bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Odor-Tracking Performance of Silk Moth Using a Sensory–Motor Intervention System
Authors: Shigaki Shunsuke , Ando Noriyasu , Sakurai Takeshi , Kurabayashi Daisuke
Published: June 2023

Synopsis

Animals can adaptively behave in different environmental conditions by converting environmental information obtained from their sensory organs into actions. This sensory–motor integration enables the accomplishment of various tasks and is essential for animal survival. This sensory–motor integration also plays an important role in localization to females, relying on sex pheromones floating in space. In this study, we focused on the localization behavior of the adult male silk moth, Bombyx mori. We investigated sensory–motor integration against time delay using odor plume tracking performance as an index when we set a certain time delay for the sensory and motor responses. Given that it is difficult to directly intervene in the sensory and motor functions of the silk moth, we constructed an intervention system based on a mobile behavior measurement system controlled by them. Using this intervention system, not only can timing the detection of the odor in the environment and timing the presentation of the odor to the silk moth be manipulated, but timing the reflection of the movement of the silk moth can also be manipulated. We analyzed the extent to which the localization strategy of the silk moth could tolerate sensory delays by setting a delay to the odor presentation. We also evaluated behavioral compensation by odor sensory feedback by setting a delay to the motor. The results of the localization experiment have shown that the localization success rate did not decrease when there was a motor delay. However, when there was a sensory delay, the success rate decreased depending on the time delay. Analysis of the change in behavior after detection of the odor stimulus has shown that the movement was more linear when we set a motor delay. However, the movement was accompanied by a large rotational movement when there was a delay in the sensory input. This result has suggested that behavior is compensated for the delay in motor function by feedback control of odor sensation, but not when accompanied by sensory delay. To compensate for this, the silk moth may acquire appropriate information from the environment by making large body movements.
The path towards sovereign territory: Reading China’s (anti)federal idea against its modern territorial constitutional imaginary
Authors: Kuo Ming-Sung
Published: June 2023

This article aims to shed light on how China has (re)imagined the geographical distribution of authority on its path towards modern statehood by unpacking the debate surrounding the constitutional status of Hong Kong in China’s territorial constitution. Challenging the conventional wisdom that China is constitutionally impervious to the federal idea, it makes a threefold argument. First, elements of federalism do exist in China, as intimated in its territorial constitution regarding Hong Kong, but have become nearly invisible as the relationship between mainland China and Hong Kong is traveling in the opposite direction. Second, the opposite development is attributable to the antifederal idea embedded in China’s modern constitutional imaginary, which has been shaped by its multifaceted experience with federalism in history. Under the antifederal idea, intimations of federalism in China’s territorial constitution are far from the bridge to a full-fledged Chinese federation, but only meant to be instrumental and transitional. Third, the antifederal idea reflects China’s modern territorial constitutional imaginary under which variegated imperial frontiers are reimagined as homogenized state territory. In conclusion, China’s encounter with Western legal concepts is formative of the Chinese modern constitutional imaginary and thus further influences its attitude towards federalism in framing the territorial constitution.
Model-driven survival prediction after congenital heart surgery
Authors: Zürn Christoph , Hübner David , Ziesenitz Victoria C , Höhn René , Schuler Lena , Schlange Tim , Gorenflo Matthias , Kari Fabian A , Kroll Johannes , Loukanov Tsvetomir , Klemm Rolf , Stiller Brigitte
Published: June 2023

OBJECTIVES

The objective of the study was to improve postoperative risk assessment in congenital heart surgery by developing a machine-learning model based on readily available peri- and postoperative parameters.

METHODS

Our bicentric retrospective data analysis from January 2014 to December 2019 of established risk parameters for dismal outcome was used to train and test a model to predict postoperative survival within the first 30 days. The Freiburg training data consisted of 780 procedures; the Heidelberg test data comprised 985 procedures. STAT mortality score, age, aortic cross-clamp time and postoperative lactate values over 24 h were considered.

RESULTS

Our model showed an area under the curve (AUC) of 94.86%, specificity of 89.48% and sensitivity of 85.00%, resulting in 3 false negatives and 99 false positives.

The STAT mortality score and the aortic cross-clamp time each showed a statistically highly significant impact on postoperative mortality. Interestingly, a child’s age was barely statistically significant. Postoperative lactate values indicated an increased mortality risk if they were either constantly at a high level or low during the first 8 h postoperatively with an increase afterwards.

When considering parameters available before, at the end of and 24 h after surgery, the predictive power of the complete model achieved the highest AUC. This, compared to the already high predictive power alone (AUC 88.9%) of the STAT mortality score, translates to an error reduction of 53.5%.

CONCLUSIONS

Our model predicts postoperative survival after congenital heart surgery with great accuracy. Compared with preoperative risk assessments, our postoperative risk assessment reduces prediction error by half. Heightened awareness of high-risk patients should improve preventive measures and thus patient safety.
Serotonergic Neurotransmission in Limbic Regions May Reflect Therapeutic Response of Depressive Patients: A PET Study With 11C-WAY-100635 and 18F-MPPF
Authors: Kitamura Soichiro , Kimura Yasuyuki , Takahata Keisuke , Moriguchi Sho , Kubota Manabu , Shimada Hitoshi , Endo Hironobu , Takado Yuhei , Kawamura Kazunori , Zhang Ming-Rong , Suhara Tetsuya , Higuchi Makoto
Published: June 2023

Background

Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors has yet to be clarified. 11C-WAY-100635 and 18F-MPPF are positron emission tomography (PET) radioligands for 5-HT1A receptors. While binding of both ligands reflects 5-HT1A receptor density, 18F-MPPF biding may also be affected by extracellular 5-HT concentrations. This dual-tracer PET study explored the neurochemical substrates underlying antidepressant effects in patients with depression.

