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Abstract BIVV003 is a gene-edited autologous cell therapy in clinical development for the potential treatment of sickle cell disease (SCD). Hematopoietic stem cells (HSC) are genetically modified with mRNA encoding zinc finger nucleases (ZFN) that target and disrupt a specific regulatory GATAA motif in the BCL11A erythroid enhancer to reactivate fetal hemoglobin (HbF). We characterized ZFN-edited HSC from healthy donors and donors with SCD. Results of preclinical studies show that ZFN-mediated editing is highly efficient, with enriched biallelic editing and high frequency of on-target indels, producing HSC capable of long-term multilineage engraftment in vivo, and express HbF in erythroid progeny. Interim results from the Phase 1/2 PRECIZN-1 study demonstrated that BIVV003 was well-tolerated in seven participants with SCD, of whom five of the six with more than 3 months of follow-up displayed increased total hemoglobin and HbF, and no severe vaso-occlusive crises. Our data suggest BIVV003 represents a compelling and novel cell therapy for the potential treatment of SCD.

The success of cellular immunotherapies such as chimeric antigen receptor (CAR) T cell therapy has led to their implementation as a revolutionary treatment option for cancer patients. However, the safe translation of such novel immunotherapies, from non-clinical assessment to first-in-human studies is still hampered by the lack of suitable in vitro and in vivo models recapitulating the complexity of the human immune system. Additionally, using cells derived from human healthy volunteers in such test systems may not adequately reflect the altered state of the patient's immune system thus potentially underestimating the risk of life-threatening conditions, such as cytokine release syndrome (CRS) following CAR T cell therapy. The IMI2/EU project imSAVAR (immune safety avatar: non-clinical mimicking of the immune system effects of immunomodulatory therapies) aims at creating a platform for novel tools and models for enhanced non-clinical prediction of possible adverse events associated with immunomodulatory therapies. This platform shall in the future guide early non-clinical safety assessment of novel immune therapeutics thereby also reducing the costs of their development. Therefore, we review current opportunities and challenges associated with non-clinical in vitro and in vivo models for the safety assessment of CAR T cell therapy ranging from organ-on-chip models up to advanced biomarker screening.

Abstract Background Cucurbita pepo cv Dayangua (CPD) is an edible plant with diverse pharmacological properties. The current research on CPD has primarily focused on initial investigations of its chemical composition and pharmacological effects, and no comprehensive toxicity assessment has been conducted to date. Methods In the present study, the toxicity of CPD was evaluated through both acute and sub-chronic oral toxicity tests in mice. 16S rDNA sequencing was used to analyze the composition of the gut microbiota of mice at different time points to observe the effect of CPD on these microbial communities. Results In the acute toxicity test, CPD exhibited low toxicity, with a median lethal dose (LD50) > 2000 mg/kg. The sub-chronic toxicity test indicated that CPD administration at doses of 200, 400, and 600 mg/kg did not cause mortality or significant organ damage in mice. Furthermore, analysis of the gut microbiota after gavage administration of CPD at 400 and 600 mg/kg revealed an improved abundance of some beneficial gut bacteria. Conclusions In summary, no acute or sub-chronic toxic effects were observed in mice following the oral administration of CPD. CPD did not affect the structure and diversity of the gut microbiota and may contribute to an increase in the number of beneficial gut bacteria.

Abstract Background Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. Methods This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. Results There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p

Dynamics of gut microbiota and their associations with the corresponding hematological injuries postradiation remain to be elucidated. Using single whole-body exposure to 60Co-γ ray radiation at the sublethal dose of 2.5 Gy, we developed a beagle model of acute radiation syndrome (ARS) and then monitored the longitudinal changes of gut microbiome and hematology for 45 days. We found that the absolute counts of circulating lymphocytes, neutrophils, and platelets were sharply declined postradiation, accompanied by a largely shifted composition of gut microbiome that manifested as a significantly increased ratio of Firmicutes to Bacteroidetes. In irradiated beagles, alterations in hematological parameters reached a nadir on day 14, sustaining for 1 week, which were gradually returned to the normal levels thereafter. However, no structural recovery of gut microbiota was observed throughout the study. Fecal metagenomics revealed that irradiation increased the relative abundances of genus Streptococcus, species Lactobacillus animalis and Lactobacillus murinus, but decreased those of genera Prevotella and Bacteroides. Metagenomic functions prediction demonstrated that 26 altered KEGG pathways were significantly enriched on Day 14 and 35 postradiation. Furthermore, a total of 43 bacterial species were found to correlate well with hematological parameters by Spearman’s analysis. Our results provide an insight into the longitudinal changes in intestinal microbiota at different clinical stages during ARS in canine. Several key microbes those tightly associated with the hematological alterations may serve as biomarkers to discriminate the different phases of host with ARS.

Clostridioides difficile infection (CDI) results in significant morbidity and mortality in hospitalised patients. Here the authors engineer probiotics to restore intestinal bile salt metabolism in response to antibiotic-induced microbiome dysbiosis significantly inhibit Clostridioides difficile infection in model mice, presenting a microbiome-based antimicrobial strategy

Numerous deaths from infectious diseases have raised public awareness of their dangers, promoting global antimicrobial research. However, antibiotic demand and use, on the other hand, have increased antibiotic levels in natural ecosystems. Natural selection and adaptation induced antibiotic resistance gene mutations in bacterial populations. Dissemination of antibiotic resistance genes in ecosystems resulted in the emergence of antibiotic-resistant bacteria, leading to a variety of antibiotic-resistant diseases on a global scale. This review paper provides an overview of the antibiotic discovery history, antibiotic screening techniques, and industrial antibiotic production processes. In addition, the emergence of antibiotic-resistant microorganisms and the antibiotics’ impact on the environment have been reviewed, and suggestions were given. The ecological perspective on antibiotic resistance has also been discussed. New drug development seems to be the prime requisite now to control microbes that no longer respond to the drug.

