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Background/purpose: In Taiwan, there are very few dental radiology curricula in medical radiation education system. This study assessed the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan., Materials and Methods: This study used the questionnaire survey to evaluate the participants' learning outcomes after finishing the dental radiology course for the continuing education of medical radiation technologists in Taiwan., Results: In this study, 85 participants filled out the questionnaires completely after finishing the dental radiology course. The majority of participants agreed that dental radiology courses were rare in the medical radiation school curricula and the continuing education courses of medical radiation technologists. Moreover, most of participants found this course to be helpful in raising their basic knowledge about the dental radiology, their attitude towards the dental radiology, and their interest in further learning of the dental radiology. They were satisfied with the courses. The degree of agreement for each question was high with all the mean scores for each question being between 3.87 and 4.61. The numbers (rates) of respondents who answered as agree were between 58 (68.24%) and 84 (98.82%)., Conclusion: The dental radiology course for the continuing education of medical radiation technologists is found to increase the participants' basic knowledge about the dental radiology, and their awareness and understanding of the radiation protection in dental radiography. Thus, this model can be further used for the dental radiology course for the continuing education of medical radiation technologists in Taiwan., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Objectives . Studies have highlighted that healthcare workers are exposed to various forms of psychological distress. This study aimed to assess the psychological well-being of pharmacy staff during the COVID-19 pandemic and the associating factors. Methods . The cross-sectional study explored the psychological well-being of pharmacy staff during the COVID-19 pandemic. An adopted questionnaire was employed to collect quantitative data from January 1, 2021 to June 30, 2021. Results . A total of 515 respondents were recruited. Those who perceived good health status were 1.9 times more likely to have normal depression scores (relative risk ratio [RRR] = 0.53; B  = -0.64), and 2.4 times (RRR = 0.41; B  = -0.88) more likely to have normal stress scores. Those who were greatly affected by COVID-19 in their work were found to be 1.2 times (RRR = 1.20; B  = 0.18) more likely to have moderate anxiety scores and 1.44 times (RRR = 1.44; B  = 0.36) more likely to have severe depression scores. Respondents with higher work characteristic scores were more likely to have normal depression, stress and anxiety scores. Conclusions . Good health status perception and work characteristics appeared to be the factors affecting respondents' scores in all dimensions of psychological well-being. Hence, improving both domains will be key in improving overall psychological well-being.

Background: Tuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission., Objectives: This study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption., Methods: A multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance., Results: Of 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0-2), medium (3-5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001)., Conclusion: The predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the level of family caregivers' (FC) burden and the extent to which patient- and caregiver-related factors influence the caregiving burden among FCs of urologic cancer (UC) patients., Method: A cross-sectional survey was conducted on caregivers of UC patients who sought cancer care. The modified caregiver strain index (MCSI) was used to assess FC burden., Results: Just over half (54.3%) of FCs had moderate/high MCSI scores (score 9-26). By demographics, FCs who were unemployed (OR = 5.55, 95%CI 1.50-20.60) and perceived their current health condition as moderate/poor (OR = 6.05, 95%CI 1.95-18.78) reported higher odds of increased FC burden. Patient performance status played a pivotal role in exacerbating FC burden, whereby the odds of higher FC burden was 13 times higher in caregivers of UC patients having an Eastern Cooperative Oncology Group (ECOG) performance rating score of 3-4 (OR = 13.06, 95%CI 1.44-111.26) than those with a score of 0. Perceived lower levels of confidence in care provision were significantly associated with a higher level of strain (OR = 6.76, 985%CI 1.02-44.90)., Conclusion: Care recipient performance status was a strong patient-related factor associated with higher FC burden regardless of duration of caregiving and other caregiver-related factors after adjusting for caregiver demographics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption., Methods: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant., Results: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%)., Conclusion: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem., (© 2024 John Wiley & Sons Ltd.)

Aims: This study presents a protocol for the Pharmacy Integrated Community Care (PICC) program, meticulously designed to enhance Hemoglobin A1c (HbA1c) levels and augment knowledge about diabetes mellitus (DM) among individuals diagnosed with Type 2 Diabetes Mellitus (T2DM) in the Sarawak State of Malaysia., Methods: From 1 May to December 31, 2023, a prospective, multicenter, parallel-design randomised controlled trial will be conducted with two groups, each consisting of 47 participants. The intervention group will receive a structured, four-session group-based program guided by experienced pharmacists, focusing on medication adherence and diabetes management. The control group will follow the standard Diabetes Mellitus Adherence Clinic program. The primary outcomes of this study encompass enhancements in knowledge regarding diabetes medication management and adherence, followed by subsequent changes in HbA1c levels., Conclusions: The successful implementation of the PICC program holds promise for enhancing health outcomes in the T2DM population, potentially leading to more effective diabetes management initiatives and better health practices in the community., Trial Registration Clinicaltrialsgov Identifier: NCT05106231., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Lysosomes are central to metabolic homeostasis. The microphthalmia bHLH-LZ transcription factors (MiT/TFEs) family members MITF, TFEB, and TFE3 promote the transcription of lysosomal and autophagic genes and are often deregulated in cancer. Here, we show that the GATOR2 complex, an activator of the metabolic regulator TORC1, maintains lysosomal function by protecting MiT/TFEs from proteasomal degradation independent of TORC1, GATOR1, and the RAG GTPase. We determine that in GATOR2 knockout HeLa cells, members of the MiT/TFEs family are ubiquitylated by a trio of E3 ligases and are degraded, resulting in lysosome dysfunction. Additionally, we demonstrate that GATOR2 protects MiT/TFE proteins in pancreatic ductal adenocarcinoma and Xp11 translocation renal cell carcinoma, two cancers that are driven by MiT/TFE hyperactivation. In summary, we find that the GATOR2 complex has independent roles in TORC1 regulation and MiT/TFE protein protection and thus is central to coordinating cellular metabolism with control of the lysosomal-autophagic system., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: The COVID-19 pandemic has fueled the widespread adoption of telemedicine in healthcare, particularly in Sarawak, Malaysia. This study investigates the use and acceptance of Sarawak's inaugural multidisciplinary geriatric telemedicine service, TELEG., Methods: This cross-sectional study took place at the Sarawak Heart Centre's geriatric department from July 1, 2021, to April 30, 2022. Convenient sampling included all TELEG-enrolled patients during this period, to achieve minimum sample size of 148. TELEG's utilization was assessed in terms of medication therapy and treatment plan optimization, as well as enhanced healthcare accessibility. Participants' acceptance of TELEG was measured using the Service User Technology Acceptability Questionnaire (SUTAQ) administered through Google Forms. Descriptive statistics percentages illustrated the proportion of participants who found TELEG moderately to highly acceptable. Associations between baseline characteristics and overall acceptance were explored through bivariate analyses, including Pearson's correlation test, independent t-test, and ANOVA. The influence of six SUTAQ dimensions on overall acceptance, multivariable linear regression using enter method was employed. Statistical significance was determined by p-values less than 0.5., Results: Among 180 geriatric patients enrolled in TELEG during the study period, 149 agreed to participate. TELEG led to medication therapy optimization for 88.6% of participants, primarily involving dose adjustment (44.7%), de-prescribing (31.8%), and prescribing (15.9%). Additionally, 53.8% received treatment plan optimization, predominantly in the form of self-care education (56.3%), referrals for further treatment (33.8%), additional laboratory investigations (29.6%), and increased monitoring (26.8%). Among those educated in self-care (n = 40), dietary intake (27.5%), lower limb exercise (25.0%), and COVID-19 vaccination (12.5%) were the most common topics. All participants expressed moderate to high acceptance of TELEG (mean = 4.9, SD = 0.65, on a scale of 1 to 6). Notably, care personnel concern (B = 0.256; p < 0.001) had the most significant impact on overall acceptance., Conclusion: This pioneering study evaluates the utilization and user acceptance of a geriatric telemedicine service in the region, providing valuable insights to support its expansion. Follow-up surveys or interviews to gain insights into users' experiences are crucial to further enhance acceptance., (© 2024. The Author(s).)

