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Background: Although substance use may have adverse impacts on cancer outcomes, little is known regarding patterns of concurrent substance use with cannabis among cancer patients. Our objective was to examine predictors of concurrent substance use with cannabis among cancer patients since their cancer diagnosis and explore perceptions of cannabis among these patients., Methods: Patients treated at a National Cancer Institute-designated comprehensive cancer center were invited to participate in an electronic survey regarding medical cannabis from August to November 2021. Survey data were linked to internal data resources including electronic health records and patient intake forms to obtain history of substance use (defined as within at least 3 months of cancer diagnosis) of cigarettes, injection drugs, high levels of alcohol, or clinically unsupervised prescription drugs (total n = 1094). Concurrent substance users were defined as those with any reported substance use and cannabis use at the time of cancer diagnosis. We used descriptive statistics (χ2 or exact tests) to compare groups and estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) to identify predictors of substance use among users and nonusers of cannabis., Results: Approximately 45% (n = 489) of the sample reported cannabis use since their cancer diagnosis. Of patients who reported using cannabis, 20% self-reported concurrent polysubstance use, while 8% of cannabis nonusers reported substance use (P < .001). Among patients who use cannabis, those who reported 2 or more self-reported treatment-related symptoms (eg, pain, fatigue) were more likely to have self-reported concurrent substance use (AOR = 3.15, 95% CI = 1.07 to 9.27) compared with those without any symptoms. Among nonusers, those with lower educational background were more likely to have a history of concurrent substance use (AOR = 3.74, 95% CI = 1.57 to 8.92). Patients who use cannabis with concurrent substance use were more likely to report improved sleep (P = .04), increased appetite (P = .03), and treatment of additional medical conditions (P = .04) as perceived benefits of cannabis use., Conclusions: High symptom burden may be associated with concurrent substance use with cannabis among cancer patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study introduces an improved quantum-behavior particle swarm optimization (IQPSO), tailored for the task of maximum power point tracking (MPPT) within photovoltaic generation systems (PGSs). The power stage of the MPPT system comprises a series of buck-boost converters, while the control stage contains a microprocessor executing the biomimetic algorithm. Leveraging the series buck-boost converter, the MPPT system achieves optimal operation at the maximum power point under both ideal ambient conditions and partial shade conditions (PSCs). The proposed IQPSO addresses the premature convergence issue of QPSO, enhancing tracking accuracy and reducing tracking time by estimating the maximum power point and adjusting the probability distribution. Employing exponential decay, IQPSO facilitates a reduction in tracking time, consequently enhancing convergence efficiency and search capability. Through single-peak experiments, multi-peak experiments, irradiance-changing experiments, and full-day experiments, it is demonstrated that the tracking accuracy and tracking time of IQPSO outperform existing biomimetic algorithms, such as the QPSO, firefly algorithm (FA), and PSO.

Background: Handgrip strength (HGS) is acknowledged as a key indicator of overall physical fitness and is associated with various health outcomes., Objectives: This research investigates the correlation between HGS and quality of life (QoL), focusing on its relation to pulmonary function in the general adult population., Method: The study involved 19,402 participants aged 40 and above, spanning from 2014 to 2019, who underwent pulmonary function and HGS tests. Participants were categorized based on lung function, and regression analyses were employed to examine the relationship between HGS and QoL, with adjustments made for lung function., Results: The average age of the cohort was 58.2 years, comprising 44.6% males and 41.2% smokers. Out of the 18,708 participants who completed the European Quality of Life Scale-Five Dimensions (EQ-5D-3L) assessment, higher severity levels in mobility, self-care, usual activities, pain or discomfort, and anxiety or depression were linked to lower HGS in both sexes. Additionally, among the 3,723 participants who completed the Health-related Quality of Life Instrument with 8 Items (HINT-8) assessment, higher severity levels in pain, work, and depression were associated with lower HGS in men. In women, higher severity levels in climbing stairs, pain, vitality, and work correlated with lower HGS., Conclusions: As problems indicated by EQ-5D worsened, there was a consistent decrease in handgrip strength (HGS) across both genders. The HINT-8 assessment further revealed that increased severity in pain and work-related issues led to reduced HGS in both men and women. This study highlights the relationship between HGS and Quality of Life (QoL), taking lung function into consideration, and underscores the importance of HGS as a potential marker of physical health and fitness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6-guided opioid prescribing for patients with cancer and reported pilot outcome data., Methods: Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient-reported pain and symptom scores at baseline and up to 8 weeks, were assessed., Results: Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3-37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6-genotype-guided recommendations to change therapy (n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow-up questionnaires (n = 48), there was no difference in change in mean composite pain score (-1.01 ± 2.1 vs. -0.41 ± 2.5; p = 0.19) or symptom severity at last follow-up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm (n = 26) and genotype-guided arm (n = 22), respectively., Conclusion: Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype-guided recommendations was low, impacting assessment of pain-related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success., (© 2023 Pharmacotherapy Publications, Inc.)

