bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic cycles of accumulation and chaos in the world capitalist system: a missing link
Authors: Galanis Giorgos , Koutny Christian , Weber Isabella 
Published: April 2024

Abstract
We re-examine the systemic cycles of accumulation (SCA) of Arrighi (2010) and Arrighi and Silver (1999) which provide a framework for the analysis of the cyclical patterns of geographical expansion of trade and production and the related shifts of hegemonic power within the world capitalist system. Within the SCA framework, the last stage of a hegemonic cycle is characterized by what is called ‘systemic chaos’. However, the drivers of these dynamics have not been explicitly analyzed. This article fills this gap by providing a link between the accumulation process and systemic chaos. Introducing the logistic map into the SCA analysis, our approach provides the missing detailed understanding of how systemic chaos is an outcome of the contradictory socioeconomic dynamics of capital accumulation itself while being based on the key insights of the SCA framework of hegemonic cycles.
Pathogenesis of sleep-disordered breathing in the setting of opioid use: a multiple mediation analysis using physiology
Authors: Orr Jeremy E , Malhotra Atul , Gruenberg Eli , Marin Traci , Sands Scott A , Alex Raichel M , Owens Robert L , Schmickl Christopher N 
Published: April 2024

Abstract

Study Objectives
Opioid medications are commonly used and are known to impact both breathing and sleep and are linked with adverse health outcomes including death. Clinical data indicate that chronic opioid use causes central sleep apnea, and might also worsen obstructive sleep apnea. The mechanisms by which opioids influence sleep-disordered breathing (SDB) pathogenesis are not established.

Methods
Patients who underwent clinically indicated polysomnography confirming SDB (AHI ≥ 5/hour) were included. Each patient using opioids was matched by sex, age, and body mass index (BMI) to three control individuals not using opioids. Physiology known to influence SDB pathogenesis was determined from validated polysomnography-based signal analysis. PSG and physiology parameters of interest were compared between opioid and control individuals, adjusted for covariates. Mediation analysis was used to evaluate the link between opioids, physiology, and polysomnographic metrics.

Results
One hundred and seventy-eight individuals using opioids were matched to 534 controls (median [IQR] age 59 [50,65] years, BMI 33 [29,41] kg/m2, 57% female, and daily morphine equivalent 30 [20,80] mg). Compared with controls, opioids were associated with increased central apneas (2.8 vs. 1.7 events/hr; p = .001) and worsened hypoxemia (5 vs. 3% sleep with SpO2 &lt; 88%; p = .013), with similar overall apnea–hypopnea index. The use of opioids was associated with higher loop gain, a lower respiratory rate (RR), and higher RR variability. Higher loop gain and increased RR variability mediated the effect of opioids on central apnea, but did not mediate the effect on hypoxemia.

Conclusions
Opioids have multi-level effects impacting SDB. Targeting these factors may help mitigate the deleterious respiratory consequences of chronic opioid use.
Co-culture of RhoA-overexpressed microtia chondrocytes and adipose-derived stem cells in the construction of tissue-engineered ear-shaped cartilage
Authors: Wu Yi , Wang Jian , Li Xiu , Wang Kang , Huang Zonglin , Wang Qian , Fu Xin , Jiang Haiyue , Pan Bo , Xiao Ran 
Published: April 2024

