bluuebunny/crossref_metadata_2025 huggingface dataset:
Systemic absorption and safety of topical terbinafine hydrochloride 10% solution (MOB015B): a phase 1 maximal usage trial in patients with moderate-to-severe onychomycosis
Authors: Tavakkol Amir , DuBois Janet C. , Gupta Aditya K.
Published: August 2024

Topical antifungals may be considered to treat onychomycosis with minimal risk of systemic side effects. In this study, we assess the safety, tolerability, systemic exposure, and pharmacokinetic characteristics of topical terbinafine hydrochloride 10% solution (MOB015B) in adults with moderate-to-severe onychomycosis. Clinically and mycologically confirmed patients with toenail onychomycosis (
N
= 20) were enrolled in this single-center, open-label study . Each patient had ≥50% involvement of both great toenails and at least four additional toenails affected. MOB015B was applied once daily to all toenails for 28 days. Blood was drawn on days 1, 14, and 28. Plasma concentrations of MOB015B after the first dose were quantifiable in all subjects by 24 h. Steady-state levels in plasma were reached by day 28. The mean systemic exposure on day 28 of 0.72 ng/mL for maximum plasma concentration (C
max
) was approximately 2,000 times lower than the mean plasma level of 1.39 µg/mL seen after oral administration of 250 mg terbinafine for 28 days. Adverse events (five patients), such as headache (
n
= 3), seasonal allergy (
n
= 1), and neck pain (
n
= 1), were considered unrelated to MOB015B; no application site reactions or study discontinuations due to an adverse event were observed. MOB015B applied to all affected toenails under maximal usage conditions for 28 days demonstrated very low levels of terbinafine in plasma (C
max
<1 ng/mL after 28 days), consistent with a favorable safety and tolerability profile.

CLINICAL TRIALS

This study is registered with

ClinicalTrials.gov
as
NCT03244280

.
Multicenter evaluation of activity of aztreonam in combination with avibactam, relebactam, and vaborbactam against metallo-β-lactamase-producing carbapenem-resistant gram-negative bacilli
Authors: Tao Lili , Dahlquist Ashley , Harris Harley , Jacobs Emily , Wenzler Eric , Simner Patricia J. , Humphries Romney
Published: August 2024

Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-β-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and
Stenotrophomonas maltophilia
. However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited. We performed a multicenter study to evaluate the
in vitro
activities of ATM in combination with AVI, vaborbactam (VAB), relebactam (REL), tazobactam (TAZ) as well as with their commercially available formulations against CREs and
S. maltophilia
using broth microdilution. AVI restored ATM activity for MBL-producing CREs (ATM: 9.8% vs ATM-AVI: 78.0%) and
S. maltophilia
(ATM: 0% vs ATM-AVI: 93.3%). REL also moderately restored activity of ATM in MBL-producing CREs (ATM: 9.8% vs ATM-REL: 42.7%) and
S. maltophilia
(ATM: 0% vs ATM-REL: 68.9%). VAB and TAZ demonstrated very limited effect on the activity of ATM against CR-GNB evaluated. The combination of ATM with ceftazidime-AVI (CAZ-AVI) demonstrated maximum activity against CREs. Although ATM-CAZ-AVI is the most potent regimen available for CREs and
S. maltophilia
, ATM-IMI-REL might be a reasonable alternative.
CRISPR-Cas inhibits plasmid transfer and immunizes bacteria against antibiotic resistance acquisition in manure
Authors: Upreti Chahat , Kumar Pranav , Durso Lisa M. , Palmer Kelli L.
Published: August 2024

The horizontal transfer of antibiotic resistance genes among bacteria is a pressing global issue. The bacterial defense system clustered regularly interspaced short palindromic repeats (CRISPR)-Cas acts as a barrier to the spread of antibiotic resistance plasmids, and CRISPR-Cas-based antimicrobials can be effective to selectively deplete antibiotic-resistant bacteria. While significant surveillance efforts monitor the spread of antibiotic-resistant bacteria in the clinical context, a major, often overlooked aspect of the issue is resistance emergence in agriculture. Farm animals are commonly treated with antibiotics, and antibiotic resistance in agriculture is on the rise. Yet, CRISPR-Cas efficacy has not been investigated in this setting. Here, we evaluate the prevalence of CRISPR-Cas in agricultural
Enterococcus faecalis
strains and its antiplasmid efficacy in an agricultural niche: manure. Analyzing 1,986
E. faecalis
genomes from human and animal hosts, we show that the prevalence of CRISPR-Cas subtypes is similar between clinical and agricultural
E. faecalis
strains. Using plasmid conjugation assays, we found that CRISPR-Cas is a significant barrier against resistance plasmid transfer in manure. Finally, we used a CRISPR-based antimicrobial approach to cure resistant
E. faecalis
of erythromycin resistance, but this was limited by delivery efficiency of the CRISPR antimicrobial in manure. However, immunization of bacteria against resistance gene acquisition in manure was highly effective. Together, our results show that
E. faecalis
CRISPR-Cas is prevalent and effective in an agricultural setting and has the potential to be utilized for depleting antibiotic-resistant populations. Our work has broad implications for tackling antibiotic resistance in the increasingly relevant agricultural setting, in line with a One Health approach.

IMPORTANCE

Antibiotic resistance is a growing global health crisis in human and veterinary medicine. Previous work has shown technologies based on CRISPR-Cas—a bacterial defense system—to be effective in tackling antibiotic resistance. Here we test if CRISPR-Cas is present and effective in agricultural niches, specifically in the ubiquitously present bacterium,
Enterococcus faecalis
. We show that CRISPR-Cas is both prevalent and functional in manure and has the potential to be used to specifically kill bacteria carrying antibiotic resistance genes. This study demonstrates the utility of CRISPR-Cas-based strategies for control of antibiotic resistance in agricultural settings.
The megaplasmid pCER270 of
Bacillus cereus
emetic strain affects the timing of the sporulation process, spore resistance properties, and germination
Authors: Perchat Stéphane , Nevers Alicia , Kranzler Markus , Ehling-Schulz Monika , Lereclus Didier , Gohar Michel
Published: August 2024

The
Bacillus cereus
group includes closely related spore-forming Gram-positive bacteria. In this group, plasmids play a crucial role in species differentiation and are essential for pathogenesis and adaptation to ecological niches. The
B. cereus
emetic strains are characterized by the presence of the pCER270 megaplasmid, which encodes the non-ribosomal peptide synthetase for the production of cereulide, the emetic toxin. This plasmid carries several genes that may be involved in the sporulation process. Furthermore, a transcriptomic analysis has revealed that pCER270 influences the expression of chromosome genes, particularly under sporulation conditions. In this study, we investigated the role of pCER270 on spore properties in different species of the
B. cereus
group. We showed that pCER270 plays a role in spore wet heat resistance and germination, with varying degrees of impact depending on the genetic background. In addition, pCER270 ensures that sporulation occurs at the appropriate time by delaying the expression of sporulation genes. This regulation of sporulation timing is controlled by the pCER270-borne Rap-Phr system, which likely regulates the phosphorylation state of Spo0A. Acquisition of the pCER270 plasmid by new strains could give them an advantage in adapting to new environments and lead to the emergence of new pathogenic strains.

IMPORTANCE

The acquisition of new mobile genetic elements, such as plasmids, is essential for the pathogenesis and adaptation of bacteria belonging to the
Bacillus cereus
group. This can confer new phenotypic traits and beneficial functions that enable bacteria to adapt to changing environments and colonize new ecological niches. Emetic
B. cereus
strains cause food poisoning linked to the production of cereulide, the emetic toxin whose synthesis is due to the presence of plasmid pCER270. In the environment, cereulide provides a competitive advantage in producing bacteria against various competitors or predators. This study demonstrates that pCER270 also regulates the sporulation process, resulting in spores with improved heat resistance and germination capacity. The transfer of plasmid pCER270 among different strains of the
B. cereus
group may enhance their adaptation to new environments. This raises the question of the emergence of new pathogenic strains, which could pose a serious threat to human health.
Nitrate assimilation compensates for cell wall biosynthesis in the absence of
Aspergillus fumigatus
phosphoglucose isomerase
Authors: Gong Xiufang , Zhou Yao , Qin Qijian , Wang Bin , Wang Linqi , Jin Cheng , Fang Wenxia
Published: August 2024

Phosphoglucose isomerase (PGI) links glycolysis, the pentose phosphate pathway (PPP), and the synthesis of cell wall precursors in fungi by facilitating the reversible conversion between glucose-6-phosphate (Glc6p) and fructose-6-phosphate (Fru6P). In a previous study, we established the essential role of PGI in cell wall biosynthesis in the opportunistic human fungal pathogen
Aspergillus fumigatus
, highlighting its potential as a therapeutic target. In this study, we conducted transcriptomic analysis and discovered that the Δ
pgi
mutant exhibited enhanced glycolysis, reduced PPP, and an upregulation of cell wall precursor biosynthesis pathways. Phenotypic analysis revealed defective protein
N
-glycosylation in the mutant, notably the absence of glycosylated virulence factors DPP V and catalase 1. Interestingly, the cell wall defects in the mutant were not accompanied by activation of the MpkA-dependent cell wall integrity (CWI) signaling pathway. Instead, nitrate assimilation was activated in the Δ
pgi
mutant, stimulating glutamine synthesis and providing amino donors for chitin precursor biosynthesis. Blocking the nitrate assimilation pathway severely impaired the growth of the Δ
pgi
mutant, highlighting the crucial role of nitrate assimilation in rescuing cell wall defects. This study unveils the connection between nitrogen assimilation and cell wall compensation in
A. fumigatus
.

IMPORTANCE

Aspergillus fumigatus
is a common and serious human fungal pathogen that causes a variety of diseases. Given the limited availability of antifungal drugs and increasing drug resistance, it is imperative to understand the fungus’ survival mechanisms for effective control of fungal infections. Our previous study highlighted the essential role of
A. fumigatus
PGI in maintaining cell wall integrity, phosphate sugar homeostasis, and virulence. The present study further illuminates the involvement of PGI in protein
N
-glycosylation. Furthermore, this research reveals that the nitrogen assimilation pathway, rather than the canonical MpkA-dependent CWI pathway, compensates for cell wall deficiencies in the mutant. These findings offer valuable insights into a novel adaptation mechanism of
A. fumigatus
to address cell wall defects, which could hold promise for the treatment of infections.
Practical Guidance for Clinical Microbiology Laboratories: Updated guidance for processing respiratory tract samples from people with cystic fibrosis
Authors: Saiman Lisa , Waters Valerie , LiPuma John J. , Hoffman Lucas R. , Alby Kevin , Zhang Sean X. , Yau Yvonne C. , Downey Damian G. , Sermet-Gaudelus Isabelle , Bouchara Jean-Philippe , Kidd Timothy J. , Bell Scott C. , Brown A. Whitney
Published: August 2024

This guidance presents recommendations for clinical microbiology laboratories for processing respiratory samples from people with cystic fibrosis (pwCF). Appropriate processing of respiratory samples is crucial to detect bacterial and fungal pathogens, guide treatment, monitor the epidemiology of cystic fibrosis (CF) pathogens, and assess therapeutic interventions. Thanks to CF transmembrane conductance regulator modulator therapy, the health of pwCF has improved, but as a result, fewer pwCF spontaneously expectorate sputum. Thus, the collection of sputum samples has decreased, while the collection of other types of respiratory samples such as oropharyngeal and bronchoalveolar lavage samples has increased. To optimize the detection of microorganisms, including
Pseudomonas aeruginosa
,
Staphylococcus aureus
,
Haemophilus influenzae
, and
Burkholderia cepacia
complex; other less common non-lactose fermenting Gram-negative bacilli, e.g.,
Stenotrophomonas maltophilia
,
Inquilinus
,
Achromobacter
,
Ralstonia
, and
Pandoraea
species; and yeasts and filamentous fungi, non-selective and selective culture media are recommended for all types of respiratory samples, including samples obtained from pwCF after lung transplantation. There are no consensus recommendations for laboratory practices to detect, characterize, and report small colony variants (SCVs) of
S. aureus
, although studies are ongoing to address the potential clinical impact of SCVs. Accurate identification of less common Gram-negative bacilli, e.g.,
S. maltophilia
,
Inquilinus
,
Achromobacter
,
Ralstonia
, and
Pandoraea
species, as well as yeasts and filamentous fungi, is recommended to understand their epidemiology and clinical importance in pwCF. However, conventional biochemical tests and automated platforms may not accurately identify CF pathogens. MALDI-TOF MS provides excellent genus-level identification, but databases may lack representation of CF pathogens to the species-level. Thus, DNA sequence analysis should be routinely available to laboratories for selected clinical circumstances. Antimicrobial susceptibility testing (AST) is not recommended for every routine surveillance culture obtained from pwCF, although selective AST may be helpful, e.g., for unusual pathogens or exacerbations unresponsive to initial therapy. While this guidance reflects current care paradigms for pwCF, recommendations will continue to evolve as CF research expands the evidence base for laboratory practices.
NLRP3 inflammasome inhibition decreases
Schistosomiasis japonica
-induced granulomatous inflammation and fibrosis in BALB/c mice
Authors: Lu Yaqi , Liu Jing , Tang Wangxian , Zhang Heng
Published: August 2024

To research the role of the NLRP3 inflammasome in
Schistosoma japonicum
-induced granuloma formation and liver fibrosis. In
in vivo
tests, BALB/c mice were used. shNLRP3 plasmid based on adeno-associated virus serotype 8 (AAV8-shNLRP3) was injected to block NLRP3 inflammasome via tail vein. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected to assess liver injury. H&E staining was used for routine histopathological assessment; Masson’s trichrome staining was used to detect fibrous tissues and collagen fibers. Hepatic expression of NLRP3, procaspase-1, bioactive caspase-1, collagen-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and α-smooth muscle actin (α-SMA) were detected by western blot. Serum levels of IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The inflammatory cell infiltration and hepatic expression of IL-1β around the granuloma were detected by immunohistochemistry staining. Treatment of
S. japonicum
infected mice with AAV8-shNLRP3 significantly reduced the hepatic levels of bioactive caspase-1 and IL-1β, as well as circulating IL-1β concentrations, while reducing the amounts of myeloperoxidase (MPO) and F4/80 positive cells around the granuloma. Moreover, collagen deposition, TIMP-1, and α-SMA, which are markers of hepatic stellate cell (HSC) activation, were reduced around the liver granuloma. These findings highlight a therapeutic potential of AAV8-shNLRP3 in schistosomiasis cirrhosis.
The CpxAR signaling system confers a fitness advantage for flea gut colonization by the plague bacillus
Authors: Robin Brandon , Dewitte Amélie , Alaimo Véronique , Lecoeur Cecile , Pierre François , Billon Gabriel , Sebbane Florent , Bontemps-Gallo Sébastien
Published: August 2024

The adaptation of
Yersinia pestis
, the flea-borne plague agent, to fluctuating environmental conditions is essential for the successful colonization of the flea vector. A previous comparative transcriptomic analysis showed that the Cpx pathway of
Y. pestis
is up-regulated in infected fleas. The CpxAR two-component system is a component of the envelope stress response and is critical for maintaining the integrity of the cell. Here, a phenotypic screening revealed a survival defect of the
cpxAR
mutant to oxidative stress and copper. The measured copper concentration in the digestive tract contents of fed fleas increased fourfold during the digestive process. By direct analysis of phosphorylation of CpxR by a Phos-Tag gel approach, we demonstrated that biologically relevant concentrations of copper triggered the system. Then, a competitive challenge highlighted the role of the CpxAR system in bacterial fitness during flea infection. Lastly, an
in vitro
sequential exposure to copper and then H
2
O
2
to mimic the flea suggests a model in which, within the insect digestive tract, the CpxAR system would be triggered by copper, establishing an oxidative stress response.

IMPORTANCE

The bacterium
Yersinia pestis
is the agent of flea-borne plague. Our knowledge of the mechanisms used by the plague bacillus to infect the flea vector is limited. The up-regulation of the envelope stress response under the control of the Cpx signaling pathway was previously shown in a transcriptomic study. Here, our
in vivo
and
in vitro
approaches suggest a model in which
Y. pestis
uses the CpxAR phosphorelay system to sense and respond to the copper present in the flea gut, thereby optimizing the flea gut colonization. In other words, the system is essential for bacterial fitness in the flea.
A spike-based mRNA vaccine that induces durable and broad protection against porcine deltacoronavirus in piglets
Authors: Li Jizong , Xiao Li , Chen Zhuoqi , Fan Liyuan , Wang Wei , Guo Rongli , He Zhaoming , Hu Hongpeng , Jiang Jianhao , Zhao Lixiang , Zhong Tianyi , Fan Baochao , Zhu Xing , Li Bin
Published: August 2024

Coronaviruses (CoVs) are important pathogens for humans and other vertebrates, causing severe respiratory and intestinal infections that have become a threat to public health because of the potential for interspecies transmission between animals and humans. Therefore, the development of safe, effective vaccines remains a top priority for the control of CoV infection. The unique immunological characteristics of vaccines featuring messenger RNA (mRNA) present an advantageous tool for coronavirus vaccine development. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines: one encoding full-length spike (S) protein and the other encoding the spike ectodomain (Se) from porcine deltacoronavirus (PDCoV). Fourteen days after primary immunization, both mRNA vaccines induced high levels of immunoglobulin G and neutralizing antibodies in mice, with the S vaccine showing better performance than the Se vaccine. Passive immune protection of the S mRNA vaccine in suckling piglets was confirmed by the induction of robust PDCoV-specific humoral and cellular immune responses. The S mRNA vaccine also showed better protective effects than the inactivated vaccine. Our results suggest that the novel PDCoV-S mRNA-LNP vaccine may have the potential to combat PDCoV infection.

IMPORTANCE

As an emerging porcine enteropathogenic coronavirus, porcine deltacoronavirus (PDCoV) has the potential for cross-species transmission, attracting extensive attention. Messenger RNA (mRNA) vaccines are a promising option for combating emerging and re-emerging infectious diseases, as evidenced by the demonstrated efficacy of the COVID-19 mRNA vaccine. Here, we first demonstrated that PDCoV-S mRNA-lipid nanoparticle (LNP) vaccines could induce potent humoral and cellular immune responses in mice. An evaluation of passive immune protection of S mRNA vaccines in suckling piglets confirmed that the protective effect of mRNA vaccine was better than that of inactivated vaccine. This study suggests that the PDCoV-S mRNA-LNP vaccine may serve as a potential and novel vaccine candidate for combating PDCoV infection.
Phenotypic and genomic analysis of the hypervirulent methicillin-resistant
Staphylococcus aureus
ST630 clone in China
Authors: Shi Junhong , Xiao Yanghua , Shen Li , Wan Cailing , Wang Bingjie , Zhou Peiyao , Zhang Jiao , Han Weihua , Yu Fangyou
Published: August 2024

Methicillin-resistant
Staphylococcus aureus
(MRSA) sequence type 630 (ST630) is a rarely reported lineage worldwide. This study aimed to trace the dissemination of the emerging MRSA ST630 clones in China and investigate their virulence potential. We collected 22 ST630-MRSA isolates from across China and performed whole-genome sequencing analysis and virulence characterization on these isolates. Epidemiological results showed that MRSA ST630 isolates were primarily isolated from pus/wound secretions, mainly originating from Jiangxi province, and carried diverse virulence and drug resistance genes. Staphylococcal cassette chromosome mec type V (SCCmec V) predominated (11/22, 50.0%) among the MRSA ST630 isolates. Interestingly, nearly half (45.5%) of the 22 ST630-MRSA isolates tested lacked intact SCCmec elements. Phylogenetic analysis demonstrated that ST630-MRSA could be divided into two distinct clades, with widespread dissemination mainly in Chinese regions. Five representative isolates were selected for phenotypic assays, including hemolysin activity, real-time fluorescence quantitative PCR, western blot analysis, hydrogen peroxide killing assay, blood killing assay, cell adhesion and invasion assay, and mouse skin abscess model. The results showed that, compared to the USA300-LAC strain, ST630 isolates exhibited particularly strong invasiveness and virulence in the aforementioned phenotypic assays. This study described the emergence of a highly virulent ST630-MRSA lineage and improved our insight into the molecular epidemiology of ST630 clones in China.

IMPORTANCE

Methicillin-resistant
Staphylococcus aureus
(MRSA) sequence type 630 (ST630) is an emerging clone with an increasing isolation rate in China. This study raises awareness of the hypervirulent MRSA ST630 clones in China and alerts people to their widespread dissemination. ST630-staphylococcal cassette chromosome mec V is a noteworthy clone in China, and we present the first comprehensive genetic and phenotypic analysis of this lineage. Our findings provide valuable insights for the prevention and control of infections caused by this emerging MRSA clone.
Molecular detection using hybridization capture and next-generation sequencing reveals cross-species transmission of feline coronavirus type-1 between a domestic cat and a captive wild felid
Authors: Olarte-Castillo Ximena A. , Goodman Laura B. , Whittaker Gary R.
Published: August 2024

Feline coronavirus (FCoV) infection normally causes mild or subclinical signs and is common in domestic cats. However, in some cats, FCoV infection can also lead to the development of feline infectious peritonitis (FIP)—a typically lethal disease. FCoV has two serotypes or genotypes, FCoV-1 and FCoV-2, both of which can cause FIP. The main difference between the genotypes is the viral spike (S) protein that determines tropism and pathogenicity, crucial mechanisms in the development of FIP. Subclinical infection and FIP have both been reported in wild felids, including in threatened species. Due to the high genetic variability of the S gene and the technical challenges to sequencing it, detection and characterization of FCoV in wild felids have mainly centered on other more conserved genes. Therefore, the genotype causing FIP in most wild felids remains unknown. Here, we report a retrospective molecular epidemiological investigation of FCoV in a zoological institution in the U.Ss. In 2008, a domestic cat (
Felis catus
) and a Pallas’ cat (
Otocolobus manul
) sharing the same room succumbed to FIP. Using
in situ
hybridization, we detected FCoV RNA in different tissues of both felids. Using hybridization capture and next-generation sequencing, we detected, sequenced, and characterized the whole genome of the FCoV infecting both felids. Our data show for the first time that FCoV-1 can be transmitted between domestic and wild felids and extends the known host range of FCoV-1. Our findings highlight the importance of identifying the genotype causing FIP, to develop effective control measures.

IMPORTANCE

Feline coronavirus (FCoV) is highly prevalent in domestic cats worldwide and has also been reported in wild felids, including endangered species, in which it has caused substantial population declines. Characterizing the genetic diversity of FCoV is crucial due to recent reports of novel pathogenic recombinant variants causing high mortality in feral cats in Cyprus. In this retrospective molecular epidemiology study, we used archived samples collected in a zoological institution in the U.S. in which a domestic and a wild felid succumbed to FCoV. Using hybridization capture (HC) and next-generation sequencing, we show for the first time that FCoV can be naturally transmitted between domestic and wild felids. We demonstrate the efficacy of HC for detecting and sequencing the whole genome of FCoV, which is essential to characterize its different genotypes.
Tears of blood: an unusual case of haemolacria due to conjunctival vascular malformation successfully managed by embolisation
Authors: Kiran Anjali , Nagesh Chinmay , Jhalaksreemol Krishna Rani Vasu , Jayadev Chaitra
Published: August 2024

A boy in his mid-teens presented with progressively increasing bleeding from the right eye and nostril intermittently over a period of 6 weeks. A complete ophthalmic examination revealed nothing significant. His otorhinological examination and haematological investigations were within normal limits. The patient came a month later with frank bleeding from the right eye. Ophthalmic examination revealed hyperaemia and maceration of the right lower palpebral conjunctiva. A histopathological examination of conjunctival scrapings from the site showed abnormal dilated blood vessels suggestive of a vascular malformation. Digital subtraction angiography confirmed the presence of a conjunctival micro arteriovenous malformation supplied by the external carotid and ophthalmic artery branches. He underwent successful transarterial Onyx embolisation resulting in complete resolution of the haemolacria.
Reattachment rate with pneumatic retinopexy versus pars plana vitrectomy for single break rhegmatogenous retinal detachment
Authors: Pecaku Aurora , Martins Melo Isabela , Shor Reut , Francisconi Carolina L M , Marafon Samara Barbara , Chaudhary Varun , Hillier Roxane Jo , Muni Rajeev H
Published: August 2024

Aim

To assess the primary reattachment rate (PARR) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) meeting the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomised Trial (PIVOT) criteria with a single break in detached retina.

Methods

A post hoc analysis of two clinical trials. To be included, patients with primary RRD had to meet PIVOT criteria but could have only one break in the detached retina. Patients with additional pathology in the attached retina were included in a secondary analysis. The primary outcome was PARR following PnR versus PPV at 1-year postoperatively.

Results

162 patients were included. 53% (86/162) underwent PnR and 47% (76/162) had a PPV. 99% (85/86) and 86.8% (66/76) completed the 1-year follow-up visits in the PnR and PPV groups, respectively. PARR was 88.2% (75/85) in the PnR group and 90.9% (60/66) in the PPV group (p=0.6) with a mean postoperative logMAR best-corrected visual acuity of 0.19±0.25 versus 0.34±0.37 (Snellen 20/30 vs 20/44) (p=0.01) each in the PnR and PPV groups, respectively.

In an additional analysis of patients who were also allowed to have any pathology in the attached retina, the PARR was 85% (91/107) and 91.6% (66/72) in the PnR and PPV groups, respectively (p=0.18).

Conclusions

PnR and PPV provide similar long-term PARR in a substantial proportion of patients meeting PIVOT criteria with only a single break in the detached retina. Therefore, in patients meeting these specific criteria, PnR is an appropriate first-line therapy as it offers superior functional outcomes without compromising PARR.
Digital training for self-injectable contraceptives: a feasibility and acceptability pilot study
Authors: Mills Rhiana , Krong Rapha , Kithinji Fiona , Baraitser Paula
Published: August 2024

Background

Self-injectable contraceptives, namely subcutaneous depot medroxyprogesterone acetate 104 mg micronised formulation delivered via uniject system, reduce the need to travel to a facility for contraceptive access, but the initial, in-person, training may be a barrier to starting this method. This article reports on a small, exploratory pilot in Kenya to test the feasibility and acceptability of digital self-injection training.

Methods

Participants (n=11) who were currently using injectable contraceptives, intramuscular depot medroxyprogesterone acetate 150 mg injected by a healthcare worker, received digital self-injection training from a trained clinician via a WhatsApp video call. Participants administered a simulated self-injection on a model and an actual self-injection (under supervision) on themselves. The participants’ self-injection proficiency, a measure of the feasibility of remote training, was documented using a checklist, and participants were administered a questionnaire about their training experience. The training was observed, and content analysis was used to understand the functionality of training.

Results

All participants were proficient when performing the self-injection on themselves after receiving the remote training and reported that the training was acceptable. A barrier to training via a video call was lack of access to quality digital devices. Eight training ‘lessons learnt’ emerged from the training observations.

Conclusions

Training participants to administer self-injectable contraceptives via WhatsApp video call was feasible and acceptable. Training lessons learnt offer pragmatic adaptations for communicating about a practical skill via a digital channel. Further research is needed to ascertain the efficacy of digital training for self-injection and feasibility and acceptability for wider groups.
Hydrogen peroxide irrigation as an adjunct to digital rectal examination for detection of penetrating low rectal injuries
Authors: O'Brien Matthew , Diebel Lawrence
Published: August 2024

Background

Rectal trauma carries significant morbidity, particularly if there is a delay in diagnosis. Digital rectal examination has a relatively low sensitivity. Proctoscopy and sigmoidoscopy are available but can be limited in situations with increased fecal burden or uncooperative patients. We suggest more sensitive bedside techniques are necessary to diagnose low rectal injury, and here present a case report to demonstrate proof of concept using hydrogen peroxide to directly visualize an injury.

Methods

Digital rectal examination was performed in a patient after multiple gunshot wounds and was negative for gross blood. Suspicion for low rectal injury remained high, and hydrogen peroxide was used to evaluate bullet trajectory. Approximately 25 mL of 3% hydrogen peroxide was instilled into the bullet tract.

Results

Hydrogen peroxide evaluation of the bullet tract was performed in less than 1 min with minimal supplies and preparation. It revealed an extraperitoneal injury where the rectal examination had been falsely negative.

Conclusion

Hydrogen peroxide may be used to evaluate a suspected penetrating injury of the rectum. Considering the potential of this modality to diagnose injuries in a timely and reliable manner, additional investigation may be warranted.
Quantification and practical solution for bottom boundary effects on long-term permafrost models
Authors: Ross C.R. , Beddoe R.A. , Siemens G.A.
Published: August 2024

Permafrost models are commonly used to simulate future ground temperatures under the influence of climate change and/or proposed infrastructure. Most, if not all model input decisions are made based on limited subsurface knowledge. Shallow model domains offer more efficient run-times especially with gridded one-dimensional schemes as well as two-dimensional and three-dimensional simulations over longer time periods. Recent focus has been on the development of surface boundaries; however, less attention is given to the bottom boundary condition. In this paper, first we quantify the effect of model domain depth and bottom boundary condition type on long-term ground temperature evolution in transient model simulations. Model domains less than 100 m deep with the bottom boundary condition set to both geothermal gradient and a perfectly insulated base ( q = 0) show significant overwarming and overestimate thawing in cold permafrost. Guidance is provided to interrogate model results to avoid bottom boundary condition effects. For cases where further models are needed, a practical solution to this challenge is developed to obtain model depth-independent results. This solution allows for reduced computational requirements while maintaining consistent results for century-scale transient simulations considering climate change effects on thawing permafrost.
The Neighbourhood Bat Watch project reveals that rapid declines of bats after white-nose syndrome are exacerbated by a high rate of colony exclusion
Authors: Fontaine Amélie , Larocque Guillaume , Elliott Kyle H. , Simard Anouk
Published: August 2024

Long-term and large-scale monitoring of wildlife populations is fundamental to answer questions relevant to conservation. Participatory (or “citizen”) science has become a popular tool to collect additional data and for monitoring trends across larger scales. As white-nose syndrome (WNS), a disease caused by a fungal pathogen, spreads throughout North American bat populations, a participatory science project was initiated in 2012, asking the public to help monitor bat maternity colonies in Quebec, Canada. Using historical data from 1997 to 2011 and the Neighbourhood Bat Watch database from 2012 to 2022, we examined variation in the distribution and size of maternity colonies in relation to WNS invasion and maternity colony exclusions from buildings in Québec. Based on 580 emergence counts from 144 colonies, colony size of little brown bats ( Myotis lucifugus (LeConte, 1831)) declined from 77% to 85% during the WNS invasion period, while trends during the epidemic and established periods varied depending on the species and geographical region. Out of the 287 colonies with long-term monitoring, 102 (36%) have subsequently been excluded from buildings. The probability of exclusion was higher in the north than the south, and in houses than in outbuildings. The Neighbourhood Bat Watch allowed us to estimate trends in bat populations and rate of colony exclusions, therefore informing where conservation efforts are most needed.
The dense QCD equation of state within a modified NJL model
Authors: Zhang Fang
Published: August 2024

In this paper, we study the 2-flavor equation of state of the quantum chromodynamics at zero temperature and finite chemical potentials with a modified Nambu–Jona–Lasinio model, where the beta equilibrium and electric charge neutrality conditions of the system (including u, d quarks, electrons and muons) are considered. The related chiral phase transition is also discussed in this paper. For comparison, we show the results with four different parameter sets, and find only quantitative differences. As chemical potential increases, the crossover instead of first-order chiral phase transition happens. Finally, we calculate the binding energy per baryon for different parameter sets, and find that the 2-flavor quark system with a smaller [Formula: see text] (or a larger m) possesses the lower binding energy per baryon, indicated to be more stable than the other case.
Quantum Chicken game under fluctuating quantum field
Authors: Huang Zhiming , Zou Xiangfu , Peng Minjing , Wang Tianqing , Chen Qiongdi
Published: August 2024

In this paper, we study the quantum Chicken game under fluctuating massless scalar field subjected to a reflecting boundary. The noisy scheme of quantum Chicken game affected by fluctuating scalar field is constructed. Then we analyze the influences of vacuum fluctuation, two-atom separation and boundary on the game payoff and Nash equilibrium. It is shown that for different strategy profiles, vacuum fluctuation, two-atom distance and atom-boundary distance have different influences on game payoffs. Vacuum fluctuation and two-atom distance may produce positive or negative effects on game payoffs dependent on the specific strategies. It is found that boundary can effectively promote the game payoffs corresponding to those strategy profiles with which payoffs are degraded by vacuum fluctuation. Furthermore, Nash equilibrium of the game is broken under the influence of fluctuating quantum field, but the game symmetry does not change. For long-time evolution, ([Formula: see text]) and ([Formula: see text]) turn into new Nash equilibria. The results would be helpful for understanding and conducting quantum Chicken game in an open quantum system.
Influence of baffle size and position on natural convective heat transport in a skewed cavity by finite element method
Authors: Hasan Md. Shamim , Fayz-Al-Asad Md. , Iqbal Zahoor , Sarker Md. Manirul Alam , Al Samman Fathia M. , Alhagyan Mohammed , Alqarni M. M. , Gargouri Ameni
Published: August 2024

This paper explores natural convection heat removal performance in accordance with the variation of the baffle size and position in a skewed cavity. In this skewed cavity, the top and bottom walls are considered to be adiabatic. The inclined left wall is deliberated at a sinusoidal cool temperature, and the other wall is treated at a hot temperature. The baffle is connected to the hot temperature wall. The dimensionless governing equations will be solved by the Galerkin weighted residual (GWR) technique of the finite element method. The influence of Rayleigh number ([Formula: see text]), baffle sizes ([Formula: see text], 0.35, and 0.50), and baffle positions ([Formula: see text], 0.50, and 0.75) in a fluid with [Formula: see text] were investigated in this research. The comparisons between the outcome of this work and previously published work in a literature review by Elatar et al. 8 have been produced to examine the reliability and consistency of the data. The results of the simulation are represented by streamlines, isotherms, local and mean Nusselt numbers, mean fluid temperature, and baffle effectiveness. The results demonstrate that as the Rayleigh number grows, the heat removal performance rate continues to develop in this study. Also, the results revealed that the heat transport rate decreased when gradually raising the baffle length. Baffles can significantly improve the mixing of fluid inside the enclosure, which can mean reductions in reaction times and operating costs, along with increases in heat exchange and efficiency.
TANGENT MEASURES OF NON-HOMOGENEOUS CANTOR SETS SATISFYING THE STRONG SEPARATION CONDITION
Authors: WANG YONGTAO , XUE YUMEI
Published: August 2024

This paper investigates tangent measures in the sense of Preiss for non-homogeneous Cantor sets on [Formula: see text] generated by specific iterated function systems that satisfy the strong separation condition. Through the dynamics of “zooming in” on any typical point, we derive an explicit and uniform formula for the tangent measures associated with this category of non-homogeneous Cantor sets on [Formula: see text].
40
Ar/
39
Ar chronostratigraphy and geochemistry of Harrats Ishara and Kura in the Hamd–Jizl Basin, Madinah, Saudi Arabia
Authors: Szymanski Eugene , Stockli Daniel Fritz
Published: August 2024

An extensive system of mafic dykes, volcanic centers, and provincial flood basalts (harrat) have erupted within the Arabian flank of the Red Sea rift since the early Oligocene. The age, spatial distribution, and composition of these features correlates with distinct changes in rift flank structural architecture as the margin progressed through successive deformational phases. A widespread pre-rift dyke swarm in the proto-Red Sea region
c.
25 Ma created thermomechanical crustal conditions favourable for diffuse continental rifting and inboard extensional strain markers like the Hamd–Jizl Basin (HJB) originated amagmatically
c.
23 Ma. Six million years later, basalt flows from Harrats Ishara and Kura entered the HJB at several points along strike during a 4.5 million year-long eruptive phase. Two distinct volcanic units developed in Harrat Ishara: a predominantly alkali-olivine basalt with an age range of 18.0–14.3 Ma (Ishara A) and a mostly olivine transitional basalt with an age range of 16.6–12.1 Ma (Ishara B). The contemporaneous eruption of these units indicates that multiple magma sources operated simultaneously during the middle Miocene. Both units generally decrease in alkalinity and rare earth element abundances up section, signaling either ongoing melt fractionation processes or output from different magma chambers with time.
QuanTest: Entanglement-Guided Testing of Quantum Neural Network Systems
Authors: Shi Jinjing , Xiao Zimeng , Shi Heyuan , Jiang Yu , Li Xuelong
Published: August 2024

Quantum Neural Network (QNN) combines the deep learning (DL) principle with the fundamental theory of quantum mechanics to achieve machine learning tasks with quantum acceleration. Recently, QNN systems have been found to manifest robustness issues similar to classical DL systems. There is an urgent need for ways to test their correctness and security. However, QNN systems differ significantly from traditional quantum software and classical DL systems, posing critical challenges for QNN testing. These challenges include the inapplicability of traditional quantum software testing methods to QNN systems due to differences in programming paradigms and decision logic representations, the dependence of quantum test sample generation on perturbation operators, and the absence of effective information in quantum neurons. In this article, we propose QuanTest, a quantum entanglement-guided adversarial testing framework to uncover potential erroneous behaviors in QNN systems. We design a quantum entanglement adequacy criterion to quantify the entanglement acquired by the input quantum states from the QNN system, along with two similarity metrics to measure the proximity of generated quantum adversarial examples to the original inputs. Subsequently, QuanTest formulates the problem of generating test inputs that maximize the quantum entanglement adequacy and capture incorrect behaviors of the QNN system as a joint optimization problem and solves it in a gradient-based manner to generate quantum adversarial examples. Experimental results demonstrate that QuanTest possesses the capability to capture erroneous behaviors in QNN systems (generating 67.48–96.05% more high-quality test samples than the random noise under the same perturbation size constraints). The entanglement-guided approach proves effective in adversarial testing, generating more adversarial examples (maximum increase reached 21.32%).
Liquid Binary and Ternary Electrolytes Mixtures for Low-Temperature Sulfurized Carbon Batteries
Authors: Elizalde Segovia Rodrigo , Qi Binbin , Prakasan Sasidharan , Wang Tuo , Raji Abdul-Rahman O. , Villegas Salvatierra Rodrigo
Published: August 2024

Active sulfurized carbon (SC) has been proposed as promising alternative to enable sulfur as the next generation cathode material due its ability to confine sulfur and suppresses polysulfide shuttling. Pragmatic cell performance of SC electrodes needs to extend over a wide range of temperatures from -20 °C to 60 °C. Low-temperature performance of SC cells is mainly limited by electrolyte wettability, ionic mobility between the electrodes, and the nature of the formed solid electrolyte interphase. In this work we have utilized electrolyte binary and ternary mixtures based on carbonates, ethers, and fluorinated solvents to enhance the SC cell discharge performance up to -20 °C. To understand the effects of electrolyte mixtures in the cell performance we have utilized electrochemical impedance spectroscopy (EIS) as a function of temperature and voltage. The lower cell resistance translates into a higher rate capability, cyclability, and low-temperature performance. Based on the EIS response and its spectra deconvolution we proposed an apparent electrical equivalent circuit that permits the elucidation of resistance elements and their magnitude such as the ohmic, electron charge transfer, surface film, and mass transport resistance to provide a phenomenological understanding on how the mixtures can enhance the electrochemical performance. Furthermore, differential capacity analysis and Hybrid Pulse Power Characterization (HPPC), are utilized to support the characterization. Finally, best performance electrolyte mixtures were utilized to build >0.5 Ah pouch cells for testing at low temperatures, discharge rates, and pressure conditions.
Dopamine Functionalized TiO2 1D Lepidocrocite Mesoporous Particles As a Sulfur Host
Authors: Cardoza Neal Amadeus , Hassig Mary Qin , Yim Taber , Schwenk Gregory R , Barsoum Michel W. , Kalra Vibha
Published: August 2024

Lithium sulfur batteries are attractive because of their high specific capacities. However, a variety of issues, chiefly polysulfides and the polysulfide shuttle still hinder their development. In our past work we demonstrated a new form of titania-based nanomaterials which we labelled 1 dimensional lepidocrocite nanofilaments (1DLs) as a sulfur (S) host for Li-S batteries1. 1DL is synthesized using a facile bottom-up scalable reaction, directly from commercial 3D bulk solids at ambient pressures and near ambient temperatures2. Moreover, these materials self-assemble into a plethora of microstructures – from individual 1D nanofilaments 5x7 Å2 in cross-section to 2D flakes to mesoscopic particles, all comprised of 1DL - depending on the synthesis and washing parameters. The multitude of structures allows for a variety of applications like electrocatalysis and hydrogen production3. Here we introduce a new structure of 1DLs - mesoporous particles - as S hosts. We further show that by employing a facile, aqueous, 1-step surface functionalization with dopamine – confirmed through changes in the FTIR peaks and an increase in the d-spacing in XRD (inst in Fig 1b) – we increase their interaction with S. The surface functionalization results in a reduction of the 1DL bandgap energy, Eg, to ~1.84 eV, which is a ≈ 50% reduction over un-functionalized 1DL. Additionally, the surface functionalization renders a more conformal coating of S on the 1DL, leading to increased S utilization and interaction with the 1DL, seen in a 20% reduction in of polysulfide shuttle current and 750 mAh.gs
-1 at 0.5 C at a loading of 2 mg.cm-2 (seen in Fig 1a and 1b). This is further seen in the increased interactions of the thiosulfate species and Lewis acid-base interactions, shown in our prior work with S and 1DL.

References

Cardoza, N. A.; Badr, H. O.; Pereira, R.; Barsoum, M. W.; Kalra, V. One-Dimensional, Titania Lepidocrocite-Based Nanofilaments and Their Polysulfide Anchoring Capabilities in Lithium–Sulfur Batteries. ACS Appl. Mater. Interfaces 2023, 15 (44), 50973–50980.

Badr, H. O.; Cope, J.; Kono, T.; Torita, T.; Lagunas, F.; Castiel, E.; Klie, R. F.; Barsoum, M. W. Titanium Oxide-Based 1D Nanofilaments, 2D Sheets, and Mesoporous Particles: Synthesis, Characterization, and Ion Intercalation. Matter 2023, 6 (10), 3538–3554.

Badr, H. O.; Natu, V.; Neațu, Ștefan; Neațu, F.; Kuncser, A.; Rostas, A. M.; Racey, M.; Barsoum, M. W.; Florea, M. Photo-Stable, 1D-Nanofilaments TiO2-Based Lepidocrocite for Photocatalytic Hydrogen Production in Water-Methanol Mixtures. Matter 2023, 6 (9), 2853–2869.

Figure 1