bluuebunny/crossref_metadata_2025 huggingface dataset:
B-153 Improving Accuracy of IgG subclasses Quantitation in Serum Using Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS) on SCIEX 7500
Authors: Yi R , Holmes D T , Mattman A
Published: October 2024

Background

Serum IgG subclasses (IgGSC) are most often measured for identification of selective immunodeficiency disease and IgG4-related disease (IgG4RD). Traditional nephelometric (IN) assays suffer from errors related to antigen excess and cross-reactivity that can impact the accuracy of results. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been the routine testing methodology for serum IgG subclasses at St. Paul’s Hospital since 2015 due to the simplicity and freedom from inter-subclass cross-reactivity problems. In brief, 20 μL of serum sample is denatured, reduced, alkylated and digested, processed semi-automatically on Hamilton Starlet liquid handler. This is followed by analysis on a SCIEX 5500 QTRAP LC-MS/MS. However, when the method was migrated to the SCIEX 7500, it suffered from calibration curve splitting and poor between-device comparability. It was hypothesized that this could be caused by detuning of some high concentration analytes, suboptimal internal standard (IS) concentrations and, suboptimal IS multiple reaction monitoring (MRM) transition choices, and matrix effects from artificial calibrators.

Methods

Several modifications were made to improve accuracy and robustness: 1) new in-house calibrators were prepared using patient sample pool instead of using Binding Site IgG Subclass Kit calibrators. 2) More IS MRM transitions were added to the method with each analyte MRM quantitated using its own IS MRM using the same fragment ion. The IS concentration was also increased 5-fold for IgG1 and Total IgG. 3) To avoid problems arising from selectively ion detuning, the injection volume was reduced from 10 μL to 1 μL which permitted collision energies (CEs) to be normalized for each analyte/IS MRM pair.

Results

The new SCIEX 7500 method compares well with the original method (N=168) with Passing Bablok regression slopes of 0.94, 1.1, 1.0, 0.98, and 0.98 for IgG1-4 and IgG total respectively with corresponding intercepts of 0.3, -0.1, 0.0, 0.0, and 0.41 g/L and R^2 of 0.96, 0.95, 0.99, 0.98, and 0.95. Median differences were -1.76%, 1.07%, 1.06%, 6.13% and 1.91%. In a typical batch of 90 patient samples and four sets of calibrators, the calibration curves overlap well. Use of patient-based calibrators allowed calibration values to be centered in the range of typical patient sample values, particularly for IgG4, where the calibration curve was extended to 3.46 g/L compared with the previous high calibrator value of 0.48 g/L.

Conclusions

The new IgG subclass quantitation method on SCEIX 7500 LC-MS/MS system is robust with excellent reproducibility and between-device comparability.
B-159 Fast Cleanup for 19 Steroid Analytes in Serum Using Supported Liquid Extraction (SLE)
Authors: Chakravarti R , Marin S , Tackett B
Published: October 2024

Background

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool that holds promise in designing the future of steroid analysis in the clinical laboratory. It is already widely used in steroid analysis in endocrinology and is being utilized increasingly in newer applications for individual steroids and panels relevant in clinical research. LC-MS/MS is gaining user base owing to greater sensitivity and specificity and gradually even replacing some of the legacy test methods. Improved sample preparation, modern chromatography methods, and sensitive, faster scanning mass spectrometers have all played a role in improving LC-MS/MS. Steroid analysis for clinical research can require very low limits of detection which demand high recoveries and very clean extracted samples. Supported Liquid Extraction (SLE) can provide very clean extracted samples with less method development and a streamlined workflow compared to solid phase extraction (SPE). Laboratories desire high-throughput methods which consolidate analytes into one panel with fast chromatographic run times. Chromatographic separation of steroid isomers with the same m/z is necessary for accurate quantitation by LCMS/MS. Meeting these criteria can be challenging in a single LC-MS/MS method.

Methods

Each 200 µL serum sample was pretreated with 200 µL of pH 6 Ammonium Acetate buffer (aq) before being loaded onto a Novum™ PRO SLE, MAX 96-well plate, following the standard SLE protocol. Samples were eluted using 2 × 900 µL of Dichloromethane or Ethyl Acetate. After evaporation of the elution solvent, samples were reconstituted in 100 µL of 0.5 mM Ammonium Fluoride / Methanol (60:40, v/v). A Kinetex™ 2.6 μm C18, 50 x 3.0 mm column using a gradient of 0.5 mM Ammonium Fluoride (aq) and Methanol on an Agilent® 1290 Infinity UHPLC and SCIEX® 7500 Triple Quad™ were used for quantitation.

Results

Here, we present an effective sample extraction method and LC-MS/MS analysis method for the quantitation of a 19-analyte steroid panel from serum. The Kinetex 2.6 μm C18 column provided a fast 8-minute chromatographic separation and good selectivity for steroid analytes in both positive ion mode and negative ion mode. Calibration curves with a linear fit and 1/x weighting, showed good linearity with R2 of >0.99 for all analytes except 17-OH-Pregnenolone and DHEAS when using Dichloromethane as the elution solvent, and R2 of >0.980 for all analytes when using Ethyl Acetate as the elution the solvent. Accuracy of samples using Dichloromethane as the elution solvent were 80-112 %, except for 17-OH-Pregnenolone and DHEAS. Accuracy of all samples using the Ethyl Acetate elution solvent were 91-118 %.

