bluuebunny/crossref_metadata_2025 huggingface dataset:
Clostridioides difficile infection in a skilled nursing facility (SNF): cost savings of an automated, standardized probiotic antimicrobial stewardship programme (ASP) policy
Authors: Olson Bridget , Ship Noam , Butera Michael L , Warm Kenneth , Oen Roger , Howard John
Published: September 2023

Background

With multiple comorbidities and frequent exposures to antibiotics, patients in skilled nursing facilities (SNFs) are much more vulnerable to healthcare-acquired infections. We conducted a quality-improvement, retrospective analysis of all patients with Clostridioides difficile infection (CDI) from 2009 to 2021 at an SNF. Probiotics were initially added to a bundle of antimicrobial stewardship programme (ASP) CDI prevention strategies. Formulations and durations of probiotics were standardized for both oral and enteral administration. To reach all eligible patients, an ASP probiotic policy provided probiotics with every antibiotic course.

Objectives

To assess the value of providing probiotic therapy to SNF patients at risk for CDI.

Patients and methods

Patients receiving oral or enteral feeding with antibiotics ordered were eligible to receive probiotics. The incremental cost of CDI prevention, treatment and related care were calculated and compared for each phase of probiotic policy change and feeding type. ASP records for the oral probiotic and level of treatment were used in modelling the cost-effectiveness.

Results

From quality improvement initiatives aimed at preventing facility-onset (FO) CDI, to ASP policies, probiotic formulations and delegation of ordering authority, the days of acute care treatment required was significantly reduced over the different phases of implementation [152 to 48, OR = 0.22 (0.16–0.31) to 4, OR = 0.08 (0.03–0.23)] after reducing total CDI from 5.8 to 0.3 cases per 10 000 patient-days. The annual cost of oral probiotics increased from $6019 to $14 652 but the modelled net annual savings for the facility was $72 544–$154 085.

Conclusions

With optimization, the use of probiotics for CDI prevention at an SNF was safe, efficacious and cost-effective.
The practice of non-recognition and economic sanctions: The case study of Ukraine, Manchuria and South Africa
Authors: Nguyen Quoc Tan Trung
Published: September 2023

Russia’s invasion of Ukraine again proves the essential role of collective non-recognition against unlawful situations, despite contentious debates concerning the status of the principle of non-recognition in the international legal system. However, an old but unsettled question also resurfaces: How should we perceive the relationship between the practice of non-recognition and economic sanctions? Some scholars contend that the practice of non-recognition must entail economic punishments and isolation and be ‘as oppressive as possible’. For quite some time, the economic language has dominated as the only language that matters facing any unlawful situations. Unfortunately, this tendency also undermines a long history of innovative development of other forms of declaratory and institutional non-recognition. This article, by examining the current non-recognition campaign in the case of Ukraine, together with case studies of Manchuria and of the South African apartheid regime, endeavours to provide more perspectives concerning the relationship between non-recognition and economic sanctions. The article argues that, compared to other forms of non-recognition, economic sanctions have never been a reliable factor in demonstrating international attitudes and the legal beliefs of the international community.
The Life-Cycle Effects of Pension Reforms: A Structural Approach
Authors: Daminato Claudio , Padula Mario
Published: September 2023

To assess the life-cycle welfare effects of pension reforms, we provide a dynamic stochastic model of saving, portfolio choice, and retirement featuring a rich characterisation of the pension system. Relying on the exogenous variation from a sequence of Italian pension reforms, we identify and estimate the model, which is then used to draw implications of alternative pension policies. The validated model predicts substantial social security wealth effects on retirement, with the offset between public pension wealth and private savings softened when households can adjust their retirement decisions. We further find important distributional effects of pension reforms, with households’ welfare decreasing more the later in the working life they face the reform. Our findings have implications for the design of pension policies and the support they might generate.
Risk, Contract Terms, and Maturity in the Sovereign Debt Market
Authors: Bradley Michael , De Lira Salvatierra Irving Arturo , Gulati Mitu , Panizza Ugo
Published: September 2023

In this article, we examine the relations between risk, the choice of foreign or local contract terms (parameters), and maturity in the sovereign debt market. Our primary finding is that the maturities of bonds that carry a meaningful degree of risk are greater when the bonds are written under foreign parameters. This finding is consistent with the Credible Commitment Theory. Relinquishing certain key contractual parameters (governing law, jurisdiction, currency, listing) precludes the issuing sovereign from taking actions that would diminish the wealth of its bondholders after the bonds have been issued. Correspondingly, the yield on lower-grade bonds, written under foreign parameters, is less than the yield on bonds written under local parameters. Investors are willing to pay a premium for lower-grade bonds if they are written in foreign parameters. Finally, we find a positive relation between maturity and S&P ratings for the subsample of lower-grade bonds. However, we find no such relation for the subset of high-grade bonds.
On the relationships between some meta-mathematical properties of arithmetical theories
Authors: Cheng Yong
Published: September 2023

