bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding migration power in international studies
Authors: Fernández-Molina Irene , Tsourapas Gerasimos
Published: October 2024

Where and how does power operate in the governance of international migration? Migrants and refugees are increasingly used for strategic purposes in international politics, but scholarship on this matter has yet to engage thoroughly with the central International Relations concept of power. This article draws on the thinking of Michael Barnett and Raymond Duvall to propose a well-rounded picture of the multiple forms of power in, through or against migration that are mobilized by states and other international actors. We thus conceptualize migration power across two relational dimensions: the nature of the social relations between the actors involved (interactive or constitutive) and the specificity of such relations (direct or diffuse). This leads us to distinguish between four complementary types of migration power—compulsory, institutional, structural and productive—and to identify the main causal mechanisms through which they operate. We argue that power in international migration governance is diffuse, wielded by a wide range of actors, unevenly spread across its different dimensions, and yet, deeply asymmetrical in its distribution along intersecting axes: namely global North vs South, as well as state vs non-state. Beyond academia, the recognition of this complexity can encourage more reflexivity in policy-making and more sensitivity among practitioners.
Estimating the fishing rate for maximum nutritional yield (FMNY) optimizes fish production for human health
Authors: Lӧfstedt Anneli , Kell Laurence T , de Roos Baukje , Fernandes Paul G
Published: October 2024

Fisheries management is largely based on the principle of achieving the maximum sustainable yield (MSY) with little regard for nutritional value. Management strategies maximizing nutrients rather than yield, however, may provide a smarter contribution to global food and nutrition security. Here, we present a novel fisheries management strategy: fishing at maximum nutritional yield (FMNY), the exploitation rate at which essential nutrients are maximized. Combining top-down population modelling approaches with bottom-up nutrient compositional analysis, we compared nutrient yields across seasons for Europe’s most valuable fishery (Atlantic mackerel, Scomber scombrus). FMNY estimates differed between nutrients, but were equal to, or lower than, FMSY. An autumn fishery provided higher amounts of lipids, omega-3 fatty acids, and protein, whereas vitamin D3, and calcium were maximized in winter. Aligning national fisheries policies and nutrition objectives is paramount to realising the potential of seafood in building healthier food systems. Developing novel fisheries management strategies, such as FMNY, where fisheries are optimised for human nutrition will, therefore, contribute to nutrient sustainability and help improve human health and diets.
Rights-Based Legal Considerations for Tuberculosis Isolation Practices in Community Settings in the Postpandemic Era
Authors: Bonomo Elizabeth J , Shah Maunank
Published: October 2024

State and local governments are free to enact infectious disease control laws to protect the public health but must conform those laws to right-based limitations imposed by the United States Constitution. Tuberculosis (TB) control laws that empower public health agencies and their representatives to institute restrictions on movement and activities for persons with TB have remained largely unchanged for decades and warrant review to ensure consistency with modern legal principles. During the coronavirus disease 2019 pandemic, there was increased attention to the tension between nonpharmaceutical public health interventions (masking, isolation, lockdowns) intended to reduce transmission and improve community health and their potential negative consequences on learning, mental health, individual finances, and the economy at large. Increasing evidence suggests that much of TB transmission is likely to have occurred prior to diagnosis and treatment initiation, and there is limited scientific evidence for the efficacy of community-based isolation in reducing TB incidence or TB mortality; by contrast, there is evidence that treatment rapidly reduces infectiousness and that prolonged isolation may have deleterious health and financial effects for persons with TB. The postpandemic era presents an opportunity to reassess public health authorities' legal obligations in designing voluntary and involuntary isolation policies for persons with tuberculosis. In so doing, state and local governments can recalibrate the balance between respect for individual constitutional rights and achieving public health TB goals.
Genomic Epidemiology of Extrapulmonary Nontuberculous Mycobacteria Isolates at Emerging Infections Program Sites—United States, 2019–2020
Authors: Masters Thao L , Toney Nadege Charles , Ewing Thomas O , McAllister Gillian A , Mathis Marsenia H , Grigg Cheri , Magill Shelley S , Jackson Kelly A , Byram Rebecca , See Isaac , Salfinger Max , Barter Devra , Johnston Helen , Lynfield Ruth , Vagnone Paula Snippes , Tourdot Laura , Anderson Bridget J , Dumyati Ghinwa , Pierce Rebecca , Lutgring Joseph D , Gargis Amy , McKay Susannah L
Published: October 2024

Background

Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections. Although isolation of NTM from clinical specimens has increased nationally, few studies delineated the molecular characteristics of extrapulmonary NTM.

Methods

Extrapulmonary isolates were collected by 4 Emerging Infections Program sites from October 2019 to March 2020 and underwent laboratory characterization, including matrix-assisted laser desorption ionization–time of flight mass spectrometry, Sanger DNA sequencing, and whole genome sequencing. Bioinformatics analyses were employed to identify species, sequence types (STs), antimicrobial resistance (AR), and virulence genes; isolates were further characterized by phylogenetic analyses.

