bluuebunny/crossref_metadata_2025 huggingface dataset:
Weak sovereignty and interstate war
Authors: Wolford Scott , Rider Toby J.
Published: May 2024

International agreements save the costs of war, but complying with their terms can be costly. We analyse a model of interstate crisis bargaining in which one state may be unwilling or unable to make a costly investment that guarantees its subjects’ compliance. In equilibrium, peace is assured when the domestic government is militarily strong enough to demand terms that its subjects tolerate. When the domestic government is militarily weaker, peace requires that the foreign state compensate it for either the costs of enforcement or its subjects’ violations, and these prospective costs of peace may also lead the foreign state to solve the enforcement problem with war because peace is relatively costly. We also show that war due to enforcement problems is more common in militarily weak states and that equilibria at which the foreign state subsidizes enforcement are more common when the costs of violation fall disproportionately on the domestic state. The American invasion of Mexico in 1916 and the Red Army's peaceful withdrawal from East Germany in 1989 demonstrate the model's usefulness.
Mediterranean diet as a strategy for preserving kidney function in patients with coronary heart disease with type 2 diabetes and obesity: a secondary analysis of CORDIOPREV randomized controlled trial
Authors: Podadera-Herreros Alicia , Arenas-de Larriva Antonio P. , Gutierrez-Mariscal Francisco M. , Alcala-Diaz Juan F. , Ojeda-Rodriguez Ana , Rodriguez-Cantalejo Fernando , Cardelo Magdalena P. , Rodriguez-Cano Diego , Torres-Peña Jose D. , Luque Raul M. , Ordovas Jose M. , Perez-Martinez Pablo , Delgado-Lista Javier , Lopez-Miranda Jose , Yubero-Serrano Elena M.
Published: May 2024

Background

Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function.

Methods

1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention.

Results

Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024).

Conclusions

Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease.

Trial registration

URL, http://www.cordioprev.es/index.php/en. Clinicaltrials.gov number, NCT00924937
Time to diagnosis and determinants of diagnostic delays of people living with a rare disease: results of a Rare Barometer retrospective patient survey
Authors: Faye Fatoumata , Crocione Claudia , Anido de Peña Roberta , Bellagambi Simona , Escati Peñaloza Luciana , Hunter Amy , Jensen Lene , Oosterwijk Cor , Schoeters Eva , de Vicente Daniel , Faivre Laurence , Wilbur Michael , Le Cam Yann , Dubief Jessie
Published: May 2024

Timely diagnosis is one of the most serious challenges faced by people living with a rare disease (PLWRD), and this study estimates that in Europe, the average total diagnosis time (TDT) is close to 5 years. We investigated the duration of the TDT for PLWRD in Europe, the difficulties associated with their diagnosis odyssey and the main determinants of diagnosis delays for all rare diseases (RD). We conducted a survey of PLWRD and their families using Rare Barometer, the survey initiative of EURORDIS-Rare Diseases Europe. In geographical Europe, we surveyed 6507 people living with 1675 RD in 41 countries. We then performed a descriptive analysis and ordinal logistic regressions to identify the main determinants of diagnosis delays. Average TDT is 4.7 years. 56% of respondents were diagnosed more than 6 months after a first medical contact. The main determinants of diagnosis delays are symptom onset before 30 years of age, especially during childhood (OR = 3.11; 95% CI: 2.4–4.0) and adolescence (OR = 4.79; 95% CI: 3.7–6.2), being a woman (OR = 1.22; 95% CI:1.1–1.4), living in Northern Europe (OR = 2.15; 95% CI:1.8–2.6) or Western Europe (OR = 1.96; 95% CI:1.6–2.3), the number of healthcare professionals consulted (OR = 5.15; 95% CI:4.1–6.4), misdiagnosis (OR = 2.48; 95% CI:2.1–2.9), referral to a centre of expertise (OR = 1.17; 95% CI:1.0–1.3), unmet needs for psychological support (OR = 1.34; 95% CI:1.2–1.5) and financial support (OR = 1.16; 95% CI:1.0–1.3), having a genetic disease (OR = 1.33; 95% CI:1.1–1.5) and a family history of an RD (OR = 1.36; 95% CI:1.1–1.6). These determinants can inform policies and actions to improve access to diagnosis for all PLWRD.
Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD
Authors: Akula M. , McNamee S. M. , Love Z. , Nasraty N. , Chan N. P. M. , Whalen M. , Avola M. O. , Olivares A. M. , Leehy B. D. , Jelcick A. S. , Singh P. , Upadhyay A. K. , Chen D. F. , Haider N. B.
Published: May 2024

Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5. In this translational study, we examined the efficacy of RORA at attenuating retinal degeneration and improving the inflammatory response in Abca4 knockout (Abca4−/−) mice. AAV5-hRORA-treated mice showed reduced deposits, restored CD59 expression and attenuated amyloid precursor protein (APP) expression compared with untreated eyes. This molecular rescue correlated with statistically significant improvement in photoreceptor function. This is the first study evaluating the impact of RORA modifier gene therapy on rescuing retinal degeneration. Our studies demonstrate efficacy of RORA in improving STGD and dry AMD-like disease.
Characteristic craniofacial defects associated with a novel USP9X truncation mutation
Authors: Nagata Namiki , Kurosaka Hiroshi , Higashi Kotaro , Yamaguchi Masaya , Yamamoto Sayuri , Inubushi Toshihiro , Nagata Miho , Ishihara Yasuki , Yonei Ayumi , Miyashita Yohei , Asano Yoshihiro , Sakai Norio , Sakata Yasushi , Kawabata Shigetada , Yamashiro Takashi
Published: May 2024

Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.
Deterministic positioning and alignment of a single-molecule exciton in plasmonic nanodimer for strong coupling
Authors: Liu Renming , Geng Ming , Ai Jindong , Fan Xinyi , Liu Zhixiang , Lu Yu-Wei , Kuang Yanmin , Liu Jing-Feng , Guo Lijun , Wu Lin
Published: May 2024

Experimental realization of strong coupling between a single exciton and plasmons remains challenging as it requires deterministic positioning of the single exciton and alignment of its dipole moment with the plasmonic fields. This study aims to combine the host–guest chemistry approach with the cucurbit[7]uril-mediated active self-assembly to precisely integrate a single methylene blue molecule in an Au nanodimer at the deterministic position (gap center of the nanodimer) with the maximum electric field (EFmax) and perfectly align its transition dipole moment with the EFmax, yielding a large spectral Rabi splitting of 116 meV for a single-molecule exciton—matching the analytical model and numerical simulations. Statistical analysis of vibrational spectroscopy and dark-field scattering spectra confirm the realization of the single exciton strong coupling at room temperature. Our work may suggest an approach for achieving the strong coupling between a deterministic single exciton and plasmons, contributing to the development of room-temperature single-qubit quantum devices.
Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy
Authors: Mistretta Maxime , Cimino Mena , Campagne Pascal , Volant Stevenn , Kornobis Etienne , Hebert Olivier , Rochais Christophe , Dallemagne Patrick , Lecoutey Cédric , Tisnerat Camille , Lepailleur Alban , Ayotte Yann , LaPlante Steven R. , Gangneux Nicolas , Záhorszká Monika , Korduláková Jana , Vichier-Guerre Sophie , Bonhomme Frédéric , Pokorny Laura , Albert Marvin , Tinevez Jean-Yves , Manina Giulia
Published: May 2024

Drug-recalcitrant infections are a leading global-health concern. Bacterial cells benefit from phenotypic variation, which can suggest effective antimicrobial strategies. However, probing phenotypic variation entails spatiotemporal analysis of individual cells that is technically challenging, and hard to integrate into drug discovery. In this work, we develop a multi-condition microfluidic platform suitable for imaging two-dimensional growth of bacterial cells during transitions between separate environmental conditions. With this platform, we implement a dynamic single-cell screening for pheno-tuning compounds, which induce a phenotypic change and decrease cell-to-cell variation, aiming to undermine the entire bacterial population and make it more vulnerable to other drugs. We apply this strategy to mycobacteria, as tuberculosis poses a major public-health threat. Our lead compound impairs Mycobacterium tuberculosis via a peculiar mode of action and enhances other anti-tubercular drugs. This work proves that harnessing phenotypic variation represents a successful approach to tackle pathogens that are increasingly difficult to treat.
Conserved regulatory switches for the transition from natal down to juvenile feather in birds
Authors: Chen Chih-Kuan , Chang Yao-Ming , Jiang Ting-Xin , Yue ZhiCao , Liu Tzu-Yu , Lu Jiayi , Yu Zhou , Lin Jinn-Jy , Vu Trieu-Duc , Huang Tao-Yu , Harn Hans I-Chen , Ng Chen Siang , Wu Ping , Chuong Cheng-Ming , Li Wen‐Hsiung
Published: May 2024

The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs.
Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration
Authors: Fernández-Calvet Ariadna , Matilla-Cuenca Leticia , Izco María , Navarro Susanna , Serrano Miriam , Ventura Salvador , Blesa Javier , Herráiz Maite , Alkorta-Aranburu Gorka , Galera Sergio , Ruiz de los Mozos Igor , Mansego María Luisa , Toledo-Arana Alejandro , Alvarez-Erviti Lydia , Valle Jaione
Published: May 2024

Age-related neurodegenerative diseases involving amyloid aggregation remain one of the biggest challenges of modern medicine. Alterations in the gastrointestinal microbiome play an active role in the aetiology of neurological disorders. Here, we dissect the amyloidogenic properties of biofilm-associated proteins (BAPs) of the gut microbiota and their implications for synucleinopathies. We demonstrate that BAPs are naturally assembled as amyloid-like fibrils in insoluble fractions isolated from the human gut microbiota. We show that BAP genes are part of the accessory genomes, revealing microbiome variability. Remarkably, the abundance of certain BAP genes in the gut microbiome is correlated with Parkinson’s disease (PD) incidence. Using cultured dopaminergic neurons and Caenorhabditis elegans models, we report that BAP-derived amyloids induce α-synuclein aggregation. Our results show that the chaperone-mediated autophagy is compromised by BAP amyloids. Indeed, inoculation of BAP fibrils into the brains of wild-type mice promote key pathological features of PD. Therefore, our findings establish the use of BAP amyloids as potential targets and biomarkers of α-synucleinopathies.
Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration
Authors: Mao Zhinan , Bi Xuewei , Yu Chunhao , Chen Lei , Shen Jie , Huang Yongcan , Wu Zihong , Qi Hui , Guan Juan , Shu Xiong , Yu Binsheng , Zheng Yufeng
Published: May 2024

