bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixed infection of ITPase-encoding potyvirid and secovirid in Mercurialis perennis: evidences for a convergent euphorbia-specific viral counterstrike
Authors: Mahillon Mathieu , Brodard Justine , Dubuis Nathalie , Gugerli Paul , Blouin Arnaud G. , Schumpp Olivier 
Published: January 2024

Abstract
Background
In cellular organisms, inosine triphosphate pyrophosphatases (ITPases) prevent the incorporation of mutagenic deaminated purines into nucleic acids. These enzymes have also been detected in the genomes of several plant RNA viruses infecting two euphorbia species. In particular, two ipomoviruses produce replicase-associated ITPases to cope with high concentration of non-canonical nucleotides found in cassava tissues.

Method
Using high-throughput RNA sequencing on the wild euphorbia species Mercurialis perennis, two new members of the families Potyviridae and Secoviridae were identified. Both viruses encode for a putative ITPase, and were found in mixed infection with a new partitivirid. Following biological and genomic characterization of these viruses, the origin and function of the phytoviral ITPases were investigated.

Results
While the potyvirid was shown to be pathogenic, the secovirid and partitivirid could not be transmitted. The secovirid was found belonging to a proposed new Comovirinae genus tentatively named "Mercomovirus", which also accommodates other viruses identified through transcriptome mining, and for which an asymptomatic pollen-associated lifestyle is suspected. Homology and phylogenetic analyses inferred that the ITPases encoded by the potyvirid and secovirid were likely acquired through independent horizontal gene transfer events, forming lineages distinct from the enzymes found in cassava ipomoviruses. Possible origins from cellular organisms are discussed for these proteins. In parallel, the endogenous ITPase of M. perennis was predicted to encode for a C-terminal nuclear localization signal, which appears to be conserved among the ITPases of euphorbias but absent in other plant families. This subcellular localization is in line with the idea that nucleic acids remain protected in the nucleus, while deaminated nucleotides accumulate in the cytoplasm where they act as antiviral molecules.

Conclusion
Three new RNA viruses infecting M. perennis are described, two of which encoding for ITPases. These enzymes have distinct origins, and are likely required by viruses to circumvent high level of cytoplasmic non-canonical nucleotides. This putative plant defense mechanism has emerged early in the evolution of euphorbias, and seems to specifically target certain groups of RNA viruses infecting perennial hosts.

Graphical Abstract
Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice
Authors: Tong Xiao J. , Akdemir Gokhan , Wadhwa Meetu , Verkman Alan S. , Smith Alex J. 
Published: January 2024

AbstractIt has been proposed that cerebrospinal fluid (CSF) can enter and leave the retina and optic nerve along perivascular spaces surrounding the central retinal vessels as part of an aquaporin-4 (AQP4) dependent ocular ‘glymphatic’ system. Here, we injected fluorescent dextrans and antibodies into the CSF of mice at the cisterna magna and measured their distribution in the optic nerve and retina. We found that uptake of dextrans in the perivascular spaces and parenchyma of the optic nerve is highly sensitive to the cisternal injection rate, where high injection rates, in which dextran disperses fully in the sub-arachnoid space, led to uptake along the full length of the optic nerve. Accumulation of dextrans in the optic nerve did not differ significantly in wild-type and AQP4 knockout mice. Dextrans did not enter the retina, even when intracranial pressure was greatly increased over intraocular pressure. However, elevation of intraocular pressure reduced accumulation of fluorescent dextrans in the optic nerve head, and intravitreally injected dextrans left the retina via perivascular spaces surrounding the central retinal vessels. Human IgG distributed throughout the perivascular and parenchymal areas of the optic nerve to a similar extent as dextran following cisternal injection. However, uptake of a cisternally injected AQP4-IgG antibody, derived from a seropositive neuromyelitis optica spectrum disorder subject, was limited by AQP4 binding. We conclude that large molecules injected in the CSF can accumulate along the length of the optic nerve if they are fully dispersed in the optic nerve sub-arachnoid space but that they do not enter the retina.
Patterns of remission from alcohol dependence in the United Kingdom: results from an online panel general population survey
Authors: Cunningham John A. , Schell Christina , Walker Hollie , Godinho Alexandra 
Published: January 2024

Abstract
Background
Previous research has demonstrated that remissions from alcohol use disorders can occur without accessing treatment. The current study explored the prevalence of such untreated remissions in the UK and further, examined the extent to which people who resolved an alcohol use disorder regarded themselves as ever, or currently, being in recovery.

