bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations for Compressible Film Cooling: A Computational Study of the Effects of Transonic Flows and Varying Mainstream Mach Number
Authors: Fox Dale W. , Furgeson Michael , Bogard David G. 
Published: June 2024

Abstract
Recent evidence suggests that film cooling flows with engine-realistic mainstream Mach number have declined performance in comparison to those with conventional low-speed laboratory conditions. Consideration and understanding of these effects are fundamental to improving film cooling research. This computational study investigates the film cooling performance of a 7-7-7 shaped film cooling hole with respect to varying mainstream Mach number, with constant Reynolds number. The cases studied include mainstream Mach numbers from 0.15 to 0.75, with a fixed, engine realistic, hole Reynolds number of Red=10,100. Significant results are then evaluated against varying stagnation temperature ratio and blowing ratio. The results showed that at a blowing ratio of 1.75, the adiabatic effectiveness declines significantly with increasing mainstream Mach number. The decreased performance is due to supersonic flows and shocks in the film cooling hole that disrupt flow in the diffuser section of the hole. These characteristics are observed across all stagnation temperature ratios considered. In addition to these insights, the study discusses the importance of proper thermal scaling and definition of adiabatic effectiveness when operating at high mainstream Mach number. It is demonstrated that the effects of high-speed flow challenge the efficacy of the conventional parameters used to characterize film cooling performance.
Performance evaluation of the Panbio COVID-19/Flu A&B Panel for detection of SARS-CoV-2, influenza A, and influenza B antigens using mid-turbinate nasal swabs
Authors: Yu Shao-Hua , Kim Keun-Ju , Lee Chien-Chang , Puebla Yanely Pineiro , Zabat Gelza Mae A. , Shih Hong-Mo , Hsueh Po-Ren 
Published: June 2024

ABSTRACT

The Panbio COVID-19/Flu A&B Panel (Abbott) is an
in vitro
diagnostic rapid test designed for the qualitative detection of nucleocapsid proteins SARS-CoV-2 and nucleoprotein influenza A and B antigens in nasal mid-turbinate (NMT) swab specimens from symptomatic individuals meeting COVID-19 and influenza clinical and/or epidemiological criteria. This study, the largest global one to date using fresh samples, aimed to assess the diagnostic sensitivity and specificity of the Panbio COVID-19/Flu A&B Panel in freshly collected NMT swab specimens from individuals suspected of respiratory viral infection consistent with COVID-19 and/or influenza within the first 5 days of symptom onset compared with results obtained with the cobas SARS-CoV-2 and influenza A/B qualitative assay (cobas 6800/8800 systems), which were tested using nasopharyngeal swab samples. A total of 512 evaluable subjects were enrolled in the COVID-19 cohort across 18 sites, and 1,148 evaluable subjects were enrolled in the influenza cohort across 22 sites in the Asia-Pacific, Europe, and the USA. The Panbio COVID-19/Flu A&B Panel demonstrated a sensitivity of 80.4% and a specificity of 99.7% for COVID-19. For influenza A, the sensitivity and specificity rates were 80.6% and 99.3%, respectively. Likewise, for influenza B, the sensitivity and specificity rates were 80.8% and 99.4%, respectively. In conclusion, the Panbio COVID-19/Flu A&B Panel emerges as a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.4% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B.

IMPORTANCE
The Panbio COVID-19/Flu A&B Panel is a suitable rapid test for detecting COVID-19 and influenza in symptomatic subjects across diverse global populations, exhibiting high sensitivity. The assay achieved a sensitivity of 94.0% in samples with Ct ≤24 for COVID-19 and 92.6% in samples with Ct ≤30 for influenza A and B.
Educational activity of enzyme kinetics in an undergraduate biochemistry course: invertase enzyme as a model
Authors: Al-Odat Ibrahim 
Published: June 2024