Methods

Eleven patients with depression, including 9 treated with antidepressants, and 16 age- and sex-matched healthy individuals underwent PET scans with 11C-WAY-100635 and 18F-MPPF. Radioligand binding was determined by calculating the nondisplaceable binding potential (BPND).

Results

Patients treated with antidepressants showed significantly lower 18F-MPPF BPND in neocortical regions and raphe nuclei, but not in limbic regions, than controls. No significant group differences in 11C-WAY-100635 BPND were found in any of the regions. Significant correlations of BPND between 11C-WAY-100635 and 18F-MPPF were observed in limbic regions and raphe nuclei of healthy controls, but no such associations were found in antidepressant-treated patients. Moreover, 18F-MPPF BPND in limbic regions was significantly correlated with the severity of depressive symptoms.

Conclusions

These results suggest a diversity of antidepressant-induced extracellular 5-HT elevations in the limbic system among depressive patients, which is associated with the individual variability of clinical symptoms following the treatment.
Lossy compression of general random variables
Authors: Riegler Erwin , Koliander Günther , Bölcskei Helmut
Published: June 2023

This paper is concerned with the lossy compression of general random variables, specifically with rate-distortion theory and quantization of random variables taking values in general measurable spaces such as, e.g. manifolds and fractal sets. Manifold structures are prevalent in data science, e.g. in compressed sensing, machine learning, image processing and handwritten digit recognition. Fractal sets find application in image compression and in the modeling of Ethernet traffic. Our main contributions are bounds on the rate-distortion function and the quantization error. These bounds are very general and essentially only require the existence of reference measures satisfying certain regularity conditions in terms of small ball probabilities. To illustrate the wide applicability of our results, we particularize them to random variables taking values in (i) manifolds, namely, hyperspheres and Grassmannians and (ii) self-similar sets characterized by iterated function systems satisfying the weak separation property.
Finite volumes for the Stefan–Maxwell cross-diffusion system
Authors: Cancès Clément , Ehrlacher Virginie , Monasse Laurent
Published: June 2023

The aim of this work is to propose a provably convergent finite volume scheme for the so-called Stefan–Maxwell model, which describes the evolution of the composition of a multi-component mixture and reads as a cross-diffusion system. The scheme proposed here relies on a two-point flux approximation, and preserves at the discrete level some fundamental theoretical properties of the continuous models, namely the non-negativity of the solutions, the conservation of mass and the preservation of the volume-filling constraints. In addition, the scheme satisfies a discrete entropy–entropy dissipation relation, very close to the relation that holds at the continuous level. In this article, we present this scheme together with its numerical analysis, and finally illustrate its behaviour with some numerical results.
De Novo Human Angiotensin-Converting Enzyme 2 Decoy NL-CVX1 Protects Mice From Severe Disease After Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Rebelo Maria , Tang Cong , Coelho Ana R , Labão-Almeida Carlos , Schneider Matthias M , Tatalick Laurie , Ruivo Pedro , de Miranda Marta Pires , Gomes Andreia , Carvalho Tânia , Walker Matthew J , Ausserwoeger Hannes , Pedro Simas J , Veldhoen Marc , Knowles Tuomas P J , Silva Daniel-Adriano , Shoultz David , Bernardes Gonçalo J L
Published: June 2023

The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding domain of the SARS-CoV-2 spike protein. Using a transgenic mouse model of SARS-CoV-2 infection, we showed that a single prophylactic intranasal dose of NL-CVX1 conferred complete protection from severe disease following SARS-CoV-2 infection. Multiple therapeutic administrations of NL-CVX1 also protected mice from succumbing to infection. Finally, we showed that infected mice treated with NL-CVX1 developed both anti-SARS-CoV-2 antibodies and memory T cells and were protected against reinfection a month after treatment. Overall, these observations suggest NL-CVX1 is a promising therapeutic candidate for preventing and treating severe SARS-CoV-2 infections.
Ebola Virus Disease Features Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in the Rhesus Macaque Model
Authors: Liu David X , Pahar Bapi , Cooper Timothy K , Perry Donna L , Xu Huanbin , Huzella Louis M , Adams Ricky D , Hischak Amanda M W , Hart Randy J , Bernbaum Rebecca , Rivera Deja , Anthony Scott , Claire Marisa St , Byrum Russell , Cooper Kurt , Reeder Rebecca , Kurtz Jonathan , Hadley Kyra , Wada Jiro , Crozier Ian , Worwa Gabriella , Bennett Richard S , Warren Travis , Holbrook Michael R , Schmaljohn Connie S , Hensley Lisa E
Published: June 2023

Background

Ebola virus (EBOV) disease (EVD) is one of the most severe and fatal viral hemorrhagic fevers and appears to mimic many clinical and laboratory manifestations of hemophagocytic lymphohistiocytosis syndrome (HLS), also known as macrophage activation syndrome. However, a clear association is yet to be firmly established for effective host-targeted, immunomodulatory therapeutic approaches to improve outcomes in patients with severe EVD.

