bluuebunny/crossref_metadata_2025_split huggingface dataset:
New insights in the targets of action of dimethyl fumarate in endothelial cells: effects on energetic metabolism and serine synthesis in vitro and in vivo
Authors: Ocaña Mª Carmen , Bernal Manuel , Yang Chendong , Caro Carlos , Domínguez Alejandro , Vu Hieu S. , Cárdenas Casimiro , García-Martín María Luisa , DeBerardinis Ralph J. , Quesada Ana R. , Martínez-Poveda Beatriz , Medina Miguel Ángel 
Published: October 2023

AbstractDimethyl fumarate is an ester from the Krebs cycle intermediate fumarate. This drug is approved and currently used for the treatment of psoriasis and multiple sclerosis, and its anti-angiogenic activity was reported some years ago. Due to the current clinical relevance of this compound and the recently manifested importance of endothelial cell metabolism on the angiogenic switch, we wanted to elucidate whether dimethyl fumarate has an effect on energetic metabolism of endothelial cells. Different experimental approximations were performed in endothelial cells, including proteomics, isotope tracing and metabolomics experimental approaches, in this work we studied the possible role of dimethyl fumarate in endothelial cell energetic metabolism. We demonstrate for the first time that dimethyl fumarate promotes glycolysis and diminishes cell respiration in endothelial cells, which could be a consequence of a down-regulation of serine and glycine synthesis through inhibition of PHGDH activity in these cells. Dimethyl fumarate alters the energetic metabolism of endothelial cells in vitro and in vivo through an unknown mechanism, which could be the cause or the consequence of its pharmacological activity. This new discovery on the targets of this compound could open a new field of study regarding the mechanism of action of dimethyl fumarate.
Protected areas reduce deforestation and degradation and enhance woody growth across African woodlands
Authors: McNicol Iain M. , Keane Aidan , Burgess Neil D. , Bowers Samuel J. , Mitchard Edward T. A. , Ryan Casey M. 
Published: October 2023

AbstractProtected areas are increasingly promoted for their capacity to sequester carbon, alongside biodiversity benefits. However, we have limited understanding of whether they are effective at reducing deforestation and degradation, or promoting vegetation growth, and the impact that this has on changes to aboveground woody carbon stocks. Here we present a new satellite radar-based map of vegetation carbon change across southern Africa’s woodlands and combine this with a matching approach to assess the effect of protected areas on carbon dynamics. We show that protection has a positive effect on aboveground carbon, with stocks increasing faster in protected areas (+0.53% per year) compared to comparable lands not under protection (+0.08% per year). The positive effect of protection reflects lower rates of deforestation (−39%) and degradation (−25%), as well as a greater prevalence of vegetation growth (+12%) inside protected lands. Areas under strict protection had similar outcomes to other types of protection after controlling for differences in location, with effect scores instead varying more by country, and the level of threat. These results highlight the potential for protected areas to sequester aboveground carbon, although we caution that in some areas this may have negative impacts on biodiversity, and human wellbeing.
Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients
Authors: Yuda Junichiro , Will Christine , Phillips Darren C. , Abraham Linu , Alvey Cory , Avigdor Abraham , Buck Wayne , Besenhofer Lauren , Boghaert Erwin , Cheng Dong , Cojocari Dan , Doyle Kelly , Hansen T. Matthew , Huang Kevin , Johnson Eric F. , Judd Andrew S. , Judge Russell A. , Kalvass John C. , Kunzer Aaron , Lam Lloyd T. , Li Rachel , Martin Ruth L. , Mastracchio Anthony , Mitten Mike , Petrich Adam , Wang Jin , Ward James E. , Zhang Haichao , Wang Xilu , Wolff Johannes E. , Bell-McGuinn Katherine M. , Souers Andrew J. 
Published: October 2023

Abstract
Background
MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

Methods
Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines. The ability of ABBV-467 to induce tumor growth inhibition was investigated in xenograft models of human multiple myeloma and acute myelogenous leukemia. The first-in-human study was a multicenter, open-label, dose-escalation study assessing safety, pharmacokinetics, and efficacy of ABBV-467 monotherapy.

