Enhancing thalassemia gene carrier identification in non-anemic populations using artificial intelligence erythrocyte morphology analysis and machine learning.

BACKGROUND: Non-anemic thalassemia trait (TT) accounted for a high proportion of TT cases in South China. OBJECTIVE: To use artificial intelligence (AI) analysis of erythrocyte morphology and machine learning (ML) to identify TT gene carriers in a non-anemic population. METHODS: Digital morphological data from 76 TT gene carriers and 97 controls were collected. The AI technology-based Mindray MC-100i was used to quantitatively analyze the percentage of abnormal erythrocytes. Further, ML was used to construct a prediction model. RESULTS: Non-anemic TT carriers accounted for over 60% of the TT cases. Random Forest was selected as the prediction model and named TT@Normal. The TT@Normal algorithm showed outstanding performance in the training, validation, and external validation sets and could efficiently identify TT carriers in the non-anemic population. The top three weights in the TT@Normal model were the target cells, microcytes, and teardrop cells. Elevated percentages of abnormal erythrocytes should raise a strong suspicion of being a TT gene carrier. TT@Normal could be promoted and used as a visualization and sharing tool. It is accessible through a URL link and can be used by medical staff online to predict the possibility of TT gene carriage in a non-anemic population. CONCLUSIONS: The ML-based model TT@Normal could efficiently identify TT carriers in non-anemic people. Elevated percentages of target cells, microcytes, and teardrop cells should raise a strong suspicion of being a TT gene carrier.

Effects of a competence-based approach for clerkship teaching under alternating clinical placements: An explanatory sequential mixed-methods research.

BACKGROUND: It is unclear whether alternating placements during clinical clerkship, without an explicit emphasis on clinical competencies, would bring about optimal educational outcomes. METHODS: This is an explanatory sequential mixed-methods research. We enrolled a convenience sample of 41 eight-year programme medical students in Sun Yat-sen University who received alternating placements during clerkship. The effects of competence-based approach (n = 21) versus traditional approach (n = 20) to clerkship teaching were compared. In the quantitative phase, course satisfaction was measured via an online survey and academic performance was determined through final scores on summative assessment. Then, in the qualitative phase, students were invited for semi-structured interviews about their learning experiences, and the transcripts were used for thematic analysis. RESULTS: Quantitative findings showed that students in the study group rated high course satisfaction and performed significantly better in their final scores compared with those in the control group. Qualitative findings from thematic analysis showed that students were relatively neutral about their preference on placement models, but clearly perceived, capitalised, and appreciated that their competencies were being cultivated by an instructor who was regarded as a positive role model. CONCLUSION: A competence-based approach to clerkship teaching resulted in better course satisfaction and academic performance, and was perceived, capitalised, and appreciated by students.

Artificial Intelligence-based online platform assists blood cell morphology learning: A mixed-methods sequential explanatory designed research.

BACKGROUND: The study aimed to evaluate the effectiveness of learning blood cell morphology by learning on our Artificial intelligence (AI)-based online platform. METHODS: Our study is based on mixed-methods sequential explanatory design and crossover design. Thirty-one third-year medical students were randomly divided into two groups. The two groups had platform learning and microscopy learning in diferent sequences with pretests and posttests, respectively. Students were interviewed, and the records were coded and analyzed by NVivo 12.0. RESULTS: For both groups, test scores increased significantly after online-platform learning. Feasibility was the most mentioned advantage of the platform. The AI system could inspire the students to compare the similarities and differences between cells and help them understand the cells better. Students had positive perspectives on the online-learning platform. CONCLUSION: The AI-based online platform could assist medical students in blood cell morphology learning. The AI system could function as a more knowledgeable other (MKO) and guide the students through their zone of proximal development (ZPD) to achieve mastery. It could be an effective and beneficial complement to microscopy learning. Students had very positive perspectives on the AI-based online learning platform. It should be integrated into the course and curriculum to facilitate the students.[Box: see text].

Immature platelet fraction related parameters in the differential diagnosis of thrombocytopenia.

