bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrathin silicon nitride microchip for in situ/operando microscopy with high spatial resolution and spectral visibility
Authors: Koo Kunmo , Li Zhiwei , Liu Yukun , Ribet Stephanie M. , Fu Xianbiao , Jia Ying , Chen Xinqi , Shekhawat Gajendra , Smeets Paul J. M. , dos Reis Roberto , Park Jungjae , Yuk Jong Min , Hu Xiaobing , Dravid Vinayak P.
Published: January 2024

Utilization of in situ/operando methods with broad beams and localized probes has accelerated our understanding of fluid-surface interactions in recent decades. The closed-cell microchips based on silicon nitride (SiN
x
) are widely used as “nanoscale reactors” inside the high-vacuum electron microscopes. However, the field has been stalled by the high background scattering from encapsulation (typically ~100 nanometers) that severely limits the figures of merit for in situ performance. This adverse effect is particularly notorious for gas cell as the sealing membranes dominate the overall scattering, thereby blurring any meaningful signals and limiting the resolution. Herein, we show that by adopting the back-supporting strategy, encapsulating membrane can be reduced substantially, down to ~10 nanometers while maintaining structural resiliency. The systematic gas cell work demonstrates advantages in figures of merit for hitherto the highest spatial resolution and spectral visibility. Furthermore, this strategy can be broadly adopted into other types of microchips, thus having broader impact beyond the in situ/operando fields.
A female woolly mammoth’s lifetime movements end in an ancient Alaskan hunter-gatherer camp
Authors: Rowe Audrey G. , Bataille Clement P. , Baleka Sina , Combs Evelynn A. , Crass Barbara A. , Fisher Daniel C. , Ghosh Sambit , Holmes Charles E. , Krasinski Kathryn E. , Lanoë François , Murchie Tyler J. , Poinar Hendrik , Potter Ben , Rasic Jeffrey T. , Reuther Joshua , Smith Gerad M. , Spaleta Karen J. , Wygal Brian T. , Wooller Matthew J.
Published: January 2024

Woolly mammoths in mainland Alaska overlapped with the region’s first people for at least a millennium. However, it is unclear how mammoths used the space shared with people. Here, we use detailed isotopic analyses of a female mammoth tusk found in a 14,000-year-old archaeological site to show that she moved ~1000 kilometers from northwestern Canada to inhabit an area with the highest density of early archaeological sites in interior Alaska until her death. DNA from the tusk and other local contemporaneous archaeological mammoth remains revealed that multiple mammoth herds congregated in this region. Early Alaskans seem to have structured their settlements partly based on mammoth prevalence and made use of mammoths for raw materials and likely food.
Four-dimensional computational ultrasound imaging of brain hemodynamics
Authors: Brown Michael D. , Generowicz Bastian S. , Dijkhuizen Stephanie , Koekkoek Sebastiaan K. E. , Strydis Christos , Bosch Johannes G. , Arvanitis Petros , Springeling Geert , Leus Geert J. T. , De Zeeuw Chris I. , Kruizinga Pieter
Published: January 2024

Four-dimensional ultrasound imaging of complex biological systems such as the brain is technically challenging because of the spatiotemporal sampling requirements. We present computational ultrasound imaging (cUSi), an imaging method that uses complex ultrasound fields that can be generated with simple hardware and a physical wave prediction model to alleviate the sampling constraints. cUSi allows for high-resolution four-dimensional imaging of brain hemodynamics in awake and anesthetized mice.
Local heating and Raman thermometry in a single molecule
Authors: Meng Qiushi , Zhang Junxian , Zhang Yao , Chu Weizhe , Mao Wenjie , Zhang Yang , Yang Jinlong , Luo Yi , Dong Zhenchao , Hou J. G.
Published: January 2024

Because of the nonequilibrium nature of thermal effects at the nanoscale, the characterization of local thermal effects within a single molecule is highly challenging. Here, we demonstrate a way to characterize the local thermal properties of a single fullerene (C
60
) molecule during current-induced heating processes through tip-enhanced anti-Stokes Raman spectroscopy. Although the measured vibron populations are far from equilibrium with the environment, we can still define an “effective temperature (
T
eff
)” statistically via a Bose-Einstein distribution, suggesting a local equilibrium within the molecule. With increased current heating,
T
eff
is found to rise up to about 1150 K until the C
60
cage is decomposed. Such a decomposition temperature is similar to that reported for ensemble C
60
samples, thus justifying the validity of our methodology. Moreover, the possible reaction pathway and product can be identified because of the chemical sensitivity of Raman spectroscopy. Our findings provide a practical method for noninvasively detecting the local heating effect inside a single molecule under nonequilibrium conditions.
NorA efflux pump mediates
Staphylococcus aureus
response to
Pseudomonas aeruginosa
pyocyanin toxicity
Authors: Truong-Bolduc Q. C. , Yonker L. M. , Wang Y. , Lawton B. G. , Hooper D. C.
Published: January 2024