Methods

Twenty-four rhesus monkeys were exposed intramuscularly to the EBOV Kikwit isolate and euthanized at prescheduled time points or when they reached the end-stage disease criteria. Three additional monkeys were mock-exposed and used as uninfected controls.

Results

EBOV-exposed monkeys presented with clinicopathologic features of HLS, including fever, multiple organomegaly, pancytopenia, hemophagocytosis, hyperfibrinogenemia with disseminated intravascular coagulation, hypertriglyceridemia, hypercytokinemia, increased concentrations of soluble CD163 and CD25 in serum, and the loss of activated natural killer cells.

Conclusions

Our data suggest that EVD in the rhesus macaque model mimics pathophysiologic features of HLS/macrophage activation syndrome. Hence, regulating inflammation and immune function might provide an effective treatment for controlling the pathogenesis of acute EVD.
Human Papillomavirus 16 Lineage A Variants Associated With Persistent Genital Infections in Men: The HPV Infection in Men (HIM) Study
Authors: Ferreira Matthew Thomas , Mendoza López Rossana Veronica , Gonçalves Milena Giulia , Ferreira Silvaneide , Sirak Bradley , Baggio Maria Luizai , Lazcano-Ponce Eduardo , Nyitray Alan G , Giuliano Anna R , Villa Luisa L , Sichero Laura ,   for the HIM Study group, Lin Huiyi , Messina Jane , Campbell Christine Pierce , Sirak Bradley , Gage Christine , Ingles Donna J , Isaacs Kim , Kennedy Kayoko , Bobanic Andrea , Rahman Shams , Schabath Matthew , Nyitray Alan , Rathwell Julie , de Paula Lenice Galan , Cintra Ricardo , Cernicchiaro Filomena , Ribeiro Graça , Otero Rosária , Bocalon Roberta , Antunes Juliana , Silva Fernanda , Terreri Rossana , Valdez Aurelio Cruz , de Jesús Alvear Vásquez René , Juárez Oscar Rojas , del Carmen González Sosa Rossana , Vences Rosangel Ríos , Segura Martha Huerta , Galván Alicia Rodríguez , Rodríguez Paula Román , Vélez Ana Laura Landa , García Griselda Díaz , Abarca Verónica Chávez , Quevedo Gisela Flores , del Pilar Hernández Nevárez María , Martínez Guillermina Sánchez , Rojas Adriana Ortiz , Flores Carlos Omar Barrera , Mangone Flavia Rotea , Pavanelli Ana Carolina
Published: June 2023

Background

Human papillomavirus (HPV) 16 non-A lineage variants have higher carcinogenic potential for cervical cancer. HPV-16 variants natural history among males is not established. We evaluated HPV-16 variants prevalence and persistence in the external genitalia of men enrolled in the prospective HPV Infection in Men (HIM) Study.

Methods

The HIM Study included men from the United States, Brazil, and Mexico. HPV-16 variants were distinguished using polymerase chain reaction sequencing. The prevalence of HPV-16 variants was assessed, and associations with infection persistence were estimated.

Results

We characterized the HPV-16 variants for 1700 genital swab samples from 753 men and 22 external genital lesions in 17 men. The prevalence of HPV-16 lineages differed by country and marital status (P < .001). Overall, 90.9% of participants harbored lineage A variants. The prevalence of non-A lineages was heterogenous among countries. HPV-16 lineage A variants were associated with a 2.69-fold increased risk of long-term persistent infections compared with non-A lineages. All high-grade penile intraepithelial neoplasia harbored lineage A variants and occurred in the context of long-term persistent infections with the same variants.

Conclusions

The prevalence and persistence of HPV-16 variants observed at the male external genitalia suggest differences in the natural history of these variants between men and women, which may be associated with intrinsic differences in the infected genital epithelia.
Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants
Authors: Tuffy Kevin M , Ahani Bahar , Aksyuk Anastasia A , Avila Miles , Brady Tyler , Kijak Gustavo H , Koh Gavin , Levin Myron J , Roe Tiffany L , Schuko Nicolette , Thissen Jesse , Ustianowski Andrew , Zhang Tianhui , Kelly Elizabeth J , Streicher Katie
Published: June 2023

Background

We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.

Methods

Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.

Results

At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases. SARS-CoV-2 neutralizing antibody titers were similar in breakthrough and nonbreakthrough cases.

Conclusions

Symptomatic COVID-19 breakthrough cases in PROVENT were not due to resistance-associated substitutions in AZD7442 binding sites or lack of AZD7442 exposure.

Clinical Trials Registration

NCT04625725.
A CCR4 antagonist attenuates atopic dermatitis-like skin inflammation by inhibiting the recruitment and expansion of Th2 cells and Th17 cells
Authors: Sato Masako , Matsuo Kazuhiko , Susami Yoko , Yamashita Ayaka , Hayasaka Haruko , Hara Yuta , Nishiwaki Keiji , Oiso Naoki , Kawada Akira , Otsuka Atsushi , Nakayama Takashi
Published: June 2023

