bluuebunny/crossref_metadata_2025_split huggingface dataset:
TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids
Authors: Sun Yi , Maggs Luke , Panda Apekshya , Wright Samuel J. , Cicerchia Angelina M. , Jenney Anne , Perricone Matthew D. , Mills Caitlin E. , Cattaneo Giulia , Ventin Marco , Chen Feng , Rasmussen Martin Q. , Miranda Alex , Revach Or-Yam , Fang Jacy , Fu Amina , Bowling Peter J. , Sharova Tatyana , Lawless Aleigha , Sorger Peter K. , Bardeesy Nabeel , Wang Xinhui , Flaherty Keith T. , Boland Genevieve M. , Mehta Arnav , Sade-Feldman Moshe , Ferrone Cristina R. , Jenkins Russell W. 
Published: January 2025

Abstract
Novel therapeutic strategies are needed to improve the efficacy of chimeric antigen receptor (CAR) T cells as a treatment of solid tumors. Multiple tumor microenvironmental factors are thought to contribute to resistance to CAR T-cell therapy in solid tumors, and appropriate model systems to identify and examine these factors using clinically relevant biospecimens are limited. In this study, we examined the activity of B7-H3–directed CAR T cells (B7-H3.CAR-T) using 3D microfluidic cultures of patient-derived organotypic tumor spheroids (PDOTS) and then confirmed the activity of B7-H3.CAR T cells in PDOTS. Although B7-H3 expression in PDOTS was associated with B7-H3.CAR-T sensitivity, mechanistic studies revealed dynamic upregulation of co-inhibitory receptors on CAR T-cells following target cell encounter that led to CAR T-cell dysfunction and limited efficacy against B7-H3–expressing tumors. PD-1 blockade restored CAR T-cell activity in monotypic and organotypic tumor spheroids with improved tumor control and upregulation of effector cytokines. Given the emerging role of TANK-binding kinase 1 (TBK1) as an immune evasion gene, we examined the effect of TBK1 inhibition on CAR T-cell efficacy. Similar to PD-1 blockade, TBK1 inhibition restored CAR T-cell activity in monotypic and organotypic tumor spheroids, prevented CAR T-cell dysfunction, and enhanced CAR T-cell proliferation. Inhibition or deletion of TBK1 also enhanced the sensitivity of cancer cells to immune-mediated killing. Taken together, our results demonstrate the feasibility and utility of ex vivo profiling of CAR T cells using PDOTS and suggest that targeting TBK1 could be used to enhance CAR T-cell efficacy by overcoming tumor-intrinsic and -extrinsic resistance mechanisms.
Evaluating Ovarian Cancer Risk–Reducing Salpingectomy Acceptance: A Survey
Authors: Lukey Alexandra , Sowamber Ramlogan , Huntsman David , Pearce Celeste Leigh , Howard A. Fuchsia , Meza Rafael , Law Michael R. , Phung Minh Tung , Hanley Gillian E. 
Published: January 2025

Abstract
With evidence that salpingectomy is effective in preventing high-grade serous carcinoma, it is time to consider offering this procedure to people at higher-than-average lifetime risk for ovarian cancer, despite not having a pathogenic genetic variant that increases the risk for ovarian cancer. This targeted approach has potential to be effective at reducing ovarian cancer incidence, and unlike opportunistic salpingectomy, it is focused on people with an increased lifetime risk of ovarian cancer. However, the acceptability of this approach within the population of potential patients remains unknown. We conducted an online survey of adults in British Columbia, Canada, who were defined as “at risk” for ovarian cancer (i.e., people born with ovaries). Participants completed a questionnaire on demographics, ovarian cancer risk and protective factors, concerns about risk-reducing salpingectomy (RSS), and the risk they considered high enough to warrant RRS. We included 211 participants. Among these participants, 42% (n = 88) indicated that they would consider RRS at any lifetime risk or any risk above the population average. Another 20 participants chose risks between 1.5% and 4% for a cumulative 51% of the sample choosing risks below thresholds for oophorectomy. In contrast, 6% (n = 12) indicated that they would not consider the procedure at any risk level. None of the factors collected were associated with the likelihood that a person would find RRS acceptable. Overall, our participants showed broad interest in RRS as an ovarian cancer prevention strategy. These results suggest that there would likely be uptake if RRS was offered.