In 1999, the Polynomial Reconstruction Problem (PRP) was put forward as a new hard mathematics problem. A univariate PRP scheme by Augot and Finiasz was introduced at Eurocrypt in 2003, and this cryptosystem was fully cryptanalyzed in 2004. In 2013, a bivariate PRP cryptosystem was developed, which is a modified version of Augot and Finiasz's original work. This study describes a decryption failure that can occur in both cryptosystems. We demonstrate that when the error has a weight greater than the number of monomials in a secret polynomial, p , decryption failure can occur. The result of this study also determines the upper bound that should be applied to avoid decryption failure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

In recent research, Durandal, a signature scheme based on rank metrics following Schnorr's approach, was introduced to conceal secret key information by selectively manipulating the vector subspace of signatures. Later, an enhancement, namely the SHMW signature scheme, with smaller keys and signatures while maintaining EUF-CMA security, was proposed. Both Durandal and SHMW require adversaries to solve hard problems (i.e., Rank Support Learning, Rank Syndrome Decoding, and Affine Rank Syndrome Decoding) for secret key retrieval, in which the parameters are designed to withstand at least 128-bit computational complexity. The authors claimed that the security of the SHMW scheme is deemed superior to that of the original Durandal scheme. In this paper, we introduce a novel approach to identifying weak keys within the Durandal framework to prove the superiority of the SHMW scheme. This approach exploits the extra information in the signature to compute an intersection space that contains the secret key. Consequently, a cryptanalysis of the SHMW signature scheme was carried out to demonstrate the insecurity of the selected keys within the SHWM scheme. In particular, we proposed an algorithm to recover an extended support that contains the secret key used in the signature schemes. Applying our approach to the SHMW scheme, we can recover its secret key with only 97-bit complexity, although it was claimed that the proposed parameters achieve a 128-bit security level. The results of our proposed approaches show that the security level of the SHMW signature scheme is inferior compared to that of the original Durandal scheme., Competing Interests: The authors declare that they do not have any known competing financial interests or personal relationships that could have influenced the work reported in this paper., (© 2024 The Author(s).)

Background: This study aimed to evaluate the implementation stage of Malaysia's GeKo-Integrated Service Delivery (ISD) model for frailty management in primary care and explore its effectiveness in improving frailty scores., Methods: The implementation stage of Malaysia's first three GeKo- ISD clinics was assessed using the WHO-ICOPE (Integrated Care of the Older Persons) scorecard. This involved evaluating documents related to the GeKo services and conducting in-depth interviews with key informants identified from those documents. The efficacy of GeKo-ISD was assessed by documenting the change in mean frailty scores between baseline and 3 months post intervention, measured by the Pictorial Fit Frail Scale Malay Version (PFFS-M), in patients who received GeKo-ISD care from October 2022 to April 2023., Results: All three GeKo clinics achieved the sustaining implementation level, scoring a total of 50 out of 52. The paired t-test reported a significant reduction (p= 0.001) in the PFFS-M scores from baseline to 3 months after the GeKo-ISD intervention. The mean (SD) scores were 8.6 (4.6) at baseline and 7.0 (4.1) at 3 months post-intervention., Conclusion: GeKo-ISD is a comprehensive approach of integrated care for older people, leveraging existing public funded primary care infrastructure. It shows promise, was impacted by the pandemic but now, with support from the government, exists in 32 centers across one state in Malaysia., Competing Interests: Dr. Olga Theou and Kenneth Rockwood have asserted copyright of the Pictorial Fit-Frail Scale, which is made freely available for education, research, and not-for-profit health care. Licenses for commercial use are facilitated through the Dalhousie Office of Commercialization and Industry Engagement. All other authors have no conflict of interest to disclose in relation to this research.

