bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative risk factors for blood transfusion in women requiring surgical management of ectopic pregnancy: a retrospective cohort study
Authors: Cullifer Rachel , Johnson Christina , Huynh Terri , Yeonjoo Yi , Pacis Michelle , Hoffman Matthew , Swartz Sarah , Makai Gretchen 
Published: November 2024

ObjectiveThis study identifies preoperative risk factors associated with blood transfusion in women undergoing surgery for ectopic pregnancy. A retrospective chart review of 252 cases was performed at a single academic-affiliated community hospital system between January 2014 and October 2017. Univariate analysis was performed using non-parametric testing where appropriate, and significant variables were incorporated in multivariate modelling.MethodsIn this cohort of 252 women, the overall transfusion rate was 8.7% (n=22). Increasing age (OR 1.12, 95% CI 1.03 to 1.22), lower systolic blood pressure (SBP) on presentation (OR 0.96, 95% CI 0.93 to 1.00), lower minimum systolic and diastolic blood pressure (DBP) (OR 0.92, 95% CI 0.89 to 1.95 and OR 0.9, 95% CI 0.84 to 0.93) and lower preoperative haemoglobin (g/L) (OR 0.46, 95% CI 0.33 to 0.62) were associated with higher rates of blood transfusion. Women who had prior care in their current pregnancy and women treated in a women’s specific emergency room (compared with a general emergency room) were less likely to be transfused (OR 0.16, 95% CI 0.05 to 0.51 and OR 0.09, 95% CI 0.03 to 0.30, respectively). Our study used a model in which variance in transfusion can reliably be explained by location of presentation to care, pain alone as a presenting complaint and haemoglobin level (Area under the curve (AUC) =0.87).ConclusionHistory of caesarean section and a presenting complaint of pain alone are newly identified indicators for women at higher risk of transfusion at the time of surgical management of ectopic pregnancy. Additionally, care provided in women’s specific emergency rooms may decrease the risk of blood transfusion in this population.
Phase I dose escalation study of IO-108, an anti-LILRB2 antibody, in patients with advanced solid tumors
Authors: Taylor Matthew H , Naing Aung , Powderly John , Woodard Paul , Chung Luke , Lin Wen Hong , Tian Hongyu , Siemers Nathan , Xiang Hong , Deng Rong , Hong Kyu , Valencia Donna , Huang Tao , Zhu Ying , Liao X Charlene , Schebye Xiao Min , Patel Manish R 
Published: November 2024

PurposeIn this first-in-human dose escalation study, the safety and efficacy of IO-108, a fully human monoclonal antibody targeting leukocyte immunoglobulin-like receptor B2 (LILRB2), was investigated in patients with advanced solid tumors as monotherapy and in combination with pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody.MethodsThe study included patients with histologically or cytologically confirmed advanced and relapsed solid tumors, with measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1. Patients were treated with escalating doses of IO-108 every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. Safety and tolerability were the primary objectives. Secondary and exploratory objectives included: pharmacokinetics, clinical efficacy, immunogenicity and biomarkers.ResultsOf 25 patients enrolled, 12 were treated with IO-108 monotherapy and 13 received combination therapy. IO-108 was well-tolerated up to the maximally administered dose of 1,800 mg every 3 weeks (Q3W) as monotherapy and in combination with pembrolizumab. No dose-limiting toxicity was observed, and a maximum tolerated dose was not reached. Treatment-related adverse events (TRAEs) occurred in 6 (50.0%) patients treated with IO-108 monotherapy and 6 (46.2%) patients treated with IO-108+pembrolizumab. All TRAEs were mild or moderate (Grade 1 or 2), and no TRAEs led to treatment discontinuation or death. IO-108 exhibited a dose-proportional increase in exposure. Full receptor occupancy (RO) in peripheral blood was achieved at doses ≥600 mg. The overall response rate was 9% (1/11) in the monotherapy and 23% (3/13) in the combination therapy. A patient with treatment-refractory Merkel cell carcinoma treated with IO-108 monotherapy achieved a durable complete response (CR) for more than 2 years. Pharmacodynamic gene expression changes reflecting increased tumor infiltration of T cells were associated with clinical benefits in both monotherapy and combination therapy. Additionally, baseline tumor inflammation gene signature (TIS) scores correlated with clinical benefit.ConclusionIO-108 is well tolerated and has led to objective response as monotherapy and in combination with pembrolizumab. The complete response and the pharmacodynamic changes in the monotherapy cohort demonstrate single agent activity of IO-108 and provide proof of concept that targeting myeloid-suppressive pathways through LILRB2 inhibition may potentiate the clinical efficacy of anti-PD-1 immune checkpoint inhibitors.Trial registration numberNCT05054348.
Development of a predictive model for systemic lupus erythematosus incidence risk based on environmental exposure factors
Authors: Zhang Ying , Zhao Cheng , Lei Yu , Li Qilin , Jin Hui , Lu Qianjin 
Published: November 2024

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterised by a loss of immune tolerance, affecting multiple organs and significantly impairing patients’ health and quality of life. While hereditary elements are essential in the onset of SLE, external environmental influences are also significant. Currently, there are few predictive models for SLE that takes into account the impact of occupational and living environmental exposures. Therefore, we collected basic information, occupational background and living environmental exposure data from patients with SLE to construct a predictive model that facilitates easier intervention.MethodsWe conducted a study comparing 316 individuals diagnosed with SLE and 851 healthy volunteers in a case–control design, collecting their basic information, occupational exposure history and environmental exposure data. Subjects were randomly allocated into training and validation groups using a 70/30 split. Using three-feature selection methods, we constructed four predictive models with multivariate logistic regression. Model performance and clinical utility were evaluated via receiver operating characteristic, calibration and decision curves. Leave-one-out cross-validation further validated the models. The best model was used to create a dynamic nomogram, visually representing the predicted relative risk of SLE onset.ResultsThe ForestMDG model demonstrated strong predictive ability, with an area under the curve of 0.903 (95% CI 0.880 to 0.925) in the training set and 0.851 (95% CI 0.809 to 0.894) in the validation set, as indicated by model performance evaluation. Calibration and decision curves demonstrated accurate results along with practical clinical value. Leave-one-out cross-validation confirmed that the ForestMDG model had the best accuracy (0.8338). Finally, we developed a dynamic nomogram for practical use, which is accessible via the following link:https://yingzhang99321.shinyapps.io/dynnomapp/.ConclusionWe created a user-friendly dynamic nomogram for predicting the relative risk of SLE onset based on occupational and living environmental exposures.Trial registration numberChiCTR2000038187.
A study of stable wormhole solution with non-commutative geometry in the framework of linear $$f(R,{\mathcal {L}}_m, T)$$ gravity
Authors: Loewer Niklas , Tayde Moreshwar , Sahoo P. K. 
Published: November 2024

AbstractThis research delves into the potential existence of traversable wormholes (WHs) within the framework of modified, curvature based gravity. The modification includes linear perturbations of the matter Lagrangian and the trace of the energy-momentum tensor with specific coupling strengths $$\alpha $$
α
and $$\beta $$
β
and can thus be viewed as a special case of linear f(R, T)-gravity with a variable matter coupling or as the simplest additively separable $$f(R,{\mathcal {L}}_m,T)$$

f
(
R
,

L
m

,
T
)

-model. A thorough examination of static WH solutions is undertaken using a constant redshift function; therefore, our work can be regarded as the first-order approximation of WH theories in $$f(R,{\mathcal {L}}_m,T)$$

f
(
R
,

L
m

,
T
)

. The analysis involves deriving WH shape functions based on non-commutative geometry, with a particular focus on Gaussian and Lorentzian matter distributions $$\rho $$
ρ
. Constraints on the coupling parameters are developed so that the shape function satisfies both the flaring-out and asymptotic flatness conditions. Moreover, for positive coupling parameters, violating the null energy condition (NEC) at the WH throat $$r_0$$

r
0

demands the presence of exotic matter. For negative couplings, however, we find that exotic matter can be avoided by establishing the upper bound $$\beta +\alpha /2<-\frac{1}{\rho r_0^2}-8\pi $$

β
+
α
/
2
<
-

1

ρ

r
0
2

-
8
π

. Additionally, the effects of gravitational lensing are explored, revealing the repulsive force of our modified gravity for large negative couplings. Lastly, the stability of the derived WH solutions is verified using the Tolman–Oppenheimer–Volkoff (TOV) formalism.
Geothermal potential in the Croatian Part of Pannonian Basin: mapping geothermal plays
Authors: Novak Zelenika Kristina , Gluhak Popović Barbara , Pleić Marija , Durn Tatjana 
Published: November 2024

The Croatian part of the Pannonian Basin System (CPBS) represents the southwestern margin of the Pannonian Basin, characterized by a high geothermal gradient (4.9°C/100 m). There is a rich tradition of using geothermal aquifers for balneological, recreational and medicinal purposes. The estimation of geothermal potential is crucial at a time when Europe is increasingly turning to renewable energy sources.
There are three main geothermal plays in the CPBS: pre-rift, syn-rift and post-rift play. Temperature maps were created for each geothermal play. Temperature measurements in a total of 75 wells were used as input data. A correlation between depth and temperature was established and the assumption that the highest temperatures are to be expected in the deepest parts of the basins for all three geothermal plays was confirmed.
Temperature maps of the pre-rift, syn-rift and post-rift geothermal plays were created by applying the depth-temperature functions on the depth maps. The highest temperatures of the pre-rift, syn-rift and post-rift plays are expected in the deepest parts of the Drava and Sava basins.
Masquerade: Verifiable Multi-Party Aggregation with Secure Multiplicative Commitments
Authors: Mouris Dimitris , Tsoutsos Nektarios Georgios 
Published: November 2024

In crowd-sourced data aggregation over the Internet, participants share their data points with curators. However, a lack of strong privacy guarantees may discourage participation, which motivates the need for privacy-preserving aggregation protocols. Moreover, existing solutions remain limited with respect to public auditing without revealing the participants’ data. In realistic applications, however, there is an increasing need for public verifiability (i.e., verifying the protocol correctness) while preserving the privacy of the participants’ inputs, since the participants do not always trust the data curators. At the same time, while publicly distributed ledgers may provide public auditing, these schemes are not designed to protect sensitive information.
In this work, we introduce two protocols, dubbed Masquerade and zk-Masquerade, for computing private statistics, such as sum, average, and histograms, without revealing anything about participants’ data. We propose a tailored multiplicative commitment scheme to ensure the integrity of data aggregations and publish all the participants’ commitments on a ledger to provide public verifiability. zk-Masquerade detects malicious participants who attempt to poison the aggregation results by adopting two zero-knowledge proof protocols that ensure the validity of shared data points before being aggregated and enable a broad range of numerical and categorical studies. In our experiments, we use homomorphic ciphertexts and commitments for a variable number of participants and evaluate the runtime and the communication cost of our protocols.
PEG-BCT-100 and canavanine synergistically induce apoptosis in arginine biosynthetic enzyme-deficient pancreatic cancer
Authors: Kwong Tsz Tung , Deng Hao Hao , Wong Chi-Hang , Chan Anthony W.H. , Chan Landon Long , Chok Siu-Ho K. , Cheng Paul N. , Chan Stephen 
Published: November 2024

Abstract
Arginine deprivation using arginase emerges as a potential cancer treatment approach, as some cancers have been found to be arginine-auxotrophic, relying on exogenous arginine for their growth. In this study, we evaluated the combination of a pegylated recombinant human arginase (PEG-BCT-100), which is currently undergoing clinical trials with a toxic arginine analog, canavanine in pancreatic cancer. Remarkable synergistic anti-tumor effect was observed both in vitro and in vivo. Specifically, the combination treatment induced apoptotic cell death in pancreatic cancer cells, while normal fibroblast cells remained viable. Our findings also suggested that pancreatic tumors lacking the key enzymes in arginine biosynthesis, argininosuccinate synthetase 1 (ASS1) and ornithine transcarbamylase (OTC) were more susceptible to the treatment. From our in-house cohort and online database analysis, we found that the majority of the pancreatic cancer patients exhibited deficiencies in both ASS1 and OTC enzymes, suggesting that the combination of arginine deprivation and canavanine could be particularly effective in these patients. The ASS1- and OTC-negativity could also serve as predictive biomarkers for the response in other arginine-dependent cancers.
Renal Proximal Tubule Cell-Specific Megalin Deletion Does Not Affect Atherosclerosis But Induces Tubulointerstitial Nephritis in Mice Fed a Western Diet
Authors: Amioka Naofumi , Franklin Michael K. , Kukida Masayoshi , Zhu Liyuan , Moorleghen Jessica J. , Howatt Deborah A. , Katsumata Yuriko , Mullick Adam E. , Yanagita Motoko , Martinez-Irizarry Michelle M. , Sandoval Ruben M. , Dunn Kenneth W. , Sawada Hisashi , Daugherty Alan , Lu Hong S. 
Published: November 2024

BACKGROUND:
Pharmacological inhibition of megalin (also known as LRP2 [low-density lipoprotein receptor-related protein-2]) attenuates atherosclerosis in hypercholesterolemic mice. Since megalin is abundant in renal proximal tubule cells (PTCs), the purpose of this study was to determine whether PTC-specific deletion of megalin reduces hypercholesterolemia-induced atherosclerosis in mice.

METHODS:

Female
Lrp2
f/f mice were bred with male
Ndrg1
-
Cre ERT2
+/0 mice to develop PTC-LRP2 +/+ and PTC-LRP2 −/− littermates. To study atherosclerosis, all mice were bred to an LDL (low-density lipoprotein) receptor −/− background and fed a Western diet to induce atherosclerosis.

RESULTS:
PTC-specific megalin deletion did not attenuate atherosclerosis in LDL receptor −/− mice in either sex. Serendipitously, we discovered that PTC-specific megalin deletion led to interstitial infiltration of CD68+ cells and tubular atrophy. The pathology was only evident in male PTC-LRP2 −/− mice fed a Western diet but not in mice fed a normal laboratory diet. Renal pathologies were also observed in male PTC-LRP2 −/− mice in an LDL receptor +/+ background fed the same Western diet, demonstrating that the renal pathologies were dependent on diet and not on hypercholesterolemia. In contrast, female PTC-LRP2 −/− mice had no apparent renal pathologies. In vivo multiphoton microscopy demonstrated that PTC-specific megalin deletion dramatically diminished ALB (albumin) accumulation in PTCs within 10 days of Western diet feeding. RNA-sequencing analyses demonstrated the upregulation of inflammation-related pathways in the kidney.

CONCLUSIONS:
PTC-specific megalin deletion does not affect atherosclerosis but leads to tubulointerstitial nephritis in mice fed a Western diet, with severe pathologies in male mice.
Patient Preferences for Features Associated With Leadless Versus Conventional Transvenous Cardiac Pacemakers
Authors: Reed Shelby D. , Yang Jui-Chen , Wallace Matthew J. , Sutphin Jessie , Johnson F. Reed , Ozdemir Semra , Delgado Stephanie M. , Goates Scott , Harbert Nicole , Lo Monica , Rajagopalan Bharath , Ip James E. , Al-Khatib Sana M. 
Published: November 2024

BACKGROUND:
Regulatory approval of the first dual-chamber leadless pacemaker system provides patients an alternative to conventional transvenous pacemakers. The study objective was to quantify the preferences of patients for pacemaker features.

METHODS:
Patients with a de novo (ie, initial) pacemaker indication were recruited from 7 US sites to complete a Web-based discrete-choice experiment survey between May 11, 2022, and May 24, 2023. Patients chose between pairs of experimentally designed, hypothetical pacemakers that varied according to type (removable leadless, nonremovable leadless, or conventional transvenous); battery life (5, 8, 12, or 15 years); time since regulatory approval (2 or 10 years); discomfort for 6 months (none or discomfort); and complication risk and infection risk (1%, 5%, or 10%/20% for each). Patients’ choice data were analyzed using random-parameter logit models and latent-class analysis.

RESULTS:

Among 117 participants, the mean (SD) age was 67.3 (14.6) years, 94% were white, and 42% were female. On average, patients’ survey responses revealed a preference for removable leadless pacemakers (β, 0.340; SE, 0.096) over both nonremovable leadless pacemakers (β, −0.310; SE, 0.131;
P
=0.001) and conventional transvenous pacemakers (β, −0.030; SE, 0.119;
P
=0.031). However, latent-class analysis revealed 2 distinct preference classes. One class preferred leadless pacemakers (50.5%), and the other class preferred conventional transvenous pacemakers (49.5%). The conventional pacemaker class prioritized pacemakers with 10 rather than 2 years since regulatory approval (
P
<0.001), whereas the leadless pacemaker class was insensitive to years since regulatory approval (
P
=0.83). Complication risks and infection risks were found to be the most influential. All else equal, patients would accept maximum risks of complications or infections ranging about 5% to 18% to receive their preferred pacemaker type.

CONCLUSIONS:
Latent-class analysis revealed strong patient preferences for the type of pacemaker, with a nearly equal split between recent leadless pacemaker technology and conventional transvenous pacemakers. These findings can inform shared decision-making between health care providers and patients.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT05327101.
A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease
Authors: Derks Wouter , Rode Julian , Collin Sofia , Rost Fabian , Heinke Paula , Hariharan Anjana , Pickel Lauren , Simonova Irina , Lázár Enikő , Graham Evan , Jashari Ramadan , Andrä Michaela , Jeppsson Anders , Salehpour Mehran , Alkass Kanar , Druid Henrik , Kyriakopoulos Christos P. , Taleb Iosif , Shankar Thirupura S. , Selzman Craig H. , Sadek Hesham , Jovinge Stefan , Brusch Lutz , Frisén Jonas , Drakos Stavros , Bergmann Olaf 
Published: November 2024

BACKGROUND:
Cardiomyocytes in the adult human heart show a regenerative capacity, with an annual renewal rate of ≈0.5%. Whether this regenerative capacity of human cardiomyocytes is employed in heart failure has been controversial.

METHODS:

We determined cardiomyocyte renewal in 52 patients with advanced heart failure, 28 of whom received left ventricular assist device support. We measured the concentration of nuclear bomb test–derived
14
C in cardiomyocyte genomic DNA and performed mathematical modeling to establish cardiomyocyte renewal in heart failure with and without LVAD unloading.

RESULTS:
We show that cardiomyocyte generation is minimal in end-stage heart failure patients at rates 18 to 50× lower compared with the healthy heart. However, patients receiving left ventricle support device therapy, who showed significant functional and structural cardiac improvement, had a >6-fold increase in cardiomyocyte renewal relative to the healthy heart.

CONCLUSIONS:
Our findings reveal a substantial cardiomyocyte regeneration potential in human heart disease, which could be exploited therapeutically.
Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS
Authors: Ji Yuekai , Zhang Michael J. , Wang Wendy , Norby Faye L. , Eaton Anne A. , Inciardi Riccardo M. , Alonso Alvaro , Sedaghat Sanaz , Ganz Peter , Van’t Hof Jeremy , Solomon Scott D. , Chaves Paulo H.M. , Heckbert Susan R. , Shah Amil M. , Chen Lin Yee 
Published: November 2024

BACKGROUND:
Coagulation factor XI (FXI) inhibitors are a promising and novel class of anticoagulants, but a recent animal study found that FXI inhibition exacerbated diastolic dysfunction and heart failure (HF). In the ARIC study (Atherosclerosis Risk in Communities), we investigated whether plasma FXI level was associated with cardiovascular events and cardiac function.

METHODS:
ARIC was our primary analytic cohort. We included 4471 participants (median age, 75 years; 57% female; 17% Black) who attended visit 5 (2011–2013) with Somalogic-quantified plasma FXI levels and echocardiographic cardiac function. Prevalent HF and atrial fibrillation (AF) cases were defined as having HF or AF diagnosed at or before each participant’s visit 5 exam date. Incident HF and AF events were ascertained through 2021. Associations were assessed using Cox, logistic, and linear regression models. Primary prospective associations were also validated in the CHS (Cardiovascular Health Study) using an orthogonal FXI assay (enzyme-linked immunosorbent assay).

RESULTS:

At ARIC visit 5, there were 665 and 419 participants with prevalent HF and AF, respectively. During a median follow-up of 9 years, there were 580 and 788 incident HF and AF events, respectively. Lower FXI level was associated prospectively with higher incidence of HF (hazard ratio [HR], 1.36 [for each 1-unit decrement of log
2
-transformed FXI level] [95% CI, 1.01–1.83]) but not incident AF, and cross-sectionally with increased odds of AF (odds ratio [OR], 1.96 [95% CI, 1.23–3.07]) but not HF. In age-stratified analyses, decreased FXI was associated with higher incidence of HF in participants ≥75 years of age (HR, 1.57 [95% CI, 1.08–2.28]) but not <75 years of age (HR, 1.11 [95% CI, 0.68–1.79]). The inverse FXI–HF association was validated in CHS (HR, 1.18 [95% CI, 1.02–1.36]). At ARIC visit 5, lower FXI level was also associated with higher prevalence of diastolic dysfunction and worse E/A ratio, left atrial (LA) volume index, LA function, and left ventricular mass index, but not left ventricular ejection fraction or global longitudinal strain.

CONCLUSIONS:
Decreased FXI level is associated with greater incidence of HF, especially in older adults. It is also associated with prevalent AF, worse diastolic function, worse LA function, and greater LA size. More research is needed to assess potential unwanted effects of FXI inhibition on the risk of cardiovascular events and cardiac function.