bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational discovery of co-expressed antigens as dual targeting candidates for cancer therapy through bulk, single-cell, and spatial transcriptomics
Authors: Chekalin Evgenii , Paithankar Shreya , Shankar Rama , Xing Jing , Xu Wenfeng , Chen Bin 
Published: June 2024

Abstract

Motivation
Bispecific antibodies (bsAbs) that bind to two distinct surface antigens on cancer cells are emerging as an appealing therapeutic strategy in cancer immunotherapy. However, considering the vast number of surface proteins, experimental identification of potential antigen pairs that are selectively expressed in cancer cells and not in normal cells is both costly and time-consuming. Recent studies have utilized large bulk RNA-seq databases to propose bispecific targets for various cancers. However, co-expressed pairs derived from bulk RNA-seq do not necessarily indicate true co-expression of both markers in malignant cells. Single-cell RNA-seq (scRNA-seq) can circumvent this issue but the issues in low coverage of transcripts impede the large-scale characterization of co-expressed pairs.

Results
We present a computational pipeline for bsAbs target identification which combines the advantages of bulk and scRNA-seq while minimizing the issues associated with using these approaches separately. We select hepatocellular carcinoma (HCC) as a case study to demonstrate the utility of the approach. First, using the bulk RNA-seq samples in the OCTAD database, we identified target pairs that most distinctly differentiate tumor cases from healthy controls. Next, we confirmed our findings on the scRNA-seq database comprising 39 361 healthy cells from vital organs and 18 000 cells from HCC tumors. The top pair was GPC3–MUC13, where both genes are co-expressed on the surface of over 30% of malignant hepatocytes and have very low expression in other cells. Finally, we leveraged the emerging spatial transcriptomic to validate the co-expressed pair in situ.

Availability and implementation
A standalone R package (https://github.com/Bin-Chen-Lab/bsAbsFinder).
Successful Preoperative Transjugular Intrahepatic Portosystemic Shunt for Portal Decompression in Patients With Inflammatory Bowel Disease and Cirrhosis Requiring Surgical Intervention
Authors: Karime Christian , Vattikonda Asrita , Hashash Jana G , Rosser Barry G , Merchea Amit , Stocchi Luca , Farraye Francis A 
Published: June 2024

Abstract

Background
Colorectal surgery in patients with inflammatory bowel disease (IBD) and cirrhosis has increased morbidity, which may preclude surgery. Preoperative transjugular intrahepatic portosystemic shunt (TIPS) is postulated to reduce surgical risk. In this retrospective single-center study, we characterized perioperative outcomes in patients with IBD and cirrhosis who underwent preoperative TIPS.

Methods
We identified patients with IBD and cirrhosis who had undergone preoperative TIPS for portal decompression between 2010 and 2023. All other indications for TIPS led to patient exclusion. Demographic and medical data were collected, including portal pressure measurements. Primary outcome of interest was perioperative outcomes.

Results
Ten patients met the inclusion criteria. The most common surgical indications were dysplasia (50%) and refractory IBD (50%). TIPS was performed at a median of 47 days (IQR 34–80) before surgery, with reduction in portal pressures (22.5 vs. 18.5 mmHg, P &lt; .01) and portosystemic gradient (12.5 vs. 5.5 mmHg, P &lt; .01). Perioperative complications occurred in 80% of patients, including surgical site bleeding (30%), wound dehiscence (10%), systemic infection (30%), liver function elevation (50%), and coagulopathy (50%). No patients required re-operation, with median length of stay being 7 days (IQR 5.5–9.3). The 30-day readmission rate was 40%, most commonly for infection (75%), with 2 patients having intra-abdominal abscesses and 1 patient with concern for bowel ischemia. Ninety-day and one-year survival was 100% and 90%, respectively. Patients with primary sclerosing cholangitis (PSC)-cirrhosis were noted to have higher perioperative morbidity and a 30-day readmission rate.

