bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning‐assisted search for novel coagulants: When machine learning can be efficient even if data availability is low
Authors: Rovenchak Andrij , Druchok Maksym 
Published: January 2024

AbstractDesign of new drugs is a challenging process: a candidate molecule should satisfy multiple conditions to act properly and make the least side‐effect—perfect candidates selectively attach to and influence only targets, leaving off‐targets intact. The amount of experimental data about various properties of molecules constantly grows, promoting data‐driven approaches. However, the applicability of typical predictive machine learning techniques can be substantially limited by a lack of experimental data about a particular target. For example, there are many known Thrombin inhibitors (acting as anticoagulants), but a very limited number of known Protein C inhibitors (coagulants). In this study, we present our approach to suggest new inhibitor candidates by building an effective representation of chemical space. For this aim, we developed a deep learning model—autoencoder, trained on a large set of molecules in the SMILES format to map the chemical space. Further, we applied different sampling strategies to generate novel coagulant candidates. Symmetrically, we tested our approach on anticoagulant candidates, where we were able to predict their inhibition towards Thrombin. We also compare our approach with MegaMolBART—another deep learning generative model, but exploiting similar principles of navigation in a chemical space.
Machine learning‐guided design of potent darunavir analogs targeting HIV‐1 proteases: A computational approach for antiretroviral drug discovery
Authors: Chuntakaruk Hathaichanok , Boonpalit Kajjana , Kinchagawat Jiramet , Nakarin Fahsai , Khotavivattana Tanatorn , Aonbangkhen Chanat , Shigeta Yasuteru , Hengphasatporn Kowit , Nutanong Sarana , Rungrotmongkol Thanyada , Hannongbua Supot 
Published: January 2024

AbstractIn the pursuit of novel antiretroviral therapies for human immunodeficiency virus type‐1 (HIV‐1) proteases (PRs), recent improvements in drug discovery have embraced machine learning (ML) techniques to guide the design process. This study employs ensemble learning models to identify crucial substructures as significant features for drug development. Using molecular docking techniques, a collection of 160 darunavir (DRV) analogs was designed based on these key substructures and subsequently screened using molecular docking techniques. Chemical structures with high fitness scores were selected, combined, and one‐dimensional (1D) screening based on beyond Lipinski's rule of five (bRo5) and ADME (absorption, distribution, metabolism, and excretion) prediction implemented in the Combined Analog generator Tool (CAT) program. A total of 473 screened analogs were subjected to docking analysis through convolutional neural networks scoring function against both the wild‐type (WT) and 12 major mutated PRs. DRV analogs with negative changes in binding free energy () compared to DRV could be categorized into four attractive groups based on their interactions with the majority of vital PRs. The analysis of interaction profiles revealed that potent designed analogs, targeting both WT and mutant PRs, exhibited interactions with common key amino acid residues. This observation further confirms that the ML model‐guided approach effectively identified the substructures that play a crucial role in potent analogs. It is expected to function as a powerful computational tool, offering valuable guidance in the identification of chemical substructures for synthesis and subsequent experimental testing.
Novel 8‐wire basket catheter is useful for endoscopic removal of common bile duct stones up to 10 mm: A multicenter prospective study
Authors: Kaneko Takashi , Ishii Tomohiro , Hamanaka Jun , Goda Yoshihiro , Irie Kuniyasu , Doba Nobutaka , Kunishi Yosuke , Miwa Haruo , Sugimori Kazuya , Maeda Shin 
Published: January 2024

AbstractBackground/PurposeEndoscopic treatment of common bile duct (CBD) stones involves the use of basket or balloon catheters; however, what is the appropriate device remains controversial. In this study we aimed to prospectively evaluate the usefulness of a novel 8‐wire helical basket (8WB) catheter made of Nitinol for the removal of CBD stones ≤10 mm.MethodsWe conducted a multicenter prospective trial. Patients with CBD stones ≤10 mm were enrolled. The primary endpoint was the rate of complete stone removal within 10 min using the 8WB. The number of cases was determined using a previous study of stone removal by a conventional basket catheter as a historical control.ResultsA total of 155 patients were enrolled and 139 were ultimately included in the analysis. Patients with a single stone were the most common (84 cases, 60.4%), with a median maximum stone diameter of 5 mm. The median stone removal time using the 8WB was 6 min. The complete stone removal rate was 95.0% (132/139). Adverse events were observed in 14 patients (10.1%).ConclusionsThe novel 8WB catheter is useful in the treatment of CBD stones ≤10 mm, presenting a high complete stone removal rate in this study.Trial registration number: jRCT1032200324.
Liver‐directed gene therapy for inherited metabolic diseases
Authors: Baruteau Julien , Brunetti‐Pierri Nicola , Gissen Paul 
Published: January 2024

