bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the root and canal morphology in the permanent dentition of Saudi Arabian population using cone beam computed and micro-computed tomography – a systematic review
Authors: Mustafa Mohammed , Batul Rumesa , Karobari Mohmed Isaqali , Alamri Hadi Mohammed , Abdulwahed Abdulaziz , Almokhatieb Ahmed A. , Hashem Qamar , Alsakaker Abdullah , Alam Mohammad Khursheed , Ahmed Hany Mohamed Aly 
Published: March 2024

AbstractIntroductionRoot canal treatment procedures require a thorough understanding of root and canal anatomy. The purpose of this systematic review was to examine the morphological differences of teeth root and their canals assessed using cone-beam computed and micro-computed tomography in Saudi Arabian population.MethodologyAn electronic search was conducted in PubMed / Medline, Scopus, Google Scholar, and Web of Science databases until January 2023 to retrieve related studies. “Root canal morphology,” “Saudi Arabia,” “Micro-CT,” and “cone-beam computed tomography” were used as keywords. A modified version of previously published risk of bias assessment tool was used to determine the quality assessment of included studies.ResultsThe literature search revealed 47 studies that matched the criteria for inclusion, out of which 44 studies used cone beam computed tomography (CBCT) and three were micro-computed tomography (micro-CT) studies. According to the modified version of risk of bias assessment tool, the studies were categorized as low, moderate, and high risk of bias. A total of 47,612 samples were included which comprised of either maxillary teeth (5,412), or mandibular teeth (20,572), and mixed teeth (21,327). 265 samples were used in micro-CT studies while 47,347 teeth samples were used in CBCT studies. Among the CBCT studies, except for three, all the studies were retrospective studies. Frequently used imaging machine and software were 3D Accuitomo 170 and Morita’s i-Dixel 3D imaging software respectively. Minimum and maximum voxel sizes were 75 and 300 μm, Vertucci’s classification was mostly used to classify the root canal morphology of the teeth. The included micro-CT studies were in-vitro studies where SkyScan 1172 X-ray scanner was the imaging machine with pixel size ranging between 13.4 and 27.4 μm. Vertucci, Ahmed et al. and Pomeranz et al. classifications were applied to classify the root canal morphology.ConclusionThis systematic review revealed wide variations in root and canal morphology of Saudi population using high resolution imaging techniques. Clinicians should be aware of the common and unusual root and canal anatomy before commencing root canal treatment. Future micro-CT studies are needed to provide additional qualitative and quantitative data presentations.
Predictors of student preparedness for advanced pharmacy practice experiences
Authors: Rao Shantanu 
Published: March 2024

Abstract
Background
A capstone course often serves as the final checkpoint of student readiness before the commencement of experiential training. The purpose of this study was to determine if the assessment components from the capstone course can serve as predictors of student performance during their Advanced Pharmacy Practice Experiences (APPEs).

Methods
Student data was analyzed to observe the correlation between performance in the Pharmacy Curriculum Outcomes Assessment (PCOA), student performance in the capstone course, and the overall grade point average (GPA) earned during APPEs. Spearman rank correlation analysis, multiple linear regression, and Mann-Whitney U test were used for statistical analysis.

Results
A statistically significant positive correlation was observed between the overall APPE GPA and students’ capstone course grade, top drug competency exam score, pharmacy calculation competency exam score, and PCOA exam score. A significant regression equation was obtained during the analysis: (F(5, 97) = 5.62, p < 0.001), with an R2 = 0.225 (adjusted R2 = 0.185). In the linear regression model, capstone GPA emerged as a significant predictor (β = 0.155; p = 0.019) of APPE GPA amongst the tested variables. Additionally, students scoring < 73% on the top drug competency exam in the capstone course or less than the reference group in the PCOA exam were found to have significantly lower GPA during their APPEs compared to other students.

Conclusion
Performance on the top drug competency exam and the PCOA exam can serve as potential predictors of success during APPEs.
Core outcomes for speech-language services in Ontario schools: a group concept mapping study and guiding framework
Authors: Cahill Peter T. , Ferro Mark A. , Ng Stella , Turkstra Lyn S. , Campbell Wenonah N. 
Published: March 2024

Abstract
Background
Establishing the most important outcomes for school-based speech-language therapy is essential to guide future research and program evaluation for these services. Many health disciplines have developed core outcomes sets (COS) for this purpose. A COS encompasses the most important outcomes for particular health services as identified by appropriate interested parties. These interested parties usually represent health care providers and those with the health condition. In this paper, we report the development of a guiding framework for a COS for speech-language therapy services in schools in a Canadian context.

Methods
Using a group concept mapping method, we identified the outcomes for inclusion in the COS guiding framework through the elicited opinions of key interested parties: speech-language therapists, teachers, and family members of children with speech, language, and communication needs. We extracted 103 statements (potential outcomes) from a previous data set of interview transcripts. We then asked participants to sort the statements into conceptually similar groups, which were aggregated and transformed into a cluster map using multidimensional scaling followed by hierarchical cluster analysis. Participants also rated each statement on 5-point scales for importance and feasibility. We calculated mean ratings for individual statements and for all statements in a cluster, for all participants and for participant groups separately.

Results
We identified seven core outcomes for school-based speech-language services in Ontario, Canada. These included: classroom-based services, a holistic approach, support for teachers, care coordination, accessible services, family supports, and student success. All outcomes were rated highly for importance. Feasibility ratings were consistently below importance ratings. All participant groups concurred that a holistic approach was the most important outcome and accessible services was the least feasible outcome to achieve.

Conclusions
The seven outcomes identified in this study are recommended to guide the development of a full COS to direct future research and program evaluation for school-based speech-language services. These outcomes have not been widely included in previous research and should be incorporated into future research alongside specific intervention outcomes. Data for some outcomes may be available from non-traditional sources such as administrative data sets. Consequently, their use for program evaluations should be accompanied by appropriate institutional support to allow speech-language therapists to make meaningful use of appropriate outcomes data.
Ultrasensitive and visual detection of Feline herpesvirus type-1 and Feline calicivirus using one-tube dRPA-Cas12a/Cas13a assay
Authors: Jiang Fumei , Liu Yunjia , Yang Xiaonong , Li Yan , Huang Jian 
Published: March 2024

Abstract
Background
Feline herpesvirus type 1 (FHV) and Feline calicivirus (FCV) are the primary co-infecting pathogens that cause upper respiratory tract disease in cats. However, there are currently no visual detection assays available for on-site testing. Here, we develop an ultrasensitive and visual detection method based on dual recombinase polymerase amplification (dRPA) reaction and the hybrid Cas12a/Cas13a trans-cleavage activities in a one-tube reaction system, referred to as one-tube dRPA-Cas12a/Cas13a assay.

Results
The recombinant plasmid DNAs, crRNAs, and RPA oligonucleotides targeting the FCV ORF1 gene and FHV-1 TK gene were meticulously prepared. Subsequently, dual RPA reactions were performed followed by screening of essential reaction components for hybrid CRISPR-Cas12a (targeting the FHV-1 TK gene) and CRISPR-Cas13a (targeting the FCV ORF1 gene) trans-cleavage reaction. As a result, we successfully established an ultra-sensitive and visually detectable method for simultaneous detection of FCV and FHV-1 nucleic acids using dRPA and CRISPR/Cas-powered technology in one-tube reaction system. Visual readouts were displayed using either a fluorescence detector (Fluor-based assay) or lateral flow dipsticks (LDF-based assay). As expected, this optimized assay exhibited high specificity towards only FHV-1 and FCV without cross-reactivity with other feline pathogens while achieving accurate detection for both targets with limit of detection at 2.4 × 10− 1 copies/μL for the FHV-1 TK gene and 5.5 copies/μL for the FCV ORF1 gene, respectively. Furthermore, field detection was conducted using the dRPA-Cas12a/Cas13a assay and the reference real-time PCR methods for 56 clinical samples collected from cats with URTD. Comparatively, the results of Fluor-based assay were in exceptional concordance with the reference real-time PCR methods, resulting in high sensitivity (100% for both FHV-1 and FCV), specificity (100% for both FHV-1 and FCV), as well as consistency (Kappa values were 1.00 for FHV-1 and FCV). However, several discordant results for FHV-1 detection were observed by LDF-based assay, which suggests its prudent use and interpretaion for clinical detection. In spite of this, incorporating dRPA-Cas12a/Cas13a assay and visual readouts will facilitate rapid and accurate detection of FHV-1 and FCV in resource-limited settings.