Abstract
Microtia is a congenital auricle dysplasia with a high incidence and tissue engineering technology provides a promising strategy to reconstruct auricles. We previously described that the engineered cartilage constructed from microtia chondrocytes exhibited inferior levels of biochemical and biomechanical properties, which was proposed to be resulted of the decreased migration ability of microtia chondrocytes. In the current study, we found that Rho GTPase members were deficient in microtia chondrocytes. By overexpressing RhoA, Rac1, and CDC42, respectively, we further demonstrated that RhoA took great responsibility for the decreased migration ability of microtia chondrocytes. Moreover, we constructed PGA/PLA scaffold-based cartilages to verify the chondrogenic ability of RhoA overexpressed microtia chondrocytes, and the results showed that overexpressing RhoA was of limited help in improving the quality of microtia chondrocyte engineered cartilage. However, coculture of adipose-derived stem cells (ADSCs) significantly improved the biochemical and biomechanical properties of engineered cartilage. Especially, coculture of RhoA overexpressed microtia chondrocytes and ADSCs produced an excellent effect on the wet weight, cartilage-specific extracellular matrix, and biomechanical property of engineered cartilage. Furthermore, we presented that coculture of RhoA overexpressed microtia chondrocytes and ADSCs combined with human ear-shaped PGA/PLA scaffold and titanium alloy stent fabricated by CAD/CAM and 3D printing technology effectively constructed and maintained auricle structure in vivo. Collectively, our results provide evidence for the essential role of RhoA in microtia chondrocytes and a developed strategy for the construction of patient-specific tissue-engineered auricular cartilage.
Brain Function and Pain Interference after Pediatric Intensive Interdisciplinary Pain Treatment
Authors: Epp Spencer , Walker Andrew , Boudes Elodie , Bray Signe , Noel Melanie , Rayner Laura , Rasic Nivez , Miller Jillian Vinall 
Published: April 2024

Background and Objectives:
Intensive interdisciplinary pain treatments (IIPTs) are programs that aim to improve functioning in youth with severe chronic pain. Little is known about how the brain changes following IIPT, however, decreased brain responses to emotional stimuli have been identified previously in pediatric chronic pain relative to healthy controls. We examined whether IIPT increased brain responses to emotional stimuli, and whether this change was associated with a reduction in pain interference.

Methods:
Twenty youth with chronic pain aged 14-18 years were scanned using fMRI, pre- and post-IIPT. During the fMRI, patients were presented with emotional stimuli (i.e., faces expressing happiness/fear), neutral expressions, and control (i.e., scrambled) images. Patients completed a measure of pain interference pre- and post-IIPT. Paired t-tests were used to examine differences in brain activation in response to emotional versus neutral stimuli, pre- to post-IIPT. Data from significant brain clusters were entered into linear mixed models to examine the relationships between brain activation and impairment pre- and post-IIPT.

Results:
Patients demonstrated a decrease in middle frontal gyrus (MFG) activation in response to emotional stimuli (happy + fear) relative to scrambled images, between pre- and post-IIPT (P<0.05). Lower MFG activation was associated with lower pain interference, pre- and-post IIPT (P<0.05).

Conclusion:
Contrary to our hypothesis, IIPT was associated with a reduction in MFG activation to emotional stimuli, and this change was associated with reduced pain interference. The MFG is a highly interconnected brain area involved in both pain chronification and antinociception. With further validation of these results, the MFG may represent an important biomarker for evaluating patient treatment response and target for future pain interventions.
An Interpretable Machine Learning Approach to Predict Survival Outcomes in Spinal and Sacropelvic Chordomas
Authors: Karabacak Mert , Carr Matthew T. , Schupper Alexander J. , Bhimani Abhiraj D. , Steinberger Jeremy , Margetis Konstantinos 
Published: April 2024

Study Design.
Retrospective, population-based cohort study.

Objective.
This study aimed to develop machine learning (ML) models to predict five-year and 10-year mortality in spinal and sacropelvic chordoma patients and integrate them into a web application for enhanced prognostication.

Summary of Background Data.
Past research has uncovered factors influencing survival in spinal chordoma patients. While identifying individual predictors is important, personalized survival predictions are equally vital. Though prior efforts have resulted in nomograms aiming to serve this purpose, they cannot capture complex interactions within data and rely on statistical assumptions that may not fit real-world data.

Methods.
Adult spinal and sacropelvic chordoma patients were identified from the National Cancer Database. Sociodemographic, clinicopathologic, diagnostic, and treatment-related variables were utilized as predictive features. Five supervised ML algorithms (TabPFN, CatBoost, XGBoost, LightGBM, and Random Forest) were implemented to predict mortality at five and 10 years postdiagnosis. Model performance was primarily evaluated using the area under the receiver operating characteristic (AUROC). SHapley Additive exPlanations (SHAP) values and partial dependence plots provided feature importance and interpretability. The top models were integrated into a web application.

