bluuebunny/crossref_metadata_2025 huggingface dataset:
CYCLIC VARIATION OF PLASMINOGEN ACTIVATION IN HUMAN UTERINE FLUID AND THE INFLUENCE OF AN INTRAUTERINE DEVICE
Authors: Casslén Bertil , Ohlsson Kjell
Published: September 2024

Activation of plasminogen to plasmin in uterine fluid results in the formation of plasmin‐α2‐antiplasmm complexes. The degree of plasminogen activation was studied during the menstrual cycle in IUD‐users and non‐users. The absence of free plasminogen in the presence of plasmin complexes indicated complete activation of the zymogen. The simultaneous occurrence of free plasminogen and plasmin complexes was interpreted to represent incomplete activation. Results were correlated with the concentration of α2‐antiplasmin, a major inhibitor of urokinase and plasmin. In the midcycle phase of IUD‐non‐users, plasminogen activation was complete and the concentration of α2‐antiplasmin was low. In the luteal phase of the same population the concentration of α2‐arttiplasmin was high and there was no plasminogen activation. In contrast, IUD‐users generally had an incomplete activation of plasminogen throughout the menstrual cycle. Also, their concentrations of α2‐antiplasmin were increased in the proliferative and midcycle phases.
THE PLACENTA IN INTRAUTERINE FETAL DEPRIVATION
Authors: Diamant Y. Z. , Kissilevitz R.
Published: September 2024

Sixteen placentas from pregnancies complicated by mild preeclamptic toxemia, 11 placentas from pregnancies associated with severe pre‐eclampsia and intrauterine growth retardation (IGR), 14 placentas from IGR gestation of non‐toxemic origin, and 47 placentas from normal pregnancies terminated at 38–40 weeks by the birth of live babies, were investigated for total organ weight, DNA, protein content (PC), triglyceride (TG), cholesterol (CL), phospholipid phosphorus (P‐PL), percentage of dry matter, and for activity of enzymes with a regulatory function in the pathway of glycolysis, gluconeogenesis and NADPH generation. Feto/placental weight ratios and Apgar scores were also calculated. Placentas from pregnancies complicated by mild toxemia showed a significantly reduced proportion of dry matter, total DNA and PC. No significant changes in lipid content or enzyme activity were detected. The infants had normal birth weight and high Apgar scores. Placentas from pregnancies associated with severe pre‐eclamptic toxemia and IGR of non‐toxemic origin showed profound metabolic changes, not necessarily of the same nature. In placentas from severe toxemia, in addition to a decreased dry matter, DNA and PC, a significant increase in intracellular and whole placenta TG and P‐PL concentrations was observed as well as a decrease in CL/TG and CL/PL ratios. Concomitantly, the activity of pyruvate kinase (PK)—which regulates the energy generating glycolytic pathway at the cellular and whole placental levels—was decreased. The activity of enzymes that are connected with gluconeogenic and NADPH generating pathways, was also reduced when calculated per whole organ weight. These placental metabolic changes were accompanied by a significant reduction in placental and baby body weights and by decreased newborn Apgar scores. In contrast, in placentas from IGR pregnancies of non‐toxemic origin, the intracellular TG and PL contents were unchanged and whole placental concentrations were also decreased, despite a reduced DNA and whole placental PC. The CL/TG and CL/PL ratios also remained unchanged. PK activity proved significantly elevated at the cellular level and showed no changes when calculated per total placental weight. The same pattern was seen in the activity of enzymes related to NADPH generation whereas the activity of gluconeogenic enzymes was significantly decreased when calculated per whole placenta. On the basis of these results, it is suggested that IGR in severe toxemia may be closely connected with acceleration of the aging processes of placental tissue. On the other hand, in cases of IGR of non‐toxemic origin, the metabolic compensation at the cellular level in the small placenta facilitates adequate support for fetal growth. It therefore seems unlikely that in this group the IGR is of placental origin.
GRANULAR CELL TUMOR IN THE PERINEUM
Authors: Hansborg Niels , Refn Hanne
Published: September 2024

Granular cell tumor is a lesion which clinically often resembles a fibroma. The tumor is, however, frequently ill‐defined, and it may be mistaken for a malignant growth. The granular cell tumor is only rarely located to the perineum. A total of 55 cases have been reported. The diagnosis can be obtained by frozen section microscopy. Recurrence is prevented by excising the whole lesion. The development of malignancy is extremely rare.
Associations between income/employment status and diabetes care processes, health behaviors, and health outcomes in Japan: A cross‐sectional study using claims data linked to a questionnaire survey
Authors: Yamaoka Takuya , Sugiyama Takehiro , Ihana‐Sugiyama Noriko , Kimura Akiko , Yamamoto Kouko , Imai Kenjiro , Kuroda Naoaki , Ohsugi Mitsuru , Ueki Kohjiro , Yamauchi Toshimasa , Tamiya Nanako
Published: September 2024

Aims/Introduction

We aimed to explore the associations between income/employment status and diabetes care processes, health behaviors and health outcomes.

Materials and Methods

This cross‐sectional study used health insurance claims data between April 2021 and March 2022, and a questionnaire survey between December 2022 and January 2023 in Tsukuba City. The study analyzed the participants with diabetes (other than type 1) from those selected by stratified random sampling. We evaluated diabetes care processes, health behaviors and health outcomes by calculating weighted proportions among the groups. We also assessed the associations between income/employment status and these variables using multivariable modified Poisson regression models.

Results

Of the 264 identified participants, 161 (64.2%) were men and 168 (72.8%) were aged ≥65 years old. Compared with the low‐income groups, the high‐income group had a higher proportion of sodium–glucose cotransporter 2 inhibitors or glucagon‐like peptide‐1 receptor agonists use (adjusted risk ratio [aRR] 1.70, 95% confidence interval (CI) 1.07–2.72), a higher proportion of attendance to annual health checkups for ≥2 years (aRR 1.68, 95% CI 1.07–2.64) and a lower proportion of all‐cause hospitalization (aRR 0.15, 95% CI 0.04–0.48); additionally, the middle‐income group had a lower proportion of high total outpatient medical expenses (aRR 0.57, 95% CI 0.35–0.92). Compared to the no work time group, the full‐time work group had a lower proportion of exercise habits (aRR 0.59, 95% CI 0.35–0.99) and a higher proportion of good self‐reported health (aRR 2.08, 95% CI 1.22–3.55).

Conclusions

Several variables were associated with income/employment status. Policy intervention should focus on high‐risk groups identified by considering these associations.
Influence of acclimatization time on barometric whole‐body plethysmography in cats with lower airway disease
Authors: Hörner‐Schmid Lina , Gareis Hannah , Palić Jelena , Schulz Bianka
Published: September 2024

Background

Barometric whole‐body plethysmography (BWBP) is used as a noninvasive method to assess lung function in cats with lower airway disease (LAD). The duration of the acclimatization period in the measuring chamber varies between the studies.

Objectives

To assess the influence of acclimatization time on variables indicative of lung function.

Animals

Twenty‐four client‐owned cats with LAD and 8 healthy cats.

Methods

In the prospective case‐control study for each cat, a 30‐minute dataset was collected. Data for the three 10‐minute periods were statistically compared.

Results

The variables pause (T1 median: 0.8, range: [0.7‐1]; T3: 0.9 [0.8‐1.1]; P ≤ .01), peak inspiratory flow (PIF; T1: 84.9 [71.6‐112.7]; T3: 75 [63.6‐108.3]; P ≤ .001), peak expiratory flow (PEF; T1: 53.2 [41.5‐76.6]; T3: 42.5 [34.6‐57.8]; P ≤ .01), and a quotient of PEF and expiratory flow at 50% expired volume (PEF/EF50; T1: 1.2 [1.1‐1.4]; T3: 1.2 [1.1‐1.5]; P ≤ .01) varied significantly between first and third time period in cats with LAD. In healthy cats PIF (T1: 76.4 [66.3‐85.2]; T2: 69.5 [58.3‐85.2]; P ≤ .01), PEF (T1: 40 [32.8‐58.6]; T2: 34.3, [29.8‐44.6]; P ≤ .01), and PEF/EF50 (T1: 13.1 [11.6‐14.6]; T3: 13.6 [12.4‐16.3]; P ≤ .01) changed significantly between first and second time period. Enhanced pause did not change significantly in either group.

Conclusions and Clinical Importance

Acclimatization time has a significant influence on multiple variables in BWBP. Manual correction of the data for tidal breathing flow‐volume loop might be necessary.
Treatment of a urethral stricture by image‐guided placement of a custom‐made absorbable stent in a standing, sedated horse
Authors: Baltrimaite Milda , Kearney Clodagh , O'Brien Anne , Duggan Michael , Cuq Benoît
Published: September 2024

A 10‐year‐old Irish Sport Horse gelding developed complications from a general anesthesia resulting in sling support and recurrent urinary catheterization. The horse subsequently presented signs of dysuria and pollakiuria, was diagnosed with sabulous cystitis, and developed a urethral stricture from the repeated catheterizations, which was confirmed on urethroscopy. Clinical signs persisted despite conservative management with topical corticosteroids and urethral bougienage with balloon dilators. An image‐guided approach was used to treat the stricture with a custom‐made polydioxanone stent placed in the urethra after which the horse was able to void normally and fully empty his bladder. Repeat urethroscopy and ultrasonography 6 months after the procedure showed the stent to have completely reabsorbed with urethra remaining patent. Nineten months after the procedure, the owner reports the horse remaining at his intended level of athletic performance with no dysuria.
Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation
Authors: Suri Anandini , Zhang Zidong , Neuschwander‐Tetri Brent , Lomas David A. , Heyer‐Chauhan Nina , Burling Keith , Loomba Rohit , Brenner David A. , Nagy Rosemary , Wilson Andrew , Carpenter Danielle , Blomenkamp Keith , Teckman Jeffrey
Published: September 2024

Background and Aims

The course of adults with ZZ alpha‐1‐antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined.

Methods

A prospective cohort, including protocol liver biopsies, was enrolled to address these questions.

Results

We enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0–6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0–1, 36% Ishak 2–3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis.

Conclusion

In AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.
Job satisfaction and workplace representation in Europe
Authors: Addison John T. , Teixeira Paulino
Published: September 2024

The backdrop to this inquiry into the relationship between worker job satisfaction and workplace representation in European nations is twofold. The first is that the bulk of research has focused on union membership and job satisfaction in Anglophone nations with their very different industrial relations systems and bargaining arrangements. The second and more immediate context is the dramatic shift from negative to positive in the association between union membership and job satisfaction (inter al.) observed in the most recent literature. Using data on 28 European nations from the last two waves of the European Working Conditions Survey, however, we report that workers in establishments with formal workplace representation record lower job satisfaction than their counterparts in plants without such representation. These findings of conditional correlation are then upgraded by constructing a pseudo‐panel with cohort fixed effects to take account of unobserved worker heterogeneity. First‐difference estimates suggest that the negative relationship between worker representation and job satisfaction found in cross section continues to hold. Next, an endogenous treatment effects model is deployed to address the possible endogeneity of worker representation. The results are supportive of a causal negative relationship between job satisfaction and worker representation. One interpretation of our findings is that in the matter of the association between unions and job satisfaction the jury is still out.
Looking beyond, around and within cultural differences and dialogues across the open access ecosystem
Authors: Céspedes Lucía , Maggio Lauren A.
Published: September 2024

Céspedes and Maggio turn a lens on publication practices in their contribution to this special issue's focus on cross‐cultural dialogue.
Photodegradation in terrestrial ecosystems
Authors: Austin Amy T. , Ballaré Carlos L.
Published: September 2024

The first step in carbon (C) turnover, where senesced plant biomass is converted through various pathways into compounds that are released to the atmosphere or incorporated into the soil, is termed litter decomposition. This review is focused on recent advances of how solar radiation can affect this important process in terrestrial ecosystems. We explore the photochemical degradation of plant litter and its consequences for biotic decomposition and C cycling. The ubiquitous presence of lignin in plant tissues poses an important challenge for enzymatic litter decomposition due to its biological recalcitrance, creating a substantial bottleneck for decomposer organisms. The recognition that lignin is also photolabile and can be rapidly altered by natural doses of sunlight to increase access to cell wall carbohydrates and even bolster the activity of cell wall degrading enzymes highlights a novel role for lignin in modulating rates of litter decomposition. Lignin represents a key functional connector between photochemistry and biochemistry with important consequences for our understanding of how sunlight exposure may affect litter decomposition in a wide range of terrestrial ecosystems. A mechanistic understanding of how sunlight controls litter decomposition and C turnover can help inform management and other decisions related to mitigating human impact on the planet.
New evidence for five cephalic appendages in trilobites and implications for segmentation of the trilobite head
Authors: Hou Jin‐bo , Hopkins Melanie J.
Published: September 2024

Head segments play a critical role in revealing the relationships within major arthropod groups but the accurate determination of their number and relationship is challenging because of the decoupling of dorsal tergites and ventral appendages. In recent decades, trilobites have been considered to have four pairs of cephalic appendages and, commonly, five dorsal segments, which has served as the basis for understanding euarthropod cephalic evolution. Based on multiple analytical techniques applied to well‐preserved soft‐bodied specimens of the Upper Ordovician olenid Triarthrus eatoni and middle Cambrian corynexochid Olenoides serratus, we argue that an additional pair of cephalic biramous appendages occurred just behind the antennae, indicating that trilobites had five pairs of cephalic appendages and six dorsally expressed segments. We propose that the mismatch between the four dorsal furrows and five ventral appendages in Olenoides may be reconciled by considering the morphology of the hypostome that marks the position of the antenna and the bifurcation of the first glabellar furrow that has two muscle attachment sites fused. The fusion of clustered attachment sites of the cephalic biramous appendages may have aided feeding ability by gathering the limb bases close to the mouth.
Withania somnifera osmotin (WsOsm) confers stress tolerance in tobacco and establishes novel interactions with the defensin protein (WsDF)
Authors: Singh Varinder , Hallan Vipin , Pati Pratap Kumar
Published: September 2024

Pathogenesis‐related proteins (PR), including osmotins, play a vital role in plant defense, being activated in response to diverse biotic and abiotic stresses. Despite their significance, the mechanistic insights into the role of osmotins in plant defense have not been extensively explored. The present study explores the cloning and characterization of the osmotin gene (WsOsm) from Withania somnifera, aiming to illuminate its role in plant defense mechanisms. Quantitative real‐time PCR analysis revealed significant induction of WsOsm in response to various phytohormones e.g. abscisic acid, salicylic acid, methyl jasmonate, brassinosteroids, and ethrel, as well as biotic and abiotic stresses like heat, cold, salt, and drought. To further elucidate WsOsm's functional role, we overexpressed the gene in Nicotiana tabacum, resulting in heightened resistance against the Alternaria solani pathogen. Additionally, we observed enhancements in shoot length, root length, and root biomass in the transgenic tobacco plants compared to wild plants. Notably, the WsOsm‐ overexpressing seedlings demonstrated improved salt and drought stress tolerance, particularly at the seedling stage. Confocal histological analysis of H2O2 and biochemical studies of antioxidant enzyme activities revealed higher levels in the WsOsm overexpressing lines, indicating enhanced antioxidant defense. Furthermore, a pull‐down assay and mass spectrometry analysis revealed a potential interaction between WsOsm and defensin, a known antifungal PR protein (WsDF). This suggests a novel role of WsOsm in mediating plant defense responses by interacting with other PR proteins. Overall, these findings pave the way for potential future applications of WsOsm in developing stress‐tolerant crops and improving plant defense strategies against pathogens.
Changes in leaf lifespan, nitrogen resorption, and mean residence time of leaf nitrogen along a soil fertility gradient in an evergreen oak tree
Authors: Oikawa Shimpei
Published: September 2024