Results

Among 45 isolates, the predominant species were Mycobacterium avium (n = 20, 44%), Mycobacterium chelonae (n = 7, 16%), and Mycobacterium fortuitum (n = 6, 13%). The collection represented 31 STs across 10 species; the most common ST was ST11 (M. avium, n = 7). M. fortuitum and Mycobacterium abscessus isolates harbored multiple genes conferring resistance to aminoglycosides, β-lactams, and macrolides. No known AR mutations were detected in rpoB, 16S, or 23S rRNAs. Slow-growing NTM species harbored multiple virulence genes, including type VII secretion components, adhesion factors, and phospholipase C.

Conclusions

Continued active laboratory- and population-based surveillance will further inform the prevalence of NTM species and STs, monitor emerging clones, and allow AR characterization.
Training in the symptothermal method to ameliorate unmet need for family planning: knowledge, attitudes and satisfaction
Authors: Igben-Pender Catherine E , Omemo Peter , Ng'wena Gideon
Published: October 2024

Background

Addressing the unmet need for family planning to prevent unintended pregnancies is a high priority for women's health, and training as an element of the symptothermal method (STM) is deemed to be an effective strategy. This study assessed training on knowledge, attitudes and satisfaction with STM to ameliorate the unmet need for family planning.

Methods

The study adopted a pre–post study design. A total of 136 women participated in this study. Knowledge and attitudes were assessed pre- and post-training as well as the level of satisfaction, using cycle charts and questionnaires. The χ2 test (p<0.05) was used to analyse data on sociodemographics, attitudinal characteristics and satisfaction. Paired samples t-test (p<0.05) was used to establish the mean difference of the two groups (knowledge and attitudes pre- and post-training).

Results

The paired samples t-test established that women have significant (t=−058.716, p=0.001) knowledge post-training (1.0000±0.00000) compared with pre-training (0.0682±0.01587) on STM. There was no significant (t=−1.419, p=0.158) difference in attitudes towards STM pre- and post-training. There was a significant level of satisfaction (p=0.001).

Conclusions

Our interventional study has enabled women to acquire robust knowledge, positive attitudes and satisfaction with the utilization of STM. This has ameliorated unmet need for family planning among participants.
Outsourcing Empire: International Monetary Power in the Age of Offshore Finance
Authors: Binder Andrea
Published: October 2024

Offshore finance allows foreign banks to create US dollars under the laws of an offshore jurisdiction. How and why does this affect international monetary power? Conceptually, I argue that offshore finance bifurcates across borders the shared power of the state and banks to create money, combining the US dollar with mostly English law. Empirically, I demonstrate that more US dollars are created offshore outside US jurisdiction than onshore within it. Offshore finance increases liquidity, at higher risk, and leads to a cross-border entanglement of issuing country, offshore financial centers, borrowers, and global banks. In short, offshore finance changes the power inherent in money. Consequently, international monetary power has become the ability to get access to offshore dollars in combination with the capacity to determine international liquidity and to set, select, or circumvent the related rules. It is constrained by the hierarchically organized social credit relations that money consists of. The international monetary power of the United States has become an instance of indirect rule with global banks having been delegated the prerogative of US dollar creation. As is common with indirect rule, it entails a difficult balancing act between geographical reach and centralization of power.
Policies, Places and Practices: Why Environmental Law Scholars Should Care About the Levelling-Up and Regeneration Act 2023
Authors: Ogden-Jones Rhiannon
Published: October 2024

The Levelling-Up and Regeneration Act 2023 has marked major reforms in how planning law legally conceptualises policies, places and practices. These reforms have an impact not only on the scope of planning law but also on the shape of environmental law in England and Wales. In particular, the Levelling-Up and Regeneration Act 2023 changes how different forms of national and local policy legally interact, creates new administrative regulation for protected landscapes and establishes a new framework for environmental impact assessment called the Environmental Outcome Reports. This introduction to the legislation illustrates the importance of understanding the planning law reform for environmental law scholarship more generally.
Thymic stromal lymphopoietin signaling in B cells from progenitors to plasma cells
Authors: Domeier Phillip P , Ziegler Steven F
Published: October 2024

Thymic stromal lymphopoietin is an established pleotropic alarmin cytokine that is generated at barrier tissues to induce type 2 immune responses, but its role in regulating the diversity of B cells is poorly understood. Here, we will highlight the key findings that underpin our limited understanding of the role thymic stromal lymphopoietin in modulating different stages of B cell development. We will also provide an overview of how thymic stromal lymphopoietin drives B cell-mediated immune disease and how novel thymic stromal lymphopoietin-blocking biologics could be used to modulate B cell responses. Thymic stromal lymphopoietin is critical for the regulation, diversity, and longevity of humoral immunity.
Clinical efficacy and safety of neoadjuvant chemotherapy with paclitaxel and cisplatin in combination with concurrent chemoradiotherapy for locally advanced cervical cancer: a systematic review and meta-analysis
Authors: Yeshe Penpa , Li Fang
Published: October 2024

