Multiscale design of cell-free biologically active architectural structures.

Cell-free protein expression systems are here combined with 3D-printed structures to study the challenges and opportunities as biofabrication enters the spaces of architecture and design. Harnessing large-scale additive manufacturing of biological materials, we examined the addition of cell-free protein expression systems ("TXTL" i.e., biological transcription-translation machinery without the use of living cells) to printed structures. This allowed us to consider programmable, living-like, responsive systems for product design and indoor architectural applications. This emergent, pluripotent technology offers exciting potential in support of health, resource optimization, and reduction of energy use in the built environment, setting a new path to interactivity with mechanical, optical, and (bio) chemical properties throughout structures. We propose a roadmap towards creating healthier, functional and more durable systems by deploying a multiscale platform containing biologically-active components encapsulated within biopolymer lattices operating at three design scales: (i) supporting cell-free protein expression in a biopolymer matrix (microscale), (ii) varying material properties of porosity and strength within two-dimensional lattices to support biological and structural functions (mesoscale), and (iii) obtaining folded indoor surfaces that are structurally sound at the meter scale and biologically active (we label that regime macroscale). We embedded commercially available cell-free protein expression systems within silk fibroin and sodium alginate biopolymer matrices and used green fluorescent protein as the reporter to confirm their compatibility. We demonstrate mechanical attachment of freeze-dried bioactive pellets into printed foldable fibrous biopolymer lattices showing the first steps towards modular multiscale fabrication of large structures with biologically active zones. Our results discuss challenges to experimental setup affecting expression levels and show the potential of robust cell-free protein-expressing biosites within custom-printed structures at scales relevant to everyday consumer products and human habitats.

Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Inner southern magnetosphere observation of Mercury via SERENA ion sensors in BepiColombo mission.

Mercury's southern inner magnetosphere is an unexplored region as it was not observed by earlier space missions. In October 2021, BepiColombo mission has passed through this region during its first Mercury flyby. Here, we describe the observations of SERENA ion sensors nearby and inside Mercury's magnetosphere. An intermittent high-energy signal, possibly due to an interplanetary magnetic flux rope, has been observed downstream Mercury, together with low energy solar wind. Low energy ions, possibly due to satellite outgassing, were detected outside the magnetosphere. The dayside magnetopause and bow-shock crossing were much closer to the planet than expected, signature of a highly eroded magnetosphere. Different ion populations have been observed inside the magnetosphere, like low latitude boundary layer at magnetopause inbound and partial ring current at dawn close to the planet. These observations are important for understanding the weak magnetosphere behavior so close to the Sun, revealing details never reached before.

Validation of the International Trauma Questionnaire-Child and Adolescent Version (ITQ-CA) in a Chinese mental health service seeking adolescent sample.

BACKGROUND: The International Trauma Questionnaire-Child and Adolescent version (ITQ-CA) is a self-report measure that assesses posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD) based on the diagnostic formulation of the 11th version of the International Classification of Diseases (ICD-11). This study aimed to provide a Chinese translation and psychometric evaluation of the ITQ-CA using a sample of mental-health service seeking adolescents in Mainland China. METHODS: The ITQ-CA was translated and back-translated from English to simplified Chinese and finalized with consensus from an expert panel. Adolescents ages 12-17 were recruited via convenience sampling from an outpatient psychiatric clinic in Mainland China. Participants completed the ITQ-CA; measures of four criterion variables (depression, anxiety, stress, adverse childhood experiences); and the PTSD Checklist for DSM-5 (PCL-5). Construct validity, concurrent validity, and comparison of PTSD caseness between ICD-11 and DSM-5 measures were assessed. RESULTS: The final sample consisted of 111 Chinese adolescents (78% female; mean age of 15.23), all diagnosed with a major depressive disorder. Confirmatory factor analysis indicated the two-factor second-order model provided optimal fit. All criterion variables were positively and significant correlated with the six ITQ-CA symptom cluster summed scores. In the present sample, 69 participants (62.16%) met symptom criteria for ICD-PTSD or CPTSD using the ITQ-CA, and 73 participants (65.77%) met caseness for DSM-5 PTSD using the PCL-5. Rates of PTSD symptom cluster endorsement and caseness deriving from both diagnostic systems were comparable. CONCLUSIONS: The Chinese ITQ-CA has acceptable psychometric properties and confers additional benefits in identifying complex presentations of trauma-related responses in younger people seeking mental health services.

Anxiety, depression and stress among internally displaced persons and host community in an armed conflict region: A comparative study.

This study compares the psychological profile of Internally Displaced Persons (IDPs) and individuals living in host communities in the war-affected setting. We conducted a cross-sectional survey from October-November 2019. Subjects were recruited from six IDPs camps and the surrounding host communities within the metropolis of Maiduguri, Nigeria by convenience sampling. Data were collected using the Hausa version of Depression Anxiety Stress Scale-21, and analysed by logistic regression using adjusted odds ratio (AOR) at 95% Confidence Interval (CI). A total of 562 subjects were recruited. Living in IDP camp was the most significantly predictor of depression, anxiety, and stress. The common predictors were living in an IDP camp, and marital status (separated). Aged 18-29years was a protective factor compared to those ≥50years. Living in IDP camps, separated from partners, lack of education and pre-conflict employment were significant predictors of depression, anxiety and stress.

Water Circular Economy at the Kwinana Industrial Area, Western Australia-the Dimensions and Value of Industrial Symbiosis.

The major industrial companies located in the Kwinana Industrial Area (KIA) produce many industrial, agricultural and mining chemicals and refined materials, for national and international markets. With over 150 documented product and by-product exchanges, Kwinana is considered to be one of the best examples of industrial symbiosis (IS) in the world. A new model of IS comprised of four dimensions is under development, whereby whilst each dimension is unique, collectively, they interact to characterise an industrial estate, thus contributing to the evolutionary understanding of IS. We investigate the basis for this model through an analysis of two water circular economy examples as they relate to Western Australia's premier industrial area, the KIA. Case studies will consider a managed aquifer recharge (MAR) project that failed and the process water interconnectedness of enterprises operating successfully as a sub-ecology within the industrial cluster. Apart from the traditional product and by-product dimension of IS, three additional dimensions seem to be playing a crucial role in the KIA, these being the skilled workforce, support industry and governance dimensions. We provide additional context for the water-related examples of the circular economy at Kwinana by exploring a new four-dimensional model for IS.

A change in clinical practice for aural foreign bodies - what we learnt from the coronavirus disease 2019 pandemic.

OBJECTIVE: This case series, conducted during the coronavirus disease 2019 pandemic, investigates the impact of leaving aural foreign bodies in situ for a prolonged period of time, including the risk of complications and success rates of subsequent removal attempts. METHOD: A retrospective study of aural foreign body referrals over a six-month period was carried out. RESULTS: Thirty-four patients with 35 foreign bodies were identified (6 organic and 29 inorganic). The duration of foreign bodies left in situ ranged from 1 to 78 days. Four patients suffered from traumatic removal upon initial attempts. First attempts made by non-ENT specialists (68.8 per cent) all failed and were associated with a high risk of trauma (36.4 per cent). CONCLUSION: Because of the coronavirus disease 2019 pandemic, this is the first case series to specifically investigate the relationship between the duration of aural foreign bodies left in situ and the risk of complications. Our data suggest that prolonged duration does not increase the incidence of complications.

Comparative analysis of Student's live online learning readiness during the coronavirus (COVID-19) pandemic in the higher education sector.

Amid the coronavirus outbreak, many countries are facing a dramatic situation in terms of the global economy and human social activities, including education. The shutdown of schools is affecting many students around the world, with face-to-face classes suspended. Many countries facing the disastrous situation imposed class suspension at an early stage of the coronavirus outbreak, and Asia was one of the earliest regions to implement live online learning. Despite previous research on online teaching and learning, students' readiness to participate in the real-time online learning implemented during the coronavirus outbreak is not yet well understood. This study explored several key factors in the research framework related to learning motivation, learning readiness and student's self-efficacy in participating in live online learning during the coronavirus outbreak, taking into account gender differences and differences among sub-degree (SD), undergraduate (UG) and postgraduate (PG) students. Technology readiness was used instead of conventional online/internet self-efficacy to determine students' live online learning readiness. The hypothetical model was validated using confirmatory factor analysis (CFA). The results revealed no statistically significant differences between males and females. On the other hand, the mean scores for PG students were higher than for UG and SD students based on the post hoc test. We argue that during the coronavirus outbreak, gender differences were reduced because students are forced to learn more initiatively. We also suggest that students studying at a higher education degree level may have higher expectations of their academic achievement and were significantly different in their online learning readiness. This study has important implications for educators in implementing live online learning, particularly for the design of teaching contexts for students from different educational levels. More virtual activities should be considered to enhance the motivation for students undertaking lower-level degrees, and encouragement of student-to-student interactions can be considered.

An analysis of the continuing professional development needs of radiographers and radiation therapists in Singapore.

INTRODUCTION: Continuing Professional development (CPD) is deemed essential for the Radiographers (DR) and Radiation Therapists (RT) after Singapore commenced state registration. Diagnostic imaging and radiotherapy treatment services are constantly revolutionizing and those working in this field requires sufficient knowledge of the uptrends for training and development. The purpose of this survey is to identify the current training needs of the registered DR and RT in Singapore, and to understand their views about CPD activities. METHODS: An online questionnaire was disseminated by the Singapore Society of Radiographers (SSR) to all registered DR and RT in Singapore, and all practicing in restructured and private hospitals were included. Data collection took place from January 2018 to April 2018. RESULTS: 102 responses were analysed, where 89 were DR and 13 were RT. CPD was provided in 72.5% (n = 74) of the participants' institutions, and 69.6% (n = 71) of participants were aware of CPD. Interestingly, participants were significantly more likely to be unaware of CPD when working in an institution which do not offer CPD. Training programme objective was the most important factor for selecting a programme. 93.1% (n = 95) preferred SSR to support them for CPD. There were a few constraints to CPD engagements identified such as financial factors, lack of time, and institution availability. CONCLUSION: There was significant intrinsic motivation in a quality CPD activity. CPD activities should be current, accessible and relevant for the healthcare professionals to increase participation, which directly contributes to high standards of clinical care. IMPLICATIONS FOR PRACTICE: Local healthcare institutions should be aware and address needs, gaps and aspirations of the local DR and RT community to ensure adequate preparation has been made upon initiation of mandatory CPD.

SERENA: Particle Instrument Suite for Determining the Sun-Mercury Interaction from BepiColombo.

The ESA-JAXA BepiColombo mission to Mercury will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric particle dynamics at Mercury as well as their interactions with solar wind, solar radiation, and interplanetary dust. The particle instrument suite SERENA (Search for Exospheric Refilling and Emitted Natural Abundances) is flying in space on-board the BepiColombo Mercury Planetary Orbiter (MPO) and is the only instrument for ion and neutral particle detection aboard the MPO. It comprises four independent sensors: ELENA for neutral particle flow detection, Strofio for neutral gas detection, PICAM for planetary ions observations, and MIPA, mostly for solar wind ion measurements. SERENA is managed by a System Control Unit located inside the ELENA box. In the present paper the scientific goals of this suite are described, and then the four units are detailed, as well as their major features and calibration results. Finally, the SERENA operational activities are shown during the orbital path around Mercury, with also some reference to the activities planned during the long cruise phase.

Childhood Adversity, Resilience, and Mental Health: A Sequential Mixed-Methods Study of Chinese Young Adults.

Resilience is a key health protective factor for those with adverse childhood experiences (ACEs), but little research has explored how it manifests in early adulthood or across cultures. The purpose of this study was to generate a fuller understanding of resilience and its contribution to the relationships between mental health problems and ACEs among Chinese young adults in Hong Kong. Using a sequential explanatory mixed-methods design, 433 Chinese young adults aged 18 to 24 years were surveyed online to examine the relationships between ACEs, resilience, and mental health problems (depression, anxiety, maladjustment, and posttraumatic stress symptoms). Among them, 34 participants with ACEs were purposively selected and interviewed to explore cultural factors that influenced their resilience. Quantitative data were analyzed using multiple hierarchical regression analyses; qualitative data were analyzed using a qualitative descriptive approach. Higher cumulative ACE exposure was associated with higher severity of adjustment disorder and odds for screening positive for posttraumatic stress disorders, but not for symptoms of depression or anxiety. Resilience significantly contributed to explaining variances across all mental health outcomes over and beyond ACEs and in a protective fashion. Four themes emerged from qualitative interviews: (a) Privacy, emotional restraint, and "saving face"; (b) Conforming to preserve harmony; (c) A will to excel; and (d) Viewing adversity as a matter of luck. These findings suggest Chinese young adults' resilience was influenced by cultural norms of restraint, conformity, competition, and superstition. The present study provides a model for future studies using a mixed-methods design to deeply examine resilience among younger people exposed to early adversities within sociocultural, historical, or geographical contexts.

Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease.

BACKGROUND: Success in personalized medicine in complex disease is critically dependent on biomarker discovery. We profiled serum proteins using a novel proximity extension assay [PEA] to identify diagnostic and prognostic biomarkers in inflammatory bowel disease [IBD]. METHODS: We conducted a prospective case-control study in an inception cohort of 552 patients [328 IBD, 224 non-IBD], profiling proteins recruited across six centres. Treatment escalation was characterized by the need for biological agents or surgery after initial disease remission. Nested leave-one-out cross-validation was used to examine the performance of diagnostic and prognostic proteins. RESULTS: A total of 66 serum proteins differentiated IBD from symptomatic non-IBD controls, including matrix metallopeptidase-12 [MMP-12; Holm-adjusted p = 4.1 × 10-23] and oncostatin-M [OSM; p = 3.7 × 10-16]. Nine of these proteins are associated with cis-germline variation [59 independent single nucleotide polymorphisms]. Fifteen proteins, all members of tumour necrosis factor-independent pathways including interleukin-1 (IL-1) and OSM, predicted escalation, over a median follow-up of 518 [interquartile range 224-756] days. Nested cross-validation of the entire data set allowed characterization of five-protein models [96% comprising five core proteins ITGAV, EpCAM, IL18, SLAMF7 and IL8], which define a high-risk subgroup in IBD [hazard ratio 3.90, confidence interval: 2.43-6.26], or allowed distinct two- and three-protein models for ulcerative colitis and Crohn's disease respectively. CONCLUSION: We have characterized a simple oligo-protein panel that has the potential to identify IBD from symptomatic controls and to predict future disease course. Further prospective work is required to validate our findings.

Autonomous atmospheric water seeping MOF matrix.

The atmosphere contains an abundance of fresh water, but this resource has yet to be harvested efficiently. To date, passive atmospheric water sorbents have required a desorption step that relies on steady solar irradiation. Since the availability and intensity of solar radiation vary, these limit on-demand desorption and hence the amount of harvestable water. Here, we report a polymer-metal-organic framework that provides simultaneous and uninterrupted sorption and release of atmospheric water. The adaptable nature of the hydro-active polymer, and its hybridization with a metal-organic framework, enables enhanced sorption kinetics, water uptake, and spontaneous water oozing. We demonstrate continuous water delivery for 1440 hours, producing 6 g of fresh water per gram of sorbent at 90% relative humidity (RH) per day without active condensation. This leads to a total liquid delivery efficiency of 95% and an autonomous liquid delivery efficiency of 71%, the record among reported atmospheric water harvesters.

Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.

BACKGROUND: MicroRNAs [miRNAs] are cell-specific small non-coding RNAs that can regulate gene expression and have been implicated in inflammatory bowel disease [IBD] pathogenesis. Here we define the cell-specific miRNA profiles and investigate its biomarker potential in IBD. METHODS: In a two-stage prospective multi-centre case control study, next generation sequencing was performed on a discovery cohort of immunomagnetically separated leukocytes from 32 patients (nine Crohn's disease [CD], 14 ulcerative colitis [UC], eight healthy controls) and differentially expressed signals were validated in whole blood in 294 patients [97 UC, 98 CD, 98 non-IBD, 1 IBDU] using quantitative PCR. Correlations were analysed with phenotype, including need for early treatment escalation as a marker of progressive disease using Cox proportional hazards. RESULTS: In stage 1, each leukocyte subset [CD4+ and CD8+ T-cells and CD14+ monocytes] was analysed in IBD and controls. Three specific miRNAs differentiated IBD from controls in CD4+ T-cells, including miR-1307-3p [p = 0.01], miR-3615 [p = 0.02] and miR-4792 [p = 0.01]. In the extension cohort, in stage 2, miR-1307-3p was able to predict disease progression in IBD (hazard ratio [HR] 1.98, interquartile range [IQR]: 1.20-3.27; logrank p = 1.80 × 10-3), in particular CD [HR 2.81; IQR: 1.11-3.53, p = 6.50 × 10-4]. Using blood-based multimarker miRNA models, the estimated chance of escalation in CD was 83% if two or more criteria were met and 90% for UC if three or more criteria are met. INTERPRETATION: We have identified and validated unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These miRNAs may be able to predict treatment escalation and have the potential for clinical translation; further prospective evaluation is now indicated.

Caregiver strain on informal caregivers when providing care for older patients undergoing major abdominal surgery: a longitudinal prospective cohort study.

BACKGROUND: Health-care systems nowadays rely on complementary patient care by informal caregivers. The need for, and burden on, informal caregivers will likely increase in the upcoming years. This study aimed to examine the burden on caregivers when providing care for elderly patients undergoing major abdominal surgery. METHODS: A single-centre longitudinal cohort study was conducted between November 2015 and June 2018 in the Amphia hospital in Breda, the Netherlands. Patients aged 70+ undergoing elective surgery for colorectal carcinoma (CRC) or an abdominal aortic aneurysm (AAA) were included in this study. Informal caregiver burden was assessed and compared over time using the Caregiver Strain Index (CSI) at the outpatient clinic visit, at discharge, 2 weeks post-discharge and after 6 and 12 months. The effects of patient- and caregiver-related factors on the experienced caregiver strain were examined. RESULTS: CSI scores of 248 caregivers were significantly increased at discharge (3.5 vs 2.6; p < 0.001) and 2 weeks post-discharge (3.3 vs 2.6; p < 0.001). After 12 months, scores dropped below baseline scores (1.8 vs 2.6; p = 0.012). The highest strain was observed 2 weeks post-discharge for AAA patients and at discharge for CRC patients. Older age, physical or cognitive impairment and burden of comorbidity were associated with an increased caregiver strain at baseline. Type of surgery was independently associated with the change in mean CSI scores over time; a bigger change in caregiver burden is observed after open surgery. CONCLUSION: In the early postoperative period, perceived caregiver strain was significantly increased. Psychological support for caregivers may be advisable, with timing of this support depending on diagnosis and patient-related factors. TRIAL REGISTRATION: This manuscript was retrospectively registered on 05-04-2016 in the Netherlands Trial Register (NTR5932). http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5932.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

Effect of conservative treatment in aortoiliac occlusive disease.

Objective: To determine the effect of primary conservative treatment without revascularization in patients with proven aortoiliac occlusive disease (AIOD) presenting with intermittent claudication (IC).Background: The initial treatment of IC should focus on supervised exercise therapy (SET) and pharmacotherapy. Nowadays, primary endovascular revascularization (EVR) has become increasingly popular in patients with all types of AIOD. But in daily practice, EVR is often performed without initially extensive exercise.Method: This is a single centre retrospective study from December 2012 to September 2017. Primary outcomes were maximum walking distance (MWD) and patient satisfaction. Secondary outcomes were revascularization rate and mortality.Results: Twenty-four patients were included. Mean age was 64 years (SD: 9). Mean follow-up was 28 months (SD: 17). Nineteen patients (80%) had SET. In 18 (75%) patients, the MWD was improved compared to the initial situation. In five (21%) patients, the MWD stayed the same. The MWD of one (4%) patient decreased. Overall satisfaction rate was 87%. Three patients (13%) were not satisfied with the conservative treatment and eventually got an EVR. There was no disease related death.Conclusions: Conservative treatment, especially with SET, has acceptable subjective symptom outcomes in selected patients with AIOD. It could be a good alternative treatment for certain patients with AIOD and IC.