ABSTRACT

This article aims to simplify and facilitate the process of practical teaching of enzyme kinetics by utilizing minimal teaching laboratory requirements. Simultaneously, it ensures that students comprehend the enzyme kinetics experiment effectively. The focus is on teaching students how to estimate the maximum velocity (Vmax) and Michaelis constant (Km) of β-fructofuranosidase enzyme (also known as invertase) isolated from dry yeast. The invertase enzyme catalyzes the hydrolysis of sucrose substrate into glucose and fructose, employing the Michaelis-Menten approach of evaluating invertase enzyme kinetics as well as Lineweaver-Burk linear graphic approach of evaluating the Michaelis-Menten enzyme kinetics. The practical experiment seeks to reinforce the concepts of initial velocity dependence on substrate concentration. The data presented in the work were generated from a genuine practical biochemistry course enrolled by second-year undergraduate students in the Department of Pharmacy and the Department of Medical Laboratory Science. While there were minor variations in the invertase enzyme kinetic parameters among students, they successfully carried out the experiment. The students accurately estimated the Vmax and Km of the invertase enzyme in the sucrose hydrolysis chemical reaction. Moreover, they demonstrated an understanding of the meanings of the kinetic parameters (Km and Vmax) and the utility of the Lineweaver-Burk plot.
Mutations in nonstructural proteins essential for pathogenicity in SARS-CoV-2-infected mice
Authors: Pan Ruangang , Li Pengfei , Meyerholz David K. , Perlman Stanley 
Published: June 2024

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in substantial morbidity and mortality. The basis of severe disease in humans is difficult to determine without the use of experimental animal models. Mice are resistant to infection with ancestral strains of SARS-CoV-2, although many variants that arose later in the pandemic were able to directly infect mice. In almost all cases, viruses that naturally infected mice or were engineered to enable mouse infection required mouse passage to become virulent. In most cases, changes in structural and nonstructural changes occurred during mouse adaptation. However, the mechanism of increased virulence in mice is not understood. Here, using a recently described strain of mouse-adapted SARS-CoV-2 (rSARS2-MA30
N501Y
), we engineered a series of recombinant viruses that expressed a subset of the mutations present in rSARS2-MA30
N501Y
. Mutations were detected in the spike protein and in three nonstructural proteins (nsp4, nsp8, and nsp9). We found that infection of mice with recombinant SARS-CoV-2 expressing only the S protein mutations caused very mild infection. Addition of the mutations in nsp4 and nsp8 was required for complete virulence. Of note, all these recombinant viruses replicated equivalently in cultured cells. The innate immune response was delayed after infection with virulent compared to attenuated viruses. Further, using a lineage tracking system, we found that attenuated virus was highly inhibited in the ability to infect the parenchyma, but not the airway after infection. Together, these results indicate that mutations in both the S protein and nonstructural proteins are required for maximal virulence during mouse adaptation.

IMPORTANCE
Understanding the pathogenesis of coronavirus disease 2019 (COVID-19) requires the study of experimental animals after infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). For this purpose, several mouse-adapted SARS-CoV-2 strains have been developed. Here, using a strain of mouse-adapted virus that causes a range of diseases ranging from mild to severe, we show that mutations in both a structural protein [spike (S) protein] and nonstructural proteins are required for maximal virulence. Thus, changes in the S protein, the most widely studied viral protein, while required for mouse adaptation, are not sufficient to result in a virulent virus.
The interferon-induced protein, IFIT2, requires RNA-binding activity and neuronal expression to protect mice from intranasal vesicular stomatitis virus infection
Authors: Poddar Darshana , Sharma Nikhil , Ogino Tomoaki , Qi Xu , Kessler Patricia M. , Mendries Hiran , Dutta Ranjan , Sen Ganes C. 
Published: June 2024

ABSTRACT

The interferon (IFN) system protects mammals from diseases caused by virus infections. IFN synthesis is induced by pattern recognition receptor signaling pathways activated by virus infection. IFN is secreted from the infected cells and acts upon neighboring cells by binding cell surface receptors and triggering induction of hundreds of IFN-stimulated genes and proteins, many of which block different steps of virus replication. The IFN-induced tetratricopeptide repeat proteins (IFIT) are a family of RNA-binding proteins. We and others have previously reported that IFIT2 protects mice from many neurotropic RNA viruses; indeed, Ifit2−/− mice are very susceptible to intranasal or subcutaneous infections with vesicular stomatitis virus (VSV). Here, using a newly generated conditional knockout mouse, we report that ablation of Ifit2 expression only in neuronal cells was sufficient to render mice susceptible to neuropathogenesis caused by intranasal, but not subcutaneous, infection of VSV. Another genetically modified mouse line, expressing a mutant IFIT2 that cannot bind RNA, was as susceptible to VSV infection as
Ifit2
−/− mice. These results demonstrated that IFIT2 RNA-binding activity is essential for protecting mice against neurological diseases caused by intranasal infection of VSV.

