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© 2021 International Endodontic Journal. Published by John Wiley & Sons LtdReproducible, skilfully conducted and unbiased laboratory studies provide new knowledge, which can inform clinical research and eventually translate into better patient care. To help researchers improve the quality and reproducibility of their research prior to a publication peer-review, this paper describes the process that was followed during the development of the Preferred Reporting Items for Laboratory studies in Endodontology (PRILE) 2021 guidelines and which used a well-documented consensus-based methodology. A steering committee was created with eight individuals (PM, RO, OP, IR, JS, EP, JJ and SP), plus the project leaders (PD, VN). The steering committee prepared an initial checklist by combining and adapting items from the modified Consolidated Statement of Reporting Trials checklist for reporting in vitro studies of dental materials and the Clinical and Laboratory Images in Publications principles as well as adding several new items. The steering committee then formed a PRILE Delphi Group (PDG) and PRILE Online Meeting Group (POMG) to provide expert advice and feedback on the initial draft checklist and flowchart. The members of the PDG participated in an online Delphi process to achieve consensus on the items within the PRILE 2021 checklist and the accompanying flowchart for clarity and suitability. The PRILE checklist and flowchart developed by the online Delphi process were discussed further by the POMG. This online meeting was conducted on 12 February 2021 via the Zoom platform. Following this meeting, the steering committee developed a final version of the PRILE 2021 guidelines and flowchart, which was piloted by several authors when writing up a laboratory study for publication. Authors are encouraged to use the PRILE 2021 guidelines and flowchart to improve the clarity, completeness and quality of reports describing laboratory studies in Endodontology. The PRILE 2021 checklist and flowchart are freely available and downloadable from the Preferred Reporting Items for study Designs in Endodontology website (http://pride-endodonticguidelines.org/prile/).

Metabolic reprogramming in cancer enhances macromolecule biosynthesis and supports cell survival. Oncogenic drivers affect metabolism by altering distinct metabolic processes and render cancer cells sensitive to perturbations of the metabolic network. This study aimed to identify selective metabolic dependencies in breast cancer by investigating 17 breast cancer cells lines representative of the genetic diversity of the disease. Using a functional screen, we demonstrate here that monocarboxylate transporter 4 (MCT4) is an important regulator of breast cancer cell survival. MCT4 supports pH maintenance, lactate secretion and non-oxidative glucose metabolism in breast cancer cells. Moreover, MCT4 depletion caused an increased dependence of cancer cells on mitochondrial respiration and glutamine metabolism. MCT4 depletion reduced the ability of breast cancer cells to grow in a three-dimensional (3D) matrix or as multilayered spheroids. Moreover, MCT4 expression is regulated by the PI3K-Akt signalling pathway and highly expressed in HER2-positive breast cancers. These results suggest that MCT4 is a potential therapeutic target in defined breast cancer subtypes and reveal novel avenues for combination treatment.

We examine poverty's effect in two ways. First, we study the relationship between poverty and capacity for innovation in the U.S. states; second, we study the combined effects of poverty and innovation capacity on U.S. state economic output and employment. Because many of the relationships among poverty, innovation capacity and economic performance are simultaneous, we employ the Arellano Bond Difference GMM estimator to estimate various models using panel data (1980–1999). The findings reveal a negative indirect effect of socio-economic need (poverty) on human and U.S. state and local financial innovation capacity, though there is no empirical link between poverty and federal financial capacity. We find no statistically significant evidence of the contemporaneous effect of poverty on state economic performance, holding innovation capacity constant. This suggests that poverty primarily affects state economic performance indirectly through reduction of innovation capacity. Overall, our findings suggest that U.S. officials ought to be concerned about the role poverty plays in diminishing their state economies' capacity to innovate.

Autophagy is a catabolic process by which cytoplasmic components are sequestered and transported by autophagosomes to lysosomes for degradation, enabling recycling of these components and providing cells with amino acids during starvation. It is a highly regulated process and its deregulation contributes to multiple diseases. Despite its importance in cell homeostasis, autophagy is not fully understood. To find new proteins that modulate starvation-induced autophagy, we performed a genome-wide siRNA screen in a stable human cell line expressing GFP–LC3, the marker-protein for autophagosomes. Using stringent validation criteria, our screen identified nine novel autophagy regulators. Among the hits required for autophagosome formation are SCOC (short coiled-coil protein), a Golgi protein, which interacts with fasciculation and elongation protein zeta 1 (FEZ1), an ULK1-binding protein. SCOC forms a starvation-sensitive trimeric complex with UVRAG (UV radiation resistance associated gene) and FEZ1 and may regulate ULK1 and Beclin 1 complex activities. A second candidate WAC is required for starvation-induced autophagy but also acts as a potential negative regulator of the ubiquitin-proteasome system. The identification of these novel regulatory proteins with diverse functions in autophagy contributes towards a fuller understanding of autophagosome formation.

Following failed auctions for sewer debt in April 2008, major bond rating companies downgraded Jefferson County, Alabama’s bond rating to D (default) triggering massive mandatory payments by the county to its creditors. At the time of writing, the county teeters on the brink of actual default and bankruptcy, unable to pay service on its $3.3 billion sewer debt portfolio. If the county defaults, it will be the largest municipal bankruptcy in United States history, eclipsing Orange County, California’s 1994 default. The intriguingly complex tale of the Jefferson County debt crisis is recounted here by identifying and examining failures of transparency and accountability by local bureaucratic and political actors, private financial institutions, as well as the larger regulatory framework governing public finance. Enhanced regulation of local government and the financial sector plus greater local government capacity to close accountability gaps and thus prevent future crises of similar scale in this or other jurisdictions are recommended.

Local administrative professionals typically are accountable to multiple stakeholders, including other governmental units, special interests in the business and nonprofit sectors, and citizens. How are these accountability relationships ordered? What is the position of citizens in that hierarchy, particularly the influence of citizen participation? Focusing on patterns of hearing participation and citizen impact on budgeting decisions for the Community Development Block Grant program, this statistical analysis employs ordered probit regression. The authors find that communities in which grant administrators feel most accountable to citizens for grant performance have higher degrees of citizen participation in hearings and higher levels of perceived citizen impact on budgetary processes. This relationship holds even in the presence of simultaneity between bureaucratic accountability to citizens and citizen participation. The findings point to the importance of instilling a public service ethic among government employees that places a high value on engaging as well as listening to citizens.

More than five decades have passed since Charles Tiebout wrote his seminal 1956 paper, often cited as the classic apologetic for locally based systems of metropolitan governance. This essay traces the impact of Tiebout’s work and subsequent scholarship in public choice, identifying important lessons and lingering issues. Although public choice has demonstrated that polycentric systems are adept and flexible in producing and providing municipal services and a variety of interlocal agreements, the presence of municipal boundaries gives rise to a host of spillover problems, such as urban sprawl and segregation. These spillovers are particularly nefarious because, unlike the natural cooperation that seems to occur in service provision, municipalities tend to assert narrow self-interest in the face of these types of externalities. The essay proposes that, commensurate with the growing salience of equity among the pillars of public administration, interjurisdictional spillovers and their attendant equity impacts will be the central challenge for thinkers studying metropolitan governance in the 21st century.

Objective. This article comments on the findings of Romero and Liserio's “Saving Open Spaces.” Their primary claim is that open-space ballots are not related in any way to actual land-use patterns. Methods. First, I present a number of methodological problems with their approach and demonstrate a sample selection bias using their original data. Second, I present some alternate models using data from 350 municipalities in the greater Philadelphia area. Results. I demonstrate that the sample selection bias in Romero and Liserio's model is so acute that all their parameter estimates are jointly zero. With other data, I find that sprawl votes are related to land-use patterns using a number of different measures. Conclusions. I conclude that open-space votes are related to land-use patterns and that this may be explained as a rational response to sprawl by community planning bureaucracies.

Extramedullary haematopoiesis (EMH) is a rare disorder and is characterised by the appearance of haemopoietic tissue outside of the bone marrow. The most common of the previously recognised sites of EMH are the spleen and the liver. This case-report describes a unique case of pelvic EMH secondary to herditary spherocytosis with regression of the lesion following splenectomy. Current principles of managing EMH are also discussed.

DE ZWAAN, MARTINA, JAMES E. MITCHELL, L. MICHAEL HOWELL, NANCY MONSON, LORRAINE SWAN-KREMEIER, JAMES L. ROERIG, RONETTE L. KOLOTKIN, AND ROSS D. CROSBY. Two measures of health-related quality of life in morbid obesity. Obes Res. 2002;10:1143–1151. Objective: To compare health-related quality of life (HRQOL) measures in obese presurgery patients with and without binge-eating disorder (BED) and to investigate the relationship between a generic [short form-36 (SF-36)] and a disease-specific HRQOL measure [Impact of Weight on Quality of Life Questionnaire (IWQOL)] and measures of eating-related and general psychopathology. Research Methods and Procedures: One hundred ten patients ages 19 to 62 years with a mean body mass index of 48.4 8.3 kg/m 2 who were evaluated for gastric bypass surgery were asked to fill out questionnaires assessing eating-related and general psychopathology (depression, selfesteem), as well as the two HRQOL questionnaires. BED was assessed by self-report. Results: Nineteen (17.3%) patients met criteria for BED. Significant differences between patients with and without BED were found for four of the eight subscales of the SF-36 —with effect sizes ranging from 0.44 to 0.75—and for the total score and three of the five subscales of the IWQOL-Lite—with effect sizes from 0.57 to 0.74. The mental composite score of the SF-36 as well as the IWQOL total score correlated significantly with the measures of psychopathology. Discussion: This is the first study comparing the results of HRQOL measures in morbidly obese presurgery patients with and without BED. The results indicate that BED has a profound negative impact on HRQOL that exceeds the influence of obesity. Both HRQOL measures were able to reliably discriminate between patients with and without BED. Depression and self-esteem influenced HRQOL in a similar way as binge eating.

Transforming growth factor (TGF)‐β family members play a central role in mesoderm induction during early embryogenesis in Xenopus . Although a number of target genes induced as an immediate‐early response to activin‐like members of the family have been described, little is known about the molecular mechanisms involved. Our systematic analysis of the activin induction of the target gene XFKH1 reveals two regions that mediate activin‐responsive transcription: one, in the first intron, is targeted directly by the activin‐signalling pathway; the other, in the 5′ flanking sequences, responds to activin indirectly, possibly being required for maintenance of gene expression. We demonstrate that a 107 bp region of the XFKH1 first intron acts as an enhancer and confers activin inducibility onto a minimal uninducible promoter in the absence of new protein synthesis. It bears little sequence similarity to other activin responsive sequences. We further demonstrate that overexpression of a constitutively active derivative of Xenopus Smad2 (XSmad2), which has been implicated as a component of the activin signalling pathway, is sufficient for direct activation of transcription via this enhancer. Moreover, we show that XSmad2 acts indirectly on the proximal promoter element induced by activin via an indirect mechanism. These results establish the XFKH1 intron enhancer as a direct nuclear target of the activin signalling pathway in Xenopus embryos, and provide strong new evidence that XSmad2 is a transducer of activin signals.