Methods
Participants were recruited using the Prolific online platform. Participants who met criteria for lifetime alcohol dependence (ICD-10) were asked about their drinking at its heaviest, use of treatment services, whether they identified as being in recovery, and their current alcohol consumption (to identify those who were abstinent or drinking in a moderate fashion).

Results
A total of 3,994 participants completed surveys to identify 166 participants with lifetime alcohol dependence who were currently abstinent (n = 67) or drinking in a moderate fashion (n = 99). Participants who were currently abstinent were more likely to have accessed treatment than those who were currently moderate drinkers (44.4% versus 16.0%; Fischer’s exact test = 0.001). Further, those who were abstinent were heavier drinkers prior to remission [Mean (SD) drinks per week = 53.6 (31.7) versus 29.1 (21.7); t-test = 5.6, 118.7 df, p < .001] and were more likely to have ever identified themselves as ‘in recovery’ (51.5% versus 18.9%; Fischer’s exact test = 0.001) than current moderate drinkers.

Conclusions
While participants with an abstinent remission were more likely than those currently drinking in a moderate fashion to have accessed treatment and to identify as being ‘in recovery,’ the majority of participants reduced their drinking without treatment (and did not regard themselves as in recovery).
Investigating the complexity of the double distance problems
Authors: Braga Marília D. V. , Brockmann Leonie R. , Klerx Katharina , Stoye Jens 
Published: January 2024

Abstract
Background
Two genomes $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
over the same set of gene families form a canonical pair when each of them has exactly one gene from each family. Denote by $$n_*$$

n

∗

the number of common families of $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
. Different distances of canonical genomes can be derived from a structure called breakpoint graph, which represents the relation between the two given genomes as a collection of cycles of even length and paths. Let $$c_i$$

c
i

and $$p_j$$

p
j

be respectively the numbers of cycles of length i and of paths of length j in the breakpoint graph of genomes $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
. Then, the breakpoint distance of $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
is equal to $$n_*-\left( c_2+\frac{p_0}{2}\right)$$

n

∗

-

c
2

+

p
0

2

. Similarly, when the considered rearrangements are those modeled by the double-cut-and-join (DCJ) operation, the rearrangement distance of $$\mathbb {A}$$
A
and $$\mathbb {B}$$
B
is $$n_*-\left( c+\frac{p_e }{2}\right)$$

n

∗

-

c
+

p
e

2

, where c is the total number of cycles and $$p_e$$

p
e

is the total number of paths of even length.

Motivation
The distance formulation is a basic unit for several other combinatorial problems related to genome evolution and ancestral reconstruction, such as median or double distance. Interestingly, both median and double distance problems can be solved in polynomial time for the breakpoint distance, while they are NP-hard for the rearrangement distance. One way of exploring the complexity space between these two extremes is to consider a $$\sigma _k$$

σ
k

distance, defined to be $$n_*-\left( c_2+c_4+\ldots +c_k+\frac{p_0+p_2+\ldots +p_{k-2}}{2}\right)$$

n

∗

-

c
2

+

c
4

+
…
+

c
k

+

p
0

+

p
2

+
…
+

p

k
-
2

2

, and increasingly investigate the complexities of median and double distance for the $$\sigma _4$$

σ
4

distance, then the $$\sigma _6$$

σ
6

distance, and so on.

Results
While for the median much effort was done in our and in other research groups but no progress was obtained even for the $$\sigma _4$$

σ
4

distance, for solving the double distance under $$\sigma _4$$

σ
4

and $$\sigma _6$$

σ
6

distances we could devise linear time algorithms, which we present here.
Influence of therapeutic plasma exchange treatment on short-term mortality of critically ill adult patients with sepsis-induced organ dysfunction: a systematic review and meta-analysis
Authors: Kuklin Vladimir , Sovershaev Michael , Bjerner Johan , Keith Philip , Scott L. Keith , Thomas Owen Matthew Truscott , Szpirt Wladimir , Rock Gail , Stegmayr Bernd 
Published: January 2024

Abstract
Introduction
The impact of therapeutic plasma exchange (TPE) on short-term mortality in adult patients with sepsis-induced organ dysfunction remains uncertain. The objective of the study is to assess the effect of adjunct TPE in this setting through a comprehensive literature review.