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.
Mycobacterial biotin synthases require an auxiliary protein to convert dethiobiotin into biotin
Authors: Qu Di , Ge Peng , Botella Laure , Park Sae Woong , Lee Ha-Na , Thornton Natalie , Bean James M. , Krieger Inna V. , Sacchettini James C. , Ehrt Sabine , Aldrich Courtney C. , Schnappinger Dirk
Published: May 2024

Lipid biosynthesis in the pathogen Mycobacterium tuberculosis depends on biotin for posttranslational modification of key enzymes. However, the mycobacterial biotin synthetic pathway is not fully understood. Here, we show that rv1590, a gene of previously unknown function, is required by M. tuberculosis to synthesize biotin. Chemical–generic interaction experiments mapped the function of rv1590 to the conversion of dethiobiotin to biotin, which is catalyzed by biotin synthases (BioB). Biochemical studies confirmed that in contrast to BioB of Escherichia coli, BioB of M. tuberculosis requires Rv1590 (which we named “biotin synthase auxiliary protein” or BsaP), for activity. We found homologs of bsaP associated with bioB in many actinobacterial genomes, and confirmed that BioB of Mycobacteriumsmegmatis also requires BsaP. Structural comparisons of BsaP-associated biotin synthases with BsaP-independent biotin synthases suggest that the need for BsaP is determined by the [2Fe–2S] cluster that inserts sulfur into dethiobiotin. Our findings open new opportunities to seek BioB inhibitors to treat infections with M. tuberculosis and other pathogens.
Spontaneously established reverse electric field to enhance the performance of triboelectric nanogenerators via improving Coulombic efficiency
Authors: Gao Yikui , He Lixia , Liu Di , Zhang Jiayue , Zhou Linglin , Wang Zhong Lin , Wang Jie
Published: May 2024

Mechanical energy harvesting using triboelectric nanogenerators is a highly desirable and sustainable method for the reliable power supply of widely distributed electronics in the new era; however, its practical viability is seriously challenged by the limited performance because of the inevitable side-discharge and low Coulombic-efficiency issues arising from electrostatic breakdown. Here, we report an important progress on these fundamental problems that the spontaneously established reverse electric field between the electrode and triboelectric layer can restrict the side-discharge problem in triboelectric nanogenerators. The demonstration employed by direct-current triboelectric nanogenerators leads to a high Coulombic efficiency (increased from 28.2% to 94.8%) and substantial enhancement of output power. More importantly, we demonstrate this strategy is universal for other mode triboelectric nanogenerators, and a record-high average power density of 6.15 W m−2 Hz−1 is realized. Furthermore, Coulombic efficiency is verified as a new figure-of-merit to quantitatively evaluate the practical performance of triboelectric nanogenerators.
Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years
Authors: Perofsky Amanda C. , Hansen Chelsea L. , Burstein Roy , Boyle Shanda , Prentice Robin , Marshall Cooper , Reinhart David , Capodanno Ben , Truong Melissa , Schwabe-Fry Kristen , Kuchta Kayla , Pfau Brian , Acker Zack , Lee Jover , Sibley Thomas R. , McDermot Evan , Rodriguez-Salas Leslie , Stone Jeremy , Gamboa Luis , Han Peter D. , Adler Amanda , Waghmare Alpana , Jackson Michael L. , Famulare Michael , Shendure Jay , Bedford Trevor , Chu Helen Y. , Englund Janet A. , Starita Lea M. , Viboud Cécile
Published: May 2024

Many studies have used mobile device location data to model SARS-CoV-2 dynamics, yet relationships between mobility behavior and endemic respiratory pathogens are less understood. We studied the effects of population mobility on the transmission of 17 endemic viruses and SARS-CoV-2 in Seattle over a 4-year period, 2018-2022. Before 2020, visits to schools and daycares, within-city mixing, and visitor inflow preceded or coincided with seasonal outbreaks of endemic viruses. Pathogen circulation dropped substantially after the initiation of COVID-19 stay-at-home orders in March 2020. During this period, mobility was a positive, leading indicator of transmission of all endemic viruses and lagging and negatively correlated with SARS-CoV-2 activity. Mobility was briefly predictive of SARS-CoV-2 transmission when restrictions relaxed but associations weakened in subsequent waves. The rebound of endemic viruses was heterogeneously timed but exhibited stronger, longer-lasting relationships with mobility than SARS-CoV-2. Overall, mobility is most predictive of respiratory virus transmission during periods of dramatic behavioral change and at the beginning of epidemic waves.
Ion pair sites for efficient electrochemical extraction of uranium in real nuclear wastewater
Authors: Lin Tao , Chen Tao , Jiao Chi , Zhang Haoyu , Hou Kai , Jin Hongxiang , Liu Yan , Zhu Wenkun , He Rong
Published: May 2024