Systemic sclerosis associated with lung interstitial lung disease (SSc-ILD) is the most common cause of death among patients with SSc. Mesenchymal stem cell (MSCs) transplantations had been treated by SSc patients that showed in the previous case report. The therapeutic mechanisms and effects of MSCs on SSc-ILD are still obscure. In this study, we investigated the therapeutic effects and mechanisms of treatment of BM-MSC derived from C57BL/6 on the topoisomerase I (TOPO I) induced SSc-ILD-like mice model. The mice were immunized with a mixture of recombinant human TOPO I in PBS solution (500 U/mL) and completed Freund's adjuvant [CFA; 1:1 (volume/volume)] twice per week for 9 weeks. On week 10, the mice were sacrificed to analyze the related pathological parameters. Lung and skin pathologies were analyzed using histochemical staining. CD4 T-helper (T H ) cell differentiation in lung and skin-draining lymph nodes was detected using flow cytometry. Our results revealed that allogeneic and syngeneic MSCs exhibited similar repressive effects on TOPO I-induced IgG1 and IgG2a in the SSc group. After intravascular (IV) treatment with syngeneic or allogeneic MSCs, the dermal thickness and fibrosis dramatically condensed and significantly reduced airway hyperresponsiveness. These findings showed that both allogeneic and syngeneic MSCs have therapeutic potential for SSc-ILD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The "draw-and-talk" technique has become popular in medical training, as it can help healthcare practitioners develop empathic understanding of patients and contribute to personal transformation. We adopted this method to make the teaching of transitional care planning more relevant to post-graduate residents undergoing their internal medicine training at a medical center in Taiwan., Methods: Before the conventional lecture on discharge planning, trainees were invited to draw their "home" and "life as older adults" and share their drawings with others. Subsequently, they were guided to consider whether their home would be livable if they either had a disability or were old. The drawings and narratives were analyzed thematically, and feedback on the session was collected., Results: Trainees were initially of the opinion that they did not have any role in discharge planning. However, the emphasis on the self-experience of drawing and the thematic use of "home" and "elderly life" led to reflective discussions about post-discharge care. The session provoked constructive self-reflection and meta-cognitive awareness and encouraged residents to actively participate in transition care plans. Response to the draw-and-talk session was overwhelmingly favorable., Conclusions: Post-graduate residents in Taiwan conventionally do not have much interest or autonomy regarding their patients' lives outside the hospital. The use of drawing and reflection is a simple and inexpensive method to contextualize discharge planning in participants' real lives, engage them in actively visualizing the healthcare needs of older adults and patients with disability, and initiate thinking about the impact of discharge preparations, follow-up care, and barriers to care at home. Draw-and-talk might be helpful in improving residents' knowledge and empathy toward patients preparing for discharge, which is crucial for the quality of transitional care., (© 2022. The Author(s).)

Here, we describe a case of a patient with multiple myeloma who reported symptoms of lucid dreams. This patient was taking methadone for neoplasm related pain. The patient was also taking pregabalin which was initially started at dosing of 50 mg taken orally three times a day. Five days after initiation of pregabalin, the dosing was increased to 100 mg taken orally three times daily. The patient developed lucid dreams during a hospital stay and methadone was initially thought to be the cause of her lucid dreams. Methadone dosing was decreased with no success, and her lucid dreams persisted. On the patient's thirteenth day of hospital admission, the pregabalin dose was decreased from 100 mg three times a day to 75 mg twice daily. Five days later, the pregabalin was decreased from 75 mg twice daily to 50 mg twice daily. Pregabalin was continued for five more days and then discontinued. Resolution of the lucid dreams occurred following discontinuation of pregabalin. To our knowledge, this is the first reported case of an association between pregabalin and lucid dreams. Given that pregabalin is a widely used medication, we found this case to be relevant to describe this unique presentation.