CCR4 is a major trafficking receptor for T-helper (Th) 2 cells and Th17 cells and is considered as a potential therapeutic target for atopic dermatitis (AD). The CCR4 ligands CCL17 and CCL22 have been reported to be upregulated in the skin lesions of AD patients. Of note, thymic stromal lymphopoietin (TSLP), a master regulator of the Th2 immune response, promotes the expression of CCL17 and CCL22 in AD skin lesions. Here, we investigated the role of CCR4 in an AD mouse model induced by MC903, a TSLP inducer. Topical application of MC903 to ear skin increased the expression of not only TSLP but also CCL17, CCL22, the Th2 cytokine IL-4, and the Th17 cytokine IL-17A. Consistently, MC903 induced AD-like skin lesions as shown by increased epidermal thickness; increased infiltration of eosinophils, mast cells, type 2 innate lymphoid cells, Th2 cells, and Th17 cells; and elevated serum levels of total IgE. We also found increased expansion of Th2 cells and Th17 cells in the regional lymph nodes (LNs) of AD mice. Compound 22, a CCR4 inhibitor, ameliorated AD-like skin lesions with reduction of Th2 cells and Th17 cells in the skin lesions and regional LNs. We further confirmed that compound 22 diminished the expansion of Th2 cells and Th17 cells in the coculture of CD11c+ dendritic cells (DCs) and CD4+ T cells derived from the regional LNs of AD mice. Collectively, CCR4 antagonists may exhibit anti-allergic effects by inhibiting both the recruitment and expansion of Th2 cells and Th17 cells in AD.
High satisfaction among patients at HIV clinics in Harare, Zimbabwe: a time and motion evaluation and patient satisfaction study
Authors: Link Abigail , Tshimanga Mufuta , Cochrane Barbara , Kasprzyk Danuta
Published: June 2023

Patient satisfaction is an important component of health and healthcare utilization, which measures the perceived needs and expectations for healthcare services. Patient satisfaction surveys are effective in improving health outcomes by informing health facilities on service and provider gaps and guiding the development of effective action plans and policies for quality improvement within a healthcare organization. Although patient satisfaction and patient flow analyses have been conducted in Zimbabwe, the combination of these two quality improvement measures in the context of Human Immunodeficiency Virus (HIV) clinics has not previously been evaluated. This study assessed and evaluated patient flow and patient satisfaction to enhance care quality and improve HIV service delivery to optimize patient health. We collected time and motion data from HIV patients who attended three purposively selected City of Harare Polyclinics in Harare, Zimbabwe. All patients who sought care at the clinic were given time and motion forms to track their movement and the time spent at each service area. After services were completed, patients were invited to participate in a satisfaction survey regarding their services and care. The average waiting time from clinic arrival to see the provider was 2 hr and 14 min. The areas with the longest waiting time and bottlenecks occurred at registration (49 min) and the HIV clinic waiting area (44 min). Despite these extended times, the overall patient satisfaction for HIV services was high at 72%, with over half (59%) reporting that there was nothing they did not like about their services. Patients were most satisfied with services provided (34%), timely service (27%), and antiretroviral medications (19%). The areas of least satisfaction were related to time delays (24%) and cashier delays (6%). Despite prolonged waiting times, patients’ overall satisfaction with their clinic experience remains high. Perceptions of satisfaction are influenced by experience, culture, and context. However, there are still several areas of recommendations to improve service, care, and quality. Specifically, reducing or eliminating service fees, increasing clinic hour times, and having available medication were most cited. Support from the Zimbabwe Ministry of Health and Child Care, City of Harare, and other decision-makers is needed to improve patient satisfaction and address patients’ recommendations within the City of Harare Polyclinic organization in accordance with the 2016–20 National Health Strategies for Zimbabwe.
From Satanic Minister to Holy Model: The Sacralization of the Medieval Jongleur
Authors: Dickason Kathryn
Published: June 2023

Few figures in the medieval West were as religiously ambivalent as the medieval jongleur, a broad French term for a popular entertainer. Ecclesiastical authorities typically critiqued jongleurs, aligning them with avarice, folly, and prostitution. However, by the thirteenth century, the jongleur emerged as a more complex figure. Far from being a disciple of the devil, the jongleur could imitate the humility of King David and, by extension, the Passion of Christ. In religious texts and imagery, the jongleur’s embodied performance could exemplify a sacred rite. Showcasing the medieval European jongleur, this article argues that the divide between the sacred and the profane is not as rigid as much scholarship assumes. Ultimately, this study shows the importance of bodily performance in Western medieval religion and therefore complicates the presumed binary between written/Western and embodied/Eastern religiosity.
Antimicrobial susceptibility of Clostridioides difficile to omadacycline and comparator antimicrobials
Authors: Skinner Andrew M , Petrella Laurica A , Cheknis Adam , Johnson Stuart
Published: June 2023

Background

Omadacycline is a novel aminomethylcycline tetracycline antimicrobial that was approved for the treatment of community-associated bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Omadacycline has demonstrated a high degree of in vitro activity towards Clostridioides difficile and previous data have hypothesized that use of omadacycline for CABP or ABSSSI may decrease the risk of C. difficile infections.

Objectives

To compare the in vitro antimicrobial activity of omadacycline versus commonly used antimicrobials for the approved indications of use.

Methods

We compared the antimicrobial activity of eight antimicrobials approved for CABP and ABSSSI against omadacycline by agar dilution on 200 clinically relevant contemporary C. difficile isolates representing local and national prevalent strain types.

Results

The in vitro omadacycline geometric mean MIC was 0.07 mg/L. Ceftriaxone resistance was noted in >50% of all isolates tested. The epidemic strain group, identified as restriction endonuclease analysis (REA) group BI, was commonly resistant to azithromycin (92%), moxifloxacin (86%) and clindamycin (78%). REA group DH strains had an elevated trimethoprim/sulfamethoxazole geometric mean MIC of 17.30 mg/L compared with the geometric mean MIC of 8.14 mg/L noted in all other isolates. In the REA group BK isolates that had a doxycycline MIC of ≥2 mg/L, the omadacycline MIC was <0.5 mg/L.