Electrochemical uranium extraction from nuclear wastewater represents an emerging strategy for recycling uranium resources. However, in nuclear fuel production which generates the majority of uranium-containing nuclear wastewater, fluoride ion (F−) co-exists with uranyl (UO22+), resulting in the complex species of UO2Fx and thus decreasing extraction efficiency. Herein, we construct Tiδ+-PO43− ion pair extraction sites in Ti(OH)PO4 for efficient electrochemical uranium extraction in wastewater from nuclear fuel production. These sites selectively bind with UO2Fx through the combined Ti-F and multiple O-U-O bonds. In the uranium extraction, the uranium species undergo a crystalline transition from U3O7 to K3UO2F5. In real nuclear wastewater, the uranium is electrochemically extracted with a high efficiency of 99.6% and finally purified as uranium oxide powder, corresponding to an extraction capacity of 6829 mg g−1 without saturation. This work paves an efficient way for electrochemical uranium recycling in real wastewater of nuclear production.
Efficient multimode Wigner tomography
Authors: He Kevin , Yuan Ming , Wong Yat , Chakram Srivatsan , Seif Alireza , Jiang Liang , Schuster David I.
Published: May 2024

Advancements in quantum system lifetimes and control have enabled the creation of increasingly complex quantum states, such as those on multiple bosonic cavity modes. When characterizing these states, traditional tomography scales exponentially with the number of modes in both computational and experimental measurement requirement, which becomes prohibitive as the system size increases. Here, we implement a state reconstruction method whose sampling requirement instead scales polynomially with system size, and thus mode number, for states that can be represented within such a polynomial subspace. We demonstrate this improved scaling with Wigner tomography of multimode entangled W states of up to 4 modes on a 3D circuit quantum electrodynamics (cQED) system. This approach performs similarly in efficiency to existing matrix inversion methods for 2 modes, and demonstrates a noticeable improvement for 3 and 4 modes, with even greater theoretical gains at higher mode numbers.
FAIR assessment of nanosafety data reusability with community standards
Authors: Ammar Ammar , Evelo Chris , Willighagen Egon
Published: May 2024

Nanomaterials hold great promise for improving our society, and it is crucial to understand their effects on biological systems in order to enhance their properties and ensure their safety. However, the lack of consistency in experimental reporting, the absence of universally accepted machine-readable metadata standards, and the challenge of combining such standards hamper the reusability of previously produced data for risk assessment. Fortunately, the research community has responded to these challenges by developing minimum reporting standards that address several of these issues. By converting twelve published minimum reporting standards into a machine-readable representation using FAIR maturity indicators, we have created a machine-friendly approach to annotate and assess datasets’ reusability according to those standards. Furthermore, our NanoSafety Data Reusability Assessment (NSDRA) framework includes a metadata generator web application that can be integrated into experimental data management, and a new web application that can summarize the reusability of nanosafety datasets for one or more subsets of maturity indicators, tailored to specific computational risk assessment use cases. This approach enhances the transparency, communication, and reusability of experimental data and metadata. With this improved FAIR approach, we can facilitate the reuse of nanosafety research for exploration, toxicity prediction, and regulation, thereby advancing the field and benefiting society as a whole.
Tensile testing data of additive manufactured ASTM D638 standard specimens with embedded internal geometrical features
Authors: AbouelNour Youssef , Rakauskas Nick , Naquila Gabrielle , Gupta Nikhil
Published: May 2024

Additive manufacturing (AM) is now widely used for research and industrial production. The benchmark data for mechanical properties of additively manufactured specimens is very useful for many communities. This data article presents a tensile testing dataset of ASTM D638 size specimens without and with embedded internal geometrical features printed using polylactic acid (PLA) in a Fused Filament Fabrication (FFF) additive manufacturing process. The added features can mimic defects of various shapes and sizes. This work is a supplement to the published research article Assisted defect detection by in-process monitoring of additive manufacturing using optical imaging and infrared thermography (Additive Manufacturing, 2023, 103483). The printed specimens were tensile tested. Stress-strain graphs were developed and used to calculate the mechanical properties such as ultimate tensile strength (UTS) and strain at UTS. The mechanical properties, the correlations between mechanical properties and size, shape and location of geometrical features (defects), and the trends in mechanical properties can be useful in benchmarking the results of other researchers.
Factors associated with physical inactivity among Palestinians with type 2 diabetes mellitus treated in resource-limited settings
Authors: Shawahna Ramzi , Jaber Mohammad , Zmiro Arob , Kashkoush Sewar
Published: May 2024

This study determined the prevalence and the associated factors with meeting the recommended amount of physical activity among type 2 diabetes mellitus (T2DM) patients receiving care in resource-limited settings of the West Bank of Palestine. Physical activity was assessed using the World Health Organization’s Global Physical Activity Questionnaire. Associations were examined using multivariate logistic regression. Of the 302 patients included, 117 (38.7%) met the recommended amount of physical activity. Being younger than 58 years [aOR = 2.1 (95% CI 1.0–4.3], were employed [aOR = 2.3 (95% CI 1.1–4.9)], had high income [aOR = 3.9 (95% CI 1.3–11.9)], had thought that physical activity was crucial for T2DM patients [aOR = 32.7 (95% CI 3.9–275.5)], did not have comorbidities [aOR = 2.2 (95% CI 1.1–4.4)], had normal weight [aOR = 2.8 (95% CI 1.3–6.0)], and those who were overweight [aOR = 2.6 (95% CI 1.1–6.0)] were more likely to meet the recommended amount of physical activity compared to the patients who were 58 years or older, had low income, did not think that physical activity was crucial for T2DM patients, had comorbidities, and were obese, respectively. There is a need to increase physical activity among T2DM patients in resource limited settings.
Reanalysis of cluster randomised trial data to account for exposure misclassification using a per-protocol and complier-restricted approach
Authors: Dufault Suzanne M. , Tanamas Stephanie K. , Indriani Citra , Ahmad Riris Andono , Utarini Adi , Jewell Nicholas P. , Simmons Cameron P. , Anders Katherine L.
Published: May 2024

The intention-to-treat (ITT) analysis of the Applying Wolbachia to Eliminate Dengue (AWED) trial estimated a protective efficacy of 77.1% for participants resident in areas randomised to receive releases of wMel-infected Aedes aegypti mosquitoes, an emerging dengue preventive intervention. The limiting assumptions of ITT analyses in cluster randomised trials and the mobility of mosquitoes and humans across cluster boundaries indicate the primary analysis is likely to underestimate the full public health benefit. Using spatiotemporally-resolved data on the distribution of Wolbachia mosquitoes and on the mobility of AWED participants (n = 6306), we perform complier-restricted and per-protocol re-examinations of the efficacy of the Wolbachia intervention. Increased intervention efficacy was estimated in all analyses by the refined exposure measures. The complier-restricted analysis returned an estimated efficacy of 80.7% (95% CI 65.9, 89.0) and the per-protocol analysis estimated 82.7% (71.7, 88.4) efficacy when comparing participants with an estimated wMel exposure of $$\ge$$
≥
80% compared to those with <20%. These reanalyses demonstrate how human and mosquito movement can lead to underestimation of intervention effects in trials of vector interventions and indicate that the protective efficacy of Wolbachia is even higher than reported in the primary trial results.
Multi-scale coupled attention for visual object detection
Authors: Li Fei , Yan Hongping , Shi Linsu
Published: May 2024

The application of deep neural network has achieved remarkable success in object detection. However, the network structures should be still evolved consistently and tuned finely to acquire better performance. This gears to the continuous demands on high performance in those complex scenes, where multi-scale objects to be detected are located here and there. To this end, this paper proposes a network structure called Multi-Scale Coupled Attention (MSCA) under the framework of self-attention learning with methodologies of importance assessment. Architecturally, it consists of a Multi-Scale Coupled Channel Attention (MSCCA) module, and a Multi-Scale Coupled Spatial Attention (MSCSA) module. Specifically, the MSCCA module is developed to achieve the goal of self-attention learning linearly on the multi-scale channels. In parallel, the MSCSA module is constructed to achieve this goal nonlinearly on the multi-scale spatial grids. The MSCCA and MSSCA modules can be connected together into a sequence, which can be used as a plugin to develop end-to-end learning models for object detection. Finally, our proposed network is compared on two public datasets with 13 classical or state-of-the-art models, including the Faster R-CNN, Cascade R-CNN, RetinaNet, SSD, PP-YOLO, YOLO v3, YOLO v5, YOLO v7, YOLOX, DETR, conditional DETR, UP-DETR and FP-DETR. Comparative experimental results with numerical scores, the ablation study, and the performance behaviour all demonstrate the effectiveness of our proposed model.
Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma
Authors: Leek Lindsay V. M. , Notohardjo Jessica C. L. , de Joode Karlijn , Velker Eline L. , Haanen John B. A. G. , Suijkerbuijk Karijn P. M. , Aarts Maureen J. B. , de Groot Jan Willem B. , Kapiteijn Ellen , van den Berkmortel Franchette W. P. J. , Westgeest Hans M. , de Gruijl Tanja D. , Retel Valesca P. , Cuppen Edwin , van der Veldt Astrid A. M. , Labots Mariette , Voest Emile E. , van de Haar Joris , van den Eertwegh Alfons J. M.
Published: May 2024

