bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-transcriptome assembly combined with multiple association analysis provides new insights into the regulatory network of specialized metabolites in the tea plant Camellia sinensis
Authors: Kong Weilong , Jiang Mengwei , Wang Yibin , Chen Shuai , Zhang Shengcheng , Lei Wenlong , Chai Kun , Wang Pengjie , Liu Renyi , Zhang Xingtan 
Published: July 2022

Abstract
Specialized metabolites not only play important roles in biotic and abiotic stress adaptation of tea plants (Camellia sinensis (L.) O. Kuntze) but also contribute to the unique flavor of tea, the most important nonalcoholic beverage. However, the molecular networks and major genes that regulate specialized metabolites in tea plants are not well understood. Here, we constructed a population-level pan-transcriptome of the tea plant leaf using second-leaf transcriptome data from 134 accessions to investigate global expression differences in the population, expression presence or absence variations (ePAVs), and differentially expressed genes (DEGs) between pure Camellia sinensis var. assamica (CSA) and pure Camellia sinensis var. sinensis (CSS) accessions. Next, we used a genome-wide association study, a quantitative trait transcript study, and a transcriptome-wide association study to integrate genotypes, accumulation levels of specialized metabolites, and expression levels of pan-transcriptome genes to identify candidate regulatory genes for flavor-related metabolites and to construct a regulatory network for specialized metabolites in tea plants. The pan-transcriptome contains 30 482 expressed genes, 4940 and 5506 of which were newly annotated from a de novo transcriptome assembly without a reference and a genome reference-based assembly, respectively. DEGs and ePAVs indicated that CSA and CSS were clearly differentiated at the population transcriptome level, and they were closely related to abiotic tolerance and secondary metabolite synthesis phenotypes of CSA and CSS based on gene annotations. The regulatory network contained 212 specialized metabolites, 3843 candidate genes, and 3407 eQTLs, highlighting many pleiotropic candidate genes, candidate gene-rich eQTLs, and potential regulators of specialized metabolites. These included important transcription factors in the AP2/ERF-ERF, MYB, WD40, and bHLH families. CsTGY14G0001296, an ortholog of AtANS, appeared to be directly related to variation in proanthocyanins in the tea plant population, and the CsTGY11G0002074 gene encoding F3′5′H was found to contribute to the biased distribution of catechins between pure CSAs and pure CSSs. Together, these results provide a new understanding of the metabolite diversity in tea plants and offer new insights for more effective breeding of better-flavored tea varieties.
The forgotten group of donor-conceived persons
Authors: Pennings Guido 
Published: July 2022

ABSTRACT
A forgotten group of donor-conceived persons is those who believe that gamete donation is morally wrong and should be prohibited. Although they share the two main arguments with the anti-anonymity group, i.e. the psychological harm as a consequence of lacking the necessary information for identity construction, and the violation of a fundamental human right, namely the right to be cared for by one’s genetic parents, their voices are largely ignored in the debate. The anti-donation group also has a large part of the ideology of the family in common with the anti-anonymity group. The paper concludes that the anti-donation position should be accepted as an equivalent position. Moreover, given the similarities between the two positions, people who accept the claims of the anti-anonymity donor-conceived persons should explain why the claims of the anti-donation group should not be honoured.
Trends in Medical Management of Moderately to Severely Active Ulcerative Colitis: A Nationwide Retrospective Analysis
Authors: Yuan William , Marwaha Jayson S , Rakowsky Shana T , Palmer Nathan P , Kohane Isaac S , Rubin David T , Brat Gabriel A , Feuerstein Joseph D 
Published: July 2022

Abstract

Background
With an increasing number of therapeutic options available for the management of ulcerative colitis (UC), the variability in treatment and prescribing patterns is not well known. While recent guidelines have provided updates on how these therapeutic options should be used, patterns of long-term use of these drugs over the past 2 decades remain unclear.

Methods
We analyzed a retrospective, nationwide cohort of more than 1.7 million prescriptions for trends in prescribing behaviors and to evaluate practices suggested in guidelines relating to ordering biologics, step-up therapy, and combination therapy. The primary outcome was 30-day steroid-free remission and secondary outcomes included hospitalization, cost, and additional steroid usage. A pipeline was created to identify cohorts of patients under active UC medical management grouped by prescribing strategies to evaluate comparative outcomes between strategies. Cox proportional hazards and multivariate regression models were utilized to assess postexposure outcomes and adjust for confounders.

