bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe tricuspid bioprosthetic valve stenosis as an unusual cause of pulmonary embolism: a case report
Authors: Naser Jwan A , Arghami Arman , Eleid Mackram F , Pislaru Sorin V 
Published: May 2021

Abstract

Background
Bioprosthetic tricuspid valve stenosis (TS) is an uncommon and frequently under-diagnosed condition. Although the resulting right heart failure symptoms are well-known, the associated thrombogenic potential is under-recognized.

Case summary
A 44-year-old woman with bioprosthetic tricuspid valve (TV) replacement in 2001 was referred for urgent consultation due to acute worsening of dyspnoea and severe swelling and pain in her left arm and neck. She was diagnosed with atrial fibrillation 6 months before the presentation and was found to have right atrial (RA) thrombus with pulmonary embolism and extensive retrograde venous extension 1 month prior. Review of studies done at her local institution revealed 10 mmHg mean gradient (MG) across the bioprosthetic TV that was only reported as mild–moderate TS. Echocardiography done at our instruction confirmed suspicion of severe TS with calcified immobile leaflets. Computed tomography showed persistent RA thrombus and therefore surgical replacement of the TV was undertaken. Subsequently, patient’s dyspnoea rapidly improved.

Discussion
Progressive dyspnoea and symptoms of right heart failure in a patient with a history of bioprosthetic TV replacement should be investigated for prosthetic valve dysfunction. Due to its rarity, TS diagnosis can be overlooked on routine echocardiography. In our patient, despite a measured MG of 10 mmHg, the presence of critical TS was not initially recognized. As TS is associated with increased thrombogenic potential and given the rare occurrence of in situ RA thrombosis, physicians must have a high index of suspicion for TS in the appropriate clinical context.
How to Illegalize Past Injustice: Reinterpreting the Rules of Intertemporality
Authors: von Arnauld Andreas 
Published: May 2021

Abstract
Attempts to legally tackle cases of historical injustice are often confronted with the problem that the events in question were not considered illegal at their time and that, in general, legal rules should not be applied retroactively. The present article suggests a conceptual framework to carefully stretch the dogmas of intertemporal law by introducing, via ethical principles as part of positive law of the time, contemporary contestation of inhumane actions and practices. Even though such contestation might not yet be enough to overturn a widely shared apologetic view among lawyers and states, it is argued that the violation of ethical-legal principles as such should give rise to a duty to give satisfaction under the law of state responsibility. In most cases of historical injustice brought to court, members of victimized groups aim at acknowledgment of their plight and at a reappraisal of the past that includes their experiences. In line with this objective, the present article makes a special case for a state obligation to negotiate with the victims of historical injustice or their descendants.
Toxicity and membrane perturbation properties of the ribotoxin-like protein Ageritin
Authors: Lampitella Erosantonio , Landi Nicola , Oliva Rosario , Gaglione Rosa , Bosso Andrea , De Lise Federica , Ragucci Sara , Arciello Angela , Petraccone Luigi , Pizzo Elio , Del Vecchio Pompea , Di Maro Antimo 
Published: May 2021

AbstractAgeritin is the prototype of a new ribotoxin-like protein family, which has been recently identified also in basidiomycetes. The protein exhibits specific RNase activity through the cleavage of a single phosphodiester bond located at sarcin/ricin loop of the large rRNA, thus inhibiting protein biosynthesis at early stages. Conversely to other ribotoxins, its activity requires the presence of divalent cations. In the present study, we report the activity of Ageritin on both prokaryotic and eukaryotic cells showing that the protein has a prominent effect on cancer cells viability and no effects on eukaryotic and bacterial cells. In order to rationalize these findings, the ability of the protein to interact with various liposomes mimicking normal, cancer and bacterial cell membranes was explored. The collected results indicate that Ageritin can interact with DPPC/DPPS/Chol vesicles, used as a model of cancer cell membranes, and with DPPC/DPPG vesicles, used as a model of bacterial cell membranes, suggesting a selective interaction with anionic lipids. However, a different perturbation of the two model membranes, mediated by cholesterol redistribution, was observed and this might be at the basis of Ageritin selective toxicity towards cancer cells.
Knockdown of insulin-like growth factor 2 gene disrupts mitochondrial functions in the liver
Authors: Gui Weiwei , Zhu Yiyi , Sun Shuiya , Zhu Weifen , Tan Bowen , Zhao Hanxin , Shang Chengxin , Zheng Fenping , Lin Xihua , Li Hong 
Published: May 2021

