bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of some phthalazine molecules as novel VEGFR-2 target inhibitors through 3D-QSAR modeling, molecular docking and dynamic simulation and pharmacokinetics profiling
Authors: Umar Abdullahi Bello , Abdullahi Sagiru Hamza , Patil Rajesh B. , Uzairu Adamu , Shallangwa Gideon Adamu , Uba Sani
Published: October 2024

Breast cancer is one of the dominant cause of cancer-related mortality in females, with an incidence of approximately 1.3 million cases annually, necessitating the development of effective therapeutic strategies. In this study, 3D-QSAR models were reported based on Phthalazine derivatives as VEGFR-2 inhibitors. The activities of these derivatives were correlated with the steric (S), electrostatic (E), hydrogen bond acceptor (A), and donor (D), and hydrophobic (H) fields, which served as critical parameters in model development. Statistical studies of these models showed that the best models are; CoMFA_S (Q2 = 0.623, R2 = 0.941), and CoMSIA_E + D (Q2 = 0.615, R2 = 0.977). Based on the insights from the model fields and docking simulation of the template (compound 17), twelve molecules were designed. These novel molecules exhibited stronger potency compared to the template and the standard, Sorafenib. Compound 17A emerged as the most potent, with pIC50 = 5.98, for CoMFA_S and 5.85, for CoMSIA_E + D, and a strong docking affinity of − 97.271 kcal/mol, therefore subjected to a 100-ns MD simulation. Results indicate better interaction and stabilizing potential over Sorafenib, due to the lower RMSD, RMSF, Rg, values and favorable hydrogen bond analyses. These conclusions were validated by Gibbs free energy analysis and MM-GBSA calculations, revealing a more favorable interaction free energy of − 18.48 kcal/mol related to Sorafenib. Furthermore, these designed compounds demonstrated promising pharmacokinetic profiles.
Speaking Sense: A Hybrid Source of Justification for Self-Knowledge
Authors: Gregory Daniel
Published: October 2024

Nico Silins [(2012). ‘Judgment as a Guide to Belief.’ In D. Smithies and D. Stoljar (eds), Introspection and Consciousness, pp. 295–327. Oxford: Oxford University Press; (2013). ‘Introspection and Inference.’ Philosophical Studies163, 291–315; (2020). ‘The Evil Demon Inside.’ Philosophy and Phenomenological Research100, 325–343] argues that conscious judgements justify self-attribution of belief in the content judged. In defending his view, he makes use of Moore's paradox, seeking to show how his theory can explain what seems irrational or absurd about sentences of the form, ‘p and I do not believe that p’. I show why his argument strategy is not available to defend the view that conscious judgements can justify the self-attribution of belief in the content judged. I then propose an amended version of his theory, which holds that sincerely asserting a proposition – whether aloud or silently – justifies self-ascribing belief in the proposition expressed. In doing so, I draw on an argument which I made in Gregory [(2018). ‘The Feeling of Sincerity: Inner Speech and the Phenomenology of Assertion.’ Thought7, 225–236] that there is something it is like to make a sincere assertion which is different from what it is like to make an insincere assertion. The phenomenology of sincere assertion provides immediate justification for self-ascription of belief in a proposition which has been sincerely asserted; nonetheless, it may be that we need to interpret our own assertions in order to determine which propositions they express. This paves the way for showing how two competing schools of thought about self-knowledge – one which holds that self-knowledge is immediate and one which holds that self-knowledge is inferential – might be combined.
Clinical characteristics associated with hospital-onset bacteremia and fungemia among cancer and transplant patients
Authors: Yu Kalvin C. , O’Horo John C. , Ai ChinEn , Jung Molly , Bastow Samantha
Published: October 2024

Objective:

This study quantified the burden of hospital-onset bacteremia and fungemia (HOB) among cancer and transplant patients compared to other patients.

Methods:

A retrospective cross-sectional study used data from 41 hospitals between October 2015 and June 2019. Hospitalizations were segmented into categories using diagnosis-related groups (DRG): myeloproliferative (MP) cancer, solid tumor cancer, transplant, and non-cancer/non-transplant (“reference group”). To quantify the association between DRG and HOB, multivariable adjusted Poisson regression models were fit. Analyses were stratified by length of stay (LOS).

Results:

Of 645,315 patients, 59% were female and the majority 41 years of age or older (76%). Hospitalizations with MP cancer and transplant demonstrated higher HOB burden compared to the reference group, regardless of LOS category. For all hospitalizations, the >30 days LOS category had a higher burden of HOB. The median time to reportable HOB was within 30 days regardless of duration of hospitalization (reference, 8 days; solid tumor cancer, 8 days; transplant, 12 days; MP cancer, 13 days).