Abstract Background Sugarcane mosaic disease (SMD) is a major viral disease of sugarcane (Saccharum spp.) worldwide. Sorghum mosaic virus (SrMV) is the dominant pathogen of SMD in the sugarcane planting areas of China. There is no report on miRNAs and their regulatory networks in sugarcane response to SrMV infection. Results In this study, small RNA sequencing (sRNA-seq) of samples from the leaves of SMD-susceptible variety ROC22 and -resistant variety FN39 infected by SrMV was performed. A total of 132 mature miRNAs (55 known miRNAs and 77 novel miRNAs) corresponding to 1,037 target genes were identified. After the SrMV attack, there were 30 differentially expressed miRNAs (17 up-regulated and 13 down-regulated) in FN39 and 19 in ROC22 (16 up-regulated and 3 down-regulated). Besides, there were 18 and 7 variety-specific differentially expressed miRNAs for FN39 and ROC22, respectively. KEGG enrichment analysis showed that the differentially expressed miRNAs targeted genes involved in several disease resistance-related pathways, such as mRNA surveillance, plant pathway interaction, sulfur metabolism, and regulation of autophagy. The reliability of sequencing data, and the expression patterns / regulation relationships between the selected differentially expressed miRNAs and their target genes in ROC22 and FN39 were confirmed by quantitative real-time PCR. A regulatory network diagram of differentially expressed miRNAs and their predicted target genes in sugarcane response to SrMV infection was sketched. In addition, precursor sequences of three candidate differentially expressed novel miRNAs (nov_3741, nov_22650 and nov_40875) were cloned from the ROC22 leaf infected by SrMV. Transient overexpression demonstrated that they could induce the accumulation of hydrogen peroxide and the expression level of hypersensitive response marker genes, salicylic acid-responsive genes and ethylene synthesis-depended genes in Nicotiana benthamiana. It is thus speculated that these three miRNAs may be involved in regulating the early immune response of sugarcane plants following SrMV infection. Conclusions This study lays a foundation for revealing the miRNA regulation mechanism in the interaction of sugarcane and SrMV, and also provides a resource for miRNAs and their predicted target genes for SrMV resistance improvement in sugarcane.

Abstract Background The purpose of this study was to apply the Predisposing, Reinforcing, and Enabling Constructs in Educational Diagnosis and Evaluation (PRECEDE) model to analyze the factors influencing preschool educators’ ability to teach health education through life skills. Methods This cross-sectional study utilized stratified random sampling and administered survey questionnaires to 503 preschool educators in public and private kindergartens in Taipei City and New Taipei City in 2019. Descriptive and hierarchical regression analyses were conducted. The PRECEDE model demonstrated a significant correlation between the enabling, reinforcing, and predisposing factors explored in this study and the preschool educators’ ability to teach health education through life skills. Results The variables explained 25% of the total variance in the ability to teach health education through life skills. When controlled in individual layers, the background variables and the enabling, reinforcing, and predisposing factors demonstrated explanatory powers of 6, 5, 7, and 7%, respectively, with respect to the ability to teach health education by utilizing life skills. Conclusions Enhancement of the enabling, reinforcing, and predisposing factors can improve preschool educators’ ability to teach health education through life skills. The support provided by the governmental policies for related training can facilitate the effective implementation of health promotion programs in kindergartens. Preschool educators must also receive on-the-job training to facilitate the effective transaction of the health education curriculum. Health classes centered on life skills in kindergartens are vital and must be incorporated into the curricula.

Abstract Rodents living alongside humans increases the probability of encounter and also the transmission of rodent-borne diseases. Singapore’s cosmopolitan urban landscape provides a perfect setting to study the prevalence of four rodent-borne pathogens: Seoul hantavirus (SEOV), Leptospira species, Rickettsia typhi and Yersinia pestis, and identify the potential risk factors which may influence rodent density and transmission of rodent-borne diseases. A total of 1143 rodents were trapped from 10 unique landscape structures throughout Singapore. Real-time quantitative Polymerase Chain Reactions were used to detect pathogenic and intermediate Leptospira spp. and Yersinia pestis, whereas the seroprevalence of SEOV and R. typhi were analysed by Enzyme-Linked Immunosorbent Assay and Immunofluorescence Assay respectively. Multivariable logistic regression analysis was used to evaluate the association between prevalence of infection in rodent reservoirs and risk factors. Most of the rodents were caught in public residential developments (62.2%). Among the tested rodents, 42.4% were infected with Leptospira spp., while 35.5% and 32.2% were seropositive for SEOV and R. typhi respectively, whereas Yersinia pestis was not detected. Furthermore, risk factors including habitat, species, gender, and weight of rodents, influenced prevalence of infection to a varying extent. This study highlights the presence of Leptospira spp., SEOV and R. typhi in Singapore’s rodent population, suggesting the need for effective rodent management and sanitation strategies to prevent further circulation and transmission to humans.

Syphilis, a chronic multisystemic disease caused by spirochete Treponema pallidum subspecies pallidum infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a T. pallidum placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund’s adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited T. pallidum dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized, T. pallidum-challenged animals were not infected by T. pallidum, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.

Abstract Background Plasma membrane intrinsic proteins (PIPs) are plant channel proteins involved in water deficit and salinity tolerance. PIPs play a major role in plant cell water balance and responses to salt stress. Although sugarcane is prone to high salt stress, there is no report on PIPs in sugarcane. Results In the present study, eight PIP family genes, termed ScPIP1–1, ScPIP1–2, ScPIP1–3, ScPIP1–4, ScPIP2–1, ScPIP2–2, ScPIP2–4 and ScPIP2–5, were obtained based on the sugarcane transcriptome database. Then, ScPIP2–1 in sugarcane was cloned and characterized. Confocal microscopy observation indicated that ScPIP2–1 was located in the plasma membrane and cytoplasm. A yeast two-hybridization experiment revealed that ScPIP2–1 does not have transcriptional activity. Real time quantitative PCR (RT-qPCR) analysis showed that ScPIP2–1 was mainly expressed in the leaf, root and bud, and its expression levels in both below- and aboveground tissues of ROC22 were up-regulated by abscisic acid (ABA), polyethylene glycol (PEG) 6000 and sodium chloride (NaCl) stresses. The chlorophyll content and ion leakage measurement suggested that ScPIP2–1 played a significant role in salt stress resistance in Nicotiana benthamiana through the transient expression test. Overexpression of ScPIP2–1 in Arabidopsis thaliana proved that this gene enhanced the salt tolerance of transgenic plants at the phenotypic (healthier state, more stable relative water content and longer root length), physiologic (more stable ion leakage, lower malondialdehyde content, higher proline content and superoxide dismutase activity) and molecular levels (higher expression levels of AtKIN2, AtP5CS1, AtP5CS2, AtDREB2, AtRD29A, AtNHX1, AtSOS1 and AtHKT1 genes and a lower expression level of the AtTRX5 gene). Conclusions This study revealed that the ScPIP2–1-mediated osmotic stress signaling cascade played a positive role in plant response to salt stress.