Significance:
This study found that many participants were willing to consider RRS to prevent ovarian cancer. Further research on RRS should be undertaken to understand how this can be best used for ovarian cancer prevention.
Differential Neural Mechanisms Underlying Inhibition of Color and Dynamic Motion Distractors
Authors: van Moorselaar Dirk , Wang Ningkai , Theeuwes Jan 
Published: January 2025

Abstract
Navigating visually complex environments requires focusing on relevant information while filtering out (salient) distractions. The signal suppression hypothesis posits that salient stimuli generate an automatic saliency signal that captures attention unless overridden by learned suppression mechanisms. In support of this, ERP studies have demonstrated that salient stimuli that do not capture attention elicit a distractor positivity (PD), a putative neural index of suppression. Yet, to date, this hypothesis has been primarily tested with color singletons, leaving it unclear if the PD reflects general suppression or is specific to color singletons. This study compared lateralized ERPs elicited by color singleton and dynamic motion distractors using a variant of the additional singleton paradigm that has been shown to result in proactive suppression of colored distractors. Behavioral results showed a singleton presence benefit for both distractor types, indicating distractor suppression. However, ERP data revealed clear differences in the underlying neural mechanisms: Color singletons elicited a PD component indicative of proactive suppression, whereas motion singletons elicited a later positivity preceded by an N2pc, suggesting reactive suppression. Our findings suggest that motion singletons, unlike color singletons, are suppressed reactively after initial capture. This study highlights the importance of considering distractor feature dimensions in understanding attentional suppression mechanisms and underscores the need for caution in establishing proactive suppression based on a single metric. Further research is needed to clarify the conditions under which the early PD reliably indicates proactive suppression and to explore the neural processes underlying the suppression of various salient distractors.
Understanding Visual Perception
Authors: Purves Dale 
Published: January 2025

Abstract
Visual perception can be thought of in two fundamentally different ways: (1) that what we see is determined by circuitry for detecting and representing object features and conditions in the physical world or (2) that what we see is determined empirically by neural associations based on the relative success of accumulated trial-and-error behavior. The evidence reviewed here indicates that the qualities we perceive are determined empirically. The reasons for this way of seeing are discussed.
Gradual Domain Adaptation via Normalizing Flows
Authors: Sagawa Shogo , Hino Hideitsu 
Published: January 2025

Abstract
Standard domain adaptation methods do not work well when a large gap exists between the source and target domains. Gradual domain adaptation is one of the approaches used to address the problem. It involves leveraging the intermediate domain, which gradually shifts from the source domain to the target domain. In previous work, it is assumed that the number of intermediate domains is large and the distance between adjacent domains is small; hence, the gradual domain adaptation algorithm, involving self-training with unlabeled data sets, is applicable. In practice, however, gradual self-training will fail because the number of intermediate domains is limited and the distance between adjacent domains is large. We propose the use of normalizing flows to deal with this problem while maintaining the framework of unsupervised domain adaptation. The proposed method learns a transformation from the distribution of the target domains to the gaussian mixture distribution via the source domain. We evaluate our proposed method by experiments using real-world data sets and confirm that it mitigates the problem we have explained and improves the classification performance.
Aposematism vs. scavenging? camera trapping unveils low and seasonal-dependent consumption of toxic salamander carcasses by wild boars
Authors: Velo-Antón Guillermo , Ledo María Comesaña , Pardavila Xosé 
Published: January 2025

