bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasonographic features of intestinal lipogranulomatous lymphangitis in 10 dogs
Authors: De Magistris Angela V. , Linta Nikolina , Specchi Swan , Procoli Fabio , Sabattini Silvia , Diana Alessia , Donato Pamela Di 
Published: June 2023

AbstractIntestinal lipogranulomatous lymphangitis (ILL) is a granulomatous inflammation of the lymphatic vessels of the intestinal wall and mesentery characterized by lipogranulomas. The purpose of this retrospective, multi‐center, case series study is to report the ultrasonographic features of canine ILL. Ten dogs with a histologically confirmed ILL undergoing preoperative abdominal ultrasound were retrospectively included. Additional CT was available in two cases. Lesion distribution was focal in eight dogs and multifocal in two. All dogs presented with intestinal wall thickening and two had a concomitant mesenteric mass adjacent to the intestinal lesion. All lesions were in the small intestine. Ultrasonographic features were altered wall layering with predominantly muscular and to a lesser extent submucosal layer thickening. Other findings included hyperechoic nodular tissue within the muscular, serosa/subserosal, and mucosal layers, hyperechoic perilesional mesentery, enlarged submucosal blood/lymphatic vessels, mild peritoneal effusion, intestinal corrugation, and mild lymphadenomegaly. The two intestinal to mesenteric masses presented heterogeneous echostructure, predominantly hyperechoic with multiple hypo/anechoic cavitations filled with mixed fluid and fat attenuation content on CT. Histopathological findings included lymphangiectasia, granulomatous inflammation, and structured lipogranulomas affecting mainly submucosa, muscularis, and serosa. The intestinal to mesenteric cavitary masses revealed severe granulomatous peritonitis with steatonecrosis. In conclusion, ILL should be considered as a differential diagnosis for dogs with this combination of ultrasonographic features.
Knowledge assessment among subjects with chronic venous leg ulcer in outpatient setting: Translation and adaptation of a tool to identify subjects at risk of poor understanding
Authors: Martinato Matteo , Ranzato Caterina , Faggian Eleonora , Foletto Matilde , Moreal Chiara , Guidone Nicola , Acar Aslihan Senturk , Masiero Flavia , Beghin Fabio , Peruzzo Stefiania , Gregori Dario , Comoretto Rosanna Irene 
Published: June 2023

AbstractPromotion of self‐care is an important issue in the treatment of chronic diseases such as venous leg ulcers, as adequate self‐care can prevent complications and ulcer recurrence. However, only a few tools have been developed and tested to assess the knowledge of patients with venous leg ulcers. This study aimed to translate, adapt and validate in an Italian language and context a questionnaire to assess the knowledge of patients with venous leg ulcers about their disease (pathophysiology, risk factors, lifestyle changes due to ulcer) and the proper management of the ulcer to prevent recurrence. This is a cross‐sectional study divided into two phases: (1) translation and cross‐cultural adaptation of the ‘Educational Interventions in Venous Leg Ulcer Patients’ tool in a six‐stage process and (2) validation and reliability study with patients with active ulceration. There was great agreement for the English‐to‐Italian translation. In content validation, the tool showed good applicability among experts. Adjustments were made to improve semantic equivalence, and the questionnaire was made to be easy and quick to administer. The results of the target population showed a low level of knowledge among the patients. Knowing the deficiencies of the patients makes it possible to create educational projects to improve their abilities. Now more than ever, it is necessary to improve self‐care and patient knowledge, allowing home care, improving autonomy, and avoiding hospital care that results in higher costs and risks. This questionnaire could be used in future studies to identify topics that need to be reinforced through education and to improve the awareness and self‐care of these patients.
The Evolution of World-Class Endurance Training: The Scientist’s View on Current and Future Trends
Authors: Sandbakk Øyvind , Pyne David B. , McGawley Kerry , Foster Carl , Talsnes Rune Kjøsen , Solli Guro Strøm , Millet Grégoire P. , Seiler Stephen , Laursen Paul B. , Haugen Thomas , Tønnessen Espen , Wilber Randy , van Erp Teun , Stellingwerff Trent , Holmberg Hans-Christer , Bucher Sandbakk Silvana 
Published: June 2023

Background: Elite sport is continuously evolving. World records keep falling and athletes from a longer list of countries are involved. Purpose: This commentary was designed to provide insights into present and future trends associated with world-class endurance training based on the perspectives, experience, and knowledge of an expert panel of 25 applied sport scientists. Results: The key drivers of development observed in the past 10–15 years were related to (1) more accessible scientific knowledge for coaches and athletes combined with (2) better integration of practical and scientific exchange across multidisciplinary perspectives within professionalized elite athlete support structures, as well as (3) utilization of new technological advances. Based on these perspectives, we discerned and exemplified the main trends in the practice of endurance sports into the following categories: better understanding of sport-specific demands; improved competition execution; larger, more specific, and more precise training loads; improved training quality; and a more professional and healthier lifestyle. The main areas expected to drive future improvements were associated with more extensive use of advanced technology for monitoring and prescribing training and recovery, more precise use of environmental and nutritional interventions, better understanding of athlete–equipment interactions, and greater emphasis on preventing injuries and illnesses. Conclusions: These expert insights can serve as a platform and inspiration to develop new hypotheses and ideas, encourage future collaboration between researchers and sport practitioners, and, perhaps most important, stimulate curiosity and further collaborative studies about the training, physiology, and performance of endurance athletes.
Nonsense-mediated decay machinery in
Plasmodium falciparum
is inefficient and non-essential
Authors: McHugh Emma , Bulloch Michaela S. , Batinovic Steven , Patrick Cameron J. , Sarna Drishti K. , Ralph Stuart A. 
Published: June 2023

ABSTRACT

Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite
Plasmodium falciparum
shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the
P. falciparum
orthologs of two core NMD components:
Pf
UPF1 (PF3D7_1005500) and
Pf
UPF2 (PF3D7_0925800). We localize both
Pf
UPF1 and
Pf
UPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in
P. falciparum
, they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in
P. falciparum
has no functional role and that NMD is not required for parasite growth
ex vivo
.

IMPORTANCE
In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.
Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes
Authors: She Rui , Al-sari Naba Hassan , Mattila Ismo Matias , Sejling Anne-Sophie , Pedersen Jens , Legido-Quigley Cristina , Pedersen-Bjergaard Ulrik 
Published: June 2023

IntroductionHypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.Research design and methodsTwenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.ResultsIn total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10−3) and isoleucine (p=2.2×10−3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.ConclusionsIn individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.Trial registration numberNCT01337362.
Terminal Ediacaran–Late Ordovician evolution of the NE Laurentia palaeocontinent: rift–drift–onset of Taconic Orogeny, sea-level change and ‘Hawke Bay’ onlap (not offlap)
Authors: Landing Ed , Webster Mark , Bowser Samuel S. 
Published: June 2023

Abstract

Rodinia break-up with late Ediacaran rifting defined a NE Laurentia triple junction (New York Promontory–Ottawa–Bonnechere aulacogen (OBA)–Quebec Reentrant). Rifting persisted to
c.
510 Ma. The oldest passive-margin shelf units (Forestdale Marble and Moosalamoo Phyllite) underlie a sandstone (Cheshire) commonly regarded as the oldest passive unit. Late Dyeran–Middle Cambrian rifting led to the oldest OBa sedimentation and formed the Franklin Basin (NW Vermont). Cambrian–Darriwillian shelf–slope facies are linked eustatically – not Taconic Orogeny onset. Onlap and shelf carbonates are coeval with black slope mud; and lowstand shelf unconformities with green, oxic slope mud. Early–middle Dyeran eustatic change defined slope units: (1) Browns Pond Formation dysoxic–anoxic (d–a) interval with debrite cap (Holcombville Member, new); (2) Middle Granville Formation Oxic Interval (new); and (3) lower Hatch Hill Formation d–a interval. Our analysis leads to two controversial conclusions: (i) the existence of the Dashwoods and other micro-continental blocks due to hyperextension is not supported by cover sequences linking Laurentia to proposed Dashwoods areas (i.e. Green Mountains) and an arc origin of the type Dashwoods; and (ii) ‘Hawke Bay Event(s)’, widely interpreted as Cambrian global regressive event(s), is a local highstand systems tract facies with shelf sand bypass onto the Hatch Hill Formation slope in its NE Laurentia type region.
Bias and Extrapolation in Markovian Linear Stochastic Approximation with Constant Stepsizes
Authors: Huo Dongyan (Lucy) , Chen Yudong , Xie Qiaomin 
Published: June 2023

We consider Linear Stochastic Approximation (LSA) with constant stepsize and Markovian data. Viewing the joint process of the data and LSA iterate as a time-homogeneous Markov chain, we prove its convergence to a unique limiting and stationary distribution in Wasserstein distance and establish non-asymptotic, geometric convergence rates. Furthermore, we show that the bias vector of this limit admits an infinite series expansion with respect to the stepsize. Consequently, the bias is proportional to the stepsize up to higher order terms. This result stands in contrast with LSA under i.i.d. data, for which the bias vanishes. In the reversible chain setting, we provide a general characterization of the relationship between the bias and the mixing time of the Markovian data, establishing that they are roughly proportional to each other.
Polyak-Ruppert averaging reduces the variance of the LSA iterates but does not affect the bias. The above characterization allows us to show that the bias can be reduced using Richardson-Romberg extrapolation with m≥ 2 stepsizes, which eliminates the m-1 leading terms in the bias expansion. This extrapolation scheme leads to an exponentially smaller bias and an improved mean squared error, both in theory and empirically. Our results immediately apply to the Temporal Difference learning algorithm with linear function approximation, Markovian data, and constant stepsizes.
A Targeted Thorium-227 Conjugate Demonstrates Efficacy in Preclinical Models of Acquired Drug Resistance and Combination Potential with Chemotherapeutics and Antiangiogenic Therapies
Authors: Zitzmann-Kolbe Sabine , Kristian Alexander , Zopf Dieter , Kamfenkel Claudia , Politz Oliver , Ellingsen Christine , Hilbig Jochen , Juul Mark U. , Fonslet Jesper , Nielsen Carsten H. , Schatz Christoph A. , Bjerke Roger M. , Cuthbertson Alan S. , Mumberg Dominik , Hagemann Urs B. 
Published: June 2023

Abstract
Targeted alpha therapies (TAT) are an innovative class of therapies for cancer treatment. The unique mode-of-action of TATs is the induction of deleterious DNA double-strand breaks. Difficult-to-treat cancers, such as gynecologic cancers upregulating the chemoresistance P-glycoprotein (p-gp) and overexpressing the membrane protein mesothelin (MSLN), are promising targets for TATs. Here, based on the previous encouraging findings with monotherapy, we investigated the efficacy of the mesothelin-targeted thorium-227 conjugate (MSLN-TTC) both as monotherapy and in combination with chemotherapies and antiangiogenic compounds in ovarian and cervical cancer models expressing p-gp. MSLN-TTC monotherapy showed equal cytotoxicity in vitro in p-gp–positive and -negative cancer cells, while chemotherapeutics dramatically lost activity on p-gp–positive cancer cells. In vivo, MSLN-TTC exhibited dose-dependent tumor growth inhibition with treatment/control ratios of 0.03–0.44 in various xenograft models irrespective of p-gp expression status. Furthermore, MSLN-TTC was more efficacious in p-gp–expressing tumors than chemotherapeutics. In the MSLN-expressing ST206B ovarian cancer patient-derived xenograft model, MSLN-TTC accumulated specifically in the tumor, which combined with pegylated liposomal doxorubicin (Doxil), docetaxel, bevacizumab, or regorafenib treatment induced additive-to-synergistic antitumor efficacy and substantially increased response rates compared with respective monotherapies. The combination treatments were well tolerated and only transient decreases in white and red blood cells were observed. In summary, we demonstrate that MSLN-TTC treatment shows efficacy in p-gp–expressing models of chemoresistance and has combination potential with chemo- and antiangiogenic therapies.
Global, Regional, and National Advances Toward the Management of Rheumatic Heart Disease Based on the Global Burden of Disease Study 2019
Authors: Ruan Renjie , Liu Xiaozhu , Zhang Yunrui , Tang Ming , He Bo , Zhang Qing‐Wei , Shu Tingting 
Published: June 2023

Background
Population growth, aging, and major alterations in epidemiologic trends inadvertently modulate the status of rheumatic heart disease (RHD) epidemiology. This investigation predicted RHD burden pattern and temporal trends to provide epidemiologic evidence.

Methods and Results
Prevalence, mortality, and disability‐adjusted life‐years data for RHD were obtained from the GBD (Global Burden of Disease) study. We performed decomposition analysis and frontier analysis to assess variations and burden in RHD from 1990 to 2019. In 2019, there were >40.50 million RHD cases worldwide, along with nearly 0.31 million RHD‐related deaths and 10.67 million years of healthy life lost to RHD. The RHD burden was commonly concentrated within lower sociodemographic index regions and countries. RHD primarily affects women (22.52 million cases in 2019), and the largest age‐specific prevalence rate was at 25 to 29 years in women and 20 to 24 years in men. Multiple reports demonstrated prominent downregulation of RHD‐related mortality and disability‐adjusted life‐years at the global, regional, and national levels. Decomposition analysis revealed that the observed improvements in RHD burden were primarily due to epidemiological alteration; however, it was negatively affected by population growth and aging. Frontier analysis revealed that the age‐standardized prevalence rates were negatively linked to sociodemographic index, whereas Somalia and Burkina Faso, with lower sociodemographic index, showed the lowest overall difference from the frontier boundaries of mortality and disability‐adjusted life‐years.

Conclusions
RHD remains a major global public health issue. Countries such as Somalia and Burkina Faso are particularly successful in managing adverse outcomes from RHD and may serve as a template for other countries.
Electron Leak From the Mitochondrial Electron Transport Chain Complex I at Site I
Q
Is Crucial for Oxygen Sensing in Rabbit and Human Ductus Arteriosus
Authors: Read Austin D. , Bentley Rachel E. T. , Martin Ashley Y. , Mewburn Jeffrey D. , Alizadeh Elahe , Wu Danchen , Lima Patricia D. A. , Dunham‐Snary Kimberly J. , Thébaud Bernard , Sharp Willard , Archer Stephen L. 
Published: June 2023

Background

As partial pressure of oxygen (pO
2
) rises with the first breath, the ductus arteriosus (DA) constricts, diverting blood flow to the pulmonary circulation. The DA's O
2
sensor resides within smooth muscle cells. The DA smooth muscle cells’ mitochondrial electron transport chain (ETC) produces reactive oxygen species (ROS) in proportion to oxygen tension, causing vasoconstriction by regulating redox‐sensitive ion channels and enzymes. To identify which ETC complex contributes most to DA O
2
sensing and determine whether ROS mediate O
2
sensing independent of metabolism, we used electron leak suppressors, S1QEL (suppressor of site I
Q
electron leak) and S3QEL (suppressor of site III
Qo
electron leak), which decrease ROS production by inhibiting electron leak from quinone sites I
Q
and III
Qo
, respectively.

