bluuebunny/crossref_metadata_2025 huggingface dataset:
Global supply chains amplify economic costs of future extreme heat risk
Authors: Sun Yida , Zhu Shupeng , Wang Daoping , Duan Jianping , Lu Hui , Yin Hao , Tan Chang , Zhang Lingrui , Zhao Mengzhen , Cai Wenjia , Wang Yong , Hu Yixin , Tao Shu , Guan Dabo
Published: March 2024

Evidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input–output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)–0.05 ± 0.03 (SSP 585) percentage points during 2030–2040 to 0.05 ± 0.01–0.15 ± 0.04 percentage points during 2050–2060. By 2060, the expected global economic losses reach a total of 0.6–4.6% with losses attributed to health loss (37–45%), labour productivity loss (18–37%) and indirect loss (12–43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0–3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.
Last-mile delivery increases vaccine uptake in Sierra Leone
Authors: Meriggi Niccolò F. , Voors Maarten , Levine Madison , Ramakrishna Vasudha , Kangbai Desmond Maada , Rozelle Michael , Tyler Ella , Kallon Sellu , Nabieu Junisa , Cundy Sarah , Mobarak Ahmed Mushfiq
Published: March 2024

Less than 30% of people in Africa received a dose of the COVID-19 vaccine even 18 months after vaccine development1. Here, motivated by the observation that residents of remote, rural areas of Sierra Leone faced severe access difficulties2, we conducted an intervention with last-mile delivery of doses and health professionals to the most inaccessible areas, along with community mobilization. A cluster randomized controlled trial in 150 communities showed that this intervention with mobile vaccination teams increased the immunization rate by about 26 percentage points within 48–72 h. Moreover, auxiliary populations visited our community vaccination points, which more than doubled the number of inoculations administered. The additional people vaccinated per intervention site translated to an implementation cost of US $33 per person vaccinated. Transportation to reach remote villages accounted for a large share of total intervention costs. Therefore, bundling multiple maternal and child health interventions in the same visit would further reduce costs per person treated. Current research on vaccine delivery maintains a large focus on individual behavioural issues such as hesitancy. Our study demonstrates that prioritizing mobile services to overcome access difficulties faced by remote populations in developing countries can generate increased returns in terms of uptake of health services3.
The evolution of menopause in toothed whales
Authors: Ellis Samuel , Franks Daniel W. , Nielsen Mia Lybkær Kronborg , Weiss Michael N. , Croft Darren P.
Published: March 2024

Understanding how and why menopause has evolved is a long-standing challenge across disciplines. Females can typically maximize their reproductive success by reproducing for the whole of their adult life. In humans, however, women cease reproduction several decades before the end of their natural lifespan1,2. Although progress has been made in understanding the adaptive value of menopause in humans3,4, the generality of these findings remains unclear. Toothed whales are the only mammal taxon in which menopause has evolved several times5, providing a unique opportunity to test the theories of how and why menopause evolves in a comparative context. Here, we assemble and analyse a comparative database to test competing evolutionary hypotheses. We find that menopause evolved in toothed whales by females extending their lifespan without increasing their reproductive lifespan, as predicted by the ‘live-long’ hypotheses. We further show that menopause results in females increasing their opportunity for intergenerational help by increasing their lifespan overlap with their grandoffspring and offspring without increasing their reproductive overlap with their daughters. Our results provide an informative comparison for the evolution of human life history and demonstrate that the same pathway that led to menopause in humans can also explain the evolution of menopause in toothed whales.
Mitochondrial complex I activity in microglia sustains neuroinflammation
Authors: Peruzzotti-Jametti L. , Willis C. M. , Krzak G. , Hamel R. , Pirvan L. , Ionescu R.-B. , Reisz J. A. , Prag H. A. , Garcia-Segura M. E. , Wu V. , Xiang Y. , Barlas B. , Casey A. M. , van den Bosch A. M. R. , Nicaise A. M. , Roth L. , Bates G. R. , Huang H. , Prasad P. , Vincent A. E. , Frezza C. , Viscomi C. , Balmus G. , Takats Z. , Marioni J. C. , D’Alessandro A. , Murphy M. P. , Mohorianu I. , Pluchino S.
Published: March 2024

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.
Substrate-induced condensation activates plant TIR domain proteins
Authors: Song Wen , Liu Li , Yu Dongli , Bernardy Hanna , Jirschitzka Jan , Huang Shijia , Jia Aolin , Jemielniak Wictoria , Acker Julia , Laessle Henriette , Wang Junli , Shen Qiaochu , Chen Weijie , Li Pilong , Parker Jane E. , Han Zhifu , Schulze-Lefert Paul , Chai Jijie
Published: March 2024

