bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrastructural identification and molecular characterization of two new parabasalid species that naturally colonize laboratory mice,Tritrichomonas musculusandTritrichomonas casperi
Authors: Tuzlak Leila , Alves-Ferreira Eliza V.C. , Kennard Andrea , Shehata Christina , Schwartz Cindi L. , Grigg Michael E.
Published: January 2023

Tritrichomonas murisis a flagellated protist isolated from the cecum of wild mice in the Czech Republic. This commensal protist has been shown previously to alter immune phenotypes in laboratory mice. Other trichomonads, previously referred to asTritrichomonas musculisandTritrichomonas rainier, also naturally colonize laboratory mice and cause immune alterations. This report formally describes two new trichomonads,Tritrichomonas musculusn. sp., andTritrichomonas casperin. sp., at the ultrastructural and molecular level. These two protists were isolated from laboratory mice, and were differentiated by their size and the structure of their undulating membrane and posterior flagellum. Analysis at the18S rRNAand trans-ITSgenetic loci supported their designation as distinct species, related toT. muris. To further assess the true extent of parabasalid diversity infecting laboratory mice, 135 mice were screened at the NIH using pan-parabasalid primers that amplify the trans-ITSregion. Forty-four percent of mice were positive for parabasalids, encompassing a total of 8 distinct sequence types.Tritrichomonas casperiandTrichomitus-like protists were dominant.T. musculusandT. rainierwere also detected, butT. muriswas not. Our work establishes a previously underappreciated diversity of commensal trichomonad protists that naturally colonize the enteric cavity of laboratory mice.
The intracellular symbiontWolbachiaaltersDrosophiladevelopment and metabolism to buffer against nutritional stress
Authors: Lindsey Amelia RI , Tennessen Jason M , Gelaw Michael A , Jones Megan W , Parish Audrey J , Newton Irene LG , Nemkov Travis , D’Alessandro Angelo , Rai Madhulika , Stark Nicole
Published: January 2023

The intracellular bacteriumWolbachiais a common symbiont of many arthropods and nematodes, well studied for its impacts on host reproductive biology. However, its broad success as a vertically transmitted infection cannot be attributed to manipulations of host reproduction alone. Using theDrosophila melanogastermodel and their natively associatedWolbachiastrain “wMel”, we show thatWolbachiainfection supports fly development and buffers against nutritional stress.Wolbachiainfection across several fly genotypes and a range of nutrient conditions resulted in reduced pupal mortality, increased adult emergence, and larger size. We determined that the exogenous supplementation of pyrimidines partially rescued developmental phenotypes in theWolbachia-free flies, and thatWolbachiatiters were responsive to reduced gene expression of the fly’sde novopyrimidine synthesis pathway. In parallel, transcriptomic and metabolomic analyses indicated thatWolbachiaimpacts larval biology far beyond pyrimidine metabolism.Wolbachia-infected larvae had strong signatures of shifts in glutathione and mitochondrial metabolism, plus significant changes in the expression of key developmental regulators includingNotch, the insulin receptor (lnR), and the juvenile hormone receptorMethoprene-tolerant(Met). We propose thatWolbachiaacts as a beneficial symbiont to support fly development and enhance host fitness, especially during periods of nutrient stress.

SIGNIFICANCE

Wolbachiais a bacterial symbiont of arthropods and nematodes, well described for its manipulations of arthropod reproduction. However, many have theorized there must be more to this symbiosis, even in well-studiedWolbachia-host relationships such as withDrosophila. Reproductive impacts alone cannot explain the success and ubiquity of this bacterium. Here, we useDrosophila melanogasterand their nativeWolbachiainfections to show thatWolbachiasupports fly development and significantly buffers flies against nutritional stress. These developmental advantages might help explain the ubiquity ofWolbachiainfections.
Population-level comparisons of gene regulatory networks modeled on high-throughput single-cell transcriptomics data
Authors: Osorio Daniel , Capasso Anna , Eckhardt S. Gail , Giri Uma , Somma Alexander , Pitts Todd M. , Lieu Christopher H. , Messersmith Wells A. , Bagby Stacey M. , Singh Harinder , Das Jishnu , Sahni Nidhi , Yi S. Stephen , Kuijjer Marieke L.
Published: January 2023

Single-cell technologies enable high-resolution studies of phenotype-defining molecular mechanisms. However, data sparsity and cellular heterogeneity make modeling biological variability across single-cell samples difficult. We presentSCORPION, a tool that uses a message-passing algorithm to reconstruct comparable gene regulatory networks from single cell/nuclei RNA-seq data that are suitable for population-level comparisons by leveraging the same baseline priors. Using synthetic data, we found thatSCORPIONoutperforms 12 other gene regulatory network reconstruction techniques. Using supervised experiments, we show thatSCORPIONcan accurately identify differences in regulatory networks between wild-type and transcription factor-perturbed cells. We demonstrateSCORPION’s scalability to population-level analyses using a single-cell RNA-seq atlas containing 200,436 cells from colorectal cancer and adjacent healthy tissues. The differences detected bySCORPIONbetween tumor regions are consistent across population cohorts, as well as with our understanding of disease progression and elucidate phenotypic regulators that may impact patient survival.
Base editing as a genetic treatment for spinal muscular atrophy
Authors: Alves Christiano R. R. , Ha Leillani L. , Yaworski Rebecca , Lazzarotto Cicera R. , Christie Kathleen A. , Reilly Aoife , Beauvais Ariane , Doll Roman M. , de la Cruz Demitri , Maguire Casey A. , Swoboda Kathryn J. , Tsai Shengdar Q. , Kothary Rashmi , Kleinstiver Benjamin P.
Published: January 2023

Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in theSMN1gene. Despite the development of various therapies, outcomes can remain suboptimal in SMA infants and the duration of such therapies are uncertain.SMN2is a paralogous gene that mainly differs fromSMN1by a C•G-to-T•A transition in exon 7, resulting in the skipping of exon 7 in mostSMN2transcripts and production of only low levels of survival motor neuron (SMN) protein. Genome editing technologies targeted to theSMN2exon 7 mutation could offer a therapeutic strategy to restore SMN protein expression to normal levels irrespective of the patientSMN1mutation. Here, we optimized a base editing approach to precisely editSMN2, reverting the exon 7 mutation via an A•T-to-G•C base edit. We tested a range of different adenosine base editors (ABEs) and Cas9 enzymes, resulting in up to 99% intended editing in SMA patient-derived fibroblasts with concomitant increases inSMN2exon 7 transcript expression and SMN protein levels. We generated and characterized ABEs fused to high-fidelity Cas9 variants which reduced potential off-target editing. Delivery of these optimized ABEs via dual adeno-associated virus (AAV) vectors resulted in preciseSMN2editingin vivoin an SMA mouse model. This base editing approach to correctSMN2should provide a long-lasting genetic treatment for SMA with advantages compared to current nucleic acid, small molecule, or exogenous gene replacement therapies. More broadly, our work highlights the potential of PAMless SpRY base editors to install edits efficiently and safely.
Structural preferences shape the entropic force of disordered protein ensembles
Authors: Yu Feng , Sukenik Shahar
Published: January 2023

Intrinsically disordered protein regions (IDRs) make up over 30% of the human proteome and instead of a native, well-folded structure exist in a dynamic conformational ensemble. Tethering IDRs to a surface (for example, the surface of a well-folded region of the same protein) can reduce the number of accessible conformations in IDR ensembles. This reduces the ensemble’s conformational entropy, generating an effective entropic force that pulls away from the point of tethering. Recent experimental work has shown that this entropic force causes measurable, physiologically relevant changes to protein function, but how the magnitude of this force depends on the IDR sequence remains unexplored. Here we use all-atom simulations to analyze how structural preferences encoded in dozens of IDR ensembles contribute to the entropic force they exert upon tethering. We show that sequence-encoded structural preferences play an important role in determining the magnitude of this force and that compact, spherical ensembles generate an entropic force that can be several times higher than more extended ensembles. We further show that changes in the surrounding solution’s chemistry can modulate IDR entropic force strength. We propose that the entropic force is a sequence-dependent, environmentally tunable property of terminal IDR sequences.
Abnormal chondrocyte intercalation in a zebrafish model ofcblCsyndrome restored by an MMACHC cobalamin binding mutant
Authors: Paz David , Pinales Briana E. , Castellanos Barbara S. , Perez Isaiah , Gil Claudia B. , Jimenez Madrigal Lourdes , Reyes-Nava Nayeli G. , Castro Victoria L. , Sloan Jennifer L. , Quintana Anita M.
Published: January 2023

Variants in theMMACHCgene cause combined methylmalonic acidemia and homocystinuriacblCtype, the most common inborn error of intracellular cobalamin (vitamin B12) metabolism.cblCis associated with neurodevelopmental, hematological, ocular, and biochemical abnormalities. In a subset of patients, mild craniofacial dysmorphia has also been described. Mouse models ofMmachcdeletion are embryonic lethal but cause severe craniofacial phenotypes such as facial clefts.MMACHCencodes an enzyme required for cobalamin processing and variants in this gene result in the accumulation of two metabolites: methylmalonic acid (MMA) and homocysteine (HC). Interestingly, other inborn errors of cobalamin metabolism, such ascblXsyndrome, are associated with mild facial phenotypes. However, the presence and severity of MMA and HC accumulation incblXsyndrome is not consistent with the presence or absence of facial phenotypes. Thus, the mechanisms by which mutation ofMMACHCcause craniofacial defects have not been completely elucidated. Here we have characterized the craniofacial phenotypes in a zebrafish model ofcblC(hg13) and performed restoration experiments with either wildtype or a cobalamin binding deficient MMACHC protein. Homozygous mutants did not display gross morphological defects in facial development, but did have abnormal chondrocyte intercalation, which was fully penetrant. Abnormal chondrocyte intercalation was not associated with defects in the expression/localization of neural crest specific markers,sox10orbarx1. Most importantly, chondrocyte organization was fully restored by wildtype MMACHC and a cobalamin binding deficient variant of MMACHC protein. Collectively, these data suggest that mutation ofMMACHCcauses mild to moderate craniofacial phenotypes that are independent of cobalamin binding.
High sensitivity proteome-scale search for crosslinked peptides using CRIMP 2.0
Authors: Crowder D. Alex , Sarpe Vladimir , Amaral Bruno C. , Brodie Nicholas I. , Michael Andrew R. M. , Schriemer David
Published: January 2023