Results
Here we show that administration of ABBV-467 to MCL-1-dependent tumor cell lines triggers rapid and mechanism-based apoptosis. In vivo, intermittent dosing of ABBV-467 as monotherapy or in combination with venetoclax inhibits the growth of xenografts from human hematologic cancers. Results from a clinical trial evaluating ABBV-467 in patients with multiple myeloma based on these preclinical data indicate that treatment with ABBV-467 can result in disease control (seen in 1 patient), but may also cause increases in cardiac troponin levels in the plasma in some patients (seen in 4 of 8 patients), without other corresponding cardiac findings.

Conclusions
The selectivity of ABBV-467 suggests that treatment-induced troponin release is a consequence of MCL-1 inhibition and therefore may represent a class effect of MCL-1 inhibitors in human patients.
The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension
Authors: Staehr Christian , Aalkjaer Christian , Matchkov Vladimir V. 
Published: October 2023

Abstract
In the vascular wall, the Na,K-ATPase plays an important role in the control of arterial tone. Through cSrc signaling, it contributes to the modulation of Ca2+ sensitivity in vascular smooth muscle cells. This review focuses on the potential implication of Na,K-ATPase-dependent intracellular signaling pathways in severe vascular disorders; ischemic stroke, familial migraine, and arterial hypertension. We propose similarity in the detrimental Na,K-ATPase-dependent signaling seen in these pathological conditions. The review includes a retrospective proteomics analysis investigating temporal changes after ischemic stroke. The analysis revealed that the expression of Na,K-ATPase α isoforms is down-regulated in the days and weeks following reperfusion, while downstream Na,K-ATPase-dependent cSrc kinase is up-regulated. These results are important since previous studies have linked the Na,K-ATPase-dependent cSrc signaling to futile recanalization and vasospasm after stroke. The review also explores a link between the Na,K-ATPase and migraine with aura, as reduced expression or pharmacological inhibition of the Na,K-ATPase leads to cSrc kinase signaling up-regulation and cerebral hypoperfusion. The review discusses the role of an endogenous cardiotonic steroid-like compound, ouabain, which binds to the Na,K-ATPase and initiates the intracellular cSrc signaling, in the pathophysiology of arterial hypertension. Currently, our understanding of the precise control mechanisms governing the Na,K-ATPase/cSrc kinase regulation in the vascular wall is limited. Understanding the role of vascular Na,K-ATPase signaling is essential for developing targeted treatments for cerebrovascular disorders and hypertension, as the Na,K-ATPase is implicated in the pathogenesis of these conditions and may contribute to their comorbidity.
Understanding biochemistry: basic aspects of statistics for life sciences
Authors: Reid Donald 
Published: October 2023

Abstract
If the biological world is one thing it is variable. As scientists we seek to measure, quantify and explain the causes of this variation. The approach we take to this is remarkably similar whether our research is exploring global temperature, blood pressure, cancer incidence or enzyme kinetics. This approach involves defining clear research questions and applying statistical methods to answer them robustly. This article will introduce a practical example that will be used throughout, specifically whether genetic variation can explain variation in coffee consumption. We assume little experience with statistics and walk through the statistical approach that biologists can use, firstly by describing our data with summary statistics and then by using statistical tests to help arrive at answers to our research question. A General Linear Model (GLM) approach will be used as this is what many common statistical tests are. We explore how to visualise and report results, while checking the assumptions of our analysis. The better we can understand and apply statistics to biological problems, the better we can communicate results and future research to others. The popular statistical programming language R will be used throughout.
Personalized federated learning via directed acyclic graph based blockchain
Authors: Huang Chenglong , Liu Erwu , Wang Rui , Liu Yan , Zhang Hanfu , Geng Yuanzhe , Wang Jie , Han Shaoyi 
Published: October 2023