Endogenous transporters protect
Staphylococcus aureus
against antibiotics and also contribute to bacterial defense from environmental toxins. We evaluated the effect of overexpression of four efflux pumps, NorA, NorB, NorC, and Tet38, on
S. aureus
survival following exposure to pyocyanin (PYO) of
Pseudomonas aeruginosa
, using a well diffusion assay. We measured the PYO-created inhibition zone and found that only an overexpression of NorA reduced
S. aureus
susceptibility to pyocyanin killing. The MIC
PYO
of the NorA overexpressor increased threefold compared to that of wild-type RN6390 and was reduced 2.5-fold with reserpine, suggesting that increased NorA efflux caused PYO resistance. The PYO-created inhibition zone of a
ΔnorA
mutant was consistently larger than that of a plasmid-borne NorA overexpressor. PYO also produced a modest increase in
norA
expression (1.8-fold at 0.25 µg/mL PYO) that gradually decreased with increasing PYO concentrations. Well diffusion assays carried out using
P. aeruginosa
showed that
ΔnorA
mutant was less susceptible to killing by PYO-deficient mutants PA14

phzM

and PA14

phzS

than to killing by PA14. NorA overexpression led to reduced killing by all tested
P. aeruginosa
. We evaluated the NorA–PYO interaction using a collection of 22 clinical isolates from adult and pediatric cystic fibrosis (CF) patients, which included both
S. aureus
(CF-SA) and
P. aeruginosa
(CF-PA). We found that when isolated alone, CF-PA and CF-SA expressed varying levels of PYO and
norA
transcripts, but all four CF-PA/CF-SA pairs isolated concurrently from CF patients produced a low level of PYO and low
norA
transcript levels, respectively, suggesting a partial adaptation of the two bacteria in circumstances of persistent co-colonization.
Effects of
Neolamarckia cadamba
leaves extract on microbial community and antibiotic resistance genes in cecal contents and feces of broilers challenged with lipopolysaccharides
Authors: Wang Cheng , Wu Shuo , Zhou Wei , Hu Lei , Hu Qi , Cao Yong , Wang Li , Chen Xiaoyang , Zhang Qing
Published: January 2024

The effects of
Neolamarckia cadamba
leaves extract (NCLE), with effective ingredients of flavonoids, on antibiotic resistance genes (ARGs) and relevant microorganisms in cecal contents and feces of broilers treated with or without lipopolysaccharide stimulation (LPS) were investigated. LPS stimulation increased (
P
< 0.05) the relative abundance of ARGs and mobile genetic elements (MGEs), such as
tet(W/N/W
),
APH(3')-IIIa
,
ErmB
,
tet (44
),
ANT (6)-Ia
,
tet(O
),
tet (32
),
Vang_ACT_CHL
,
myrA
,
ANT (6)-Ib
,
IncQ1
,
tniB
, and
rep2
in cecal contents. However, the difference disappeared (
P
> 0.05) when NCLE was added at the same time. These differential ARGs and MGEs were mainly correlated (
P
< 0.01) with
Clostridiales
bacterium,
Lachnospiraceae
bacterium, and
Candidatus Woodwardibium gallinarum
. These species increased in LPS-stimulated broilers and decreased when NCLE was applied at the same time. In feces, LPS stimulation decreased (
P
< 0.05) the relative abundance of
tet(Q
),
adeF
,
ErmF
,
Mef(En2
),
OXA-347
,
tet (40
),
npmA
,
tmrB, CfxA3,
and
ISCrsp1,
while the LPS + NCLE treated group showed no significant effect (
P
> 0.05) on these ARGs. These differential ARGs and MGEs in feces were mainly correlated (
P
< 0.01) with
Clostridiales
bacterium,
Pseudoflavonifractor sp
. An184,
Flavonifractor sp
. An10,
Ruminococcaceae
bacterium, etc. These species increased in LPS-stimulated broilers and increased when NCLE was applied at the same time. In conclusion, LPS stimulation and NCLE influenced microbial communities and associated ARGs in both cecal contents and feces of broilers. NCLE alleviated the change of ARGs and MGEs in LPS-induced broilers by maintaining the microbial balance.

IMPORTANCE

Antibiotics showed a positive effect on gut health regulation and growth performance improvement in livestock breeding, but the antimicrobial resistance threat and environment pollution problem are increasingly severe with antibiotics abuse. As alternatives, plant extract containing bioactive substances are increasingly used to improve immunity and promote productivity. However, little is known about their effects on diversity and abundance of ARGs. Here, we investigated the effects of NCLE, with effective ingredients of flavonoids, on ARGs and relevant microorganisms in cecal contents and feces of broilers treated with or without lipopolysaccharide stimulation. We found that NCLE reduced the abundance of ARGs in cecal contents of lipopolysaccharide-induced broilers by maintaining the microbial balance. This study provides a comprehensive view of cecal and fecal microbial community, ARGs, and MGEs of broiler following LPS stimulation and NCLE treatment. It might be used to understand and control ARGs dissemination in livestock production.
PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge
Authors: Zhao Yongxiang , Fan Baochao , Song Xu , Gao Jie , Guo Rongli , Yi Cheng , He Zhaoming , Hu Hongpeng , Jiang Jianhao , Zhao Lixiang , Zhong Tianyi , Li Bin
Published: January 2024

Porcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important to develop a highly effective vaccine to control PEDV infection. Here, we report a PEDV spike (S) mRNA vaccine that primes a potent antibody response and antigen-specific T-cell responses in immunized piglets. Active and passive immunization can protect piglets against PED following the virus challenge. This study highlights the efficiency of the PEDV-S mRNA vaccine and represents a viable approach for developing an efficient PEDV vaccine.
Characterization of a selective, iron-chelating antifungal compound that disrupts fungal metabolism and synergizes with fluconazole
Authors: Corrales Jeanne , Ramos-Alonso Lucia , González-Sabín Javier , Ríos-Lombardía Nicolás , Trevijano-Contador Nuria , Engen Berg Henriette , Sved Skottvoll Frøydis , Moris Francisco , Zaragoza Oscar , Chymkowitch Pierre , Garcia Ignacio , Enserink Jorrit M.
Published: January 2024

Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of novel, selective antifungal therapies is challenging due to similarities between fungal and mammalian cells. An attractive source of potential antifungal treatments is provided by ecological niches co-inhabited by bacteria, fungi, and multicellular organisms, where complex relationships between multiple organisms have resulted in evolution of a wide variety of selective antimicrobials. Here, we characterized several analogs of one such natural compound, collismycin A. We show that NR-6226C has antifungal activity against several pathogenic
Candida
species, including
C. albicans
and
C. glabrata
, whereas it only has little toxicity against mammalian cells. Mechanistically, NR-6226C selectively chelates iron, which is a limiting factor for pathogenic fungi during infection. As a result, NR-6226C treatment causes severe mitochondrial dysfunction, leading to formation of reactive oxygen species, metabolic reprogramming, and a severe reduction in ATP levels. Using an
in vivo
model for fungal infections, we show that NR-6226C significantly increases survival of
Candida
-infected
Galleria mellonella
larvae. Finally, our data indicate that NR-6226C synergizes strongly with fluconazole in inhibition of
C. albicans
. Taken together, NR-6226C is a promising antifungal compound that acts by chelating iron and disrupting mitochondrial functions.

IMPORTANCE

Drug-resistant fungal infections are an emerging global threat, and pan-resistance to current antifungal therapies is an increasing problem. Clearly, there is a need for new antifungal drugs. In this study, we characterized a novel antifungal agent, the collismycin analog NR-6226C. NR-6226C has a favorable toxicity profile for human cells, which is essential for further clinical development. We unraveled the mechanism of action of NR-6226C and found that it disrupts iron homeostasis and thereby depletes fungal cells of energy. Importantly, NR-6226C strongly potentiates the antifungal activity of fluconazole, thereby providing inroads for combination therapy that may reduce or prevent azole resistance. Thus, NR-6226C is a promising compound for further development into antifungal treatment.
Rapid detection of
Staphylococcus aureus
in blood culture samples using human IgG-based lateral flow assay
Authors: Srisrattakarn Arpasiri , Charoensri Nicha , Prompipak Jeerati , Ouancharee Wajeeorn , Saiboonjan Bhanubong , Tippayawat Patcharaporn , Chanawong Aroonwadee , Wonglakorn Lumyai , Kanwattanee Ekgarak , Piyapatthanakul Sirikan , Masmalai Thitimar , Ariyapim Anisara , Kendal Rinjong Promson , Lulitanond Aroonlug
Published: January 2024

Staphylococcus aureus
is one of the most common pathogens. The conventional workflow for identifying this organism is time-consuming and takes up to several days. Therefore, we developed a colloidal gold-based lateral flow immunoassay (LFIA) using human IgG as a conjugated antibody to detect
S. aureus
. One hundred and thirty-eight clinical isolates, including 79
S
.
aureus
and 59 non-
S
.
aureus
were spiked in blood samples, and incubated at 37°C for 24 h. The bacterial antigens were simply extracted before being tested by the developed LFIA strips. The results were read by the naked eye within 15 min. Conventional PCR was used as a reference method. The sensitivity and specificity of the developed LFIA were 100% (95% CI: 94.2%–100.0% and 92.4%–100.0%, respectively) in spiked blood culture samples. The detection limits of the LFIA for the purified protein A and bacterial colonies were 10
−3
µg/mL and 10
7
CFU/mL, respectively. The performance of the LFIA testing in 221 bacterial colony isolates and 118 positive blood culture bottles from three hospitals by their medical technologists showed 98.1% (95% CI: 94.1%–99.5%) and 89.7% (95% CI: 79.3%–95.4%) sensitivity, respectively. The LFIA is a quick, easy, and sensitive method for detecting
S. aureus
without expensive equipment. It might have the potential for early diagnosis of routine service in low-resource laboratories, leading to a rapid and effective treatment.

IMPORTANCE

In this study, we modified our previously developed lateral flow immunoassay (LFIA) test for the detection of
Staphylococcus aureus
by using an in-house human IgG as a conjugated antibody instead of the specific commercial antibody. It gave comparable results to the former developed-LFIA test and helped cost reduction.
ACE2 and TMPRSS2 distribution in the respiratory tract of different animal species and its correlation with SARS-CoV-2 tissue tropism
Authors: Carossino Mariano , Izadmehr Sudeh , Trujillo Jessie D. , Gaudreault Natasha N. , Dittmar Wellesley , Morozov Igor , Balasuriya Udeni B. R. , Cordon-Cardo Carlos , García-Sastre Adolfo , Richt Juergen A.
Published: January 2024