Objectives: Older adults with cancer are increasingly inquiring about and using cannabis. Despite this, few studies have examined cannabis use in patients with cancer aged 65 years and older as a separate group and identified characteristics associated with use. The current study sought to determine the rate of cannabis use in older adult patients with cancer and to identify demographic and clinical correlates of use., Methods: We conducted a retrospective review of patients with cancer referred for specialised symptom management between January 2014 and May 2017 who underwent routine urine drug testing for tetrahydrocannabinol as part of their initial clinic visit., Results: Approximately 8% (n=24) of patients with cancer aged 65 years and older tested positive for tetrahydrocannabinol compared with 30% (n=51) of young adults and 21% (n=154) of adults. At the univariate level, more cannabis users had lower performance status than non-users (p=0.02, Fisher's exact test). There were no other demographic and clinical characteristics significantly associated with cannabis use in older adults., Conclusions: Older adult patients made up nearly 25% (n=301) of the total sample and had a rate of cannabis use of 8%. As one of the first studies to assess cannabis use via objective testing rather than self-report, this study adds significantly to the emerging literature on cannabis use in people aged 65 years and older. Findings suggest the rate of use in older adults living with cancer is higher than that among older adults in the general population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Traditional lecture-based medical ethics and law courses deliver knowledge but may not improve students' learning motivation. To bridge this theory-to-practice gap and facilitate students' learning effectiveness, we applied situated-learning theory to design an interdisciplinary court-based learning (CBL) component within the curriculum. Our study aimed to investigate students' learning feedbacks and propose a creative course design., Methods: A total of 135 fourth-year medical students participated in this course. The CBL component included 1 h of introduction, 1 h of court attendance, and 2 h of interdisciplinary discussion with senior physicians, judges, and prosecutors. After the class, we conducted a survey using a mixed-methods approach to gauge students' perceptions of engagement, performance, and satisfaction., Results: A total of 97 questionnaires were received (72% response rate). Over 70% of respondents were satisfied and felt that the class was useful except for role-playing activities (60%). More than 60% reported a better understanding of the practical applications of medical law. Approximately half (54%) reported less anxiety about medical disputes. 73% reported that the lecture provided awareness of potential medical disputes, and most respondents expressed an interest in medical law courses after the court visit (78%). 80% of the respondents were able to display empathy and apply mediation skills. Qualitative analyses showed that students demonstrated new knowledge, including recognizing the significance of the medical profession, distinguishing the importance of physician-patient communication, having confidence in the fairness of the justice system, and being willing to increase their legal knowledge., Conclusions: CBL curriculum increases students' learning motivation in strengthening medical professionalism and medical law, develops students' empathy for patients and communication skills, as well as builds up students' trust in the justice system. This novel course design can be applied to teach medical ethics and law., (© 2022. The Author(s).)

The vancomycin-resistant Enterococci (VRE) have progressively become a severe medical problem. Although clinics have started to reduce vancomycin prescription, vancomycin resistance has not been contained. We found that the transfer of vancomycin resistance in Enterococcus faecalis increased more than 30-fold upon treatment by streptomycin. Notably, treatment with an antibiotic caused the bacteria to become resistant to another. The response was even stronger in the well-studied plasmid pCF10 and the number of transconjugants increased about 100,000-fold. We tested four different antibiotics, and all of them induced conjugal response. Through a mathematical model based on gene regulation, we found a plausible explanation. Via quorum sensing, the change of the cell density triggers the conjugation. Moreover, we searched for generality and found a similar strategy in Bacillus subtilis . The outcome of the present study suggests that even common antibiotics must not be overused., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shu, Chen, Chang, Chen, Liu, Huang, You and Wu.)

Background: Fibroblast growth factor 23 (FGF23), an important regulator of phosphate and vitamin D metabolism, has also been suggested to perform metabolic functions. This retrospective study evaluated the relationship between metabolic syndrome (MetS) and fasting FGF23 levels in patients undergoing kidney transplantation (KT)., Methods: Serum carboxyl-terminal FGF23 levels were measured in fasting blood samples of 74 KT patients using a commercially available enzyme-linked immunosorbent assay. MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation., Results: Twenty-four KT patients (32.4%) had MetS. Hypertension (P = .008); diabetes (P = .002), body weight (P < .001); body mass index (P < .001); waist circumference (P < .004); body fat mass (P < .001); systolic blood pressure (P = .008); and levels of triglycerides (P = .003), blood urea nitrogen (P = .007), and insulin (P = .004); homeostasis model assessment of insulin resistance (P = .001); and FGF23 (P = .002) were higher, whereas high-density lipoprotein cholesterol (P = .049) levels were lower in KT patients with MetS. Multivariable logistic regression analysis including significant variables revealed that FGF23 (odds ratio 1.030, 95% confidence interval [CI] 1.000-1.060, P = .048) was an independent predictor of MetS in KT patients. The area under the receiver operating characteristic curve to evaluate the ability of serum FGF23 in discriminating KT patients with MetS was 0.727 (95% CI 0.611-0.824, P = .0005)., Conclusion: These results revealed that a high serum FGF23 level was positively associated with MetS in KT patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aryl hydrocarbon receptor (AhR) is a ligand-dependent-activated transcriptional factor that regulates the metabolism of xenobiotic and endogenous compounds. Recent studies have shown that AhR is a novel master regulator of the mucosal immune system, including lungs and intestine. To elucidate the role of AhR in chronic severe asthma, AhR wild-type and knockout mice (AhR -/- ) were sensitized and challenged with ovalbumin for 4 weeks. To uncover the underlying mechanisms, inflammatory cells profile and cytokines production were analyzed in bronchial lavage fluid (BALF) and lung tissue. Compared to wild-type mice, AhR -/- mice had exacerbated asthma symptoms, including airway inflammation, mucus production, airway hyperresponsiveness, and airway remodeling. BALF monocytes, neutrophils, eosinophils, and lymphocytes were all enhanced in OVA-immunized AhR -/- mice. In OVA-immunized AhR -/- mice, T helper (Th) 17 cell-specific cytokine IL-17A, as well as airway remodeling factors, including epithelial-mesenchymal transition (EMT) markers and vascular endothelial growth factor (VEGF), were all enhanced in lung tissue. Moreover, human cohort studies showed that AhR gene expression in bronchial epithelial cells decreases in severe asthma patients. Loss of AhR leads to worsening of allergic asthma symptoms, indicating its importance in maintaining normal lung function and mediating disease severity., (© 2020 Federation of American Societies for Experimental Biology.)