Methods
The National Library of Medicine’s Medline, Ovid (Embase), the Cochrane Library database and clinicaltrial.gov from January 01, 1966, until October 01, 2022, were searched for terms: therapeutic plasma exchange, plasmapheresis, sepsis, and septic shock. We reviewed, selected and extracted data from relevant randomized clinical trials (RCTs) and matched cohort studies (MCSs) comparing short-term mortality in critically ill adult septic patients treated with standard therapy versus those receiving adjunct TPE. Risk of bias was assessed in the RCTs using Cochrane Collaboration tool and in MCSs using ROBINS-I tool. Summary statistics, risk ratios (RRs), and confidence intervals (CIs) were calculated using random effects model.

Results
This systematic review included 937 adult critically ill septic patients from five RCTs (n = 367) and fifteen MCSs (n = 570). Of these total, 543 received treatment with TPE in addition to standard care. The meta-analysis includes all five RCTs and only six MCSs (n = 627). The adjunct TPE treatment (n = 300) showed a significant reduction in short-term mortality (RR 0.59, 95% CI 0.47–0.74, I2 3%) compared to standard therapy alone (n = 327). The systematic review of all 20 trials revealed that adding TPE to the standard therapy of critically ill septic patients resulted in faster clinical and/or laboratory recovery.

Conclusions
Our comprehensive and up-to-date review demonstrates that adjunct TPE may provide potential survival benefits when compared to standard care for critically ill adult patients with sepsis-induced organ dysfunction. While results of this meta-analysis are encouraging, large well-designed randomized trials are required to identify the optimal patient population and TPE procedure characteristics prior to widespread adoption into practice.
Application of a recombinant novel trypsin from Trichinella spiralis for serodiagnosis of trichinellosis
Authors: Han Lu Lu , Lu Qi Qi , Li Yang Li , Zheng Wen Wen , Ren Pian , Liu Ruo Dan , Cui Jing , Wang Zhong Quan 
Published: January 2024

Abstract
Background
The excretory/secretory (ES) antigen of Trichinella spiralis muscle larvae (ML) is currently the most widely used diagnostic antigen to detect T. spiralis infection. However, this antigen has certain drawbacks, such as a complicated ES antigen preparation process and lower sensitivity during the early phase of infection. The aim of this study was to investigate the features of a novel T. spiralis trypsin (TsTryp) and evaluate its potential diagnostic value for trichinellosis.

Methods
The TsTryp gene was cloned and recombinant TsTryp (rTsTryp) expressed. Western blotting and an enzyme-linked immunosorbent assay (ELISA) were performed to confirm the antigenicity of rTsTryp. The expression pattern and distribution signature of TsTryp at various life-cycle stages of T. spiralis were analyzed by quantitative PCR, western blotting and the immunofluorescence test. An ELISA with rTsTryp and ML ES antigens was used to detect immunoglobulins G and M (IgG, IgM) in serum samples of infected mice, swine and humans. The seropositive results were further confirmed by western blot with rTsTryp and ML ES antigens.

Results
TsTryp expression was observed in diverse T. spiralis life-cycle phases, with particularly high expression in the early developmental phase (intestinal infectious larvae and adults), with distribution observed mainly at the nematode outer cuticle and stichosome. rTsTryp was identified by T. spiralis-infected mouse sera and anti-rTsTryp sera. Natural TsTryp protease was detected in somatic soluble and ES antigens of the nematode. In mice infected with 200 T. spiralis ML, serum-specific IgG was first detected by rTsTryp-ELISA at 8 days post-infection (dpi), reaching 100% positivity at 12 dpi, and first detected by ES-ELISA at 10 dpi, reaching 100% positivity at 14 dpi. Specific IgG was detected by rTsTryp 2 days earlier than by ES antigens. When specific IgG was determined in serum samples from trichinellosis patients, the sensitivity of rTsTryp-ELISA and ES antigens-ELISA was 98.1% (51/52 samples) and 94.2% (49/52 samples), respectively (P = 0.308), but the specificity of rTsTryp was significantly higher than that of ES antigens (98.7% vs. 95.4%; P = 0.030). Additionally, rTsTryp conferred a lower cross-reaction, with only three serum samples in total testing positive from 11 clonorchiasis, 20 cysticercosis and 24 echinococcosis patients (1 sample from each patient group).

Conclusions
TsTryp was shown to be an early and highly expressed antigen at intestinal T. spiralis stages, indicating that rTsTryp represents a valuable diagnostic antigen for the serodiagnosis of early Trichinella infection.

