bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension‐specific association of cardio‐ankle vascular index with subclinical left ventricular function in a Chinese population: Danyang study
Authors: Zhang Xue , Li Yibo , Wang Xinyue , Zhou Tianna , Gao Yun , Hua Mulian , Zhang Siqi , Chen Chao , Zhao Xixuan , He Anxia , Liang Junya , Liu Ming 
Published: April 2024

AbstractThe association of cardio‐ankle vascular index (CAVI), with subclinical cardiac dysfunction in hypertensive patients is unclear. We aim to examine their relationship in hypertensive patients compared with that in normotensive subjects. Our study included 1887 subjects enrolled from Danyang between 2018 and 2019. CAVI was measured using VaSera VS‐1500A device. We performed conventional echocardiography to measure ejection fraction (EF) and E/A, tissue Doppler to measure mitral annular early diastolic velocities (e’), and speckle‐tracking to estimate left ventricular (LV) global longitudinal strain (GLS). LV mass index (76.3, 80.0, and 84.0 g/m2), and E/e’ (7.6, 8.2, and 8.8) were increased and GLS (21.1, 21.0, and 20.4%), E/A (1.2, 1.0, and 0.8) and e’ velocity (11.2, 9.4, and 8.2 cm/s) was decreased from tertiles 1–3 of CAVI on unadjusted analyses (P < .001). After adjustment for covariates, GLS, E/A, and e’ were still significantly decreased from tertiles 1–3 of CAVI (P ≤ .04). Further sensitive analyses revealed a similar association pattern for diastolic function but not systolic function. Compared with the lowest tertile, subjects with a top tertile of CAVI were at higher risk of subclinical LV systolic dysfunction in hypertensive patients (OR = 2.61; P = .005). Increased CAVI is associated with worse subclinical diastolic function. However, this relationship of CAVI to subclinical systolic function was more prominent in hypertensive patients.
Litigation with negative expected value suits: An experimental analysis
Authors: Deck Cary , Pecorino Paul , Solomon Michael 
Published: April 2024

AbstractThe existence of lawsuits providing plaintiffs a negative expected value (NEV) at trial has important theoretical implications for signaling models of litigation. The signaling equilibrium possible when there are no NEV suits breaks down because plaintiffs with NEV suits do not have a credible threat to proceed to trial, which undermines the ability to signal type. Using a laboratory experiment, we analyze behavior with and without the possibility of NEV suits. Absent NEV suits, behavior largely follows predicted patterns. However, the possibility of NEV suits is not found to cause the signaling equilibrium to unravel or to cause the dispute rate to increase. Plaintiffs only drop NEV lawsuits three‐fourths of the time, the rejection rate by defendants for revealing demands rises less than predicted and, contra theory, the rejection rate on demands in the semi‐pooling range remains unchanged.
Management of hyperplastic tissue response following connective tissue grafting
Authors: Pohl Snjezana , Gluckman Howard 
Published: April 2024

AbstractObjectiveWhile connective tissue graft shrinkage is a well‐documented post‐transplantation reaction, there is a literature gap concerning hyperplastic tissue response. Despite its infrequent occurrence, investigation is warranted due to its capacity to compromise esthetics, disrupt lip dynamics, and promote food retention. Moreover, efforts to mitigate hyperplastic tissue response often prove challenging, and there is a potential risk of exacerbating gingival tissue rebound.Clinical ConsiderationsThis report presents a potential solution to managing tissue overgrowth after connective tissue grafting in five clinical cases. The patients underwent corrective surgery involving internal excision of excessive tissue while preserving the overlying mucosa. The surgical approach was tailored to excise hyperplastic tissue with minimal trauma, aiming to optimize esthetic outcomes. Subsequent follow‐up assessments spanning 1–5 years demonstrated stable results, with no indications of relapse or recurrence of tissue overgrowth.ConclusionsWithin the limitations of this case series, surgical internal excision holds promise as a viable treatment modality for addressing post‐transplantation hyperplastic tissue response.Clinical SignificanceThis case series addresses the challenge of uncontrolled tissue overgrowth following connective tissue grafting, a concern for which previous attempts have proven unsuccessful. Internal in‐toto excision emerges as a promising approach for effectively eliminating overgrown tissue, offering potential advancements in the clinical management of this complication.
Vincristine‐induced adverse events related to body weight in dogs treated for lymphoma
Authors: Sztukowski Keira E. , Yaufman Zachary , Cook Matthew R. , Aarnes Turi K. , Husbands Brian D. 
Published: April 2024

AbstractBackgroundTraditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs).Hypothesis/ObjectivesEvaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs.AnimalsOne hundred and thirty‐eight dogs with newly diagnosed lymphoma were treated with vincristine.MethodsA multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post‐administration. Data were evaluated using logistic regression or ordinal logistic regression.ResultsThirty‐eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m2. Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37).Conclusions and Clinical ImportanceVincristine dosed at ≤0.6 mg/m2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg.
Oral cinacalcet administration decreases serum ionized calcium and parathyroid hormone concentrations in healthy dogs
Authors: Clark Hannah E. , Trepanier Lauren A. , Wood Michael W. 
Published: April 2024

AbstractCinacalcet is an oral calcimimetic that has potential to non‐invasively treat primary hyperparathyroidism in dogs (Canis lupis familiaris). There is minimal data assessing its efficacy in dogs. This study aimed to determine whether a single dose of cinacalcet decreases serum ionized calcium (iCa), total calcium (tCa), and parathyroid hormone (PTH) concentrations. Twelve dogs received a median dose of 0.49 mg/kg (range 0.30–0.69 mg/kg) cinacalcet per os. Venous blood samples were collected at time 0 (before cinacalcet administration), 3, 8, and 24 h following cinacalcet administration. PTH, iCa, and tCa concentrations were measured at each time point and compared to 0 hour concentrations. A significant (50%) decrease in serum PTH occurred at 3 h with a median PTH of 4.6 pmol/L (range 2.7–10.8) at baseline and 1.65 pmol/L (range 0.5–14.7) at 3 h; p = .005. A significant, but not clinically relevant, decrease in serum iCa from a median baseline of 1.340 mmol/L (range 1.32–1.41) to a 3 h median of 1.325 mmol/L (range 1.26–1.39), p = .043, was also observed. tCa concentrations were not different. This study showed that a single dose of cinacalcet leads to transient decreases in iCa and PTH concentrations in healthy dogs.
Resolving to believe: Kierkegaard's direct doxastic voluntarism
Authors: Quanbeck Z 
Published: April 2024

AbstractAccording to a traditional interpretation of Kierkegaard, he endorses a strong form of direct doxastic voluntarism on which we can, by brute force of will, make a “leap of faith” to believe propositions that we ourselves take to be improbable and absurd. Yet most leading Kierkegaard scholars now wholly reject this reading, instead interpreting Kierkegaard as holding that the will can affect what we believe only indirectly. This paper argues that Kierkegaard does in fact endorse a restricted, sophisticated, and plausible version of direct doxastic voluntarism. On Kierkegaard's view, when we take ourselves to be in an epistemically permissive situation, we have the ability to form outright beliefs (but not credences) at will in virtue of our ability to voluntarily 1) open or close inquiry and 2) determine our attitude towards epistemic risk.
A novel frameshift mutation in RHAG leads to Rhnull phenotype in a Chinese individual
Authors: Qing Yun , Zou Hai‐Man , Liu Bu‐Jin , Cui Dan‐Li , Yang Jun‐Hong , Huang Xia 
Published: April 2024

AbstractBackgroundWe recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family.MethodsRed blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis.ResultsSerologic tests showed a D–C–E–c–e– phenotype in the proband associated with the suspicion of anti‐Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents.ConclusionWe identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.
A Mixed-Methods Investigation of How Digital Immersion Affects Design for Additive Manufacturing Evaluations
Authors: Mathur Jayant , Miller Scarlett R. , Simpson Timothy W. , Meisel Nicholas A. 
Published: April 2024

Abstract
Applications for additive manufacturing (AM) continue to increase as more industries adopt the technology within their product development processes. There is a growing demand for designers to acquire and hone their design for AM (DfAM) intuition and generate innovative solutions with AM. Resources that promote DfAM intuition, however, historically default to physical or digitally non-immersive modalities. Immersive virtual reality (VR) naturally supports 3D spatial perception and reasoning, suggesting its intuitive role in evaluating geometrically complex designs and fostering DfAM intuition. However, the effects of immersion on DfAM evaluations are not well-established in the literature. This study contributes to this gap in the literature by examining DfAM evaluations for a variety of designs across modalities using varying degrees of immersion. Specifically, it observes the effects on the outcomes of the DfAM evaluation, the effort required of evaluators, and their engagement with the designs. Findings indicate that the outcomes from DfAM evaluations in immersive and non-immersive modalities are similar without statistically observable differences in the cognitive load experienced during the evaluations. Active engagement with the designs, however, is observed to be significantly different between immersive and non-immersive modalities. By contrast, passive engagement remains similar across the modalities. These findings have interesting implications on how organizations train designers in DfAM, as well as on the role of immersive modalities in design processes. Organizations can provide DfAM resources across different levels of immersion, enabling designers to customize how they acquire DfAM intuition and solve complex engineering problems.
The Ca
2+
-dependent phosphatase calcineurin dephosphorylates TBK1 to suppress antiviral innate immunity
Authors: Qu Yang , Wang Siyuan , Jiang Hui , Wang Qingyi , Liao Ying , Qiu Xusheng , Tan Lei , Song Cuiping , Ding Chan , Sun Yingjie , Yang Zengqi 
Published: April 2024