The meta-analysis was to evaluate the therapeutic benefits of neoadjuvant chemotherapy (NACT), primarily consisting of platinum-based regimens in conjunction with paclitaxel, when integrated with concurrent chemoradiotherapy (CCRT) for individuals afflicted with locally advanced cervical cancer (LACC). The outcomes were determined by overall survival (OS), progression-free survival (PFS), complete response rate (CRR), objective response rate, recurrence rate and adverse events. The assessment of these outcomes was based on the relative risk (RR) accompanied by its 95% confidence interval (CI). Eight articles were included for analysis. LACC patients who underwent treatment with paclitaxel combined with cisplatin (TP)-based NACT in conjunction with CCRT demonstrated improved OS at 2 (RR: 1.11, 95% CI: 1.07, 1.16, P < 0.001), 3 (RR: 1.30, 95% CI: 1.23, 1.37, P < 0.001) and 5 years (RR: 1.20, 95% CI: 1.10, 1.32, P < 0.001), as well as PFS at 1 (RR: 1.03, 95% CI: 1.00, 1.06, P = 0.035), 2 (RR: 1.21, 95% CI: 1.04, 1.40, P = 0.012), 3 (RR: 1.26, 95% CI: 1.17, 1.34, P < 0.001) and 5 (RR: 1.39, 95% CI: 1.25, 1.55, P < 0.001) years, when compared with patients who received CCRT alone. Moreover, the TP-based NACT in conjunction with CCRT achieved a higher CRR and exhibited a lower rate of disease recurrence (RR:1.28, 95% CI:1.08, 1.50, P = 0.003). No significant differences in the risk of adverse effects including anemia, leukopenia, thrombocytopenia, radiocystitis and radiation enteritis between the group treated with TP-based NACT combined with CCRT and the group treated with CCRT alone were observed. The combination of TP-based NACT and CCRT demonstrates superior clinical efficacy than CCRT alone. This study may contribute to reducing the burden of LACC by using TP-based NACT plus CCRT.
Genomic and biochemical analyses of lipid biosynthesis in Cyanophora paradoxa: limited role of the chloroplast in fatty acid synthesis
Authors: Sato Naoki , Ikemura Eri , Uemura Mana , Awai Koichiro
Published: October 2024

Archaeplastida, a group of photosynthetic organisms with primary plastids, consists of green algae (plus land plants), red algae, and glaucophytes. In contrast to green and red algae, information on lipids and lipid biosynthesis is still incomplete in the glaucophytes. The chloroplast is the site of photosynthesis and fatty acid synthesis in all photosynthetic organisms known to date. However, the genomic data of the glaucophyte Cyanophora paradoxa indicated the lack of acetyl-CoA carboxylase and most components of fatty acid synthase in the chloroplast. Instead, multifunctional fatty acid synthase and acetyl-CoA carboxylase are likely to reside in the cytosol. To examine this hypothesis, we measured fatty acid synthesis in isolated chloroplasts and whole cells using stable isotope labeling. The chloroplasts had very low fatty acid synthesis activity, if any. Most processes of fatty acid synthesis, including elongation and desaturation, must be performed within the cytosol, and the fatty acids imported into the chloroplasts are assembled into the chloroplast lipids by the enzymes common to other algae and plants. Cyanophora paradoxa is a rare organism in which fatty acid synthesis and photosynthesis are not tightly linked. This could question the common origin of these two biosynthetic processes in Archaeplastida.
Lean methodology in health care practice: an example of application for clinical laboratory urinalysis processing
Authors: Kontautas Evaldas , Rajackaitė Ema , Jacikė Živilė , Šepetienė Ramunė
Published: October 2024

Background

Improving quality and laboratory testing turnaround time (TAT) is a constant challenge for a clinical laboratory. The formulas that describe the best way to manage these goals are outlined in International Organization for Standardization standards. According to standards, improvement must be timely and continuous. Lean methodology is a tool to meet this requirement. One of the fundamental elements of Lean is a systematic approach to process improvement by removing waste to create value for the end-user (eg, patient) of the service. This methodology can be adapted in resource-limited settings.

Objective

The aim of this study was to test the application of Lean methodology in urinalysis.

Methods

Lean has various collections of tools and concepts. We applied the most useful for the clinical laboratory: Gemba walk, Takt time, cycle time, and value-stream mapping. Finally, we created and approved workplace standards to improve the performance of urinalysis.

Results

We compared the TATs of urinalysis tests before optimization, immediately after, and long after (~5 months). We found that TATs had significantly shortened. The TATs of emergency (STAT) urine tests immediately after optimization improved: automated microscopy to 16% (P =.194), fully automated test-strip to 23% (P = .0172), and standardized urine sediment examination to 20% (P =.0048). The TATs of routine urine tests also improved immediately after optimization: automated microscopy to 18% (P <.0001), fully automated test-strip to 11% (P =.0025), and standardized urine sediment examination to 18% (P =.0011). After 5 months of Lean application within the urinalysis laboratory, TATs of routine urine tests remained improved; however, the improvement of STAT urine test TATs dropped to approximately 4%.

