bluuebunny/crossref_metadata_2025_split huggingface dataset:
Only the NAD precursor nicotinamide riboside maintains cardioprotection under clinically relevant conditions, possibly through activation of glycolysis
Authors: Xiao Y , Phelp P , Bakker D , Nederlof R , Hollmann M W , Weber N C , Zuurbier C J 
Published: October 2021

Abstract

Purpose
Cardioprotective strategies against ischaemia-reperfusion injury (IRI) that remain effective in the clinical arena need to be developed. Here, we examined the efficacy of the cardioprotective compounds fingolimod (Fingo), empagliflozin (Empa), melatonin (Mela) and nicotinamide riboside (NR) in the presence of drugs routinely used clinically in IRI conditions such as cardiac by-pass surgery and PCI procedures (opiates, benzodiazepines, P2Y12 antagonist, propofol). Furthermore, we examine the mechanism of protection of effective compound(s).

Methods
Following pilot dose-response curves of each compound, cardioprotective efficacy of Fingo, Empa, Mela and NR in an in vivo rat model employing a clinically relevant anaesthetic background therapy (fentanyl-midazolam) were examined alone or in combination. Drugs were administered 30 min before 25 min left ascending coronary (LAD) ischaemia. Infarct size (IS) was determined following 2 h of reperfusion. Effective treatments were then tested in the presence of a P2Y12 antagonist (cangrelor) or propofol anaesthesia. Finally, the underlying metabolic mechanism of the efficient compound(s) was explored in an ex vivo Langendorff-perfused mouse heart model of cardiac IRI.

Results
We found that among these four compounds, only singular NR was able to reduce IS (30±14% vs 60±16%, P=0.009 vs control, Fig.1A) in vivo in the presence of clinically relevant background anaesthesia. NR still reduced IS in the presence of cangrelor (51±18% vs 71±4%, P=0.016 vs control, Fig.1B), but lost protection in the presence of propofol anaesthesia (62±16% vs 60±14%, P=0.839 vs control, Fig.1C). Furthermore, NR showed protection in the ex vivo model of IRI, where isolated hearts were perfused with glucose (G) and free fatty acid (FFA) palmitate (G+FFA): (IS%: 40±14% vs 64±12%, P=0.003 vs control; LDH release: 28.3±7.2 U/min/GWW vs 37.8±3.7 U/min/GWW, P=0.005 vs control; Rate-Pressure-Product (RPP) recovery (43±12% vs 31±8%, P=0.031 vs control, Fig.2A-C). However, NR's protection was lost when 1) glycolysis was by-passed, by replacing glucose in the perfusate with lactate (L) and pyruvate (P) (LP+FFA) or 2) glycolysis was overly activated by adding insulin to the perfusate (G+FFA+insulin) (Fig.2).

Conclusion
Our data suggests that NR is a promising cardioprotective agent to target cardiac ischaemia-reperfusion injury in clinical conditions employing opioid agonists, benzodiazepines and platelet P2Y12 inhibitors. This protection may, at least partly, be due to NR stimulation of cardiac glycolysis.

Funding Acknowledgement
Type of funding sources: None.
ADAR Editing in Viruses: An Evolutionary Force to Reckon with
Authors: Piontkivska Helen , Wales-McGrath Benjamin , Miyamoto Michael , Wayne Marta L 
Published: October 2021

AbstractAdenosine Deaminases that Act on RNA (ADARs) are RNA editing enzymes that play a dynamic and nuanced role in regulating transcriptome and proteome diversity. This editing can be highly selective, affecting a specific site within a transcript, or nonselective, resulting in hyperediting. ADAR editing is important for regulating neural functions and autoimmunity, and has a key role in the innate immune response to viral infections, where editing can have a range of pro- or antiviral effects and can contribute to viral evolution. Here we examine the role of ADAR editing across a broad range of viral groups. We propose that the effect of ADAR editing on viral replication, whether pro- or antiviral, is better viewed as an axis rather than a binary, and that the specific position of a given virus on this axis is highly dependent on virus- and host-specific factors, and can change over the course of infection. However, more research needs to be devoted to understanding these dynamic factors and how they affect virus–ADAR interactions and viral evolution. Another area that warrants significant attention is the effect of virus–ADAR interactions on host–ADAR interactions, particularly in light of the crucial role of ADAR in regulating neural functions. Answering these questions will be essential to developing our understanding of the relationship between ADAR editing and viral infection. In turn, this will further our understanding of the effects of viruses such as SARS-CoV-2, as well as many others, and thereby influence our approach to treating these deadly diseases.
The Effect of Delay Duration on Delay Discounting Across Adulthood
Authors: Leverett Shelby , Garza Christopher , Seaman Kendra 
Published: October 2021