In this work, we aim at understanding incompleteness in an abstract way via metamathematical properties of formal theories. We systematically examine the relationships between the following twelve important metamathematical properties of arithmetical theories: Rosser, EI (effectively inseparable), RI (recursively inseparable), TP (Turing persistent), EHU (essentially hereditarily undecidable), EU (essentially undecidable), Creative, $\textbf{0}^{\prime }$ (theories with Turing degree $\textbf{0}^{\prime }$), REW (all RE sets are weakly representable), RFD (all recursive functions are definable), RSS (all recursive sets are strongly representable), RSW (all recursive sets are weakly representable). Given any two properties $P$ and $Q$ in the above list, we examine whether $P$ implies $Q$.
Streptomyces lividans 66 produces a protease inhibitor via a tRNA-utilizing enzyme interacting with a C-minus NRPS
Authors: Aguilar César , Verdel-Aranda Karina , Ramos-Aboites Hilda E , Licona-Cassani Cuauhtémoc , Barona-Gómez Francisco
Published: September 2023

Small peptide aldehydes (SPAs) with protease inhibitory activity are naturally occurring compounds shown to be synthesized by non-ribosomal peptide synthetases (NRPS). SPAs are widely used in biotechnology and have been utilized as therapeutic agents. They are also physiologically relevant and have been postulated to regulate the development of their producing microorganisms. Previously, we identified an NRPS-like biosynthetic gene cluster (BGC) in Streptomyces lividans 66 that lacked a condensation (C) domain but included a tRNA-utilizing enzyme (tRUE) belonging to the leucyl/phenylalanyl (L/F) transferase family. This system was predicted to direct the synthesis of a novel SPA, which we named livipeptin. Using evolutionary genome mining approaches, here, we confirm the presence of L/F transferase tRUEs within the genomes of diverse Streptomyces and related organisms, including fusions with the anticipated C-minus NRPS-like protein. We then demonstrate genetic functional cooperation between the identified L/F-transferase divergent tRUE homolog with the C-minus NRPS, leading to the synthesis of a metabolic fraction with protease inhibitory activity. Semisynthetic assays in the presence of RNAse revealed that the productive interaction between the tRUE and the C-minus NRPS enzymes is indeed tRNA dependent. We expect our findings to boost the discovery of SPAs, as well as the development of protease-mediated biotechnologies, by exploiting the uncovered genetic basis for synthesizing putative acetyl-leu/phe-arginine protease inhibitors. Furthermore, these results will facilitate the purification and structural elucidation of livipeptin, which has proven difficult to chemically characterize.

Significance

The discovery of natural products biosynthetic genes marks a significant advancement in our understanding of these metabolites, for example of their evolution, activity, and biosynthesis, but also opens biotechnological opportunities and knowledge to advance genome mining approaches. We made this possible by uncovering a new biosynthetic pathway in Streptomyces lividans 66 shown to direct the synthesis of a strong protease inhibitor, termed livipeptin, following unprecedented biosynthetic rules and genes. Thus, by shedding light on the genetic mechanisms predicted to govern the production of acetyl-leu/phe-arginine protease inhibitors, including the elusive livipeptin, this study enables novel protease-mediated biotechnologies as well as approaches for discovering protease inhibitors from genome data.
Remote Work and City Decline: Lessons From the Garment District
Authors: Gillette Clayton P
Published: September 2023

The dramatic rise of remote work threatens the traditional source of urban growth—the unique ability of dense cities to provide a setting in which firms and employees share productive resources, match needs with skills, and transmit knowledge at low cost. These “agglomeration benefits” have induced cities to pursue clusters of related firms that have served as the basis for local economic development and technological innovation. Remote work reduces the necessity for related firms to co-locate, and its popularity has led commentators to predict significant decrease in city business activity, tax revenues, and services as traditional clusters dissipate. It remains unclear how cities will react to the remote work phenomenon. Prior episodes of cluster decline, however, reveal that cities have difficulty pivoting to new economic models when outmoded ones threaten local decay. Instead, cities tend to support existing clusters, notwithstanding that the impending decline is a function of external forces rather than of local policies. This article addresses the potential mismatch between cluster decline that may flow from remote work and city responses. The article theorizes that continued municipal efforts to support a declining cluster emerge from the ability of affected firms to coalesce, exercise political influence, and exploit fragmented municipal decision making to preserve the status quo, maintain or increase municipal subsidies for the cluster, and deter entry by competitors for city resources. Those strategies impede the city’s transition to a more productive economy in the face of looming cluster decline. The article then turns to the history of the garment industry in New York City to illustrate the theory. That history provides a cautionary tale about how cities should and should not respond to the threats they face from remote work.
Welcome to Waco! The impact of judge shopping on litigation
Authors: Helmers Christian , Love Brian J
Published: September 2023

