bluuebunny/crossref_metadata_2025 huggingface dataset:
The first reported case of intravascular ultrasound-guided reverse overlapping stenting of a long calcified lesion using ultra-low contrast and metallic roadmaps: case report
Authors: Leesar Massoud A , Chen Shao-Liang
Published: December 2023

Background

Percutaneous coronary intervention (PCI) of a long calcified coronary lesion in patients with chronic kidney disease (CKD) is challenging and can lead to stent under-expansion and contrast-induced acute kidney injury (CI-AKI). We described the first case of intravascular ultrasound (IVUS)-guided reverse overlapping stenting of long calcified left anterior descending (LAD) coronary lesion using ultra-low contrast and the metallic roadmaps to prevent CI-AKI after PCI.

Case summary

A 77-year-old man with a history of hypertension, type 2 diabetes, and CKD was admitted with angina class 4 and ruled in for non-ST-elevation myocardial infarction. His ejection fraction was 40%. He was referred for cardiac catheterization and PCI. Coronary angiography showed a long calcified stenosis of the LAD. IVUS catheter was advanced at least 10 mm distal to the lesion or stent edge. IVUS images were obtained with automated pullback (1 mm/s) using a commercially available IVUS system with a 60-MHz mechanical transducer (Boston Scientific, Natick, Massachusetts). IVUS showed calcified plaque fractures after balloon angioplasty and intracoronary lithotripsy. The first stent was deployed proximally using the guidewire in the diagonal branch as a metallic roadmap, and the second stent was deployed distally overlapping at the distal edge of the first stent as a roadmap with no contrast injection. Percutaneous coronary intervention was completed successfully using only 12 mL contrast. Glomerular filtration rate remained stable after PCI. Glomerular filtration rate and ejection fraction improved at 12-month follow-up.

Discussion

We described the first case of the reverse overlapping stenting technique guided by IVUS with no contrast in a patient with CKD and a long calcified LAD lesion. Conventionally, in long lesions, the first stent is deployed distally and the second stent proximally, which requires contrast injection for stent deployment. We demonstrated that the above technique resulted in preventing CI-AKI and improving creatinine as well as ejection fraction at follow-up.
Factors predicting normalization of reproductive hormones after cessation of anabolic-androgenic steroids in men: a single center retrospective study
Authors: Grant Bonnie , Campbell John , Pradeep Anjali , Burns Angela D , Bassett Paul , Abbara Ali , Saket Priyadarshi , Minhas Sukhbinder , Dhillo Waljit S , McVeigh James , Bhasin Shalender , Jayasena Channa N
Published: December 2023

Objective

Symptomatic hypogonadism discourages men from stopping anabolic-androgenic steroids (AAS). Some men illicitly take drugs temporarily stimulating endogenous testosterone following AAS cessation (post-cycle therapy; PCT) to lessen hypogonadal symptoms. We investigated whether prior PCT use was associated with the normalization of reproductive hormones following AAS cessation.

Methods

Retrospective analysis of 641 men attending a clinic between 2015-2022 for a single, nonfasting, random blood test <36 months following AAS cessation, with or without PCT. Normalized reproductive hormones (ie, a combination of reference range serum luteinizing hormone, follicle-stimulating hormone, and total testosterone levels) were the surrogate marker of biochemical recovery.

Results

Normalization of reproductive hormones was achieved in 48.2% of men. PCT use was associated with faster biochemical recovery (13.0 (IQR8.0-19.0) weeks, PCT; 26.0 (IQR10.5-52) weeks, no-PCT; P < .001). Odds of biochemical recovery during multivariable analysis were: (1) higher with PCT (OR3.80) vs no-PCT (P = .001), in men stopping AAS ≤3 months previously; (2) reduced when 2 (OR0.55), 3 (OR0.46), or 4 (OR0.25) AAS were administered vs 1 drug (P = .009); (3) lower with AAS >6 vs ≤3 months previously (OR0.34, P = .01); (4) higher with last reported AAS >3 months (OR 5.68) vs ≤3 months (P = .001). PCT use was not associated with biochemical recovery in men stopping AAS >3 months previously.

Conclusion

Without evidence-based withdrawal protocols, men commonly try avoiding post-AAS hypogonadism with PCT, which is illicit, ill-defined, and not recommended. Only half of men had complete biochemical testicular recovery after stopping AAS. The surprising association of self-reported PCT use with short-term biochemical recovery from AAS-induced hypogonadism warrants further investigation.
The wreck of the Gloucester revisited
Authors: Holman Peter
Published: December 2023

The wreck of the frigate Gloucester off Norfolk on 6 May 1682 has always figured in histories of the Restoration period; it was taking James, Duke of York (the future James II and VII) to Edinburgh to collect his wife Mary of Modena and his daughter Princess Anne after his years of exile in Scotland. It has long been known that there were royal musicians on board, two of whom were drowned, though interest in the subject has been rekindled by the discovery of the wreck and an exhibition of artefacts from it in Norwich in 2023. Some other historic wrecks have proved to contain musical instruments, including the Mary Rose and several Dutch ships, though the Gloucester is unique in that a musical artefact—a brass trumpet mouthpiece—can be matched to documentary evidence concerning the musicians on board.