Background: Remuscularization of the mammalian heart can be achieved after cell transplantation of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs). However, several hurdles remain before implementation into clinical practice. Poor survival of the implanted cells is related to insufficient vascularization, and the potential for fatal arrhythmogenesis is associated with the fetal cell-like nature of immature CMs., Methods: We generated 3 lines of hiPSC-derived endothelial cells (ECs) and hiPSC-CMs from 3 independent donors and tested hiPSC-CM sarcomeric length, gap junction protein, and calcium-handling ability in coculture with ECs. Next, we examined the therapeutic effect of the cotransplantation of hiPSC-ECs and hiPSC-CMs in nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice undergoing myocardial infarction (n≥4). Cardiac function was assessed by echocardiography, whereas arrhythmic events were recorded using 3-lead ECGs. We further used healthy non-human primates (n=4) with cell injection to study the cell engraftment, maturation, and integration of transplanted hiPSC-CMs, alone or along with hiPSC-ECs, by histological analysis. Last, we tested the cell therapy in ischemic reperfusion injury in non-human primates (n=4, 3, and 4 for EC+CM, CM, and control, respectively). Cardiac function was evaluated by echocardiography and cardiac MRI, whereas arrhythmic events were monitored by telemetric ECG recorders. Cell engraftment, angiogenesis, and host-graft integration of human grafts were also investigated., Results: We demonstrated that human iPSC-ECs promote the maturity and function of hiPSC-CMs in vitro and in vivo. When cocultured with ECs, CMs showed more mature phenotypes in cellular structure and function. In the mouse model, cotransplantation augmented the EC-accompanied vascularization in the grafts, promoted the maturity of CMs at the infarct area, and improved cardiac function after myocardial infarction. Furthermore, in non-human primates, transplantation of ECs and CMs significantly enhanced graft size and vasculature and improved cardiac function after ischemic reperfusion., Conclusions: These results demonstrate the synergistic effect of combining iPSC-derived ECs and CMs for therapy in the postmyocardial infarction heart, enabling a promising strategy toward clinical translation., Competing Interests: Disclosures None.

Omecamtiv mecarbil (OM, CK-1827452) is recognized as an activator of myosin and has been demonstrated to be beneficial for the treatment of systolic heart failure. However, the mechanisms by which this compound interacts with ionic currents in electrically excitable cells remain largely unknown. The objective of this study was to investigate the effects of OM on ionic currents in GH3 pituitary cells and Neuro-2a neuroblastoma cells. In GH 3 cells, whole-cell current recordings showed that the addition of OM had different potencies in stimulating the transient ( I Na(T) ) and late components ( I Na(L) ) of the voltage-gated Na + current ( I Na ) with different potencies in GH 3 cells. The EC 50 value required to observe the stimulatory effect of this compound on I Na(T) or I Na(L) in GH 3 cells was found to be 15.8 and 2.3 µM, respectively. Exposure to OM did not affect the current versus voltage relationship of I Na(T) . However, the steady-state inactivation curve of the current was observed to shift towards a depolarized potential of approximately 11 mV, with no changes in the slope factor of the curve. The addition of OM resulted in an increase in the decaying time constant during the cumulative inhibition of I Na(T) in response to pulse-train depolarizing stimuli. Furthermore, the presence of OM led to a shortening of the recovery time constant in the slow inactivation of I Na(T) . Adding OM also resulted in an augmentation of the strength of the window Na + current, which was evoked by a short ascending ramp voltage. However, the OM exposure had little to no effect on the magnitude of L-type Ca 2+ currents in GH 3 cells. On the other hand, the delayed-rectifier K + currents in GH 3 cells were observed to be mildly suppressed in its presence. Neuro-2a cells also showed a susceptibility to the differential stimulation of I Na(T) or I Na(L) upon the addition of OM. Molecular analysis revealed potential interactions between the OM molecule and hNa V 1.7 channels. Overall, the direct stimulation of I Na(T) and I Na(L) by OM is assumed to not be mediated by an interaction with myosin, and this has potential implications for its pharmacological or therapeutic actions occurring in vivo.

Behavioural sleep problems are very common in children and are concerns for many parents. This review discusses normal sleep physiology and sleep development and focuses on common behavioural sleep problems in childhood, including behavioural insomnia of childhood, parasomnias and sleep-related movement disorders, highlighting their clinical features and management. Behavioural insomnia of childhood is characterised by learned difficulties in falling asleep and/or staying asleep. Management includes establishing bedtime routines and behavioural techniques. Parasomnias include confusional arousals, sleepwalking, sleep terrors and nightmares, and these usually resolve with time. Management includes parental reassurance and behavioural interventions such as scheduled awakening. With regards to sleep enuresis, management includes behavioural modifications, enuresis alarm and desmopressin. Sleep-related movement disorders include sleep-related bruxism and sleep-related rhythmic movements, of which body rocking is the most common. Early identification and management of behavioural sleep problems may prevent their negative impact on children as well as their families., Competing Interests: None

Target of Rapamycin Complex I (TORC1) is a central regulator of metabolism in eukaryotes that responds to a wide array of negative and positive inputs. The GTPase-activating protein toward Rags (GATOR) signaling pathway acts upstream of TORC1 and is comprised of two subcomplexes. The trimeric GATOR1 complex inhibits TORC1 activity in response to amino acid limitation by serving as a GTPase-activating protein (GAP) for the TORC1 activator RagA/B, a component of the lysosomally located Rag GTPase. The multi-protein GATOR2 complex inhibits the activity of GATOR1 and thus promotes TORC1 activation. Here we report that Wdr59, originally assigned to the GATOR2 complex based on studies performed in tissue culture cells, unexpectedly has a dual function in TORC1 regulation in Drosophila . We find that in the ovary and the eye imaginal disc brain complex, Wdr59 inhibits TORC1 activity by opposing the GATOR2-dependent inhibition of GATOR1. Conversely, in the Drosophila fat body, Wdr59 promotes the accumulation of the GATOR2 component Mio and is required for TORC1 activation. Similarly, in mammalian HeLa cells, Wdr59 prevents the proteolytic destruction of GATOR2 proteins Mio and Wdr24. Consistent with the reduced levels of the TORC1-activating GATOR2 complex, Wdr59KOs HeLa cells have reduced TORC1 activity which is restored along with GATOR2 protein levels upon proteasome inhibition. Taken together, our data support the model that the Wdr59 component of the GATOR2 complex functions to promote or inhibit TORC1 activity depending on cellular context.