Graphical Abstract
Experimental hut and field evaluation of a metofluthrin-based spatial repellent against pyrethroid-resistant Anopheles funestus in Siaya County, western Kenya
Authors: Agumba Silas , Moshi Vincent , Muchoki Margaret , Omondi Seline , Kosgei Jackline , Walker Edward D. , Abong’o Bernard , Achee Nicole , Grieco John , Ochomo Eric 
Published: January 2024

Abstract
Background
Spatial repellents (SR) may complement current vector control tools and provide additional coverage when people are not under their bednets or are outdoors. Here we assessed the efficacy of a metofluthrin-based SR in reducing exposure to pyrethroid-resistant Anopheles funestus in Siaya County, western Kenya.

Methods
Metofluthrin was vaporized using an emanator configured to a liquid petroleum gas (LPG) canister, placed inside experimental huts (phase 1) or outdoors (phase 2), and evaluated for reductions in human landing rate, density, knockdown and mortality rates of An. funestus, which are present in high density in the area. To demonstrate the mosquito recruiting effect of LPG, a hut with only an LPG cooker but no metofluthrin was added as a comparator and compared with an LPG cooker burning alongside the emanator and a third hut with no LPG cooker as control. Phase 2 evaluated the protective range of the SR product while emanating from the centre of a team of mosquito collectors sitting outdoors in north, south, east and west directions at 5, 10 and 20 feet from the emanating device.

Results
Combustion of LPG with a cook stove increased the density of An. funestus indoors by 51% over controls with no cook stove. In contrast, huts with metofluthrin vaporized with LPG combustion had lower indoor density of An. funestus (99.3% less than controls), with knockdown and mortality rates of 95.5 and 87.7%, respectively, in the mosquitoes collected in the treated huts. In the outdoor study (phase 2), the outdoor landing rate was significantly lower at 5 and 10 feet than at 20 feet from the emanator.

Conclusions
Vaporized metofluthrin almost completely prevented An. funestus landing indoors and led to 10 times lower landing rates within 10 feet of the emanator outdoors, the first product to demonstrate such potential. Cooking with LPG inside the house could increase exposure to Anopheles mosquito bites, but the use of the metofluthrin canister eliminates this risk.

Graphical abstract
Cas13b-mediated RNA targeted therapy alleviates genetic dilated cardiomyopathy in mice
Authors: Li Jiacheng , Xuan He , Kuang Xin , Li Yahuan , Lian Hong , Yu Nie 
Published: January 2024

Abstract
Background
Recent advances in gene editing technology have opened up new avenues for in vivo gene therapy, which holds great promise as a potential treatment method for dilated cardiomyopathy (DCM). The CRISPR-Cas13 system has been shown to be an effective tool for knocking down RNA expression in mammalian cells. PspCas13b, a type VI-B effector that can be packed into adeno-associated viruses and improve RNA knockdown efficiency, is a potential treatment for diseases characterized by abnormal gene expression.

Results
Using PspCas13b, we were able to efficiently and specifically knockdown the mutant transcripts in the AC16 cell line carrying the heterozygous human TNNT2R141W (hTNNT2R141W) mutation. We used adeno-associated virus vector serotype 9 to deliver PspCas13b with specific single guide RNA into the hTNNT2R141W transgenic DCM mouse model, effectively knocking down hTNNT2R141W transcript expression. PspCas13b-mediated knockdown significantly increased myofilament sensitivity to Ca2+, improved cardiac function, and reduced myocardial fibrosis in hTNNT2R141W DCM mice.

Conclusions
These findings suggest that targeting genes through Cas13b is a promising approach for in vivo gene therapy for genetic diseases caused by aberrant gene expression. Our study provides further evidence of Cas13b’s application in genetic disease therapy and paves the way for future applicability of genetic therapies for cardiomyopathy.
COUP-TFII regulates early bipotential gonad signaling and commitment to ovarian progenitors
Authors: Ferreira Lucas G. A. , Kizys Marina M. L. , Gama Gabriel A. C. , Pachernegg Svenja , Robevska Gorjana , Sinclair Andrew H. , Ayers Katie L. , Dias-da-Silva Magnus R. 
Published: January 2024

Abstract
Background
The absence of expression of the Y-chromosome linked testis-determining gene SRY in early supporting gonadal cells (ESGC) leads bipotential gonads into ovarian development. However, genetic variants in NR2F2, encoding three isoforms of the transcription factor COUP-TFII, represent a novel cause of SRY-negative 46,XX testicular/ovotesticular differences of sex development (T/OT-DSD). Thus, we hypothesized that COUP-TFII is part of the ovarian developmental network. COUP-TFII is known to be expressed in interstitial/mesenchymal cells giving rise to steroidogenic cells in fetal gonads, however its expression and function in ESGCs have yet to be explored.

Results
By differentiating induced pluripotent stem cells into bipotential gonad-like cells in vitro and by analyzing single cell RNA-sequencing datasets of human fetal gonads, we identified that NR2F2 expression is highly upregulated during bipotential gonad development along with markers of bipotential state. NR2F2 expression was detected in early cell populations that precede the steroidogenic cell emergence and that retain a multipotent state in the undifferentiated gonad. The ESGCs differentiating into fetal Sertoli cells lost NR2F2 expression, whereas pre-granulosa cells remained NR2F2-positive. When examining the NR2F2 transcript variants individually, we demonstrated that the canonical isoform A, disrupted by frameshift variants previously reported in 46,XX T/OT-DSD patients, is nearly 1000-fold more highly expressed than other isoforms in bipotential gonad-like cells. To investigate the genetic network under COUP-TFII regulation in human gonadal cell context, we generated a NR2F2 knockout (KO) in the human granulosa-like cell line COV434 and studied NR2F2-KO COV434 cell transcriptome. NR2F2 ablation downregulated markers of ESGC and pre-granulosa cells. NR2F2-KO COV434 cells lost the enrichment for female-supporting gonadal progenitor and acquired gene signatures more similar to gonadal interstitial cells.

Conclusions
Our findings suggest that COUP-TFII has a role in maintaining a multipotent state necessary for commitment to the ovarian development. We propose that COUP-TFII regulates cell fate during gonad development and impairment of its function may disrupt the transcriptional plasticity of ESGCs. During early gonad development, disruption of ESGC plasticity may drive them into commitment to the testicular pathway, as observed in 46,XX OT-DSD patients with NR2F2 haploinsufficiency.
A new pilot assignment scheme for mitigating pilot contamination in uplink massive multi-input–multi-output (MIMO) systems
Authors: Gidena Haftom Tesfay , Weldemichael Kiros Siyoum 
Published: January 2024

AbstractPilot contamination is a serious issue in massive multi–input–multi–output systems which significantly degrades system performance. In this paper, we investigate a new pilot assignment scheme by integrating two-dimensional genetic algorithm with Tabu-Search algorithm (TS) to mitigate the pilot contamination problem. Firstly, we design a two-dimensional genetic algorithm equipped with elitism strategy as a principal algorithm for solving the pilot assignment problem; then, aiming to enhance the convergence speed of the genetic algorithm to the ideal optimal solution, we integrate TS with the genetic algorithm. This integrated pilot assignment scheme, henceforth designated as GATS-PA, is found to be powerful in mitigating the pilot contamination problem. Numerical simulation results verify that the proposed pilot assignment scheme is very close to the ideal optimal solution with few numbers of iterations and outperforms existing methods in terms of enhancing the average uplink rate per user over a wide range of simulation parameters.
Tconns: a novel time-varying context-aware offloading strategy for mobile edge computing
Authors: Zheng Meiguang , Li Jie , Hu Yu , Xiao Hui , Hu Zhigang 
Published: January 2024

AbstractMobility is a fundamental feature of mobile edge computing. Due to the mobility of users, the contextual attributes of cloudlets such as server resources and network state will dynamically change with time during offloading, showing time-varying and fuzzy characteristics. To this end, how to make efficient offloading decision to provide low-latency, low-power and highly reliable services in MEC has become a critical issue. In this paper, we propose a time-varying context-aware cloudlet decision algorithm based on neutrosophic set, TConNS $${\text {(The Code of TConNS is available at https://github.com/zhengLabs/NSO)}}$$

(The Code of TConNS is available at https://github.com/zhengLabs/NSO)

. Firstly, we establish a representation model of the multi-dimensional time-varying context of candidate cloudlets, including the mobile residence time. Secondly, we adopt the backward generator of cloud model theory to transform the contextual raw data into a single-valued neutrosophic set with the expression ability for fuzzy information. Finally, we use a series of appropriate operations under the own unique computing system of neutrosophic set to obtain the best cloudlet. Extensive experiments show that TConNS reduces the average response time by about 49% and the average energy consumption by about 46%, and also reduces the number of task failures.