bluuebunny/crossref_metadata_2025 huggingface dataset:
New molecular evidence on the members of the genus Ortholinea (Cnidaria, Myxozoa) and the description of Ortholinea hamsiensis n. sp. infecting the urinary bladder of European anchovy Engraulis engrasicolus in the Black Sea
Authors: Okkay Sevilay , Gürkanlı Cem Tolga , Çiftçi Yılmaz , Özer Ahmet
Published: March 2024

Members of the genus Ortholinea are among the worldwide distributed myxozoan parasites that mainly infect marine fish. In this study, a new myxosporean species, Ortholinea hamsiensis n. sp., was isolated from the urinary bladder of European anchovy Engraulis engrasicolus collected from the Sinop coasts of the Black Sea. The prevalence and density values of infection were 1.4% and 1–5 individuals in the field of view (1 + ), respectively. Mature myxospores are subspherical with slight tapering down to the less pronounced tip in the frontal view and subspherical in the sutural view. Myxospores measured 9.1 ± 0.25 (8.8–9.9) μm in length, 9.2 ± 0.11 (8.9–9.4) μm in thickness, and 8.4 ± 0.33 (8.2-9.1) μm in width. Two polar capsules equal in size measured 3.1 ± 0.11 (3.0–3.3) μm in length and 2.7 ± 0.11 (2.6–2.9) μm in width. The polar tubule had 3–4 coils. Along with morphological peculiarities, the results of the 18S rDNA also revealed it to be a new species for science compared to the other species of the genus. In this study, another myxosporean species O. gobiusi was also detected in round goby Neogobius melanostomus with a prevalence of infection value of 4.8% and a density of 1–5 individuals in the field of view (1 + ). The present study also provided the first data of 18S rDNA of O. gobiusi from N. melanostomus and type species of the genus O. divergens from Gobius niger and the phylogenetic relationships of these species with other Ortholinea species have been revealed.
Jews and German Politics: The Case of Habsburg Moravia, 1867–1918
Authors: Rozenblit Marsha L.
Published: March 2024

In the Austrian province of Moravia, Jews, most of whom spoke German, continued to participate in and support the German political community until the end of the Habsburg monarchy. Unlike in nearby Bohemia, German liberals in Moravia did not abandon the Jews as the franchise expanded and antisemitism grew. Indeed, the German Progressive Party continued to attract voters in the cities of the province and did not resort to antisemitism in order to do so. Although there were only a small number of Jews in the province—just over 40,000—they played a large role among the voters in the urban curia. After the Moravian Compromise of 1905, when German parties no longer had to compete with Czech parties, Jews often formed the majority of all voters for German parties in the small market towns of the largely Czech-speaking south and central part of the province. The perception of the need for Jewish support in elections created a situation in which the German liberals did not turn to antisemitic politics and the Jewish/German liberal alliance remained strong.
Participation, autonomy and control are shared concepts within older people's interpretations of independence: a qualitative interview study
Authors: Taylor Emily , Frost Julia , Ball Susan , Clegg Andrew , Brown Lesley , Goodwin Victoria A.
Published: March 2024

To date, support for independence in older people has been largely focused on achieving practice- and policy-orientated goals such as maintenance of function, remaining in one's own home and reducing the impact of receiving care. Uncertainty about what independence means to older people means that these goals may not align with what matters and should be considered for a more person-centred approach to independence. This study aimed to improve understanding of the meaning and facilitators of independence from older people's perspectives. Semi-structured interviews were conducted with 14 community-dwelling people aged 75+, purposively sampled for maximum variance in demographic characteristics. Interviews, conducted by phone or online, were recorded and transcribed. Analysis was conducted using a framework approach to organise, and facilitate comparison of, inductively and deductively generated codes. Patterns were identified and interpreted into themes. Transcripts and themes were reviewed with the research team. Disagreements in interpretations were resolved through discussion. Two themes were identified. The first theme, ‘Older people draw on personal values and experiences to develop unique interpretations of independence’, was underpinned by three concepts: participation, autonomy and control. The concepts reflected patterns identified within participants’ meanings of independence. The second theme, ‘It's not what you have, but how you think about it that creates independence’, represented participants’ shared prioritisation of psychological attributes over physical or environmental resources for maintaining independence. Participation, autonomy and control are shared concepts within older people's diverse interpretations of independence. This paper addresses uncertainty around what independence means to older people and contributes three key concepts that should be considered when operationalising person-centred support for independence.
Manipulation in politics and public policy
Authors: Dowding Keith , Oprea Alexandra
Published: March 2024