The pathogenesis of thrombocytopenia can be divided into increased destruction (ID) of platelets in the peripheral blood and decreased production (DP) of platelets in the bone marrow. This study aimed to analyze the efficacy of immature platelet fraction (IPF) related parameters, including the IPF count (IPF#), IPF percentage (IPF%) and highly fluorescence IPF percentage (H-IPF%), measured by XN-9000, in the differential diagnosis of thrombocytopenia. One hundred and twenty healthy volunteers were enrolled in the healthy control (HC) group, and 180 thrombocytopenia patients were grouped into either the increased destruction (ID) group or the decreased production (DP) group according to their final diagnosis. IPF# was significantly lower in the DP group than in the ID and HC groups (P < .01). Among the three groups, the ID group had the highest IPF% and H-IPF%, and the HC group had the lowest IPF% and H-IPF%. The differences between the three groups were all statistically significant (P < .01). In differentiating the ID patients from the DP patients, the areas under the operating characteristics curve of IPF#, IPF% and H-IPF% were 0.859, 0.944 and 0.930, respectively. False positive rates were below 0.04 when IPF#, IPF% and H-IPF% were above 2.65, 7.55 and 2.35, respectively. IPF related parameters showed high efficacy in the differential diagnosis of thrombocytopenia. However, due to the small numerical values of the IPF related parameters in some thrombocytopenia patients, the fluctuations of IPF% and H-IPF% should also be taken into consideration. Though H-IPF% is a new parameter, its effectiveness in the differential diagnosis of thrombocytopenia is not better than IPF%'s.

Roles of α-1,3-glucosyltransferase in growth and polysaccharides biosynthesis of Ganoderma lucidum.

Ganoderma lucidum polysaccharides are valuable natural compounds possessing significant biological activity, with glycosyltransferases playing a crucial role in their biosynthesis. Although the function of ß-1,3-glucosyltransferase in polysaccharides production is well understood, the role of α-1,3-glucosyltransferase in edible fungi remains unclear. In this study, over-expression of the α-1,3-glucosyltransferase gene in G. lucidum (glagt) was found to suppress the growth, with the maximum biomass and mycelial growth rate decreasing by 21.78 % and 79.61 %, respectively, a behavior distinct from ß-1,3-glucosyltransferase. The fungal pellet diameter decreased by 38 % and the cell-wall thickness by 32.44 %, whereas intracellular and extracellular polysaccharides production increased by 27.58 % and 66.08 %, respectively. In the transcription level, overexpressing the glagt gene i) downregulated the citrate synthase and isocitrate dehydrogenase gene in the TCA cycle, disrupting energy metabolism and fungal growth; ii) upregulated key enzymes involved in UDP-glucose synthesis and glycosyltransferases (gl24465, gl24971, and gl22535); and iii) universally increased the transcriptional level of glucosidases gl21451, gl30087, and gl24581 by 22 %-397 %, contributing to cell-wall thinning to facilitate polysaccharides export. Conversely, the glagt gene downregulation promoted G. lucidum growth and decreased polysaccharides production. The results elucidate the roles of GLAGT and are expected to inspire in-depth exploration of polysaccharides biosynthesis pathways.

TT@MHA: A machine learning-based webpage tool for discriminating thalassemia trait from microcytic hypochromic anemia patients.

BACKGROUND: Iron deficiency anemia (IDA) and thalassemia trait (TT) are the most common causes of microcytic hypochromic anemia (MHA) and are endemic in lower resource settings and rural areas with poor medical infrastructure. Accurate discrimination between IDA and TT is an essential issue for MHA patients. Although various discriminant formulas have been reported, distinguishing between IDA and TT is still a challenging problem due to the diversity of anemic populations. METHODS: We retrospectively collected laboratory data from 798 MHA patients. High proportions of α-TT (43.33 %) and TT concomitant with IDA (TT&IDA) patients (14.04 %) were found among TT patients. Five machine learning (ML) approaches, including Liner SVC (L-SVC), support vector machine learning (SVM), Extreme gradient boosting (XGB), Logistic Regression (LR), and Random Forest (RF), were applied to develop a discriminant model. Performance was assessed and compared with six existing discriminant formulas. RESULTS: The RF model was chosen as the discriminant algorithm, namely TT@MHA. TT@MHA was tested in an interlaboratory cohort with a sensitivity, specificity, accuracy, and AUC of 91.91 %, 91.00 %, 91.53 %, and 0.942, respectively. A webpage tool of TT@MHA (https://dxonline.deepwise.com/prediction/index.html?baseUrl=%2Fapi%2F&id=26408&topicName=undefined&from=share&platformType=wisdom) was developed to facilitate the healthcare providers in rural areas. CONCLUSION: The ML-based TT@MHA algorithm, with high sensitivity and specificity, could help discriminate TT patients from MHA patients, especially in populations with high proportions of α-TT patients and TT&IDA patients. Moreover, a user-friendly webpage tool for TT@MHA could facilitate healthcare providers in rural areas where advanced technologies are not accessible.

Effects of different wheat bran fermentation sources on growth performance, nutrient digestibility, serum antioxidant capacity and fecal microbiota in growing pigs.