Abstract
Even though insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in nonalcoholic fatty liver disease (NAFLD), its role in the progression of NAFLD and the potential mechanism remain largely unclear. Using in vitro models, we found that IGF2 was the key overexpressed gene in steatosis, suggesting a possible association between IGF2 and NAFLD. Interestingly, loss-of-function experiments revealed that inhibition of IGF2 protein impaired mitochondrial biogenesis and respiration. It additionally disrupted the expression changes of mitochondrial fusion and fission-related proteins necessary in maintaining mitochondrial homeostasis. Consistently, IGF2 knockdown reduced the mitochondrial membrane potential and increased the production of reactive oxygen species. Mechanistically, IGF2 regulates mitochondrial functions by modulating the expression of SIRT1 and its downstream gene PGC1α. This research opens a new Frontier on the role of IGF2 in energy metabolism, which potentially participates in the development of NAFLD. As such, IGF2 is a potential therapeutic target against NAFLD.
Amelioration of cyclophosphamide toxicity via modulation of metabolizing enzymes by avocado (Persea americana) extract
Authors: Motawi Tarek Mohamed Kamal , William Mira Magdy , Nooh Mohammed Mostafa , Abd-Elgawad Hanan Muhammad 
Published: May 2021

Abstract

Objectives
Cyclophosphamide (CPA) is highly effective in treating several human tumours and autoimmune disorders; but, it triggers deleterious side effects. Avocado, Persea americana (Mill.), is a widely consumed fruit with pronounced nutritional and medicinal value. Though many studies examined the protective mechanisms of natural products against CPA toxicity, almost none investigated the modulation of CPA metabolism as a potential underlying mechanism for protection. Here, we investigated the modulating effect of avocado extract (AE) on certain CPA metabolizing enzymes and its correlation with the extent of CPA-induced pulmonary toxicity and urotoxicity.

Methods
Rats received oral AE (0.9 g/kg body weight/day) 7 days before a single CPA injection (150 mg/kg body weight) and continued AE intake for 2, 7 or 28 days to study three phases of CPA-induced urotoxicity and pulmonary toxicity.

Key findings
CPA acutely elevated then reduced hepatic microsomal cytochrome P450 2B6 (CYP2B6) content and significantly suppressed bladder and lung glutathione-S-transferase activity. Furthermore, CPA elevated lung myeloperoxidase activity, DNA content and hydroxyproline level and bladder blood content. AE ameliorated CPA-induced derangements through suppression of CYP2B6 and myeloperoxidase and augmentation of glutathione-S-transferase activity in CPA-treated rats.

Conclusions
AE modulation of CPA metabolizing enzymes and potential anti-inflammatory effect may mitigate CPA-induced toxicity.
Coupled macro-spin model with two variables for polarity reversals in the Earth and the Sun
Authors: Kunitomo Ariyoshi , Nakamichi Akika , Hara Tetsuya 
Published: May 2021

Abstract
Geomagnetism is extremely complex and straightforward magnetohydrodynamics simulations are still unable to reveal all its dynamics. Recently, a simple macro-spin model for geomagnetism has been suggested. This model is based on the idea that geomagnetism can be described by interactions with many local dynamo elements (macro-spins). This model can reproduce some complex features of geomagnetism by solving a simple set of ordinary differential equations with a minimal number of variables. In this paper, we complete this macro-spin model by considering the full set of variables in three dimensions. Utilizing this model, we can address several basic features of geomagnetism which could not be described in the previous minimal model: migration of the north and south magnetic poles, a precise comparison of the detailed surface distribution of magnetic fields with the observed data, etc. Moreover, by applying this model to solar magnetism, we can reproduce the periodic polarity reversals and the power index of the power spectrum from this complete spin model. Finally, we elucidate the statistical properties of pole migration.
Sodium buffered formic acid concentration and feed pH is stable over a 3-month period
Authors: Huss A R , Jones C K , Stark C R , Fleming S A , Dilger R N , Jendza J A 
Published: May 2021

Abstract
Promoting feed hygiene with organic acids is an effective method to prevent foodborne illnesses from bacterial infection. The stability and acidification of mash and pelleted feed with sodium buffered formic acid was investigated. The acid product was incorporated to reach total formate inclusion levels of 0, 6, or 12 g/kg for swine nursery feed; 0, 4, or 9 g/kg for swine finishing feed; and 0, 3, or 6 g/kg for broiler grower feed. Samples were analyzed for total formate and pH on d 4, 32, 60, or 88 post-manufacturing. The concentration of formate remained stable across an 88-d period (P &lt; 0.01). Treatment with the formic acid product decreased feed pH with increasing inclusion levels (all P &lt; 0.01). Within each inclusion level of acid and across time, pH tended to increase in pelleted feed and decrease in mash feeds (all P &lt; 0.01); however, these changes were small (0.1 units pH). These data suggest that sodium buffered formic acid can be applied to both mash and pelleted feed to provide continuous acidification over a 3-month period.
Experience and Education in Residency Training: Capturing the Resident Experience by Mapping Clinical Data
Authors: Rhee David W. , Chun Jonathan W. , Stern David T. , Sartori Daniel J. 
Published: May 2021

Problem
Internal medicine training programs operate under the assumption that the 3-year residency training period is sufficient for trainees to achieve the depth and breadth of clinical experience necessary for independent practice; however, the medical conditions to which residents are exposed in clinical practice are not easily measured. As a result, residents’ clinical educational experiences are poorly understood.

Approach
A crosswalk tool (a repository of International Classification of Diseases [ICD]-10 codes linked to medical content areas) was developed to query routinely collected inpatient principal diagnosis codes and translate them into an educationally meaningful taxonomy. This tool provides a robust characterization of residents’ inpatient clinical experiences.

Outcomes
This pilot study has provided proof of principle that the crosswalk tool can effectively map 1 year of resident-attributed diagnosis codes to both the broad content category level (e.g., “cardiovascular disease”) and to the more specific condition category level (e.g., “myocardial disease”). The authors uncovered content areas in their training program that are overrepresented and some that are underrepresented relative to material on the American Board of Internal Medicine (ABIM) Certification Exam.

Next Steps
The crosswalk tool introduced here translated residents’ patient care activities into discrete, measurable educational content and enabled 1 internal medicine residency program to characterize residents’ inpatient educational experience with a high degree of resolution. Leaders of other programs seeking to profile the clinical exposure of their trainees may adopt this strategy. Such clinical content mapping drives innovation in the experiential curriculum, enables comparison across practice sites, and lays the groundwork to test associations between individual clinical exposure and competency-based outcomes, which, in turn, will allow medical educators to draw conclusions regarding how clinical experience reflects clinical competency.
A Multicenter Observational Study Evaluating Outcomes Associated With Antibiotic Combination Versus Monotherapy in Patients With Septic Shock
Authors: Torisson Gustav , Bruun Madsen Martin , Schmidt Davidsen Agnes , Perner Anders , Lipman Jeffrey , Dulhunty Joel , Sjövall Fredrik 
Published: May 2021

Objectives:
To explore the association between antibiotic combination therapy and in-hospital mortality in patients with septic shock in two tertiary ICUs in different countries.

Design:
Retrospective observational study.

Setting:
ICUs of two tertiary hospitals, Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia, and Rigshospitalet, Copenhagen, Denmark.

Patients:
Adult patients with antibiotic treatment greater than or equal to 72 hours and vasopressor therapy greater than or equal to 24 hours.

Intervention:
Combination versus mono antibiotic therapy.

