bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploration of wound‐related complications post‐kidney transplantation
Authors: Sun Huaibin , Liu Kao , Peng Zhiguo , Liu Shengli
Published: December 2023

An essential intervention for patients with end‐stage renal disease is kidney transplantation. Nonetheless, patient outcomes are substantially affected by complications associated with postoperative wounds. The purpose of this research was to determine the prevalence, risk factors and repercussions of wound‐related complications among kidney transplant recipients. A cross‐sectional observational study was undertaken at Qilu Hospital of Shandong University Department of Organ Transplantation, China. Included in the study were 118 patients who had undergone kidney transplantation during the specified time period. Medical record evaluations, questionnaires and patient interviews were utilized to collect data, with an emphasis on demographics, transplant information, postoperative care and wound complications. Infection, dehiscence, lymphocoele, delayed wound healing, seroma formation and haematoma were classified as complications. The presence of comorbidities, age over 50 and living donor transplants were identified as significant risk factors for postoperative complications. The most prevalent complications observed were delayed wound healing (21.2%) and infections (16.9%) (p < 0.05). Antibiotics were found to be effective in managing infections, while prolonged conservative management was necessary for delayed wound healing. Prominent complications that recurred were infections and wound healing delays. No statistically significant correlation was observed between gender, BMI and prior transplants with the occurrence of complications (p > 0.05). The research highlighted the significance of taking into account patient‐specific variables, including age and concurrent medical conditions, when conducting post‐kidney transplantation treatment. The results supported the use of individualized strategies in postoperative care, particularly for populations at high risk, in order to reduce the incidence and severity of complications associated with wounds in pursuit to enhancing clinical practices and formulating focused intervention strategies to improve patient outcomes following transplantation.
Healthcare resource utilization and healthcare costs in patients with type 2 diabetes mellitus initiating sodium‐glucose cotransporter 2 inhibitors vs dipeptidyl peptidase‐4 inhibitors in Japan: A real‐world administrative database analysis
Authors: Kashiwagi Atsunori , Shoji Shingo , Kosakai Yoshinori , Yoshinaga Yoko , Rokuda Mitsuhiro
Published: December 2023

Aims/Introduction

Healthcare resource utilization (HCRU) and healthcare costs are important factors to consider when selecting appropriate treatment for type 2 diabetes mellitus. We compared the HCRU and healthcare costs of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) vs dipeptidyl peptidase‐4 inhibitors (DPP4i) in patients with type 2 diabetes mellitus in Japan.

Materials and Methods

This was a Japanese retrospective cohort study conducted using the JMDC Claims Database (January 1, 2015–December 31, 2021). Patients newly treated with an SGLT2i (31,872 patients) or a DPP4i (73,279 patients) were matched 1:1, using propensity score, after excluding patients without continuous SGLT2i or DPP4i prescriptions after the index date. HCRU and healthcare costs were compared between the treatment groups in the full cohort and subcohorts/subgroups of different baseline characteristics, including body mass index (BMI).

Results

After matching, patient characteristics were well balanced (17,767 patients each). Patients receiving an SGLT2i vs those receiving a DPP4i had significantly lower numbers of hospitalizations per person per month (PPPM) and outpatient visits PPPM, and had shorter lengths of stay per hospitalization. Healthcare costs, including all‐cause overall healthcare costs PPPM and all‐cause hospitalization costs PPPM, were generally lower in patients receiving an SGLT2i than those receiving a DPP4i. Similar results were observed among patients with a higher BMI but not among patients with a lower BMI.

Conclusions

SGLT2i were associated with lower HCRU and healthcare costs than DPP4i, suggesting economic benefits with SGLT2i vs DPP4i in type 2 diabetes mellitus management.
The rise of empirical online platform research in the new millennium
Authors: Cheng Hsing Kenneth , Daniel Sokol D. , Zang Xinyu
Published: December 2023

Online platforms have emerged as a dominant business model in numerous industries in the new millennium. In light of the substantial and burgeoning body of empirical platform research, this article synthesizes extant studies and identifies the evolution of underlying research methodologies and topics. Building upon a database of 860 empirical online platform papers in premier journals during the first two decades of the new millennium, this article presents a categorization framework based on the online platform type (including search platforms, e‐commerce platforms, online communities, and mobile platforms) and research perspective (including platform participants, platform orchestrators, and platform ecosystems). We provide a critical review of noteworthy trends and highlight directions for future research in each category of the proposed framework. A comprehensive bibliometric analysis is then conducted to visualize and track scholarship in empirical online platform research. Lastly, we adopt an interdisciplinary lens to synthesize our critical review of empirical online platform research into lessons and research opportunities that emerge from multiple disciplines.
Preeclampsia prediction model using demographic, clinical, and sonographic data in the second trimester of Japanese nulliparous women
Authors: Shinohara Satoshi , Yoshihara Tatsuya , Mochizuki Kana , Yasuda Genki , Kasai Mayuko , Sunami Rei
Published: December 2023

Aim

This study aimed to clarify the factors influencing preeclampsia (PE) development in nulliparous Japanese women and to develop a PE prediction model using second trimester sonographic and clinical data readily available to obstetricians.