Conclusion

The application of the Lean methodology shows significant improvement in TATs of processes in our laboratory.
An Unexpected Descendant of Benjamin Hobson’s Chinese Treatise on Natural Philosophy: The Bowu Xinbian Tushuo (‘Illustrated Account of Natural Philosophy’, 1898)
Authors: Lu Di
Published: October 2024

The English medical missionary Benjamin Hobson (1816-1873) published one of his well known Chinese books, the Bowu Xinbian (‘Natural Philosophy’), in Canton in 1854. Over forty years later, Chen Xiutang produced a lesser known book in Shanghai, the Bowu Xinbian Tushuo (‘Illustrated Account of Natural Philosophy’, 1898). Both books contributed to the circulation of Western natural knowledge in Chinese society. Yet their relationship and the content of Chen’s book have never been explored. A comparative analysis of the two books reveals that the third part of Hobson’s book, authored by both Hobson and Chen, provided the basis of Chen’s own book. The removal of Chen’s name from the second edition of Hobson's book probably served as a major cause behind the publication of Chen’s book.
Operando Freezing Cryogenic Electron Microscopy of Active Battery Materials
Authors: Dutta Nikita S , Carroll Gerard Michael , Neale Nathan R , Han Sang-Don , Al-Jassim Mowafak , Jungjohann Katherine
Published: October 2024

Understanding structural and chemical evolution of battery materials during operation is critical to achieving safe, efficient, and long-lasting energy storage. Cryogenic electron microscopy (cryo-EM) has become a valuable tool in battery characterization, leveraging low temperatures to improve stability of sensitive materials under electron beam irradiation. However, typical cryo-EM sample preparations leave extended time between the electrochemical point of interest and ex situ freezing of samples, during which active structures may relax, degrade, or otherwise evolve. Here, we detail a method for operando freezing cryo-EM to preserve and characterize native electrode and interfacial structures that arise during battery cycling, based on an operando plunge freezer and cold sample removal process. We validate the method on multiple electrode materials and quantify and discuss the freezing rate achieved. Operando freezing cryo-EM can be used to directly visualize transient features that arise at active electrochemical interfaces, to enable deeper understanding of structural evolution and interfacial chemistry in batteries and other electrochemical systems.
Establishment of closed 35S ribosomal RNA gene chromatin in stationary Saccharomyces cerevisiae cells
Authors: Babl Virginia , Girke Philipp , Kruse Sebastian , Pinz Sophia , Hannig Katharina , Schächner Christopher , Hergert Kristin , Wittner Manuel , Seufert Wolfgang , Milkereit Philipp , Tschochner Herbert , Griesenbeck Joachim
Published: October 2024

As a first step in eukaryotic ribosome biogenesis RNA polymerase (Pol) I synthesizes a large ribosomal RNA (rRNA) precursor from multicopy rRNA gene loci. This process is essential for cellular growth and regulated in response to the cell’s physiological state. rRNA gene transcription is downregulated upon growth to stationary phase in the yeast Saccharomyces cerevisiae. This reduction correlates with characteristic changes in rRNA gene chromatin structure from a transcriptionally active ‘open’ state to a non-transcribed ‘closed’ state. The conserved lysine deacetylase Rpd3 was shown to be required for this chromatin transition. We found that Rpd3 is needed for tight repression of Pol I transcription upon growth to stationary phase as a prerequisite for the establishment of the closed chromatin state. We provide evidence that Rpd3 regulates Pol I transcription by adjusting cellular levels of the Pol I preinitiation complex component core factor (CF). Importantly, our study identifies CF as the complex limiting the number of open rRNA genes in exponentially growing and stationary cells.
Revisiting the y-ome of Escherichia coli
Authors: Moore Lisa R , Caspi Ron , Boyd Dana , Berkmen Mehmet , Mackie Amanda , Paley Suzanne , Karp Peter D
Published: October 2024

The model organism Escherichia coli K-12 has one of the most extensively annotated genomes in terms of functional characterization, yet a significant number of genes, ∼35%, are still considered poorly characterized. Initially genes without known functional understanding were given ‘y’ gene names. However, due to inconsistency in changing ‘y’ names to non-‘y’ names over the years, gene name alone does not provide sufficient information as to the characterization level of genes. Attempts to characterize y-ome genes, i.e. those that lack experimental evidence for function, are ongoing, and recent categorization based on the level of experimental evidence has helped clarify those genes that are well characterized versus uncharacterized. EcoCyc, the most comprehensive, curated genome database for E. coli K-12 substr. MG1655, has updated this approach by expanding the categories to include Partially characterized genes using a set of computational rules that includes keywords, experimental evidence codes and Gene Ontology terms. Approximately half of the previously categorized y-ome genes are now categorized as Partially characterized, leaving 15.5% (738) as Uncharacterized genes in EcoCyc. This new categorization scheme is searchable in the EcoCyc database, will be updated as new experimental evidence is curated and provides important information for research decisions.
OrgXenomics: an integrated proteomic knowledge base for patient-derived organoid and xenograft
Authors: Zhang Yintao , Lian Xichen , Xu Hangwei , Zhu Sisi , Zhang Hao , Ni Ziheng , Fu Tingting , Liu Shuiping , Tao Lin , Zhou Ying , Zhu Feng
Published: October 2024