Conclusions

The-96 well plate extraction method was robust, reproducible, and can be automated. SLE using Novum Pro MAX combined with a fast LC method provides a simple, rapid, high-throughput workflow for identification and quantitation of 19 steroids from serum.
B-166 Differentiation of Aziridine Functionality from Related Functional Groups in Protonated Analytes by Using Selective Ion-Molecule Reactions
Authors: Anyaeche R , Alzarieni K , Kumar R , Milton J , Kaur J , Sheng H , Kenttämaa H
Published: October 2024

Background

The development of better methods for the rapid and reliable identification of unknown compounds in mixtures is urgently needed in drug development. Aziridines, in particular, are used for drug synthesis but are potentially mutagenic and carcinogenic compounds. However, the detection and identification of these compounds pose challenges for many analytical methods, such as Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), and X-ray crystallography. These techniques are time-consuming and often require large quantities of highly pure compounds.

Methods

Therefore, this study demonstrates that selective gas-phase ion-molecule reactions of protonated analytes with neutral tris(dimethylamino)borane (TDMAB), followed by diagnostic collision-activated dissociation (CAD), can be used to differentiate aziridines from structurally related compounds in a modified linear quadrupole ion trap (LQIT) mass spectrometer. The experiments were performed using an atmospheric pressure chemical ionization (APCI) source in positive ion detection mode. TDMAB was purchased from Sigma-Aldrich and used without purification. It was introduced into the ion trap (2 mtorr of helium buffer gas) via an external reagent mixing manifold through a syringe pump at a flow rate of 10 μL h-1 and diluted with helium before entering the ion trap through a variable leak valve. All analytes were prepared at a concentration of 1 mM in methanol. The protonated analytes were transferred into the ion trap, isolated, and allowed to react with TDMAB (MS2 experiments).

Results

Product ions formed upon reactions of the analyte ions with TDMAB were subjected to a collision-activated dissociation (CAD) experiment (MS3 experiments). CAD on product ions produced diagnostic fragment ions with 25- and 43 m/z-units lower m/z values than the adduct - DMA product ions. Quantum chemical calculations were employed using the Gaussian 16 program calculated at the M06-2X/6-311++G(d,p) level of theory to provide theoretical foundation and to explore the underlying mechanisms of the observed gas-phase reactions. None of the tested structurally related analytes produced a similar fragmentation pattern

Conclusions

The innovative approach presented in this study offers a promising avenue for enhancing efficiency and accuracy in drug development. The successful differentiation of aziridine is an alternative method in overcoming the limitation of traditional techniques. The findings from the research contributes to the advancement of analytical techniques, addressing critical issues in identifying impurities in drug products. The versatility of the methods extends beyond drug developments, making it applicable in various other fields such as in molecular diagnostics, metabolism and laboratory medicines.
B-189 Alinity m You-Create Lab-Developed Test for hepatitis delta virus
Authors: Sasaki M , Wang X , Toolsie D , Cloherty G , Lucic D
Published: October 2024

Background

Lab developed tests (LDTs) play an important role in the realm of infectious diseases. Current molecular diagnostic platforms offer fully automated high-throughput performance capable of running LDTs. The Alinity m platform enables users to run LDTs concurrently with other FDA cleared or approved IVD assays with its Alinity m You-Create feature. Here, we investigated the performance of an LDT assay targeting hepatitis delta virus (HDV) using commercially available PCR reagents.

Methods

Alinity m You-Create LDT for HDV was evaluated using Applied Biosystems TaqMan Fast Virus 1-Step Multiplex Master Mix, No ROX, (ThermoFisher, Cat: 5555532). Sample extraction utilized Alinity m Sample Prep Kit 2. Alinity m You-Create HDV LDT analytical performance for sensitivity, linearity and precision was assessed using panels prepared by diluting the HDV 1st WHO international standard in negative plasma. Alinity m You-Create HDV LDT clinical performance was assessed by comparing 45 HDV positive samples previously tested on the m2000 HDV LDT. Assay specificity was assessed testing 97 HDV negative, HBV and/or HCV positive (by serology or nucleic acid amplification test).

Results

Alinity m You-Create HDV LDT had 100% detection as low as 2.5 IU/mL with SD ≤0.25 Log IU/mL for panels that were ≥2.5 IU/mL. Coefficient of correlation between Alinity m You-Create HDV LDT and m2000 HDV LDT was 0.969 and the mean bias was -0.16 Log IU/mL. All HDV negative specimens were undetected by Alinity m You-Create HDV LDT.

Conclusions

This study demonstrated successful implementation of an LDT for HDV on the Alinity m platform using the Alinity m You-Create feature using commercially available PCR reagents. The Alinity m You-Create feature for HDV has not been approved by FDA for use in the detection or diagnosis for HDV and its safety and effectiveness has not been established.
B-206 Tick-borne disease molecular testing positivity and coinfection incidence in the northeastern united states: 2021-2023
Authors: Pratt G , Matsushita F , Bi C , Rao L V
Published: October 2024

Background

The CDC estimates that Lyme disease affects hundreds of thousands of people each year in the United States. Tick-borne diseases caused by pathogens such as Anaplasma phagocytophilum, Babesia microti, Ehrlichia chaffeensis, and species of Borrelia follow a seasonal pattern due to the life cycle of disease-carrying ticks. In endemic areas, like the northeastern United States, the risk of coinfection by multiple tick-borne disease pathogens is higher and can complicate patient treatment. For example, while Anaplasma and Borrelia can be treated with doxycycline a Babesia coinfection would not be resolved with this medication. In this study, we performed a retrospective analysis of tick-borne disease molecular testing results to monitor positivity rates and incidence of coinfection.