Methods

This historical cohort study examined the obstetric records of nulliparous women who delivered at Yamanashi Prefectural Central Hospital from January 2019 to May 2023. A model was constructed to predict the PE development rate, with a focus on 796 nulliparous women. The assessed outcome was PE, excluding superimposed PE. Data on maternal age, assisted reproductive technology, mean arterial pressure, uterine artery notching, and umbilical artery resistance index were extracted. Multivariable logistic regression analysis was conducted on these five factors.

Results

The incidence of PE was 4.3% (34/796). Multivariable analysis indicated significant odds ratios for the association of PE with mean arterial pressure (adjusted odds ratio: 1.06, 95% confidence interval: 1.03–1.10) and uterine artery notching (adjusted odds ratio: 6.28, 95% confidence interval: 2.82–14.0) in nulliparous women. The PE prediction formula was established as follows:

Probability of PE development (%) = (odds/1 + odds) × 100, odds = ex and x = −11.3 + 0.039 × maternal age (years) + 0.91 × assisted reproductive technology + 0.061 × mean arterial pressure (mmHg) + 1.84 × uterine artery notching + 1.84 × umbilical artery resistance index.

The sensitivity and specificity of this model were 58.8% and 84.5%, respectively (area under the curve: 0.79).

Conclusions

This study is the first to provide a prediction formula targeting the Japanese population. Our specialized model for nulliparous women could guide obstetricians to educate women regarding the precise prospect of PE development.
Sleep‐dependent memory consolidation of televised content in infants
Authors: Hermesch Neele , Konrad Carolin , Barr Rachel , Herbert Jane S. , Seehagen Sabine
Published: December 2023

Infants face the constant challenge of selecting information for encoding and storage from a continuous incoming stream of data. Sleep might help in this process by selectively consolidating new memory traces that are likely to be of future relevance. Using a deferred imitation paradigm and an experimental design, we asked whether 15‐ and 24‐month‐old infants (N = 105) who slept soon after encoding a televised demonstration of target actions would show higher imitation scores (retention) after a 24‐h delay than same‐aged infants who stayed awake for ≥4 h after encoding. In light of infants’ well‐known difficulties in learning and remembering information from screens, we tested if increasing the relevance of the televised content via standardised caregiver verbalisations might yield the highest imitation scores in the sleep condition. Regardless of sleep condition, 24‐month‐olds exhibited retention of target actions while 15‐month‐olds consistently failed to do so. For 24‐month‐olds, temporal recall was facilitated by sleep, but not by parental verbalisations. Correlational analyses revealed that more time asleep within 4 h after encoding was associated with better retention of the target actions and their temporal order in 24‐months‐olds. These results suggest that sleep facilitates memory consolidation of screen‐based content in late infancy and that this effect might not hinge on caregivers’ verbal engagement during viewing.
Assisted migration in a warmer and drier climate: less climate buffering capacity, less facilitation and more fires at temperate latitudes?
Authors: Michalet Richard , Carcaillet Christopher , Delerue Florian , Domec Jean‐Christophe , Lenoir Jonathan
Published: December 2023

Assisted tree migration has been proposed as a conceptual solution to mitigate lags in biotic responses to anthropogenic climate change. The rationale behind this concept is that tree species currently growing under warmer and drier climates will be more resistant and resilient to the new climatic conditions than tree species naturally growing in currently wetter and colder climates. However, we hypothesize that, by being more stress‐tolerant to warmer and drier conditions, translocated species should exhibit different functional attributes, which could induce important ecological and societal costs and overcome the desired benefits of maintaining wood production and other ecosystem services. We used principal component analysis (PCA) to analyze variation in seven traits of 106 tree and tall shrub species from contrasting latitudinal distributions in western North America and Europe to predict the potential functional changes of forest ecosystems due to the translocation of tree species from low to high latitudes. We show that species from both continents differed primarily by their position on the leaf economy spectrum (LES) and their size traits. Even though, in Europe, differences in LES were significantly correlated to species southern latitudinal positions, in both continents differences in size traits were significantly correlated to latitude. These results suggest that assisted migration by translocating more conservative species of shorter stature in currently cooler climates should decrease the buffering capacity of forest canopies, decrease facilitation for understory species, and increase wildfire risks, whose effects have the potential to accelerate climate warming through negative atmospheric feedback processes. As an alternative solution to assisted migration that may accelerate rather than mitigate climate change, we recommend that foresters gradually diversify the vertical structure and layering of the existing forest canopy to maintain a sustainable water cycle and energy balance between the soil, the tree and the atmosphere without increasing the wildfire risk.
Association of maternal cancer with congenital anomalies in offspring
Authors: Auger Nathalie , Maniraho Amanda , Ayoub Aimina , Arbour Laura
Published: December 2023

Background

Congenital anomalies are common, but the possibility that maternal cancer increases the chance of having a child with a birth defect is not fully understood.

Objectives

To examine the association between maternal cancer before or during pregnancy and the risk of birth defects in offspring.

Methods

We conducted a retrospective cohort study of live births in Quebec, Canada, between 1989 and 2022 using hospital data. The main exposure measure was maternal cancer before or during pregnancy. The outcome included birth defects detected in offspring during gestation or at birth. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association of maternal cancer with birth defects using log‐binomial regression models adjusted for potential confounders.