Plant nucleotide-binding leucine-rich repeat (NLR) immune receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain mediate recognition of strain-specific pathogen effectors, typically via their C-terminal ligand-sensing domains1. Effector binding enables TIR-encoded enzymatic activities that are required for TIR–NLR (TNL)-mediated immunity2,3. Many truncated TNL proteins lack effector-sensing domains but retain similar enzymatic and immune activities4,5. The mechanism underlying the activation of these TIR domain proteins remain unclear. Here we show that binding of the TIR substrates NAD+ and ATP induces phase separation of TIR domain proteins in vitro. A similar condensation occurs with a TIR domain protein expressed via its native promoter in response to pathogen inoculation in planta. The formation of TIR condensates is mediated by conserved self-association interfaces and a predicted intrinsically disordered loop region of TIRs. Mutations that disrupt TIR condensates impair the cell death activity of TIR domain proteins. Our data reveal phase separation as a mechanism for the activation of TIR domain proteins and provide insight into substrate-induced autonomous activation of TIR signalling to confer plant immunity.
Geographical distribution of radon and associated health risks in drinking water samples collected from the Mulazai area of Peshawar, Pakistan
Authors: Shah Syed Samran Ali , Asif Abdul Rahim , Ilahi Manzoor , Haroon Haseeb , Islam Ihtisham , Qadir Adnan , Nisar Irfan , Sani Malik Muhammad Usman , Iqbal Rashid , Rahman Muhammed Habib ur , Arslan Muhammad , Alwahibi Mona S. , Elshikh Mohamed S. , Ditta Allah
Published: March 2024

Geospatial methods, such as GIS and remote sensing, map radon levels, pinpoint high-risk areas and connect geological traits to radon presence. These findings direct health planning, focusing tests, mitigation, and policies where radon levels are high. Overall, geospatial analyses offer vital insights, shaping interventions and policies to reduce health risks from radon exposure. There is a formidable threat to human well-being posed by the naturally occurring carcinogenic radon (222Rn) gas due to high solubility in water. Under the current scenario, it is crucial to assess the extent of 222Rn pollution in our drinking water sources across various regions and thoroughly investigate the potential health hazards it poses. In this regard, the present study was conducted to investigate the concentration of 222Rn in groundwater samples collected from handpumps and wells and to estimate health risks associated with the consumption of 222Rn-contaminated water. For this purpose, groundwater samples (n = 30) were collected from handpumps, and wells located in the Mulazai area, District Peshawar. The RAD7 radon detector was used as per international standards to assess the concentration of 222Rn in the collected water samples. The results unveiled that the levels of 222Rn in the collected samples exceeded the acceptable thresholds set by the US Environmental Protection Agency (US-EPA) of 11.1 Bq L−1. Nevertheless, it was determined that the average annual dose was below the recommended limit of 0.1 mSv per year, as advised by both the European Union Council and the World Health Organization. In order to avoid the harmful effects of such excessive 222Rn concentrations on human health, proper ventilation and storage of water in storage reservoirs for a long time before use is recommended to lower the 222Rn concentration.
Genetic diversity of variants involved in drug response among Tunisian and Italian populations toward personalized medicine
Authors: Jmel Haifa , Sarno Stefania , Giuliani Cristina , Boukhalfa Wided , Abdelhak Sonia , Luiselli Donata , Kefi Rym
Published: March 2024

Adverse drug reactions (ADR) represent a significant contributor to morbidity and mortality, imposing a substantial financial burden. Genetic ancestry plays a crucial role in drug response. The aim of this study is to characterize the genetic variability of selected pharmacogenes involved with ADR in Tunisians and Italians, with a comparative analysis against global populations. A cohort of 135 healthy Tunisians and 737 Italians were genotyped using a SNP array. Variants located in 25 Very Important Pharmacogenes implicated in ADR were extracted from the genotyping data. Distribution analysis of common variants in Tunisian and Italian populations in comparison to 24 publicly available worldwide populations was performed using PLINK and R software. Results from Principle Component and ADMIXTURE analyses showed a high genetic similarity among Mediterranean populations, distinguishing them from Sub-Saharan African and Asian populations. The Fst comparative analysis identified 27 variants exhibiting significant differentiation between the studied populations. Among these variants, four SNPs rs622342, rs3846662, rs7294, rs5215 located in SLC22A1, HMGCR, VKORC1 and KCNJ11 genes respectively, are reported to be associated with ethnic variability in drug responses. In conclusion, correlating the frequencies of genotype risk variants with their associated ADRs would enhance drug outcomes and the implementation of personalized medicine in the studied populations.
Adaptation to numerosity affects the pupillary light response
Authors: Caponi Camilla , Castaldi Elisa , Burr David Charles , Binda Paola
Published: March 2024

We recently showed that the gain of the pupillary light response depends on numerosity, with weaker responses to fewer items. Here we show that this effect holds when the stimuli are physically identical but are perceived as less numerous due to numerosity adaptation. Twenty-eight participants adapted to low (10 dots) or high (160 dots) numerosities and subsequently watched arrays of 10–40 dots, with variable or homogeneous dot size. Luminance was constant across all stimuli. Pupil size was measured with passive viewing, and the effects of adaptation were checked in a separate psychophysical session. We found that perceived numerosity was systematically lower, and pupillary light responses correspondingly smaller, following adaptation to high rather than low numerosities. This is consistent with numerosity being a primary visual feature, spontaneously encoded even when task irrelevant, and affecting automatic and unconscious behaviours like the pupillary light response.
Uplift modeling to predict individual treatment effects of renal replacement therapy in sepsis-associated acute kidney injury patients
Authors: Li Guanggang , Li Bo , Song Bin , Liu Dandan , Sun Yue , Ju Hongyan , Xu Xiuping , Mao Jingkun , Zhou Feihu
Published: March 2024