AbstractCommon federated learning (FL) lacks consideration of clients' personalized requirements, which performs poorly for the scenario with data and resource heterogeneity. In order to overcome the challenge of heterogeneous characteristics, this letter proposes a novel decentralized personalized federated learning (PFL) architecture that first utilizes a directed acyclic graph (DAG) blockchain technology to achieve PFL efficiently, which is called PFLDAG. Simulation results demonstrate that PFLDAG approximately improves accuracy by 80% compared with the classic Google FedAvg algorithm, and by 10% compared with IFCA cluster PFL which considers personalized requirements. In addition, the approach also substantially improves the convergence speed.
Three‐dimensional metal‐only phoenix cell and its application for reflectarrays
Authors: An Zhihang , Makdissy Tony , Garcia Vigueras María , Vaudreuil Sébastien , Gillard Raphaël 
Published: October 2023

AbstractA 3D metal‐only waveguide‐based phoenix cell for reflectarray is presented. The proposed cell consists of two concentric square waveguides and a metallic block in the centre, which offers two operation modes. The first mode uses its cross section to tune reflection phase while the second mode varies the heights of two waveguides to manipulate reflection phase. The principle of the two different modes is analysed in detail. A metal‐only reflectarray antenna at 20 GHz is designed based on the first mode of the phoenix cell. It is fabricated using selective laser melting 3D printing technology. A good agreement between simulations and measurements is achieved. The measured gain at 19.75 GHz is 30.25 dBi with an aperture efficiency of 51.17% respectively. Also, the measured 1‐dB gain bandwidth is 15% (19–22 GHz). A dual band metal‐only reflectarray operating at 20 and 25 GHz is designed based on the second mode of the phoenix cell. The two metal‐only reflectarray antennas fully demonstrate the capabilities of the proposed 3D metal‐only phoenix cell.
Acquired Thrombocytopenia in Contemporary Transcatheter Aortic Valve Prosthesis
Authors: Petrov Asen , Taghizadeh-Waghefi Ali , Diab Abdel-Hannan , Breuer Linda , Arzt Sebastian , Matschke Klaus Ehrhard , Alexiou Konstantin 
Published: October 2023

Abstract
Background Postprocedural thrombocytopenia is a known phenomenon following transcatheter aortic valve implantation (TAVI). The aim of this study is to evaluate whether postinterventional platelet kinetics differ when comparing the current generation of balloon-expandable valve (BEV) and self-expanding valve (SEV) prostheses.
Methods We performed a retrospective analysis of patients undergoing TAVI at our facility between 2017 and 2019. Patients were stratified according to the type of prosthesis used: BEV or SEV. Hematocrit-corrected platelet counts were calculated to account for dilution. Nadir platelet counts (lowest recorded platelet count), drop platelet counts (DPC; highest relative platelet drop from baseline), and severity of thrombocytopenia during the discourse and at discharge were assessed.
Results Of the 277 included patients, 212 received SEV and 65 BEV. BEV patients were younger (81.8 ± 4.4 years vs 79.7 ± 6.8 years, p = 0.03). Further demographic characteristics were similar between groups. Implanted SEV were larger (p < 0.001) and had shorter procedural times (p < 0.01). There were no significant differences in postprocedural discourse. Postinterventional platelet drop was more pronounced in BEV patients in several evaluated metrics: mean DPC (24.3 ± 10.9% vs 18.8 ± 14.8%, p < 0.01), patients with DPC > 30% (n = 19, 29.2%, vs n = 33, 15.6%, p = 0.02), and also when comparing platelet kinetics.
Conclusion Despite improvements in outcome, the current generation of balloon-expandable TAVI prostheses carries a predisposition for postprocedural thrombocytopenia even when the effects of dilution are accounted for.
Concepts, Terminology, and Innovations in Follicular Unit Excision Hair Restoration Surgery
Authors: Gupta Aditya K. , Polla Ravi Shruthi 
Published: October 2023

AbstractFollicular unit excision (FUE) has emerged as the preferred method for hair transplants. Standardized terms and definitions established by members of the International Society of Hair Restoration Surgery and prominent hair restoration surgeons have become the standard, enabling effective knowledge sharing. This chapter provides an overview of the terminology relating to the field.The historical evolution of FUE and its pivotal role in modern hair transplantation is summarized. Anatomical terminology and graft-related definitions follow, providing insights into the scalp's complex structures and graft characteristics. The subsequent sections detail the terminology associated with graft excision and extraction, shedding light on the precise techniques and procedures employed. An exploration of various FUE techniques and the evolving landscape of FUE devices underscores the continual refinement of hair restoration practices. The chapter proceeds to discuss the “safe'” scalp donor zones, donor assessment terminology, and elements in identifying the optimal donor area for a successful FUE procedure. Additionally, punch dynamics and technique characteristics are examined, emphasizing their pivotal role in achieving superior FUE outcomes. The chapter concludes by discussing the classification of punches and graft evaluation terms, offering insights into the tools, and criteria used to assess graft quality and viability.
Evaluation of a Bidentate ‘Clamp-Like’ Halogen-Bond Donor Motif Based on Iodonium(III) Moieties
Authors: Huber Stefan M. , Reinhard Dominik L. , Kutzinski Dana , Hatta Masahito , Engelage Elric 
Published: October 2023

AbstractA new motif for iodine(III)-based halogen-bond donors consisting of a 1,3-phenylene core and two cyclic five-membered diaryliodonium(III) wings was designed and its potential as a catalyst was evaluated. Its properties were analyzed in the solid state by X-ray crystallography and in solution by benchmark catalytic activation of a nitro-Michael addition between 5-methoxyindole and trans-β-nitrostyrene.
Desmopressin Dose Requirements in Adults with Congenital and Acquired
Central Diabetes Insipidus
Authors: Pedersen Aslak Nykjær , Andreassen Mikkel , Rasmussen Aase Krogh , Krogh Jesper 
Published: October 2023

AbstractCentral diabetes insipidus is a rare disorder characterized by a deficiency of
vasopressin. The first line drug to treat this disorder is a synthetic analogue
of vasopressin, desmopressin.The primary aim of this retrospective register
study was to compare desmopressin dose requirements in patients with acquired
and congenital DI, and secondly to assess the influence of BMI on dose
requirement and risk of hyponatremia with different drug administrations. We
included all patients with suspected DI attending the endocrine department at
Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were
included whereof 130/222 (58.6%) were females and median age was
53 years (IQR 35 to 63). The etiology included 7/222 (3.2%)
congenital and 215/222 (96.8%) acquired. After converting nasal
and sublingual doses to equivalent oral doses, the median daily dose requirement
was 600 μg in patients with congenital etiology compared to
200 μg in patients with acquired etiology (p=0.005). We
found no association between BMI and desmopressin dose requirements
(p=0.6). During the past 12 months, 66/215 (30.7%) had
sodium levels<136 mmol/l including 20/215
(9.3%) with sodium levels<131 mmol/l. No
increased risk of hyponatremia was found, when nasal and oral were compared
(p=0.9). Daily desmopressin dose requirements were higher in patients
with congenital DI compared to patients with acquired DI. However, this result
was associated with uncertainty due to the small congenital group. BMI did not
influence daily dose requirements and nor did type of administration influence
the risk of hyponatremia.
Acquired Hemophilia A: A Rare, Acquired Coagulopathy in the Postpartum Setting
Authors: Oberlin Austin , Krenitsky Nicole M. , Gandhi Christy , Akpan Imo Joseph , Eisenberger Andrew , Landau Ruth , Yurteri-Kaplan Ladin , Nathan Lisa , Sheen Jean-Ju , LaSala Anita , D'Alton Mary 
Published: October 2023

AbstractPostpartum hemorrhage (PPH) remains a leading cause of maternal morbidity. Pregnancy-associated acquired hemophilia A (AHA) caused by autoantibodies against factor VIII can present with recurrent episodes of postpartum bleeding.
Case 1 A 50-year-old G2P0112 presented with vaginal bleeding 22 days postcaesarean. She underwent dilation and curettage, hysterectomy, and interventional radiology (IR) embolization before AHA diagnosis. She was hospitalized for 32 days and received 23 units of blood product. She remains without relapse of AHA after 5 years.
Case 2 A 48-year-old G3P1021 presented with vaginal bleeding 8 days postcaesarean. She underwent three surgeries and IR embolization before AHA diagnosis. She was hospitalized for 18 days and received 39 units of blood product. Prednisone and cyclophosphamide were continued after discharge.AHA is a rare cause of PPH. An isolated prolonged activated partial thromboplastin time (aPTT) should prompt further workup in postpartum patients with refractory bleeding. Rapid recognition of AHA can prevent significant morbidity related to hemorrhage, massive transfusion, and multiple surgeries.
Increased Body Mass Index is Associated with Worse Mid- To Long-Term Patient Outcomes after Surgical Repair of Multiligamentous Knee Injuries
Authors: Tan Danny , Ferrante Stephanie , DiBartola Alex , Magnussen Robert , Welder Eric , Crouser Nisha , Kaeding Christopher , Flanigan David , Duerr Robert A. 
Published: October 2023