Conclusion:

MP cancer and transplant patients had a higher burden of HOB compared to other hospitalized patients regardless of LOS. Whether these infections are preventable should be further evaluated to inform quality metrics involving reportable bacteremia and fungemia.
Carbohydrate intakes, food sources and tracking in Australian young children
Authors: Tesfaye Tinsae Shemelise , Szymlek-Gay Ewa A. , Campbell Karen J. , Zheng Miaobing
Published: October 2024

Carbohydrate intake and key food sources of carbohydrates in early childhood are poorly understood. The present study described total carbohydrate intake and subtypes (i.e. starch, sugar), their primary food sources and their tracking among young Australian children. Data from children at ages 9 months (n 393), 18 months (n 284), 3·5 years (n 244) and 5 years (n 240) from the Melbourne InFANT Program were used. Three 24-hour recalls assessed dietary intakes. The 2007 AUSNUT Food Composition Database was used to calculate carbohydrates intake and food groups. Descriptive statistics summarised total carbohydrate and subtype intake and their main food sources. Tracking was examined using Pearson correlations of residualised scores between time points. Total carbohydrate, starch and sugar intakes (g/d) increased across early childhood. The percentage of energy from total carbohydrates (% E) remained stable overtime (48·4–50·5 %). From ages 9 months to 5 years, the %E from total sugar decreased from 29·4 % to 22·6 %, while the %E from starch increased from 16·7 % to 26·0 %. Sources of total carbohydrate intake changed from infant formula at 9 months to bread/cereals, fruits and milk/milk products at 18 months, 3·5 and 5 years. Across all time points, the primary sources of total sugar intake were fruit, milk/milk products and cakes/cookies, whereas main food groups for starch intake included bread/cereals, cakes/cookies and pasta. Weak to moderate tracking of total carbohydrates, total sugar and starch (g/d) was observed. These findings may have the potential to inform the refinement of carbohydrate intake recommendations and design of interventions to improve children’s carbohydrate intake.
A first record of a suspected intestinal myiasis caused by Muscina stabulans (Fallén 1817) (Diptera: Muscidae) in Southern South America
Authors: Aballay Fernando H. , Saloña-Bordas Marta I. , Perotti M. Alejandra
Published: October 2024

We report a case of a suspected intestinal myiasis of a child from Southeast Argentina. Diptera larvae were sampled by a physician from the nappy worn by the child and submitted for examination and identification to the Laboratorio de Artrópodos (Universidad Nacional de Mar del Plata). Based on diagnosis of the anterior and posterior spiracles and mouthparts, the larvae were identified as the false stable fly Muscina stabulans (Fallén, 1817) (Diptera: Muscidae). A comparison of diagnostic characters between Argentinean and European third instars of this species is presented. Muscina stabulans is a prevalent species in the district of General Pueyrredón, Buenos Aires province, where the case occurred. Its abundance in the area coincidentally peaked at the time of the infestation. This is the 1st report of M. stabulans as a suspect of intestinal myiasis for the whole of the southern cone of South America (Chile and Argentina).
Social processes as the missing link: cross-sectionally testing a conceptual model on social mediators of early psychopathological development
Authors: Achterhof Robin , Kirtley Olivia J. , Lafit Ginette , Hiekkaranta Anu P. , Hagemann Noëmi , Hermans Karlijn S. F. M. , Lecei Aleksandra , Boets Bart , Henquet Cécile , Schneider Maude , Sips Rob , Vaessen Thomas , van Winkel Ruud , Viechtbauer Wolfgang , Reininghaus Ulrich , Myin-Germeys Inez
Published: October 2024

Background

Research suggests that most mental health conditions have their onset in the critically social period of adolescence. Yet, we lack understanding of the potential social processes underlying early psychopathological development. We propose a conceptual model where daily-life social interactions and social skills form an intermediate link between known risk and protective factors (adverse childhood experiences, bullying, social support, maladaptive parenting) and psychopathology in adolescents – that is explored using cross-sectional data.

Methods

N = 1913 Flemish adolescent participants (Mean age = 13.8; 63% girls) were assessed as part of the SIGMA study, a large-scale, accelerated longitudinal study of adolescent mental health and development. Self-report questionnaires (on risk/protective factors, social skills, and psychopathology) were completed during class time; daily-life social interactions were measured during a subsequent six-day experience-sampling period.

Results

Registered uncorrected multilevel linear regression results revealed significant associations between all risk/protective factors and psychopathology, between all risk/protective factors and social processes, and between all social processes and psychopathology. Social processes (social skills, quantity/quality of daily social interactions) were uniquely predicted by each risk/protective factor and were uniquely associated with both general and specific types of psychopathology. For older participants, some relationships between social processes and psychopathology were stronger.

Conclusions

Unique associations between risk/protective factors and psychopathology signify the distinct relevance of these factors for youth mental health, whereas the broad associations with social processes support these processes as broad correlates. Results align with the idea of a social pathway toward early psychopathology, although follow-up longitudinal research is required to verify any mediation effect.
Associations between polygenic scores for cognitive and non-cognitive factors of educational attainment and measures of behavior, psychopathology, and neuroimaging in the adolescent brain cognitive development study
Authors: Gorelik Aaron J. , Paul Sarah E. , Miller Alex P. , Baranger David A. A. , Lin Shuyu , Zhang Wei , Elsayed Nourhan M. , Modi Hailey , Addala Pooja , Bijsterbosch Janine , Barch Deanna M. , Karcher Nicole R. , Hatoum Alexander S. , Agrawal Arpana , Bogdan Ryan , Johnson Emma C.
Published: October 2024

Background

Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.

Methods

Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.

