bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Filtered Containment Venting Strategies for Mitigating Severe Accident Consequences at a Generic Single-Unit CANDU
Authors: Shah M. D. , Morreale A. C. , Lebel L. S. 
Published: August 2022

Abstract
In many jurisdictions, filtered containment venting systems are an integral part of severe accident management guidelines but are normally only used as a last resort, to be manually activated when the containment pressure approaches the containment failure limit. This approach fails to utilize the capability of the filtered venting system to better control containment pressure throughout an accident and to create capacity for possible future pressurization based on the accident progression. In this paper, smart venting strategies are explored, using a generic single-unit Canada Deuterium Uranium (CANDU) (660 MWel) plant model in MAAP-CANDU, as a means to mitigate the consequences of a severe accident. These strategies are able to account for both current conditions as well as possible future pressurization. The use of strategic venting offers an improvement in maintaining containment integrity, as well as reducing I-131 releases to the environment by about 10% to 31% compared to last-resort venting while being feasible for manual operator actions. Overall, this comprehensive analysis demonstrates the capability of a smart venting strategy paired with a filtered containment venting system as an active mitigation tool.
Costing Participation in Sport: The Best Option Dilemma of a Student-Athlete
Authors: Alcorn Michael , Abeza Gashaw , O’Reilly Norm 
Published: August 2022

Rebecca Griffin, a student-athlete, is coming off the best off-season training program of her 8 years as a rower. She is highly motivated knowing that a strong summer season could propel her to be both a major contributor to her university team in the fall and a contender to make it to the National Under 23 team. However, before she can pursue her athletic dreams, she needs to decide where she is going to row this summer and figure out if she can afford to pay for it. She needs to assess and consider the benefits and drawbacks of her summer rowing club options. Her considerations include club registration fees, travel, equipment, coaching, and competition entry costs for each, and how they will contribute to her career goals in rowing. Therefore, while working toward her goals, Rebecca must consider the affordability of her options, and make the best decision she can.
Physical Activity Influences Cortisol and Dehydroepiandrosterone (Sulfate) Levels in Older Adults: A Systematic Review and Meta-Analysis
Authors: De Nys Len , Ofosu Esther F. , Ryde Gemma C. , Connelly Jenni , Whittaker Anna C. 
Published: August 2022

Age-related changes affect the ratio between two steroid hormones of the hypothalamic-pituitary-adrenal axis, cortisol and dehydroepiandrosterone (sulfate) (DHEA[S]). Physical activity (PA) may buffer the effects of chronic stress and counteract the aging decline of DHEA(S). Therefore, a systematic review was conducted to understand how PA influences physiological markers of cortisol and/or DHEA(S) and whether there is a difference in observational associations or experimental effects in older adults aged 65 years and older. A narrative synthesis was performed on nine observational studies, and meta-analyses were performed on 22 randomized controlled trials. There was low- to moderate-quality evidence that regular PA beneficially reduces cortisol and increases DHEA(S) levels. Subgroup analyses showed no clinically important differences between men and women, different exercise modalities, or health states. The findings cautiously suggest that regular PA of older adults’ own choice that they find enjoyable could be recommended to improve cortisol and/or DHEA(S) levels.
Transitional care innovation for Medicaid-insured individuals: early findings
Authors: Brooks Carthon J Margo , Brom Heather , French Rachel , Daus Marguerite , Grantham-Murillo Marsha , Bennett Jovan , Ryskina Kira , Ponietowicz Eileen , Cacchione Pamela 
Published: August 2022

BackgroundChronically ill adults insured by Medicaid experience health inequities following hospitalisation.Local problemPostacute outcomes, including rates of 30-day readmissions and postacute emergency department (ED), were higher among Medicaid-insured individuals compared with commercially insured individuals and social needs were inconsistently addressed.MethodsAn interdisciplinary team introduced a clinical pathway called ‘THRIVE’ to provide postacute wrap-around services for individuals insured by Medicaid.InterventionEnrolment into the THRIVE clinical pathway occurred during hospitalisation and multidisciplinary services were deployed into homes within 48 hours of discharge to address clinical and social needs.ResultsCompared with those not enrolled in THRIVE (n=437), individuals who participated in the THRIVE clinical pathway (n=42) experienced fewer readmissions (14.3% vs 28.4%) and ED visits (14.3% vs 28.8 %).ConclusionTHRIVE is a promising clinical pathway that increases access to ambulatory care after discharge and may reduce readmissions and ED visits.
Population study on diagnosis, treatment and outcomes of critically ill patients with tuberculosis (2008–2018)
Authors: So Christina , Ling Lowell , Wong Wai Tat , Zhang Jack Zhenhe , Ho Chun Ming , Ng Pauline Yeung , Shum Hoi Ping , Yeung Alwin Wai Tak , Sin Kai Cheuk , Chan Jacky , Au Ka Fai , Liong Ting , Ho Eunise , Chow Fu Loi , Ho Laptin , Chan Kai Man , Joynt Gavin Matthew 
Published: August 2022

