bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of pharmacokinetic/pharmacodynamic concepts to the development of treatment regimens for sporadic canine urinary tract infections: Challenges and paths forward
Authors: Martinez Marilyn N. , Miller Ron A. , Martín‐Jiménez Tomás , Sharkey Michele J. 
Published: July 2022

AbstractAntimicrobial efficacy can be predicted based on infection site exposure to the antimicrobial agent relative to the in vitro susceptibility of the pathogen to that agent. When infections occur in soft tissues (e.g., muscle, blood, and ligaments), exposure at the infection site is generally assumed to reflect an equilibrium between the unbound concentrations in plasma and that in the interstitial fluids. In contrast, for sporadic urinary tract infections (UTIs) in dogs and uncomplicated UTIs in humans, the primary site of infection is the bladder wall. Infection develops when bacteria invade the host bladder urothelium (specifically, the umbrella cells that form the urine‐contacting layer of the stratified uroepithelium) within which these bacteria can avoid exposure to host defenses and antimicrobial agents. Traditionally, pathogen susceptibility has been estimated using standardized in vitro tests that measure the minimal concentration that will inhibit pathogen growth (MIC). When using exposure–response relationships during drug development to explore dose optimization, these relationships can either be based upon an assessment of a correlation between clinical outcome, drug exposure at the infection site, and pathogen MIC, or upon benchmark exposure‐response relationships (i.e., pharmacokinetic/pharmacodynamic indices) typically used for the various drug classes. When using the latter approach, it is essential that the unbound concentrations at the infection site be considered relative to the MIC within the biological matrix to which the pathogen will be exposed. For soft tissue infections, this typically is the unbound plasma concentrations versus MICs determined in standardized media such as cation‐adjusted Mueller Hinton broth, which is how many indices were originally established. However, for UTIs, it is the unbound drug concentrations within the urine versus the MICs in the actual urine biophase that needs to be considered. The importance of these relationships and how they are influenced by drug resistance, resilience, and inoculum are discussed in this review using fluoroquinolones and beta‐lactams as examples.
Improving sustainable crop protection using population genetics concepts
Authors: Saubin Méline , Louet Clémentine , Bousset Lydia , Fabre Frédéric , Frey Pascal , Fudal Isabelle , Grognard Frédéric , Hamelin Frédéric , Mailleret Ludovic , Stoeckel Solenn , Touzeau Suzanne , Petre Benjamin , Halkett Fabien 
Published: July 2022

AbstractGrowing genetically resistant plants allows pathogen populations to be controlled and reduces the use of pesticides. However, pathogens can quickly overcome such resistance. In this context, how can we achieve sustainable crop protection? This crucial question has remained largely unanswered despite decades of intense debate and research effort. In this study, we used a bibliographic analysis to show that the research field of resistance durability has evolved into three subfields: (1) “plant breeding” (generating new genetic material), (2) “molecular interactions” (exploring the molecular dialogue governing plant–pathogen interactions) and (3) “epidemiology and evolution” (explaining and forecasting of pathogen population dynamics resulting from selection pressure[s] exerted by resistant plants). We argue that this triple split of the field impedes integrated research progress and ultimately compromises the sustainable management of genetic resistance. After identifying a gap among the three subfields, we argue that the theoretical framework of population genetics could bridge this gap. Indeed, population genetics formally explains the evolution of all heritable traits, and allows genetic changes to be tracked along with variation in population dynamics. This provides an integrated view of pathogen adaptation, in particular via evolutionary–epidemiological feedbacks. In this Opinion Note, we detail examples illustrating how such a framework can better inform best practices for developing and managing genetically resistant cultivars.
Visualizing and quantifying small and nonstationary structural motions in video measurement
Authors: Cai Enjian , Zhang Yi , Quek Ser Tong 
Published: July 2022

AbstractRapid advancement in vision recording technologies is increasing the importance and production of video data in a wide range of applications. This paper proposed a novel perspective of multifrequency phase inference for characterizing especially challenging nonstationary and often small motions in optical measurement. The model estimates and adjusts the phase information by the multi‐frequency phase retrieval, which is derived from the maximum likelihood formulation with block matching 3D sparsity priors. Estimated phase jumps are removed by a robust solution of the 2D phase unwrapping problem. These considerations are supported by applications of dynamic response identification in structural health monitoring. When compared to state‐of‐the‐art techniques, the proposed method readily yielded high‐quality magnifications on real videos, with less noise and better anti‐noise performance. The proposed method also demonstrated uniformly high skill in extracting clearer time‐domain motion estimation of video components.
THE KENTISH EOLITHS OF BENJAMIN HARRISON: Their Rise and Fall in Museum Collections and What This Tells Us about the Circumstances of Their Survival
Authors: Ellen Roy , Muthana Angela 
Published: July 2022

abstractStudies focusing on the history of collections generally emphasize what is estimable about them, but how should we make sense of collections that, once held in high regard, have subsequently been judged worthless? Such is the case for eoliths, stone objects resembling early artifacts, which held a pivotal position in arguments concerning the origins of human tool‐making, but which are now largely considered nonartifactual. This article discusses the circumstances in which eolith collections were assembled, with reference to national and local museums in southeast England, but is mainly concerned with how and why, with the passing of the eolithic heyday, so many objects described as eoliths were lost, why others remain in museums, and what this tells us about curatorial practice.
H2S improves salt‐stress recovery via organic acid turn‐over in apple seedlings
Authors: Du Minghui , Zhang Peng , Wang Ge , Zhang Xinyi , Zhang Weiwei , Yang Hongqiang , Bao Zhilong , Ma Fangfang 
Published: July 2022

AbstractSignalling roles of hydrogen sulphide (H2S) in stress biology are widely reported but not sufficiently established to urge its use in agronomic practice. Our lack of quantitative understanding of the metabolic rewiring in H2S signalling makes it difficult to elucidate its functions in stress tolerance on the biochemical level. Here, Malus hupehensis Rehd. var. pingyiensis seedlings were first treated with salt stress for 2 weeks and then treated with four different concentrations of NaHS. Through vigorous investigations, including phenotypic analysis, 13C transient labelling and targeted metabolic and transcriptomic analysis, for the first time in the seedlings of a woody fruit crop, we found out that H2S recycles fixed carbons through glycolysis and tricarboxylic acid cycle to inhibit the futile accumulation of carbohydrates, to maintain an efficient CO2 assimilation, to keep a balanced starch metabolism, to produce sufficient H2O2, to maintain malate/γ‐aminobutyric acid homeostasis via an H2O2‐induced anion channel (aluminium‐activated malate transporter) and eventually to improve salt‐stress recovery. Our results systematically demonstrate the vital roles of central carbon metabolism in H2S signalling and clarify the mode of action of H2S in apple seedlings. We conclude that H2S signalling interacts with central carbon metabolism in a bottom‐up manner to recover plant growth after salt stress.
A review on PUVA pricks—A debilitating adverse event
Authors: Wyckmans Martin , Bervoets An 
Published: July 2022

AbstractPurposePUVA phototherapy is indicated for various dermatological conditions. Adverse events due to PUVA phototherapy are seen in a sizable number of patients and can result in therapy cessation. This review will focus on PUVA pricks, an adverse event first reported by Tegner in 1979.MethodsArticles were retrieved from PubMed starting from January 1979 until February 2021 yielding 1228 unique articles. Articles were included when they described individual patient characteristics, and patients were treated with PUVA therapy.ResultsAfter screening, 33 patients were extracted from 9 articles, published between 1979 and 2005.ConclusionPUVA pricks are paroxysmal episodes of burning or prickling pain, akin to peripheral neuropathy of the unmyelinated C‐fibers. Increased excitability of TRPV1 and TRPA1 channels while under PUVA therapy might be a contributing factor. Effective topical treatment options for PUVA pricks are capsaicin 8% cream, urea 4%, or petrolatum emollients. Antiepileptics such as phenytoin, clonazepam, and gabapentin are acceptable oral treatment options. A possible role of N‐acetylcysteine in the prevention of PUVA pricks is discussed, though further research is required.
Principles of Proportionate Punishment: Comments on John Deigh, From Psychology to Morality: Essays in Ethical Naturalism
Authors: Berman Mitchell N. 
Published: July 2022

AbstractJohn Deigh's new volume of previously published essays covers expansive ground—from moral psychology to the history of ethics, from James, Nietzsche and Freud to Hume, Sidgwick, and Strawson. Fully one quarter of the book, however, explores the philosophy of punishment. Deigh's dominant concern in this portion of the book is to develop and defend a novel principle of proportionality in punishment, one which provides that the severity of just punishment is a function of the damage the offense threatens or inflicts on the civil order. That is a welcome project, for philosophers of punishment widely agree that proportionality remains an elusive concept. Yet whether Deigh has solved the puzzle is uncertain. This essay raises doubts and sketches an alternative solution.
Training residents in minimally invasive surgery; confirming competence or hoping for the best?
Authors: Fransson Boel A. 
Published: July 2022

AbstractBackgroundVeterinary minimally invasive surgery (MIS) is rapidly developing, and most surgeons are performing MIS in their clinical practice. The technical skills of presented surgical techniques are increasingly complex. Required training of American College of Veterinary Surgeons (ACVS) surgical residents in soft tissue MIS (laparoscopy/thoracoscopy) are limited to traditional apprentice training. Unfortunately, such training has been found insufficient to create competent MIS surgeons.Aim of the reviewThis review discusses development of MIS training for Doctor of Medicine (M.D.) residents in context of veterinary applicability and investigates comparative evidence for how to best train veterinary residents in soft tissue MIS.ConclusionsA structured curriculum, with validated tasks and clear training goals have been found imperative for training success. Such a curriculum includes both didactic sessions and manual skills training, with video tutorials and reading material to inform and motivate the residents.Implications of key findingsACVS residents and diplomates may benefit if a MIS curriculum was developed and made available to all training programs.
Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis
Authors: Barberio Brigida , Gracie David J , Black Christopher J , Ford Alexander C 
Published: July 2022

ObjectiveThere are numerous biological therapies and small molecules licensed for luminal Crohn’s disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.DesignWe searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score.ResultsWe identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82).ConclusionIn a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission.
Nasopharyngeal lipidomic endotypes of infants with bronchiolitis and risk of childhood asthma: a multicentre prospective study
Authors: Fujiogi Michimasa , Zhu Zhaozhong , Raita Yoshihiko , Ooka Tadao , Celedon Juan C , Freishtat Robert , Camargo Carlos A , Hasegawa Kohei 
Published: July 2022

BackgroundBronchiolitis is the leading cause of hospitalisation of US infants and an important risk factor for childhood asthma. Recent evidence suggests that bronchiolitis is clinically heterogeneous. We sought to derive bronchiolitis endotypes by integrating clinical, virus and lipidomics data and to examine their relationship with subsequent asthma risk.MethodsThis is a multicentre prospective cohort study of infants (age <12 months) hospitalised for bronchiolitis. We identified endotypes by applying clustering approaches to clinical, virus and nasopharyngeal airway lipidomic data measured at hospitalisation. We then determined their longitudinal association with the risk for developing asthma by age 6 years by fitting a mixed-effects logistic regression model. To account for multiple comparisons of the lipidomics data, we computed the false discovery rate (FDR). To understand the underlying biological mechanism of the endotypes, we also applied pathway analyses to the lipidomics data.ResultsOf 917 infants with bronchiolitis (median age, 3 months), we identified clinically and biologically meaningful lipidomic endotypes: (A) cinicalclassiclipidmixed(n=263), (B) clinicalseverelipidsphingolipids-high(n=281), (C) clinicalmoderatelipidphospholipids-high(n=212) and (D) clinicalatopiclipidsphingolipids-low(n=161). Endotype A infants were characterised by ‘classic’ clinical presentation of bronchiolitis. Profile D infants were characterised by a higher proportion of parental asthma, IgE sensitisation and rhinovirus infection and low sphingolipids (eg, sphingomyelins, ceramides). Compared with endotype A, profile D infants had a significantly higher risk of asthma (22% vs 50%; unadjusted OR, 3.60; 95% CI 2.31 to 5.62; p<0.001). Additionally, endotype D had a significantly lower abundance of polyunsaturated fatty acids (eg, docosahexaenoic acid; FDR=0.01). The pathway analysis revealed that sphingolipid metabolism pathway was differentially expressed in endotype D (FDR=0.048).ConclusionsIn this multicentre prospective cohort study of infants with bronchiolitis, integrated clustering of clinical, virus and lipidomic data identified clinically and biologically distinct endotypes that have a significantly differential risk for developing asthma.Delete
Luteolin-Rich Extract of Thespesia garckeana F. Hoffm. (Snot Apple) Contains Potential Drug-Like Candidates and Modulates Glycemic and Oxidoinflammatory Aberrations in Experimental Animals
Authors: Alozieuwa Uchenna Blessing , Lawal Bashir , Sani Saidu , Onikanni Amos Sunday , Osuji Obinna , Ibrahim Yunusa Olatunji , Babalola Shukurat Bisola , Mostafa-Hedeab Gomaa , Alsayegh Abdulrahman A. , Albogami Sarah , Batiha Gaber El-Saber , Wu Alexander T. H. , Huang Hsu-Shan , Conte-Junior Carlos Adam 
Published: July 2022

The present study evaluated the polyphenolic contents and hypoglycemic, antioxidant, and anti-inflammatory effects of the diethyl ether fraction of Thespesia garckeana using various in vitro and in vivo models. Total phenol and flavonoid contents of the extract were

613.65
±
2.38

and

152.83
±
1.56

mg/100 g dry weight, respectively. The extract exhibited in vitro antioxidant activities against DPPH, FRAP, LPO, and ABTS with respective half-maximal inhibitory concentration (IC50) values of

30.91
±
0.23

,

16.81
±
0.51

,

41.29
±
1.82

, and

42.39
±
2.24

μg/mL. In vitro anti-inflammatory studies using membrane stabilization, protein denaturation, and proteinase activities revealed the effectiveness of the extract with respective IC50 values of

54.45
±
2.89

,

93.62
±
3.04

, and

56.60
±
2.34

μg/mL, while in vitro hypoglycemic analysis of the extract revealed inhibition of α-amylase (IC50

64.59
±
3.29

μg/mL) and enhancement of glucose uptake by yeast cells. Interestingly, the extract demonstrated in vivo hypoglycemic and anti-inflammatory effects in streptozotocin- (STZ-) induced diabetic and xylene-induced ear swelling models, respectively. In addition, the extract improved insulin secretion, attenuated pancreatic tissue distortion and oxidative stress, and increased the activities of superoxide dismutase (SOD), catalase, and reduced glutathione (GSH), while reducing the concentration of LPO in the diabetic rats. A high-performance liquid chromatography (HPLC) analysis identified the presence of catechin (

6.81
e
−
1

ppm), rutin (

8.46

e
−
1

ppm), myricetin, apigenin (

4.019

e
−
1

ppm), and luteolin (15.09 ppm) with respective retention times (RTs) of 13.64, 24.269, 27.781, 29.58, and 32.23 min, and these were subjected to a pharmacoinformatics analysis, which revealed their drug-likeness and good pharmacokinetic properties. A docking analysis hinted at the potential of luteolin, the most abundant compound in the extract, for targeting glucose-metabolizing enzymes. Thus, the present study provides preclinical insights into the bioactive constituents of T. garckeana, its antioxidant and anti-inflammatory effects, and its potential for the treatment of diabetes.
Safety and Efficacy of Single Condylar Knee Prosthesis When Treating Knee Single Compartment Osteoarthritis: A Prospective, Case-Randomized Controlled Study
Authors: Wang Shaofeng , Wang Yang , Wang Jiong 
Published: July 2022

Objective. The aim of this study is to explore the safety and efficacy of single condylar knee prosthesis when treating knee single compartment osteoarthritis by measuring the decrease of hemoglobin, total postoperative blood loss, maximum reduction of HCT, and knee joint activity. Methods. A total of 80 patients with knee joint single compartment osteoarthritis treated in our hospital from January 2020 to December 2021 were studied. They were randomly assigned to a study group (n = 40) and a control group (n = 40). The study group was treated with total knee prosthesis, while the control group was treated with simple knee prosthesis. The decrease rate of hemoglobin, the amount of bleeding, and the maximum decrease of hematocrit were compared after treatment. The range of motion of knee joint was evaluated by the Fugl-Meyer motor function scale (FM-B) and Berg balance scale (BBS). Results. The decrease of hemoglobin in the study group at 24 hours, 36 hours, and 48 hours after treatment was remarkably lower (

P

< 0.05). The total blood loss and the maximum reduction of hematocrit(HCT) in the study group were lower (

P

< 0.05). The range of motion (ROM) of the knee joint in the study group at 6 and 12 months after treatment was remarkably higher than that before treatment and remarkably higher compared to the control group (

P

< 0.05). The FM-B scale and BBS scale of the studied cohort at 6 and 12 months after treatment were remarkably higher than those before treatment and were remarkably higher compared to the control’s (

P

< 0.05). Conclusion. The unicondylar knee prosthesis is safer and more effective in the treatment of noncompartmental osteoarthritis of the knee, facilitating less trauma and perioperative blood loss and enhancing the patient’s motion and balance.
Construction and Validation of Prediction Model of Severe Abdominal Pain Post-Transarterial Chemoembolization in Patients with HBV-Associated Primary Liver Cancer
Authors: Yang Yaobo , Chen Sipan , Yan Zhaoyong , Jiao Yang , Yan Xiang , Li Yulong 
Published: July 2022

Objective. This study is aimed at constructing and evaluating a prediction model of severe abdominal pain post-transcatheter arterial chemoembolization in patients with HBV-related primary liver cancer. Methods. Patients with HBV-associated primary liver cancer who received transarterial chemoembolization (TACE) from March 2019 to March 2022 in the Interventional Therapy Department of our hospital were selected as the subjects, and the included 160 patients were randomly divided into modeling group (

n
=
120

) and validation group (

n
=
40

) in a ratio of 3 : 1. Visual analog scale (VAS) was used to assess pain severity. 120 patients in the modeling group were divided into no/mild abdominal pain group and severe abdominal pain group. The clinical data of the patients, including gender, age, TACE treatment history, vascular invasion, maximum diameter of tumor, infarction degree, preoperative Eastern Oncology Collaboration Group (ECOG) score, and Lipiodol dosage, were analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model for severe abdominal pain post-TACE. Results. A total of 116 patients (72.50%) had severe abdominal pain after TACE. Univariate analysis showed that severe abdominal pain after TACE in the modeling group was associated with TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score (all

P
<
0.05

), but not related to gender, age, vascular invasion, and Lipiodol dosage (all

P
>
0.05

). Logistic regression analysis showed that TACE treatment history, maximum tumor diameter, infarction degree, and preoperative ECOG score were all independent influencing factors for acute abdominal pain post-TACE in HBV-HCC patients (all

P
<
0.05

). The prediction model equation was

Y
=
−
3.673
+
1.722
×
TACE

treatment

history
+
1.175
×
tumor

maximum

diameter
+
2.064
×
infarction

degree
+
1.555
×
preoperative

ECOG

score

. Goodness-of-fit test results showed no significant difference between the established prediction model and the observed value (

χ

2

=
1.645

,

P
=
0.560

) and

R

2

=
0.821

, suggesting that the prediction ability of the model was relatively accurate. ROC analysis results showed that the area under the curve (AUC) of severe abdominal pain after TACE was 0.916 (0.862~0.970) and 0.902 (95% CI: 0.841~0.963) in the modeling group and the verification group, respectively. Conclusion. TACE treatment history, tumor maximum diameter, infarction degree, and preoperative ECOG score are independent influencing factors for severe abdominal pain post-TACE in patients with HBV-HCC, and the prediction model established on this basis has good application value.