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.01, 95% CI 2.10–7.67, Cox P = 2.63e−05) and PFS (HR = 3.72, 95% CI 2.06–6.73, Cox P = 1.38e−05) in univariate analysis. In multivariate analysis, the association of hypoalbuminemia with PFS was independent of serum LDH, IFN-γ signature expression, TMB, age, ECOG PS, treatment line, treatment type (combination or monotherapy), brain and liver metastasis (HR = 2.76, 95% CI 1.24–6.13, Cox P = 0.0131). Our validation cohort confirmed the prognostic power of hypoalbuminemia for OS (HR = 1.98, 95% CI 1.16–3.38; Cox P = 0.0127) and was complementary to serum LDH in analyses for both OS (LDH-adjusted HR = 2.12, 95% CI 1.2–3.72, Cox P = 0.00925) and PFS (LDH-adjusted HR = 1.91, 95% CI 1.08–3.38, Cox P = 0.0261). In conclusion, pretreatment hypoalbuminemia was a powerful predictor of outcome in ICI in melanoma and showed remarkable complementarity to previously established biomarkers, including high LDH.
Sustained attention operates via dissociable neural mechanisms across different eccentric locations
Authors: Phangwiwat Tanagrit , Phunchongharn Phond , Wongsawat Yodchanan , Chatnuntawech Itthi , Wang Sisi , Chunharas Chaipat , Sprague Thomas C. , Woodman Geoffrey F. , Itthipuripat Sirawaj
Published: May 2024

In primates, foveal and peripheral vision have distinct neural architectures and functions. However, it has been debated if selective attention operates via the same or different neural mechanisms across eccentricities. We tested these alternative accounts by examining the effects of selective attention on the steady-state visually evoked potential (SSVEP) and the fronto-parietal signal measured via EEG from human subjects performing a sustained visuospatial attention task. With a negligible level of eye movements, both SSVEP and SND exhibited the heterogeneous patterns of attentional modulations across eccentricities. Specifically, the attentional modulations of these signals peaked at the parafoveal locations and such modulations wore off as visual stimuli appeared closer to the fovea or further away towards the periphery. However, with a relatively higher level of eye movements, the heterogeneous patterns of attentional modulations of these neural signals were less robust. These data demonstrate that the top-down influence of covert visuospatial attention on early sensory processing in human cortex depends on eccentricity and the level of saccadic responses. Taken together, the results suggest that sustained visuospatial attention operates differently across different eccentric locations, providing new understanding of how attention augments sensory representations regardless of where the attended stimulus appears.
Autophagy favors survival of corpora lutea during the long-lasting pregnancy of the South American plains vizcacha, Lagostomus maximus (Rodentia, Caviomorpha)
Authors: Caram Daira A. , Inserra Pablo I. F. , Vitullo Alfredo D. , Leopardo Noelia P.
Published: May 2024

The corpus luteum (CL) is a transient endocrine gland that plays a crucial role in establishing and maintaining pregnancy. Although autophagy and apoptosis have been suggested as cooperative mechanisms, their interaction within the CL of pregnant mammals has not been thoroughly investigated. To understand the collaborative function of autophagy and apoptosis in the CL, we analyzed both mechanisms during pregnancy in the South American plains vizcacha, Lagostomus maximus. This rodent undergoes a decline in progesterone levels during mid-gestation, a reactivation of the hypothalamus-hypophysis-gonadal axis, and the incorporation of new functional secondary CL. Our analysis of autophagy markers BECLIN 1 (BECN1), SEQUESTOSOME1 (SQSTM1), Microtubule-associated protein light chain 3 (LC3B), and lysosomal-associated membrane protein 1 (LAMP1) and anti- and pro-apoptotic markers BCL2 and ACTIVE CASPASE 3 (A-C3) revealed interactive behaviors between both processes. Healthy primary and secondary CL exhibited positive expression of BECN1, SQSTM1, LC3B, and LAMP1, while regressed CL displayed enhanced expression of these autophagy markers along with nuclear A-C3. Transmission electron microscopy revealed a significant formation of autophagic vesicles in regressed CL during full-term pregnancy, whereas healthy CL exhibited a low number of autophagy vesicles. The co-localization between LC3B and SQSTM1 and LC3B with LAMP1 was observed in both healthy and regressed CL during pregnancy, while co-localization of BECN1 and BCL2 was only detected in healthy CL. LC3B and ACTIVE CASPASE 3 co-localization were detected in a subset of luteal cells within the regressing CL. We propose that autophagy could act as a survival mechanism in the CL, allowing the pregnancy to progress until full-term, while also serving as a mechanism to eliminate remnants of regressed CL, thereby providing the necessary space for subsequent follicular maturation.
One-pot synthesis of quinazolinone heterocyclic compounds using functionalized SBA-15 with natural material ellagic acid as a novel nanocatalyst
Authors: Mohassel Yazdi Nazanin , Naimi-Jamal Mohammad Reza
Published: May 2024

The nanoporous compound SBA-15 was functionalized using (3-aminopropyl)trimethoxysilane (APTES). Then the obtained product was modified with ellagic acid (ELA), a bioactive polyphenolic compound. The structure of the prepared nanoporous composition SBA-15@ELA was extensively characterized and confirmed by various techniques, such as Fourier-transform infrared (FT-IR) spectroscopy, Energy dispersive X-ray (EDX) elemental analysis, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM) and N2 adsorption–desorption isotherms (BET). The novel, recoverable, heterogenous SBA-15@ELA nanoporous compound was used to investigate its catalytic effect in the synthesis of 4-oxo-quinazoline derivatives (19 examples) with high yields (78–96%), as an important class of nitrogen-containing heterocyclic compounds. The use of an inexpensive mesoporous catalyst with a high surface area, along with easy recovery by simple filtration are among the advantages of this catalysis research work. The catalyst has been used in at least 6 consecutive runs without a significant loss of its activity.
T cell activation and deficits in T regulatory cells are associated with major depressive disorder and severity of depression
Authors: Rachayon Muanpetch , Jirakran Ketsupar , Sodsai Pimpayao , Sughondhabirom Atapol , Maes Michael
Published: May 2024

Major depressive disorder (MDD) is associated with T cell activation, but no studies have examined the combined effects of T cell activation and deficits in T regulatory (Treg) cells on the severity of acute phase MDD. Using flow cytometry, we determined the percentage and median fluorescence intensity of CD69, CD71, CD40L, and HLADR-bearing CD3+, CD4+, and CD8+ cells, and cannabinoid type 1 receptor (CB1), CD152 and GARP (glycoprotein A repetitions predominant)-bearing CD25+ FoxP3 T regulatory (Treg) cells in 30 MDD patients and 20 healthy controls in unstimulated and stimulated (anti-CD3/CD28) conditions. Based on cytokine levels, we assessed M1 macrophage, T helper (Th)-1 cell, immune-inflammatory response system (IRS), T cell growth, and neurotoxicity immune profiles. We found that the immune profiles (including IRS and neurotoxicity) were significantly predicted by decreased numbers of CD152 or GARP-bearing CD25+ FoxP3 cells or CD152 and GARP expression in combination with increases in activated T cells (especially CD8+ CD40L+ percentage and expression). MDD patients showed significantly increased numbers of CD3+ CD71+, CD3+ CD40L+, CD4+ CD71+, CD4+ CD40L+, CD4+ HLADR+, and CD8+ HLADR+ T cells, increased CD3+ CD71+, CD4+ CD71+ and CD4+ HLADR+ expression, and lowered CD25+ FoxP3 expression and CD25+ FoxP+ CB1+ numbers as compared with controls. The Hamilton Depression Rating Scale score was strongly predicted (between 30 and 40% of its variance) by a lower number of CB1 or GARP-bearing Treg cells and one or more activated T cell subtypes (especially CD8+ CD40L+). In conclusion, increased T helper and cytotoxic cell activation along with decreased Treg homeostatic defenses are important parts of MDD that lead to enhanced immune responses and, as a result, neuroimmunotoxicity.
Investigation of N$$_3$$C$$_5$$ and B$$_3$$C$$_5$$ bilayers as anode materials for Li-ion batteries by first-principles calculations
Authors: Kasprzak Grzegorz T. , Jarosik Marcin W. , Durajski Artur P.
Published: May 2024

The best choice today for a realistic method of increasing the energy density of a metal-ion battery is to find novel, effective electrode materials. In this paper, we present a theoretical investigation of the properties of hitherto unreported two-dimensional B$$_3$$

3

C$$_5$$

5

and N$$_3$$

3

C$$_5$$

5

bilayer systems as potential anode materials for lithium-ion batteries. The simulation results show that N$$_3$$

3

C$$_5$$

5

bilayer is not suitable for anode material due to its thermal instability. On the other hand B$$_3$$

3

C$$_5$$

5

is stable, has good electrical conductivity, and is intrinsically metallic before and after lithium intercalation. The low diffusion barrier (0.27 eV) of Li atoms shows a good charge and discharge rate for B$$_3$$

3

C$$_5$$

5

bilayer. Moreover, the high theoretical specific capacity (579.57 mAh/g) connected with moderate volume expansion effect during charge/discharge processes indicates that B$$_3$$

3

C$$_5$$

5

is a promising anode material for Li-ion batteries.
Optical genome mapping unveils hidden structural variants in neurodevelopmental disorders
Authors: Schrauwen Isabelle , Rajendran Yasmin , Acharya Anushree , Öhman Susanna , Arvio Maria , Paetau Ritva , Siren Auli , Avela Kristiina , Granvik Johanna , Leal Suzanne M. , Määttä Tuomo , Kokkonen Hannaleena , Järvelä Irma
Published: May 2024