Abstract

Objectives
Literature about the relationship between age and delay discounting, or the willingness to wait for delayed rewards, is mixed. We posit that some of this heterogeneity may be attributable to inconsistent delay durations across studies. Here we investigate how delay duration influences discounting across adulthood by systematically varying the duration of the delay between the smaller, sooner and the larger, later option.

Methods
288 healthy participants (age range: 25–84 years) completed an online delay discounting task that probed 12 different time delays across 3 discount rates. Discounting was analyzed in 2 statistical models that treated delay duration as either a categorical or a continuous predictor.

Results
Longer delays were generally associated with decreased discounting. However, this was dependent on both age of the participant and delay duration. Both models revealed that, at short to moderate time delays, older adults discounted less than younger adults. However, at very long delays (5 and 10 years), older adults discounted at similar rates to younger adults.

Discussion
Results suggest that delay length can moderate the relationship between age and discounting. Using delays longer than those tested here (&gt;10 years) could reveal yet another trend (i.e., a reversal) to those found here. Future research should investigate whether this reversal in discounting exists, why it exists, and where the inflection point lies.
An Extension of the Three Gap Theorem to Interval Exchange Transformations
Authors: Taha Diaaeldin 
Published: October 2021

AbstractThe three gap theorem asserts that for any real $\alpha $ and any positive integer $N$, the fractional parts of the sequence $0, \alpha , 2\alpha , \cdots , (N-1)\alpha $ have at most three distinct gap lengths. In this note, we extend the three gap theorem to arbitrary orbits of interval exchange transformations, and in the process, we generalize the three gap theorem and a result by Boshernitzan.
Ceding Control and Taking it Back: The Origins of Free Movement in EU Law
Authors: Barnard Catherine , Fraser Butlin Sarah 
Published: October 2021

Abstract
Given the emphasis, at the time of the 2016 referendum, on the need to take back control of UK immigration policy, the article raises the question as to why the founding EU States decided not only to cede control in this sensitive field but also to allow such a generous approach to economic migration (to include not just workers but also their family members and to include equal access to benefits, including to housing) (the ‘why’ question). We also wanted to know whether any of the concerns which so resonated in the 2016 referendum campaign, especially about benefit tourism and pressure on public services, were ventilated at the time (the ‘risks’ question). Given that the contemporaneous academic literature did not offer much insight, we went to the archives and traced the evolution of the debates on economic migration in the period leading up to the signing of the Treaty of Rome, and again in the run up to the adoption of the key Regulation on workers, Regulation 1612/68 (now Regulation 492/11). We suggest that in respect of the ‘why’ question there was no single—or simple—explanation as to why the founding states agreed to the introduction of free movement but various justifications were offered. In respect of the ‘risks’ question, our research revealed little contemporaneous discussion of the concerns that subsequently took hold, primarily in the UK but also elsewhere. More striking were the extensive debates on adequate housing for migrant workers and their families. This was less couched in terms of risk but in terms of the paucity of provision of adequate housing for all families. The article concludes by considering the question as to why there was so little attention paid to the radical nature of free movement.
Modern Slavery and Directors’ Disqualification: A Convergence of Opportunity and Challenge
Authors: Mamutse Blanca 
Published: October 2021

Abstract
Prevention and elimination of modern slavery is a priority of this era, eliciting responses at an international level and in domestic laws. The duty of organisations to ensure transparency in their supply chains is the strongest representation of corporate responsibility in this field. Less attention has been given to the current/potential role of insolvency mechanisms, in relation to companies’ commission of modern slavery offences, and in relation to their failure to comply with their supply-chain obligations. This paper engages with this novel question by examining the proposition to incorporate a directors’ disqualification sanction into the United Kingdom framework governing companies’ modern slavery supply chain obligations. This represents an opportunity, insofar as the disqualification regime is ostensibly well-placed to address weaknesses in companies’ compliance with their responsibilities. However, it represents a challenge in that adoption and implementation would have to navigate drawbacks such as the limitations of existing grounds for disqualification and potential weaknesses in the design and enforcement of a bespoke sanction. Moreover, it should confront uncertainty as to whether disqualification is an effective tool for preventing misconduct by the professional/executive class of managers at the helm of large companies. Increased emphasis on regulating the human rights obligations of companies makes it imperative that this question is addressed.
GIST case turned out to be a perforated peptic ulcer: a case report
Authors: Miratashi Yazdi Seyed Amir , Habibi Pedram , Eftekhar Javadi Arezoo , Hajebi Reza 
Published: October 2021

Abstract
Gastrointestinal stromal tumors (GISTs) are tumors arising from the fourth layer of the stomach. They are the most common form of mesenchymal neoplasms in the gastrointestinal tract. The diagnosis for the aforementioned tumors is made through endoscopic ultrasonography (EUS) with no further inspection through biopsies and aspirations. Regarding the fact that biopsies are not made in these cases, pathological misdiagnoses, however rare and effectless in the final outcome of the surgery, do occur. Here, we present a case of a 35-year-old male diagnosed with GIST through the means of EUS however, the post-op pathology report showed something very interesting. This patient was reported to be a case of perforated peptic ulcer and we found vegetable fiber component in the tissue of this patient. Bearing in mind the finding, misdiagnoses of GIST patients are probable, and careful planning prior to the surgery is recommended.
Spontaneous resolution of gastric perforation caused by an ingested foreign body: a case report
Authors: Williams Taylor Raines , Okoli Joel 
Published: October 2021

Abstract
Foreign body ingestions are commonly seen and are usually uneventful. Very rarely, ingested foreign bodies will cause perforation of the gastrointestinal tract, which can lead to peritonitis, abscesses or fistulation. This is the case of a patient with vague abdominal pain after voluntary ingestion of bleach and an ink pen. The ink pen was found lodged in the gastric antral wall on esophagogastroduodenoscopy. The foreign body spontaneously migrated into the gastric lumen and was successfully removed with endoscopy.
A Case Report of External Cardiac Pads Used for Internal Cardiac Defibrillation During Resuscitative Thoracotomy
Authors: Brown Samuel , Mool Jason L , Young William E , Hollensteiner Kourtney M , Cyr Ashley , Yi Fia , Gausepohl Andrew J 
Published: October 2021

ABSTRACTThis is a case report regarding the use of non-conventional methods to perform internal cardiac defibrillation on a trauma patient in an austere environment. The patient was a polytrauma causality of an improvised explosive device who arrived to a far forward resuscitative surgical team during a recent armed conflict. After arrival, the patient lost pulses. An emergency resuscitative thoracotomy was performed, and the patient was noted to have ventricular fibrillation on direct cardiac visualization. In the absence of standard surgical defibrillation paddles, the team applied external defibrillator stickers directly to the patient’s myocardium to deliver an electrical shock. The procedure successfully led to the return of spontaneous circulation. This report highlights a novel approach to resuscitation in resource-limited environments by a military surgical team.
Chest Pain and Fever in a Healthcare Provider During the Global Coronavirus Pandemic
Authors: Zavala Armando , Stark Christopher M 
Published: October 2021

ABSTRACT
The coronavirus disease 2019 (COVID-19) global pandemic has posed unique challenges to healthcare providers that work in austere environments. Military healthcare providers advise commanders on endemic disease risk, prevention, and management during field training exercises. Healthcare workers are at increased risk of exposure to infectious pathogens. We present a case of a military healthcare provider who presented with fever, cough, and fatigue during the COVID-19 global pandemic that was diagnosed with a primary pulmonary coccidioidal infection. Treatment after appropriate diagnosis consisted of supportive care. Respiratory and pain symptoms resolved by 2 months post-diagnosis. Although COVID-19 must be closely monitored in the field training environment, it is important to maintain a high index of suspicion of endemic infectious diseases as a potential etiology for respiratory illnesses.
Overweight BMI (25–29) in Active Duty Military: Excess Fat or More Lean Mass? A Look at the Evidence
Authors: Clerc Philip G , Mayer Stéphanie B , Graybill Sky 
Published: October 2021

ABSTRACT
Many active duty service members and their health care providers feel that the current body mass index (BMI) standard for diagnosing obesity, BMI ≥30 kg/m2, may unfairly overclassify as obese those with higher muscle mass. Unfortunately, a closer look at the data available for service members repeatedly demonstrates the exact opposite: we are actually underestimating the rates of obesity in service members using current BMI cutoffs when compared with body fat mass as measured by either dual-energy X-ray absorptiometry or bioelectrical impedance analysis as the gold standard. Using a lower BMI threshold and refining positive results via history, exam, labs, and/or more specific measurements of body composition would more accurately estimate body fat percentage in active duty service members while remaining convenient and scalable. Given the current obesity epidemic in our nation, this suggests the critical need for new approaches to screening, as well as treatment, of overweight and obesity in our military to improve service readiness.
Complications of Nonpermanent Facial Fillers: A Systematic Review
Authors: Oranges Carlo M. , Brucato Davide , Schaefer Dirk J. , Kalbermatten Daniel F. , Harder Yves 
Published: October 2021

Background:
A variety of complications after injection of nonpermanent fillers for facial rejuvenation have been reported so far. However, to date, the overall complication rate is still a matter of debate. The aim of this study was to perform a systematic review of literature to assess the type and severity of associated complications following injections in different anatomical regions of the face.

Methods:
The entire PubMed/Medline database was screened to identify case reports and clinical studies describing complications that have occurred after injection of nonpermanent fillers in the face. These complications have been reviewed and analyzed according to their occurrence in different anatomical regions of the face.

Results:
Forty-six articles including a total of 164 patients reported on a total of 436 complications during the time period between January 2003 and February 2020. The majority of the complications were reported after injections to the nose and the nasolabial fold (n = 230), the forehead and the eyebrows (n = 53), and the glabellar region (n = 36). Out of 436 complications, 163 have been classified as severe or permanent including skin necrosis (n = 46), loss of vision (n = 35), or encephalitis (n = 1), whereas 273 complications were classified as mild or transient, such as local edema (n = 74), skin erythema (n = 69), and filler migration (n = 2). The most severe complications were observed in treatments of nose, glabella, and forehead.

Conclusions:
Nonpermanent facial fillers are associated with rare but potentially severe complications. Severity and impact of complications depend on the anatomical region of the face and eventually require profound knowledge of facial anatomy.
Nuclear cataract, moderate oblique corneal astigmatism, and glaucoma in a highly myopic eye implanted with a foldable iris-fixated phakic IOL
Authors: Menapace Rupert 
Published: October 2021

A 65-year-old woman had undergone bilateral foldable iris-fixated phakic intraocular lens (pIOL) implantation in 2008 to correct for high myopia of −10 diopters (D). 12 years later, she presented with nuclear and subcortical cataract in her right eye. The Artiflex pIOL (Figure 1

JOURNAL/jcrs/04.03/02158034-202111000-00021/figure1/v/2023-08-19T002621Z/r/image-tiff

) was well centered and fixed to the iris. Endothelial cell count (ECC) was 2159 per mm2 and corneal thickness 515 µm. Residual correction in her distance glass was −1.75 + 1.5 × 60. Topography showed a symmetric bowtie with a mean simulated keratometry of 1.3 D at an axis of 67 degrees (Figure 2

JOURNAL/jcrs/04.03/02158034-202111000-00021/figure2/v/2023-08-19T002621Z/r/image-tiff

). Keratometry was 1.5 @ 65. Left eye refraction was −1.5 + 1.0 × 175. The patient had also developed chronic open-angle glaucoma with intraocular pressure measurements exceeding 30 mm Hg, which was currently regulated with topical medication.
What would be your surgical approach for cataract surgery with IOL removal and replacement when also considering the possible later need for superior glaucoma filtering surgery?
Mouse Model of Critical Persistent Inflammation, Immunosuppression, and Catabolism Syndrome
Authors: Chen Xiancheng , Li Xiaojing , Lu Huimin , Xu Yali , Wei Yu , Cao Ke , Zhu Zhanghua , Chen Ming , Yu Wenkui 
Published: October 2021

ABSTRACT
Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a growing challenge in intensive care units (ICUs). PIICS causes a severe illness with high mortality. Currently, treatment is expensive, and the outcomes are dismal. Herein, we established a PIICS model to study the disease pathophysiology and its potential treatment. Using a modified sublethal cecal ligation and puncture (CLP) to induce sepsis (day 1) and the injection of lipopolysaccharide (LPS) to induce an aggravated inflammation response (day 11), CLP + LPS mice recapitulating PIICS features were successfully generated (day 14). Adult male mice were divided into CLP + LPS, CLP + daily chronic stress (DCS), CLP, DCS, LPS, and sham control groups. A survival curve was generated, and phenotypes were analyzed using markers for catabolism, inflammation, and immunosuppression. The CLP + LPS model showed two mortality peaks (after CLP and after LPS), whereas the CLP + DCS and CLP groups showed one peak. Surviving CLP + LPS mice exhibited significantly increased catabolism and inflammatory cytokine levels and aggravated inflammation, including organ inflammation. CLP + LPS mice exhibited strong immune suppression as evidenced by decreased splenic cluster of differentiation (CD)8+ and interferon-γ+CD8+ T cell counts and a concomitant and significant increase in the myeloid-derived suppressor cell population. This CLP+LPS-induced PIICS model differs from acute sepsis models, showing two mortality peaks and a protracted course of 14 days. Compared to previous PIICS models, ours shows a re-aggravated status and higher catabolism, inflammation, and immunosuppression levels. Our aim was to use the PIICS model to simulate PIICS pathophysiology and course in the ICU, enabling investigation of its mechanism and treatment.
Early Graft Loss Following Transplantation From Expanded Criteria Donors
Authors: Larkins Nicholas G. , Wong Germaine , Johnson David W. , Hawley Carmel , Teixeira-Pinto Armando , Pleass Henry , Pilmore Helen , Lim Wai H. 
Published: October 2021

Background.
Expanded criteria donor (ECD) kidneys are associated with higher graft loss rates than standard criteria donor kidneys. We sought to determine factors associated with early graft loss and their discrimination ability for this outcome compared with kidney donor risk index.

Methods.
Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for ECD transplants between 1997 and 2014. The primary outcome was early graft loss (all-cause graft loss within 3 y of transplantation). Death-censored graft loss was substituted as a sensitivity analysis. Era-adjusted odds ratios were calculated by multivariable logistic regression for donor, recipient, and transplant factors available at transplantation. Discrimination was assessed by c-statistic, with 95% confidence intervals (CIs) calculated by bootstrapping.

Results.
Of 2152 ECD kidney transplants, early graft loss occurred in 406 (19%) and was associated with recipient diabetes, smoking, First Nations recipients, and oliguria. Of factors defining ECD (age, elevated terminal creatinine, hypertension, death from cerebrovascular accident), all but mode of death were associated with early graft loss. The multivariable model, including known donor, recipient, and transplant factors, was moderately good at predicting early graft loss (c-statistic 0.65; 95% CI, 0.62-0.68). Recipient factors (c-statistic 0.62; 95% CI, 0.59-0.65) performed equally well compared with donor factors (c-statistic 0.60; 95% CI, 0.57-0.64) or the kidney donor risk index (c-statistic 0.60; 95% CI, 0.56-0.63).

Conclusions.
Early graft loss occurs in approximately one-fifth of ECD kidney transplants. The discriminatory value of commonly used recipient, donor, and transplant factors are approximately comparable and limited.