bluuebunny/crossref_metadata_2025_split huggingface dataset:
All the single cells: if you like it then you should put some virus on it
Authors: Adams Sophia K. , Ducharme Grace E. , Loveday Emma K. 
Published: June 2024

ABSTRACT

Across a rich 70-year history, single-cell virology has revealed the impact of host and pathogen heterogeneity during virus infections. Recent technological innovations have enabled higher-resolution analyses of cellular and viral heterogeneity. Furthermore, single-cell analysis has revealed extreme phenotypes and provided additional insights into host-pathogen dynamics. Using a single-cell approach to explore fundamental virology questions, contemporary researchers have contributed to a revival of interest in single-cell virology with increased insights and enthusiasm.
Yeast and filamentous
Candida auris
stimulate distinct immune responses in the skin
Authors: Bryak Garrett , Cox Abigail , Lionakis Michail S. , Thangamani Shankar 
Published: June 2024

ABSTRACT

Candida auris
, an emerging multidrug-resistant fungal pathogen, predominately colonizes the human skin long term leading to subsequent life-threatening invasive infections. Fungal morphology is believed to play a critical role in modulating mucocutaneous antifungal immunity. In this study, we used an intradermal mouse model of
C. auris
infection to examine fungal colonization and the associated innate and adaptive immune response to yeast and filamentous
C. auris
strains. Our results indicate that mice infected with a filamentous
C. auris
had significantly decreased fungal load compared to mice infected with the yeast form. Mice infected with yeast and filamentous forms of
C. auris
stimulated distinct innate immune responses. Phagocytic cells (CD11b
+
Ly6G
+
neutrophils, CD11b
+
Ly6C
hi
inflammatory monocytes, and CD11b
+
MHCII
+
CD64
+
macrophages) were differentially recruited to mouse skin tissue infected with yeast and filamentous
C. auris
. The percentage and absolute number of interleukin 17 (IL-17) producing innate lymphoid cells, TCRγδ
+
, and CD4
+
T cells in the skin tissue of mice infected with filamentous
C. auris
were significantly increased compared to the wild-type of yeast strain. Furthermore, complementation of filamentous mutant strain of
C. auris
(Δ
elm1 + ELM1
) strain exhibited wild-type yeast morphology
in vivo
and induced comparable level of skin immune responses similar to mice infected with yeast strain. Collectively, our findings indicate that yeast and filamentous
C. auris
induce distinct local immune responses in the skin. The decreased fungal load observed in mouse skin infected with filamentous
C. auris
is associated with a potent IL-17 immune response induced by this morphotype.

IMPORTANCE

Candida auris
is a globally emerging fungal pathogen that transmits among individuals in hospitals and nursing home residents. Unlike other
Candida
species,
C. auris
predominantly colonizes and persists in skin tissue resulting in outbreaks of systemic infections. Understanding the factors that regulate
C. auris
skin colonization and host immune response is critical to develop novel preventive and therapeutic approaches against this emerging pathogen. We identified that yeast and filamentous forms of
C. auris
induce distinct skin immune responses in the skin. These findings may help explain the differential colonization and persistence of
C. auris
morphotypes in skin tissue. Understanding the skin immune responses induced by yeast and filamentous
C. auris
is important to develop novel vaccine strategies to combat this emerging fungal pathogen.
Co-occurrence of ST412
Klebsiella pneumoniae
isolates with hypermucoviscous and non-mucoviscous phenotypes in a short-term hospitalized patient
Authors: Liang Qinghua , Chen Nan , Wang Wei , Zhang Biying , Luo Jinjing , Zhong Ying , Zhang Feiyang , Zhang Zhikun , Martín–Rodríguez Alberto J. , Wang Ying , Xiang Li , Xiong Xia , Hu Renjing , Zhou Yingshun 
Published: June 2024

ABSTRACT

Hypermucoviscosity (HMV) is a phenotype that is commonly associated with hypervirulence in
Klebsiella pneumoniae
. The factors that contribute to the emergence of HMV subpopulations remain unclear. In this study, eight
K. pneumoniae
strains were recovered from an inpatient who had been hospitalized for 20 days. Three of the isolates exhibited a non-HMV phenotype, which was concomitant with higher biofilm formation than the other five HMV isolates. All eight isolates were highly susceptible to serum killing, albeit HMV strains were remarkably more infective than non-HMV counterparts in a mouse model of infection. Whole genome sequencing (WGS) showed that the eight isolates belonged to the K57-ST412 lineage. Average nucleotide identity (FastANIb) analysis indicated that eight isolates share 99.96% to 99.99% similarity and were confirmed to be the same clone. Through comparative genomics analysis, 12 non-synonymous mutations were found among these isolates, eight of which in the non-HMV variants, including
rmpA
(c.285delG) and
wbaP
(c.1305T > A), which are assumed to be associated with the non-HMV phenotype. Mutations in
manB
(c.1318G > A),
dmsB
(c.577C > T) and
tkt
(c.1928C > A) occurred in HMV isolates only. RNA-Seq revealed transcripts of genes involved in energy metabolism, carbohydrate metabolism and membrane transport, including
cysP
,
cydA
,
narK
,
tktA
,
pduQ
,
aceB
,
metN,
and
lsrA
, to be significantly dysregulated in the non-HMV strains, suggesting a contribution to HMV phenotype development. This study suggests that co-occurrence of HMV and non-HMV phenotypes in the same clonal population may be mediated by mutational mechanisms as well as by certain genes involved in membrane transport and central metabolism.

IMPORTANCE

K. pneumoniae
with a hypermucoviscosity (HMV) phenotype is a community-acquired pathogen that is associated with increased invasiveness and pathogenicity, and underlying diseases are the most common comorbid risk factors inducing metastatic complications. HMV was earlier attributed to the overproduction of capsular polysaccharide, and more data point to the possibility of several causes contributing to this bacterial phenotype. Here, we describe a unique event in which the same clonal population showed both HMV and non-HMV characteristics. Studies have demonstrated that this process is influenced by mutational processes and genes related to transport and central metabolism. These findings provide fresh insight into the mechanisms behind co-occurrence of HMV and non-HMV phenotypes in monoclonal populations as well as potentially being critical in developing strategies to control the further spread of HMV
K. pneumoniae
.
Examining homoacetogens in feces from adult and juvenile kangaroos with the aim of finding competitive strains to hydrogenotrophic methanogens
Authors: Stefanini Renan , Karekar Supriya , Ale Enriquez Fuad , Ahring Birgitte 
Published: June 2024

ABSTRACT

We examined the microbial populations present in fecal samples of macropods capable of utilizing a mixture of hydrogen and carbon dioxide (70:30) percent. The feces samples were cultured under anaerobic conditions, and production of methane or acetic acids characteristic for methanogenesis and homoacetogenesis was measured. While the feces of adult macropods mainly produced methane from the substrate, the sample from a 2-month-old juvenile kangaroo only produced acetic acid and no methane. The stable highly enriched culture of the joey kangaroo was sequenced to examine the V3 and V4 regions of the 16S rRNA gene. The results showed that over 70% of gene copies belonged to the Clostridia class, with
Paraclostridium
and
Blautia
as the most predominant genera. The culture further showed the presence of
Actinomyces
spp., a genus which has only been identified in the GI tract of macropods in a few studies, and where none, to our knowledge, have been classified as homoacetogenic. The joey kangaroo mixed culture showed a doubling time of 3.54 h and a specific growth rate of 0.199/h, faster than what has been observed for homoacetogenic bacteria in general.

IMPORTANCE

Enteric methane emissions from cattle are a significant contributor to greenhouse gas emissions worldwide. Methane emissions not only contribute to climate change but also represent a loss of energy from the animal's diet. However, methanogens play an important role as hydrogen sink to rumen systems; without it, the performance of hydrolytic organisms diminishes. Therefore, effective strategies of methanogen inhibition would be enhanced in conjunction with the addition of alternative hydrogen sinks to the rumen. The significance of our research is to identify homoacetogens present in the GI tract of kangaroos and to present their performance
in vitro
, demonstrating their capability to serve as alternatives to rumen methanogens.
Novel de novo heterozygous CACNA1A gene variant in generalised dystonia: a case report
Authors: Alshareet Mohammed , Alakkas Aljoharah , Alsinaidi Omar A , Bawazeer Shahad , Peer-Zada Abdul Ali 
Published: June 2024

BackgroundDystonia is a genetic or non-genetic movement disorder with typical patterned and twisting movements due to abnormal muscle contractions that may be associated with tremor. Genetic and phenotypic heterogeneity leads to variable clinical presentation.MethodologyNext-generation sequencing technologies are being currently used in the workup of patients with inherited dystonia to determine the specific cause in the individuals with autosomal dominant, recessive, X-linked or mitochondrial inheritance patterns. Calcium voltage-gated channel subunit alpha1 A (CACNA1A) gene variants are rare in dystonias.ResultsWe here present a 20-year-old man with a history of delayed milestones, flexor posturing, dysarthria, dysphagia and a negative family history from consanguineous parents. Neurological examination revealed right lateral scoliosis of the neck and generalised dystonic posturing affecting both upper and lower limbs. MRI of the brain was unremarkable. Molecular genetic results revealed a heterozygous variant in the CACNA1A gene (CHR19: NM_023035.2, c. 1602G>A; p. Met534Ile). Segregation analyses in both the parents revealed wild-type CACNA1A gene suggesting de novo nature of the variant with a likely pathogenic classification.ConclusionDystonia is one of the clinical phenotypes that can be associated with CACNA1A gene mutations and we recommend that this gene either be included in the dystonia panel offered or tested when the initial primary genetic result is negative.
Adaptive leadership in crisis: a healthcare system’s resilience journey
Authors: Aouad Marie , Jalbout Hastie Maya , Yazbeck Karam Vanda 
Published: June 2024

BackgroundAmid the complexities of a healthcare system facing economic collapse, pandemic challenges, a devastating human-made disaster, and critical staffing shortages, effective leadership becomes paramount. This article explores the adaptive leadership approach in the face of unprecedented challenges, drawing from the experiences of a healthcare system in Lebanon.MethodsAnchored in Maslow’s hierarchy of needs and guided by the adaptive leadership framework, leaders addressed challenges resulting from the economic crisis, compounded by the COVID-19 pandemic and a catastrophic explosion in Beirut, which tested the resilience of the healthcare system.ResultsChallenges ranged from resource shortages and financial strain to the critical staffing upheaval and psychological impact on healthcare workers. Prioritising physiological, safety, belongingness, self-esteem and self-actualisation needs, leaders implemented innovative strategies, including volunteer mobilisation, recruitment plans, makeshift clinics and psychological support. Transparent communication, self-esteem recognition and fostering resilience emerged as crucial components.ConclusionThe article provides insights into the practical application of adaptive leadership and Maslow’s hierarchy of needs in navigating multifaceted crises within a healthcare setting. It underscores the significance of fostering resilience, prioritising the well-being of healthcare professionals and leveraging innovative solutions to ensure the continued delivery of high-quality care amid unprecedented challenges.
New rat model of spinal cord infarction with long-lasting functional disabilities generated by intraspinal injection of endothelin-1
Authors: Otani Masayuki , Kushida Yoshihiro , Kuroda Yasumasa , Wakao Shohei , Oguma Yo , Sasaki Keisuke , Katahira Shintaro , Terai Ryohei , Ryoke Rie , Nonaka Hiroi , Kawashima Ryuta , Saiki Yoshikatsu , Dezawa Mari 
Published: June 2024

BackgroundThe current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days.ObjectiveWe aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage.MethodsIn 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining.ResultsThe puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5–6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration.ConclusionsSelective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days.
Revisiting big bang nucleosynthesis with a new particle species: effect of co-annihilation with nucleons
Authors: Ghosh Deep 
Published: June 2024

AbstractIn big bang nucleosynthesis (BBN), the light matter abundance is dictated by the neutron-to-proton (n/p) ratio which is controlled by the standard weak processes in the early universe. Here, we study the effect of an extra particle species ($$\chi $$
χ
) which co-annihilates with neutron (proton), thereby potentially changing the (n/p) ratio in addition to the former processes. We find a novel interplay between the co-annihilation and the weak interaction in deciding the (n/p) ratio and the yield of $$\chi $$
χ
. Large co-annihilation strength ($$G_D$$

G
D

) in comparison to the weak coupling ($$G_F$$

G
F

), potentially can alter the number of nucleons in the thermal bath modifying the (n/p) ratio from its standard evolution. We find that the standard BBN prediction is restored for $$G_D/G_F \lesssim 10^{-2}$$

G
D

/

G
F

≲

10

-
2

, while the mass of $$\chi $$
χ
being much smaller than the neutron mass. When the mass of $$\chi $$
χ
is comparable to the neutron mass, we can allow large $$G_D/G_F ~(\gtrsim 10^2)$$

G
D

/

G
F

(
≳

10
2

)

values, as the thermal abundance of $$\chi $$
χ
becomes Boltzmann-suppressed. Therefore, the (n/p) ratio is restored to its standard value via dominant weak processes in later epochs. We also discuss the stability of the new particle in an effective theory framework for co-annihilation. Further, the co-annihilation interaction generates elastic scattering of $$\chi $$
χ
and nucleons at the next-to-leading order. This provides a way to probe the scenario in direct detection experiments, if $$\chi $$
χ
is accidentally stable over cosmological timescale.
Practical derivations of fermion and gauge boson reduction formulae in curved spacetimes
Authors: Huhtala Jesse , Vilja Iiro 
Published: June 2024

AbstractLSZ-type reduction formulae are derived for gauge fields and fermions in curved spacetime. The formulae are derived using a conserved current method applicable also to flat spacetimes. The method generalizes to more general quantum field theories. The formulae are then applied to a couple of basic problems to illustrate their use.
Health Coaching Improves Outcomes of Informal Caregivers of Adults With Chronic Heart Failure: A Randomized Controlled Trial
Authors: Riegel Barbara , Quinn Ryan , Hirschman Karen B. , Thomas Gladys , Ashare Rebecca , Stawnychy Michael A. , Bowles Kathryn H. , Aryal Subhash , Wald Joyce W. 
Published: June 2024

BACKGROUND:
Caring for someone with heart failure takes an emotional and physical toll. Engaging in self-care may decrease stress and improve the health of informal caregivers. We conducted a randomized controlled trial testing the efficacy of a virtual health coaching intervention, compared with health information alone, on the self-care, stress, coping, and health status of heart failure caregivers.

METHODS:
We enrolled 250 caregivers providing care at least 8 hours/week, reporting poor self-care, and able to use technology. All received a tablet device programmed with websites providing vetted information on heart failure and caregiving. Half were randomized to also receive 10 synchronous support sessions virtually with a health coach over 6 months. Data on self-care, stress, coping, and health status were collected at baseline and 3 and 6 months. Linear mixed-effects models were used to assess the interaction between time and treatment group.

RESULTS:

The sample was majority female (85.2%), White (62.2%), spouses (59.8%), and aged 55±13.6 years. Many were employed full time (41.8%). They had been caring for the patient 8 hours/day for a median of 3.25 years. In the intention-to-treat analysis, caregivers who received the health coach intervention had statistically and clinically greater improvement across 6 months compared with the control group in the primary outcome of self-care maintenance (5.05±1.99;
P
=0.01) and stress (−4.50±1.00;
P
<0.0001). Self-care neglect declined significantly (−0.65±0.32;
P
=0.04), but the difference between the treatment arms disappeared when the results were adjusted for multiple comparisons. Mental health status improved statistically but not clinically (3.35±1.61;
P
=0.04). Active coping improved in both groups but not significantly more in the intervention group (
P
=0.10). Physical health status was unchanged (
P
=0.27).

CONCLUSIONS:
This virtual health coaching intervention was effective in improving self-care and stress in heart failure caregivers.
Prevalence, Characteristics, and Impact on Prognosis of Aortic Stenosis in Patients With Cardiac Amyloidosis
Authors: Annabi Mohamed‐Salah , Carter‐Storch Rasmus , Zaroui Amira , Galat Arnault , Oghina Silvia , Kharoubi Mounira , Bezard Mélanie , Derumeaux Geneviève , Fanen Pascale , Lemonnier François , Poullot Elsa , Itti Emmanuel , Gallet Romain , Teiger Emmanuel , Pibarot Philippe , Damy Thibaud , Clavel Marie‐Annick 
Published: June 2024

Background
Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA.

Methods and Results

We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light‐chain (AL) CA. CA patients' echocardiograms were re‐analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population‐based controls, all types of CA had higher age‐ and sex‐standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09–3.64]; ATTRv: SRR, 3.41; 95%CI [1.64–4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25–14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56–1.14]; ATTRv: SRR, 1.27; 95%CI [0.85–1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71–4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all‐cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42–1.19];
P
=0.19).

Conclusions
Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
Validating a Curvature‐Based Marker of Cervical Carotid Tortuosity for Risk Assessment in Heritable Aortopathies
Authors: Lee Jin Vivian , Huguenard Anna L. , Dacey Ralph G. , Braverman Alan C. , Osbun Joshua W. 
Published: June 2024

Background
Cervical arterial tortuosity is associated with adverse outcomes in Loeys‐Dietz syndrome and other heritable aortopathies.

Methods and Results

A method to assess tortuosity based on curvature of the vessel centerline in 3‐dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys‐Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow‐up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow‐up). Logistic regression was performed to assess the likelihood of clinical end point according to baseline carotid tortuosity. Total absolute curvature at baseline was 11.13±5.76 and was relatively unchanged at 8 to 10 years (fold change: 0.026±0.298,
P
=1.00), whereas tortuosity index at baseline was 0.262±0.131, with greater variability at 8 to 10 years (fold change: 0.302±0.656,
P
=0.818). Baseline total absolute curvature correlated with aortic root diameter (
r
=0.456,
P
=0.004) and was independently associated with aortic events during the 4‐year follow‐up (adjusted odds ratio [OR], 2.64 [95% CI, 1.02–6.85]). Baseline tortuosity index correlated with age (
r
=0.532,
P
<0.001) and was not associated with events (adjusted OR, 1.88 [95% CI, 0.79–4.51]). Finally, baseline total absolute curvature had good discrimination of 4‐year outcomes (area under the curve=0.724,
P
=0.014), which may be prognostic or predictive.

Conclusions
Here we introduce cervical carotid tortuosity as a promising quantitative biomarker with validated, standardized characteristics. Specifically, we recommend the adoption of a curvature‐based measure, total absolute curvature, for early detection or monitoring of disease progression in Loeys‐Dietz syndrome.