Background: The computer simulation presented in this study aimed to investigate the effect of contact tracing on coronavirus disease 2019 (COVID-19) transmission and infection in the context of rising vaccination rates., Methods: This study proposed a deterministic, compartmental model with contact tracing and vaccination components. We defined contact tracing effectiveness as the proportion of contacts of a positive case that was successfully traced and the vaccination rate as the proportion of daily doses administered per population in Malaysia. Sensitivity analyses on the untraced and infectious populations were conducted., Results: At a vaccination rate of 1.4%, contact tracing with an effectiveness of 70% could delay the peak of untraced asymptomatic cases by 17 d and reduce it by 70% compared with 30% contact tracing effectiveness. A similar trend was observed for symptomatic cases when a similar experiment setting was used. We also performed sensitivity analyses by using different combinations of contact tracing effectiveness and vaccination rates. In all scenarios, the effect of contact tracing on COVID-19 incidence persisted for both asymptomatic and symptomatic cases., Conclusions: While vaccines are progressively rolled out, efficient contact tracing must be rapidly implemented concurrently to reach, find, test, isolate and support the affected populations to bring COVID-19 under control., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Diagnostic accuracy of double-contrast barium enema (DCBE) depends upon the barium sulfate coating efficiency in the colon., Objective: To evaluate effects of three laxatives on barium sulfate coating efficiency in the large intestine, sigmoid colon, and hepatic flexure in DCBE., Methods: This retrospective study included patients receiving DCBE after pre-procedure cleansing with Dulcolax ® with castor oil (DC), Klean-Prep ® (KP), or Fleet ® . Patients' DCBE images were reviewed., Results: Among 373 cases of DCBE, 151 received DC, 147 received KP, and 75 received Fleet. For DCBE, the optimal extent of barium sulfate residue coated on the wall of the large intestine is less than one-fourth of bowel wall width; the DC group had a higher percentage of less than one-fourth of bowel wall than that of the KP or Fleet group (both p < 0.0167). DC, KP and Fleet have comparable barium sulfate coating efficiency in the sigmoid colon. However, in the hepatic flexure, the DC group had a higher percentage of barium sulfate coating without interruption than that of the KP or Fleet groups (both p < 0.0167)., Conclusion: DC has a better barium sulfate coating efficiency in the hepatic flexure compared with KP and Fleet., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Routine categorization of DLBCL patients into GCB and non-GCB groups by Hans' criteria could not accurately predict chemotherapy resistance and disease progression in patients treated with standard R-CHOP therapy. There is a need to identify better biomarker predictors to enhance assisted selection of chemotherapy regimens for DLBCL patients., Aim of the Study: To identify dysregulated miRNAs and mRNAs that are predictive of resistance to R-CHOP chemotherapy or disease progression in patients with DLBCL., Methods: miRNA and mRNA profiling were performed on archival FFPE samples of the DLBCL patients. miRabel and miRNet bioinformatic tools were applied to determine experimental validated miRNA-mRNA target interaction. The significance of the genomic predictive values was assessed using adjusted odds ratios (AOR) and 95% confidence intervals (CI)., Results: 19/36 were R-CHOP therapy-resistant whilst 17/36 were R-CHOP therapy-sensitive. Ten dysregulated miRNAs and 12 dysregulated mRNAs were identified in therapy-resistant DLBCL patients. These dysregulated miRNAs and mRNA cause therapy resistance and disease progression in DLBCL patients, most likely via upregulation of the anti-apoptotic protein bcl2, activation of the JAK/STAT signalling pathway and dysregulation of p53 pathway. Downregulation of hsa-miR-548d-3p and overexpression of HOXA9 mRNA were significantly associated with therapy resistance and disease progression in DLBCL patients [hsa-miR-548d-3p AOR: 0.258, 95%CI: 0.097-0.684, p = 0.006]., Conclusion: DLBCL patients with downregulation of hsa-miR-548d-3p and overexpression of HOXA9 mRNA are more likely to experience R-CHOP therapy resistance and disease progression., (© 2022 John Wiley & Sons Ltd.)

Background/purpose: The development of dental radiology in Taiwan has been over a century. This study explored mainly the profile of dental radiation workers and their occupational radiation exposure in Taiwan from 2013 to 2020., Materials and Methods: This study used the secondary data analysis to survey mainly the changes of manpower of the dental radiation workers and their occupational radiation exposure in Taiwan from 2013 to 2020., Results: The number of monitored dental radiation workers increased from 678 in 2013 to 770 in 2020. However, the proportion of monitored dental radiation workers to the total monitored medical radiation workers decreased from 4.29% in 2013 to 3.67% in 2020. Although the number of monitored dental radiation workers increased, the number of the measurably exposed dental radiation workers decreased from 2013 to 2020. The annual collective exposure dose fluctuated from 5.21 man-Sv to 15.47 man-Sv, but it showed a decreasing trend. Furthermore, the mean annual effective exposure dose of total monitored dental radiation workers (0.01-0.02 mSv) and that of the measurably exposed dental radiation workers (0.15-1.11 mSv) were relatively low among various medical radiation workers. In overall, the proportion of medical radiation technologists to dentists varied from 0.41 to 0.45., Conclusion: Although the number of monitored dental radiation workers increase, the number of the measurably exposed dental radiation workers, the proportion of the measurably exposed dental radiation workers to the total monitored dental radiation workers, and the annual collective exposure dose for monitored dental radiation workers decrease from 2013 to 2020., Competing Interests: A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. JDS Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distinguish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to disclose all and any potential conflicts of interest., (© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Optimizing the Diels-Alder (DA) reaction for aqueous coupling has resulted in practical methods to link molecules such as drugs and diagnostic agents to proteins. Both normal electron demand (NED) and inverse electron demand (IED) DA coupling schemes have been employed, but neither mechanism entails a common multipurpose reactive group. This report focuses on expanding the bioconjugation toolbox for cyclopentadiene through the identification of reactive groups that couple through NED or IED mechanisms in aqueous solution. Dienophiles and tetrazine derivatives were screened for reactivity and selectivity toward antibodies bearing cyclopentadiene amino acids to yield bioconjugates. Twelve NED dienophiles and four tetrazine-based IED substrates were identified as capable of practical biocoupling. Furthermore, tetrazine ligation to cyclopentadiene occurred at a rate of 3.3 ± 0.5 M -1 s -1 and was capable of bioorthogonal transformations, as evidenced by the selective protein labeling in serum. Finally, an antibody-drug conjugate (ADC)-bearing monomethyl auristatin E was prepared via tetrazine conjugation to cyclopentadiene. The resulting ADC was stable and demonstrated potent activity in vitro . These findings expand the utility of cyclopentadiene as a tool to couple entities to proteins via dual DA addition mechanisms.

Since December 2019, the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected ~435 million people and caused ~6 million related deaths as of March 2022. To combat COVID-19, there have been many attempts to repurpose FDA-approved drugs or revive old drugs. However, many of the current treatment options have been known to cause adverse drug reactions. We employed a population-based drug screening platform using 13 human leukocyte antigen (HLA) homozygous human induced pluripotent cell (iPSC) lines to assess the cardiotoxicity and neurotoxicity of the first line of anti-COVID-19 drugs. We also infected iPSC-derived cells to understand the viral infection of cardiomyocytes and neurons. We found that iPSC-derived cardiomyocytes express the ACE2 receptor which correlated with a higher infection of the SARS-CoV-2 virus (r = 0.86). However, we were unable to detect ACE2 expression in neurons which correlated with a low infection rate. We then assessed the toxicity of anti-COVID-19 drugs and identified two cardiotoxic compounds (remdesivir and arbidol) and four neurotoxic compounds (arbidol, remdesivir, hydroxychloroquine, and chloroquine). These data show that this platform can quickly and easily be employed to further our understanding of cell-specific infection and identify drug toxicity of potential treatment options helping clinicians better decide on treatment options.