AbstractGene therapy clinical trials are rapidly expanding for inherited metabolic liver diseases whilst two gene therapy products have now been approved for liver based monogenic disorders. Liver‐directed gene therapy has recently become an option for treatment of haemophilias and is likely to become one of the favoured therapeutic strategies for inherited metabolic liver diseases in the near future. In this review, we present the different gene therapy vectors and strategies for liver‐targeting, including gene editing. We highlight the current development of viral and nonviral gene therapy for a number of inherited metabolic liver diseases including urea cycle defects, organic acidaemias, Crigler–Najjar disease, Wilson disease, glycogen storage disease Type Ia, phenylketonuria and maple syrup urine disease. We describe the main limitations and open questions for further gene therapy development: immunogenicity, inflammatory response, genotoxicity, gene therapy administration in a fibrotic liver. The follow‐up of a constantly growing number of gene therapy treated patients allows better understanding of its benefits and limitations and provides strategies to design safer and more efficacious treatments. Undoubtedly, liver‐targeting gene therapy offers a promising avenue for innovative therapies with an unprecedented potential to address the unmet needs of patients suffering from inherited metabolic diseases.
Chemical Shift‐Encoded MRI of the Lumbar Vertebral Bone Marrow for Detecting Osteoporosis With Low Trabecular Bone Quality in Patients With Breast Cancer Receiving Aromatase Inhibitors
Authors: Misaka Tomofumi , Hashimoto Yukihiko , Ashikaga Ryuichiro , Ishida Takayuki 
Published: January 2024

BackgroundOsteoporosis with low trabecular bone quality (OLB) in patients with breast cancer receiving aromatase inhibitor (AI) therapy is associated with an increased risk of vertebral fractures. The capability of chemical shift‐encoded MRI (CSE‐MRI) in detecting OLB needs to be investigated.PurposeTo assess the diagnostic performance of proton density fat fraction (PDFF) and R2* measurements from CSE‐MRI for detecting OLB in postmenopausal women with breast cancer undergoing AI therapy.Study TypeProspective.Population126 postmenopausal females (mean age: 69.5 ± 8.8 years) receiving AIs (average period: 41.6 ± 26.5 months) after breast cancer surgery.Field Strength/Sequence1.5‐T, three‐dimensional CSE‐MRI (six echoes), T1‐weighted Dixon, short tau inversion recovery, and diffusion‐weighted images.AssessmentBoth CSE‐MRI and dual‐energy x‐ray absorptiometry were performed on the same day. Measurements included averaged PDFF, R2*, bone mineral density (BMD), and trabecular bone score (TBS) from L1 to L4 vertebrae. A T‐score ≤ −2.5 from BMD measurements indicated osteoporosis, whereas T‐scores of ≤ − 2.5 plus TBS ≤‐3.7 indicated OLB. The diagnostic performance of PDFF, R2*, and the combination of PDFF and R2* for identifying osteoporosis or OLB was assessed.Statistical TestsStudent's t‐test; Mann–Whitney U test; χ2 or Fisher exact tests; Pearson correlation; multivariate analysis; Receiver operating characteristic (ROC) analysis with the area under the curve (AUC); logistic regression model; intraclass correlation coefficient. A P‐value <0.05 was considered statistically significant.ResultsFor detecting osteoporosis, AUC values were 0.59 (PDFF), 0.66 (R2*), and 0.65 (combined PDFF and R2*). Significant mean differences were noted between patients with and without OLB for PDFF (66.11 ± 5.36 vs. 57.49 ± 6.43) and R2* (46.62 ± 9.24 vs. 63.36 ± 12.44). AUC values for detecting OLB were 0.75 (PDFF), 0.82 (R2*), and 0.84 (combined PDFF and R2*).Data ConclusionR2* may perform better than PDFF for identifying OLB in patients with breast cancer receiving AIs.Level of Evidence2Technical EfficacyStage 4
Ethically treated yet closely monitored: Ethical leadership, leaders' close monitoring, employees' uncertainty, and employees' organizational citizenship behavior
Authors: Sun Ui Young , Park Haeseen , Yun Seokhwa 
Published: January 2024

