bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of human antibodies from vaccinated volunteers for protection against
Yersinia pestis
infection
Authors: Zhang Li , Zheng Binyang , Lu Jing , Wu Haisheng , Wu Hailian , Zhang Qi , Jiao Lei , Pan Hongxing , Zhou Jianfang 
Published: August 2024

ABSTRACT

Yersinia pestis
has a broad host range and has caused lethal bubonic and pneumonic plague in humans. With the emergence of multiple resistant strains and the potential for biothreat use, there is an urgent need for new therapeutic strategies that can protect populations from natural or deliberate infection. Targeting F1 has been proven to be the main strategy for developing vaccines and therapeutic antibodies, but data on anti-F1 antibodies, especially in humans, are scarce. To date, three human anti-F1 monoclonal antibodies (m252, αF1Ig2, and αF1Ig8) from naive populations have been reported. Here, we constructed an antibody library from vaccinees immunized with the plague subunit vaccine IIa by phage display. The genetic basis, epitopes, and biological functions of the obtained mAbs were assessed and evaluated in plague-challenged mice. Three human mAbs, namely, F3, F19, and F23, were identified. Their biolayer responses were 0.4, 0.6, and 0.6 nm, respectively. The dissociation constants (K
D
) of the F1 antigen were 1 pM, 0.165 nM, and 1 pM, respectively. Although derived from distinct Ab lineages, that is, VH3-30-D3-10-JH4 (F3&F23) and VH3-43-D6-19-JH4 (F19), these mAbs share similar binding sites in F1 with some overlap with αF1Ig8 but are distinct from αF1Ig2. Each of them provided a significant protective effect for Balb/c mice against a 100 median lethal dose (MLD) challenge of a virulent
Y. pestis
strain when administered at a dose of 100 µg. No synergistic or antagonistic effects were observed among them. These mAbs are novel and excellent candidates for further drug development and use in clinical practice.

IMPORTANCE

In this study, we identified three human monoclonal antibodies with a high affinity to F1 protein of
Yersinia pestis
. We discovered that they have relatively lower somatic hypermutations compared with antibodies, m252, αF1Ig2, and αF1Ig8, derived from the naive library reported previously. We also observed that these mAbs share similar binding sites in F1 with some overlapping with αF1Ig8 but distinct from that of αF1Ig2. Furthermore, each of them could provide complete protection for mice against a lethal dose of
Yersinia pestis
challenge. Our data provided new insights into the anti-F1 Ab repertories and their associated epitopes during vaccination in humans. The findings support the additional novel protective human anti-F1Abs for potential therapeutics against plaque.
Functional characterization of two survival factor 1 genes in
Mucor lusitanicus
Authors: Jáger Olivér , Szebenyi Csilla , Abu Saleem Tammam Khaliefeh Siliman , Molnár Anna , Kovács Vanda , Kiss Karina , Homa Mónika , Vágó Bernadett , Kiss-Vetráb Sándor , Varga Mónika , Sinka Rita , Vágvölgyi Csaba , Nagy Gábor , Papp Tamás 
Published: August 2024

ABSTRACT

Survival factor 1 (Svf1) protein has been described in some ascomycetous fungi where it was found to be contributing to several essential physiological processes, such as response to osmotic, oxidative and cold stresses, sphingolipid biosynthesis, morphogenesis, sporulation, antifungal resistance, and pathogenicity. It was also suggested that it can be a novel central regulator affecting the expression of various genes. In the present study, function of this protein and the encoding genes is described for the first time in a fungus (i.e., in
Mucor lusitanicus
) belonging to the order Mucorales.
M. lusitanicus
has two putative
svf1
genes named
svf1a
and
svf1b
. Expression of both genes was proven. Although the expression of
svf1a
was affected by several environmental stresses and knocking out the gene affected adaptation to low temperatures and the sporulation ability, the main survival factor functions, such as participation in the maintenance of the viability, the response to oxidative and cold stresses, and the sphingolipid biosynthesis, could be associated with Svf1b, suggesting a central regulatory role to this protein. Interestingly, knockout of both genes affected the pathogenicity of the fungus in a
Drosophila
model.