Willows (Salix spp.) are promising extractors of cadmium (Cd), with fast growth, high biomass production, and high Cd accumulation capacity. However, the molecular mechanisms underlying Cd uptake and detoxification are currently poorly understood. Analysis of the Cd uptake among 30 willow genotypes in hydroponic systems showed that the S. suchowensis and S. integra hybrids, Jw8–26 and Jw9–6, exhibited distinct Cd accumulation and resistance characteristics. Jw8–26 was a high Cd-accumulating and tolerant willow, while Jw9–6 was a low Cd-accumulating and relatively Cd-intolerant willow. Therefore, these two genotypes were ideal specimens for determining the molecular mechanisms of Cd uptake and detoxification. To identify relevant genes in Cd handling, the parent S. suchowensis was treated with Cd and RNA-seq analysis was performed. SsIRT, SsHMA, and SsGST, in addition to the transcription factors SsERF, SsMYB, and SsZAT were identified as being associated with Cd uptake and resistance. Because membrane-localised heavy metal transporters mediate Cd transfer to plant tissues, a total of 17 SsIRT and 12 SsHMA family members in S. suchowensis were identified. Subsequently, a thorough bioinformatics analysis of the SsIRT and SsHMA families was conducted, and their transcript levels were analysed in the roots of the two hybrids. The transcript levels of SsIRT9 in roots were positively correlated with the observed differences in Cd accumulation in Jw8–26 versus Jw9–6. Jw8–26 displayed higher SsIRT9 expression levels and higher Cd accumulation than Jw9–6; therefore, SsIRT9 may be involved in Cd uptake. Gene expression analysis also revealed that SsHMA1 was a candidate gene associated with Cd resistance. These results lay the foundation for understanding the molecular mechanism of Cd transfer and detoxification in willows, and provide guidance for the screening and breeding of high Cd-accumulating and tolerant willow genotypes via genetic engineering.

Chronic infection with hepatitis B virus (HBV) is incurable, as the current therapeutics cannot eliminate its persistent genomic material, cccDNA. Screening systems for cccDNA-targeting therapeutics are unavailable, as low copies of cccDNA in vitro complicate detection. To address this, cccDNA copies were massively increased to levels detectable via automated plate readers. This was achieved via continuous infection in a contact-free co-culture of an HBV generator (clone F881), which stably produced clinically relevant amounts of HBV, and HBV acceptors selected to carry high cccDNA loads. cccDNA-targeted therapeutics were then identified via reduced cccDNA-specific fluorescence, taking differences in the cell numbers and viability into account. Amongst the drugs tested, the H1 antihistamine Bilastine, HBVCP inhibitors and, surprisingly, current HBV therapeutics downregulated the cccDNA significantly, reflecting the assay’s accuracy and sensitivity in identifying drugs that induce subtle changes in cccDNA levels, which take years to manifest in vivo. Bilastine was the only therapeutic that did not reduce HBV production from F881, indicating it to be a novel direct suppressor of cccDNA levels. When further assessed, only the structurally similar antihistamines Pitolisant and Nizatidine suppressed cccDNA levels when other H1 antihistamines could not. Taken together, our rapid fluorescence cccDNA-targeted drug screen successfully identified a class of molecules with the potential to treat hepatitis B.

The COVID-19 pandemic accelerated the adoption of technology and greatly transformed the way humans communicate. Since the start of the pandemic, the delivery of lectures and workshops shifted from face-to-face to online. However, this shift in the mode of teaching may or may not suit learners. This study was conducted to determine the students' perception of the mode of teaching, their learning experience after attending the online classes throughout the semester, and the major challenges they faced during the classes. The participants were Year 1 students from an AutoCAD workshop, Year 3 students from a Traffic Engineering Course, and Year 4 students from a Highway and Pavement Design course. The results show that prerecorded classes with the addition of live-streaming classes were more preferred in computing classes because students can learn at their own pace, especially when learning the new software. For lecture-based courses, physical classes or a mix of physical and online classes were favored by students because physical classes can be more interactive. There were also challenges encountered by the students during online classes such as poor internet connection and distractions at home. Thus, instructors need to personally communicate with the students to understand their learning preference so that the necessary adjustments can be made to the mode of teaching, particularly with the use of hybrid teaching.

Abstract Objective To explore the effects of the autonomous sensory meridian response (ASMR) on the psychological cravings and anxiety of women compulsorily isolated for detoxification. Method Around 122 women were recruited in a female drug detoxification center. Except for the 12‐week training of ASMR, the experimental conditions of the experimental group (n = 60) were the same as those of the control group (n = 62). The addiction Stroop task was used to assess the level of psychological cravings and the State‐Trait Anxiety Inventory was used to assess the level of anxiety. Results After the training, the decrease in state anxiety of the experimental group was larger than that of the control group, and the reaction time of the experimental group in the Stroop was also significantly lower than before the training. Conclusions ASMR could thus reduce to a certain extent the state anxiety and attentional bias for drug‐related clues under signaling psychological cravings among women compulsorily isolated for detoxification. HIGHLIGHTS Intervention effects on psychological cravings and anxiety of women isolated for detoxification Basis for role of ASMR in regulating psychological cravings and anxiety in forced abstainers ASMR intervention reduced forced abstainers’ attentional bias to drug‐related clues

The selected functional properties of rice husk/wood blended particleboards which include thermal analysis, limiting oxygen index, morphological analysis, and mechanical properties have been investigated. Rice husk/wood particleboards were produced with one step hot press casting technique using citric acid to improve the compatibility in the particleboards with calcium oxide and aluminum oxide as flame retardants. The results showed improvement in the mechanical properties, flame retardancy, and thermal stability with the addition of flame retardants to the particleboards. The aluminum oxide synergy with citric acid in rice husk/wood particleboards gave the best flame retardancy.

Background: Epilepsy in childhood is a common and diverse neurological disorder. We conducted a genetic and phenotype analysis of a Chinese cohort of infants and children with epilepsy.Methods: We conducted a pedigree analysis of 260 Chinese patients with epilepsy onset during infancy or childhood by whole exome sequencing (WES).Results: Of the 260 probands analyzed, a genetic diagnosis was established in 135 patients. One-hundred eighty-eight phenotypes were detected in those 135 positive/likely positive patients, 106 patients had more than two phenotypes, and 67 patients had more than three phenotypes. A total of 142 variants of 81 genes were detected among the positive/likely positive patients. Among these 142 variants, of which 87 of 66 genes were novel.Conclusion: Our findings extend the variant spectrum of genes related to epilepsy. Our results will be useful for genetic testing and counseling for patients with epilepsy.

Abstract Background Calcineurin B-like protein (CBL)-interacting protein kinases (CIPKs) are the primary components of calcium sensors, and play crucial roles in plant developmental processes, hormone signaling transduction, and in the response to exogenous stresses. Results In this study, 48 CIPK genes (SsCIPKs) were identified from the genome of Saccharum spontaneum. Phylogenetic reconstruction suggested that the SsCIPK gene family may have undergone six gene duplication events from the last common ancestor (LCA) of SsCIPKs. Whole-genome duplications (WGDs) served as the driving force for the amplification of SsCIPKs. The Nonsynonymous to synonymous substitution ratio (Ka/Ks) analysis showed that the duplicated genes were possibly under strong purifying selection pressure. The divergence time of these duplicated genes had an average duplication time of approximately 35.66 Mya, suggesting that these duplication events occurred after the divergence of the monocots and eudicots (165 Mya). The evolution of gene structure analysis showed that the SsCIPK family genes may involve intron losses. Ten ScCIPK genes were amplified from sugarcane (Saccharum spp. hybrids). The results of real-time quantitative polymerase chain reaction (qRT-PCR) demonstrated that these ten ScCIPK genes had different expression patterns under abscisic acid (ABA), polyethylene glycol (PEG), and sodium chloride (NaCl) stresses. Prokaryotic expression implied that the recombinant proteins of ScCIPK3, − 15 and − 17 could only slightly enhance growth under salinity stress conditions, but the ScCIPK21 did not. Transient N. benthamiana plants overexpressing ScCIPKs demonstrated that the ScCIPK genes were involved in responding to external stressors through the ethylene synthesis pathway as well as to bacterial infections. Conclusions In generally, a comprehensive genome-wide analysis of evolutionary relationship, gene structure, motif composition, and gene duplications of SsCIPK family genes were performed in S. spontaneum. The functional study of expression patterns in sugarcane and allogenic expressions in E. coli and N. benthamiana showed that ScCIPKs played various roles in response to different stresses. Thus, these results improve our understanding of the evolution of the CIPK gene family in sugarcane as well as provide a basis for in-depth functional studies of CIPK genes in sugarcane.

Objectives: Voriconazole serum concentration, which is affected by several factors, is associated with treatment response and toxicity. There is paucity of data on voriconazole therapeutic drug monitoring (TDM) among Southeast Asians, who exhibit a higher prevalence of CYP2C19-poor metabolisers compared with Caucasians and East Asians. Hence, there are concerns for higher risk of voriconazole accumulation and toxicity.We aim to determine the utility of voriconazole TDM through establishing: (1) proportion of patients achieving therapeutic troughs without dose adjustments; (2) characterisation of patients with sub-therapeutic, therapeutic and supra-therapeutic levels; (3) appropriate dose titrations/dose required for therapeutic troughs; (4) correlation between troughs and adverse events, treatment response/fungal breakthrough. Patients and methods: A single-centre retrospective analysis of data from adults (≥21 years old) with ≥1 voriconazole trough measured at Singapore General Hospital from 2015 to 2017 was performed. Results: Thirty-two patients (45.7%) among 70 patients achieved therapeutic troughs (defined as 2.0–5.5 mg/L) without dose adjustments. Eleven patients (15.7%) experienced hepatotoxicity (troughs 0.5 to >7.5 mg/L). Neurotoxicity occurred in three patients (4.3%) (troughs ≥6.7 mg/L) and all patients had symptom resolution upon dose reduction. Treatment failure of invasive fungal infection appeared less in patients with therapeutic troughs compared with sub-therapeutic troughs (11.4% vs. 14.2%). Two patients experienced treatment failure despite supra-therapeutic voriconazole troughs. Conclusions: TDM should be implemented due to significant unpredictability in dose exposure. TDM can reduce unnecessary switches to alternatives due to intolerability and rule in the possibility of resistant organisms in the event of treatment failure despite therapeutic troughs, alerting clinicians to switch to alternatives promptly.

Introduction: This study aimed to determine the views and practices of healthcare providers and barriers they encountered when implementing the national health screening program for men in a public primary care setting in Malaysia. Methods: An online survey was conducted among healthcare providers across public health clinics in Malaysia. All family medicine specialists, medical officers, nurses and assistant medical officers involved in the screening program for adult men were invited to answer a 51-item questionnaire via email or WhatsApp. The questionnaire comprised five sections: participants’ socio-demographic information, current screening practices, barriers and facilitators to using the screening tool, and views on the content and format of the screening tool. Results: A total of 231 healthcare providers from 129 health clinics participated in this survey. Among them, 37.44% perceived the implementation of the screening program as a “top-down decision.” Although 37.44% found the screening tool for adult men “useful,” some felt that it was “time consuming” to fill out (38.2%) and “lengthy” (28.3%). In addition, ‘adult men refuse to answer’ (24.1%) was cited as the most common patient-related barrier. Conclusions: This study provided useful insights into the challenges encountered by the public healthcare providers when implementing a national screening program for men. The screening tool for adult men should be revised to make it more user-friendly. Further studies should explore the reasons why men were reluctant to participate in health screenings, thus enhancing the implementation of screening programs in primary care.

In this study (Part II), the empirical formulation of corrosion model of a ship’s ballast tank was developed to predict nonlinear time-dependent corrosion wastage based on the advanced data processing technique proposed by Part I. The detail on how to propose generalised mathematical formulation of corrosion model was precisely documented in the previous paper (Part I). The statistical scatter of corrosion data at any exposure time was investigated by the refined method and formulated based on a 2-parameter Weibull distribution which selected the best fit PDF. Throughout the nine (9) steps, empirical formulation of the ship’s seawater ballast tank was successfully proposed and four (4) key step results were also obtained. The proposed method in Part I was verified and confirmed by this application of seawater ballast tank, thus making it possible to predict accurate behaviours of nonlinear time-dependent corrosion. Developed procedures and obtained corrosion damage model for ship’s seawater ballast tank can be used for development of engineering software.

PURPOSECurrently, limited information is available on care provided to breast cancer survivors in Singapore. This study aims to assess the quality of post-treatment cancer survivorship care among breast cancer survivors on the basis of compliance with international guidelines up to 5 years post-primary treatment.METHODSThis study analyzed a cohort of 189 nonmetastatic breast cancer survivors recruited from the National Cancer Centre Singapore, Changi General Hospital, and KK Women's and Children's Hospital between November 2011 and September 2015. Data were retrieved from electronic medical records in 6-month intervals. Adherence to guidelines was assessed in four areas: (1) recurrent cancer surveillance, (2) monitoring and detecting late effects, (3) health care resource utilization, and (4) preventive care. Descriptive statistics, Kaplan-Meier, and regression analyses were conducted.RESULTSAnnual surveillance mammogram adherence rates were ≥ 83% consistently. The most common new diagnosis was osteoporosis at an incidence rate of 102 (95% CI, 77.6 to 135) cases per 1,000 person-years. Overall, ≤ 10.1% of survivors had an emergency department or hospitalization visit. Oncologist services were overutilized, with a median of 6 (interquartile range: 4-10) visits in the first 6 months before reducing to a median of 2 (interquartile range: 1-3) visits biannually 3 years post-treatment. Bone mineral density test utilization rate adhered to guidelines for 92.2% of aromatase inhibitor recipients but only for 36.4% of premenopausal tamoxifen recipients.CONCLUSIONOverall, adherence rates to surveillance and osteoporosis preventive care were high. Extensive utilization of oncologist services up to 5 years post-primary treatment could be reversed with strategies to engage and coordinate survivorship care with primary care providers, leveraging their strengths to improve adherence to health promotion and chronic disease management.

