bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical implications of mineralocorticoid receptor overactivation
Authors: El Mouhayyar Christopher , Chhikara Monika , Tang Mengyao , Nigwekar Sagar U
Published: November 2024

The mineralocorticoid receptor (MR) is a nuclear transcription factor that plays a critical role in regulating fluid, electrolytes, blood pressure, and hemodynamic stability. In conditions such as chronic kidney disease (CKD) and heart failure (HF), MR overactivation leads to increased salt and water retention, inflammatory and fibrotic gene expression, and organ injury. The MR is essential for transcriptional regulation and is implicated in metabolic, proinflammatory, and pro-fibrotic pathways. It is widely expressed in various cell types throughout the body, including the gastrointestinal tract, heart, brain, kidneys, immune cells, and vasculature. Animal studies suggest that MR activation induces oxidative stress in the kidneys and mediates renal inflammation and fibrosis. Immune cell-specific deletion of MR has shown protection against cardiac fibrosis, indicating the MR's role in pathological remodeling. In vascular smooth muscle cells, the MR regulates vascular tone and vasoconstriction.

Mineralocorticoid receptor antagonists (MRAs) can be categorized based on their chemical structure as either steroidal or nonsteroidal. Steroidal MRAs (sMRA), such as spironolactone and eplerenone, have demonstrated cardiovascular benefits but are limited by hyperkalemia, gynecomastia, and sexual dysfunction. Nonsteroidal MRAs (nsMRA) have shown promise in preclinical studies and clinical trials. They offer a promising alternative by effectively blocking MR without hormone-like effects, potentially improving cardiovascular and renal disease management.

Further education is necessary regarding the significance of MRA utilization in CKD and HF, balancing benefits with the risk of hyperkalemia. This risk could be mitigated by combining MRAs with potassium-binding agents. Studies are underway to explore the synergistic effects between nsMRAs and other agents, such as SGLT-2i inhibitors and Glucagon-like peptide-1 agonists, to optimize cardiorenal outcomes.

Overall, MR overactivation remains a significant therapeutic target, with nsMRAs showing promise as pivotal therapies in CKD and HF management. This review highlights the evolving landscape of MR-targeted therapies, their molecular mechanisms, and clinical implications in cardiorenal diseases.
Predictive Model for Outcomes in Inflammatory Bowel Disease Patients Receiving Maintenance Infliximab Therapy
Authors: Wong Rochelle , Charilaou Paris , Hemperly Amy , Qin Lihui , Pan Yushan , Mathani Prerna , Longman Randy , Boland Brigid S , Dulai Parambir S , Holmer Ariela K , Lukin Dana , Singh Siddharth , Valasek Mark A , Sandborn William J , Scherl Ellen , Vande Casteele Niels , Battat Robert
Published: November 2024

Background

No models predict future outcomes in inflammatory bowel disease (IBD) patients receiving maintenance infliximab therapy. We created a predictive model for unfavorable outcomes.

Methods

Adult patients with IBD receiving maintenance infliximab therapy at 2 centers with matched serum infliximab concentrations and blinded histologic scores (Robarts Histopathologic Index [RHI]) were included. The primary endpoint was an unfavorable outcome of active objective inflammation or need for IBD-related surgery or hospitalization at 6–18 months follow-up. Internal variables were identified using univariable analyses, modeling used multivariable analysis, and performance was assessed (area under receiver-operating curve [AUC]) and externally validated.

Results

In 81 patients, 40.7% developed unfavorable outcomes at follow-up. Infliximab concentration <9.3 µg/mL (odds ratio [OR] 5.3, P = .001) and RHI > 12 (OR 3.4, P = .03) were the only factors associated with developing the primary unfavorable outcome. A prediction score assigning 1 point to each variable had good discrimination and performed similarly on internal (AUC 0.71) and external (AUC 0.73) cohorts. The risk of primary unfavorable outcomes in internal and external cohorts, respectively, was 23% and 15% for a score of 0, 46% and 50% for a score of 1, and 100% and 75% for a score of 2. Infliximab concentration alone performed similar to the 2-predictor model in internal (AUC 0.65, P = .5 vs. 2-predictor model) and external (AUC 0.70, P = .9, vs. 2-predictor model) cohorts.

Conclusions

Using unbiased variable selection, a 2-predictor model using infliximab concentrations and histology identified IBD patients on maintenance infliximab therapy at high risk of future unfavorable outcomes. For practical applicability, infliximab concentrations alone performed similarly well.
Accuracy of left ventricular mechanical dyssynchrony indices for mechanical characteristics of left bundle branch block using cardiovascular magnetic resonance feature tracking
Authors: Loewenstein Daniel E , Wieslander Björn , Heiberg Einar , Axelsson Jimmy , Klem Igor , Nijveldt Robin , Schelbert Erik B , Sörensson Peder , Sigfridsson Andreas , Strauss David G , Kim Raymond J , Atwater Brett D , Ugander Martin
Published: November 2024

Aims

More than 90% of patients with left bundle branch block (LBBB) and reduced left ventricular (LV) ejection fraction have LV dyssynchrony and a high probability of response to cardiac resynchronization therapy (CRT). A subgroup of patients with non-specific intraventricular conduction delay (IVCD) have a LBBB-like LV activation pattern when studied using invasive mapping and advanced echocardiographic techniques. These patients also frequently benefit from CRT, but these patients have proven difficult to identify using electrocardiogram criteria. Cardiovascular magnetic resonance (CMR) imaging indices of dyssynchrony may identify patients with IVCD who may benefit from CRT, but their relative accuracies for identification of LV dyssynchrony remain unknown. We compared the LV dyssynchrony classification accuracy of two commonly available CMR indices in a study population of patients with severely reduced LV ejection fraction and no scar and either LBBB or QRS duration <120 ms and normal QRS axis (controls).

