bluuebunny/crossref_metadata_2025 huggingface dataset:
Securities and Derivatives Exchanges in the United States
Authors: Dombalagian Onnig H
Published: May 2022

This chapter evaluates securities and derivatives exchanges in the United States. Securities and derivatives exchanges have long enjoyed a central role in the ordering of US trading markets, insofar as they established much of the contemporary framework for coordinating the interests and obligations of brokers, floor traders, specialists and market makers, listed companies and sponsors of exchange-traded products, and other market participants. Congress enshrined this role by vesting exchanges with broad rulemaking and disciplinary authority in eponymous legislation, while at the same time ensuring accountability through governance requirements, public transparency and access standards, and federal oversight of their self-regulatory activities. The past several decades have threatened to disrupt such arrangements as US exchanges have lost primacy of place in their respective markets. To face these challenges, exchanges have demutualized to compete more effectively with alternative trading venues, while ceding much of the authority they exercised over listed issuers, brokers, and dealers to federal regulators and non-market self-regulatory organizations (SROs). Addressing, in turn, the role of exchanges’ listing rules for the corporate governance of listed companies, the regulatory requirements pertaining to the provision of liquidity to market participants, as well as the legal and regulatory regime for the dissemination of market information, the chapter builds on the theoretical framework developed in the previous chapter and discusses the applicable provisions in US securities regulation.
Alternative Trading Venues in the United States
Authors: Rauterberg Gabriel
Published: May 2022

This chapter focuses on alternative trading systems (ATSs) in the United States. It begins by describing the basic architecture of the US equity market, organized around the types of trading venues; and then analyses some of the criticisms that politicians, media commentators, and scholars have made of ATSs. The chapter then argues that ATSs have stronger incentives to innovate than exchanges. Beyond batched auctions, ATSs have introduced multiple other innovations, including different ranking systems for executing orders beyond exchanges' price, display, and time priority rules; order-initiated auctions; and innovative order types, including ones that allow execution instructions across multiple securities, such as aggregate limits on transactions across many securities. Finally, the chapter discusses the welfare implications of the different innovation incentives of ATSs and exchanges.
Central Counterparties Insolvency and Resolution in the EU
Authors: Binder Jens-Hinrich
Published: May 2022

This chapter assesses the international policy debate on insolvency management in relation to central counterparties (CCPs), as well as the general context in the European regulatory framework for the licensing and ongoing regulation of CCPs. It then turns to a closer examination of the new Regulation, which has been strongly influenced by the Financial Stability Board’s (FSB) ‘Key Attributes of Effective Insolvency Regimes for Financial Institutions’ of 2014, but is far more detailed and prescriptive. While the prudential requirements for CCPs’ own risk mitigation and loss management arrangements established under the European Market Infrastructure Regulation (EMIR) have been taken as the basis for recovery measures, the Regulation introduces some key features of recovery and resolution regimes for banking institutions also in relation to CCPs. Just as banks, CCP operators, under the Regulation, will be required to engage in rigorous recovery planning, while resolution authorities are required, in turn, to develop resolution plans in order to prepare for future contingencies. For the actual resolution stage, the Regulation prescribes a number of statutory tools, some of which have also been adapted from the corresponding regime for failing banks.
Credit Risk-Mitigation Techniques and Credit Risk Protection
Authors: Joosen Bart PM
Published: May 2022

This chapter assesses credit risk mitigation (CRM) techniques and credit risk protection. Managing the risk of default of bank counterparties is, if possible, the most important objective of banks engaged in lending. The lower the counterparty’s creditworthiness, the stronger the collateral must be for a bank to be prepared to extend its credit. From the perspective of prudential supervision, CRM techniques will be subjected to an in-depth test to determine whether the reduction in credit risk envisaged by the bank may actually lead to a reduction in the weighting of the credit risk on the item concerned for the purpose of capital adequacy. Each bank applies its own techniques and terms and conditions related to lending and credit risk management; this is how banks distinguish themselves from each other. The chapter then looks at the developments in the regulation of CRM in the Basel standards or in Capital Requirements Regulation (CRR), considering the genesis of the rules regarding capital market-driven CRM techniques and the use of financial collateral. It also identifies the general principles of CRM and of funded and unfunded credit protection.
Covered Bonds and Securitization Positions as HQLA
Authors: Grünewald Seraina
Published: May 2022

This chapter reviews the differences in treatment of covered bond and securitisation positions with a view to calculating liquidity requirements (both the Liquidity Coverage Ratio and the Net Stable Funding Ratio) by Basel III on the one hand and the EU framework on the other. It begins by explaining the concept of high-quality liquid assets (HQLA). Covered bonds are debt obligations issued by banks and secured by a pool of cover assets to which investors have direct recourse as preferred creditors, while retaining a claim against the issuing bank in the event of default as ordinary creditors. Securitisations, on the other hand, represent transactions or schemes with an exposure or pool of exposures whose credit risk is tranched, which possess the following characteristics: (1) payments in the transaction or scheme depend on the performance of the exposure or pool of exposures; and (2) the subordination of tranches determines the distribution of losses throughout the ongoing life of the transaction or scheme. The chapter then addresses the implications of the EU’s efforts to integrate and improve the efficiency of the covered bonds market, culminating in the recent adoption of the Covered Bonds Directive and Regulation.
Supervisory Review and Evaluation Process (SREP) in the Context of the Exercise of Supervisory Powers and Extraordinary Measures
Authors: Lamandini Marco , D’Ambrosio Raffaele , Muñoz David Ramos
Published: May 2022