Renal replacement therapy (RRT) is a crucial treatment for sepsis-associated acute kidney injury (S-AKI), but it is uncertain which S-AKI patients should receive immediate RRT. Identifying the characteristics of patients who may benefit the most from RRT is an important task. This retrospective study utilized a public database and enrolled S-AKI patients, who were divided into RRT and non-RRT groups. Uplift modeling was used to estimate the individual treatment effect (ITE) of RRT. The validity of different models was compared using a qini curve. After labeling the patients in the validation cohort, we characterized the patients who would benefit the most from RRT and created a nomogram. A total of 8289 patients were assessed, among whom 591 received RRT, and 7698 did not receive RRT. The RRT group had a higher severity of illness than the non-RRT group, with a Sequential Organ Failure Assessment (SOFA) score of 9 (IQR 6,11) vs. 5 (IQR 3,7). The 28-day mortality rate was higher in the RRT group than the non-RRT group (34.83% vs. 14.61%, p < 0.0001). Propensity score matching (PSM) was used to balance baseline characteristics, 458 RRT patients and an equal number of non-RRT patients were enrolled for further research. After PSM, 28-day mortality of RRT and non-RRT groups were 32.3% vs. 39.3%, P = 0.033. Using uplift modeling, we found that urine output, fluid input, mean blood pressure, body temperature, and lactate were the top 5 factors that had the most influence on RRT effect. The area under the uplift curve (AUUC) of the class transformation model was 0.068, the AUUC of SOFA was 0.018, and the AUUC of Kdigo-stage was 0.050. The class transformation model was more efficient in predicting individual treatment effect. A logistic regression model was developed, and a nomogram was drawn to predict whether an S-AKI patient can benefit from RRT. Six factors were taken into account (urine output, creatinine, lactate, white blood cell count, glucose, respiratory rate). Uplift modeling can better predict the ITE of RRT on S-AKI patients than conventional score systems such as Kdigo and SOFA. We also found that white blood cell count is related to the benefits of RRT, suggesting that changes in inflammation levels may be associated with the effects of RRT on S-AKI patients.
Phage-layer interferometry: a companion diagnostic for phage therapy and a bacterial testing platform
Authors: Needham Patrick , Page Richard C. , Yehl Kevin
Published: March 2024

The continuing and rapid emergence of antibiotic resistance (AMR) calls for innovations in antimicrobial therapies. A promising, ‘re-emerging’ approach is the application of bacteriophage viruses to selectively infect and kill pathogenic bacteria, referred to as phage therapy. In practice, phage therapy is personalized and requires companion diagnostics to identify efficacious phages, which are then formulated into a therapeutic cocktail. The predominant means for phage screening involves optical-based assays, but these methods cannot be carried out in complex media, such as colored solutions, inhomogeneous mixtures, or high-viscosity samples, which are often conditions encountered in vivo. Moreover, these assays cannot distinguish phage binding and lysis parameters, which are important for standardizing phage cocktail formulation. To address these challenges, we developed Phage-layer Interferometry (PLI) as a companion diagnostic. Herein, PLI is assessed as a quantitative phage screening method and prototyped as a bacterial detection platform. Importantly, PLI is amenable to automation and is functional in complex, opaque media, such as baby formula. Due to these newfound capabilities, we foresee immediate and broad impact of PLI for combating AMR and protecting against foodborne illnesses.
VpROM: a novel variational autoencoder-boosted reduced order model for the treatment of parametric dependencies in nonlinear systems
Authors: Simpson Thomas , Vlachas Konstantinos , Garland Anthony , Dervilis Nikolaos , Chatzi Eleni
Published: March 2024

Reduced Order Models (ROMs) are of considerable importance in many areas of engineering in which computational time presents difficulties. Established approaches employ projection-based reduction, such as Proper Orthogonal Decomposition. The limitation of the linear nature of such operators is typically tackled via a library of local reduction subspaces, which requires the assembly of numerous local ROMs to address parametric dependencies. Our work attempts to define a more generalisable mapping between parametric inputs and reduced bases for the purpose of generative modeling. We propose the use of Variational Autoencoders (VAEs) in place of the typically utilised clustering or interpolation operations, for inferring the fundamental vectors, termed as modes, which approximate the manifold of the model response for any and each parametric input state. The derived ROM still relies on projection bases, built on the basis of full-order model simulations, thus retaining the imprinted physical connotation. However, it additionally exploits a matrix of coefficients that relates each local sample response and dynamics to the global phenomena across the parametric input domain. The VAE scheme is utilised for approximating these coefficients for any input state. This coupling leads to a high-precision low-order representation, which is particularly suited for problems where model dependencies or excitation traits cause the dynamic behavior to span multiple response regimes. Moreover, the probabilistic treatment of the VAE representation allows for uncertainty quantification on the reduction bases, which may then be propagated to the ROM response. The performance of the proposed approach is validated on an open-source simulation benchmark featuring hysteresis and multi-parametric dependencies, and on a large-scale wind turbine tower characterised by nonlinear material behavior and model uncertainty.
Advanced age-related macular degeneration and risk factors in eyes with pachydrusen
Authors: Nam Seung Wan , Noh Hoon , Yoon Je Moon , Ham Don-Il
Published: March 2024

