bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers
Authors: Ko Andrew H. , Chao Joseph , Noel Marcus S. , Shankaran Veena , Sohal Davendra , Crow Mary , Oberstein Paul E. , Scott Aaron J. , McRee Autumn J. , Rocha Lima Caio Max Sao Pedro , Fong Lawrence , Keenan Bridget P. , Soto Maira , Filbert Erin L. , Hsu Frank J. , Yang Xiaodong
Published: February 2025

AbstractPurpose:
Neoadjuvant chemoradiation (NCRT) followed by surgical resection represents a standard approach for patients with locally advanced esophageal/gastroesophageal junction (GEJ) cancers. Sotigalimab is a high-affinity CD40 agonist antibody capable of inducing and expanding antitumor immune responses by activating dendritic cells, T and B lymphocytes, NK cells, and M1 macrophages. This study examined the safety and efficacy of combining sotigalimab with NCRT in patients with esophageal or GEJ cancers.
Patients and Methods:
Patients with resectable (T1-3 Nx) adenocarcinoma or squamous cell carcinoma of the esophagus or GEJ were eligible. T1N0 and cervical tumors were excluded. Study treatment: weekly carboplatin/paclitaxel with concurrent radiation 5,040 cGy plus 3 to 4 doses of sotigalimab prior to Ivor Lewis esophagectomy. Primary efficacy endpoint was the pathologic complete response (path CR) rate.
Results:
Thirty-three patients were enrolled (adenocarcinoma 76%, squamous cell carcinoma 24%; and clinical stage III 67%). Ninety percent of patients received all planned doses of sotigalimab. The most common adverse events attributed to sotigalimab were nausea, fever/chills, fatigue, and cytokine release syndrome; most of these were grade 1 to 2. Grade ≥3 cytokine release syndrome was observed in 3 patients (9%). Twenty-five of the 29 efficacy-evaluable patients underwent an R0 resection (87.9%), with an overall path CR rate of 37.9% (11/29). Post-tumor samples demonstrated increased infiltration and activation of dendritic cells, monocytes, and cytotoxic T cells compared with baseline.
Conclusions:
Sotigalimab combined with NCRT for esophageal or GEJ cancers was generally well tolerated and achieved path CR rates that compare favorably with historical data and are promising for this treatment strategy. Clinical trial information: NCT03165994.
Significance:
The current study represents the first report to evaluate a CD40 agonist antibody in combination with concurrent chemoradiation in the neoadjuvant setting for patients with esophageal/GEJ cancers. This novel strategy was both safe and feasible, producing encouraging path CR rates that compare favorably with historical data. Our findings support the further evaluation of how immune-based therapies may be incorporated into perioperative treatment paradigms for upper gastrointestinal malignancies.
Group Acceptance and Commitment Therapy versus Cognitive Behavioral Therapy/Exposure Response Prevention for Obsessive Compulsive Disorder: A Block Randomized Controlled Trial
Authors: Nielsen Sara Kerstine Kaya , Stuart Anne Christine , Winding Christensen , Øllgaard Mette , Wolitzky-Taylor Kate , Daniel Sarah I.F. , Vangkilde Signe , Rosenberg Nicole , Hageman Ida , Jørgensen Martin B.
Published: February 2025

Introduction: Acceptance and Commitment Therapy (ACT) may be as effective for treating Obsessive Compulsive Disorder (OCD) as the gold standard treatment, Cognitive Behavioral Therapy (CBT) with Exposure Response Prevention (ERP), but ACT has never been directly compared to CBT/ERP in a randomized control trial. Objective: This study aimed to compare the efficacy of group-based ACT and CBT/ERP in two outpatient mental health service clinics for adults with OCD. Methods: A total of 176 patients with OCD participated in a single-blinded, non-inferiority, block randomized controlled trial. Patients were assigned to either the ACT (n = 101) or CBT/ERP (n = 75) groups for 14 weekly sessions. The primary outcome was the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at post-treatment and at the 6-months follow-up with pre-specified non-inferiority criteria. Quality of life, measured using the Quality of Life Inventory (QOLI), was the secondary outcome. Results: Linear mixed models showed that Y-BOCS scores in the ACT group were non-inferior to those in the CBT/ERP group both post-treatment and at 6, and 12-months of follow-up. QOLI scores also showed no significant differences in ACT compared to CBT/ERP across the three measurement points. Conclusions: This randomized controlled trial demonstrated that group-delivered ACT is non-inferior to CBT/ERP in reducing OCD symptoms and improving the quality of life of patients with OCD in outpatient mental health services. These findings suggest that ACT may serve as a viable alternative to CBT/ERP in adults with OCD in outpatient mental health settings, although further replication is necessary.
Resenha de Electronic Music School: a Contemporary Approach to Teaching Musical Creativity. KUHN, Will; HEIN, Ethan. New York: Oxford Univertsity Press, 2021.
Authors: Miotto Orlando Cagnini
Published: February 2025

Resenha do livro de Will Kunh e Ethan Hein, publicado em 2021 pela Oxford University Press.
Exploring the Identities, Barriers, and Interventions for Motherscholars During a Global Pandemic
Authors: Brooks Tiffany P. , Hughes Amber N. , Azim Katharina , Bender Stacey Herzog , Blanks Jones Jasmine L. , Parker-Barnes Lucy , Frazier Kathryn E. , Greene-Rooks Jennifer , Pennell Summer Melody , Richardson Ivanna , Bielski Lynn M. , Raftery-Helmer Jacquelyn N.
Published: February 2025

