bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards the understanding of the core of general personality disorder factor: g-PD and its relation to hostile attributions
Authors: Zajenkowska Anna , Nowakowska Iwona , Cieciuch Jan , Gawęda Łukasz , Rogoza Radosław , Pinkham Amy , Czajkowska-Łukasiewicz Katarzyna
Published: March 2024

There is a general consensus that personality disorders (PDs) share a general factor (g-PD) overlapping with the general factor of psychopathology (p-factor). The general psychopathology factor is related to many social dysfunctions, but its nature still remains to some extent ambiguous. We posit that hostile attributions may be explanatory for the factor common for all PDs, i.e., interpersonal problems and difficulty in building long-lasting and satisfying relationships of all kinds. Thus, the main objective of the current project was to expand the existing knowledge about underlying factors of g-PD with regard to hostile attributions. We performed a cross-sectional study on a representative, community sample of Poles (N = 1031). Our hypotheses were primarily confirmed as hostile attributions predicted p-factor. However, the relation was positive only for hostile attributions related to ambiguous situations involving relational harm and physical harm done by female authorities and negative in case of hostile attributions in situations involving physical harm done by peers. Additionally, paranoia-like thoughts strongly related to hostile attributions and independently predicted g-PD. The results contribute to the current discussion on the nature of the g-PD, confirm that hostile attributions and paranoia are a crucial aspect of personality pathology, and indicate the importance of working on these cognitions in the course of therapeutic work.
Patterns and predictors of alcohol misuse trajectories from adolescence through early midlife
Authors: Stephenson Mallory , Barr Peter , Thomas Nathaniel , Cooke Megan , Latvala Antti , Rose Richard J. , Kaprio Jaakko , Dick Danielle , Salvatore Jessica E.
Published: March 2024

We took a multilevel developmental contextual approach and characterized trajectories of alcohol misuse from adolescence through early midlife, examined genetic and environmental contributions to individual differences in those trajectories, and identified adolescent and young adult factors associated with change in alcohol misuse. Data were from two longitudinal population-based studies. FinnTwin16 is a study of Finnish twins assessed at 16, 17, 18, 25, and 35 years (N = 5659; 52% female; 32% monozygotic). The National Longitudinal Study of Adolescent to Adult Health (Add Health) is a study of adolescents from the United States, who were assessed at five time points from 1994 to 2018 (N = 18026; 50% female; 64% White, 21% Black, 4% Native American, 7% Asian, 9% Other race/ethnicity). Alcohol misuse was measured as frequency of intoxication in FinnTwin16 and frequency of binge drinking in Add Health. In both samples, trajectories of alcohol misuse were best described by a quadratic growth curve: Alcohol misuse increased across adolescence, peaked in young adulthood, and declined into early midlife. Individual differences in these trajectories were primarily explained by environmental factors. Several adolescent and young adult correlates were related to the course of alcohol misuse, including other substance use, physical and mental health, and parenthood.
Public Reason, Bioethics, and Public Policy: A Seductive Delusion or Ambitious Aspiration?
Authors: Fleck Leonard M.
Published: March 2024

Can Rawlsian public reason sufficiently justify public policies that regulate or restrain controversial medical and technological interventions in bioethics (and the broader social world), such as abortion, physician aid-in-dying, CRISPER-cas9 gene editing of embryos, surrogate mothers, pre-implantation genetic diagnosis of eight-cell embryos, and so on? The first part of this essay briefly explicates the central concepts that define Rawlsian political liberalism. The latter half of this essay then demonstrates how a commitment to Rawlsian public reason can ameliorate (not completely resolve) many of the policy disagreements related to bioethically controversial medical interventions today. The goal of public reason is to reduce the size of the disagreement by eliminating features of the disagreement that violate the norms of public reason. The norms of public reason are those norms that are politically necessary to preserve the liberal, pluralistic, democratic character of this society. What remains is reasonable disagreement to be addressed through normal democratic deliberative processes. Specific issues addressed from a public reason perspective include personal responsibility for excessive health costs, the utility of a metaphysical definition of death for organ transplantation, and the moral status of excess embryos generated through IVF and/or their use in medical research.
Six elements test vs D-KEFS: what does “Ecological Validity” tell us?
Authors: Suchy Yana , Gereau Mora Michelle , Brothers Stacey Lipio , DesRuisseaux Libby A.
Published: March 2024

Objective:

Extensive research shows that tests of executive functioning (EF) predict instrumental activities of daily living (IADLs) but are nevertheless often criticized for having poor ecological validity. The Modified Six Elements Test (MSET) is a pencil-and-paper test that was developed to mimic the demands of daily life, with the assumption that this would result in a more ecologically valid test. Although the MSET has been extensively validated in its ability to capture cognitive deficits in various populations, support for its ability to predict functioning in daily life is mixed. This study aimed to examine the MSET’s ability to predict IADLs assessed via three different modalities relative to traditional EF measures.

Method:

Participants (93 adults aged 60 – 85) completed the MSET, traditional measures of EF (Delis-Kaplan Executive Function System; D-KEFS), and self-reported and performance-based IADLs in the lab. Participants then completed three weeks of IADL tasks at home, using the Daily Assessment of Independent Living and Executive Skills (DAILIES) protocol.

Results:

The MSET predicted only IADLs completed at home, while the D-KEFS predicted IADLs across all three modalities. Further, the D-KEFS predicted home-based IADLs beyond the MSET when pitted against each other, whereas the MSET did not contribute beyond the D-KEFS.

Conclusions:

Traditional EF tests (D-KEFS) appear to be superior to the MSET in predicting IADLs in community-dwelling older adults. The present results argue against replacing traditional measures with the MSET when addressing functional independence of generally high-functioning and cognitive healthy older adult patients.
Time series analysis of GSS bonds
Authors: Dey D.
Published: March 2024

The market for green bonds, and environmentally aligned investment solutions, is increasing. As of 2022, the market of green bonds exceeded USD 2 trillion in issuance, with India, for example, having issued its first-ever sovereign green bonds totally R80bn (c.USD1bn) in January 2023. This paper lays the foundation for future papers and summarises the initial stages of our analysis, where we try to replicate the S&P Green Bond Index (i.e. this is a time series problem) over a period using non-traditional techniques. The models we use include neural networks such as CNNs, LSTMs and GRUs. We extend our analysis and use an open-source decision tree model called XGBoost. For the purposes of this paper, we use 1 day’s prior index information to predict today’s value and repeat this over a period of time. We ignore for example stationarity considerations and extending the input window/output horizon in our analysis, as these will be discussed in future papers. The paper explains the methodology used in our analysis, gives details of general underlying background information to the architecture models (CNNs, LSTMs, GRUs and XGBoost), as well as background to regularisation techniques specifically L2 regularisation, loss curves and hyperparameter optimisation, in particular, the open-source library Optuna.
Three approaches to assessing dietary quality in Mexican adolescents from 2006 to 2018 with data from national health and nutrition surveys
Authors: Gaona-Pineda Elsa Berenice , López-Olmedo Nancy , Moreno-Macías Hortensia , Shamah-Levy Teresa
Published: March 2024

Objective:

To assess trends in the dietary quality of Mexican adolescents from 2006 to 2018, both overall and by sociodemographic indicators, using adaptations of the EAT-Lancet Planetary Health (PH) recommendations, optimal intake estimated by the Global Burden of Disease (GBD) and 2015 Mexican Dietary Guidelines (MDG) in nationally representative samples.

Design:

Using dietary data from a semi-quantitative FFQ, dietary quality indexes were constructed as adaptations of three dietary intake recommendations. Trends in adherence to recommendations were evaluated with multivariate quantile regression models with survey year as the main independent variable and adjusted for age, sex, energy intake, dwelling area, geographical region, household assets condition, and student/non-student status. P values and CI were Bonferroni-corrected.

Setting:

Mexico.

Participants:

Non-pregnant or lactating adolescents aged 12–19 years (n 16 520).

Results:

Adherence to the PH index was about 40 %, GBD was nearly 35 % and MDG was about 37 %. The lowest adherences were for added sugars, sugar-sweetened beverages, nuts and seeds, red meats, processed meats, and legumes (<28 %). No 2006–2018 trends in total adherence were found in any index. Nevertheless, negative adherence trends were identified for poultry (β = –2·4), and saturated fats (β = –0·93), and positive for unsaturated oils (β = 1·23), in the PH. In MDG, relevant trends were found for plain water (β = 1·63) and foods rich in fats (β = –1·24).

Conclusions:

Mexican adolescents have demonstrated poor dietary quality by these three approaches. Therefore, this population has a high-risk profile for diet-associated chronic diseases. Further research and appropriate public policies are needed.
Between Faith and Judgement: Kant’s Dual Conception of Moral Certainty
Authors: Di Giulio Sara
Published: March 2024

There are two main meanings in Kant’s concept of moral certainty (moralische Gewissheit, certitudo moralis): first, it applies to the kind of certainty embodied in rational faith in the existence of God and a future life; second, it applies to the conscientiousness (Gewissenhaftigkeit) required of an agent in the practice of moral judgement. Despite the growing attention to Kant’s theory of conscience and his concept of conscientiousness, this article is the first to discuss ‘moral certainty’ as the aim of ‘conscientiousness’ and to highlight the relevance of both notions in regard to moral education and the purposes of Kant’s ethical doctrines of method.
Die Hand erhoben
Authors: Loos Mike , Bartelworth Theresa , Rothert Sona
Published: March 2024

Jedes Kind hat ein Recht darauf, ohne Gewalt groß zu werden! Maris’ Geschichte zeigt, wie Kinder reagieren können, wenn sie körperlich verletzt werden.

Mit ihrem kleinen roten Koffer findet sich Maris in einer Wohngruppe wieder. „Weil es bei ihr zu Hause gerade nicht so schön ist.“ Das hat die Frau vom Jugendamt heute Morgen so gesagt. Und hier fängt die Geschichte an – an einem Ort für Kinder, die körperliche Gewalt erfahren haben. In den nächsten Tagen muss sich Maris vielen Fragen stellen: Muss sie für immer hierbleiben? Was passiert mit ihrer Familie? Darf man über Gewalt sprechen? Und überhaupt: Warum wird Kindern wehgetan? Mit drei neuen Freund:innen sucht sie nach Antworten.
Zusammen mit den Kindern in der Geschichte entdecken die jungen Leser:innen Hilfsangebote und erfahren, wie ihre Familien professionell unterstützt werden können. Maris’ Reise bestärkt die Betroffenen darin, sich anderen anzuvertrauen und aktiv zu werden.
„Die Hand erhoben“ ist ein Band aus der Reihe „Psychologische Kinderbücher“.Das Buch liefert Eltern, Angehörigen, Therapeut:innen und Kindern wichtige Informationen zum Thema „körperliche Gewalt“ sowie praktische Aufgaben und Übungen.
Die Arbeitsmaterialien zu diesem Buch können nach erfolgter Registrierung von der Hogrefe Website heruntergeladen werden.
Structure and Tectonic Evolution of the NW Sulu Sea Basin (SE Asia)
Authors: Cadenas Patricia , Ranero César R.
Published: March 2024

We discuss the tectonic structure, seismic stratigraphy and evolution of the NW Sulu Sea using reprocessed 2D reflection profiles. The NW Sulu Sea is located between the Palawan continental shelf and the Cagayan Ridge and represents the northern part of the Sulu Sea, a marginal sea resulting from Paleogene extension and subsequent Neogene contraction due to convergence between the Palawan and the Philippine blocks. The basin consists of six seismo‐stratigraphic units overlying crystalline basement. Syn‐orogenic depocenters contain calibrated Middle Miocene to, possibly, Lower Miocene units, while rift‐related depocenters consist of uncalibrated but tentatively dated Paleogene to Lower Miocene units. Thickness and depth maps of the main units and bounding horizons differentiate the Piedra‐Blanca and the Rasa domains, separated by the NW‐Sulu‐Break major tectonic structure. Fault‐bounded rift‐related depocenters are strongly segmented. We interpret that NW‐SE and NE‐SW trending zones accommodate shape and trend variations of these depocenters. We suggest that these zones may link rift segments, recording different extensional deformation. Miocene thrusting and folding in the Piedra‐Blanca Domain and mudflow with associated gravitational structures in the Rasa Domain influenced the deposition of syn‐orogenic units. Rift structures inherited from rift segmentation may have conditioned the style and distribution of contractional deformation during the subsequent incipient reactivation during contraction. In the context of SE Asia, our results support that the timing of rifting of the NW Sulu Sea overlaps with the opening of the South China Sea and the North Palawan margin, which may indicate a common geodynamic driving force triggering extension.
Multi‐Platform Observations of Severe Typhoon Koinu
Authors: He J. Y. , Chan P. W. , Choy C. W. , Cheung P. , Chan Y. W. , Lam C. C. , He Y. H. , Rong P. , Su H. , Li Z. M.
Published: March 2024

Severe Typhoon Koinu passed south of Hong Kong on 8 and 9 October 2023, triggering the issuance of the Increasing Gale or Storm Signal No. 9, the second highest tropical cyclone (TC) warning signal in Hong Kong. Koinu was a difficult case for TC warning service due to its compact size and rather erratic movement over the coastal waters of Guangdong. To monitor Koinu's movement and wind structure, the Hong Kong Observatory utilized various observational platforms, including meteorological aircraft, ocean radar, and synthetic aperture radar on polar orbiting satellites. The paper presents major observations derived from these measurements. The aircraft probe and dropsonde data suggested boundary layer inflow, warm core structure, eyewall updraft, and high turbulence in the eyewall of the typhoon. The weather radar observations indicated the occurrence of a waterspout in the vicinity of the typhoon. Additionally, the study highlights the forecasting performance of the AI‐based Pangu‐Weather model, which could outperform the conventional global numerical weather prediction models in forecasting TC track in the region. The documentation of these observations aims to provide valuable references for weather forecasters and stimulate further research on forecasting this type of tropical cyclone.
Thermal Stability of F‐Rich Phlogopite and K‐Richterite During Partial Melting of Metasomatized Mantle Peridotite With Implications for Deep Earth Volatile Cycles
Authors: Steenstra E. S. , Klaver M. , Berndt J. , Flemetakis S. , Rohrbach A. , Klemme S.
Published: March 2024

Phlogopite and K‐richterite constitute important carrier phases for H and F in Earth's lithosphere and mantle. The relative importance depends on their stabilities at high pressure and temperature, which in turn depends on bulk composition. Most previous experimental studies focused on the thermal stability of phlogopite and K‐richterite were conducted using simplified chemical compositions. Here, partial melting experiments on metasomatized and carbonated, OH ± F‐bearing near‐natural peridotite were performed at high pressures (2 and 5 GPa) and temperatures (1,100–1,350°C) to assess the thermal stability of F‐free versus F‐bearing phlogopite and K‐richterite. Experimental results demonstrate that the thermal stability of F‐bearing phlogopite is increased by >55°C/wt.% F, relative to F‐free phlogopite, whereas K‐richterite is absent in all experiments with significant degrees of melting (>2%). The thermal stability of phlogopite containing several wt.% F exceeds continental and oceanic geotherms within the upper 150 km. Fluorine‐rich phlogopite would therefore be stable in virtually all of the continental lithosphere, only to be decomposed during large, regional melting events such as continental break‐up, thereby acting as a major long‐term sink for F and/or H. This could even be the case for the oceanic asthenosphere, depending on the oceanic geotherm of the area of interest.
Deciphering Controls of Pore‐Pressure Evolution on Sediment Bed Erosion by Debris Flows
Authors: Zheng Hongchao , Hu Xinli , Shi Zhenming , Shen Danyi , De Haas Tjalling
Published: March 2024

Pore‐fluid pressure (PP) plays an important role in bed erosion, but the mechanisms that control PP evolution and the resulting feedbacks on flow dynamics are unclear. Here, we develop a general formulation, allowing quantification of the propensity for PP evolution of saturated and unsaturated bed sediments. We conduct erosion experiments by systematically varying grain composition and water content of beds, for investigating effects of PP evolution on flow erosion. With increasing water content, PP shows a slight rise in deforming beds with drained behavior but significant larger rise in undrained beds. Regardless of bed composition, the erosion rate of beds presents a synchronous change tendency with PP evolution due to the loss in basal friction. PP instigates positive feedback that induces a remarkable gain of flow velocity and momentum on wet beds with undrained behavior. Our results help explain observations of volume growth and long run out of debris flows.
Genome-wide CRISPR/Cas9 screen shows that loss of GET4 increases mitochondria-endoplasmic reticulum contact sites and is neuroprotective
Authors: Wilson Emma L. , Yu Yizhou , Leal Nuno S. , Woodward James A. , Patikas Nikolaos , Morris Jordan L. , Field Sarah F. , Plumbly William , Paupe Vincent , Chowdhury Suvagata R. , Antrobus Robin , Lindop Georgina E. , Adia Yusuf M. , Loh Samantha H. Y. , Prudent Julien , Martins L. Miguel , Metzakopian Emmanouil
Published: March 2024

Organelles form membrane contact sites between each other, allowing for the transfer of molecules and signals. Mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) are cellular subdomains characterized by close apposition of mitochondria and ER membranes. They have been implicated in many diseases, including neurodegenerative, metabolic, and cardiac diseases. Although MERCS have been extensively studied, much remains to be explored. To uncover novel regulators of MERCS, we conducted a genome-wide, flow cytometry-based screen using an engineered MERCS reporter cell line. We found 410 genes whose downregulation promotes MERCS and 230 genes whose downregulation decreases MERCS. From these, 29 genes were selected from each population for arrayed screening and 25 were validated from the high population and 13 from the low population. GET4 and BAG6 were highlighted as the top 2 genes that upon suppression increased MERCS from both the pooled and arrayed screens, and these were subjected to further investigation. Multiple microscopy analyses confirmed that loss of GET4 or BAG6 increased MERCS. GET4 and BAG6 were also observed to interact with the known MERCS proteins, inositol 1,4,5-trisphosphate receptors (IP3R) and glucose-regulated protein 75 (GRP75). In addition, we found that loss of GET4 increased mitochondrial calcium uptake upon ER-Ca2+ release and mitochondrial respiration. Finally, we show that loss of GET4 rescues motor ability, improves lifespan and prevents neurodegeneration in a Drosophila model of Alzheimer’s disease (Aβ42Arc). Together, these results suggest that GET4 is involved in decreasing MERCS and that its loss is neuroprotective.
Delivery of a BET protein degrader via a CEACAM6-targeted antibody–drug conjugate inhibits tumour growth in pancreatic cancer models
Authors: Nakazawa Youya , Miyano Masayuki , Tsukamoto Shuntaro , Kogai Hiroyuki , Yamamoto Akihiko , Iso Kentaro , Inoue Satoshi , Yamane Yoshinobu , Yabe Yuki , Umihara Hirotatsu , Taguchi Junichi , Akagi Tsuyoshi , Yamaguchi Atsumi , Koga Minaho , Toshimitsu Kohta , Hirayama Toshifumi , Mukai Yohei , Machinaga Akihito
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis of all cancers. To improve PDAC therapy, we establish screening systems based on organoid and co-culture technologies and find a payload of antibody–drug conjugate (ADC), a bromodomain and extra-terminal (BET) protein degrader named EBET. We select CEACAM6/CD66c as an ADC target and developed an antibody, #84.7, with minimal reactivity to CEACAM6-expressing normal cells. EBET-conjugated #84.7 (84-EBET) has lethal effects on various PDAC organoids and bystander efficacy on CEACAM6-negative PDAC cells and cancer-associated fibroblasts. In mouse studies, a single injection of 84-EBET induces marked tumor regression in various PDAC-patient-derived xenografts, with a decrease in the inflammatory phenotype of stromal cells and without significant body weight loss. Combination with standard chemotherapy or PD-1 antibody induces more profound and sustained regression without toxicity enhancement. Our preclinical evidence demonstrates potential efficacy by delivering BET protein degrader to PDAC and its microenvironment via CEACAM6-targeted ADC.
Enabling large-scale screening of Barrett’s esophagus using weakly supervised deep learning in histopathology
Authors: Bouzid Kenza , Sharma Harshita , Killcoyne Sarah , Castro Daniel C. , Schwaighofer Anton , Ilse Max , Salvatelli Valentina , Oktay Ozan , Murthy Sumanth , Bordeaux Lucas , Moore Luiza , O’Donovan Maria , Thieme Anja , Nori Aditya , Gehrung Marcel , Alvarez-Valle Javier
Published: March 2024

Timely detection of Barrett’s esophagus, the pre-malignant condition of esophageal adenocarcinoma, can improve patient survival rates. The Cytosponge-TFF3 test, a non-endoscopic minimally invasive procedure, has been used for diagnosing intestinal metaplasia in Barrett’s. However, it depends on pathologist’s assessment of two slides stained with H&E and the immunohistochemical biomarker TFF3. This resource-intensive clinical workflow limits large-scale screening in the at-risk population. To improve screening capacity, we propose a deep learning approach for detecting Barrett’s from routinely stained H&E slides. The approach solely relies on diagnostic labels, eliminating the need for expensive localized expert annotations. We train and independently validate our approach on two clinical trial datasets, totaling 1866 patients. We achieve 91.4% and 87.3% AUROCs on discovery and external test datasets for the H&E model, comparable to the TFF3 model. Our proposed semi-automated clinical workflow can reduce pathologists’ workload to 48% without sacrificing diagnostic performance, enabling pathologists to prioritize high risk cases.
The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3’-UTR and promoting Rag1 mRNA expression
Authors: Xu Meng , Ito-Kureha Taku , Kang Hyun-Seo , Chernev Aleksandar , Raj Timsse , Hoefig Kai P. , Hohn Christine , Giesert Florian , Wang Yinhu , Pan Wenliang , Ziętara Natalia , Straub Tobias , Feederle Regina , Daniel Carolin , Adler Barbara , König Julian , Feske Stefan , Tsokos George C. , Wurst Wolfgang , Urlaub Henning , Sattler Michael , Kisielow Jan , Wulczyn F. Gregory , Łyszkiewicz Marcin , Heissmeyer Vigo
Published: March 2024

The regulation of thymocyte development by RNA-binding proteins (RBPs) is largely unexplored. We identify 642 RBPs in the thymus and focus on Arpp21, which shows selective and dynamic expression in early thymocytes. Arpp21 is downregulated in response to T cell receptor (TCR) and Ca2+ signals. Downregulation requires Stim1/Stim2 and CaMK4 expression and involves Arpp21 protein phosphorylation, polyubiquitination and proteasomal degradation. Arpp21 directly binds RNA through its R3H domain, with a preference for uridine-rich motifs, promoting the expression of target mRNAs. Analysis of the Arpp21–bound transcriptome reveals strong interactions with the Rag1 3′-UTR. Arpp21–deficient thymocytes show reduced Rag1 expression, delayed TCR rearrangement and a less diverse TCR repertoire. This phenotype is recapitulated in Rag1 3′-UTR mutant mice harboring a deletion of the Arpp21 response region. These findings show how thymocyte-specific Arpp21 promotes Rag1 expression to enable TCR repertoire diversity until signals from the TCR terminate Arpp21 and Rag1 activities.
Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study
Authors: Cezard Genevieve I. , Denholm Rachel E. , Knight Rochelle , Wei Yinghui , Teece Lucy , Toms Renin , Forbes Harriet J. , Walker Alex J. , Fisher Louis , Massey Jon , Hopcroft Lisa E. M. , Horne Elsie M. F. , Taylor Kurt , Palmer Tom , Arab Marwa Al , Cuitun Coronado Jose Ignacio , Ip Samantha H. Y. , Davy Simon , Dillingham Iain , Bacon Sebastian , Mehrkar Amir , Morton Caroline E. , Greaves Felix , Hyams Catherine , Davey Smith George , Macleod John , Chaturvedi Nishi , Goldacre Ben , Whiteley William N. , Wood Angela M. , Sterne Jonathan A. C. , Walker Venexia ,   On behalf of the Longitudinal Health and Wellbeing and Data and Connectivity UK COVID-19 National Core Studies, CONVALESCENCE study and the OpenSAFELY collaborative
Published: March 2024

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a ‘pre-vaccination’ cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and ‘vaccinated’ and ‘unvaccinated’ cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.
Identification of gene regulatory networks affected across drug-resistant epilepsies
Authors: François Liesbeth , Romagnolo Alessia , Luinenburg Mark J. , Anink Jasper J. , Godard Patrice , Rajman Marek , van Eyll Jonathan , Mühlebner Angelika , Skelton Andrew , Mills James D. , Dedeurwaerdere Stefanie , Aronica Eleonora
Published: March 2024

Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering opportunities for drug-target discovery and development.
Simulating photosynthetic energy transport on a photonic network
Authors: Tang Hao , Shang Xiao-Wen , Shi Zi-Yu , He Tian-Shen , Feng Zhen , Wang Tian-Yu , Shi Ruoxi , Wang Hui-Ming , Tan Xi , Xu Xiao-Yun , Wang Yao , Gao Jun , Kim M. S. , Jin Xian-Min
Published: March 2024

Quantum effects in photosynthetic energy transport in nature, especially for the typical Fenna-Matthews-Olson (FMO) complexes, are extensively studied in quantum biology. Such energy transport processes can be investigated as open quantum systems that blend the quantum coherence and environmental noise, and have been experimentally simulated on a few quantum devices. However, the existing experiments always lack a solid quantum simulation for the FMO energy transport due to their constraints to map a variety of issues in actual FMO complexes that have rich biological meanings. Here we successfully map the full coupling profile of the seven-site FMO structure by comprehensive characterisation and precise control of the evanescent coupling of the three-dimensional waveguide array. By applying a stochastic dynamical modulation on each waveguide, we introduce the base site energy and the dephasing term in coloured noise to faithfully simulate the power spectral density of the FMO complexes. We show our photonic model well interprets the phenomena including reorganisation energy, vibrational assistance, exciton transfer and energy localisation. We further experimentally demonstrate the existence of an optimal transport efficiency at certain dephasing strength, providing a window to closely investigate environment-assisted quantum transport.
Co-densification of rice straw and cow dung in different food-to-microorganism ratios for biogas production
Authors: Singh Prakash , Dogra Pallavi , TG Induchoodan , Kalamdhad Ajay S.
Published: March 2024

Agricultural residues such as rice straw (RS) are desirable raw materials for biogas generation. However, the recalcitrant nature of RS hinders biogas production, and its low bulk density increases storage space requirements, transportation needs, and overall costs. These challenges could be resolved by pretreatment and pelletization. In this study, various thermal pretreatments were performed, and the best conditions (temperature and time) were identified. Also, rice straw and cow dung pellets (RCP) at different food-to-microorganism (F/M) ratios (0.5–2.5) were prepared. Parameters such as bulk density, moisture absorption, and drop shatter tests were conducted to evaluate the physical properties. Finally, the biochemical methane potential (BMP) study of the best RCP with varying total solids (TS: 4–12%) content was investigated. The results indicate that hot air oven pretreatment (for 60 min at 120 °C) resulted in maximum solubilization. In physical characteristics, RCP with an F/M ratio of 2.5 pellets was ideal. The bulk density of RCP 2.5 was found to be around 25 times that of the raw. Also, the TS 8% yielded maximum biomethane (279 mL/g-VSconsumed) as compared to other TS contents. Overall, this study will propel the growth of bioenergy while simultaneously tackling the pressing issues related to RS management.
Seepage evolution characteristics and water inrush mechanism in collapse column under mining influence
Authors: Yongjiang Wu , Zhengzheng Cao , Zhenhua Li , Feng Du , Wenqiang Wang , Minglei Zhai , Zijie Hong , Yi Xue
Published: March 2024

To obtain the seepage evolution rule and water inrush mechanism of the collapse column, a multi-field coupled mechanical model for water inrush disasters caused by the collapse column is established in this paper, on the basis of the specific engineering conditions of the 1908 working face in the Qianjin coal mine. The mechanical model is composed of internal column elements within the collapse column and surrounding rock masses. The research focuses on the seepage evolution rule in the roof collapse column under different mining conditions and investigates the permeation instability mechanism of collapse column based on the transition of flow state. The research results indicate that the seepage pathway evolves continuously, ultimately forming a channel for water inrush, as the working face advances towards the collapse column. Besides, the water inflow increases rapidly when the working face advances 100 m, then gradually stabilizes, indicating that the seepage channel entry of the collapse column is in a stable stage. Meanwhile, mass loss in the collapse column gradually moves upward. the collapse column remains stable as a whole in the initial stage of water flow, with a small permeability, exhibiting linear flow. As time steps increases, particle loss in collapse column gradually extends to the upper part, forming a stable seepage channel. The flow velocity shows fluctuations with a slow declining trend over time.
Enhancing co-seismic landslide susceptibility, building exposure, and risk analysis through machine learning
Authors: Pyakurel Ajaya , K.C. Diwakar , Dahal Bhim Kumar
Published: March 2024

Landslides are devastating natural disasters that generally occur on fragile slopes. Landslides are influenced by many factors, such as geology, topography, natural drainage, land cover, rainfall and earthquakes, although the underlying mechanism is too complex and very difficult to explain in detail. In this study, the susceptibility mapping of co-seismic landslides is carried out using a machine learning approach, considering six districts covering an area of 12,887 km2 in Nepal. Landslide inventory map is prepared by taking 23,164 post seismic landslide data points that occurred after the 7.8 MW 2015 Gorkha earthquake. Twelve causative factors, including distance from the rupture plane, peak ground acceleration and distance from the fault, are considered input parameters. The overall accuracy of the model is 87.2%, the area under the ROC curve is 0.94, the Kappa coefficient is 0.744 and the RMSE value is 0.358, which indicates that the performance of the model is excellent with the causative factors considered. The susceptibility thus developed shows that Sindhupalchowk district has the largest percentage of area under high and very high susceptibility classes, and the most susceptible local unit in Sindhupalchowk is the Barhabise municipality, with 19.98% and 20.34% of its area under high and very high susceptibility classes, respectively. For the analysis of building exposure to co-seismic landslide susceptibility, a building footprint map is developed and overlaid on the co-seismic landslide susceptibility map. The results show that the Sindhupalchowk and Dhading districts have the largest and smallest number of houses exposed to co-seismic landslide susceptibility. Additionally, when conducting a risk analysis based on susceptibility mapping, as well as considering socio-economic and structural vulnerability in Barhabise municipality, revealed that only 106 (1.1%) of the total 9591 households, were found to be at high risk. As this is the first study of co-seismic landslide risk study carried out in Nepal and covers a regional to the municipal level, this can be a reference for future studies in Nepal and other parts of the world and can be helpful in planning development activities for government bodies.
Evaluation of molecular inhibitors of loop-mediated isothermal amplification (LAMP)
Authors: Nwe May Khat , Jangpromma Nisachon , Taemaitree Lapatrada
Published: March 2024

Loop-mediated isothermal amplification (LAMP) is a cost-effective and easy-to-perform assay that enables the direct detection of DNA. Its use in point-of-care diagnostic tests is growing, while it has the potential to be used in presumptive on-the-field forensic tests. Samples are often collected from complex matrices that contain high levels of contaminants. Herein, we evaluate the effect of seven common DNA amplification inhibitors on LAMP – bile salts, calcium chloride, hematin, humic acid, immunoglobulin G, tannic acid and urea. We study the effect of each inhibitor individually in real-time detection systems coupled with end-point measurements to delineate their inhibitory effects from the matrix in which they may be found. Our studies show LAMP inhibitors generally delay the onset of amplicon formation and quench fluorescence at similar or higher concentrations compared to PCR, but that end-point measurements of LAMP amplicons are unaffected. This is important as LAMP amplicons can be detected in non-fluorometric ways thus contributing to the assertions that LAMP is more robust to inhibitors than PCR.
Investigations on the effect of natural veined calcite on the mechanical properties of limestone
Authors: Chen Qingzhi , Liu Yuanming , Teng Zhaolei , Ou Xun , Zhang Quan
Published: March 2024

The damage behavior of limestone rock masses containing calcite mineral filling under uniaxial compression experimental conditions is unclear, and the fracture mechanism of the rock masses needs to be further explored. In this study, uniaxial compression tests were conducted on limestone rock specimens containing veined calcite by combining acoustic emission and digital image correlation techniques. The effects of veined calcite on the generation and development of cracks on the surface of the specimens until the formation of macroscopic penetration and the strength properties of the rock mass were analyzed. The results showed that the transversely distributed veined calcite caused significant stress concentrations in the rock specimens. The longitudinally distributed veined calcite caused cracks in the specimens or influenced the expansion path of the longitudinal principal cracks. The final damage pattern of the specimens didn’t differ significantly from that of conventional rock masses due to the presence of veined calcite. The presence of the veined calcite had effect on the uniaxial compressive capacity of the rock, but the load variation process of the specimen with time still conformed to the load variation pattern during the uniaxial compressive test of conventional rocks.
Arthroscopic debridement improves range of motion for heterotopic ossification after total knee replacement: a retrospective cohort study
Authors: Zhang Dong-Liang , Zhang Wei , Ren Yi-Ming , Zhao Wen-Jun , Sun He-Jun , Tian Zheng-Wei , Tian Meng-Qiang
Published: March 2024

The presence of heterotopic ossification (HO) after primary total knee replacement (TKR) is rare and associated with limited mobility and stiffness of the knee. This study aimed to identify if the arthroscopic debridement after TKR could decrease HO and improve the function and range of motion. Thirty HO patients after TKR were retrospectively separated into 2 cohorts. 15 patients of group A accepted the arthroscopic debridement, while 15 patients of group B only had non-operative treatment, mainly including oral nonsteroidal anti-inflammatory drugs (NSAIDs) and rehabilitative treatment. Visual analog scale (VAS) scores, knee society knee scores (KSS), range of motion (knee flexion and knee extension) were obtained before treatment and at 1 month, 3 months, and 6 months after treatment. Radiography of after-treatment was also evaluated to assess the changes in HO. There were 3 males and 27 females with a mean age of 67.4 ± 0.8 years in group A and 68.2 ± 1.3 in group B. The onset time of HO was 3–6 months. The maximum size of the ossification was < 2 cm in 23 knees, 2 cm < heterotopic bone < 5 cm in 6 knees and > 5 cm in 1 knee. The size of HO decreased gradually in all knees by X-ray film at the last follow-up. There were no significant differences in VAS scores after replacement between two groups (p > 0.05). The average range of motion preoperatively in group A was − 15.2–90.6°, which postoperatively increased to − 4.2–110.0°. Meanwhile, the KSS scores and average range of motion of the group A were better than those of the group B at each follow-up time after treatment. Arthroscopic debridement can decrease HO seen from postoperative X-rays, improve the function and range of motion, as well as the pain remission between two groups are comparable. Consequently, arthroscopic resection of HO after TKR is recommended as soon as there is aggravating joint stiffness.
NT-proBNP ratio is a potential predictor for COVID-19 outcomes in adult Chinese patients: a retrospective study
Authors: Li Dan , He Wu , Yu Bo , Wang Dao Wen , Ni Li
Published: March 2024

Despite the progressive decline in the virulence of the novel coronavirus, there has been no corresponding reduction in its associated hospital mortality. Our aim was to redefine an accurate predictor of mortality risk in COVID-19 patients, enabling effective management and resource allocation. We conducted a retrospective analysis of 2917 adult Chinese patients diagnosed with COVID-19 who were admitted to our hospital during two waves of epidemics, involving the Beta and Omicron variants. Upon admission, NT-proBNP levels were measured, and we collected demographic, clinical, and laboratory data. We introduced a new concept called the NT-proBNP ratio, which measures the NT-proBNP level relative to age-specific maximum normal values. The primary outcome was all-cause in-hospital mortality. Our analysis revealed a higher in-hospital mortality rate in 2022, as shown by the Kaplan–Meier Survival Curve. To assess the predictive value of the NT-proBNP ratio, we employed the time-dependent receiver operating characteristic (ROC) curve. Notably, the NT-proBNP ratio emerged as the strongest predictor of mortality in adult Chinese hospitalized COVID-19 patients (area under the curve, AUC = 0.826; adjusted hazard ratio [HR], 3.959; 95% confidence interval [CI] 3.001–5.221; P < 0.001). This finding consistently held true for both the 2020 and 2022 subgroups. The NT-proBNP ratio demonstrates potential predictive capability compared to several established risk factors, including NT-proBNP, hsCRP, and neutrophil-to-lymphocyte ratio, when it comes to forecasting in-hospital mortality among adult Chinese patients with COVID-19.

Trial registration Clinical Trial Registration: www.clinicaltrials.gov NCT05615792.
Single-cell RNA sequencing reveals critical modulators of extracellular matrix of penile cavernous cells in erectile dysfunction
Authors: Luo Chao , Peng Yaqian , Gu Jiang , Li Tao , Wang Qiang , Qi Xiaolan , Wei Anyang
Published: March 2024

Erectile dysfunction (ED) is a common and difficult to treat disease, and has a high incidence rate worldwide. As a marker of vascular disease, ED usually occurs in cardiovascular disease, 2–5 years prior to cardiovascular disease events. The extracellular matrix (ECM) network plays a crucial role in maintaining cardiac homeostasis, not only by providing structural support, but also by promoting force transmission, and by transducing key signals to intracardiac cells. However, the relationship between ECM and ED remains unclear. To help fill this gap, we profiled single-cell RNA-seq (scRNA-seq) to obtain transcriptome maps of 82,554 cavernous single cells from ED and non-ED samples. Cellular composition of cavernous tissues was explored by uniform manifold approximation and projection. Pseudo-time cell trajectory combined with gene enrichment analysis were performed to unveil the molecular pathways of cell fate determination. The relationship between cavernous cells and the ECM, and the changes in related genes were elucidated. The CellChat identified ligand-receptor pairs (e.g., PTN-SDC2, PTN-NCL, and MDK-SDC2) among the major cell types in the cavernous tissue microenvironment. Differential analysis revealed that the cell type-specific transcriptomic changes in ED are related to ECM and extracellular structure organization, external encapsulating structure organization, and regulation of vasculature development. Trajectory analysis predicted the underlying target genes to modulate ECM (e.g., COL3A1, MDK, MMP2, and POSTN). Together, this study highlights potential cell–cell interactions and the main regulatory factors of ECM, and reveals that genes may represent potential marker features of ED progression.
Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy
Authors: Kubota Masashi , Kawakita Mutsushi , Yoshida Satomi , Kimura Hiroko , Sumiyoshi Takayuki , Yamasaki Toshinari , Okumura Kazuhiro , Yoshimura Koji , Matsui Yoshiyuki , Sugiyama Kyohei , Okuno Hiroshi , Segawa Takehiko , Shimizu Yosuke , Ito Noriyuki , Onishi Hiroyuki , Ishitoya Satoshi , Soda Takeshi , Yoshida Toru , Uemura Yuichi , Iwamura Hiroshi , Okubo Kazutoshi , Suzuki Ryosuke , Fukuzawa Shigeki , Akao Toshiya , Kurahashi Ryoma , Shimatani Kimihiro , Sekine Yuya , Negoro Hiromitsu , Akamatsu Shusuke , Kamoto Toshiyuki , Ogawa Osamu , Kawakami Koji , Kobayashi Takashi , Goto Takayuki
Published: March 2024

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien–Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54–8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23–8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78–34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83–7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14–16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.