Many philosophical accounts of manipulation are blind to the extent to which actual people fall short of the rational ideal, while prominent accounts in political science are under-inclusive. We offer necessary and sufficient conditions – Suitable Reason and Testimonial Honesty – distinguishing manipulative from non-manipulative influence; develop a ‘hypothetical disclosure test’ to measure the degree of manipulation; and provide further criteria to assess and compare the morality of manipulation across cases. We discuss multiple examples drawn from politics and from public policy with particular attention to recent debates about the ethics and politics of nudge.
The future of neuroscience in developmental psychopathology
Authors: Hyde Luke W. , Bezek Jessica L. , Michael Cleanthis
Published: March 2024

Developmental psychopathology started as an intersection of fields and is now a field itself. As we contemplate the future of this field, we consider the ways in which a newer, interdisciplinary field – human developmental neuroscience – can inform, and be informed by, developmental psychopathology. To do so, we outline principles of developmental psychopathology and how they are and/or can be implemented in developmental neuroscience. In turn, we highlight how the collaboration between these fields can lead to richer models and more impactful translation. In doing so, we describe the ways in which models from developmental psychopathology can enrich developmental neuroscience and future directions for developmental psychopathology.
Antidirected subgraphs of oriented graphs
Authors: Stein Maya , Zárate-Guerén Camila
Published: March 2024

We show that for every
$\eta \gt 0$
every sufficiently large
$n$
-vertex oriented graph
$D$
of minimum semidegree exceeding
$(1+\eta )\frac k2$
contains every balanced antidirected tree with
$k$
edges and bounded maximum degree, if
$k\ge \eta n$
. In particular, this asymptotically confirms a conjecture of the first author for long antidirected paths and dense digraphs.

Further, we show that in the same setting,
$D$
contains every
$k$
-edge antidirected subdivision of a sufficiently small complete graph, if the paths of the subdivision that have length
$1$
or
$2$
span a forest. As a special case, we can find all antidirected cycles of length at most
$k$
.

Finally, we address a conjecture of Addario-Berry, Havet, Linhares Sales, Reed, and Thomassé for antidirected trees in digraphs. We show that this conjecture is asymptotically true in
$n$
-vertex oriented graphs for all balanced antidirected trees of bounded maximum degree and of size linear in
$n$
.
Creating a flow restrictor in ductal stenting: a novel technique
Authors: Doan Tam T. , Nguyen Yen T. K. , Tran Phung C. B.
Published: March 2024

Ductal stenting has transformed the care of neonates with ductal-dependent critical CHD, especially in low-income countries. In small infants, a 3.5- or 4-mm stent may lead to too much pulmonary blood flow resulting in pulmonary oedema. We herein presented a novel technique to restrict ductal stent flow in a premature neonate with pulmonary atresia and intact ventricular septum following radiofrequency perforation of the pulmonary valve.
Leukotriene B4 levels in CHD-associated paediatric pulmonary hypertension
Authors: Vuran Gamze , Yılmazer Murat Muhtar , Gerçeker Engin , Zihni Cüneyt , Meşe Timur
Published: March 2024

Background:

The aim of this study is to evaluate the role of leukotriene B4, an inflammatory mediator, in the development of pulmonary hypertension in paediatric patients with CHD with left-right shunt.

Methods:

The study included forty patients with CHD with left-right shunts. Based on haemodynamic data obtained from cardiac diagnostic catheterisation, 25 patients who met the criteria for pulmonary arterial hypertension were included in the patient group. The control group comprised 15 patients who did not meet the criteria. The standard cardiac haemodynamic study was conducted. Leukotriene B4 levels were assessed in blood samples taken from both pulmonary arteries and peripheral veins.

Results:

The median age of patients with pulmonary arterial hypertension was 10 months (range: 3–168), while the median age of the control group was 50 months (range: 3–194). In the pulmonary hypertension group, the median pulmonary artery systolic/diastolic/mean pressures were 38/18/24 mmHg, compared to 26/10/18 mmHg in the control group. Leukotriene B4 levels in pulmonary artery blood samples were significantly higher in the pulmonary arterial hypertension group compared to the controls (p < 0.05). Peripheral leukotriene B4 levels were also elevated in the pulmonary arterial hypertension group in comparison to the control group, though the difference was not statistically significant.