The use of anticholinergic medications is increasing in younger ages, yet information about xerostomia, the most common anticholinergic side effect, is limited. This case–control retrospective study examines the relationship between anticholinergic medication-induced xerostomia and caries status among adults between 18 and 65 years of age. The study sample comprised 649 cases with xerostomia and 649 age- and gender-matched controls. The anticholinergic burden was estimated using the anticholinergic drug scale (ADS). Caries experience was recorded by calculating the Decayed, Missing, Filled Tooth (DMFT) index. Individuals with xerostomia had a higher mean DMFT index (16.02 ± 9.50), which corresponded with a higher level of anticholinergic exposure from medications (3.26 ± 2.81) compared to their age and gender-matched controls without xerostomia (13.83 + 8.83 and 1.89 ± 2.45, respectively). Logistic regression analysis verified the effects of DMFT, the total number of AC medications, and the ADS burden on xerostomia status. Comparing adults with or without xerostomia revealed statistical differences in several risk factors, such as smoking, diabetes, sleep apnea, and the utilization of anticholinergic medications. A personalized dental care plan should include the evaluation of the anticholinergic burden from medications regardless of the patient’s age to prevent increased caries severity.

The plant cell wall is dynamically modified during host–pathogen interactions and acts as a crucial factor controlling plant immunity. In the context of recently revised models of plant primary cell walls (PCWs), pectin is considered to be important in determining the mechanical properties of PCWs. A secondary cell wall is present in some cell types and lignin is normally present and acts to strengthen wall rigidity. In this review, we summarize the recent advances in understanding cell-wall-mediated defense responses against pathogens in Brassica napus L. (B. napus). A major part of this response involves pectin and lignin, and these two major cell wall components contribute greatly to immune responses in B. napus. Crosstalk between pectin and lignin metabolism has been detected in B. napus upon pathogen infection, suggesting a synergistic action of pectin and lignin metabolism in regulating cell wall integrity as well as wall-mediated immunity. The transcriptional regulation of cell-wall-mediated immunity in B. napus along with that in Arabidopsis is discussed, and directions for future work are proposed for a better understanding of wall-mediated plant immunity in B. napus.

Japanese encephalitis virus (JEV) is an important arbovirus in Asia that can cause serious neurological disease. JEV is transmitted by mosquitoes in an enzootic cycle involving porcine and avian reservoirs, in which humans are accidental, dead-end hosts. JEV is currently not endemic in Singapore, after pig farming was abolished in 1992; the last known human case was reported in 2005. However, due to its location along the East-Asian Australasian Flyway (EAAF), Singapore is vulnerable to JEV re-introduction from the endemic regions. Serological and genetic evidence in the last decade suggests JEV’s presence in the local fauna. In the present study, we report the genetic characterization and the first isolation of JEV from 3214 mosquito pools consisting of 41,843 Culex mosquitoes, which were trapped from April 2014 to May 2021. The findings demonstrated the presence of genotype I of JEV (n = 10), in contrast to the previous reports of the presence of genotype II of JEV in Singapore. The genetic analyses also suggested that JEV has entered Singapore on several occasions and has potentially established an enzootic cycle in the local fauna. These observations have important implications in the risk assessment and the control of Japanese encephalitis in non-endemic countries, such as Singapore, that are at risk for JEV transmission.

The complete mitogenome of Saccharum spp. hybrid 15a-53 was determined in this study, which contains two distinct circular chromosomes, Chromosome 1 and 2. The length of Chromosome 1 is 300,848 bp with the GC content of 43.93%, while Chromosome 2 is 144,713 bp in length with the GC content of 43.57%. In Chromosome 1, 7.14% of the genome (21,468 nucleotides) is coding DNA and 92.86% (279,380 nucleotides) are intergenic region, while in Chromosome 2, 8.20% of genome (11,865 nucleotides) are coding DNA and 91.80% (132,848 nucleotides) are intergenic region. Chromosome 1 contains 20 protein-coding genes (three atp genes, three ccm genes, two cox genes, one mat gene, one mtt gene, six nad genes, and four rps genes), and 21 non-coding genes (15 tRNA and six rRNAs), while in Chromosome 2, there are 13 protein-coding genes (four nad genes, three rps genes, two atp genes, one ccm gene, one cob gene, one cox gene, and one rpl gene) and five tRNA genes. Maximum Likelihood phylogenetic analysis indicated that 15a-53 is close to S. spp. hybrid ROC22, S. spp. hybrid FN15 and S. officinarum Khon Kaen 3. The complete mitochondrial genome herein will provide useful sequence information for phylogenetic and evolutionary studies for Saccharum and Poaceae.

Abstract Background Non-coding RNAs and especially microRNAs have been discovered to act as master regulators of cancer initiation and progression. The aim of our study was to discover and characterize the function of yet functionally uncharacterized microRNAs in human breast carcinogenesis. Methods In an unbiased approach, we utilized an established model system for breast cancer (BC) stem cell formation (“mammosphere assay”) to identify whole miRNome alterations in breast carcinogenesis. Clinical samples of BC patients were used to evaluate the human relevance of the newly identified miRNA candidates. One promising candidate, miR-1287-5p, was further explored on its impact on several hallmarks of cancer. The molecular mode of action was characterized by whole transcriptome analysis, in silico prediction tools, miRNA-interaction assays, pheno-copy assays, and drug sensitivity assays. Results Among several other microRNAs, miR-1287-5p was significantly downregulated in mammospheres and human BC tissue compared to normal breast tissue (p

Abstract Background Sugarcane smut is a fungal disease caused by Sporisorium scitamineum. Cultivation of smut-resistant sugarcane varieties is the most effective way to control this disease. The interaction between sugarcane and S. scitamineum is a complex network system. However, to date, there is no report on the identification of microRNA (miRNA) target genes of sugarcane in response to smut pathogen infection by degradome technology. Results TaqMan qRT-PCR detection and enzyme activity determination showed that S. scitamineum rapidly proliferated and incurred significant enzyme activity changes in the reactive oxygen species metabolic pathway and phenylpropanoid metabolic pathway at 2 d and 5 d after inoculation, which was the best time points to study target gene degradation during sugarcane and S. scitamineum interaction. A total of 122.33 Mb of raw data was obtained from degradome sequencing analysis of YC05–179 (smut-resistant) and ROC22 (smut-susceptible) after inoculation. The Q30 of each sample was > 93%, and the sequence used for degradation site analysis exactly matched the sugarcane reference sequence. A total of 309 target genes were predicted in sugarcane, corresponding to 97 known miRNAs and 112 novel miRNAs, and 337 degradation sites, suggesting that miRNAs can efficiently direct cleavage at multiple sites in the predicted target mRNAs. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the predicted target genes were involved in various regulatory processes, such as signal transduction mechanisms, inorganic ion transport and metabolism, defense mechanisms, translation, posttranslational modifications, energy production and conversion, and glycerolipid metabolism. qRT-PCR analysis of the expression level of 13 predicted target genes and their corresponding miRNAs revealed that there was no obvious negative regulatory relationship between miRNAs and their target genes. In addition, a number of putative resistance-related target genes regulated by miRNA-mediated cleavage were accumulated in sugarcane during S. scitamineum infection, suggesting that feedback regulation of miRNAs may be involved in the response of sugarcane to S. scitamineum infection. Conclusions This study elucidates the underlying response of sugarcane to S. scitamineum infection, and also provides a resource for miRNAs and their predicted target genes for smut resistance improvement in sugarcane.

Zinc (Zn) is a major soil contaminant and high Zn levels can disrupt growth, survival, and reproduction of fungi. Some fungal species evolved Zn tolerance through cell processes mitigating Zn toxicity, although the genes and detailed mechanisms underlying mycorrhizal fungal Zn tolerance remain unexplored. To fill this gap in knowledge, we investigated the gene expression of Zn tolerance in the ectomycorrhizal fungus Suillus luteus. We found that Zn tolerance in this species is mainly a constitutive trait that can also be environmentally dependent. Zinc tolerance in S. luteus is associated with differences in the expression of genes involved in metal exclusion and immobilization, as well as recognition and mitigation of metal-induced oxidative stress. Differentially expressed genes were predicted to be involved in transmembrane transport, metal chelation, oxidoreductase activity, and signal transduction. Some of these genes were previously reported as candidates for S. luteus Zn tolerance, while others are reported here for the first time. Our results contribute to understanding the mechanisms of fungal metal tolerance and pave the way for further research on the role of fungal metal tolerance in mycorrhizal associations.

Problem During the coronavirus disease 2019 (COVID-19) pandemic, medical oxygen therapy was urgently needed for patients with hypoxaemia. Many low- and middle-income countries lacked the medical devices for oxygen therapy and experience in their use. Approach In addition to providing medical devices for oxygen therapy for countries in need, the World Health Organization (WHO) and partners developed training videos to help local health workers select, use and maintain this equipment. Diverse health professionals, including engineers and clinicians from resource-constrained countries, collaborated in developing draft videos in their local settings. A production team refined these drafts and delivered the training videos through the platform OpenWHO. Local setting OpenWHO is WHO's free open-access platform providing courses for health workers and others. The courses, based on WHO's scientific and operational guidance, can be easily adapted, contextualized and translated. Relevant changes The production team refined the drafts into 32 training videos. More than 17 505 health workers participated in the OpenWHO course on COVID-19 respiratory equipment between 28 February 2022 and 30 November 2023. Participants were from 189 countries and 38% (6027/16 047) were from low- and lower-middle-income countries. Lessons learnt Involving volunteer biomedical engineers and clinicians from low- and middle-income countries helped provide an appropriate training resource. WHO should continue to develop such training tools and offer them through OpenWHO, especially for emergencies. Probleme Lors de la pandemie de coronavirus en 2019 (COVID-19), les patients atteints d'hypoxemie ont eu besoin d'une oxygenotherapie medicale d'urgence. De nombreux pays a revenus faibles ou intermediaires manquaient alors de dispositifs medicaux pour assurer cette oxygenotherapie et d'experience dans leur utilisation. Approche L'Organisation mondiale de la sante (OMS) et ses partenaires ont non seulement fourni des dispositifs medicaux d'oxygenotherapie aux pays qui en avaient besoin, mais ils ont egalement elabore des videos de formation pour aider les professionnels de la sante locaux a selectionner, utiliser et entretenir ce materiel. Differents professionnels de la sante, dont des ingenieurs et des cliniciens issus de pays aux ressources limitees, ont coopere a l'elaboration de projets de videos dans leur environnement local. Une equipe de production a perfectionne ces projets et a diffuse les videos de formation par l'intermediaire de la plateforme OpenWHO. Environnement local OpenWHO est une plateforme gratuite et en acces libre de l'OMS qui propose des formations aux agents de sante et a d'autres personnes. Les formations, basees sur les orientations scientifiques et operationnelles de l'OMS, peuvent etre facilement adaptees, contextualisees et traduites. Changements significatifs Lequipe de production a perfectionne les projets et a realise 32 videos de formation a partir de ces projets. Plus de 17 505 agents de sante ont participe a la formation OpenWHO sur les appareils respiratoires dans le cadre de la pandemie de COVID-19 entre le 28 fevrier 2022 et le 30 novembre 2023. Les participants etaient originaires de 189 pays, et 38% d'entre eux (6027/16 047) provenaient de pays a revenus faibles ou intermediaires de la tranche inferieure. Lecons tirees La participation d'ingenieurs biomedicaux et de cliniciens volontaires issus de pays a revenus faibles ou intermediaires a permis de fournir des ressources de formation appropriees. L'OMS devrait continuer a elaborer de tels outils de formation et les proposer sur la plateforme OpenWHO, en particulier pour les situations d'urgence. Situacion Durante la pandemia de la enfermedad por coronavirus de 2019 (COVID-19), se necesito urgentemente oxigenoterapia medica para los pacientes con hipoxemia. Muchos paises de ingresos bajos y medios carecian de los dispositivos medicos necesarios para la oxigenoterapia y de experiencia en su uso. Enfoque Ademas de proporcionar dispositivos medicos para oxigenoterapia a los paises necesitados, la Organizacion Mundial de la Salud (OMS) y sus asociados elaboraron videos de formacion para ayudar al personal sanitario local a seleccionar, utilizar y mantener estos equipos. Varios profesionales sanitarios, entre ellos ingenieros y medicos de paises con recursos limitados, colaboraron en la elaboracion de los borradores de los videos en sus entornos locales. Un equipo de produccion perfecciono estos borradores y entrego los videos de formacion a traves de la plataforma OpenWHO. Marco regional OpenWHO es la plataforma gratuita de libre acceso de la OMS que ofrece cursos para el personal sanitario y otras personas. Los cursos, basados en las orientaciones cientificas y operativas de la OMS, pueden adaptarse, contextualizarse y traducirse facilmente. Cambios importantes El equipo de produccion mejoro los borradores hasta convertirlos en 32 videos de formacion. Mas de 17 505 agentes de salud participaron en el curso OpenWHO sobre equipos respiratorios COVID-19 entre el 28 de febrero de 2022 y el 30 de noviembre de 2023. Los participantes procedian de 189 paises y el 38% (6027/16 047) de paises de ingresos bajos y medios bajos. Lecciones aprendidas La participacion de ingenieros biomedicos y medicos voluntarios de paises de ingresos bajos y medios contribuyo a proporcionar un recurso de formacion adecuado. La OMS deberia seguir desarrollando estas herramientas de formacion y ofrecerlas a traves de OpenWHO, en especial para emergencias., Introduction During the coronavirus disease 2019 (COVID-19) pandemic, oxygen therapy and respiratory medical technologies were vital to treat and monitor COVID-19 patients with hypoxaemia. (1,2) As a result, large amounts [...]

