bluuebunny/crossref_metadata_2025 huggingface dataset:
B-340 Performance of a Quality System for Targeted Monoclonal Antibodies in a Reference Clinical Pharmacokinetic Laboratory
Authors: McFarland J , McLachlan O , Tsang J , Gowhari M , Ho J , Hughes P , Dervieux T
Published: September 2023

Background

The homogenous mobility shift assay (HMSA) laboratory developed test (LDT) quantifies monoclonal antibody drug and anti-drug antibody levels and is useful for the management of inflammatory bowel diseases (IBD). We report the implementation and performance of a quality system for these LDTs, as well as longitudinal trends of exposure and immunization prevalence from a reference clinical pharmacokinetic (PK) laboratory (Prometheus Laboratories, Inc.).

Methods

Quality control (QC) HMSA data was evaluated to verify conformance to specifications for infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), ustekinumab (UST) and their respective anti-drug antibodies (antibody to IFX [ATI], ADA [ATA], VDZ [ATV], and UST [ATU]). A QC panel consisting of five serum specimens spanning the reportable range per each drug or anti-drug antibody LDT was established, stored at subzero temperature, and tested monthly over a period of two years. Acceptable performance consisted of 80%–120% accuracy from the target value. All specimens were blinded to operator and processed with the clinical PK load of testing. Exposure and immunization prevalence over three years of testing was evaluated. All patient data were de-identified before analysis. Median drug level (interquartile ranges [IQR]), and anti-drug percent positivity by international classification of disease was also estimated (ICD-10 based).

Results

The QC results establish that the drug (IFX, ADA, VDZ, UST) and anti-drug (ATI, ATA, ATV, ATU) LDTs report acceptable performance with 80%–120% accuracy over the two-year evaluation period. Median drug concentrations with IQR were assessed for the clinical sample set differentiated by disease classification as depicted in Fig. 1. Anti-drug positivity levels were higher for ATI (mean: 11.5%) and ATA (mean: 13.6%) than those from ATV (mean 2.0%) and ATU (mean: 0.6%).

Conclusion

The QC data presented supports the performance of HMSA for therapeutic drug monitoring (TDM) of IBD and other immune mediated inflammatory diseases.
B-341 Analytical Performances of Homogeneous Mobility Shift Assay for Infliximab and Biosimilars and Resulting Exposure Assessments in Large Cohort of Patients With Inflammatory Bowel Diseases
Authors: McFarland J , Tsang J , Ho J , McLachlan O , Gowhari M , Hughes P , Dervieux T
Published: September 2023

Background

Biosimilar for infliximab (IFX) are currently available for the treatment of various immune mediated inflammatory diseases including inflammatory bowel disease (IBD). We have validated the homogenous mobility shift assay (HMSA) for IFX biosimilars and describe exposure from a large population of patients with IBD treated with IFX and biosimilars.

Methods

Validation of the biosimilars, infliximab-dyyb (Inflectra®) and infliximab-abda (Renflexis®), was conducted in a reference clinical laboratory (Prometheus Laboratories, Inc.) for performance equivalence to the 1st international World Health Organization (WHO) IFX standard (16/170) by HMSA. The evaluated performance characteristics consisted of accuracy, precision, sensitivity, specificity, range, and linearity using spiked human serum. Following validation and implementation in the clinical laboratory, the drug median with interquartile range (IQR) and antibody to drug (ATI) prevalence and percentage relative to low-titer antibody cut-point of 10 U/mL (Am J Gastroenterol 2021;00:1-12), using de-identified patients, was evaluated by comparing treatment with IFX or the two validated biosimilars.

Results

The reportable range for the biosimilars was 0.98 μg/mL (precision: 5.5% CV; accuracy: 110.7% recovery) to 34 µg/mL (precision: 6.3% CV; accuracy: 105.4% recovery). Biosimilar intra-day, inter-day precision (CV) and accuracy (% recovery) across the reportable range were 3.8%, 3.6% and 105.1%, respectively. Furthermore, HMSA calibrated with IFX originator or biosimilar showed congruent results when compared to calibration with the WHO standard for the determination of drug concentrations using 20 clinical samples spanning the reportable range (Fig. 1). Median drug concentrations with IQR were 10.9 µg/mL (4.8–19.7 µg/mL) for infliximab originator, 9.8 µg/mL (3.9–18.1) for infliximab-dyyb, and 9.5 µg/mL (3.6–18.3) for infliximab-abda over a three-year period of testing, which also demonstrated similar ATI positivity rates.

