bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of 2 Novel Phosphodiesterase 2 Inhibitors Hcyb1 and PF-05180999 on Depression- and Anxiety-Like Behavior
Authors: Yan Yuqing , Zhao Yuhan , Lu Yue , Acharya Abhinav P , Wang Wei , Zhan Chang-Guo , Ye Jianghong , Du Fu , Zhu Xiongwei , Xu Ying 
Published: May 2023

Abstract

Background
Phosphodiesterase 2A (PDE2A) represents a novel target for new therapies addressing psychiatric disorders. To date, the development of PDE2A inhibitors suitable for human clinical evaluation has been hampered by the poor brain accessibility and metabolic stability of the available compounds.

Methods
Corticosterone (CORT)-induced neuronal cell lesion and restraint stress mouse model were used to measure the neuroprotective effect in cells and antidepressant-like behavior in mice.

Results
The cell-based assay showed that both Hcyb1 and PF were potent in protecting cells against stress hormone CORT insults by stimulating cAMP and cGMP signaling in hippocampal cells (HT-22). Administration of both compounds before treatment of CORT to cells increased cAMP/cGMP, VASP phosphorylation at Ser239 and Ser157, cAMP response element binding protein phosphorylation at Ser133, and brain derived neurotrophic factor BDNF expression. Further in vivo study showed that both Hcyb1 and PF displayed ­antidepressant- and anxiolytic-like effects against restraint stress as indicated by reduced immobility time in the forced swimming and tail suspension tasks as well as increased open arm entries and time spent in open arms and holes visit in elevated plus maze and hole-board tests, respectively. The biochemical study confirmed that these antidepressant- and anxiolytic-like effects of Hcyb1 and PF were related to cAMP and cGMP signaling in the hippocampus.

Conclusions
The results extend the previous studies and validate that PDE2A is a tractable target for drug development in the treatment of emotional disorders such as depression and anxiety.
Rigidity of Automorphic Galois Representations Over CM Fields
Authors: A’Campo Lambert 
Published: May 2023

Abstract
We show the vanishing of adjoint Bloch–Kato Selmer groups of automorphic Galois representations over CM fields. This proves their rigidity in the sense that they have no deformations that are de Rham. In order for this to make sense, we also prove that automorphic Galois representations over CM fields are de Rham themselves. Our methods draw heavily from the 10 author paper, where these Galois representations were studied extensively. Another crucial piece of inspiration comes from the work of P. Allen who used the smoothness of certain local deformation rings in characteristic $0$ to obtain rigidity in the polarized case.
Efficacy of favipiravir against influenza virus resistant to both baloxavir and neuraminidase inhibitors
Authors: Kiso Maki , Yamayoshi Seiya , Kawaoka Yoshihiro 
Published: May 2023

Abstract

Objectives
Widespread resistance of influenza viruses to neuraminidase (NA) inhibitor or polymerase inhibitor, baloxavir, is a major public health concern. The amino acid mutations R152K in NA and I38T in polymerase acidic (PA) are responsible for resistance to NA inhibitors and baloxavir, respectively.

Methods
We generated recombinant A(H1N1)pdm09 viruses possessing NA-R152K, PA-I38T or both mutations by using a plasmid-based reverse genetics system, characterized their virological properties in vitro and in vivo, and examined whether oseltamivir, baloxavir and favipiravir are effective against these mutant viruses.

Results
The three mutant viruses showed similar or superior growth kinetics and virulence to those of wild-type virus. Although oseltamivir and baloxavir blocked the replication of the wild-type virus in vitro, oseltamivir and baloxavir failed to suppress the replication of the NA-R152K and PA-I38T viruses in vitro, respectively. Mutant virus possessing both mutations grew in the presence of oseltamivir or baloxavir in vitro. Baloxavir treatment protected mice from lethal infection with wild-type or NA-R152K virus, but failed to protect mice from lethal infection with PA-I38T or PA-I38T/NA-R152K virus. Favipiravir treatment protected mice from lethal infection with all viruses tested, whereas oseltamivir treatment did not protect at all.