IMPORTANCE

Interferon’s (IFN’s) antiviral effects are mediated by the proteins encoded by the interferon-stimulated genes. IFN-stimulated genes (IFIT2) is one such protein, which inhibits replication of many RNA viruses in the mouse brain and the resultant neuropathology. Our study sheds light on how IFIT2 works. By ablating Ifit2 expression only in neuronal cells, using a newly generated conditional knockout mouse line, we showed that Ifit2 induction in the neurons of the infected mouse was necessary for antiviral function of interferon. IFIT2 has no known enzyme activity; instead, it functions by binding to cellular or viral proteins or RNAs. We engineered a new mouse line that expressed a mutant IFIT2 that cannot bind RNA. These mice were very susceptible to infection with vesicular stomatitis virus indicating that the RNA-binding property of IFIT2 was essential for its antiviral function
in vivo
.
Glycine restores the sensitivity to antibiotics in multidrug-resistant bacteria
Authors: Giordano Cesira , Barnini Simona 
Published: June 2024

ABSTRACT

The management of infections caused by multiresistant bacteria has become of fundamental importance for any medical practice. Glycine is the most common and the simplest non-essential amino acid in humans. Glycine is very effective in improving health and supporting growth and wellbeing of humans and animals. Instead, for many bacteria, high concentrations of glycine induce lysis or deep morphological alterations. The effect of glycine on multidrug resistant (MDR) microorganisms has not yet been extensively researched. The present study was conducted 1) to establish the effect of glycine on different nosocomial pathogens isolated during routine diagnostic investigations; 2) to determine the minimum inhibitory concentration of glycine and the type of activity performed (bacteriostatic or bactericidal) on representative isolates; 3) to test the interaction between glycine and meropenem, cefiderocol, or colistin. The data reported here show a dose-dependent activity of glycine on bacteria and its bactericidal activity on MDR bacteria. Furthermore, we found that the action of glycine restores
in vitro
the susceptibility of multiresistant nosocomial pathogens to the tested antibiotics.

IMPORTANCE

Antimicrobial resistance is a constantly growing concern throughout the world, and Italy is among the Western countries where antimicrobial resistance is most widespread. In Tuscany, carbapenemase-producing
Enterobacterales
are now even endemic. In this study, we challenged some resistant bacteria with a well-known molecule, glycine, the antibacterial properties of which have been known since the past century. This study could bring new insights into combining antibiotics with the simplest of all amino acids. The restoration of sensitivity to the aforementioned antibiotics by a natural compound, already used for clinical purposes, is of extreme importance in an era of proliferation of multiresistant bacteria. The
in vivo
use of this amino acid in evaluating its effectiveness against infections should be investigated. The low cost of this molecule can also make it easy to use even in low-income countries.
Application of Intraoperative Radiotherapy in Early‐Stage Breast Cancer Patients in a Clinical Setting
Authors: Wang Ao , Quint Elchanan , Kukeev Ivan , Agassi Ravit , Belochitski Olga , Barski Gay , Vaynshtein Julie 
Published: June 2024

Background: Intraoperative radiation therapy (IORT) has gained popularity in recent years as an alternative to external beam whole breast radiation therapy (WBRT) for early‐stage breast cancer. Here, we report 43‐month recurrence and survival outcomes in a multiethnic cohort treated with IORT in a clinical context.Method: Two hundred and eleven patients with low‐risk features were treated with IORT for early‐stage breast cancer from 2014 to 2021. Selection criteria were based on Group Europeen de Curietherapie‐European Society for Therapeutic Radiology and Oncology (GEC‐ESTRO) guidelines: preferably unifocal intraductal carcinoma (IDC), aged > 50, tumor size ≤ 2.0 cm, and without lymph node involvement. All patients received 20 Gy of radiation dose during the lumpectomy. Information on patient and tumor characteristics was collected.Results: The mean age of this cohort was 67.5 years; 95.2% of patients are Jewish, and the rest are Bedouins (4.7%). Most tumors were intraductal carcinoma (97.2%) and stage 1 (94.8%). The mean follow‐up time was 43.4 months. Bedouins had larger tumor sizes (mean 1.21 vs. 1.13 cm) and were younger at diagnosis than Jewish patients (mean 65.4 vs. 67.6 years), although the differences are not significant. The overall recurrence rate was 1.4%. One case of local recurrence (0.5%) and two cases of metastasis (0.9%) were observed during the study period. One patient died from metastasis.Conclusion: Our findings suggest that IORT in selected low‐risk patients can achieve an excellent prognosis with low rates of recurrence and metastasis.
Lactate Induces Tumor Progression via LAR Motif-Dependent Yin-Yang 1 Degradation
Authors: Du Shujuan , Chen Xiaoting , Han Xiao , Wang Yuyan , Yu Dan , Li Ying , Zhu Caixia , Tong Yin , Gao Shujun , Wang Junwen , Wei Fang , Cai Qiliang 
Published: June 2024