Results.
From the NCDB, 1206 adult patients diagnosed with histologically confirmed spinal and sacropelvic chordomas were retrieved for the five-year mortality outcome [423 (35.1%) with five-year mortality] and 801 patients for the 10-year mortality outcome [588 (73.4%) with 10-year mortality]. Top-performing models for both of the outcomes were the models created with the CatBoost algorithm. The CatBoost model for five-year mortality predictions displayed a mean AUROC of 0.801, and the CatBoost model predicting 10-year mortality yielded a mean AUROC of 0.814.

Conclusions.
This study developed ML models that can accurately predict five-year to 10-year survival probabilities in spinal chordoma patients. Integrating these interpretable, personalized prognostic models into a web application provides quantitative survival estimates for a given patient. The local interpretability enables transparency into how predictions are influenced. Further external validation is warranted to support generalizability and clinical utility.
No-touch saphenous vein: current understanding of the conduit ‘less handled’
Authors: Deng Mimi X. , Lee Grace S. , Vervoort Dominique , Fremes Stephen E. 
Published: April 2024

Purpose of review
The no-touch technique is an established method to harvest the saphenous vein (NT-SV), which is the most commonly used conduit in coronary artery bypass grafting. Herein, we summarize the foundational evidence, as well as highlight recent innovations and ongoing clinical trials involving NT-SV.

Recent findings
Through preservation of perivascular tissue for atraumatic handling and omission of manual distension, the NT-SV maintains endothelial nitrous oxide synthase levels and experiences less vascular smooth muscle cell activation, which translates to slower progression of atherosclerosis and less size mismatch of the graft and target vessel. These biomolecular advantages allow NT-SV to provide superior graft patency compared to conventional skeletonized saphenous vein and approximating that of the radial artery. Nonetheless, the clinical benefits of NT-SV for mortality and reduction in major adverse cardiac and cerebrovascular events are insufficiently studied in the long-term. The drawback of NT-SV is the short-term harvest site complications, which may potentially be addressed by the advent of endoscopic no-touch technique.

Summary
NT-SV is a promising conduit, and its role will be further clarified in upcoming clinical trials and as follow-up lengthens. However, conduit selection and harvest technique should ultimately be personalized to the individual patient.
Effectiveness and safety of remimazolam combined with alfentanil in hysteroscopic examination: A prospective, randomized, single-blind trial
Authors: Huang Bei , Li Nan-Ping , Tan Gang-Kai , Liang Na 
Published: April 2024

Background:
Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50).

Methods:
Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0.2 mg/kg remimazolam (group A), 0.25 mg/kg remimazolam besylate (group B), 0.3 mg/kg remimazolam (group C), and 2 mg/kg propofol (group D), with 52 patients in each group. One minute after losing consciousness, patients received an intravenous injection of alfentanil at 5 µg/kg, followed by a continuous infusion of alfentanil at 0.5 µg/kg/min. If patients showed frowning, movement, or MOAA/S > 1, sedatives were added: 0.05 mg/kg/dose of remimazolam for groups A, B, and C, and 0.5 mg/kg/dose of propofol for group D. Step 2: Dixon’s up-and-down method was used to calculate the ED50 of remimazolam combined with alfentanil during hysteroscopic examination.

Main results:
The sedation success rates of the remimazolam groups were 88.46%, 94.23%, and 98.08%, respectively, compared to 96.15% in the propofol group, with no significant difference (P = .175). MAP in groups A and B was higher than in group D (P < .05), and significantly higher in group C than in group D (P = .0016). SpO2 values in groups A, B, and C were higher than in group D at T2 to T3 (P < .001). HR in groups A, B, and C was significantly higher than in group D (P < .001). The ED50 of remimazolam combined with alfentanil in hysteroscopy was 0.244 mg/kg, 95%CI (0.195–0.22) and ED95 was 0.282 mg/kg, 95%CI (0.261–1.619).