We analyze the effect of judge shopping in patent litigation following the appointment of a former patent litigator as the sole district judge assigned to the Waco Division of the US District Court for the Western District of Texas (WDTX). We find that patent enforcers’ ability to select, with certainty, a judge widely regarded as patentee-friendly increased the number of cases filed, especially by non-practicing entities. We show that the increase in litigation was driven by both an influx of cases that would not have been filed but for the judge’s appointment and a geographic reallocation of cases that would have been filed regardless. Overall, judge shopping in the WDTX induced over a 33-month period an increase of around 460 patent cases that otherwise would not have been filed. (JEL: K41, O34).
A new species of Simulium (Asiosimulium) (Diptera: Simuliidae) from northeastern Thailand, with its phylogenetic relationships with related species in the subgenus Asiosimulium
Authors: Aupalee Kittipat , Srisuka Wichai , Taai Kritsana , Takaoka Hiroyuki , Saeung Atiporn
Published: September 2023

Simulium (Asiosimulium) khongchiamense sp. nov. is described based on females, males, pupae, and mature larvae collected from Khong Chiam District, Ubon Ratchathani Province, northeastern Thailand. It is characterized in the female by the medium-long sensory vesicle, scutum with 3 dark longitudinal vittae and elongate cercus; in the male by the number of upper-eye (large) facets in 17 or 18 vertical rows and 18 or 19 horizontal rows, hind basitarsus moderately enlarged and ventral plate with the posterior margin moderately concave medially; in the pupa by the head and thoracic integument sparsely covered with tubercles and gill of arborescent type with 32 or 33 filaments; and in the larva by the postgenal cleft deep, reaching the posterior margin of the hypostoma and sheath of the subesophageal ganglion dark pigmented. DNA analysis based on COI gene of all known species of the subgenus Asiosimulium, except for S. shanense and S. suchitrae, indicated that this new species can be clearly differentiated from all other related species (S. phurueaense, S. oblongum, S. saeungae, S. furvum, and S. wanchaii) with interspecific genetic distances ranging between 4.79% and 19.18%. This is the eighth species of the subgenus Asiosimulium. Taxonomic notes are given to distinguish this new species from the 7 known species members in its same subgenus. Additionally, keys to species of all members in the subgenus Asiosimulium are provided.
Migration aspirations in forced transnational families: the case of Syrians in Turkey
Authors: Schiefer David , Düvell Franck , Sağıroğlu Ali Zafer
Published: September 2023

Increasingly high numbers of migrants around the globe have led migration scholars attempting to understand determinants of migration aspirations for many years. This study specifically looks at migration aspirations from two angles, (1) migration under conditions of a continuum of crises, in this case the (civil) war in Syria and precarious lives in Turkey, highlighting uncertainty and temporality entailed in crisis and (2) the role of family in migration aspirations. So far, scholarship primarily focuses on individuals in countries of origin and on voluntary migrants. Migration aspirations of forced migrants who have found refuge in another country are far less studied. Their situation, however, differs from voluntary migrants in distinct ways. Second, although the literature emphasizes the role of family for migration aspirations deep-level empirical inquiries are rare. Based on a survey among around 1,900 Syrian refugees in Turkey, this article addresses these gaps and explores the role family plays for migration aspirations among forced migrants. We take a close look by exploring how geographical family networks relate to migration aspirations and interact with other characteristics. We find that staying in Turkey seems to be the most likely option for participants at the time of the survey, but we also identify a substantial degree of uncertainty regarding migration aspirations. Furthermore, participants’ aspired places of living depend on the location of family members, above and beyond other characteristics. Moreover, (trans-)national family networks enhance or diminish effects of other determinants of migration aspirations such as perceived living conditions in Turkey.
The stellar thermal wind as a consequence of oblateness
Authors: Matilsky Loren I
Published: September 2023

In many rotating fluids, the lowest order force balance is between gravity, pressure, and rotational acceleration (‘GPR’ balance). Terrestrial GPR balance takes the form of geostrophy and hydrostasy, which together yield the terrestrial thermal wind equation. By contrast, stellar GPR balance is an oblateness equation, which determines the departures of the thermal variables from spherical symmetry; its curl yields the ‘stellar thermal wind equation’. In this sense, the stellar thermal wind should be viewed not as a consequence of geostrophy, but of baroclinicity in the oblateness. Here, we treat the full stellar oblateness, including the thermal wind, using pressure coordinates. We derive the generalized stellar thermal wind equation and identify the parameter regime for which it holds. In the case of the Sun, not considering the full oblateness has resulted in conflicting calculations of the theoretical aspherical temperature anomaly. We provide new calculation here and find that the baroclinic anomaly is ∼3–60 times smaller than the barotropic anomaly. Thus, the anomaly from the thermal wind may not be measurable helioseismically, but if measurement were possible, this would potentially yield a new way to bracket the depth of the solar tachocline.
Artificial intelligence, explainability, and the scientific method: A proof-of-concept study on novel retinal biomarker discovery
Authors: Delavari Parsa , Ozturan Gulcenur , Yuan Lei , Yilmaz Özgür , Oruc Ipek
Published: September 2023