Conclusions
Our findings indicate that favipiravir should be used to treat patients with suspected baloxavir-resistant virus infection.
Performance evaluation of the UMIC® Cefiderocol to determine MIC in Gram-negative bacteria
Authors: Dortet Laurent , Niccolai Claudia , Pfennigwerth Niels , Frisch Stefanie , Gonzalez Camille , Antonelli Alberto , Giani Tommaso , Hoenings Robert , Gatermann Soeren , Rossolini Gian Maria , Naas Thierry 
Published: May 2023

Abstract

Background
Cefiderocol is a catechol-substituted cephalosporin with potent in vitro activity against carbapenem-resistant (CR) Gram-negative bacteria (GNB). Cefiderocol susceptibility testing is complex because iron concentrations need to be taken into consideration. Here, we assessed the clinical performance of Bruker’s UMIC® Cefiderocol and corresponding iron-depleted CAMHB to determine MIC by broth microdilution (BMD) for clinically relevant GNB.

Methods
MICs of cefiderocol for 283 GN clinical isolates were determined by BMD using iron-depleted CAMHB. Frozen panels were used as a reference. The concentration range of cefiderocol was 0.03–32 mg/L. The isolates, with different degrees of susceptibility to cefiderocol, included Enterobacterales (n = 180), Pseudomonas aeruginosa (n = 49), Acinetobacter baumannii (n = 44) and Stenotrophomonas maltophilia (n = 10).

Results
The rates of categorical agreement (CA), essential agreement (EA) and bias were calculated to evaluate the performance of the UMIC® Cefiderocol, as compared with the reference method. Overall, the UMIC® Cefiderocol showed 90.8% EA (95% CI: 86.9%–93.7%) with a bias of −14.5% and a CA of 90.1% (95% CI: 86.1%–93.1%). For Enterobacterales, the UMIC® Cefiderocol showed 91.7% EA (95% CI: 86.7%–94.9%) with a bias of −25.0% and a CA of 87.8% (95% CI: 82.2%–91.8%). For non-fermenters, the UMIC® Cefiderocol showed 89.3% EA (95% CI: 81.9%–93.9%) (not significantly different from 90.0%, Student t-test) with a bias of −3.9% and a CA of 94.2% (95% CI: 87.7%–97.3%).

Conclusions
UMIC® Cefiderocol is a valid method for the determination of cefiderocol MICs even if higher than expected discrepancies were observed with NDM-producing Enterobacterales, which presented in most cases MIC values close to the breakpoint.
A new regime for below threshold mergers in EU competition law? The Illumina/Grail and Towercast judgments
Authors: Mulder Jotte , Sauter Wolf 
Published: May 2023

Abstract
The Illumina/Grail and Towercast rulings of July 2022 and March 2023 create new avenues for the control of concentrations below the European Union (EU) and national turnover thresholds. These new avenues concern (i) a referral to the European Commission by a national competition authority (NCA) and (ii) a review under the EU provision on abuse of dominance by an NCA. In both cases, the rationale seems predominantly based on the need to have effective competition law oversight on the so-called killer acquisitions of emerging competitors and undertakings that aim to extend their dominance by acquiring existing (small but) effective or particularly innovative competitors. The obvious drawback of increasing possibilities of the ex-post merger control is that this comes at a cost to legal certainty and the one-stop-shop principle that has characterized the EU merger control so far. Especially the Towercast judgment calls into question the structure, purpose, and merits of merger control in the EU over the past 35 years. Looking forward, much will depend on how the NCAs and the European Commission will use their new-found powers; some reorganization of merger vetting procedures at the national level may be required. However, it appears likely that the system of merger control in the EU will come to focus more sharply on mergers that raise serious competitive concerns and less on providing a system of comprehensive administrative review, based mainly on size. This may also provide opportunities to rationalize the application of public enforcement capacity.
Predictive Analysis of Quality Markers of Atractylodis Rhizoma Based on Fingerprint and Network Pharmacology
Authors: Zhao Yanyun , Chang Xinxin , Gu Xian , Li Yang , Zheng Yuguang , Fang Huiyong 
Published: May 2023

Abstract

Background
Atractylodes chinensis (DC.) Koidz. (A. chinensis) is a perennial herbaceous plant that is widely used as a Chinese medicine herb for gastric diseases. However, the bioactive compounds of this herbal medicine have not been defined, and quality control is imperfect.

Objective
Although the method of quality evaluation method for A. chinensis by high-performance liquid chromatography (HPLC) fingerprinting has been reported in related papers, it remains unknown whether the chemical markers selected are representative of their clinical efficacy. To develop methods for qualitative analysis and improved quality evaluation of A. chinensis.