AbstractWe evaluated the relationship between elevated body mass index (BMI) and mid- to long-term outcomes after surgical treatment of multiligamentous knee injury (MLKI). Records identified patients treated surgically for MLKI at a single institution. Inclusion criteria: minimum 2 years since surgery, complete demographics, surgical data, sustained injuries to two or more ligaments in one or both knees, and available for follow-up. Patients were contacted to complete patient-reported outcomes assessments and were classified according to mechanism of injury. Multivariate logistic regression analysis was used to predict the impact of BMI on outcome scores. A total of 77 patients (72.7% male) were included with a mean age at the time of injury of 29.4 ± 11.0 years and a mean BMI of 30.5 ± 9.4 kg/m2. The mean length of follow-up was 7.4 years. For each 10 kg/m2 increase in BMI, there is a 0.9-point decrease in Tegner activity scale (p = 0.001), a 5-point decrease in Knee Injury and Osteoarthritis Outcome Score (KOOS)-pain (p = 0.007), a 5-point decrease in KOOS-ADL (p = 0.003), a 10-point decrease in KOOS-QOL (p = 0.002), and an 11-point decrease in KOOS-Sport (p = 0.002). There were no significant correlations with BMI and Pain Catastrophizing Scale or Patient Health Questionnaire scores. Increasing BMI has a negative linear relationship with mid- to long-term clinical outcomes including pain, ability to perform activities of daily living, quality of life, and ability to perform more demanding physical activity after MLKI. BMI does not appear to have a significant relationship with knee swelling and mechanical symptoms or patients' mental health.
Oxidative C–H Sulfonylation of Hydrazones Enabled by Electrochemistry
Authors: Yang Qi-Liang , Lei Ping-Ping , Guo Hai-Ming , Hao Er-Jun , Zhang Bei-Ning , Zhou Hong-Hao , Li Wan-Wan 
Published: October 2023

AbstractAn efficient electrochemical oxidative C(sp2)–H sulfonylation of aldehyde hydrazones is described. A variety of sodium sufinates or sulfinic acids participate effectively in this protocol, which provides facile access to an array of alkyl and aromatic sulfonylated hydrazones with up to 96% yield. Large-scale synthesis and product derivatization show the potential utility of this methodology. Preliminary mechanistic investigations including radical-inhibition, electricity on/off experiments, and cyclic voltammetry support a radical pathway.
A lexical network approach to second language development
Authors: Chen Heng 
Published: October 2023

AbstractThis study investigates lexical development in second language (L2) learning from the perspective of complex dynamic system theory (CDST) using a complex network method. Based on authentic written output texts from L2 Chinese learners of different proficiency levels and language backgrounds, we successfully differentiate between different proficiency levels using a bi-gram lexical network model at a corpus level. A more in-depth investigation reveals that when compared to traditional lexical complexity indices, such as average word length and hapax legomena percentage (though Guiraud proves to be a robust predictor), the lexical network indices, such as network density and network clusters, provide a more profound understanding of L2 proficiency distinctions and a more precise approximation of the target language. Moreover, our findings illuminate the consistent manifestation of complex network characteristics within L2 Chinese lexical networks across all proficiency levels. Additionally, word association features, encompassing more than just word frequency information, provide comprehensive properties of the interlanguage system, as supported by their information gain values. We argue that studies within the CDST framework should integrate both lexical frequency and lexical network features to gain a comprehensive understanding of L2 lexical development.