The advent of induced pluripotent stem cells (iPSCs) has advanced our understanding of the molecular mechanisms of human disease, drug discovery, and regenerative medicine. As such, the use of iPSCs in drug development and validation has shown a sharp increase in the past 15 years. Furthermore, many labs have been successful in reproducing many disease phenotypes, often difficult or impossible to capture, in commonly used cell lines or animal models. However, there still remain limitations such as the variability between iPSC lines as well as their maturity. Here, we aim to discuss the strategies in generating iPSC-derived cardiomyocytes and neurons for use in disease modeling, drug development and their use in cell therapy.

Background: Guided by the best practices adapted from national and international bodies including the World Health Organization (WHO), the Centers for Disease Control (CDC), and the UK Joint Biosecurity Centre (JBC), this paper aims to develop and provide an empirical risk stratification and assessment framework for advancing the safe resumption of global travel during the COVID-19 pandemic., Method: Variables included in our model are categorized into four pillars: (i) incidence of cases, (ii) reliability of case data, (iii) vaccination, and (iv) variant surveillance. These measures are combined based on weights that reflect their corresponding importance in risk assessment within the context of the pandemic to calculate the risk score for each country. As a validation step, the outcome of the risk stratification from our model is compared against four countries., Results: Our model is found to have good agreement with these benchmarked risk designations for 27 out of the top 30 countries with the strongest travel ties to Malaysia (90%). Each factor within this model signifies its importance and can be adapted by governing bodies to address the changing needs of border control policies for the recommencement of international travel., Conclusion: In practice, the proposed model provides a turnkey solution for nations to manage transmission risk by enabling stakeholders to make informed, evidence-based decisions to minimize fluctuations of imported cases and serves as a structure to support the improvement, planning, and activation of public health control measures., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, we establish a population-based human induced pluripotent stem cell (hiPSC) drug screening platform for toxicity assessment. After recruiting 1,000 healthy donors and screening for high-frequency human leukocyte antigen (HLA) haplotypes, we identify 13 HLA-homozygous "super donors" to represent the population. These "super donors" are also expected to represent at least 477,611,135 of the global population. By differentiating these representative hiPSCs into cardiomyocytes and neurons we show their utility in a high-throughput toxicity screen. To validate hit compounds, we demonstrate dose-dependent toxicity of the hit compounds and assess functional modulation. We also show reproducible in vivo drug toxicity results using mouse models with select hit compounds. This study shows the feasibility of using a population-based hiPSC drug screening platform to assess cytotoxicity, which can be used as an innovative tool to study inter-population differences in drug toxicity and adverse drug reactions in drug discovery applications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: None.

Competing Interests: Author(s) declared no competing interest.

Background: Medical imaging plays a crucial role in modern medicine. In order to provide fast and accurate medical diagnosis, computed tomography (CT) is a commonly used tool in radiological examinations, and 640-slice CT is the most advanced CT imaging modality., Objective: To evaluate the radiation dose and the risk under 640-slice abdominal CT examination., Methods: Examinations were performed using a 640-slice CT scanner on an Alderson-Rando anthropomorphic phantom. The used scanning acquisition parameters were the same as those used on abdominal examination without contrast medium injection in clinical practice. To measure the absorbed doses, optically stimulated luminescence dosimeters (OSLDs) were put into liver, stomach, bladder, gonads, colon, small intestine, bone marrow, and skin., Results: According to the 1990 Recommendations of the International Commission on Radiological Protection (ICRP Publication 60), the calculated effective doses received from this examination were 0.90 mSv in males and 0.89 mSv in females. According to the 2007 Recommendations of the International Commission on Radiological Protection (ICRP Publication 103), the calculated effective dose received from this examination was 0.83 mSv in both sexes., Conclusions: Radiation doses obtained from the abdominal 640-slice CT examination are lower than the yearly cumulative doses received from natural radiation, revealing there is no deterministic effect and radiation risk is relatively low; therefore, this CT examination is considered safe.

Background: Radiation using conventional X-ray is associated with exposure of radiosensitive organs and typically requires the use of protection. This study is aimed at evaluating the use of bismuth shielding for radiation protection in pediatric pelvic radiography. The effects of the anteroposterior and lateral bismuth shielding were verified by direct measurements at the anatomical position of the gonads., Methods: Radiation doses were measured using optically stimulated luminescence dosimeters (OSLD) and CIRS ATOM Dosimetry Verification Phantoms. Gonad radiographs were acquired using different shields of varying material (lead, bismuth) and thickness and were compared with radiographs obtained without shielding to examine the effects on image quality and optimal reduction of radiation dose. All images were evaluated separately by three pediatric orthopedic practitioners., Results: Results showed that conventional lead gonadal shielding reduces radiation doses by 67.45%, whereas dose reduction using one layer of bismuth shielding is 76.38%. The use of two layers of bismuth shielding reduces the dose by 84.01%. Using three and four layers of bismuth shielding reduces dose by 97.33% and 99.34%, respectively. Progressively lower radiation doses can be achieved by increasing the number of bismuth layers. Images obtained using both one and two layers of bismuth shielding provided adequate diagnostic information, but those obtained using three or four layers of bismuth shielding were inadequate for diagnosis., Conclusions: Bismuth shielding reduces radiation dose exposure providing appropriate protection for children undergoing pelvic radiography. The bismuth shielding material is lighter than lead, making pediatric patients more comfortable and less apt to move, thereby avoiding repeat radiography., Competing Interests: The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2021 Bow Wang et al.)