Court documents concerned with replacing lost instruments and compensating survivors and the families of victims show that those on board included four royal trumpeters and a kettledrummer (Walter Vanbright, who was drowned); a five-man group drawn from the Twenty-Four Violins, led by the composer Thomas Farmer and including Thomas Greeting (who was also drowned); and the oboist, recorder player and bass violinist James Paisible, who had apparently been working in Edinburgh in the Duke of York’s household. Paisible may have been a member of Farmer’s string group, though there is a possibility that he was accompanied by three other French musicians, forming a separate recorder/oboe consort. An anecdote concerning James rescuing the string player Edmund Flower from drowning throws light on the musical and religious politics on board the Gloucester: the earliest version, published in 1730, claimed wrongly that the duke ‘turn’d him out of his band because he would not turn Papist’.
Effect of an intensive lifestyle intervention on the structural and functional substrate for atrial fibrillation in people with metabolic syndrome
Authors: Rossello Xavier , Ramallal Raúl , Romaguera Dora , Alonso-Gómez Ángel M , Alonso Alvaro , Tojal-Sierra Lucas , Fernández-Palomeque Carlos , Martínez-González Miguel Ángel , Garrido-Uriarte María , López Luis , Díaz Agnes , Zaldua-Irastorza Olatz , Shah Amit J , Salas-Salvadó Jordi , Fitó Montserrat , Toledo Estefania
Published: December 2023

Aims

To evaluate the effect of an intensive lifestyle intervention (ILI) on the structural and functional cardiac substrate of atrial fibrillation (AF) in overweight or obese people with metabolic syndrome (Mets).

Methods and results

Participants of the PREvención con DIeta MEDiterranea-Plus trial (n = 6874) were randomized 1:1 to an ILI programme based on an energy-reduced Mediterranean diet, increased physical activity, and cognitive-behavioural weight management or to a control intervention of low-intensity dietary advice. A core echocardiography lab evaluated left atrial (LA) strain, function, and volumes in 534 participants at baseline, 3-year, and 5-year follow-ups. Mixed models were used to evaluate the effect of the ILI on LA structure and function. In the subsample, the baseline mean age was 65 years [standard deviation (SD) 5 years], and 40% of the participants were women. The mean weight change after 5 years was −3.9 kg (SD 5.3 kg) in the ILI group and −0.3 kg (SD 5.1 kg) in the control group. Over the 5-year period, both groups experienced a worsening of LA structure and function, with increases in LA volumes and stiffness index and decreases in LA longitudinal strain, LA function index, and LA emptying fraction over time. Changes in the ILI and control groups were not significantly different for any of the primary outcomes {LA emptying fraction: −0.95% [95% confidence interval (CI) −0.93, −0.98] in the control group, −0.97% [95% CI −0.94, −1.00] in the ILI group, Pbetween groups = 0.80; LA longitudinal strain: 0.82% [95% CI 0.79, 0.85] in the control group, 0.85% [95% CI 0.82, 0.89] in the ILI group, Pbetween groups = 0.24} or any of the secondary outcomes.

Conclusion

In overweight or obese people with Mets, an ILI had no impact on the underlying structural and functional LA substrate measurements associated with AF risk.
‘Single-shot’ pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy
Authors: Pu Sijia , Liu Fangzhou , Chen Yuhan , Luo Cihua , Li Peng , Chen Yanlin , Fu Lu , Liu Huiyi , Ye Xingdong , Wu Shulin , Xue Yumei , Lin Weidong
Published: December 2023

Aims

Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath.

Methods and results

A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury.

Conclusion

This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.
The Mediating Role of Proxy Respondents on the Relationship Between Cognitive Function and Self-Rated Health
Authors: Alberth Andrew G , Miller Edward Alan , Silverstein Nina M , Stokes Jeffrey , Su Yan-Jhu
Published: December 2023

Background and Objectives

Proxy respondents are an important tool in survey research, especially among people with cognitive impairment. However, proxy respondents may be unable to accurately answer subjective survey instruments for cognitively impaired persons. This study investigates the mediating effect of proxy status on the relationship between cognitive impairment and subjectively rated health.

Research Design and Methods

Respondents from the 2018 wave of the Health and Retirement Study (N = 17,146) were included, and the Baron and Kenny method assessed the potential mediating role of having a proxy on subjectively rated health. Subjectively rated health and proxy status were dichotomously coded, and relationships between cognitive impairment, proxy status, and subjectively rated health were assessed using logistic regression.

Results

Findings indicate that cognitive impairment is inversely associated with subjectively rated health, and it is directly associated with having a proxy. They also indicate that having a proxy is inversely related to subjectively rated health. When including proxy status and cognitive impairment in the same model, cognitive impairment no longer predicted subjectively rated health. This indicates that proxy status perfectly mediated the relationship between cognitive impairment and subjectively rated health.