Women in academia face many challenges, which have been further exacerbated by the COVID-19 pandemic. This is particularly true for women in academia who are also mothers. The authors conducted a phenomenological study examining these challenges and their effects on identity utilizing Super’s (1980) Life-Span Life-Space approach and Career Construction Theory (Savickas, 1997, 2005) as the theoretical framework. The participants identified and described the various ways they navigate their mother and scholar identities and the integration of their motherscholar identity. In navigating the pandemic at work and home, participants also reported changes to their identity as spouses/partners, and a sense of loss in their identities and roles professionally and personally. The authors outlined potential mental health implications and interventions for career counselors working with motherscholars.
Assessing Airbnb’s impact on hotels through an analysis of price linkages
Authors: Xie Jinghua , Tveteraas Sigbjørn , Kidane Dejene Gizaw
Published: February 2025

Recognizing price interdependence as a key indicator of market integration, this study uses a cointegration approach to examine price linkages between Airbnb and hotel rooms, providing deeper insight into their competition within the accommodation market. Unlike methods that primarily focus on hotel performance metrics, which make it difficult to isolate Airbnb’s impact from broad factors like tourism growth, price linkage analysis offers a more precise understanding of competition grounded in market theory. We demonstrate this by applying threshold autoregressive models to analyze the price interactions between hotel and Airbnb room prices in the Norwegian market.
Short-term Adverse Events Following Ankle Arthroplasty and Ankle Arthrodesis A Matched Analysis of Recent Nationally Representative Data
Authors: Hopper Haleigh M. , Nelson Chase T. , Satalich James R. , Wu Kevin A. , Anastasio Albert T. , O’Neill Conor N. , Patel Tejas T. , Hanselman Andrew E. , Schweitzer Karl M. , Adams Samuel
Published: February 2025

Background

Surgical management of ankle osteoarthritis (AOA) includes Ankle Arthrodesis (AA) or Total Ankle Arthroplasty (TAA). The purpose of this study was to analyze data from the National Surgical Quality Improvement Project (NSQIP) to elucidate differences in outcomes between TAA and AA.

Methods

Patients who underwent TAA or AA from January 2010 to December 2020 were included in this analysis. Matched cohorts were created using 1:1 propensity score matching to match patients according to patient demographics. Independent sample t-tests and chi-square tests were used to determine whether there was a difference between groups. A binary logistic regression was performed to determine the odds ratio (OR) and 95% confidence intervals for any adverse event as related to patient demographics and comorbidities.

Results

There were 2,053 TAA and 359 AA in the unmatched cohorts. The matched cohorts included 359 patients in each group. In the matched cohorts, there was an increase in transfusions, urinary tract infection (UTI), and return to the operating room in the arthrodesis group compared with the arthroplasty group (1.95%, 0.28%, P = .038; 1.11%, 0.00%, P = .045, 3.90%, 1.11%, P = .017). The logistic regression revealed that length of hospital stay (OR = 1.157) and insulin-dependent diabetes (OR = 6.043) had an increased risk of any adverse event for TAA or AA.

Conclusion

Identification of complication rates and patient risk factors for adverse events after TAA and AA can assist surgeons and patients in their choice of treatment for AOA.

Levels of Evidence:

III (retrospective cohort study)
#StopAsianHate as Hashtag Activism: Provocateurs, Celebrities, and Fan Practices of Collective Action Against Racism
Authors: Shahin Saif , Hou Mingyi
Published: February 2025

The #StopAsianHate hashtag movement emerged as a challenge to the rising tide of racism in the United States during the coronavirus pandemic and contributed to the legislation of the Covid-19 Hate Crimes Act. Our research brings together concepts from social movement studies as well as network science and celebrity-fandom studies to examine a corpus of tweets about the movement. We employ a mixed-methods design combining structural topic modeling with digital discourse analysis. Even though the movement rose up against White Supremacist structural racism, we find that right-wing provocateurs with large followings often hijacked its hashtags to amplify sporadic Black-on-Asian violence. But the active participation of Asian celebrities such as BTS, with their own huge followings online, bolstered the movement. Their posts and statements about anti-Asian violence were heavily reposted and dominated the digital discourse. Crucially, we show how their fans helped boost the movement’s anti-racist agenda by repeatedly posting similar messages in concert, which we compare with the offline fan practice of “chanting” as a form of collective identity performance. While theories like the logic of connective action view digital activism as individualized and decentralized, our research elucidates its hierarchical structure and the oversized role of provocateurs and celebrities in raising the visibility of competing claims and agendas by re-contextualizing hashtags. At the same time, culture industries and practices can create bottom-up solidarities that can have a political impact by raising particular agendas in the digital attention economy.
Changes in Nasal Cavity Morphology Following Subcranial or Transcranial Midface Advancement
Authors: Kazmouz Sobhi , Dike Chijoke , Bruss David , Santiago Gaia , Choudhary Akriti , DiChiaro Bianca , Perez Megan , Green Kelsey , Zhao Linping , Purnell Chad A.
Published: February 2025

Background and Purpose:

In patients with craniofacial syndromes characterized by midface hypoplasia, subcranial or transcranial midface advancement is the preferred technique to attain optimal functional and esthetic results. This procedure entails the creation of oblique osteotomies in the nasal septum and occasionally results in fractures of the turbinate. The objective of this study is to evaluate the quantitative and qualitative changes to these nasal structures after craniofacial disjunction.