ABSTRACT

Tumor necrosis factor receptor-associated factor family member-associated NF-κB activator-binding kinase 1 (TBK1) plays a key role in the induction of the type 1 interferon (IFN-I) response, which is an important component of innate antiviral defense. Viruses target calcium (Ca
2+
) signaling networks, which participate in the regulation of the viral life cycle, as well as mediate the host antiviral response. Although many studies have focused on the role of Ca
2+
signaling in the regulation of IFN-I, the relationship between Ca
2+
and TBK1 in different infection models requires further elucidation. Here, we examined the effects of the Newcastle disease virus (NDV)-induced increase in intracellular Ca
2+
levels on the suppression of host antiviral responses. We demonstrated that intracellular Ca
2+
increased significantly during NDV infection, leading to impaired IFN-I production and antiviral immunity through the activation of calcineurin (CaN). Depletion of Ca²
+
was found to lead to a significant increase in virus-induced IFN-I production resulting in the inhibition of viral replication. Mechanistically, the accumulation of Ca
2+
in response to viral infection increases the phosphatase activity of CaN, which in turn dephosphorylates and inactivates TBK1 in a Ca
2+
-dependent manner. Furthermore, the inhibition of CaN on viral replication was counteracted in
TBK1
knockout cells. Together, our data demonstrate that NDV hijacks Ca
2+
signaling networks to negatively regulate innate immunity via the CaN-TBK1 signaling axis. Thus, our findings not only identify the mechanism by which viruses exploit Ca
2+
signaling to evade the host antiviral response but also, more importantly, highlight the potential role of Ca
2+
homeostasis in the viral innate immune response.

IMPORTANCE

Viral infections disrupt intracellular Ca
2+
homeostasis, which affects the regulation of various host processes to create conditions that are conducive for their own proliferation, including the host immune response. The mechanism by which viruses trigger TBK1 activation and IFN-I induction through viral pathogen-associated molecular patterns has been well defined. However, the effects of virus-mediated Ca
2+
imbalance on the IFN-I pathway requires further elucidation, especially with respect to TBK1 activation. Herein, we report that NDV infection causes an increase in intracellular free Ca
2+
that leads to activation of the serine/threonine phosphatase CaN, which subsequently dephosphorylates TBK1 and negatively regulates IFN-I production. Furthermore, depletion of Ca
2+
or inhibition of CaN activity exerts antiviral effects by promoting the production of IFN-I and inhibiting viral replication. Thus, our results reveal the potential role of Ca
2+
in the innate immune response to viruses and provide a theoretical reference for the treatment of viral infectious diseases.
Regulation of ubiquitination and antiviral activity of Cactin by deubiquitinase Usp14 in
Drosophila
Authors: Rong Qiqi , Xi Zhichong , Guo Dongyang , Xu Wen , Zhang Liqin , Wu Qingfa 
Published: April 2024

ABSTRACT

Cactin, a highly conserved protein, plays a crucial role in various physiological processes in eukaryotes, including innate immunity. Recently, the function of Cactin in the innate immunity of
Drosophila
has been explored, revealing that Cactin regulates a non-canonical signaling pathway associated with the Toll and Imd pathways
via
the Cactin-Deaf1 axis. In addition, Cactin exhibits specific antiviral activity against the
Drosophila
C virus (DCV) in
Drosophila
, with an unknown mechanism. During DCV infection, it has been confirmed that the protein level and antiviral activity of Cactin are regulated by ubiquitination. However, the precise ubiquitination and deubiquitination mechanisms of Cactin in
Drosophila
remain unexplored. In this study, we identified ubiquitin-specific protease 14 (Usp14) as a major deubiquitinase for Cactin through comprehensive deubiquitinase screening. Our results demonstrate that Usp14 interacts with the C_Cactus domain of Cactin
via
its USP domain. Usp14 efficiently removes K48- and K63-linked polyubiquitin chains from Cactin, thereby preventing its degradation through the ubiquitin-proteasome pathway. Usp14 significantly inhibits DCV replication in
Drosophila
cells by stabilizing Cactin. Moreover, Usp14-deficient fruit flies exhibit increased susceptibility to DCV infection compared to wild-type flies. Collectively, our findings reveal the regulation of ubiquitination and antiviral activity of Cactin by the deubiquitinase Usp14, providing valuable insights into the modulation of Cactin-mediated antiviral activity in
Drosophila
.