A wide range of animal species show variable susceptibility to SARS-CoV-2; however, host factors associated with varied susceptibility remain to be defined. Here, we examined whether susceptibility to SARS-CoV-2 and virus tropism in different animal species are dependent on the expression and distribution of the virus receptor angiotensin-converting enzyme 2 (
ACE2
) and the host cell factor transmembrane serine protease 2 (
TMPRSS2
). We cataloged the upper and lower respiratory tract of multiple animal species and humans in a tissue-specific manner and quantitatively evaluated the distribution and abundance of
ACE2
and
TMPRSS2
mRNA
in situ
. Our results show that: (i)
ACE2
and
TMPRSS2
mRNA are abundant in the conduction portion of the respiratory tract, (ii)
ACE2
mRNA occurs at a lower abundance compared to
TMPRSS2 mRNA,
(iii) co-expression of
ACE2-TMPRSS2
mRNAs is highest in those species with the highest susceptibility to SARS-CoV-2 infection (i.e., cats, Syrian hamsters, and white-tailed deer), and (iv) expression of
ACE2
and
TMPRSS2
mRNA was not altered following SARS-CoV-2 infection. Our results demonstrate that while specific regions of the respiratory tract are enriched in
ACE2
and
TMPRSS2
mRNAs in different animal species, this is only a partial determinant of susceptibility to SARS-CoV-2 infection.

IMPORTANCE

SARS-CoV-2 infects a wide array of domestic and wild animals, raising concerns regarding its evolutionary dynamics in animals and potential for spillback transmission of emerging variants to humans. Hence, SARS-CoV-2 infection in animals has significant public health relevance. Host factors determining animal susceptibility to SARS-CoV-2 are vastly unknown, and their characterization is critical to further understand susceptibility and viral dynamics in animal populations and anticipate potential spillback transmission. Here, we quantitatively assessed the distribution and abundance of the two most important host factors, angiotensin-converting enzyme 2 and transmembrane serine protease 2, in the respiratory tract of various animal species and humans. Our results demonstrate that while specific regions of the respiratory tract are enriched in these two host factors, they are only partial determinants of susceptibility. Detailed analysis of additional host factors is critical for our understanding of the underlying mechanisms governing viral susceptibility and reservoir hosts.
Unraveling the transcriptional features and gene expression networks of pathogenic and saprotrophic
Ophiostoma
species during the infection of
Ulmus americana
Authors: de Oliveira Thais C. , Freyria Nastasia J. , Sarmiento-Villamil Jorge Luis , Porth Ilga , Tanguay Philippe , Bernier Louis
Published: January 2024

American elm (
Ulmus americana
), highly prized for its ornamental value, has suffered two successive outbreaks of Dutch elm disease (DED) caused by ascomycete fungi belonging to the genus
Ophiostoma
. To identify the genes linked to the pathogenicity of different species and lineages of
Ophiostoma
, we inoculated 2-year-old
U. americana
saplings with six strains representing three species of DED fungi, and one strain of the saprotroph
Ophiostoma quercus
. Differential expression analyses were performed following RNA sequencing of fungal transcripts recovered at 3- and 10-days post-infection. Based on a total of 8,640
Ophiostoma
genes, we observed a difference in fungal gene expression depending on the strain inoculated and the time of incubation in host tissue. Some genes overexpressed in the more virulent strains of
Ophiostoma
encode hydrolases that possibly act synergistically. A mutant of
Ophiostoma novo-ulmi
in which the gene encoding the
ogf1
transcription factor had been deleted did not produce transcripts for the gene encoding the hydrophobin cerato-ulmin and was less virulent. Weighted gene correlation network analyses identified several candidate pathogenicity genes distributed among 13 modules of interconnected genes.

IMPORTANCE

Ophiostoma
is a genus of cosmopolitan fungi that belongs to the family Ophiostomataceae and includes the pathogens responsible for two devastating pandemics of Dutch elm disease (DED). As the mechanisms of action of DED agents remain unclear, we carried out the first comparative transcriptomic study including representative strains of the three
Ophiostoma
species causing DED, along with the phylogenetically close saprotrophic species
Ophiostoma quercus
. Statistical analyses of the fungal transcriptomes recovered at 3 and 10 days following infection of
Ulmus americana
saplings highlighted several candidate genes associated with virulence and host-pathogen interactions wherein each strain showed a distinct transcriptome. The results of this research underscore the importance of investigating the transcriptional behavior of different fungal taxa to understand their pathogenicity and virulence in relation to the timeline of infection.
Creation of the HIV-1 antisense gene
asp
coincided with the emergence of the pandemic group M and is associated with faster disease progression
Authors: Pavesi Angelo , Romerio Fabio
Published: January 2024

Despite being first identified more than three decades ago, the antisense gene
asp
of HIV-1 remains an enigma.
asp
is present uniquely in pandemic (group M) HIV-1 strains, and it is absent in all non-pandemic (out-of-M) HIV-1 strains and virtually all non-human primate lentiviruses. This suggests that the creation of
asp
may have contributed to HIV-1 fitness or worldwide spread. It also raises the question of which evolutionary processes were at play in the creation of
asp
. Here, we show that HIV-1 genomes containing an intact
asp
gene are associated with faster HIV-1 disease progression. Furthermore, we demonstrate that the creation of a full-length
asp
gene occurred via the evolution of codon usage in
env
overlapping
asp
on the opposite strand. This involved differential use of synonymous codons or conservative amino acid substitution in
env
that eliminated internal
stop
codons in
asp
, and redistribution of synonymous codons in
env
that minimized the likelihood of new premature
stops
arising in
asp
. Nevertheless, the creation of a full-length
asp
gene reduced the genetic diversity of
env
. The Luria-Delbruck fluctuation test suggests that the interrupted
asp
open reading frame (ORF) is the progenitor of the intact ORF, rather than a descendant under random genetic drift. Therefore, the existence of group-M isolates with a truncated
asp
ORF indicates an incomplete transition process. For the first time, our study links the presence of a full-length
asp
ORF to faster disease progression, thus warranting further investigation into the cellular processes and molecular mechanisms through which the ASP protein impacts HIV-1 replication, transmission, and pathogenesis.

IMPORTANCE

Overlapping genes engage in a tug-of-war, constraining each other’s evolution. The creation of a new gene overlapping an existing one comes at an evolutionary cost. Thus, its conservation must be advantageous, or it will be lost, especially if the pre-existing gene is essential for the viability of the virus or cell. We found that the creation and conservation of the HIV-1 antisense gene
asp
occurred through differential use of synonymous codons or conservative amino acid substitutions within the overlapping gene,
env
. This process did not involve amino acid changes in ENV that benefited its function, but rather it constrained the evolution of ENV. Nonetheless, the creation of
asp
brought a net selective advantage to HIV-1 because
asp
is conserved especially among high-prevalence strains. The association between the presence of an intact
asp
gene and faster HIV-1 disease progression supports that conclusion and warrants further investigation.
Medication errors involving intravenous paracetamol in children: experience from enquiries to the National Poisons Information Service
Authors: Vincent Florence , Thompson John , Gray Laurence , Bradberry Sally , Sandilands Euan , Thanacoody Ruben , Tuthill David
Published: January 2024

Introduction

Children are at higher risk of medication errors due to the complexity of drug prescribing and administration in this patient group. Intravenous (IV) paracetamol overdose differs from overdose by ingestion as there is no enteral absorptive buffering. We provide the first national UK data focusing on paediatric IV paracetamol poisoning.

Methods

All telephone enquiries to the National Poisons Information Service between 2008 and 2021 regarding children less than 18 years old in the UK concerning IV paracetamol overdose were extracted from the UK Poisons Information Database (UKPID). Data were analysed using descriptive statistics.

Results

Enquiries were made concerning 266 children, mostly involving children under the age of 1 year (n=145; 54.5%). Acute and staggered overdoses were the most frequent types of exposure. Common error themes included 10-fold overdose in 45 cases (16.9%) and inadvertent concomitant oral and IV dosing in 64 cases (24.1%). A high proportion of cases were asymptomatic (87.1%), with many calls regarding overdoses below the treatable dose of 60 mg/kg (41.4%). Treatment with the antidote acetylcysteine was advised in 113 cases (42.5%).

Conclusions

Inadvertent IV paracetamol overdose appears to occur more frequently in young children. A significant proportion were calculation errors which were often 10-fold errors. While these errors have the potential for causing serious harm, thankfully most cases were asymptomatic. Errors with IV paracetamol might be reduced by electronic prescribing support systems, better communication regarding administration and consideration of whether other routes are more appropriate.
Burkholderia-associated polymyositis
Authors: Kumar Sahil , Kumar Nitin , Panda Prasan Kumar , Jandrasupalli Kranthi Kumar
Published: January 2024

A diagnosis of polymyositis can readily be made when there is a typical history of proximal muscle weakness together with clinical findings, and there is corroboratory evidence in the form of elevated creatine kinase lactate dehydrogenase, aldolase, and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase). A muscle biopsy usually helps in making the confirmatory diagnosis. A female in her 50s presented with non-healing multiple deep necrotic ulcers with muscle weakness. The initial possibility of vasculitis ulcers remained. Later, this proved to be a case of polymyositis with mildly elevated creatine kinase (which is usually not the case), atypical skin manifestations (usually there is no skin involvement), and negative extended myositis specific antibody panel with the growth ofBurkholderia cepacia(perhaps the triggering factor). Hence, polymyositis can present with a myriad of atypical findings. Thus, thorough clinical examination and an integrated approach are necessary for early identification and treatment of the disease.
Idiopathic segmental anhidrosis in an older patient presenting with recurrent dizziness
Authors: Suzuki Morika , Watari Takashi
Published: January 2024

Dizziness is one of the most common complaints encountered in the outpatient clinic, which is difficult to diagnose, especially in older patients because of the multifactorial nature of the disease. Although not commonly recognised, anhidrosis can also cause dizziness.

We report a case of a woman in her 70s who presented with long-term recurrent dizziness. She had a history of frequent hospitalisations for heatstroke. Physical examination revealed markedly less sweating in the left axilla and soles than in the right. Minol test revealed that most of the left side of her body, including the face, was anhidrotic. She was diagnosed with idiopathic segmental anhidrosis. We administered steroid pulse therapy without observing any significant effects.