Methods:

Patients from our center were included if they underwent subcranial or transcranial midface advancements, including LeFort II, III, or monobloc procedures, and possessed suitable pre- and postoperative CT scan data. Pre- and postoperative CT scans were evaluated based on several intranasal measurements including: degree of nasal septum deviation, morphology of the inferior turbinate, width of the piriform aperture, and nasal airway volume, and qualitative airway analysis.

Results:

Eight patients were included, with a mean age at surgery of 14.2 ± 5.3 years. Following surgery, the sella-nasion (S-N) distance increased by 9.6 mm (95% CI: 5.4, 13.9). No significant postoperative changes were found in nasal septum deviation, piriform aperture width, or nasal cavity airway volume. Of the inferior turbinate dimensions measured, only the breadth, measured at 50% the length of the turbinate, decreased significantly following surgery by 0.72 mm (95% CI: 0.02, 1.41). Correlation analysis revealed a significant relationship between the increase in S-N distance and nasal septum deviation area. Qualitative analysis showed that all 8 patients developed synechiae between the nasal septum and turbinate, and all patients developed septal perforation/resorption postoperatively.

Conclusions:

Craniofacial disjunction procedures may lead to notable septal and intranasal deformities which need to be considered when planning for surgery. All patients had some degree of septal perforation, resorption and nasal synechia post operatively.
Learned Lossless Image Compression Based on Optimal Kernel Transformer Approach
Authors: Sherly Kanaga Priya Pitchumony , Helen Sulochana Chellam
Published: February 2025

Image compression is crucial for reducing storage and transmission costs, particularly in applications involving high-resolution and complex imagery. Traditional compression methods, such as JPEG, PNG, and newer lossless formats like JPEG XL and WebP, often suffer from suboptimal compression ratios (CRs) and image quality when handling modern high-definition content. To overcome these limitations, this paper proposes a novel deep learning-based lossless image compression method. The symmetrical transformer (STF) model is introduced, integrating transformer blocks in both the downsampling encoder and upsampling decoder to enhance the capture of local and global features. The model also includes a multivariate mixture distribution channel conditioning (MMCC) entropy model, which improves pixel dependency predictions by modeling complex relationships within image channels. Additionally, an automated searching of optimal kernel shapes (SOKS) is employed to dynamically configure kernel sizes, optimizing the convolutional layers for different image regions. The system also applies stripe-wise pruning (SWP), which selectively prunes unimportant features during compression, reducing computational complexity and memory usage without compromising image quality. Extensive evaluations on standard datasets, including Kodak, CLIC, and DIV2K, demonstrate the effectiveness of the proposed model. Specifically, the approach achieves significant compression efficiency, with bits-per-dimension (BPD) values of 3.06 on Kodak, 3.91 on CLIC, and 3.63 on DIV2K, outperforming traditional methods such as iVPF (3.20 BPD on Kodak), GOLLIC (3.15 BPD on Kodak), and MSPSM (3.12 BPD on Kodak). In addition to compression efficiency, the proposed method excels in inference speed, with encoding times as low as 7.80 ms per sample on Kodak, significantly faster than competing methods. These results demonstrate a substantial improvement in compression rates and image reconstruction quality, highlighting the model's potential for real-world applications, including medical imaging, remote sensing, and real-time streaming, offering a significant advancement in lossless image compression.
Exposure of A2E to blue light promotes ferroptosis in the retinal pigment epithelium
Authors: Yang Bo , Yang Kunhuan , Chen Yuling , Li Qingjian , Chen Jingmeng , Li Shiying , Wu Yalin
Published: February 2025

Background

Age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) is closely related to the etiology of autosomal recessive Stargardt’s disease (STGD1) and dry age-related macular degeneration (AMD). N-retinylidene-N-retinylethanolamine (A2E) is a leading component of RPE lipofuscin that is highly susceptible to blue light. Ferroptosis is an iron-dependent form of non-apoptotic cell death characterized by the accumulation of lipid peroxides to a lethal level, which plays an important role in retinal diseases. However, it remains unknown whether A2E functions as a physiological trigger for eliciting blue light-induced ferroptosis of RPE cells.

Methods

A2E-loaded RPE cells and Abca4
−/−
Rdh8
−/− mice were exposed to blue light, respectively. Western blotting, immunofluorescence staining, reactive oxygen species (ROS) staining, intracellular iron staining, lipid peroxidation staining, fundus imaging, optical coherence tomography (OCT), hematoxylin–eosin (HE) staining, and electroretinography (ERG) were utilized to elucidate the role of blue light in A2E induced ferroptosis in the RPE and its potential mechanisms.

Results

Exposure of A2E to blue light promoted ferroptotic cell death in RPE cells by elevating ferrous ion (Fe2+) levels and inhibiting the solute carrier family 7 membrane 11 (SLC7A11)-glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis. GPX4 inactivation and ROS generated by Fe2+ overload and GSH depletion precipitated lipid peroxidation and subsequent ferroptosis in A2E-containing RPE cells upon exposure to blue light. In addition to GSH supplement, repressing either Fe2+ by deferiprone (DFP) or lipid peroxidation with ferrostatin-1 (Fer-1) significantly protected RPE cells against ferroptosis caused by blue light illumination of A2E. Abca4
−/−
Rdh8
−/− mice featured by an accelerated deposition of A2E in the RPE is an animal model for STGD1 and dry AMD. It was observed that ferroptosis was indeed present in the RPE of Abca4
−/−
Rdh8
−/− mice following exposure to blue light. Notably, alleviating ferroptosis by intraperitoneally injected Fer-1 effectively rescued retinal function and ameliorated RPE/photoreceptor degeneration in blue light-exposed Abca4
−/−
Rdh8
−/− mice.

Conclusions

Our results suggest the importance of blue light in A2E-mediated ferroptosis in the RPE, and deeply broaden the understanding of mechanisms underlying RPE atrophy arising from lipofuscin accumulation in STGD1 and dry AMD.
Aerobic exercise training improves learning and memory performance in hypoxic-exposed rats by activating the hippocampal PKA–CREB–BDNF signaling pathway
Authors: Luo Shichen , Shi Lei , Liu Tong , Jin Qiguan
Published: February 2025

Background

This study aims to investigate the effects of aerobic exercise training on learning and memory (L&M) performance in rats exposed to altitude hypoxia and its relationship with hippocampal plasticity and the PKA–CREB–BDNF signaling pathway.

Methods

Male Sprague–Dawley rats were exposed to 14.2% hypoxia with or without 60 min of non-weight-bearing swimming training for 8 weeks. The L&M performance was evaluated using the Morris water maze, and the mRNA expression of PSD95, SYP, PKA, CREB, CBP, and BDNF in the hippocampus was detected.

Results

Chronic hypoxia exposure significantly impaired L&M performance and reduced the mRNA expression of hippocampal PSD95, SYP, PKA, CREB, CBP, and BDNF. Aerobic exercise training effectively reversed these changes by enhancing hippocampal synaptic plasticity through the activation of the PKA–CREB–BDNF signaling pathway.

Conclusion

Aerobic exercise training can alleviate the decline in L&M performance caused by altitude hypoxia exposure, possibly through the activation of the hippocampal PKA–CREB–BDNF signaling pathway.
Inverse relationship between circulating sphingosine-1-phosphate and precursor species and coronary artery calcification score in type 2 diabetes
Authors: Le Goff Wilfried , Bourron Olivier , Materne Clément , Galier Sophie , Phan Franck , Tan-Chen Sophie , Guillas Isabelle , Hartemann Agnès , Salem Joe-Elie , Redheuil Alban , Foufelle Fabienne , Le Stunff Hervé , Hajduch Eric , Guerin Maryse
Published: February 2025

Background

Sphingosine 1-phosphate (S1P) is a key mediator of lipid signaling with strong immunomodulatory and anti-inflammatory effects. Circulating S1P levels including S1P in high-density lipoproteins (HDL) were demonstrated to be inversely associated with cardiovascular diseases (CVD). However, no studies are available regarding a potential implication of S1P on the risk of CVD in type 2 diabetes (T2D). The objective of this study is to determine if the increased CVD risk in T2D may involve an alteration of circulating S1P species as well as their precursors.

Methods

A total of 168 and 31 patients with T2D (154 men and 45 women) with available Coronary artery calcification (CAC) score from the DIACART and CERABIAB cohorts, respectively, were included in the study. Quantification of S1P species and their precursors was carried out by LC–MS/MS in plasma and isolated HDL. CAC score was modeled as a binary variable (0/1 below or equal/above 100) using CAC < 100 for reference. S1P species or precursors were modeled as binary variables dichotomized at the median (0/1: below or equal/above the median). The relationships between S1P species and CAC score modeled as a binary variable (below or equal/above 100) was evaluated by linear regression analyses. In vitro experiments were conducted to evaluate the contribution of HDL-S1P content on anti-inflammatory properties of HDL particles.

Results

Multivariate analysis revealed that plasma S1P levels, especially d18:1-S1P, and sphingosine in HDL were inversely associated with the high risk of CVD (CAC > 100) in patients with T2D. Clustering of HDL according to their concentration in S1P species and their precursors revealed that S1P-impoverished HDL is a major feature of patients with a CAC > 100. In vitro analysis of monocyte adhesion and inflammation in human umbilical vein endothelial cells as well as inflammatory phenotype of human macrophages demonstrated that low HDL-S1P exhibited impaired anti-inflammatory properties in comparison to high HDL-S1P.

Conclusion

This study unraveled that circulating S1P and their precursors are biomarkers of coronary atherosclerosis in T2D, which may underlie the lower abundance of S1P and anti-inflammatory activities of HDL.

Trial registration ClinicalTrials.gov number, NCT02431234.

Graphical abstract
Association of Kawasaki disease with intellectual disability, attention deficit hyperactivity disorder, and autism spectrum disorder: a systematic review and meta-analysis
Authors: Hsu Chih-Wei , Lin Yu-Wei , Chen Yang-Chieh Brian , Wang Liang-Jen , Kuo Ho-Chang
Published: February 2025

Background

The relationship between Kawasaki disease (KD) and neurodevelopmental disorders (NDDs) remains unclear. This study aims to explore the association between them.

Method

A systematic review was conducted using PubMed and Embase databases from inception to May 1, 2024 (INPLASY202450017). We included case-control or cohort studies comparing KD patients to healthy controls in assessing attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID). The meta-analysis employed a random-effects model to calculate effect sizes using hazard ratios (HRs) with 95% confidence intervals (CIs) for the disease occurrence. Moreover, mean differences (MDs) were used to calculate intelligence quotient (IQ).

Results

Four eligible studies, including 1,454,499 participants, were analyzed for ADHD, ASD, and ID. The risk of ADHD in KD patients was higher than in healthy controls (HR[95%CI] = 1.76[1.21–2.57]). However, the risks of ASD (HR[95%CI] = 1.68[0.47–5.94]) and ID (HR[95%CI] = 1.39[0.52–2.63]) were not significantly different between KD and controls. Additionally, three studies with 365 participants were analyzed for IQ. IQ comparisons showed no significant differences in full IQ (MD[95%CI]=-0.01[-2.44–2.42]), verbal IQ (MD[95%CI]=-1.05[-4.42–2.33]), and performance IQ (MD[95%CI]=-0.08[-2.75–2.59]).

Conclusion

This study indicates that individuals with KD have a higher risk for ADHD but not for ASD or ID.

Trial registration

INPLASY, INPLASY202450017. Registered 05 May 2024, https://inplasy.com/inplasy-2024-5-0017/.
Gene-activation of surface-modified 3D printed calcium phosphate scaffolds
Authors: Laird Noah Z. , Phruttiwanichakun Pornpoj , Mohamed Esraa , Acri Timothy M. , Jaidev Leela R. , Salem Aliasger K.
Published: February 2025

Large volume bone defects that do not spontaneously heal despite surgical stabilization (“critical-sized” defects) remain a challenge to treat clinically. Recent research investigating bone regenerative implants made from 3D printed materials have shown promise as a potential alternative to current treatment methods, such as autografting, allografting, and multi-step surgical interventions. Recent work has shown that implanting 3D printed calcium phosphate cement (CPC) scaffolds loaded with bone morphogenetic protein-2 (BMP-2) can provide a one-step surgical intervention that has similar bone healing outcomes to a popular two-step intervention: the Masquelet technique. The aim of this study was to investigate whether a 3D printed CPC scaffold loaded with a lyophilized polyplex gene-delivery formulation could serve as an alternative to loading BMP-2 protein onto such scaffolds. We 3D printed CPC scaffolds, hardened them with multiple methods, and explored the impact of these hardening methods on surface texture, mechanical strength, osteogenic differentiation, and ion flux. We then gene-activated these materials with cationic polyplexes containing plasmid DNA encoding reporter genes to investigate transfection from the gene-activated scaffolds. We found that incubating CPC scaffolds in aqueous solutions after initial hardening in a humid environment could enhance scaffold mechanical strength (compressive strength of 21.28 MPa vs. 6.54 MPa) and osteogenic differentiation. We also found that when we increased the total surface area of the CPC material exposed to polyplex solutions, there was a reduction in transfection via adsorption of polyplexes to the CPC surface. This study shows that 3D printed, gene-activated CPC scaffolds are a promising avenue for future exploration in the field of bone regeneration, though the level of gene expression induced by the scaffolds must be improved.
Novel 5,6-dichlorobenzimidazole derivatives as dual BRAFWT and BRAFV600E inhibitors: design, synthesis, anti-cancer activity and molecular dynamics simulations
Authors: Temirak Ahmed , El Kerdawy Ahmed M. , Nageeb Amira M. , Abdel-Mohsen Heba T.
Published: February 2025

A new series of 1-substiuted-5,6-dichloro-2-(4-methoxyphenyl)-1H-benzo[d]imidazoles 10a–p was designed and synthesized to target both BRAFWT and BRAFV600E. The design strategy ensures that these derivatives would effectively occupy the ATP binding pocket of BRAFWT/V600E kinase domains and extend over the gate area interacting through hydrogen bonding with the surrounding key amino acids Glu500 and Asp593 and to finally occupy the allosteric hydrophobic back pocket. Some synthesized derivatives demonstrated impressive potency against BRAFWT with % inhibition approaching 91% at a concentration of 10 µM. The most potent candidate 10h demonstrated IC50 values of 1.72 and 2.76 µM on BRAFWT and BRAFV600E, respectively. At the same time, the synthesized benzimidazoles 10a–p were examined for their growth inhibitory activity on NCI-60 cancer cell lines. Again, compound 10h revealed a potent GI50 across a range of cancer cell lines. Moreover, it arrested cell cycle progression in HT29 colon cancer cell line at G2/M phase and induced apoptosis in the same cell line. Molecular dynamics simulations supported the validity of the design assumption, simultaneously, ADME prediction study displayed that the designed benzimidazoles exhibit promising physiochemical and drug-likeness properties as anticancer agents.

Graphical Abstract
Homologous recombination deficiency (HRD) testing landscape: clinical applications and technical validation for routine diagnostics
Authors: Witz Andréa , Dardare Julie , Betz Margaux , Michel Cassandra , Husson Marie , Gilson Pauline , Merlin Jean-Louis , Harlé Alexandre
Published: February 2025

The use of poly(ADP-ribose) polymerase inhibitors (PARPi) revolutionized the treatment of BRCA-mutated cancers. Identifying patients exhibiting homologous recombination deficiency (HRD) has been proved useful to predict PARPi efficacy. However, obtaining HRD status remains an arduous task due to its evolution over the time. This causes HRD status to become obsolete when obtained from genomic scars, rendering PARPi ineffective for these patients. Only two HRD tests are currently FDA-approved, both based on genomic scars detection and BRCA mutations testing. Nevertheless, new technologies for obtaining an increasingly reliable HRD status continue to evolve. Application of these tests in clinical practice is an additional challenge due to the need for lower costs and shorter time to results delay.

In this review, we describe the currently available methods for HRD testing, including the methodologies and corresponding tests for assessing HRD status, and discuss the clinical routine application of these tests and their technical validation.
Vancomycin dosing design method considering risk factors for nephrotoxicity
Authors: Matsuki Yoshihiko , Kozima Yutaro , Yanagi Megumi , Sako Ken-ichi , Watanabe Tamaki , Yasuno Nobuhiro , Watanabe Shigekazu
Published: February 2025

Background

Vancomycin (VCM) induces nephrotoxicity in a dose-dependent manner, and patients with risk factors for nephrotoxicity have been reported to develop nephrotoxicity even within the effective concentration range. In the present study, we investigated measures to set an appropriate AUCss for each case by assessing the risk of developing nephrotoxicity using logistic regression curves, separating patients into a High-risk group with risk factors associated with nephrotoxicity when VCM is used and a Low-risk group without risk factors.

Methods

A multivariate logistic regression analysis was used to identify risk factors for nephrotoxicity. The AUCss threshold was selected by a CART analysis and ROC curves, and a logistic regression analysis was used to examine the relationship between AUCss and the probability of developing nephrotoxicity.

Results and discussion

The incidence of nephrotoxicity was 31.7% (33/104) in the High-risk group and 13.0% (14/108) in the Low-risk group, and was significantly higher in the former (p = 0.001). The AUCss threshold was set at 575 mg·h/L for the High-risk group and 650 mg·h/L for the Low-risk group. The probability of developing nephrotoxicity in the High-risk group (104 patients) was high: AUCss 400 mg·h/L (16.8%), 500 mg·h/L (23.3%), and 575 mg·h/L (29.3%). The target concentration range was newly set at 400 ≤ AUCss < 500, suggesting that the target AUCss needs to be considered for each patient based on the balance between therapeutic efficacy and the prevention of adverse effects. The probability of developing nephrotoxicity in the Low-risk group (108 patients) was AUCss 500 mg·h/L (4.7%), 575 mg·h/L (8.4%), and 650 mg·h/L (14.6%). Since the Low-risk group has a high safety profile, the target concentration range was newly set at 400 ≤ AUCss < 650, suggesting the safe administration of the drug up to AUCss 650 mg·h/L while aiming for AUCss 600 mg·h/L from the initial dose design.

Conclusion

In the present study, the risk of nephrotoxicity for each AUCss was quantitatively analyzed using logistic regression curves for the High- and Low-risk groups. This allowed for the proposal of strategic individual target concentrations based on the balance between risk and benefit.
Neurosurgical Approach to Neurocysticercosis in Adults: A Comprehensive Systematic Review of Clinical and Imaging Insights
Authors: Knott Maxon V. , Berke Chandler N. , Shah Khushi Hemendra , Gurses Muhammet Enes , Bashti Malek , Lu Victor M. , Ivan Michael E. , Castro Jose G. , Komotar Ricardo J. , Shah Ashish H.
Published: February 2025

BACKGROUND AND OBJECTIVES:

Neurocysticercosis (NCC), caused by larval cysts of Taenia solium, presents a significant health challenge worldwide with diverse clinical presentations and varying management approaches. Untreated NCC can lead to increased intracranial pressure and/or hydrocephalus, with possible death. This review provides comprehensive neurosurgical insight into the heterogeneity of NCC. As there is currently no treatment algorithm for NCC, we propose a framework based on the management strategies most prevalent in the literature.

METHODS:

A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted searching PubMed, Scopus, and Embase from November 1993 to August 2023. Included articles had individual patient data on the treatments and outcomes of adult patients treated for confirmed symptomatic NCC. Relevant patient data on patient presentations, management, and outcomes and disease characteristics were collected.

RESULTS:

Our analysis included 90 studies with 205 patients. Neuroimaging was diagnostic for all, with MRI being predominant (74%). Cysts were intraparenchymal (n = 69), extraparenchymal (n = 68), spinal (n = 24), and mixed distribution (n = 16). Common symptoms included seizures (39%), headache (39%), and motor weakness/paresis (28%). 67 patients presented with hydrocephalus, 30 (45%) of which received a ventriculoperitoneal shunt. NCC was most commonly treated medically with corticosteroids (56%) and albendazole (55%). Neurosurgical intervention was most commonly performed for surgical extraction of cysts (33%). Combination of medical and surgical treatment (98%, 44/45) or surgical intervention alone (98%, 40/41) was the most successful at resolving symptoms after first treatment. Resolution of symptoms with added radiographic resolution of the cyst was common with maximal treatment (n = 137, 70%).

CONCLUSION:

NCC's diverse presentations and outcomes emphasize the importance of tailored therapeutic strategies. Limitations of this study include its retrospective nature and low sample sizes of individual studies. The prominence of corticosteroids, albendazole, and surgical procedures highlights their central role in NCC management, as well as the indispensable role of neurosurgeons.
How Good is Neurosurgical Training? Validation of a Perfused Microsurgical Aneurysm Training Simulator Using a Modified Objective Structured Assessment of Aneurysm Clipping Skills Score and Indocyanine Green Angiography
Authors: Reiser Julius , Amini Amir , Swiatek Vanessa M. , Taskaya Firat , Al-Hamid Sifian , Stein Klaus-Peter , Rashidi Ali , Sandalcioglu I. Erol , Neyazi Belal
Published: February 2025

BACKGROUND AND OBJECTIVES:

The training of cerebrovascular neurosurgeons faces significant challenges, particularly due to the decreasing volume of aneurysm clipping procedures. Traditional training methods rely heavily on clinical case availability, which limits skill development. This study aimed to implement and validate a Microsurgical Aneurysm Training Simulator (MATS) that offers a comprehensive, realistic, and cost-effective solution for neurosurgical training.

