bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of an inpatient automatic dose reduction protocol for concentrated insulin glargine upon therapeutic interchange to insulin detemir on hypoglycemia rates
Authors: Addison Janci , Glowacki Brittany , Kelley Denise , Janzen Kristin M , Wulfe Steven 
Published: November 2024

Abstract

Purpose
A previous study at Ascension Seton Hospital Network (ASHN) found a 1:1 dose conversion to insulin detemir 100 units/mL (iDet100) from insulin glargine 300 units/mL (iGlar300) increased the incidence of hypoglycemia as compared to a 1:1 conversion from insulin glargine 100 units/mL. No studies have evaluated an automatic 20% dose reduction for this specific therapeutic interchange. The purpose of this study was to compare hypoglycemia rates following implementation of a protocol specifying a minimum 20% dose reduction when converting from iGlar300 to inpatient iDet100.

Methods
This multicenter, retrospective chart review–based study was a before/after study evaluating the impact of an ASHN protocol implemented in April 2021 requiring a minimum 20% reduction when converting from home iGlar300 to inpatient iDet100. Previously, a 1:1 interchange was standard. Patients admitted between May 2019 and December 2022 were included if at least 1 dose of iDet100 was received following interchange from iGlar300. The primary endpoint was hypoglycemia incidence before and after protocol implementation. Secondary endpoints included time to first hypoglycemia and number of doses given before hypoglycemia. Logistic regression was performed to analyze the relationship between percent interchange from home dose and hypoglycemia rate.

Results
A total of 284 patients were included: 128 in the preprotocol arm and 156 in the postprotocol arm. The incidence of hypoglycemia was significantly lower in the postprotocol arm than in the preprotocol arm (11.9% vs 24.7%; P = 0.018). The median time to first hypoglycemia was longer in the postprotocol versus the preprotocol arm, though the difference was not statistically significant (13 vs 18.5 hours, P = 0.082). For each percent reduction from iGlar300 to iDet100, the likelihood of hypoglycemia was reduced by 5.3%.

Conclusion
A protocol requiring a minimum 20% dose reduction from iGlar300 to inpatient iDet100 reduced the incidence of hypoglycemia. Health systems should consider adopting a similar approach to reduce the occurrence of hypoglycemia upon interchange.
Accurate and transferable drug–target interaction prediction with DrugLAMP
Authors: Luo Zhengchao , Wu Wei , Sun Qichen , Wang Jinzhuo 
Published: November 2024

Abstract

Motivation
Accurate prediction of drug–target interactions (DTIs), especially for novel targets or drugs, is crucial for accelerating drug discovery. Recent advances in pretrained language models (PLMs) and multi-modal learning present new opportunities to enhance DTI prediction by leveraging vast unlabeled molecular data and integrating complementary information from multiple modalities.

Results
We introduce DrugLAMP (PLM-assisted multi-modal prediction), a PLM-based multi-modal framework for accurate and transferable DTI prediction. DrugLAMP integrates molecular graph and protein sequence features extracted by PLMs and traditional feature extractors. We introduce two novel multi-modal fusion modules: (i) pocket-guided co-attention (PGCA), which uses protein pocket information to guide the attention mechanism on drug features, and (ii) paired multi-modal attention (PMMA), which enables effective cross-modal interactions between drug and protein features. These modules work together to enhance the model’s ability to capture complex drug–protein interactions. Moreover, the contrastive compound-protein pre-training (2C2P) module enhances the model’s generalization to real-world scenarios by aligning features across modalities and conditions. Comprehensive experiments demonstrate DrugLAMP’s state-of-the-art performance on both standard benchmarks and challenging settings simulating real-world drug discovery, where test drugs/targets are unseen during training. Visualizations of attention maps and application to predict cryptic pockets and drug side effects further showcase DrugLAMP’s strong interpretability and generalizability. Ablation studies confirm the contributions of the proposed modules.