Results

In this study of 2,568,120 newborns, birth defects were present in 6.0% and 6.7% of infants whose mothers had cancer before or during pregnancy, respectively, compared with 5.7% of infants whose mothers never had cancer. Cancer during pregnancy was associated with heart (RR 1.58, 95% CI 1.03, 2.44), nervous system (RR 4.05, 95% CI 2.20, 7.46) and urinary defects (RR 1.72, 95% CI 1.01, 2.95). Among specific types of malignancies during pregnancy, breast cancer was the most prominent risk factor for birth defects (RR 1.55, 95% CI 1.02, 2.37). Cancer before pregnancy was not associated with any type of birth defect or with defects overall (RR 1.01, 95% CI 0.92, 1.11). Moreover, no specific type of cancer before pregnancy was associated with an increased risk of birth defects.

Conclusions

Maternal cancer during pregnancy is associated with the risk of congenital anomalies in offspring, however, cancer before pregnancy is not associated with this outcome.
Phosphorus deficiency alters root length, acid phosphatase activity, organic acids, and metabolites in root exudates of soybean cultivars
Authors: Tantriani  , Cheng Weiguo , Oikawa Akira , Tawaraya Keitaro
Published: December 2023

Phosphorus (P) deficiency alters the root morphological and physiological traits of plants. This study investigates how soybean cultivars with varying low‐P tolerance values respond to different P levels in hydroponic culture by assessing alterations in root length, acid phosphatase activity, organic acid exudation, and metabolites in root exudates. Three low‐P‐tolerant cultivars (‘Maetsue,’ ‘Kurotome,’ and ‘Fukuyutaka’) and three low‐P‐sensitive cultivars (‘Ihhon,’ ‘Chizuka,’ and ‘Komuta’) were grown under 0 (P0) and 258 μM P (P8) for 7 and 14 days after transplantation (DAT). Low‐P‐tolerant cultivars increased root length by 31% and 119%, which was lower than the 62% and 144% increases in sensitive cultivars under P0 compared to P8 at 7 and 14 DAT, respectively. Acid phosphatase activity in low‐P‐tolerant cultivars exceeded that in sensitive cultivars by 5.2‐fold and 2.0‐fold at 7 and 14 DAT. Root exudates from each cultivar revealed 177 metabolites, with higher organic acid exudation in low‐P‐tolerant than sensitive cultivars under P0. Low‐P‐tolerant cultivars increased concentrations of specific metabolites (oxalate, GABA, quinate, citrate, AMP, 4‐pyridoxate, and CMP), distinguishing them from low‐P‐sensitive cultivars under P0. The top five metabolomic pathways (purine metabolism, arginine and proline metabolism, TCA cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate, and glutamate metabolism) were more pronounced in low‐P‐tolerant cultivars at 14 DAT. These findings indicate that increasing root length was not an adaptation strategy under P deficiency; instead, tolerant cultivars exhibit enhanced root physiological traits, including increased acid phosphatase activity, organic acid exudation, specific metabolite release, and accelerated metabolic pathways under P deficiency.
Dendrobium officinale Kinura et Migo glycoprotein promotes skin wound healing by regulating extracellular matrix secretion and fibroblast proliferation on the proliferation phase
Authors: Li Jia , Zhao Qian , Gao Xiaoyu , Dai Tianyi , Bai Zilin , Sheng Jun , Tian Yang , Bai Zhongbin
Published: December 2023

Dendrobium officinale Kinura et Migo (DOKM) has a variety of medicinal applications; however, its ability to promote wound healing has not been previously reported. The purpose of this study is to investigate the proliferative phase of the wound−healing effect of DOKM glycoprotein (DOKMG) in rats and to elucidate its mechanism of action in vitro. In the present study, the ointment mixture containing DOKMG was applied to the dorsal skin wounds of the full‐thickness skin excision rat model, and the results showed that the wound healing speed was faster in the proliferative phase than vaseline. Histological analysis demonstrates that DOKMG promoted the re‐epithelialization of wound skin. Immunofluorescence staining and quantitative polymerase chain reaction assays revealed that DOKMG promotes the secretion of Fibronectin and inhibits the secretion of Collagen IV during the granulation tissue formation period, indicating that DOKMG could accelerate the formation of granulation tissue by precisely regulating extracellular matrix (ECM) secretion. In addition, we demonstrated that DOKMG enhanced the migration and proliferation of fibroblast (3T6 cell) in two‐dimensional trauma by regulating the secretion of ECM, via a mechanism that may implicate the AKT and JAK/STAT pathways under the control of epidermal growth factor receptor (EGFR) signalling. In summary, we have demonstrated that DOKMG promotes wound healing during the proliferative phase. Therefore, we suggest that DOKMG may have a potential therapeutic application for the treatment and management of cutaneous wounds.
OPTIMIZATION OF DEPROTEINIZATION METHODS, HPLC METHOD DEVELOPMENT AND VALIDATION FOR QUANTIFICATION OF 6Β-HYDROXYTESTOSTERONE IN CELL CULTURE MEDIA
Authors: Mohamad Ridhwan Mohamad Jemain , Abd Mutalib Nurliana , Abd Latip Normala , Rasol Nurulfazlina Edayah , Abu Bakar Syahrul Imran , Ismail Nor Hadiani
Published: December 2023