Objectives: This study aimed to investigate the psychological distress and its associated factors among cancer survivors in Malaysia during the COVID-19 pandemic., Methods: An anonymous Internet-based study was conducted between 23 April and 26 June 2020. During the study period, the country underwent phase 3 and phase 4 of the Movement Control Order (MCO), Conditional Movement Control Order (CMCO), and Recovery Movement Control Order (RMCO). Psychological distress was measured using the Hospital Anxiety and Depression Scale (HADS), which is a 14-item self-assessment scale for measuring distress (total HADS score; HADS-T) with two subscales, namely, anxiety (HADS-A) and depression (HADS-D). Perceived threat of infection was measured based on the health belief model., Results: From a total of 631 responses received, the proportion of participants with anxiety and depression symptoms (above threshold score of 8 on HADS-A and HADS-D) was 29.0 and 20.9%, respectively. Psychological distress (HADS-T > 16) was reported in 22.3% of the respondents. A total of 16.5% had combined anxiety and depression symptoms. The highest HADS-A (6.10; 95% CI 5.64-6.56), HADS-D (5.61; 95% CI 5.14-6.08), and HADS-T (11.71; 95% CI 10.84-12.58) scores were reported among respondents during phase 4 of the MCO. Partial least square-based structural equation modelling (PLS-SEM) revealed that self-perceived health status, perceived susceptibility, and severity of COVID-19 have the greatest effect, leading to higher HADS-A, HADS-D, and HADS-T scores., Conclusion: Heightened psychological distress was evident in cancer survivors particularly during the enforcement of the MCO over COVID-19. Providing support to address cancer survivors' psychological and emotional needs during the COVID-19 pandemic is essential., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment. We reported the generation and characterization of an iPS cell line, IBMS-iPSC-063-06, from a patient carrying the BBS2 homologous c534 + 1G > T mutation. The generated iPS cell line retains the mutation and exhibits pluripotency and differentiation ability both in vivo and in vitro condition., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Visual animals detect spatial variations of light intensity and wavelength composition. Opponent coding is a common strategy for reducing information redundancy. Neurons equipped with both spatial and spectral opponency have been identified in vertebrates but not yet in insects. The Drosophila amacrine neuron Dm8 was recently reported to show color opponency. Here, we demonstrate Dm8 exhibits spatio-chromatic opponency. Antagonistic convergence of the direct input from the UV-sensing R7s and indirect input from the broadband receptors R1-R6 through Tm3 and Mi1 is sufficient to confer Dm8's UV/Vis (ultraviolet/visible light) opponency. Using high resolution monochromatic stimuli, we show the pale and yellow subtypes of Dm8s, inheriting retinal mosaic characteristics, have distinct spectral tuning properties. Using 2D white-noise stimulus and reverse correlation analysis, we found that the UV receptive field (RF) of Dm8 has a center-inhibition/surround-excitation structure. In the absence of UV-sensing R7 inputs, the polarity of the RF is inverted owing to the excitatory input from the broadband photoreceptors R1-R6. Using a new synGRASP method based on endogenous neurotransmitter receptors, we show that neighboring Dm8s form mutual inhibitory connections mediated by the glutamate-gated chloride channel GluClα, which is essential for both Dm8's spatial opponency and animals' phototactic behavior. Our study shows spatio-chromatic opponency could arise in the early visual stage, suggesting a common information processing strategy in both invertebrates and vertebrates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aim: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Lenvatinib is a multi-kinase inhibitor that has the potential to suppress tumor progression. Our previous study suggested that lenvatinib induces cytotoxicity and apoptosis in CL-1-5-F4 cells in vitro. However, whether lenvatinib suppresses NSCLC progression in vivo remains unclear., Materials and Methods: Tumor growth inhibition and normal tissue toxicity evaluation following lenvatinib treatment were performed on CL-1-5-F4-bearing mice., Results: Tumor growth calculated by caliper and living cell intensity decreased by lenvatinib treatment as analysed by bioluminescence imaging. Phosphorylation of AKT, NF-κB, and NF-κB downstream proteins involved in tumor progression were reduced by lenvatinib in the tumor tissue. No pathological changes were found in the liver, kidney, and spleen after lenvatinib treatment., Conclusion: Induction of apoptosis and suppression of AKT/NF-κB were associated with lenvatinib-induced inhibition of the progression of NSCLC in vivo., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rationale: Mucous membrane pemphigoid (MMP) is a rare, autoimmune bullous disease that affects mucosal surfaces and skin. Early and aggressive treatment initiation may be warranted due to the risks of serious complications. However, it can be challenging to make an initial diagnosis. Viral infection such as hepatitis B virus (HBV) infection has been found to be associated with the formation of autoimmune bullous diseases., Patient Concerns: The patient was a 43-year-old male with gingivitis and recurrent swelling over the neck, cheeks, lips, and eyelids. The patient presented at oral medicine, otolaryngology, plastic surgery, and ophthalmology sequentially, and was later referred to the rheumatology, dermatology, and family medicine departments. Recurrent hemorrhagic bullae on oral mucosa and skin scarring occurred 2 years after the onset of the initial symptoms., Diagnosis: Skin biopsy with direct immunofluorescence was performed under the suspicion of MMP. Lesional hematoxylin and eosin stain and perilesional direct immunofluorescence were consistent with MMP., Interventions: Systemic Prednisolone and topical corticosteroid were used to control the disease., Outcomes: A flare-up of hepatitis B developed as a result of systemic prednisolone use. The disease went through relapses and remissions. The patient is on low-dose prednisolone (5 mg/day) with a monthly outpatient visit in the family medicine department., Lessons: It would be useful for medical practitioners in different specialties to be alert of the heterogeneous presentations of MMP. Chronic HBV infection might be a risk factor for MMP. In patients with chronic HBV infection, treatment of MMP must be closely monitored for the risk of reactivation of HBV., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Past studies pay little attention to the intention to donate hematopoietic stem cells (HSC) among blood donors. This study investigated the level of and the influence of socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC among blood donors., Methods: This cross-sectional study recruited blood donors at selected public hospitals in the Malaysian State of Sarawak in 2019. A structured questionnaire was developed based on the review of relevant literature. It gathered information on socio-demographic characteristics, knowledge, attitude, subjective norm and self-efficacy on the intention to donate HSC. Variables with a p value <0.200 in bivariate analysis were included in the variable selection for regression modeling to examine their associations with the intention to donate HSC., Results: A total of 569 blood donors participated (94.5% response rate). Overall, 87.1% reported a positive intention to donate HSC. In the regression model, the factor with the greatest association with intention to donate HSC was subjective norms about HSC donation (β = 0.35, 95% CI 0.27-0.42), followed by attitude about regulations of HSC donation (β= 0.21, 95% CI 0.13-0.35), self-efficacy on HSC donation (β = 0.15, 95% CI 0.09-0.32), attitude about the potential side effects of HSC donation (β = 0.14, 95% CI 0.02-0.10) and highest education level (β = 0.10, 95% CI 0.03-0.44)., Conclusions: The findings can be used to formulate a better strategy in promoting HSC donation among blood donors in the region., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Aim: Refugee arrivals to Europe have numbered more than one million since 2015 with the majority arriving through Greece. The healthcare needs of refugees have placed strains on Greece's healthcare system which has already been affected by its ongoing economic crisis. At the peak of arrivals during 2016, primary healthcare was primarily provided by humanitarian organizations with specialist referrals into the Greek healthcare system. There is little published literature on the type and impacts of specialist referrals for refugees in Greece. The aim of this retrospective review is to identify the type and impacts of specialist referrals for refugees into Greece's health system., Methods: This retrospective study reviewed the number and type of specialty referrals from one humanitarian organization providing primary healthcare for refugees in Greece. All consultations during an 8-month period (December 1, 2016-July 31, 2017) were reviewed., Results: Of 4168 consultations, 42% were patients aged 17 years or younger, 52% were male, and 90% were Syrian. Two hundred and thirty-three patients (11%) required a specialist referral; 25% were for dental (provided by another humanitarian organization), 10% each for obstetrics and gynecology and pediatrics, and 8% for ophthalmology. Respiratory complaints were most frequently seen, and these were more predominant in the winter months. Pediatric consultations varied according to month, likely due to population movements., Conclusion: Dentistry was noted to be a gap in humanitarian response programming and accounted for the greatest need for specialist input with referrals for women and children accounting for a large proportion of referrals., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Avicenna Journal of Medicine.)