This chapter discusses the concepts of Pillar 2 and Supervisory Review and Evaluation Process (SREP), which were adopted by Basel II to promote a better measurement and management by credit institutions of their risks and to make capital requirements more risk-sensitive and more individually tailored than under previous Basel Committee on Banking and Supervision (BCBS) standards. The SREP’s relational supervisory model helps to bridge the gap between supervisory and crisis-management situations. Should the SREP show that the institution does not meet the prudential requirements or is likely to breach the same within the following 12 months, Article 102 CRD V provides that competent authorities must require an institution to take the necessary measures at an early stage to address relevant problems. This includes relying on a wide set of supervisory powers listed in Article 104 CRD V. The EBA Guidelines extensively detail the use of these supervisory powers, giving a number of examples for each of the SREP element and, as to capital adequacy, for each of the risks to capital. They also clarify that in addition to such supervisory powers, the competent authorities may also adopt measures provided for under national law and, when applicable, early intervention measures as specified in Article 27 BRRD.
Stress-testing in Banking in the EU
Authors: Neves Pedro Duarte , Morais Luís Silva , Feteira Lúcio Tomé
Published: May 2022

This chapter examines financial stress-testing, most notably microprudential bank stress-testing in the EU. It begins by differentiating between micro and macroprudential stress tests. Microprudential stress-testing takes place at the level of individual financial institutions (micro perspective) serving as a risk management tool used both by individual banks (to gauge risk exposures for internal purposes) and supervisors (to assess the resilience of banking institutions to adverse market developments). Meanwhile, macroprudential stress tests are a tool designed to assess the system-wide resilience to shocks to support the design and calibration of macroprudential policy with the objective to identify and reduce systemic risk. Therefore, the focus is on the system-wide resilience and not on individual resilience, with the possible application for defining the size of counter-cyclical buffers. The chapter then addresses the topic of EU-wide stress tests from three perspectives, namely (i) its implementation and the methodologies used from 2009 onwards; (ii) the outcomes of such stress-testing exercises; and (iii) a comparative analysis of EU-wide stress tests with its US and UK counterparts, also including the sensitivity scenarios developed to assess the possible effects of the COVID-19 pandemic.
Applying Proportionality to the Prudential RegimeReporting and Disclosure Requirements for Smaller Banks
Authors: Hadjiemmanuil Christos
Published: May 2022

This chapter investigates the demand for proportionate regulation, in response to the great wave of prudential reregulation that followed the Global Financial Crisis (GFC). This has resulted, not only to a significant tightening of the prudential requirements, but also to a drastic increase in the intensity and complexity of day-to-day supervision, including supervisory reporting. For smaller banks, the challenge is daunting and could have grave competitive implications. Their predicament has turned the necessity and proportionality of the new prudential requirements into a central theme of the banking regulatory debate. The chapter then looks at the technique used by the Capital Requirements Regulation (CRR) II to relieve the members of the newly established class of ‘small and non-complex institutions’ from excessive and unjustifiable regulatory burdens — in particular, those relating to supervisory reporting requirements and public disclosure obligations. It also considers the streamlining and integration of all information-related obligations of banking institutions to reduce the complexity of the existing system, eliminating duplicative reporting by institutions, and improving the accessibility and usability of regulatory information.
Applicable Accounting Principles, IFRS, Local GAAP, and Compatibility with Prudential Reporting
Authors: Löw Edgar , Vogt Kevin
Published: May 2022

This chapter analyses the interdependencies, commonalities, and differences between accounting and regulatory requirements with regard to consolidation, the determination of own funds, and credit risk modelling under the International Financial Reporting Standards (IFRS 9) as well as within the Internal Ratings Based Approach. Parent institutions in a member state are supervised on a consolidated basis and are therefore in principle obliged to apply the CRR II framework on individual as well as consolidated basis. However, the scope of prudential consolidation may deviate from the IFRS or local-GAAP (General Accepted Accounting Principles) consolidation, as the prudential consolidation often narrows the circle of consolidated entities down to the entities relevant for prudential supervision, with the exclusion of ‘non-financial businesses’. The chapter then provides an answer to the question of the extent to which different accounting regulations under different accounting standards or the exercise of options have an impact on capital ratios. It also shows to what extent regulatory requirements encourage institutions to exercise accounting discretion or influence the exercise of options. Finally, the chapter assesses the extent to which supervisory regulations can be incorporated into the balance sheet in order to achieve a parallelism between accounting and supervisory law.
Leadership Lessons From the Field: Leading Others to Cope With Death
Authors: Geringer Jamie L , Durning Steven J
Published: May 2022

All healthcare leaders will inevitably face patient death and dealing with loss. While leaders have different preparation for this, many lack comfort and confidence navigating death, whether it be of a patient, family member, or colleague. Learning how to support others in dealing with death is a fundamental leadership skill.
Antibody Level Predicts the Clinical Course of Breakthrough Infection of COVID-19 Caused by Delta and Omicron Variants: A Prospective Cross-Sectional Study
Authors: Kim Min Hyung , Nam Yooju , Son Nak Hoon , Heo Namwoo , Kim Bongyoung , Kang Eawha , Shin Areum , Yang Andrew Jihoon , Park Yoon Soo , Kim Heejung , Kyong Taeyoung , Kim Yong Chan
Published: May 2022

Background

Omicron variant viruses spread rapidly, even in individuals with high vaccination rates. This study aimed to determine the utility of the antibody against spike protein level as a predictor of the disease course of coronavirus disease 2019 (COVID-19) in vaccinated patients.

Methods

Between December 11, 2021, and February 10, 2022, we performed a prospective observational cohort study in South Korea, which included patients infected with Delta and Omicron variants. A multivariable logistic regression analysis to determine the association between antibody levels and outcomes was conducted. The relationship between antibody levels and cycle threshold (Ct) values was confirmed using a generalized linear model.

Results

From 106 vaccinated patients (39 Delta and 67 Omicron), the geometric mean titers of antibodies in patients with fever (≥37.5°C), hypoxia (≤94% of SpO2), pneumonia, C-reactive protein (CRP) elevation (>8 mg/L), or lymphopenia (<1100 cells/μL) were 1201.5 U/mL, 98.8 U/mL, 774.1 U/mL, 1335.1 U/mL, and 1032.2 U/mL, respectively. Increased antibody levels were associated with a decrease in the occurrence of fever (adjusted odds ratio [aOR], 0.23; 95% CI, 0.12–0.51), hypoxia (aOR, 0.23; 95% CI, 0.08–0.7), CRP elevation (aOR, 0.52; 95% CI, 0.29–0.0.94), and lymphopenia (aOR, 0.57; 95% CI, 0.33–0.98). Ct values showed a positive correlation between antibody levels (P = .02).

Conclusions

Antibody levels are predictive of the clinical course of COVID-19 in vaccinated patients with Delta and Omicron variant infections. Our data highlight the need for concentrated efforts to monitor patients with severe acute respiratory syndrome coronavirus 2 infection who are at risk of low antibody levels.
The effects of deoxynivalenol-contaminated corn in low-complexity diets supplemented with either an immune-modulating feed additive, or fish oil on nursery pig growth performance, immune response, small intestinal morphology, and component digestibility
Authors: Lafleur Larivière Élise , Zhu Cuilan , Sharma Ankita , Karrow Niel A , Huber Lee-Anne
Published: May 2022

Three hundred twenty newly weaned pigs (21 days of age; 6.7 ± 0.3 kg BW) were used to determine the effects of supplementing low-complexity (LC) deoxynivalenol- (DON) contaminated nursery diets with a feed additive or fish oil on growth performance and immune response to an Escherichia coli lipopolysaccharide (LPS) challenge. Pens were randomly assigned to 1 of 5 dietary treatments (n = 8 pens per treatment): positive control (PC; contained multiple animal protein sources), or 1 of 4 LC diets (contained only plant-based protein sources) without (NC; negative control) or with ~ 3.5 ppm DON contamination, without (DON-) or with a feed additive containing a blend of immune-modulating components (DON+; 2 mg/kg, as-fed) or fish oil (DONω3; 2.5%, as-fed). Dietary treatments were fed during phases I and II (7 and 15 days, respectively) and a common phase III diet was fed for 20 days. On day 22, two pigs per pen were injected IM with 30 μg/kg BW LPS and 1 pig per pen with 1 mL saline. Rectal temperatures were recorded at 0, 1, 2, 3 h after injection. At 3 h, blood was collected for plasma cytokine analysis and small intestinal histomorphology was assessed. In phase I, pigs fed PC and NC did not differ for ADG, ADFI and G:F, but these outcomes were greater than for pigs fed DON+ and DONω (P < 0.05). In phase II, pigs fed NC had greater ADG and PC had greater ADFI but lower G:F than pigs fed DON- and DONω3 (P < 0.05). At the end of phase II, pigs fed DONω3 tended to have lower BW than PC and NC (P = 0.084 and 0.079, respectively). In phase III and overall, there were no differences among dietary treatments for ADG, ADFI, G:F, or final BW. The LPS injection increased rectal temperature and reduced jejunal and ileal villus height (versus saline; P < 0.05). Plasma interferon-γ concentration was only increased by LPS for pigs fed PC, NC, and DON+ compared to the saline-injected counterparts (P < 0.05). Regardless of LPS injection, jejunal villus height was greater for pigs fed DON+ than DONω3 (P < 0.05) and ileal villus height was greater for pigs fed DON+ and PC than DONω3 (P < 0.05). Therefore, nursery diet complexity did not affect growth performance or immune response to LPS. Regardless of DON contamination and feed additive inclusion in phases I and II, pigs were able to achieve nursery exit BW not different from those fed PC. The feed additive offered marginal benefits for small intestinal villus height and immune response for pigs fed DON-contaminated LC nursery diets.
Implications of Recent Epidemiological Studies for Compensation of Veterans Exposed to Plutonium
Authors: Beyea Jan
Published: May 2022

The objective of this paper is to compare post-2007 epidemiological results for plutonium workers to risk predicted by the software program NIOSH-IREP (IREP for short), which is used to determine the lowest dose for a US veteran to obtain cancer compensation. IREP output and methodology were used to predict excess relative risk per Gy (ERR Gy−1) for lung cancer at the 99th credibility percentile, which is used for compensation decisions. Also estimated were relative biological effectiveness factors (RBE) predicted for workers using IREP methodology. IREP predictions were compared to results for Mayak and Sellafield plutonium workers, separately and pooled. Indications that IREP might underpredict 99th-percentile lung cancer plutonium risk came from (1) comparison of worker RBEs and (2) from comparison of Sellafield results separately. When Sellafield and Mayak data were pooled, ERR Gy−1 comparisons at the 99th percentile roughly matched epidemiological data with regression dose range restricted to < 0.05 Gy, the most relevant region to veterans, but overpredicted for the full dose range. When four plausible distributions for lung cancer risk, including both new and old data, were combined using illustrative weighting factors, compensation cutoff dose for lung cancer matched current IREP values unless regression results below 0.05 were chosen for Sellafield, producing a two-fold reduction. A 1997 claim of a dose threshold in lung cancer dose response was not confirmed in later literature. The benefit of the doubt is given to claimants when the science is unclear. The challenge for NIOSH-IREP custodians is dealing with the Sellafield results, which might best match US claimants.
PREDICTING LESION SHRINKAGE IN EYES WITH MYOPIC CHOROIDAL NEOVASCULARIZATION FROM FEATURES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Liu Jing , Song Shuang , Yu Xiaobing
Published: May 2022

Purpose:

To identify baseline morphological predictors of lesion shrinkage in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor.

Methods:

This retrospective study included 46 eyes (41 consecutive patients) with active mCNV receiving anti–vascular endothelial growth factor treatment. Optical coherence tomography angiography was performed at baseline and 1 year after treatment. Quantitative features were obtained from optical coherence tomography angiography images using AngioTool software. Eyes were classified as “high shrinkage” or “low shrinkage” according to the median relative change in lesion area. Baseline quantitative morphological features associated with mCNV shrinkage were identified in univariate and multivariate analyses.

Results:

The mCNV area was significantly smaller after 1 year (P = 0.013), with a median relative change of −16.5%. The relative change in mCNV area was −48.3% in high-shrinkage eyes (n = 23) and −5.2% in low-shrinkage eyes (n = 23). High-shrinkage eyes had a smaller mCNV area (P = 0.013), shorter total vessel length (P = 0.023), and higher end point density (P < 0.001). Multivariate analysis showed significant associations of high shrinkage with end point density (β = −0.037, P = 0.043) and previous anti–vascular endothelial growth factor treatment (β = 0.216, P = 0.029).

Conclusion:

Morphological features of neovascularization detected by optical coherence tomography angiography can predict lesion shrinkage in eyes with mCNV receiving anti–vascular endothelial growth factor therapy. Higher end point density contributed to shrinkage, particularly of treatment-naive lesions.
PARS PLANA VITRECTOMY WITH AND WITHOUT INTERNAL LIMITING MEMBRANE PEELING FOR DIABETIC PATIENTS WITH MACULA INVOLVED TRACTIONAL RETINAL DETACHMENT
Authors: Karahan Eyyup , Sahin Vural Gözde , Girgin Yurdagul , Kayikcioglu Omer Can , Guler Cenap
Published: May 2022

Purpose:

To evaluate the effect of internal limiting membrane (ILM) peeling on anatomical and functional results in pars plana vitrectomy performed eyes with tractional retinal detachment affecting the macula because of diabetes mellitus.

Methods:

Patients without ILM peeling were considered as Group 1, and patients with ILM peeling were considered as Group 2. The main outcomes were the best-corrected visual acuity at 6 months and the rate of epiretinal membrane formation within 6 months. The rate and the indications for resurgery were determined. Parameters affecting the final best-corrected visual acuity were determined by regression analysis.

Results:

Final best-corrected visual acuity was significantly better in eyes with ILM peeled off than in eyes with no peel-off (P = 0.012). Less secondary epiretinal membrane was formed in Group 1 (P = 0.009). There was no difference between groups in resurgery rates (P = 0.143). The need for resurgery because of epiretinal membrane was higher in Group 1 rather than Group 2 (P = 0.001). The only factor affecting the final best-corrected visual acuity was ILM peeling.

Conclusion:

In patients with tractional retinal detachment affecting the macula because of diabetes, ILM peeling in addition to pars plana vitrectomy and membrane excision does not affect the need for resurgery but contributes positively to anatomical and functional outcomes.
RETINAL NEOVASCULARIZATION IN ACQUIRED PERIPHERAL RETINOSCHISIS THROUGH INNER RETINAL ISCHEMIA: OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHIC FINDINGS
Authors: Kang Min Seung , Kwon Han Jo
Published: May 2022

Purpose:

To present two cases of concomitant retinal neovascularization (RNV) in acquired peripheral retinoschisis and analyze its characteristics on optical coherence tomography angiography and based on a literature review.

Methods:

This was an observational, retrospective case study.

Results:

Case 1 presented with bullous retinoschisis and RNV near the schisis cavity. Optical coherence tomography angiography revealed no angioflow into the retinal arterioles of the cavity. An arterial filling delay to the retinoschisis with extensive leakage from the RNV was noted on fluorescein angiography. Case 2 involved the superficial retinoschisis and telangiectatic vessels inside the schisis cavity. Optical coherence tomography angiography revealed damage to the superficial capillary plexus of the cavity, absence of angioflow to the inner schisis layer, and increased angioflow to the RNV. Fluorescein angiography showed focal leakage from the RNV and diffuse leakage from telangiectasia. No vision-threatening complications were identified in either patient up to the last follow-up, subsequent to laser photocoagulation.

Conclusion:

Acquired peripheral retinoschisis is associated with RNV. Inner retinal ischemia caused by hemodynamic resistance or a damaged superficial capillary plexus can interrupt angioflow to the inner schisis retinal layer on optical coherence tomography angiographic findings and develop RNV inside or outside the retinoschisis.
Inclusion of sarcopenia improves the prognostic value of MELD score in patients after transjugular intrahepatic portosystemic shunt
Authors: Bai Yao-wei , Liu Jia-cheng , Yang Chong-tu , Wang Ying-liang , Wang Chao-yang , Ju Shu-guang , Zhou Chen , Huang Song-jiang , Li Tong-qiang , Chen Yang , Yao Wei , Xiong Bin
Published: May 2022

Objective

To explore the predictive value of model for end-stage liver disease (MELD)-Sarcopenia score for survival of cirrhotic patients after transjugular intrahepatic portosystemic shunt (TIPS) placement.

Methods

289 patients who underwent TIPS between February 2016 and December 2020 were included, they were divided into the sarcopenia group (n = 138) and non-sarcopenia group (n = 151) according to whether they were complicated with sarcopenia. Kaplan–Meier curve was used to analyze and compare the prognosis of the above two groups and multivariate Cox regression analysis was used to identify the independent prognostic factors. The performance of different predictive models was compared using C-index.

Results

During the follow-up, Kaplan–Meier analyses indicated that cumulative survival was significantly lower in sarcopenia group than that in non-sarcopenia group [74.6% vs. 92.7%, HR, 0.24 (95% confidence interval (CI), 0.12–0.46), Log-rank P < 0.001]. After multivariate Cox analysis, age [HR, 1.040 (95% CI, 1.015–1.065), P = 0.002], sarcopenia [HR, 3.948 (95% CI, 1.989–7.838), P < 0.001], albumin [HR, 0.945 (95% CI, 0.897–0.997), P = 0.037], and MELD score [HR, 1.156 (95% CI, 1.097–1.217), P < 0.001] were identified as the independent risk factors for mortality after TIPS. The C-indexes of MELD-Sarcopenia, Child-Pugh, MELD, MELD-Na, and the Freiburg index of post-TIPS survival (FIPS) scores were 0.782, 0.688, 0.719, 0.734, and 0.770, respectively.

Conclusion

Sarcopenia is independently correlated with post-TIPS mortality, and MELD-Sarcopenia score showed the best performance in predicting post-TIPS mortality than the traditional predictive models.
Effect of Repetitive Transcranial Magnetic Stimulation on the Nutritional Status and Neurological Function of Patients With Postischemic Stroke Dysphagia
Authors: Jiao Yonggang , Peng Wei , Yang Jingping , Li Cheng
Published: May 2022

Background:

This project aimed to explore the effects of repetitive transcranial magnetic stimulation (rTMS) on the nutritional status and neurological function of patients with postischemic stroke dysphagia.

Materials and Methods:

After recruiting 70 inpatients with cerebral infarction combined with dysphagia hospitalized in the Cerebrovascular Center of Guangdong Second Provincial General Hospital from June 2017 to June 2020, we assigned them randomly into a control group and an rTMS group. Patients in the control group received swallowing training, while patients of the rTMS group received swallowing training and rTMS.

Results:

Fifteen days after treatment, serum nutrition indexes and neurotrophic indexes of both groups were higher than before treatment, and their serum nerve injury indexes were lower than before treatment. After 15 days of treatment, the body nutrition indexes and neuronutrition indexes of the rTMS group were higher than those of the control group, while the nerve injury indexes of the rTMS group were lower than those of the control group.

Conclusion:

rTMS in the treatment of dysphagia after stroke can better improve nutritional status and nerve function, reducing nerve damage.
Hirayama Disease
Authors: Gritsch David , Mbonde Amir A. , Khoury Julie
Published: May 2022

Introduction:

Hirayama disease is a rare neuromuscular disorder characterized by abnormal forward displacement of the cervical spinal cord, resulting in focal ischemic changes of anterior horn cells.

Case Report:

A 15-year-old male presented with 6 months of progressive right upper extremity weakness. Electromyography/nerve conduction study indicated a chronic neurogenic process involving the C8-T1 myotome. Cervical spine magnetic resonance imaging in the neutral position demonstrated minor disk bulges without significant spinal canal narrowing. With flexion, there was a forward displacement of the dorsal dural sac and marked effacement of the subarachnoid spaces from vertebral levels C5 through C7. In addition, prominent flow voids were now seen in the dorsal epidural space consistent with engorged venous structures.

Conclusion:

The diagnosis of Hirayama disease requires a high index of suspicion, and imaging should include a series with the neck in a flexed position, as imaging in the neutral position is often unrevealing and the disorder can otherwise easily be missed.
Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease
Authors: Hodis Howard N. , Mack Wendy J.
Published: May 2022

The totality of evidence indicates menopausal hormone replacement therapy (HRT) effects are determined by timing of initiation according to age and/or time since menopause, underlying health of target tissue, and duration of therapy. Initiated in women at younger than 60 years and/or at or near menopause, HRT significantly reduces all-cause mortality and cardiovascular disease (CVD), whereas other primary CVD prevention therapies such as lipid-lowering fail to do so. The magnitude and type of HRT-associated risks, including breast cancer, stroke, and venous thromboembolism, are rare (<10 events/10,000 women), not unique to HRT, and comparable with other medications. Hormone replacement therapy is a sex-specific and time-dependent primary CVD prevention therapy that concomitantly reduces all-cause mortality, as well as other aging-related diseases with an excellent risk profile. Keeping in mind that prevention strategies must be personalized, health care providers and patients can use cumulated HRT data in making clinical decisions concerning chronic disease prevention including CVD and mortality reduction.
Update on Pregnancy Following Breast Cancer Diagnosis and Treatment
Authors: Perachino Marta , Poggio Francesca , Arecco Luca , Blondeaux Eva , Spinaci Stefano , Marrocco Camilla , Levaggi Alessia , Lambertini Matteo
Published: May 2022

Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor–positive disease and BRCA carriers.
New Approaches to the Diagnosis of Rejection and Prediction of Tolerance in Liver Transplantation
Authors: Taner Timucin , Bruner Julia , Emamaullee Juliet , Bonaccorsi-Riani Eliano , Zarrinpar Ali
Published: May 2022

Immunosuppression after liver transplantation is essential for preventing allograft rejection. However, long-term drug toxicity and associated complications necessitate investigation of immunosuppression minimization and withdrawal protocols. Development of such protocols is hindered by reliance on current paradigms for monitoring allograft function and rejection status. The current standard of care for diagnosis of rejection is histopathologic assessment and grading of liver biopsies in accordance with the Banff Rejection Activity Index. However, this method is limited by cost, sampling variability, and interobserver variation. Moreover, the invasive nature of biopsy increases the risk of patient complications. Incorporating noninvasive techniques may supplement existing methods through improved understanding of rejection causes, hepatic spatial architecture, and the role of idiopathic fibroinflammatory regions. These techniques may also aid in quantification and help integrate emerging -omics analyses with current assessments. Alternatively, emerging noninvasive methods show potential to detect and distinguish between different types of rejection while minimizing risk of adverse advents. Although biomarkers have yet to replace biopsy, preliminary studies suggest that several classes of analytes may be used to detect rejection with greater sensitivity and in earlier stages than traditional methods, possibly when coupled with artificial intelligence. Here, we provide an overview of the latest efforts in optimizing the diagnosis of rejection in liver transplantation.
Are MELD and MELDNa Still Reliable Tools to Predict Mortality on the Liver Transplant Waiting List?
Authors: Tejedor Marta , Selzner Nazia , Berenguer Marina
Published: May 2022

Liver transplantation is the only curative treatment for end-stage liver disease. Unfortunately, the scarcity of donor organs and the increasing pool of potential recipients limit access to this life-saving procedure. Allocation should account for medical and ethical factors, ensuring equal access to transplantation regardless of recipient’s gender, race, religion, or income. Based on their short-term prognosis prediction, model for end-stage liver disease (MELD) and MELD sodium (MELDNa) have been widely used to prioritize patients on the waiting list for liver transplantation resulting in a significant decrease in waiting list mortality/removal. Recent concern has been raised regarding the prognostic accuracy of MELD and MELDNa due, in part, to changes in recipients’ profile such as body mass index, comorbidities, and general condition, including nutritional status and cause of liver disease, among others. This review aims to provide a comprehensive view of the current state of MELD and MELDNa advantages and limitations and promising alternatives. Finally, it will explore future options to increase the donor pool and improve donor-recipient matching.
Therapeutic effect of anti-HMGB1 antibody in a mouse model of 4-h middle cerebral artery occlusion: comparison with tissue plasminogen activator
Authors: Nakano Takafumi , Tagashira Yui , Egashira Saki , Morimoto Mayuka , Irie Keiichi , Hosokawa Masato , Hayashi Toshinobu , Egawa Takashi , Hayakawa Kazuhide , Mishima Kenichi
Published: May 2022

Objective

Delayed tissue plasminogen activator (tPA) treatment increases the risk of intracerebral hemorrhage in patients with ischemic stroke. We previously demonstrated that tPA treatment caused hemorrhagic complications in a 4-h middle cerebral artery occlusion (MCAO) mouse model when administered after reperfusion. In the present study, we administered an anti-high mobility group box 1 (αHMGB1) antibody to 4-h MCAO mice to evaluate the usability of αHMGB1 antibody treatment in the delayed phase of ischemia, beyond the therapeutic time window of tPA.

Methods

αHMGB1 antibody, tPA and control IgG were dissolved in normal saline and administered intravenously into the tail vein of the mice after reperfusion. Infarct volume, hemorrhagic volume, brain swelling, functional outcomes and levels of pro-inflammatory cytokines, such as HMGB1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, were evaluated 24 h after MCAO.

Results

tPA treatment was not only ineffective but also caused a massive intracerebral hemorrhage. Treatment with αHMGB1 antibody reduced the infarct volume and swelling and ameliorated neurologic impairment and motor coordination without hemorrhagic complications by inhibiting HMGB1 activity. Moreover, the αHMGB1 antibody suppressed pathways of secondary inflammatory responses, such as IL-6 and TNF-α, after cerebral ischemia.

Conclusion

These results indicate that αHMGB1 antibody may be therapeutically efficient in the delayed phase of ischemia, where tPA treatment is no longer an eligible option. Treatment with an αHMGB1 antibody may be an effective therapeutic option in patients who exceed the tPA therapeutic time window.
Extracellular application of the N-methyl-D-aspartate receptor allosteric modulator rapastinel acts remotely to regulate Ca2+ inactivation at an intracellular locus
Authors: Zhang Xiao-lei , Berglund Nils A. , Burgdorf Jeffrey S. , Donello John E. , Moskal Joseph R. , Stanton Patric K.
Published: May 2022

Background

A novel N-methyl-D-aspartate receptor (NMDAR) allosteric modulator, rapastinel (RAP, formerly GLYX-13), elicits long-lasting antidepressant-like effects by enhancing long-term potentiation (LTP) of synaptic transmission. RAP elicits these effects by binding to a unique site in the extracellular region of the NMDAR complex, transiently enhancing NMDAR-gated current in pyramidal neurons of both hippocampus and medial prefrontal cortex.

Methods

We compared efficacy of RAP in modulating Schaffer collateral-evoked NMDAR-currents as a function of kinetics of the Ca2+ chelator in the intracellular solution, using whole-cell patch-clamp recordings. The intracellular solution contained either the slow Ca2+ chelator EGTA [3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecane-1,14-dioic acid, 0.5 mmol/l] or the 40–500-fold kinetically faster, more selective Ca2+ chelator BAPTA {2,2′,2″,2‴-[ethane-1,2-diylbis(oxy-2,1-phenylenenitrilo)] tetraacetic acid, 5 mmol/l}. NMDAR-gated currents were pharmacologically isolated by bath application of the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptor antagonist 6-nitro-2,3-dioxo-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (10 μmol/l) plus the GABA receptor blocker bicuculline (20 μmol/l).

Results

When the slow Ca2+ chelator EGTA was in the intracellular solution, RAP elicited significant enhancement of NMDAR-gated current at a 1 μmol/l concentration, and significantly reduced current at 10 μmol/l. In contrast, when recording with the 40–500-fold kinetically faster, more selective Ca2+ chelator BAPTA, NMDAR current increased in magnitude by 84% as BAPTA washed into the cell, and the enhancement of NMDAR current by 1 μmol/l RAP was completely blocked. Interestingly, the reduction in NMDAR current from 10 μmol/l RAP was not affected by the presence of BAPTA in the recording pipette, indicating that this effect is mediated by a different mechanism.

Conclusion

Extracellular binding of RAP to the NMDAR produces a novel, long-range reduction in affinity of the Ca2+ inactivation site on the NMDAR C-terminus accessible to the intracellular space. This action underlies enhancement in NMDAR-gated conductance elicited by RAP.
Hippocampal proteins discovery of diabetes-induced central neuropathy based on proteomics
Authors: Zhao Ying , Huan Shuai , Yang Yang , Gao Weiying , Wang Jie
Published: May 2022

Objectives

Growing evidence suggests that diabetes can cause multifactorial damage to the central nervous system (CNS) and may lead to dementia. However, the underlying mechanism of diabetes-induced central neuropathy remains sparse. In recent years, proteomics has provided better methods and means in analyzing the molecular mechanisms of disease. We applied proteomics to investigate the changes of hippocampal proteins in diabetic rats, with a view to discover the biomarkers of diabetes-induced central neuropathy and elucidated the potential biological relationships.

Methods

Male Wistar rats were randomly divided into the control group and model group. The model group rats were injected intraperitoneally with streptozotocin. Morris water maze test was performed to evaluate the learning and memory of rats, and the hippocampus was taken out. Proteomics were adopted to investigate the changes of differentially expressed proteins.

Results

Compared with the control group, the escape latency of the diabetic rats was significantly increased (P < 0.01, P < 0.05). It was presented that four differentially expressed proteins might be the potential biomarkers of diabetes-induced central neuropathy: septin 5, GRB2 related binding protein 2 (GAB2), casein kinase 1ε (CK1ε), aquaporin 4 (AQP4). These differentially expressed proteins were mainly involved in the following signaling pathways: apoptosis, glycine/serine/threonine metabolic and GTPase signaling pathway.

Conclusions

These findings provided reference insights into the underlying molecular pathogenesis of diabetes-induced CNS neuropathy.
Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses
Authors: Hagan T. , Gerritsen B. , Tomalin LE. , Fourati S. , Mulè MP. , Chawla DG. , Rychkov D. , Henrich E. , Miller HER. , Diray-Arce J. , Dunn P. , Lee A. ,   The Human Immunology Project Consortium (HIPC), Levy O. , Gottardo R. , Sarwal M. M. , Tsang JS. , Suárez-Fariñas M. , Sékaly RP. , Kleinstein SH. , Pulendran B.
Published: May 2022

Systems biology approaches have been used to define molecular signatures and mechanisms of immunity to vaccination. However, most such studies have been done with single vaccines, and comparative analysis of the response to different vaccines is lacking. We integrated temporal transcriptional data of over 3,000 samples, obtained from 820 healthy adults across 28 studies of 13 different vaccines and analyzed vaccination-induced signatures associated with the antibody response. Most vaccines induced similar kinetics of shared transcriptional signatures, including signatures of innate immunity occurring 1-3 days post-vaccination, as well as the canonical plasmablast and cell cycle signatures appearing 7 days post-vaccination. However, the yellow fever vaccine YF-17D uniquely induced an early transient signature of T and B cell activation at Day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at Days 7 and 14-21, respectively. Thus, despite the shared transcriptional response to most vaccines, at any given time point there was no evidence for a “universal signature” that could be used to predict the antibody response to all vaccines. However, accounting for the asynchronous nature of responses led to the identification of a time-adjusted signature that improved prediction antibody of responses across vaccines. These results provide a transcriptional atlas of the human immune response to vaccination and define a common, time-adjusted signature of antibody responses to vaccination.
Unlocking the strength of inducible promoters in gram-negative bacteria
Authors: Carrillo Rincón Andrés Felipe , Farny Natalie G.
Published: May 2022

Inducible promoters, such as the lac and tet promoters, are ubiquitous biotechnology tools. Inducible bacterial promoters have a consistent architecture including two key elements: the operator region recognized by the transcriptional regulator proteins (e.g., LacI and TetR, and the -10 and -35 consensus sequences required to recruit the sigma (σ) subunits of RNA polymerase to initiate transcription. Despite their widespread use in molecular biology, there remain problems with current inducible expression systems. Leaky transcription in the OFF state remains a particular challenge. Here we have updated the architecture of the lac and tet expression systems to improve their strength, control, and portability. We modified the genetic architecture of the lac and tet expression systems to contain consensus -10 and -35 sequence boxes to be strongly targeted by σ70, to incorporate of a strong ribosome binding site recognized broadly by gram-negative bacteria, and to independently control of the transcriptional regulators by optimized constitutive promoters. To test the promoters, we use the far-red fluorescent protein mCardinal, which we demonstrate significantly improves the signal-to-background ratio of promoter measurement assays over widely utilized green fluorescent proteins. We validate the improvement in OFF state control and inducibility by demonstrating production of the toxic and aggregate-prone cocaine esterase enzyme CocE. We further demonstrate portability of the promoters to additional gram-negative species Pseudomonas putida and Vibrio natriegens. Our results represent a significant improvement over existing protein expression systems that will enable advances in protein production for various biotechnology applications.

Significance

Many of the latest advances in pharmaceuticals, materials, and foods involve the production of recombinant proteins from bacterial hosts. However, the regulated production of enzymes and functional protein products that are toxic to their microbial hosts remains a challenge. Our work provides new tools that enable tight control over expression of protein products in bacterial host strains. We show that our tools function not only in the broadly utilized Escherichia coli, but also in other gram-negative bacteria including the soil organism Pseudomonas putida and the marine bacterium Vibrio natriegens. Our technology will facilitate more efficient production of a broader range of protein products in diverse microbial hosts.
Predicting individual skill learning, a cautionary tale
Authors: Abeles Dekel , Hertzage Jasmine , Shahar Moni , Censor Nitzan
Published: May 2022

People show vast variability in skill learning. What determines a person’s individual learning ability? In this study we explored the possibility to predict participants’ future learning, based on their behavior during initial skill acquisition. We recruited a large online multi-session sample of participants performing a sequential tapping skill learning task. We trained machine learning models to predict future skill learning from raw data acquired during initial skill acquisition, and from engineered features calculated from the raw data. While the models did not explain learning, strong correlations were observed between initial and final performance. In addition, the results suggest that in correspondence with other empirical fields testing human behavior, canonical experimental tasks developed and selected to detect average effects may constrain insights regarding individual variability, relevant for real-life scenarios. Overall, implementing machine learning tools on large-scale data sets may provide a powerful approach towards revealing what differentiates between high and low innate learning abilities, paving the way for learning optimization techniques which may generalize beyond motor skill learning to broad learning abilities.