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Previous work from our laboratory has demonstrated that the percentage differences of 2nd (C2) and 3rd (C3) pulse harmonics related to Kidney and Spleen were both increased toward another steady state in rats after acute hemorrhage. Therefore, it is suggested that changes in pulse spectra might represent the ability of animals to survive a model of progressive hemorrhage. In this study, the difference of the pulse spectra patterns between survivors and non-survivors after progressive hemorrhage (by loss of 5%, 10% or 20% of the estimated blood volume) in anesthetized rats is determined. Seven rats, dead within 2 hours after a loss of 20% of the estimated blood volume hemorrhage, were defined as 'non-survivors'. The other eleven rats, more than 2 hours after hemorrhage, were defined as 'survivors'. Pulse waves of arterial blood pressure before and after the hemorrhage were measured in parallel to the pulse spectrum analysis. Data among different phases were analyzed using one-way analysis of variance (ANOVA) with Duncan's test for pairwise comparisons. Differences between survivor and non-survivor groups at each phase were analyzed using Student's t-test. A mixed-effects linear regression model was applied to evaluate the relationship in harmonics, which significantly differed between the two groups. The study results showed that in rats, during progressive hemorrhage, the percentage differences of 2nd harmonic proportion increased significantly; however, the result failed to show any significant difference between survivors and non-survivors. After the third blood withdrawal process, the percentage differences of 3rd harmonic proportion increased more significantly in the survivors. In addition, the percentage differences of 1st harmonic proportion related to the Liver for the survivor group was significantly lower than that of the non-survivors. After analysis with the mixed linear regression model, C3 and C1 demonstrated a linear regression relationship, and there existed significant differences between survivors and non-survivors. These results suggest that C3 might play an important role in physiology regarding surviving capability after progressive hemorrhage.

We aimed to assess the effects of traditional Chinese medicine; marine (MT) and kuhuang (KH), either alone or in combination, on the early graft function of the recipients and overall patient survival rate after liver transplantation (LT) by using diammonium glycyrrhizinate (DG) as a positive control. A total of 151 subjects undergoing LT were included in this prospective study. According to the different regimens given in the first two post-transplant weeks, they were divided into DG group (n = 49), DG + KH group (n = 36), MT group (n = 42) and MT + KH group (n = 24). The graft function in the early post-transplant period and patient survival rate were examined. During the first two post-transplant weeks, there was no significant difference in total bilirubin, alanine transaminase, aspartate transaminase, serum creatinine, and prothrombin time between MT group and DG group. Patient survivals in these two groups were also similar. Compared to DG group, DG + KH group showed a significantly lower total bilirubin value on post-transplant day 5 (3.2 ± 2.1 mg/dL vs. 5.7 ± 5.6 mg/dL, p < 0.01) and day 7 (2.8 ± 1.8 mg/dL vs. 5.8 ± 6.1 mg/dL, p < 0.01), and higher patient survival. There was no significant difference between DG + KH group and MT + KH group. In conclusion, MT provides an alternative to DG after LT. The combination of MT and KH is highly effective in decreasing the total blirubin in the early post-transplant period and improving patient survival.

In this paper, we investigate a mathematical model of pancreatic cancer, which extends the existing pancreatic cancer models with regulatory T cells (Tregs) and Treg inhibitory therapy. The model consists of tumor-immune interaction and immune suppression from Tregs. In the absence of treatments, we first characterize the system dynamics by locating equilibrium points and determining stability properties. Next, cytokine induced killer (CIK) immunotherapy is incorporated. Numerical simulations of prognostic results illustrate that the median overall survival associated with treatment can be prolonged approximately from 7 to 13 months, which is consistent with the clinical data. Furthermore, we consider cyclophosphamide (CTX) therapy as well as the combined therapy with CIK and CTX. Intensive simulation results suggest that both CTX therapy and the combined CIK/CTX therapy can reduce the number of Tregs and increase the overall survival (OS), but Tregs and tumor cells will gradually rise to equilibrium state as long as therapies are ceased.