Results
Among 6 major drug categories, we noted major baseline differences in patient characteristics at first exposure corresponding to disease activity. We noted earlier use of biologics in patient trajectories (762 days earlier relative to UC diagnosis, 2018 vs 2008; P &lt; .001) and greater overall use of biologics over time (2.53× more in 2018 vs 2008; P &lt; .00001) . Among biologic-naive patients, adalimumab was associated with slightly lower rates of remission compared with infliximab or vedolizumab (odds ratio, 0.92; P &lt; .005). Comparisons of patients with early biologic initiation to patients who transitioned to biologics from 5-aminosalicylic acid suggest lower steroid consumption for early biologic initiation (-761 mg prednisone; P &lt; .001). Combination thiopurine-biologic therapy was associated with higher odds of remission compared with biologic monotherapy (odds ratio, 1.36; P = .01).

Conclusions
As biologic drugs have become increasingly available for UC management, they have increasingly been used at earlier stages of disease management. Large-scale analyses of prescribing behaviors provide evidence supporting early use of biologics compared with step-up therapy and use of thiopurine and biologic combination therapy.
History-Dependent Deformations of Rat Vaginas under Inflation
Authors: Dubik Justin , Tartaglione Alfonsina , Miller Kristin S , Dillard David A , De Vita Raffaella 
Published: July 2022

Abstract
The vagina is a highly inhomogeneous, anisotropic, and viscoelastic organ that undergoes significant deformations in vivo. The mechanical attributes of this organ facilitate important physiological functions during menstruation, intercourse, and birthing. Despite the crucial mechanical role that the vagina plays within the female reproductive system, the deformations that the organ can sustain over time under constant pressure, in both the longitudinal direction (LD) and circumferential direction (CD), have not been fully characterized. This experimental study focuses on quantifying the creep properties of the vagina via ex vivo inflation testing using the rat as an animal model. Toward this end, rat vaginas were subjected to three consecutively increasing constant luminal pressures (28, 55, and 83 kPa) using a custom-built experimental setup and the resulting inhomogeneous deformations were measured using the digital image correlation (DIC) method. The vagina was found to deform significantly more in the CD than the LD at any constant pressure, suggesting that the organ primarily adapts to constant pressures by significantly changing the diameter rather that the length. The change in deformation over time was significantly higher during the first inflation test at a constant pressure of 28 kPa than during the second and third inflation tests at constant pressures of 55 and 83 kPa, respectively. The findings of this study on the mechanical behavior of the vagina could serve to advance our limited knowledge about the physiology and pathophysiology of this important reproductive organ.
On the Convergence of a Novel Time-Slicing Approximation Scheme for Feynman Path Integrals
Authors: Trapasso Salvatore Ivan 
Published: July 2022

Abstract
In this note we study the properties of a sequence of approximate propagators for the Schrödinger equation, in the spirit of Feynman’s path integrals. Precisely, we consider Hamiltonian operators arising as the Weyl quantization of a quadratic form in phase space, plus a bounded potential perturbation in the form of a pseudodifferential operator with a rough symbol. The corresponding Schrödinger propagator belongs to the class of generalized metaplectic operators, a fact that naturally motivates the introduction of a manageable time-slicing approximation scheme consisting of operators of the same type. By leveraging on this design and techniques of wave packet analysis we are able to prove several convergence results with precise rates in terms of the mesh size of the time slicing subdivision, even stronger then those that can be achieved under the same assumptions using the standard Trotter approximation scheme. In particular, we prove convergence in the norm operator topology in $L^2$, as well as pointwise convergence of the corresponding integral kernels for non-exceptional times.
Ceftolozane/tazobactam for hospital-acquired/ventilator-associated bacterial pneumonia due to ESBL-producing Enterobacterales: a subgroup analysis of the ASPECT-NP clinical trial
Authors: Paterson David L , Bassetti Matteo , Motyl Mary , Johnson Matthew G , Castanheira Mariana , Jensen Erin H , Huntington Jennifer A , Yu Brian , Wolf Dominik J , Bruno Christopher J 
Published: July 2022

Abstract

Background
After the MERINO trial with piperacillin/tazobactam, the efficacy of β-lactam/tazobactam combinations in serious infections involving extended-spectrum β-lactamase (ESBL)-producing pathogens merits special evaluation.