BackgroundTuberculosis (TB) is a preventable and curable disease, but mortality remains high among those who develop sepsis and critical illness from TB.MethodsThis was a population-based, multicentre retrospective cohort study of patients admitted to all 15 publicly funded Hong Kong adult intensive care units (ICUs) between 1 April 2008 and 31 March 2019. 940 adult critically ill patients with at least one positiveMycobacterium tuberculosis(MTB) culture were identified out of 133 858 ICU admissions. Generalised linear modelling was used to determine the impact of delay in TB treatment on hospital mortality. Trend of annual Acute Physiology and Chronic Health Evaluation (APACHE) IV-adjusted standardised mortality ratio (SMR) over the 11-year period was analysed by Mann-Kendall’s trend test.ResultsICU and hospital mortality were 24.7% (232/940) and 41.1% (386/940), respectively. Of those who died in the ICU, 22.8% (53/232) never received antituberculosis drugs. SMR for ICU patients with TB remained unchanged over the study period (Kendall’s τb=0.37, p=0.876). After adjustment for age, Charlson comorbidity index, APACHE IV, albumin, vasopressors, mechanical ventilation and renal replacement therapy, delayed TB treatment was directly associated with hospital mortality. In 302/940 (32.1%) of patients, TB could only be established from MTB cultures alone as Ziehl-Neelsen staining or PCR was either not performed or negative. Among this group, only 31.1% (94/302) had concurrent MTB PCR performed.ConclusionsSurvival of ICU patients with TB has not improved over the last decade and mortality remains high. Delay in TB treatment was associated with higher hospital mortality. Use of MTB PCR may improve diagnostic yield and facilitate early treatment.
Whole genome sequencing of mesorhizobia isolated from northern Canada
Authors: Duan Yi Fan , Grogan Paul , Walker Virginia K , diCenzo George C 
Published: August 2022

Rhizobia are soil-dwelling bacteria that can form N2-fixing symbioses with legume plant species (Fabaceae). These bacteria are globally distributed; however, few studies have examined the genomics of rhizobia that live in cold environments. Here, we isolated and characterized three rhizobial strains from legume nodules collected at a pair of distant low Arctic tundra and boreal forest sites in northern Canada. Phylogenetic and average nucleotide identity measurements suggested that the three strains are members of the genus Mesorhizobium, and that each strain represents a novel genospecies. Intriguingly, whereas most mesorhizobia contain the classical determinants of nodulation and nitrogen fixation on their chromosome, whole genome sequencing revealed that all three strains carry these genes on large symbiotic megaplasmids of ∼750 to ∼1000 kb. Phylogenetic and sequence analyses of the common nodulation genes revealed highly conserved alleles amongst these northern mesorhizobia, leading us to propose that they belong to a novel symbiovar that we termed symbiovar oxytropis. Interestingly, these nod gene alleles are uncommon in mesorhizobia isolated from similar plant hosts in other climatic regions, suggesting potential functional adaptive differences.
Profile of Bioactive Compounds, Aromas, and Cup Quality of Excelsa Coffee (Coffea liberica var. dewevrei) Prepared from Diverse Postharvest Processes
Authors: Herawati Dian , Loisanjaya Michael Oscarius , Kamal Radwa Husni , Adawiyah Dede Robiatul , Andarwulan Nuri 
Published: August 2022