Testosterone is commonly used as a marker probe drug for CYP3A4 metabolic activity. Accurate measurement of its metabolite, 6β-hydroxytestosterone in cell culture media is very crucial. This study aimed to optimize solvent extraction method as well as to develop and validate HPLC analytical method for the quantification of 6β-hydroxytestosterone. Testosterone and 6β-hydroxytestost-erone were extracted from culture media using different solvents and were analyzed using BCA assay and HPLC. The separation was performed at 0.7 mL/min flow rate, using gradient elution of water:methanol for 38 minutes at 242 nm. Solvent extraction of cell culture media using methanol showed the highest crude extract recovery, yield recovery of compounds, and percentage recovery of compounds and peak areas. Thus, the methanol extraction method was applied to further validate 6β-hydroxytestosterone HPLC analytical method. The specificity of the metabolite peak was excellent without any interference. The linear range was 0.156-5.000 ppm. The precision and accuracy were within acceptable criteria of <15%. Samples were stable at 4 ºC chiller for up to 5 days, in autosampler for 24 hours, and in -20 ºC freezer for up to one month. The method was successfully developed and validated for the quantification of 6β-hydroxytestosterone in cell culture media.
Slowly recurrent Collet–Eckmann maps with non‐empty Fatou set
Authors: Aspenberg Magnus , Bylund Mats , Cui Weiwei
Published: December 2023

In this paper, we study rational Collet–Eckmann maps for which the Julia set is not the whole sphere and for which the critical points are recurrent at a slow rate. In families where the orders of the critical points are fixed, we prove that such maps are Lebesgue density points of hyperbolic maps. In particular, if all critical points are simple, these maps are Lebesgue density points of hyperbolic maps in the full space of rational maps of any degree .
Metabolic engineering of high-salinity-induced biosynthesis of γ-aminobutyric acid improves salt-stress tolerance in a glutamic acid-overproducing mutant of an ectoine-deficient
Halomonas elongata
Authors: Zou Ziyan , Kaothien-Nakayama Pulla , Ogawa-Iwamura Junpei , Nakayama Hideki
Published: December 2023

A moderately halophilic eubacterium,
Halomonas elongata
, has been used as cell factory to produce fine chemical 1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid (ectoine), which functions as a major osmolyte protecting the cells from high-salinity stress. To explore the possibility of using
H. elongata
to biosynthesize other valuable osmolytes, an ectoine-deficient salt-sensitive
H. elongata
deletion mutant strain KA1 (Δ
ectABC
), which only grows well in minimal medium containing up to 3% NaCl, was subjected to an adaptive mutagenesis screening in search of mutants with restored salt tolerance. Consequently, we obtained a mutant, which tolerates 6% NaCl in minimal medium by overproducing L-glutamic acid (Glu). However, this Glu-overproducing (GOP) strain has a lower tolerance level than the wild-type
H. elongata
, possibly because the acidity of Glu interferes with the pH homeostasis of the cell and hinders its own cellular accumulation. Enzymatic decarboxylation of Glu to γ-aminobutyric acid (GABA) by a Glu decarboxylase (GAD) could restore cellular pH homeostasis; therefore, we introduced an engineered salt-inducible
HopgadBmut
gene, which encodes a wide pH-range GAD mutant, into the genome of the
H. elongata
GOP strain. We found that the resulting
H. elongata
GOP-Gad strain exhibits higher salt tolerance than the GOP strain by accumulating high concentration of GABA as an osmolyte in the cell (176.94 µmol/g cell dry weight in minimal medium containing 7% NaCl). With
H. elongata
OUT30018 genetic background,
H. elongata
GOP-Gad strain can utilize biomass-derived carbon and nitrogen compounds as its sole carbon and nitrogen sources, making it a good candidate for the development of GABA-producing cell factories.

IMPORTANCE

While the wild-type moderately halophilic
H. elongata
can synthesize ectoine as a high-value osmolyte via the aspartic acid metabolic pathway, a mutant
H. elongata
GOP strain identified in this work opens doors for the biosynthesis of alternative valuable osmolytes via glutamic acid metabolic pathway. Further metabolic engineering to install a GAD system into the
H. elongata
GOP strain successfully created a
H. elongata
GOP-Gad strain, which acquired higher tolerance to salt stress by accumulating GABA as a major osmolyte. With the ability to assimilate biomass-derived carbon and nitrogen sources and thrive in high-salinity environment, the
H. elongata
GOP-Gad strain can be used in the development of sustainable GABA-producing cell factories.
Effects of clinically achievable pulmonary antibiotic concentrations on the recovery of bacteria:
in vitro
comparison of the BioFire FILMARRAY Pneumonia Panel versus conventional culture methods in bronchoalveolar lavage fluid
Authors: Fratoni Andrew J. , Roberts Amity L. , Nicolau David P. , Kuti Joseph L.
Published: December 2023