Methods and Results

The effects of S1QEL, S3QEL, and ETC inhibitors (rotenone and antimycin A) on DA tone, mitochondrial metabolism, O
2
‐induced changes in intracellular calcium, and ROS were studied in rabbit DA rings, and human and rabbit DA smooth muscle cells. S1QEL's effects on DA patency were assessed in rabbit kits, using micro computed tomography. In DA rings, S1QEL, but not S3QEL, reversed O
2
‐induced constriction (
P
=0.0034) without reducing phenylephrine‐induced constriction. S1QEL did not inhibit mitochondrial metabolism or ETC‐I activity. In human DA smooth muscle cells, S1QEL and rotenone inhibited O
2
‐induced increases in intracellular calcium (
P
=0.02 and 0.001, respectively), a surrogate for DA constriction. S1QEL inhibited O
2
‐induced ROS generation (
P
=0.02). In vivo, S1QEL prevented O
2
‐induced DA closure (
P
<0.0001).

Conclusions

S1QEL, but not S3QEL, inhibited O
2
‐induced rises in ROS and DA constriction ex vivo and in vivo. DA O
2
sensing relies on pO
2
‐dependent changes in electron leak at site I
Q
in ETC‐I, independent of metabolism. S1QEL offers a therapeutic means to maintain DA patency.
Addressing (In)Equality in Redress: Human Rights-Led Reform of the Investor-State Dispute Settlement Mechanism
Authors: Deva Surya , Van Ho Tara 
Published: June 2023

Abstract
In the context of ongoing debates concerning the reform of the investor-State dispute settlement (ISDS) mechanism, this article critiques the widely-accepted approach that seeks to fit international human rights law (IHRL) into the existing structure of ISDS and argues that IHRL should at least be treated as ‘primus inter pares’ vis-à-vis international investment law. Testing ISDS on the touchstone of the human rights to equality, non-discrimination, and an effective remedy, the authors demonstrate that ISDS is incompatible with IHRL. Considering various structural and systemic problems, abolishing ISDS is perhaps the only normatively sound solution to address this incompatibility with IHRL. However, as this may not be politically feasible in the near future, this article articulates eight principles for a human-rights compatible international dispute settlement mechanism. We argue that these principles should inform the current efforts to reform the ISDS mechanism to avoid the risk of making only cosmetic changes.
Models in Microeconomic Theory
Authors: Osborne Martin J. , Rubinstein Ariel 
Published: June 2023

Models in Microeconomic Theory covers basic models in current microeconomic theory. Part I (Chapters 1-7) presents models of an economic agent, discussing abstract models of preferences, choice, and decision making under uncertainty, before turning to models of the consumer, the producer, and monopoly. Part II (Chapters 8-14) introduces the concept of equilibrium, beginning, unconventionally, with the models of the jungle and an economy with indivisible goods, and continuing with models of an exchange economy, equilibrium with rational expectations, and an economy with asymmetric information. Part III (Chapters 15-16) provides an introduction to game theory, covering strategic and extensive games and the concepts of Nash equilibrium and subgame perfect equilibrium. Part IV (Chapters 17-20) gives a taste of the topics of mechanism design, matching, the axiomatic analysis of economic systems, and social choice.
The book focuses on the concepts of model and equilibrium. It states models and results precisely, and provides proofs for all results. It uses only elementary mathematics (with almost no calculus), although many of the proofs involve sustained logical arguments. It includes about 150 exercises.
With its formal but accessible style, this textbook is designed for undergraduate students of microeconomics at intermediate and advanced levels.
A market with asymmetric information
Authors: Osborne Martin J. , Rubinstein Ariel 
Published: June 2023

This chapter discusses an equilibrium concept that differs from the notions of competitive equilibrium discussed in Chapters 9–12. The models in the earlier chapters specify the precise set of economic agents who operate in the market, and an equilibrium specifies the terms of trade (prices) for which the aggregate demand and supply of these agents are equal. The model we study in this chapter does not explicitly specify the set of agents. As a consequence, the equilibrium notion is more abstract. A set of contracts is an equilibrium if no agent who offers a contract wants to withdraw it, and no agent can profit by adding a contract.
We illustrate the concept by applying it to a model central to the economics of information. The problems at the end of the chapter demonstrate the use of the concept to study other economic interactions.