We present a structured approach to combine explainability of artificial intelligence (AI) with the scientific method for scientific discovery. We demonstrate the utility of this approach in a proof-of-concept study where we uncover biomarkers from a convolutional neural network (CNN) model trained to classify patient sex in retinal images. This is a trait that is not currently recognized by diagnosticians in retinal images, yet, one successfully classified by CNNs. Our methodology consists of four phases: In Phase 1, CNN development, we train a visual geometry group (VGG) model to recognize patient sex in retinal images. In Phase 2, Inspiration, we review visualizations obtained from post hoc interpretability tools to make observations, and articulate exploratory hypotheses. Here, we listed 14 hypotheses retinal sex differences. In Phase 3, Exploration, we test all exploratory hypotheses on an independent dataset. Out of 14 exploratory hypotheses, nine revealed significant differences. In Phase 4, Verification, we re-tested the nine flagged hypotheses on a new dataset. Five were verified, revealing (i) significantly greater length, (ii) more nodes, and (iii) more branches of retinal vasculature, (iv) greater retinal area covered by the vessels in the superior temporal quadrant, and (v) darker peripapillary region in male eyes. Finally, we trained a group of ophthalmologists (N=26) to recognize the novel retinal features for sex classification. While their pretraining performance was not different from chance level or the performance of a nonexpert group (N=31), after training, their performance increased significantly (p<0.001, d=2.63). These findings showcase the potential for retinal biomarker discovery through CNN applications, with the added utility of empowering medical practitioners with new diagnostic capabilities to enhance their clinical toolkit.
Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy
Authors: Keret Shiri , Henig Israel , Zuckerman Tsila , Kaly Lisa , Shouval Aniela , Awisat Abid , Rosner Itzhak , Rozenbaum Michael , Boulman Nina , Dortort Lazar Ariela , Molad Yair , Sabbah Firas , Naffaa Mohammad E , Hardak Emilia , Slobodin Gleb , Rimar Doron
Published: September 2023

Objectives

Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive SSc compared with CYC. CYC, however, does not provide a long-term benefit in SSc. The combination of MMF and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab.

Methods

Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease >25% or an FVC increase >10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death.

Results

Twenty-one SSc patients in the combination therapy group were compared with 16 in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (P = 0.7). The hazard ratio for EFS at 24 months favoured the combination group (HR = 0.09, P = 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months.

Conclusion

MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.
Material History, Historied Materials and the Question of Epistemic Freedom in Ghana’s Medical Schools
Authors: Nott John
Published: September 2023

Medical schools rely on a wide range of tools, technologies and materials for their teaching, on books, and bodies, and on the buildings which house them. This article considers the histories of this material culture in the three oldest medical schools operating in Ghana today. Borrowing theoretical concepts from Science and Technology Studies, medical anthropology and postcolonial political economy, this article takes that the material culture of modern medical education often binds contemporary pedagogy to outdated ideas and faraway places. The agential, proselytising nature of these historied materials agitates against the localisation of biomedicine and contributes to a distracting scientific imaginary which remains centred around historical, often imperial centres of knowledge production in Europe and North America.
‘We’ll have the bill (of costs), please’
Authors: Hewitt Edward
Published: September 2023

If a beneficiary of an estate or trust is unhappy with the level of legal fees that the personal representatives (PRs) or trustees have incurred and paid out of the fund, what, if anything, can he do? Over the past decade or so, several cases have grappled with this apparently simple question. The result seems to be a patchwork quilt of subtly inconsistent decisions. The latest instalment is Kenig v Thomson Snell & Passmore LLP, which provides yet another curve in the winding road to an answer, with potentially far-reaching implications, both for beneficiaries and for solicitors instructed by PRs and trustees.
Effects of extruded pet foods containing dried yeast (Saccharomyces cerevisiae) on palatability, nutrient digestibility, and fecal quality in dogs and cats
Authors: Davenport Gary M , Block Stephanie S , Adolphe Jennifer L
Published: September 2023

Global protein shortages and sustainability concerns have increased consumer demand for non-animal-derived protein. Dried whole-cell yeast (Saccharomyces cerevisiae) may be a suitable alternative to rendered protein meals in pet foods. The objective of this study was to investigate the effects of dried yeast in dog and cat foods on indicators that pet parents typically use to evaluate the suitability of a food for their pet. For this evaluation, two dog and two cat dry extruded diets were formulated. For each species, the test diet contained 10% dried yeast (Yeast) and the control diet was devoid of yeast (Control). Palatability, apparent total tract nutrient digestibility, and fecal quality of the foods were assessed in dogs and cats. Urine pH and specific gravity were measured in cats as indicators of urinary tract health. In dogs, the Yeast diet showed equivalent or better palatability compared to the Control diet based on total food consumption (P = 0.06), average daily consumption (day 1, P = 0.10; day 2, P = 0.54), and first choice preference over 2 consecutive days (P = 0.005). Cats showed a strong preference for the Yeast diet with more than double the consumption during the 2-d test period (P = 0.001). More cats showed a first-choice preference for the Yeast diet (24 vs. 16), but the difference was not statistically significant (P = 0.21). There were no significant differences in stool quality or nutrient digestibility when fed Yeast vs. Control diets to the dogs and cats (P > 0.05). All cats produced urine with pH and specific gravity values within the normal range, though specific gravity was lower in the Control group (P = 0.003). This study provides support for the acceptability and digestibility of dog and cat diets containing dried yeast as an alternative protein source.
Competencies of junior medical doctors in managing seriously ill and injured children: time to rethink our current training approach?
Authors: Erasmus Louisa , Redfern Andrew , Smit Liezl
Published: September 2023

Background

The correct treatment of very ill and injured children is critical, yet little is known about the competencies of South African (SA) junior doctors in managing these children.