Empiric antibiotics may affect bacterial pathogen recovery using conventional culture methods (CCMs), while PCR-based diagnostics are likely less affected. Herein, we conducted an
in vitro
study of bronchoalveolar lavage fluid (BAL) inoculated with bacteria and clinically relevant antibiotic concentrations to compare the recovery between the BioFire FILMARRAY Pneumonia Panel (Pn Panel) and CCMs. Remnant clinical BAL specimens were inoculated to ~10
5
cfu/mL using 12 clinical isolates. Isolates consisted of one wild-type (WT) and one or more resistant strains of:
Escherichia coli
,
Klebsiella pneumoniae
,
Pseudomonas aeruginosa
,
Acinetobacter baumannii
, and
Staphylococcus aureus
. Piperacillin–tazobactam, cefepime, meropenem, levofloxacin, or vancomycin was added to achieve pulmonary epithelial lining fluid peak and trough concentrations. Post-exposure cfu/mL was quantified by CCMs and simultaneously tested by the PN Panel for identification and semi-quantitative genetic copies/mL. CCM results were categorized as significant growth (SG) (≥1 × 10
4
), no significant growth (NSG) (≥1 × 10
3
, <1 × 10
4
), or no growth (NG) (<1 × 10
3
). The PN Panel accurately identified all isolates, resistance genes, and reported ≥10
6
genetic copies/mL regardless of antibiotic exposure. The CCM also identified all
S. aureus
strains exposed to vancomycin. For WT Gram-negative isolates exposed to antibiotics, SG, NSG, and NG were observed in 7/52 (13%), 18/52 (35%), and 27/52 (52%) of CCM experiments, respectively. For resistant Gram-negatives isolates, SG, NSG, and NG were observed in 62/88 (70%), 17/88 (19%), and 9/88 (10%), respectively. These
in vitro
data demonstrate that the PN Panel is able to identify Gram-negative pathogens in the presence of clinically significant antibiotic concentrations when CCM may not.
Histone binding of ASF1 is required for fruiting body development but not for genome stability in the filamentous fungus
Sordaria macrospora
Authors: Breuer Jan , Busche Tobias , Kalinowski Jörn , Nowrousian Minou
Published: December 2023

The highly conserved eukaryotic histone chaperone ASF1 is involved in the assembly and disassembly of nucleosomes during transcription, DNA replication, and repair. It was the first chaperone discovered to be involved in all three of these processes. The filamentous fungus
Sordaria macrospora
is one of only two multicellular organisms where
asf1
deletions are viable, which makes it useful for
in vivo
analysis of this central regulator of eukaryotic chromatin structure. Deletion of
asf1
in
S. macrospora
leads to sterility, a reduction of DNA methylation, and upregulation of genes that are usually weakly expressed in the wild type. Here, we focused on the functions of the highly conserved core and the divergent C-terminal tail of ASF1, studied the effects of ASF1 on histone modifications, and tested its relevance for genomic stability. By co-immunoprecipitation and complementation analysis, we showed that substitutions of amino acid V94 or truncations of the C-terminal tail abolish histone binding and do not complement the sterile mutant phenotype. ∆asf1 is sensitive to the DNA-damaging agent methyl methanesulfonate, while complementation strains, even those with non-histone-binding variants, regain wild type-like resistance. The histone marks H3K27me3 and H3K56ac were shown to be influenced by the histone-binding capability of ASF1. To aid in subsequent analyses, we generated a chromosome-resolved genome assembly of
S. macrospora
. By using Hi-C, we detected a tandem duplication of around 600 kb on chromosome 2 in the mutant. Crossing experiments indicated linkage between the viability of Δasf1 strains and the presence of the duplication.

IMPORTANCE

Histone chaperones are proteins that are involved in nucleosome assembly and disassembly and can therefore influence all DNA-dependent processes including transcription, DNA replication, and repair. ASF1 is a histone chaperone that is conserved throughout eukaryotes. In contrast to most other multicellular organisms, a deletion mutant of
asf1
in the fungus
Sordaria macrospora
is viable; however, the mutant is sterile. In this study, we could show that the histone-binding ability of ASF1 is required for fertility in
S. macrospora
, whereas the function of ASF1 in maintenance of genome stability does not require histone binding. We also showed that the histone modifications H3K27me3 and H3K56ac are misregulated in the Δasf1 mutant. Furthermore, we identified a large duplication on chromosome 2 of the mutant strain that is genetically linked to the Δasf1 allele present on chromosome 6, suggesting that viability of the mutant might depend on the presence of the duplicated region.
MpaR-driven expression of an orphan terminal oxidase subunit supports
Pseudomonas aeruginosa
biofilm respiration and development during cyanogenesis
Authors: Smiley Marina K. , Sekaran Doran C. , Forouhar Farhad , Wolin Erica , Jovanovic Marko , Price-Whelan Alexa , Dietrich Lars E. P.
Published: December 2023

Pseudomonas aeruginosa
is a common, biofilm-forming pathogen that exhibits complex pathways of redox metabolism. It produces four different types of terminal oxidases for aerobic respiration, and for one of these, the
cbb
3
-type terminal oxidases, it has the capacity to produce at least 16 isoforms encoded by partially redundant operons. It also produces small-molecule virulence factors that interact with the respiratory chain, including the poison cyanide. Previous studies had indicated a role for cyanide in activating expression of an “orphan” terminal oxidase subunit gene called
ccoN4
and that the product contributes to
P. aeruginosa
cyanide resistance, fitness in biofilms, and virulence, but the mechanisms underlying this process had not been elucidated. Here, we show that the regulatory protein MpaR, which is predicted to be a pyridoxal phosphate-binding transcription factor and is encoded just upstream of
ccoN4
, controls
ccoN4
expression in response to endogenous cyanide. Paradoxically, we find that cyanide production is required to support CcoN4’s contribution to respiration in biofilms. We identify a palindromic motif required for cyanide- and MpaR-dependent expression of
ccoN4
and co-expressed adjacent loci. We also characterize the regulatory logic of this region of the chromosome. Finally, we identify residues in the putative cofactor-binding pocket of MpaR, which are required for
ccoN4
expression. Together, our findings illustrate a novel scenario in which the respiratory toxin cyanide acts as a signal to control gene expression in a bacterium that produces the compound endogenously.