Methods and results

In LBBB (n = 44) and controls (n = 36), using CMR feature-tracking circumferential strain, dyssynchrony was quantified as the circumferential uniformity ratio estimate (CURE) and the systolic stretch index (SSI). Deidentified CMR image data were made publicly available. Both CURE and SSI quantified more severe dyssynchrony in LBBB compared with controls (P<0.001 for both). SSI more frequently discriminated LBBB and normal conduction LV activation patterns than CURE [area under the receiver-operating characteristic curve (95% confidence interval) 0.96 (0.92–1.00) for SSI vs. 0.76 (0.65–0.86) for CURE, P < 0.001].

Conclusion

SSI is superior to CURE for discriminating synchronous and dyssynchronous LV activation and should be further studied in the setting of non-LBBB conduction abnormalities.
PIEZO1 attenuates Marfan syndrome aneurysm development through TGF-β signaling pathway inhibition via TGFBR2
Authors: Yang Peiwen , Liu Hao , Wang Shilin , Xiao Xiaoyue , Jiang Lang , Le Sheng , Chen Shanshan , Ye Ping , Xia Jiahong
Published: November 2024

Background and Aims

Marfan syndrome (MFS) is a hereditary disorder primarily caused by mutations in the FBN1 gene. Its critical cardiovascular manifestation is thoracic aortic aneurysm (TAA), which poses life-threatening risks. Owing to the lack of effective pharmacological therapies, surgical intervention continues to be the current definitive treatment. In this study, the role of Piezo-type mechanosensitive ion channel component 1 (Piezo1) in MFS was investigated and the activation of PIEZO1 was identified as a potential treatment for MFS.

Methods

PIEZO1 expression was detected in MFS mice (Fbn1C1041G/+) and patients. Piezo1 conditional knockout mice in vascular smooth muscle cells of MFS mice (MFS × CKO) was generated, and bioinformatics analysis and experiments in vitro and in vivo were performed to investigate the role of Piezo1 in MFS.

Results

PIEZO1 expression decreased in the aortas of MFS mice; MFS × CKO mice showed aggravated TAA, inflammation, extracellular matrix remodelling, and TGF-β pathway activation compared to MFS mice. Mechanistically, PIEZO1 knockout exacerbated the activation of the TGF-β signalling pathway by inhibiting the endocytosis and autophagy of TGF-β receptor 2 mediated by Rab GTPase 3C. Additionally, the pharmacological activation PIEZO1 through Yoda1 prevented TGF-β signalling pathway activation and reversed TAA in MFS mice.

Conclusions

Piezo1 deficiency aggravates MFS aneurysms by promoting TGF-β signalling pathway activation via TGF-β receptor 2 endocytosis and a decrease in autophagy. These data suggest that PIEZO1 may be a potential therapeutic target for MFS treatment.
Determination of 28 food safety risk factors in novel foods by ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry
Authors: Fan Sufang , Ren Xiaowei , Shi Guohua , Zhao Limin , Ma Junmei , Wen Di , Li Qiang , Zhang Yan
Published: November 2024

An analytical method was established for the determination of 24 food safety risk factors (18 heterocyclic aromatic amines, 6 mycotoxins) in synthetic meat and synthetic protein samples, 4 microcystins in microalgae samples using ultra-high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UPLC-Q/Orbitrap HRMS). The novel synthetic food was extracted using a 50% methanol solution and purified with 3 mL of n-hexane saturated with a 50% methanol solution. For microalgae samples, extraction was performed with an 80% acetonitrile solution and purified using a PRiME HLB solid-phase extraction column. An ACQUITY HSS T3 column (100 mm ×2.1mm, 1.8 μm) was used for analyte separation, with 5 mmol/L ammonium acetate containing 0.01% formic acid and methanol selected as the mobile phase. Gradient elution was adopt. Data acquisition was conducted in both positive and negative mode using full scan-data dependent secondary scan mode (Full MS-ddMS2). Matrix-matched standards were employed for quantification in the external standard method. Additionally, mzVault and Tracefinder software were used to establish a screening database for 28 food safety risk factors. The results showed that the relative deviation of the exact mass of the 28 food safety risk factors was less than 5ppm, with good linearity in the range of 1-100μg/kg, and a correlation coefficient (r2) of ≥0.9978. The detection limit ranged from 0.5 to 4 μg/kg, and the quantification limit ranged from 1 to 10 μg/kg. Method recoveries ranged from 70.0% to 119.6% with relative standard deviations of 0.4% to 14.6% (n=6). The method is simple, sensitive and accurate, suitable for rapid screening of 28 food safety risk factors in novel foods.
Effects of cashew nutshell extract inclusion into a high-grain finishing diet on methane emissions, nutrient digestibility, and ruminal fermentation in beef steers
Authors: Cuervo Wilmer , Gomez Camila , Tarnonsky Federico , Fernandez-Marenchino Ignacio , Podversich Federico , Maderal Araceli , Schulmeister Tessa M , Vargas Juan de J , DiLorenzo Nicolas
Published: November 2024

