bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Circulating Tumor Cells at 1 Year After Oncologic Resection Predict Late Recurrence in Pancreatic Cancer
Authors: Javed Ammar A. , Ding Ding , Hasanain Alina , van Oosten Floortje , Yu Jun , Cameron John L. , Burkhart Richard A. , Zheng Lei , He Jin , Wolfgang Christopher L.
Published: September 2022

Objective:

The aim of the study was to assess the association between persistent circulating tumor cells (CTCs) and subsequent recurrence in patients who were clinically recurrence free ~12 months postoperatively.

Background:

Circulating tumor cells have been proposed as biomarkers to predict survival in pancreatic cancer. Some patients demonstrate persistent CTCs postoperatively, which could represent minimal residual disease.

Methods:

Patients from previously published prospective circulating tumor cell in pancreatic cancer trial without clinical evidence of recurrence 12 months postoperatively and CTC testing performed 9 to 15 months postoperatively were included. The presence of epithelial and transitional CTCs (trCTCs) was evaluated as predictor of recurrence. Kaplan-Meier curve, log-rank test, and Cox model were used for survival analysis.

Results:

Thirty-three of 129 eligible patients (circulating tumor cell in pancreatic cancer trial) were included. The trCTC-positive and negative patients were well balanced in clinicopathologic features. Patients with trCTCs had a recurrence rate per-person-month of 10.3% compared with 3.1% in trCTCs-negative patients with a median time to recurrence of 3.9 versus 27.1 months, respectively. On multivariable analysis, trCTCs positivity was associated with higher risk of late recurrence (hazard ratio: 4.7, 95% CI, 1.2–18.3, P=0.024). Fourteen (42.4%) patients recurred during the second postoperative year. One-year postoperative trCTCs positivity was associated with a higher rate of recurrence during the second year (odds ratio:13.1, 95% CI, 1.6–1953.4, P=0.028, area under curve=0.72). Integrating clinicopathologic features with trCTCs increased the area under curve to 0.80. A majority of trCTCs-positive patients (N=5, 62.5%) had multisite recurrence, followed by local-only (N=2, 25.0%) and liver-only (N=1, 12.5%) recurrence. This was in striking contrast to trCTCs-negative patients, where a majority (N=6, 66.7%) had a local-only recurrence, followed by liver-only (N=2, 22.2%) and multisite (N=1, 11.1%) recurrence.

Conclusions:

In patients deemed to be clinically disease-free 12 months postoperatively, trCTCs positivity is associated with higher rates of subsequent recurrence with distinct patterns of recurrence. CTCs could be used a putative biomarker to guide patient prognostication and management in pancreatic cancer.
Effect estimates can be accurately calculated with data digitally extracted from interrupted time series graphs
Authors: Turner Simon Lee , Korevaar Elizabeth , Cumpston Miranda S , Kanukula Raju , Forbes Andrew B , McKenzie Joanne E
Published: September 2022

Background

Interrupted Time Series (ITS) studies are frequently used to examine the impact of population-level interventions or exposures. Systematic reviews with meta-analyses including ITS designs may inform public health and policy decision-making. Re-analysis of ITS may be required for inclusion in meta-analysis. While publications of ITS rarely provide raw data for re-analysis, graphs are often included, from which time series data can be digitally extracted. However, the accuracy of effect estimates calculated from data digitally extracted from ITS graphs is currently unknown.

Methods

Forty-three ITS with available datasets and time series graphs were included. Time series data from each graph was extracted by four researchers using digital data extraction software. Data extraction errors were analysed. Segmented linear regression models were fitted to the extracted and provided datasets, from which estimates of immediate level and slope change (and associated statistics) were calculated and compared across the datasets.

Results

Although there were some data extraction errors of time points, primarily due to complications in the original graphs, they did not translate into important differences in estimates of interruption effects (and associated statistics).

Conclusions

Using digital data extraction to obtain data from ITS graphs should be considered in reviews including ITS. Including these studies in meta-analyses, even with slight inaccuracy, is likely to outweigh the loss of information from non-inclusion.
Health services for Aboriginal and Torres Strait Islander children in remote Australia: a scoping review
Authors: Dossetor PJ , Freeman JM , Thorburn K , Oscar J , Carter M , Jeffery HE , Harley D , Elliott EJ , Martiniuk ALC
Published: September 2022

In Australia, there is a significant gap between health outcomes in Indigenous and non-Indigenous children, which may relate to inequity in health service provision, particularly in remote areas. The aim was to conduct a scoping review to identify publications in the academic and grey literature and describe 1) Existing health services for Indigenous children in remote Australia and service use, 2) Workforce challenges in remote settings, 3) Characteristics of an effective health service, and 4) Models of care and solutions. Electronic databases of medical/health literature were searched (Jan 1990 to May 2021). Grey literature was identified through investigation of websites, including of local, state and national health departments. Identified papers (n=1775) were screened and duplicates removed. Information was extracted and summarised from 116 papers that met review inclusion criteria (70 from electronic medical databases and 45 from the grey literature). This review identified that existing services struggle to meet demand. Barriers to effective child health service delivery in remote Australia include availability of trained staff, limited services, and difficult access. Aboriginal and Community Controlled Health Organisations are effective and should receive increased support including increased training and remuneration for Aboriginal Health Workers. Continuous quality assessment of existing and future programs will improve quality; as will measures that reflect aboriginal ways of knowing and being, that go beyond traditional Key Performance Indicators. Gold standard models for service delivery have community leadership and collaboration. Increased resources with a focus on primary prevention and health promotion are essential.
Fast Adaptation to Rule Switching using Neuronal Surprise
Authors: Barry Martin , Gerstner Wulfram
Published: September 2022