Results

Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.

Conclusions

While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
A novel dual-site OFC-dlPFC accelerated repetitive transcranial magnetic stimulation for depression: a pilot randomized controlled study
Authors: Cui Hailun , Ding Hui , Hu Lingyan , Zhao Yijie , Shu Yanping , Voon Valerie
Published: October 2024

Background

This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10–20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.

Methods

Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.

Results

Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.

Conclusions

Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.
The dynamic effects of becoming disabled on work, wages and wellbeing in the UK from 1991 to 2018
Authors: Dickson Matt , Skinner Tina , Forrester-Jones Rachel
Published: October 2024

Over recent decades it has consistently been shown that disabled adults in the UK fare worse in the labour market and have lower levels of wellbeing than non-disabled adults. However, this is in part due to the selection into dis-ability of those with existing socio-economic disadvantages. In this article, we use panel data from the combined British Household Panel Survey and Understanding Society, covering the 27 years from 1991 to 2018, to distinguish between the effect of selection, the effect of dis-ability onset and the effect of dis-ability duration on a range of labour market and wellbeing outcomes. We show that there is important selection both into dis-ability and into longer experience of dis-ability on the basis of observable characteristics. We also show the importance of controlling for time-invariant unobservable individual characteristics that similarly affect selection into dis-ability and duration of dis-ability. Even after controlling for both forms of selection, we find significant negative effects of dis-ability onset and duration, and offer policy solutions to address them.
Being a Husband and Caregiver: The Adjustment of Roles When Caring for a Wife Who Has Dementia
Authors: Miller Michaella , Neiterman Elena , Keller Heather , McAiney Carrie
Published: October 2024

As demographics and gender norms shift, more older men will be providing care for their wives living with dementia than ever before. Research on husbands as caregivers is limited and offers an incomplete picture of their role development and how they experience caregiving. This study examined husbands whose wives have dementia and how they provide care and construct their sense of self. Semi-structured interviews with 11 men aged 61–88 were conducted in Ontario, Canada. Data were analyzed using constant comparison analysis and a constructivist grounded theory (CGT) approach. Two categories were developed: Adapting to the Role of Caregiver and Staying a Husband. Caregiving as a husband for a wife living with dementia required revision of the role of husband to include that of caregiver by reimaging intimacy, being a protector in new ways, and finding new meanings to being a provider and the value of wealth.
Positive impact of an inpatient early childhood literacy programme on literacy practices and family experience in a paediatric heart centre
Authors: Young Allison C. , Ruth Amanda , Ginn Lauren , Sethi Louisa , Hellsten Melody , Deshotels Kirby , Pande Chetna K. , Borges Nirica M. , Wang Eric , Mummert Kelsey , Hill Stephanie , Bryant Tasha , Brown Ginger , Puri Kriti
Published: October 2024

Objective:

CHD predisposes children to neurodevelopmental delays. Frequent, prolonged hospitalisations during infancy prevent children with heart disease from participating in recommended language and cognitive development programmes, such as outpatient early childhood literacy programmes, and contribute to caregiver stress, a risk factor for adverse developmental outcomes. This study aims to describe the implementation of a single-centre inpatient early childhood literacy programme for hospitalised infants with heart disease and assess its impact on reading practices and patient–family hospital experience.

Methods:

Admitted infants ≤1 year old receive books, a calendar to track reading frequency, and reading guidance at regular intervals. Voluntary feedback is solicited from caregivers using an anonymous, QR-code survey on books. A prospective survey also assessed programme impact on hospital experience.

Results:

From February 2021 to November 2023, the Books@Heart programme provided 1,293 books to families of 840 infants, of whom 110 voluntarily submitted feedback. Caregivers reported a significant improvement in access to books (p < 0.001) and increased reading frequency after learning about Books@Heart (p = 0.003), with the proportion reading to their child daily increasing from 27% to 62%. Among 40 prospective survey responses, caregivers reported feeling a sense of personal fulfillment (60%), self-confidence (30%), connection (98%), and personal well-being (40%) while reading to their child.

Conclusion:

An inpatient early childhood literacy programme is a well-received intervention for infants with heart disease that promotes development, improves book access, increases reading exposure, and engages families. Further studies are needed to assess its impact on sustained reading practices and neurodevelopmental outcomes.
The risks of adverse events with venlafaxine for adults with major depressive disorder: a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis
Authors: Kamp C. B. , Petersen J. J. , Faltermeier P. , Juul S. , Siddiqui F. , Moncrieff J. , Horowitz M. A. , Hengartner M. P. , Kirsch I. , Gluud C. , Jakobsen J. C.
Published: October 2024

Aims

Venlafaxine is used to treat depression worldwide. Previous reviews have demonstrated that venlafaxine lowers scores on depression rating scales, producing statistically significant results but the relevance to patients remains uncertain. Knowledge of the incidence of the adverse effects associated with venlafaxine has previously been based on the results of non-randomised studies. Our primary objective was to assess the risks of adverse events with venlafaxine in the treatment of adults with major depressive disorder in randomised trials.