During past few decades, studies have demonstrated that particulate matter (PM) is the most serious environmental pollutant in industrial countries which mainly contributes for increasing prevalence of chronic respiratory inflammatory diseases. Healthy food supplements to prevent the inflammatory diseases are common and show notable effects. The effects of the extract of Pyrus nivalis, a common fruit and herbal medicine in Taiwan, on PM-induced airway inflammation in mice were investigated by feeding the extract orally for 21 days. Results obtained from lung histology and bronchial alveolar lavage fluid (BALF) cell profile showed that oral feeding of P. nivalis extract did not affect the airway inflammation. However, it increased the phagocytic activity in BALF cells and induced M1-dominant macrophage differentiation in lungs. Our study showed that extract of P. nivalis might present the beneficial and therapeutic potential for clearance of PM and pathogens in airway. PRACTICAL APPLICATIONS: Pyrus nivalis is a common fruit and also used extensively in Chinese herbology. The pharmacological effects of P. nivalis have been reported in ancient Chinese Medical literature and known to possess anti-asthma and anti-cough properties as well as to enhance function of lungs. In this study, we found that orally feeding the extract of P. nivalis did not induce airway inflammation and affect particulate matter (PM)-induced inflammatory cells infiltration in lungs but increased phagocytosis with or without PM treatment which might indicate its therapeutic potential for clearance of PM and pathogens in airway., (© 2020 Wiley Periodicals LLC.)

Background: The use of cannabis by young adult (YA) cancer patients is likely to increase as medical cannabis becomes more available. Clinically relevant data on cannabis use are needed to establish benchmarks for use, to identify patients who are more likely to use cannabis, and to assess outcomes associated with use. Objective: The current study sought to determine the rate of cannabis use in YA cancer patients ages 18 to 39, identify demographic and clinical correlates of use, and examine differences in moderate-to-severe symptoms between users and nonusers. Methods: We conducted a retrospective review of objectively measured tetrahydrocannabinol (THC), self-reported cannabis use, and cancer-related symptomatology in YA cancer patients in active treatment referred for comprehensive supportive care. Results: Approximately 30% of YA cancer patients tested positive for THC on urine drug testing. At the univariate level, cannabis users were more likely to be male, to have a lifetime history of smoking at least 100 cigarettes, and to be more recently diagnosed. Cannabis use was associated with moderate-to-severe symptomatology, including pain, nausea, lack of appetite, constipation, difficulty sleeping, and poorer overall well-being. Conclusions: YAs referred for comprehensive supportive care may be managing their cancer-related symptoms with cannabis. Further research is needed to better understand patients' perceptions of cannabis's therapeutic and adverse effects, in patients who used cannabis before diagnosis, and in patients who commenced use in response to a cancer diagnosis.

Background: The use of cannabis by cancer patients has become increasingly common. With expanding access to medical cannabis, unsanctioned cannabis use is likely to increase. Despite this, the extent to which patients seeking specialized palliative or supportive care for cancer-related symptoms are actively using cannabis has not been well established. Objective: We sought to determine the extent to which patients seeking specialized symptom management were using cannabis and to compare the severity of cancer-related symptoms between users and nonusers. Methods: We conducted a retrospective review of objectively measured tetrahydrocannabinol (THC) and subjectively reported cannabis use, its demographic and clinical correlates, and patient-reported symptoms in 816 cancer patients in active treatment referred to a supportive/palliative care outpatient clinic for specialized symptom management between January 2014 and May 2017. Results: Nearly one-fifth (19.12%) tested positive for THC on urine drug testing. Users were younger, more likely to be men, single, and to have a history of cigarette smoking. Users also were likely to be more recently diagnosed and to have received radiotherapy. Certain moderate-to-severe symptoms, such as lack of appetite, shortness of breath, tiredness, difficulty sleeping, anxiety, and depression, were associated with use after accounting for sociodemographic and clinical differences between cannabis users and nonusers. Conclusions: Findings suggest patients seeking specialized symptom management are self-treating with cannabis, despite the lack of high-quality evidence for its use in palliative care. Unsanctioned use is likely to increase in cancer patients. Accurate information is urgently needed to help manage patient expectations for its use and increase understanding of risks and benefits.

Background: Information about the frequency of cannabinoid use and the clinical characteristics of its users in oncology supportive care is limited. This study explored associations between cannabinoid use and cancer-related clinical characteristics in a cancer population., Patients and Methods: This retrospective review included 332 patients who had a urine drug test (UDT) for tetrahydrocannabinol (THC) together with completion of an Edmonton Symptom Assessment Scale (ESAS) and cannabinoid history questionnaire on the same day that urine was obtained during 1 year in the supportive care clinic., Results: The frequency of positive results for THC in a UDT was 22.9% (n=76). Significant statistical differences were seen between THC-positive and THC-negative patients for age (median of 52 [lower quartile, 44; upper quartile, 56] vs 58 [48; 67] years; P<.001), male sex (53.9% vs 39.5%; P=.034), and past or current cannabinoid use (65.8% vs 26.2%; P<.001). Statistical significance was observed in ESAS items between the THC-positive and THC-negative groups for pain (7 [lower quartile, 5; upper quartile; 8] vs 5 [3; 7]; P=.001), nausea (1 [0; 3] vs 0 [0; 3]; P=.049), appetite (4 [2; 7] vs 3 [0; 5.75]; P=.015), overall well-being (5.5 [4; 7] vs 5 [3; 6]; P=.002), spiritual well-being (5 [2; 6] vs 3 [1; 3]; P=.015), insomnia (7 [5; 9] vs 4 [2; 7]; P<.001), and total ESAS (52 [34; 66] vs 44 [29; 54]; P=.001). Among patients who reported current or past cannabinoid use, THC-positive patients had higher total scores and scores for pain, appetite, overall well-being, spiritual well-being, and insomnia than THC-negative patients., Conclusions: Patients with cancer receiving outpatient supportive care who had positive UDT results for THC had higher symptom severity scores for pain, nausea, appetite, overall and spiritual well-being, and insomnia compared with their THC-negative counterparts. These results highlight potential opportunities to improve palliative care.

Context: Cancer-related pain is a common symptom that is often treated with opioids. However, legislation aimed at containing the opioid crisis, coupled with public fears about opioid risks, may contribute to opioid stigma in cancer patients. To our knowledge, no prior research has examined opioid stigma and stigma-related behavior in this population., Objective: The objectives of this study were to describe opioid use, including reasons for use and overuse and underuse behavior; characterize opioid stigma; and identify potentially maladaptive stigma-related behaviors., Methods: Participants were 125 adults undergoing active cancer treatment seen at the Moffitt Supportive Care Medicine Clinic. Patients completed a brief, anonymous questionnaire evaluating opioid use, opioid stigma, and stigma-related behaviors., Results: Patients were primarily women (65%) aged 45-64 years (49%), most commonly diagnosed with breast (23%) and hematologic (15%) cancer. Among patients who reported opioid use (n = 109), the most common reason for use was pain relief (94%), followed by improved sleep (25%). A subset of patients reported using less (13%) or more (8%) opioid medication than advised. Opioid stigma was endorsed by 59/97 patients prescribed opioids (61%), including fear of addiction (36%), difficulty filling prescriptions (22%), and awkwardness communicating with providers (15%). Stigma-related behaviors were endorsed by 28 (29%) respondents prescribed opioids, with "taking less opioid medication than needed" as the most commonly endorsed behavior (20%)., Conclusion: To our knowledge, this study provides the first evidence of opioid stigma and its consequences in cancer patients and offers potential targets for interventions aimed at reducing stigma and encouraging safe, effective opioid use., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Cholangiocarcinoma is a malignancy arising from the biliary tract epithelial cells with poor prognosis. Tumor infiltrating lymphocytes (TIL)s and programmed cell death receptor ligand 1 (PD-L1) have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Tumor samples from 44 patients with resected and histologically verified extrahepatic cholangiocarcinoma were evaluated for CD8, CD45RO and PD-L1 expression, and their correlations with clinicopathological data and survival data were analyzed. Total 44 extrahepatic cholangiocarcinoma tissues were evaluated. CD8+ tumor infiltrating lymphocytes (TIL)s were observed in 30 (68%) tumors. Among them, 14 had CD8+CD45RO+ TILs. PD-L1 was expressed on cancer cells in 10 (22.7%) tumors in 34 evaluable extrahepatic cholangiocarciniomas. The presence of CD8+ TILs or CD8+CD45RO+ TILs was not associated with clinical staging or tumor differentiation. Extrahepatic cholangiocarcinoma with CD8+CD45RO+ TILs had longer overall survival (OS) on univariate ( P = 0.013) and multivariate ( P = 0.012) analysis. Neither CD8+TIL nor PD-L1 expression on cancer cells correlated significantly with OS. These results add to the understanding of the clinical features associated with CD8 TILs and PD-L1 expression in extrahepatic cholangiocarcinoma, and they support the potential rationale of using PD-1 blockade immunotherapy in cholangiocarcinoma., Competing Interests: CONFLICTS OF INTEREST Richard Kim received honorarium from Lilly. The other authors report no conflicts of interest for this work.

Introduction: Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of pain management. Opioid therapy is empirically selected, and patients often require adjustments in therapy to effectively alleviate pain or ameliorate adverse drug effects that interfere with quality of life. There are data suggesting CYP2D6 genotype may contribute to inter-patient variability in response to opioids through its effects on opioid metabolism. Therefore, we aim to determine if CYP2D6 genotype-guided opioid prescribing results in greater reductions in pain and symptom severity and interference with daily living compared to a conventional prescribing approach in patients with cancer., Methods: Patients with solid tumors with metastasis and a self-reported pain score ≥ 4/10 are eligible for enrollment and randomized to a genotype-guided or conventional pain management strategy. For patients in the genotype-guided arm, CYP2D6 genotype information is integrated into opioid prescribing decisions. Patients are asked to complete questionnaires regarding their pain, symptoms, and quality of life at baseline and 2, 4, 6, and 8 weeks after enrollment. The primary endpoint is differential change in pain severity by treatment strategy (genotype-guided versus conventional pain management). Secondary endpoints include change in pain and symptom interference with daily living., Conclusion: Pharmacogenetic-guided opioid selection for cancer pain management has potential clinical utility, but current evidence is limited to retrospective and observational studies. Precision Medicine Guided Treatment for Cancer Pain is a pragmatic clinical trial that seeks to determine the utility of CYP2D6 genotype-guided opioid prescribing in patients with cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Single therapy with methylphenidate or American ginseng contributes to the reduction in cancer-related fatigue (CRF) with different pharmacologic mechanisms and is relatively safe. However, the safety and efficacy of treating CRF with methylphenidate and AG combination therapy is unknown., Aim: The primary objective was to assess the clinical safety and the change in fatigue with numerical rating scale (NRS) on the Edmonton Symptom Assessment Scale (ESAS) after intervention with methylphenidate and AG combination therapy., Methods: We reviewed the electronic medical records of 857 patients seen in our Palliative Medicine outpatient clinic between February 1, 2015, and December 31, 2015. Fatigue was assessed by NRS on ESAS. Toxicity was reviewed on clinician's documents., Results: We identified 28 patients who were prescribed a combination of methylphenidate (10-40 mg/d) and AG (2000 mg/d). Ten patients did not comply with the combination therapy. Three patients had stage 2 adverse effects. Fifteen patients completed prescribed combination therapy per instructions. The mean time interval between pre- and postintervention follow-up was 30.5 days (standard deviation [SD]: 7.78). There was a significant reduction in the fatigue score (mean score 6.93-4.13) from the pre- to postscore records (mean: -2.8; SD: 1.61; P < .0002* [*refers to statistically significant]). Sixty percent of patients reported significant reduction in fatigue (cutoff value: ≥3; reduction in fatigue score from baseline: 80% ≥2, 60% ≥3, and 46.7% ≥4)., Conclusion: In our retrospective medical record review, the combination treatment of methylphenidate and AG had no discernible associated toxicities and showed potential clinical benefit in CRF.

Background: Although squamous cell anal carcinomas are relatively rare, their incidence has been increasing steadily. Because of the limited data, treatment of metastatic disease is a major therapeutic challenge. In this study, we report the safety and efficacy of epidermal growth factor receptor (EGFR) inhibitors in patients with advanced squamous cell anal carcinomas., Method: A retrospective analysis was conducted using the Moffitt Cancer Tumor Registry from January 2009 to January 2014. Eligible patients had diagnosis of advanced squamous cell anal carcinomas and received an EGFR inhibitor as part of their treatment., Result: A total of 13 patients were identified for analysis. All of them received concurrent chemoradiation as initial treatment and subsequently had recurrence. Five patients received single agent cetuximab or panitumumab, and the others received cetuximab or panitumumab with irinotecan or FOLFIRI. The objective response rate was 30.8% including 1 complete response, and the disease control rate was 46.2%. With a median follow-up of 9.6 months, the median progression-free survival and median overall survival were 4.4 months and 11.4 months, respectively., Conclusion: Our analysis suggests that EGFR inhibitors have potential efficacy and are reasonably well tolerated in patients with squamous cell anal carcinomas. These findings warrant further evaluation in a large prospective trial., (© 2017 S. Karger AG, Basel.)

Background: Phosphatase of regenerating liver (PRL) family is classified as class IVa of protein tyrosine phosphatase (PTP4A) that removes phosphate groups from phosphorylated tyrosine residues on proteins. PRL phosphatases have been implicated in a number of tumorigenesis and metastasis processes and are highly conserved. However, the understanding of PRL expression profiles during embryonic development is very limited., Results: In this study, we demonstrated and characterized the comprehensive expression pattern of Drosophila PRL, amphioxus PRL, and zebrafish PRLs during embryonic development by either whole mount immunostaining or in situ hybridization. Our results indicate that Drosophila PRL is mainly enriched in developing mid-guts and central nervous system (CNS) in embryogenesis. In amphioxus, initially PRL gene is expressed ubiquitously during early embryogenesis, but its expression become restricted to the anterior neural tube in the cerebral vesicle. In zebrafish, PRL-1 and PRL-2 share similar expression patterns, most of which are neuronal lineages. In contrast, the expression of zebrafish PRL-3 is more specific and preferential in muscle., Conclusions: This study, for the first time, elucidated the embryonic expression pattern of Drosophila, amphioxus, and zebrafish PRL genes. The shared PRL expression pattern in the developing CNS among diverse animals suggests that PRL may play conserved roles in these animals for CNS development.

In order to understand the genetic difference and phylogenic relationship within and among the Fusarium species in Section Martiella, the genetic diversity of 21 Fusarium strains in the section was examined by inter-simple sequence repeats (ISSR). Fifteen selected ISSR primers were adopted to do amplification, and a total of 239 bands were amplified, among which, 230 (96.2%) were polymorphic, with an average of 15.3 polymorphic bands per primer. The genetic similarity ranged from 0.494 to 0.933, with an average of 0.640. All the test strains were clustered into two groups at genetic similarity of 0.593. The strains 1-17 were grouped into IG-I, belonging to Fusarium solani and F. solani var. coeruleum, while the strains 18-21 were grouped into IG-II, belonging to F. ventricosum. All the 21 strains could be entirely distinguished at genetic similarity of 0. 933. The SSR loci in the Fusarium genomes were rich in polymorphism. The ISSR grouping had definite correlation with the species classification, but less correlation with the geographic origin of the strains. Within the same ISSR groups, there existed definite correlation between the genetic similarity and the geographic origin of the strains. Within the same species collected from the same regions and same host plants, there existed definite genetic difference among the strains of the same species.

Background and Aim: The majority of patients who undergo orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have a very good prognosis if the tumor is within the Milan criteria. However, 10-15% of patients will have reoccurrence after OLT. Currently, sorafenib is available for advanced HCC. The safety and efficacy of sorafenib in this population has not been reported., Methods: We retrospectively looked at 54 patients who received sorafenib for advanced HCC. Out of 54 patients, we analyzed 9 who received sorafenib after OLT for HCC reoccurrence at Cleveland Clinic., Result: The median age at the time treatment with sorafenib was initiated was 59 years (range 46-77). Two patients received prior local therapy. Most of the toxicity was expected side effects from sorafenib except in 1 patient who developed hematological toxicity. Six patients required dose reduction secondary to toxicity. There were no unexpected complications from interaction with immunosuppressive medication. One patient achieved complete radiographic remission. Median survival from the start of sorafenib had not been reached at the time of writing; however, the 4-month survival rate is currently estimated to be 84 ± 15%, and 1 patient with lung reoccurrence has been treated for almost 18 months thus far., Conclusion: Sorafenib can be used in patients with recurrent HCC after liver transplantation with tolerable toxicity; however, dose adjustment may be required. A larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients., (Copyright © 2010 S. Karger AG, Basel.)

As gastroduodenoscopy performed more frequently, case reports of human echinostomiasis are increasing in Korea. A Korean woman presented at a local clinic with complaints of abdominal pain and discomfort that had persisted for 2 weeks. Under gastroduodenoscopy, two motile flukes were found attached on the duodenal bulb, and retrieved with endoscopic forceps. She had history of eating raw frog meat. The two flukes were identified as Echinostoma hortense by egg morphology, 27 collar spines with 4 end-group spines, and surface ultrastructural characters. This report may prove frogs to be a source of human echinostome infections.

Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been associated with intrinsic aging and environmental insult. Recently, mtDNA mutations have been detected in various tumors, including head and neck tumors. However, the factors affecting the occurrence and accumulation of mtDNA deletions in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral tissues from the patients with or without betel quid chewing history. The results revealed that irrespective of the history of betel quid chewing, the incidences of the 4977bp deletion and other deletions of mtDNA were lower in the tumor portion as compared with the non-tumor portion. The average proportions of the 4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel quid chewers were 13- and 5-fold, respectively, lower than those in the corresponding non-tumor tissues. Moreover, the average proportion of 4977bp deleted mtDNA was significantly higher (P<0.05) in the non-tumor oral tissues of the patients with betel quid chewing history than that of the patients without the history of betel quid chewing. These results suggest that betel quid chewing may increase mtDNA mutation in human oral tissues and that accumulation of mtDNA deletions and subsequent cytoplasmic segregation of these mutations during cell division could be an important contributor to the early phase of oral carcinogenesis.