In humans and animals, surprise is a physiological reaction to an unexpected event, but how surprise can be linked to plausible models of neuronal activity is an open problem. We propose a self-supervised spiking neural network model where a surprise signal is extracted from an increase in neural activity after an imbalance of excitation and inhibition. The surprise signal modulates synaptic plasticity via a three-factor learning rule which increases plasticity at moments of surprise. The surprise signal remains small when transitions between sensory events follow a previously learned rule but increases immediately after rule switching. In our model, previously learned rules are protected against overwriting when learning a new rule. Our surprise-modulated spiking network model makes a step towards solving the stability-plasticity dilemma in neuroscience and the problem of continual learning in machine learning.
Behind the scene of body mass allometries
Authors: Witting Lars
Published: September 2022

I use data based life history models for 9,488 species of birds and 4,865 species of mammals to illustrate natural selection causes for the evolution of inter-specific body mass allometries. Each model integrates the growth and demography of individuals with the life history energetics and population ecology of the species. I show i) how the primary selection of resource handling and mass-specific metabolism generates the net energy of individuals, ii) how the selected net energy generates a population dynamic feedback selection where intra-specific interactive competition selects body masses that scale in proportion with net energy on the timescale of natural selection, iii) how the primary selection of metabolism selects an allometric curvature where the residual mass-specific metabolism—relative to the expectation of the mass-rescaling allometry—is an initially declining function of mass in terrestrial placentals and birds, but not in marsupials and bats, iv) how the selection of body mass buffers ecological variation in survival, and v) how the joint selection of mass and optimal foraging selects the exponents of body mass allometries from the dominant spatial dimensionality of the foraging ecology.
Kinetic modeling of transaminase values distinguishes active liver inflammation from resolution independent of absolute enzyme levels
Authors: Sherman Marc S , Goessling Wolfram
Published: September 2022

The biomarkers alanine (ALT) and aspartate (AST) aminotransferase serve an indispensable role in the diagnosis and management of liver diseases where patients often have no symptoms until organ function is threatened. Despite 70 years of widespread clinical use, the exact kinetic behavior of AST and ALT during liver injury in humans has never been quantified. Here, we used mathematical modeling to examine the individual trajectories of > 6.5 million AST and ALT levels over time in 91,086 patients with acute liver injury. Candidate mechanistic differential equation models fitted to these trajectories revealed that 40.1% of ALT and 37.5% of AST curves were well-fit by a single-exponential model, indicating a single rate-limiting step governs transaminase decline. The mechanism of this rate-limiting step was found to be transaminase clearance from the blood, rather than ongoing liver injury, highlighting that AST and ALT are lagging biomarkers of liver injury. We use this observation to infer the plasma clearance rate of AST (t1/2=15.8h) and ALT (t1/2=34.6h) in humans, and derive a calculator of real-time liver injury, the Hepatocyte Injury indeX HIX (hix.massgeneral.org) that accounts for lag due to clearance of serum transaminase. We demonstrate that this index distinguishes active from resolved liver injury on histopathology assessment, even when the absolute AST or ALT value remains markedly elevated. These observations sharply refine how transaminase patterns are interpreted in the practical care of patients with acute liver injury.

One Sentence Summary

Kinetic modeling of >6 million individual AST and ALT values from 91,000 patients enables biomarker half-life estimation and a real-time liver injury assessment.
Malaria; risk factors within urban and rural settings in the Sahelian region of Cameroon and the role of insecticide resistance in mosquitoes
Authors: Ngwa Samuel Fru , Nyasa Raymond Babila , Esemu Seraphine Nkie , Titanji Vincent P. K.
Published: September 2022

Background

Cameroon is among the 11 countries that account for 92 % of malaria infection in sub-Saharan-Africa in 2018, and Maroua III Health District and her environs witnessed a malaria outbreak in 2013 with hundreds of deaths. This study was aimed at understanding the risk factors of malaria in the urban and rural population and to investigate the level of mosquito’s resistance to Deltamethrin and Permethrin.

Methods

It was a cross-sectional community-based study carried out from August to October 2019, in which questionnaires were administered to 500 participants, to obtain information on demographics, socioeconomic, behavioral, and environmental factors thought to be associated with malaria infection in both rural and urban settings. Blood samples were collected for the diagnosis of malaria. Logistic regression analysis was used to identify risk factors for malaria. Mosquito resistance to Deltamethrin and Permethrin were investigated using the CDC Bottle Bioassay test.