Conclusion:
In hysteroscopy, the sedative effect of remimazolam is like that of propofol, with 0.25 mg/kg remimazolam showing better safety and efficacy, and less impact on the respiratory and circulatory systems. Additionally, under the influence of alfentanil, the ED50 of remimazolam in hysteroscopy is 0.244 mg/kg, with no severe adverse reactions observed.
Transverse spinal cord infarction following immunoglobulin treatment in a patient with exfoliative dermatitis: A case report
Authors: Zhang Lili , He Lanying , Huang Jing , Ren Sixie , Wang Jian 
Published: April 2024

Rationale:
Transverse spinal cord infarction (SCI) is rare but highly disabling. Aortic thrombosis was described as one of the most common etiologies. Thromboembolic complications associated with intravenous immunoglobulin (IVIG) have been reported.

Patient concerns:
A previously well, 64-year-old man who was given the treatment of IVIG (0.4 g/kg/d for 5 days) for exfoliative dermatitis 2 weeks before, progressively developed flaccid paraplegia of lower extremities, loss of all sensations below T3 level and urinary incontinence within 50 minutes.

Diagnoses:
A diagnosis of SCI and pulmonary embolism was made. IVIG was considered the possible cause.

Interventions:
Anticoagulation treatment and continuous rehabilitation were administered.

Outcomes:
The neurologic deficiency of the patient was partially improved at the 3-year follow-up.

Lessons:
The rapid development of severe deficits within 4 hours mostly contributes to the diagnosis of SCI. Heightened awareness of possible thrombotic events is encouraged for a month-long period following IVIG therapy.
A Practical guide to selecting and using new Crohn's disease therapies
Authors: Scoville Elizabeth A. , Horst Sara N. 
Published: April 2024

Purpose of review
This review details the three new agents, including two novel mechanisms of action, approved to treat Crohn's disease in recent years. We review efficacy, safety, prescribing information, and available data on positioning these new therapies.

Recent findings
Risankizumab and upadacitinib are novel mechanisms of action approved to treat moderate to severe Crohn's disease. Risankizumab targets the cytokine interleukin-23. Upadacitinib is a selective Janus kinase-1 inhibitor approved for use in individuals who have previously failed or are intolerant to an anti-TNF agent. Subcutaneous infliximab provides a novel method of administering maintenance dosing of a longstanding and efficacious therapy.

Summary
Risankizumab has shown efficacy in both biologic naïve and biologic experienced populations. The SEQUENCE trial shows superiority of risankizumab over ustekinumab for disease response in patients who have previously failed an anti-tumor necrosis factor agent. Upadacitinib has shown good efficacy in clinical trials even in the setting of a mandated steroid taper during induction. Subcutaneous infliximab maintenance therapy appears noninferior to i.v. infliximab and shows good treatment persistence in real world transitions. Additional data is needed to better understand how to position these therapies.
Comparing Video Head Impulse Testing in Patients With Acute Vestibular Dysfunction
Authors: Mochizuki Fumihiro , Ito Yusuke , Sasano Yoshiyuki , Williams Erin , Hoffer Michael E. , Komori Manabu , Koizuka Izumi 
Published: April 2024

Objective:
The video head impulse test (v-HIT) can evaluate the function of all semicircular canals (SCCs) in a short period. In this work, we sought to compare v-HIT results among 2 commercially available devices, the ICS impulse (Otometrics, Denmark) (ICS) and Eye See Cam (Interacoustics, Denmark) (ESC), among individuals with unilateral vestibular disorders.

Design:
Retrospective study (n = 15).

Setting:
St. Marianna University School of Medicine Hospital.

Patients:
Fifteen patients with acute unilateral vestibular disorders.

Intervention:
Two v-HIT devices were conducted across patients to compare the results of the 2 models.

Main Outcome Measures:
Gain values and pathological saccades for each SCC were compared across the 2 models. Monothermal caloric testing was performed to compare alongside v-HIT gain values.

Results:
There was no difference between the 2 models for the evaluation of the horizontal SCCs. There was a significant negative correlation (ESC: r = −0.52, ICS: r = −0.53) between caloric testing and the gain values of the 2 models. In the vertical SCCs, the gain values of ESC were significantly higher than the gain values of ICS. Detection of catch-up saccades in vertical SCCs was similar across the 2 models.