By 2050, the U.S. beef industry must produce an extra 40 million tons of beef to satisfy the global demand. Such an increase in inventory will undoubtedly enhance methane (CH4) production from livestock, which should be reduced by over 20%. The addition of plant secondary metabolites, such as anacardic acid present in cashew nutshell extract (CNSE), has shown promising results in reducing CH4 yield, although its effects seemed to be diet-dependent. This study evaluated the addition of CNSE to a high-grain diet (85:15 grain:forage) on in vivo CH4 emissions, nutrient digestibility, performance, feeding behavior, and ruminal fermentation parameters of beef steers. Sixteen Angus crossbred steers [599 ± 40 kg of bodyweight (BW)] and 6 ruminally cannulated crossbred steers (490 ± 51 kg of BW) were utilized in a crossover design with 2 experimental periods of 56 d each, composed by 14 d of adaptation, 35 d of measurement, and 7 d of washout. Following adaptation, steers were sorted by BW, and assigned to receive no additive (CON) or CNSE at 5 g/steer/d. Data were analyzed using the MIXED procedure of SAS. Inclusion of CNSE increased (P < 0.05) propionate concentration and molar proportion (MP; mol/100 mol), tended to decrease acetate MP (P = 0.10), reduced the acetate:propionate (A:P) ratio (P = 0.05), and MP of branched-chain volatile fatty acids (P < 0.01). Neither in vitro organic matter digestibility nor in vitro CH4 yield were affected by CNSE inclusion (P > 0.05). Steers receiving CNSE exhibited greater (P < 0.05) final BW, dry matter intake (DMI), and average daily gain (ADG) but lesser (P < 0.05) in vivo CH4 emission rate (g/d), yield (g/kg of DMI), and intensity (g/kg of ADG). Meal length, bunk visit duration, and apparent total tract digestibility of DM increased (P < 0.05) after CNSE addition. Considering CNSE-supplemented steers spent more time in the feedbunk and exhibited higher DMI, CH4 mitigation was unlikely associated with intake reduction. The addition of CNSE to a high-grain diet in beef steers demonstrated significant improvements in animal performance and reduced CH4 emissions, as the result of shifts in ruminal fermentation patterns, favoring propionate instead of acetate concentration, leading to a reduction in the A:P ratio. CNSE shows promise as a strategy to enhance beef industry sustainability.
Course and treatment of severe osteoporosis complicated by calciphylaxis: a case report
Authors: Tominaga Ayako , Wada Keiji , Kato Yoshiharu , Okazaki Ken
Published: November 2024

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is a rare disorder with many unknown treatment and diagnostic aspects. It is characterized by calcification and thrombosis of small blood vessels. This disease leads to progressive skin calcification, necrotizing ulcers, and infections and is associated with a high mortality rate. Although primarily affected sites tend to be on skin, those affecting bones are also significant. We report a case of CUA complicated with rapidly progressing multiple vertebral fractures and severe osteoporosis. The patient experienced a series of five vertebral fractures within 5 months after hospitalization, and blood tests revealed abnormally high levels of bone resorption marker bone-type tartrate-resistant acid phosphatase (TRACP-5b). Consequently, intravenous sodium thiosulfate and hyperbaric oxygen therapy were administered for the treatment of skin lesions caused by calciphylaxis, and brace therapy and denosumab treatment were initiated for vertebral fractures. This approach rapidly decreased TRACP-5b levels and arrested the chain of vertebral fractures. We concluded that to maintain the quality of life of patients with CUA, early treatment of primary skin lesions as well as comorbid conditions is essential.
A Rat’s Progress: Plague and the “Migratory Rat” in British India, 1896-1899
Authors: Lynteris Christos
Published: November 2024

Whether referring to oceanic travel on board of ships or to movement in terra firma, framings of the “migratory rat” formed a key epidemiological component of approaches to the Third Plague Pandemic (1894-1959) as the first pandemic to be understood as caused by a zoonotic disease. In this article, I examine the emergence and development of scientific framings of the migratory rat in the first, explosive years of the third plague pandemic in India (1896-1899). Examining publications and archival sources, I ask how this animal figure came to inform and transform epidemiological reasoning. Going beyond established approaches that have shown how the rat-plague relation was mobilised by colonial doctors to pathologise Indigenous lifeways, I argue that more complex and ambivalent processes were also set in motion by this figure. First, I show how the migratory rat became invested with attributes of invasiveness that assumed ontological qualities in colonial epidemiological reasoning. Second, comparing the migratory rat with the hitherto established “staggering rat,” I argue that the former embodied new approaches to both space and time in epidemiology. Third, I show how Indigenous scientists came to mobilise this complex figure to contest colonial approaches to plague.
Association of race and area of deprivation index with prostate cancer incidence and lethality: results from a contemporary North American cohort
Authors: Finati Marco , Stephens Alex , Cirulli Giuseppe Ottone , Chiarelli Giuseppe , Tinsley Shane , Morrison Chase , Sood Akshay , Buffi Nicolò , Lughezzani Giovanni , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Busetto Gian Maria , Rogers Craig , Carrieri Giuseppe , Abdollah Firas
Published: November 2024

Background

Socioeconomic and demographic factors contribute to disparity in prostate cancer (PCa) outcomes. We examined the impact of Area of Deprivation Index (ADI) and race on PCa incidence and lethality in a North American cohort.