Methods

We searched relevant databases and other sources from inception to 7 March 2024 for randomised clinical trials comparing venlafaxine versus placebo or no intervention in adults with major depressive disorder. Data were synthesised using meta-analysis and Trial Sequential Analysis. The primary outcomes were suicides or suicide attempts, serious adverse events and non-serious adverse events.

Results

We included 28 trials randomising 6,253 participants to venlafaxine versus placebo. All results were at high risk of bias, and the certainty of the evidence was very low. All trials assessed outcomes at a maximum of 12 weeks after randomisation. Meta-analysis and Trial Sequential Analysis showed insufficient information to assess the effects of venlafaxine on the risks of suicides or suicide attempts. Meta-analysis showed evidence of harm of venlafaxine versus placebo on serious adverse events (risk ratio: 2.66; 95% confidence interval: 1.67–4.25; p < 0.01; 22 trials), mainly due to a higher risk of sexual dysfunction and anorexia. Meta-analysis showed that venlafaxine also increased the risk of several non-serious adverse events: nausea, dry mouth, dizziness, sweating, somnolence, constipation, nervousness, insomnia, asthenia, tremor and decreased appetite.

Conclusions

Short-term results show that venlafaxine has uncertain effects on the risks of suicides but increases the risks of serious adverse events (especially sexual dysfunction and anorexia) and many non-serious adverse events. The long-term effects of venlafaxine for major depressive disorder are unknown. It is a particular cause for concern that there are no data on the long-term adverse effects of venlafaxine given that so many people use these drugs for several years.
Seeing or believing in hyperplexed spatial proteomics via antibodies: New and old biases for an image-based technology
Authors: Bolognesi Maddalena M. , Dall’Olio Lorenzo , Maerten Amy , Borghesi Simone , Castellani Gastone , Cattoretti Giorgio
Published: October 2024

Hyperplexed in-situ targeted proteomics via antibody immunodetection (i.e., >15 markers) is changing how we classify cells and tissues. Differently from other high-dimensional single-cell assays (flow cytometry, single-cell RNA sequencing), the human eye is a necessary component in multiple procedural steps: image segmentation, signal thresholding, antibody validation, and iconographic rendering. Established methods complement the human image evaluation, but may carry undisclosed biases in such a new context, therefore we re-evaluate all the steps in hyperplexed proteomics. We found that the human eye can discriminate less than 64 out of 256 gray levels and has limitations in discriminating luminance levels in conventional histology images. Furthermore, only images containing visible signals are selected and eye-guided digital thresholding separates signal from noise. BRAQUE, a hyperplexed proteomic tool, can extract, in a marker-agnostic fashion, granular information from markers which have a very low signal-to-noise ratio and therefore are not visualized by traditional visual rendering. By analyzing a public human lymph node dataset, we also found unpredicted staining results by validated antibodies, which highlight the need to upgrade the definition of antibody specificity in hyperplexed immunostaining. Spatially hyperplexed methods upgrade and supplant traditional image-based analysis of tissue immunostaining, beyond the human eye contribution.
Diurnal Soil Freeze‐Thaw Cycles and the Factors Determining Their Changes in Warming Climate in the Upper Brahmaputra Basin of the Tibetan Plateau
Authors: Li Ning , Cuo Lan , Zhang Yongxin , Flerchinger Gerald N.
Published: October 2024

Soil freeze‐thaw cycles play a critical role in ecosystem, hydrological and biogeochemical processes, and climate. The Tibetan Plateau (TP) has the largest area of frozen soil that undergoes freeze‐thaw cycles in the low‐mid latitudes. Evidence suggests ongoing changes in seasonal freeze‐thaw cycles during the past several decades on the TP. However, the status of diurnal freeze‐thaw cycles (DFTC) of shallow soil and their response to climate change largely remain unknown. In this study, using in‐situ observations, the latest reanalysis, machine learning, and physics‐based modeling, we conducted a comprehensive assessment of the spatiotemporal variations of DFTC and their response to climate change in the upper Brahmaputra (UB) basin. About 24 ± 8% of the basin is subjected to DFTC with a mean frequency of 87 ± 55 days during 1980–2018. The area and frequency of DFTC show small long‐term changes during 1980–2018. Air temperature impacts on the frequency of DFTC changes center mainly around the freezing point (0°C). The spatial variations in the response of DFTC to air temperature can primarily be explained by three factors: precipitation (30.4%), snow depth (22.6%) and seasonal warming/cooling rates (14.9%). Both rainfall and snow events reduce diurnal fluctuations of soil temperature, subsequently reducing DFTC frequency, primarily by decreasing daytime temperature through evaporation‐cooling and albedo‐cooling effects, respectively. These results provide an in‐depth understanding of diurnal soil freeze‐thaw status and its response to climate change.
Deciphering the Characteristics and Drivers of the Summer Monsoon Precipitation Extremes Over the Indian Himalayas
Authors: Saini Rohtash , Attada Raju
Published: October 2024