Background: A pharmacist-led structured group-based intervention (MEDIHEALTH) was formulated to improve medication adherence among Malay type 2 diabetes mellitus (T2DM) patients in the Malaysian state of Sarawak., Objectives: The objective of this study was to examine the effectiveness of MEDIHEALTH and its mechanism of impact for improving medication adherence and the glycated haemoglobin (HbA1c) level., Methods: A two group and parallel randomised controlled trial with a twelve months follow-up period was conducted at two primary health clinics in Malaysia that were surrounded by Malay communities. Malay T2DM patients whose HbA1c was >7% and total score on the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) was <26 were recruited and parallelly randomised to the MEDIHEALTH or usual care (control) groups. The extended theory of planned behaviour was employed to test the mechanism of impact. Repeated measure analysis of variance was used to assess the difference in the estimated marginal mean of the SEAMS scores and HbA1c level between the intervention and control groups at different times., Results: A total of 142 participants were recruited and randomised; three from the intervention group and eight from the control group withdrew before receiving any treatment. Hence, 68 participants in the intervention group and 63 in the control group were included for analyses. The MEDIHEALTH group had a significantly greater increase in the SEAMS score compared to the control group (p < 0.001) at one, three, six and twelve months post-intervention. There was also a significantly greater reduction in HbA1c in the MEDIHEALTH compared to the control group at one, three, six and twelve months post-intervention (p < 0.001). These improvements were mediated by enhancements in perceived behavioural control and knowledge about medications., Conclusions: The MEDIHEALTH may improve medication adherence and glycaemic control among Malay T2DM patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The Tc-99m methylene diphosphonate (MDP) whole body bone scan (WBBS) has been widely accepted as a method of choice for the initial diagnosis of bone and joint changes in patients with oncologic diseases. The WBBS has shown high sensitivity but relatively low specificity due to bone variation. This study aims to use the self-developing irregular flux viewer (IFV) system to predict possible bone lesions in planar WBBS. The study uses gradient vector flow (GVF) and self-organizing map (SOM) methods to analyze the blood fluid-dynamics and evaluate hot points. The evaluation includes a selection of 368 patients with bone metastasis from prostate cancer, lung cancer and breast cancer. Finally, we compare IFV values with BONENAVI version data. BONENAVI is a computer-assisted diagnosis system that analyzes bone scintigraphy automatically. The analysis shows that the IFV system achieves sensitivities of 93% for prostate cancer, 91% for breast cancer, and 83% for lung cancer, respectively. On the other hand, our proposed approach achieves a higher sensitivity than the results of BONEVAVI version 2.0.5 for prostate cancer (88%), breast cancer (86%) and lung cancer (82%), respectively. The study results demonstrate that the high sensitivity and specificity of the IFV system can provide assistance for image interpretation and generate prediction values for WBBS.

Recommending a retail business given a particular location of interest is nontrivial. Such a recommendation process requires careful study of demographics, trade area characteristics, sales performance, traffic, and environmental features. It is not only human effort taxing but often introduces inconsistency due to subjectivity in expert opinions. The process becomes more challenging when no sales data can be used to make a recommendation. As an attempt to overcome the challenges, this study used the machine learning approach that utilizes similarity measures to perform the recommendation. However, two challenges required careful attention when using the machine learning approach: (1) how to prepare a feature set that can commonly represent different types of retail business and (2) which similarity measure approach produces optimal recommendation accuracy? The data sets used in this study consist of points of interest, population, property, job type, and education level. Empirical studies were conducted to investigate (1) the overall accuracy of proposed similarity measure approaches to the retail business recommendation, and (2) whether the proposed approaches have a bias toward certain retail categories. In summary, the findings suggested that the proposed similarity-based techniques elicited an accuracy of above 70% and demonstrated higher accuracy when the recommendation was made within a set of similar retail businesses.