Methods

This retrospective analysis included whole blood specimens submitted to a regional clinical laboratory in the northeastern United States for tick-borne disease molecular testing. Test results from 2021-2023 were analyzed for positivity rate trends and coinfection incidence. DNA was isolated from patient specimens and tested using laboratory developed real-time Taq polymerase PCR assays.

Results

Positivity rates for all tick-borne disease pathogens studied followed typical seasonal patterns (Table). Beginning in the early spring, as nymphs ended their dormancy and began to feed, infection rates of tick-borne disease climbed. Infections peaked in mid-summer and remained elevated through late autumn. For Anaplasma, a biphasic pattern was observed, with a smaller peak in late autumn when adult ticks are most active. Coinfections with Anaplasma and Babesia were observed in 136 specimens, while coinfections with Borrelia and Babesia were observed in 145 specimens.

Conclusions

Positivity rates for tick-borne disease pathogens followed expected seasonal patterns in the northeastern US. The incidence of coinfections involving Babesia microti highlights the importance of properly identifying tick-borne infections given the different treatment regimens indicated.
B-219 Pseudo-exclusion From Paternity due to Maternal Uniparental Disomy of Chromosome 2
Authors: Levi J , Batista J G , Barroso P V , Moratori D , Batistutti V P , Osorio P S , Andrade L M , Rosenberg C
Published: October 2024

Background

Uniparental disomy (UPD) is the abnormal situation in which both members of a chromosome pair exclusively comprise material of one of the parents. The incidence of uniparental disomy (UPD) of any chromosome is estimated in 1:3500 live births; this rare condition may be relevant not only for medical genetics, but also for parental testing.

Methods

We describe a case of trio paternity test using 55 informative STR loci, 30 of these were performed whith GlobalFiler Express KIT - Thermo Fisher (GFE) and Investigator HDPlex - Qiagen (IHDP); capillary electrophoresis using 3500XL - Applied BioSystems; analyses using Genemapper IDX 4.0 - Applied BioSystems. The Y haplotype and 8 additional autosomal STRs were performed by a reference laboratory, which assists us in complex cases. Genotyping with a 1,6 million marker SNP-array (GDA-cyto, Illumina) was analyzed using NxClinical software(Bionano).

Results

Inconsistencies were observed in four loci, namely TPOX, D2S441, D2S1338 and D2S1360. All four markers mapped on chromosome 2 and were compatible with the mother´s genotype, raising the suspicion of a maternal UPD2. SNP-array analyse showed 4 large blocks with absence of heterozygosity on chromosome 2 (AOH - arr[GRCh38] 2p25.3p24.1(10587_22202427)x2 hmz, 2p21p11.2(43674352_90357502)x2 hmz, 2q22.1q31.1(141240699_170583494)x2 hmz, 2q36.3q37.3(227133255_242119896)x2 hmz), comprising a total of 112,9 Mb. No large AOH blocks were observed in any other chromosome.

Conclusions

The results indicate the presence of a UPD2. As the result of an unusually high-number of crossing-overs (n=6), several heterozygous and homozygous blocks were present on chromosome 2 (see figure 1). Rare cases of pseudo-exclusions of either maternity or paternity due to UPD have been reported. Together with the case reported here, they highlight the necessity to consider inconsistencies of markers that map into a single chromosome as likely resulting from UPD.
B-234 Evaluating the diagnostic utility of dd-cf-dna in renal allograft surveillance: a single-center perspective
Authors: Aravamudhan A , Krug K , Stoffel M , Muluhngwi P
Published: October 2024

Background

Donor-derived cell-free DNA (dd-cf-DNA) tests offer a non-invasive alternative to biopsy for allograft surveillance in solid organ transplantation. Unlike biopsies, dd-cf-DNA tests are not subject to interpretation bias and have the potential to detect subclinical rejection, which can lead to graft dysfunction and poor outcomes. At our institution, dd-cf-DNA testing is currently offered as a send out test and we sought to evaluate its efficacy in monitoring our post-transplant patients.

Methods

We retrospectively examined electronic health records of 50 renal transplant patients with dd-cf-DNA (using AlloSure and Prospera assays) between January 1st, 2019, and December 31st, 2022 to assess diagnostic utility of dd-cf-DNA relative to donor-specific antibodies (DSA) and biopsy (all predictors of graft function). Statistical analysis included correlation testing with t-tests.

Results

Overall, dd-cf-DNA levels correlated with DSA levels (p = 0.0002) and patients with both HLA-class I and II DSA had significantly higher dd-cf-DNA levels (p< 0.05). The Prospera dd-cf-DNA assay appeared to be a better predictor of DSA levels (p = 0.04) than the Allosure dd-cf-DNA assay. Though not statistically significant, there was trend towards an increase in dd-cf-DNA in patient with biopsy-proven graft injury and rejection vs no rejection. Interestingly, dd-cf-DNA levels were significantly elevated in patients with biopsy-proven antibody mediated rejection (ABMR). Because dd-cfDNA levels have been reported to be impacted by sensitizing events including prior transplant, we evaluated and observed levels of dd-cf-DNA to be higher in patients with a history of more than one graft vs single graft recipients (p< 0.0001) and this observation was prominent in the Allosure assay.