Conclusion

HMSA is validated to be used as a tool for therapeutic drug monitoring (TDM) of patients treated with IFX originator and biosimilars.
B-364 Inhibition of Hypoxia-Inducible Factor-1a (HIF-1 a) Provides a Therapeutic Approach for Hepatocellular Carcinoma (HCC)
Authors: Alghamdi U M
Published: September 2023

Background

The most frequent type of primary liver cancer in adults is hepatocellular carcinoma (HCC) which is the third-highest cause of cancer-related death worldwide. Globally, people die from liver cancer each year, with HCC accounting for around 90% of those deaths, making it a serious public health concern. Cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease are all high-risk factors for HCC development. In addition, HCC is one of the most frequent solid tumors found in humans. Due to insufficient blood supply, these solid tumors usually are devoid of oxygen and nutrients. A reduction in oxygen concentration results in the formation of a hypoxic environment that downregulates the metabolic process and is fatal to cancer cells. To circumvent this barrier to growth, cancer cells produce hypoxia-inducible factor-1 (HIF-1), which alters their metabolic pathways and allows them to survive. HIF-1alpha (HIF-1α), a cytoplasmic subunit of HIF-1 can be overexpressed in hypoxic conditions. HCC cells cannot proliferate under hypoxia without a high level of HIF-1α expression, making it as a potential cancer treatment target. Using the LOPAC (Library of Pharmacologically Active Compounds) drug library, we have identified multiple drug molecules that inhibit the expression of HIF-1α.

Methods

We constructed specific SK-HEP-1 cells, a human liver cancer cell line, expressing the luciferase reporter gene under the promoter of HIF-1α. By using the cells, we screened the (LOPAC) library. Other bioanalytical methods were used to confirm and analyze identified candidates.

Results

We successfully identified several compounds that are able to inhibit HIF-1α expression by using luciferase activity assays and Western blot analysis (WB). Further investigation was conducted to determine the molecular mechanism and function for one of the drug candidates, termed as UZ-1, in inhibiting HIF-1α in HCC by using the MTT assay and WB. UZ-1, an antirheumatic agent, showed a strong inhibitory effect on the expression of HIF-1α in SK-HEP-1 cells. In addition, it suppressed the signaling pathways associated with HIF-1α, leading to the apoptosis of HCC cells.

Conclusion

The UZ-1 molecule inhibits HIF-1α expression, as a result, and displays anticancer function in HCC cells through inducing apoptosis. Our result suggests that UZ-1 may be a potential drug candidate for the treatment of HCC.
B-365 Serum MAGE-A3 and MAGE-A4 Protein Levels as Potential Prognostic Biomarkers for Lung Cancer
Authors: Kong D , Gonzalez R , Yom J , Guo Z , Qu T , Hu X , Ren Q , Wu Z , Zewdu E , Guo H , Gilmore B , Zhao Z , Liu X , Fu W
Published: September 2023

Background

Melanoma-associated antigen 3 (MAGE-A3) and MAGE-A4 are members of Melanoma Antigen Gene (MAGE) family, which have restricted expression to the testis and are abnormally expressed in cancer cells. MAGE-A3 and MAGE-A4 are overexpressed in lung cancer and have been shown to be associated with cancer progression and poor prognosis. Elevated MAGE-A4 protein level in lung cancer serum samples has been reported in the literature, however, it is unclear whether MAGE-A3 protein can be detected in serum samples of lung cancer patients.

Methods

We developed human MAGE-A3 and MAGE-A4 sandwich ELISA kits and used them to measure serum MAGE-A3 and MAGE-A4 protein levels in 21 lung cancer patients and 30 non-cancer controls.

Results

Serum MAGE-A3 protein was detected in all 21 lung cancer patients (range: 34 to 78871 pg/mL, mean: 5600 pg/mL) and was significantly elevated compared to non-cancer controls (range: 23–308 pg/mL, mean: 140 pg/mL) (P < 0.05). Serum MAGE-A4 protein was detected in 5 of 21 (24%) lung cancer patients (range: 280 to 35096 pg/mL, mean: 1819 pg/mL), and the samples with high serum MAGE-A4 concentration matched those with high serum MAGE-A3 concentration. Serum MAGE-A4 protein was not detectable in non-cancer controls.