The risk of progression to advanced age-related macular degeneration (AMD) varies depending on the type of drusen. This retrospective longitudinal study included 248 eyes of 156 patients with pachydrusen without advanced AMD at baseline. Macular neovascularization (MNV) and geographic atrophy (GA) were evaluated. Risk factors for progression to advanced AMD were determined using multivariate Cox regression analysis. The mean age at baseline was 65.4 ± 9.1 years, and the mean follow-up duration was 6.40 ± 3.58 years. The mean total number of pachydrusen and macular pachydrusen were 4.10 ± 2.85 and 2.27 ± 1.81 per eye, respectively. Pachydrusen was accompanied by other types of drusen in 4.8% (12 eyes) of eyes at baseline. During follow-up, MNVs occurred in 2.8% (seven eyes), including polypoidal choroidal vasculopathy (PCV six eyes); however, no GA occurred. Regarding risk factors for progression to neovascular AMD, age (p = 0.023) and macular pigmentary changes (p = 0.014) were significantly associated with MNV development. The cumulative incidence of MNV was significantly higher in the group with macular pigmentary changes (17.39% vs. 0.57% at 10 years; p = 0.0005). The number of macular pachydrusen and the presence of MNV in the fellow eye did not show a statistically significant relationship with MNV development. Age and macular pigmentary changes are risk factors for MNV development in the eyes with pachydrusen. Eyes with pachydrusen appear to have a risk profile for advanced AMD that is different from that of AMD eyes with drusen or drusenoid deposits other than pachydrusen.
Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway
Authors: Zhu Chunyang , Lu Yangyang , Wang Shasha , Song Jialin , Ding Yixin , Wang Yan , Dong Chen , Liu Jiani , Qiu Wensheng , Qi Weiwei
Published: March 2024

Effective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)—NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.
Friction injury of the central vein caused by catheter for hemodialysis: an in vitro study
Authors: Wang Zhaoxing , Wang Kunpeng , Xu Yan
Published: March 2024

Vascular injury such as central venous stenosis (CVS) is a common complication in hemodialysis patients with central venous catheters (CVCs), yet the impact of the microstructure and partial physic characteristics of catheter surface on the chronic injury of central vein has not been elucidated. In this study, the microscopic morphology of tips and bodies of six different brands of polyurethane CVCs was observed and their roughness was assessed. Subsequently, an in vitro model was established to measure the coefficients of friction (COF) between CVCs (tips and bodies) and the vena cava intima of Japanese rabbits under the same condition in a linear reciprocating mode, and changes in the intima of vessels after friction were observed. The study found that there was a significant variation in surface roughness among different brands of CVCs (tips P < 0.001, bodies P = 0.02), and the COF was positively correlated with the catheter surface roughness (tips P = 0.005, R = 0.945, bodies P = 0.01, R = 0.909). Besides, the endovascular roughness increased after friction. These findings suggest that the high roughness surface of CVCs may cause chronic mechanical friction injury to the central venous intima, which is one of the potential factors leading to CVS or occlusion. This provides a breakthrough for reducing complications, improving patient prognosis, and advancing catheter surface lubrication technology.
A high-content screen reveals new regulators of nuclear membrane stability
Authors: Gunn Amanda L. , Yashchenko Artem I. , Dubrulle Julien , Johnson Jodiene , Hatch Emily M.
Published: March 2024

Nuclear membrane rupture is a physiological response to multiple in vivo processes, such as cell migration, that can cause extensive genome instability and upregulate invasive and inflammatory pathways. However, the underlying molecular mechanisms of rupture are unclear and few regulators have been identified. In this study, we developed a reporter that is size excluded from re-compartmentalization following nuclear rupture events. This allows for robust detection of factors influencing nuclear integrity in fixed cells. We combined this with an automated image analysis pipeline in a high-content siRNA screen to identify new proteins that both increase and decrease nuclear rupture frequency in cancer cells. Pathway analysis identified an enrichment of nuclear membrane and ER factors in our hits and we demonstrate that one of these, the protein phosphatase CTDNEP1, is required for nuclear stability. Analysis of known rupture determinants, including an automated quantitative analysis of nuclear lamina gaps, are consistent with CTDNEP1 acting independently of actin and nuclear lamina organization. Our findings provide new insights into the molecular mechanism of nuclear rupture and define a highly adaptable program for rupture analysis that removes a substantial barrier to new discoveries in the field.
Characteristics of resistivity variation in deep granite and in-situ detection applications
Authors: Fu Zhen , Zhang Yuezheng , Ji Hongguang , Zhang Chunrui , Chen Dongsheng , Qin Yuan
Published: March 2024