Crosslinking mass spectrometry (XL-MS) is a valuable technique for the generation of point-to-point distance measurements in protein space. Applications involvingin situchemical crosslinking have created the possibility of mapping whole protein interactomes with high spatial resolution. However, an XL-MS experiment carried out directly on cells requires highly efficient software that can detect crosslinked peptides with sensitivity and controlled error rates. Many algorithmic approaches invoke a filtering strategy designed to reduce the size of the database prior to mounting a search for crosslinks, but concern has been expressed over the possibility of reduced sensitivity with such strategies. Here we present a full upgrade to CRIMP, the crosslinking app in the Mass Spec Studio, which implements a new strategy for the detection of both component peptides in the MS2spectrum. Using several published datasets, we demonstrate that this pre-searching method is sensitive and fast, permitting whole proteome searches on a conventional desktop computer for both cleavable and noncleavable crosslinkers. We introduce a new strategy for scoring crosslinks, adapted from computer vision algorithms, that properly resolves conflicting XL hits from other crosslinking reaction products, and we present a method for enhancing the detection of protein-protein interactions that relies upon compositional data.
Netrin-1 binding to Unc5B regulates Blood-Retina Barrier integrity
Authors: Furtado Jessica , Geraldo Luiz Henrique , Leser Felipe Saceanu , Poulet Mathilde , Park Hyojin , Pibouin-Fragner Laurence , Eichmann Anne , Boyé Kevin
Published: January 2023

Background

The blood brain barrier (BBB) preserves neuronal function in the central nervous system (CNS) by tightly controlling metabolite exchanges with the blood. In the eye, the retina is likewise protected by the blood-retina barrier (BRB) to maintain phototransduction. We showed that the secreted guidance cue Netrin-1 regulated BBB integrity, by binding to endothelial Unc5B and regulating canonical β-catenin dependent expression of BBB gene expression

Objective

Here, we investigated if Netrin-1-binding to endothelial Unc5B also controlled BRB integrity, and if this process involved Norrin/β-catenin signaling, which is the major known driver of BRB development and maintenance.

Methods

We analyzed Tamoxifen-inducible loss- and gain-of-function alleles ofUnc5B, Ntn1andCtnnb1in conjunction with tracer injections and biochemical signaling studies.

Results

Inducible endothelialUnc5Bdeletion, and inducible globalNtn1deletion in postnatal mice reduced phosphorylation of the Norrin receptor LRP5, leading to reduced β-catenin and LEF1 expression, conversion of retina endothelial cells from a barrier-competent Claudin-5+/PLVAP-state to a Claudin-5-/PLVAP+ leaky phenotype, and extravasation of injected low molecular weight tracers. InducibleCtnnb1gain of function rescued vascular leak inUnc5Bmutants, andNtn1overexpression induced BRB tightening. Unc5B expression in pericytes contributed to BRB permeability, via regulation of endothelial Unc5B. Mechanistically, Netrin-1-Unc5B signaling promoted β-catenin dependent BRB signaling by enhancing phosphorylation of the Norrin receptor LRP5 via the Discs large homologue 1 (Dlg1) intracellular scaffolding protein.

Conclusions

The data identify Netrin1-Unc5B as novel regulators of BRB integrity, with implications for diseases associated with BRB disruption.
Explaining reward crowdfunding backers' intentions and behavior
Authors: Baah-Peprah Prince
Published: January 2023

Purpose

Earlier research into crowdfunding adoption has drawn on social psychology, trust, signaling and well-being theories. Despite its wide appeal and use, the technology acceptance model (TAM) has received little attention in terms of explaining the adoption of crowdfunding platforms. The current study examines the applicability of two versions of this framework: the original TAM1 and the extended TAM2 frameworks.

Design/methodology/approach

Data were collected through a survey distributed to the users of Finland's leading reward crowdfunding website, Mesenaatti, who have backed crowdfunding campaigns previously. The authors employed structural equation modelling (SEM–lavaan package) and conducted a series of quality tests to alleviate concerns with certain biases.

Findings

Analyses of 556 observations exhibit support for all hypotheses underlying both TAM frameworks, with two exceptions. Contrary to expectations, voluntariness does not moderate the effect of subjective norms on contribution intentions, and the effect of perceived ease-of-use is primarily mediated by perceived usefulness, rather than directly influencing intentions.