Patient-derived models (PDMs, particularly organoids and xenografts) are irreplaceable tools for precision medicine, from target development to lead identification, then to preclinical evaluation, and finally to clinical decision-making. So far, PDM-based proteomics has emerged to be one of the cutting-edge directions and massive data have been accumulated. However, such PDM-based proteomic data have not been provided by any of the available databases, and proteomics profiles of all proteins in proteomic study are also completely absent from existing databases. Herein, an integrated database named ‘OrgXenomics’ was thus developed to provide the proteomic data for PDMs, which was unique in (a) explicitly describing the establishment detail for a wide array of models, (b) systematically providing the proteomic profiles (expression/function/interaction) for all proteins in studied proteomic analysis and (c) comprehensively giving the raw data for diverse organoid/xenograft-based proteomic studies of various diseases. Our OrgXenomics was expected to server as one good complement to existing proteomic databases, and had great implication for the practice of precision medicine, which could be accessed at: https://idrblab.org/orgxenomics/
MolBiC: the cell-based landscape illustrating molecular bioactivities
Authors: Ge Yichao , Yang Mengjie , Yu Xinyuan , Zhou Ying , Zhang Yintao , Mou Minjie , Chen Zhen , Sun Xiuna , Ni Feng , Fu Tingting , Liu Shuiping , Han Lianyi , Zhu Feng
Published: October 2024

The measurement of cell-based molecular bioactivity (CMB) is critical for almost every step of drug development. With the booming application of AI in biomedicine, it is essential to have the CMB data to promote the learning of cell-based patterns for guiding modern drug discovery, but no database providing such information has been constructed yet. In this study, we introduce MolBiC, a knowledge base designed to describe valuable data on molecular bioactivity measured within a cellular context. MolBiC features 550 093 experimentally validated CMBs, encompassing 321 086 molecules and 2666 targets across 988 cell lines. Our MolBiC database is unique in describing the valuable data of CMB, which meets the critical demands for CMB-based big data promoting the learning of cell-based molecular/pharmaceutical pattern in drug discovery and development. MolBiC is now freely accessible without any login requirement at: https://idrblab.org/MolBiC/.
Self-assembly and condensation of intermolecular poly(UG) RNA quadruplexes
Authors: Roschdi Saeed , Montemayor Eric J , Vivek Rahul , Bingman Craig A , Butcher Samuel E
Published: October 2024

Poly(UG) or ‘pUG’ dinucleotide repeats are highly abundant sequences in eukaryotic RNAs. In Caenorhabditis elegans, pUGs are added to RNA 3′ ends to direct gene silencing within Mutator foci, a germ granule condensate. Here, we show that pUG RNAs efficiently self-assemble into gel condensates through quadruplex (G4) interactions. Short pUG sequences form right-handed intermolecular G4s (pUG G4s), while longer pUGs form left-handed intramolecular G4s (pUG folds). We determined a 1.05 Å crystal structure of an intermolecular pUG G4, which reveals an eight stranded G4 dimer involving 48 nucleotides, 7 different G and U quartet conformations, 7 coordinated potassium ions, 8 sodium ions and a buried water molecule. A comparison of the intermolecular pUG G4 and intramolecular pUG fold structures provides insights into the molecular basis for G4 handedness and illustrates how a simple dinucleotide repeat sequence can form complex structures with diverse topologies.
The MdERF61-mdm-miR397b-MdLAC7b module regulates apple resistance to Fusarium solani via lignin biosynthesis
Authors: Zhou Zhe , Zhang Haiqing , Yao Jia-Long , Gao Qiming , Wang Yarong , Liu Zhenzhen , Zhang Yaru , Tian Yi , Yan Zhenli , Zhu Yanmin , Zhang Hengtao
Published: October 2024

Apple replant disease (ARD) is a worldwide problem that threatens the industry. However, the genetic mechanism underlying plant disease resistance against ARD remains unclear. In this study, a negative regulatory microRNA in Malus domestica, mdm-miR397b, and its direct target MdLAC7b (Laccase) was selected for examination based on our previous small RNA and degradome sequencing results. Overexpressing the mdm-miR397b-MdLAC7b module altered the lignin deposition and jasmonic acid contents in apple roots, which also led to increased resistance to Fusarium solani. Additionally, Y1H library screening using mdm-miR397b promoter recombinants identified a transcription factor, MdERF61, that represses mdm-miR397b transcriptional activity by directly binding to 2 GCC-boxes in the mdm-miR397b promoter. In summary, our results suggest that the MdERF61-mdm-miR397b-MdLAC7b module plays a crucial role in apple resistance to F. solani and offers insights for enhancing plant resistance to soil-borne diseases in apples.
The Weakness of Authoritarian Regimes: Rwanda as a Difficult But Convincing Case
Authors: Longman Timothy
Published: October 2024

The lack of academic attention to the functioning of authoritarian regimes has allowed an erroneous impression that dictatorships are inherently strong and stable. Marie-Eve Desrosiers uses the difficult case of Rwanda, whose 1994 genocide against the Tutsi has widely been seen as a sign of state strength, to demonstrate the fragility of authoritarian rule. Looking at the First and Second Republics, which governed Rwanda from 1962 until 1994, Desrosiers explores both the vulnerability of the regimes and how they adjusted over time in attempts to strengthen control. Desrosiers argues for greater awareness of shifting strategies and changes in governance across time, what she calls “authoritarian trajectories,” to better understand how authoritarian regimes actually work and how the public responds to them. Although not focused on the 1994 genocide, Desrosiers' analysis helps explain why genocide emerged as a strategy to shore up Rwanda's failing regime.
How Do Short-Term Incentives Affect Long-Term Productivity?
Authors: Almeida Heitor , Ersahin Nuri , Fos Vyacheslav , Irani Rustom M , Kronlund Mathias
Published: October 2024