Conclusions

Among 200 contemporary C. difficile isolates, there were no notable elevations in the in vitro omadacycline MIC, indicating a high level of activity towards C. difficile in comparison with commonly used antimicrobials for CABP and ABSSSI.
In vitro and in vivo susceptibility to cefalexin and amoxicillin/clavulanate in canine low-level methicillin-resistant Staphylococcus pseudintermedius
Authors: Pirolo Mattia , Menezes Mareliza , Damborg Peter , Wegener Alice , Duim Birgitta , Broens Els , Jessen Lisbeth Rem , Schjærff Mette , Guardabassi Luca
Published: June 2023

Background

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) lineages harbouring staphylococcal cassette chromosome (SCC) mec types IV, V and ΨSCCmec57395 usually display low oxacillin MICs (0.5–2 mg/L).

Objectives

To evaluate how oxacillin MICs correlate with PBP mutations and susceptibility to β-lactams approved for veterinary use.

Methods

Associations between MICs and PBP mutations were investigated by broth microdilution, time–kill and genome sequence analyses in 117 canine MRSP strains harbouring these SCCmec types. Clinical outcome was retrospectively evaluated in 11 MRSP-infected dogs treated with β-lactams.

Results

Low-level MRSP was defined by an oxacillin MIC <4 mg/L. Regardless of strain genotype, all low-level MRSP isolates (n = 89) were cefalexin susceptible, whereas no strains were amoxicillin/clavulanate susceptible according to clinical breakpoints. Exposure to 2× MIC of cefalexin resulted in complete killing within 8 h. High (≥4 mg/L) oxacillin MICs were associated with substitutions in native PBP2, PBP3, PBP4 and acquired PBP2a, one of which (V390M in PBP3) was statistically significant by multivariable modelling. Eight of 11 dogs responded to systemic therapy with first-generation cephalosporins (n = 4) or amoxicillin/clavulanate (n = 4) alone or with concurrent topical treatment, including 6 of 7 dogs infected with low-level MRSP.

Conclusions

Oxacillin MIC variability in MRSP is influenced by mutations in multiple PBPs and correlates with cefalexin susceptibility. The expert rule recommending that strains with oxacillin MIC ≥0.5 mg/L are reported as resistant to all β-lactams should be reassessed based on these results, which are highly clinically relevant in light of the shortage of effective antimicrobials for systemic treatment of MRSP infections in veterinary medicine.
NT-proBNP Reference Intervals in Healthy U.S. Children, Adolescents, and Adults
Authors: Mu Scott , Echouffo-Tcheugui Justin B , Ndumele Chiadi E , Coresh Josef , Juraschek Stephen , Brady Tammy , McEvoy John William , Ozkan Bige , Tang Olive , Christenson Robert H , Selvin Elizabeth
Published: June 2023

Background

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker used in the clinical management of heart failure. We sought to create updated reference intervals for NT-proBNP for healthy US children, adolescents, and adults.

Methods

We identified a population of healthy individuals using the 1999 to 2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We measured serum NT-proBNP in 12 346 adults and 15 752 children and adolescents with the Elecsys NT-proBNP assay on the Roche e601 autoanalyzer. We compared 4 methods for reference interval calculation, and presented the final reference intervals using the robust method partitioned by age and sex categories.

Results

NT-proBNP values were available for 1949 healthy adults and 5250 healthy children and adolescents. NT-proBNP concentrations in males and females varied according to age, being higher in early childhood, relatively lower in late adolescence, and highest through middle age and older age. Females tended to have higher NT-proBNP concentrations compared to men from late adolescence until middle age. The upper reference limit, or 97.5th percentile, for 50 to 59 year-old men was 225 ng/L (90% CI: 158 to 236), and for 50 to 59 year-old women, 292 ng/L (90% CI: 242 to 348).

Conclusions

Among healthy individuals, NT-proBNP concentrations varied greatly according age and sex. The reference intervals presented here should inform future clinical decision limits and suggest that age- and sex-specific intervals may be necessary to more precisely characterize risk.
Virulence and antimicrobial resistance of Shiga toxin-producing Escherichia coli from dairy goat and sheep farms in The Netherlands
Authors: van Hoek Angela H A M , Lee Seungeun , van den Berg Redmar R , Rapallini Michel , van Overbeeke Lennert , Opsteegh Marieke , Bergval Indra , Wit Ben , van der Weijden Coen , van der Giessen Joke , van der Voort Menno
Published: June 2023

Aims

The aim of our study was to investigate the virulence and resistance of STEC from small ruminants farms in The Netherlands. Moreover, the potential transmission of STEC between animals and humans on farms was evaluated.

Methods and results

From 182 farms, in total, 287 unique STEC isolates were successfully recovered from animal samples. In addition, STEC was isolated from eight out of 144 human samples. The most detected serotype was O146:H21; however, among other serotypes also O26:H11, O157:H7, and O182:H25 isolates were present. Whole genome sequencing covering all human isolates and 50 of the animal isolates revealed a diversity of stx1, stx2, and eae sub-types and an additional 57 virulence factors. The assessed antimicrobial resistance phenotype, as determined by microdilution, was concordant with the genetic profiles identified by WGS. WGS also showed that three of the human isolates could be linked to an animal isolate from the same farm.