This study investigates the physical processes behind extreme precipitation events (EPEs) in the Himalayas, notorious for causing frequent floods and significant loss of life and property. Due to the presence of complex terrain, understanding the driving factors of these EPEs is challenging. Here, we decipher the precipitation characteristics and their driving factors responsible for the occurrence of EPEs in the Western Himalayas (WH) for the period 1979–2020. EPEs are defined as events exceeding the 99th percentile threshold. The extreme precipitation in the WH is contributed by both large‐scale precipitation (accounting for 61%) and convective precipitation (39%). Moreover, 25.49% of EPEs in this region are directly associated with monsoon depressions. The presence of distinct upper‐tropospheric gyres flanking the WH, along with a prominent zonal wave pattern, promotes a southward extension of the trough. This intensifies the low‐level convergence of moisture‐laden winds from the adjoining seas, resulting in substantial moisture availability for the EPEs. An omega‐type blocking pattern emerges 4 days before EPEs, facilitating the intrusion of an extratropical cyclonic circulation. This circulation, characterized by its slow eastward and equatorward movement, leads to low‐level moisture flux convergence and ascending motions, which in turn trigger the EPEs. This highlights the crucial role of extratropical signals in driving EPEs and implies that tropical‐extratropical interactions play an important role in these EPEs. Furthermore, the shifting of the Intertropical Convergence Zone is strongly linked to the enhancement of the intensity of EPEs. Moreover, moisture budget analysis shows that EPEs over the WH are primarily driven by vertical advection, with the dynamic (thermodynamic) terms explaining 92% (8%) contribution. The intensified diabatic heating structure further enhances the convection, facilitating the development of deep convection which controls the local thermodynamics of these EREs. Lastly, our study demonstrated that most intensified and persistent EPEs over the Himalayas are found to be linked with Quasi‐Resonance Amplification, which is driven by baroclinic waves with 5 and 8 zonal wave numbers that contribute to these EPEs.
Bridging Hydrological Ensemble Simulation and Learning Using Deep Neural Operators
Authors: Sun Alexander Y. , Jiang Peishi , Shuai Pin , Chen Xingyuan
Published: October 2024

Ensemble‐based simulation and learning (ESnL) has long been used in hydrology for parameter inference, but computational demands of process‐based ESnL can be quite high. To address this issue, we propose a deep neural operator learning approach. Neural operators are generic machine learning algorithms that can learn functional mappings between infinite‐dimensional spaces, providing a highly flexible tool for scientific machine learning. Our approach is built upon DeepONet, a specific deep neural operator, and is designed to address several common problems in hydrology, namely, model parameter estimation, prediction at ungaged locations, and uncertainty quantification. Here we demonstrate the effectiveness of our DeepONet‐based workflow using an existing large model ensemble created for an eastern U.S. watershed that is instrumented with 10 streamflow gages. Results suggest DeepONet achieves high efficiency in learning an ML surrogate model from the model ensemble, with the modified Kling‐Gupta Efficiency exceeding 0.9 on holdout test sets. Parameter inference, carried out using the trained DeepONet surrogate model and genetic algorithm, also yields robust results. Additionally, we formulate and train a separate DeepONet model for physics‐informed, seq‐to‐seq streamflow forecasting, which further reduces biases in the pre‐trained DeepONet surrogate model. While this study focuses primarily on a single watershed, our approach is general and may be extended to enable learning from model ensembles across multiple basins or models. Thus, this research represents a significant contribution to the application of hybrid machine learning in hydrology.
C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease
Authors: Xia Ziru , Wei Zhaonan , Li Xin , Liu Yunzi , Gu Xiangchen , Tong Jianhua , Huang Siyi , Zhang Xiaoyue , Wang Weiming
Published: October 2024

Diabetic kidney disease (DKD) is a prevalent and debilitating complication of diabetes characterized by progressive renal function decline and a lack of effective treatment options. Here, we investigated the role of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in DKD pathogenesis. Analysis of renal biopsy samples revealed increased C/EBPα expression in patients with DKD. Using RNA sequencing and proteomics, we explored the mechanisms through which the C/EBPα contributes to DKD. Our findings demonstrated that C/EBPα exacerbated tubular injury by promoting acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. We identified that C/EBPα upregulated ACSL4 expression by binding to its transcription regulatory sequence (TRS), leading to elevated lipid peroxidation and ferroptosis. Furthermore, inhibition or genetic ablation of C/EBPα attenuated ferroptosis and mitigated tubular injury in DKD. These results highlighted the C/EBPα-ACSL4-ferroptosis pathway as a promising therapeutic target for DKD treatment.
The effect of digital therapeutics intervention on improving hypertension management in adults: a meta-analysis of randomized controlled trial
Authors: Liu Lu , Guo Jiayue , Jiao Xitong , You Lili
Published: October 2024