Conclusion:
For the horizontal SCCs, there was no difference in test results between the 2 models. However, in the vertical SCCs, gain values were variable across the 2 devices. Larger scale studies are needed to develop normative ranges for the vertical canals.
Bioisosteric analogs of MDMA with improved pharmacological profile
Authors: Alberto-Silva Ana Sofia , Hemmer Selina , Bock Hailey A. , Alves da Silva Leticia , Scott Kenneth R. , Kastner Nina , Bhatt Manan , Niello Marco , Jäntsch Kathrin , Kudlacek Oliver , Bossi Elena , Stockner Thomas , Meyer Markus R. , McCorvy John D. , Brandt Simon D. , Kavanagh Pierce , Sitte Harald H. 
Published: April 2024

Abstract3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is re-emerging in clinical settings as a candidate for the treatment of specific psychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile.In vitromethods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubation with isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry.In silicomethods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin and dopamine transporters (hSERT and hDAT, respectively) but decreased activity at 5-HT2A/2B/2Creceptors. Regarding their hepatic metabolism, they differed from MDMA, withN-demethylation being the only metabolic route shared, and without forming phase II metabolites. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA analogs might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT and hDAT, but displaying a reduced activity at 5-HT2A/2B/2Creceptors and reduced hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.
Somatic embryogenesis of grapevine (Vitis vinifera) expresses a transcriptomic hourglass
Authors: Koska Sara , Leljak-Levanić Dunja , Malenica Nenad , Villi Kian Bigović , Futo Momir , Čorak Nina , Jagić Mateja , Tušar Anja , Kasalo Niko , Domazet-Lošo Mirjana , Vlahoviček Kristian , Domazet-Lošo Tomislav 
Published: April 2024

AbstractAt the molecular level, multicellular eukaryotic lineages and bacterial biofilms show predictable evolutionary footprints in their development. For instance, the zygotic embryogenesis ofArabidopsis, which is initiated by gamete fusion, shows hourglass-shaped ontogeny-phylogeny correlations at the transcriptome level. However, many plants are capable of yielding a fully viable next generation by somatic embryogenesis — a comparable developmental process that usually starts by the embryogenic induction of a diploid somatic cell. This leads to the question: is the hourglass-shaped ontogeny-phylogeny correlation preserved in somatic embryogenesis? To explore the correspondence between ontogeny and phylogeny in this alternative developmental route in plants, we developed a new and highly efficient model of somatic embryogenesis in grapevine (Vitis vinifera) and sequenced its developmental transcriptomes. By combining the evolutionary properties of grapevine genes with their expression values, which were recovered from early induction until the formation of juvenile plants, we found a strongly supported hourglass-shaped developmental trajectory. However, in contrast to zygotic embryogenesis inArabidopsiswhere the torpedo stage was evolutionary the most inert, we found that in the somatic embryogenesis of grapevine the heart stage expressed evolutionary the oldest and the most conserved transcriptome. This is a surprising finding because it suggests a better evolutionary system-level analogy between animal development and plant somatic embryogenesis than zygotic embryogenesis. We conclude that macroevolutionary logic is deeply hardwired in plant ontogeny and that somatic embryogenesis is likely a primordial embryogenic program in plants.
Punctuational evolution is pervasive in distal site metastatic colonization
Authors: Butler George , Amend Sarah R. , Axelrod Robert , Venditti Chris , Pienta Kenneth J. 
Published: April 2024

AbstractThe evolution of metastasis represents a lethal stage of cancer progression. Yet, the evolutionary kinetics of metastatic disease remain unresolved. Here, using single cell CRISPR-Cas9 lineage tracing data, we show that in metastatic disease, gradual molecular evolution is punctuated by episodes of rapid evolutionary change associated with lineage divergence. By measuring punctuational effects across the metastatic cascade, we show that punctuational effects contribute more to the molecular diversity at distal site metastases compared to the paired primary tumor, suggesting qualitatively different modes of evolution may drive primary and metastatic tumor progression. This is the first empirical evidence for distinct patterns of molecular evolution at early and late stages of metastasis and demonstrates the complex interplay of cell intrinsic and extrinsic factors that shape lethal cancer.