IMPORTANCE

Viral infections pose a severe threat to human health, marked by high pathogenicity and mortality rates. Innate antiviral pathways, such as Toll, Imd, and JAK-STAT, are generally conserved across insects and mammals. Recently, the multi-functionality of Cactin in innate immunity has been identified in
Drosophila
. In addition to regulating a non-canonical signaling pathway through the Cactin-Deaf1 axis, Cactin exhibits specialized antiviral activity against the
Drosophila
C virus (DCV) with an unknown mechanism. A previous study emphasized the significance of the Cactin level, regulated by the ubiquitin-proteasome pathway, in modulating antiviral signaling. However, the regulatory mechanisms governing Cactin remain unexplored. In this study, we demonstrate that Usp14 stabilizes Cactin by preventing its ubiquitination and subsequent degradation. Furthermore, Usp14 plays a crucial role in regulating the antiviral function mediated by Cactin. Therefore, our findings elucidate the regulatory mechanism of Cactin in
Drosophila
, offering a potential target for the prevention and treatment of viral infections.
Ascitic microbiota alteration is associated with portal vein tumor thrombosis occurrence and prognosis in hepatocellular carcinoma
Authors: Guo Yingyun , Tian Shan , Zhan Na , Liu Chuan , Li Jiao , Hu Jiaming , Qiu Meiqi , Huang Binglu , Dong Weiguo 
Published: April 2024

ABSTRACT

Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups.
Gammaproteobacteria
and
Acinetobacter
were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.

IMPORTANCE

First, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis.
Gammaproteobacteria
and
Acinetobacter
were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.
Characterization of the transcriptionally active form of dephosphorylated DctD complexed with dephospho-IIA
Glc
Authors: Kang Sebin , Jang Bo-Ram , Lee Kyu-Ho 
Published: April 2024

ABSTRACT

Bacterial enhancer-binding proteins (bEBPs) acquire a transcriptionally active state via phosphorylation. However, transcriptional activation by the dephosphorylated form of bEBP has been observed in DctD, which belongs to Group I bEBP. The formation of a complex between dephosphorylated DctD (d-DctD) and dephosphorylated IIA
Glc
(d-IIA
Glc
) is a prerequisite for the transcriptional activity of d-DctD. In the present study, characteristics of the transcriptionally active complex composed of d-IIA
Glc
and phosphorylation-deficient DctD (DctD
D57Q
) of
Vibrio vulnificus
were investigated in its multimeric conformation and DNA-binding ability. DctD
D57Q
formed a homodimer that could not bind to the DNA. In contrast, when DctD
D57Q
formed a complex with d-IIA
Glc
in a 1:1 molar ratio, it produced two conformations: dimer and dodecamer of the complex. Only the dodecameric complex exhibited ATP-hydrolyzing activity and DNA-binding affinity. For successful DNA-binding and transcriptional activation by the dodecameric d-IIA
Glc
/DctD
D57Q
complex, extended upstream activator sequences were required, which encompass the nucleotide sequences homologous to the known DctD-binding site and additional nucleotides downstream. This is the first report to demonstrate the molecular characteristics of a dephosphorylated bEBP complexed with another protein to form a transcriptionally active dodecameric complex, which has an affinity for a specific DNA-binding sequence.

IMPORTANCE

Response regulators belonging to the bacterial two-component regulatory system activate the transcription initiation of their regulons when they are phosphorylated by cognate sensor kinases and oligomerized to the appropriate multimeric states. Recently, it has been shown that a dephosphorylated response regulator, DctD, could activate transcription in a phosphorylation-independent manner in
Vibrio vulnificus
. The dephosphorylated DctD activated transcription as efficiently as phosphorylated DctD when it formed a complex with dephosphorylated form of IIA
Glc
, a component of the glucose-phosphotransferase system. Functional mimicry of this complex with the typical form of transcriptionally active phosphorylated DctD led us to study the molecular characteristics of this heterodimeric complex. Through systematic analyses, it was surprisingly determined that a multimer constituted with 12 complexes gained the ability to hydrolyze ATP and recognize specific upstream activator sequences containing a typical inverted-repeat sequence flanked by distinct nucleotides.