Digital therapeutics (DTx) intervention is an emerging therapy for the treatment and long-term management of hypertension. We aim to systematically evaluate the overall effect of DTx intervention on improving hypertension management. The systematic review and meta-analysis of RCTs was conducted and the PubMed, EMBASE, Web of Science, and Cochrane Library were searched to identify eligible RCTs published between Jan 1, 1982 and Sep 10, 2023. Random-effect models were utilized to pool estimates of net changes in systolic blood pressure (BP), diastolic BP, BP control rate, body mass index, weight, waist circumference, and physical activity between the DTx group and control group. 15 RCTs were included with a total of 3789 participants. Compared with the control group, DTx intervention was associated with significant changes in systolic BP, diastolic BP, and BP control rate of –3.75 mmHg(95% CI –5.74 to 1.77), –1.79 mmHg (95% CI –2.81 to –0.77) and 1.47% (95% CI 1.10 to 1.95), respectively. In addition, DTx intervention was statistically significant for improving other risk factors such as lower BMI (−0.5 kg/m2, 95% CI –0.86 to −0.15), increased physical activity (66.73 min/week, 95%CI 49.64 to 83.81), and reduced waist circumference (−2.91 cm, 95% CI −5.15 to −0.66). No difference between groups was demonstrated in weight (P = 0.30). Subgroup analyses revealed consistent effects of the change in SBP and DBP across study duration, age, sample size, patient baseline status, and intervention scenario settings(P > 0.05). DTx intervention may be useful for lowering BP and long-term management of hypertension. More large-size trials providing evidence on the same product are needed.
Impact of retinal traction induced by epiretinal membrane on aniseikonia
Authors: Hirano Masayuki , Minakawa Shun , Imamura Yuta , Yamamoto Naoko
Published: October 2024

We investigated the effect of retinal traction caused by epiretinal membranes (ERMs) on aniseikonia and retinal microstructures in 81 unilateral ERMs. Retinal traction was quantified by measuring the maximum depth of the retinal fold (MDRF) using en face optical coherence tomography (OCT) images. Measurements included the mean inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), central retinal thickness (CRT), and interocular ratios of the foveal avascular zone (FAZ) area (FAZ ratio). Significant correlations were found between the preoperative MDRF and preoperative aniseikonia (P < 0.001), INL thickness (P < 0.001), CRT (P < 0.001), and FAZ ratio (P = 0.003). Preoperative aniseikonia was significantly correlated with preoperative INL and OPL-ONL thicknesses (P < 0.001 and P = 0.020, respectively) and CRT (P = 0.003). Multiple regression analysis revealed that preoperative aniseikonia was significantly associated with preoperative MDRF, INL, and OPL-ONL thicknesses (P = 0.029, 0.006, and 0.006, respectively). Twenty-nine eyes underwent membrane peeling, resolving all retinal folds 6 months postoperatively. A significant correlation was observed between preoperative MDRF and postoperative aniseikonia (P = 0.011). Our findings suggest that retinal traction by ERM is significantly associated with aniseikonia both pre- and postoperatively, alongside other OCT parameters.
An in vitro evaluation of tensile strength of molar endocrown milled from various computer aided design and manufacturing materials
Authors: Taha Ahmed Ismail , Saad Aya Ehab
Published: October 2024

New computer-aided design and computer-aided manufacturing (CAD-CAM) materials have been reported to have suitable mechanical and physical properties for endocrown restorations. However, there is a lack of literature on evaluating the retention of endocrown using these materials. This in vitro study aimed to compare the retention of endocrowns fabricated from 3 different CAD-CAM materials. Sixty human mandibular third molars were divided into 3 groups (n = 20) according to the material used: (e.max CAD, Ivoclar AG, Schaan, Liechtenstein), (HC, Shofu, Koyoto, Japan), and (Brilliant Crios, Coltene, Altstätten, Switzerland) (n = 20). Specimens were stored in distilled water at 37 °C for 1 week and subjected to 5000 thermal cycles. A universal testing machine (5500R/1123, Instron, Norwood, USA) was used to measure the tensile force. All results were statistically analyzed using one-way ANOVA (α = 0.05), and different failure modes were demonstrated. The results revealed that e. max CAD showed the highest mean tensile force value (402.35 ± 15.812) N, and the lowest mean tensile force value was for Brilliant Coris (118.90 ± 12.430) N (P < .001). It is concluded that e.max CAD endocrowns showed the highest tensile force values after thermocycling in comparison to other materials with a significant difference, which may have a promising impact on the survival of endocrown restorations.
Leveraging weak complementary labels enhances semantic segmentation of hepatocellular carcinoma and intrahepatic cholangiocarcinoma
Authors: Hägele Miriam , Eschrich Johannes , Ruff Lukas , Alber Maximilian , Schallenberg Simon , Guillot Adrien , Roderburg Christoph , Tacke Frank , Klauschen Frederick
Published: October 2024

In this paper we present a deep learning segmentation approach to classify and quantify the two most prevalent primary liver cancers – hepatocellular carcinoma and intrahepatic cholangiocarcinoma – from hematoxylin and eosin (H&E) stained whole slide images. While semantic segmentation of medical images typically requires costly pixel-level annotations by domain experts, there often exists additional information which is routinely obtained in clinical diagnostics but rarely utilized for model training. We propose to leverage such weak information from patient diagnoses by deriving complementary labels that indicate to which class a sample cannot belong to. To integrate these labels, we formulate a complementary loss for segmentation. Motivated by the medical application, we demonstrate for general segmentation tasks that including additional patches with solely weak complementary labels during model training can significantly improve the predictive performance and robustness of a model. On the task of diagnostic differentiation between hepatocellular carcinoma and intrahepatic cholangiocarcinoma, we achieve a balanced accuracy of 0.91 (CI 95%: 0.86-0.95) at case level for 165 hold-out patients. Furthermore, we also show that leveraging complementary labels improves the robustness of segmentation and increases performance at case level.
Medical large language models are susceptible to targeted misinformation attacks
Authors: Han Tianyu , Nebelung Sven , Khader Firas , Wang Tianci , Müller-Franzes Gustav , Kuhl Christiane , Försch Sebastian , Kleesiek Jens , Haarburger Christoph , Bressem Keno K. , Kather Jakob Nikolas , Truhn Daniel
Published: October 2024