Conclusions
The one-tube dRPA-Cas12a/Cas13a assay enables simultaneously ultrasensitive and visual detection of FHV-1 and FCV with user-friendly modality, providing unparalleled convenience for FHV-1 and FCV co-infection surveillance and decision-making of URTD management.
Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women
Authors: Ekström Magnus , Sundh Josefin , Andersson Anders , Angerås Oskar , Blomberg Anders , Börjesson Mats , Caidahl Kenneth , Emilsson Össur Ingi , Engvall Jan , Frykholm Erik , Grote Ludger , Hedman Kristofer , Jernberg Tomas , Lindberg Eva , Malinovschi Andrei , Nyberg André , Rullman Eric , Sandberg Jacob , Sköld Magnus , Stenfors Nikolai , Sundström Johan , Tanash Hanan , Zaigham Suneela , Carlhäll Carl-Johan 
Published: March 2024

Abstract
Background
Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.

Methods
Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50–64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.

Results
We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0–29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6–66.0%), stress (31.6–76.8%), respiratory disease (20.1–37.1%), depression (17.1–26.6%), cardiac disease (6.3–12.7%), anemia (0.8–3.3%), and peripheral arterial disease (0.3–0.8%). Stress was the main factor in women and current smokers.

Conclusion
Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting—supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.
Hepatic insulin resistance and muscle insulin resistance are characterized by distinct postprandial plasma metabolite profiles: a cross-sectional study
Authors: Gijbels Anouk , Erdős Balázs , Trouwborst Inez , Jardon Kelly M. , Adriaens Michiel E. , Goossens Gijs H. , Blaak Ellen E. , Feskens Edith J. M. , Afman Lydia A. 
Published: March 2024

AbstractBackgroundTissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR.MethodsThis cross-sectional study included data from 214 women and men with BMI 25–40 kg/m2, aged 40–75 years, and with predominant muscle IR or liver IR. Tissue-specific IR was assessed using the muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI), which were calculated from the glucose and insulin responses during a 7-point oral glucose tolerance test. Plasma samples were collected before (T = 0) and after (T = 30, 60, 120, 240 min) consumption of a high-fat mixed meal and 247 metabolite measures, including lipoproteins, cholesterol, triacylglycerol (TAG), ketone bodies, and amino acids, were quantified using nuclear magnetic resonance spectroscopy. Differences in postprandial plasma metabolite iAUCs between muscle and liver IR were tested using ANCOVA with adjustment for age, sex, center, BMI, and waist-to-hip ratio.P-values were adjusted for a false discovery rate (FDR) of 0.05 using the Benjamini–Hochberg method.ResultsSixty-eight postprandial metabolite iAUCs were significantly different between liver and muscle IR. Liver IR was characterized by greater plasma iAUCs of large VLDL (p = 0.004), very large VLDL (p = 0.002), and medium-sized LDL particles (p = 0.026), and by greater iAUCs of TAG in small VLDL (p = 0.025), large VLDL (p = 0.003), very large VLDL (p = 0.002), all LDL subclasses (allp < 0.05), and small HDL particles (p = 0.011), compared to muscle IR. In liver IR, the postprandial plasma fatty acid (FA) profile consisted of a higher percentage of saturated FA (p = 0.013), and a lower percentage of polyunsaturated FA (p = 0.008), compared to muscle IR.ConclusionPeople with muscle IR or liver IR have distinct postprandial plasma metabolite profiles, with more unfavorable postprandial metabolite responses in those with liver IR compared to muscle IR.
Engineering Saccharomyces cerevisiae for targeted hydrolysis and fermentation of glucuronoxylan through CRISPR/Cas9 genome editing
Authors: Ravn Jonas L. , Manfrão-Netto João H.C. , Schaubeder Jana B. , Torello Pianale Luca , Spirk Stefan , Ciklic Iván F. , Geijer Cecilia 
Published: March 2024

Abstract
Background
The abundance of glucuronoxylan (GX) in agricultural and forestry residual side streams positions it as a promising feedstock for microbial conversion into valuable compounds. By engineering strains of the widely employed cell factory Saccharomyces cerevisiae with the ability to directly hydrolyze and ferment GX polymers, we can avoid the need for harsh chemical pretreatments and costly enzymatic hydrolysis steps prior to fermentation. However, for an economically viable bioproduction process, the engineered strains must efficiently express and secrete enzymes that act in synergy to hydrolyze the targeted polymers.

Results
The aim of this study was to equip the xylose-fermenting S. cerevisiae strain CEN.PK XXX with xylanolytic enzymes targeting beechwood GX. Using a targeted enzyme approach, we matched hydrolytic enzyme activities to the chemical features of the GX substrate and determined that besides endo-1,4-β-xylanase and β-xylosidase activities, α-methyl-glucuronidase activity was of great importance for GX hydrolysis and yeast growth. We also created a library of strains expressing different combinations of enzymes, and screened for yeast strains that could express and secrete the enzymes and metabolize the GX hydrolysis products efficiently. While strains engineered with BmXyn11A xylanase and XylA β-xylosidase could grow relatively well in beechwood GX, strains further engineered with Agu115 α-methyl-glucuronidase did not display an additional growth benefit, likely due to inefficient expression and secretion of this enzyme. Co-cultures of strains expressing complementary enzymes as well as external enzyme supplementation boosted yeast growth and ethanol fermentation of GX, and ethanol titers reached a maximum of 1.33 g L− 1 after 48 h under oxygen limited condition in bioreactor fermentations.

Conclusion
This work underscored the importance of identifying an optimal enzyme combination for successful engineering of S. cerevisiae strains that can hydrolyze and assimilate GX. The enzymes must exhibit high and balanced activities, be compatible with the yeast’s expression and secretion system, and the nature of the hydrolysis products must be such that they can be taken up and metabolized by the yeast. The engineered strains, particularly when co-cultivated, display robust growth and fermentation of GX, and represent a significant step forward towards a sustainable and cost-effective bioprocessing of GX-rich biomass. They also provide valuable insights for future strain and process development targets.
Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects
Authors: Wang Yufei , Buck Alicia , Piel Brandon , Zerefa Luann , Murugan Nithyassree , Coherd Christian D. , Miklosi Andras G. , Johal Haraman , Bastos Ricardo Nunes , Huang Kun , Ficial Miriam , Laimon Yasmin Nabil , Signoretti Sabina , Zhong Zhou , Hoang Song-My , Kastrunes Gabriella M. , Grimaud Marion , Fayed Atef , Yuan Hsien-Chi , Nguyen Quang-De , Thai Tran , Ivanova Elena V. , Paweletz Cloud P. , Wu Ming-Ru , Choueiri Toni K. , Wee Jon O. , Freeman Gordon J. , Barbie David A. , Marasco Wayne A. 
Published: March 2024

AbstractOne of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.
Nanoscale engineering of gold nanostars for enhanced photoacoustic imaging
Authors: Zhang Rui , Thoröe-Boveleth Sven , Chigrin Dmitry N. , Kiessling Fabian , Lammers Twan , Pallares Roger M. 
Published: March 2024

AbstractPhotoacoustic (PA) imaging is a diagnostic modality that combines the high contrast resolution of optical imaging with the high tissue penetration of ultrasound. While certain endogenous chromophores can be visualized via PA imaging, many diagnostic assessments require the administration of external probes. Anisotropic gold nanoparticles are particularly valued as contrast agents, since they produce strong PA signals and do not photobleach. However, the synthesis of anisotropic nanoparticles typically requires cytotoxic reagents, which can hinder their biological application. In this work, we developed new PA probes based on nanostar cores and polymeric shells. These AuNS were obtained through one-pot synthesis with biocompatible Good’s buffers, and were subsequently functionalized with polyethylene glycol, chitosan or melanin, three coatings widely used in (pre)clinical research. Notably, the structural features of the nanostar cores strongly affected the PA signal. For instance, despite displaying similar sizes (i.e. 45 nm), AuNS obtained with MOPS buffer generated between 2 and 3-fold greater signal intensities in the region between 700 and 800 nm than nanostars obtained with HEPES and EPPS buffers, and up to 25-fold stronger signals than spherical gold nanoparticles. A point source analytical model demonstrated that AuNS synthesized with MOPS displayed greater absorption coefficients than the other particles, corroborating the stronger PA responses. Furthermore, the AuNS shell not only improved the biocompatibility of the nanoconstructs but also affected their performance, with melanin coating enhancing the signal more than 4-fold, due to its own PA capacity, as demonstrated by both in vitro and ex vivo imaging. Taken together, these results highlight the strengths of gold nanoconstructs as PA probes and offer insights into the design rules for the nanoengineering of new nanodiagnostic agents.