Discussion and Implications

Measuring the experiences of people with cognitive impairment is challenging in survey research due to the limiting features of cognitive impairment. Although having a proxy respondent helps address attrition-related measurement challenges in survey research, findings indicate that proxies report worse subjectively rated health for people with cognitive impairment compared to individuals with comparable levels of cognitive impairment without a proxy. Future research may benefit from exploring optimal proxy-respondent characteristics.
Decadal comparisons identify the drivers of persistent changes in the zooplankton community structure in the northwest Atlantic
Authors: Pershing Andrew J , Kemberling Adam
Published: December 2023

Plankton community structure changes seasonally in response to the annual cycles of stratification, temperature, and primary productivity. These communities also change from year-to-year, in some cases exhibiting persistent regime shifts. How changes in physical conditions structure the plankton community and why conditions persist is a fundamental question in oceanography. Continuous plankton recorders have been used to sample the plankton community across the Gulf of Maine since 1961. Historically, this community has had a classic subarctic structure dominated by Calanus finmarchicus. However, during the 1990s, C. finmarchicus became less prominent, and a more diverse community of smaller copepods emerged. This shift was related to an influx of cold, low-salinity water. We show that a similar community shift occurred around 2012. We use high-resolution hydrographic data to link the shift to an influx of saltier water and warmer conditions. By comparing the 1990s with the recent decade, we develop a synthesis for how physical changes lead to community shifts. Our synthesis suggests that the link between the 1990s and 2010s is enhanced water column stratification. We further propose that ecological interactions link declines in C. finmarchicus with the emergence of the more diverse community, drawing parallels with classic food web ecology.
Assessing environmental and operational efficiencies: a multi-objective optimization problem in a two-stage network data envelopment analysis
Authors: Omid Azadeh , Azar Adel , Taleb Mushtaq
Published: December 2023

Accepted by: Ali Emrouznejad

The environmental efficiency of industries plays an important role in economic development of countries. Accordingly, dividing the internal network structure of industries into two sub-processes, including green and operational stages, enables decision-makers to assess both of the efficiencies simultaneously. Such assessment can be implemented using a non-parametric methodology termed data envelopment analysis (DEA). Standard DEA models consider the whole system of decision-making units (DMUs) as a single process (i.e. black-box). The black-box approach ignores modelling of the internal network structure of the assessed DMUs. This issue tackled by network DEA models since it considers the internal network structure of DMUs. In the network DEA, the efficiency evaluation of system stages is essential to identify its overall efficiency, resulting to a multi-objective optimization problem. Therefore, the network DEA is a widely welcomed methodology proposed for solving multi-objective problems. This paper assesses the operational and environmental efficiencies of a network structure system by converting the multi-objective optimization problem into a linear single objective function. In this investigation, a technique of tri-objective function problem is proposed. The proposed technique transforms into a single objective function by keeping one objective function and shifting the other two objective functions into the model’s constraints. The applicability and usefulness of the proposed technique have been tested using a data set of 20 industries. The developed approach provides valuable evaluations to decision-makers to rank DMUs by considering their green and operational efficiency simultaneously.
Analyzing Chinese banking performance with a trigonometric envelopment analysis for ideal solutions model
Authors: Antunes Jorge , Tan Yong , Wanke Peter
Published: December 2023

Accepted by: Prof. Ali Emrouznejad

Non-parametric data envelopment analysis (DEA) is susceptible to the curse of dimensionality, a challenge that can be mitigated through the use of the multi-criteria decision-making (MCDM) method. Conversely, DEA can overcome the limitations of the MCDM method by defining the weights of the decision-making unit to calculate the data envelop. This study addresses this issue by introducing a novel model, the Trigonometric Envelopment Analysis for Ideal Solutions (TEA-IS). TEA-IS combines DEA and the Technique for Order Performance by Similarity to Ideal Solution approaches. The proposed method is employed to assess the efficiency and performance of 367 Chinese banks over a 19-year period using various financial variables. The TEA-IS model leverages machine learning techniques to predict positive or negative outcomes for Chinese banks, taking into account various influencing factors. Our results indicate that TEA-IS scores demonstrate superior discriminatory power and reliability compared with non-parametric and MCDM methods. Furthermore, our findings reveal the presence of synergy amongst Chinese banks and illustrate a pattern of volatility in the Chinese banking industry’s performance. Notably, performance improved from 2000 to 2005, declined during the period from 2006 to 2013 and subsequently experienced a recovery until 2018. The majority of Chinese banks in the sample are categorized as medium performers with lower synergy levels. Additionally, the study underscores the positive impact of bank listing and age on bank performance, suggesting that regional banks outperform domestic ones.
Effect of directive laboratory comments on prescribing response to positive throat swab cultures
Authors: Bloomfield Max , van der Werff Koen , Todd Sue , Balm Michelle , Blackmore Tim
Published: December 2023

Background

In patients without ethnicity risk factors for acute rheumatic fever (ARF), our local guidelines recommend limiting antibiotic use following a positive throat swab culture (TSC). If symptoms are severe, a 5–7 day course is recommended. Despite this, most local patients with a positive TSC for group A Streptococcus (GAS) or Streptococcus dysgalactiae subsp. equisimilis (SDSE) were being prescribed 10 days of antibiotics. In response, we added comments to positive TSC reports recommending shorter treatment durations in those without ARF risk factors. No other antimicrobial stewardship initiatives were implemented.