Conclusion

Our findings suggest that serum MAGE-A3 and MAGE-A4 may serve as potential prognostic biomarkers for lung cancer. The detection of elevated serum MAGE-A3 and MAGE-A4 in lung cancer patients indicates their specificity for the disease. Larger studies with more samples, different cancer stages, and longer follow-up are needed to validate these results and establish the clinical utility of serum MAGE-A3 and MAGE-A4 levels as prognostic markers for lung cancer. If further validated, these biomarkers could aid in early diagnosis and better management of lung cancer.
B-367 Analytical Validation of New CLIA Based TPS Assay as a Biomarker in Cancer Management
Authors: Jagarlamudi K , Damico Y , Pellegrini P , Torstensson M , Xia Z , Xue L
Published: September 2023

Background

Tissue polypeptide-specific antigen (TPS) has been described as a potentially useful serum marker of tumor activity in adult epithelial tumors such as breast, ovarian, prostate, and other malignancies. Here we developed and analytically validated Chemiluminescence immunoassay (CLIA) for TPS on the CIA series analyzer and FOSUN series analyzer in collaboration with Jiangsu ZECEN Biotech Co., Ltd (Jiangsu and Beijing, China).

Methods

The TPS-CLIA relies on two monoclonal antibodies generated against peptides that bind to cytokeratin 18 (CK18). The TPS-CLIA assay has been analytically validated and a reference range was established by using sera from blood donors (n = 101), and potential applicability was demonstrated in sera from patients with different malignant diseases (n = 54). The same serum samples were also analyzed with TPS-ELISA for comparison.

Results

The TPS-CLIA had a limit of the blank of 6 U/L with a limit of detection of 10 U/L and a dynamic range of 10–1200 U/L. The total assay precision was below 20% and no hook effect was observed up to 3265 U/L. Linear dilution of high endogenous TPS sera at 1:4 to 1:256 had shown a recovery in the range of 85%–115%. No significant interference was observed with bilirubin, hemoglobin, and triglycerides (<10%, Table 1). The assay binds to CK18 and no cross-reactivity was observed with CK8 or CK19. The cut-off value (95% CI) based on the blood donor sera was 80 U/L (range = 10–116). There was a significant correlation between TPS-CLIA and TPS-ELISA assay (r = 0.93; P < 0.0001) in different malignancies. More analytical parameters of TPS-CLIA are summarized as shown in Table 1.

Conclusion

The new TPS-CLIA provides a unique, robust, and convenient method for measuring cytokeratin 18 levels in serum. This can improve the clinical applications of TPS as a biomarker in cancer management.
B-382 Accurate and Early Detection of Colorectal Cancer Using a Multilocus DNA Methylation Markers-based Testing in Peripheral Blood Mononuclear Cells
Authors: Wang C , Li P , Xie Y
Published: September 2023

Background

An effective blood-based method for the diagnosis of colorectal cancer (CRC) has not yet been developed. Molecular alterations of immune cells occur early in tumorigenesis, providing the theoretical underpinning for early cancer diagnosis. Therefore, we aimed to develop an effective multi-molecular simultaneous detection method based on peripheral blood mononuclear cells (PBMCs) to improve the diagnosis of early-stage CRC.

Methods

Candidate DNA methylation markers were first identified from PBMCs using the Infinium MethylationEPIC array in the discovery phase (Shandong cohort I, n = 100) and further validated via pyrosequencing and targeted bisulfite sequencing in validation phase (Shandong cohort II, n = 202). Then, a single-tube multiplex methylation-specific quantitative PCR assay (multi-msqPCR) for simultaneous detection of five markers was established in a pilot study. After that, a CRC prediction model (CPM) based on DNA methylation and multi-msqPCR method was construct and its diagnostic performance were evaluated using the area under the receiver operating characteristic curve (AUROC) in our multicenter cohort (n = 595).

Results

Five discriminative DNA methylation markers identified by Illumina 850K microarray were successfully validated to diagnose early-stage CRC. Multi-msqPCR showed a better discriminative performance and 10-time lower detection limit than single-molecule detection in early-stage CRC. The cross-validated AUROC for CPM for early-stage CRC was 0.91 (sensitivity = 81.18%; specificity = 89.39%), significantly higher than CEA (AUROC = 0.62). CPM assay also yielded a high degree of discrimination for advanced adenoma (AA) cases (AUROC = 0.85; sensitivity = 63.04%; specificity = 89.39%). Besides, detecting CPM in multiple cancer types implied a CRC-specific diagnostic value. Our follow-up data also demonstrated that CPM could detect early-stage CRC up to 2 years before current traditional diagnostic methods.

Conclusions

CPM, in combination with epigenetic biomarkers and the multi-msqPCR method, was promising, cost-effective, and easily implementable for routine clinical diagnosis of early-stage CRC.
B-383 Exosomal PRPSAP1 in Plasma Predicts Microvascular Invasion in Hepatocellular Carcinoma
Authors: Xin Z , Zhou J , Chen H , Song M , Jiao L , Ying B
Published: September 2023

Background

Microvascular invasion (MVI), a critical predictor of postoperative tumor recurrence in hepatocellular carcinoma (HCC), is only detectable by histopathological examination of the surgical specimen. Prediction of MVI before surgery is of great significance to prognosis, especially by non-invasive means. Here, we report that exosome-derived mRNA in plasma can be promising biomarkers for MVI preoperatively.

Methods

Patients with initially suspected HCC who were undergoing hepatectomy were prospectively recruited with preoperative peripheral blood collection and followed up. Exosomal mRNA profiling was performed using RNA sequencing in the discovery cohort, and the edgeR package in R software was used to screen out significantly differential expression exosomal mRNAs between MVI and non-MVI groups. Multiplex droplet digital PCR (ddPCR) technology was utilized to verify filtered exosomal mRNAs in the validation cohort.

Results

A total of 131 HCC patients were enrolled with 37 in the discovery cohort and 94 in the validation cohort. RNA-sequencing data identified six candidate exosomal mRNAs (ZC3H3, RSAD2, PRPSAP1, HOXA2, CHPM4A and KCTD10) as potential predictors for MVI. In the validation cohort, expression levels of PRPSAP1 and HOXA2 were slightly higher and the expression level of CHMP4A was slightly lower in the MVI group than the non-MVI one, which were consistent with the discovery cohort though without statistically significant difference (P > 0.05). Further analysis between MVI number>5 and non-MVI patients validated that the expression level of exosomal PRPSAP1 was significantly higher in MVI number>5 patients (0.147 vs 0.070, P = 0.035). Altogether, exosomal PRPSAP1 in plasma was a promising biomarker predicting MVI for HCC patients.

Conclusion

We validated for the first time that high level expression of exosome-derived PRPSAP1 can preoperatively predict MVI, especially with the number >5, to improve prognosis.
B-384 Genetic Variations Predict Severe Immunotherapy-related Adverse Events for PD-1/PD-L1 Inhibitors
Authors: Xin Z , You L , Na F , Li J , Chen M , Song J , Bai L , Chen J , Zhou J , Ying B
Published: September 2023

Background

PD-1/PD-L1 inhibitors have brought remarkable benefits but can cause profound immune-related adverse events (irAEs), especially life-threatening toxicities. The host immunogenetic background is likely to play a role in irAE susceptibility. Here, we identified the variants that could predict severe irAEs in patients with cancer.

Methods

Patients with solid tumors receiving PD-1/PD-L1 blockade were recruited and followed up. Genes considered pivotal contributors to tumor-immunity and autoimmune diseases were screened out via Protein-Protein Interaction network and Cytoscape. Consequently, thirty-nine variants in eighteen genes were genotyped using the multiplex genotyping assay. Association analysis between those variants and severe irAEs (G3-G5 grades) as well as irAEs-free survival was performed.

Results

Two immunogenetic variants as predictors of severe irAEs were identified. The A allele of ADAD1 rs17388568 (OR = 2.599, 95% CI = 1.355–4.983, P = 0.003) increased the risk of severe irAEs, while the G allele of IL6 rs1800796 (OR = 0.425, 95% CI = 0.205–0.881, P = 0.018) protected patients from severe irAEs. In multivariate Cox regression analysis, ADAD1 rs17388568 (AA vs AG or GG: HR = 0.11, 95% CI = 0.025–0.49, P = 0.004) and IL6 rs1800796 (GG or GC vs CC: HR = 3.10, 95% CI = 1.315–7.29, P = 0.01) were also independent variables for severe irAEs-free survival.

Conclusion

We identified two immunogenetic polymorphisms associated with severe irAEs in PD-1/PD-L1 blockade-treated tumor patients at the first time, and they may serve as promising predictive biomarkers.
B-388 Clinical Performance of Xpert BCR-ABL Ultra Assay for Isoform p210 Quantitation
Authors: Marques F K , Mendonça C P , Zauli D A
Published: September 2023

Background

Chronic myelogenous leukemia (CML) is one of the most common hematologic neoplasms. More than 95% of patients with CML have the distinctive Philadelphia chromosome (Ph1) that results from a translocation between the chromosomes 9 and 22, and consequently in the BCR::ABL1 fusion gene. This fusion gene produces a tyrosine kinase with deregulated activity that plays a key role in the development of CML. Monitoring BCR::ABL transcript levels in patients on tyrosine kinase inhibitor (TKI) therapy using real-time quantitative PCR is standard of care in the management of CML patients. The test utilizes a quantitative, real-time reverse transcription polymerase chain reaction (RT-qPCR) to measure BCR::ABL1 to ABL1 percent ratios on the International Scale (%IS), in t(9;22) positive CML patients during monitoring of treatment with TKIs. In this context, this study evaluated clinical performance of the Xpert® BCR-ABL Ultra assay for quantitation of BCR::ABL1 p210 transcripts.

Methods

The clinical performance of assay was evaluated by comparison to an RT-qPCR assay routinely used in our institution, which also detects and quantifies the mRNA transcripts for the p210 translocation types and uses the ABL gene as an endogenous control. In total, 30 fresh peripheral blood samples of CML patients with the level of BCR::ABL1 transcripts (international scale, IS) between >50% and undetectable were enrolled in this study. All steps of protocols were performed according to manufacturer ́s instructions.

Results

The comparison of two assay revealed consistente molecular response (MR) level. Linear regression analysis showed high correlation between the assays (R2 = 0.974, P < 0.0001) The slope of regression curve were not significantly different from the value of 1 (1.003; 95% CI, range 0.943–1.069). The evaluation of MR level was identical in 21/28 (75%) samples. Two samples were excluded from the study due to failure to control ABL1 (Ct > 18). The median of ABL1 copies per sample was 66 011 copies (range 20 010–236 171) for conventional RT-qPCR assay. Xpert BCR-ABL Ultra reports %IS (MR), but this test does not report ABL1 copy numbers. If the Xpert BCR-ABL Ultra test reports a positive or negative result and the ABL1 Ct value is below 18, a minimum of 32 000 ABL1 copy numbers is guaranteed in the reaction. The BCR::ABL1 negativity was concordant in 2/8 samples.

Conclusion

We showed that the results Xpert® BCR-ABL Ultra assay (MR) are in good correlation with the results of RT-qPCR conventional method.The Xpert® BCR-ABL Ultra assay simplifies the generation of results by integrating nucleic acid extraction, amplification, and quantification of the BCR::ABL1 p210 transcripts in peripheral blood specimens. The assay turn-around-time is approximately 3 h. This does not differentiate between b2a2 or b3a2 fusion transcripts.This assay is unable to detect BCR::ABL1 p190 or other rarer translocations.
Uniformizations of Compact Sasakian Manifolds
Authors: Kasuya Hisashi , Miyatake Natsuo
Published: September 2023

We give a criterion for compact Sasakian manifolds to be deformed to Sasakian manifolds, which are locally isomorphic to circle bundles of anti-canonical bundles over Hermitian symmetric spaces as a Sasakian analogue of Simpson’s uniformization results related to variations of Hodge structure and Higgs bundles.
Reexamining the Minimum Sweat Rate Requirement for Sweat Chloride Testing
Authors: Omosule Catherine L , Dietzen Dennis J , Roper Stephen M
Published: September 2023

Background

Guidelines for sweat chloride testing endorse a minimum sweat rate for reporting results. Bilateral sweat collection is recommended, but if both sites fail to meet the minimum rate (quantity not sufficient, QNS), the test should be repeated. In this study, we examine the correlation between sweat rate and sweat chloride concentration ([Cl−]), assess the accuracy of specimens collected at suboptimal rates, and investigate the use of pooled bilateral specimens for chloride measurement.

Methods

Pearson correlation was employed to analyze the relationship between sweat rate and chloride concentration, [Cl−], in 674 macroduct collections. Weighted kappa was evaluated to determine cystic fibrosis (CF) diagnostic classification concordance for 18 tests with paired arms above vs below the minimum sweat rate. Deming regression was applied to compare [Cl−] from pooled bilateral specimens vs neat specimens in 27 collections with residual volume available after clinical testing.

Results

Pearson correlation of sweat rate vs [Cl−] was minimal (r = −0.0735) across specimens with varying rates and [Cl−]. There was substantial agreement in CF diagnostic classification between arms for bilateral collections with discordant sweat rates. Regression analysis of [Cl−] in pooled vs nonpooled specimens revealed a slope of 0.984 and an intercept of 0.796.

Conclusions

Negligible correlation of sweat rate and [Cl−] suggests the minimum sweat rate for macroduct collectors may be overly stringent. Reporting of [Cl−] in specimens with ≥10 µL (rate ≥0.3 µL/min) may reduce QNS rates without compromising diagnostic accuracy. Preliminary data suggests pooling of bilateral collections may be a feasible option to achieve the required volume for testing.
Orienting attention across binocular disparity
Authors: Caziot Baptiste , Rolfs Martin , Backus Benjamin T
Published: September 2023

The spatial distribution of covert visual attention following an exogenous cue is often described as a spotlight, which disregards depth. Here, we study the orienting of attention across binocular disparity, a key depth cue in primates. A small Gabor patch target was displayed at ±12-arcmin horizontal offset in each eye independently, resulting in four possible 3D locations. With some latency relative to target onset (0–300 ms), an attentional cue was displayed at one of five binocular locations, resulting in various combinations of relative azimuth (horizontal position) and disparity (depth). Observers’ task was to discriminate the orientation of the target. Observers’ performance decreased as the relative azimuth between the cue and the target increased. Performance also decreased with the difference in disparity, even when the azimuth remained constant. Performance varied with the delay between the cue and the target and was maximal between 100 and 150 ms. The orienting of attention in azimuth and depth followed the same time course. We mapped the 3D shape of attentional focus over time and found that the spatial envelope was approximately a Gaussian modulated in time. These results could not be explained by monocular confounds nor by eye movements. We conclude that exogenous cues direct attention not only to their visual direction but also to their depth and that binocular disparity is sufficient to define that depth. The identical time course and interaction between azimuth and depth suggest a shared mechanism, and therefore that visual attention to spatial location is an intrinsically 3D process.
The Effect of Age-Adjusted Sagittal Alignment on the Result of Posterior Decompression Surgery for Lumbar Spinal Canal Stenosis
Authors: Kawai Momotaro , Yagi Mitsuru , Okubo Toshiki , Ozaki Masahiro , Suzuki Satoshi , Takahashi Yohei , Tsuji Osahiko , Nagoshi Narihito , Matsumoto Morio , Nakamura Masaya , Watanabe Kota
Published: September 2023

Study Design.

Retrospective case series.

Objective.

The aim of this study was to compare the outcomes of posterior decompression surgery for lumbar spinal canal stenosis (LSS) in patients with preoperative sagittal malalignment (MA) with those without, after adjusting for age and sex.

Summary of Background Data.

Sagittal balance is an important factor in spine surgery and is thought to affect postoperative outcomes after LSS. However, the relationship between sagittal MA and postoperative outcomes has not been thoroughly examined.

Patients and Methods.

We included 533 patients who underwent surgical treatment for LSS and also achieved 2-year follow-up. Patients were categorized into either an MA+ group (69 patients) or a matched-alignment (MA−) group (348 patients) based on age-adjusted preoperative sagittal alignment. We compared the baseline and 2-year postoperative health-related quality of life (HRQOL) using the Visual Analog Scale and Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores. We also calculated clinical efficacy using the minimal clinically important difference based on JOABPEQ scores, and age and sex-adjusted JOABPEQ scores 2 years after surgery. Differences between groups were examined using the Mann-Whitney U test and χ2 analysis, where applicable.

Results.

Both groups showed an improved HRQOL after decompression surgery. Similar proportions of patients showed substantial improvement, as estimated by the minimal clinically important difference, in 4 out of 5 subdomains of the JOABPEQ. A significantly smaller proportion of patients in the MA+ group showed substantial improvement in lumbar function. The age and sex-adjusted HRQOL scores 2 years after surgery were lower in the MA+ group, particularly in the lumbar function and social life function subdomains of the JOABPEQ.

Conclusion.