Method
In this study, HPLC was used to establish fingerprints and conduct similarity evaluation. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to reveal the differences of these fingerprints. Network pharmacology was used to analyze the corresponding targets of the active ingredients. Meantime, an active ingredient–target–pathway network was constructed to investigate the characteristics of the medical efficacy of A. chinensis and to predict potential Q-markers.

Results
Combining network pharmacological effectiveness and composition specificity with the Q-marker concept, atractylodin (ATD), β-eudesmol, atractylenolide Ι (AT-I) and atractylenolide III (AT-III) were predicted to be potential Q-markers of A. chinensis that showed anti-inflammatory, antidepressant, anti-gastric, and antiviral effects by acting on 10 core targets and 20 key pathways.

Conclusions
The HPLC fingerprinting method established in this study is straightforward, and the identified four active constituents can be used as Q-markers of A. chinensis. These findings facilitate effective quality evaluation of A. chinensis and suggest this approach could be applied to evaluate the quality of other herbal medicines.

Highlights
The fingerprints of Atractylodis rhizoma were organically combined with network pharmacology to further clarify its criteria for quality control.
Effects of aLactobacillusfermentation product on the fecal characteristics, fecal microbial populations, immune function, and stress markers of adult dogs
Authors: Koziol Samantha A , Oba Patricia M , Soto-Diaz Katiria , Steelman Andrew J , Suchodolski Jan S , Eckhardt Erik R M , Swanson Kelly S 
Published: May 2023

AbstractThe objective of this study was to measure the effects of a Lactobacillus fermentation product (LBFP) on fecal characteristics and microbiota, blood biomarkers, immune function, and serum oxidative stress markers of adult dogs. Thirty adult beagle dogs [23 M, 7 F; mean age = 8.47 ± 2.65 yr old; mean BW = 15.43 ± 4.17 kg] were used in a completely randomized design study. All dogs were fed a basal diet to maintain BW for 5 wk, followed by baseline blood and fecal sample collections. Dogs remained on the same diet, but then were randomly assigned to a placebo (dextrose) or LBFP supplement (Limosilactobacillus fermentum and Lactobacillus delbrueckii). Both treatments were dosed at 4 mg/kg BW via gelatin capsule for 5 wk (n = 15/treatment). Fecal and blood samples were collected at that time. Change from baseline data were analyzed using the Mixed Models procedure of SAS 9.4, with P &lt; 0.05 being significant and P &lt; 0.10 being trends. Most circulating metabolites and immunoglobulins (Ig) were unaltered by treatment, but LBFP-supplemented dogs had lower changes in serum corticosteroid isoenzyme of alkaline phosphatase (P &lt; 0.05), alanine aminotransferase (P &lt; 0.10), and IgM (P &lt; 0.10) than controls. The change in fecal scores tended to be lower (P = 0.068) in LBFP-supplemented dogs than controls, signifying firmer feces in LBFP-supplemented dogs. Regarding the fecal microbiota, alpha diversity indicators tended to be higher (P = 0.087) in LBFP-supplemented dogs than controls. One fecal bacterial phylum (Actinobacteriota) was altered by treatments, with its relative abundance tending to have a greater (P &lt; 0.10) increase in controls than LBFP-supplemented dogs. Fifteen bacterial genera were altered (P &lt; 0.05 or P &lt; 0.10) by treatments, including relative abundances of fecal Peptoclostridium, Sarcina, and Faecalitalea that had a greater (P &lt; 0.05) increase in controls than LBFP-supplemented dogs. In contrast, relative abundances of fecal Faecalibaculum, Bifidobacterium, and uncultured Butyricicoccaceae had a greater (P ≤ 0.05) increase in LBFP-supplemented dogs than controls. After week 5, dogs underwent transport stress (45-min vehicle ride) to assess oxidative stress markers. The change in serum superoxide dismutase after transport had a greater (P &lt; 0.0001) increase in LBFP-supplemented dogs than controls. Our data suggest that LBFP may provide benefits to dogs by stabilizing stool quality, beneficially shifting fecal microbiota, and protecting against oxidative damage when subjected to stress.
Measuring welfare in rearing piglets: test–retest reliability of selected animal-based indicators
Authors: Witt Johanna , Krieter Joachim , Wilder Thore , Czycholl Irena 
Published: May 2023