Originality/value

First, the study extends the generalizability of TAM to the context of crowdfunding and with respect to financial contribution behavior. Second, it shows that backers' perceptions of platform usefulness and ease-of-use are important antecedents of crowdfunding contribution behavior, and that the former exerts greater influence than the latter. Third, it further clarifies the influences of relevant antecedents of crowdfunding backers' contribution intentions and behaviors. Specifically, the authors show that experience only weakly moderates the influence of subjective norms on contribution intentions, and voluntariness does not moderate this association. The authors discuss explanations for these findings and their implications for research and practice.
Cost prediction of building projects using the novel hybrid RA-ANN model
Authors: Wang Yali , Zuo Jian , Pan Min , Tu Bocun , Chang Rui-Dong , Liu Shicheng , Xiong Feng , Dong Na
Published: January 2023

Purpose

Accurate and timely cost prediction is critical to the success of construction projects which is still facing challenges especially at the early stage. In the context of rapid development of machine learning technology and the massive cost data from historical projects, this paper aims to propose a novel cost prediction model based on historical data with improved performance when only limited information about the new project is available.

Design/methodology/approach

The proposed approach combines regression analysis (RA) and artificial neural network (ANN) to build a novel hybrid cost prediction model with the former as front-end prediction and the latter as back-end correction. Firstly, the main factors influencing the cost of building projects are identified through literature research and subsequently screened by principal component analysis (PCA). Secondly the optimal RA model is determined through multi-model comparison and used for front-end prediction. Finally, ANN is applied to construct the error correction model. The hybrid RA-ANN model was trained and tested with cost data from 128 completed construction projects in China.

Findings

The results show that the hybrid cost prediction model has the advantages of both RA and ANN whose prediction accuracy is higher than that of RA and ANN only with the information such as total floor area, height and number of floors.

Originality/value

(1) The most critical influencing factors of the buildings’ cost are found out by means of PCA on the historical data. (2) A novel hybrid RA-ANN model is proposed which proved to have the advantages of both RA and ANN with higher accuracy. (3) The comparison among different models has been carried out which is helpful to future model selection.
Decision making in human resources standard practices and change management innovation initiatives: the common destiny of being affected by biases
Authors: Palmucci Dario Natale
Published: January 2023

Purpose

This work aims to shed light on the cognitive biases that may have an influence on the strategic decision-making process, with a particular focus on those impacting both human resources (HR) standard activities within organizations and new innovative change management initiatives critical for them to survive.

Design/methodology/approach

This is a conceptual paper based on a literature review on cognitive biases and managerial decision-making. The conceptual approach is employed to outline how subjective cognitive barriers can undermine managerial decisions and, in particular, the objectivity of HR practices and change management initiatives.

Findings

The discussion emphasizes that cognitive biases are ever-present elements in the decision-making process of professionals, and they influence several areas of management including HR and change management.

Research limitations/implications

Limitations of the study concern the method adopted, as it is conceptual. The implications of the paper are relevant for supervisors and employees working in the HR and innovation/R&D departments in order to create awareness within the organizational contexts and limit the negative influence of these cognitive barriers during their daily activities.

Originality/value

The research contributes to the knowledge on HR management and decision-making process by combining literature findings with practical examples and tips suggesting how to avoid biases in the decision-making process regarding HR and change management.
Responding to the COVID-19 pandemic – catching up in the food industry through business model innovation
Authors: Münch Christopher , Hartmann Evi
Published: January 2023

Purpose

The food supply chain worldwide has suffered severely due to the COVID-19 pandemic countermeasures. Previous research suggests that business model innovation (BMI) could be a viable solution for recovering from the pandemic and fostering organizational resilience. This study analyzes the capabilities that enable food companies to innovate their business model and thereby increase organizational resilience.

Design/methodology/approach

Results were obtained using a multiple-case study approach consisting of 15 companies along the entire food supply chain. Managers and decision-makers were interviewed, and the collected insights were enriched with additional material.

Findings

The results show several capabilities that enable companies to innovate their business model due to disruption. These capabilities are categorized into four phases based on the processual representation of BMIs.

Originality/value

This study contributes to the understanding of BMI in the food supply chain and provides empirical evidence on the potential for business recovery through BMI.
Knowledge trajectories in the internationalization of the firm
Authors: Barbosa Sylvio Leal , Rezende Sergio Fernando Loureiro , Versiani Angela , Galdino Katia M.
Published: January 2023

Purpose

The purpose of this paper is to analyze how the internationalizing firm accumulates knowledge from different domains throughout time, during entry and post-entry moves in a foreign market. This paper focuses on market, institutional, internationalization and technological knowledge.

Design/methodology/approach

The paper uses a comparative case study method, relying on three longitudinal cases of multinational firms' (MNEs) internationalization processes, particularly concerning MNEs' entry and post-entry moves in one foreign market (Brazil).

Findings

Throughout the internationalization processes, the internationalizing firms unevenly developed experiential knowledge within Brazil. As a result, the market, internationalization, institutional and technological knowledge followed different accumulation patterns, distinguished based on precedence, simultaneity and speed. More specifically, (1) the market and institutional knowledge trajectories evolved simultaneously; (2) the market knowledge trajectory preceded that of technological knowledge and (3) the accumulation of internationalization knowledge happened faster than that of the market, institutional and technological knowledge.