While short-read sequencing currently dominates genetic research and diagnostics, it frequently falls short of capturing certain structural variants (SVs), which are often implicated in the etiology of neurodevelopmental disorders (NDDs). Optical genome mapping (OGM) is an innovative technique capable of capturing SVs that are undetectable or challenging-to-detect via short-read methods. This study aimed to investigate NDDs using OGM, specifically focusing on cases that remained unsolved after standard exome sequencing. OGM was performed in 47 families using ultra-high molecular weight DNA. Single-molecule maps were assembled de novo, followed by SV and copy number variant calling. We identified 7 variants of interest, of which 5 (10.6%) were classified as likely pathogenic or pathogenic, located in BCL11A, OPHN1, PHF8, SON, and NFIA. We also identified an inversion disrupting NAALADL2, a gene which previously was found to harbor complex rearrangements in two NDD cases. Variants in known NDD genes or candidate variants of interest missed by exome sequencing mainly consisted of larger insertions (> 1kbp), inversions, and deletions/duplications of a low number of exons (1–4 exons). In conclusion, in addition to improving molecular diagnosis in NDDs, this technique may also reveal novel NDD genes which may harbor complex SVs often missed by standard sequencing techniques.
Changes of PM2.5 and O3 and their impact on human health in the Guangdong-Hong Kong-Macao Greater Bay Area
Authors: Zhao Hui , Chen Zeyuan , Li Chen
Published: May 2024

In recent years, the combined pollution of PM2.5 and O3 in China, particularly in economically developed regions such as the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), has garnered significant attention due to its potential implications. This study systematically investigated the changes of PM2.5 and O3 and their associated human health effects in the GBA, utilizing observational data spanning from 2015 to 2019. The findings revealed a spatial trend indicating a gradual decrease in PM2.5 levels from the northwest to the southeast, while the spatial distribution of MDA8 O3 demonstrated an opposing pattern to that of PM2.5. The monthly fluctuations of PM2.5 and MDA8 O3 exhibited V-shaped and M-shaped patterns, respectively. Higher MDA8 O3 concentrations were observed in autumn, followed by summer and spring. Over the five-year period, PM2.5 concentrations exhibited a general decline, with an annual reduction rate of 1.7 μg m−3/year, while MDA8 O3 concentrations displayed an annual increase of 3.2 μg m−3. Among the GBA regions, Macao, Foshan, Guangzhou, and Jiangmen demonstrated notable decreases in PM2.5, whereas Jiangmen, Zhongshan, and Guangzhou experienced substantial increases in MDA8 O3 levels. Long-term exposure to PM2.5 in 2019 was associated with 21,113 (95% CI 4968–31,048) all-cause deaths (AD), 1333 (95% CI 762–1714) cardiovascular deaths (CD), and 1424 (95% CI 0–2848) respiratory deaths (RD), respectively, reflecting declines of 27.6%, 28.0%, and 28.4%, respectively, compared to 2015. Conversely, in 2019, estimated AD, CD, and RD attributable to O3 were 16,286 (95% CI 8143–32,572), 7321 (95% CI 2440–14,155), and 6314 (95% CI 0–13,576), respectively, representing increases of 45.9%, 46.2%, and 44.2% over 2015, respectively. Taken together, these findings underscored a shifting focus in air pollution control in the GBA, emphasizing the imperative for coordinated control strategies targeting both PM2.5 and O3.
PPARγ regulates osteoarthritis chondrocytes apoptosis through caspase-3 dependent mitochondrial pathway
Authors: Yuan Hang , Yi Ning , Li Dong , Xu Chao , Yin Guang-Rong , Zhuang Chao , Wang Yu-Ji , Ni Su
Published: May 2024

Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a complex pathogenesis. One of the key factors contributing to its development is the apoptosis of chondrocytes triggered by oxidative stress. Involvement of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported in the regulation of oxidative stress. However, there remains unclear mechanisms that through which PPARγ influences the pathogenesis of OA. The present study aims to delve into the role of PPARγ in chondrocytes apoptosis induced by oxidative stress in the context of OA. Primary human chondrocytes, both relatively normal and OA, were isolated and cultured for the following study. Various assessments were performed, including measurements of cell proliferation, viability and cytotoxicity. Additionally, we examined cell apoptosis, levels of reactive oxygen species (ROS), nitric oxide (NO), mitochondrial membrane potential (MMP) and cytochrome C release. We also evaluated the expression of related genes and proteins, such as collagen type II (Col2a1), aggrecan, inducible nitric oxide synthase (iNOS), caspase-9, caspase-3 and PPARγ. Compared with relatively normal cartilage, the expression of PPARγ in OA cartilage was down-regulated. The proliferation of OA chondrocytes decreased, accompanied by an increase in the apoptosis rate. Down-regulation of PPARγ expression in OA chondrocytes coincided with an up-regulation of iNOS expression, leading to increased secretion of NO, endogenous ROS production, and decrease of MMP levels. Furthermore, we observed the release of cytochrome C, elevated caspase-9 and caspase-3 activities, and reduction of the components of extracellular matrix (ECM) Col2a1 and aggrecan. Accordingly, utilization of GW1929 (PPARγ Agonists) or Z-DEVD-FMK (caspase-3 inhibitor) can protect chondrocytes from mitochondrial-related apoptosis and alleviate the progression of OA. During the progression of OA, excessive oxidative stress in chondrocytes leads to apoptosis and ECM degradation. Activation of PPARγ can postpone OA by down-regulating caspase-3-dependent mitochondrial apoptosis pathway.