Previous research shows that incentives to meet short-term earnings targets can cause firms to increase share buybacks, leading to cuts in investments and employment. Using plant-level census data, we find that incentives to engage in earnings-per-share-motivated buybacks result in lower productivity at both the plant and firm level. We attribute this productivity drop to two mechanisms: reduced investment in productivity-augmenting technology, and inefficient allocation of resources across a firm’s plants. We identify multiple frictions—including labor unions, financial constraints, agency problems, and adjustment costs—that can constrain efficient reallocations across plants and thus exacerbate the consequences of firms’ short-term incentives.
Demographics and clinical features associated with abnormal small bowel motility in systemic sclerosis
Authors: Cheah Jenice X , Perin Jamie , Hughes Michael , Mecoli Christopher A , Paik Julie J , Hummers Laura K , Shah Ami A , McMahan Zsuzsanna H
Published: October 2024

Objective

The small bowel is affected in up to 50% of systemic sclerosis (SSc) patients, and some patients experience severe complications. Our aim was to use specific statistical methods to compare demographic and clinical features of SSc patients with and without abnormal small bowel to better characterize patients at risk for this complication.

Methods

SSc patients with gastrointestinal symptoms were prospectively enrolled and underwent a scintigraphy-based whole gut transit (WGT) study. A cross-sectional analysis was performed comparing clinical features between patients with and without abnormal small bowel transit by WGT. Univariate logistic regression models and multivariable models were used to examine the relationship between clinical features and abnormal small bowel transit.

Results

Of 130 patients enrolled in this study, 22 had abnormal small bowel transit. SSc patients with abnormal small bowel transit were more likely to be male [odds ratio (OR) = 3.70; 95% CI: 1.07, 12.50; P = 0.038] and have more severe cardiac involvement (OR = 3.98; 95% CI: 1.10, 14.38; P = 0.035), while they were less likely to have sicca symptoms (OR = 0.30; 95% CI: 0.10, 0.94; P = 0.039). In multivariable analyses, sicca symptoms (OR = 0.28; 95% CI: 0.08, 0.96; P = 0.043) remained negatively associated with abnormal small bowel transit. Additionally, SSc patients with abnormal small bowel transit had higher mortality than patients with normal small bowel transit [hazard ratio (HR) = 4.57; 95% CI: 1.58, 13.24; P = 0.005].

Conclusions

These findings suggest that patients with abnormal small bowel transit in SSc are more likely to be male, have more severe cardiac involvement, higher mortality and fewer sicca symptoms. Recognizing this patient subgroup is essential for risk stratification and optimizing clinical care.
Establishment of typical values in cerebral thrombectomy according to the stroke anatomical region and procedure clinical outcome
Authors: Lopes Rogério , Santos Joana
Published: October 2024

The aim of the study is to establish local diagnostic reference levels (DRLs) in cerebral thrombectomy, according to the anatomical region of ischemic stroke. This is a retrospective study from a single center involving 255 examinations. The proposed median values (P50) for thrombectomy are: 123 Gy.cm2 for air kerma-area product (PKA) and 915 mGy for air kerma (Ka,r). For middle cerebral artery (MCA) thrombectomies, the proposed DRLs are 118 Gy.cm2 for PKA and 112 Gy.cm2 for internal carotid artery (ICA). The Ka,r values for MCA and ICA are 849 and 775 mGy, respectively. It was observed that 94.9% of patients presented grade 0 on the initial modified treatment in cerebral infarction (mTICI) scale, and after thrombectomy, 63.1% of patients reached a final mTICI grade of 3. Stents were implanted in 37 patients (14.5% of cases). It was concluded that 16.1% of patients exceeded one trigger value of the Safety in Radiological Procedures' recommended parameters. Establishing DRLs is an important tool for optimizing practices and is considered a standard for quality control.
Maternal early pregnancy body mass index and risk of insomnia in the offspring
Authors: Zhu Mia Q , Cnattingius Sven , O’Brien Louise M , Villamor Eduardo
Published: October 2024

Study Objectives

To investigate the association between maternal early pregnancy body mass index (BMI) and risk of offspring insomnia.

Methods

We conducted a nationwide cohort study among 3 281 803 singleton live births in Sweden born 1983–2015. Using national registries with prospectively recorded information, we followed participants for an insomnia diagnosis from 2 to up to 35 years of age. We compared insomnia risks by early pregnancy BMI categories using hazard ratios (HR) with 95% confidence intervals (CI) from adjusted Cox models. To assess unmeasured shared familial confounding, we conducted sibling-controlled analyses among 1 724 473 full siblings and studied the relation of maternal full sisters’ BMI and insomnia risk in 1 185 998 offspring.

Results

There were 7154 insomnia diagnoses over a median follow-up age of 17.9 years. Compared with women with normal BMI, adjusted HR (95% CI) of offspring insomnia for early pregnancy BMI categories overweight, obesity class I, and obesity classes II or III were, respectively, 1.22 (1.14, 1.30), 1.60 (1.45, 1.77), and 2.11 (1.83, 2.45). Corresponding adjusted HR (95% CI) in sibling comparisons were, respectively, 1.32 (1.05, 1.65), 1.48 (1.03, 2.14), and 1.56 (0.91, 2.65). Associations with maternal sisters’ BMI were attenuated, suggesting a weak role for unmeasured shared factors. Other pregnancy, birth, and neonatal complications were associated with the risk of insomnia in offspring but did not substantially mediate the association.

Conclusions

The dose–response relation between maternal overweight and obesity severity with offspring insomnia risk is not fully explained by shared familial factors.
Serum glucose/potassium ratio as an indicator of early and delayed outcomes of acute carbon monoxide poisoning
Authors: Elmansy Alshaimma Mahmoud , Hannora Dalia Mustafa , Khalifa Heba K
Published: October 2024

Background: Carbon monoxide (CO) poisoning is a major health problem associated with a high rate of severe morbidity and mortality. Aims: This study aimed to evaluate the validity of the serum glucose/potassium (Glu/K) ratio as a quick predictor of both early and delayed unfavorable outcomes following acute CO poisoning. Patients and methods: This prospective cohort study included 136 patients with acute CO poisoning admitted at Tanta Poison Control Center, Egypt, between January 2023 and June 2024. The serum Glu/K ratio was calculated for all patients. The primary outcome was a prediction of mortality. Secondary outcomes were the prediction of delayed neurological sequelae (DNS) within six months after CO exposure, the need for mechanical ventilation, and the need for hyperbaric oxygen. A receiver operating curve analysis was applied to test the performance of the Glu/K ratio in predicting acute CO poisoning outcomes. Results: The mortality rate was 12.5% of patients with acute CO poisoning. Meanwhile, 14.7% of patients developed DNS. Furthermore, mechanical ventilation was required in 16.9% of patients. An elevated Glu/K ratio was significantly associated with the severity of acute CO poisoning. At a cut-off value of >31.62, the Glu/K ratio demonstrated an AUC of 0.649 for predicting mortality. The Glu/K ratio was employed to predict DNS at a cut-off value of 33.10, with a sensitivity of 60.0%, a specificity of 82.76%, and an AUC of 0.692. Conclusions: Early Glu/K ratio may be an effective, reliable, and convenient laboratory predictor of mortality, DNS, and the need for mechanical ventilation in patients with acute CO poisoning.
Berberine and palmatine, acting as allosteric potential ligands of α7 nAChR, synergistically regulate inflammation and phagocytosis of microglial cells
Authors: Xia Yingjie , Wang Xiaoyang , Lin Shengying , Dong Tina T. X. , Tsim Karl W. K.
Published: October 2024

Berberine and palmatine are isoquinoline quaternary alkaloids derived from Chinese medicinal herbs. These alkaloids have shown promising synergy in inhibiting acetylcholinesterase (AChE), indicating their potential in treating Alzheimer's disease (AD). Besides, the anti‐inflammatory effects of berberine and palmatine have been widely reported, although the underlying mechanism remains unclear. Here, we found that berberine and palmatine could induce calcium ion (Ca2+) influx via activating α7 nicotinic acetylcholine receptor (α7 nAChR) in cultured microglial cells, possibly serving as its allosteric potential ligands. Furthermore, we examined the synergistic anti‐inflammatory effects of berberine and palmatine in the LPS‐induced microglia, that significantly suppressed the production of TNF‐α and iNOS. Notably, this suppression was reversed by co‐treatment with a selective antagonist of α7 nAChR. Moreover, the alkaloid‐induced microglial phagocytosis was shown to be mediated by the induction of Ca2+ influx through α7 nAChR and subsequent CaMKII‐Rac1‐dependent pathway. Additionally, the combination of berberine and palmatine, at low concentration, protected against the LPS‐induced endoplasmic reticulum stress and mitochondrial dysfunction in microglia. These findings indicate the potential of berberine and palmatine, either individually or in combination, in contributing to anti‐AD drug development, which provide valuable insights into the mechanisms by which natural products, such as plant alkaloids, exert their anti‐AD effects.
LHPP deficiency aggravates liver fibrosis through TGF‐β/Smad3 signaling
Authors: Zhang Yue , Li Bi‐min , Zhang Wang , Chen Peng , Liu Linxiang , Nie Yuan , Huang Chenkai , Zhu Xuan
Published: October 2024

Liver fibrosis is characterized by a wound‐healing response and may progress to liver cirrhosis and even hepatocellular carcinoma. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor that participates in malignant diseases. However, the role of LHPP in liver fibrosis has not been determined. Herein, the function and regulatory network of LHPP were explored in liver fibrosis. The expression of LHPP in human and murine fibrotic liver tissues was assessed via immunohistochemistry and Western blot analysis. In addition, liver fibrosis was induced in wild‐type (WT) and LHPP−/− (KO) mice after carbon tetrachloride (CCl4) or thioacetamide (TAA) treatment. The effect of LHPP was systematically assessed by using specimens acquired from the above murine models. The functional role of LHPP was further explored by detecting the pathway activity of TGF‐β/Smad3 and apoptosis after interfering with LHPP in vitro. To explore whether the function of LHPP depended on the TGF‐β/Smad3 pathway in vivo, an inhibitor of the TGF‐β/Smad3 pathway was used in CCl4‐induced WT and KO mice. LHPP expression was downregulated in liver tissue samples from fibrosis patients and fibrotic mice. LHPP deficiency aggravated CCl4‐ and TAA‐induced liver fibrosis. Moreover, through immunoblot analysis, we identified the TGF‐β/Smad3 pathway as a key downstream pathway of LHPP in vivo and in vitro. The effect of LHPP deficiency was reversed by inhibiting the TGF‐β/Smad3 pathway in liver fibrosis. These results revealed that LHPP deficiency exacerbates liver fibrosis through the TGF‐β/Smad3 pathway. LHPP may be a potential therapeutic target in hepatic fibrosis.
MREDTA: A BERT and transformer‐based molecular representation encoder for predicting drug‐target binding affinity
Authors: Sun Xu , Huang Juanjuan , Fang Yabo , Jin Yixuan , Wu Jiageng , Wang Guoqing , Jia Jiwei
Published: October 2024

Drug‐target binding affinity (DTA) prediction is vital for drug repositioning. The accuracy and generalizability of DTA models remain a major challenge. Here, we develop a model composed of BERT‐Trans Block, Multi‐Trans Block, and DTI Learning modules, referred to as Molecular Representation Encoder‐based DTA prediction (MREDTA). MREDTA has three advantages: (1) extraction of both local and global molecular features simultaneously through skip connections; (2) improved sensitivity to molecular structures through the Multi‐Trans Block; (3) enhanced generalizability through the introduction of BERT. Compared with 12 advanced models, benchmark testing of KIBA and Davis datasets demonstrated optimal performance of MREDTA. In case study, we applied MREDTA to 2034 FDA‐approved drugs for treating non‐small‐cell lung cancer (NSCLC), all of which act on mutant EGFRT790M protein. The corresponding molecular docking results demonstrated the robustness of MREDTA.
Inflammatory priming of human mesenchymal stem cells induces osteogenic differentiation via the early response gene IER3
Authors: Küppers Oliver , Ahmad Mubashir , Haffner‐Luntzer Melanie , Scharffetter‐Kochanek Karin , Ignatius Anita , Fischer Verena
Published: October 2024

Mesenchymal stem cells (MSCs) have gained tremendous interest due to their overall potent pro‐regenerative and immunomodulatory properties. In recent years, various in vitro and preclinical studies have investigated different priming (“licensing”) approaches to enhance MSC functions for specific therapeutic purposes. In this study, we primed bone marrow‐derived human MSCs (hMSCs) with an inflammation cocktail designed to mimic the elevated levels of inflammatory mediators found in serum of patients with severe injuries, such as bone fractures. We observed a significantly enhanced osteogenic differentiation potential of primed hMSCs compared to untreated controls. By RNA‐sequencing analysis, we identified the immediate early response 3 (IER3) gene as one of the top‐regulated genes upon inflammatory priming. Small interfering RNA knockdown experiments established IER3 as a novel positive regulator of osteogenic differentiation. Mechanistic analysis further revealed that IER3 deletion significantly downregulated bone marrow stromal cell antigen 2 (BST2) expression and extracellular signal‐related kinase 1/2 (ERK1/2) phosphorylation in hMSCs, suggesting that IER3 regulates osteogenic differentiation through BST2 and ERK1/2 signaling pathway activation. On the basis of these findings, we propose IER3 as a novel therapeutic target to promote hMSC osteoblastogenesis, which might be of high clinical relevance, for example, in patients with osteoporosis or compromised fracture healing.
Predictor Scales of Cognitive Factors Affecting Physical Activity in Individuals Surviving Cancer: Psychometric Properties of Turkish Versions
Authors: Kaya Şura , Esin Melek Nihal
Published: October 2024

Background:

Increasing physical activity in individuals surviving cancer is crucial in reducing treatment-related side effects and recurrence. Valid and reliable measurement tools are needed that will enable the factors affecting exercise to be addressed holistically and theoretically. This study aimed to adapt the Exercise Goal-Setting Scale, Exercise Planning and Scheduling Scale, Multidimensional Outcome Expectations for Exercise Scale, and Physical Activity Neighborhood Environment Scale into Turkish language and to explore psychometric properties of the Turkish versions of these scales in individuals surviving cancer.

Methods:

This methodologically designed research collected data from 153 participants at a hospital in Istanbul, Türkiye. The scales used in the study were adapted to the Turkish language through forward and backward translation and expert opinion. Content validity was assessed with a 2-week test-retest reliability, Cronbach’s α reliability coefficient for stability, item-total correlation, and confirmatory factor analysis.

Results:

The scales showed good content validity (CVI = 0.95-0.99). Internal consistencies were acceptable to excellent (Cronbach’s α = .79-.94), and moderate to good reproducibility estimates were observed (r = .67-.84). The MOEES factor structure also showed excellent fit.

Conclusions:

This study demonstrates that the adapted scales evaluated are valid and reliable for examining physical activity based on social cognitive processes in individuals surviving cancer in Türkiye. The scales examined in the study can be used to determine the cognitive factors affecting activity and to plan effective programs when providing physical activity counseling to individuals surviving cancer in Türkiye.
Inhibiting FGFR by toadflax reverses erlotinib resistance in nonsmall cell lung cancer
Authors: Han Bateer , Ma Ying , Bao Shuguang , Gao Hui , Gao Yanqing , Guo Qiang , Li Ao , Li Meitao , Yu Rong , Wang Hongwei
Published: October 2024

This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro, investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo. In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression.