bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic postsurgical pain (CPSP): an underestimated problem after incisional hernia treatment
Authors: Widder A. , Reese L. , Lock J. F. , Wiegering A. , Germer C.-T. , Rittner H. L. , Dietz U. A. , Schlegel N. , Meir M. 
Published: March 2024

Abstract
Background
Chronic postsurgical pain (CPSP) is a potential long-term problem following open incisional hernia repair which may affect the quality of life of patients despite successful anatomical repair of the hernia. The aim of this manuscript was to identify the incidence and outcome of patients following open incisional hernia repair in respect of risk factors to develop CPSP.

Methods
A single-center retrospective analysis of patients who underwent open incisional hernia repair between 2015 and 2021 was performed. Pre-existing conditions (e.g., diabetes mellitus and malignancy), hernia complexity, postoperative complications, and postoperative pain medication were analyzed using the local database. Quality of life and CPSP were assessed using the EuraHS Quality of Life (QoL) questionnaire.

Results
A total of 182 cases were retrospectively included in a detailed analysis based on the complete EuraHS (QoL) questionnaire. During the average follow-up period of 46 months, this long-term follow-up revealed a 54.4% incidence of CPSP and including a rate of 14.8% for severe CPSP (sCPSP) after open incisional hernia surgery. The complexity of the hernia and the demographic variables were not different between the group with and without CPSP. Patients with CPSP reported significantly reduced QoL. The analgesics score which includes the need of pain medication in the initial days after surgery was significantly higher in patients with CPSP than in those without (no CPSP: 2.86 vs. CPSP: 3.35; p = 0.047).

Conclusion
The presence of CPSP after open incisional hernia repair represents a frequent and underestimated long-term problem which has been not been recognized to this extent before. CPSP impairs QoL in these patients. Patients at risk to develop CPSP can be identified in the perioperative setting by the need of high doses of pain medication using the analgesics score. Possibly timely adjustment of pain medication, even in the domestic setting, could alleviate the chronicity or severity of CPSP.
Convergence rates for sums-of-squares hierarchies with correlative sparsity
Authors: Korda Milan , Magron Victor , Ríos-Zertuche Rodolfo 
Published: March 2024

Abstract
This work derives upper bounds on the convergence rate of the moment-sum-of-squares hierarchy with correlative sparsity for global minimization of polynomials on compact basic semialgebraic sets. The main conclusion is that both sparse hierarchies based on the Schmüdgen and Putinar Positivstellensätze enjoy a polynomial rate of convergence that depends on the size of the largest clique in the sparsity graph but not on the ambient dimension. Interestingly, the sparse bounds outperform the best currently available bounds for the dense hierarchy when the maximum clique size is sufficiently small compared to the ambient dimension and the performance is measured by the running time of an interior point method required to obtain a bound on the global minimum of a given accuracy.
A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice
Authors: Varghese Della , Cruz Giovanna I. , Johanson Colden , Toland Liz , Miranda Miguel , Faherty Eleanor C. , Harland David , Kaplan Henry G. 
Published: March 2024

Abstract
Purpose
Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US).

Methods
HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported.

Results
Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50–66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8–13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0–9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively.

Conclusion
This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression.
PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site
Authors: Junior João Neif Antonio , Preto Daniel D.’Almeida , Lazarini Maria Eduarda Zanatta Neder , de Lima Marcos Alves , Bonatelli Murilo , Berardinelli Gustavo Noriz , da Silva Vinicius Duval , Pinheiro Céline , Reis Rui Manuel , Cárcano Flavio Mavignier 
Published: March 2024

Abstract
Background
Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features.

Methods
The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis.

Results
Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months, p-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively).

Conclusion
PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.
Contest competition and injury in adult male sub-Antarctic fur seals
Authors: Bester M. N. , Rossouw G. J. , van Staden P. J. 
Published: March 2024

AbstractWe recorded intra-sexual behaviour of adult male sub-Antarctic fur seals Arctocephalus tropicalis at Gough Island, Southern Ocean, during the 1975/76 summer breeding season. Our re-analysed data address male ‘contest competition’, which relates to the costs of intra-sexual disputes, including fights. We considered the risks/benefits of fighting through investigation of injuries (n = 353) sustained by adult males (n = 124) in fights. Injuries were predominantly on the forequarters, especially around the insertion areas of the front flippers (41%) with its sparse pelage, compared to the neck and chest areas combined (29%), an area which is well protected by thick pelage. The infliction of serious, sometimes debilitating, injuries to competitors increases a male’s access to females. Injuries predominate in injured, defeated males that gather at non-breeding sites, suggesting that injuries inflicted by dominant males were successful in excluding competing males from breeding sites.
Targeted HIV Self-Testing Identifies Persons with Undiagnosed HIV and Active Engagement Links them to Care: The GetaKit Study
Authors: O’Byrne Patrick , Kroch Abigail , Orser Lauren , Ho Nikki , Musten Alexandra , Haines Marlene , Lindsay Jennifer 
Published: March 2024

AbstractCurrent international HIV testing guidelines recommend that HIV negative persons from HIV priority groups complete repeat screening every 3–6 months; local guidelines in our jurisdiction recommend that such retesting should occur every 3 months. Such an approach allows for timely HIV diagnosis and linkage to care – and aligns with the UNAIDS 95-95-95 targets to have 95% of undiagnosed persons be aware of their HIV status. To meet these aims, new approaches to HIV testing have been developed, including our HIV self-testing initiative, GetaKit.ca, which uses an online screening algorithm to determine eligibility and has built in pathways for re-test reminders, linkage HIV prevention care, and rapid follow-up for positive test results. To understand self-testing frequency in relation to our local recommendations for resting every 3 months, we evaluated data from participants who ordered repeat HIV self-tests through GetaKit.ca. Descriptive analyses were performed on participant characteristics and chi-square tests were performed on aggregated participant risk data. During the study period, 5235 HIV self-tests were distributed to 3627 participants, of whom, 26% ordered more than once and 27% belonged to an HIV priority population. Participants who retested were more likely to have been white, male, and part of an HIV priority population; they were also more likely to have completed prior STI or HIV testing or had a prior STI diagnosis, compared to those who did not. We identified 16 new HIV diagnoses, 2 of which were among repeat testers. Our results suggest that HIV self-testing can be useful to help meet UNAIDS targets to identify undiagnosed infections; however, such efforts are less likely to be successful without adequate linkage to follow-up services, including HIV treatment and prevention care.
Constructing a Novel Amino Acid Metabolism Signature: A New Perspective on Pheochromocytoma Diagnosis, Immune Landscape, and Immunotherapy
Authors: Yan Zechen , Luan Yongkun , Wang Yu , Ren Yilin , Li Zhiyuan , Zhao Luyang , Shen Linnuo , Yang Xiaojie , Liu Tonghu , Gao Yukui , Sun Weibo 
Published: March 2024

Abstract
Pheochromocytoma/paraganglioma (PGPG) is a rare neuroendocrine tumor. Amino acid metabolism is crucial for energy production, redox balance, and metabolic pathways in tumor cell proliferation. This study aimed to build a risk model using amino acid metabolism-related genes, enhancing PGPG diagnosis and treatment decisions. We analyzed RNA-sequencing data from the PCPG cohort in the GEO dataset as our training set and validated our findings using the TCGA dataset and an additional clinical cohort. WGCNA and LASSO were utilized to identify hub genes and develop risk prediction models. The single-sample gene set enrichment analysis, MCPCOUNTER, and ESTIMATE algorithm calculated the relationship between amino acid metabolism and immune cell infiltration in PCPG. The TIDE algorithm predicted the immunotherapy efficacy for PCPG patients. The analysis identified 292 genes with differential expression, which are involved in amino acid metabolism and immune pathways. Six genes (DDC, SYT11, GCLM, PSMB7, TYRO3, AGMAT) were identified as crucial for the risk prediction model. Patients with a high-risk profile demonstrated reduced immune infiltration but potentially higher benefits from immunotherapy. Notably, DDC and SYT11 showed strong diagnostic and prognostic potential. Validation through quantitative Real-Time Polymerase Chain Reaction and immunohistochemistry confirmed their differential expression, underscoring their significance in PCPG diagnosis and in predicting immunotherapy response. This study’s integration of amino acid metabolism-related genes into a risk prediction model offers critical clinical insights for PCPG risk stratification, potential immunotherapy responses, drug development, and treatment planning, marking a significant step forward in the management of this complex condition.
OX40/OX40 ligand and its role in precision immune oncology
Authors: Thapa Bicky , Kato Shumei , Nishizaki Daisuke , Miyashita Hirotaka , Lee Suzanna , Nesline Mary K. , Previs Rebecca A. , Conroy Jeffery M. , DePietro Paul , Pabla Sarabjot , Kurzrock Razelle 
Published: March 2024

AbstractImmune checkpoint inhibitors have changed the treatment landscape for various malignancies; however, their benefit is limited to a subset of patients. The immune machinery includes both mediators of suppression/immune evasion, such as PD-1, PD-L1, CTLA-4, and LAG-3, all of which can be inhibited by specific antibodies, and immune-stimulatory molecules, such as T-cell co-stimulatory receptors that belong to the tumor necrosis factor receptor superfamily (TNFRSF), including OX40 receptor (CD134; TNFRSF4), 4-1BB (CD137; TNFRSF9), and glucocorticoid-induced TNFR-related (GITR) protein (CD357; TNFRSF18). In particular, OX40 and its binding ligand OX40L (CD134L; TNFSF4; CD252) are critical for immunoregulation. When OX40 on activated T cells binds OX40L on antigen-presenting cells, T-cell activation and immune stimulation are initiated via enhanced T-cell survival, proliferation and cytotoxicity, memory T-cell formation, and abrogation of regulatory T cell (Treg) immunosuppressive functions. OX40 agonists are in clinical trials both as monotherapy and in combination with other immunotherapy agents, in particular specific checkpoint inhibitors, for cancer treatment. To date, however, only a minority of patients respond. Transcriptomic profiling reveals that OX40 and OX40L expression vary between and within tumor types, and that only ~ 17% of cancer patients have high OX40 and low OX40L, one of the expression patterns that might be theoretically amenable to OX40 agonist enhancement. Taken together, the data suggest that the OX40/OX40L machinery is a critical part of the immune stimulatory system and that understanding endogenous expression patterns of these molecules and co-existing checkpoints merits further investigation in the context of a precision immunotherapy strategy for cancer therapy.
A survey of interventions to actively conserve the frozen North
Authors: van Wijngaarden Albert , Moore John C. , Alfthan Bjorn , Kurvits Tiina , Kullerud Lars 
Published: March 2024

AbstractThe frozen elements of the high North are thawing as the region warms much faster than the global mean. The dangers of sea level rise due to melting glacier ice, increased concentrations of greenhouse gases from thawing permafrost, and alterations in the key high latitude physical systems spurred many authors, and more recently international agencies and supra-state actors, to investigate “emergency measures” that might help conserve the frozen North. However, the efficacy and feasibility of many of these ideas remains highly uncertain, and some might come with significant risks, or could be even outright dangerous to the ecosystems and people of the North. To date, no review has evaluated all suggested schemes. The objectives of this first phase literature survey (which can be found in a separate compendium (https://doi.org/10.5281/zenodo.10602506), are to consider all proposed interventions in a common evaluation space, and identify knowledge gaps in active conservation proposals. We found 61 interventions with a high latitude focus, across atmosphere, land, oceans, ice and industry domains. We grade them on a simple three-point evaluation system across 12 different categories. From this initial review we can identify which ideas scored low marks on most categories and are therefore likely not worthwhile pursuing; some groups of interventions, like traditional land-based mitigation efforts, score relatively highly while ocean-based and sea ice measures, score lower and have higher uncertainties overall. This review will provide the basis for a further in-depth expert assessment that will form phase two of the project over the next few years sponsored by University of the Arctic.
Calibrated EMOS: applications to temperature and wind speed forecasting
Authors: Gaetan Carlo , Giummolè Federica , Mameli Valentina 
Published: March 2024

AbstractEnsembles of meteorological quantities obtained from numerical models can be used for forecasting weather variables. Unfortunately, such ensembles are often biased and under-dispersed and therefore need to be post-processed. Ensemble model output statistics (EMOS) is a widely used post-processing technique to reduce bias and dispersion errors of numerical ensembles. In the EMOS approach, a full probabilistic prediction is given in the form of a predictive distribution with parameters depending on the ensemble forecast members. Parameters are then estimated and substituted, thus obtaining a so-called estimative predictive distribution. Nonetheless, estimative distributions may perform poorly in terms of the coverage probability of the corresponding quantiles. This work proposes the use of predictive distributions based on a bootstrap adjustment of estimative predictive distributions, in the context of EMOS models. These distributions are calibrated, which means that the corresponding quantiles provide exact coverage probabilities, in contrast to the estimative distributions. The introduction of the bootstrap calibrated procedure for EMOS is the innovative aspect of this study. The performance of the suggested calibrated EMOS is evaluated in two simulation studies, comparing the different predictive distributions by means of the log-score, the continuous ranked probability score, and the coverage of the corresponding predictive quantiles. The results of these simulation studies show that the proposed calibrated predictive distributions improve estimative solutions, both reducing the mean scores and producing quantiles with exact coverage levels. The good performance of the new calibrated EMOS is further stressed in two real data applications, one about maximum daily temperatures at sites located in the Veneto region (Italy) and the other one about wind speed forecasts at weather stations over Germany.
Intentionality, pointing, and early symbolic cognition
Authors: van Mazijk Corijn 
Published: March 2024

AbstractConcepts such as “symbolism” and “symbolic cognition” often remain unspecified in discussions the symbolic capacities of earlier hominins. In this paper, I use conceptual tools from phenomenology to reflect on the origins of early symbolic cognition. In particular, I discuss the possible early use of pointing gestures around the time of the earliest known stone tool industries. I argue that unlike more basic social acts such as expression, gaze following, and attention-getters, which are used by extant non-human great apes, communicative pointing involves key elements that are characteristic of symbolic cognition. In particular, it involves “third order intentionality” as well as “shared practice horizons”: shared frameworks of understanding which are required for the interpretation of communicative acts whose meaning is not codified indexically or iconically in the signaling behavior. In the final part, I briefly review some indications for the use of pointing gestures around the time of the Lomekwian and Oldowan industries, as a way to sustain cooperation and possibly learning by instruction. It is suggested that pointing is more complex than is standardly acknowledged, and that it may have been an important communicative act for Early Stone Age hominins in transitioning to more fully symbolic speech capacities.
The Connection Between Sleep Problems and Emotional and Behavioural Difficulties in Autistic Children: A Network Analysis
Authors: Sommers Lucy , Papadopoulos Nicole , Fuller-Tyszkiewicz Matthew , Sciberras Emma , McGillivray Jane , Howlin Patricia , Rinehart Nicole 
Published: March 2024

AbstractThe interactions between sleep problems, autism symptoms and emotional and behavioural difficulties were explored using network analysis in 240 autistic children (mean age: 8.8 years, range 5–13 years) with moderate to severe sleep problems. Findings revealed a highly connected and interpretable network, with three separate clusters identified of the modelled variables. Depression, anxiety and behavioural difficulties were the most central variables of the network. Depression, anxiety and restricted repetitive and stereotyped patterns behaviours (RRBs) were the strongest bridging variables in the network model, transmitting activation both within and between other symptom clusters. The results highlight that depression and anxiety were highly connected symptoms within the network, suggesting support in these areas could be helpful, as well as future research.
Curcumin coating: a novel solution to mitigate inherent carbon nanotube toxicity
Authors: Rele Samiksha , Thakur Chanchal Kiran , Khan Fatima , Baral Budhadev , Saini Vaishali , Karthikeyan Chandrabose , Moorthy N. S. Hari Narayana , Jha Hem Chandra 
Published: March 2024

Abstract
Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1β, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.

Graphical Abstract
(a) Synthesis of Curcumin-coated-Lysine-functionalized MWCNTs. (b) Flow of research depicting experimental groups and studies performed along with the underlying techniques used.