The dysregulation of the metabolic regulator TOR complex I (TORC1) contributes to a wide array of human pathologies. Tuberous sclerosis complex (TSC) is a potent inhibitor of TORC1. Here, we demonstrate that the Rag GTPase acts in both the amino-acid-sensing and growth factor signaling pathways to control TORC1 activity through the regulation of TSC dynamics in HeLa cells and Drosophila. We find that TSC lysosomal-cytosolic exchange increases in response to both amino acid and growth factor restriction. Moreover, the rate of exchange mirrors TSC function, with depletions of the Rag GTPase blocking TSC lysosomal mobility and rescuing TORC1 activity. Finally, we show that the GATOR2 complex controls the phosphorylation of TSC2, which is essential for TSC exchange. Our data support the model that the amino acid and growth factor signaling pathways converge on the Rag GTPase to inhibit TORC1 activity through the regulation of TSC dynamics., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: About 20%-30% of diffuse large B-cell lymphoma (DLBCL) patients experience early disease progression despite R-CHOP chemotherapy treatment. Revised international prognostic index (R-IPI) score could risk stratify DLBCL patients but does not identify exactly which patient will be resistant to R-CHOP therapy or experience early relapse., Aims of the Study: To analyse pre-treatment clinical features of DLBCL patients that are predictive of R-CHOP therapy resistance and early disease relapse after R-CHOP therapy treatment., Methods Used to Conduct the Study: A total of 698 lymphoma patients were screened and 134 R-CHOP-treated DLBCL patients were included. The Lugano 2014 criteria was applied for assessment of treatment response. DLBCL patients were divided into R-CHOP resistance/early relapse group and R-CHOP sensitive/late relapse group., Results of the Study: 81 of 134 (60%) were R-CHOP sensitive/late relapse, while 53 (40%) were R-CHOP resistance/early relapse. The median follow-up period was 59 months ± standard error 3.6. Five-year overall survival rate of R-CHOP resistance/early relapse group was 2.1%, while it was 89% for RCHOP sensitive/late relapse group. Having more than one extranodal site of DLBCL disease is an independent risk factor for R-CHOP resistance/early relapse [odds ratio = 5.268 (1.888-14.702), P = .002]. The commonest extranodal sites were head and neck, gastrointestinal tract, respiratory system, vertebra and bones. Advanced age (>60 years), advanced disease stage (lll-lV), raised pre-treatment lactate dehydrogenase level, bone marrow involvement of DLBCL disease high Eastern Cooperative Oncology Group status (2-4) and high R-IPI score (3-5) showed no significant association with R-CHOP therapy resistance/early disease relapse (multivariate analysis: P > .05)., Conclusion and Clinical Implications: DLBCL patients with more than one extranodal site are 5.268 times more likely to be R-CHOP therapy resistance or experience early disease relapse after R-CHOP therapy. Therefore, correlative studies are warranted in DLBCL patients with more than one extranodal site of disease to explore possible underlying mechanisms of chemoresistance., (© 2020 John Wiley & Sons Ltd.)

Background: The Taiwan Human Disease iPSC Service Consortium was established to accelerate Taiwan's growing stem cell research initiatives and provide a platform for researchers interested in utilizing induced pluripotent stem cell (iPSC) technology. The consortium has generated and characterized 83 iPSC lines: 11 normal and 72 disease iPSC lines covering 21 different diseases, several of which are of high incidence in Taiwan. Whether there are any reprogramming-induced recurrent copy number variant (CNV) hotspots in iPSCs is still largely unknown., Methods: We performed genome-wide copy number variant screening of 83 Han Taiwanese iPSC lines and compared them with 1093 control subjects using an Affymetrix genome-wide human SNP array., Results: In the iPSCs, we identified ten specific CNV loci and seven "polymorphic" CNV regions that are associated with the reprogramming process. Additionally, we established several differentiation protocols for our iPSC lines. We demonstrated that our iPSC-derived cardiomyocytes respond to pharmacological agents and were successfully engrafted into the mouse myocardium demonstrating their potential application in cell therapy., Conclusions: The CNV hotspots induced by cell reprogramming have successfully been identified in the current study. This finding may be used as a reference index for evaluating iPSC quality for future clinical applications. Our aim was to establish a national iPSC resource center generating iPSCs, made available to researchers, to benefit the stem cell community in Taiwan and throughout the world.

Objective: This study examined the prevalence of self-perceived burden (SPB) and its association with health-related quality of life (HRQoL) among urologic cancer patients., Methods: This was a prospective, cross-sectional study. A total of 429 respondents diagnosed with urologic cancers (prostate, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed by using a structured questionnaire. SPB and HRQoL were measured by the Self-perceived Burden Scale and the Functional Assessment of Cancer Therapy-General 7 Item Scale respectively., Results and Conclusion: Self-perceived burden was experienced by 73.2% of the respondents. Respondents who had a lower education level, a monthly household income

Background: There is no evidence on effectiveness of advance care planning (ACP) among patients with heart failure (HF). We examined the effect of an ACP program in facilitating end of life (EOL) care consistent with the preferences of patients with HF (primary aim), and on their decisional conflict, discussion with surrogates, illness understanding, anxiety, depression, and quality of life (secondary aims)., Methods: We randomized 282 patients with HF to receive ACP (n=93) or usual care (control arm, n=189). Primary outcomes were assessed among deceased (n=89) and secondary outcomes from baseline and 6 follow-ups conducted every 4 months., Results: Deceased patients in the ACP arm were no more likely than those in control arm to have wishes followed for EOL treatments (ACP: 35%, Control: 44%; P= .47), or place of death (ACP: 52%, Control: 51%; P = .1.00). A higher proportion in the ACP arm had wishes followed for cardiopulmonary resuscitation (ACP: 83%, Control: 62%; P = .12). At first follow-up, patients with ACP had lower decisional conflict (β = -10.8, P< .01) and were more likely to discuss preferences with surrogates (β = 1.3, P = .04). ACP did not influence other outcomes., Conclusion: This trial did not confirm that our ACP program was effective in facilitating EOL care consistent with patient preferences. The program led to short-term improvements in the decision-making., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: This study examined the prevalence of financial toxicity (FT) and associated factors among urologic cancer patients. The association between FT and health-related quality of life (HRQoL) was also investigated., Methods: A total of 429 respondents diagnosed with urologic cancers (prostate cancer, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed using a structured questionnaire. Objective and subjective FT were measured by catastrophic health expenditure (healthcare-cost-to-income ratio greater than 40%) and the Personal Financial Well-being Scale, respectively. HRQoL was measured with the Functional Assessment of Cancer Therapy - General 7 Items scale., Results: Objective and subjective FT were experienced by 16.1 and 47.3% of the respondents, respectively. Respondents who sought treatment at a private hospital and had out-of-pocket health expenditures were more likely to experience objective FT, after adjustment for covariates. Respondents who were female and had a monthly household income less than MYR 5000 were more likely to experience average to high subjective FT. Greater objective FT (OR = 2.75, 95% CI 1.09-6.95) and subjective FT (OR = 4.68, 95% CI 2.63-8.30) were associated with poor HRQoL., Conclusions: The significant association between both objective and subjective FT and HRQoL highlights the importance of reducing FT among urologic cancer patients. Subjective FT was found to have a greater negative impact on HRQoL.