Measurements and Main Results:
Combination antibiotic therapy was defined as receiving two or more antibiotics from different classes, started within 12 hours of each other and with an overlapping duration of greater than or equal to 12 hours. Bivariate and multiple logistic regression analysis were performed comparing combination antibiotic therapy versus antibiotic monotherapy on in-hospital mortality. The analysis was adjusted for age, gender, centre, Acute Physiology and Chronic Health Evaluation II score, and chronic health evaluation. In total, 1,667 patients were included with 953 (57%) receiving combination therapy. Patients given combination therapy were older (60 ± 16 vs 56 ± 18), more likely admitted to Rigshospitalet (58% vs 16%), and had a higher Acute Physiology and Chronic Health Evaluation II score (26 ± 8 vs 23 ± 8). Combination therapy was associated with an increased mortality in univariate analysis (odds ratio = 1.33; 95% CI, 1.07–1.66); however, there was no significant association in the adjusted analysis (odds ratio = 0.88; 95% CI, 0.68–1.15).

Conclusions:
In this retrospective study, no association was found between use of combination therapy and in-hospital mortality. The large differences between centers probably reflect local traditions and lack of definitive evidence.
Disentangling heterogeneity of psychosis expression in the general population: sex-specific moderation effects of environmental risk factors on symptom networks
Authors: Betz Linda T. , Penzel Nora , Rosen Marlene , Bhui Kamaldeep , Upthegrove Rachel , Kambeitz Joseph 
Published: May 2021

AbstractBackgroundPsychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called ‘symptom network’. Differences in demographics, as well as exposure to adversities and risk factors, may produce substantial heterogeneity in symptom networks, highlighting potential etiological divergence in psychosis risk.MethodsTo explore this idea in a data-driven way, we employed a novel recursive partitioning approach in the 2007 English National Survey of Psychiatric Morbidity survey (N = 7,242). We sought to identify ‘network phenotypes’ by explaining heterogeneity in symptom networks through potential moderators, including age, sex, ethnicity, deprivation, childhood abuse, separation from parents, bullying, domestic violence, cannabis use, and alcohol.ResultsSex was the primary source of heterogeneity in symptom networks. Additional heterogeneity was explained by interpersonal trauma (childhood abuse, domestic violence) in women and domestic violence, cannabis use, ethnicity in men. Among women, especially those exposed to early interpersonal trauma, an affective loading within psychosis may have distinct relevance. Men, particularly those from minority ethnic groups, demonstrated a strong network connection between hallucinatory experiences and persecutory ideation.ConclusionSymptom networks of psychosis expression in the general population are highly heterogeneous. The structure of symptom networks seems to reflect distinct sex-related adversities, etiologies, and mechanisms of symptom-expression. Disentangling the complex interplay of sex, minority ethnic group status, and other risk factors may help optimize early intervention and prevention strategies in psychosis.
Short-Duration RAGE Antagonism Transiently Disrupts Tendon Homeostasis and does not Alter Diabetic Tendon Healing
Authors: Nichols Anne E. C. , Muscat Samantha N. , Loiselle Alayna E. 
Published: May 2021

AbstractObesity and type II Diabetes Mellitus (T2DM) have substantial pathological effects on tendon homeostasis, including loss of collagen organization and increased risk of tendon rupture. Moreover, following rupture or acute injury, the healing process is impaired by T2DM. We have previously demonstrating that restoring normal metabolic function in a murine model of obesity/ T2DM is insufficient to blunt or reverse the progression of diabetic tendinopathy, indicating the need for identification of novel therapeutic approaches to both maintain tendon homeostasis, and to improve the healing process. RAGE, the Receptor for Advanced Glycation Endproducts has been implicated as a key driver of several diabetic pathologies. We have demonstrated that pharmacological antagonism of RAGE is sufficient to partially improve tendon healing in non-diabetic animals. Therefore, in the current study we tested the efficacy of blunted RAGE signaling, via treatment with a RAGE Antagonist Peptide (RAP), to improve tendon healing in the context of T2DM. While our study did not find a beneficial effect of short-term RAP treatment on the healing process of T2DM mice, we did identify several important challenges brought about by this model of diet-induced obesity and T2DM. Both high fat (HFD) and low fat diet (LFD) feeding shifted the temporal molecular profile of healing compared to standard laboratory chow fed mice. Moreover, RAP treatment resulted in a transient disruption in homeostasis in the contralateral control tendons of both HFD and LFD mice, and this was due to a potential interaction with the systemic response to tendon injury as this response was not observed in HFD and LFD fed mice that did not undergo tendon repair surgery. Collectively, these data highlight the complications associated with models of diet induced obesity, and the lean control diets that should be considered in future studies.
Optimal Chemotherapy Scheduling for Non-Genetic Drug Resistance
Authors: Paryad-Zanjani Sasan , Saint-Antoine Michael M. , Singh Abhyudai 
Published: May 2021

AbstractOne of the most difficult challenges in cancer therapy is the emergence of drug resistance within tumors. Sometimes drug resistance can emerge as the result of mutations and Darwinian selection. However, recently another phenomenon has been discovered, in which tumor cells switch back and forth between drug-sensitive and pre-resistant states. Upon exposure to the drug, sensitive cells die off, and pre-resistant cells become locked in to a state of permanent drug resistance. In this paper, we explore the implications of this transient state switching for therapy scheduling. We propose a model to describe the phenomenon and estimate parameters from experimental melanoma data. We then compare the performance of continuous and alternating drug schedules, and use sensitivity analysis to explore how different conditions affect the efficacy of each schedule. We find that for our estimated parameters, a continuous therapy schedule is optimal. However we also find that an alternating schedule can be optimal for other, hypothetical parameter sets, depending on the difference in growth rate between pre-drug and post-drug cells, the delay between exposure to the drug and emergence of resistance, and the rate at which pre-resistant cells become resistant relative to the rate at which they switch back to the sensitive state.
Background rates of five thrombosis with thrombocytopenia syndromes of special interest for COVID-19 vaccine safety surveillance: incidence between 2017 and 2019 and patient profiles from 25.4 million people in six European countries
Authors: Burn Edward , Li Xintong , Kostka Kristin , Morgan Stewart Henry , Reich Christian , Seager Sarah , Duarte-Salles Talita , Fernandez-Bertolin Sergio , Aragón María , Reyes Carlen , Martinez-Hernandez Eugenia , Marti Edelmira , Delmestri Antonella , Verhamme Katia , Rijnbeek Peter , Horban Scott , Morales Daniel R , Prieto-Alhambra Daniel 
Published: May 2021

AbstractBackgroundThrombosis with thrombocytopenia syndrome (TTS) has been reported among individuals vaccinated with adenovirus-vectored COVID-19 vaccines. In this study we describe the background incidence of TTS in 6 European countries.MethodsElectronic medical records from France, Netherlands, Italy, Germany, Spain, and the United Kingdom informed the study. Incidence rates of cerebral venous sinus thrombosis (CVST), splanchnic vein thrombosis (SVT), deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke, all with concurrent thrombocytopenia, were estimated among the general population between 2017 to 2019. A range of additional adverse events of special interest for COVID-19 vaccinations were also studied in a similar manner.FindingsA total of 25,432,658 individuals were included. Background rates ranged from 1.0 (0.7 to 1.4) to 8.5 (7.4 to 9.9) per 100,000 person-years for DVT with thrombocytopenia, from 0.5 (0.3 to 0.6) to 20.8 (18.9 to 22.8) for PE with thrombocytopenia, from 0.1 (0.0 to 0.1) to 2.5 (2.2 to 2.7) for SVT with thrombocytopenia, and from 0.2 (0.0 to 0.4) to 30.9 (28.6 to 33.3) for stroke with thrombocytopenia. CVST with thrombocytopenia was only identified in one database, with incidence rate of 0.1 (0.1 to 0.2) per 100,000 person-years. The incidence of TTS increased with age, with those affected typically having more comorbidities and greater medication use than the general population. TTS was also more often seen in men than women. A sizeable proportion of those affected were seen to have been taking antithrombotic and anticoagulant therapies prior to their TTS event.InterpretationAlthough rates vary across databases, TTS has consistently been seen to be a very rare event among the general population. While still very rare, rates of TTS are typically higher among older individuals, and those affected were also seen to generally be male and have more comorbidities and greater medication use than the general population.FundingThis study was funded by the European Medicines Agency (EMA/2017/09/PE Lot 3).