Although anhidrosis is a rare disorder, a careful interview and physical examination should be conducted to confirm a history of heatstroke and the absence of sweating to avoid missing the disease.
Pasteurella multocidabacteraemia with liver abscess
Authors: Sia Tonnii , Yong Eunice
Published: January 2024

A previously healthy woman in her mid-70s presented with right upper quadrant abdominal pain, fever, intermittent chills and malaise for 1 week. She was clinically septic with raised inflammatory markers. Her blood culture revealedPasteurella multocida, which was susceptible to penicillin and amoxicillin-clavulanic acid. CT of liver revealed an abscess of 8.0×7.9×8.5 cm at the left lobe of the liver. However, the abscess was not amenable for surgical or radiological drainage. She was a farmer and had close contact with her pet cats. She was occasionally scratched by her cats when caring for them. The liver abscess resolved completely without drainage after prolonged antimicrobial therapy of 109 days. She commenced on 63 days of intravenous antimicrobials and 46 days of oral amoxicillin-clavulanic acid. This case illustratedP. multocidabacteraemia with a large liver abscess in an immunocompetent adult after non-bite exposure.
Diffuse intra-abdominal sarcomatosis in myxoid pleomorphic liposarcoma
Authors: Tseng William W , Liang Yu , Nguyen Bao , Agulnik Mark , Creytens David
Published: January 2024

We present a case of an extremely rare type of soft-tissue sarcoma with an atypical clinical presentation. The patient, a female in her 20s with Li Fraumeni syndrome, had prior surgery for a large intra-abdominal tumour that was given the diagnosis of malignant myxoid spindle cell neoplasm. Her recurrence manifested as diffuse intra-abdominal sarcomatosis for which she ultimately underwent subtotal debulking with palliative intent. Final pathology rendered the diagnosis of myxoid pleomorphic liposarcoma, a newly described entity, distinct from the more common liposarcoma subtypes. The optimal treatment for this typically aggressive disease is currently unknown; until that is better defined, management should be carried out by sarcoma specialists.
Depression, anxiety and stress among female student-athletes: a systematic review and meta-analysis
Authors: Beisecker Ling , Harrison Patrick , Josephson Marzia , DeFreese J D
Published: January 2024

Objective

To identify, quantify and analyse determinants of depression, anxiety and stress symptoms among female student-athletes.

Design

Systematic review and meta-analysis.

Data sources

Five online databases (PubMed, CINAHL, PsychInfo, SportDiscus and Web of Science) searched from inception through 14 September 2023. Hand-searches and contacting authors for eligible studies.

Eligibility criteria for selecting studies

Articles were included if they were published in English, included female student-athletes competing at National Collegiate Athletic Association institutions, and measured symptom-level depression, anxiety and/or stress.

Results and summary

We screened 2415 articles; 52 studies (N=13 849) were included in the systematic review with 13 studies qualifying for meta-analysis. Seventeen determinants were identified including injury (eg, concussions), health (eg, sleep hygiene) and social factors (eg, social support). As data specific to female student-athletes was delineated from studies that included other populations, we observed 16 studies (30.7%) reported that identifying as female was a meaningful determinant of depression, anxiety and stress in athletes. Results of the meta-analysis (k=13, N=5004) suggested a small but significant association (r=0.15, 95% CI 0.05 to 0.24, p=0.004) between other determinants and depression, anxiety, and stress among female student-athletes.

Conclusion

Coaches, trainers and clinicians are key contributors in supporting female student-athlete mental health, with responsibilities for integrating mental skill training, sleep hygiene education and regular assessments. Comprehensive mental health and tailored education programmes considering determinants such as injury, health and social factors specific to female student-athletes are needed to enhance mental health equity in sport.

PROSPERO registration number

CRD42022362163.
Association of urinary albumin-to-creatinine ratio with cardiometabolic risk markers and pre-diabetes in adults with normoglycemia, normoalbuminuria, and normotension with parental type 2 diabetes
Authors: Everett Matthew , Rushing Natasha , Asuzu Peace , Wan Jim , Dagogo-Jack Samuel
Published: January 2024

Introduction

This is a post hoc analysis of urinary albumin-to-creatinine ratio (uACR) within the normoalbuminuric range in relation to cardiometabolic risk factors among initially normoglycemic, normotensive participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) Study.

Research design and methods

308 healthy African American (AA) and European American (EA) participants in the POP-ABC Study underwent baseline assessments, including oral glucose tolerance test, anthropometry, urinary albumin-to-creatinine ratio (uACR), lipids, adipocytokines, insulin sensitivity and secretion. Participants were followed quarterly for 5.5 years (mean 2.62 years) for the primary outcome of incident pre-diabetes.

Results

The cohort’s mean fasting glucose was 92.1±6.90 mg/dL, 2-hour plasma glucose was 123±25.0 mg/dL, systolic blood pressure was 123±15.9 mm Hg, and diastolic blood pressure was 74±8.80 mm Hg. Baseline uACR levels (range 1–29 mg/g) were similar in AA versus EA participants (6.40 mg/g±4.80 vs 6.80±5.40 mg/g, p=0.52), higher in women than men (7.30 mg/g±5.30 vs 4.60±3.90 mg/g, p<0.0001), and showed significant associations with cardiometabolic risk factors, including age, insulin sensitivity, high-density lipoprotein cholesterol, and adiponectin levels (p=0.03–0.004). During 5.5 years of follow-up, 104 participants developed pre-diabetes and 204 maintained normoglycemia. Baseline uACR quartiles were associated with incident pre-diabetes (r=0.19, p=0.0011).

Conclusions

Baseline uACR levels were associated with cardiometabolic risk markers and incident pre-diabetes risk among adults with normoglycemia, normoalbuminuria and normotension with parental diabetes.
Increased glycemic variability in pregnant women with Roux-en-Y gastric bypass compared with sleeve gastrectomy
Authors: Alexiadou Kleopatra , Ansari Saleem , Jones Bryony , Yu Christina , Dornhorst Anne , Oliver Nick , Tsironis Christos , Purkayastha Sanjay , Ahmed Ahmed , Agha-Jaffar Rochan , Khoo Bernard , Tan Tricia M-M
Published: January 2024

Introduction

Bariatric surgery is associated with adverse pregnancy outcomes such as reduced birth weight and premature birth. One possible mechanism for this is increased glycemic variability (GV) which occurs after bariatric surgery. The objective of this study was to compare the effect of Roux-en-Y gastric bypass (RYGB) versus vertical sleeve gastrectomy (SG) on GV during pregnancy and to investigate the relationships of GV, type of bariatric surgery and maternal and neonatal outcomes.

Research design and methods

Fourteen pregnant women after RYGB and 14 after SG were investigated with continuous glucose monitoring in their second or third trimester in this observational study carried out as part of routine clinical care.

Results

Pregnant women with RYGB had similar mean interstitial glucose values but significantly increased indices of GV and a lower %time in range 3.9–7.8 mmol/L (70–140 mg/dL), compared with SG.

Conclusions

Pregnant women who have undergone RYGB have greater GV during pregnancy compared with those who have undergone SG. Further research is needed to establish the relationship between GV and pregnancy outcomes to determine the preferred bariatric operation in women of reproductive age, and whether interventions to reduce GV might improve outcomes.
Evaluation of the use of modelling in resource allocation decisions for HIV and TB
Authors: Bowring Anna L , ten Brink Debra , Martin-Hughes Rowan , Fraser-Hurt Nicole , Cheikh Nejma , Scott Nick
Published: January 2024

Introduction

Globally, resources for health spending, including HIV and tuberculosis (TB), are constrained, and a substantial gap exists between spending and estimated needs. Optima is an allocative efficiency modelling tool that has been used since 2010 in over 50 settings to generate evidence for country-level HIV and TB resource allocation decisions. This evaluation assessed the utilisation of modelling to inform financing priorities from the perspective of country stakeholders and their international partners.

Methods

In October to December 2021, the World Bank and Burnet Institute led 16 semi-structured small-group virtual interviews with 54 representatives from national governments and international health and funding organisations. Interviews probed participants’ roles and satisfaction with Optima analyses and how model findings have had been used and impacted resource allocation. Interviewed stakeholders represented nine countries and 11 different disease programme-country contexts with prior Optima modelling analyses. Interview notes were thematically analysed to assess factors influencing the utilisation of modelling evidence in health policy and outcomes.

Results

Common influences on utilisation of Optima findings encompassed the perceived validity of findings, health system financing mechanisms, the extent of stakeholder participation in the modelling process–including engagement of funding organisations, sociopolitical context and timeliness of the analysis. Using workshops can facilitate effective stakeholder engagement and collaboration. Model findings were often used conceptually to localise global evidence and facilitate discussion. Secondary outputs included informing strategic and financial planning, funding advocacy, grant proposals and influencing investment shifts.

Conclusion

Allocative efficiency modelling has supported evidence-informed decision-making in numerous contexts and enhanced the conceptual and practical understanding of allocative efficiency. Most immediately, greater involvement of country stakeholders in modelling studies and timing studies to key strategic and financial planning decisions may increase the impact on decision-making. Better consideration for integrated disease modelling, equity goals and financing constraints may improve relevance and utilisation of modelling findings.
Development of a cross-sectoral antimicrobial resistance capability assessment framework
Authors: Ferdinand Angeline S , McEwan Callum , Lin Chantel , Betham Kassandra , Kandan Karishma , Tamolsaian Gilam , Pugeva Barry , McKenzie Joanna , Browning Glenn , Gilkerson James , Coppo Mauricio , James Rodney , Peel Trisha , Levy Steph , Townell Nicola , Jenney Adam , Stewardson Andrew , Cameron Donna , Macintyre Alison , Buising Kirsty , Howden Benjamin P
Published: January 2024

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity. This paper describes the development of a framework comprising five assessment tools which provide a detailed assessment of country capacity to address AMR within both the human and animal health sectors. The framework is flexible to meet the needs of implementers, as tools can be used separately to assess the capacity of individual institutions or as a whole to align priority-setting and capacity-building with AMR National Action Plans (NAPs) or national policies. Development of the tools was conducted by a multidisciplinary team across three phases: (1) review of existing tools; (2) adaptation of existing tools; and (3) piloting, refinement and finalisation. The framework may be best used by projects which aim to build capacity and foster cross-sectoral collaborations towards the surveillance of AMR, and by LMICs wishing to conduct their own assessments to better understand capacity and capabilities to inform future investments or the implementation of NAPs for AMR.
Potential impact of a new sepsis prediction model for the primary care setting: early health economic evaluation using an observational cohort
Authors: Loots Feike J , van der Meulen Miriam P , Smits Marleen , Hopstaken Rogier M , de Bont Eefje GPM , van Bussel Bas CT , Latten Gideon HP , Oosterheert Jan Jelrik , van Zanten Arthur RH , Verheij Theo JM , Frederix Geert WJ
Published: January 2024

Objectives

To estimate the potential referral rate and cost impact at different cut-off points of a recently developed sepsis prediction model for general practitioners (GPs).

Design

Prospective observational study with decision tree modelling.

Setting

Four out-of-hours GP services in the Netherlands.