Methods

This survey documents SA junior doctors’ reported resuscitation training opportunities, experience, skills and knowledge.

Results

A total of 118 doctors (interns, medical officers and registrars) from paediatric departments affiliated with 7 medical schools, participated. Resuscitations were not rare events with 71% (84/118) reporting participation in >10 resuscitations during the preceding 2 years. Yet a third of doctors have not attended an accredited resuscitation training course within the last 2 years; 34% (12/35) medical officers and 29% (18/63) registrars, respectively, with 42% (49/118) of all participants never receiving any formal resuscitation training during employment. Feedback on performance is not standard practice with only 8% (10/118) reporting consistent debriefing after a resuscitation. Although 72% (85/118) reported their resuscitation knowledge as adequate, 56% (66/118) passed the knowledge test.

Conclusion

This study recognized missed learning opportunities in junior doctors’ training, assessment, debriefing and knowledge which may adversely affect the quality of care in managing paediatric emergencies. This has implications for departmental and post-graduate training programmes.
General purpose models for intravenous anesthetics, the next generation for target-controlled infusion and total intravenous anesthesia?
Authors: Vellinga Remco , Eleveld Douglas J. , Struys Michel M.R.F. , van den Berg Johannes P.
Published: September 2023

Purpose of review

There are various pharmacokinetic-dynamic models available, which describe the time course of drug concentration and effect and which can be incorporated into target-controlled infusion (TCI) systems. For anesthesia and sedation, most of these models are derived from narrow patient populations, which restricts applicability for the overall population, including (small) children, elderly, and obese patients. This forces clinicians to select specific models for specific populations.

Recent findings

Recently, general purpose models have been developed for propofol and remifentanil using data from multiple studies and broad, diverse patient groups. General-purpose models might reduce the risks associated with extrapolation, incorrect usage, and unfamiliarity with a specific TCI-model, as they offer less restrictive boundaries (i.e., the patient “doesn’t fit in the selected model”) compared with the earlier, simpler models. Extrapolation of a model can lead to delayed recovery or inadequate anesthesia. If multiple models for the same drug are implemented in the pump, it is possible to select the wrong model for that specific case; this can be overcome with one general purpose model implemented in the pump.

This article examines the usability of these general-purpose models in relation to the more traditional models.
Recent Progress in the Development and Clinical Application of New Drugs for Transthyretin Cardiac Amyloidosis
Authors: Zhou Juan , Li Yanfang , Geng Jing , Zhou Hong , Liu Lian , Peng Xiaochun
Published: September 2023

Transthyretincardiac amyloidosis is a rare disease that has gained significant attention in recent years because of misfolding of transthyretin fibrils produced by the liver, leading to their deposition in the myocardium. The disease has an insidious onset, nonspecific clinical manifestations, and historically lacked effective drugs, making early diagnosis and treatment challenging. The survival time of patients largely depends on the extent of heart involvement at the time of diagnosis, and conventional treatments for cardiovascular disease do not provide significant benefits. Effective management of the disease requires treatment of its underlying cause. Orthotopic liver transplantation and combined hepato-heart transplantation have been clinically effective means of treating transthyretin cardiac amyloidosis mutants for many years. However, transplantation has many limitations in clinical practice. In recent years, the development of new drugs has brought new hope to patients. This review presents the latest advances in drug development and clinical application to provide a reference for clinicians managing transthyretin cardiac amyloidosis.
Potential Biomarker of Acute Anthracycline-induced Cardiotoxicity Among Children With Acute Lymphoblastic Leukemia: Cardiac Adriamycin-responsive Protein
Authors: Li Yiyang , Tian Chuan , Huang Si , Wang Yajun , Qiu Jiapeng , Ning Fan , Guo Junhao , Chen Qikang , Chen Riling , Ma Guoda
Published: September 2023

This study aimed to investigate whether serum cardiac adriamycin-responsive protein (CARP) can serve as a sensitive and specific biomarker of anthracyclines (ANT)-induced cardiotoxicity. Fifty-five children with acute lymphoblastic leukemia were recruited. Before and after the administration of ANT, serum levels of CARP, high-sensitivity troponin T, creatine kinase-MB, and electrocardiogram were measured. Postchemotherapeutic clinical manifestations of cardiotoxicity were also investigated. Adverse cardiac events (ACEs) were graded according to the Common Terminology Criteria for Adverse Events 4.0. Then, the CARP expression was statistically analyzed among different groups. The receiver operating characteristic curve was used to evaluate the efficacy of CARP in predicting acute ANT-induced cardiotoxicity. After ANT chemotherapy, the serum CARP concentration increased in the non-ACEs group but decreased in the ACEs group (P < 0.05). In addition, not only the serum CARP levels (△CARP) was negatively correlated with the grade of ACEs (R=−0.754, P < 0.0001) but also the extent of QT interval corrected (QTc) prolongation (△QTc; R=−0.5592, P < 0.01). The area under the receiver operating characteristic curve of CARP was 90.94% (P < 0.0001), and the sensitivity and specificity were 88.64% and 91.67%, respectively, all of which are superior to △high-sensitivity troponin T, △creatine kinase-MB, and △QTc. In conclusion, serum CARP could serve as a novel sensitive and specific biomarker of acute ANT-induced cardiotoxicity, which is negatively associated with ACE grade.
MiR-590-3p Promotes the Phenotypic Switching of Vascular Smooth Muscle Cells by Targeting Lysyl Oxidase
Authors: Wang Lei , Zhang Lin , Cui Li-kun , Yue Xiao , Huang Li , Liu Na , Zhu Meng-die , Wang Zheng-bin
Published: September 2023

We investigated the clinical characteristics of patients with acute aortic dissection (AAD) and miR-590-3p levels in serum, tissue, and vascular smooth muscle cells. The effect of miR-590-3p on the vascular smooth muscle cell phenotype was assessed, and the regulation of lysyl oxidase by miR-5903p was determined. C57BL/6 mice were used to investigate the incidence of AAD and effects of miR-5903p on AAD. The miR-590-3p levels were measured in the aortae of mice, and hematoxylin and eosin staining and Masson staining were performed to identify the morphological features of the aorta. Comparative analysis revealed significant differences in clinical characteristics between patients with AAD and healthy control subjects, with most patients with AAD exhibiting concomitant hypertension and nearly 50% having atherosclerosis. Lysyl oxidase was a direct target of miR-590-3p. Lysyl oxidase overexpression inhibited switching of the vascular smooth muscle cell phenotype from contractile to synthetic, but miR-590-3p overexpression significantly reversed this change. In the mouse model, miR-590-3p upregulation increased the incidence of AAD to 93.3%, and its incidence decreased to 13.3% after miR-590-3p inhibition. Hematoxylin and eosin and Masson staining revealed that the miR-590-3p agomiR group had a greater loss of the contractile phenotype in the dissected aortic wall and an increased number of muscle fibers in the aortic wall, which contributed to thickening of the aortic wall and the formation of a false lumen in aortic dissection. miR-590-3p might be pivotal in the pathogenesis of AAD. Thus, targeting miR-590-3p or its downstream pathways could represent a therapeutic approach for AAD.
First Series of Free Flap Reconstruction Using a Dedicated Robotic System in a Multidisciplinary Microsurgical Center
Authors: Beier Justus P. , Hackenberg Stephan , Boos Anja M. , Modabber Ali , Duong Dinh Thien An , Hölzle Frank
Published: September 2023

Robotic microsurgery is a novel technology for microsurgical free flap transplantation in reconstructive surgery. Recently, the first free flap transplantation using a dedicated robotic system for microsurgery (Symani Surgical System; Medical Microinstruments) was published for a single reconstructive case. For broader future application, evaluating its potential benefits in different anatomical regions, anastomotic configurations, and clinical scenarios is necessary. In this world-wide first free flap series using this robotic system, we describe our experience with this new technology in a multidisciplinary microsurgical center. The robotic system was used for different free flaps in a range of reconstructive applications in plastic surgery, oral and maxillofacial surgery, and head and neck surgery. A total of 23 flaps were performed, with all 23 arterial and a selection of two venous anastomoses being performed with the robotic system. Time for anastomoses was significantly longer than commonly. Five of the arterial robotic anastomoses had to be redone. All but one flap survived. We could show that this new dedicated microsurgical robotic system is feasible for carrying out robot-assisted anastomoses in end-to-end, as well as end-to-side fashion under varying clinical conditions and in different microsurgical subspecialties. However, some drawbacks still need to be overcome, which are partly related to individual and institutional learning curves, to finally estimate the potential benefit for robotic free flap surgery. Multidisciplinary application of the robotic system may accelerate this process by putting together different microsurgical backgrounds, while economic burden of establishing this new technology is spread among several departments.
Bodily maps of emotions and pain: tactile and hedonic sensitivity in healthy controls and patients experiencing chronic pain
Authors: Ojala Juhani , Suvilehto Juulia T. , Nummenmaa Lauri , Kalso Eija
Published: September 2023