SummaryDrawing on uncertainty management theory, we propose that employees' uncertainty is a distinct key mechanism explaining the relationship between ethical leadership and employees' organizational citizenship behavior (OCB). We contend that ethical leadership, by promoting a work environment governed by moral principles, reduces employees' sense of uncertainty and thereby fosters their OCB. However, we suggest that leaders' close monitoring, which ethical leaders may utilize to be informed about employees' adherence to their moral standards, nullifies these positive implications of ethical leadership. To test these contentions, we conducted an online vignette study (Study 1) and a field study (Study 2). In Study 1, we found a significant and negative main effect of ethical leadership on employees' uncertainty, but this effect was negated when leaders' close monitoring was high. In Study 2, we replicated the findings—ethical leadership was negatively related to employees' uncertainty and this relationship became nonsignificant when leaders' close monitoring was high. In addition, uncertainty was negatively related to employees' OCB toward the organization (OCBO) but not their OCB toward individuals (OCBI). Consequently, uncertainty mediated the relationship between ethical leadership and OCBO, and this mediation was moderated by close monitoring. However, such mediation and moderated mediation did not occur for OCBI. Taken together, our research reveals that close monitoring is not a viable strategy to be implemented alongside ethical leadership for managing employees' uncertainty and fostering their OCB.
Loose and Tight: Creative Formation but Rigid Use of Nominal Compounds in Conspiracist Texts
Authors: Miani Alessandro , van der Plas Lonneke , Bangerter Adrian 
Published: January 2024

ABSTRACTConspiracy theories (CTs) are spectacular narratives, widely spread, that pose societal threats. We test whether CTs might be linguistically creative products, which would facilitate their transmission and thereby account for their widespread popularity. We analyzed nominal compounds (e.g., mind control, carbon dioxide; N = 1,713,568) from a large corpus of conspiracist and mainstream texts matched by topic. In conspiracist texts, compounds showed greater originality, divergence, and sophistication, but they were used with lower frequency and were more often repeated in different contexts. This pattern suggests a creative aspect in the generation of compounds, coupled with rigidity in their use. We interpret these findings as an effect of loosely defined conceptual boundaries among conspiracist writers, in conjunction with social functions like status or group signaling. Our findings not only contribute to the discourse on creativity in CTs but also provide insights into the communicative advantage of CTs.
Efficacy of all‐inside devices in reducing gap and step‐off in knee extension for ramp lesion repair: A cadaveric study
Authors: Kato Jiro , Fukushima Hiroaki , Hanaki Shunta , Kawanishi Yusuke , Kobayashi Makoto , Ota Kyohei , Yoshida Masato , Takenaga Tetsuya , Kawaguchi Yohei , Kuroyanagi Gen , Sakai Hiroaki , Murakami Hideki , Nozaki Masahiro 
Published: January 2024

AbstractPurposeThe aim of this study is to assess the dynamics of the tear site of meniscal ramp lesions, particularly considering knee flexion angles, and validate anchor fixation using an all‐inside device.MethodsEight Thiel‐embalmed paired cadaveric knees with their whole bodies were used in this study. The ramp lesions were created arthroscopically, and ramp lesion dynamics were evaluated by gradually extending the knee from 90° of knee flexion. Changes in the gap and step‐off (0: no step‐off; 1: cross‐sectional overlap exists; and 2: tibial articular surface exposed) were evaluated at 90°, 60°, 30°, and 10° of knee flexion. After dynamic evaluation, all‐inside repairs of the ramp lesions using all‐inside devices were conducted. Dissection was performed to confirm the position of anchor fixation.ResultsAs the knee was extended, the gap significantly decreased at all knee flexion angles. Similarly, the step‐off grade decreased as the knee was extended, and the step‐off completely disappeared in all cases when the knee was extended from 30° to 10°. The average knee flexion angle at which the gap and step‐off completely disappeared was 22.5°. After suturing the ramp lesion, arthroscopic evaluation showed that the gap had disappeared and the step‐off had been repaired in all cases. Anchor fixation locations were not found within the joint but were fixed to the semimembranosus tendon or its surrounding articular capsule. Overall, 31% (5/16) anchors were fixed to the attachment site of the semimembranosus tendon, whereas the remaining were fixed to the articular capsule, located peripherally to the semimembranosus tendon.ConclusionSuturing with an all‐inside device for ramp lesions is a good option, and the repair in knee extension was found to be reasonable, considering the dynamics of ramp lesions in this study.Level of EvidenceLevel IV.
Gastroesophageal Reflux and Chronic Rhinosinusitis: A Mendelian Randomization Study
Authors: Guo Tao , Xie Hui 
Published: January 2024