Objectives

To assess the effect of these comments on antibiotic course duration after positive TSC.

Methods

All community TSC results from 1 October 2021 to 31 March 2023 (1 year pre- to 6 months post-change) were matched to antibiotic dispensing data. Patients who had been empirically dispensed an antibiotic prior to the culture report were excluded. The outcome of interest was the antibiotic duration dispensed in the 5 day period after the TSC report.

Results

Following introduction of the comments, median course duration reduced from 10 (IQR 5–10) to 7 days (IQR 0–10; P < 0.01) and from 7 (IQR 0–10) to 0 days (IQR 0–5; P < 0.01) following GAS- and SDSE-positive TSC, respectively, in those without ARF risk factors. The percentage of people receiving 10 days of antibiotics decreased from 63.0% to 37.0% (P < 0.01) and 41.2% to 14.6% (P < 0.01) for GAS and SDSE, respectively.

Conclusions

The introduction of comments providing direct prescribing advice to requestors appears to have been highly effective at improving guideline-compliant prescribing following positive TSC report.
Development of a Rapid Qualitative Screen for Anticoagulant Presence
Authors: Wong Selena , Slingerland Jenna , Dickerson Jane A , Pak Jennifer , Roach Gavin D , Saifee Nabiha H
Published: December 2023

Background

Direct oral anticoagulants (DOACs) and fondaparinux with stable pharmacokinetics are commonly used anticoagulants for outpatient care. Due to the lack of monitoring requirements, drug-specific assays are not available in most hospital laboratories, but drug levels are needed in some urgent/emergency situations. This study describes the development of a qualitative screen for the presence of DOAC or fondaparinux using coagulation tests found in most laboratories.

Methods

The DOAC screen is composed of a heparin anti-Xa activity assay and thrombin time (TT) assay. The STA®-Liquid-Anti-Xa assay calibrated with Stago Multi Hep® and STA®-TT were run on STA-R Max® analyzers. The anti-Xa activity and TT assays were repeated 5 times in samples of commercially available calibrators and controls for each drug: fondaparinux, dabigatran, rivaroxaban, apixaban, and edoxaban. Statistical analysis and correlations were performed for anti-Xa activity and TT results for each drug and pooled normal plasma.

Results

A significant correlation was found between heparin-calibrated anti-Xa levels and fondaparinux, rivaroxaban, apixiban, and edoxaban (r2 = 0.99–1.0). Dabigatran showed a strong linear correlation (r2 = 0.99) with TT. Anti-Xa levels >0.3 IU/mL and TT >25 seconds were determined as cutoffs at our lab for the detection of clinically relevant drug levels of factor Xa inhibitor and direct thrombin inhibitor, respectively.

Conclusions

Our study demonstrates that commonly available heparin anti-Xa activity and TT assays can be used to qualitatively detect DOACs and fondaparinux and provides a method to establish a qualitative interpretation.
Explainable Machine Learning Models for Rapid Risk Stratification in the Emergency Department: A Multicenter Study
Authors: van Doorn William P T M , Helmich Floris , van Dam Paul M E L , Jacobs Leo H J , Stassen Patricia M , Bekers Otto , Meex Steven J R
Published: December 2023

Background

Risk stratification of patients presenting to the emergency department (ED) is important for appropriate triage. Diagnostic laboratory tests are an essential part of the workup and risk stratification of these patients. Using machine learning, the prognostic power and clinical value of these tests can be amplified greatly. In this study, we applied machine learning to develop an accurate and explainable clinical decision support tool model that predicts the likelihood of 31-day mortality in ED patients (the RISKINDEX). This tool was developed and evaluated in four Dutch hospitals.

Methods

Machine learning models included patient characteristics and available laboratory data collected within the first 2 h after ED presentation, and were trained using 5 years of data from consecutive ED patients from the Maastricht University Medical Center (Maastricht), Meander Medical Center (Amersfoort), and Zuyderland Medical Center (Sittard and Heerlen). A sixth year of data was used to evaluate the models using area under the receiver-operating-characteristic curve (AUROC) and calibration curves. The Shapley additive explanations (SHAP) algorithm was used to obtain explainable machine learning models.

Results

The present study included 266 327 patients with 7.1 million laboratory results available. Models show high diagnostic performance with AUROCs of 0.94, 0.98, 0.88, and 0.90 for Maastricht, Amersfoort, Sittard and Heerlen, respectively. The SHAP algorithm was utilized to visualize patient characteristics and laboratory data patterns that underlie individual RISKINDEX predictions.