Originality/value

This paper shows how knowledge accumulation in internationalization processes varies throughout time and according to the type of knowledge involved. While most of the literature relies on cross-sectional studies that discount the changing nature of knowledge, this paper shows that the internationalizing firm accumulates market, internationalization, institutional and technological knowledge following three temporal dimensions: precedence, simultaneity and speed.
Retail inventory policy under demand uncertainty and inventory-level-dependent demand
Authors: Srivastava Mohit , Mehta Peeyush , Swami Sanjeev
Published: January 2023

Purpose

The purpose of this paper is to determine the inventory replenishment policies when demand rate is a function of the inventory space allocated to the products on retail shelves. Existing results on inventory policies with inventory-level-dependent demand (ILDD) assume deterministic functional forms of the demand rate. In this paper, the authors model the inventory decisions when demand is a function of shelf-space allocation and random uncertainty. The authors provide managerial insights of this paper's results.

Design/methodology/approach

The demand rate is assumed to be a function of shelf-space allocation based on two settings in the literature. First, the authors model the demand rate as a function of initial shelf-space allocation. In the next setting, the authors assume that the demand rate is a function of instantaneous inventory level on shelves. In both the settings, the authors also model random demand uncertainty in addition to the shelf-space dependency of demand rate. The objective is to maximize the expected profit and determine the inventory parameters.

Findings

In addition to the demand uncertainty, the authors consider linear, power and exponential functional forms of demand rate. Inventory policy that maximizes expected profit is determined when demand rate is a function of initial allocation and displayed inventory level. The results are implementable for practitioners for optimizing the shelf-space allocation and related inventory policy.

Originality/value

Most of the extant results on inventory policy with shelf-space-dependent demand do not model the demand uncertainty. The authors model a variety of functional forms of demand rate with ILDD in addition to the demand uncertainty. The results are a building block for more applications in inventory management for real-life applications.
Reported shocks, households' resilience and local food commercialization in Thailand
Authors: Wang Menglan , Do Manh Hung
Published: January 2023

Purpose

The authors examine the factors affecting households' resilience capacities and the impacts of these capacities on household consumption and crop commercialization.

Design/methodology/approach

The authors use panel data of 1,648 households from Thailand collected in three years, 2010, 2013 and 2016. The authors employ an econometric model with an instrumental variable approach to address endogenous issues.

Findings

The study results show that the experience of shocks in previous years positively correlates with households' savings per capita and income diversification. Further, a better absorptive capacity in the form of better savings and a better adaptive capacity in the form of higher income diversification have a significant and positive influence on household expenditure per capita and crop commercialization.

Practical implications

Development policies and programs aiming to improve income, increase savings and provide income diversification opportunities are strongly recommended.

Originality/value

The authors provide empirical evidence on the determinants of resilience strategies and their impacts on local food commercialization from a country in the middle-income group.
Designing a branding model for academic libraries affiliated with the Ministry of Science, Research and Technology in Iran
Authors: Sahli Farzane , Alidousti Sirous , Naghshineh Nader
Published: January 2023

Purpose

This study identifies factors affecting brand building for academic libraries affiliated with the Ministry of Science, Research and Technology (MSRT) in Iran.

Design/methodology/approach

This research applied the grounded theory method based on the three open, axial and selective coding steps (Strauss and Corbin, 1998). The research tool was interviews conducted with 20 experts in librarianship, marketing and branding.

Findings

Library building architecture, library information resources and services, librarians' branding, marketing activities and library management are the causal conditions affecting brand building. The national economic situation, the digital publishing situation in the country and different characteristics of the new library community are the intervening conditions affecting brand building. The role of other libraries in society in the scientific education of the new generation provides contextual conditions for brand building. The higher education system and the library parent organization play a part in the operative actions/interactions for brand building. The consequences of brand building are brand image development, brand excellence and brand behavioral loyalty for libraries. Library brand identity is also a core category in brand building.

Originality/value

Facing steep challenges by emergent services, academic libraries are ill-prepared to meet the needs of the new information society solely with traditional services and functions. Academic libraries are required to rebrand themselves to be more successful at delivering a strong performance within a changing information environment by enhancing their brand image and establishing a more effective relationship with users.
Lean Six Sigma to reduce the acute myocardial infarction mortality rate: a single center study
Authors: Rosa Angelo , Trunfio Teresa Angela , Marolla Giuliano , Costantino Antonietta , Nardella Davide , McDermott Olivia
Published: January 2023

Purpose

Cardiovascular diseases are the leading cause of death worldwide. In Italy, acute myocardial infarction (AMI) is a major cause of hospitalization and healthcare costs. AMI is a myocardial necrosis event caused by an unstable ischemic syndrome. The Italian government has defined an indicator called “AMI: 30-day mortality” to assess the quality of the overall care pathway of the heart attacked patient. In order to guarantee high standards, all hospitals had to implement techniques to increase the quality of care pathway. The aim of the paper is to identify the root cause and understand the mortality rate for AMI and redesign the patient management process in order to improve it.