Abstract
The metabolic reprogramming of aerobic glycolysis contributes to tumorigenesis. High plasma lactate is a critical regulator in the development of many human malignancies; however, the underlying molecular mechanisms of cancer progression in response to lactate (LA) remain elusive. Here, we show that the reduction of Yin-Yang 1 (YY1) expression correlated with high LA commonly occurs in various cancer cell types, including B-lymphoma and cervical cancer. Mechanistically, LA induces YY1 nuclear export and degradation via HSP70-mediated autophagy adjacent to mitochondria in a histidine (His)-rich LA-responsive (LAR) motif-dependent manner. The mutation of the LAR motif blocks LA-mediated YY1 cytoplasmic accumulation and in turn enhances cell apoptosis. Furthermore, low expression of YY1 promotes colony formation, invasion, angiogenesis, and growth of cancer cells in response to LA in vitro and in vivo using a murine xenograft model. Taken together, our findings reveal a key LAR element and may serve as therapeutic target for intervening cancer progression.
Implications: We have shown that lactate can induce YY1 degradation via its His-rich LAR motif and low expression of YY1 promotes cancer cell progression in response to lactate, leading to better prediction of YY1 targeting therapy.
Sex Differences in Outcomes of an Intensive Risk Factor Modification Program in Patients With Atrial Fibrillation
Authors: Noubiap Jean Jacques , Pathak Rajeev K. , Thomas Gijo , Elliot Adrian D. , Sanders Prashanthan , Middeldorp Melissa E. 
Published: June 2024

BACKGROUND:
The outcomes of atrial fibrillation (AF) seem to be variable between males and females. We therefore aimed to determine sex differences in weight loss, cardiorespiratory fitness gain, and recurrence and progression of AF following risk factor management.

METHODS:

Of 1415 consecutive patients referred for electrophysiology management of AF, 825 had a body mass index of ≥27 kg/m
2
; after exclusions, 355 (males, 234; females, 121) were offered risk factor management and participation in a tailored exercise program.

RESULTS:

Females were older than males (65.5±10.4 versus 62.5±10.6 years;
P
=0.013) with a higher body mass index (34.1±5.4 versus 32.6±4.1 kg/m
2
;
P
=0.003) and more commonly paroxysmal AF (67.8% versus 48.3%;
P
<0.001). There was no sex difference in clinic attendance (58.7% versus 60%;
P
=0.82), weight loss (
P
=0.86), fitness gain (
P
=0.44), or improvement in AF symptoms (
P
=0.35). Weight loss (≥10% compared with <10%) was associated with lower total AF recurrence in males (hazard ratio, 0.41 [95% CI, 0.23–0.73]) and females (hazard ratio, 0.41 [95% CI, 0.20–0.83]). Fitness gain (≥2 metabolic equivalents compared with <2 metabolic equivalents) was associated with lower total AF recurrence in females (hazard ratio, 0.13 [95% CI, 0.05–0.30]) but not in males (hazard ratio, 0.63 [95% CI, 0.38–1.04];
P
=0.002). There was a trend toward more reversal from persistent to paroxysmal AF in males compared with females (21.8% versus 14.0%;
P
=0.079).

CONCLUSIONS:
Males and females with AF demonstrate a similar degree of weight loss and fitness gain through structured risk factor management. However, fitness had a much greater benefit for total arrhythmia recurrence in females compared with males, whereas there was a trend toward more AF reversal in males.

REGISTRATION:

URL:
https://anzctr.org.au
; Unique identifier: ACTRN12614001123639.
Myocardial Blood Flow by Magnetic Resonance in Patients With Suspected Coronary Stenosis: Comparison to PET and Invasive Physiology
Authors: Rasmussen Laust Dupont , Murphy Theodore , Milidonis Xenios , Eftekhari Ashkan , Karim Salma Raghad , Westra Jelmer , Dahl Jonathan Nørtoft , Isaksen Christin , Brix Lau , Ejlersen June Anita , Nyegaard Mette , Johansen Jane Kirk , Søndergaard Hanne Maare , Mortensen Jesper , Gormsen Lars Christian , Christiansen Evald Høj , Chiribiri Amedeo , Petersen Steffen E. , Bøttcher Morten , Winther Simon 
Published: June 2024

BACKGROUND:
Despite recent guideline recommendations, quantitative perfusion (QP) estimates of myocardial blood flow from cardiac magnetic resonance (CMR) have only been sparsely validated. Furthermore, the additional diagnostic value of utilizing QP in addition to the traditional visual expert interpretation of stress-perfusion CMR remains unknown. The aim was to investigate the correlation between myocardial blood flow measurements estimated by CMR, positron emission tomography, and invasive coronary thermodilution. The second aim is to investigate the diagnostic performance of CMR-QP to identify obstructive coronary artery disease (CAD).

METHODS:
Prospectively enrolled symptomatic patients with >50% diameter stenosis on computed tomography angiography underwent dual-bolus CMR and positron emission tomography with rest and adenosine-stress myocardial blood flow measurements. Subsequently, an invasive coronary angiography (ICA) with fractional flow reserve and thermodilution-based coronary flow reserve was performed. Obstructive CAD was defined as both anatomically severe (>70% diameter stenosis on quantitative coronary angiography) or hemodynamically obstructive (ICA with fractional flow reserve ≤0.80).

RESULTS:

About 359 patients completed all investigations. Myocardial blood flow and reserve measurements correlated weakly between estimates from CMR-QP, positron emission tomography, and ICA-coronary flow reserve (r<0.40 for all comparisons). In the diagnosis of anatomically severe CAD, the interpretation of CMR-QP by an expert reader improved the sensitivity in comparison to visual analysis alone (82% versus 88% [
P
=0.03]) without compromising specificity (77% versus 74% [
P
=0.28]). In the diagnosis of hemodynamically obstructive CAD, the accuracy was only moderate for a visual expert read and remained unchanged when additional CMR-QP measurements were interpreted.

CONCLUSIONS:
CMR-QP correlates weakly to myocardial blood flow measurements by other modalities but improves diagnosis of anatomically severe CAD.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03481712.
Ultrasound-Guided Transfemoral Access for Coronary Procedures: A Pooled Learning Curve Analysis From the FAUST and UNIVERSAL Trials
Authors: d’Entremont Marc-André , Seto Arnold H. , Alrashidi Sulaiman , Alansari Omar , Brochu Bradley , Lemaire-Paquette Samuel , Heenan Laura , Skuriat Elizabeth , Tyrwhitt Jessica , Raco Michael , Tsang Michael B. , Valettas Nicholas , Velianou James , Sheth Tej , Sibbald Matthew , Mehta Shamir R. , Pinilla-Echeverri Natalia , Schwalm Jon-David , Natarajan Madhu K. , Abu-Fadel Mazen , Kelly Andrew , Akl Elie , Tawadros Sarah , Faidi Walaa , Bauer John , Moxham Rachel , Nkurunziza James , Dutra Gustavo , Winter Jose , Couture Étienne L. , Jolly Sanjit S. 
Published: June 2024

BACKGROUND:
The learning curve for new operators performing ultrasound-guided transfemoral access (TFA) remains uncertain.

METHODS:
We performed a pooled analysis of the FAUST (Femoral Arterial Access With Ultrasound Trial) and UNIVERSAL (Routine Ultrasound Guidance for Vascular Access for Cardiac Procedures) trials, both multicenter randomized controlled trials of 1:1 ultrasound-guided versus non–ultrasound-guided TFA for coronary procedures. Outcomes included the composite of major bleeding or vascular complications and successful common femoral artery cannulation. Participants were stratified by the operators’ accrued case volume. We used adjusted repeated-measurement logistic regression, with random intercepts for operator clustering, for comparison against the non–ultrasound-guided TFA group and to model the learning curve.

RESULTS:
The FAUST and UNIVERSAL trials randomized a total of 1624 patients, of which 810 were randomized to non–ultrasound-guided TFA and 814 to ultrasound-guided TFA (cases 1–10, 391; 11–20, 183; and >20, 240). Participants who had operators who performed >20 ultrasound-guided TFAs had a decreased risk for the primary end point (5/240 [2.1%] versus 64/810 [7.9%]; adjusted odds ratio, 0.26 [95% CI, 0.09–0.61]) compared with non–ultrasound-guided TFA. Operators who performed >20 ultrasound-guided procedures had increased odds of successfully cannulating the common femoral artery (224/246 [91.1%] versus 327/382 [85.6%]; adjusted odds ratio, 1.76 [95% CI, 1.08–2.89]) compared with non–ultrasound-guided TFA. The learning curve plots demonstrated growing competence with increasing accrued cases.

CONCLUSIONS:
New operators should perform at least 20 ultrasound-guided TFA to decrease access site complications and increase proper cannulation compared with non–ultrasound-guided TFA. Additional accrued cases may lead to increased proficiency. Training programs should consider these findings in the transradial era.