The study is aimed at evaluating bioactive compounds, volatile compounds, and cup quality of Excelsa coffee (Coffea liberica var. dewevrei) from different postharvest processing procedures, i.e., natural, honey, semiwashed, and wine. The green beans from each procedure were roasted at light to medium levels. Sample analysis was performed using HPLC and GC-MS instruments for bioactive compounds and volatile compounds, respectively, followed by a cupping test. As the results, postharvest processing significantly altered content of bioactive compounds (caffeoylquinic acids (CQAs) and alkaloids) in Excelsa green beans; the lowest quantity of CQAs and alkaloids was found in wine and semiwashed green beans, respectively. Significant degradation of 5-CQA and its transformation to 3-CQA and 4-CQA occurred in all light-medium roasting levels. In general, alkaloids were stable during roasting, and only trigonelline was slightly declined. Roasting process also generated 17 potent volatile compounds in Excelsa beans including 2-ethylpyrazine, 2,3-dimethylpyrazine, 2,5-dimethylpyrazine, 2,5-dimethyl-3-ethylpyrazine, guaiacol, 4-vinyl-guaiacol, and isovaleric acid and its esters. Furthermore, cupping test revealed that Excelsa coffee samples obtained from different postharvest processing were categorized as very good coffee (

cupping

score
>
80

). This finding may encourage the commercialization of all observed Excelsa coffee beans.
Efficacy of CD40 Agonists Is Mediated by Distinct cDC Subsets and Subverted by Suppressive Macrophages
Authors: Murgaski Aleksandar , Kiss Máté , Van Damme Helena , Kancheva Daliya , Vanmeerbeek Isaure , Keirsse Jiri , Hadadi Eva , Brughmans Jan , Arnouk Sana M. , Hamouda Ahmed E.I. , Debraekeleer Ayla , Bosteels Victor , Elkrim Yvon , Boon Louis , Hoves Sabine , Vandamme Niels , Deschoemaeker Sofie , Janssens Sophie , Garg Abhishek D. , Vande Velde Greetje , Schmittnaegel Martina , Ries Carola H. , Laoui Damya 
Published: August 2022

AbstractAgonistic αCD40 therapy has been shown to inhibit cancer progression in only a fraction of patients. Understanding the cancer cell–intrinsic and microenvironmental determinants of αCD40 therapy response is therefore crucial to identify responsive patient populations and to design efficient combinatorial treatments. Here, we show that the therapeutic efficacy of αCD40 in subcutaneous melanoma relies on preexisting, type 1 classical dendritic cell (cDC1)–primed CD8+ T cells. However, after administration of αCD40, cDC1s were dispensable for antitumor efficacy. Instead, the abundance of activated cDCs, potentially derived from cDC2 cells, increased and further activated antitumor CD8+ T cells. Hence, distinct cDC subsets contributed to the induction of αCD40 responses. In contrast, lung carcinomas, characterized by a high abundance of macrophages, were resistant to αCD40 therapy. Combining αCD40 therapy with macrophage depletion led to tumor growth inhibition only in the presence of strong neoantigens. Accordingly, treatment with immunogenic cell death–inducing chemotherapy sensitized lung tumors to αCD40 therapy in subcutaneous and orthotopic settings. These insights into the microenvironmental regulators of response to αCD40 suggest that different tumor types would benefit from different combinations of therapies to optimize the clinical application of CD40 agonists.Significance:This work highlights the temporal roles of different dendritic cell subsets in promoting CD8+ T-cell–driven responses to CD40 agonist therapy in cancer.
Ancient Human Endogenous Retroviruses Contribute to Genetic Evolution and Regulate Cancer Cell Type–Specific Gene Expression
Authors: Chen Mingyue , Jia Lei , Zheng Xiaofeng , Han Mingshu , Li Lin , Zhang Lei 
Published: August 2022

Abstract

Human endogenous retroviruses (HERV), a type of transposable elements (TE), play crucial roles in human placental morphogenesis, immune response, and cancer progression. Emerging evidence suggests that TEs have been a rich source of regulatory elements in the human genome, but little is known about the global impact of HERVs on transcriptional networks in cancer. Using genome-wide approaches, we show that HERVs are composed primarily of three ancient superfamilies: ERVL-MaLR, ERVL, and ERV1. This analysis suggests that the integration of exonic, intronic, and intergenic HERVs, as well as human or Hominidae gene-specific HERVs, contributes to human genomic innovation. HERVs exonized in genes are located mainly in the 3′ untranslated region (UTR) or 3′ end and participate in basic biological processes. Active HERVs are located mainly in intronic and intergenic regions and tend to function as enhancers and contribute to cancer cell type–specific gene expression. More importantly, HERVs may also define chromatin topologically associating domain (TAD) and loop boundaries in a cell type–specific manner. Taken together, these findings reveal that ancient HERV elements are a source of diverse regulatory sequences, including 3′ UTRs, 5′ UTRs, promoters, and enhancers, and they contribute to genetic innovation and cancer cell type–specific gene expression, highlighting the previously underestimated importance of these elements.