Large language models (LLMs) have broad medical knowledge and can reason about medical information across many domains, holding promising potential for diverse medical applications in the near future. In this study, we demonstrate a concerning vulnerability of LLMs in medicine. Through targeted manipulation of just 1.1% of the weights of the LLM, we can deliberately inject incorrect biomedical facts. The erroneous information is then propagated in the model’s output while maintaining performance on other biomedical tasks. We validate our findings in a set of 1025 incorrect biomedical facts. This peculiar susceptibility raises serious security and trustworthiness concerns for the application of LLMs in healthcare settings. It accentuates the need for robust protective measures, thorough verification mechanisms, and stringent management of access to these models, ensuring their reliable and safe use in medical practice.
Rapid in situ carbon-13 hyperpolarization and imaging of acetate and pyruvate esters without external polarizer
Authors: Mohiuddin Obaid , de Maissin Henri , Pravdivtsev Andrey N. , Brahms Arne , Herzog Marvin , Schröder Leif , Chekmenev Eduard Y. , Herges Rainer , Hövener Jan-Bernd , Zaitsev Maxim , von Elverfeldt Dominik , Schmidt Andreas B.
Published: October 2024

Hyperpolarized 13C MRI visualizes real-time metabolic processes in vivo. In this study, we achieved high 13C polarization in situ in the bore of an MRI system for precursor molecules of most widely employed hyperpolarized agents: [1-13C]acetate and [1-13C]pyruvate ethyl esters in their perdeuterated forms, enhancing hyperpolarization lifetimes, hyperpolarized to P13C ≈ 28% at 80 mM concentration and P13C ≈ 19% at 10 mM concentration, respectively. Using vinyl esters as unsaturated Parahydrogen-Induced Polarization via Side-Arm Hydrogenation (PHIP-SAH) precursors and our novel polarization setup, we achieved these hyperpolarization levels by fast side-arm hydrogenation in acetone-d6 at elevated temperatures (up to 90°C) and hydrogenation pressures (up to 32 bar). We optimized the hyperpolarization process, reducing it to under 10 s, and employed advanced pulse sequences to enhance the polarization transfer efficiency. The hyperpolarization system has a small footprint, allowing it to be positioned in the same magnet, where 13C MRI is performed. We exemplified the utility of the design with sub-second in situ 13C MRI of ethyl [1-13C]pyruvate-d6. However, challenges remain in side-arm cleavage and purification in the MRI system to extract highly polarized aqueous agent solutions. Our results showcase efficient and rapid 13C hyperpolarization of these metabolite precursors in an MRI system with minimal additional hardware, promising to enhance future throughput and access to hyperpolarized 13C MRI.
Tight junction protein LSR is a host defense factor against SARS-CoV-2 infection in the small intestine
Authors: An Yanan , Wang Chao , Wang Ziqi , Kong Feng , Liu Hao , Jiang Min , Liu Ti , Zhang Shu , Du Kaige , Yin Liang , Jiao Peng , Li Ying , Fan Baozhen , Zhou Chengjun , Wang Mingxia , Sun Hui , Lei Jie , Zhao Shengtian , Gong Yongfeng
Published: October 2024

The identification of host factors with antiviral potential is important for developing effective prevention and therapeutic strategies against SARS-CoV-2 infection. Here, by using immortalized cell lines, intestinal organoids, ex vivo intestinal tissues and humanized ACE2 mouse model as proof-of-principle systems, we have identified lipolysis-stimulated lipoprotein receptor (LSR) as a crucial host defense factor against SARS-CoV-2 infection in the small intestine. Loss of endogenous LSR enhances ACE2-dependent infection by SARS-CoV-2 Spike (S) protein-pseudotyped virus and authentic SARS-CoV-2 virus, and exogenous administration of LSR protects against viral infection. Mechanistically, LSR interacts with ACE2 both in cis and in trans, preventing its binding to S protein, and thus inhibiting viral entry and S protein-mediated cell–cell fusion. Finally, a small LSR-derived peptide blocks S protein binding to the ACE2 receptor in vitro. These results identify both a previously unknown function for LSR in antiviral host defense against SARS-CoV-2, with potential implications for peptide-based pan-variant therapeutic interventions.
Biodegradable fluorescent protein chromophore nanoparticles for hypoxic two-photon photodynamic therapy
Authors: Feng Wan , Qian Ying
Published: October 2024

This article reports a biodegradable red fluorescent protein chromophore analogues nanoparticle DPFP-SS-FA for hypoxic two-photon PDT.
Sequence-function space of radical SAM cyclophane synthases reveal conserved active site residues that influence substrate specificity
Authors: Phan Chin-Soon , Morinaka Brandon I.
Published: October 2024