Results

Malaria prevalence was 52.2%, which was significantly higher (p = 0.016) in rural areas (57.6%) as compared to urban areas (46.8%). The overall prevalence of asymptomatic malaria parasitemia in the population was 43.4% in contrast to symptomatic malaria which was 8.8%. In rural areas, risk factors were households using treated bed nets older than 3 years (AOR: 2.45 95% CI: 1.30 to 4.61 P-value: 0.006); households whose water source are unprotected wells (AOR: 3.04 95% CI: 1.21 to 7.64 P-value: 0.018). In urban areas, risk factors were households surrounded by farmland with crops (AOR: 2.08 95% CI: 1.14 to 3.80 P-value 0.017) and households using treated bed nets older than 3 years (AOR: 2.70 95% CI: 1.52 to 4.78 P-value 0.001). The age group 2-10years was significantly associated (p<0.001) with malaria in both rural and urban settings of the district. The geometric mean parasite density was found to decrease with increasing age of participants in the entire health district. The overall mortality of Anopheles species was 93.57% (91.19% in rural and 95.83% in urban areas) for deltamethrin, which was more sensitive than 83.85% (85.24% in rural and 82.46% in urban areas) for permethrin.

Conclusion

Relevant data for malaria control in Maroua III health district, a typical Sahelian environment, has been generated, and indicates that most of the burden of malaria is borne by school children. Deltamethrine was more effective than permethrine in the control of mosquito populations within these areas.
Dynamics of annatto pigment synthesis and accumulation revealed by integrated chemical, anatomical, and RNA-Seq analyses
Authors: Moreira Viviane Santos , de Souza Vinicius Carius , Soares Virgínia Lúcia Fontes , Sousa Aurizangela Oliveira , de Nascimento Katiucia Ticila de Souza , de Santana Monique Reis , Rebouças Tiyoko Nair Hojo , Leitão Carlos André Espolador , Goliatt Priscila Vanessa Zabala Capriles , Faria Daniele Vidal , Otoni Wagner Campos , Costa Marcio Gilberto Cardoso
Published: September 2022

Bixin is a commercially valuable apocarotenoid pigment found in the seed aril of Bixa orellana. The dynamics and regulation of its biosynthesis and accumulation during seed development remain largely unknown. Here, we combined chemical, anatomical, and transcriptomic data to provide stage-specific resolution of the cellular and molecular events occurring during B. orellana seed development. Seeds at five developmental stages (S1–S5) were used for analysis of bixin content and seed anatomy, and three of them (S1, S3 and S4) selected for Illumina HiSeq sequencing. Bixin accumulated sharply during seed development, particularly during the S2 stage, peaking at the S4 stage, and then decreasing slightly in the S5 stage. Anatomical analysis revealed that bixin accumulated in the large central vacuole of specialized cells, which were scattered throughout the developing mesotesta at the S2 stage, but enlarged progressively at later stages, until they occupied most of the parenchyma in the aril. A total of 13 million reads were generated and assembled into 73,381 protein-encoding contigs, from which 312 were identified as containing 1-deoxy-D-xylulose-5-phosphate/2-C-methyl-D-erythritol-4-phosphate (DOXP/MEP), carotenoid, and bixin pathways genes. Differential expression analysis of these genes revealed that 50 of them were differentially expressed between all the seed developmental stages, including seven carotenoid cleavage dioxygenases, eight aldehyde dehydrogenases and 22 methyltransferases. Taken together, these results provide a comprehensive description of the cellular and molecular events related to the dynamics of bixin synthesis and accumulation during seed development in B. orellana.
What is the effectiveness of financial support schemes for individuals requested to self-isolate following a positive Covid test or positive contact: A rapid review
Authors: Winfield Tom , Elston Lauren , Washington Jenni , Hasler Elise , Lewis Ruth , Cooper Alison , Edwards Adrian G
Published: September 2022

Testing for COVID-19 has been deployed globally as a tool to interrupt transmission through isolating positive contacts from the broader population. Financial support systems have been deployed to increase the isolation compliance, there is uncertainty as to the effectiveness of these measures.
Three reviews were identified, as well as four primary studies that were published after the review search dates.
Six studies showed that financial support for isolation was associated with a higher compliance to isolate. Two epidemiological modelling studies found that increased levels of social isolation were associated with a reduction in COVID-19 transmission. The findings from a DCE demonstrated a positive relationship with longer isolation duration and higher financial requirements. An economic model showed that support programmes have the potential to be a cost-effective intervention. A retrospective observational study offered evidence supporting the viability of delivering medically assisted isolation hotels for people unable to isolate at home. Further to the COVID-19 literature, two household surveys found that financial support and improved social restriction information was associated with compliance with H1N1 isolation
Policy and practice implications: There is limited evidence to suggest that financial support for isolation can increase compliance, lower social engagement, and reduce infection levels. There is insufficient evidence to inform the optimal scale of financial support required There was no evidence related to effectiveness of financial support for disadvantaged populations who are required to isolate or any insight to the impact of financial support on equality
The overall certainty in the evidence is relatively low. Most studies relied on participant reported data on preference or behaviour, and where observational data were used there were issues with data quality and unobserved cofounders.
Hospital-wide Natural Language Processing summarising the health data of 1 million patients
Authors: Bean Daniel , Kraljevic Zeljko , Shek Anthony , Teo James , Dobson Richard
Published: September 2022