Significance:
Genome-wide analyses show that human endogenous retroviruses mediate cancer cell type–specific gene expression, epigenetic modification, and 3D chromatin architecture, elucidating the relationship between HERVs and diverse cancers.
Inhibition of Melanoma Cell–Intrinsic Tim-3 Stimulates MAPK-Dependent Tumorigenesis
Authors: Schatton Tobias , Itoh Yuta , Martins Christina , Rasbach Erik , Singh Praveen , Silva Mariana , Mucciarone Kyla , Heppt Markus V. , Geddes-Sweeney Jenna , Stewart Kate , Brandenburg Anne , Liang Jennifer , Dimitroff Charles J. , Mihm Martin C. , Landsberg Jennifer , Schlapbach Christoph , Lian Christine G. , Murphy George F. , Kupper Thomas S. , Ramsey Matthew R. , Barthel Steven R. 
Published: August 2022

Abstract

T-cell immunoglobulin mucin family member 3 (Tim-3) is an immune checkpoint receptor that dampens effector functions and causes terminal exhaustion of cytotoxic T cells. Tim-3 inhibitors are under investigation in immuno-oncology (IO) trials, because blockade of T-cell-Tim-3 enhances antitumor immunity. Here, we identify an additional role for Tim-3 as a growth-suppressive receptor intrinsic to melanoma cells. Inhibition of melanoma cell-Tim-3 promoted tumor growth in both immunocompetent and immunocompromised mice, while melanoma-specific Tim-3 overexpression attenuated tumorigenesis. Ab-mediated Tim-3 blockade inhibited growth of immunogenic murine melanomas in T-cell–competent hosts, consistent with established antitumor effects of T-cell-Tim-3 inhibition. In contrast, Tim-3 Ab administration stimulated tumorigenesis of both highly and lesser immunogenic murine and human melanomas in T-cell–deficient mice, confirming growth-promoting effects of melanoma-Tim-3 antagonism. Melanoma-Tim-3 activation suppressed, while its blockade enhanced, phosphorylation of pro-proliferative downstream MAPK signaling mediators. Finally, pharmacologic MAPK inhibition reversed unwanted Tim-3 Ab-mediated tumorigenesis in T-cell–deficient mice and enhanced desired antitumor activity of Tim-3 interference in T-cell–competent hosts. These results identify melanoma-Tim-3 blockade as a mechanism that antagonizes T-cell-Tim-3–directed IO therapeutic efficacy. They further reveal MAPK targeting as a combination strategy for circumventing adverse consequences of unintended melanoma-Tim-3 inhibition.

Significance:
Tim-3 is a growth-suppressive receptor intrinsic to melanoma cells, the blockade of which promotes MAPK-dependent tumorigenesis and thus counteracts antitumor activity of T-cell–directed Tim-3 inhibition.
Prophylactic Antibiotics in Patients with Traumatic Pneumocephalus or Cerebrospinal Fluid Leak
Authors: Wang Hsin-Ping , Reif Rebecca J. , Kalkwarf Kyle J. , Jensen Hanna K. , Jenkins Allison K. , Bhavaraju Avi 
Published: August 2022