METHODS:

MATS was designed using semiautomated algorithms and additive manufacturing to replicate a bifurcation aneurysm of the middle cerebral artery. The simulator includes a pulsatile perfusion system and is compatible with indocyanine-green angiography. The simulation was evaluated by medical students, residents, and experienced neurosurgeons through face, content, and construct validity assessments. Performance was measured using a modified Objective Structured Assessment of Aneurysm Clipping Skills.

RESULTS:

MATS demonstrated high face and content validity, particularly in replicating the visual and procedural aspects of aneurysm clipping. Participants across all experience levels showed significant improvements in modified Objective Structured Assessment of Aneurysm Clipping Skills scores, with medical students displaying the most pronounced learning curve. The simulators compatibility with indocyanine green angiography was confirmed, though limitations were noted in replicating physiological perfusion pressures and the visual impact of subarachnoid hemorrhage during aneurysm rupture simulations.

CONCLUSION:

MATS is a validated, cost-effective, and reproducible tool that significantly enhances neurosurgical training by improving technical skills, especially in inexperienced participants. While the simulator effectively mimics key aspects of aneurysm surgery, further research is needed to assess its predictive validity and its potential impact on actual surgical outcomes.
Focusing on the Future: Making the Reinstatement Process More Effective for Vulnerable Students
Authors: Bowlus Angela
Published: February 2025

Reinstatement from suspension is a complex process. Students hoping to be reinstated must demonstrate, usually through a written appeal, that previous issues are resolved and that they have a plan for academic success. Writing reinstatement appeals requires students to be vulnerable and share intimate details of their lives with complete strangers to persuade them that they are ready for and capable of returning. That complexity and vulnerability could discourage students from returning to complete their degrees. This study used a narrative theory framework to understand the importance of student narratives and identify whether focus can be placed on the characteristics of success rather than invoking past trauma placing students in a vulnerable position.
Research on the impact of COVID-19 on the financial system: Evidence from Indonesia
Authors: Darjana Darjana , Wiyono Sudarso Kaderi , Koesrindartoto Deddy Priatmodjo
Published: February 2025

This study investigates the financial system vulnerability and pandemic impact on the financial system of Indonesia in 2015–2021. Two kinds of analysis are involved, i.e.: cross-section analysis at a certain point in time and time-series analysis along a certain time-period. To measure the risks, the research employs risk profile and network analysis using the Financial Account Balance Sheet from Bank of Indonesia. The balance sheet of one institutional sector is associated to the balance sheet of another sector from both assets and liabilities, such as corporations, households, and the financial sectors. Afterwards, Difference-in-Differences (DID) method and the macroeconomic linkages exercises the COVID-19 impact on the financial system. The result shows as the key findings that the financial system is more vulnerable during the pandemic for banks, corporations, and governments, indicated by the more declining net-worth, along with the external balance slowdown. Furthermore, the macroeconomic linkages show that during the pandemic, the financial system is more reliant on the banks, government, and the Rest of the World (ROW).
Calculating punitive damage multiplier in intellectual property cases: An empirical study and the enhanced model
Authors: Shang Jiangang , Xu Weiqi , Xu Weina , Wu Keyao
Published: February 2025

The application of punitive damages in intellectual property cases in China has encountered notable deficiencies within the judicial context. These deficiencies, including a limited range of applicability, frequent recourse to statutory damages, difficulties in ascertaining the appropriate damages base, and a marked reliance on subjective factors in calculating multipliers, undermine judicial consistency and fairness. In this study, we conducted a comprehensive quantitative analysis by selecting 79 pertinent judgments from a dataset of 3,478 intellectual property rulings. Initially, we developed a multiple linear regression model to assess punitive damages. Upon encountering negative estimated coefficients, we improved the model to a Beta Generalized Linear Model. The efficacy of the new model was validated through an improved R-squared value compared to the original model and by analyzing an additional 45 cases. Both models highlight the scope of infringement and the reputation of intellectual property assets as critical variables. They suggest that wider infringements lead to greater economic penalties and emphasize the significant market value and potential financial losses of intellectual property. Significantly, this study represents a pioneering initiative in China, establishing a model to assist in the legal determination of punitive damages in IP cases.
Metabolic pathways of Alternative Lengthening of Telomeres in pan-carcinoma
Authors: Armendáriz-Castillo Isaac , García-Cárdenas Jennyfer , Espinosa Pamela , Hidalgo-Fernández Katherine , Peña-Zúñiga Lizbeth , Martínez Ronie , Moromenacho Juan , Herrera-Yela Andrés , Cruz-Varela Jonathan , Saucedo-Sariñana Anilú , Cerdán María-Esperanza , López-Cortés Andrés , Guerrero Santiago
Published: February 2025

Alternative Lengthening of Telomeres (ALT) is a telomerase-independent mechanism deployed by several aggressive cancers to maintain telomere length. This contributes to their malignancy and resistance to conventional therapies. In prior studies, we have identified key proteins linked to the ALT process using multi-omic data integration strategies. In this work, we combined metabolomic datasets with our earlier results to identify targetable metabolic pathways for ALT-positive tumors. 39 ALT-related proteins were found to interact with 42 different metabolites in our analysis. Additional networking analysis revealed a complex interaction between metabolites and ALT-related proteins, suggesting that pan-cancer oncogenes may have an impact on these pathways. Three metabolic pathways have been primarily related with the ALT mechanism: purine metabolism, cysteine and methionine metabolism, and nicotinate and nicotinamide metabolism. Lastly, we prioritized FDA-approved drugs (azathioprine, thioguanine, and mercaptopurine) that could target ALT-positive tumors through purine metabolism. This work provides a wide perspective of the metabolomic pathways associated with ALT and reveals potential therapeutic targets that require further experimental validation.
Isolation and characterization of bacteriophage against clinical isolates of AmpC beta lactamase–Producing Klebsiella pneumoniae from hospital wastewater
Authors: Abusalah Manal Abdel Haleem A. , Abusalah Mai Abdel Haleem A. , Yean Yean Chan , Aziah Ismail , Zaidah Abdul Rahman
Published: February 2025

Background

The increasing incidence of AmpC β-lactamase producing by K. pneumoniae has raised global alarm. Consequently, there is a crucial need for effective methods to inactivate pathogenic bacteria and mitigate the associated risks. Bacteriophage therapy has been demonstrated to be an effective and alternative approach for targeting and inactivating K. pneumoniae that produces AmpC.

This study aimed to isolate and characterize the Klebsiella pneumoniae AmpC-specific phages from hospital wastewater.

Methods

The hospital wastewater samples were collected from the sewage water effluent of a tertiary hospital at Universiti Sains Malaysia, located on the east coast of Malaysia. These samples underwent serial filtration and centrifugation processes for phage recovery. The phage solutions were undergoing a screening test by spot assay using clinical isolates of Klebsiella pneumoniae AmpC strain as amplification hosts. The isolated AmpC-phages were further studied and characterised to determine the phage’s host range, temperature, pH, and chloroform stabilities. High-Resolution Transmission Electron Microscopy (HRTEM) was performed to determine the phage type.

Results

Thirty HWW samples were analyzed using four K. pneumoniae AmpC strains resulting in a total of 120 screening plates. The AmpC—Klebsiella pneumoniae (AmpC-KP) phages were detected in 31.70% (38/120) of the plates. The AmpC-KP phages had lytic diameters ranging from 1–3 mm, and a phage titer ranged from4×103–3.2×107 PFU/ml. The phages had a narrow–host range stable at a temperature range from -20–50˚C. The phages were also stable at pH ranging from 4 to 9 and at different concentrations of chloroform (5%,10%). Based on HRTEM, Siphoviridea was identified.

Conclusions

The AmpC-phages were abundant in hospital wastewater, and HWW was a good source for AmpC-KP phages. The isolated AmpC phages had a high effectivity and specificity for AmpC-KP with a narrow host range and could survive under harsh conditions such as (temperature, pH, and chloroform).
A systematic review of automated hyperpartisan news detection
Authors: Maggini Michele Joshua , Bassi Davide , Piot Paloma , Dias Gaël , Otero Pablo Gamallo
Published: February 2025

Hyperpartisan news consists of articles with strong biases that support specific political parties. The spread of such news increases polarization among readers, which threatens social unity and democratic stability. Automated tools can help identify hyperpartisan news in the daily flood of articles, offering a way to tackle these problems. With recent advances in machine learning and deep learning, there are now more methods available to address this issue. This literature review collects and organizes the different methods used in previous studies on hyperpartisan news detection. Using the PRISMA methodology, we reviewed and systematized approaches and datasets from 81 articles published from January 2015 to 2024. Our analysis includes several steps: differentiating hyperpartisan news detection from similar tasks, identifying text sources, labeling methods, and evaluating models. We found some key gaps: there is no clear definition of hyperpartisanship in Computer Science, and most datasets are in English, highlighting the need for more datasets in minority languages. Moreover, the tendency is that deep learning models perform better than traditional machine learning, but Large Language Models’ (LLMs) capacities in this domain have been limitedly studied. This paper is the first to systematically review hyperpartisan news detection, laying a solid groundwork for future research.
Innovative approaches in QSPR modelling using topological indices for the development of cancer treatments
Authors: Shi Xiaolong , Kosari Saeed , Ghods Masoud , Kheirkhahan Negar
Published: February 2025

This paper provides a comprehensive review of quantitative structure-property relationships (QSPR) about to cancer drugs, with a focus on the application of topological indices (TI) and data analysis techniques. Cancer is a serious and life-threatening disease for which no complete cure currently exists. Consequently, extensive research is ongoing to develop new therapeutic agents. The application of topological indices in chemistry and medicine, particularly in the investigation of the molecular, pharmacological, and therapeutic properties of drugs, has become a significant tool. This article investigates the potential of Temperature indices in analyzing the physicochemical properties of drugs used for cancer treatment. The approach employs QSPR modeling to establish correlations between the molecular structure of a compound and its physical and chemical properties. The analysis covers a range of Cancer drugs, including Aminopterin, Convolutamide A, Convolutamydine A, Daunorubicin, Minocycline, Podophyllotoxin, Caulibugulone E, Perfragilin A, Melatonin, Tambjamine K, Amathaspiramide E, and Aspidostomide E. The findings demonstrate that optimal regression models (Fifty-eight models) incorporating TI can effectively predict physicochemical properties, such as Boiling Point (BP), Enthalpy (EN), Flash Point (FP), Molar Refractivity (MR), Polar Surface Area (PSA), Surface Tension (ST), Molecular Volume (MV), and Complexity (COM). This research suggests that temperature-based topological indices (TI) are promising tools for the development and optimization of cancer drugs, as demonstrated by statistically significant results with a p-value less than 0.05. In addition to the linear regression model, which performed the best, two other machine learning models, namely SVR and Random Forest, were also used for further analysis and comparison of their performance in predicting the physicochemical properties of drugs, to assess the advantages and disadvantages of each model.