Electronic health records (EHRs) represent a major repository of real world clinical trajectories, interventions and outcomes. While modern enterprise EHR’s try to capture data in structured standardised formats, a significant bulk of the available information captured in the EHR is still recorded only in unstructured text format and can only be transformed into structured codes by manual processes. Recently, Natural Language Processing (NLP) algorithms have reached a level of performance suitable for large scale and accurate information extraction from clinical text. Here we describe the application of open-source named-entity-recognition and linkage (NER+L) methods (CogStack, MedCAT) to the entire text content of a large UK hospital trust (King’s College Hospital, London). The resulting dataset contains 157M SNOMED concepts generated from 9.5M documents for 1.07M patients over a period of 9 years. We present a summary of prevalence and disease onset as well as a patient embedding that captures major comorbidity patterns at scale. NLP has the potential to transform the health data lifecycle, through large-scale automation of a traditionally manual task.
Cellular Heterogeneity of Pluripotent Stem Cell Derived Cardiomyocyte Grafts is Mechanistically Linked to Treatable Arrhythmias
Authors: Selvakumar Dinesh , Clayton Zoe E. , Prowse Andrew , Dingwall Steve , George Jacob , Shah Haisam , Chen Siqi , Hume Robert D. , Tjahjadi Laurentius , Igoor Sindhu , Skelton Rhys J.P. , Hing Alfred , Paterson Hugh , Foster Sheryl L. , Pearson Lachlan , Wilkie Emma , Jeyaprakash Prajith , Wu Zhixuan , McArthur Jeffrey R. , Barry Tony , Lu Juntang , Tran Vu , Bennett Richard , Kotake Yasuhito , Campbell Timothy , Turnbull Samual , Nguyen Quan , Ni Guiyan , Grieve Stuart M. , Palpant Nathan J. , Pathan Faraz , Kizana Eddy , Kumar Saurabh , Gray Peter P. , Chong James J.H.
Published: September 2022

Background

Exciting pre-clinical data have confirmed that human pluripotent stem cell derived cardiomyocytes (PSC-CMs) can remuscularise the injured or diseased heart, with several clinical trials now in planning or recruitment stages worldwide. However, ventricular arrhythmias are a predictable complication following engraftment of intramyocardially injected PSC-CMs. Therefore, there is an urgent unmet need to gain mechanistic insights and treatment strategies to control or prevent these engraftment arrhythmias (EAs).

Methods

We used a porcine model of myocardial infarction and PSC-CM transplantation to investigate efficacy of pharmacologic and catheter based anti-arrhythmic strategies in mitigating EAs. Furthermore, cell doses were robustly phenotyped using single cell ribonucleic acid sequencing and high parameter flow cytometry to identify cellular characteristics predictive of arrhythmogenesis.

Results

Combination therapy with amiodarone and ivabradine significantly reduced EA rate and burden following PSC-CM transplantation. Catheter ablation was also a feasible and effective treatment strategy which could be considered in the case of pharmacologically refractory arrhythmias. In addition, we show that EAs are mechanistically linked to cellular heterogeneity in the input PSC-CM and resultant graft. Specifically, we identify atrial and pacemaker-like cardiomyocytes as culprit arrhythmogenic subpopulations. We further describe two unique surface marker signatures, SIRPA+/CD90-/CD200+ and SIRPA+/CD90-/CD200-, which identify arrhythmogenic and non-arrhythmogenic cardiomyocytes respectively.

Conclusion

Our data deepens mechanistic understanding of EAs and suggests that modifications to current PSC-CM production and/or selection protocols could ameliorate this problem. We further show that current clinical pharmacologic and interventional anti-arrhythmic strategies can control and potentially abolish these arrhythmias, an important safety consideration given several impending clinical trials.
Colistin resistance mutations in phoQ sensitize Klebsiella pneumoniae to IgM-mediated complement killing
Authors: van der Lans Sjors P.A. , Janet-Maitre Manon , Masson Frerich M. , Walker Kimberly A. , Doorduijn Dennis J. , Janssen Axel B. , van Schaik Willem , Attrée Ina , Rooijakkers Suzan H. M. , Bardoel Bart W.
Published: September 2022

The Gram-negative bacterium Klebsiella pneumoniae is notorious for a strong increase of infections with antibiotic resistant strains. To treat infections with antibiotic resistant K. pneumoniae, clinicians increasingly need to use the last resort antibiotic colistin. K. pneumoniae can develop colistin resistance by modifying its membranes. During infection the membranes of Gram-negative bacteria are also targeted by the human immune system via the complement system. Gram-negative bacteria have an outer and inner membrane separated by a thin cell wall. Activation of the complement system leads to the formation of the membrane attack complex (MAC), a pore that inserts into the outer membrane, and ultimately leads to lysis of the bacterium. As both colistin and the MAC interact with the outer membrane of Gram-negative bacteria, we wondered if developing colistin resistance influences MAC-mediated killing of K. pneumoniae.