Introduction Pneumocephalus and cerebrospinal fluid (CSF) leaks are uncommon after trauma, but they expose the sterile CSF to environmental pathogens and create theoretical risk of central nervous system infection (CNSI). Prophylactic antibiotics are commonly given to these patients, but there is a paucity of evidence to guide this practice. We aim to quantify the incidences of these entities and analyze the efficacy of prophylactic antibiotics in preventing CNSIs. Methods A retrospective cohort study was conducted using our institutional trauma registry. All patients admitted from January 2014 to July 2020 with traumatic pneumocephalus (TP) or basilar skull fracture with CSF leak (BSF-CSF) were included. ICD-9 and ICD-10 codes were used to identify CNSIs. CNSI rates among defined prophylactic antibiotic regimens, no antibiotics, and other antibiotic regimens were evaluated. ANOVA was used to analyze differences between the groups. Results 365 patients met inclusion criteria: 360 with TP; 5 with BSF-CSF. 1.1% (4/365) of patients developed CNSI, all with isolated traumatic pneumocephalus. 1.4% of patients (1/72) without antibiotics; 1.2% (3/249) receiving IV antibiotics outside of a defined regimen; and 1.1% (1/88) on a designated prophylactic regimen developed CNSIs. ANOVA indicated the incidence of CNSI was not significantly different among patients who received antibiotics or not, regardless of the regimen (p-value 0.958). Conclusion TP and BSF-CSF are rare diagnoses among trauma patients. The rate of CNSI is marginal and antibiotics do not appear to confer a protective advantage. A larger trial is needed to elucidate the true effect of antibiotics on preventing CNSIs in patients with these uncommon diagnoses.
Bringing about Change: The Introduction of Secure Units
Authors: Stocking B 
Published: August 2022

The introduction of regional secure units into the NHS was studied as one example of the diffusion of patient care innovations. As well as the general history of secure units events in four Regions were studied in detail for the period from 1974 up to mid-1983. It is concluded that secure units became gradually more acceptable over time as (i) the need for such units was recognized, (ii) the climat, of opinion changed in psychiatric hospitals from seeing secure units as a retrograde step, following the acceptance of more open door policies, to seeing secure units as a prestige development which might safeguard the future of a particular hospital, (iii) government loosened the definitions of what secure units should be and how they should operate so that there was more room for different regions to assess their own needs. Regions which were able to move relatively fast on secure unit development were those where there-was already a ‘product champion’ present to promote the ideas, usually a forensic psychiatrist, and where there was also managerial support and designated responsibility for secure unit development at local and regional level. It is concluded that while public reaction was a hindrance it did not slow down secure unit development as much as might have been expected.
Ceftazidime versus Aminoglycoside and (Ureido)Penicillin Combination in the Empirical Treatment of Serious Infection
Authors: Finer N , Goustas P 
Published: August 2022

Urgent treatment of serious infections with broad spectrum antibiotics usually starts before bacteriological evidence of the infective organism(s) becomes available. In this study 471 patients with a clinical diagnosis of sepsis were treated empirically with ceftazidime (CAZ) monotherapy (249 patients), or with an aminoglycoside+(ureido)penicillin combination (AG+PEN) (222 patients) to establish clinical outcome and bacteriological response. Up to 72 h post-treatment 94.5% of patients in the CAZ group and 93.8% in the AG+PEN group were treated successfully (treatment difference 0.7%, P<0.01, 95% confidence interval −3.8%, 5.2%), 2–4 weeks after treatment neither regimen proved clinically superior. The differences in bacteriological response up to 72 h, and at 2–4 weeks after treatment, were 5.6% and 12.4% in favour of CAZ, however, these were not statistically significant. Overall, 56 patients reported 72 adverse events in the CAZ group, compared with 33 patients reporting 41 adverse events in the AG+PEN group. Deaths, 40 on CAZ and 21 on AG+PEN, were mainly related to their underlying condition. The two regimens were shown to be clinically equivalent in seriously ill patients treated empirically.
Perceived Religiousness is Protective for Colorectal Cancer: Data from the Melbourne Colorectal Cancer Study
Authors: Kune Gabriel A , Kune Susan , Watson Lyndsey F 
Published: August 2022

The perceived or self-reported degree of ‘religiousness’ was obtained by interview from 715 colorectal cancer patients and 727 age/sex matched community controls, as part of a large, comprehensive population-based study of colorectal cancer incidence, aetiology and survival (The Melbourne Colorectal Cancer Study) conducted in Melbourne, Australia. Self-reported or perceived ‘religiousness’, as defined in the study, was a statistically significant protective factor [relative risk (RR)=0.70, 95% confidence interval (CI)=0.6–0.9, P=0.002]. This statistically significant protection remained after the previously determined major risk factors found in the study, namely a family history of colorectal cancer, dietary risk factors, beer consumption, number of children and age at birth of the first child, were statistically corrected for ( P=0.004). There was no association between Dukes' staging of the cancer and perceived degree of ‘religiousness’ ( P=0.42). Although self-reported or perceived ‘religiousness’ was associated with a median survival time of 62 months compared with 52 months in those self-reporting as being ‘non-religious’, this difference was not statistically significant ( P=0.64).