Abstract
Aposematic species rely on primary and secondary antipredator strategies. Yet, some opportunistic and generalist species may consume them, although this has been largely supported by indirect evidence such as dietary analyses or clay model experiments. Here, we studied the role of the wild boar, Sus scrofa, as a consumer and possible predator of an aposematic and toxic salamander, Salamandra salamandra gallaica. We investigated this behaviour using camera traps and salamander carcasses on a small island where both species co-occur. Our results show a very low proportion of salamanders consumed by wild boars (3.8%), which indicates that fire salamanders might not completely rely on their aposematic strategy to avoid being consumed by this generalist species. The number of predation events does not differ between wild boar age classes, but it does between seasons, with a higher consumption in spring, which can be associated with an increase in animal consumption when fruits (e.g., acorns) are no longer available on this island. We also highlight the need for temporal studies targeting predator-prey interactions through behavioural data and complementary approaches to better understand the possible impact of opportunistic and generalist species in the ecosystem. This is particularly important in management plans involving the control of generalist species such as the wild boar, which is considered one of the most invasive species globally and a threat to countless species worldwide.
Response of juvenile male and female guppies to acute predation cues
Authors: Dumaresq Synnott Félixe , Brusseau Alix J.P. , Crane Adam L. , Brown Grant E. 
Published: January 2025

Abstract
Within aquatic ecosystems, chemosensory cues are widely used as publicly available risk assessment information, allowing prey to optimize behavioural decisions. In sexually dimorphic species, males and females often have different responses to local predation threats. According to the ‘distracted male’ hypothesis, reproductively active males should show a reduced response to risk cues compared to conspecific females due to the potentially high costs of lost courtship and mating opportunities among males. Recent evidence supports this hypothesis, showing that adult male guppies (Poecilia reticulata) show a reduced or absent response to chemosensory risk cues. Here, we further test the ‘distracted male’ hypothesis by testing non-reproductive male and female guppies, collected from the Lopinot River (high predation) or the Upper Aripo River (low predation). We found that juvenile male and female guppies exhibited similar response patterns. Consistent with our predictions, both juvenile male and female guppies collected from a high predation site exhibited a similar antipredator response (reduced number of lines crossed) when exposed to conspecific alarm cues or a novel odour (vs. water control). Those collected from a low predation site showed similar responses to conspecific alarm cues and no response to a novel odour or the water control. Combined, our results suggest that unlike adult guppies, non-reproductive male and female guppies make similar behavioural decisions in response to acute predation cues. As predicted by the ‘distracted male’ hypothesis, the previously reported absence of a response to chemosensory risk assessment cues among adult males may be due to a devaluation of risk assessment information in favour of continued mating.
Probiotic viability in the gastrointestinal tract in a randomised placebo controlled trial: combining molecular biology and novel cultivation techniques
Authors: Sen A. , Kimura M. , Ejima R. , Arai S. , Mitsuyama E. , Kaneko H. , Mishima R. , Muto N. , Hiraku A. , Kato K. , Kuwano Y. , Maruyama H. , Nakamura M. , Iwabuchi N. , Nakano M. , Odamaki T. , Tanaka M. 
Published: January 2025

Abstract
Understanding the viability of ingested probiotics within the gastrointestinal tract is essential for evaluating their efficacy and deciphering their mechanisms of action. Detecting Bifidobacterium longum subspecies longum BB536 is particularly challenging owing to its indistinguishability from the naturally abundant B. longum species in the human gut. We aimed to address this challenge by developing a selective culture medium for B. longum BB536 and employing a propidium monoazide-quantitative polymerase chain reaction (PMA-qPCR) method to verify the survival of the probiotic after consumption. To achieve this, we designed a novel lactose-mupirocin-trimethoprim (LMT) medium that facilitates the cultivation of B. longum BB536 under anaerobic conditions at 42 °C. We screened 52 healthy adults and enrolled 39 who met the eligibility criteria. The participants were randomised into two groups, with 34 completing the protocol: 17 received commercial yogurt containing B. longum BB536 (9.30 log10 cfu/day) and 17 received a placebo. Prior to the intervention, B. longum BB536 was undetectable in all participants. However, following supplementation, LMT culturing identified viable B. longum BB536, with average counts of 6.33 ± 0.69 log10 cfu/g on day 3 and 6.16 ± 0.74 log10 cfu/g on day 17. PMA–qPCR further validated these results, showing viable cell counts of 6.09 ± 0.68 log10 cells/g wet faeces on day 3 and 6.44 ± 0.64 log10 cells/g wet faeces on day 17. While each method detected B. longum BB536 in some participants where the other did not, no participant tested negative by both methods at any time point. This complementarity between LMT culturing and PMA–qPCR ensures a comprehensive detection strategy, confirming the presence and resilience of B. longum BB536 in the gastrointestinal tract and underscoring its potential as a beneficial probiotic strain (UMIN000052110).
Japan Conference of Clinical Research: registration number: BYG2B-01; University Hospital Medical Information Network: study protocol registration UMIN000052110.
Flies and beetles-mediated transmission of pathogens in domestic pigs: a systematic review
Authors: Makovska I. , Chantziaras I. , Dhaka P. , Courtens L. , Kox L. , Dewulf J. 
Published: January 2025