During the construction of deep vertical shafts, water inrush and flooding accidents are prone to occur, which seriously affect construction safety. Accurately determining the groundwater conditions is a prerequisite for effectively controlling water hazards and conducting risk management. In order to ensure the accuracy of the resistivity method in deep vertical well water exploration construction, a combination of indoor rock physics, mechanical testing, and on-site engineering measurements was used to analyze the influencing factors of granite resistivity. The corresponding relationship between resistivity and formation integrity was revealed, and water exploration experiments were conducted in the working face of deep underground mines. The results show that: (1) Rock resistivity is influenced by metallic minerals, saturation, temperature, ion content of fracture water, and joints. Regarding deep subsurface detection issues, the main factors affecting the detection results are water content and rock integrity. (2) During the loading process, rock resistivity exhibits significant stage response characteristics, which are closely related to rock integrity and damage accumulation. (3) A degradation model for aquifer zoning based on resistivity benchmark line was established. When the formation resistivity is higher than the benchmark line, it indicates a well-integrated formation with low water content. (4) Resistivity cloud maps and zoning degradation models can be used to visually determine and evaluate the occurrence status of formations and the effectiveness of grouting.
Insights from Turkey's big data: unraveling the preventability, pathogenesis, and risk management of Alzheimer's disease (AD)
Authors: Yiğit Talip , Ata Naim , Dinçer Murat , Ülgü M. Mahir , Birinci Şuayip , Ayvalı M. Okan
Published: March 2024

Extensive research into dementia has more recently honed in on several key areas. These areas include the advancement of techniques such as the accumulation of amyloid-β and tau proteins, the monitoring of cerebral hypometabolism rates etc. The primary objective of this study is to explore the intricate interplay between Alzheimer's disease (AD)—other dementias (D) and various chronic illnesses in terms of time, intensity, and connectivity. In this context, we retrospectively examined data of 149,786 individuals aged 65 and above who received diagnoses of AD and D in the year 2020. At first, logistic regression (LR) analysis has been made with “sex”, “age” and “foreigner” (citizenship status) independent variables for AD and D. The LR models shows that while “sex” and “age” variables have a small rate on the risk of developing AD/D, it is detected that being a foreigner increase the risk of AD and D as 69.8% and 88.5% respectively. Besides, the LR models have middle-level success prediction rate for both of the two dependent variables. Additionally, we used the parallel coordinates graphs method within the R Studio to visualize their relationships and connections. The findings of this investigation strongly suggest that AD/D don’t stand as isolated conditions, but rather stem from intricate interactions and progressive processes involving diverse chronic diseases over time. Notably, ailments including hypertension, coronary artery disease, diabetes, hyperlipidemia, and psychological disorders, contribute substantially to the emergence of both AD and D. This study highlights that the fight against AD/D can only be possible with next-generation prophylactic interventions that can predict and manage risks. Such an approach holds the potential to potentially lower AD and dementia to levels that are amenable to treatment.
Strengthened impact of boreal winter North Pacific Oscillation on ENSO development in warming climate
Authors: Chen Shangfeng , Chen Wen , Xie Shang-Ping , Yu Bin , Wu Renguang , Wang Zhibiao , Lan Xiaoqing , Graf Hans-F
Published: March 2024

The North Pacific Oscillation (NPO), an important mode of atmospheric variability, is a crucial trigger for the development of El Niño-Southern Oscillation (ENSO) via the seasonal footprinting mechanism. How the NPO effect on ENSO changes in response to greenhouse warming remains unclear, however. Here, using climate model simulations under high-emission scenarios, we show that greenhouse warming leads to an enhanced influence of NPO on ENSO as is manifested by enhanced responses of winter sea surface temperature (SST), precipitation and wind anomalies in the equatorial Pacific to the preceding winter NPO. The strengthened NPO impact is also reflected in an increased frequency of NPO events that are followed by ENSO events. Warmer background SST enhances the wind-evaporation-SST feedback over the subtropical North Pacific due to a nonlinear SST-evaporation relationship. This strengthens the NPO-generated surface zonal wind anomalies over the equatorial western-central Pacific, which trigger ENSO. Increased impact of winter NPO on ENSO could enable prediction of interannual variability at longer leads.
Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa
Authors: Tartaglia Grace , Fuentes Ignacia , Patel Neil , Varughese Abigail , Israel Lauren E , Park Pyung Hun , Alexander Michael H , Poojan Shiv , Cao Qingqing , Solomon Brenda , Padron Zachary M , Dyer Jonathan A , Mellerio Jemima E , McGrath John A , Palisson Francis , Salas-Alanis Julio , Han Lin , South Andrew P
Published: March 2024

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.
Effect of impurities on radical formation in gibbsite radiolysis
Authors: Hlushko Hanna , Ramos-Ballesteros Alejandro , Chen Ping , Zhang Xin , Rosso Kevin M. , Pearce Carolyn I. , LaVerne Jay A.
Published: March 2024