Conclusions

Our findings suggest that dd-cf-DNA testing holds promise as a valuable tool for graft surveillance and early detection of ABMR. The lack of correlation with biopsy-confirmed rejections may be attributed to the dd-cf-DNA assays’ ability to detect rejection events earlier in the disease progression process compared to biopsy. Time course analysis will be beneficial. Additionally, the observed differences between AlloSure and Prospera emphasize the significance of thoroughly evaluating and selecting assays, particularly in multi-transplant recipients. We highlight that our initial analysis is limited due to a small sample size. However, we aim to assess 200 patients by the conclusion of this study.
B-296 Assessment of Clozapine Assay on The Automated, High-performance Beckman AU Analyzer
Authors: McCormick D , Eubanks C , Walker C , Swartzwelder J , Jones J , Li J
Published: October 2024

Background

Treatment-resistant schizophrenia (TRS) affects approximately one in three patients with schizophrenia. The timely initiation of clozapine therapy is crucial for achieving remission in TRS patients. However, long turnaround times (TATs) associated with sending clozapine tests to reference laboratories cause significant challenges, leading to delays in treatment initiation and compromising patient outcomes. To address this issue, we implemented in-house clozapine testing on Beckman AU analyzers, aiming to facilitate early clozapine initiation and enhance confidence in prescribing and monitoring clozapine therapy for TRS patients.

Methods

The Beckman AU clozapine assay is a homogenous competitive nanoparticle agglutination assay. Precision and linearity were assessed for the Beckman AU DxC700 clozapine assay using manufacturer-provided standards. We conducted a correlation study involving 31 samples analyzed on both Beckman AU DxC 700 and LC-MS/MS methods. Data analysis was performed using Deming and Linear regression methods. Additionally, we analyzed 356 clozapine tests performed in-house on Beckman AU DxC700 between March 15th and Sept 10th, 2023, and compared them with 1399 clozapine tests sent to a reference laboratory using the LC-MS/MS method from March 13th, 2020, to March 13th, 2023. Turnaround time was evaluated.

Results

The Beckman AU DxC700 clozapine assay exhibited excellent performance across the measuring range, with intra-assay and inter-assay coefficients of variation ranging from 1.7-3.6% and 2.2-5.3%, respectively. The assay demonstrated linearity over the five recommended ranges (68-1500 ng/mL) without significant bias observed. The Beckman AU DxC700 and LC-MS/MS clozapine assays displayed excellent correlation (R2=0.948, slope=0.941, intercept=6.3). Implementation of in-house clozapine testing led to a significant reduction in total turnaround time, from 3922 minutes to 116 minutes. The time from sample receipt to results also decreased substantially, from 3894 minutes to 32 minutes.

Conclusions

The clozapine assay was validated and routinely measured in-house using the Beckman AU DxC700 automated assay. Moreover, we validated the correlation by confirming that the results from Beckman AU DxC had around 6% lower bias comparing with LC-MS/MS. Turnaround time serves as a critical quality indicator for evaluating testing process effectiveness and efficiency, as well as clinician and patient satisfaction. The implementation of in-house clozapine testing significantly improved pre-analytical, analytical, and post-analytical Turnaround times.
B-305 High-risk HPV Scenario Among Young People: Data From a Clinical Laboratory (2019-2023)
Authors: Feres M C , Perez B B , Souza M F , Ramadan-Boscolo D R , Tufik S
Published: October 2024

Background

Human papillomavirus (HPV) infection is the most common sexually transmitted infections and occurs early after the start of sexual life. There are more than 150 types of HPV, classified considering the affected area, symptoms, and oncogenic potential. The types of HPV that cause cancerous lesions are classified as high-risk HPV types. HPV is the main cause of cervical cancer in women and is strongly associated with penile cancer in men. Despite the existence of vaccination, it is still not easily accessible to the entire population of Brazil. In this context, the authors are periodically analyzing the positivity of high-risk HPV infection in secretion and cell scraping samples.

Methods

14,806 results were analyzed from a laboratory in São Paulo/Brazil. 4,935 real-time PCR tests were carried out from January/2019 to December/2023 for the detection of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 high risk types. In this study, there was a special focus on HPV types 16 and 18, as they are the main high-risk types for cervical cancer. The other high-risk genotypes were detected, but not differentiated.

Results

The most ages affected by the infection in both sexes were 25 to 40 years old. Infections with other high-risk types HPV were more frequent in relation to types 16 and 18, Table 1.