Abstract Background This study was carried out to gauge the prevalence of academic dishonesty among academics in Malaysian universities. A direct comparison was made between academics of healthcare and non-healthcare courses to note the difference in the level of academic integrity between the two groups. In addition, the predisposing factors and implications of academic dishonesty, as well as the different measures perceived to be effective at curbing this problem were also investigated. Methods A cross-sectional study design with mixed qualitative and quantitative approaches was employed and data collection was carried out primarily using self-administered questionnaire. Results Approximately half (52.5%, n = 74) of all respondents (n = 141) reported having personally encountered at least one case of academic dishonesty involving their peers. The results also revealed the significantly higher prevalence of various forms of academic misconduct among healthcare academics compared to their non-healthcare counterparts. Although respondents were generally conscious of the negative implications associated with academic dishonesty, more than half of all cases of misconduct were not reported due to the indifferent attitude among academics. Low levels of self-discipline and integrity were found to be the major factors leading to academic misdeeds and respondents opined that university managements should be more proactive in addressing this issue. Conclusions The outcome of this study should serve as a clarion call for all relevant stakeholders to start making immediate amends in order to improve the current state of affairs in academia.

Blast crisis develops in a minority of patients with chronic myeloid leukemia even in the era of tyrosine kinase inhibitor (TKI) therapy. Reports suggest that we know little about the mechanism of BCR-ABL and AML1-ETO co-expression in blast crisis of chronic myeloid leukemia, and that other chromosomal abnormalities also coexist. Here, we document an unusual and interesting case of a 51-year-old female diagnosed in the chronic phase of chronic myeloid leukemia. After undergoing TKI treatment for 3 months, her bone marrow aspirates in the chronic phase had transformed to blast crisis. Molecular genetic testing indicated she was positive for p210 form of BCR-ABL (copy number decreased from 108.91% to 56.96%) and AML1-ETO fusion (copy number, 5.65%) genes and had additional chromosomal abnormalities of t(8; 21)(q22; q22)/t(9; 22)(q34; q11), t(2; 5)(p24; q13) and an additional +8 chromosome.

Abstract Background Sugarcane (Saccharum spp. hybrids) is considered the most globally important sugar-producing crop and raw material for biofuel. Insect attack is a major issue in sugarcane cultivation, resulting in yield losses and sucrose content reductions. Stem borer (Diatraea saccharalis F.) causes serious yield losses in sugarcane worldwide. However, insect-resistant germplasms for sugarcane are not available in any collections all over the world, and the molecular mechanism of insect resistance has not been elucidated. In this study, cry1Ac transgenic sugarcane lines were obtained and the biological characteristics and transgene dosage effect were investigated and a global exploration of gene expression by transcriptome analysis was performed. Results The transgene copies of foreign cry1Ac were variable and random. The correlation between the cry1Ac protein and cry1Ac gene copies differed between the transgenic lines from FN15 and ROC22. The medium copy lines from FN15 showed a significant linear relationship, while ROC22 showed no definite dosage effect. The transgenic lines with medium copies of cry1Ac showed an elite phenotype. Transcriptome analysis by RNA sequencing indicated that up/down regulated differentially expressed genes were abundant among the cry1Ac sugarcane lines and the receptor variety. Foreign cry1Ac gene and endogenous borer stress-related genes may have a synergistic effect. Three lines, namely, A1, A5, and A6, were selected for their excellent stem borer resistance and phenotypic traits and are expected to be used directly as cultivars or crossing parents for sugarcane borer resistance breeding. Conclusions Cry1Ac gene integration dramatically improved sugarcane insect resistance. The elite transgenic offspring contained medium transgene copies. Foreign cry1Ac gene integration and endogenous borer stress-related genes may have a synergistic effect on sugarcane insect resistance improvement.

The antidiabetic drug metformin has been associated with reduced colorectal cancer (CRC) risk and improved prognosis of CRC patients. However, the detailed mechanisms underlying such beneficial effects remain unknown. In this study, we aimed to evaluate metformin activity in CRC models and unveil the underlying molecular mechanisms. We showed that metformin inhibits CRC cell proliferation by arresting cells in the G1 phase of the cell cycle and dramatically reduces colony formation of CRC cells. We discovered that metformin causes a robust reduction of MYC protein level. Through the use of luciferase assay and coincubation with either protein synthesis or proteasome inhibitors, we demonstrated that regulation of MYC by metformin is independent of the proteasome and 3′ UTR‐mediated regulation, but depends on protein synthesis. Data from polysome profiling and ribopuromycylation assays showed that metformin induced widespread inhibition of protein synthesis. Repression of protein synthesis by metformin preferentially affects cell cycle‐associated proteins, by altering signaling through the mTOR‐4EBP‐eIF4E and MNK1‐eIF4G‐eIF4E axes. The inhibition of MYC protein synthesis may underlie metformin's beneficial effects on CRC risk and prognosis.

Abstract Background Sugarcane (Saccharum L. plant) is an important crop for sugar and bio-energy production around the world. Among sugarcane diseases, smut caused by Sporisorium scitamineum is one of the major fungal diseases causing severe losses to the sugarcane industry. The use of PCR reference genes is essential to the normalization of data on gene expression involving the sugarcane-S. scitamineum interaction system; however, no report that addresses criteria in selecting these reference genes has been published to date. Results In this study, 10 sugarcane genes and eight S. scitamineum genes were selected as candidate PCR reference genes in the sugarcane-S. scitamineum interaction system. The stability and reliability of these 18 candidate genes were analyzed in smut-resistant (NCo376) and -susceptible (YC71–374) genotypes using the statistical algorithms geNorm, NormFinder, BestKeeper, and deltaCt method. Subsequently, the relative expression levels of the sugarcane chitinase I-3 gene and S. scitamineum chorismate mutase gene were determined to validate the applicability of these sugarcane and S. scitamineum PCR reference genes, respectively. We finally found that the acyl-CoA dehydrogenase gene (ACAD), serine/arginine repetitive matrix protein 1 gene (SARMp1), or their combination (ACAD + SARMp1) could be utilized as the most suitable reference genes for normalization of sugarcane gene expression in sugarcane bud tissues after S. scitamineum infection. Similarly, the inosine 5′-monophosphate dehydrogenase gene (S10), the SEC65-signal recognition particle subunit gene (S11), or their combination (S10 + S11) were suitable for normalization of S. scitamineum gene expression in sugarcane bud tissues. Conclusions The PCR reference genes ACAD, SARMp1, S10, and S11 may be employed in gene transcriptional studies involving the sugarcane-S. scitamineum interaction system.

Abstract Background Currently, several fatigue measurement instruments are available to evaluate and measure cancer-related fatigue. Amongst them, Multidimensional Fatigue Syndrome Inventory-Short Form (MFSI-SF) is a self-reported instrument and a multidimensional scale that aims to capture the global, somatic, affective, cognitive and behavioural symptoms of fatigue. This study examines the psychometric properties and measurement equivalence of the English and Chinese versions of MFSI-SF in breast cancer and lymphoma patients in Singapore. Methods Patients were recruited from National Cancer Centre Singapore. Validity, reliability and responsiveness of MFSI-SF were evaluated in this study. Convergent validity was evaluated by correlating total and subscales of MFSI-SF to known related constructs in EORTC QLQ-C30. Known group validity was assessed based on patients’ cancer stage, pain, insomnia and depression symptoms. Reliability was evaluated by Cronbach’s α. Responsiveness analyses were performed with patients who have undergone at least one cycle of chemotherapy. Multiple regression was used to compare the total and subscale scores of MSFI-SF between the two language versions. Results Data from 246 (160 English and 86 Chinese version) breast cancer and lymphoma patients were included in the study. Moderate to high correlations were observed between correlated MFSI-SF subscales and EORTC QLQ-C30 domains (|r| = 0.524 to 0.774) except for a poor correlation (r = 0.394) observed between MFSI-SF vigour subscale and EORTC QLQ-C30 role functioning subscale. Total MFSI-SF scores could differentiate between patients with higher depression, pain and insomnia status. Internal consistency of MFSI-SF was also high (α = 0.749 to 0.944). Moderate correlation was observed between change in total MFSI-SF score and change in fatigue symptom scale score and global QoL score on EORTC QLQ-C30 (|r| = 0.478 and 0.404 respectively). Poor correlations were observed between change in scores of hypothesised subscales (|r| = 0.202 to 0.361) except for a moderate correlation between change in MFSI-SF emotional fatigue score and change in EORTC QLQ-C30 emotional functioning domain score. Measurement equivalence was established for all subscales and total MFSI-SF score except for the emotional and vigour subscales. Conclusions This study supports the use of MFSI-SF as a reasonably valid scale with good internal consistency for measuring fatigue levels in the Singapore cancer population.

Introduction: This study aims to study the changing trends and outcomes associated with the adoption of minimally invasive distal pancreatectomy (MIDP) at a single centre. Materials and Methods: Retrospective review of sixty consecutive patients who underwent MIDP from September 2006 to November 2016 at a single institution. To study the evolution of MIDP, the study population was divided into three groups consisting of twenty patients (Group I, Group II and Group III). Results: Sixty patients underwent MIDP with 11 (18.3%) requiring open conversions. The median operation time was 305 (range: 85–775) min and the median post-operative stay was 6 (range: 3–73) days. Fifteen procedures were spleen-saving pancreatectomies. Major post-operative morbidity (>Grade 2) occurred in 12 (20.0%) patients and there was no mortality or reoperations. There were 33 (55.0%) pancreatic fistulas, of which 15 (25.0%) were Grade B fistulas of which 12 (20.0%) required percutaneous drainage. Comparison between the three groups demonstrated a statistically significant increase in the frequency of procedures performed, increase in robotic-assisted procedures and proportion of asymptomatic tumours resected. There also tended to be non-significant decrease in open conversion rates from 25% to 5% between the three groups and increase in tumour size resected from 24 to 40 mm. Conclusion: Comparison between the three groups demonstrated that MIDP was performed with increased frequency. There was a statistically significant increase in the frequency of resections performed for asymptomatic tumours and resections performed through robotic assistance. There was also a non-significant trend towards a decrease in open conversions and increase in the size of tumours resected.

Cultural competence is a continuously developing process that requires transition-to-practice program training to enable new graduate nurses (NGNs) to transfer their knowledge and skills to clinical practice in a culturally sensitive manner. The development and implementation of residency programs, including a cultural competence curriculum, could support this transition. This study aimed to evaluate the preliminary effects of a hybrid learning module of cultural competence for NGNs. A quasi-experimental design was used in a 3,000-bed hospital in North Taiwan. We randomly allocated 37 NGNs to the experimental and control groups. The Cultural Competence Scale for Pre-Graduate Students to Licensed Professionals (CS-SP) was adopted to measure cultural competence before and after the intervention. We evaluated the correlations between learning time and cultural competence scores using a paired t-test, chi-square test, and Mann--Whitney test for statistical analysis. The curriculum for the learning application comprised three courses covering six topics. The experimental group scored significantly higher in awareness and skills after the intervention (p < 0.05), but there was no significant improvement in knowledge or self-efficacy. The control group showed no significant differences in any of the cultural competence subscale scores after intervention. The Mann-Whitney test showed that different learning times led to significant differences in the mean cultural competence scores (Z = 3.04, p < 0.05). Integrating cultural competency education into web-based NGNs' postgraduate year of nursing programs improved their cultural competence awareness and skills. The learning application can be adapted to target NGNs at different stages of the postgraduate year of nursing programs to maximize its benefits.