Methods

Our cohort included men who received at least 1 prostate-Specifig Antigen (pSA) test within our Health System (1995-2022). An ADI score was assigned to each patient based on their residential census block, ranked as a percentile of deprivation relative to the national level. Individuals were further categorized into quartiles, where the fourth one (ADI 75-100) represented those living in the most deprived areas. We investigated PCa incidence and lethality, using cumulative incidence estimates and competing-risk regression. An ADI × Race interaction term examined whether the relationship between ADI and outcomes varied based on race.

Results

We included 134 366 patients, 25% of whom were non-Hispanic Black (NHB). Median (IQR) follow-up was 8.8 (5-17) years. At multivariate analysis, individuals from the third quartile (ADI 50-74, 95% CI = 0.83 to 0.95) and the fourth quartile (ADI ≥75, 95% CI = 0.75 to 0.86) showed significant reduced hazard ratios for PCa incidence, when compared with the first quartile (ADI <25, all P < .001). In contrast to the overall cohort, PCa incidence increased with ADI in NHB men, who were persistently at higher hazard for both PCa incidence and lethality than non-Hispanic White (NHW), across all ADI strata (all P < .001).

Conclusions

Living in more deprived areas was associated with lower PCa incidence and higher lethal disease rate. Conversely, PCa incidence increased with ADI for NHB, who consistently showed worse outcomes than NHW individuals, regardless of ADI.
Defects and waves in anisotropic and layered media: Stroh formalism in terms of the Cartesian system of vector functions
Authors: Qu Yilin , Zhu Feng , Pan Ernian
Published: November 2024

When waves propagate through anisotropic elastic media, P- and SV-type waves (Rayleigh waves) are generally coupled with SH-type waves (Love waves). In contrast, in isotropic elastic media, SH/Love waves are decoupled and separate from other body/surface waves. However, the conditions under which these waves in anisotropic media may be decoupled remain unclear. In this paper, we introduce a Cartesian vector function system, named as the Cartesian LMN vector system, and derive solutions using this system within the Stroh formalism. This approach inherently accounts for both coupling and decoupling cases. Various source functions based on the Cartesian LMN vector system are derived. The Cartesian LMN system further enables a straightforward reduction to two-dimensional wave problems, including simplified source functions for line forces and lattice dislocations.
Renewable energy and energy justice in the Middle East: international human rights, environmental and climate change law and policy perspectives
Authors: Maniruzzaman A F M , Al-Saleem Khalid
Published: November 2024

The concept of energy justice is now a divisive issue throughout the world. Clean energy is becoming increasingly unavailable to a large portion of the population. Against this backdrop, this article explores the legal aspects of renewable energy and energy justice in three major, traditionally energy-rich countries representing the Middle East: the Kingdom of Saudi Arabia (KSA), Iran, and Iraq. It critically evaluates these countries’ legal challenges of renewable energy and energy justice. The research found that renewable energy is becoming more necessary for sustainable development and resilience to climate change. Natural resource abundance, increasing energy use, and a commitment to global climate change goals all pose unique challenges and opportunities for countries in the Middle East region. From international human rights, environmental, and climate change law perspectives, this article analyses the current regulatory processes and legislative frameworks aimed at increasing the use of renewable energy sources and ensuring energy justice. Renewable energy in the Middle East has been influenced by regional initiatives, international treaties, and national legislation, all of which are examined in detail.
icecube AGN neutrino candidate PKS 1717+177: dark deflector bends nuclear jet
Authors: Britzen S , Kovačević A B , Zajaček M , Popović L Č , Pashchenko I N , Kun E , Pánis R , Jaron F , Plšek T , Tursunov A , Stuchlík Z
Published: November 2024

The BL Lac object PKS 1717+177 has been identified as potential neutrino-emitting active galactic nuclei in the point source stacking analysis of icecube data. We explore peculiarities in the morphology and kinematics of the jet and examine multiwavelength light curves for distinctive effects which might allow to pinpoint a likely neutrino generation mechanism. We re-modelled 34 high-resolution radio interferometric Very Long Baseline Array observations obtained at 15 GHz (between 1999 December 27 and 2023 May 3). A correlation and periodicity analysis of optical Katzman Automatic Imaging Telescope and Tuorla data, as well as for Fermi-LAT $\gamma$-ray data has been performed. The nuclear jet appears deflected and bent at about 0.5 mas distance from the radio core by an encounter with a dark, unseen object. The deviation of the jet evolves over 23.5 yr from a simple apparent bend into a significantly meandering structure with increasing amplitude: a zig-zag line. To our knowledge, this is the first time that the temporal evolution of a jet deviation can be traced. The turning point shifts with time and the jet seems to brighten up almost periodically at the point of deviation. The radio core as well as the jet contribute approximately equally to the total flux-density at 15 GHz. We discuss scenarios which could explain the complex jet bending and quasi-regular flaring. We propose that the jet could either be deflected by the magnetosphere of a second massive black hole, by the pressure gradient due to a circumnuclear dense cloud, or via gravitational lensing by an intervening black hole.
TPCNet: representation learning for H i mapping
Authors: Nguyen Hiep , Tang Haiyang , Alger Matthew , Marchal Antoine , Muller Eric G M , Ong Cheng Soon , McClure-Griffiths N M
Published: November 2024

We introduce TPCNet, a neural network predictor that combines convolutional and transformer architectures with positional encodings, for neutral atomic hydrogen (H i) spectral analysis. Trained on synthetic data sets, our models predict cold neutral gas fraction ($f_\mathrm{CNM}$) and H i opacity correction factor ($\mathcal {R_{\mathrm{H\,{\small I}}}}$) from emission spectra based on the learned relationships between the desired output parameters and observables (optically thin column density and peak brightness). As a follow-up to Murray et al.’s shallow Convolutional Neural Network (CNN), we construct deep CNN models and compare them to TPCNet models. TPCNet outperforms deep CNNs, achieving a 10 per cent average increase in testing accuracy, algorithmic (training) stability, and convergence speed. Our findings highlight the robustness of the proposed model with sinusoidal positional encoding applied directly to the spectral input, addressing perturbations in training data set shuffling and convolutional network weight initializations. Higher spectral resolutions with increased spectral channels offer advantages, albeit with increased training time. Diverse synthetic data sets enhance model performance and generalization, as demonstrated by producing $f_\mathrm{CNM}$ and $\mathcal {R_{\mathrm{H\,{\small I}}}}$ values consistent with evaluation ground truths. Applications of TPCNet to observed emission data reveal strong agreement between the predictions and Gaussian decomposition-based estimates (from emission and absorption surveys), emphasizing its potential in H i spectral analysis.
Stable oxygen isotopes reveal different thermal regimes during the Early Pliocene in the southern North Sea Basin: a multi-species approach
Authors: Cudennec Jean-François , Schöne Bernd R , Leng Melanie , Harper Elizabeth M , Gofas Serge , Wesselingh Frank P , Johnson Andrew L A
Published: November 2024

Oxygen stable isotope (δ18O) analysis of marine biogenic carbonates is widely used to study the temperature at which the hard parts precipitated. This technique enables investigation of the environmental conditions experienced by carbonate-shelled organisms throughout their life. We used this approach on four bivalve species from the Coralline Crag Formation (Early Pliocene; UK), where warm- and cold-associated species co-occur in the Ramsholt Member. Our results reveal species-specific differences in reconstructed temperature. Two distinct climatic settings were identified: a cold setting with seafloor temperatures of 7.3 °C in winter and 12.4 °C in summer, and a warm one with seafloor temperatures of 10.4 °C in winter to above 14 °C in summer. These absolute temperatures were calculated using a modelled value of seawater δ18O (+0.1‰) that is open to question, but the disparity in temperatures exists whatever value is used. Interestingly, the reconstructed temperatures for some of the studied species align with those of their modern relatives: Arctica islandica records the coldest temperatures in this dataset, while Centrocardita squamulosa ampla indicates warmer conditions. Aequipecten opercularis, a eurythermal pectinid, exhibited the broadest range of temperatures. The interval during which the Coralline Crag was deposited (c. 4.4‒3.8 Ma) is generally regarded as relatively warm. However, the presence of A. islandica and the absolute seawater temperatures derived from shell δ18O suggest the occurrence of sufficiently long cool periods for the establishment and survival of this long-lived species. Data from specimens of C. squamulosa ampla and A. islandica collected from a single bed point to glacial/interglacial-type climate fluctuation. These results confirm that the presence of A. islandica is a marker for cold temperate environments. These results also confirm that assemblage information is not sufficient to determine palaeoclimatic conditions, and that reconstructed temperatures from shell δ18O can reveal time-averaging in fossil shell beds.
Presidential legislative initiatives under semi-presidentialism: What accounts for their success and failure?
Authors: Jastramskis Mažvydas , Pukelis Lukas , Palujanskaitė Miglė
Published: November 2024

Few presidents in Europe have the power to propose legislation directly to Parliament. Accordingly, presidential legal initiatives in Europe are not very well researched or understood. This paper seeks to address this research gap by providing an analysis of presidential legal initiatives in Lithuania. We have assembled a dataset of all the presidential legal initiatives proposed in Lithuania since 1993. Using this dataset, we find that factors in the political environment significantly affect the success of presidential legislative initiatives. Additionally, we find that the success of these initiatives partly depends on policy content, as initiatives in foreign and defense policy, on average, tend to be more successful. Lastly, non-partisan presidents in Lithuania become more successful over time; our results suggest a consolidation of consultation mechanisms between the presidents and the legislature.
Accumulation of acyl plastoquinol and triacylglycerol in six cyanobacterial species with different sets of genes encoding type-2 diacylglycerol acyltransferase-like proteins
Authors: Tanikawa Riko , Sakaguchi Haruna , Ishikawa Toshiki , Hihara Yukako
Published: November 2024

Recently, acyl plastoquinol (APQ) and plastoquinone-B (PQ-B), which are fatty acid esters of plastoquinol and plastoquinone-C respectively, have been identified as the major neutral lipids in cyanobacteria. In Synechocystis sp. PCC 6803, Slr2103 having homology with the eukaryotic enzyme for triacylglycerol (TAG) synthesis, diacylglycerol acyltransferase 2 (DGAT2), was identified as responsible for the synthesis of these plastoquinone-related lipids. On the other hand, TAG synthesis in cyanobacteria remains controversial due to the low accumulation level within cyanobacterial cells together with the high contamination level from the environment. In this study, to quantify more precisely and elucidate the relationship between the accumulation of neutral lipids and the presence or absence of DGAT2-like genes, plastoquinone-related lipids and TAG were analyzed directly from total lipids of six cyanobacterial species with different sets of genes encoding DGAT2-like proteins belonging to two distinct subclades. The results showed that the synthesis of these neutral lipids is highly dependent on clade A DGAT2-like proteins under the culture conditions used in this study, although accumulation level of TAG was quite low. In contrast to APQ highly abundant in saturated fatty acids, the fatty acid composition of TAG was species-specific and partly reflected the total lipid composition. Gloeobacter violaceus PCC 7421, which lacks a DGAT2-like gene, accumulated APQ with a high proportion of C18:0, suggesting APQ synthesis by an unidentified acyltransferase.
Protein translation can fluidize bacterial cytoplasm
Authors: Bera Palash , Wasim Abdul , Bakshi Somenath , Mondal Jagannath
Published: November 2024

The cytoplasm of bacterial cells is densely packed with highly polydisperse macromolecules that exhibit size-dependent glassy dynamics. Recent research has revealed that metabolic activities in living cells can counteract the glassy nature of these macromolecules, allowing the cell to maintain critical fluidity for its growth and function. While it has been proposed that the crowded cytoplasm is responsible for this glassy behavior, a detailed analysis of the size-dependent nature of the glassy dynamics and an explanation for how cellular activity induces its fluidization remains elusive. Here, we use a combination of computational models and targeted experiments to show that entropic segregation of the protein synthesis machinery from the chromosomal DNA causes size-dependent spatial organization of molecules within the cell, and the resultant crowding leads to size-dependent glassy dynamics. Furthermore, Brownian dynamics simulations of this in silico system supports a new hypothesis: protein synthesis in living cells contributes to the metabolism-dependent fluidization of the cytoplasm. The main protein synthesis machinery, ribosomes, frequently shift between fast and slow diffusive states. These states correspond to the independent movement of ribosomal subunits and the actively translating ribosome chains called polysomes, respectively. Our simulations demonstrate that the frequent transitions of the numerous ribosomes, which constitute a significant portion of the cell proteome, greatly enhance the mobility of other macromolecules within the bacterial cytoplasm. Considering that ribosomal protein synthesis is the largest consumer of ATP in growing bacterial cells, the translation process can serve as the primary mechanism for fluidizing the cytoplasm in metabolically active cells.
Insights into the regulation of CHIP E3 ligase-mediated ubiquitination of neuronal protein BNIP-H
Authors: Shankar Srihari , Liu Yaochen , Tulsian Nikhil Kumar , Low Boon C , Lin Qingsong , Sivaraman J
Published: November 2024

BCL2/adenovirus E1B 19-kDa protein-interacting protein 2 homolog (BNIP-H or Caytaxin), a pivotal adaptor protein that facilitates cerebellar cortex growth and synaptic transmission, is posttranslationally modified to regulate neuronal function. This study reports the ubiquitination of BNIP-H by Carboxyl terminus of Hsc70-Interacting Protein (CHIP), a U-box containing E3 ligase that is also regulated via autoubiquitination. Specifically, it was observed that CHIP autoubiquitinated itself primarily at Lys23 and Lys31 in vitro. Mutation of these residues shows the autoubiquitination of successive lysines of CHIP. In total, nine lysines on CHIP were identified as the autoubiquitination sites, the collective mutation of which almost completely terminated its autoubiquitination. Additionally, CHIP-mediated ubiquitination of BNIP-H is completely inhibited when BNIP-H bears arginine mutations at four key lysine residues. Next, using hydrogen deuterium exchange mass spectrometry, a model of a plausible mechanism was proposed. The model suggests transient N-terminal interactions between the CHIP and BNIP-H which allows for the swinging of U-box domain of CHIP to ubiquitinate BNIP-H. Following complex dissociation, BNIP-H population is regulated via the ubiquitin-proteasome pathway. Collectively, these results aid in our understanding of CHIP-mediated BNIP-H ubiquitination and provide further insight into the roles of these proteins in neuritogenesis and neurotransmission.
Optimizing the Accuracy and Precision of the Minimal Detectable Change Statistic: Secondary Analysis of Test-retest Data From the NIH Toolbox Study
Authors: Graber Jeremy , Loyd Brian J , Hoogeboom Thomas J , Miller Caitlin J , Kittelson Andrew J
Published: November 2024

Objective

The minimal detectable change (MDC) statistic is often used by clinicians to monitor change in patients. However, the way in which the MDC is traditionally calculated might be suboptimal in terms of accuracy and precision, potentially resulting in erroneous clinical decisions. This study compared the performance of the MDC statistic as traditionally calculated to that of 2 regression-based alternatives.

Methods

This analysis used test-retest data from adults who participated in usual walking speed (n = 169) or grip strength (n = 178) assessments as part of the NIH Toolbox Study. Three approaches for MDC calculation were compared: the traditional approach (MDCTrad), simple linear regression (MDCSLR), and generalized additive models for location, scale, and shape (MDCGAMLSS). These approaches were compared in terms of accuracy and precision across all levels of measurement and separately for initial test values above and below the median.

Results

Each of the 3 approaches accurately modeled detectable change thresholds when performance was averaged across all test values. However, MDCTrad demonstrated inaccuracies when performance was considered separately for initial test values below or above the median. For walking speed, average precision improved by 12% with MDCSLR and 16% with MDCGAMLSS, compared to MDCTrad. For grip strength, average precision improved by 3% with MDCSLR and 21% with MDCGAMLSS, compared to MDCTrad.

Conclusion

MDCSLR and MDCGAMLSS appeared to more accurately and precisely model detectable change thresholds, compared to MDCTRAD. In general, MDCGAMLSS demonstrated the best overall performance in this within-sample analysis.

Impact

Improved precision and accuracy in detectable change thresholds for walking speed or grip strength might facilitate clinicians’ ability to promptly detect a decline in function and intervene and to confidently detect improvements in function over time.

Lay Summary

This study compared the performance of the MDC statistic as traditionally calculated to 2 regression-based alternatives.
68Ga-FAPI and 18F-NaF PET/CT in psoriatic arthritis: a comparative study
Authors: Yang Fan , Lu Chaofan , Pan Qingqing , Zhang Rui , Yang Meng , Wang Qian , Li Mengtao , Zeng Xiaofeng , Luo Yaping , Leng Xiaomei
Published: November 2024

Objectives

As fibroblast-like synoviocyte activation and bone formation are associated with PsA, PET using the tracers of 68Ga-fibroblast activation protein inhibitor (FAPI) and 18F-sodium fluoride (NaF) may sensitively detect the disease. In this prospective study, we aimed to evaluate the performance of 68Ga-FAPI PET/CT in PsA and to compare it with 18F-NaF PET/CT.

Methods

Sixteen participants (female 7/16, age 42.31 ± 10.66 years) with PsA were prospectively enrolled and underwent dual-tracer PET/CT, clinical assessment and ultrasonography. PET/CT images were scored for PET-positive lesions at the peripheral joints, entheses, and axial joints.

Results

The positivity rate of 68Ga-FAPI in peripheral joints was higher than that in entheses and axial joints (21.84% vs 12.15% vs 0%), whereas high positivity rates of 18F-NaF in peripheral joints, entheses, and axial joints were observed (85.23%, 78.13% and 75%, respectively). The DAS 28 was higher in the PET-positive than in the PET-negative group with 68Ga-FAPI (5.25 ± 1.84 vs 2.55 ± 0.94, P = 0.037), but not with 18F-NaF. In addition, the PET joint count at 68Ga-FAPI PET/CT was positively correlated with the tender joint count (r = 0.604, P = 0.017), swollen joint count (r = 0.773, P = 0.001), DAS28-CRP (r = 0.556, P = 0.032), Psoriatic Arthritis Disease Activity Score (PASDAS) (r = 0.540, P = 0.038) and PsASon13 (r = 0.701, P = 0.005), while no correlation was observed in 18F-NaF PET/CT.

Conclusion

The positivity rates of 68Ga-FAPI- and 18F-NaF PET/CT were different in patients with PsA in peripheral joints, entheses, and axial joints. The extent of joint involvement as shown in 68Ga-FAPI PET/CT correlated with clinical and US variables as well as with disease activity.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT05686876.
Pulmonary involvement in systemic sclerosis: can sex play a role?
Authors: Koletsos Nikolaos , Kaltsonoudis Evripidis , Trentzidis Konstantinos , Pelechas Elftherios , Gerolymatou Nafsika , Memi Tereza , Voulgari Paraskevi V
Published: November 2024

Objectives

Systemic sclerosis (SSc) is a rare and complex autoimmune disease with significant complications. During the past few years, research interest has focused on the differences between female and male patients. However, there is a lack of data regarding the role of sex in the presence of small airway disease (SAD). Therefore, we aimed to investigate the impact of sex on pulmonary involvement in a cohort of SSc patients, focusing primarily on small airways.

Methods

For this retrospective study, consecutive patients with a diagnosis of SSc that visited our department up to January 2024 were recruited. Demographic data, disease manifestations, serological profile and internal organ involvement were compared between the two groups.

Results

In total, 393 patients (female-to-male ratio 6:1) were included. Median time to diagnosis after the onset of Raynaud’s was significantly longer for female patients. Electrocardiogram abnormalities were more common in male patients, while telangiectasias, calcinosis and arthralgias were more common in female individuals. Moreover, male SSc patients exhibited a higher prevalence of ILD and shorter time until the diagnosis of ILD. However, female individuals demonstrated a lower maximal-mid expiratory flow rate (MMEF) and higher ratio of residual volume to total lung capacity. Interestingly, sex remained an independent predictor of MMEF, in the multivariate analysis.

Conclusion

Our results showed that, although ILD is more common in male SSc patients, SAD was more prevalent among female individuals. Importantly, female sex remained an independent predictor of SAD. This study further supports the presence of sex-related differences in SSc, with important implications in disease course and management.
The politics of missions: a gloomy perspective
Authors: Molica Francesco
Published: November 2024

This article discusses the so far understudied role of politics in the development of transformative innovation policies (TIPs) and mission-oriented innovation policies (MOIPs). The topic is explored through four dimensions foreshadowing critical bottlenecks and obstacles which are somewhat neglected by the current scholarly discussion around TIPs and MOIPs. The first dimension concerns the relationship to the historical time of different political visions, affecting their inclination towards the transformative ambition of TIPs and MOIPs. The second pertains to the exercise of power and its relation to TIPs and MOIPs’ emphasis on distributed agency and participation. The third addresses the capacity to deliver policy changes, a key precondition for TIPs and MOIPs. Finally, the fourth dimension relates to how political systems deal with diverse values and beliefs, essential for the experimental nature of TIPs and MOIPs. The article concludes that the current trend towards conservatism, centralization, and political polarization in many advanced economies challenges the effective adoption and deployment of TIPs and MOIPs.
Status Threat, Meritocracy, and the Politics of Solidarity in the Seoul Subway
Authors: Kang Youbin
Published: November 2024