Maintenance management in wind energy industry has great impact on the overall wind power cost. Maintenance services are either supported by wind turbine manufacturers within warranty period, or managed by wind farm owners. With condition-based maintenance (CBM) strategy, maintenance activities are scheduled based on the predicted health conditions of wind turbine components, and accurate prognostics methods are critical for effective CBM. The reported studies on integrated health prognostics considered the uncertainty in crack initiation time (CIT) uncertainty, but did not incorporate time-varying loading conditions, which could also have a significant impact on future health condition and remaining useful life (RUL) prediction. Constant loads were generally used to approximate the actual time-varying loading conditions. In this paper, an integrated prognostics method is proposed for wind turbine gearboxes considering both time-varying loading conditions and CIT uncertainty. As new condition monitoring observations are available, the distributions of both material model parameter and CIT are updated via Bayesian inference, and the failure time prediction is updated accordingly. An example is provided to demonstrate that the proposed time-varying load approach presents more benefits considering the uncertainty of CIT, with significant accuracy improvement comparing to the constant-load approach.

Introduction: We have analyzed the clinical features and outcomes of malignant tumors of foot. Methods: Between January 2010 to January 2017, 21 patients of malignant tumors of calcaneum and talus were treated. These included 14 cases of osteosarcoma, 7 cases of Ewing’s sarcoma. Talus was involved in 8 cases and calcaneum involved in 11 cases. Mean follow-up for all patients was 30 months (range 24–70 months). Results: In osteosarcoma of calcaneum and talus the presenting symptom was local pain in 63% and swelling in 37%. Patients with Ewing’s sarcoma presented with swelling in 100% cases. The mean delay in diagnosis for osteosarcoma and Ewing’s sarcoma was 8.8 months (range 6–12 months) and 9.5 months (range 6–12 months), respectively. Patients with delay in diagnoses of more than six months and less than six months had disease free survival of 11.5 months and 15 months, respectively and $p$ value 0.3. Patients with delay in diagnoses of more than six months and less than six months had metastases in 5 and 1cases, respectively. The mean disease free interval (DFI) for osteosarcoma and Ewing’s sarcoma was 16 months and 5.5 months, respectively. The correlation between osteosarcoma and Ewing’s sarcoma of calcaneum and foot with delay in diagnosis and DFI did not reach statistical significance ($p$ value 0.93 and 0.14, respectively). Conclusion: An index of suspicion, proper examination with close scrutiny of the radiographs is required in patients presenting malignant of bones of foot. Osteosarcoma of calcaneum and talus most commonly presented with local pain and Ewing’s sarcoma present with swelling. The time interval between the onset of symptoms and diagnosis (delay in diagnosis) for calcaneum and talus osteosarcoma was similar to Ewing’s sarcoma.

Purpose of the Study: The aim is to report the natural history, type of treatment received and quality of life improvement of adolescent patients with isthmic low-grade lumbosacral spondylolisthesis with a slip of less than 25%.

Methods: The complete records of 299 prospective patients (127 males and 172 females) with isthmic low-grade lumbosacral spondylolisthesis referred to an orthopedic clinic were reviewed. Radiological parameters, Micheli scale, and quality of life measured by the SRS-22 questionnaire were measured at the first visit and a minimum 5-year follow-up.

Results: The average follow-up time is 5.7 ± 1.4 years. The main complaint at the initial presentation was lower back pain in 107 patients, and three patients had lower back pain and lower limbs radiculopathy. Scoliosis was found in 38 patients in the initial radiograph. One-hundred-eighty-nine patients (63%) were asymptomatic at the time of presentation. At the last follow-up; SRS-22 were 4.21 ± 0.6, 4.21 ± 0.7, 4.31 ± 0.5, 4.21 ± 0.7, 4.2 ± 0.7 for total, pain, function, mental, and self-image scores, respectively. The patients with grade one lumbosacral spondylolisthesis with normal morphology of the sacrum had responded well to the nonsurgical treatment modalities. No patient has progressed during the follow-up, and no patient underwent surgical intervention for back pain. The slip percent was relatively lower in patients with low back pain. The average slip percentage was 15.5 ± 8.4 among the asymptomatic patients and 13 ± 9 among patients who presented with low back pain ($P$-value = 0.009).

Conclusion: Adolescent patients with grade one isthmic lumbosacral spondylolisthesis have very good prognosis with nonoperative modalities and they have an almost normal quality of life at the end of follow-up. A long follow-up in an outpatient clinic with X-Rays series might not be indicated for all patients with low-grade spondylolisthesis, specifically if the slip is less than 25%.

Do Asian Breast Cancer Patients Have Poorer Survival Than Their Western Counterparts? A Comparison Between Singapore and Stockholm.

Large Family With Both Parents Affected by Distinct BRCA1 Mutations: Implications For Genetic Testing.

The development of prognostic molecular signatures considering the inter-patient heterogeneity is a key challenge for the precision medicine. We propose a joint model of this heterogeneity and the patient survival, assuming that tumor expression results from a mixture of a subset of independent signatures. We deconvolute the omics data using a non-parametric independent component analysis with a double sparseness structure for the source and the weight matrices, corresponding to the gene-component and individual-component associations, respectively. In a simulation study, our approach identified the correct number of components and reconstructed with high accuracy the weight ($>$0.85) and the source ($>$0.75) matrices sparseness. The selection rate of components with high-to-moderate prognostic impacts was close to 95%, while the weak impacts were selected with a frequency close to the observed false positive rate ($<$25%). When applied to the expression of 1063 genes from 614 breast cancer patients, our model identified 15 components, including six associated to patient survival, and related to three known prognostic pathways in early breast cancer (i.e. immune system, proliferation, and stromal invasion). The proposed algorithm provides a new insight into the individual molecular heterogeneity that is associated with patient prognosis to better understand the complex tumor mechanisms.

Prognosis of patients with hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. An accurate staging system for cancer patients with HCC provides guidance in terms of both patient assessment and therapeutic decisions. Staging is also essential for comparison of groups in clinical trials and for comparison between different studies. Because numerous studies have reported divergent outcomes and predictors of survival after resection in patients with HCC, a number of different classification schemes for HCC have been proposed. Several of these staging systems rely heavily on clinical parameters and integrated scoring schemes (Okuda, Barcelona Clinic Liver Cancer Staging, Cancer of the Liver Italian Program). Others, such as the Liver Cancer Study Group of Japan and the Japanese Integrated Staging Score incorporate pathologic data after resection, yet still rely on the computation of a score to determine prognosis. Recently, a new staging system validated in Japan, the United States, and Europe has been adopted by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC). This HCC staging system is based on a multivariate analysis and has been independently validated. Because the new AJCC/UICC staging system is easily obtained, is objective, and has been independently validated, we strongly propose it as the prognostic staging system of choice for HCC after resection of HCC.

It is now mandatory to perform cytogenetics (CG) study in all new cases of leukemia owing to its usefulness in disease diagnosis, classification and prognostication. The technique of fluorescence in-situ hybridization (FISH), applicable to both interphase and metaphase cells on a variety of samples has proved to be useful in supplementing convention CG, especially in the detection of clinically significant changes when CG is unsuccessful or when genetic abnormalities are cryptic. With improvements in the test sensitivity, FISH can be applied in monitoring molecular response to treatment and detection of residual disease, especially in the setting of monitoring for BCR-ABL in chronic myeloid leukemia patients following imatinib therapy. Newer molecular CG tests such as multicolor karyotyping and comparative genomic hybridization have a clinical potential as they enable resolution of complex karyotypic aberrations and global scanning of genomic imbalances, respectively. In the horizon, important information gained from gene expression profile studies will be useful for the design of tests, molecular based or otherwise, that are suited for routine diagnostic service. However, CG and molecular data must also be integrated with clinical and pathological findings before a definitive diagnosis is made.

Cancer is a leading cause of mortality worldwide and the major exhausting factor for social resources in healthcare, medical treatment, and the loss of working force. Therefore, developing cancer therapy methods and appropriate prognosis or assessment for cancer therapies are of critical importance. Due to the high cost in exploration and assessment of cancer therapy methods, mathematical modeling of the immune system is viewed as a potentially powerful tool in the development of improved treatment regimens and prediction of disease progression. In the present work, several general principles in mathematical modeling of immune–tumor interactions and cancer therapies are summarized first. Secondly, the acquisition of the parameter values and model calibration are discussed according to mathematical techniques in qualitative analysis. Moreover, various therapy strategies are tested on the constructed mathematical model, from which constructive suggestions for developing new clinical treatment methods are provided. Additionally, some general guidance for new therapies are also discussed by analyzing the sensitivity of the system parameters. In the end, we also discuss essential difficulties in building the mathematical model for cancer patients.

Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide, and is caused by complex interactions of multiple risk factors such as environmental (Helicobacter pylori and Epstein–Barr Virus), hereditary (genetic alterations and epigenetic modifications), as well as dietary and lifestyle factors. GC is usually detected at an advanced stage, with a dismal prognosis. Even for patients with similar clinical or pathologic stage receiving similar treatment, the outcomes are still uneven and unpredictable. To better incorporate genetic and epigenetic profiles into GC prognostic predication, gene expression signatures have been developed to predict GC outcomes. More recently, the advancement of high-throughput sequencing technology, also known as next-generation sequencing (NGS) technology, and analysis has provided the basis for accurate molecular classification of GC tumors. Here, we summarized and updated the literature related to NGS studies of GC, including whole-genome sequencing, whole-exome sequencing, RNA sequencing, and targeted sequencing, and discussed current progresses. NGS has facilitated the identification of genetic/epigenetic targets for screening as well as development of targeted agent therapy, thus enabling individualized patient management and treatment.

As breast cancer is a substantial threat to the lives of women, it has become a major health issue in the world over the past 50 years, and its incidence has increased in the recent years. Early diagnosis and suitable treatment is relatively important. In the process of breast screening, tissue biopsy is an important operation in determining the presence of breast cancer. It not only provides an accurate diagnosis of the disease but also determines the prognosis for breast cancer. The main goal of this study is to develop a breast cancer diagnosis system based on histopathology and a sequence of image-processing technologies to analyze H&E stained images of breast tissues. The proposed system can automatically detect the mitosis of nuclei and analyze the size and the shape of nuclei to evaluate the duct structure of the breast tissue. Moreover, it provides physicians quantitative prognosis and classification of tissue malignancy, which will improve the diagnostic accuracy and efficiency of the cancer.

According to statistics, up to 40% of emergency admissions are due to chest tightness or chest pain. However, merely based on the patient’s current symptoms such as chest pain, it is difficult for a physician to give an instant diagnosis as most cardiovascular diseases are chronic. To address this issue, it is necessary to provide a set of tools to indicate the patient’s status during hospitalization to help the physician in diagnosis. It is thus our primary objective to design and develop a wearable heart rate monitoring system and prediction tool that can measure the patient’s heart rate parameters, allow him/her to move around easily, and which also can effectively improve the medical personnel’s working efficiency. This research utilizes conductive filament to design textile to integrate electric circuit with clothing. Using a conductive vest and chest belt that can be worn comfortably, our system can continuously record patients’ physiological index parameters during their hospitalization. Physiological index parameters of multiple patients can then be transmitted wirelessly and recorded in a physician-end computer. At the end of their hospitalization, the patient’s original physiological indices together with the recorded heart rate variability (HRV) parameters can then be summarized to assess the risk score of their discharging from hospital. This paper adopts the concept of TIMI risk score, while adding every index of HRV measured when subjects are hospitalized. The risk score can hence be used to provide emergency physicians as a basis for an early prognosis and subsequently a better hospital-discharging assessment of patients with chest pain. The accuracy of the proposed prognosis has been verified with the 3-day and 30-day recall rate of the patients and the result has been shown to be promising for chest pain patients in emergency admission units.

The metallothionein (MT) family is a class of low-molecular-weight, cysteine-rich proteins (MT-1, MT-2, MT-3, and MT-4) with high affinity for metal ions. Apart from their involvement in metal ion homeostasis and detoxification, protection against oxidative damage, and cell proliferation and apoptosis, they are also implicated in drug and radiotherapy resistance and several aspects of the carcinogenic process. Variable MT expression has been observed in different cancer types, reaching statistically significant correlation with clinicopathological parameters in some cases; nevertheless, MT expression as a marker of prognosis or as a predictor for the response to either chemotherapy or radiotherapy remains unclear. The present review examines the expression of MT in different human tumors in correlation with resistance to radiation therapy or chemotherapy and patients' final outcome. Detailed studies focused on the expression of MT isoforms and isotypes in different tumor types could elucidate the role of this group of proteins in patients' prognosis and resistance to treatment strategies.

Mammoth efforts have been made in an attempt to understand the etiology of breast neoplasia. Metallothioneins (MTs) are ubiquitous, low-molecular-weight, metal-binding proteins. In addition to their essential roles in metal homeostasis, MTs have been reported to be overexpressed in breast cancers. Generally, MTs are involved in many processes that support tumorigenesis, encompassing the promotion of cell proliferation and metastasis as well as the disruption of apoptotic mechanisms in breast cancers. There is also increasing evidence which shows the association of MT with tumor grade and chemoresistance, supporting the notion that MT could potentially be a biomarker of prognosis. In this chapter, we shall focus on the contributions of individual MT isoforms in relation to breast carcinogenesis and its eventual pathological outcome.

There have been some results reported concerning the expression of metallothionein (MT) in colorectal tumors. This paper reviews four aspects: the contribution of MT in colorectal carcinogenesis, the prognostic significance of MT, MT expression in colorectal liver metastases, and the clinical significance of MT as a drug-resistance protein.