Design/methodology/approach

A Lean Six Sigma (LSS) approach was used in this study to analyze the patient flow in order to reduce 30-days mortality rate from AMI registered by Complex Operative Unit (COU) of Cardiology of an Italian hospital. Value stream mapping (VSM) and Ishikawa diagrams were implemented as tools of analysis.

Findings

Process improvement using LSS methodology made it possible to reduce the overall times from 115 minutes to 75 minutes, with a reduction of 35%. In addition, the corrective actions such as the activation of a post-discharge outpatient clinic and telephone contacts allowed the 30-day mortality rate to be lowered from 16% before the project to 8% after the project. In this way, the limit value set by the Italian government was reached.

Research limitations/implications

The limitation of the study is that it is single-centered and was applied to a facility with a limited number of cases.

Practical implications

The LSS approach has brought significant benefits to the process of managing patients with AMI. Corrective actions such as the activation of an effective shared protocol or telephone interview with checklist can become the gold standard in reducing mortality. The limitation of the study is that it is single-centered and was applied to a facility with a limited number of cases.

Originality/value

LSS, applied for the first time to the management of cardiovascular diseases in Italy, is a methodology which has proved to be strategic for the improvement of healthcare process. The simple solutions implemented could serve as a guide for other hospitals to pursue the national AMI mortality target.
Cutaneous manifestations in elderly patients with confirmed coronavirus disease 2019 and the disease outcomes: A systematic review
Authors: Yusharyahya Shannaz Nadia , Japranata Valdi Ven , Jonlean Reganedgary , Legiawati Lili , Astriningrum Rinadewi
Published: January 2023

Cutaneous manifestations in coronavirus disease 2019 (COVID‐19) patients may possess prognostic value for identifying potentially severe cases. This systematic review investigated whether dermatological features are associated with COVID‐19 outcomes in elderly patients. Literature retrieval was conducted on May 11, 2022, from databases, hand‐searching, and tracing citations. Following selection against eligibility criteria, the remaining records were evaluated utilizing the National Heart, Lung, and Blood Institute Study Quality Assessment Tool or Newcastle–Ottawa Scale. The pooled individual data were subsequently analyzed using the Cochran–Mantel–Haenszel test to calculate the odds ratio (ORs) and confidence intervals (CIs) for the severity and mortality of each skin lesion type. We incorporated 70 articles, including 180 and 117 entries, with information regarding disease severity and mortality. Further analysis revealed that vascular type was the skin lesion most frequently noticed in confirmed COVID‐19 elderly patients (46.2%) and was associated with an increased risk of developing advanced disease (OR 7.32, 95% CI 3.39–15.81) and the ensuing termination (OR 5.73, 95% CI 2.46–13.36). The converse phenomenon was observed in maculopapular type (severity OR 0.27, 95% CI 0.14–0.52; mortality OR 0.10, 95% CI 0.03–0.36). In conclusion, skin manifestations may predict COVID‐19 severity and mortality in the senior group.
Mirror tomography of sparse ocean‐bottom seismometer data: Two‐dimensional synthetic studies
Authors: Liu Bin
Published: January 2023

First‐arrival travel‐time tomography is frequently used in ocean‐bottom seismometer surveys for estimating subsurface velocity. However, due to a lack of seismometer stations or ray sampling, the tomographic images’ spatial resolution and quality are typically low. Inspired by the multiple imaging of ocean‐bottom seismometer data, in this study, I developed a mirror tomography method to incorporate the travel times of refraction multiples in first‐arrival travel‐time tomography. Specifically, the travel times of refraction multiples were treated as virtual first‐arrival travel times from the mirror positions of the stations. This technique enhances ray coverage and stabilizes the inversion. I confirmed that the travel times of refraction multiples were consistent with the first‐arrival travel times calculated using numerical modelling at the mirror position of the station. Synthetic examples showed that the mirror tomography scheme may enhance ray coverage and model resolution. Mirror tomography may compensate for the uneven distribution of travel‐time picks caused by the loss of the ocean‐bottom seismometer.
Disorder or difference? How clinician‐patient interaction and patient age shape the process and meaning of autism diagnosis
Authors: Turowetz Jason , Wiscons Lucas Z. , Maynard Douglas W.
Published: January 2023

This article follows Blaxter’s foundational call for a sociology of diagnosis that addresses the dual aspects of diagnosis‐as‐category and diagnosis‐as‐process. Drawing on video recordings from an autism clinic, we show how the process of attaching the diagnosis to a child involves interactions between clinicians, parents and children, and that in the course of such interactions, a diagnostic category officially defined in terms of deficits can instead be formulated in terms of valuable social and cognitive differences. More specifically, we show that the child’s age is crucial for how clinicians formulate the diagnosis: with younger children, clinicians treat autism exclusively as a deficit to be remedied, whereas with older children, clinicians may treat autism either as a deficit or as a social‐cognitive difference. Further, because older children are often co‐recipients of diagnostic news, we find that clinicians carefully manage the implications such news may have for their self/identity. Finally, we suggest that (1) the equation of a diagnostic category with dysfunction is achieved in interaction; (2) the meaning of a diagnosis may vary with characteristics of its recipients; and (3) that meaning can be worked up by clinicians and recipients in ways that centre difference rather than deficit.
The role, targets and mechanisms of traditional Chinese medicine in regulating the balance of T helper type 17/regulatory Tcells in rheumatoid arthritis
Authors: Wang Tao , Wang Zhandong , Qi Wenxia , Jiang Ganggang , Wang Gang
Published: January 2023

Rheumatoid arthritis (RA) is a persistent systemic autoimmune disease, having all the hallmarks of joint swelling, joint tenderness, and progressive joint destruction, with synovitis and pannus formation as the basic pathological changes. T‐lymphocyte infiltration is the key to its pathogenesis. During the growth of RA, the share of regulatory T (Treg) cells decreases, while the percentage of T helper type 17 (Th17) cells increases, giving rise to an imbalance of Th17/Treg cells. Modern medicine has made great advances in the treatment of RA and the selection of available drugs, but there are also the disadvantages of gastrointestinal reaction, high price, and low patient compliance. Therapy of RA remains a problem. Traditional Chinese medicine (TCM) has RA therapy developments, both in experimental research and clinical research, and its advantages of lasting effects and less detrimental reactions and fewer adverse effects are accepted by most patients. Numerous clinical and experimental studies have been performed in TCM on regulating Th17/Treg balance. However, the detailed mechanism of TCM intervention in Th17/Treg equilibrium in preventing and treating RA has not been discovered. In this article, the theory of regulating Th17/Treg cell equilibrium in RA is described from the perspectives of single Chinese medicine, active components of Chinese medicine, Chinese medicine compounds, and other therapies of TCM. It was found that TCM can regulate Th17/Treg cell balance and inhibit immunoreaction by intervening in cytokines, transcription factors, and signal pathways. It enables us to comprehensively and deeply understand the mechanism of TCM intervening in Th17/Treg balance in RA; provides direction for clinical therapy of RA; and offers new thoughts for understanding the pathogenesis of RA.
Effectiveness and safety of generic tofacitinib in spondyloarthritis: A real‐world retrospective analysis from India
Authors: Phatak Sanat , Khenat Aditya , Malandkar Mansi , Amin Sanjiv
Published: January 2023

Background

Clinical trial evidence demonstrates the efficacy of tofacitinib in ankylosing spondylitis and psoriatic arthritis (PsA). Real‐world data from spondyloarthritis (SpA) patients are scarce; there are few reports of its effectiveness and safety from low‐ to middle‐income countries like India, despite its widespread usage.

Methods

This was a retrospective analysis of clinical and laboratory records of 100 patients with SpA prescribed generic tofacitinib from a single center in Mumbai, India. Disease activity was measured using the Ankylosing Spondylitis Disease Activity Score C‐Reactive Protein (ASDAS‐CRP) in all patients, along with disease‐specific outcome measures in the subgroups. We used paired t test for response to tofacitinib. We compared Δ ASDAS‐CRP in patients with active peripheral arthritis and in patients without. We defined clinical tofacitinib failure as the physician's decision to change or add a disease‐modifying antirheumatic drug (DMARD), and performed logistic regression to identify factors associated with tofacitinib failure.

Results

Among 100 patients (71 male, median age 42.5 years), 57 had axial SpA, 10 had peripheral SpA, 4 had inflammatory bowel disease‐SpA and 29 had PsA. One‐third had received biologic DMARDs previously. Patients received tofacitinib for a median of 192 days. There was a significant improvement in ASDAS‐CRP in all types of SpA. Patients with active peripheral arthritis had a significantly greater fall in ASDAS‐CRP. There were no serious adverse events, 19 patients had mild COVID‐19; no patient had tuberculosis. Ten patients had tofacitinib failure; no baseline parameter could predict failure.

Interpretation

In the real‐world setting, generic tofacitinib showed good effectiveness and tolerable safety profile in Indian patients with SpA.
Circ_0043256 upregulates KLF2 expression by absorbing miR‐1206 to suppress the tumorigenesis of lung cancer
Authors: Zhou Ying , Liu Hongliu , Wang Rui , Zhang Mingtao
Published: January 2023

Background

Circular RNAs (circRNAs) have been reported to play roles in lung cancer development. The purpose of this work was to explore the function and mechanism of circ_0043256 in lung cancer tumorigenesis.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were used for the detection of the levels of genes and proteins. Cell growth, angiogenesis ability, migration, and invasion were analyzed by using 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, flow cytometry, tube formation assay, transwell assay, and murine xenograft model, respectively. The target between miR‐1206 and circ_0043256 or Krüppel‐like factor 2 (KLF2) was verified by dual‐luciferase reporter assay.

Results

Circ_0043256 was a stable circRNA, which was found to be decreased in lung cancer tissues and cells. Functionally, forced expression of circ_0043256 suppressed lung cancer cell growth, angiopoiesis, migration, and invasion. Mechanistically, circ_0043256 directly bound to miR‐1206 and miR‐1206 targeted KLF2, circ_0043256 could regulate KLF2 expression via absorbing miR‐1206. Rescue assay showed that miR‐1206 overexpression reversed the anticancer effects of circ_0043256 on lung cancer cells. Moreover, inhibition of miR‐1206 could suppress the malignant phenotypes of lung cancer cells, which was attenuated by KLF2 knockdown. Pre‐clinically, lentivirus‐mediated circ_0043256 overexpression impeded lung cancer growth in nude mice.

Conclusion

Forced expression of circ_0043256 could impede the tumorigenesis of lung cancer via miR‐1206/KLF2 axis, indicating a potential therapeutic approach for lung cancer.
Analyst workload and information production: Evidence from IPO assignments
Authors: Pisciotta Kevin
Published: January 2023

I examine how changes in analysts' workloads affect their information production. Examining determinants of analysts' information production is important because analyst research affects stock prices and capital allocation decisions. Using periods when analysts work on IPOs to proxy for shocks to their workloads, I predict and find that the accuracy, quantity, and timeliness of analysts' forecasts for non‐IPO firms decline when they are working on IPOs, and they herd closer to the consensus. The reductions in research quality are larger for less experienced analysts, larger IPOs, and less important portfolio firms. Last, I predict and find that information asymmetry increases for non‐IPO firms covered by analysts who are working on IPOs, consistent with analysts' reduction in research quality during IPO assignments negatively affecting the information environment of non‐IPO firms. In sum, I provide the first evidence that analysts' work on IPO deals imposes negative externalities on both the quality of research they produce for the non‐IPO firms they cover and the information environments of these firms, highlighting at least one reason why analyst workload is important to firms and investors.
The predictive validity of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for moderate‐ to high‐risk cannabis, methamphetamine and opioid use after release from prison
Authors: Cumming Craig , Kinner Stuart A. , McKetin Rebecca , Young Jesse T. , Li Ian , Preen David B.
Published: January 2023

Background and aims

Illicit substance use is common among people entering prisons, as is returning to substance use after release from prison. We aimed to assess the predictive validity of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for returning to substance use after release from prison.

Design

A longitudinal design with baseline survey conducted between 2008 and 2010 in the 6 weeks before expected prison release and up to three follow‐up surveys in the 6 months after release.

Setting

Prisons in Queensland, Australia.

Participants

A total of 1054 adults within 6 weeks of expected release from prison.

Measurements

The ASSIST was used to assess problematic use of cannabis, methamphetamine, heroin and other non‐prescribed opioids in the 3 months before incarceration. Post‐incarceration substance use was measured at 1, 3 and 6 months after release. We calculated the area under the receiver operating characteristic curve (AUROC) and the optimal ASSIST cut‐off score for each substance, using Youden’s index (J).

Findings

Forty‐one per cent (n = 434) of the cohort reported any substance use during follow‐up: 33% (n = 344) used cannabis, 20% (n = 209) methamphetamine, 10% (n = 109) heroin and 9% (n = 97) illicit other opioids. The optimal ASSIST cut‐off score was ≥ 4 for heroin, methamphetamine and cannabis and ≥ 1 for other opioids. Using these cut‐offs, the AUROC was highest for heroin in predicting both any use (AUROC = 0.82) and weekly use (AUROC = 0.88) in the past 4 weeks. AUROCs for other drugs ranged from 0.73 to 0.79.

Conclusions

The ASSIST shows promise as an accurate and potentially scalable tool that may be useful for predicting a return to substance use after release from prison and could inform service delivery. The substantial rates of returning to substance use after release from prison suggest that prison serves to interrupt rather than cease substance use.
When teams disagree: Investigating the incidence and causes of dissent occurring in cancer multidisciplinary team meetings
Authors: Chambers Anthony J. , Enoch Jade F. , Wong Jasmine , Spigelman Allan
Published: January 2023

Aim

Multidisciplinary teams (MDT) are commonly involved in the care of patients with cancer. How frequently dissent occurs within MDT has not been studied. This study aimed to determine how frequently dissent was documented in cancer MDT meetings at our institution, the reasons for this, and the opinions of MDT members on how dissent should be documented and communicated.

Methods

A retrospective review of records from cancer MDT meetings at our institution from 2016 to 2020 was performed to identify cases where dissent was documented and the reasons for this. MDT members were invited to complete an online survey assessing their perceptions of how frequently dissent occurred, how comfortable they felt voicing dissenting opinions, and their opinions on how dissent should be documented and communicated.

Results

Dissent was recorded in 30 of 7737 MDT case discussions (0.39%). The incidence of dissent varied from 0 to 1.2% between cancer streams. The most common reason for dissent involved the role of surgery. 27% of survey respondents felt either very or somewhat uncomfortable voicing dissenting opinions. Only 3% felt that dissent should not be documented, and none that it should not be communicated in some way, although there were wide ranging of views on how this should occur.

Conclusion

Dissent was rarely documented within cancer MDT meetings at our institution, likely due to underreporting. Measuring the incidence of dissent within an MDT may be a useful performance metric. MDT should develop policies for how dissent should be managed, documented, and communicated.