Objectives
To further confirm the efficacy of ceftolozane/tazobactam in treating hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) involving ESBL-positive and/or AmpC-producing Enterobacterales.

Methods
Retrospective subgroup analysis of the ASPECT-NP trial comparing ceftolozane/tazobactam with meropenem for treating HABP/VABP in mechanically ventilated adults (ClinicalTrials.gov NCT02070757). ESBLs were identified using whole genome sequencing. Chromosomal AmpC production was quantified employing a high-sensitivity mRNA transcription assay.

Results
Overall, 61/726 (8.4%) participants had all baseline lower respiratory tract (LRT) isolates susceptible to both study treatments and ≥1 baseline ESBL-positive/AmpC-overproducing Enterobacterales isolate. In this subgroup (ceftolozane/tazobactam n = 30, meropenem n = 31), baseline characteristics were generally comparable between treatment arms. The most frequent ESBL-positive and/or AmpC-overproducing Enterobacterales isolates (ceftolozane/tazobactam n = 31, meropenem n = 35) overall were Klebsiella pneumoniae (50.0%), Escherichia coli (22.7%), and Proteus mirabilis (7.6%). The most prevalent ESBLs were CTX-M-15 (75.8%), other CTX-M (19.7%), and SHV (4.5%); 10.6% of isolates overproduced chromosomal AmpC. Overall, 28 day all-cause mortality was 6.7% (2/30) with ceftolozane/tazobactam and 32.3% (10/31) with meropenem (25.6% difference, 95% CI: 5.54 to 43.84). Clinical cure rate at test-of-cure, 7–14 days after end of therapy, was 73.3% (22/30) with ceftolozane/tazobactam and 61.3% (19/31) with meropenem (12.0% difference, 95% CI: −11.21 to +33.51). Per-isolate microbiological response at test-of-cure was 64.5% (20/31) with ceftolozane/tazobactam and 74.3% (26/35) with meropenem (−9.8% difference, 95% CI: −30.80 to +12.00).

Conclusions
These data confirm ceftolozane/tazobactam as an effective treatment option for HABP/VABP involving ceftolozane/tazobactam-susceptible ESBL-positive and/or AmpC-producing Enterobacterales.
Molecular and biochemical characterization of novel PAM-like MBL variants, PAM-2 and PAM-3, from clinical isolates of Pseudomonas tohonis
Authors: Yamada Kageto , Yoshizumi Ayumi , Nagasawa Tatsuya , Aoki Kotaro , Sasaki Masakazu , Murakami Hinako , Morita Toshisuke , Ishii Yoshikazu , Tateda Kazuhiro 
Published: July 2022

Abstract

Background
There is no comprehensive study on PAM-like MBLs.

Objectives
Our aim was to characterize novel B3 MBL variants, PAM-2 and PAM-3, from Pseudomonas tohonis clinical isolates.

Methods
We evaluated the antimicrobial susceptibility and the MBL gene composition of three novel P. tohonis clinical isolates identified at a Japanese hospital, using the broth microdilution method and WGS, respectively. We characterized the PAM-2 and PAM-3 proteins using recombinant protein expression and biochemical evaluations.

Results
Low carbapenem MICs (meropenem MIC = 0.125–1 mg/L) were observed for all three P. tohonis isolates; however, the isolates produced MBLs. We identified blaPAM-2 and blaPAM-3 as potential genes, belonging to a novel subclass of B3 MBLs. Their genomic sequence was similar to that of blaPAM-1 from Pseudomonas alcaligenes. PAM-2 and PAM-3 comprised 287 amino acids and exhibited 90% amino acid identity with PAM-1, 73% identity with POM-1 from Pseudomonas otitidis and 61% identity with L1 from Stenotrophomonas maltophilia. Biochemical evaluations of recombinant PAM-2 and PAM-3 revealed similar kcat/Km ratios and demonstrated catalytic activity against all the tested β-lactams, except for aztreonam. In addition, the kcat/Km ratio for imipenem was 40-fold lower than that for meropenem.