Availability and implementation
Source code and datasets are freely available at https://github.com/Lzcstan/DrugLAMP. All data originate from public sources.
Invariant Probabilistic Prediction
Authors: Henzi Alexander , Shen Xinwei , Law Michael , Bühlmann Peter 
Published: November 2024

Abstract
In recent years, there has been a growing interest in statistical methods that exhibit robust performance under distribution changes between training and test data. While most of the related research focuses on point predictions with the squared error loss, this article turns the focus towards probabilistic predictions, which aim to comprehensively quantify the uncertainty of an outcome variable given covariates. Within a causality-inspired framework, we investigate the invariance and robustness of probabilistic predictions with respect to proper scoring rules. We show that arbitrary distribution shifts do not, in general, admit invariant and robust probabilistic predictions, in contrast to the setting of point prediction. We illustrate how to choose evaluation metrics and restrict the class of distribution shifts to allow for identifiability and invariance in the prototypical Gaussian heteroscedastic linear model. Motivated by these findings, we propose a method to yield invariant probabilistic predictions and study the consistency of the underlying parameters. Finally, we demonstrate the empirical performance of our proposed procedure via simulations and on single-cell data.
A review of consent policies in dermatological surgery in the UK and the impact of leaner pathways and teledermatology on consent
Authors: Potluru Aparna , Sokol Daniel , Wernham Aaron 
Published: November 2024

Abstract
Obtaining valid consent is an ethical and legal requirement in clinical practice, ensuring patients are adequately informed about their treatments. Recent updates in consent policies, including General Medical Council guidance, the Patterson Inquiry report, and key legal rulings like Montgomery, emphasize a shift towards patient-centred care and the importance of a comprehensive patient–clinician dialogue. Budget constraints and increasing National Health Service demand have led to the adoption of digital solutions and streamlined pathways, such as teledermatology and direct booking to surgery, potentially compromising the consent process. This review examines the current state of informed consent in UK dermatology, particularly in light of the Montgomery ruling, which requires clinicians to ensure patients are aware of all material risks and alternatives associated with their treatments. The two-stage consent process, involving consent at two distinct points, is advocated to allow patients adequate time for reflection and decision making. However, challenges remain in pathways like one-stop clinics and direct booking for surgery, where limited face-to-face interaction and time constraints can undermine the quality of informed consent. To mitigate these issues, integrating multimedia tools and standardized procedure-specific consent forms can enhance patient comprehension and satisfaction. These tools ensure consistent and clear communication of risks, benefits and alternatives, maintaining robust informed consent amid evolving healthcare delivery models. Sustaining a thorough and individualized dialogue throughout the patient care journey is essential for upholding patient autonomy and shared decision making in dermatological surgery.
Efficacy and tolerability of 1.6% phenol-croton peeling vs. topical 5% imiquimod in the treatment of actinic cheilitis: a randomized controlled trial
Authors: Garbers Luiz Eduardo Fabrício de Melo , Miola Anna Carolina , de Souza Vinicius , de Castro Brommonschenkel Christina , de Oliveira Lima Flávio , Minicucci Eliana Maria , Miot Hélio Amante 
Published: November 2024

Abstract

Background
Trials evaluating the effectiveness of topical treatments for actinic cheilitis (AC) are scarce. Despite no comparative data, phenol-croton peeling has been reported as effective in treating this condition.

Objective
To assess for the treatment of AC the efficacy and tolerability of a single session of 1.6% phenol-croton peeling vs. topical 5% imiquimod cream applied for 30 days for the treatment of AC.

Methods
An open, randomized controlled trial was conducted to compare the effectiveness and tolerability of 1.6% phenol-croton peeling vs. topical 5% imiquimod for the treatment of AC [protocol registered at ReBEC (Brazilian Registry of Clinical Trials) – RBR-1044sz68]. Thirty-six patients with biopsy-proven AC were allocated into two groups (1 : 1): the imiquimod group received 5% topical imiquimod three times a week for 30 days, and the croton group underwent one session of 1.6% phenol-croton peeling. The primary outcome was the clearance of AC after 56 days. Secondary outcomes included clinical and histological parameters, adverse effects and clinical results after 180 days.

Results
Complete clinical clearance of AC (defined as clearance of both leukoplakia and hyperkeratosis) at day 56 and day 180 occurred in 17 of 18 (94%) participants from the croton group but in none of the 18 participants in the imiquimod group (P &lt; 0.01). Improvement in all clinical parameters was more prominent in the croton group (P ≤ 0.01). Complete histological normalization at day 56 occurred in 72% of the croton group and only 17% in the imiquimod group (P &lt; 0.01). Histological parameters such as atypia (keratinocyte intraepithelial neoplasia score), solar elastosis and hyperkeratosis reduced in intensity only in the croton group (P &lt; 0.05). Adverse effects were most intense on day 7 in the croton group and persisted until day 21 in the imiquimod group. The study was prematurely terminated at the interim analysis.

Conclusions
A single session of 1.6% phenol-croton peeling produced clinically and histologically superior results with a shorter recovery period compared with imiquimod for treating AC.
Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century
Authors: Janani Leila , Phillips Rachel , Van Vogt Ellie , Liu Xinxue , Waddington Claire , Cro Suzie 
Published: November 2024

Abstract
Vaccines are crucial for protecting health globally; however, their widespread use relies on rigorous clinical development programmes. This includes Phase 3 randomized controlled trials (RCTs) to confirm their safety, immunogenicity, and efficacy. Traditionally, such trials used fixed designs with predetermined assumptions, lacking the flexibility to change during the trial or stop early due to overwhelming evidence of either efficacy or futility. Modern vaccine trials benefit from innovative approaches like adaptive designs, allowing for planned trial adaptations based on accumulating data. Here, we provide an overview of the evolution of Phase 3 vaccine trial design and statistical analysis methods from traditional to more innovative contemporary methods. This includes adaptive trial designs, which offer ethical advantages and enable early termination if indicated; Bayesian methods, which combine prior knowledge and observed trial data to increase efficiency and enhance result interpretation; modern statistical analysis methods, which enable more accurate and precise inferences; the estimand framework, which ensures the primary question of interest is addressed in a trial; novel approaches using machine learning methods to assess heterogeneity of treatment effects; and statistical advances in safety analysis to evaluate reactogenicity and clinical adverse events. We conclude with insights into the future direction of vaccine trials, aiming to inform clinicians and researchers about conventional and novel RCT design and analysis approaches to facilitate the conduct of efficient, timely trials.
Repetition of critical search features modulates EEG lateralized potentials in visual search
Authors: Oxner Matt , Mazza Veronica , Müller Matthias M 
Published: November 2024

Abstract
In visual search, the repetition of target and distractor colors enables both successful search and effective distractor handling. Nevertheless, the specific consequences of trial-to-trial feature repetition in different search contexts are poorly understood. Here, we investigated how feature repetition shapes the electrophysiological and behavioral correlates of target processing and distractor handling, testing theoretically informed predictions with single-trial mixed-effects modeling. In two experiments, the colors of a fixed-shape target and singleton distractor changed unpredictably across trials. Targets were color singletons in Experiment 1, allowing efficient search among pop-out items, but were not uniquely colored in Experiment 2, encouraging slower shape-feature search. Interference by the distractor occurred only in pop-out search but was reduced by repetition. This was paralleled by the contralateral electroencephalography (EEG) response: Following a search color change, the target-related N2pc was greatly reduced, and salient distractors elicited an N2pc followed by an enhanced PD. This biphasic response was absent in Experiment 2, where color was less useful to search. Overall, distractor positivities were not sensitive to feature repetition, suggesting that they are unrelated to preparatory suppression. Attention-related lateralization components are not universally elicited by target or distractor feature values but are driven specifically by expected features important to the search task.
Brain functional gradients are related to cortical folding gradient
Authors: He Zhibin , Zhang Tuo , Wang Qiyu , Zhang Songyao , Cao Guannan , Liu Tianming , Zhao Shijie , Jiang Xi , Guo Lei , Yuan Yixuan , Han Junwei 
Published: November 2024

Abstract
Cortical folding is closely linked to brain functions, with gyri acting more like local functional “hubs” to integrate information than sulci do. However, understanding how anatomical constraints relate to complex functions remains fragmented. One possible reason is that the relationship is estimated on brain mosaics divided by brain functions and cortical folding patterns. The boundaries of these hypothetical hard-segmented mosaics could be subject to the selection of functional/morphological features and as well as the thresholds. In contrast, functional gradient and folding gradient could provide a more feasible and unitless platform to mitigate the uncertainty introduced by boundary definition. Based on the MRI datasets, we used cortical surface curvature as the folding gradient and related it to the functional connectivity transition gradient. We found that, at the local scale, the functional gradient exhibits different function transition patterns between convex/concave cortices, with positive/negative curvatures, respectively. At the global scale, a cortex with more positive curvature could provide more function transition efficiency and play a more dominant role in more abstractive functional networks. These results reveal a novel relation between cortical morphology and brain functions, providing new clues to how anatomical constraint is related to the rise of an efficient brain function architecture.
Transport and immunomodulatory effect of Hericium erinaceus peptide LPGKVIAS
Authors: Sun Ronggui , Xu Hui , Xie Minhao , Liu Jianhui , Hu Qiuhui , Su Anxiang , Mariga Alfred Mugambi , Yang Wenjian 
Published: November 2024

Abstract
Hericium erinaceus–derived peptides have been found to exhibit various bioactivities, including immunoregulatory properties. This study investigated the transport, absorption, and potential immunomodulatory activities of a new peptide, Leu-Pro-Gly-Lys-Val-Ile-Ala-Ser (LPGKVIAS), derived from H. erinaceus. Transport and absorption of LPGKVIAS were analyzed by near-infrared fluorescence in vivo imaging in mice injected with a fluorescence probe–labeled LPGKVIAS. RNA sequencing was used to explore the immunological effects of the peptide on mouse splenocytes. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that LPGKVAS upregulated differentially expressed genes involved in immune regulation. Notably, activation of the lysosome–phagosome pathway in splenocytes of mice treated with LPGKVIAS was identified as a crucial immune defense mechanism against pathogen infection. Furthermore, reverse transcription–polymerase chain reaction studies validated the gene expression data, supporting the potential application of the peptide LPGKVIAS as an immunomodulator.
Investigating the influence of groundwater on the in-situ behaviour of Poisson's ratio using downhole array data
Authors: He Hong-Jun , Miao Yu , Shi Yang 
Published: November 2024

SUMMARY
Poisson's ratio is a commonly used parameter in geotechnical engineering research. Although most studies on its dynamic behaviour have been performed using laboratory tests, which are not necessarily representative of the anticipative soil behaviour in practice, especially nonlinear behaviour. By contrast, the in-situ studies using seismic data are limited and inadequate. Hence, in this study, we first performed the in-situ estimations of Poisson's ratios at various strains for seven research cases by applying seismic interferometry to seismic data from three seismic downhole arrays. Then, we proposed a proxy named equivalent water content, Weq, which was calculated by using site information and used to evaluate the influence of groundwater. Finally, by calculating the Weq for each research case, the in-situ dynamic behaviours of Poisson's ratio and the ratio between compression and shear wave velocities were investigated for sites with low shear stiffness and high water content. It was found that there were significant relationships between the proposed proxy and the in-situ behaviours of Poisson's ratio and the ratio between compression and shear wave velocities. The small-strain Poisson's ratio and the ratio between small-strain compression and shear wave velocities increased with Weq at the change rates, which gradually decreased and increased, respectively. The nonlinear variation of Poisson's ratio at each shear strain decreased with increases in Weq and shear modulus ratio at the change rates, which gradually decreased and increased, respectively. By constructing an analysis model, three formulae were further proposed to describe the above relationships, which can be utilized to build the empirical equations for preliminarily estimating the small-strain Poisson's ratio, the ratio between small-strain compression and shear wave velocities and the nonlinear variation of Poisson's ratio without requiring compression wave velocity.
Crustal and uppermost mantle structure of the Iranian Makran subduction zone from ambient noise and earthquake surface wave tomography
Authors: Mehrdar Ali , Motaghi Khalil , Ghods Abdolreza , Sobouti Farhad , Priestley Keith , Pachhai Surya , Shabanian Esmaeil , Zarunizadeh Zahra , Zeynaddini-Meymand Reza , El-Hussain Issa 
Published: November 2024