The present study aimed to evaluate the application of different wheat bran fermentation sources in growing pigs. A total of 320 pigs (43 ± 0.21 kg), were randomly allocated to 5 groups in a 21-d trial. The control group was fed a basal diet (CON) containing raw wheat bran, and the other four treatments were fed the diets in which the raw wheat bran in the basal diet was substituted with Aspergillus niger (WBA), Bacillus licheniformis (WBB), Candida utilis (WBC), and Lactobacillus plantarum (WBL) fermented wheat bran, respectively. The results showed that compared to the CON group, the crude fiber and pH values were decreased (p < 0.05), while the gross energy (GE), crude protein (CP), and lactic acid values were increased (p < 0.05) in all the wheat bran fermented by different strains. Compared with other treatments, feeding B. licheniformis fermented wheat bran had higher final weight, average daily gain, as well as lower feed-to-gain ratio. Compared with CON group, pigs fed with fermented wheat bran diets had higher dry matter, CP, and GE availability, serum total protein, albumin and superoxide dismutase levels, and fecal Lactobacillus counts, as well as lower malondialdehyde level and fecal Escherichia coli count. Collectively, our findings suggested that feeding fermented wheat bran, especially B. licheniformis fermented wheat bran, showed beneficial effects on the growth performance, nutrient digestibility, serum antioxidant capacity, and the gut microbiota structure of growing pigs.

Effects of dietary supplementation with microencapsulated Galla chinensis tannins on growth performance, antioxidant capacity, and lipid metabolism of young broiler chickens.

This study aimed to investigate the impacts of dietary supplementation with Galla chinensis tannins (GCT) on the growth performance, antioxidant capacity, and lipid metabolism of young broilers. Overall, a total of 216 healthy 1 day-old broilers were randomly allocated to CON group and GCT group, and provided with a basal diet or a basal diet added with 300 mg/kg microencapsulated GCT, respectively, in a 21 days trial. Our findings indicated that dietary GCT addition had no significant effects (p > 0.05) on growth performance. However, GCT supplementation led to a significant reduction in the total cholesterol (TC) concentration in the serum and liver (p < 0.05). Furthermore, GCT supplementation significantly increased the ratios of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and HDL to TC in the serum, in addition to elevating the activities of enzymes related to lipid metabolism in the liver (p < 0.05). Dietary GCT addition also improved the antioxidant capacity of the broilers, as evidenced by a significant decrease in the concentration of malondialdehyde in serum and liver (p < 0.05). Additionally, the GCT group exhibited significantly increased expressions of hepatic genes associated with antioxidant enzymes (HO-1, GPX1, SOD2, SIRT1, CPT-1, and PPARα) (p < 0.05), while the mRNA expression of SREBP-1 was significantly decreased (p < 0.05) compared with the CON group. In conclusion, dietary addition of 300 mg/kg microencapsulated GCT improved the antioxidant status and lipid metabolism of broilers without affecting their growth performance.

Case Report: CD19 and CD20 monoclonal antibodies with sequential chemotherapy for refractory acute B-lymphocytic leukemia in children.

Objective: This paper observes the efficacy of chemotherapy combined with CD19 and CD20 monoclonal antibodies in clearing minimal residual disease (MRD) and bridging transplantation for refractory acute B-lymphoblastic leukemia (B-ALL) in children and reviews the literature. Methods: A 4-year-old boy diagnosed with B-ALL in our hospital was treated with the SCCLG-ALL-2016 protocol. MRD and gene quantification decreased after induction but remained persistently positive, with poor efficacy. After this patient received three cycles of consolidation chemotherapy combined with blinatumomab and rituximab, MRD and fusion gene quantification became negative, and he received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Results: During the use of monoclonal antibodies, neurotoxicity, CRS, or other side effects did not occur. Before transplantation, MRD became negative, and the bone marrow had been in complete remission since transplantation (13 months). Conclusion: Chemotherapy combined with blinatumomab for refractory B-ALL in children can bring a better remission rate for patients and is a means of bridging transplantation. Nevertheless, sequential CD20 monoclonal antibody therapy is the first report , and no adverse effects were observed in our case. It is well tolerated and can be used as one of the treatments for refractory B-ALL.

The Diagnostic Efficacy of Age-Adjusted D-Dimer Cutoff Value and Pretest Probability Scores for Deep Venous Thrombosis.