Conclusions
P. tohonis harbours a species-specific PAM-family MBL gene. This enzyme has higher hydrolytic activity against meropenem compared with that against imipenem.
Evaluation of the French surveillance system for epidemiological surveillance of antimicrobial resistance in the community and nursing homes
Authors: Collineau Lucie , Godebert Euriel , Thibaut Sonia , Lemenand Olivier , Birgand Gabriel , Caillon Jocelyne , Bourely Clémence 
Published: July 2022

Abstract

Background
Antimicrobial resistance (AMR) has been widely recognized as a major public health issue, which can be addressed through effective AMR surveillance systems. In 2018, a national surveillance programme for AMR in the community and nursing homes called Mission PRIMO was established in France. It builds on an existing network called MedQual-Ville that had been monitoring AMR mainly in the west of France community since 2003.

Objectives and Methods
To evaluate the MedQual-Ville surveillance activities and to formulate practical recommendations for improvement, using a semi-quantitative evaluation framework called OASIS.

Results
The evaluation showed that MedQual-Ville is overall a well-performing surveillance system. Its major strengths rely on excellent coordination and internal communication with clinical laboratories that participate on a voluntary basis. Surveillance objectives and procedures are clear to all participants. Hence, the quality and reliability of the data being produced is very high. At this stage, the major area for improvement is representativeness, with poor coverage achieved in several densely populated areas. Besides, the utility and impact of surveillance data could be improved by strengthening communication towards end-users, especially local prescribers.

Conclusions
There is currently no European programme or guidance for AMR surveillance in the community and nursing homes. Our results partly fill this gap, by evaluating how surveillance is being performed in France and providing recommendations that could be applicable to other countries with similar health systems. This work also highlighted the relevance of OASIS for evaluation of surveillance systems in the human sector.
Cloning and expression of the thioredoxin gene in Cherax quadricarinatus (Von Martens, 1868) (Decapoda: Astacidea: Parastacidae) under bacterial stress
Authors: Xing Zenghou , Liu Zhuoliang , Liu Jinfeng , Xu Youhou , Lu Min , Felix Dan Solomon , Zhang Hong , Wang Pengliang , Yang Jialin , Zhu Peng 
Published: July 2022

Abstract
As a member of the thioredoxin (Trx) system, the Trx1 gene plays essential roles in the pathogenesis of various diseases. The function of Trx in bacterial infections in the freshwater crayfish Cherax quadricarinatus (Von Martens, 1868), however, has not been clarified. We cloned thioredoxin 1 (CqTrx1) from C. quadrangularis, and its expression was investigated. The results showed that the coding sequence of the CqTrx1 gene was 318 bp, encoding a polypeptide of 105 amino acids, contains the conserved motif CGPC (Cys-Gly-Pro-Cys), and was 75.24% and 66.67% identical to sequences of the shrimps Macrobrachium rosenbergii (De Man, 1879) and Fenneropenaeus chinensis (Osbeck, 1765), respectively. The CqTrx1 transcript existed in all organs tested, with the highest expression level in the intestinal tract and the lowest expression level in the gonads. Under the stress of Vibrio algolyticus, V. parahaemolyticus, or Aeromonas hydrophila, the expression level of CqTrx in the gills was 3.1, 4, and 7 times that in the control group at 3, 9, and 24 h, respectively, indicating that CqTrx1 plays an essential role in shrimp antibacterial immunity.
The death of Roe and the future of ex vivo embryos
Authors: Greely Henry T 
Published: July 2022