SUMMARY
The Makran subduction zone is a distinctive segment within the Alpine–Himalayan system, where one of the final remnants of the once-expansive Neo-Tethys Ocean is being subducted beneath the Eurasian Plate. Limited seismic data has left several questions unanswered about the structure of the subducting oceanic lithosphere, the transition from the wide and thick Makran accretionary prism to the Zagros Collision Zone, variations in sedimentary cover thickness along and perpendicular to the accretionary prism, and fluctuations in the thickness of sedimentary cover within the fore-arc Jaz Murian Depression (JMD). In this study, we utilize ambient-noise and earthquake surface wave tomography within a period range of 5–50 s to construct a high-resolution 3-D shear-wave velocity model down to a depth of 60 km for the Iranian Makran and northern Oman. Using a new data set from 65 seismic stations located in southeastern Iran and northern Oman, our analysis reveals a sharp velocity contrast within the oceanic lithosphere of the Gulf of Oman, just north of Muscat, with abnormally low-velocity oceanic lithosphere extending westward from this contrast, revealing subduction of a segmented oceanic lithosphere beneath the Makran. Our study finds no lithospheric-scale seismic velocity contrast along the Zendan-Minab-Palami fault, as usually thought as a transition boundary between the Zagros and Makran. Our velocity model shows that the wide accretionary prism of western Makran consists of two zones: a southern low-velocity zone associated with younger sediments and a northern high-velocity zone corresponding to older sediments. A considerable thinning of the sedimentary cover is observed east of longitude 59°E within the coastal Makran tectono-stratigraphic unit, aligning with the structural trend of the Pan-African Semail Gap Fault observed both onshore and offshore Oman. Additionally, a thick sedimentary basin is located beneath the eastern section of the JMD, with the thickness decreasing towards the west.
Development partner influence on domestic health financing contributions in Senegal: a mixed-methods case study
Authors: Federspiel Frederik , Borghi Josephine , Mbaye Elhadji Mamadou , Jensen Henning Tarp , Martinez Alvarez Melisa 
Published: November 2024

Abstract
Sustainable and equitably contributed domestic health financing is essential for improving health and making progress towards Universal Health Coverage (UHC) in low- and middle-income countries. In this study, we explore the pathways through which development partners influence the combination of domestic health financing sources in Senegal. We performed a qualitative case study that comprised 32 key stakeholder interviews and a purposive document review, supplemented by descriptive statistical analysis of World Health Organization and Organization for Economic Cooperation and Development data on health financing sources in Senegal. We developed a novel framework to analyse the different mechanisms and directions of development partner influence on domestic health financing contributions. We identified development partner influence via four mechanisms: setting aims and standards, lobbying/negotiation, providing policy/technical advice, and providing external financing. Overall, development partners worked to increase tax-based government contributions and expand Community-Based Health Insurance (CBHI), which is seemingly equity enhancing. Fungibility and intrinsic equity issues related to CBHI may, however, limit equity gains. We encourage stakeholders in the health financing sphere to use our framework and analysis to unpack how development partners affect domestic health financing in other settings. This could help identify dynamics that do not optimally enhance equity and support progress towards UHC to help achieve more coherent policy-making across all domains of development partner activities in support of UHC. Future research should investigate the role of international creditors, lending, and loan conditionalities on domestic health financing in recipient countries, including equity implications.