The generation and stabilization of gamma radiation-induced hydrogen atoms in gibbsite (Al(OH)3) nanoplates is directly related to the nature of residual ions from synthetic precursors used, whether nitrates or chlorides.
Routes to high-performance layered oxide cathodes for sodium-ion batteries
Authors: Wang Jingqiang , Zhu Yan-Fang , Su Yu , Guo Jun-Xu , Chen Shuangqiang , Liu Hua-Kun , Dou Shi-Xue , Chou Shu-Lei , Xiao Yao
Published: March 2024

Various optimization strategies are reviewed and summarized to formulate design principles for layered oxide cathodes for sodium-ion batteries.
Promising in vitro and in silico biological activity of tetradentate Schiff base copper(ii) complexes with a propylenediamine bridge
Authors: Mijatović Aleksandar , Šeba Tino , Gligorijević Nevenka , Ćoćić Dušan , Spasić Snežana , Lolić Aleksandar , Aranđelović Sandra , Nikolić Milan , Gabričević Mario , Baošić Rada
Published: March 2024

Analyzed tetradentate Schiff base copper(ii) complexes (with a propylenediamine bridge) show promising antioxidant and antiproliferative activity and the ability to bind to macromolecular targets such as HSA and DNA.
Shining a light on fungicide- water: enhanced photocatalytic degradation using the CoTiO3/CaTiO3 nanocomposite and experimental and theoretical viewpoints on improved intervalence charge transfer from O2− to Ti4+ and from Co2+ to Ti4+ ions and spatial charge transfer
Authors: Narendran Moorthy Gnanasekar , Vijayakumar Elayaperumal , Govinda Raj Muniyandi , Preetha Rajaraman , John Alphin Joseph , Mahaan Ramalingam , Neppolian Bernaurdshaw , John Bosco Aruljothy
Published: March 2024

An enhanced degradation rate is achieved for the optimized CoTiO3/CaTiO3 (CCO 75 : 25) composite for highly effective photocatalytic carbendazim degradation.
Metal-free assembly of diverse polysubstituted pyridines via an efficient cascade approach using tertiary enaminones and α,β-unsaturated sulfonylketimines
Authors: Li Xiang , Pang Qiwen , Zhang Yang , Li Yang , Yang Qian-Qian , Lin Xinyu , Xie Xin , Huang Wei
Published: March 2024

A metal-free, scalable, and cascade protocol for assembling diverse polysubstituted pyridines from tertiary enaminones and α,β-unsaturated sulfonylketimines by cleaving C–N/N–S bonds is reported.
Structure–activity relationship study of anti-wear additives in rapeseed oil based on machine learning and logistic regression
Authors: Liu Jianfang , Yi Chenglingzi , Zhang Yaoyun , Yang Sicheng , Liu Ting , Zhang Rongrong , Jia Dan , Peng Shuai , Yang Qing
Published: March 2024

Anti-wear performance is a crucial quality of lubricants, and it is important to conduct research into the structure–activity relationship of anti-wear additives in bio-based lubricants.
Development of a tannic acid- and silicate ion-functionalized PVA–starch composite hydrogel forin situskeletal muscle repairing
Authors: Li Longkang , Li Huipeng , Diao Zhentian , Zhou Huan , Bai Yanjie , Yang Lei
Published: March 2024

Injectable, antioxidant and antimicrobial PVA-starch hydrogel functionalised with tannins and silicate ions for in situ skeletal muscle repair.
Overcoming aggregation with laser heated nanoelectrospray mass spectrometry: thermal stability and pathways for loss of bicarbonate from carbonic anhydrase II
Authors: Jordan Jacob S. , Lee Katherine J. , Williams Evan R.
Published: March 2024

Laser-heated electrospray ionization with mass spectrometry enables melting temperature measurements of aggregation-prone proteins from which thermochemical and mechanistic information about protein unfolding and ligand loss is deduced.
ECM-based bioadhesive hydrogel for sutureless repair of deep anterior corneal defects
Authors: Borouman Safieh , Sigaroodi Faraz , Ahmadi Tafti Seyed Mohsen , Khoshmaram Keyvan , Soleimani Masoud , Khani Mohammad-Mehdi
Published: March 2024

A photocurable bioadhesive hydrogel with improved mechanical properties was designed by incorporating the decellularized corneal-derived hydrogel into the GelMA/PEGDA double network for corneal regeneration.
Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30
Authors: Mondal Milon , Cao Fangyuan , Conole Daniel , Auner Holger W. , Tate Edward W.
Published: March 2024

IMP-2586 and IMP-2587 are selective and potent small molecule USP30 activity-based probes that engage USP30 rapidly in intact cells.
On-line generated ozone as a reactive cell gas for tandem quadrupole inductively coupled plasma mass spectrometry
Authors: Zhu Yanbei
Published: March 2024

ICP-QMS/QMS with on-line generated ozone as the cell gas showed greatly improved sensitivities for mass-shift mode measurements.
Adsorption and activation of small molecules on boron nitride catalysts
Authors: Miao Baiyu , Qiu Zhihuan , Zhen Ziheng , Yang Youwei , Yang Zhibo , Xiao Tiantian , Lv Jing , Huang Shouying , Wang Yue , Ma Xinbin
Published: March 2024

Reviewing adsorption and activation regimes of typical small molecules on h-BN and strategies to enhance activation capacity and catalytic performance.
Overcoming passivation through improved mass transport in dense ionic fluids
Authors: Daskalopoulou Evangelia , Hunt Philip , Elgar Christopher E. , Yang Minjun , Abbott Andrew P. , Hartley Jennifer M.
Published: March 2024

Formation of metal passivation layers during electrochemical dissolution is prevented by the use of ultrasound. Migration becomes the main method of mass transport across the electrical double layer.
An atomically dispersed Co catalyst for efficient oxidative fabrication of benzoheterocycles under ambient oxygen conditions
Authors: Chen Jia-Yue , Li Ke-Ming , Sun Yu-Xuan , Xiao Yao , Guo Feng-Shuo , Huang Yao-Bing , Lu Qiang
Published: March 2024

The first Co1/NC SAC is reported to produce benzoheterocycles under oxygen conditions, and the yields of 2-PBO, 2-PBT and 2-PBM were 99%, 95% and 99%, respectively.
Self-assembled organic molecules with a fused aromatic ring as hole-transport layers for inverted perovskite solar cells: the effect of linkers on performance
Authors: Cheng Haoliang , Huang Zu-Sheng
Published: March 2024

Two D–π–A structured SAMs (FNE29 and DT-1) with different linkers are self-assembled onto the indium tin oxide (ITO) substrates as HTLs for inverted PSCs. The results indicate that the SAMs with large conjugated fused linkers have obvious advantages as HTLs because of its fast hole transfer.
Amination of polylactic acid to alanine using a Ru–Co bimetallic catalyst
Authors: Cui Meng , Liu Guyue , Ma Cankun , Cao Zihan , Ye Yu , Shen Yongfu , Zhang Xiuqin
Published: March 2024

A Ru–Co/TiO2 catalyst was efficient for the amination of PLA to alanine without external hydrogen. This was the first attempt to introduce a non-precious metal into the catalyst for the reaction through thermocatalysis.
Bimetallic palladium nickel nanoparticles loaded on ammonia-alkalized multi-walled carbon nanotubes for efficient dehydrogenation of formic acid
Authors: Yang Yanqiu , Xu LinLin , Liu Tong
Published: March 2024

Ultrafine PdCr nanoparticles are immobilized on amino-modified mullite-type SmMn2O5 by co-precipitation. It exhibits remarkable catalytic activity for formic acid decomposition.
Thermally-activated upconversion based on triplet fusion for deep red photoactivation of Ru(ii) complexes
Authors: Niu Pengfei , Da Xuwen , Hu Rui , Yu Tianjun , Chen Jinping , Zhou Qianxiong , Luo Guiwen , Zeng Yi , Li Yi
Published: March 2024

A solid-state triplet–triplet annihilation upconversion system sensitized by endothermic triplet energy transfer was developed to deep red photoactivate Ru(ii) chemotherapeutic complexes.
Preparation of anisotropic polyimide aerogels for thermal protection with outstanding flexible resilience using the freeze-drying method
Authors: Xu Bing , Liang Hongtan , Hu Jie , Shu Jing , Zhang Lei , Fan Guozhi , Zhang Zhipeng , Wang Zhen , Pan Dehua
Published: March 2024

Anisotropic polyimide aerogels for thermal protection with outstanding flexible resilience.
Coupled plasma etching and electrodeposition of CoP/NiO nanosheets with surface reconstruction for water-splitting
Authors: Liao Qingdian , You Tao , Liu Xuesong , Deng Kuan , Liu Peng , Tian Wen , Ji Junyi
Published: March 2024

Plasma etching and electrodeposition were employed to construct a CoP/PNF composite. The latter underwent significant surface reconstruction, which resulted in improved electrocatalytic stability during water-splitting.
Raman micro-spectroscopy as a tool to study immunometabolism
Authors: Xu Jiabao , Morten Karl J
Published: March 2024

In the past two decades, immunometabolism has emerged as a crucial field, unraveling the intricate molecular connections between cellular metabolism and immune function across various cell types, tissues, and diseases. This review explores the insights gained from studies using the emerging technology, Raman micro-spectroscopy, to investigate immunometabolism. Raman micro-spectroscopy provides an exciting opportunity to directly study metabolism at the single cell level where it can be combined with other Raman-based technologies and platforms such as single cell RNA sequencing. The review showcases applications of Raman micro-spectroscopy to study the immune system including cell identification, activation, and autoimmune disease diagnosis, offering a rapid, label-free, and minimally invasive analytical approach. The review spotlights three promising Raman technologies, Raman-activated cell sorting, Raman stable isotope probing, and Raman imaging. The synergy of Raman technologies with machine learning is poised to enhance the understanding of complex Raman phenotypes, enabling biomarker discovery and comprehensive investigations in immunometabolism. The review encourages further exploration of these evolving technologies in the rapidly advancing field of immunometabolism.
The SRG/eROSITA All-Sky Survey
Authors: Liu A. , Bulbul E. , Kluge M. , Ghirardini V. , Zhang X. , Sanders J. S. , Artis E. , Bahar Y. E. , Balzer F. , Brüggen M. , Clerc N. , Comparat J. , Garrel C. , Gatuzz E. , Grandis S. , Lamer G. , Merloni A. , Migkas K. , Nandra K. , Predehl P. , Ramos-Ceja M. E. , Reiprich T. H. , Seppi R. , Zelmer S.
Published: March 2024