IMPORTANCE

Mucor lusitanicus
is a widely used model organism to study various biological processes in the basal fungal group Mucorales. Several members of this group can be agents of mucormycosis, an opportunistic fungal infection, which is associated with high mortality, rapid progression, and wide resistance to the commonly used antifungal agents. Svf1 proteins have so far only been identified in fungi, where they have been involved in pathogenicity and resistance to antifungal agents in many cases. Only a limited number of factors affecting the stress response, antifungal resistance, and virulence of Mucorales fungi have been revealed. Elucidating the function of a fungus-specific protein that may regulate these processes may bring us closer to understanding the pathogenesis of these fungi.
One-tube detection of
Salmonella
Typhimurium using LAMP and CRISPR-Cas12b
Authors: Gong Jiansen , Jiang Yi , Zhang Di , Li Tingting , Fu Lixia , Dou Xinhong 
Published: August 2024

ABSTRACT

Salmonella enterica
serovar Typhimurium (ST) is a predominant serovar causing foodborne illnesses worldwide. Traditional detection methods often face challenges, including the need for specialized equipment, skilled operators, and lengthy procedures. To address these limitations, we developed a rapid, sensitive, and specific ST detection method by integrating loop-mediated isothermal amplification (LAMP) with the clustered regularly interspaced short palindromic repeats and associated protein 12b (CRISPR/Cas12b) system, all within a single tube. Our results indicate that the LAMP–CRISPR/Cas12b reaction can be completed isothermally in under 1 h without requiring specialized instruments. The platform’s limit of detection (LoD) is 12.5 copies per reaction. Additionally, the system demonstrated 100% inclusivity and exclusivity when tested against 30 reference strains, highlighting its specificity. In practical applications, the LoDs for ST in pure nucleic acid and contaminated fecal samples were 2.32 and 23.2 CFU/mL, respectively, with higher sensitivity observed in pure nucleic acid samples. Overall, our findings underscore the potential of the one-tube LAMP–CRISPR/Cas12b platform as a rapid, sensitive, and specific tool for ST detection, particularly in resource-limited settings.

IMPORTANCE

Here, we have provided a novel one-step method for
Salmonella
Typhimurium detection in one pot by integrating the LAMP assay with the CRISPR/Cas12b system, offering significant advantages in terms of simplicity, speed, and accuracy.
MALDI-TOF mass spectrometry from nucleic acid: development and evaluation of a novel platform for identification of mycobacteria and detection of genetic markers of resistance
Authors: DeCurtis Emily K. , Machado Iara , Kuss-Duerkop Sharon K. , Wang Yongbao , Khare Reeti 
Published: August 2024

ABSTRACT

Complete identification methods are critical for evaluating nontuberculous mycobacteria (NTM). Here, we describe a novel diagnostic method for identification of eight NTM,
Mycobacterium tuberculosis
complex, and three drug resistance markers using PCR/matrix-assisted, laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) from cultured organisms. With this technology, a multiplex end-point PCR is performed for targets of interest. Detection probes that are extended in the presence of a target are added. The extended probes have greater molecular weight and can be detected by MALDI-TOF MS. An AFB Primary Panel was designed to differentiate
Mycobacterium avium
;
Mycobacterium intracellulare
subsp.
chimaera
;
Mycobacterium avium
complex (other);
Mycobacterium abscessus
subsp.
abscessus
,
bolletii
, and
massiliense
;
Mycobacterium kansasii
, and
M. tuberculosis
complex. This design should cover 90% (3,483/3,691) of mycobacteria seen onsite. A development set of unblinded isolates (
n
= 217) was used to develop PCR primers, detection probes, and probe barcodes. It demonstrated 99.1% (215/217) agreement with reference methods. An evaluation set using blinded isolates (
n
= 320) showed an overall sensitivity of 94.3% (range by target: 90.0–100%). Overall specificity from negative media, non-target mycobacteria, and bacteria was 99.1% (108/109; range by target: 94.4–100%). Three drug resistance markers
erm
(41),
rrl,
and
rrs
demonstrated 100%, 91%, and 100% sensitivity, respectively, and >99% specificity. Limit of detection per target ranged from 2.2 × 10
3
to 9.9 × 10
6
CFU/mL. The AFB Primary Panel allows for mycobacterial speciation, subspeciation, and resistance mutation detection, which is essential for diagnosis, appropriate therapy, identifying outbreaks, and managing treatment-refractory disease. It can perform with high-throughput and high specificity and sensitivity from isolates.