Abstract
The “Welfare Quality protocols” (WQP) were developed in 2009 as objective welfare assessment tools. The WQP are based on four welfare principles: 1) “good feeding”, 2) “good housing”, 3) “good health”, and 4) “appropriate behavior”. The included WQP-indicators were developed for growing pigs and are recommended for rearing piglets, although, to the authors’ knowledge, they have not been tested in this age class. Therefore, the present study tested selected indicators from different welfare assessment protocols with regard to test–retest reliability (TRR), consistency over time, in an on-farm study on rearing pigs. This allows to investigate whether the WQP-indicators developed for growing pigs can be recommended for rearing piglets and whether the additional indicators should be included in the WQP.
In total 28 selected pen- or individual-level indicators were used by one observer to assess the animal welfare of rearing piglets on three pig farms. Per batch 40 to 125 piglets were randomly selected and individually marked to record the weekly assessments. This procedure was repeated in three consecutive batches per farm and resulted in a total of 759 rearing piglets being assessed.
Spearman’s rank correlation co-efficient (RS), intraclass correlation co-efficient (ICC), and limits of agreement (LoA) were calculated to evaluate their TRR, especially if the TRR was influenced by the group of assessed animals (batch comparisons) or the age of the assessed piglets (age class comparisons). From the 28 indicators, 12 had a very low prevalence of &lt;1% making an assumption about their TRR meaningless. From the pen level indicators, “sneezing” achieved acceptable TRR for both comparisons and “behavioral observations” (BO) achieved in general good values (e.g., “positive social behavior”: (RS: 0.34 to 0.89; ICC: 0.00 to 0.90; LoA ϵ [−2.93; 7.41] to ϵ [−18.9; 11.5]) for both comparisons (batch, age class). The WQP-indicators of sufficient TRR, such as “tail lesions”, “lameness”, “wounds on the body”, “human–animal-relationship test” and “BO”, cannot cover the four welfare principles adequately. In particular, problems remained with the welfare principles of “good feeding”, “good housing”, and partly “good health”. However, these grievances could be overcome by including further indicators from other sources outside the WQP which have acceptable to good results for TRR in this study, such as “back posture”, “ear lesions”, “normal behavior”, and “tail posture”.
Optimization of 13-tetradecenyl acetate sex pheromone for trapping Melanotus communis (Coleoptera: Elateridae)
Authors: Schoeppner Emma , Millar Jocelyn G , Kuhar Thomas P , Doughty Hélène , Cherry Ronald H , Hall Grace , Knowles Caitlin G , Williams Livy , Huseth Anders S 
Published: May 2023

Abstract
Corn wireworm, Melanotus communis Gyllenhal (Coleoptera: Elateridae), is an economically important larval pest of root and tuber crops in the United States. Previous work to estimate field-level abundance of M. communis has focused on grain-based larval baits placed in soil. However, this sampling method is labor intensive and may not estimate population size accurately. Recent discovery of the M. communis sex pheromone, 13-tetradecenyl acetate, provides a new method to monitor this pest during the adult stage. Early studies with this pheromone showed that different trapping methods might enhance catch and improve trap servicing. We hypothesized that placing lures on elevated traps would increase M. communis capture relative to the in-ground pitfall trapping that is currently used. We had 2 objectives for this study: (a) to compare pheromone captures among in-ground pitfall traps, on-ground pitfalls, elevated pitfalls (1 m), or elevated sticky cards (1 m) and (b) test lure longevity by aging the lures outdoors at 8-, 6-, 4-, 2-, and 0-wk intervals prior to trap deployment in the field. Experiments were conducted in North Carolina, Virginia, South Carolina, and Florida during the 2021 and 2022 field seasons. Results highlight large variation in M. communis abundance across the 4 states. We showed that 1 m elevated pheromone traps caught the most beetles. The age of the lure prior to deployment had a significant effect on trap catch. The lures that were aged for fewer weeks attracted significantly more beetles, with 0- and 2-wk-old lures capturing the greatest numbers.
CYP6CX2 and CYP6CX3 mediate thiamethoxam resistance in field whitefly, Bemisia tabaci (Hemiptera:Aleyrodidae)
Authors: Yang Jing , Fu Buli , Gong Peipan , Zhang Chengjia , Wei Xuegao , Yin Cheng , Huang Mingjiao , He Chao , Du Tianhua , Liang Jinjin , Liu Shaonan , Ji Yao , Xue Hu , Wang Chao , Hu Jinyu , Du He , Zhang Rong , Yang Xin , Zhang Youjun 
Published: May 2023