IMPORTANCE

Cyanide is an inhibitor of heme-copper oxidases, which are required for aerobic respiration in all eukaryotes and many prokaryotes. This fast-acting poison can arise from diverse sources, but mechanisms by which bacteria sense it are poorly understood. We investigated the regulatory response to cyanide in the pathogenic bacterium
Pseudomonas aeruginosa
, which produces cyanide as a virulence factor. Although
P. aeruginosa
has the capacity to produce a cyanide-resistant oxidase, it relies primarily on heme-copper oxidases and even makes additional heme-copper oxidase proteins specifically under cyanide-producing conditions. We found that the protein MpaR controls expression of cyanide-inducible genes in
P. aeruginosa
and elucidated the molecular details of this regulation. MpaR contains a DNA-binding domain and a domain predicted to bind pyridoxal phosphate (vitamin B6), a compound that is known to react spontaneously with cyanide. These observations provide insight into the understudied phenomenon of cyanide-dependent regulation of gene expression in bacteria.
A naturally occurring HA-stabilizing amino acid (HA1-Y17) in an A(H9N2) low-pathogenic influenza virus contributes to airborne transmission
Authors: Sun Xiangjie , Belser Jessica A. , Pulit-Penaloza Joanna A. , Brock Nicole , Kieran Troy J. , Zeng Hui , Pappas Claudia , Tumpey Terrence M. , Maines Taronna R.
Published: December 2023

Airborne transmissibility is a prerequisite for a pandemic influenza A virus (IAV), and a better understanding of how zoonotic IAV evolves to acquire a transmissible phenotype is essential for pandemic preparedness. Select contemporary influenza A(H9N2) viruses such as A/Anhui-Lujiang/39/2018 (AL/39) have exhibited a limited transmission capability by the airborne route in the ferret model; therefore, it is of great importance to identify viral factors that contribute to enhanced transmission. To investigate the role of virus acid stability in virus airborne transmission, we rescued a pair of isogenic A(H9N2) viruses, including the wild-type (wt) AL/39 and the mutant virus bearing a naturally occurring substitution HA1-Y17H, with a resulting difference in virus pH thresholds for hemagglutinin activation. We next assessed virus replication, airborne transmission, and fitness in a co-infection competition model in ferrets. We found that the HA1-Y17H mutant virus yielded only non-productive airborne transmission despite possessing a comparative replication as the wt virus in the ferret upper respiratory tract. Furthermore, ferrets inoculated with the wt virus emitted more virus-laden particles into the air than the HA1-Y17H mutant virus-inoculated animals. During ferret co-infection experiments, the wt virus was the dominant species in multiple types of specimens following different inoculation routes. Taken together, our study demonstrates that an acid-stable IAV had a greater capacity to establish a productive infection in the ferret upper respiratory tract and was emitted in greater quantities from infected animals, features that may contribute to virus airborne transmission in a synergistic manner in mammalian hosts.

IMPORTANCE

Despite the accumulation of evidence showing that airborne transmissible influenza A virus (IAV) typically has a lower pH threshold for hemagglutinin (HA) fusion activation, the underlying mechanism for such a link remains unclear. In our study, by using a pair of isogenic recombinant A(H9N2) viruses with a phenotypical difference in virus airborne transmission in a ferret model due to an acid-destabilizing mutation (HA1-Y17H) in the HA, we demonstrate that an acid-stable A(H9N2) virus possesses a multitude of advantages over its less stable counterpart, including better fitness in the ferret respiratory tract, more effective aerosol emission from infected animals, and improved host susceptibility. Our study provides supporting evidence for the requirement of acid stability in efficient airborne transmission of IAV and sheds light on fundamental mechanisms for virus airborne transmission.
Tapentadol dependence through intravenous injection (‘shooting’) of crushed tablets associated with cutaneous pseudoallergic reactions
Authors: Avula Vijaya Chandra Reddy , Vullanki Sreeja S , Munivenkatappa Shashidhara
Published: December 2023

Tapentadol is a synthetic opioid analgesic with a low risk of abuse and diversion. The rising trend of abuse of tapentadol is largely attributable to its intrinsic pharmacological profile and easy availability due to poor regulatory control. We report a case of intravenous injection of crushed tapentadol tablets that presented with cutaneous adverse drug reactions. Cutaneous adverse reactions are common in injection drug abuse, and clinical examination is a must to inspect the injection sites. Stringent regulatory measures are required to restrict the increasing abuse of tapentadol in India.
Role of 3D transoesophageal echocardiography in correct diagnosis of congenital isolated double orifice mitral valve in a young adult misdiagnosed as rheumatic heart disease
Authors: Nalawade Digvijay , Malani Susheel Kumar , Chigullapalli Sridevi , Chaudhary Prakash
Published: December 2023