IMPORTANCE
Even closely related mycobacteria can have unique treatment patterns, but differentiating these organisms is a challenge. Here, we tested an innovative platform that combines two commonly used technologies and creates something new: matrix-assisted, laser-desorption ionization time-of flight mass spectrometry was performed on PCR amplicons instead of on proteins. This created a robust system with the advantages of PCR (high discriminatory power, high throughput, detection of resistance) with the advantages of mass spectrometry (more targets, lower operational cost) in order to identify closely related mycobacterial organisms.
Gut
Lactococcus garvieae
promotes protective immunity to foodborne
Clostridium perfringens
infection
Authors: Wang Xue-Yin , Meng Fan-Hua , Zhang Ming-Yue , Li Fen-Xin , Lei Yu-Xin , Ma Zhao-Guo , Li Jia-Qi , Lou Ya-Nan , Chu Yue-Feng , Ma Ke , Yu Shui-Xing 
Published: August 2024

ABSTRACT

The gut microbiota, a pivotal component of the intestinal mucosal barrier, is critical for host resistance to enteric pathogen infection. Here, we report a novel function of the potentially probiotic
Lactococcus garvieae
strain LG1 (
L. garvieae
strain LG1) in maintaining intestinal mucosal barrier integrity and protecting against foodborne
Clostridium perfringens
(
C. perfringens
) infection.
L. garvieae
was isolated from the intestinal contents of Chinese Mongolian sheep (MS) and exhibited potential probiotic properties. In a
C. perfringens
enterocolitis model,
L. garvieae-
pretreated mice were less susceptible to
C. perfringens
infection compared with Phosphate buffered solution (PBS)
-
pretreated mice, which manifested as higher survival rates, lower pathogen loads, less weight loss, mild clinical symptoms and intestinal damage, and minor inflammation. Further mechanistic analysis showed that
L. garvieae
could ameliorate the disruption of intestinal permeability and maintain the integrity of the intestinal mucosal barrier by promoting the expression of tight junction proteins and mucoproteins. Moreover,
L. garvieae
was also able to facilitate antimicrobial peptide expression and ameliorate dysbiosis of the gut microbiota caused by
C. perfringens
. Together, these findings highlight the prospect of immunomodulatory potentially probiotic
L. garvieae
and might offer valuable strategies for prophylaxis and/or treatment of pathogenic
C. perfringens
mucosal infection.

IMPORTANCE

C. perfringens
necrotic enteritis leads to losses of about US $2 billion to the poultry industry worldwide every year. Worse, US Centers for Disease Control and Prevention (CDC) has estimated that
C. perfringens
causes nearly 1 million foodborne illnesses in the United States annually. Nowadays, the treatment recommendation is a combination of a broad-spectrum synergistic penicillin with clindamycin or a carbapenem, despite growing scientific concern over antibiotic resistance. The global understanding of the gut microbiome for
C. perfringens
infection may provide important insights into the intervention.
L. garvieae
originated from Mongolian sheep intestine, exhibited potentially probiotic properties, and was able to limit
C. perfringens
enterocolitis and pathogenic colonization. Importantly, we found that
L. garvieae
limits
C. perfringens
invasion via improving intestinal mucosal barrier function. Also,
L. garvieae
alleviates
C. perfringens
-induced gut microbiota dysbiosis. It allowed us to convince that utilization of probiotics to promote protective immunity against pathogens infection is of pivotal importance.
Chronological dynamics of the gut microbiome in response to the pasture grazing system in geese
Authors: Ali Qasim , Ma Sen , Farooq Umar , Liu Boshuai , Wang Zhichang , Sun Hao , Cui Yalei , Li Defeng , Shi Yinghua 
Published: August 2024

ABSTRACT

It is commonly accepted that dietary fibers are good for gut health. The effect of fibers on the diversity and metabolic activities of the cecal microflora, however, differ with the passage of time. Therefore, we investigated the time-series impacts of the pasture grazing system (a high dietary fiber source) on the cecal microbiome and short-chain fatty acids in Wanpu geese, comparing it to commercial feeding (a low dietary fiber source). The cecal microbiota composition and SCFA concentrations were evaluated by 16S rRNA gene sequencing and gas chromatography, respectively. We found that pasture produced a generally quick positive response to Bacteroidales, Lactobacillales, Gastranaerophilales (at 45 days), Lachnospirales, and Oscillospirales (at 60 days and 90 days) irrespective of Erysipelotrichales (at 45 days),
Clostridia_UCG-014
,
RF39
(at 60 days), Christensenellales, and Peptostreptococcales-Tissierellales (at 90 days) in geese. Meanwhile, we found that Lactobacillales, Gastranaerophilales, Lachnospirales, and Oscillospirales were significantly correlated with short-chain fatty acids in pasture grazing geese. Indeed, the correlation of cecal microbiota with SCFAs led to altered microbial functions evinced by COG; KEGG pathway levels 1, 2, and 3; BugBase; and FAPROTAX databases. This study emphasizes the importance of dietary fiber sources in influencing beneficial impacts in regulating geese microbiota homeostasis and metabolic functions such as energy and lipid metabolism.