Abstract
The presence of flies and beetles in pig farms is common and raises concerns about their potential role in pathogen transmission. These concerns become even more significant when live insect larvae are used as animal feed. If not fully consumed by pigs, the larvae may remain on the farm, develop into adults, and thereby pose health risks. In order to implement effective biosecurity measures on farms, it is important to have a comprehensive understanding of how these insects contribute to pathogen transmission. This systematic review, conducted in accordance with PRISMA guidelines, seeks to evaluate the available evidence regarding the role of flies and beetles in transmitting pathogens to domestic pigs. A comprehensive search of PubMed®, Scopus, and Web of Science databases, focusing on peer-reviewed literature published between 2007 and 2023 in Europe and North America was conducted. The search identified 1,062 initial records, of which 39 articles met the inclusion criteria after screening and evaluation. Among the selected studies, 87% (34/39) focused exclusively on flies, 3% (1/39) focused on beetles, and 10% (4/39) included both. Flies were mainly identified as mechanical vectors for 26 pathogenic agents, including viruses, bacteria, and parasites while beetles were associated with the potential transmission of two viruses and one bacterium. Overall, only three studies provided evidence of pathogen transmission (African Swine Fever Virus, Porcine Reproductive and Respiratory Syndrome Virus, and Vesicular Stomatitis New Jersey Virus), which were based on experimental studies involving flies, and one study documented canthariasis caused by Tenebrio molitor larvae. In conclusion, this review identified a number of pathogenic agents that may be transmitted by insects to domestic pigs. The review also demonstrated a scarcity of studies that have convincingly proven the role of insects in pathogen transmission.
Osteochondral Allograft Transplantation as a Salvage Procedure After Failed Index Cartilage Surgery of the Knee: A Systematic Review
Authors: Gopinatth Varun , Tartibi Sina , Smith Matthew V. , Matava Matthew J. , Brophy Robert H. , Knapik Derrick M. 
Published: January 2025

Background: Osteochondral allograft transplantation (OCA) is well established as a viable chondral restoration procedure for the treatment of symptomatic, focal chondral defects of the knee. The efficacy of secondary OCA in the setting of failed index cartilage repair or restoration is poorly understood. Purpose: To evaluate radiographic and clinical outcomes, failures, and reoperations after OCA after failed index cartilage repair or restoration of the knee. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was conducted in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was conducted by querying PubMed, MEDLINE, Scopus, the Cochrane Database for Systematic Reviews, and the Cochrane Central Register for Controlled Trials databases from inception through September 2023 to identify studies reporting on outcomes of patients undergoing OCA after failed index chondral repair or restoration. Results: A total of 6 studies, entailing 349 patients, met inclusion criteria. The mean patient age was 34.6 ± 10.2 years. The mean chondral defect size at the time of secondary OCA was 5.8 cm2 (range, 4.0-9.5 cm2), and the most common defect location was the medial femoral condyle (53.6%; n = 171/319). The most common index chondral procedures were marrow stimulation (73.8%; n = 256/347 patients), OCA (11.8%; n = 41/347), and autologous chondrocyte implantation (4.9%; n = 17/347). The overall failure rate after secondary OCA was 16.6% (95% CI, 8.8%-24.4%). The overall reoperation rate was 42.8% (95% CI, 31.7%-53.9%). Failure and reoperation rates were associated with increasing chondral defect size ( P < .01). Defects 9-10 cm2 had a reoperation rate of 67% and a failure rate of 39%. The 5-year survival rate after secondary OCA was 79% to 87.8%, and the 10-year survival rate was 61% to 82%. A total of 42 clinical outcome scores were reported, and 71.0% (n = 22/31) of patient-reported outcome measures yielded significant improvement from preoperative to postoperative levels for patients undergoing secondary OCA. Conclusion: After index chondral surgery, the overall failure rate after secondary OCA was 16.6%, with an overall reoperation rate of 42.8%. The majority of clinical outcomes reported suggest improvement when compared with preoperative values. Larger chondral defects may be associated with higher rates of failure and reoperation.
Malpractice Liability Exposure and the Sports Medicine Team Physician: Caring for Professional Athletes in the National Football League, Major League Baseball, and National Hockey League
Authors: Pang Michael , Hasan Sayyida S. , Woo Joshua J. , Olsen Reena J. , Ramkumar Prem N. 
Published: January 2025

Background: Orthopaedic surgeons play a critical role in ensuring the health and safety of professional athletes. Despite the privilege of treating elite athletes, there exists great financial exposure to individual physicians in the event of a malpractice lawsuit. Hypothesis/Purpose: The purpose of this study was to evaluate and model malpractice liability exposure of the sports medicine surgeon caring for athletes in the National Football League (NFL), Major League Baseball (MLB), and National Hockey League (NHL) with respect to player position and additional supplemental malpractice insurance needs. It was hypothesized that routine liability coverage cannot adequately address the demands of caring for elite athletes in professional sports leagues. Study Design: Economic and Decision Analysis; Level of evidence, 3. Methods: In total, 2447 NFL, 992 MLB, and 980 NHL player contracts from the 2022-2023 season were aggregated from a publicly available online database. Position, team, total contract value, and mean yearly salary were noted. Risk ratios were calculated with respect to 1 million US dollars (USD) and 3 million USD of annual occurrence-based malpractice liability awards and used to generate a “covered-to-treat” analysis. Supplemental malpractice liability insurance was quantified. Results: Assuming 1 million and 3 million USD occurrence-based awards covered by malpractice liability insurance, team physicians can fully treat 17.3% and 50.0% of NFL players, 43.2% and 59.7% of MLB players, and 13.6% and 41.0% of NHL players, without incurring additional personal financial risk, from a risk-based medicolegal model. Liability policies of 52.6 million, 108.1 million, and 64.1 million USD are required to treat 95% of NFL, MLB, and NHL players, respectively. Positions carrying the greatest risk ratios are quarterback (QB) (9.9) in the NFL, right field (15.1) in the MLB, and center (5.7) in the NHL. Conclusion: Sports medicine specialists caring for elite athletes face potential personal financial risk due to insufficient medicolegal coverage. While coverage may vary among different practice settings including private, academic, or public state institutions, medical malpractice risk is crucial in partnerships between sports franchises, hospitals, players, agents, and physicians to protect sports medicine physicians and offer the highest-quality care.
Transtracheal Ultrasound as a Preventive Tool for ETT Related Adverse Events and Malpositioning in the ICU
Authors: Yamane David , Dela Cruz Philip , Wilby Mary Heekin , Ivanovic Sasa , Munoz Mark , Hawkins Katrina , Davison Danielle 
Published: January 2025

Introduction Endotracheal tube (ETT) malpositioning can result in a myriad of complications. Daily chest radiographs (CXR) is the gold standard in monitoring these complications. Point-of-care transtracheal ultrasound (TTUS) is an emerging imaging modality for ETT positioning. We compared ETT malpositioning related adverse events and diagnostic accuracy of ETT malpositioning of a combined TTUS and CXR surveillance protocol to CXR alone. Methods We performed a randomized control trial of mechanically ventilated patients in an academic multidisciplinary ICU. In the intervention group, the clinical team was provided the results of the TTUS with CXR results to aid in clinical decision making. In the control group only CXR results were used. Adverse events included bronchial migration, vocal cord herniation, balloon rupture, unplanned extubation, and the development of aspiration pneumonia. Data was analyzed via Fisher's Exact Test. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated.