bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight into the gas–liquid transition from the Berthelot model
Authors: Mi Li-Qin , Li Dandan , Li Shanshan , Li Zhong-Heng
Published: June 2024

We extend the parametric method developed for the van der Waals model by Lekner [Am. J. Phys. 50(2), 161–163 (1982)] to other equations of state, particularly the Berthelot model, thereby making the testing of these equations of state much faster and simpler. We systematically investigate important properties of first-order phase transitions in the Berthelot model. Thermodynamic properties near the critical point are discussed and the predictions of the Berthelot and van der Waals models are compared with experimental data. The Berthelot equation affords an improved fit to the density–temperature coexistence curve for many substances when compared to the van der Waals equation. A failure of the Berthelot model is its prediction of latent heat and heat capacities that are convex functions at lower temperatures. We also examine two modifications of the Berthelot equation of state that, like the van der Waals model, are also solvable by the parameter method. These, which we call the cPF and dPF models, reduce to the van der Waals and Berthelot models in different limits of their parameters. They give improved fits to the experimental data away from the critical point but involve an additional fitting parameter.
Torricelli's experiment and conservation of momentum
Authors: Alvaro-Berlanga D. , Planet R. , Fernandez-Nieves A.
Published: June 2024

Torricelli's law states that the speed of a fluid as it flows out of an orifice of a large reservoir open to the atmosphere is equal to 2gh, where g is the acceleration of gravity and h is the distance between the free surface of the fluid in the reservoir and the orifice. Obtaining the flow rate from this speed is not at all trivial, despite how simple the situation seems, as the fluid jet issued at the orifice does not have a constant cross section and the motion of the fluid near the orifice is not really known. Here, we use Torricelli's experiment as a practical way to illustrate how to properly apply the momentum balance equation to solve hydrodynamic problems. We compare the horizontal component of the force exerted by the container on the fluid using both momentum conservation and the integral of the stress tensor; this results in a contradiction that we use to review, after considering simple experimental results, the assumptions made during the calculations, to finally resolve the discrepancy and rationalize the intricacies of this every-day situation.
JAK inhibition enhances checkpoint blockade immunotherapy in patients with Hodgkin lymphoma
Authors: Zak Jaroslav , Pratumchai Isaraphorn , Marro Brett S. , Marquardt Kristi L. , Zavareh Reza Beheshti , Lairson Luke L. , Oldstone Michael B. A. , Varner Judith A. , Hegerova Livia , Cao Qing , Farooq Umar , Kenkre Vaishalee P. , Bachanova Veronika , Teijaro John R.
Published: June 2024

Unleashing antitumor T cell activity by checkpoint inhibitor immunotherapy is effective in cancer patients, but clinical responses are limited. Cytokine signaling through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway correlates with checkpoint immunotherapy resistance. We report a phase I clinical trial of the JAK inhibitor ruxolitinib with anti–PD-1 antibody nivolumab in Hodgkin lymphoma patients relapsed or refractory following checkpoint inhibitor immunotherapy. The combination yielded a best overall response rate of 53% (10/19). Ruxolitinib significantly reduced neutrophil-to-lymphocyte ratios and percentages of myeloid suppressor cells but increased numbers of cytokine-producing T cells. Ruxolitinib rescued the function of exhausted T cells and enhanced the efficacy of immune checkpoint blockade in preclinical solid tumor and lymphoma models. This synergy was characterized by a switch from suppressive to immunostimulatory myeloid cells, which enhanced T cell division.
Temperature-dependent emissions dominate aerosol and ozone formation in Los Angeles
Authors: Pfannerstill Eva Y. , Arata Caleb , Zhu Qindan , Schulze Benjamin C. , Ward Ryan , Woods Roy , Harkins Colin , Schwantes Rebecca H. , Seinfeld John H. , Bucholtz Anthony , Cohen Ronald C. , Goldstein Allen H.
Published: June 2024

Despite declines in transportation emissions, urban North America and Europe still face unhealthy air pollution levels. This has challenged conventional understanding of the sources of their volatile organic compound (VOC) precursors. Using airborne flux measurements to map emissions of a wide range of VOCs, we demonstrate that biogenic terpenoid emissions contribute ~60% of emitted VOC OH reactivity, ozone, and secondary organic aerosol formation potential in summertime Los Angeles and that this contribution strongly increases with temperature. This implies that control of nitrogen oxides is key to reducing ozone formation in Los Angeles. We also show some anthropogenic VOC emissions increase with temperature, which is an effect not represented in current inventories. Air pollution mitigation efforts must consider that climate warming will strongly change emission amounts and composition.
GPTs are GPTs: Labor market impact potential of LLMs
Authors: Eloundou Tyna , Manning Sam , Mishkin Pamela , Rock Daniel
Published: June 2024

Research is needed to estimate how jobs may be affected
Cellular senescence in normal physiology
Authors: de Magalhães João Pedro
Published: June 2024

Long associated with aging, senescent cells can promote health and have physiological roles
Water-hydroxide trapping in cobalt tungstate for proton exchange membrane water electrolysis
Authors: Ram Ranit , Xia Lu , Benzidi Hind , Guha Anku , Golovanova Viktoria , Garzón Manjón Alba , Llorens Rauret David , Sanz Berman Pol , Dimitropoulos Marinos , Mundet Bernat , Pastor Ernest , Celorrio Veronica , Mesa Camilo A. , Das Aparna M. , Pinilla-Sánchez Adrián , Giménez Sixto , Arbiol Jordi , López Núria , García de Arquer F. Pelayo
Published: June 2024

The oxygen evolution reaction is the bottleneck to energy-efficient water-based electrolysis for the production of hydrogen and other solar fuels. In proton exchange membrane water electrolysis (PEMWE), precious metals have generally been necessary for the stable catalysis of this reaction. In this work, we report that delamination of cobalt tungstate enables high activity and durability through the stabilization of oxide and water-hydroxide networks of the lattice defects in acid. The resulting catalysts achieve lower overpotentials, a current density of 1.8 amperes per square centimeter at 2 volts, and stable operation up to 1 ampere per square centimeter in a PEMWE system at industrial conditions (80°C) at 1.77 volts; a threefold improvement in activity; and stable operation at 1 ampere per square centimeter over the course of 600 hours.
Two Zn
2
Cys
6
-type transcription factors respond to aromatic compounds and regulate the expression of laccases in the white-rot fungus
Trametes hirsuta
Authors: Wang Chenkai , Zhang Xinlei , Wu Kun , Liu Shenglong , Li Xiang , Zhu Chaona , Xiao Yazhong , Fang Zemin , Liu Juanjuan
Published: June 2024

White-rot fungi differentially express laccases when they encounter aromatic compounds. However, the underlying mechanisms are still being explored. Here, proteomics analysis revealed that in addition to increased laccase activity, proteins involved in sphingolipid metabolism and toluene degradation as well as some cytochrome P450s (CYP450s) were differentially expressed and significantly enriched during 48 h of
o
-toluidine exposure, in
Trametes hirsuta
AH28-2. Two Zn
2
Cys
6
-type transcription factors (TFs), TH8421 and TH4300, were upregulated. Bioinformatics docking and isothermal titration calorimetry assays showed that each of them could bind directly to
o
-toluidine and another aromatic monomer, guaiacol. Binding to aromatic compounds promoted the formation of TH8421/TH4300 heterodimers.
TH8421
and
TH4300
silencing in
T. hirsuta
AH28-2 led to decreased transcriptional levels and activities of LacA and LacB upon
o
-toluidine and guaiacol exposure. EMSA and ChIP-qPCR analysis further showed that TH8421 and TH4300 bound directly with the promoter regions of
lacA
and
lacB
containing CGG or CCG motifs. Furthermore, the two TFs were involved in direct and positive regulation of the transcription of some CYP450s. Together, TH8421 and TH4300, two key regulators found in
T. hirsuta
AH28-2, function as heterodimers to simultaneously trigger the expression of downstream laccases and intracellular enzymes. Monomeric aromatic compounds act as ligands to promote heterodimer formation and enhance the transcriptional activities of the two TFs.

IMPORTANCE

White-rot fungi differentially express laccase isoenzymes when exposed to aromatic compounds. Clarification of the molecular mechanisms underlying differential laccase expression is essential to elucidate how white-rot fungi respond to the environment. Our study shows that two Zn
2
Cys
6
-type transcription factors form heterodimers, interact with the promoters of laccase genes, and positively regulate laccase transcription in
Trametes hirsuta
AH28-2. Aromatic monomer addition induces faster heterodimer formation and rate of activity. These findings not only identify two new transcription factors involved in fungal laccase transcription but also deepen our understanding of the mechanisms underlying the response to aromatics exposure in white-rot fungi.
Comparative reservoir competence of
Peromyscus leucopus
, C57BL/6J, and C3H/HeN for
Borrelia burgdorferi
B31
Authors: Bourgeois Jeffrey S. , You Stephanie S. , Clendenen Luke H. , Shrestha Muskan , Petnicki-Ocwieja Tanja , Telford Sam R. , Hu Linden T.
Published: June 2024

Borrelia burgdorferi
, a Lyme disease spirochete, causes a range of acute and chronic maladies in humans. However, a primary vertebrate reservoir in the United States, the white-footed deermouse
Peromyscus leucopus
, is reported not to have reduced fitness following infection. Although laboratory strains of
Mus musculus
mice have successfully been leveraged to model acute human Lyme disease, the ability of these rodents to model
B. burgdorferi-P. leucopus
interactions remains understudied. Here, we compared infection of
P. leucopus
with
B. burgdorferi
B31 with infection of the traditional
B. burgdorferi
murine models—C57BL/6J and C3H/HeN
Mus musculus
, which develop signs of inflammation akin to human disease. We find that
B. burgdorferi
was able to reach much higher burdens (10- to 30-times higher) in multiple
M. musculus
skin sites and that the overall dynamics of infection differed between the two rodent species. We also found that
P. leucopus
remained transmissive to larval
Ixodes scapularis
for a far shorter period than either
M. musculus
strain. In line with these observations, we found that
P. leucopus
does launch a modest but sustained inflammatory response against
B. burgdorferi
in the skin, which we hypothesize leads to reduced bacterial viability and rodent-to-tick transmission in these hosts. Similarly, we also observe evidence of inflammation in infected
P. leucopus
hearts. These observations provide new insight into reservoir species and the
B. burgdorferi
enzootic cycle.

IMPORTANCE

A Lyme disease-causing bacteria,
Borrelia burgdorferi
, must alternate between infecting a vertebrate host—usually rodents or birds—and ticks. In order to be successful in that endeavor, the bacteria must avoid being killed by the vertebrate host before it can infect a new larval tick. In this work, we examine how
B. burgdorferi
and one of its primary vertebrate reservoirs,
Peromyscus leucopus
, interact during an experimental infection. We find that
B. burgdorferi
appears to colonize its natural host less successfully than conventional laboratory mouse models, which aligns with a sustained seemingly anti-bacterial response by
P. leucopus
against the microbe. These data enhance our understanding of
P. leucopus
host-pathogen interactions and could potentially serve as a foundation to uncover ways to disrupt the spread of
B. burgdorferi
in nature.
Sub-genomic RNAi-assisted strain evolution of filamentous fungi for enhanced protein production
Authors: Sun Xianhua , Gao Fei , Fan Chao , Yang Shuyan , Zhao Tong , Tu Tao , Luo Huiying , Yao Bin , Huang Huoqing , Su Xiaoyun
Published: June 2024

Genetic engineering at the genomic scale provides a rapid means to evolve microbes for desirable traits. However, in many filamentous fungi, such trials are daunted by low transformation efficiency. Differentially expressed genes under certain conditions may contain important regulatory factors. Accordingly, although manipulating these subsets of genes only can largely reduce the time and labor, engineering at such a sub-genomic level may also be able to improve the microbial performance. Herein, first using the industrially important cellulase-producing filamentous fungus
Trichoderma reesei
as a model organism, we constructed suppression subtractive hybridization (SSH) libraries enriched with differentially expressed genes under cellulase induction (MM-Avicel) and cellulase repression conditions (MM-Glucose). The libraries, in combination with RNA interference, enabled sub-genomic engineering of
T. reesei
for enhanced cellulase production. The ability of
T. reesei
to produce endoglucanase was improved by 2.8~3.3-fold. In addition, novel regulatory genes (
tre49304
,
tre120391
, and
tre123541
) were identified to affect cellulase expression in
T. reesei
. Iterative manipulation using the same strategy further increased the yield of endoglucanase activity to 75.6 U/mL, which was seven times as high as that of the wild type (10.8 U/mL). Moreover, using
Humicola insolens
as an example, such a sub-genomic RNAi-assisted strain evolution proved to be also useful in other industrially important filamentous fungi.
H. insolens
is a filamentous fungus commonly used to produce catalase, albeit with similarly low transformation efficiency and scarce knowledge underlying the regulation of catalase expression. By combining SSH and RNAi, a strain of
H. insolens
producing 28,500 ± 288 U/mL of catalase was obtained, which was 1.9 times as high as that of the parent strain.

IMPORTANCE

Genetic engineering at the genomic scale provides an unparalleled advantage in microbial strain improvement, which has previously been limited only to the organisms with high transformation efficiency such as
Saccharomyces cerevisiae
and
Escherichia coli
. Herein, using the filamentous fungus
Trichoderma reesei
as a model organism, we demonstrated that the advantage of suppression subtractive hybridization (SSH) to enrich differentially expressed genes and the convenience of RNA interference to manipulate a multitude of genes could be combined to overcome the inadequate transformation efficiency. With this sub-genomic evolution strategy,
T. reesei
could be iteratively engineered for higher cellulase production. Intriguingly,
Humicola insolens
, a fungus with even little knowledge in gene expression regulation, was also improved for catalase production. The same strategy may also be expanded to engineering other microorganisms for enhanced production of proteins, organic acids, and secondary metabolites.
Recognition of
Chlamydia trachomatis
by Toll-like receptor 9 is altered during persistence
Authors: Diallo Aissata , Overman Grace , Sah Prakash , Liechti George W.
Published: June 2024

Toll-like receptor 9 (TLR9) is an innate immune receptor that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA (gDNA). Previous bioinformatic studies have demonstrated that the genome of the human pathogen
Chlamydia trachomatis
contains TLR9 stimulatory motifs, and correlative studies have implied a link between human TLR9 (hTLR9) genotype variants and susceptibility to infection. Here, we present our evaluation of the stimulatory potential of
C. trachomatis
gDNA and its recognition by hTLR9- and murine TLR9 (mTLR9)-expressing cells. Utilizing reporter cell lines, we demonstrate that purified gDNA from
C. trachomatis
can stimulate hTLR9 signaling, albeit at lower levels than gDNA prepared from other Gram-negative bacteria. Interestingly, we found that while
C. trachomatis
is capable of signaling through hTLR9 and mTLR9 during live infections in HEK293 reporter cell lines, signaling only occurs at later developmental time points. Chlamydia-specific induction of hTLR9 is blocked when protein synthesis is inhibited prior to the RB-to-EB conversion, exacerbated by the inhibition of lipooligosaccharide biosynthesis, and is significantly altered during the induction of aberrance/persistence. Our observations support the hypothesis that chlamydial gDNA is released during the conversion between the pathogen’s replicative and infectious forms and during treatment with antibiotics targeting peptidoglycan assembly. Given that
C. trachomatis
inclusions do not co-localize with TLR9-containing vacuoles in the pro-monocytic cell line U937, our findings also hint that chlamydial gDNA is capable of egress from the inclusion, and traffics to TLR9-containing vacuoles via an as yet unknown pathway.
Ribosomal-processing cysteine protease homolog modulates
Streptococcus mutans
glucan production and interkingdom interactions
Authors: Treerat Puthayalai , de Mattos Camilla , Burnside Molly , Zhang Hua , Zhu Yanting , Zou Zhengzhong , Anderson David , Wu Hui , Merritt Justin , Kreth Jens
Published: June 2024

Glucan-dependent biofilm formation is a crucial process in the establishment of
Streptococcus mutans
as a cariogenic oral microbe. The process of glucan formation has been investigated in great detail, with glycosyltransferases GtfB, GtfC, and GtfD shown to be indispensable for the synthesis of glucans from sucrose. Glucan production can be visualized during biofilm formation through fluorescent labeling, and its abundance, as well as the effect of glucans on general biofilm architecture, is a common phenotype to study
S. mutans
virulence regulation. Here, we describe an entirely new phenotype associated with glucan production, caused by a mutation in the open reading frame SMU_848, which is located in an operon encoding ribosome-associated proteins. This mutation led to the excess production and accumulation of glucan-containing droplets on the surface of biofilms formed on agar plates after prolonged incubation. While not characterized in
S. mutans
, SMU_848 shows homology to the phage-related ribosomal protease Prp, essential in cleaving off the N-terminal extension of ribosomal protein L27 for functional ribosome assembly in
Staphylococcus aureus
. We present a further characterization of SMU_848/Prp, demonstrating that the deletion of this gene leads to significant changes in
S. mutans gtfBC
expression. Surprisingly, it also profoundly impacts the interkingdom interaction between
S. mutans
and
Candida albicans
, a relevant dual-species interaction implicated in severe early childhood caries. The presented data support a potential broader role for SMU_848/Prp, possibly extending its functionality beyond the ribosomal network to influence important ecological processes.

IMPORTANCE

Streptococcus mutans
is an important member of the oral biofilm and is implicated in the initiation of caries. One of the main virulence mechanisms is the glucan-dependent formation of biofilms. We identified a new player in the regulation of glucan production, SMU_848, which is part of an operon that also encodes for ribosomal proteins L27 and L21. A mutation in SMU_848, which encodes a phage-related ribosomal protease Prp, leads to a significant accumulation of glucan-containing droplets on
S. mutans
biofilms, a previously unknown phenotype. Further investigations expanded our knowledge about the role of SMU_848 beyond its role in glucan production, including significant involvement in interkingdom interactions, thus potentially playing a global role in the virulence regulation of
S. mutans
.
Herpes simplex virus type-1 cVAC formation in neuronal cells is mediated by dynein motor function and glycoprotein retrieval from the plasma membrane
Authors: White Shaowen , Roller Richard
Published: June 2024

Herpesvirus assembly requires the cytoplasmic association of large macromolecular and membrane structures that derive from both the nucleus and cytoplasmic membrane systems. Results from the study of human cytomegalovirus (HCMV) in cells where it organizes a perinuclear cytoplasmic virus assembly compartment (cVAC) show a clear requirement for the minus-end-directed microtubule motor, dynein, for virus assembly. In contrast, the assembly of herpes simplex virus -1 (HSV-1) in epithelial cells where it forms multiple dispersed, peripheral assembly sites is only mildly inhibited by the microtubule-depolymerizing agent, nocodazole. Here, we make use of a neuronal cell line system in which HSV-1 forms a single cVAC and show that dynein and its co-factor dynactin localize to the cVAC, and dynactin is associated with membranes that contain the virion tegument protein pUL11. We also show that the virus membrane-associated structural proteins pUL51 and the viral envelope glycoprotein gE arrive at the cVAC by different routes. Specifically, gE arrives at the cVAC after retrieval from the plasma membrane, suggesting the need for an intact retrograde transport system. Finally, we demonstrate that inhibition of dynactin function profoundly inhibits cVAC formation and virus production during the cytoplasmic assembly phase of infection.

IMPORTANCE

Many viruses reorganize cytoplasmic membrane systems and macromolecular transport systems to promote the production of progeny virions. Clarifying the mechanisms by which they accomplish this may reveal novel therapeutic strategies and illustrate mechanisms that are critical for normal cellular organization. Here, we explore the mechanism by which HSV-1 moves macromolecular and membrane cargo to generate a virus assembly compartment in the infected cell. We find that the virus makes use of a well-characterized, microtubule-based transport system that is stabilized against drugs that disrupt microtubules.
The respiratory and fecal microbiota of beef calves from birth to weaning
Authors: Uddin Muhammed Salah , Ortiz Guluarte Jose , Waldner Matthew , Alexander Trevor W.
Published: June 2024

The development and growth of animals coincide with the establishment and maturation of their microbiotas. To evaluate the respiratory and fecal microbiotas of beef calves from birth to weaning, a total of 30 pregnant cows, and their calves at birth, were enrolled in this study. Deep nasal swabs and feces were collected from calves longitudinally, starting on the day of birth and ending on the day of weaning. Nasopharyngeal, vaginal, and fecal samples were also collected from cows, and the microbiotas of all samples were analyzed. The fecal microbiota of calves was enriched with
Lactobacillus
during the first 8 weeks of life, before being displaced by genera associated with fiber digestion, and then increasing in diversity across time. In contrast, the diversity of calf respiratory microbiota generally decreased with age. At birth, the calf and cow nasal microbiotas were highly similar, indicating colonization from dam contact. This was supported by microbial source-tracking analysis. The structure of the calf nasal microbiota remained similar to that of the cows, until weaning, when it diverged. The changes were driven by a decrease in
Lactobacillus
and an increase in genera typically associated with bovine respiratory disease, including
Mannheimia
,
Pasteurella
, and
Mycoplasma
. These three genera colonized calves early in life, though
Mannheimia
was initially transferred from the cow reproductive tract. Path analysis was used to model the interrelationships of calf respiratory and fecal microbiotas. It was observed that respiratory
Lactobacillus
and fecal
Oscillospiraceae
UCG-005 negatively affected the abundance of
Mannheimia
or
Pasteurella
.

IMPORTANCE

In beef cattle production, bovine respiratory disease (BRD) accounts for most of the feedlot morbidities and mortalities. Metaphylaxis is a common management tool to mitigate BRD, however its use has led to increased antimicrobial resistance. Novel methods to mitigate BRD are needed, including microbiota-based strategies. However, information on the respiratory bacteria of beef calves prior to weaning was limited. In this study, it was shown that the microbiota of cows influenced the initial composition of both respiratory and fecal microbiotas in calves. While colonization of the respiratory tract of calves by BRD-associated genera occurred early in life, their relative abundances increased at weaning, and were negatively correlated with respiratory and gut bacteria. Thus, microbiotas of both the respiratory and gastrointestinal tracts have important roles in antagonism of respiratory pathogens and are potential targets for enhancing calf respiratory health. Modulation may be most beneficial, if done prior to weaning, before opportunistic pathogens establish colonization.
c-di-AMP accumulation impairs toxin expression of
Bacillus anthracis
by down-regulating potassium importers
Authors: Hu Jia , Yao Junmin , Lei Chengfeng , Sun Xiulian
Published: June 2024

The Gram-positive bacterium
Bacillus anthracis
is the causative agent of anthrax and a bioterrorism threat worldwide. As a crucial second messenger in many bacterial species, cyclic di-AMP (c-di-AMP) modulates various key processes for bacterial homeostasis and pathogenesis. Overaccumulation of c-di-AMP alters cellular growth and reduces anthrax toxin expression as well as virulence in
Bacillus anthracis
by unresolved underlying mechanisms. In this report, we discovered that c-di-AMP binds to a series of receptors involved in potassium uptake in
B. anthracis
. By analyzing Kdp and Ktr mutants for osmotic stress, gene expression, and anthrax toxin expression, we also showed that c-di-AMP inhibits Kdp operon expression through binding to the KdpD and
ydaO
riboswitch; up-regulating intracellular potassium promotes anthrax toxin expression in c-di-AMP accumulated
B. anthracis
. Decreased anthrax toxin expression at high c-di-AMP occurs through the inhibition of potassium uptake. Understanding the molecular basis of how potassium uptake affects anthrax toxin has the potential to provide new insight into the control of
B. anthracis.

IMPORTANCE

The bacterial second messenger cyclic di-AMP (c-di-AMP) is a conserved global regulator of potassium homeostasis. How c-di-AMP regulates bacterial virulence is unknown. With this study, we provide a link between potassium uptake and anthrax toxin expression in
Bacillus anthracis
. c-di-AMP accumulation might inhibit anthrax toxin expression by suppressing potassium uptake.
Potential bed-day savings and caregiver perspectives of transitioning hospital-level management of infants with bronchiolitis to the home: a mixed-methods study
Authors: Lawrence Joanna , Hiscock Harriet , Bryant Penelope A , Greig Genevieve , Sharma Anurag , Walpola Ramesh
Published: June 2024

Objective

Home management of infants admitted to hospital with bronchiolitis would alleviate pressure on hospital beds. We aim to understand the proportion of children requiring active care interventions (ie, oxygen, fluids), caregiver perspectives and potential impact of transitioning hospital-level care of infants with bronchiolitis to home.

Methods

This is a mixed-methods study in an Australian tertiary paediatric hospital. Semistructured interviews with caregivers of infants with bronchiolitis focused on attitudes towards managing bronchiolitis at home. Interviews were analysed using inductive thematic analysis. Data on bronchiolitis admissions among infants aged 1–12 months were extracted from the electronic medical record from April 2016 to October 2020. Potential bed-days saved were calculated.

Results

18 parents were interviewed, with themes emerging of ‘hospital is safe’, ‘hospital incurs costs’ and ‘knowledge is power’. During 4.5 years, 2367 infants were admitted to hospital with bronchiolitis: a total of 4557 bed-days. Of these, 40% of infants were admitted for monitoring alone, 25% for nasogastric fluid support, 17% for oxygen therapy and 7.5% for both fluids and oxygen. 11% received treatments not currently feasible at home (high-flow oxygen, intravenous fluids). Oxygen therapy accounted for the largest number of bed-days (242 bed-days/year).

Conclusion

Managing bronchiolitis at home could have a substantial impact on hospital bed demand, with an estimated 344 bed-days saved per year if all interventions were offered. Parent willingness to transfer to home balances the perceived safety of the hospital versus the financial, logistic and emotional costs. Empowering parents with knowledge was seen as a substantial facilitator of supporting transition to the home.
Severe non-hepatic hyperammonaemic encephalopathy in an immunocompromised adolescent with enterocolitis
Authors: Borrie Adrienne Elizabeth , Pike Meghan , Villeneuve Stephanie , Verma Neeraj
Published: June 2024

Non-hepatic causes of hyperammonaemia are uncommon relative to hepatic aetiologies. An adolescent female was admitted to the hospital with a diagnosis of very severe aplastic anaemia. During her treatment with immunosuppressive therapy, she developed neutropenic enterocolitis, pseudomonal bacteraemia and hyperammonaemia. A combination of intermittent haemodialysis and high-volume continuous veno-venous haemodiafiltration (CVVHDF) was required to manage the hyperammonaemia. Despite a thorough investigation, there were no hepatic, metabolic or genetic aetiologies identified that explained the hyperammonaemia. The hyperammonaemia resolved only after the surgical resection of her inflamed colon, following which she was successfully weaned off from the renal support. This is a novel case report of hyperammonaemia of non-hepatic origin secondary to widespread inflammation of the colon requiring surgical resection in an immunocompromised patient. This case also highlights the role of high-volume CVVHDF in augmenting haemodialysis in the management of severe refractory hyperammonaemia.
Mid-aortic syndrome presented as dilated cardiomyopathy
Authors: Pang Kah Yit , Yubbu Putri , Ali Norliza , Koh Ghee Tiong
Published: June 2024

Mid-aortic syndrome (MAS) is a rare vascular disease that usually leads to renovascular hypertension. With the predominant manifestations being intractable arterial hypertension and lower extremity arterial insufficiency, it has rarely been associated with dilated cardiomyopathy. We report a young girl with congestive heart failure, where the cause was initially attributed to dilated cardiomyopathy. A repeated echocardiogram 6 months later brought the physician’s suspicion of MAS because of the abnormal colour of Doppler from the subcostal view. Further assessment using CT angiography revealed discrete thoracic coarctation at the level of T10, with the narrowest diameter of 2.1 mm, thus confirming the diagnosis. Her inflammatory markers and connective tissue screening were negative. She underwent successful stenting of coarctation of the aorta, which later caused improvement in her cardiac function. We highlighted the importance of looking for treatable causes of dilated cardiomyopathy and vigilant clinical and echocardiogram assessment with high suspicion to diagnose MAS.
Misidentification ofBrucella melitensisasOchrobactrumspecies: potential pitfalls in the diagnosis of brucellosis
Authors: Howley Fergal , Abukhodair Sultan , de Barra Eoghan , O'Connell Karina , McNally Cora
Published: June 2024

We describe a case of brucellosis in a man in his 20s, who presented to the emergency department with a 1-month history of fevers, dry cough and knee pain. Blood cultures were positive after 55 hours andOchrobactrum daejeonensewas identified on matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry.Ochrobactrumspp are Gram-negative organisms that are phylogenetically related toBrucellaspp but commercially available MALDI-TOF libraries cannot distinguish between the two genera. Further positive blood cultures forO. daejeonensecombined with characteristic growth patterns forBrucellaspp led to targeted questioning of the patient regarding potential exposure risks, which revealed a history of consumption of unpasteurised camel milk in the Middle East 3 months earlier. Treatment of brucellosis was initiated and subsequent whole genome sequencing identified the blood culture isolate asBrucella melitensisconfirming the diagnosis of brucellosis. This case highlights the challenges in the diagnosis of brucellosis in low-incidence settings.
Is radial extracorporeal shock wave therapy (rESWT), sham-rESWT or a standardised exercise programme in combination with advice plus customised foot orthoses more effective than advice plus customised foot orthoses alone in the treatment of plantar fasciopathy? A double-blind, randomised, sham-controlled trial
Authors: Heide Marte , Røe Cecilie , Mørk Marianne , Myhre Kjersti , Brunborg Cathrine , Brox Jens Ivar , Hoksrud Aasne Fenne
Published: June 2024

Objectives

To assess whether radial extracorporeal shock wave therapy (rESWT), sham-rESWT or a standardised exercise programme in combination with advice plus customised foot orthoses is more effective than advice plus customised foot orthoses alone in alleviating heel pain in patients with plantar fasciopathy.

Methods

200 patients with plantar fasciopathy were included in a four-arm, parallel-group, sham-controlled, observer-blinded, partly patient-blinded trial. At baseline, before randomisation, all patients received advice plus customised foot orthoses. Patients were randomised to rESWT (n=50), sham-rESWT (n=50), exercise (n=50) or advice plus customised foot orthoses alone (n=50). Patients in the rESWT and sham-rESWT groups received three treatments. The exercise programme comprised two exercises performed three times a week for 12 weeks, including eight supervised sessions with a physiotherapist. Patients allocated to advice plus customised foot orthoses did not receive additional treatment. The primary outcome was change in heel pain during activity in the previous week per Numeric Rating Scale (0–10) from baseline to 6-month follow-up. The outcome was collected at baseline, and 3, 6 and 12 months.

Results

The primary analysis showed no statistically significant between-group differences in mean change in heel pain during activity for rESWT versus advice plus customised foot orthoses (−0.02, 95% CI −1.01 to 0.96), sham-rESWT versus advice plus customised foot orthoses (0.52, 95% CI −0.49 to 1.53) and exercise versus advice plus customised foot orthoses (−0.11, 95% CI −1.11 to 0.89) at 6 months.

Conclusion

In patients with plantar fasciopathy, there was no additional benefit of rESWT, sham-rESWT or a standardised exercise programme over advice plus customised foot orthoses in alleviating heel pain.

Trial registration number

NCT03472989.
Annual hepatitis C testing and positive tests among gay and bisexual men in Australia from 2016 to 2022: a serial cross-sectional analysis of sentinel surveillance data
Authors: Harney Brendan L , Sacks-Davis Rachel , Traeger Michael , van Santen Daniela K , Wilkinson Anna L , Asselin Jason , Fairley Christopher K , Roth Norm , Bloch Mark , Matthews Gail , Donovan Basil , Guy Rebecca , Hellard Margaret E , Doyle Joseph S
Published: June 2024

Objective

Guidelines recommend annual hepatitis C virus (HCV) testing for gay and bisexual men (GBM) with HIV and GBM prescribed HIV pre-exposure prophylaxis (PrEP). However, there is a limited understanding of HCV testing among GBM. We aimed to examine trends in HCV testing and positivity from 2016 to 2022.

Methods

Using sentinel surveillance data, we examined the proportion of GBM with at least one test and the proportion with a positive test in each year for HCV antibody testing among GBM with no previous HCV positive test, HCV RNA testing among GBM with a positive antibody test but no previous positive RNA test (naïve RNA testing), and HCV RNA testing among people who had a previous RNA positive test and a subsequent negative test (RNA follow-up testing). Trends were examined using logistic regression from 2016 to 2019 and 2020 to 2022.

Results

Among GBM with HIV, from 2016 to 2019 antibody testing was stable averaging 55% tested annually. Declines were observed for both naïve HCV RNA testing (75.4%–41.4%: p<0.001) and follow-up HCV RNA testing (70.1%–44.5%: p<0.001). Test positivity declined for HCV antibody tests (2.0%–1.3%: p=0.001), HCV RNA naïve tests (75.4%–41.4%: p<0.001) and HCV RNA follow-up tests (11.3%–3.3%: p=0.001). There were minimal or no significant trends from 2020 to 2022.

Among GBM prescribed PrEP, antibody testing declined from 2016 to 2019 (79.4%–69.4%: p<0.001) and was stable from 2020 to 2022. Naïve and follow-up HCV RNA testing was stable with an average of 55% and 60% tested each year, respectively. From 2016–2019, the proportion positive from HCV RNA naïve tests declined (44.1%–27.5%: p<0.046) with no significant change thereafter. Positive follow-up HCV RNA tests fluctuated with no or one new positive test among this group in most years.

Conclusion

The proportion of GBM with positive HCV tests has declined, however a substantial proportion are not tested annually. A renewed focus on HCV testing, and treatment where required, is warranted to achieve HCV elimination among GBM in Australia.
A relative stability scale of nitrogen donor ligand ruthenium complexes based on their stability constants calculated from first principles by DFT methods
Authors: Salmon Kyle , Schlaf Marcel
Published: June 2024

Using DFT calculations (M06/def2-TZVP/SMD solvent model) a relative stability scale is established from first principles for a series of iron and ruthenium complexes with ligand frameworks based on chelating pyridine- and pyrrole-type (porphyrin and phthalocyanine) ligands by determining the equilibrium constants for the complex formation reactions [M(H2O)6]2+ + nL → [M(L)n(H2O)m]2+ + (6 − m) H2O; M=Fe, Ru in aqueous solution through Hess's law and the van't Hoff equation. For a subset of the iron complexes, comparison against the available experimental data systematically underestimates the calculated constants by multiple orders of magnitude for the high-spin hexaaqua complex as the starting material, but shows a linear correlation trend between the experimental and calculated values. A similar correlation exists between the calculated values for the iron and ruthenium complexes. For the latter, for which no experimental data are available, the values are very high. On the relative scale calculated, the stability constants for the macrocyclic porphyrin and phthalocyanine complexes are unexpectedly low when calculated from the neutral ligand, but very high when calculated for reactions starting from the deprotonated ligand in its dianionic state. The limitations of the model are discussed, in particular with regards to the likely very large influence of solvation energies and hydrogen-bond networks not explicitly formulated in the SMD solvent model employed and Brønsted acid–base reactions between complexes and ligands, and its merits critically evaluated.
Gravitational lensing from clusters of galaxies to test disformal couplings theories
Authors: Zamani Saboura , Salzano Vincenzo , Bettoni Dario
Published: June 2024

In this study, we investigate the potential existence of a non-minimal coupling between dark matter and gravity using a compilation of galaxy clusters. We focus on the disformal scenario of a non-minimal model with an associated coupling length L. Within the Newtonian approximation, this model introduces a modification to the Poisson equation, characterized by a term proportional to $$L^2 \nabla ^2 \rho $$

L
2

∇
2

ρ

, where $$\rho $$
ρ
represents the density of the DM field. We have tested the model by examining strong and weak gravitational lensing data available for a selection of 19 high-mass galaxy clusters observed by the CLASH survey. We have employed a Markov Chain Monte Carlo code to explore the parameter space, and two different statistical approaches to analyse our results: a standard marginalisation and a profile distribution method. Notably, the profile distribution analysis helps out to bypass some volume-effects in the posterior distribution, and reveals lower Navarro–Frenk–White concentrations and masses in the non-minimal coupling model compared to general relativity case. We also found a nearly perfect correlation between the coupling constant L and the standard Navarro–Frenk–White scale parameter $$r_s$$

r
s

, hinting at a compelling link between these two lengths.
Generation of the CMB cosmic birefringence through axion-like particles, sterile and active neutrinos
Authors: Mahmoudi Somayyeh , Sadegh Mahdi , Khodagholizadeh Jafar , Motie Iman , Xue She-Sheng , Blanchard Alain
Published: June 2024

The cosmic birefringence (CB) angle refers to the rotation of the linear polarization plane of Cosmic Microwave Background (CMB) radiations when parity-violating theories are considered. We analyzed the Quantum Boltzmann equation for an ensemble of CMB photons interacting with the right-handed sterile neutrino dark matter (DM) and axion-like particles (ALPs) DM in the presence of the scalar metric perturbation. We used the birefringence angle of CMB to study those probable candidates of DM. It is shown that the CB angle contribution of sterile neutrino is much less that two other sources considered here. Next, we combined the results of the cosmic neutrinos’ contribution and the contribution of the ALPs to producing the CMB birefringence and discussed the uncertainty on the parameter space of axions caused by the share of CMB-cosmic neutrino interaction in generating this effect. Finally, we plotted the EB power spectrum of the CMB and showed that this spectrum behaves differently in the presence of cosmic neutrinos and ALPs interactions in small l. Hence, future observed data for $$C^{l}_{EB},$$

C

EB

l

,

will help us to distinguish the CB angle value due to the various sources of its production.
COMPETITION BETWEEN PLASMID-BEARING AND PLASMID-FREE ORGANISMS IN A CHEMOSTAT WITH DISTINCT REMOVAL RATES AND AN EXTERNAL INHIBITOR
Authors: HAMIDI NABIL , DELLAL MOHAMED , LAKRIB MUSTAPHA
Published: June 2024

A mathematical model of competition between plasmid-bearing and plasmid-free organisms for a single limiting resource in a chemostat with distinct removal rates and in the presence of an external inhibitor is analyzed. This model was previously introduced in the special case where the growth rate functions and the absorption rate of the inhibitor follow the Monod kinetics and the removal rates are the same as the dilution rate. Here, we consider the general case of monotonic growth and absorption functions, and distinct removal rates. Through the three operating parameters of the model, represented by the dilution rate, the input concentrations of the substrate and the inhibitor, we give necessary and sufficient conditions for existence and stability of all equilibria. To better understand the richness of the model’s behavior with respect to those operating parameters, we determine the operating diagram theoretically and numerically. This diagram is very useful to understand the model from both the mathematical and biological points of view.
Input-Relational Verification of Deep Neural Networks
Authors: Banerjee Debangshu , Xu Changming , Singh Gagandeep
Published: June 2024

We consider the verification of input-relational properties defined over deep neural networks (DNNs) such as robustness against universal adversarial perturbations, monotonicity, etc. Precise verification of these properties requires reasoning about multiple executions of the same DNN. We introduce a novel concept of difference tracking to compute the difference between the outputs of two executions of the same DNN at all layers. We design a new abstract domain, DiffPoly for efficient difference tracking that can scale large DNNs. DiffPoly is equipped with custom abstract transformers for common activation functions (ReLU, Tanh, Sigmoid, etc.) and affine layers and can create precise linear cross-execution constraints. We implement an input-relational verifier for DNNs called RaVeN which uses DiffPoly and linear program formulations to handle a wide range of input-relational properties. Our experimental results on challenging benchmarks show that by leveraging precise linear constraints defined over multiple executions of the DNN, RaVeN gains substantial precision over baselines on a wide range of datasets, networks, and input-relational properties.
Verified Extraction from Coq to OCaml
Authors: Forster Yannick , Sozeau Matthieu , Tabareau Nicolas
Published: June 2024

One of the central claims of fame of the Coq proof assistant is extraction, i.e. the ability to obtain efficient programs in industrial programming languages such as OCaml, Haskell, or Scheme from programs written in Coq’s expressive dependent type theory. Extraction is of great practical usefulness, used crucially e.g. in the CompCert project. However, for such executables obtained by extraction, the extraction process is part of the trusted code base (TCB), as are Coq’s kernel and the compiler used to compile the extracted code. The extraction process contains intricate semantic transformation of programs that rely on subtle operational features of both the source and target language. Its code has also evolved since the last theoretical exposition in the seminal PhD thesis of Pierre Letouzey. Furthermore, while the exact correctness statements for the execution of extracted code are described clearly in academic literature, the interoperability with unverified code has never been investigated formally, and yet is used in virtually every project relying on extraction. In this paper, we describe the development of a novel extraction pipeline from Coq to OCaml, implemented and verified in Coq itself, with a clear correctness theorem and guarantees for safe interoperability. We build our work on the MetaCoq project, which aims at decreasing the TCB of Coq’s kernel by re-implementing it in Coq itself and proving it correct w.r.t. a formal specification of Coq’s type theory in Coq. Since OCaml does not have a formal specification, we make use of the project specifying the semantics of the intermediate language of the OCaml compiler. Our work fills some gaps in the literature and highlights important differences between the operational semantics of Coq programs and their extraction. In particular, we focus on the guarantees that can be provided for interoperability with unverified code, and prove that extracted programs of first-order data type are correct and can safely interoperate, whereas for higher-order programs already simple interoperations can lead to incorrect behaviour and even outright segfaults.
Compilation of Qubit Circuits to Optimized Qutrit Circuits
Authors: Sharma Ritvik , Achour Sara
Published: June 2024

Quantum computers are a revolutionary class of computational platforms that are capable of solving computationally hard problems. However, today’s quantum hardware is subject to noise and decoherence issues that together limit the scale and complexity of the quantum circuits that can be implemented. Recently, practitioners have developed qutrit-based quantum hardware platforms that compute over 0, 1, and 2 states, and have presented circuit depth reduction techniques using qutrits’ higher energy 2 states to temporarily store information. However, thus far, such quantum circuits that use higher order states for temporary storage need to be manually crafted by hardware designers. We present , an optimizing compiler for qutrit circuits that implement qubit computations. deploys a qutrit circuit decomposition algorithm and a rewrite engine to construct and optimize qutrit circuits. We evaluate against hand-optimized qutrit circuits and qubit circuits, and find delivers up to 65% depth improvement over manual qutrit implementations, and 43-75% depth improvement over qubit circuits. We also perform a fidelity analysis and find -optimized qutrit circuits deliver up to 8.9× higher fidelity circuits than their manually implemented counterparts.