Conclusions
In patients with IBD and cirrhosis, preoperative TIPS facilitated successful surgical intervention despite heightened risk. Nevertheless, significant complications were noted, in particular for patients with PSC-cirrhosis.
Multiple stressors lead to complex responses in reproductive behaviors in an African cichlid
Authors: Williams Bethany , Pintor Lauren , Gray Suzanne 
Published: June 2024

Abstract
Exposure to multiple environmental stressors is a common occurrence that can affect organisms in predictable or unpredictable ways. Hypoxia and turbidity in aquatic environments are 2 stressors that can affect reproductive behaviors by altering energy availability and the visual environment, respectively. Here we examine the relative effects of population and the rearing environment (oxygen concentration and turbidity) on reproductive behaviors. We reared cichlid fish (the Egyptian mouthbrooder, Pseudocrenilabrus multicolor) from 2 populations (a swamp and river) until sexual maturity, in a full factorial design (hypoxic/normoxic × clear/turbid) and then quantified male competitive and courtship behaviors and female preference under their respective rearing conditions. Overall, we found that the rearing environment was more important than population for determining behavior, indicating there were few heritable differences in reproductive behavior between the 2 populations. Unexpectedly, males in the hypoxic rearing treatment performed more competitive and courtship behaviors. Under turbid conditions, males performed fewer competitive and courtship behaviors. We predicted that females would prefer males from their own population. However, under the hypoxic and turbid combination females from both populations preferred males from the other population. Our results suggest that reproductive behaviors are affected by interactions among male traits, female preferences, and environmental conditions.
Chronic kidney disease and transvenous cardiac implantable electronic device infection—is there an impact on healthcare utilization, costs, disease progression, and mortality?
Authors: Wright David J , Trucco María Emilce , Zhou Jiani , Wolff Claudia , Holbrook Reece , Margetta Jamie , El-Chami Mikhael F 
Published: June 2024

Abstract

Aims
Cardiac implantable electronic device (CIED) infections are a burden to hospitals and costly for healthcare systems. Chronic kidney disease (CKD) increases the risk of CIED infections, but its differential impact on healthcare utilization, costs, and outcomes is not known.

Methods and results
This retrospective analysis used de-identified Medicare Fee-for-Service claims to identify patients implanted with a CIED from July 2016 to December 2020. Outcomes were defined as hospital days and costs within 12 months post-implant, post-infection CKD progression, and mortality. Generalized linear models were used to calculate results by CKD and infection status while controlling for other comorbidities, with differences between cohorts representing the incremental effect associated with CKD. A total of 584 543 patients had a CIED implant, of which 26% had CKD and 1.4% had a device infection. The average total days in hospital for infected patients was 23.5 days with CKD vs. 14.5 days (P &lt; 0.001) without. The average cost of infection was $121 756 with CKD vs. $55 366 without (P &lt; 0.001), leading to an incremental cost associated with CKD of $66 390. Infected patients with CKD were more likely to have septicaemia or severe sepsis than those without CKD (11.0 vs. 4.6%, P &lt; 0.001). After infection, CKD patients were more likely to experience CKD progression (hazard ratio 1.26, P &lt; 0.001) and mortality (hazard ratio 1.89, P &lt; 0.001).

Conclusion
Cardiac implantable electronic device infection in patients with CKD was associated with more healthcare utilization, higher cost, greater disease progression, and greater mortality compared to patients without CKD.
Does social need fulfillment moderate the association between socioeconomic status and health risk behaviours during pregnancy?
Authors: Weiland Stella , Jansen Danielle E M C , Groen Henk , de Jong Dorien R , Erwich Jan Jaap H M , Berger Marjolein Y , Hoek Annemieke , Peters Lilian L 
Published: June 2024

Abstract
Socioeconomic differences in health risk behaviours during pregnancy may be influenced by social relations. In this study, we aimed to investigate if social need fulfillment moderates the association between socioeconomic status (SES) and health risk behaviours (smoking and/or alcohol consumption) during pregnancy. We used baseline data from the Lifelines Cohort Study merged with data from the Lifelines Reproductive Origin of Adult Health and Disease (ROAHD) cohort. Education level was used to determine SES, categorized into low, middle, and high, with middle SES as the reference category. Social need fulfillment was taken as indicator for social relations and was measured with the validated Social Production Function Instrument for the Level of Well-being scale. The dependent variable was smoking and/or alcohol consumption during pregnancy. Univariable and multivariable logistic regression analysis was conducted to assess the association of SES and social need fulfillment with health risk behaviours and to test for effect modification. We included 1107 pregnant women. The results showed that women with a high SES had statistically significantly lower odds of health risk behaviours during pregnancy. The interaction effect between SES and social need fulfillment on health risk behaviours was not statistically significant, indicating that no moderation effect is present. The results indicate that social need fulfillment does not modify the effect of SES on health risk behaviours during pregnancy. However, in literature, social relations are identified as an important influence on health risk behaviours. More research is needed to identify which measure of social relations is the most relevant regarding the association with health risk behaviours.
Medical occupational check-ups during the COVID-19 pandemic in the European Union
Authors: Fošum Matyáš , Štěpánek Ladislav , Ivanová Kateřina , Nakládalová Marie 
Published: June 2024

Abstract
Given the enormous scale of the COVID-19 pandemic affecting the healthcare sector, limited human resource capacity, and efforts to prevent the spread of COVID-19, occupational health protection could not escape changes. The aim was to identify and compare the regulations regarding the provision of medical occupational check-ups (MOCs) during the pandemic in all European Union member states (EU MS). The study employed the Delphi method, involving experts from EU MS to assess MOC regulations between January 2020 and May 2021. Experts were queried regarding the existence and specifics of MOC regulations, particularly for entrance and periodic MOCs at hazardous and non-hazardous workplaces. Out of the 27 EU MS surveyed, 13 EU MS did not regulate MOCs, while 14 EU MS (51.6%) regulated the provision of MOCs. The regulations were changes in the way MOCs were provided, modifications (postponement in time, alternative provision, e.g. using telemedicine or online connection, or replacing the medical certificate of fitness to work based on the MOC with a declaration by the worker), or interruption without compensation, even for hazardous works. The regulations were in effect for different lengths of time and varied in some countries during the study period. The cumulative duration of MOC interruptions in all EU MS during the study period was 137 months (7.5% of the cumulative study period of 1836 months). Given the different approaches to the provision of MOCs in EU MS, it has proved appropriate to develop an optimal unified framework plan for future similar situations.
Testing the radiation cascade in postglacial radiations of whitefish and their parasites: founder events and host ecology drive parasite evolution
Authors: Brabec Jan , Gauthier Jérémy , Selz Oliver M , Knudsen Rune , Bilat Julia , Alvarez Nadir , Seehausen Ole , Feulner Philine G D , Præbel Kim , Blasco-Costa Isabel 
Published: June 2024

Abstract
Reciprocal effects of adaptive radiations on the evolution of interspecific interactions, like parasitism, remain barely explored. We test whether the recent radiations of European whitefish (Coregonus spp.) across and within perialpine and subarctic lakes promote its parasite Proteocephalus fallax (Platyhelminthes: Cestoda) to undergo host repertoire expansion via opportunity and ecological fitting, or adaptive radiation by specialization. Using de novo genomic data, we examined P. fallax differentiation across lakes, within lakes across sympatric host species, and the contributions of host genetics versus host habitat use and trophic preferences. Whitefish intralake radiations prompted parasite host repertoire expansion in all lakes, whereas P. fallax differentiation remains incipient among sympatric fish hosts. Whitefish genetic differentiation per se did not explain the genetic differentiation among its parasite populations, ruling out codivergence with the host. Instead, incipient parasite differentiation was driven by whitefish phenotypic radiation in trophic preferences and habitat use in an arena of parasite opportunity and ecological fitting to utilize resources from emerging hosts. Whilst the whitefish radiation provides a substrate for the parasite to differentiate along the same water-depth ecological axis as Coregonus spp., the role of the intermediate hosts in parasite speciation may be overlooked. Parasite multiple-level ecological fitting to both fish and crustacean intermediate hosts resources may be responsible for parasite population substructure in Coregonus spp. We propose parasites’ delayed arrival was key to the initial burst of postglacial intralake whitefish diversification, followed by opportunistic tapeworm host repertoire expansion and a delayed nonadaptive radiation cascade of incipient tapeworm differentiation. At the geographical scale, dispersal, founder events, and genetic drift following colonization of spatially heterogeneous landscapes drove strong parasite differentiation. We argue that these microevolutionary processes result in the mirroring of host–parasite phylogenies through phylogenetic tracking at macroevolutionary and geographical scales.
Linking the 1940 U.S. Census to the National Social Life, Health, and Aging Project: Novel Opportunity to Understand the Effects of Early-Life Residential Environment on Cognitive Aging
Authors: Lee Haena , Warren John Robert , Iveniuk James , Riley Alicia , Hawkley Louise , Hanis-Martin Jen , Choi Kyung Won 
Published: June 2024

Abstract

Objectives
The 1940 Census is a valuable resource for understanding various aspects of historical populations in the United States. Recently, the National Social Life, Health and Aging Project integrated 1940 Census data into its extensive data set, providing researchers with an opportunity to explore new avenues of life course investigation. We leverage the newly introduced measures of childhood residential environment and evaluate their potential predictive utility in older adult cognitive functioning net of childhood and adulthood characteristics known to be key risk factors for poor cognition.

Methods
We analyzed 777 respondents who were children in 1940 (age &lt;17) that have been linked to the 1940 U.S. Census. We used childhood geographic location, homeownership status, household composition, and parental nativity as predictors. Cognitive function was measured using the Montreal Cognitive Assessment.

Results
Regression analysis showed that growing up in an urban area was associated with better cognitive function, while being born in the South was linked to poorer cognitive function, even after controlling for childhood health, parental education, educational attainment, stroke, and smoking status. Additionally, childhood multigenerational household was associated with better cognitive function, and childhood family size was associated with poorer cognitive function. However, these associations became statistically insignificant with the inclusion of educational attainment. We did not find homeownership and parental nativity to be associated with cognitive function.

Discussion
The findings may shed light on the potential long-term effects of childhood circumstances on cognitive aging processes. Implications for current literature and directions for future research are discussed.
Chemical induction of DNA demethylation by 5-Azacytidine enhances tomato fruit defense against gray mold through dicer-like protein DCL2c
Authors: Chang Xiaorong , Liu Liyao , Liu Ziwei , Qiao Liping , Shi Ruixi , Lu Laifeng 
Published: June 2024

Abstract
Postharvest decay, primarily caused by pathogenic fungi in ripening fruits and fresh vegetables, poses a challenge to agricultural sustainability and results in significant economic losses. The regulation of the fruit ripening by DNA methylation has been well demonstrated, while defense response of fruit underlying epigenetic regulation against postharvest decay remains uncertain. In the present study, treatment of tomato fruits with the DNA methyltransferase inhibitor 5-Azacytidine (5-Aza) notably decreased their susceptibility to gray mold. Following 5-Aza treatment, we observed a substantial increase in activities of chitinase (CHI) and glucanase (GLU) in tomato fruits, as well as an increase in the expression of the dicer-like SlDCL2 gene family. Suppression of SlDCL2c through double-stranded RNA-induced RNA interference (RNAi) resulted in a decrease in the expression of chitinases CHI3, CHI9, Class V chitinase, and endochitinase 4 by 71%, 29%, 55%, 64%, as well as glucanases Cel1, Cel2, and GluB by 19%, 93%, and 87%, respectively. This was accompanied by decreased activities of resistance-related enzymes, including CHI and GLU. The expression levels of genes phenylalanine ammonia-lyase PAL2, peroxidase POD 12, POD P7, CCR1, CYP84A2, and COMT in phenylpropanoid biosynthesis pathway also decreased by 33%, 53%, 18%, 50%, 30%, and 24% in SlDCL2c-RNAi fruit, resulting in decreased activities of PAL and POD. Consequently, the lesion diameter of gray mold in SlDCL2c-RNAi fruit increased by 55% compared to the control group. Overall, the present study indicated that DNA methyltransferase inhibitor 5-Aza reduces susceptibility of tomato fruit to gray mold through regulation of DCL2c-mediated inducible defense response.
Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells
Authors: Patel Ashna , Kutuzov Mikhail A , Dustin Michael L , van der Merwe P Anton , Dushek Omer 
Published: June 2024

Abstract
CD8+ T cells contribute to immune responses by producing cytokines when their T-cell receptors (TCRs) recognise peptide antigens on major-histocompability-complex class I. However, excessive cytokine production can be harmful. For example, cytokine release syndrome is a common toxicity observed in treatments that activate T cells, including chimeric antigen receptor (CAR)-T-cell therapy. While the engagement of costimulatory receptors is well known to enhance cytokine production, we have limited knowledge of their ability to regulate the kinetics of cytokine production by CAR-T cells. Here we compare early (0–12 h) and late (12–20 h) production of IFN-gg, IL-2, and TNF-a production by T cells stimulated via TCR or CARs in the presence or absence ligands for CD2, LFA-1, CD28, CD27, and 4-1BB. For T cells expressing TCRs and 1st-generation CARs, activation by antigen alone was sufficient to stimulate early cytokine production, while co-stimulation by CD2 and 4-1BB was required to maintain late cytokine production. In contrast, T cells expressing 2nd-generation CARs, which have intrinsic costimulatory signalling motifs, produce high levels of cytokines in both early and late periods in the absence of costimulatory receptor ligands. Losing the requirement for costimulation for sustained cytokine production may contribute to the effectiveness and/or toxicity of 2nd-generation CAR-T-cell therapy.
Coloniality, Race, and Europeanness: Britain’s Borders after Brexit
Authors: Lewicki Aleksandra 
Published: June 2024

Abstract
The scholarship on the politics of immigration often frames governments’ responses to far-right mobilization as a return to border closures and a rowing back on neoliberalism. In this article, I draw on and expand the scholarship on coloniality to address the limitations of this diagnosis. Specifically, I explore the role of political mobilization in the making of the post-Brexit border regime. My research draws on the analysis of legal and policy initiatives between 2020 and 2023 and twenty-three research interviews with individuals who express their opposition to immigration via engagement in think tanks, grassroots organizations and vigilante groups. The interview data indicates multiple connections between these milieus and shows that each engages in action repertoires beyond the nation-state. And while this prompts border closures, the post-Brexit border regime also encodes openings and loopholes for the circulation of financial elites and precariously employed workers. Thus, I argue that state and non-state actors co-produce a neoliberal border regime of stratified rights, partial inclusions, and gradual exclusions. These variegated entitlements draw on and reinvigorate the racial order of coloniality. The post-Brexit immigration regime enables the free mobility of those racialized as “West European,” facilitates disposable labor mobility of those racialized as “Eastern European,” and restricts the movement of those racialized as “non-European.” This racial imaginary does not only operate via binary distinctions of (non)-Britishness but puts people in complex hierarchical relations to “Europeanness.”
Spiritual Fitness and Moral Responsibility in the Contemporary United States Military
Authors: Kellison Rosemary 
Published: June 2024

Abstract
In an effort to increase resilience and decrease moral injury among servicemembers and veterans, the US military has in recent years invested in the promotion of “spiritual fitness” among its members. The military’s definition of spiritual fitness relies heavily on a popular contemporary American conceptualization of spirituality as essentially individual. Military materials strongly imply that spiritually fit servicemembers adopt military values as their own and consequently act in ways that serve the military’s interests. By tying morality so closely to the individual “spirit,” the concept of spiritual fitness serves to locate moral responsibility for harmful acts performed during war within the individual servicemember, obscuring the role that military leadership and the military as an institution play in shaping and constraining servicemembers’ values and actions. This case shows that an ethics-focused approach adds a crucial dimension to religion scholars’ critical analysis of how categories like spirituality are deployed by powerful institutions.