Superclusters of galaxies mark the large-scale overdense regions in the Universe. Superclusters provide an ideal environment to study structure formation and to search for the emission of the intergalactic medium such as cosmic filaments and WHIM. In this work, we present the largest-to-date catalog of X-ray-selected superclusters identified in the first SRG/eROSITA All-Sky Survey (eRASS1). By applying the Friends-of-Friends (FoF) method on the galaxy clusters detected in eRASS1, we identified 1338 supercluster systems in the western Galactic hemisphere up to redshift 0.8, including 818 cluster pairs and 520 rich superclusters with ≥3 members. The most massive and richest supercluster system is the Shapley supercluster at redshift 0.05 with 45 members and a total mass of 2.58 ± 0.51 × 1016M⊙. The most extensive system has a projected length of 127 Mpc. The sizes of the superclusters we identified in this work are comparable to the structures found with galaxy survey data. We also found a good association between the eRASS1 superclusters and the large-scale structures formed by optical galaxies. We note that 3948 clusters, corresponding to 45% of the cluster sample, were identified as supercluster members. The reliability of each supercluster was estimated by considering the uncertainties in the redshifts of the galaxy clusters and the peculiar velocities of clusters. Furthermore, 63% of the systems have a reliability larger than 0.7. The eRASS1 supercluster catalog provided in this work represents the most extensive sample of superclusters selected in the X-ray band in terms of the unprecedented sample volume, sky coverage, redshift range, the availability of X-ray properties, and the well-understood selection function of the parent cluster sample, which enables direct comparisons with numerical simulations. This legacy catalog will greatly advance our understanding of superclusters and the cosmic large-scale structure.
Hydrothermal synthesis and characterization of selenium-doped MoS2 for enhanced optoelectronic properties
Authors: Rai Soumya , Shreya  , Phogat Peeyush , Jha Ranjana , Singh Sukhvir
Published: March 2024

Transition metal dichalcogenides show layered crystal structure with Van der Waals forces spanning the adjacent layers. Robust covalent bonds within each 2D sheet contribute to their outstanding electrical and optical properties. The incorporation of a chalcogen atom as a composite leads to enhanced optical and electrical characteristics of the TMDs, which could make them potential candidates for opto-electronic applications. In the present study, we have described the synthesis and characterizations of Se doped MoS2 nanolayers using a facile one-step hydrothermal method. XRD analysis revealed the diffraction peaks corresponding to MoS2 as well as Se which suggested the successful incorporation of selenium into MoS2 nanolayers. Optical analysis revealed an increased band gap of 1.01 eV after the addition of selenium, determined through UV-visible spectroscopy with a refractive index of 3.36. The morphological analysis by FESEM showed the formation of nanolayers and the EDX pattern showed the presence of Mo, S and Se. The enhanced bandgap of the as-synthesized material and the increased absorption in the UV region ensures its usage for the fabrication of efficient broadband photodetectors. Our future research focuses on the potential application of Se doped MoS2 nanolayers in the field of efficient photodetectors.
Medikamentöse Therapie der portalen Hypertension
Authors: Martin Anna , Goeser Tobias , Kasper Philipp
Published: March 2024

In western industrialized nations, liver cirrhosis is the most common cause of portal hypertension. Portal hypertension is defined by a persistent increase in portal pressure >7mmHg. An HVPG >10mmHg defines the presence of clinically significant portal hypertension. The presence of clinically significant portal hypertension (CSPH) in patients with liver cirrhosis is a key risk factor for the transition from a compensated to a decompensated stage of the disease. CPSH can be determined invasively by measuring HPVG or noninvasively by measuring liver stiffness, platelet count and spleen stiffness. If acute decompensation manifests itself (e.g. ascites, esophageal variceal bleeding), this is associated with a significant increase in patient morbidity and mortality. Non-selective beta blockers (NSBB) are the standard medical therapy for portal hypertension in the presence of CSPH. Due to the additional α1-antiadrenergic effects, carvedilol leads to a greater reduction in portal pressure compared to traditional NSBB (e.g. Propanolol). In patients with compensated liver cirrhosis, carvedilol is better than traditional NSBB at reducing the risk of variceal bleeding and the occurrence of hepatic decompensation. The early identification of CSPH and evaluation of drug therapy to reduce portal hypertension is therefore crucial to improve the prognosis of patients.