Conclusions

Our clinical decision support tool has excellent diagnostic performance in predicting 31-day mortality in ED patients. Follow-up studies will assess whether implementation of these algorithms can improve clinically relevant end points.
The Role of Artificial Intelligence for Providing Scientific Content for Laboratory Medicine
Authors: Wu Alan H B , Jaffe Allan S , Peacock William Franklin , Kavsak Pete , Greene Dina , Christenson Robert H
Published: December 2023

Background

Artificial intelligence (AI) promises to become an important tool in the practice of laboratory medicine. AI programs are available online that can provide concise medical and laboratory information within seconds after a question is submitted.

Methods

We posed the following contemporary and relevant question for clinical chemists using an AI program: “Should labs eliminate CK-MB testing?” The results of this inquiry were critically reviewed by a cardiologist, emergency department physician, and clinical laboratorians for accuracy and appropriateness.

Results

An AI report answering this question was generated within 15 s. The experts felt that the information was inaccurate with the statements that CK-MB results are released earlier than cardiac troponin (cTn), and are more useful for detection of myocardial injury in patients with renal insufficiencies. The summary omitted discussion on the ongoing debate for periprocedural detection of acute myocardial infarction (MI), the perceived value for detection of reinfarction, the value in risk stratification compared to cTn, the economic justification for testing both CK-MB and cTn, and medicolegal aspects of testing when results are discordant.

Conclusions

At this time, AI does not appear to be ready to be used by clinical laboratories for answering important practice questions.
Implementing Next-Generation Sequencing Process Changes to Increase Capacity and Improve Timeliness of Molecular Biomarker Profiling for Lung Cancer Patients
Authors: Semenuk Laura J , Kartolo Baskoro A , Feilotter Harriet E , Lee Shawna M , Savage Colleen A , Boag Alexander H , Digby Geneviève C , Mates Mihaela
Published: December 2023

Background

Faced with expansion of molecular tumor biomarker profiling, the molecular genetics laboratory at Kingston Health Science Centre experienced significant pressures to maintain the provincially mandated 2-week turnaround time (TAT) for lung cancer (LC) patients. We used quality improvement methodology to identify opportunities for improved efficiencies and report the impact of the initiative.

Methods

We set a target of reducing average TAT from accessioning to clinical molecular lab report for LC patients. Process measures included percentage of cases reaching TAT within target and number of cases. We developed a value stream map and used lean methodology to identify baseline inefficiencies. Plan-Do-Study-Act cycles were implemented to streamline, standardize, and automate laboratory workflows. Statistical process control (SPC) charts assessed for significance by special cause variation.

Results

A total of 257 LC cases were included (39 baseline January–May 2021; 218 post-expansion of testing June 2021). The average time for baseline TAT was 12.8 days, peaking at 23.4 days after expansion of testing, and improved to 13.9 days following improvement interventions, demonstrating statistical significance by special cause variation (nonrandom variation) on SPC charts.

Conclusions

The implementation of standardized manual and automated laboratory processes improved timeliness of biomarker reporting despite the increasing volume of testing at our center.
Merlin/NF2 regulates SLC7A11/xCT expression and cell viability under glucose deprivation at high cell density in glioblastoma cells
Authors: Yamaguchi Itsuki , Katoh Hironori
Published: December 2023

The cystine/glutamate transporter SLC7A11/xCT is highly expressed in many cancer cells and plays an important role in antioxidant activity by supplying cysteine for glutathione synthesis. Under glucose-depleted conditions, however, SLC7A11-mediated cystine uptake causes oxidative stress and cell death called disulfidptosis, a new form of cell death. We previously reported that high cell density (HD) promotes lysosomal degradation of SLC7A11 in glioblastoma cells, allowing them to survive under glucose-depleted conditions. In this study, we found that the neurofibromatosis type 2 gene, Merlin/NF2 is a key regulator of SLC7A11 in glioblastoma cells at HD. Deletion of Merlin increased SLC7A11 protein level and cystine uptake at HD, leading to promotion of cell death under glucose deprivation. Furthermore, HD significantly decreased SLC7A11 mRNA level, which was restored by Merlin deletion. This study suggests that Merlin suppresses glucose deprivation-induced cell death by downregulating SLC7A11 expression in glioblastoma cells at HD.
Sprouting of afferent and efferent inputs to pelvic organs after spinal cord injury
Authors: Zhao Shunyi , Tang Chuanxi , Weinberger Jeremy , Gao Dianshuai , Hou Shaoping
Published: December 2023

Neural plasticity occurs within the central and peripheral nervous systems after spinal cord injury (SCI). Although central alterations have extensively been studied, it is largely unknown whether afferent and efferent fibers in pelvic viscera undergo similar morphological changes. Using a rat spinal cord transection model, we conducted immunohistochemistry to investigate afferent and efferent innervations to the kidney, colon, and bladder. Approximately 3–4 weeks after injury, immunostaining demonstrated that tyrosine hydroxylase (TH)-labeled postganglionic sympathetic fibers and calcitonin gene-related peptide (CGRP)-immunoreactive sensory terminals sprout in the renal pelvis and colon. Morphologically, sprouted afferent or efferent projections showed a disorganized structure. In the bladder, however, denser CGRP-positive primary sensory fibers emerged in rats with SCI, whereas TH-positive sympathetic efferent fibers did not change. Numerous CGRP-positive afferents were observed in the muscle layer and the lamina propria of the bladder following SCI. TH-positive efferent inputs displayed hypertrophy with large diameters, but their innervation patterns were sustained. Collectively, afferent or efferent inputs sprout widely in the pelvic organs after SCI, which may be one of the morphological bases underlying functional adaptation or maladaptation.
Easier In than Out: Lessons Learned from the Termination of the Iraq Sanctions Regime
Authors: Grauvogel Julia , Attia Hana
Published: December 2023

Sanctions senders respond to the abrupt escalation of crises, such as the Iraqi invasion of Kuwait in 1990 or the Russian invasion of Ukraine in February 2022. To react quickly, they often decide on coercive measures without a long-term exit strategy in mind. Similarly, research has long prioritized questions of sanctions onset and effectiveness, while studies on their termination remain scarce. In response, we reconstruct previously neglected debates about ending sanctions for the “watershed case” of the UN embargo against Iraq. Based on a conceptual framework that emphasizes a more process-oriented and signaling perspective on sanctions termination, we analyze archival data as well as governmental and UN documents. We find that the United States depicted the lifting of sanctions as an all-or-nothing question, which impeded a more gradual approach toward ending the measures. We show that senders significantly disagreed over the requirements for ending sanctions and over whether possibly signaling the end of Iraq’s isolation was politically desirable. In the second step, we then draw implications from the case of Iraq to study contemporary sanctions termination. We use novel data on the termination of all EU, UN, and US sanctions from 1990 to 2018 to explore whether the Iraq case inspired changes in senders’ approaches. We find that the use of review provisions and sunset clauses significantly increased post-Iraq. Finally, we discuss whether disagreements over termination requirements in the case of Russia risk the repetition of past pitfalls when it comes to the process of ending sanctions.
Self-perceived leadership and entrepreneurship skills: profiling healthcare professionals
Authors: Sacre Hala , Iskandar Katia , Haddad Chadia , Shahine Mayssam , Hajj Aline , Zeenny Rony M , Akel Marwan , Salameh Pascale
Published: December 2023

Background

Healthcare is a complex system with overarching challenges that arise from the different hierarchically organized structures and the diversity of people interacting and communicating in the same environment. This complexity can be addressed by strengthening healthcare professional leadership and entrepreneurship competencies. This study aims to evaluate the self-perception of healthcare professionals regarding these skills and their association with demographic characteristics and university attributes.

Method

A cross-sectional survey conducted online from July to December 2021 recruited 245 Lebanese health professionals from different health-related institutions (hospitals, pharmaceutical industry, health professions universities, and others) using snowball sampling. A cluster analysis was performed based on the socio-demographic and work characteristics of the participants to classify their profiles. Bivariate and multivariate analyses were performed after ensuring the adequacy of the models. Significance was set at a P value < 0.05.

Results

Cluster analysis showed two distinct profiles, reflected by Cluster 1 for older individuals with moderate/high management versus Cluster 2 for younger people with low management profiles. The logistic regression showed that Cluster 1 was significantly associated with higher leadership with administrative, interpersonal, and conceptual skills. The interpersonal skills represented best Cluster 1 (ORa = 7.47), followed by the conceptual skills (ORa = 4.40). Linear regression analysis showed that Cluster 1 was significantly associated with higher decision-making (β = 0.69) and higher tolerance of ambiguity (β = 1.01). No association was found between other subscales, total entrepreneurship scales, and belonging to any cluster (P > 0.05).

Conclusion

Although most healthcare professionals showed moderate to high perceptions related to their leadership and entrepreneurship, younger ones were aware of the need to develop these skills to meet the challenges of the complex dynamic health system. Educating students and training professionals to acquire these skills would create value in emerging health services while fostering innovation, creativity, and quality improvement in the workplace.
Implementation and Perceived Effectiveness of Prospective Audit and Feedback and Preauthorization by US Pediatric Antimicrobial Stewardship Programs
Authors: Manice Christina S , Muralidhar Nivedita , Campbell Jeffrey I , Nakamura Mari M
Published: December 2023

Background

Antimicrobial stewardship programs (ASPs) promote optimal antimicrobial use to prevent resistance, improve outcomes, and reduce costs. We explored how pediatric ASPs enact prospective audit and feedback (PAF) and preauthorization and characterized programs’ perceptions of how these choices affected attainment of stewardship goals.

Methods

We conducted focus groups with US pediatric ASP practitioners, organized by predominant strategy: PAF, preauthorization, or a hybrid. We asked open-ended questions about organization, staffing, and operation of these strategies, as well as rationales for and perceived advantages and disadvantages of these choices. We used applied thematic analysis to analyze transcripts, organizing coded text into themes and categories. We formulated a conceptual model for how the design and performance of PAF and preauthorization affect stewardship goals and stewards’ work experiences.