The ability of plants to retain nitrogen (N) for a long period of time is critical to their N use efficiency, growth, and fitness, particularly in infertile environments. The mean residence time of leaf N (MRTL) and its two determinants, leaf lifespan and N resorption efficiency (rN, the fraction of the total leaf N pool that is resorbed during leaf senescence), have been hypothesized to increase plastically with decreasing soil N fertility but this remains to be fully tested. To avoid confusion by random changes in these characteristics in a relatively narrow N fertility range, MRTL, leaf lifespan, and N resorption efficiency were measured in Quercus glauca over a broad N fertility range. In the high to moderate N fertility range, leaf lifespan and rN increased with decreasing N addition rate, and thus the MRTL increased. However, in the moderate to low N fertility range, leaf lifespan increased but rN decreased significantly, so MRTL decreased. The decrease in rN occurred because the senesced leaf N concentration was almost constant at the lower limit while the green leaf N concentration decreased in this range. The hump‐shaped quadratic responses of MRTL and rN along the N fertility gradient suggest that incorrect conclusions about the response of these traits to N fertility variation may be drawn from experiments that include only a few fertility levels, and N recycling within leaf canopy alone cannot achieve efficient N use in infertile environments.
Optimal Support for Elite Sprinters Using a Minimal, Adequate, and Accurate Approach
Authors: Washif Jad Adrian , Pyne David B.
Published: September 2024

Background: In high-performance sport, the support provided by sport scientists and other staff can be a valuable resource for coaches and athletes. Purpose: We propose and detail here the approach of “minimal, adequate, and accurate” sport-science support to ensure that programs of work and solutions are both economical and effective. Methods: Our support provision advocates for utilization of “minimal” resources (employing the least amount of time, tools, and funding) necessary to achieve the desired outcomes. We strive for “adequate” information that fulfills specific objectives without excess and with the requirement that methods and data used are “accurate” (valid and reliable). To illustrate the principles of this approach, we outline a real-world example of supporting 100-m track (athletics) sprinters preparing and competing in an international competition. The provision of performance support emphasizes an integrated approach, combining knowledge and insights from multiple sport-science disciplines. The key facets managed under this approach are (1) neuromuscular readiness, (2) wellness monitoring, (3) movement observation, (4) motivation, (5) biomechanics and performance analysis, and (6) qualitative feedback. These facets are based on the specific performance determinants and influencing factors of an event (100-m dash). Conclusions: Application of this quantitative and qualitative approach can enhance the ability to make informed decisions. Nevertheless, the approach must be planned, evaluated, and refined on a regular basis to enable effective decision making in sport-science support. The 3-element approach of “minimal, adequate, and accurate” should be codesigned and supported by the athletes, coaches, and staff to ensure successful implementation.
Microbial dietary preference and interactions affect the export of lipids to the deep ocean
Authors: Behrendt Lars , Alcolombri Uria , Hunter Jonathan E. , Smriga Steven , Mincer Tracy , Lowenstein Daniel P. , Yawata Yutaka , Peaudecerf François J. , Fernandez Vicente I. , Fredricks Helen F. , Almblad Henrik , Harrison Joe J. , Stocker Roman , Van Mooy Benjamin A. S.
Published: September 2024

Lipids comprise a significant fraction of sinking organic matter in the ocean and play a crucial role in the carbon cycle. Despite this, our understanding of the processes that control lipid degradation is limited. We combined nanolipidomics and imaging to study the bacterial degradation of diverse algal lipid droplets and found that bacteria isolated from marine particles exhibited distinct dietary preferences, ranging from selective to promiscuous degraders. Dietary preference was associated with a distinct set of lipid degradation genes rather than with taxonomic origin. Using synthetic communities composed of isolates with distinct dietary preferences, we showed that lipid degradation is modulated by microbial interactions. A particle export model incorporating these dynamics indicates that metabolic specialization and community dynamics may influence lipid transport efficiency in the ocean’s mesopelagic zone.
Biogenic secondary organic aerosol participates in plant interactions and herbivory defense
Authors: Yu Hao , Buchholz Angela , Pullinen Iida , Saarela Silja , Li Zijun , Virtanen Annele , Blande James D.
Published: September 2024

Biogenic secondary organic aerosols (SOAs) can be formed from the oxidation of plant volatiles in the atmosphere. Herbivore-induced plant volatiles (HIPVs) can elicit plant defenses, but whether such ecological functions persist after they form SOAs was previously unknown. Here we show that Scots pine seedlings damaged by large pine weevils feeding on their roots release HIPVs that trigger defenses in neighboring conspecific plants. The biological activity persisted after HIPVs had been oxidized to form SOAs, which was indicated by receivers displaying enhanced photosynthesis, primed volatile defenses, and reduced weevil damage. The elemental composition and quantity of SOAs likely determines their biological functions. This work demonstrates that plant-derived SOAs can mediate interactions between plants, highlighting their ecological significance in ecosystems.
Characterization of a Lewis adduct in its inner and outer forms
Authors: Liu Wei-Chun , Gabbaï François P.
Published: September 2024

The entrance channel of bimolecular reactions sometimes involves the formation of outer complexes as weakly bound, fleeting intermediates. Here, we characterize such an outer complex in a system that models the bimolecular, C-O bond–forming reaction of a phosphine oxide Lewis base with a carbenium Lewis acid. Crystallographic studies show that the C-O distance in the outer form exceeds that of the final or inner adduct by 1.1 angstroms. As the system samples the two forms of the complex, which correspond to minima on the corresponding potential energy surface, the C-O linkage switches from a secondary interaction in the outer complex to a dative bond in the inner complex. This phenomenon is harnessed as a functional feature to stabilize xanthylium-based photoredox catalysts.
Post-2030 global goals need explicit targets for cities and businesses
Authors: Bai Xuemei
Published: September 2024

The 17
Sustainable Development Goals
(SDGs), universally adopted by all
193 United Nations (UN) Member States
in 2015, represent a shared vision for people and the planet. With a framework containing 169 targets and 248 indicators, the SDGs stipulate an aspirational agenda for global society to achieve by 2030. Since their adoption, SDGs have been impactful in some respects. They frequently appear in government documents and national leaders' speeches, and all but a handful of countries have reported progress via
Voluntary National Reviews
. SDGs have been a source of inspiration for the research community—a quick search in Elsevier’s SCOPUS database would show more than 9000 research articles published to date with SDGs in their title.
Decoding the surface of a complex oxide
Authors: Giessibl Franz J. , Weymouth Alfred John
Published: September 2024

Atomic force microscopy reveals the elusive structure of the aluminum oxide surface
ChatGPT to the rescue?
Authors: Thorp H. Holden
Published: September 2024

For years, but especially since the pandemic, this page and many others in
Science
and elsewhere have been filled with lamentations about the spread of scientific misinformation—and hand wringing on how to prevent it. High-speed sharing and the relentless activity of social media influencers have made this difficult problem even worse. Dangerous skepticism about the COVID-19 vaccine, for example, continues to stoke wider hesitancy to other vaccines, a disastrous consequence for public health. Solutions to blunt scientific misinformation have been elusive. Now a new study, reported in this issue of
Science
, suggests that artificial intelligence (AI) could provide a means to dispel misinformation and in a way that lasts.
The burden of a gene
Authors: Kaiser Jocelyn
Published: September 2024

A variant called
APOE4
is notorious for its link to Alzheimer’s. Can new insights into its function help stave off disease?
Strong El Niños primed Earth for mass extinction
Authors: Voosen Paul
Published: September 2024

Extreme weather sparked by ocean shifts set stage for Great Dying 250 million years ago
Old poliovirus sample hints at recent lab leak
Authors: Kupferschmidt Kai
Published: September 2024

Strain that infected a Chinese child in 2014 is close to one Albert Sabin sent to Paris in 1960
Recent increase in
Candida auris
frequency in the SENTRY surveillance program: antifungal activity and genotypic characterization
Authors: Castanheira Mariana , Deshpande Lalitagauri M. , Rhomberg Paul R. , Carvalhaes Cecilia G.
Published: September 2024

We observed an increase in the frequency of
Candida auris
among invasive candidiasis isolates in the 2022 SENTRY Antifungal Surveillance Program compared to prior years: ≤0.1% before 2018, 0.4%–0.6% from 2018 to 2021, and 1.6% in 2022.
C. auris
isolates were collected in seven countries, but 28 (35.9%) isolates were recovered in the USA (five states; more common in New York, Texas, and New Jersey) and 26 (33.3%) in Panama. Greece and Turkey had 12 and 9 isolates, respectively. Overall, 82.1% of the isolates were resistant to fluconazole; 17.9% were resistant to amphotericin B; and 1.3% were resistant to caspofungin, anidulafungin, or micafungin (Centers for Disease Control and Prevention tentative resistance breakpoints). Rezafungin inhibited 96.2% of the isolates (Clinical and Laboratory Standards Institute susceptibility breakpoint). Pandrug resistance was not observed, but 17.9% of the isolates were resistant to fluconazole and amphotericin B. South Asian (Clade I) isolates were most common (
n
= 40, 51.3%); of these, 97.5% were resistant to fluconazole and 30.0% were resistant to amphotericin B. Thirty (38.5%) isolates belonged to the South American region (Clade IV), and 56.7% of those were resistant to fluconazole and 6.7% to amphotericin B. Seven isolates belonged to the South African Clade III and one to East Asian Clade II. Erg11 (Y132F, K143R, and F126L) and MRR1 (N647T) alterations were detected. One isolate that was resistant to all echinocandins carried an FKS R1354G alteration. Two isolates displayed elevated rezafungin minimum inhibitory concentration (MIC) values but low MIC values against other echinocandins and no FKS alterations. As
C. auris
is spreading globally, monitoring this species is prudent.
Characterization of bi-segmented and tri-segmented recombinant Pichinde virus particles
Authors: Murphy Hannah , Huang Qinfeng , Jensen Jacob , Weber Noah , Mendonça Luiza , Ly Hinh , Liang Yuying
Published: September 2024

