bluuebunny/crossref_metadata_2025_split huggingface dataset:
Harmonizing tumor mutational burden analysis: Insights from a multicenter study using in silico reference data sets in clinical whole-exome sequencing (WES)
Authors: Yu Lijia , Zhang Yuanfeng , Wang Duo , Li Lin , Zhang Rui , Li Jinming 
Published: May 2024

Abstract

Objectives
Tumor mutational burden (TMB) is a significant biomarker for predicting immune checkpoint inhibitor response, but the clinical performance of whole-exome sequencing (WES)–based TMB estimation has received less attention compared to panel-based methods. This study aimed to assess the reliability and comparability of WES-based TMB analysis among laboratories under routine testing conditions.

Methods
A multicenter study was conducted involving 24 laboratories in China using in silico reference data sets. The accuracy and comparability of TMB estimation were evaluated using matched tumor-normal data sets. Factors such as accuracy of variant calls, limit of detection (LOD) of WES test, size of regions of interest (ROIs) used for TMB calculation, and TMB cutoff points were analyzed.

Results
The laboratories consistently underestimated the expected TMB scores in matched tumor-normal samples, with only 50% falling within the ±30% TMB interval. Samples with low TMB score (&lt;2.5) received the consensus interpretation. Accuracy of variant calls, LOD of the WES test, ROI, and TMB cutoff points were important factors causing interlaboratory deviations.

Conclusions
This study highlights real-world challenges in WES-based TMB analysis that need to be improved and optimized. This research will aid in the selection of more reasonable analytical procedures to minimize potential methodologic biases in estimating TMB in clinical exome sequencing tests. Harmonizing TMB estimation in clinical testing conditions is crucial for accurately evaluating patients’ response to immunotherapy.
Divergent effects of olfactory receptors on transient receptor potential vanilloid 1 activation by capsaicin and eugenol
Authors: Moriyama Sakura , Takita Yukie , Hinuma Shuji , Kuroda Shun'ichi 
Published: May 2024

ABSTRACT
We analyzed the effects of olfactory receptors (ORs) on transient receptor potential vanilloid 1 (TRPV1) activation using HEK293T cells co-expressing TRPV1 and OR51E1. We demonstrate here that the effect of OR51E1 on TRPV1 activation varies depending on the two TRPV1 ligands: capsaicin and eugenol. Notably, both of these ligands are vanilloid analogs. OR51E1 enhanced the response of TRPV1 to capsaicin but diminished that to eugenol. OR51E2 also showed similar effects. Based on the susceptibility to the OR's modulatory effects, various TRPV1 ligands could be classified into capsaicin and eugenol types. Activation of OR51E1 enhanced cAMP production. In addition, forskolin exhibited almost identical effects as ORs on TRPV1 responses to both types of ligands. These results suggest that OR51E1-induced cAMP elevation leads to a modification of TRPV1, presumably phosphorylation of TRPV1, which amplifies the susceptibility of TRPV1 to the two types of ligands differently.
BindingSiteDTI: differential-scale binding site modelling for drug–target interaction prediction
Authors: Pan Feng , Yin Chong , Liu Si-Qi , Huang Tao , Bian Zhaoxiang , Yuen Pong Chi 
Published: May 2024

Abstract

Motivation
Enhanced by contemporary computational advances, the prediction of drug–target interactions (DTIs) has become crucial in developing de novo and effective drugs. Existing deep learning approaches to DTI prediction are frequently beleaguered by a tendency to overfit specific molecular representations, which significantly impedes their predictive reliability and utility in novel drug discovery contexts. Furthermore, existing DTI networks often disregard the molecular size variance between macro molecules (targets) and micro molecules (drugs) by treating them at an equivalent scale that undermines the accurate elucidation of their interaction.

Results
We propose a novel DTI network with a differential-scale scheme to model the binding site for enhancing DTI prediction, which is named as BindingSiteDTI. It explicitly extracts multiscale substructures from targets with different scales of molecular size and fixed-scale substructures from drugs, facilitating the identification of structurally similar substructural tokens, and models the concealed relationships at the substructural level to construct interaction feature. Experiments conducted on popular benchmarks, including DUD-E, human, and BindingDB, shown that BindingSiteDTI contains significant improvements compared with recent DTI prediction methods.

Availability and implementation
The source code of BindingSiteDTI can be accessed at https://github.com/MagicPF/BindingSiteDTI.
Artificial intelligence-based tools with automated segmentation and measurement on CT images to assist accurate and fast diagnosis in acute pancreatitis
Authors: Pan Xuhang , Jiao Kaijian , Li Xinyu , Feng Linshuang , Tian Yige , Wu Lei , Zhang Peng , Wang Kejun , Chen Suping , Yang Bo , Chen Wen 
Published: May 2024

Abstract

Objectives
To develop an artificial intelligence (AI) tool with automated pancreas segmentation and measurement of pancreatic morphological information on CT images to assist improved and faster diagnosis in acute pancreatitis.

Methods
This study retrospectively contained 1124 patients suspected for AP and received non-contrast and enhanced abdominal CT examination between September 2013 and September 2022. Patients were divided into training (N = 688), validation (N = 145), testing dataset [N = 291; N = 104 for normal pancreas, N = 98 for AP, N = 89 for AP complicated with PDAC (AP&PDAC)]. A model based on convolutional neural network (MSAnet) was developed. The pancreas segmentation and measurement were performed via eight open-source models and MSAnet based tools, and the efficacy was evaluated using dice similarity coefficient (DSC) and intersection over union (IoU). The DSC and IoU for patients with different ages were also compared. The outline of tumour and oedema in the AP and were segmented by clustering. The diagnostic efficacy for radiologists with or without the assistance of MSAnet tool in AP and AP&PDAC was evaluated using receiver operation curve and confusion matrix.

Results
Among all models, MSAnet based tool showed best performance on the training and validation dataset, and had high efficacy on testing dataset. The performance was age-affected. With assistance of the AI tool, the diagnosis time was significantly shortened by 26.8% and 32.7% for junior and senior radiologists, respectively. The area under curve (AUC) in diagnosis of AP was improved from 0.91 to 0.96 for junior radiologist and 0.98 to 0.99 for senior radiologist. In AP&PDAC diagnosis, AUC was increased from 0.85 to 0.92 for junior and 0.97 to 0.99 for senior.

Conclusion
MSAnet based tools showed good pancreas segmentation and measurement performance, which help radiologists improve diagnosis efficacy and workflow in both AP and AP with PDAC conditions.

Advances in knowledge
This study developed an AI tool with automated pancreas segmentation and measurement and provided evidence for AI tool assistance in improving the workflow and accuracy of AP diagnosis.
Are survival outcomes dependent on the tumour dose threshold of 139 Gy in patients with chemorefractory metastatic colorectal cancer treated with yttrium-90 radioembolization using glass particles? A real-world single-centre study
Authors: Topcuoglu Osman Melih , Orhan Tolga , Gormez Ayşegul , Alan Nalan 
Published: May 2024

Abstract

Objectives
To compare the survival and objective response rate (ORR) of the patients receiving estimated tumour absorbed dose (ETAD) &lt;140 Gy versus ETAD ≥140 Gy in patients with advanced chemorefractory colorectal carcinoma liver metastases (CRCLM) treated with yttrium-90 transarterial radioembolization (90Y TARE).

Methods
Between August 2016 and August 2023 adult patients with unresectable, chemorefractory CRCLM treated with 90Y TARE using glass particles, were retrospectively enrolled. Primary outcomes were overall survival (OS) and hepatic progression free survival (hPFS). Secondary outcome was ORR.

Results
A total of 40 patients with a mean age of 66.2 ± 7.8 years met the inclusion criteria. Mean ETAD for group 1 (ETAD &lt;140 Gy) and group 2 (ETAD ≥140) were 131.2 ± 17.4 Gy versus 195 ± 45.6 Gy, respectively. The mean OS and hPFS for group 1 versus group 2 were 12 ± 10.3 months and 8.1 ± 9.3 months versus 9.3 ± 3 months and 7.1 ± 8.4 months, respectively and there were no significant differences (P = .181 and P = .366, respectively). ORR did not show significant difference between the groups (P = .432).

Conclusion
In real-world practice, no significant difference was found in OS, hPFS, and ORR between patients who received ETAD &lt;140 Gy versus ETAD ≥140 Gy in patients with CRCLM, in this series.

Advances in knowledge
This study demonstrated that increased tumour absorbed doses in radioembolization may not provide additional significant advantage for OS and hPFS for patients with CRCLM.
Pollination by birds, non-flying mammals, and European honeybees in a heathland shrub, Banksia catoglypta (Proteaceae)
Authors: Wawrzyczek Stanislaw K , Davis Robert A , Krauss Siegfried L , Hoebee Susan E , Ashton Louis M , Phillips Ryan D 
Published: May 2024

Abstract
Vertebrate pollination has evolved in many plant lineages, with pollination by birds the most prevalent strategy. However, in Banksia (Proteaceae) many species are visited by a combination of nectarivorous birds, non-flying mammals (NFMs), and insects, though the relative importance of these pollen vectors for reproduction remains poorly understood. Here, we investigate the contribution to fruit set of birds, NFMs, and insects in Banksia catoglypta—a heathland shrub from south-west Australia. This species flowers in winter and produces large, golden-yellow inflorescences that are typically presented near the ground and consist of rigid, strongly scented flowers with a long stigma-nectary distance—suggesting pollination by vertebrates. The primary floral visitors were white-cheeked honeyeaters (Phylidonyris niger), honey possums (Tarsipes rostratus), house mice (Mus musculus), and introduced European honeybees (Apis mellifera), all of which carried B. catoglypta pollen. Banksia catoglypta was found to be obligately outcrossing with no evidence of pollen limitation. Selective exclusion of flying pollinators revealed that inflorescences pollinated solely by NFMs produced 50% fewer fruit than open-pollinated controls. Therefore, while mammals are pollinators of B. catoglypta, they may contribute comparatively little to fruit set in some Banksia species displaying floral traits considered adaptations to NFM pollination. Exclusion of vertebrate pollinators had no effect on fruit set, demonstrating that European honeybees can be effective pollinators of some primarily vertebrate-pollinated plants.
A Certificateless Linearly Homomorphic Signature Scheme Based on Lattice for Network Coding
Authors: Dong Songshou , Yao Yanqing , Zhou Yihua , Yang Yuguang 
Published: May 2024

Abstract
Homomorphic signature is an extremely important public key authentication technique for network coding to defend against pollution attacks. However, there are many problems with previous homomorphic signature schemes which require key escrow, cannot resist malicious key generation center (KGC), and are insecure in the post-quantum era. Therefore, we propose a lattice-based certificateless linearly homomorphic signature scheme. In our scheme, certificateless structure can avoid key escrow and malicious KGC. The lattice structure ensures that our scheme is secure in the post-quantum era. The bimodal Gaussian distribution is used to improve the security and the efficiency. Compared with the previous schemes, our scheme has smaller storage space (no key escrow), can avoid malicious KGC, is more secure in the post-quantum era, and has higher signature efficiency. At the same time, our scheme is more suitable for network coding. Finally, under random oracle model, we proved that our scheme is weakly context hiding and existentially unforgeable against adaptive chosen message attacks against external attackers and the internal KGC.
Epigenetic and gene therapy in human and veterinary medicine
Authors: Bártová Eva 
Published: May 2024

Abstract
Gene therapy is a focus of interest in both human and veterinary medicine, especially in recent years due to the potential applications of CRISPR/Cas9 technology. Another relatively new approach is that of epigenetic therapy, which involves an intervention based on epigenetic marks, including DNA methylation, histone post-translational modifications, and post-transcription modifications of distinct RNAs. The epigenome results from enzymatic reactions, which regulate gene expression without altering DNA sequences. In contrast to conventional CRISP/Cas9 techniques, the recently established methodology of epigenetic editing mediated by the CRISPR/dCas9 system is designed to target specific genes without causing DNA breaks. Both natural epigenetic processes and epigenetic editing regulate gene expression and thereby contribute to maintaining the balance between physiological functions and pathophysiological states. From this perspective, knowledge of specific epigenetic marks has immense potential in both human and veterinary medicine. For instance, the use of epigenetic drugs (chemical compounds with therapeutic potential affecting the epigenome) seems to be promising for the treatment of cancer, metabolic, and infectious diseases. Also, there is evidence that an epigenetic diet (nutrition-like factors affecting epigenome) should be considered as part of a healthy lifestyle and could contribute to the prevention of pathophysiological processes. In summary, epigenetic-based approaches in human and veterinary medicine have increasing significance in targeting aberrant gene expression associated with various diseases. In this case, CRISPR/dCas9, epigenetic targeting, and some epigenetic nutrition factors could contribute to reversing an abnormal epigenetic landscape to a healthy physiological state.
Comparison of treatment effects between clear aligners and fixed appliances in patients treated with miniscrew-assisted molar distalization
Authors: Wang Yunlei , Zhou Shunquan , Zheng Jie , Yan Lin , Ngan Peter , Hua Fang , He Hong 
Published: May 2024

Summary

Objectives
The biomechanics in achieving molar distalization may differ between fixed appliances and clear aligners in the control of tooth movement. The objective of this study was to compare the treatment effects between clear aligners (CA) and fixed appliances (FA) in patients treated with miniscrew-assisted molar distalization.

Methods
The sample consisted of 46 subjects with mild-to-moderate crowding. A total of 22 patients treated with clear aligners (age, 25.66 ± 6.11 years old) and 24 patients treated with fixed appliances (age, 24.04 ± 4.95 years old) for miniscrew-assisted molar distalization were included in this study. The dental and skeletal changes were evaluated by the pre- and post-treatment lateral cephalograms.

Results
Significant changes were found with the vertical variables SN-OP angle (2.24 ± 3.22°, P &lt; .05) and SN-MP angle (0.73 ± 1.15°, P &lt; .05) for the FA group when compared with the CA group (SN-OP angle 0.41 ± 2.26° and SN-MP angle −0.21 ± 1.38°, P &gt; .05). Both treatment groups achieved a 2–3 mm. molar distalization with significant intrusion of the upper molars. The CA group showed significantly less distal tipping of molars (U6^PP angle −2.29 ± 3.29° and L6^MP angle −2.92 ± 2.49°, P &lt; .05) compared to the FA group (−5.24 ± 4.28° and −5.53 ± 5.03°, P &lt; .05). In addition, significant retraction and lingual inclination of the upper and lower incisors were found in both groups.

Limitations
The changes of tooth position were evaluated by 2D lateral cephalograms, not 3D measurements.

Conclusions
Compared to fixed appliances, clear aligners seemed to have better control of vertical dimension and distal tipping of molars in patients treated with miniscrew-assisted molar distalization.
Overcoming antibiotic resistance: non-thermal plasma and antibiotics combination inhibits important pathogens
Authors: Vaňková Eva , Julák Jaroslav , Machková Anna , Obrová Klára , Klančnik Anja , Smole Možina Sonja , Scholtz Vladimír 
Published: May 2024

Abstract
Antibiotic resistance (ATBR) is increasing every year as the overuse of antibiotics (ATBs) and the lack of newly emerging antimicrobial agents lead to an efficient pathogen escape from ATBs action. This trend is alarming and the World Health Organization warned in 2021 that ATBR could become the leading cause of death worldwide by 2050. The development of novel ATBs is not fast enough considering the situation, and alternative strategies are therefore urgently required. One such alternative may be the use of non-thermal plasma (NTP), a well-established antimicrobial agent actively used in a growing number of medical fields. Despite its efficiency, NTP alone is not always sufficient to completely eliminate pathogens. However, NTP combined with ATBs is more potent and evidence has been emerging over the last few years proving this is a robust and highly effective strategy to fight resistant pathogens. This minireview summarizes experimental research addressing the potential of the NTP-ATBs combination, particularly for inhibiting planktonic and biofilm growth and treating infections in mouse models caused by methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. The published studies highlight this combination as a promising solution to emerging ATBR, and further research is therefore highly desirable.
TWISP: a transgenic worm for interrogating signal propagation in Caenorhabditis elegans
Authors: Sharma Anuj Kumar , Randi Francesco , Kumar Sandeep , Dvali Sophie , Leifer Andrew M 
Published: May 2024

Abstract
Genetically encoded optical indicators and actuators of neural activity allow for all-optical investigations of signaling in the nervous system. But commonly used indicators, actuators, and expression strategies are poorly suited for systematic measurements of signal propagation at brain scale and cellular resolution. Large-scale measurements of the brain require indicators and actuators with compatible excitation spectra to avoid optical crosstalk. They must be highly expressed in every neuron but at the same time avoid lethality and permit the animal to reach adulthood. Their expression must also be compatible with additional fluorescent labels to locate and identify neurons, such as those in the NeuroPAL cell identification system. We present TWISP, a transgenic worm for interrogating signal propagation, that addresses these needs and enables optical measurements of evoked calcium activity at brain scale and cellular resolution in the nervous system of the nematode Caenorhabditis elegans. In every neuron we express a nonconventional optical actuator, the gustatory receptor homolog GUR-3 + PRDX-2, under the control of a drug-inducible system QF + hGR, and a calcium indicator GCAMP6s, in a background with additional fluorophores from the NeuroPAL cell ID system. We show that this combination, but not others tested, avoids optical crosstalk, creates strong expression in the adult, and generates stable transgenic lines for systematic measurements of signal propagation in the worm brain.
Numerical simulation of 3-D seismic wave based on alternative flux finite-difference WENO scheme
Authors: Xu Tianhong , Zhang Zhenguo 
Published: May 2024

SUMMARY
High-frequency non-physical oscillations may occur due to shock waves in seismic wavefield and dynamic rupture simulation. In this study, we introduced the alternative flux finite-difference weighted essentially non-oscillatory scheme to address potential shock wave issues in computational seismology effectively. The wavefield of the body-fitted curvilinear domain was accurately computed through conservative grid mapping, ensuring accurate implementation of free surface boundary conditions on irregular surfaces using characteristic boundary conditions and minimizing artificial boundary reflections with exponential decay absorbing layers. Finally, we compared our scheme with the GRTM for flat surfaces and the CGFDM3D-EQR for irregular surfaces to demonstrate its correctness and accuracy, and validated its non-oscillatory characteristics. The aforementioned scheme is anticipated to assume a significant function in simulating more intricate seismic wavefields or dynamic ruptures.
Fictional friends and enemies as first aid after ostracism? Experimentally investigating the potential of para-/orthosocial relationships in belongingness need restoration and emotion regulation
Authors: Lutz Sarah , Schneider Frank M , Reich Sabine , Schimmel Michelle , Oechler Hannah , Beinlich Laura 
Published: May 2024

Abstract
Being socially excluded seriously threatens individuals’ need to belong and emotional well-being. This article investigates to what extent different coping strategies help overcome these detrimental effects: thinking about real-life friends/enemies (i.e., orthosocial relationships, OSRs) and thinking about (dis)liked media characters (i.e., parasocial relationships, PSRs). Across three experiments (NPilot = 129, NStudy1 = 132, NStudy2 = 855), we first induced social exclusion using a virtual ball-tossing game. Afterward, we manipulated different relationship types and valences and compared them to non- or less-relational control conditions. As hypothesized, belongingness and emotional well-being increased from pre- to post-coping. This effect was fully mediated by perceived relationship closeness to the respective person(a). Highlighting that PSRs represent more than surrogates (i.e., secondary replacements of OSR), both relationship types did not differ in coping effectiveness. Moreover, positive relationships were more effective in fulfilling both coping goals than negative ones.