Conclusions

Although the male population represented only 1.19% of processes tests, a higher frequency of HPV positive results was detected (9.04%) compared to female patients (7.55%).
B-330 Reducing Inappropriate Fecal Immunochemical Test
Authors: Cai F , Gifford J L , Bourbonnie J , Sadrzadeh H
Published: October 2024

Background

Colorectal cancer is the third most common cancer worldwide. The risk of colorectal cancer increases with age and predominantly affects individuals over the age of 50. Regular screening is crucial for early detection and prevention of colorectal cancer. Pre-cancerous polyps and colorectal cancers can bleed into the gastrointestinal tract. While the presence of blood in the stool cannot always be seen visually, it can be detected by the Fecal Immunochemical Test (FIT), currently the most sensitive method for directly measuring hemoglobin in this specimen type. In our province, FIT is recommended for testing average-risk asymptomatic patients aged 50 to 74 every 1-2 years. Patients aged 40 to 49 or 75 to 84 can be tested if they meet specific criteria. Like many other tests in the lab, FIT can be used inappropriately. The focus of this study was to examine the utilization of FIT in our institution.

Methods

Data were collected from our institution's laboratory information system for the FIT performed on-site from July to December 2023.

Results

We performed 91,545 FIT tests during the 6-month period with an overall positive rate of 6.8%. Of the total tests performed, 87.9% were for patients aged 50-74 years, 10.6% for patients aged 40-49 or 75-84 years, and 1.2% for patients outside the approved age range. Each year, we performed over 2,000 FIT tests for patients outside the accepted screening age, with an estimated cost of over 30,000 CAD.

Conclusions

Our results showed a significant number of FITs were ordered inappropriately by healthcare providers. Considering the relatively high cost of FIT kits, labor, reagents, etc., the overall cost per reportable is significant. Thus, we have started engaging healthcare providers involved in FIT testing to strategize approaches to improve utilization.
The CsTIE1–CsAGL16 module regulates lateral branch outgrowth and drought tolerance in cucumber
Authors: Chen Jiacai , Chen Guangxin , Guo Jingyu , He Yuting , Liu Liu , Wang Shaoyun , Gu Chaoheng , Han Lijie , Li Min , Song Weiyuan , Wang Liming , Zhang Xiaolan , Zhao Jianyu
Published: October 2024

Drought stress and lateral branches are both important factors affecting crop yield. Cucumber is a widely planted vegetable crop that requires a large amount of water during its production and varieties with few lateral branches are preferred. However, the mechanisms regulating cucumber drought tolerance and lateral branch development remain largely unclear. The MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) was recently found to be a key positive regulator in cucumber shoot branching acting by stimulating abscisic acid (ABA) catabolism. In this study, we demonstrated that cucumber TCP interactor containing EAR motif protein 1 (CsTIE1) directly interacts with CsAGL16 at protein level and promotes lateral branch outgrowth through the CsAGL16–CsCYP707A4 mediated ABA pathway in cucumber. Additionally, mutation of CsAGL16 resulted in decreased drought tolerance, while overexpression of CsAGL16 significantly enhanced drought tolerance in cucumber. Similarly, the drought resistance of Cstie1 mutants was significantly reduced. However, overexpression of CsAGL16 can enhance the drought tolerance of Cstie1 mutants and promote their lateral branch outgrowth. These results indicated that the CsTIE1–CsAGL16 module was crucial for both lateral branch development and drought response, providing a strategy for cultivating drought-tolerant cucumber varieties with appropriate branch outgrowth.
Voters Share Polls That Say What They Want to Hear: Experimental Evidence From Spain and the USA
Authors: Fernández-Roldán Alejandro , Barnfield Matthew
Published: October 2024

Pre-election polls are published continuously, particularly in the run-up to elections. Increasingly, polls are commissioned by the media and gain traction through their propagation on social media. But polls differ along many dimensions, including in their estimated vote shares and the corresponding portrayal of the state of public opinion. We rely on recent evidence to argue that these factors are likely to affect people’s willingness to share polls with their networks. To test this claim, we conduct two studies. In the first, we expose Spanish voters to a random selection of recent, real, 2023 general election vote intention polls. In the second, a conjoint analysis presents US voters with abstract, hypothetical 2024 presidential election polls. Across both studies, we find no evidence of any effect of polling firms, fieldwork dates, or sample sizes on intentions to share polls. Above all, our results suggest that the main factor consistently affecting voters’ proclivity to share polls is the result of the poll itself. Our findings are consistent with the literature that suggests that voters’ reception of poll results is usually driven by directional goals, and may have significant implications in light of the unique epistemic value of reposting on social media.
Non-Density of the Exceptional Components of the Noether–Lefschetz Locus
Authors: Baldi Gregorio , Klingler Bruno , Ullmo Emmanuel
Published: October 2024

We study when the Picard group of smooth surfaces of degree $d\geq 5$ in $\mathbb{P}^{3}$ acquires extra classes. In particular we show that the so-called exceptional components of the Noether–Lefschetz locus are not Zariski dense. This answers a 1991 question of C. Voisin. We also obtain similar results for the Noether–Lefschetz locus for suitable $(Y,L)$, where $Y$ is a smooth projective three-fold and $L$ a very ample line bundle. Both results are applications of the Zilber–Pink viewpoint recently developed by the authors for arbitrary (polarized, integral) variations of Hodge structures.
Large-Angle Rocking Beam Electron Diffraction of Large Unit Cell Crystals Using Direct Electron Detector
Authors: Busch Robert , Ni Hsu-Chih , Shao Yu-Tsun , Zuo Jian-Min
Published: October 2024

We report a large-angle rocking beam electron diffraction (LARBED) technique for electron diffraction analysis. Diffraction patterns are recorded in a scanning transmission electron microscope (STEM) using a direct electron detector with large dynamical range and fast readout. We use a nanobeam for diffraction and perform the beam double rocking by synchronizing the detector with the STEM scan coils for the recording. Using this approach, large-angle convergent beam electron diffraction (LACBED) patterns of different reflections are obtained simultaneously. By using a nanobeam, instead of a focused beam, the LARBED technique can be applied to beam-sensitive crystals as well as crystals with large unit cells. This paper describes the implementation of LARBED and evaluates the performance using silicon and gadolinium gallium garnet crystals as test samples. We demonstrate that our method provides an effective and robust way for recording LARBED patterns and paves the way for quantitative electron diffraction of large unit cell and beam-sensitive crystals.
Utilization of Advanced Microscopy Techniques and Energy-dispersive X-ray Spectroscopy to Characterize Three Piper Species Related to Kava
Authors: Adams Sebastian John , Chittiboyina Amar G , Khan Ikhlas A
Published: October 2024

Macro- and microscopic techniques have long been used to describe plant materials and establish plant structural profiles. These techniques are commonly used in botanical authentication to identify the genuine and closely allied species used in botanical research. Advanced microscopic techniques were used in this study to differentiate three different Piper species used as kava or kava-kava. The genuine species is Piper methysticum and the other two species commonly called false-kava or kava-kava, are Piper auritum and Piper excelsum. Macroscopic characteristics, including a black-spotted stem and fibrous root, are characteristic of P. methysticum, whereas the stem of P. auritum is greenish with no spots, and the P. excelsum stem is purple-pink. Microscopic attributes include the characteristic collenchyma of stems and the pattern of arrangement of peripheral and medullary vascular bundles. The starch grains are smaller in P. excelsum than in the other two species. Energy-dispersive X-ray spectroscopy analysis of the crystals indicates the expected calcium, magnesium, and silica, along with lesser amounts of sodium, and potassium. The crystals present in the Piper species vary in shape, size, and elemental composition. Combining macro- and microscopical techniques and resulting characteristics are instrumental in differentiating the three Piper species.
Dietary protein intake and the tubular handling of indoxyl sulfate
Authors: Lauriola Mara , Farré Ricard , Dejongh Sander , de Loor Henriette , Evenepoel Pieter , Masereeuw Rosalinde , Zadora Ward , Meijers Björn
Published: October 2024

Background

Chronic kidney disease (CKD) patients are advised to limit their protein intake. A high protein diet is known to induce glomerular hyperfiltration, as well as hypertrophy of the remnant kidney, and glomerulosclerosis. Whether the diet causes changes in kidney tubule transport via gut microbiome metabolites is still unknown. We hypothesized that protein intake affects not only the intestinal generation and absorption, but also the kidney disposal of microbial amino acid metabolites.

Methods

We combined data from animal models and human studies. 5/6th nephrectomy rats were administered a high (HP) or low-protein (LP) diet for 7 weeks. Plasma and urine concentration of the uremic toxins (UTs) indoxyl sulfate (IS), p-cresyl sulfate (PCS) and p-cresyl glucuronide (PCG) were measured. Their fractional excretion (FE) was calculated. The expression of kidney membrane transporters organic anion transporter 1 (OAT1), OAT3, BCRP, OCT2 and MRP4 was analyzed. Differences in FE of UTs between individuals with higher and lower protein intake in two CKD cohorts were sought.

Results

CKD rats on an HP diet showed increased plasma levels of PCS and PCG but not IS compared with rats on an LP diet. Conversely, urinary excretion and FE of IS were higher in the HP CKD group. BCRP, MRP4 and OCT2 were not influenced by the diet. OAT1 and OAT3 were upregulated in the HP CKD group. In two independent cohorts of CKD patients, individuals with a high dietary protein intake showed a significantly higher FE of IS.

Conclusions

A HP diet leads to a higher generation and/or absorption of amino acid–derived UT precursors in CKD rodent models and humans, most likely via gut microbiome modulation. We demonstrate that dietary protein intake modulates transcription and expression of OAT1 and OAT3, corroborating the existence of the remote sensing and signaling hypothesis. Dietary protein intake influences kidney physiology beyond glomerular filtration.
Xitudingzi Volcano, a Trachytic Monogenetic Volcano in the Changbaishan Volcanic Field, China: Petrogenesis, Magma Plumbing System and Implications for Non-basaltic Monogenetic Volcanism
Authors: Guo Jiannan , Shan Xuanlong , Yi Jian , Wu Chengzhi , Liu Pengcheng
Published: October 2024

The Changbaishan volcanic field is the largest Quaternary volcanic field in China and includes the most dangerous polygenetic volcano, Tianchi volcano. In addition to the Tianchi volcano, the Changbaishan volcanic field contains two other polygenetic volcanoes (Wangtian'e volcano and Namphothe volcano) and at least 150 monogenetic volcanoes. The compositions of these monogenetic volcanoes range from basalt to rhyolite. Basaltic monogenetic volcanoes are the most abundant and spread throughout the volcanic field, whereas intermediate to evolved monogenetic volcanoes are found only within the Touxi subfield. We know very little about these non-basaltic monogenetic volcanoes, especially the magmatic petrogenesis, volcanological origins and structure of the magma plumbing system beneath them. Therefore, in this study, the Xitudingzi volcano within the Touxi subfield is used as an example to study the petrogenesis of silicic magma and explore the structure of the magma system by combining new 40Ar/39Ar dating, whole-rock geochemistry, Sr–Nd isotopes and mineral chemistry. The 40Ar/39Ar chronology results showed that the Xitudingzi volcano erupted at 1.17 Ma; this volcano is younger than the other monogenetic volcanoes in the Touxi subfield. The geochemical results indicated that the eruption products of the Xitudingzi volcano are trachytic and formed from the assimilation fractional crystallization (AFC) process of an alkaline basaltic parental magma. The results from the Rhyolite-MELTS and thermobarometry indicated that the magma plumbing system of the Xitudingzi volcano contained two magma chambers at depths of 8 and 19 km, respectively. The trachytic magma of Xitudingzi was produced by the AFC process from the alkaline basaltic magmas in the deep magma chamber and then transported to the shallow magma chamber. Furthermore, differences in the trace element concentrations between the different units of the Xitudingzi volcano indicated that the shallow pre-eruptive magma chamber was compositionally zoned. Based on the results from our study, the upper crustal magma plumbing system of the Xitutingzi volcano existed independently of the magma plumbing system of the cone-construction stage of the Tianchi volcano, even though the two volcanoes had similar ages of activity, as well as the same chemical composition of eruptive products. Based on these results and other existing studies, a relatively thick crust and the developed faults are likely the key factors for the formation of intermediate to evolved monogenetic volcanos in the Touxi volcanic field.
Complementary roles of eDNA metabarcoding and microscopy in plankton monitoring across seven habitats
Authors: Chen Xingyu , Wei Qianqian , Niu Yanning , Jiang Xiaodong
Published: October 2024

Plankton biodiversity in aquatic ecosystems is currently investigated by labor-intensive and time-consuming microscope identification. Environmental DNA (eDNA) metabarcoding is emerging as a highly effective and objective tool for assessing biodiversity. In this study, we compared the effectiveness of eDNA metabarcoding with conventional microscope identification for monitoring plankton biodiversity in seven habitats. The eDNA metabarcoding identified a rich diversity of 190 families, 410 genera and 871 species within the planktonic community across seven habitats. In contrast, traditional microscope identification only identified 51 families, 75 genera and 96 species. In addition, primer choice influenced the detected plankton community diversity, with the V4 primers performing poorly for detecting Cladocera and Euglenophyta taxa and the V9 primers revealing more eukaryotic plankton species. Despite primer-specific differences in species detection, there was substantial overlap between the species detected by eDNA metabarcoding strategies and microscope identification. These results suggest that eDNA metabarcoding can be used as a complementary method alongside microscope identification rather than replacing them entirely.
Assessment of imposter syndrome among postgraduate residents using Clance imposter phenomenon scale: a multicentric, cross-sectional study
Authors: Amir Nehal , Eeman Nabiha , Ahmed Muhammad Nouman , Nazakat Ayesha , Azhar Irteeqa , Azhar Maimoona , Mumtaz Hassan
Published: October 2024

Background

Imposter syndrome develops when high-achieving individuals, despite external measurements of achievement, have a chronic sense of self-doubt paired with a fear of being exposed as a hoax. This endangers one’s mental health and well-being. The objective of the study was to determine the prevalence and severity of imposter syndrome among postgraduate residents and to identify the risk factors associated with imposter syndrome.

Methods

This is a cross-sectional study conducted among the postgraduate trainees working in four different training hospitals in Pakistan. Imposter syndrome was assessed using the Clance Imposter Phenomenon Scale.

Results

A total of 146 postgraduate residents participated in this study. The majority had significant imposter syndrome, with females more suffered than males. Trainees of the pediatrics department were affected the most while of the dentistry were least to be affected. Multiple factors including marital status, number of children, working hours, extracurricular activities, and private practice have been shown to affect the prevalence of imposter syndrome.

Conclusion

Imposter syndrome is a prevalent phenomenon among the residents of Pakistan. Efforts to identify and establish a proper relationship between general demographics and imposter syndrome are required for the healthy work experience of the trainees.
Capturing Intersections of Discrimination
Authors: Slemon Allie , Handlovsky Ingrid , Dhari Shivinder
Published: October 2024

While prior literature has established that nursing students experience racism, mental health stigma, and ableism within their programs, there is a dearth of knowledge of how students experience discrimination more broadly, across intersecting identities. This analysis draws on Crenshaw’s intersectionality theory to conduct an intersectional analysis of cross-sectional survey data of nursing students’ experiences of discrimination. Results illustrate that discrimination operates in complex ways across students’ social locations, as experiences of intersecting impacts of racism, homophobia/transphobia, mental health stigma, religious discrimination, ableism, and other forms of discrimination. Such experiences further unfold across clinical, classroom, and policy contexts.
Return to Play After Injuries to the Cervical Spine
Authors: Kazarian Gregory S. , Qureshi Sheeraz
Published: October 2024

Return to play (RTP) after sports-related traumatic injuries to the cervical spine is important for athletes and teams, especially at the elite level. While early RTP may be incentivized for athletes and organizations, treating clinicians must have a thorough understanding of cervical spine injuries, treatments, and RTP guidelines to make safe recommendations. In general, patients can RTP when asymptomatic from prior injury with no neurological deficits and a full, painless, active range of motion of the neck. However, injury diagnosis, injury symptoms and severity, history of cervical spine injuries, anatomic variants/anomalies, history of treatment/surgery, and any ongoing or persistent symptoms may modify RTP recommendations. In the current review, we summarize the common cervical spine injuries associated with contact sports and the available guidelines for RTP. It is important to note, however, that despite these guidelines, there is little consensus among treating physicians regarding these recommendations. Therefore, clinical judgment should be used to ensure conservative decisions are made and patient safety is maintained.
Redo coronary artery bypass grafting: when and how
Authors: Yang Benjamin , Koprivanac Marijan , Bakaeen Faisal G.
Published: October 2024

Purpose of review

Redo coronary artery bypass grafting (CABG) remains technically challenging with significant procedural risk but may be the best option for patients in whom repeat revascularization is indicated. This review summarizes the latest data regarding risk of redo CABG, who should receive this surgery, and how to achieve best outcomes.

Recent findings

Over the past two decades, the risk of performing redo CABG has declined and is approaching that of primary CABG in the hands of experienced surgeons. Nonetheless, patients for whom redo CABG is indicated tend to be older and have more complex medical comorbidities. Preoperative imaging is paramount in guiding sternal re-entry and mediastinal dissection, and in how to best employ rescue strategies when needed.

Patients with complex, progressive coronary disease with unprotected left anterior descending (LAD) coronary artery disease and prior coronary bypass may benefit from the durable, complete revascularization that redo CABG can offer with internal thoracic artery bypass to the LAD and, when possible, arterial inflow to other important coronary targets. Preoperative imaging, careful planning, meticulous surgical technique, myocardial protection, and an experienced surgical team are critical for optimal outcomes.
Age-related differences in psychometric properties of World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0): a retrospective analysis
Authors: Karsikas Mika , Saltychev Mikhail , Juhola Juhani
Published: October 2024

The aim of this study was to detect a possible age-related differential item functioning (DIF) of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) among people with musculoskeletal disorders. This was a cross-sectional study of 1739 consecutive patients with chronic musculoskeletal pain at a university clinic. Difficulty and discrimination parameters were calculated for each of 12 items of the WHODAS 2.0 using item response theory. The presence of DIF was assessed both numerically and graphically. When considering differences in both difficulty and discrimination, a statistically significant DIF was observed for all the items except for the item ‘washing’ (P values <0.001). The DIF was mostly uniform. Items ‘standing’, ‘household responsibilities’, ‘learning a new task’, ‘emotional affectedness’, ‘concentrating’, ‘washing’ and ‘dressing’ showed better precision among older patients. Items ‘walking’, ‘dealing with strangers’, ‘maintaining a friendship’ and ‘day-to-day work’ were more informative among younger patients. Difficulty and discrimination parameters were alike for all 12 items. The DIF was mostly uniform. These results can be taken into account when applying the WHODAS 2.0 to people with musculoskeletal complaints, especially when the studied groups are predominated by people of certain age.
Perspectives on the Practice of Collaborative Care: Topical Themes and Future Directions From the Lens of a Collaborative Care Child Psychiatrist
Authors: Romba Courtney
Published: October 2024

The increasing shortage of psychiatrists in the workforce is a well-documented and alarming trend. In light of this workforce shortage, psychiatrists bear a professional and ethical responsibility to identify strategies to increase access to mental health treatment and thereby reduce the impact of the psychiatrist shortage on patients and on the greater health system. One such strategy is the collaborative care model (CoCM), which has demonstrated efficacy in the mental health treatment of both pediatric and adult populations. In this article, the CoCM is presented as one effective strategy to address the behavioral workforce shortage. Current themes observed from the clinical practice of psychiatric collaborative care in a pediatric collaborative care setting are discussed with contemplation of future directions.
Joker Sign After Drooling Radioactive Saliva
Authors: Kim MinJeong , Han Yeon-Hee , Jeong Hwan-Jeong , Jeong Jae Seok , Lim Seok Tae
Published: October 2024

A 28-year-old man underwent high-dose radioactive iodine therapy after total thyroidectomy due to papillary thyroid carcinomas. After 2 weeks, a linear reddish line was observed extending from the right corner of the mouth to the cheek, resembling the appearance of the Joker. Through a detailed interview, it was determined that the patient had developed radiation dermatitis because of radioactive saliva drooling while sleeping on one side. Although this is expected to be infrequent, educating patients on avoiding saliva contact with the skin during and after radioactive iodine therapy is crucial due to the potential skin damage and cancer risk.
Intratracheal Ectopic Thyroid Tissue Mimicking a Subglottic Mass in a Patient With Thyroid Follicular Carcinoma on SPECT/CT
Authors: Aydinbelge Dizdar Nur , Cinar Alev , Ozmen Ozlem , Senlik Semra Demirtas
Published: October 2024

Intratracheal ectopic thyroid tissue is an extremely rare condition with limited cases reported in the literature. It can be asymptomatic or present with symptoms such as dysphagia, bleeding, dysphonia, dyspnea, and a sensation of a foreign body in the throat, depending on its localization. Due to its various clinical presentations, it poses a diagnostic dilemma. Herein, we aimed to present the contribution of thyroid scintigraphy and SPECT/CT to the diagnosis and management of a case with follicular carcinoma in the orthotopic thyroid gland as well as an ectopic intratracheal thyroid causing cough and airway obstruction mimicking a subglottic mass.