Using clinical isolates that developed colistin resistance, we found that the strain Kp209_CSTR became more sensitive to MAC-mediated killing compared to the wild-type strain. MAC-mediated membrane permeabilization of Kp209_CSTR required antibody dependent activation of the classical complement pathway. Strikingly, Kp209_CSTR was bound by IgM in human serum that did not recognise the wild-type strain. Depletion of Kp209_CSTR-specific antibodies from serum prevented MAC-mediated membrane permeabilization, which was restored by adding back IgM. Genomic sequence comparison revealed that Kp209_CSTR has a deletion in the phoQ gene. RNAseq analysis suggested that this mutation locks PhoQ in a constitutively active state. These results indicate that PhoQ activation in Kp209_CSTR leads to both colistin resistance and sensitivity to MAC-mediated killing. Together, our results show that developing colistin resistance can sensitize K. pneumoniae to killing by the immune system.
A toxin-antitoxin system ensures plasmid stability in Coxiella burnetii
Authors: Wachter Shaun , Cockrell Diane C , Miller Heather E , Virtaneva Kimmo , Kanakabandi Kishore , Darwitz Benjamin , Heinzen Robert A , Beare Paul A
Published: September 2022

Coxiella burnetii is the causative agent of Q fever. All C. burnetii isolates encode either an autonomous replicating plasmid (QpH1, QpDG, QpRS, or QpDV) or QpRS-like chromosomally integrated plasmid sequences. The role of the ORFs present on these sequences is unknown. Here, the role of the ORFs encoded on QpH1 was investigated. Using a new C. burnetii shuttle vector (pB-TyrB-QpH1ori) we cured Nine Mile Phase II of QpH1. The ΔQpH1 strain grew normally in axenic media but had a significant growth defect in Vero cells, indicating QpH1 was important for C. burnetii virulence. We developed an inducible CRISPR interference system to examine the role of individual QpH1 plasmid genes. CRISPRi of cbuA0027 resulted in significant growth defects in axenic media and THP-1 cells. The cbuA0028/cbuA0027 operon encodes CBUA0028 and CBUA0027, which are homologous to the HigB2 toxin and HigA2 anti-toxin, respectively, from Vibrio cholerae. Consistent with toxin-antitoxin systems, overexpression of cbuA0028 resulted in a severe intracellular growth defect that was rescued by co-expression of cbuA0027. CBUA0028 inhibited protein translation. CBUA0027 bound the cbuA0028 promoter (PcbuA0028) and CBUA0028, with the resulting complex binding also PcbuA0028. In summary, our data indicates C. burnetii maintains an autonomously replicating plasmid because of a plasmid-based toxin-antitoxin system.
Listeria monocytogenes genes supporting growth under standard laboratory cultivation conditions and during macrophage infection
Authors: Fischer Martin A. , Engelgeh Tim , Rothe Patricia , Fuchs Stephan , Thürmer Andrea , Halbedel Sven
Published: September 2022

The Gram-positive bacterium Listeria monocytogenes occurs widespread in the environment and infects humans when ingested along with contaminated food. Such infections are particularly dangerous for risk group patients, for whom they represent a life-threatening disease. To invent novel strategies to control contamination and disease, it is important to identify those cellular processes that maintain pathogen growth inside and outside the host. Here, we have applied transposon insertion sequencing (Tn-Seq) to L. monocytogenes for the identification of such processes on a genome-wide scale. Our approach identified 394 open reading frames that are required for growth under standard laboratory conditions and 42 further genes, which become necessary during intracellular growth in macrophages. Most of these genes encode components of the translation machinery and act in chromosome-related processes, cell division, and biosynthesis of the cellular envelope. Several cofactor biosynthesis pathways and 29 genes with unknown functions are also required for growth, suggesting novel options for the development of antilisterial drugs. Among the genes specifically required during intracellular growth are known virulence factors, genes compensating intracellular auxotrophies, and several cell division genes. Our experiments also highlight the importance of PASTA kinase signaling for general viability and of glycine metabolism and chromosome segregation for efficient intracellular growth of L. monocytogenes.
City spatial structure and smart city innovation: the case of China
Authors: Chen Yongtai , Li Rui , Zeng En-yu , Li Pengfei
Published: September 2022

Purpose

This study aims to analyze the relevance of the city spatial structure for smart city innovation from the perspective of agglomeration externalities, and discusses whether there is heterogeneity in innovation across different geographical areas and population scales of cities.

Design/methodology/approach

The authors construct the centralization and concentration indexes to conceptualize the city spatial structure of 286 cities (prefecture-level) in China based on the LandScan Global Population Dataset from 2001 to 2016. A fixed-effects panel data model is employed to analyze the relationship between the spatial structure and the innovation ability of smart cities; the results were validated through robustness tests and heterogeneity analyses.

Findings

The study found that the more concentrated and more evenly the distribution of urban population, namely the more city spatial structure tends to be weak-monocentricity, the higher the level of innovation in smart cities. The relevance of the weak-monocentricity structure and smart city innovation varies significantly depending on their geographical location and the size of the city. This result is more applicable to cities in the eastern and central regions, as well as to cities with smaller populations.

Originality/value

The adjustment and optimization of the city spatial structure is important for enhancing smart city construction. Unlike previous studies, which mostly use a single dimension of “the proportion of population in sub-centres to the population of all central areas” to measure city spatial structure, the authors employed the spatial centralization and spatial concentration. It is hoped that this study can guide smart city construction from the perspective of the development model of city spatial structure.
A study of Silicon Valley firms' accounting losses
Authors: Ivanov Stoyu I. , Faulkner Matthew
Published: September 2022

Purpose

Small firms, which represent much of the Silicon Valley region, tend to experience losses due to their small scale, small customer base and lack of diversification. The authors study the impact of accounting conservatism and losses on firm value and as such this study is an appropriate addition to this growing field of financial management.

Design/methodology/approach

The authors use methodology developed in prior literature to examine Silicon Valley and non-Silicon Valley firms' and their behavior when facing losses and the factors, which might play a role in their valuation. The authors focus particularly on earnings and accounting conservatism. Accounting conservatism captures how fast firms record losses relative to gains. The faster losses are recognized than gains the more accounting conservatism is exhibited. The authors examine the seemingly unrelated estimation of differences in means for our independent variables of interest across the two samples of Silicon Valley and non-Silicon Valley firms, both earnings and accounting conservatism. The authors use matched sample analysis of these firms based on four digit SIC code, size and date. In robustness, the authors run a more in-depth propensity score matched sample analysis.

Findings

The authors document that market values of Silicon Valley firms with accounting losses are affected less by negative earnings than other firms with accounting losses in the United States outside of the Silicon Valley region, noting the “lose big, win bigger” sentiment of Silicon Valley. Additionally, the authors document that accounting conservatism does play a role in influencing valuations of companies with accounting losses both in Silicon Valley and the rest of the United States, marginally more for Silicon Valley firms.

Originality/value

This study would be of interest to fund managers who need to consider smaller firms for inclusion in their portfolios. A lot of small firms have experienced losses ever since going public, especially Silicon Valley start-up firms.
Phospholipase D and phosphatidic acid mediate regulation in the biosynthesis of spermidine and ganoderic acids by activating GlMyb in Ganoderma lucidum under heat stress
Authors: Han Xiaofei , Wang Zi , Shi Lingyan , Zhu Jing , Shi Liang , Ren Ang , Zhao Mingwen
Published: September 2022

Polyamines are essential for all kinds of organisms and take part in the regulation of multiple biological processes. Our previous study revealed that heat stress promoted the conversion of putrescine to spermidine and subsequently promoted the accumulation of ganoderic acids (GAs). However, how heat stress affects polyamine homeostasis remains unclear. To explore the underlying mechanism by which heat stress promoted spermidine biosynthesis, we assessed the effects of signalling molecules that respond to heat stress on spermidine biosynthesis. Our data suggested that heat stress‐induced spermidine biosynthesis and GAs accumulation via a phospholipase D (PLD)‐mediated phosphatidic acid (PA) signal. Further research revealed that the transcription factor GlMyb promoted spermidine biosynthesis via regulating spermidine synthase genes (spds1 and spds2) expression by directly bonding to their promoters and it responded to heat stress and PA signal. In summary, heat stress activated GlMyb by PLD‐mediated PA signalling and subsequently induced the expression of spds1 and spds2 to promote the biosynthesis of spermidine and the accumulation of GAs. Our findings firstly reveal a detailed mechanism by which heat signalling regulates polyamine homeostasis by PLD‐mediated PA signal in fungi and provide a greater understanding of how organisms alter polyamine levels in response to environmental changes.
Evangelization and Language Change: A Transition from the Progressive Aspect to the Future Tense in Two Mayan Languages
Authors: Vinogradov Igor
Published: September 2022

This paper revisits the role that evangelization may have played in the diachronic development of Amerindian languages, with a focus on grammatical changes. Based on an analysis of written materials dating back to the colonial period and first‐hand fieldwork data, it discusses the semantic transition from the progressive aspect to the future tense that occurred similarly in the verbal systems of Q’eqchi’ and Poqomchi’, two Mayan languages spoken in Guatemala. Although the diachronic path is shared, the morphemes and constructions involved are clearly different in the two languages. The spread of this particular change from one language to the other is attributed to contact between their speakers that could be reinforced by the considerable number of translations of authoritative religious texts made by Dominican missionaries during the colonial period.
Knowledge Politics, Historic Memory and The Virginia House‐wife
Authors: Pellissier Marie
Published: September 2022

Over the two centuries since its publication, Mary Randolph's 1824 cookbook has become embedded in discourses of historic memory. These discourses have obscured the racial and gendered politics, resistance and conflict present in the book. Randolph's text, when read closely, illuminates the kitchen spaces in which enslaved Black cooks both cooperated and came into conflict with the white women who enslaved them. White supremacy is embedded in the text, and has also shaped its legacy, as museums and historic sites in Virginia and across the nation have used The Virginia House‐wife to bolster simplified and nostalgic views of the antebellum and colonial past.
Age alters the oncogenic trajectory toward luminal mammary tumors that activate unfolded proteins responses
Authors: Jenkins Edmund Charles , Chattopadhyay Mrittika , Gomez Maria , Torre Denis , Ma'ayan Avi , Torres‐Martin Miguel , Sia Daniela , Germain Doris
Published: September 2022

A major limitation in the use of mouse models in breast cancer research is that most mice develop estrogen receptor‐alpha (ERα)‐negative mammary tumors, while in humans, the majority of breast cancers are ERα‐positive. Therefore, developing mouse models that best mimic the disease in humans is of fundamental need. Here, using an inducible MMTV‐rtTA/TetO‐NeuNT mouse model, we show that despite being driven by the same oncogene, mammary tumors in young mice are ERα‐negative, while they are ERα‐positive in aged mice. To further elucidate the mechanisms for this observation, we performed RNAseq analysis and identified genes that are uniquely expressed in aged female‐derived mammary tumors. We found these genes to be involved in the activation of the ERα axis of the mitochondrial UPR and the ERα‐mediated regulation of XBP‐1s, a gene involved in the endoplasmic reticulum UPR. Collectively, our results indicate that aging alters the oncogenic trajectory towards the ERα‐positive subtype of breast cancers, and that mammary tumors in aged mice are characterized by the upregulation of multiple UPR stress responses regulated by the ERα.
Effects of exposure to mother's and father's alcohol use on young children's normative perceptions of alcohol
Authors: Cook Megan , Smit Koen , Voogt Carmen , Kuntsche Sandra , Kuntsche Emmanuel
Published: September 2022

Background

While consumption of alcohol does not often begin until early adolescence, young children are highly capable of internalizing normative information through observational learning. We used a longitudinal multiple‐informant family study to examine the impact of exposure to mothers' and fathers' drinking on young children's normative perceptions of who drinks alcohol.

Methods

Three hundred twenty‐nine children (4 to 6 years old at baseline [Mage 4.78 (SD = 0.725)], 51% girls) completed the Dutch electronic appropriate beverage task [eABT] where they attributed alcoholic beverages to a variety of persons depicted in an illustrated scenario. Their parents completed an online survey that included information on alcohol use and exposure.

Results

Children more frequently exposed to their mothers' drinking provided females shown in the eABT illustrations with alcohol significantly more often than children less frequently exposed to mothers' drinking. There was no effect of mother's exposure on providing males in the eABT with alcoholic beverages. Similarly, children more frequently exposed to their fathers' drinking provided fathers with alcoholic beverages significantly more often than children less frequently exposed to their fathers' drinking. There was no effect of father's exposure on providing the females with alcoholic beverages, nor was there an effect of father's exposure on providing “other males” with alcohol. These patterns held after adjusting for age and sex.

Conclusions

This study demonstrates that there are gender‐specific effects of exposure to parents' (particularly mothers') drinking on young children's perceptions of person‐specific drinking norms. The findings provide unique evidence in a young population group of effects on an understudied dimension of alcohol‐related perceptions with implications for future drinking behavior.
The effects of agricultural policy on supply and productivity: Evidence from differential changes in distortions
Authors: Hendricks Nathan P. , Smith Aaron , Villoria Nelson B. , Stigler Matthieu
Published: September 2022

Incentives in agriculture are highly distorted. It has long been argued that these distortions were a key explanation for differences in supply and productivity across countries, but the empirical evidence is limited. We revisit this issue using data on policy distortions across 63 countries for the period 1961–2011. We estimate the effects of differential changes in agricultural distortions across countries on supply and productivity. We highlight concerns in our analysis and previous work about endogeneity that biases the estimated effect downward—countries that lose comparative advantage are likely to increase support for agriculture. We address these concerns by including country and region‐time fixed effects, along with a rich set of controls. Overall, we find evidence that enhanced incentives through policy changes can increase the rate of production growth, with about half of the increase due to productivity increases. This result is strongest in Sub‐Saharan Africa where anti‐agricultural policies on exports were reduced and in Europe where pro‐agricultural policies on imports were reduced, driven largely by external pressure. Endogeneity appears to be strongest in Asia where countries have followed the typical pattern of raising support for agriculture during industrialization due to a rising farm‐urban income gap.
Background context affects word‐object mapping
Authors: Tippenhauer Nicholas , Saylor Megan M.
Published: September 2022

Children encounter new words across variable and noisy contexts. This variability may affect word learning, but the literature includes discrepant findings. The current experiment investigated one source of these discrepant findings: whether contexts with familiar, nameable objects are associated with less robust label learning. Two year olds were exposed to word‐object pairings on variable contexts that either included nameable objects or did not. Target selection was more robust when exposure occurred without other nameable objects. The difference was present immediately, but not after a delay. This study provides the evidence that context effects are context‐bound.
De novo NUF2 variant in a novel inherited bone marrow failure syndrome including microcephaly and renal hypoplasia
Authors: Vial Yoann , Lainey Elodie , Leblanc Thierry , Baudouin Véronique , Dourthe Marie Emilie , Gressens Pierre , Verloes Alain , Cavé Hélène , Drunat Séverine
Published: September 2022

In a patient with severe microcephaly, congenital bone marrow failure, growth retardation, and renal hypoplasia, we identified a likely pathogenic variant in NUF2 that impairs the cell's ability to properly complete mitosis. Interestingly, these clinical features as well as the observed cellular alterations are highly reminiscent of what is reported in Fanconi Anaemia supporting a unifying causal role of the variant in the disease. This case provides the first evidence that a kinetochore defect, previously associated with microcephaly, can be responsible for an inherited bone marrow failure syndrome, highlighting the unique pathological link between neurogenesis and haematopoiesis.
Disparities in spatial accessibility to public dental services relative to estimated need for oral health care among refugee populations in Victoria
Authors: Veginadu Prabhakar , Gussy Mark , Calache Hanny , Masood Mohd
Published: September 2022

Objectives

To examine the spatial accessibility to public dental services (PDS) relative to the estimated oral health needs of refugee populations within the state of Victoria, Australia.

Methods

The study employed enhanced two‐step floating catchment area method to measure spatial accessibility to PDS by driving and public transit modes at statistical area level 2 (SA2). Principal component analysis of select census‐derived socioeconomic variables specific to the refugee population was conducted to derive an area‐based indicator of refugee oral health needs, also at SA2 level. Individual indices were then developed for each of these components using standardized z‐scores. Finally, an integrated need‐accessibility index was developed to identify low‐accessibility areas associated with high needs.

Results

The results show clear contrast in spatial accessibility to PDS for the refugee populations between metropolitan and rural areas as well as between driving and public transit modes. There are critical limitations in accessibility for refugees living in the rural areas and those dependent on public transit mode for travel. Also, there is evident disparity between the estimated oral health needs of refugees in metropolitan and rural areas. Overall, approximately 29% of all SA2s with refugee population are in the ‘High’ needs category, which comprise 19.8% of the total Victorian refugee population. Integrating accessibility and oral health needs measures revealed that about 30% and 18% of refugee population are identified as under‐serviced, when considering driving and public transit modes respectively.

Conclusion

The findings provide implications for researchers and policy makers to address the inequalities in access to PDS among the refugee population in Victoria. The methodology outlined in this study provides a complementary approach in planning oral health service provision in the absence of population level data at a small‐area scale on access to dental services or need for oral health care.
Outreach dental care program for older adults using residential care or day care services in Hong Kong: A cohort study
Authors: Yang Stella X. , Lo Edward C. M. , Leung Katherine C. M.
Published: September 2022

Aim

To evaluate the effects of an outreach dental care program (ODCP) on the oral health status and oral health‐related quality of life (OHRQoL) of older adults who used residential or day care services in Hong Kong.

Methods

Older adults who had received dental treatments provided in the ODCP were recruited. Clinical examinations were performed by one calibrated examiner (SXY) at baseline and 1‐year follow‐up in the residential homes or day care centres. Face‐to‐face interviews were conducted using the transition scale of the Oral Health Impacts on Daily Living (OHIDL) questionnaire to investigate the perceived change in OHRQoL at baseline, 2‐month and 1‐year follow‐ups. The Wilcoxon matched‐pair signed‐rank test or McNemar/McNemar‐Bowker test was used to explore the change in oral health status after dental treatments. Factors associated with the perceived change in OHRQoL were explored with binary logistic regression.

Results

Four hundred and thirteen older adults (mean age = 83.8 years) participated in the study at baseline, and 377 (91.3%) and 359 (86.9%) were successfully followed 2 months and 1 year after receiving the outreach dental service, respectively. At the 1‐year follow‐up, the number of decayed teeth and functional tooth units, and the prevalence of poor denture hygiene decreased while there was more dental plaque deposition and a higher proportion of participants with gingival bleeding upon probing. More than 50% of the participants perceived no change or an improvement in OHRQoL in all domains at both follow‐ups. Older adults who perceived their oral health status as ‘healthy or fair’ and those who suffered from toothache at baseline had a higher chance to perceive having a better or at least the same OHRQoL at the 2‐month and 1‐year follow‐ups, respectively.

Conclusions

The ODCP in Hong Kong can solve some of the dental problems of older adults using long‐term care services and keep most of them from deterioration in OHRQoL, especially those suffering from toothache.
Exclusion of Disperse Orange 3 is possible from the textile dye mix present in the Swedish baseline patch test series. A study by the Swedish Contact Dermatitis Research Group
Authors: Isaksson Marléne , Antelmi Annarita , Dahlin Jakob , Stenton Joanna , Svedman Cecilia , Zimerson Erik , Glas Bo , Hagvall Lina , Lagrelius Maria , Löwnertz Anna , Malinauskiene Laura , Matura Mihaly , Bruze Magnus
Published: September 2022

Background

The textile dye mix (TDM) 6.6% in petrolatum contains Disperse Blue (DB) 35, Disperse Yellow 3, Disperse Orange (DO) 1 and 3, Disperse Red 1 and 17, and DB 106 and 124. The most frequent allergen in TDM‐positive patients is DO 3. Around 85% of para‐phenylenediamine (PPD)‐allergic dermatitis patients have been positive to DO 3. There has been a discussion to exclude DO 3 from TDM 6.6% because of strong simultaneous reactions to TDM and PPD.

Objectives

To study if DO 3 can be excluded from TDM 6.6%.

Methods

Patch tests were performed on 1481 dermatitis patients with TDM 6.6%, TDM 7.0% (without DO 3 but the other disperse dyes at 1.0% each), DO 3 1.0%, and PPD 1.0% pet.

Results

Contact allergy to TDM 6.6% was 3.6% and to TDM 7.0% was 3.0%. All 26 DO 3‐positive patients were positive to PPD. The 44 patients positive to TDM 7.0% plus the 13 positive to PPD and TDM 6.6% but negative to TDM 7.0% were 57, outnumbering the 53 positive to TDM 6.6%.

Conclusion

TDM 7.0% can replace TDM 6.6% in the Swedish baseline series, since TDM 7.0% together with PPD 1.0% will detect patients with textile dye allergy.