All experiments were carried out in a prototype vortexing fluidized bed combustor (VFBC). The dimension of the combustion chamber is 0.7 x 1.4 x 2 m, and the freeboard section is 1 m i.d. and 4 m in height. Paper sludge was used as the feeding material. Two types of coal particles were employed as the supplementary fuel. In order to understand the characteristics of the VFBC system for paper sludge incineration, the effect of various operating parameters, such as the primary airflow, excess air ratio, and secondary airflow rates, on temperature distribution, ash elutriation, combustion efficiency, and pollutant emissions were investigated.

X-ray absorption near-edge structure (XANES) measurements have been performed on nitrogen-doped diamond films with three different dopant concentrations and iron-layer-stabilized carbon nanotube (CNT) structures with various diameters at the C K-absorption edge using the sample drain current mode. The C K-edge XANES spectra of these N-doped diamond films resemble that of the undoped diamond regardless of the dopant concentration, which suggest that the overall bonding configuration of the C atom is unaltered. N dopants are found to reduce the intensities of both the sp2- and sp3-bond-derived resonance features in the XANES spectra. On the other hand, the C K-edge XANES spectra of CNTs indicate that the intensities of the pi* and sigma* bands and the interlayer-state features vary with the diameter of the CNT. This phenomenon may be caused by the Fe-layer-catalysed bending of the graphite sheet and the interaction between C and Fe atoms.

Since its introduction in 1952, isoniazid has remained one of the drugs of choice in the treatment and prophylaxis of tuberculosis. In populations with a high prevalence rate of tuberculosis or suicide rate, acute ingestion of isoniazid has occasionally been reported. Acute intoxication by isoniazid is known to cause symptoms of seizures, metabolic acidosis, coma, and even death. These clinical symptoms, however, are not well recognized by physicians in Taiwan, even though the prevalence rate of tuberculosis is relatively high here. This report concerns the case of a 25-year-old female with a past history of tuberculosis who presented with the symptoms of refractory seizures, metabolic acidosis and deep coma after intentional ingestion of some unknown drug. Although implicating agents were not recognized initially, she was successfully revived with basic resuscitation, anticonvulsants and correction of metabolic acidosis. A review of her history revealed that her ingestion of five grams of isoniazid in this case was responsible for the entire clinical spectrum. Given easy access to isoniazid in Taiwan, a diagnosis of isoniazid poisoning should always be considered in patients who present with the classical symptoms of refractory seizures, metabolic acidosis and coma.

Based on a galactose oxidase/NaB[3H]4 technique of radiolabeling macromolecules, the major glycoconjugate (lipophosphoglycan) of Leishmania donovani promastigotes was determined to be located on the cell surface. Incorporated radioactivity was analyzed by gel filtration on Sephadex G-100, chromatography on ricin agglutinin-coupled agarose, and lability to mild acid hydrolysis. Lipophosphoglycan was present throughout the various phases of growth of promastigotes, but was preferentially expressed during the latter part of logarithmic phase and in the stationary phase. In addition, metabolically labeled lipophosphoglycan was released into the culture medium. Expression of this unusual glycoconjugate on the cell surface of L. donovani suggests that it may play a major role in host cell-parasite interactions.

The LAC12 gene of Kluyveromyces lactis codes for an inducible lactose permease. We have determined the nucleotide sequence of a DNA fragment which includes the complete LAC12 gene. The 4.7-kilobase (kb) mRNA carrying LAC12 contained two open reading frames, ORFI (1761 bases) and ORFII (1266 bases), separated by a 573-base pair noncoding region. Mung bean and exonuclease VII mapping showed that there was no splicing of the 4.7-kb transcript and thus no intron between the two open reading frames. Chromosomal disruption of ORFI with the URA3 gene destroyed lactose transport activity, suggesting that ORFI codes for a component of the permease. Disruption of ORFII and the noncoding region between the two open reading frames did not affect the lactose permease function, indicating that they do not comprise a part of the permease. We do not know if ORFII is translated, but in either case, the structure of the 4.7-kb mRNA is unusual. We discuss possible origins for it. The peptide predicted from ORFI is hydrophobic as would be expected for a membrane-bound protein. Compared with other membrane proteins, LAC12 (ORFI) protein showed sequence similarity to the human glucose and the Escherichia coli xylose-H+ and arabinose-H+ transporters. No obvious amino acid sequence similarity was found with the lactose permease of E. coli.

Polyacrylamide gel slabs can be dried quickly without elaborate tools and the results are similar or even better than those obtained with a commercial drying apparatus. The discontinuous, sodium dodecyl sulfate, and gradient polyacrylamide gel slabs yielded similar results regardless of the staining methods, e.g., Coomassie blue, periodate-Schiff's reagent, or ammoniacal silver.

We present a case of acute leukemic infiltration in the distal phalanx of the thumb, resulting in a chronic felon with bone involement.