Pain is an unpleasant sensory and emotional experience. Both pain and emotions are warning signals against outside harm. Interoception, bodily sensations of emotions can be assessed with the emBODY tool where participants colour the body parts where they feel different emotions. Bodily maps of emotions (BMoE) have been shown to be similar between healthy individuals independent of age, sex, cultural background, and language. We used this tool to analyze how these body maps may differ between healthy controls and patients with persistent pain. We recruited 118 patients with chronic pain. An algorithm-selected matched controls from 2348 individuals who were recruited through social media, message boards, and student mailing lists. After providing background information, the participants completed the bodily topography colouring tasks with the emBODY tool using tablets (patients) and online using their own devices (controls), for pain, sensitivity for tactile, nociceptive and hedonic stimuli, and for the 6 basic emotions and a neutral state. Patients with pain coloured significantly larger areas for pain and more negative emotions. On the whole, their BMoEs were dampened compared with healthy controls. They also coloured more areas for nociceptive but not for tactile or hedonic sensitivity. Patients and controls marked different body areas as sensitive to nociceptive and tactile stimulation, but there was no difference in sensitivity to hedonic touch. Our findings suggest that emotional processing changes when pain persists, and this can be assessed with these colouring tasks. BMoEs may offer a new approach to assessing pain.
Immediate CT change after thrombectomy predicting symptomatic hemorrhagic transformation
Authors: Yang Shang-Jung , Lu Yueh-Hsun , Huang Yi-Chen , Chan Lung , Ting Wei-Yi
Published: September 2023

Background:

The prognostic value of contrast accumulation from noncontrast brain computed tomography (CT) conducted immediately after intra mechanical thrombectomy (MT) in patients with acute ischemic stroke to predict symptomatic hemorrhage was studied.

Methods:

Patients with acute ischemic stroke treated using MT between February 2015 and April 2019 were included. Contrast accumulation was defined as a high attenuation area observed on noncontrast brain CT conducted immediately after thrombectomy treatment, and the patients were categorized into (1) symptomatic hemorrhage, (2) asymptomatic hemorrhage, and (3) no hemorrhage according to the presence of hemorrhagic transformation and their clinical conditions. The pattern and extent of contrast accumulation were compared between patients with and without symptomatic hemorrhage. The maximal Hounsfield unit (HU) of cortical involvement in contrast accumulation was evaluated by calculating the sensitivity, specificity, odds ratio, and area under the receiver operating characteristic (ROC) curve.

Results:

In total, 101 patients with anterior circulation acute ischemic stroke were treated by endovascular intervention. Nine patients developed symptomatic hemorrhage and 17 developed asymptomatic hemorrhage. Contrast accumulation was associated with all types of hemorrhagic transformation (p < 0.01), and cortical involvement pattern was more frequently associated with symptomatic hemorrhage (p < 0.01). The area under the ROC curve was 0.887. The sensitivity and specificity for HU > 100 in cortical involvement predicting symptomatic hemorrhage after endovascular treatment were 77.8% and 95.7%, respectively, with an odds ratio of 77.0 (95% CI, 11.94-496.50; p < 0.01).

Conclusion:

Cortical involvement of contrast accumulation with a maximal HU > 100 predicts symptomatic hemorrhage after endovascular reperfusion treatment.
Efficacy and safety of once-daily prolonged-release tacrolimus versus twice-daily tacrolimus in kidney transplant recipients: A meta-analysis and trial sequential analysis
Authors: Wang Tair-Shin , Huang Kuan-Hua , Hsueh Kuan-Chun , Chen Hsin-An , Tam Ka-Wai , Sun Shu-Hui , Chen Cheng-Fong , Wang Chien-Ying , Tung Min-Che , Wang Yuan-Hung
Published: September 2023

Background:

Kidney transplantation is the most important treatment for end-stage renal disease. Immunosuppressive therapies can prevent acute rejection for kidney transplant recipients. Tacrolimus is usually administered to prevent graft rejection after transplantation. Previous studies have indicated that once-daily tacrolimus may improve medication adherence. Therefore, this meta-analysis aimed to compare clinical outcomes between once-daily and twice-daily tacrolimus in de novo renal transplant patients.

Methods:

Eligible studies were identified from the Cochrane Library Database, PubMed, and Embase until July 2022. Those randomized controlled trials (RCTs) evaluating once-daily versus twice-daily tacrolimus formulations in de novo renal transplantation were included. A summary risk ratio (RR) and standardized mean difference (SMD) with the 95% confidence interval (CI) were estimated using a random-effects model.

Results:

In total, nine RCTs were included. There were no differences in biopsy-confirmed acute rejection rates between patients with once-daily and those with twice-daily tacrolimus (RR, 0.91; 95% CI, 0.73-1.13) in 12 months. Regarding renal function, there was no significant difference between the once-daily and twice-daily tacrolimus groups (SMD, −0.03; 95% CI, −0.12 to 0.07). In addition, the risk of graft failure, death, and adverse events in the first year was similar for the once-daily and twice-daily tacrolimus groups.