How do educational credentials, status beliefs, and the labor process influence solidarity? In response to pro-labor employment policies that aimed at reversing precarious outsourcing contracts in the Seoul Subway, a cohort of younger, educated workers organized in opposition. Although their efforts were unsuccessful, the opposition marks a surprising shift in trade unionism. Drawing from archival research, ethnographic observations, and 60 interviews, I find that status anxieties were key drivers of the countermovement. This group of workers rejected the traditional “solidarity” approach in favor of a “skills” approach, citing the violation of meritocratic ideals habituated in educational systems and enabled in smaller, more independent work settings. Using employment data from the transit authority, I show how the resulting politics of skills classifications reiterates and reproduces extant gender and age inequalities of the workplace. This paper provides a workplace-specific case study of the conditions under which cultural beliefs about stratification take hold and raises questions about the fairness and effectiveness of relying on credentialing and education as tools for social mobility, given their role in perpetuating structural inequalities.
Are Modern Cryptic Species Detectable in the Fossil Record? A Case Study on Agamid Lizards
Authors: Ramm Till , Gray Jaimi A , Hipsley Christy A , Hocknull Scott , Melville Jane , Müller Johannes
Published: November 2024

Comparisons of extant and extinct biodiversity are often dependent on objective morphology-based identifications of fossils and assume a well-established and comparable taxonomy for both fossil and modern taxa. However, since many modern (cryptic) species are delimitated mainly via external morphology and/or molecular data, it is often unclear to what degree fossilized (osteological) remains allow classification to a similar level. When intraspecific morphological variation in extant taxa is poorly known, the definition of extinct species as well as the referral of fossils to extant species can be heavily biased, particularly if fossils are represented by incomplete isolated skeletal elements. This problem is especially pronounced in squamates (lizards and snakes) owing to a lack of osteological comparative knowledge for many lower taxonomic groups, concomitant with a recent increase of molecular studies revealing great cryptic diversity. Here, we apply a quantitative approach using 3D geometric morphometrics on 238 individuals of 14 genera of extant Australian and Papua New Guinean agamid lizards to test the value of 2 isolated skull bones (frontals and maxillae) for inferring taxonomic and ecological affinities. We further test for the consistency of intra- and interspecific morphological variability of these elements as a proxy for extinct taxonomic richness. We show that both bones are diagnostic at the generic level, and both can infer microhabitat and are of paleoecological utility. However, species-level diversity is likely underestimated by both elements, with ~30–40% of species pairs showing no significant differences in shape. Mean intraspecific morphological variability is largely consistent across species and bones and thus a useful proxy for extinct species diversity. Reducing sample size and landmark completeness to approximate fossil specimens led to decreased classification accuracy and increased variance of morphological disparity, raising further doubts on the transferability of modern species borders to the fossil record of agamids. Our results highlight the need to establish appropriate levels of morphology-based taxonomic or ecological groupings prior to comparing extant and extinct biodiversity.
Phylogenetic analysis of Neotropical Dryinus using morphological characters: new proposed classification for species groups and description of a new genus (Hymenoptera: Dryinidae)
Authors: Martins André L , Melo Gabriel A R
Published: November 2024

Dryinus is a cosmopolitan genus and the most diverse group within Dryininae. Herein, we present the first phylogenetic analyses for species groups of Dryinus from the Neotropical region, including three extant genera of Dryininae, one fossil, and a rich taxon sampling of extant species. A total of 116 characters were coded to 42 terminal taxa, including 28 species representing Dryinus of the Neotropics. Our analyses showed that Dryinus is paraphyletic, with the two species D. caraibicus (Olmi) and D. lamellatus (Olmi) coming out separately from the remaining species. A new genus, Dirrhinodryinus, is here described to accommodate them. Based on the phylogeny, Dryinus s.s. is divided into six species groups: autumnalis, catarinae, constans, fiorii, ruficeps, and magnificus. Of the four previously recognized species groups, only two were recovered here: autumnalis and constans. Additionally, we corroborated the synonym of Megadryinus under Dryinus. Considering the evidence that the Neotropical Dryinus form an independent clade, our expectation is that the new classification proposed here will not be applicable to the fauna of other biogeographic regions.
Dual-Energy Computed Tomography: Technology, Applications, and Advantages
Authors: Tran Julia , Yaghmai Vahid , Shi James
Published: November 2024

Dual-energy computed tomography (DECT) is a powerful imaging modality with diverse clinical applications. Unlike conventional CT, DECT acquires images at 2 energy levels to precisely identify and quantify various tissue types. There are several DECT acquisition techniques, each with distinct advantages and disadvantages related to radiation dose, image quality, and other considerations. Material decomposition algorithms are applied to DECT imaging data to separate tissues into their constituent components such as iodine, calcium, or uric acid. Postprocessing techniques generate specialized images and quantitative maps by adjusting the attenuation of each component. For example, removing the attenuation from iodine generates virtual noncontrast images. Material-specific maps, such as uric acid or gout maps, overlay a material’s specific attenuation on a standard CT scan to map their distribution. DECT improves everyday interpretation as hypervascular lesions can be more easily identified, contrast enhancement can be determined on a single postcontrast acquisition, imaging artifacts can be reduced, and noncontrast scans can be generated without additional radiation to patients.