The uncharacterized rSAM enzyme HtkB from Pandoraea sp. catalyzes a HisC2-to-LysCβ crosslink. ColabFold and mutagenesis was used to reveal residues D214 in HtkB and H204 in HaaB are important for substrate specificity.
The impact of low-energy phonon lifetimes on the magnetic relaxation in a dysprosocenium single-molecule magnet
Authors: Nabi Rizwan , Atkinson Benjamin E. , Staab Jakob K. , Skelton Jonathan M. , Chilton Nicholas F.
Published: October 2024

Calculation of phonons, phonon scattering, spin–phonon coupling and magnetic relaxation rates for a dysprosocenium single-molecule magnet show that strong scattering of low-energy modes is a significant contribution to their high-performance.
Ultrafine PtCo alloy nanoparticles integrated into porous N-doped nanosheets for durable oxygen reduction reaction
Authors: Chen Baoliang , Zhao Lei , Zhu Zhaozhao , Xiong Pei , Li Zhao , Chen Jun Song , Li Lanlan , Wu Rui
Published: October 2024

The PtCo–CoNC–P catalyst, featuring sub-3 nm small-size PtCo alloy nanoparticles integrated into a porous nitrogen-doped nanosheet, exhibits exceptional durability after 30 000 cycles of accelerated durability tests.
Copper(i) and cobalt(ii) frameworks with a tetraphenylethene–imidazole ligand for the electroreduction of CO2 to CH4
Authors: Wang Fang-Fang , Wang Yu-Jie , Qiu Zhao-Feng , Zhang Kai-Yang , Zhao Yue , Sun Wei-Yin
Published: October 2024

Two new MOFs with different metal centers were synthesized and applied to the electroreduction of CO2. Cu-MOF was found to show the capacity for the electrocatalytic conversion of CO2 to CH4, while Co-MOF is unsuitable due to its low stability.
Eco-inspired synthesis of MgO-infused g-C3N4 nanocomposites from tulsi seeds for advanced photocatalytic environmental remediation
Authors: Dahiya Sweety , Sharma Anshu , Chaudhary Sudesh
Published: October 2024

This study develops MgO-doped g-C3N4 nanocomposites using tulsi seed extract, achieving 98% methylene blue and 54% tetracycline removal. The optimized 1.5 mM MgO composite enhances photocatalytic and antibacterial performance for sustained use.
Ultrasound mechanisms and their effect on solid synthesis and processing: a review
Authors: Devos Cedric , Bampouli Ariana , Brozzi Elena , Stefanidis Georgios D. , Dusselier Michiel , Van Gerven Tom , Kuhn Simon
Published: October 2024

Ultrasound intensifies a wide range of processes involving solids, enhancing control over their formation and post-treatment. This review summarizes key ultrasonic mechanisms and effects in solids' synthesis and processing.
The gas phase ozonolysis and secondary OH production of cashmeran, a musk compound from fragrant volatile chemical products
Authors: Akande Ayomide A. , Borduas-Dedekind Nadine
Published: October 2024

We quantified the lifetime of cashmeran, a musk compound, against 20 ppbv of O3 to be 85 days. In the presence of O2, cashmeran may influence the oxidative capacity indoors via production of secondary OH radicals (up to 5.1 × 105 molec cm−3).
Safe-by-design assessment of an SiO2@ZnO multi-component nanomaterial used in construction
Authors: Brunelli A. , Serrano-Lotina A. , Bañares M. A. , Alcolea-Rodriguez V. , Blosi M. , Costa A. , Ortelli S. , Peijnenburg W. , Fito C. , Fernandez E. G. , Hermosilla J. S. , Soeteman-Hernández L. G. , Garmendia Aguirre I. , Rauscher H. , Murphy F. , Stone V. , Balbuena J. , Cormano J. M. L. , Pizzol L. , Hristozov D. , Marcomini A. , Badetti E.
Published: October 2024

Implementation of the safe and sustainable by design framework using cement mortar containing an SiO2@ZnO multi-component nanomaterial for NOx degradation as a case study.
Removal of Cu2+ from AMD by goethite modified biochar combined with sodium alginate: characterization, performance and mechanisms
Authors: Yang Hong , Zhang Ruixue , An Li , Wu Pan , Fu Yuran , Zou Jiajun , Yu Min
Published: October 2024

An innovative method for resource utilization of agricultural waste crops.
Iodine solid sorbent design: a literature review of the critical criteria for consideration
Authors: Riley Brian J. , Turner Joshua R. , McFarlane Joanna , Chong Saehwa , Carlson Krista , Matyáš Josef
Published: October 2024

Designing sorbents for iodine capture in different conditions requires selection and optimization of a large and diverse range of variables.
High-throughput development of tough metallic glass films
Authors: Wu Yuzhou , Huang Yue , Wang Yebei , Wang Fuchao , Gao Yunhe , Sun Yingying , Jian Meichen , Song Lijian , Tong Yu , Zhang Yan , Wang Chao , Liu Yanhui , Wang Jun-Qiang , Huo Juntao , Gao Meng
Published: October 2024

An experimental framework for high-throughput development of tough metallic glass films as strain-sensing materials for application in the field of soft electronics was proposed.