Mammarenaviruses include several highly virulent pathogens (e.g., Lassa virus) capable of causing severe hemorrhagic fever diseases for which there are no approved vaccines and limited treatment options. Mammarenaviruses are enveloped, bi-segmented ambisense RNA viruses. There is limited knowledge about cellular proteins incorporated into progeny virion particles and their potential biological roles in viral infection. Pichinde virus (PICV) is a prototypic arenavirus used to characterize mammarenavirus replication and pathogenesis. We have developed a recombinant PICV with a tri-segmented RNA genome as a viral vector platform. Whether the tri-segmented virion differs from the wild-type bi-segmented one in viral particle morphology and protein composition has not been addressed. In this study, recombinant PICV (rPICV) virions with a bi-segmented (rP18bi) and a tri-segmented (rP18tri) genome were purified by density-gradient ultracentrifugation and analyzed by cryo-electron microscopy and mass spectrometry. Both virion types are pleomorphic with spherical morphology and have no significant difference in size despite rP18tri having denser particles. Both virion types also contain similar sets of cellular proteins. Among the highly enriched virion-associated cellular proteins are components of the endosomal sorting complex required for transport pathway and vesicle trafficking, such as ALIX, Tsg101, VPS, CHMP, and Ras-associated binding proteins, which have known functions in virus assembly and budding. Other enriched cellular proteins include peripheral and transmembrane proteins, chaperone proteins, and ribosomal proteins; their biological roles in viral infection warrant further analysis. Our study provides important insights into mammarenavirus particle formation and aids in the future development of viral vectors and antiviral discovery.

IMPORTANCE

Mammarenaviruses, such as Lassa virus, are enveloped RNA viruses that can cause severe hemorrhagic fever diseases (Lassa fever) with no approved vaccine and limited therapeutic options. Cellular proteins incorporated into progeny virion particles and their biological roles in mammarenavirus infection have not been well characterized. Pichinde virus (PICV) is a prototypic mammarenavirus used as a surrogate model for Lassa fever. We used cryo-electron microscopy and proteomic analysis to characterize the morphology and protein contents of the purified PICV particles that package either two (bi-segmented) or three (tri-segmented) genomic RNA segments. Our results demonstrate a similar virion morphology but different particle density for the bi- and tri-segmented viral particles and reveal major virion-associated cellular proteins. This study provides important insights into the virus-host interactions that can be used for antiviral development and optimizing arenavirus-based vaccine vectors.
SARS-CoV-2 infection perturbs the gastrointestinal tract and induces modest microbial translocation across the intestinal barrier
Authors: Brooks Kelsie , Nelson Christine E. , Aguilar Cynthia , Hoang Timothy N. , Ortiz Alexandra M. , Langner Charlotte A. , Yee Debra S. , Flynn Jacob K. , Vrba Sophia , Laidlaw Elizabeth , Vannella Kevin M. , Grazioli Alison , Saharia Kapil K. , Purcell Madeleine , Singireddy Shreya , Wu Jocelyn , Stankiewicz Jason , Chertow Daniel S. , Sereti Irini , Paiardini Mirko , Hickman Heather D. , Via Laura E. , Barber Daniel L. , Brenchley Jason M.
Published: September 2024

SARS-CoV-2 infects
via
the respiratory tract, but COVID-19 includes an array of non-respiratory symptoms, among them gastrointestinal (GI) manifestations such as vomiting and diarrhea. Here we investigated the GI pathology of SARS-CoV-2 infections in rhesus macaques and humans. Macaques experienced mild infection with USA-WA1/2020 and shed viral RNA in the respiratory tract and stool, including subgenomic RNA indicative of replication in the GI tract. Intestinal immune cell populations were disturbed, with significantly fewer proliferating (Ki67+) jejunal B cells in SARS-CoV-2-infected macaques than uninfected ones. Modest translocation of bacteria/bacterial antigen was observed across the colonic epithelium, with a corresponding significant increase in plasma soluble CD14 (sCD14) that may be induced by LPS. Human plasma demonstrated significant decreases in interleukin (IL)-6 and sCD14 upon recovery from COVID-19, suggesting resolution of inflammation and response to translocated bacteria. sCD14 significantly positively correlated with zonulin, an indicator of gut barrier integrity, and IL-6. These results demonstrate that GI perturbations such as microbial translocation can occur in even mild SARS-CoV-2 infections and may contribute to the COVID-19 inflammatory state.

IMPORTANCE

This study investigates gastrointestinal (GI) barrier disruption in SARS-CoV-2 infections and how it may contribute to disease. We observed bacteria or bacterial products crossing from the colon interior (the lumen) to the lamina propria during SARS-CoV-2 infection in macaques. Bacteria/bacterial products are tolerated in the lumen but may induce immune responses if they translocate to the lamina propria. We also observed a significant increase in soluble CD14, which is associated with an immune response to bacterial products. In addition, we observed that humans recovering from COVID-19 experienced a significant decrease in soluble CD14, as well as the inflammatory marker interleukin (IL)-6. IL-6 and sCD14 correlated significantly across macaque and human samples. These findings suggest that SARS-CoV-2 infection results in GI barrier disruption that permits microbial translocation and a corresponding immune response. These findings could aid in developing interventions to improve COVID-19 patient outcomes.
Salbutamol safety in children under 2 years of age with acute wheezing: a meta-analysis of randomised controlled trials
Authors: Pierantoni Luca , Muratore Edoardo , Cerasi Sara , Zama Daniele , Del Bono Chiara , Gori Davide , Masetti Riccardo , Lanari Marcello
Published: September 2024

Objective

To evaluate the safety of short-term use of inhaled salbutamol in children under 2 years of age with acute wheezing.

Data sources

Electronic databases (PubMed, Trip, MEDLINE) and the Cochrane Library were searched for studies published up to October 2022.

Study selection

The search was restricted to randomised controlled trials published in English regarding the safety of inhaled salbutamol in wheezing children under the age of 2.

Data extraction and synthesis

The literature search strategy yielded 3532 references. The meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Main outcome(s) and measure(s)

The incidence of adverse reactions associated with inhaled salbutamol administration compared with placebo.

Results

A total of 24 records were included. In 7 studies involving 597 patients, inhaled salbutamol was compared with controls and no statistically significant difference in the incidence of adverse drug reactions was found between the two groups (OR 2.12, 95% CI 0.69 to 6.51; p=0.19). Salbutamol administration via nebulisation was associated with an increased incidence of adverse reactions (OR 6.76, 95% CI 2.01 to 22.71; p=0.002). None of the studies reported severe cardiac side effects that necessitated withdrawal from the study following salbutamol administration. Only one study reported a significant non-cardiac side effect (severe tremulousness) that necessitated withdrawal from therapy.

Conclusions

Inhaled salbutamol can be safely used in children under 2 years of age with acute wheeze with the administration via a metered-dose inhaler being potentially safer than a nebulised formulation. Neither of the formulations was associated with severe adverse effects.
Electroacupuncture versus solifenacin succinate for female overactive bladder: study protocol for a multicentre, randomised, controlled, double-dummy, non-inferiority trial
Authors: Chen Bingli , Yin Ping , Li Juanjuan , Hou Wenguang , Fan Qian , Huai Yisheng , Liu Lumin , Hu Junwei , Chow Sandra Teresa , Li Xu , Ming Shuren , Chen Yue-Lai
Published: September 2024

Introduction

Overactive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for OAB are currently limited. Previous research has proposed that electroacupuncture could be a viable treatment for OAB in women, but there is a lack of high-quality clinical evidence. This study aims to evaluate the effectiveness of electroacupuncture as a safe and efficient non-pharmacological treatment for female OAB by comparing it with solifenacin succinate.

Methods and analysis

This study is a multicentre, single-blind, double-dummy randomised controlled non-inferiority clinical trial involving 204 eligible female participants with OAB. Participants will be randomly assigned in a 1:1 ratio to either the electroacupuncture group (receiving electroacupuncture and placebo) or the solifenacin succinate group (receiving sham electroacupuncture and solifenacin succinate). Each participant will undergo 12 sessions of electroacupuncture (or sham electroacupuncture) treatment and solifenacin succinate (or placebo) treatment over a 4-week period. The primary outcome measure will be the percentage change in the number of micturition episodes every 24 hours at week 4 compared with baseline. Secondary outcomes will include a percentage reduction in the number of micturition episodes every 24 hours at 2th, 8th and 16th weeks of the trial, Overactive Bladder Symptom Score, number of urinary incontinence and urgency episodes every 24 hours based on a 3-day voiding diary, OAB Questionnaire, Generalised Anxiety Disorder Scale-7, King’s Health Questionnaire and Participant Self-evaluation of Therapeutic Effects. Adverse events will be monitored throughout the study. Efficacy analyses will be conducted on both the intention-to-treat population and the per-protocol set population.

Ethics and dissemination

Ethical approval has been obtained from the Medical Ethics Committee of Longhua Hospital Shanghai University of Traditional Chinese Medicine (approval number: 2022LCSY097). Each participant will sign a written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal.

Trial registration number 

NCT05798403.
Protocol for a clinically annotated biorepository of samples from Australian immune-compromised patients to investigate the host–microbiome interaction
Authors: Smibert Olivia C , Trubiano Jason A , Kwong Jason C , Markey Kate A , Slavin Monica A
Published: September 2024

Introduction

The human gut microbiota has the potential to modulate the outcomes of several human diseases. This effect is likely to be mediated through interaction with the host immune system. This protocol details the establishment of a biorepository of clinically annotated samples, which we will use to explore correlations between the gut microbiota and the immune system of immune-compromised patients. We aim to identify microbiome-related risk factors for adverse outcomes.

Methods and analyses

This is a protocol for the development of a biorepository of clinically annotated samples collected prospectively across three centres in Melbourne, Australia. Participants will be recruited across the following clinical streams: (1) acute leukaemia and allogeneic stem cell transplant; (2) end-stage liver disease and liver transplant; (3) patients receiving any cancer immunotherapies (eg, chimeric antigen receptor therapy); (4) deceased organ donors and (5) healthy adult controls. Participants will be asked to provide paired peripheral blood and microbiota samples (stool and saliva) at either (1) single time point for healthy controls and deceased organ donors or (2) longitudinally over multiple prespecified or event-driven time points for the remaining cohorts. Sampling of fluid from bronchoalveolar lavage and colonoscopy or biopsy of tissues undertaken during routine care will also be performed.

Ethics and dissemination

Ethical approval has been obtained from the relevant local ethics committee (The Royal Melbourne Hospital Human Research Ethics Committee). The results of this study will be disseminated by various scientific platforms including social media, international presentations and publication in peer-reviewed journals.

Trial registration number

ACTRN12623001105639. Date registered 20 October 2023.
Effects of yoga compared with health promotion on health-related quality of life in adults with post-COVID-19 condition: protocol for a randomised controlled trial
Authors: Brodén Mikaela , Welfordsson Paul , Niemi Maria , Diwan Vinod , Shah Komal , Pattanadara Vijayakumar , Hallgren Mats
Published: September 2024

Introduction

Post-COVID-19 condition (post COVID, also known as long COVID) is a global public health issue estimated to affect over 100 million people. Common symptoms include fatigue, dyspnoea and cognitive dysfunction (‘brain fog’). Over time, these symptoms have an adverse effect on mental health, physical activity and quality of life (QoL). The condition requires innovative and feasible treatment approaches that can be effective and self-managed. Physical activity is essential for good health; however, aerobic exercise or weightlifting may not be suitable for post COVID patients who experience fatigue or breathlessness. The benefits of yoga include improved flexibility, mobility, body strength and balance. It is also shown to reduce symptoms of fatigue and improve breathing efficiency, mental health and QoL. This study protocol describes the rationale and methods for a randomised controlled trial (RCT) of a yoga-based intervention designed for adults with post COVID.

Methods and analysis

A two-group, parallel, RCT with blinded follow-up assessments. Participants will be randomised with a 1:1 allocation to either a 12-week yoga-based intervention or a 12-week health promotion (active comparison) intervention. In total, 88 participants aged 30–65 years will be recruited and randomised. The primary outcome is health-related QoL (36-item Short-Form). Secondary outcomes are dyspnoea, fatigue, sleep quality, cognitive functions, mental fatigue, depression, anxiety, physical activity, demographic data and physical health measures. Data will be analysed as intention-to-treat basis, using linear mixed modelling. All assessments are conducted at Karolinska Institutet in Stockholm, Sweden. The yoga-based intervention will take place at a yoga studio centrally located in Stockholm city.

Ethics and dissemination

The study is approved by the Swedish Ethical Review Authority, reference number 2023/06518-01. All participants must sign written informed consent before enrolment and are free to withdraw from the study at any point. Key results will be available through research articles and seminars.

Trial registration number

German Clinical Trials Register, DRKS00032837.
Fatherhood and men’s participation in antenatal care in rural sub-Saharan Africa: a scoping review protocol
Authors: Musiwa Anthony Shuko , Mavhu Webster , Nyamwanza Owen , Chadambuka Elizabeth , Couban Rachel , Mbuagbaw Lawrence
Published: September 2024

Introduction

Men’s participation is imperative for improving antenatal care (ANC) access and mother and child health outcomes in sub-Saharan Africa (SSA). Research looking at improving men’s participation in ANC often focuses on their instrumental and psychosocial roles and on biomedical ANC systems. There is limited understanding of how context-specific cultural experiences of fatherhood influence men’s participation in ANC within broader communal support networks and across different ANC systems in SSA. Against this background, and to understand how local communities in SSA conceive men’s participation in ANC, a scoping review will be undertaken to synthesise existing literature around local cultural experiences of fatherhood and men’s participation in ANC in rural settings in SSA.

Methods and analysis

The classical scoping review methodology developed by Arksey and O’Malley will be used to conduct the scoping review described above. Empirical studies published between 1 January 2000 and 31 August 2024 will be systematically searched for in key online databases (eg, PubMed/MEDLINE, CINAHL, EMBASE, PsycINFO, Cochrane Library, African Index Medicus, African Journals Online) and grey literature (eg, reports from key organisations like UNICEF and the WHO). Literature reviews, personal opinion articles and theoretical or conceptual articles that do not systematically analyse data, and non-English texts, will be excluded. Data will be extracted from the included texts in the form of study characteristics, which will be analysed using descriptive statistics, and key issues to be analysed thematically.

Ethics and dissemination

No ethical approvals are needed for this scoping review since data will be abstracted from already-published literature and no additional data will be collected. The findings will be shared with policymakers, practitioners, researchers, students and local communities through peer-reviewed journal publication(s), conference presentations, public lectures and policy-focused stakeholder and community meetings in and outside SSA.