Conclusion:

The discovery of elevated leukotriene B4 levels in pulmonary artery samples from paediatric patients with pulmonary arterial hypertension secondary to CHD with left-to-right shunt suggests that local inflammation may have a pathological role in the development of pulmonary arterial hypertension.
Up-to-date understanding of overtraining syndrome and overlap with related disorders
Authors: Haghighat Nekisa , Stull Todd
Published: March 2024

Abstract: Introduction: The rigorous training regimens of elite athletes are, by nature, emotionally, physically, and mentally demanding. These regimens can result in marked improvements in athletic performance when they incorporate adequate intervals of rest and recovery. Continued training in the absence of adequate recovery progresses to a constellation of symptoms that affect medical and mental health, which is referred to as overtraining syndrome (OTS). Method: A literature review was conducted using PubMed, a database of reference on medical research maintained by the US national Library of Medicine and the National Institute of Health. Search terms included “overtraining syndrome”, “Unexplained Underperformance” (UUPS), “Burnout” in athletes. Results: The collection of the published work provides insight into the multidimensional composition and complexity of OTS in athletes. OTS progresses along a continuum without adequate recovery. Conclusion: Decreased athletic performance in the setting of increased training intensity without appropriate recovery, often accompanied by changes in mood, motivation, and general well-being are the distinctive features of OTS. OTS is preceded by stages of underperformance that are reversable and preventable, highlighting the importance of recognizing, managing, and preventing overtraining in athletes in order to prevent long-term negative outcomes is a maladaptive response to an imbalance between exercise and recovery.
Understanding the Impact of Precipitation Bias‐Correction and Statistical Downscaling Methods on Projected Changes in Flood Extremes
Authors: Michalek Alexander T. , Villarini Gabriele , Kim Taereem
Published: March 2024

This study evaluates five bias correction and statistical downscaling (BCSD) techniques for daily precipitation and examines their impacts on the projected changes in flood extremes (i.e., 1%, 0.5%, and 0.2% floods). We use climate model outputs from the Coupled Model Intercomparison Project Phase 6 (CMIP6) to conduct hydrologic simulations across watersheds in Iowa and determine historical and future flood extreme estimates based on generalized extreme value distribution fitting. Projected changes in these extremes are examined with respect to four Shared Socioeconomic Pathways (SSPs) alongside five BCSD techniques. We find the magnitude of the estimates of future annual exceedance probabilities (AEPs) are expected to increase under all SSPs, especially for the emission scenarios with higher greenhouse gases concentrations (i.e., SSP370 and SSP585). Our results also suggest the choice of BCSD impacts the magnitude of the projected changes, with the SSPs that play a more limited role compared to the choice of downscaling method. The variability in projected flood changes across Iowa is similar across the downscaling technique but increases as the AEP increases. Our findings provide insights into the impact of downscaling techniques on flood extremes' projections and useful information for climate planning across the state.
Authigenic Carbonate Burial Within the Late Devonian Western Canada Sedimentary Basin and Its Impact on the Global Carbon Cycle
Authors: Gazdewich Sean , Hauck Tyler , Husson Jon
Published: March 2024

Stable carbon isotope ratios (δ13C values) of marine carbonates are widely used to infer the relative burial rates of organic carbon, a source of oxygen to the ocean‐atmosphere system. This inference, however, is based on the assumption that ocean‐atmospheric carbon is buried either as organic carbon or as marine carbonate minerals. The burial of authigenic carbonate minerals formed within sediments after deposition, with low δ13C values (i.e., similar to organic carbon), has been proposed to explain high δ13C values in marine carbonates without the need for high burial fluxes of organic carbon. To test this hypothesis, we focus on the Late Devonian, a time period with both pervasive ocean anoxia and a severe reduction in shallow‐water carbonate deposition—conditions hypothesized to promote authigenic carbonate formation. We present sedimentological and geochemical data from limestones and black shales of the Wabamun Group, Besa River and Exshaw formations of the Western Canada Sedimentary Basin. These data are compared to inorganic and organic weight percent measurements of North American shales acquired from the USGS National Geochemical Database (N = 4,437). Results show that basinal shale lack authigenic carbonate with low δ13C values and that the mean δ13C value of carbonate in these shales (−0.3‰) do not differ substantially from mean δ13C of carbonates in platform carbonates of a similar age (0.6‰). Furthermore, inorganic carbon content in Late Devonian shales (mean weight percent = 0.55%, N = 54) is lower than average Phanerozoic North American shale (mean of 1.95%, N = 4,055). Lastly, organic carbon‐to‐inorganic carbon ratios (OC:IC) of North American shales are well above 1 (mean = 3.72 for Late Devonian shales (N = 374), 2.25 for shales (N = 3,653) of all other ages). Therefore, even if the burial of fine‐grained siliciclastic formations carrying authigenic carbonates were to increase, the concomitant increase in organic carbon burial would be even larger. Together, data from this study do not provide evidence that the burial of authigenic carbonate would have a significant effect on global carbon isotope mass balance.
Air Quality and Health Impacts of Onshore Oil and Gas Flaring and Venting Activities Estimated Using Refined Satellite‐Based Emissions
Authors: Tran Huy , Polka Erin , Buonocore Jonathan J. , Roy Ananya , Trask Beth , Hull Hillary , Arunachalam Saravanan
Published: March 2024

Emissions from flaring and venting (FV) in oil and gas (O&G) production are difficult to quantify due to their intermittent activities and lack of adequate monitoring and reporting. Given their potentially significant contribution to total emissions from the O&G sector in the United States, we estimate emissions from FV using Visible Infrared Imaging Radiometer Suite satellite observations and state/local reported data on flared gas volume. These refined estimates are higher than those reported in the National Emission Inventory: by up to 15 times for fine particulate matter (PM2.5), two times for sulfur dioxides, and 22% higher for nitrogen oxides (NOx). Annual average contributions of FV to ozone (O3), NO2, and PM2.5 in the conterminous U.S. (CONUS) are less than 0.15%, but significant contributions of up to 60% are found in O&G fields with FV. FV contributions are higher in winter than in summer months for O3 and PM2.5; an inverse behavior is found for NO2. Nitrate aerosol contributions to PM2.5 are highest in the Denver basin whereas in the Permian and Bakken basins, sulfate and elemental carbon aerosols are the major contributors. Over four simulated months in 2016 for the entire CONUS, FV contributes 210 additional instances of exceedances to the daily maximum 8‐hr average O3 and has negligible contributions to exceedance of NO2 and PM2.5, given the current form of the national ambient air quality standards. FV emissions are found to cause over $7.4 billion in health damages, 710 premature deaths, and 73,000 asthma exacerbations among children annually.
Thermal Stressing of Volcanic Rock: Microcracking and Crack Closure Monitored Through Acoustic Emission, Ultrasonic Velocity, and Thermal Expansion
Authors: Griffiths L. , Heap M. J. , Lengliné O. , Baud P. , Schmittbuhl J. , Gilg H. A.
Published: March 2024

Microcracking due to thermal stresses affects the mechanical and flow properties of rocks, which is significant for thermally dynamic environments such as volcanoes and geothermal reservoirs. Compared with other crustal rocks like granite, volcanic rocks have a complex and variable response to temperature; it remains unclear how thermal microcracks form and how they are affected by temperature. We heated and cooled samples of low‐porosity basalts containing different amounts of microcracks and a porous andesite over three cycles, whilst monitoring microstructural changes by acoustic emission (AE) monitoring and measurement of P‐wave velocity (vP; up to 450°C) and thermal expansion coefficient (TEC; up to 700°C). During the second and third cycles, the TEC was positive throughout and the rate of detected AE was low. In contrast to studies on granite, we measured a strong and reversible increase in vP with increasing temperature (by 15%–40% at 450°C), which we interpret as due to microcrack closure. During the first cycle, AE and vP measurements indicated thermal microcracking within the andesite and the basalt with a low initial microcrack density. For these samples, strong inflexions in the TEC indicated stress relaxation during heating, preceding significant thermal microcracking during cooling. The basalt with a high initial microcrack density underwent little microcracking throughout all cycles. Our results and a review of the literature relate the initial microstructure to the occurrence of thermal microcracking and explore the potentially significant influence of temperature on volcanic rock properties.
Impact of Ancient Tectonics on Intracontinental Deformation Partitioning: Insights From Crustal Structures of the East Junggar‐Altai Area
Authors: Yang Xusong , Tian Xiaobo , Wan Bo , Yuan Huaiyu , Zhao Liang , Xiao Wenjiao
Published: March 2024

Compressive stress generated at collision fronts can propagate over long distances, inducing deformation within the continent's interior. Nevertheless, the factors governing the partitioning of intracontinental deformation remain enigmatic. The Altai Mountains serve as a type‐example of ongoing intracontinental deformation. Here, we investigate the crustal architecture of the Chinese Altai Mountains, using receiver functions obtained from newly deployed dense seismic nodal arrays. The new seismic results reveal distinct crustal features, including (a) a negative polarity discontinuity beneath Chinese Altai Mountains, suggesting a low‐velocity layer; (b) a north‐dipping mid‐crustal structure beneath the suture zone between East Junggar and Chinese Altai, indicating underthrusting of East Junggar's lower crust beneath the Chinese Altai Mountains; (c) a double Moho structure beneath East Junggar, revealing a high‐velocity lower crustal layer. In conjunction with constraints from previous multi‐disciplinary regional studies, the double Moho structures are interpreted as mafic restite from Late Paleozoic magma underplating. The addition of mafic materials can significantly enhance the rheological strength of East Junggar's crust, causing it to function as an indenter that thrust beneath the Chinese Altai Mountains during the subsequent convergence process. As a consequence, significant deformation occurs in the Chinese Altai region, resulting in the emergence of decollements, as evident by the negative polarity discontinuity. The presence of pre‐existing decollements makes the Altai Mountains region more susceptible to deformation, thereby facilitating the concentration of intracontinental deformation. These findings illuminate the evolution history of the Chinese Altai Mountains and highlight the great impacts of ancient tectonics on intracontinental deformation partitioning.
Loop Current Eddies as a Possible Cause of the Rapid Sea Level Rise in the Gulf of Mexico
Authors: Thirion Gabriel , Birol Florence , Jouanno Julien
Published: March 2024

The Gulf of Mexico (GOM), with its densely populated coastline, is one of the world's most vulnerable regions to climate change and sea level (SL) rise. Over the last three decades, various works have been conducted to assess coastal SL trends around the basin using tide gauge stations, separately from studies dealing with regional dynamical processes. Using altimetry, Argo, and eddy atlas products over the period from January 1993 to December 2020, we have analyzed the regional SL variations in the area to define their characteristics and explore their possible dynamical causes. We observe a mean GIA‐corrected SL rise rate of 4.81 ± 0.85 mm yr−1, which is 25% higher than that of the adjacent Caribbean Sea and 44% higher than that of the global ocean. This result highlights the singular SL evolution in the GOM over the 28‐year study period. Over 2010–2020, the SL trend in the GOM has even accelerated, along with a strong warming of the upper‐layer (0.58 ± 0.17°C), which explains ∼60% of the SL rise rate through the thermosteric effect. Finally, the heat input estimates emphasize the role of the Loop Current eddies as a major contributor to the recent acceleration of SL rise due to upper‐layer warming.
A Mechanism for the Summer Monsoon Precipitation Variability Over Northwest India Driven by Moisture Deficit Transport
Authors: Singh Rahul , Sandeep S.
Published: March 2024

A large reservoir of saturation deficit air is known to exist over the northern Arabian Sea and the adjoining land regions during the peak of Indian summer monsoon (ISM). The strengthening of monsoon low‐level jet (LLJ) in the northern parts of the Arabian Sea during the break phase of ISM helps in transporting this dry air toward northwestern India. Here, we show that, a weakening (strengthening) of the zonal flow over the northern Arabian Sea can reduce (enhance) the influx of the unsaturated air to the Northwest India and thereby enhance (reduce) precipitation there. The variability in the zonal flow over the northern Arabian Sea is a direct geostrophic response to the variability in the meridional pressure gradient over the Northwest India. The interannual variability in the mean sea level pressure over the region explains the inter‐annual variability of ISM precipitation during July–August over northwestern India. The contribution of El Niño Southern Oscillation in the interannual variability of precipitation over this region is not significant.
Mapping the Ocean’s Motion Energy
Authors: Meduna Veronika
Published: March 2024

The ocean is a central component of Earth’s climate system. But it is in perpetual motion, and understanding the transfer of kinetic energy is key to better ocean models.
Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective
Authors: Nguyen Tram T. T. , Kim Yoon Tae , Jeong Geunyeol , Jin Mirim
Published: March 2024

Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (sHLH/MAS) is a life-threatening immune disorder triggered by rheumatic disease, infections, malignancies, or medications. Characterized by the presence of hemophagocytic macrophages and a fulminant cytokine storm, sHLH/MAS leads to hyperferritinemia and multiorgan failure and rapidly progresses to death. The high mortality rate and the lack of specific treatments necessitate the development of a new drug. However, the complex and largely unknown immunopathologic mechanisms of sHLH/MAS, which involve dysfunction of various immune cells, diverse etiologies, and different clinical contexts make this effort challenging. This review introduces the terminology, diagnosis, and clinical features of sHLH/MAS. From a translational perspective, this review focuses on the immunopathological mechanisms linked to various etiologies, emphasizing potential drug targets, including key molecules and signaling pathways. We also discuss immunomodulatory biologics, existing drugs under clinical evaluation, and novel therapies in clinical trials. This systematic review aims to provide insights and highlight opportunities for the development of novel sHLH/MAS therapeutics.
Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries
Authors: Lübke Johannes , Christen Deborah , Schwaab Juliana , Kaiser Anne , Naumann Nicole , Shoumariyeh Khalid , Jentzsch Madlen , Sockel Katja , Schaffrath Judith , Ayuk Francis A. , Stelljes Matthias , Hilgendorf Inken , Sala Elisa , Kaivers Jennifer , Schönland Stefan , Wittke Christoph , Hertenstein Bernd , Radsak Markus , Kaiser Ulrich , Brückl Valeska , Kröger Nicolaus , Brümmendorf Tim H. , Hofmann Wolf-Karsten , Klein Stefan , Jost Edgar , Reiter Andreas , Panse Jens
Published: March 2024

We identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received an allogeneic hematopoietic cell transplantation (alloHCT) performed in Germany from 1999–2021. Median overall survival (OS) of ASM/SM-AHN (n = 30, 45%), SM-AML (n = 28, 39%) and MCL ± AHN (n = 13, 19%) was 9.0, 3.3 and 0.9 years (P = 0.007). Improved median OS was associated with response of SM (17/41, 41%; HR 0.4 [0.2–0.9], P = 0.035) and/or of AHN (26/43, 60%, HR 0.3 [0.1–0.7], P = 0.004) prior to alloHCT. Adverse predictors for OS included absence of KIT D816V (10/61, 16%, HR 2.9 [1.2–6.5], P < 0.001) and a complex karyotype (9/60, 15%, HR 4.2 [1.8–10.0], P = 0.016). HLA-match, conditioning type or transplantation at centers reporting above-average alloHCTs (≥7) had no impact on OS. Taking into account competing events at years 1, 3 and 5, relapse-related mortality and non-relapse mortality rate were 15%/23%, 20%/30% and 23%/35%, respectively. Irrespective of subtype, subsequent treatment response was achieved in 13/30 (43%) patients and was highest on midostaurin/avapritinib (7/9, 78%). We conclude that outcome of alloHCT in AdvSM is more affected by disease phenotype and treatment response prior to transplant than by transplant characteristics.
Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1
Authors: Xie Xiong , Lan Qiaoshuai , Zhao Jinyi , Zhang Sulin , Liu Lu , Zhang Yumin , Xu Wei , Shao Maolin , Peng Jingjing , Xia Shuai , Zhu Yan , Zhang Keke , Zhang Xianglei , Zhang Ruxue , Li Jian , Dai Wenhao , Ge Zhen , Hu Shulei , Yu Changyue , Wang Jiang , Ma Dakota , Zheng Mingyue , Yang Haitao , Xiao Gengfu , Rao Zihe , Lu Lu , Zhang Leike , Bai Fang , Zhao Yao , Jiang Shibo , Liu Hong
Published: March 2024

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.
Impact of dental visiting patterns on oral health: A systematic review of longitudinal studies
Authors: Mohd Khairuddin Aina Najwa , Bogale Birke , Kang Jing , Gallagher Jennifer E.
Published: March 2024

Aim

To systematically review longitudinal studies investigating the impact of dental visiting patterns on oral health across the life course.

Methods

Five databases (MEDLINE, Embase, Scopus, Web of Science, CINAHL) were searched up to March 2023. Results were screened based on eligibility criteria in a two-stage process: title and abstract, and full-text review. A backward search of reference lists and a forward search of citations of the included papers was also conducted. The quality of the included papers was assessed using the Newcastle-Ottawa Scale. Key study information was extracted and a narrative synthesis of the findings was performed.

Results

Eleven papers from five longitudinal studies in five countries (Australia, Brazil, China, New Zealand, Sweden) met the inclusion criteria. Studies of moderate to high quality consistently reported that regular dental attendance was associated with having less dental caries experience, fewer missing teeth and better oral health-related quality of life. Inconsistent findings were observed for decayed teeth, and no association was found for periodontal condition.

Conclusions

This review highlights an association between regular dental visiting pattern and improved oral health, notably less dental caries experience and better oral health-related quality of life. Dental attendance emerges as an important predictor of oral health across the life course, underscoring the importance of routine dental care.

Registration information

The PROSPERO registration number is CRD42023396380.
Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas
Authors: Polo-Generelo Salvador , Rodríguez-Mateo Cristina , Torres Belén , Pintor-Tortolero José , Guerrero-Martínez José A. , König Julian , Vázquez Jesús , Bonzón-Kulichenco Elena , Padillo-Ruiz Javier , de la Portilla Fernando , Reyes José C. , Pintor-Toro José A.
Published: March 2024

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.
Real-world effects of anti-vascular endothelial growth factor injection frequency on visual outcomes in patients with diabetic macular oedema
Authors: Payne Carter J. , Gupta Urvi , Maatouk Christopher M. , Kuo Blanche L. , Perkins Scott W. , Singh Rishi P. , Talcott Katherine E.
Published: March 2024

Background and objective

Anti-vascular endothelial growth factor (VEGF) injections are often administered less frequently in real-world treatment of diabetic macular oedema (DMO) than what was studied in clinical trials. This study aims to characterise real-world DMO treatment patterns and the effect of treatment intervals on patient outcomes.

Study design/patients and methods

This was a retrospective study of 291 patients with DMO treated with anti-VEGF therapy. 12- and 24-month best visual acuity (BVA) and central subfield thickness (CST) were compared between injection interval groups, which were determined by averaging the two most recent injection intervals. Multiple linear regressions were performed to identify factors associated with injection interval, BVA, and CST.

Results

48.8% of patients received injections less than or equal to every 8 weeks (≤ q8w), 27.5% between every 8 to 12 weeks (q8–12w), and 23.7% greater than every 12 weeks (> q12w). Baseline CST was similar (p = 0.32), but BVA differed significantly in q8–12w patients (p = 0.0095). BVA and CST at 12 months were similar, but q8–12w patients experienced greater 12-month BVA improvement (7.36 ± 12.4 letters) than > q12w patients (1.26 ± 12.3 letters; p = 0.0056). 24-month BVA and CST changes were similar between groups (p = 0.30 and 0.87). Baseline BVA, HbA1c, and sex were associated with 12-month BVA, and baseline BVA and CST were associated with 12-month CST.

Conclusion

Many patients experienced improvements in BVA and CST over 12 months of treatment despite receiving less frequent anti-VEGF therapy than recommended in the pivotal trials. The present study showed that extended treatment intervals with bevacizumab were effective in preserving vision of many individuals with high baseline BVA.
Capsules and their traits shape phage susceptibility and plasmid conjugation efficiency
Authors: Haudiquet Matthieu , Le Bris Julie , Nucci Amandine , Bonnin Rémy A. , Domingo-Calap Pilar , Rocha Eduardo P. C. , Rendueles Olaya
Published: March 2024

Bacterial evolution is affected by mobile genetic elements like phages and conjugative plasmids, offering new adaptive traits while incurring fitness costs. Their infection is affected by the bacterial capsule. Yet, its importance has been difficult to quantify because of the high diversity of confounding mechanisms in bacterial genomes such as anti-viral systems and surface receptor modifications. Swapping capsule loci between Klebsiella pneumoniae strains allowed us to quantify their impact on plasmid and phage infection independently of genetic background. Capsule swaps systematically invert phage susceptibility, revealing serotypes as key determinants of phage infection. Capsule types also influence conjugation efficiency in both donor and recipient cells, a mechanism shaped by capsule volume and conjugative pilus structure. Comparative genomics confirmed that more permissive serotypes in the lab correspond to the strains acquiring more conjugative plasmids in nature. The least capsule-sensitive pili (F-like) are the most frequent in the species’ plasmids, and are the only ones associated with both antibiotic resistance and virulence factors, driving the convergence between virulence and antibiotics resistance in the population. These results show how traits of cellular envelopes define slow and fast lanes of infection by mobile genetic elements, with implications for population dynamics and horizontal gene transfer.
Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma
Authors: Grandclément C. , Estoppey C. , Dheilly E. , Panagopoulou M. , Monney T. , Dreyfus C. , Loyau J. , Labanca V. , Drake A. , De Angelis S. , Rubod A. , Frei J. , Caro L. N. , Blein S. , Martini E. , Chimen M. , Matthes T. , Kaya Z. , Edwards C. M. , Edwards J. R. , Menoret E. , Kervoelen C. , Pellat-Deceunynck C. , Moreau P. , Mbow M. L. , Srivastava A. , Dyson M. R. , Zhukovsky E. A. , Perro M. , Sammicheli S.
Published: March 2024

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.
Integration of graph neural networks and genome-scale metabolic models for predicting gene essentiality
Authors: Hasibi Ramin , Michoel Tom , Oyarzún Diego A.
Published: March 2024

Genome-scale metabolic models are powerful tools for understanding cellular physiology. Flux balance analysis (FBA), in particular, is an optimization-based approach widely employed for predicting metabolic phenotypes. In model microbes such as Escherichia coli, FBA has been successful at predicting essential genes, i.e. those genes that impair survival when deleted. A central assumption in this approach is that both wild type and deletion strains optimize the same fitness objective. Although the optimality assumption may hold for the wild type metabolic network, deletion strains are not subject to the same evolutionary pressures and knock-out mutants may steer their metabolism to meet other objectives for survival. Here, we present FlowGAT, a hybrid FBA-machine learning strategy for predicting essentiality directly from wild type metabolic phenotypes. The approach is based on graph-structured representation of metabolic fluxes predicted by FBA, where nodes correspond to enzymatic reactions and edges quantify the propagation of metabolite mass flow between a reaction and its neighbours. We integrate this information into a graph neural network that can be trained on knock-out fitness assay data. Comparisons across different model architectures reveal that FlowGAT predictions for E. coli are close to those of FBA for several growth conditions. This suggests that essentiality of enzymatic genes can be predicted by exploiting the inherent network structure of metabolism. Our approach demonstrates the benefits of combining the mechanistic insights afforded by genome-scale models with the ability of deep learning to infer patterns from complex datasets.
The anti-aromatic dianion and aromatic tetraanion of [18]annulene
Authors: Stawski Wojciech , Zhu Yikun , Rončević Igor , Wei Zheng , Petrukhina Marina A. , Anderson Harry L.
Published: March 2024

π-Conjugated macrocycles behave differently from analogous linear chains because their electronic wavefunctions resemble a quantum particle on a ring, leading to aromaticity or anti-aromaticity. [18]Annulene, (CH)18, is the archetypal non-benzenoid aromatic hydrocarbon. Molecules with circuits of 4n + 2 π electrons, such as [18]annulene (n = 4), are aromatic, with enhanced stability and diatropic ring currents (magnetic shielding inside the ring), whereas those with 4n π electrons, such as the dianion of [18]annulene, are expected to be anti-aromatic and exhibit the opposite behaviour. Here we use 1H NMR spectroscopy to re-evaluate the structure of the [18]annulene dianion. We also show that it can be reduced further to an aromatic tetraanion, which has the same shape as the dianion. The crystal structure of the tetraanion lithium salt confirms its geometry and reveals a metallocene-like sandwich, with five Li+ cations intercalated between two [18]annulene tetraanions. We also report a heteroleptic sandwich, with [18]annulene and corannulene tetraanion decks.
Chimpanzees use social information to acquire a skill they fail to innovate
Authors: van Leeuwen Edwin J. C. , DeTroy Sarah E. , Haun Daniel B. M. , Call Josep
Published: March 2024

Cumulative cultural evolution has been claimed to be a uniquely human phenomenon pivotal to the biological success of our species. One plausible condition for cumulative cultural evolution to emerge is individuals’ ability to use social learning to acquire know-how that they cannot easily innovate by themselves. It has been suggested that chimpanzees may be capable of such know-how social learning, but this assertion remains largely untested. Here we show that chimpanzees use social learning to acquire a skill that they failed to independently innovate. By teaching chimpanzees how to solve a sequential task (one chimpanzee in each of the two tested groups, n = 66) and using network-based diffusion analysis, we found that 14 naive chimpanzees learned to operate a puzzle box that they failed to operate during the preceding three months of exposure to all necessary materials. In conjunction, we present evidence for the hypothesis that social learning in chimpanzees is necessary and sufficient to acquire a new, complex skill after the initial innovation.
DeltaDTM: A global coastal digital terrain model
Authors: Pronk Maarten , Hooijer Aljosja , Eilander Dirk , Haag Arjen , de Jong Tjalling , Vousdoukas Michalis , Vernimmen Ronald , Ledoux Hugo , Eleveld Marieke
Published: March 2024

Coastal elevation data are essential for a wide variety of applications, such as coastal management, flood modelling, and adaptation planning. Low-lying coastal areas (found below 10 m +Mean Sea Level (MSL)) are at risk of future extreme water levels, subsidence and changing extreme weather patterns. However, current freely available elevation datasets are not sufficiently accurate to model these risks. We present DeltaDTM, a global coastal Digital Terrain Model (DTM) available in the public domain, with a horizontal spatial resolution of 1 arcsecond (∼30 m) and a vertical mean absolute error (MAE) of 0.45 m overall. DeltaDTM corrects CopernicusDEM with spaceborne lidar from the ICESat-2 and GEDI missions. Specifically, we correct the elevation bias in CopernicusDEM, apply filters to remove non-terrain cells, and fill the gaps using interpolation. Notably, our classification approach produces more accurate results than regression methods recently used by others to correct DEMs, that achieve an overall MAE of 0.72 m at best. We conclude that DeltaDTM will be a valuable resource for coastal flood impact modelling and other applications.
Analytical solutions for the Klein–Gordon equation with combined exponential type and ring-shaped potentials
Authors: Ahmadov A. I. , Nagiyev Sh. M. , Ikot A. N. , Tarverdiyeva V. A.
Published: March 2024

In this study, we have successfully obtained the analytical solutions for the Klein–Gordon equation with new proposed a non-central exponential potential $$V\left( r \right) = D\left[ {1 - \sigma_{0} \coth (\alpha r)} \right]^{2} + (\eta_{1} + \eta_{2} \cos \theta )/r^{2} \sin^{2} \theta$$

V

r

=
D

1
-

σ
0

coth

(
α
r
)

2

+

(

η
1

+

η
2

cos
θ
)

/

r
2

sin
2

θ

. Our approach involves a proper approximation of the centrifugal term, with $${l}{\prime}$$

l
′

representing the generalized orbital angular momentum quantum number, and the utilization of the Nikiforov–Uvarov method. The resulting radial and angular wave functions are expressed in terms of Jacobi polynomials, and the corresponding energy equation is also derived. Our calculations of the eigenvalues for arbitrary quantum numbers demonstrated significant sensitivity to potential parameters and quantum numbers. Additionally, we evaluate the dependence of energy eigenvalues on screening parameter $$\alpha$$
α
for arbitrary quantum numbers $$n_{r}$$

n
r

and $$N$$
N
to establish the accuracy of our findings. Furthermore, we determine the non-relativistic limits of the radial wave function and energy equation, which align with corresponding previous results in the case where $$\eta_{1} = \eta_{2} = 0$$

η
1

=

η
2

=
0

.