Results

Eighteen physicians and 14 pharmacists from 24 hospitals participated in five focus groups. Stewards described myriad advantages and limitations of PAF and preauthorization that support or detract from stewardship goals. For example, PAF uncovered institutional trends in antibiotic use and fostered relationship building but was time-consuming. Preauthorization efficiently reduced broad-spectrum antimicrobial use, yet offered limited educational opportunities. How these strategies facilitated or impeded appropriate antimicrobial use in turn affected stewards’ professional satisfaction, creating a feedback loop that could reinforced positive or negative outcomes.

Conclusions

ASPs reported differing emphasis on and implementation of PAF and preauthorization. Each strategy entailed contrasting benefits and trade-offs for steward satisfaction and perceived efficacy, suggesting that a hybrid approach could enable ASPs to maximize strengths of each to mitigate drawbacks of the other.
Identification and estimation of causal peer effects using double negative controls for unmeasured network confounding
Authors: Egami Naoki , Tchetgen Tchetgen Eric J
Published: December 2023

Identification and estimation of causal peer effects are challenging in observational studies for two reasons. The first is the identification challenge due to unmeasured network confounding, for example, homophily bias and contextual confounding. The second is network dependence of observations. We establish a framework that leverages a pair of negative control outcome and exposure variables (double negative controls) to non-parametrically identify causal peer effects in the presence of unmeasured network confounding. We then propose a generalised method of moments estimator and establish its consistency and asymptotic normality under an assumption about ψ-network dependence. Finally, we provide a consistent variance estimator.
Unveiling hidden variability components in accreting X-ray binaries using both the Fourier power and cross-spectra
Authors: Méndez Mariano , Peirano Valentina , García Federico , Belloni Tomaso , Altamirano Diego , Alabarta Kevin
Published: December 2023

We present a novel method for measuring the lags of (weak) variability components in neutron-star and black-hole low-mass X-ray binaries (LMXBs). For this we assume that the power and cross-spectra of these sources consists of a number of components that are coherent in different energy bands, but are incoherent with one another. The technique is based on fitting simultaneously the power spectrum (PS) and the Real and Imaginary parts of the cross-spectrum (CS) with a combination of Lorentzian functions. We show that, because the PS of LMXBs is insensitive to signals with a large Imaginary part and a small Real part in the CS, this approach allows us to uncover new variability components that are only detected in the CS. We also demonstrate that, contrary to earlier claims, the frequency of the type-C quasi-periodic oscillation (QPO) in the black-hole binary GRS 1915+105 does not depend on energy. Rather, the apparent energy dependence of the QPO frequency can be explained by the presence of a separate QPO component with a slightly higher frequency than that of the QPO, whose rms amplitude increases faster with energy than the rms amplitude of the QPO. From all the above we conclude that, as in the case of the PS, the CS of black-hole and neutron-star binaries can be fitted by a combination of Lorentzian components. Our findings provide evidence that the frequency-dependent part of the transfer function of these systems can be described by a combination of responses, each of them acting over relatively well-defined time-scales. This conclusion challenges models that assume that the main contribution to the lags comes from a global, broadband, transfer function of the accreting system.
H3 K27M-altered glioma and diffuse intrinsic pontine glioma: Semi-systematic review of treatment landscape and future directions
Authors: van den Bent Martin , Saratsis Amanda M , Geurts Marjolein , Franceschi Enrico
Published: December 2023

H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors. This review will detail treatment interventions applied to diffuse midline glioma and diffuse intrinsic pontine glioma (DIPG) prior to the identification of the H3 K27M mutation, the current standard-of-care for H3 K27M-mutant diffuse glioma treatment, and ongoing clinical trials listed on www.clinicaltrials.gov evaluating novel therapeutics in this population. Current clinical trials were identified using clinicaltrials.gov, and studies qualifying for this analysis were active or ongoing interventional trials that evaluated a therapy in at least 1 treatment arm or cohort comprised exclusively of patients with DIPG and H3 K27M-mutant glioma. Forty-one studies met these criteria, including trials evaluating H3 K27M vaccination, chimeric antigen receptor T-cell therapy, and small molecule inhibitors. Ongoing evaluation of novel therapeutics is necessary to identify safe and effective interventions in this underserved patient population.
Effects of intermittent fasting combined with physical exercise on cardiometabolic outcomes: systematic review and meta-analysis of clinical studies
Authors: Kazeminasab Fatemeh , Baharlooie Maryam , Karimi Bahareh , Mokhtari Khatereh , Rosenkranz Sara K , Santos Heitor O
Published: December 2023

Context

Different intermittent fasting (IF) protocols have been proven to be efficient in improving cardiometabolic markers, but further research is needed to examine whether or not combining IF regimens plus physical exercise is superior to control diets (ie, nonfasting eating) plus physical exercise in this setting.

Objective

The aim of this study was to determine whether or not combining IF plus exercise interventions is more favorable than a control diet plus exercise for improving cardiometabolic health outcomes.

Data Source

PubMed, Scopus, and Web of Science were comprehensively searched until April 2023.