Abstract
Cytochrome P450 monooxygenases (P450s) are well-known for their crucial roles in the detoxification of xenobiotics. However, whether CYP6CX2 and CYP6CX3, 2 genes from our Bemisia tabaci (B. tabaci) MED/Q genome data were associated with detoxification metabolism and confer resistance to thiamethoxam is unclear. In this study, we investigated the role of CYP6CX2 and CYP6CX3 in mediating whitefly thiamethoxam resistance. Our results showed that mRNA levels of CYP6CX2 and CYP6CX3 were up-regulated after exposure to thiamethoxam. Transcriptional levels of 2 genes were overexpressed in laboratory and field thiamethoxam resistant strains by RT-qPCR. These results indicate that the enhanced expression of CYP6CX2 and CYP6CX3 appears to confer thiamethoxam resistance in B. tabaci. Moreover, linear regression analysis showed that the expression levels of CYP6CX2 and CYP6CX3 were positively correlated with thiamethoxam resistance levels among populations. The susceptibility of whitefly adults was markedly increased after silencing 2 genes by RNA interference (RNAi) which further confirming their major role in thiamethoxam resistance. Our findings provide information to better understand the roles of P450s in resistance to neonicotinoids and suggest that these genes may be applied to develop target genes for sustainable management tactic of agricultural pests such as B. tabaci.
Ethnic Conflict and the Informational Dividend of Democracy
Authors: Laurent-Lucchetti Jérémy , Rohner Dominic , Thoenig Mathias 
Published: May 2023

Abstract
Prevailing theories of democracy focus on class conflict. In contrast, we study democratic transition when ethnic tensions are more salient than the poor/rich divide, building a model where (i) ethnic groups negotiate about allocating the economic surplus and (ii) military and political mobilizations rest on the unobserved strength of ethnic attachment. Free and fair elections elicit information and restore inter-ethnic bargaining efficiency. Autocrats can rationally choose democratic transition, even if they risk losing power, as elections reduce the opposition’s informational rent. The predictions of our framework are consistent with novel country-level and ethnic group-level panel correlational evidence on democratization in the post-decolonization period.
Wounded Healers: Abortion and the Affective Practices of Pro-Life Health Care
Authors: Licskai Megann 
Published: May 2023

Abstract
For some post-Roe abortion providers, the emotional cost of their abortion practice was untenable. By the 1980s, former abortion providers had become prominent anti-abortion advocates. Although physicians such as Beverly McMillan grounded their pro-life conversions in medical technologies and “fetological” research, affective connections to the fetus animated their activism. McMillan explained that through abortion practice, the medical profession – her vocation – had gone astray, and her pro-life activism was the cure to the resulting emotional damage. For these physicians, emotional well-being could only be recovered through principled attempts to right the perceived wrongs of the medical profession. Another group of emotionally-engaged pro-life health workers emerged from their pasts as abortion patients. Myriad post-abortion narratives followed the same trajectory: the woman reluctantly underwent an abortion, and was subsequently plagued by apathy, depression, grief, guilt, and substance-use disorders. Pro-life research came to understand this cluster of symptoms as Post-abortion Syndrome (PAS). Some women, such as Susan Stanford-Rue, opted to heal from their pain by becoming PAS counselors. Just as the “reformed” physicians combined their affective experiences with their medical expertise to argue against abortion, the counselors merged emotion and psychiatric language to redefine what it meant to be an “aborted woman” and therefore a PAS counselor. Examining pro-life publications, Christian counseling manuals, and activist speeches, this article argues that, for these activists, science and technology provided the rationale to make abortion unthinkable, but it was the activists’ emotional framework that made this rationale pro-life in the first place.
Estimating SARS-CoV-2 seroprevalence
Authors: Rosin Samuel P , Shook-Sa Bonnie E , Cole Stephen R , Hudgens Michael G 
Published: May 2023

Abstract
Governments and public health authorities use seroprevalence studies to guide responses to the COVID-19 pandemic. Seroprevalence surveys estimate the proportion of individuals who have detectable SARS-CoV-2 antibodies. However, serologic assays are prone to misclassification error, and non-probability sampling may induce selection bias. In this paper, non-parametric and parametric seroprevalence estimators are considered that address both challenges by leveraging validation data and assuming equal probabilities of sample inclusion within covariate-defined strata. Both estimators are shown to be consistent and asymptotically normal, and consistent variance estimators are derived. Simulation studies are presented comparing the estimators over a range of scenarios. The methods are used to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in New York City, Belgium, and North Carolina.