Abstract
This article examines the possible effects of the end of a federal constitutional right to abortion on clinical practice and research involving ex vivo human embryos. It first analyzes the likely outcomes of Dobbs v. Mississippi, concluding the Supreme Court will either overrule the federal constitutional abortion right or restrict it in a way that leads to its rapid disappearance. Next, the article discusses a possible increase in use of preimplantation genetic testing as one result. It then forecasts the likely ramifications of such a court decision on state legislation affecting ex vivo human embryos in two ways. It examines the possibility that victory over Roe will inspire embryo support groups to push for limitations on in vitro fertilization, perhaps on its destruction of embryos and more likely on permissible grounds for prospective parents to use in choosing embryos for transfer. It ends by discussing the prospects of new laws in some states banning or limiting research with human embryos.
Larvicidal Activity of Two Rutaceae Plant Essential Oils and Their Constituents Against Aedes albopictus (Diptera: Culicidae) in Multiple Formulations
Authors: Jian Rongchao , Lin Yuan , Li Yuling , Wu Weifeng , Ren Xiaofei , Liang Zhanyuan , Kong Lingjia , Cai Jinglin , Lao Canyao , Wu Min , Chen Wenhua , Chen Jing , Hong Weiqian David , Sheng Zhaojun 
Published: July 2022

Abstract
Aedes albopictus (Skuse) is a vector of several arboviruses, such as dengue, chikungunya, West Nile, and Zika viruses. At present, the use of synthetic insecticides is the main vector control strategy. However, the widespread and long-term use of insecticides has aroused several problems, including insecticide resistance, environmental pollution, and non-target species effects, thereby encouraging researchers to search for new alternatives derived from natural products. In recent decades, essential oils (EOs) as natural alternatives to control mosquitoes have received increasing attention. In the initial larvicidal activity screen, two Rutaceae plants (Citrus aurantium and Citrus paradisi) EOs were selected and evaluated for killing Ae. albopictus larvae. The LC50 values of C. aurantium and C. paradisi EOs against Ae. albopictus were 91.7 and 100.9 ppm, respectively. The main components of C. aurantium EO include diethyl o-phthalate (37.32%), limonene (10.04%), and methyl dihydrojasmonate (6.48%). The main components of C. paradisi EO include limonene (60.51%), diethyl o-phthalate (11.75%), linalool (7.90%), and styralyl acetate (6.28%). Among these main components of the two EOs, limonene showed potent larvicidal activity, with the LC50 value of 39.7 ppm. The nanoemulsions of limonene were prepared and characterized. The duration of larvicidal activity was greater in the limonene nanoemulsions than when limonene was applied in solvent. This study demonstrates that EOs of plants in family Rutaceae are a potential resource to develop new larvicides, and nanoemulsification is an effective method for improving the physicochemical properties and efficacy of natural products as larvicides.
Assessing childhood unintentional injury literature in Africa and Zimbabwe: a protocol for a scoping literature review
Authors: Mazingi Dennis , Paterson Amy , Muguti Godfrey , Peter Noel , Bandyopadhyay Soham , Handa Ashok , Lakhoo Kokila 
Published: July 2022

Abstract
Injury is a looming calamity whose burden is growing rapidly and threatens to become an emergency in affected nations. The burden is experienced disproportionately in low and middle countries but attention in these countries has been focused on competing priorities of infectious diseases. Despite this, the burden of trauma deaths from injury now exceeds the deaths from human immunodeficiency virus, tuberculosis and malaria combined. This trend is expected to continue as a result of continued epidemiological transition as well as demographic changes that will see Africa's paediatric and adolescent population grow to a billion. The objective of this scoping review is to map the existing literature in unintentional injury in children in Africa. We aim to highlight areas where there is a gap in knowledge and provide an impetus for further research in this area in the continent. A systematic search of white and grey literature will be undertaken.
Early Phonological Traditions in a Contemporary Hebrew Sociolect
Authors: Henshke Yehudit 
Published: July 2022

Abstract
The article traces the place of, and changing attitudes in the research toward, the Mizrahi sociolect of Modern Hebrew in Israel. Initially defined by Haim Blanc in the 1950s as paralleling Askhenazoid Hebrew, Blanc’s sociolinguistic definition did not evoke scholarly interest. Many scholars noted the widespread adoption of the Ashkenazoid variety and even predicted the disappearance of the Mizrahi sociolect. A shift came in the twenty-first century. A comprehensive field study by the author showed the continued, widespread existence and distribution of the Mizrahi sociolect and its impact in many linguistic spheres. This article focuses on chosen phonological issues from Mizrahi Hebrew: the realization of pharyngeals, and of ṣere, and the preservation of precise, early Hebrew forms: šeʿur and the vowel in the second radical of III-y verbs, such as x̠iketi.