Conclusion:

Our major findings suggest that de novo renal transplantation recipients receiving once-daily tacrolimus immediately after transplantation have comparable efficacy and safety with those recipients who received twice-daily tacrolimus. Therefore, once-daily tacrolimus medication can be an alternative for de novo renal transplantation recipients.
Effect of Implementing a Commercial Electronic Early Warning System on Outcomes of Hospitalized Patients
Authors: Singh Siddhartha , Laud Purushottam W. , Crotty Bradley H. , Nanchal Rahul S. , Hanson Ryan , Penlesky Annie C. , Fletcher Kathlyn E. , Stadler Michael E. , Dong Yilu , Nattinger Ann B.
Published: September 2023

Despite the widespread adoption of early warning systems (EWSs), it is uncertain if their implementation improves patient outcomes. The authors report a pre-post quasi-experimental evaluation of a commercially available EWS on patient outcomes at a 700-bed academic medical center. The EWS risk scores were visible in the electronic medical record by bedside clinicians. The EWS risk scores were also monitored remotely 24/7 by critical care trained nurses who actively contacted bedside nurses when a patient’s risk levels increased. The primary outcome was inpatient mortality. Secondary outcomes were rapid response team calls and activation of cardiopulmonary arrest (code-4) response teams. The study team conducted a regression discontinuity analysis adjusting for age, gender, insurance, severity of illness, risk of mortality, and hospital occupancy at admission. The analysis included 53,229 hospitalizations. Adjusted analysis showed no significant change in inpatient mortality, rapid response team call, or code-4 activations after implementing the EWS. This study confirms the continued uncertainty in the effectiveness of EWSs and the need for further rigorous examinations of EWSs.
Comparative Perspectives on Diagnostic Error Discussions Between Inpatient and Outpatient Pediatric Providers
Authors: Ladell Meagan M. , Shafer Grant , Ziniel Sonja I. , Grubenhoff Joseph A.
Published: September 2023

Diagnostic error remains understudied and underaddressed despite causing significant morbidity and mortality. One barrier to addressing this issue remains provider discomfort. Survey studies have shown significantly more discomfort among providers in discussing diagnostic error compared with other forms of error. Whether the comfort in discussing diagnostic error differs depending on practice setting has not been previously studied. The objective of this study was to assess differences in provider willingness to discuss diagnostic error in the inpatient versus outpatient setting. A multicenter survey was sent out to 3881 providers between May and June 2018. This survey was designed to assess comfort level of discussing diagnostic error and looking at barriers to discussing diagnostic error. Forty-three percent versus 22% of inpatient versus outpatient providers (P = 0.004) were comfortable discussing short-term diagnostic error publicly. Similarly, 76% versus 60% of inpatient versus outpatient providers (P = 0.010) were comfortable discussing short-term diagnostic error privately. A higher percentage of inpatient (64%) compared with outpatient providers (46%) (P = 0.043) were comfortable discussing long-term diagnostic error privately. Forty percent versus 24% of inpatient versus outpatient providers (P = 0.018) were comfortable discussing long-term error publicly. No difference in barriers cited depending on practice setting. Inpatient providers are more comfortable discussing diagnostic error than their outpatient counterparts. More study is needed to determine the etiology of this discrepancy and to develop strategies to increase outpatient provider comfort.
A Paradigm Shift in Heart Preservation: Improved Post-transplant Outcomes in Recipients of Donor Hearts Preserved With the SherpaPak System
Authors: Shudo Yasuhiro , Leacche Marzia , Copeland Hannah , Silvestry Scott , Pham Si M. , Molina Ezequiel , Schroder Jacob N. , Sciortino Christopher M. , Jacobs Jeffrey P. , Kawabori Masashi , Meyer Dan M. , Zuckermann Andreas , D’Alessandro David A.
Published: September 2023

Traditional ice storage has been the historic standard for preserving donor’s hearts. However, this approach provides variability in cooling, increasing risks of freezing injury. To date, no preservation technology has been reported to improve survival after transplantation. The Paragonix SherpaPak Cardiac Transport System (SCTS) is a controlled hypothermic technology clinically used since 2018. Real-world evidence on clinical benefits of SCTS compared to conventional ice cold storage (ICS) was evaluated. Between October 2015 and January 2022, 569 US adults receiving donor hearts preserved and transported either in SCTS (n = 255) or ICS (n = 314) were analyzed from the Global Utilization And Registry Database for Improved heArt preservatioN (GUARDIAN-Heart) registry. Propensity matching and a subgroup analysis of >240 minutes ischemic time were performed to evaluate comparative outcomes. Overall, the SCTS cohort had significantly lower rates of severe primary graft dysfunction (PGD) (p = 0.03). When propensity matched, SCTS had improving 1-year survival (p = 0.10), significantly lower rates of severe PGD (p = 0.011), and lower overall post-transplant MCS utilization (p = 0.098). For patients with ischemic times >4 hours, the SCTS cohort had reduced post-transplant MCS utilization (p = 0.01), reduced incidence of severe PGD (p = 0.005), and improved 30-day survival (p = 0.02). A multivariate analysis of independent risk factors revealed that compared to SCTS, use of ice results in a 3.4-fold greater chance of severe PGD (p = 0.014). Utilization of SCTS is associated with a trend toward increased post-transplant survival and significantly lower severe PGD and MCS utilization. These findings fundamentally challenge the decades-long status quo of transporting donor hearts using ice.