IMPORTANCE
Low dietary fiber diet sources cause gut microbial and short-chain fatty acid alterations that lead to compromised animal health. The establishment of an artificial pasture grazing system at the expense of ryegrass is a good source of dietary fiber for geese. Our results described the importance of pasture in maintaining the gut microbiota, SCFAs, and potential microbial functions reported by COG; KEGG pathway levels 1, 2, and 3; BugBase; and FAPROTAX databases.
Utilising the Ipzo parameter for more reliable estimates of undrained shear strength directly from CPTU data in saturated natural clay-like soils
Authors: Ramsey N. , Tho K.K. 
Published: August 2024

Ramsey and Tho illustrated the ability of the Ipzo parameter to estimate plasticity index in a wide range of saturated natural soils and highlighted the potential of the Ipzo parameter for improving the reliability of estimations of other soil properties affected by plasticity index. In this note, an improved method is proposed for estimating undrained shear strength in clay-like soils using CPTU data, where clay-like is defined as Ipzo ≥ 12%. The improved method is validated using a geographically and geologically diverse “Nkt1-database” comprising 54 anisotropically consolidated undrained triaxial compression tests, with complementary CPTU measurements from 36 geological units at 18 globally distributed marine sites.
Prospect for measurement of the CP-violating phase $$\phi _s$$ in the $$B_{s}\rightarrow J/\psi \phi $$ channel at a future Z factory
Authors: Li Xiaomei , Ruan Manqi , Zhao Mingrui 
Published: August 2024

AbstractThe CP-violating phase $$\phi _s$$

ϕ
s

, the $$B_{s}$$

B
s

decay width ($$\varGamma _s$$

Γ
s

), and the $$B_{s}$$

B
s

decay width difference ($$\varDelta \varGamma _s$$

Δ

Γ
s

) are sensitive probes to new physics and can constrain the heavy quark expansion theory. The potential for the measurement at future Z factories is studied in this manuscript. It is found that operating at Tera-Z mode, the expected precision can reach: $$\sigma (\phi _s) = 4.6~\textrm{mrad}$$

σ
(

ϕ
s

)
=
4.6

mrad

, $$\sigma (\varDelta \varGamma _s) = 2.4~\mathrm {ns^{-1}}$$

σ

(
Δ

Γ
s

)

=
2.4

ns

-
1

and $$\sigma (\varGamma _s) = 0.72~\mathrm {ns^{-1}}$$

σ

(

Γ
s

)

=
0.72

ns

-
1

. The precision of $$\phi _s $$

ϕ
s

is 40% larger than the expected precision with the LHCb experiment at HL-LHC. If operating at 10-Tera-Z mode, the precision of $$\phi _s $$

ϕ
s

can be measured at 45% of the precision obtained from the LHCb experiment at HL-LHC. However, the measurement of $$\varGamma _s$$

Γ
s

and $$\varDelta \varGamma _s$$

Δ

Γ
s

cannot benefit from the excellent time resolution and tagging power of the future Z-factories. Only operating at 10-Tera-Z mode can the $$\varGamma _s$$

Γ
s

and $$\varDelta \varGamma _s$$

Δ

Γ
s

reach an 18% larger precision than the precision expected to be obtained from LHCb at HL-LHC. The control of penguin contamination at the future Z-factories is also discussed.
Efficient computation of Fourier–Bessel transforms for transverse-momentum dependent parton distributions and other functions
Authors: Diehl Markus , Grocholski Oskar 
Published: August 2024

AbstractWe present a method for the numerical computation of Fourier–Bessel transforms on a finite or infinite interval. The function to be transformed needs to be evaluated on a grid of points that is independent of the argument of the Bessel function. We demonstrate the accuracy of the algorithm for a wide range of functions, including those that appear in the context of transverse-momentum dependent parton distributions in Quantum Chromodynamics.
Pac-Sim: Simulation of Multi-threaded Workloads using Intelligent, Live Sampling
Authors: Liu Changxi , Sabu Alen , Chaudhari Akanksha , Kang Qingxuan , Carlson Trevor E. 
Published: August 2024

High-performance, multi-core processors are the key to accelerating workloads in several application domains. To continue to scale performance at the limit of Moore’s Law and Dennard scaling, software and hardware designers have turned to dynamic solutions that adapt to the needs of applications in a transparent, automatic way. For example, modern hardware improves its performance and power efficiency by changing the hardware configuration, like the frequency and voltage of cores, according to a number of parameters, such as the technology used or the workload running at the time. With this level of dynamism, it is essential to simulate next-generation multi-core processors in a way that can both respond to system changes and accurately determine system performance metrics. Currently, no sampled simulation platform can achieve these goals of dynamic, fast, and accurate simulation of multi-threaded workloads.
In this work, we propose a solution that allows for fast, accurate simulation in the presence of both hardware and software dynamism. To accomplish this goal, we present Pac-Sim, a novel sampled simulation methodology for fast, accurate sampled simulation that requires no upfront analysis of the workload. With our proposed methodology, it is now possible to simulate long-running dynamically scheduled multi-threaded programs with significant simulation speedups, even in the presence of dynamic hardware events. We evaluate Pac-Sim using the SPEC CPU2017, NPB, and PARSEC multi-threaded benchmarks with both static and dynamic thread scheduling. The experimental results show that Pac-Sim achieves a very low sampling error of 1.63% and 3.81% on average for statically and dynamically scheduled benchmarks, respectively. Pac-Sim also demonstrates significant simulation speedups as high as 523.5× (210.3× on average) for the training input set of SPEC CPU2017 running eight threads.
Case 328: Brown Tumor in Hyperparathyroidism Due to Parathyroid Adenoma
Authors: Agostinis Cristina , Lupi Elide 
Published: August 2024

History A 45-year-old female patient with diffuse osteoarticular pain, particularly low back pain, was referred by a rheumatologist for an updated radiologic evaluation. The patient had experienced these symptoms for many years and was diagnosed with human leukocyte antigen B27–negative spondyloarthritis approximately 11 years prior, based on findings of bilateral erosive sacroiliitis at pelvic radiography and bone scintigraphy with technetium 99m (99mTc) methylene diphosphonate. After 3 years of treatment with a tumor necrosis factor–α inhibitor (adalimumab), which was effective for pain, the patient was lost to follow-up. At the current presentation, approximately 8 years after being lost to follow-up, the patient presented with worsening low back pain. The presence of nonobstructing kidney stones on US images confounded the underlying cause of worsening pain. The patient also experienced fatigue and depressed mood. Routine blood tests revealed a normal blood cell count, creatinine level of 0.64 mg/dL (56.58 μmol/L) (normal range, 0.30–1.1 mg/dL [26.52–97.24 μmol/L]), C-reactive protein level of 1.1 mg/dL (normal, <1 mg/dL), and vitamin D level of 21 ng/mL (52.42 nmol/L) (normal range, 30–100 ng/mL [74.88–249.60 nmol/L]). Noncontrast MRI of the thoracic and lumbar spine, MRI of the sacroiliac joints, and CT of the abdomen and pelvis were performed.
Case 332
Authors: Adler Cameron , Menias Christine 
Published: August 2024

History A 65-year-old male patient with a history of sarcomatoid renal cell carcinoma and prior right nephrectomy developed recurrent disease adjacent to the inferior vena cava. The patient underwent surveillance imaging 7 months after initiation of treatment with maximum-dose pazopanib and less than 1 month after completing a 2-month regimen of palliative stereotactic body radiation therapy to the right nephrectomy bed and site of recurrence. (Stereotactic body radiation therapy was initiated 5 months after pazopanib treatment was initiated.) One month after initiating treatment with pazopanib and 6 months before the surveillance imaging, the patient developed diarrhea and required ongoing treatment with loperamide to control symptoms. He denied any fatigue, mouth sores, or extremity pain, but described some abdominal pain and discomfort associated with the diarrhea. He was not experiencing any fevers, and vital signs were normal. White blood cell count was normal at 5100/μL (5.1 ×109/L) (normal range, 4200–10 200/μL [4.2–10.2 ×109/L]), with all components of the differential count also being normal. A normal serum albumin level of 3.9 g/dL (39 g/L) (normal range, 3.5–5.0 g/dL [35–50 g/L]) and low serum total protein level of 6.1 g/dL (61 g/L) (normal range, 6.3–7.9 g/dL [63–79 g/L]) were noted. A comprehensive metabolic panel was performed, indicating a serum chloride level of 98 mmol/L (normal, 100–108 mmol/L) and alkaline phosphatase level of 121 U/L (2.02 μkat/L) (normal, 45–115 U/L [0.75–1.92 μkat/L]). The patient underwent surveillance imaging with contrast-enhanced CT of the abdomen and pelvis in the venous phase ( Figure ).