Conclusions

The obtained STEC isolates showed great diversity in serotype, virulence, and resistance factors. Further analysis by WGS allowed for an in-depth assessment of the virulence and resistance factors present and to determine the relatedness of human and animal isolates.
Validation and Standardization of Gallic Acid and Ellagic Acid in Quercus Infectoria, Terminalia Chebula, and Pistacia Integerrima
Authors: Saini Anil Kumar , Zahiruddin Sultan , Newton Kakumani Godwin , Sawant Laxman , Mitra Ranjan , Kumar Rai Rajiva , Ahmad Sayeed
Published: June 2023

Background

Due to its medicinal properties, Pistacia integerrima is in high demand and is extensively used as a key ingredient in various formulations. However, its popularity has led to its inclusion on the International Union for Conservation of Nature threatened category list. In Ayurvedic texts, such as Bhaishajaya Ratnavali, Quercus infectoria is recommended as a substitute for P. integerrima in different formulations. Additionally, Yogratnakar highlights that Terminalia chebula shares similar therapeutic properties with P. integerrima.

Objective

The objective of the current study was to gather scientific data on metabolite profiling and marker-based comparative analysis of Q. infectoria, T. chebula, and P. integerrima.

Methods

In present study, hydroalcoholic and aqueous extracts of all three plants were prepared and standardized for the comparative evaluation of secondary metabolites. TLC was carried out for the comparative fingerprinting of the extracts using chloroform–methanol–glacial acetic acid–water (60 + 8 + 32 + 10, by volume) as a solvent system. A fast, sensitive, selective, and robust HPLC method was developed to determine gallic acid and ellagic acid from both extracts of all three plants. The method was validated for precision, robustness, accuracy, LOD and LOQ as per the International Conference on Harmonization guidelines.

Results

The TLC analysis revealed the presence of several metabolites, and the pattern of metabolites in the plants exhibited a certain degree of similarity. A highly precise and reliable quantification technique was created for gallic acid and ellagic acid, operating within a linear concentration range of 81.18–288.22 µg/mL and 3.83–13.66 µg/mL, respectively. The correlation coefficients for gallic acid and ellagic acid were 0.997 and 0.996, indicating good linear relationships. The gallic acid content in all three plants ranged from 3.74 to 10.16% w/w, while the ellagic acid content ranged from 0.10 to 1.24% w/w.

Conclusion

The study contributes to the scientific understanding of the metabolite profiles and comparative analysis of Q. infectoria, T. chebula, and P. integerrima. The findings provide valuable insights into the chemical composition of these plants and can be used for various applications in herbal medicine.

Highlights

This pioneering scientific approach highlights the phytochemical similarities between Q. infectoria, T. chebula and P. integerrima.
Characterization of extensive 2-fluorodeschloroketamine metabolism in pooled human liver microsomes, urine and hair from an addicted patient using high-resolution accurate mass spectrometry
Authors: Joseph Delphine , Lesueur Camille , Zerizer Fanny , Fenot Alexia , Alvarez Jean Claude , Larabi Islam Amine
Published: June 2023

2-Fluorodeschloroketamine (2F-DCK) is a ketamine derivative involved in acute intoxications and deaths. The aim of this study is to investigate its metabolism using pooled human liver microsomes (pHLMs) and to apply it to authentic samples (urine, hair and seized materials) from a drug user. 2F-DCK (100 µM) incubates with pHLMs were analyzed by liquid chromatography–high-resolution accurate mass (LC–HRAM; Q-Exactive, Thermo Fisher Scientific®) according to a previously published protocol. Spectra annotation was performed using Compound Discoverer® software and the metabolic scheme was drawn using ChemDraw software. Urine (200 µL) and hair (previously decontaminated using dichloromethane and segmented into three segments: A, 0–3 cm; B, 3–6 cm; C, 6–9 cm) were extracted with a mixture of hexane:ethyl acetate (1:1) and chloroform:isopropanol (4:1). About 10 µL of both reconstituted residues were analyzed by LC–HRAM. Hair was also analyzed by LC–MS-MS (TSQ Vantage, Thermo Fisher Scientific®) for 2F-DCK and deschloroketamine (DCK) quantification. The two presumed 2F-DCK crystals consumed by the patient were dissolved in methanol (1 mg/mL) and 10 µL were analyzed by LC–MS-MS (Quantum Access Max, Thermo Fisher Scientific®). Twenty-six putative 2F-DCK metabolites were identified, 15 being reported for the first time. Thirteen metabolites were detected in pHLMs, 10 confirmed in both the patient’s urine and hair and all were found in at least one of the two samples. Twenty-three metabolites were detected in urine and 20 in hair. Our research confirms the reliability of nor-2F-DCK as a target analyte and suggests OH-dihydro-nor-2F-DCK and dehydro-nor-2F-DCK as new target analytes in urine and hair, respectively. This is the first study to report DCK as a 2F-DCK metabolite using pHLMs and to determine its concentrations in hair (A/B/C, 885/1,500/1,850 pg/mg) following chronic use. Finally, the two seized crystals contained 2F-DCK at 67% and 96% with traces of DCK (0.4% and 0.6%) related to cross-contamination by container exchange.
Case report of a fatal 3-hydroxyphencyclidine intoxication, including blood and hair results
Authors: Ameline Alice , Baudry Morgane , Garnier Delphine , Raul Jean-Sébastien , Kintz Pascal
Published: June 2023

3-Hydroxyphencyclidine (3-OH-PCP) is a hydroxy derivative of phencyclidine, synthesized in 1978 to investigate the structure–activity relationship of phencyclidine derivates. In vitro studies have shown that 3-OH-PCP, like phencyclidine, acts on the N-methyl-D-aspartate receptor and has a higher affinity for this receptor than phencyclidine. The authors report the case of a 38-year-old man, known for drug addiction, found dead at home with two plastic bags of powders found near his body. Using liquid chromatography coupled to tandem mass spectrometry, peripheral blood toxicological analysis revealed consumption of 3-OH-PCP with a concentration of 3-OH-PCP being 524 ng/mL. Blood also tested positive for nordiazepam, methylphenidate, amisulpride, methadone and benzoylecgonine, all at concentrations near those observed after recreational abuse. The blood concentration of 3-OH-PCP is the highest ever reported in the literature. Hair testing also revealed 3-OH-PCP, at 174 pg/mg, which may correspond to a chronic consumption of this molecule. A nuclear magnetic resonance analysis of the two powders highlighted 3-OH-PCP and 5-methoxy-dimethyltryptamine, estimated to have a purity of 85.4 and 91.3%, respectively, using the Electronic Reference To access In vivo Concentrations method.
Identification of postmortem paliperidone metabolite in human blood by LC–Q-Orbitrap-MS
Authors: Yamagishi Yoshikazu , Inokuchi Go , Hoshioka Yumi , Nagasawa Sayaka , Iwase Hirotaro , Ogra Yasumitsu
Published: June 2023

Paliperidone is a widely used antipsychotic agent detected in many fatal intoxications and suicide cases. In forensic toxicology, the accurate determination of blood paliperidone concentrations is required to prove death by paliperidone poisoning. However, the lethal concentration of paliperidone in blood at autopsy differs from that at the time of death. In this study, we found that paliperidone was decomposed by hemoglobin (Hb) through the Fenton reaction in a temperature-dependent fashion. The mechanism underlying paliperidone decomposition involves the cleavage of its C–N bond linker moiety. The mass spectra obtained by liquid chromatography–quadrupole orbitrap mass spectrometry revealed the formation of 6-fluoro-3-(4-piperidinyl)benzisoxazole (PM1) in Hb/H2O2 solution incubated with paliperidone, as well as in the blood of individuals who died from intentional ingestion of paliperidone. These results suggest that PM1 is the only metabolite produced from paliperidone as a result of temperature-dependent, postmortem changes induced by Hb via the Fenton reaction and may be useful as a biomarker to correct for the concentration of paliperidone in blood at the time of death in clinical cases.
Fashion and Image as Anthropographic Elements in Nineteenth-century Colombia
Authors: Bermúdez-Castillo Jairo , Barraza Astrid Barrios , Delgado Osorio Claudia Patricia , Verastegui Maristela
Published: June 2023

This article is the product of a research project about the role of image in the creation of the Colombian nation during the nineteenth century. Part of that image depended on the individuals it identified, their social status, their lifestyle, and their occupation. The image of fashion as a characteristic social identifier, as an icon, was a bearer of anthropographic symbols. In nineteenth-century Colombia, those symbols were connected to a republican identity characterized by its colonial heritage, determined by race, and by garments distinctive of specific social classes: formerly subjects and, later, citizens. Thus, the image that fashion conveyed as the “skin of the skin” of the republican ancestors, the elite, and the people constitutes a legacy that encompasses everything, from the manufacture of textiles and the indigenous ruana, to a kind of textile mestizaje with aspects of European provenance. Items from collections in museums, libraries, and archives, were compared to texts composed by travelers and illustrators, in order to unveil elements of national identity in what emerges as the landscape of fashion in Colombia during the nineteenth century.
Regulators as Guardians of Trust? The Contingent and Modest Positive Effect of Targeted Transparency on Citizen Trust in Regulated Sectors
Authors: Grimmelikhuijsen Stephan , de Vries Femke , Bouwman Robin
Published: June 2023

Targeted transparency has become an essential tool for regulation. Through information disclosure, regulatory agencies try to get regulated companies to improve their practices and comply with regulations. In the past, regulation was associated with distrust in regulated sectors. Recent research suggests that regulation, especially targeted transparency, may also increase citizen trust in regulated sectors. However, empirical evidence on whether transparency as a regulatory tool undermines or decreases trust in a sector is lacking. We contribute to this debate by investigating the effect of targeted transparency on citizen trust through a large-scale representative survey experiment (n = 5,303). We used 12 transparency frames in three regulated domains in the Netherlands (consumer rights, healthcare safety, and nuclear plant safety). Our findings suggest that, in general, targeted transparency does not undermine trust, but has a positive effect on trust in regulated sectors. However, this effect is small and contextual, depending on the regulatory domain and type of transparency frame.
Pooling resources: Statistics, swimming and why winners don’t always finish first
Authors: Rice Caity , Winter Peter , Rowson Alan , Peters Jeroen
Published: June 2023

Caity Rice, Peter Winter, Alan Rowson and Jeroen Peters explain how statistics can be used to compare swimming performances between athletes across all age groups and with different disability classifications, creating inclusive and competitive events
How “normal” is the normal distribution?
Authors: Waynforth David
Published: June 2023

David Waynforth describes how non-normal distributions occur for good reasons in human biology, and can be invaluable when teaching medical students
Interaction of ammonium nutrition with essential mineral cations
Authors: Coleto Inmaculada , Marín-Peña Agustín J , Urbano-Gámez José Alberto , González-Hernández Ana Isabel , Shi Weiming , Li Guangjie , Marino Daniel
Published: June 2023

Plant growth and development depend on sufficient nutrient availability in soils. Agricultural soils are generally nitrogen (N) deficient, and thus soils need to be supplemented with fertilizers. Ammonium (NH4+) is a major inorganic N source. However, at high concentrations, NH4+ becomes a stressor that inhibits plant growth. The cause of NH4+ stress or toxicity is multifactorial, but the interaction of NH4+ with other nutrients is among the main determinants of plants’ sensitivity towards high NH4+ supply. In addition, NH4+ uptake and assimilation provoke the acidification of the cell external medium (apoplast/rhizosphere), which has a clear impact on nutrient availability. This review summarizes current knowledge, at both the physiological and the molecular level, of the interaction of NH4+ nutrition with essential mineral elements that are absorbed as cations, both macronutrients (K+, Ca2+, Mg2+) and micronutrients (Fe2+/3+, Mn2+, Cu+/2+, Zn2+, Ni2+). We hypothesize that considering these nutritional interactions, and soil pH, when formulating fertilizers may be key in order to boost the use of NH4+-based fertilizers, which have less environmental impact compared with nitrate-based ones. In addition, we are convinced that better understanding of these interactions will help to identify novel targets with the potential to improve crop productivity.
HvSL1andHvMADS16promote stamen identity to restrict multiple ovary formation in barley
Authors: Selva Caterina , Yang Xiujuan , Shirley Neil J , Whitford Ryan , Baumann Ute , Tucker Matthew R
Published: June 2023

Correct floral development is the result of a sophisticated balance of molecular cues. Floral mutants provide insight into the main genetic determinants that integrate these cues, as well as providing opportunities to assess functional variation across species. In this study, we characterize the barley (Hordeum vulgare) multiovary mutants mov2.g and mov1, and propose causative gene sequences: a C2H2 zinc-finger gene HvSL1 and a B-class gene HvMADS16, respectively. In the absence of HvSL1, florets lack stamens but exhibit functional supernumerary carpels, resulting in multiple grains per floret. Deletion of HvMADS16 in mov1 causes homeotic conversion of lodicules and stamens into bract-like organs and carpels that contain non-functional ovules. Based on developmental, genetic, and molecular data, we propose a model by which stamen specification in barley is defined by HvSL1 acting upstream of HvMADS16. The present work identifies strong conservation of stamen formation pathways with other cereals, but also reveals intriguing species-specific differences. The findings lay the foundation for a better understanding of floral architecture in Triticeae, a key target for crop improvement.
Exogenous monoterpenes mitigate H2O2-induced lipid damage but do not attenuate photosynthetic decline during water deficit in tomato
Authors: Zhou Hao , Ashworth Kirsti , Dodd Ian C
Published: June 2023

Although monoterpenes are suggested to mediate oxidative status, their role in abiotic stress responses is currently unclear. Here, a foliar spray of monoterpenes increased antioxidant capacity and decreased oxidative stress of Solanum lycopersicum under water deficit stress. The foliar content of monoterpenes increased with spray concentration indicating foliar uptake of exogenous monoterpenes. Exogenous monoterpene application substantially decreased foliar accumulation of hydrogen peroxide (H2O2) and lipid peroxidation (malondialdehyde). However, it appears that monoterpenes prevent the accumulation of reactive oxygen species rather than mitigating subsequent reactive oxygen species-induced damage. Low spray concentration (1.25 mM) proved most effective in decreasing oxidative stress but did not up-regulate the activity of key antioxidant enzymes (superoxide dismutase and ascorbate peroxidase) even though higher (2.5 and 5 mM) spray concentrations did, suggesting a complex role for monoterpenes in mediating antioxidant processes. Furthermore, soil drying caused similar photosynthetic limitations in all plants irrespective of monoterpene treatments, apparently driven by strong reductions in stomatal conductance as photosystem II efficiency only decreased in very dry soil. We suggest that exogenous monoterpenes may mitigate drought-induced oxidative stress by direct quenching and/or up-regulating endogenous antioxidative processes. The protective properties of specific monoterpenes and endogenous antioxidants require further investigation.
The first reported case of double trisomy 10 and 20 in a product of conception
Authors: Fernandez De La Vega Joshua , Lahiji Arian Pourmehdi , Raymond Caitlin , Han Song , Thaker Harshwardhan , Dong Jianli
Published: June 2023

Background

Double trisomies are rare findings among products of conception and are often lethal to the developing embryo or fetus.

Methods

Here we describe a double trisomy case with symptoms of threatened miscarriage at 9 weeks gestation. Ultrasound revealed an anembryonic pregnancy. Pregnancy was terminated by dilation and curettage at gestational age 11 weeks and 6 days. Histologic examination and chromosome microarray were performed on a formalin-fixed product of conception (POC) sample to identify the cause of the anembryonic pregnancy.

Results

Chromosome microarray analysis revealed a female chromosome complement with double trisomies 10 and 20, arr(10,20)x3, consistent with a karyotype of 48,XX,+10,+20.

Conclusion

To the best of our knowledge, this is the first reported case of double trisomy 10 and 20 in a POC. Due to nonspecific histopathological findings, chromosomal microarray is a powerful tool in identifying and differentiating chromosomal aneuploidies.