factor in achieving European living standards and guaranteeing social-economic rights of a person and citizen, plays an important role in reforming all the spheres of public life, democratization of Ukrainian society, and providing Ukraine's integration into the European political and legal space. Complementarity research is becoming relevant at the present stage of global economic development, when the market situation is characterized by a fairly high rate of transformation, and innovation becomes the main competitive factor. The author considers the emergence of the complementarity concept in research works made in various areas (e.g., the concept of institutional complementarity), and also highlights the features of compensatory and supplemental complementarity. Unconditional following global examples without taking into account the state of real socio-economic and institutional structures in a certain state will not give a favourable result from implementing reforms and introducing innovations due to the lack of complementary connections. Therefore, the conditions for the emergence of new institutional changes and the impact of "social elevators" on social development in the long run are analyzed. The presence of complex unresolved problems in the development of our state actualizes the study of the complementary context of innovative development, aimed at rethinking the role of social justice in solving major economic problems. Due to a complementary approach, the economic system will be able to increase such features as adaptability and continuity by developing mechanisms of self-preservation, and will acquire systematic innovative development with a ripple effect.

Crystallographic texture evolution and martensite transformation in the strain hardening process of a ferrite-based low density steel

The strain-induced martensite transformation is of great importance in the strain hardening process of ferrite based low-density steel. Based on the microstructure analysis, the texture evolution and martensite transformation behavior in the strain hardening process were studied. The results show that martensite transformation accompanied by TWIP effect and high density dislocations maintains the continuous hardening stage. As the strain increases, the texture of retained austenite evolves towards the F orientation {111}<112>, which is not conducive to martensite transformation. After the strain of 5%, the number of austenite grains with high Schmid factor orientations is gradually increased, and then significantly reduced when the strain is over 10 % due to the occurrence of martensitic transformation, which results in a high martensitic transformation rate. However, the unfavorable orientation and the reduced grain size of austenite slow down the martensite transformation at the final hardening stage. Moreover, because of the coordination deformation of austenite grains, strain preferentially spreads between adjacent austenite grains. Consequently, the martensite transformation rate in strain hardening process is dependent on the orientation and grain size evolution of austenite, leading to a differential contribution to each strain hardening stage.