Participants

357 acutely ill adult patients assessed during home visits.

Primary and secondary outcome measures

The primary outcome is the cost per patient from a healthcare perspective in four scenarios based on different cut-off points for referral of the sepsis prediction model. Second, the number of hospital referrals for the different scenarios is estimated. The potential impact of referral of patients with sepsis on mortality and hospital admission was estimated by an expert panel. Using these study data, a decision tree with a time horizon of 1 month was built to estimate the referral rate and cost impact in case the model would be implemented.

Results

Referral rates at a low cut-off (score 2 or 3 on a scale from 0 to 6) of the prediction model were higher than observed for patients with sepsis (99% and 91%, respectively, compared with 88% observed). However, referral was also substantially higher for patients who did not need hospital assessment. As a consequence, cost-savings due to referral of patients with sepsis were offset by increased costs due to unnecessary referral for all cut-offs of the prediction model.

Conclusions

Guidance for referral of adult patients with suspected sepsis in the primary care setting using any cut-off point of the sepsis prediction model is not likely to save costs. The model should only be incorporated in sepsis guidelines for GPs if improvement of care can be demonstrated in an implementation study.

Trial registration number

Dutch Trial Register (NTR 7026).
Protocol for the CHINT study: a cross-sectional observational study of risk factors for cancer and other non-communicable diseases in the Chinese community of Milan
Authors: Avancini Alice , Baldassari Ivan , Gargano Giuliana , Lu Ming , Jing Hao , Zhao Hongwei , Zhang Ji , Sieri Sabina , Mussa Francesca Romana , Krogh Vittorio , Apolone Giovanni , Pala Valeria
Published: January 2024

Introduction

The Chinese community in Italy is the largest in Europe. The area of Milan hosts the largest Chinese Italian community—about 41 000 people. Since little is known of the health practices of Chinese persons in Italy, we designed the CHINT study (survey of risk factors for cancer and other non-communicable diseases (NCDs) in the Chinese community of Milan) to investigate lifestyle-related risk factors for these diseases in this community. We expect the study to reveal potentially unhealthy lifestyle behaviours that may be addressed in future prevention programmes.

Methods and analysis

The CHINT study is a cross-sectional study on a sample of around 600 adults recruited from the Chinese community of Milan and surrounding areas. The non-random sample is clustered by age, sex, occupation and socioeconomic characteristics and is being recruited with the active cooperation of stakeholders within the Chinese community. The study employs face-to-face meetings, text messaging and WeChat. At the first recruitment meeting, participants’ physical measurements are taken and a lifestyle questionnaire is administered which enquires about physical activity, the consumption of salt, fruit and vegetables, tobacco and alcohol, and the presence of other risk factors for NCDs. A food frequency questionnaire is in preparation. By analysis of physical data and the results of the two questionnaires, the prevalence and distribution of NCD risk factors, and characteristics associated with these factors, will be identified. Factors associated with recruitment and compliance/retention will be investigated to identify predictors of willingness to participate future intervention studies.

Ethics and dissemination

The study has been approved by the ethics committee of the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy. All participants are required to provide written informed consent. Findings will be disseminated through peer-reviewed scientific publications, conferences and public meetings involving the Chinese community and the lay public.
Using electronic health records to enhance surveillance of diabetes in children, adolescents and young adults: a study protocol for the DiCAYA Network
Authors: Hirsch Annemarie G , Conderino Sarah , Crume Tessa L , Liese Angela D , Bellatorre Anna , Bendik Stefanie , Divers Jasmin , Anthopolos Rebecca , Dixon Brian E , Guo Yi , Imperatore Giuseppina , Lee David C , Reynolds Kristi , Rosenman Marc , Shao Hui , Utidjian Levon , Thorpe Lorna E
Published: January 2024

Introduction

Traditional survey-based surveillance is costly, limited in its ability to distinguish diabetes types and time-consuming, resulting in reporting delays. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network seeks to advance diabetes surveillance efforts in youth and young adults through the use of large-volume electronic health record (EHR) data. The network has two primary aims, namely: (1) to refine and validate EHR-based computable phenotype algorithms for accurate identification of type 1 and type 2 diabetes among youth and young adults and (2) to estimate the incidence and prevalence of type 1 and type 2 diabetes among youth and young adults and trends therein. The network aims to augment diabetes surveillance capacity in the USA and assess performance of EHR-based surveillance. This paper describes the DiCAYA Network and how these aims will be achieved.

Methods and analysis

The DiCAYA Network is spread across eight geographically diverse US-based centres and a coordinating centre. Three centres conduct diabetes surveillance in youth aged 0–17 years only (component A), three centres conduct surveillance in young adults aged 18–44 years only (component B) and two centres conduct surveillance in components A and B. The network will assess the validity of computable phenotype definitions to determine diabetes status and type based on sensitivity, specificity, positive predictive value and negative predictive value of the phenotypes against the gold standard of manually abstracted medical charts. Prevalence and incidence rates will be presented as unadjusted estimates and as race/ethnicity, sex and age-adjusted estimates using Poisson regression.

Ethics and dissemination

The DiCAYA Network is well positioned to advance diabetes surveillance methods. The network will disseminate EHR-based surveillance methodology that can be broadly adopted and will report diabetes prevalence and incidence for key demographic subgroups of youth and young adults in a large set of regions across the USA.