Psoas muscle area is an independent survival prognosticator in patients undergoing surgery for long-bone metastases.

BACKGROUND: Predictive analytics is gaining popularity as an aid to treatment planning for patients with bone metastases, whose expected survival should be considered. Decreased psoas muscle area (PMA), a morphometric indicator of suboptimal nutritional status, has been associated with mortality in various cancers, but never been integrated into current survival prediction algorithms (SPA) for patients with skeletal metastases. This study investigates whether decreased PMA predicts worse survival in patients with extremity metastases and whether incorporating PMA into three modern SPAs (PATHFx, SORG-NG, and SORG-MLA) improves their performance. METHODS: One hundred eighty-five patients surgically treated for long-bone metastases between 2014 and 2019 were divided into three PMA tertiles (small, medium, and large) based on their psoas size on CT. Kaplan-Meier, multivariable regression, and Cox proportional hazards analyses were employed to compare survival between tertiles and examine factors associated with mortality. Logistic regression analysis was used to assess whether incorporating adjusted PMA values enhanced the three SPAs' discriminatory abilities. The clinical utility of incorporating PMA into these SPAs was evaluated by decision curve analysis (DCA). RESULTS: Patients with small PMA had worse 90-day and 1-year survival after surgery (log-rank test p < 0.001). Patients in the large PMA group had a higher chance of surviving 90 days (odds ratio, OR, 3.72, p = 0.02) and 1 year than those in the small PMA group (OR 3.28, p = 0.004). All three SPAs had increased AUC after incorporation of adjusted PMA. DCA indicated increased net benefits at threshold probabilities >0.5 after the addition of adjusted PMA to these SPAs. CONCLUSIONS: Decreased PMA on CT is associated with worse survival in surgically treated patients with extremity metastases, even after controlling for three contemporary SPAs. Physicians should consider the additional prognostic value of PMA on survival in patients undergoing consideration for operative management due to extremity metastases.

Studying Cellular Focal Adhesion Parameters with Imaging and MATLAB Analysis.

Cell signaling is highly integrated for the process of various cell activities. Although previous studies have shown how individual genes contribute to cell migration, it remains unclear how the integration of these signaling pathways is involved in the modulation of cell migration. In our two-hit migration screen, we revealed that serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) worked synergistically, and the suppression of both genes could further lead to suppression in cell migration. Furthermore, based on our analysis of cellular focal adhesion (FA) parameters using MATLAB analysis, we are able to find out the synergistic reduction of STK40 and MAPK that further abolished the increased FA by shSTK40. While FA identification in previous studies includes image analysis using manual selection, our protocol provides a semi-automatic manual selection of FAs using MATLAB. Here, we provide a method that can shorten the amount of time required for manual identification of FAs and increase the precision for discerning individual FAs for various analyses, such as FA numbers, area, and mean signals.

Determining patients with spinal metastases suitable for surgical intervention: A cost-effective analysis.

BACKGROUND: Both nonoperative and operative treatments for spinal metastasis are expensive interventions. Patients' expected 3-month survival is believed to be a key factor to determine the most suitable treatment. However, to the best of our knowledge, no previous study lends support to the hypothesis. We sought to determine the cost-effectiveness of operative and nonoperative interventions, stratified by patients' predicted probability of 3-month survival. METHODS: A Markov model with four defined health states was used to estimate the quality-adjusted life years (QALYs) and costs for operative intervention with postoperative radiotherapy and radiotherapy alone (palliative low-dose external beam radiotherapy) of spine metastases. Transition probabilities for the model, including the risks of mortality and functional deterioration, were obtained from secondary and our institutional data. Willingness to pay thresholds were prespecified at $100,000 and $150,000. The analyses were censored after 5-year simulation from a health system perspective and discounted outcomes at 3% per year. Sensitivity analyses were conducted to test the robustness of the study design. RESULTS: The incremental cost-effectiveness ratios were $140,907 per QALY for patients with a 3-month survival probability >50%, $3,178,510 per QALY for patients with a 3-month survival probability <50%, and $168,385 per QALY for patients with independent ambulatory and 3-month survival probability >50%. CONCLUSIONS: This study emphasizes the need to choose patients carefully and estimate preoperative survival for those with spinal metastases. In addition to reaffirming previous research regarding the influence of ambulatory status on cost-effectiveness, our study goes a step further by highlighting that operative intervention with postoperative radiotherapy could be more cost-effective than radiotherapy alone for patients with a better survival outlook. Accurate survival prediction tools and larger future studies could offer more detailed insights for clinical decisions.

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth.

Cyclic anthraquinone derivatives (cAQs), which link two side chains of 1,5-disubstituted anthraquinone as a threading DNA intercalator, have been developed as G-quartet (G4) DNA-specific ligands. Among the cAQs, cAQ-mBen linked through the 1,3-position of benzene had the strongest affinity for G4 recognition and stabilization in vitro and was confirmed to bind to the G4 structure in vivo, selectively inhibiting cancer cell proliferation in correlation with telomerase expression levels and triggering cell apoptosis. RNA-sequencing analysis further indicated that differentially expressed genes regulated by cAQ-mBen were profiled with more potential quadruplex-forming sequences. In the treatment of the tumor-bearing mouse model, cAQ-mBen could effectively reduce tumor tissue and had less adverse effects on healthy tissue. These results suggest that cAQ-mBen can be a potential cancer therapeutic agent as a G4 binder.

Comparison of eight modern preoperative scoring systems for survival prediction in patients with extremity metastasis.

BACKGROUND: Survival is an important factor to consider when clinicians make treatment decisions for patients with skeletal metastasis. Several preoperative scoring systems (PSSs) have been developed to aid in survival prediction. Although we previously validated the Skeletal Oncology Research Group Machine-learning Algorithm (SORG-MLA) in Taiwanese patients of Han Chinese descent, the performance of other existing PSSs remains largely unknown outside their respective development cohorts. We aim to determine which PSS performs best in this unique population and provide a direct comparison between these models. METHODS: We retrospectively included 356 patients undergoing surgical treatment for extremity metastasis at a tertiary center in Taiwan to validate and compare eight PSSs. Discrimination (c-index), decision curve (DCA), calibration (ratio of observed:expected survivors), and overall performance (Brier score) analyses were conducted to evaluate these models' performance in our cohort. RESULTS: The discriminatory ability of all PSSs declined in our Taiwanese cohort compared with their Western validations. SORG-MLA is the only PSS that still demonstrated excellent discrimination (c-indexes>0.8) in our patients. SORG-MLA also brought the most net benefit across a wide range of risk probabilities on DCA with its 3-month and 12-month survival predictions. CONCLUSIONS: Clinicians should consider potential ethnogeographic variations of a PSS's performance when applying it onto their specific patient populations. Further international validation studies are needed to ensure that existing PSSs are generalizable and can be integrated into the shared treatment decision-making process. As cancer treatment keeps advancing, researchers developing a new prediction model or refining an existing one could potentially improve their algorithm's performance by using data gathered from more recent patients that are reflective of the current state of cancer care.

Heterogenous adsorption mechanisms for describing enantioselective retention in normal-phase liquid chromatography.

In this study, the enantioselective retention behaviors of methyl mandelate (MM) and benzoin (B) were investigated using Chiralpak IB as a sorbent and ethanol, 1-propanol, and 1-butanol as solvent modifiers in the normal-phase mode. For both MM and B, similar chiral recognition mechanisms were observed, potentially involving at least two types of chiral adsorption sites. With a retention model describing local retention behaviors, an enantioselectivity model based on a three-site model was proposed to describe the data. Fitted parameters were also used to analyze the contributions of each type of adsorption site to the apparent retention behavior. Combining the local retention model with the three-site model provided a qualitative and quantitative explanation for the correlation between modifier concentration and enantioselectivity. Overall, our results indicated that heterogeneous adsorption mechanisms are a key aspect in understanding enantioselective retention behaviors. Distinct local adsorption sites contribute differently to apparent retention behaviors, with these contributions being influenced by the mobile phase composition to varying degrees. Hence, enantioselectivity changes with variations in modifier concentration.

Anti-microRNA-1976 as a Novel Approach to Enhance Chemosensitivity in XAF1+ Pancreatic and Liver Cancer.

The current cancer treatments using chemoagents are not satisfactory in terms of outcomes and prognosis. Chemoagent treatments result in cell death or arrest, but the accompanying cellular responses are not well-studied. Exosomes, which are extracellular vesicles secreted by living cells, might mediate cellular responses through microRNAs. We found that miR-1976 was highly enriched in exosomes secreted after chemoagent treatment. We developed a novel approach for in situ mRNA target screening and discovered several miR-1976-specific mRNA targets, including the proapoptotic gene XAF1, which was targeted by miR-1976 and which suppressed chemoagent-induced cell apoptosis. Increased RPS6KA1 gene transcription was associated with the increase in its intronic pre-miR-1976 expression. Blockade of miR-1976 could enhance chemosensitivities of hepatoma and pancreatic cancer cells in an XAF1-dependent manner, as evidenced by increased levels of cell apoptosis, reduced IC50 in cell toxicity assays, and suppressed tumor growth in animal xenograft experiments in vivo. We propose that intracellular levels of miR-1976 determine chemosensitivity, and its blockade could be a novel strategy and potential therapeutic application in cancer treatment.

Regulatory considerations for generic products of non-biological complex drugs.

The Non-Biological Complex Drug (NBCD) Working Group defines an NBCD as "a medicinal product, not being a biological medicine, where the active substance is not a homo-molecular structure, but consists of different (closely related and often nanoparticulate) structures that cannot be isolated and fully quantitated, characterized and/or described by physicochemical analytical means". There are concerns about the potential clinical differences between the follow-on versions and the originator products and within the individual follow-on versions. In the present study, we compare the regulatory requirements for developing generic products of NBCDs in the European Union (EU) and the United States (US). The NBCDs investigated included nanoparticle albumin-bound paclitaxel (nab-paclitaxel) injections, liposomal injections, glatiramer acetate injections, iron carbohydrate complexes, and sevelamer oral dosage forms. The demonstration of pharmaceutical comparability between the generic products and the reference products through comprehensive characterization is emphasized for all product categories investigated. However, the approval pathways and detailed requirements in terms of non-clinical and clinical aspects may differ. The general guidelines in combination with product-specific guidelines are considered effective in conveying regulatory considerations. While regulatory uncertainties still prevail, it is anticipated that through the pilot program established by the European Medicines Agency (EMA) and the FDA, harmonization of the regulatory requirements will be achieved, thereby facilitating the development of follow-on versions of NBCDs.

High-Performance P- and N-Type SiGe/Si Strained Super-Lattice FinFET and CMOS Inverter: Comparison of Si and SiGe FinFET.

This research presents the optimization and proposal of P- and N-type 3-stacked Si0.8Ge0.2/Si strained super-lattice FinFETs (SL FinFET) using Low-Pressure Chemical Vapor Deposition (LPCVD) epitaxy. Three device structures, Si FinFET, Si0.8Ge0.2 FinFET, and Si0.8Ge0.2/Si SL FinFET, were comprehensively compared with HfO2 = 4 nm/TiN = 80 nm. The strained effect was analyzed using Raman spectrum and X-ray diffraction reciprocal space mapping (RSM). The results show that Si0.8Ge0.2/Si SL FinFET exhibited the lowest average subthreshold slope (SSavg) of 88 mV/dec, the highest maximum transconductance (Gm, max) of 375.2 µS/µm, and the highest ON-OFF current ratio (ION/IOFF), approximately 106 at VOV = 0.5 V due to the strained effect. Furthermore, with the super-lattice FinFETs as complementary metal-oxide-semiconductor (CMOS) inverters, a maximum gain of 91 v/v was achieved by varying the supply voltage from 0.6 V to 1.2 V. The simulation of a Si0.8Ge0.2/Si super-lattice FinFET with the state of the art was also investigated. The proposed Si0.8Ge0.2/Si strained SL FinFET is fully compatible with the CMOS technology platform, showing promising flexibility for extending CMOS scaling.

Minor hepatectomy for hepatocellular carcinoma in a patient with portal hypertension: A case report and review of the literature.

INTRODUCTION: Curative modalities for early hepatocellular carcinoma (HCC) include liver resection (LR) and transplantation. For patients with portal hypertension (PH), liver transplantation (LT) is the preferred treatment but is oftentimes limited by organ shortage and can lead candidates to drop off due to disease progression, while hepatectomy has a higher risk of complications. This would pose a dilemma as to whether wait for donor organs or prioritize hepatectomy. PATIENT CONCERNS: The patient was a 56-year-old male, a case of liver cirrhosis due to hepatitis C with sustained virological response following direct-acting antiviral agents. He was a liver transplant candidate, presented to the gastroenterology outpatient department for a recently-diagnosed liver tumor during a regular follow-up session. Pre-operative survey revealed PH manifested by thrombocytopenia, splenomegaly, huge splenorenal shunt and varices. The patient's Child-Pugh score was 7. INTERVENTIONS AND DIAGNOSIS: Considering the patient's overall condition, tumor size and location, and a shortage of grafts, he underwent segment 5 and 6 partial hepatectomy. The pathological diagnosis was moderately differentiated HCC. OUTCOMES: His postoperative course was complicated by refractory intraabdominal infection (IAI) and recovered under aggressive antibiotics treatment. He remained recurrence-free for over a year. CONCLUSION: For patients with early resectable HCC, the approach of having a minor hepatectomy followed by salvage transplantation should serve as a compromising strategy. Tumor resection retards the progression of the disease. Comprehensive healthcare can expectantly improve clinical outcomes.

Structural Change from Nonparallel to Parallel G-Quadruplex Structures in Live Cancer Cells Detected in the Lysosomes Using Fluorescence Lifetime Imaging Microscopy.

Time-gated fluorescence lifetime imaging microscopy with the o-BMVC fluorescent probe provides a visualizing method for the study of exogenous G-quadruplexes (G4s) in live cancer cells. Previously, imaging results showed that the parallel G4s are accumulated and that nonparallel G4s are not detected in the lysosomes of CL1-0 live cells. In this work, the detection of the G4 signals from exogenous GTERT-d(FN) G4s in the lysosomes may involve a structural change in live cells from intramolecular nonparallel G4s to intermolecular parallel G4s. Moreover, the detection of the G4 signals in the lysosomes after the 48 h incubation of HT23 G4s with CL1-0 live cells indicates the occurrence of structural conversion from the nonparallel G4s to the parallel G4s of HT23 in the live cells. In addition, the detection of much stronger G4 signals from ss-GTERT-d(FN) than ss-HT23 in the lysosomes of CL1-0 live cells may be explained by the quick formation of the intermolecular parallel G4s of ss-GTERT-d(FN) and the degradation of ss-HT23 before its intramolecular parallel G4 formation. This work provides a new approach to studying G4-lysosome interactions in live cells.

Can a Bayesian belief network for survival prediction in patients with extremity metastases (PATHFx) be externally validated in an Asian cohort of 356 surgically treated patients?

BACKGROUND AND PURPOSE: Predicted survival may influence the treatment decision for patients with skeletal extremity metastasis, and PATHFx was designed to predict the likelihood of a patient dying in the next 24 months. However, the performance of prediction models could have ethnogeographical variations. We asked if PATHFx generalized well to our Taiwanese cohort consisting of 356 surgically treated patients with extremity metastasis. PATIENTS AND METHODS: We included 356 patients who underwent surgery for skeletal extremity metastasis in a tertiary center in Taiwan between 2014 and 2019 to validate PATHFx's survival predictions at 6 different time points. Model performance was assessed by concordance index (c-index), calibration analysis, decision curve analysis (DCA), Brier score, and model consistency (MC). RESULTS: The c-indexes for the 1-, 3-, 6-, 12-, 18-, and 24-month survival estimations were 0.71, 0.66, 0.65, 0.69, 0.68, and 0.67, respectively. The calibration analysis demonstrated positive calibration intercepts for survival predictions at all 6 timepoints, indicating PATHFx tended to underestimate the actual survival. The Brier scores for the 6 models were all less than their respective null model's. DCA demonstrated that only the 6-, 12-, 18-, and 24-month predictions appeared useful for clinical decision-making across a wide range of threshold probabilities. The MC was < 0.9 when the 6- and 12-month models were compared with the 12-month and 18-month models, respectively. INTERPRETATION: In this Asian cohort, PATHFx's performance was not as encouraging as those of prior validation studies. Clinicians should be cognizant of the potential decline in validity of any tools designed using data outside their particular patient population. Developers of survival prediction tools such as PATHFx might refine their algorithms using data from diverse, contemporary patients that is more reflective of the world's population.

The Impact of a Gross Anatomy Curriculum With Donor Family Interaction: Thematic Analysis of Student Letters to Silent Mentors.

PURPOSE: Tzu Chi University's anatomy curriculum incorporates interaction with donors' families and regards body donors as silent teachers and altruistic role models. In this silent mentor program (SMP), students learn about their donor's life before dissection to better appreciate the selfless donation. This study explores the influence of the program on students' humanistic literacy based on student letters to silent mentors, which students wrote near the end of the program and laid by the silent mentor during the coffining ceremony. METHOD: The study included 125 letters from third-year medical students who took the gross anatomy curriculum in academic years 2015, 2016, and 2017. With student consent, the program collated and published the letters in the open-access SMP yearbook. Using thematic analysis, the authors manually analyzed the letters in their original Mandarin, with the names of students made anonymous to ensure the authors were blind to students' identity throughout the study. RESULTS: The analysis identified 3 themes and 11 subthemes. Theme 1, my silent mentor, included 3 subthemes: life characteristics, altruistic attitude, and expectation of offering body. Theme 2, connection to silent mentor and family, included 4 subthemes: intersubjective bonding, emotive first encounter, spiritual communication, and encouragement from silent mentor. Theme 3, reflection and transformation, included 4 subthemes: reflection on life and death, professional self-expectation, inner transformation, and feedback action. CONCLUSIONS: The findings suggest that interactions with donors' families increased students' appreciation of the donation and enhanced students' humanistic literacy. Further, the letters seem to indicate that the SMP inspired students to develop a grateful, respectful, and empathic attitude toward life and their career. Thus, by implementing similar programs, gross anatomy curricula could go beyond the acquisition of structural knowledge to the cultivation of medical students' humanistic literacy.

International Validation of the SORG Machine-learning Algorithm for Predicting the Survival of Patients with Extremity Metastases Undergoing Surgical Treatment.

BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data. QUESTIONS/PURPOSES: (1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions? METHODS: All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% [116 of 356]) and breast cancer (16% [58 of 356]). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% [210 of 356]), followed by plate screw fixation (23% [81 of 356]) and endoprosthetic reconstruction (18% [65 of 356]). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index [c-index]), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study. RESULTS: The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 [95% CI 0.46 to 1.10], calibration slope 0.74 [95% CI 0.53 to 0.96]; 1-year survival prediction: calibration intercept 0.75 [95% CI 0.49 to 1.00], calibration slope 1.22 [95% CI 0.95 to 1.49]). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 [95% CI 1.01 to 3.73]) but not 1-year mortality (OR 1.07 [95% CI 0.53 to 2.17]) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively. CONCLUSION: SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE: Level III, therapeutic study.

Pilot imaging study of o-BMVC foci for discrimination of indeterminate cytology in diagnosing fine-needle aspiration of thyroid nodules.

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o-BMVC test of FNA smears is the measurement of the digital number of o-BMVC foci in the nucleus. Thus, there are three categories classified in the o-BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o-BMVC foci, and malignant for more numbers of o-BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o-BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o-BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs.

Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration.

Integrating signals is essential for cell survival, leading to the concept of synthetic lethality. However, how signaling is integrated to control cell migration remains unclear. By conducting a "two-hit" screen, we revealed the synergistic reduction of cell migration when serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) were simultaneously suppressed. Single-cell analyses showed that STK40 knockdown reduced cell motility and coordination by strengthening focal adhesion (FA) complexes. Furthermore, STK40 knockdown reduced the stability of yes-associated protein (YAP) and subsequently decreased YAP transported into the nucleus, while MAPK inhibition further weakened YAP activities in the nucleus to disturb FA remodeling. Together, we unveiled an integrated STK40-YAP-MAPK system regulating cell migration and introduced "synthetic dysmobility" as a novel strategy to collaboratively control cell migration.

Adipose-Derived Mesenchymal Stem Cells From a Hypoxic Culture Improve Neuronal Differentiation and Nerve Repair.

Hypoxic expansion has been demonstrated to enhance in vitro neuronal differentiation of bone-marrow derived mesenchymal stem cells (BMSCs). Whether adipose-derived mesenchymal stem cells (ADSCs) increase their neuronal differentiation potential following hypoxic expansion has been examined in the study. Real-time quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining were employed to detect the expression of neuronal markers and compare the differentiation efficiency of hypoxic and normoxic ADSCs. A sciatic nerve injury animal model was used to analyze the gastrocnemius muscle weights as the outcomes of hypoxic and normoxic ADSC treatments, and sections of the regenerated nerve fibers taken from the conduits were analyzed by histological staining and immunohistochemical staining. Comparisons of the treatment effects of ADSCs and BMSCs following hypoxic expansion were also conducted in vitro and in vivo. Hypoxic expansion prior to the differentiation procedure promoted the expression of the neuronal markers in ADSC differentiated neuron-like cells. Moreover, the conduit connecting the sciatic nerve gap injected with hypoxic ADSCs showed the highest recovery rate of the gastrocnemius muscle weights in the animal model, suggesting a conceivable treatment for hypoxic ADSCs. The percentages of the regenerated myelinated fibers from the hypoxic ADSCs detected by toluidine blue staining and myelin basic protein (MBP) immunostaining were higher than those of the normoxic ones. On the other hand, hypoxic expansion increased the neuronal differentiation potential of ADSCs compared with that of the hypoxic BMSCs in vitro. The outcomes of animals treated with hypoxic ADSCs and hypoxic BMSCs showed similar results, confirming that hypoxic expansion enhances the neuronal differentiation potential of ADSCs in vitro and improves in vivo therapeutic potential.

Survey of the triple-mentoring program for students at a religious medical school.

BACKGROUND: Tzu Chi University in Taiwan offers a unique mentoring program. This program differs from others as it comprises triple mentorship, namely, faculty mentors, Tzu Cheng/Yi De (TC/YD; senior volunteers), and school counselors. This study aimed to survey the role functions of the mentors from the perspective of medical students. METHODS: The Role Functions of the Mentoring Program Scale (RFMPS) was developed on the basis of literature reviews and focus groups and it underwent exploratory factor analysis for internal consistency and reliability. RFMPS comprises four role functions, namely, mental, educational, career, and humanistic/moral guidance counseling. The survey was distributed to 171 medical students via an online network with two-month intervals and was analyzed using multivariate analysis of variance. RESULTS: The overall response rate was 64% (116/171). The mean scores of the four role functions in descending order belonged to faculty mentors, TC/YD, and school counselors. For humanistic/moral guidance, students had an equal preference for the faculty mentors and TC/YD over school counselors. As for educational, career, and mental guidance counseling, students preferred faculty mentors over TC/YD and school counselors. Faculty mentors provided students with the required guidance counseling for all the four role functions, especially educational guidance; TC/YD in particular offered prominent humanistic/moral guidance and career counseling; school counselors were less preferred but guided students in need. CONCLUSIONS: Medical students value different role functions provided by faculty mentors, TC/YD, and school counselors. A diversified focus could be provided by the faculty mentors, particularly in educational, career, mental, and humanistic/moral counseling; TC/YD specialized in humanistic/moral guidance; and the school counselors carried out their role function only when needed. Humanistic/moral guidance is equally preferred to other types of guidance, which can be equally valuable in future mentoring programs.

Utilization of a Gas-Sensing System to Discriminate Smell and to Monitor Fermentation during the Manufacture of Oolong Tea Leaves.

The operational duration of shaking tea leaves is a critical factor in the manufacture of oolong tea; this duration influences the formation of its flavor and fragrance. The current method to control the duration of fermentation relies on the olfactory sense of tea masters; they monitor the entire process through their olfactory sense, and their experience decides the duration of shaking and setting. Because of this human factor and olfactory fatigue, it is difficult to define an optimum duration of shaking and setting; an inappropriate duration of shaking and setting deteriorates the quality of the tea. In this study, we used metal-oxide-semiconductor gas sensors to establish an electronic nose (E-nose) system and tested its feasibility. This research was divided into two experiments: distinguishing samples at various stages and an on-line experiment. The samples of tea leaves at various stages exhibited large differences in the level of grassy smell. From the experience of practitioners and from previous research, the samples could be categorized into three groups: before the first shaking (BS1), before the shaking group, and after the shaking group. We input the experimental results into a linear discriminant analysis to decrease the dimensions and to classify the samples into various groups. The results show that the smell can also be categorized into three groups. After distinguishing the samples with large differences, we conducted an on-line experiment in a tea factory and tried to monitor the smell variation during the manufacturing process. The results from the E-nose were similar to those of the sense of practitioners, which means that an E-nose has the possibility to replace the sensory function of practitioners in the future.