Double orifice mitral valve (DOMV) is an extremely rare congenital anomaly of the mitral valve (MV) wherein the MV orifice divides into two separate orifices by an accessory fibrous band.Isolated DOMV is a rarity and is often discovered incidentally. It may be associated with other congenital conditions wherein it is identified in early childhood. Its prevalence and prognostic relevance in adulthood remain unclear. DOMV patients may be asymptomatic or have symptoms due to mitral stenosis or regurgitation. We present a case of an asymptomatic young adult initially diagnosed with rheumatic mitral stenosis. However, after a thorough echocardiographic assessment, including three-dimensional transesophageal echocardiography, the accurate diagnosis of DOMV was made.
Exploring perceptions and operational considerations for use of a smartphone application to self-monitor blood pressure in pregnancy in Lombok, Indonesia: protocol for a qualitative study
Authors: Tamrat Tigest , Setiyawati Yuni Dwi , Barreix Maria , Gayatri Mergy , Rinjani Shannia Oktaviana , Pasaribu Melissa Paulina , Geissbuhler Antoine , Shankar Anuraj H , Tunçalp Özge
Published: December 2023

Introduction

Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal deaths globally and require close monitoring of blood pressure (BP) to mitigate potential adverse effects. Despite the recognised need for research on self-monitoring of blood pressure (SMBP) among pregnant populations, there are very few studies focused on low and middle income contexts, which carry the greatest burden of HDPs. The study aims to understand the perceptions, barriers, and operational considerations for using a smartphone software application to perform SMBP by pregnant women in Lombok, Indonesia.

Methods and analysis

This study includes a combination of focus group discussions, in-depth interviews and workshop observations. Pregnant women will also be provided with a research version of the smartphone BP application to use in their home and subsequently provide feedback on their experiences. The study will include pregnant women with current or past HDP, their partners and the healthcare workers involved in the provision of antenatal care services within the catchment area of six primary healthcare centres. Data obtained from the interviews and observations will undergo thematic analyses using a combination of both inductive and deductive approaches.

Ethics and dissemination

The study was approved by the World Health Organization (WHO) and Human Reproduction Programme (HRP) Research Project Review Panel and WHO Ethical Review Committee (A65932) as well as the Health Research Ethics Committee, Faculty of Medicine, Universitas Mataram in Indonesia (004/UN18/F7/ETIK/2023).

Findings will be disseminated through research publications and communicated to the Lombok district health offices. The analyses from this study will also inform the design of a subsequent impact evaluation.
Associations of general and central adiposity with hypertension and cardiovascular disease among South Asian populations: a systematic review and meta-analysis
Authors: Re Federica , Oguntade Ayodipupo S , Bohrmann Bastian , Bragg Fiona , Carter Jennifer L
Published: December 2023

Background

The relevance of measures of general and central adiposity for cardiovascular disease (CVD) risks in populations of European descent is well established. However, it is less well characterised in South Asian populations, who characteristically manifest larger waist circumferences (WC) for equivalent body mass index (BMI). This systematic review and meta-analysis provide an overview of the literature on the association of different anthropometric measures with CVD risk among South Asians.

Methodology

MEDLINE and Embase were searched from 1990 to the present for studies in South Asian populations investigating associations of two or more adiposity measures with CVD. Random-effects meta-analyses were conducted on the associations of BMI, WC and waist-to-hip ratio (WHR) with blood pressure, hypertension and CVD. Quality assessment was performed using the Newcastle-Ottawa scale.

Results

Titles and abstracts were screened for 7327 studies, yielding 147 full-text reviews. The final sample (n=30) included 2 prospective, 5 case-control and 23 cross-sectional studies. Studies reported generally higher risks of hypertension and CVD at higher adiposity levels. The pooled mean difference in systolic blood pressure (SBP) per 5 kg/m2higher BMI was 3 mmHg (2.90 (95% CI 1.30 to 4.50)) and 6 mmHg (6.31 (95% CI 4.81 to 7.81) per 13 cm larger WC. The odds ratio (OR) of hypertension per 5 kg/m2higher BMI was 1.33 (95% CI 1.18 to 1.51), 1.45 (95% CI 1.05 to 1.98) per 13 cm larger WC and 1.22 (95% CI 1.04 to 1.41) per 0.1-unit larger WHR. Pooled risk of CVD for BMI-defined overweight versus healthy-weight was 1.65 (95% CI 1.55 to 1.75) and 1.48 (95% CI 1.21 to 1.80) and 2.51 (95% CI 0.94 to 6.69) for normal versus large WC and WHR, respectively. Study quality was average with significant heterogeneity.

Conclusions

Measures of both general and central adiposity had similar, strong positive associations with the risk of CVD in South Asians. Larger prospective studies are required to clarify which measures of body composition are more informative for targeted CVD primary prevention in this population.
Explore the use of complementary and alternative medicine among Chinese gynaecological patients with cancer undergoing chemotherapy: a qualitative phenomenological study
Authors: Zhang Jianjun , Luo Biru , Liu Xinru , He Yalin , Zuo Yan
Published: December 2023

Objectives

To explore the use of complementary and alternative medicine (CAM) by Chinese gynaecological oncology patients undergoing chemotherapy and discuss measures to address the existing gaps.

Design

Qualitative phenomenology. Semistructured in-depth interview. Colaizzi’s method data analysis.

Setting

A tertiary general hospital.

Participants

16 gynaecological oncology patients (mean age 51.7) having undergone ≥1 chemotherapy cycle were recruited by purposive sampling.

Results

Six themes were generated. The participants were under-informed about CAM concept and options. They were open to explore various modalities after chemotherapy as long as it could alleviate symptoms. The gynaecological patients with cancer sought information about CAM from diverse sources, with professional expertise being the most desirable way to seek information. They used CAM as a strategy to support continued chemotherapy and for symptom alleviation. Financial burden was not stressed but they had concerns about sustainability of some therapies. Their attitudes toward different CAM types varied. Some were sceptical about the efficacy.

Conclusions

The Chinese gynaecological oncology patients may be under-informed about CAM. They are open to use various CAM therapies for symptom relief and as a support strategy. However, their attitudes toward specific therapies may vary. Some may host scepticism about certain CAM modalities. The patients actively seek information on CAM and treatment resources but prefer professional expertise to other sources. Financial burden due to continued CAM use is inconclusive due to possible sampling bias. Sustainability of CAM therapies is a common concern because of limited resources and access. Education on CAM should be incorporated into the curriculum of healthcare professionals. Oncologists and nurses should educate gynaecological patients with cancer on the concept and options of CAM, preferably with information tailored to patient’s individual needs. Health authorities should advocate provisions of diverse CAM services and develop the necessary technologies such as network of local care resources.
Tranexamic acid in patients with post-traumatic elbow stiffness: protocol for a randomised, double-blind, placebo-controlled trial investigating the effectiveness of tranexamic acid at reducing the recurrence of heterotopic ossification after open elbow arthrolysis
Authors: Cui Haomin , Luo Gang , Wang Yin , Luan Min , He Kuangyu , Ruan Jihao , Li Juehong , Lou Tengfei , Sun Ziyang , Chen Shuai , Yu Shiyang , Wang Wei , Fan Cunyi
Published: December 2023

Introduction

Exaggerated inflammatory response is one of the main mechanisms underlying heterotopic ossification (HO). It has been suggested that the antifibrinolytic drug tranexamic acid (TXA) can exert a significant anti-inflammatory effect during orthopaedic surgery. However, no prospective studies have yet investigated the effects of TXA on HO recurrence in patients following open elbow arthrolysis (OEA).

Methods and analysis

Here, we present a protocol for a single-centre, randomised, double-blind, placebo-controlled trial to investigate the effectiveness of TXA on HO recurrence after OEA in a single hospital. A minimum sample size of 138 eligible and consenting participants randomised into treatment and control groups in a 1:1 manner will be included. Patients will receive 2 g of intravenous TXA (experimental group) or placebo (normal saline, control group) administered before skin incision. The primary outcome is HO recurrence rate within 12 months after surgery. The secondary outcomes are the serum immune-inflammatory cytokines including erythrocyte sedimentation rate, C reactive protein, interleukin (IL)-6, IL-1β, IL-13 at the first and third day postoperatively, and elbow range of motion and functional score at 1.5, 6, 9 and 12 months after surgery. After completion of the trial, the results will be reported in accordance with the extensions of the Consolidated Standards of Reporting Trials Statement for trials. The results of this study should determine whether TXA can reduce the rates of HO occurrence after OEA.

Ethics and dissemination

Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (reference number 2022-123-(1)). The results of this study will be disseminated through presentations at academic conferences and publication in peer-reviewed journals.

Trial registration number

ChiCTR2300068106.
Prognostic value of acute National Institutes of Health Stroke Scale Items on disability: a registry study of first-ever stroke in the western part of Sweden
Authors: Hagberg Guri , Ihle-Hansen Haakon , Abzhandadze Tamar , Reinholdsson Malin , Hansen Hege Ihle , Sunnerhagen Katharina S
Published: December 2023

Objectives

We aimed to study how the individual items of the National Institutes of Health Stroke Scale (NIHSS) at admission predict functional independence 3 months post-stroke in patients with first-ever stroke.

Setting

This registry-based study used data from two Swedish stroke registers (Riksstroke, the mandatory national quality register for stroke care in Sweden, and Väststroke, a local quality stroke register in Gothenburg).

Participants

This study included patients with first-ever acute stroke admitted from November 2014 to August 2018, with available NIHSS at admission and modified Rankin Scale (mRS) at 3-month follow-up.

Primary outcome

The primary outcome variable was mRS≤1 (defined as an excellent outcome) at 3-month follow-up.

Results

We included 1471 patients, mean age was 72 (± 14.5) years, 48% were female, and 66% had mild strokes (NIHSS≤3). In adjusted binary logistic regression analysis, the NIHSS items impaired right motor arm and leg, and impairment in visual field, reduced the odds of an excellent outcome at 3 months ((OR 0.60 (95% CI 0.37 to 0.98), OR 0.60 (95% CI 0.37 to 0.97), and OR 0.65 (95% CI 0.45 to 0.94)). When exploring the effect size of associations between NIHSS items and mRS≤1 p, orientation, language and right leg motor had the largest yet small association.

Conclusions

Stroke patients with scores on the NIHSS items right motor symptoms or visual field at admission are less likely to have an excellent outcome at 3 months. Clinicians should consider the NIHSS items affected, not only the total NIHSS score, both in treatment guidance and prognostics.