ObjectiveChronic rhinosinusitis (CRS) is associated with gastroesophageal reflux (GERD). However, the causal relationship is controversial. We conducted a two‐sample Mendelian Randomization (MR) analysis to explore this potential association.MethodsBased on genome‐wide association studies (GWAS), a univariable MR was performed to explore the causal relationship of GERD with CRS. Instrumental variables (IVs) pertinent to anti‐GERD treatment were employed as a means of validation. The primary MR outcome was established using an inverse variance weighted (IVW) method, supplemented by multiple sensitivity analyses. Subsequently, a multivariable MR was conducted to account for potential confounding variables, thereby ascertaining a direct effect of GERD on CRS. Finally, a network MR analysis was carried out to elucidate the mediating role of asthma in the relationship between GERD and CRS.ResultsThe univariable MR demonstrated an association between GERD and an elevated risk of CRS (IVW OR = 1.30, 95% CI = 1.18–1.45, p = 4.19 × 10−7). Omeprazole usage was associated with a reduction in CRS risk (IVW OR = 0.64, 95% CI = 0.42–0.98, p = 0.039). The causal relationship between GERD and CRS remained after adjusting for potential confounders, such as smoking characteristics, body mass index, asthma, allergic rhinitis, in the multivariable MR analysis. Besides, the proportion of the causal effect of GERD on CRS mediated by asthma was 19.65% (95% CI = 2.69%–36.62%).ConclusionGERD was independently associated with an increased risk of CRS. The mediating role of asthma between GERD and CRS also reveals that GERD is one of the mechanisms underlying unified airway disease.Level of Evidence3 Laryngoscope, 134:3086–3092, 2024
The sensitivity of laryngeal findings in predicting high‐grade dysplasia in patients with vocal fold leukoplakia undergoing office‐based biopsies: A retrospective analysis of 100 cases
Authors: Hosri Jad , Aoun Jessica , Yammine Yara , Ghadieh Justin , Hamdan Abdul‐Latif 
Published: January 2024

AbstractObjectiveTo investigate the sensitivity of laryngeal findings in predicting high‐grade dysplasia/carcinoma in situ (CIS) and squamous cell carcinoma (SCC) in patients with vocal fold leukoplakia.MethodsA retrospective review of the medical records and video recordings of the laryngeal examination of patients with vocal fold leukoplakia who underwent un‐sedated office‐based laryngeal biopsy in a tertiary referral center between January 2022 and August 2023 was conducted. Laryngeal findings included the size, surface, projection, and edges of the lesion. Vocal fold leukoplakia was classified according to the WHO as benign, low‐grade dysplasia, high‐grade dysplasia/CIS, and squamous cell carcinoma.ResultsSeventy patients with 100 vocal fold leukoplakia were included. Size was found to have the highest sensitivity with an AUC of 0.730 (95% CI [0.618–0.842], p = 0.002) followed by surface and projection with AUCs of 0.672 (95% CI [0.548–0.795], p = 0.019) and 0.675 (95% CI [0.546–0.804], p = 0.017), respectively. Furthermore, the odds of diagnosing high‐risk lesions (high‐grade dysplasia/CIS and SCC) were the greatest when the lesion was large and rough (OR = 10.28; 95% CI [3.08–34.36]).ConclusionThe morphological features of vocal fold leukoplakia may assist the physician in predicting the risk of malignancy. Large and rough lesions were more likely to harbor high‐grade dysplasia/CIS and SCC compared to small and smooth lesions.
Dietary Cannabidiol Activates PKA/AMPK Signaling and Attenuates Chronic Inflammation and Leaky Gut in DSS‐Induced Colitis Mice
Authors: Sun Qi , Bravo Iniguez Alejandro , Tian Qiyu , Du Min , Zhu Mei‐Jun 
Published: January 2024

ScopeInflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut, accompanied by impaired epithelial integrity, increased macrophage infiltration, and enhanced colon cancer risk.Methods and ResultsCannabidiol (CBD), a phytocannabinoid isolated from cannabis plants, is supplemented into mice diet, and its beneficial effects against dextran sulfate sodium (DSS)‐induced experimental colitis is evaluated. Eight‐week‐old mice were fed a standard diet supplemented with or without CBD (200 mg kg‐1) for 5 weeks. In the 4th week of dietary treatment, mice were subjected to 2.5% DSS induction for 7 days, followed by 7 days of recovery, to induce colitis. CBD supplementation reduced body weight loss, gross bleeding, fecal consistency, and disease activity index. In addition, CBD supplementation protected the colonic structure, promoted tissue recovery, and ameliorated macrophage infiltration in the colonic tissue, which was associated with the activation of cyclic AMP‐protein kinase A, extracellular signal‐regulated kinase ½, and AMP‐activated protein kinase signaling pathways. CBD supplementation also suppressed NLRP3 inflammasome activation and related pro‐inflammatory marker secretion. Consistently, CBD feeding reduced tight junction protein claudin2 and myosin light chain kinase in DSS‐treated mice.ConclusionDietary CBD protects against inflammation and colitis symptoms induced by DSS, providing an alternative approach to IBD management.
Role of Artificial Intelligence in Multinomial Decisions and Preventative Nutrition in Alzheimer's Disease
Authors: Soares Dias Portela Ariana , Saxena Vrinda , Rosenn Eric , Wang Shu‐Han , Masieri Sibilla , Palmieri Joshua , Pasinetti Giulio Maria 
Published: January 2024

AbstractAlzheimer's disease (AD) affects 50 million people worldwide, an increase of 35 million since 2015, and it is known for memory loss and cognitive decline. Considering the morbidity associated with AD, it is important to explore lifestyle elements influencing the chances of developing AD, with special emphasis on nutritional aspects. This review will first discuss how dietary factors have an impact in AD development and the possible role of Artificial Intelligence (AI) and Machine Learning (ML) in preventative care of AD patients through nutrition. The Mediterranean‐DASH diets provide individuals with many nutrient benefits which assists the prevention of neurodegeneration by having neuroprotective roles. Lack of micronutrients, protein‐energy, and polyunsaturated fatty acids increase the chance of cognitive decline, loss of memory, and synaptic dysfunction among others.ML software has the ability to design models of algorithms from data introduced to present practical solutions that are accessible and easy to use. It can give predictions for a precise medicine approach to evaluate individuals as a whole. There is no doubt the future of nutritional science lies on customizing diets for individuals to reduce dementia risk factors, maintain overall health and brain function.
Uplift behavior of nodular diaphragm wall: Experiment and theory
Authors: Wu Jiujiang , Zhang Yi , Li Yan , Wen Hua , Wang Lijuan 
Published: January 2024

AbstractThe nodular diaphragm wall (NDW) is a novel foundation that can provide significant uplift load resistance compared to a typical diaphragm wall foundation. With the advantages of low noise, cost‐effectiveness, high work efficiency, and construction abilities close to existing buildings, NDW has excellent engineering application prospects in urbanization construction. However, the scarce knowledge on the uplift resistance, failure mode, and calculation method of the NDW has hindered its application in practice. In this paper, indoor model tests based on particle image velocimetry (PIV) technology are carried out to investigate the uplift behavior of three NDW models with different amounts and locations of nodular parts. The load transfer mechanisms of the three NDW models are discussed in detail, and special attention is given to the failure mode analysis. In addition, a theoretical analysis is implemented based on the load transfer approach. The transfer function and associated critical parameters are discussed in detail. Accordingly, an iterative procedure is proposed to interpret the load transfer information of an uplift NDW in multilayered soils under different loading levels. The findings derived in this paper are helpful to the uplift deformation, capacity calculation, and design of NDW in practical engineering.