This study seeks to evaluate the diagnostic value of D-Dimer Plus and Innovance D-Dimer as well as the age-adjusted cutoff value for D-dimer detection in combination with 4 pretest probability (PTP) scores for deep venous thrombosis (DVT). A total of 688 patients referred for lower extremity vascular compression venous ultrasonography for suspected DVT from January 2016 to May 2018 in the First Affiliated Hospital of Sun Yat-sen University underwent D-dimer tests combining with 4 PTP scores. The diagnostic efficacy of the Wells score was the highest of the 4 PTP scores. The diagnostic efficacy of Innovance D-Dimer for DVT was greater than that of D-Dimer Plus, with better sensitivity and negative predictive value, which were both greater than 98%. If the cutoff values were adjusted by age, the Innovation D-Dimer could further improve both the specificity and the positive predictive value, providing better diagnostic performance. When the 2 D-dimer detections were used in combination with 4 PTP scores for DVT diagnosis, separately, both the positive predictive value and the negative predictive value significantly improved for D-Dimer Plus, and the positive predictive values significantly improved for Innovance D-Dimer. However, the sensitivity, specificity, and negative predictive values did not obviously change. For our patients, Wells score had the best diagnostic efficacy for our patients with suspected DVT among the 4 PTP scores. Innovance D-Dimer in combination with age-adjusted cutoff values exhibited increased sensitivity and negative predictive value for DVT diagnosis and was equivalent to the diagnostic efficacy of the Innovance D-Dimer in combination with PTP scores.

Effect of ultrasound pretreatment on enzymolysis and physicochemical properties of corn starch.

In the paper, the effects of ultrasound on the enzymolysis properties of corn starch were investigated. The results showed that the rate of enzymolysis changed with the change of ultrasonic conditions. Ultrasound pretreatment starches reduced the time in liquefaction process, and resulted in significantly higher DE value in saccharification process. DE value was negatively correlated to PV, BV, SV, To, Tp, ΔHg, DO, DD, N-O'KI, RC, Mw and DP, respectively, and positively correlated to Mw/Mn. X-ray diffraction analysis showed that the relative crystallinity was reduced, and the starch exhibited an A-pattern. Scanning electron microscope indicated that the notch and groove appeared on the surfaces of starch granules. The polarized cross of starch becomes smaller or even disappear. It was concluded that enzymolysis efficiency of different ultrasound pretreatment to changes due to its effect not only on the physicochemical properties, but also on the structural characteristics of corn starch.

T-cell lymphoma with rhabdomyolysis: case report and literature review.

Rhabdomyolysis refers to the destruction or disintegration of striated muscles. This syndrome is characterized by muscle breakdown and necrosis, resulting in the leakage of intracellular muscle constituents into the circulation and extracellular fluid. We report a rare case of rhabdomyolysis complicating multi-organ failure caused by T-cell lymphoma in a 32-year-old woman. The final diagnosis was rhabdomyolysis caused by peripheral T-cell lymphoma based on bone marrow aspirate and biopsy.

Characteristics of bone marrow cell dysplasia and its effectiveness in diagnosing myelodysplastic syndrome.

BACKGROUND: Although dysplasia plays an important role in the diagnosis of myelodysplasia syndrome (MDS), its morphologic variety and irregularity result in difficulties in its clinical application. METHODS: Bone marrow smears from cases with MDS and non-clonal disease were collected and performed microscopy analysis. We respectively recorded the percentage of specific dysplastic cells (PSDC) and incidence of specific dysplasia (ISD) of each dysplastic type in three hematopoietic cell lineages for the comprehensive analysis of diagnostic efficacy to MDS. RESULTS: Compared with non-clonal anemia, the PSDCs and ISDs of the four specific dysplastic types as petal nucleus and internuclear bridging in erythroid lineage, pseudo-Pelger-Huet in granulocytic lineage and lymphoid small megakaryocyte in megakaryocytic lineage were significantly higher in MDS; and their area under the curves were all greater than 0.600. If the dysplastic rate in each lineage was higher than 10%, their corresponding false positive rates (FPRs) were below 0.033, 1 × 10-4 and 1 × 10-4, respectively. If the dysplastic rates in three cell lineages reached 0.065, 0.045 and 0.040, respectively, their corresponding FPRs were all below 0.050. CONCLUSION: Four specific dysplastic types possess higher diagnostic efficacy for the diagnosis of MDS. Though the dysplastic rate over 10% in any hematopoietic cell lineage presents a lower FPR, it is possibly considered to lower the diagnostic threshold of MDS if a specific dysplastic type with higher diagnostic efficacy presents.

Secondary lymphoblastic leukemia occurring 38 months after the primary diagnosis of multiple myeloma: A case report.

Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by the accumulation of plasma cells in the bone marrow, the subsequent destruction of bone and organ dysfunction. The present study describes the case of a 66-year-old male patient who presented with the typical clinical manifestations of MM. The patient was administered a bortezomib and dexamethasone regimen for 2 cycles and achieved complete remission. Lenalidomide, vincristine, pirarubicin, dexamethasone, melphalan and thalidomide was used successively in consolidation therapy and maintenance therapy. The patient developed secondary B-cell lymphoblastic leukemia 38 months after the primary MM diagnosis was made. Owing to the exposure of the patient to a variety of therapeutic agents, it could be inferred that multiple immune defects may have played an important role in the secondary lymphoblastic leukemia of the patient. Microscopic examination and flow cytometry detection were important in identifying the secondary malignancy in this MM case.

T-cell lymphoma with rhabdomyolysis: case report and literature review

Rhabdomyolysis refers to the destruction or disintegration of striated muscles. This syndrome is characterized by muscle breakdown and necrosis, resulting in the leakage of intracellular muscle constituents into the circulation and extracellular fluid. We report a rare case of rhabdomyolysis complicating multi-organ failure caused by T-cell lymphoma in a 32-year-old woman. The final diagnosis was rhabdomyolysis caused by peripheral T-cell lymphoma based on bone marrow aspirate and biopsy.

Nuclear HSP90 regulates the glucocorticoid responsiveness of PBMCs in patients with idiopathic nephrotic syndrome.

Resistance to glucocorticoid (GC) is a challenge for the treatment of patients with idiopathic nephrotic syndrome (INS). Most of the effects of GC are mediated by the GC receptor (GR). Heat shock protein 90 (HSP90) is an important molecular chaperone for the GR and is supposed to be the key factor in regulating GC effects. In a previous study, we found that both the expression and nuclear distribution of HSP90 were increased in GC resistant INS patients. The aim of this study is to explore how these phenomena contribute to GC resistance in INS patients. Healthy subjects and INS patients with different GC responses were recruited. The total HSP90 expression was determined by reverse transcription-PCR and flow cytometric analysis. Western blot analysis was used to evaluate the expression of nuclear HSP90. Co-immunoprecipitation and electrophoretic mobility gel shift assays were performed to explore the interaction between HSP90 and the GR in the nucleus as well as the DNA-binding activity of GR. We induced the upregulation of the expression of total HSP90 in PBMCs by treatment with interleukin-6 in vitro and found that the nuclear HSP90 level, the DNA-binding activity of the GR and the cell apoptotic responsiveness to GC remained unchanged. Furthermore, an increased nuclear HSP90 was demonstrated mainly by binding to GR in the nucleus, while the DNA-binding activity of the GR dramatically decreased in GC resistant INS patients. The present results suggest that the accumulation of HSP90 in the nucleus potentially hinders DNA-binding activity and transactivation, which may contribute to GC resistance in patients with INS.

[Immunophenotypic analysis of leukemia promyelocytes in 71 patients with acute promyelocytic leukemia].

This study was purpose to investigate the immunophenotype of leukemia promyelocytes (LP) and its significance through retrospective analysis of LP immunophenotype and data in new diagnosis of patients with acute promyelocytic leukemia (APL). The immunophenotype of leukemia cells in 71 APL patients was analyzed by means of 6 color immunotyping. The results indicated that MPO, CD33 and CD13 were consistently expressed in leukemia cells of all APL cases with highest average percentages (> 88%) of positive cells among all studied markers. CD117 was found to be positive in 50.7%, and its average percentage of positive cells was 52.5%. Leukemia cells in about 10% cases expressed CD15 weakly, and its average percentage of positive cells was 42.5%. CD34 and HLA-DR showed decreased expressions in a small number of cases and were negative in the others. CD2 and CD56 were weakly expressed in nearly 25% APL cases, and the average percentage of positive cells were 39.3% and 42.3%, respectively. Thereby, it is of the opinion that the typical immunophenotype is characterized by MPO(+)CD13(+)CD33(+)CD117(±)CD15(±)CD34(-)HLA-DR(-) in APL. CD2 and CD56 were expressed significantly higher in CD34(+) or HLA-DR(+) group (including CD34(+) HLA-DR(+), CD34(+) HLA-DR(-) and CD34(-)HLA-DR(+)) than in CD34(-) and HLA-DR(-) group. Significant differences were also found in WBC and platelet counts, percentage of peripheral blood leukemic promyelocytes and the expression of CD13 among CD15 < 10%, 10% < CD15 < 20% and CD15 > 20% groups. It is concluded that the APL has a characteristic immunophenotypic profile, flow cytometric immunophenotyping may be considered as a useful tool for rapid recognition of APL and also may be considered to have an important significance for analysing origin of leukemic cells and clinical outcome of patients.