Data Extraction

Electronic databases were searched for clinical trials that determined the effect of IF plus exercise vs a control diet plus exercise on body weight, lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], triglycerides, and total cholesterol), and systolic and diastolic blood pressure (SBP and DBP, respectively). Analyses were conducted for IF plus exercise vs a nonfasting diet plus exercise to calculate weighted mean differences (WMDs).

Data Analysis

The meta-analysis included a total of 14 studies, with a total sample of 360 adults with or without obesity. The duration ranged from 4 to 52 weeks. IF plus exercise decreased body weight (WMD = –1.83 kg; P = 0.001), LDL (WMD = –5.35 mg/dL; P = 0.03), and SBP (WMD = –2.99 mm Hg; P = 0.003) significantly more than a control diet plus exercise. HDL (WMD = 1.57 mg/dL; P = 0.4) and total cholesterol (WMD = –2.24 mg/dL; P = 0.3) did not change significantly for IF plus exercise vs a control diet plus exercise, but there was a trend for reducing triglycerides (WMD = –13.13 mg/dL; P = 0.07) and DBP (WMD = 2.13 mm Hg; P = 0.05), which shows clinical magnitude.

Conclusion

IF plus exercise improved some cardiometabolic outcomes (body weight, blood pressure, and lipid profile) compared with a control diet plus exercise.

Systematic Review Registration

PROSPERO registration no. CRD42023423878.
Curcumin supplementation effect on liver enzymes in patients with nonalcoholic fatty liver disease: a GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials
Authors: Vajdi Mahdi , Hassanizadeh Shirin , Hassanizadeh Reza , Bagherniya Mohammad
Published: December 2023

Context

Clinical evidence from investigations of the effects of curcumin on liver enzymes in patients with nonalcoholic fatty liver disease (NAFLD) have led to inconsistent results.

Objective

The aim of this systematic review and meta-analysis was to investigate the overall effects of curcumin and curcumin plus piperine supplementation on liver enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) in patients with NAFLD.

Data Sources

The Scopus, Web of Science, PubMed, and Cochrane Library databases were searched from inception through July 2023, using search terms representing NAFLD and liver enzymes. Articles were screened independently by 2 researchers based on PICOS inclusion criteria.

Data Extraction

The following data were extracted: first author’s name, study location, year of publication, mean age, study duration, study design, participants’ sex, number of participants in each group, dose of curcumin supplementation, and ALT, ALP, and AST concentrations. Risk of bias was assessed using the Cochrane Collaboration’s modified risk-of-bias tool.

Data Analysis

Fixed- or random-effects meta-analysis was performed to estimate the effects of curcumin on liver enzymes, considering heterogeneity across studies. The I2 and Cochran’s Q tests were used to assess heterogeneity between studies.

Results

Overall, 15 randomized controlled trials comprising 905 participants were eligible for this meta-analysis. Curcumin supplementation significantly reduced ALT (weighted mean difference [WMD], –4.10, 95%CI, –7.16 to –1.04) and AST (WMD, –3.27; 95%CI, –5.16 to –1.39), but not ALP (WMD, –0.49; 95%CI, –1.79 to 0.82). Curcumin plus piperine supplementation had no significant effect on ALT (WMD, –3.79; 95%CI, –13.30 to 5.72), and AST (WMD, –1.1; 95%CI, –3.32 to 1.09).

Conclusions

Curcumin supplementation improved AST and ALT levels compared with the control group. However, better-designed randomized controlled trials with larger sample sizes and of higher quality are needed to assess the effects of curcumin on ALP.

Systematic Review Registration

PROSPERO registration no. CRD42023448231.
Mutational Signature Changes in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal
Authors: LaPelusa Michael , Cann Christopher , Ciombor Kristen K , Eng Cathy
Published: December 2023

Purpose

We examined the concordance of genetic mutations between pretreatment tumor tissue and posttreatment circulating tumor DNA (ctDNA) in patients with metastatic squamous cell carcinoma of the anal canal (SCCA) and assessed the impact of therapy on this concordance.

Methods

We analyzed next-generation sequencing reports from pretreatment tumor tissue and posttreatment ctDNA in 11 patients with metastatic SCCA treated at Vanderbilt University Medical Center between 2017 and 2021.

Results

Among the mutations identified in posttreatment ctDNA, 34.5% were also found in pretreatment tumor tissue, while 47.6% of pretreatment tumor tissue mutations were found in posttreatment ctDNA. Four patients had preservation of potentially actionable mutations in both pretreatment tissue and posttreatment ctDNA, while 7 patients had newly identified mutations in posttreatment ctDNA that were not present in pretreatment tumor tissue.

Conclusion

Patients with SCCA demonstrate a high degree of temporal mutational heterogeneity. This supports the hypothesis that ctDNA can serve as a real-time tracking mechanism for solid tumors’ molecular evolution in response to therapy. Our findings highlight the potential of ctDNA in identifying emerging actionable mutations, supplementing information from tissue-based genomic assessments. Further research, ideally with larger and multi-institutional cohorts, is needed to validate our findings in this relatively rare tumor type.