The effects of posterior decompression surgery alone can still be observed at least 2 years postoperatively for patients with LSS and concomitant sagittal MA. Patients with sagittal MA may experience lower HRQOL than those without this type of MA.
Treatment of Acute Heart Failure with Acetazolamide
Authors: Veasaw Kassidy , Mahmood Uzair , Fishkin Tzvi , Frishman William H. , Aronow Wilbert S.
Published: September 2023

The primary treatment for acute heart failure includes the use of intravenous loop diuretics to reduce congestion. Successful decongestion at the time of hospital discharge improves mortality and prevents rehospitalization in these patients. Loop diuretic therapy alone may not be enough for adequate decongestion, especially as diuretic resistance becomes more common. Other therapies include the addition of thiazide diuretics, though increasing evidence might suggest a better alternative to add-on therapy. In this review, we will discuss the new evidence for the use of the diuretic acetazolamide in acute heart failure.
Direct Oral Anticoagulants: An Overview of Indications, Pharmacokinetics, Comorbidities, and Perioperative Management
Authors: Moras Errol , Gandhi Kruti , Khan Mohammad , Moras Adlyn , Choi James , Frishman William H. , Aronow Wilbert S.
Published: September 2023

Direct oral anticoagulants (DOACs) have catalyzed a significant paradigm shift in the landscape of anticoagulant therapy, emerging as pivotal agents for the prevention of stroke in atrial fibrillation and venous thromboembolism. Although the absolute advantages of DOACs over vitamin K antagonists (VKAs) may appear modest, clinical guidelines advocate for their preference across various indications, attributing this endorsement to their ease of administration and heightened safety. DOACs find application in preventing and treating diverse cardiovascular conditions. With the progressive expansion of DOAC utility, clinicians encounter intricate decisions concerning the selection of appropriate agents, determination of optimal treatment duration, and utilization within specialized patient subgroups. Extensive evidence has substantiated the noninferiority or superiority of DOACs compared with VKAs in both prophylaxis and treatment of thromboembolic events. Notably, routine monitoring to evaluate treatment efficacy is not mandated for DOACs; however, they exhibit interactions with co-administered drugs and exert influence on functional coagulation assessments. This review aims to synthesize existing literature, encompassing the delineation of appropriate clinical indications, tailored employment in patients with specific concurrent conditions, needs in monitoring parameters, seamless transitions during shifts between anticoagulant regimens, and a glimpse into forthcoming perspectives in this evolving field.
Demands and Resources
Authors: Egozi Laliv , Pardo Asher
Published: September 2023

Objective

The need to identify the main determinants of occupational burnout gained new attention with the release of management of psychosocial standards. Based on the JD-R model and COR theory, the article compares demands and resources interactions and their effects on high levels of burnout.

Methods

Employees in Israel (N = 2010) reported job demands and organizational and personal resources. One year later, 1201 of them reported their burnout. The interactions effects on next-year burnout levels were analyzed using logistic regression.

Results

The enhancing interaction better predicts next-year burnout. Each additional stressor increases the risk for very high burnout (above 4) a year later (odds ratio = 1.76; 95% confidence interval: 1.55–2.00).

Conclusions

The cumulative interaction of stressors predicts next-year burnout levels. Moreover, we used concrete comparable values of the measures that may initiate a standardization process for organizational stressors.
Effects of Time-Efficient Occupational Exercise on Cardiorespiratory Fitness in Firefighters
Authors: Knappett Helen , Haines Matthew
Published: September 2023

Objective

For a cohort of operational firefighters, we assessed the effects of workplace-based high-intensity interval training (HIIT) on cardiorespiratory fitness.

Methods

Fifteen firefighters performed HIIT or moderate-intensity continuous training for 4 weeks. Outcomes were peak oxygen uptake, time trial performance, and affective (pleasure/displeasure) responses to exercise.

Results

There was an increase in peak oxygen uptake for both conditions, although this did not reach statistical significance (P = 0.06, η
2 = 0.26) and time trial performance improved for both groups (2%, P < 0.01, η
2 = 0.51). Affective responses were more favorable for HIIT, but both conditions avoided excessive sensations of displeasure.

Conclusion

Results suggest that workplace-based HIIT improved fitness and performance to a similar magnitude to moderate-intensity continuous training while avoiding overly negative affective responses and could improve occupational health of firefighters, despite reduced time commitment.
Effectiveness of education on linear programmed dietary plan using locally available food on energy intake among HIV-infected children aged 2 to 5 years in Simiyu region: A cluster randomized control trial protocol
Authors: Carin Heriet , Katalambula Leonard , Munyogwa Mariam , Mageda Kihulya , Lyeme Halidi
Published: September 2023

Background:

Most of human immunodeficiency virus (HIV) infected children have decreased energy intake due to loss of appetite which resulted in weight loss. The diets of many HIV-infected children do not meet the recommended levels of energy intake required. However, caregivers with poor nutrition knowledge are more likely to feed their children with low-quality and diverse foods and at a lower frequency than recommended. This study aims to test the effectiveness of education on the linear programmed dietary plan using locally available food on energy intake of HIV-infected children in Tanzania mainland.

Methods:

The study will be a cluster randomized control trial study designed with both intervention and control arms and will use a quantitative approach. Care and treatment center will be the unit of randomization. The study will involve 200 asymptomatic HIV-infected children aged 2 to 5 years. The children will be randomly allocated into the intervention and control arm. The intervention will be implemented for 3 months. Participants from all groups will be assessed nutrition knowledge and attitude as well as 24-hour recall at baseline and end line. Education on how to use the energy-dense dietary plan developed by using linear programming techniques will be provided to the intervention group. The main outcome measures will be changes in knowledge, attitude, and energy intake in the intervention group compared with the control group. An unpaired t test will be used to establish the effectiveness of the intervention. A P value of less than .05 will be considered statistically significant.

Discussion:

The results of this study will provide evidence of the effectiveness of linear programmed dietary plan education on energy intake in community settings of rural Tanzania. It will form the basis for strengthening diet intake among HIV-infected children to improve energy intake using locally available food.
Positive impact of sleep on recall of multiplication facts
Authors: Spiller Jayne , Gilmore Camilla
Published: September 2023

This study tested the hypothesis that learning complex multiplication problems (e.g. 8 × 23 = 184) prior to sleep would benefit recall in adult participants compared with learning the problems prior to a period of wakefulness. This study used a within-participant design where all participants learnt complex multiplication problems in two conditions separated by one week. In one condition, learning was before bed (sleep learning condition) and in the other condition learning was in the morning (wake learning condition). In each condition, recall was tested approximately 10.5 h later. Data were collected online from 77 participants. In the subset of the sample with greater than or equal to 60% accuracy at the initial learning session (
n
= 37), the sleep learning condition participants had better recall compared with the wake learning condition. This equated to a moderate effect size, Cohen's
d
= 0.51. Regardless of initial levels of learning (
n
= 70) the same beneficial effect of sleep on recall was found with a small effect size, Cohen's
d
= 0.33. This study has identified a beneficial effect of learning prior to sleep on recall of complex multiplication problems compared with learning these problems during the daytime. Future research should explore whether similar effects are observed with children learning simple multiplication facts.
Linear analysis of ice-shelf topography response to basal melting and freezing
Authors: Stubblefield A. G. , Wearing M. G. , Meyer C. R.
Published: September 2023

Floating ice shelves in Antarctica and Greenland limit land-ice contributions to sea-level rise by resisting the flow of grounded ice. Melting at the surface and base of ice shelves can lead to destabilization by promoting thinning and fracturing. Basal melting often results in channelized features that manifest as surface topography due to buoyancy. The assumption of hydrostatic flotation commonly underlies estimates of basal melting rates. However, numerical simulations and ice-penetrating radar data have shown that narrow topographic features do not necessarily satisfy the local flotation condition. Here, we introduce a linearized model for ice-shelf topographic response to basal melting perturbations to quantify deviations from hydrostatic flotation and the stability of topography. While hydrostatic flotation is the dominant behaviour at wavelengths greater than the ice thickness, ice elevation can deviate from the perfect flotation condition at smaller wavelengths. The linearized analysis shows that channelized features can be stable when the time scale of extensional thinning is small relative to the time scale of viscous flow towards the channel. When extension is non-negligible, channels can break through the ice column. We validate the linearized analysis by comparing numerical solutions to a nonlinear ice-flow model with steady-state solutions obtained via a Green’s function.
Beak morphometry and morphogenesis across avian radiations
Authors: Mosleh Salem , Choi Gary P. T. , Musser Grace M. , James Helen F. , Abzhanov Arhat , Mahadevan L.
Published: September 2023

Adaptive avian radiations associated with the diversification of bird beaks into a multitude of forms enabling different functions are exemplified by Darwin’s finches and Hawaiian honeycreepers. To elucidate the nature of these radiations, we quantified beak shape and skull shape using a variety of geometric measures that allowed us to collapse the variability of beak shape into a minimal set of geometric parameters. Furthermore, we find that just two measures of beak shape—the ratio of the width to length and the normalized sharpening rate (increase in the transverse beak curvature near the tip relative to that at the base of the beak)—are strongly correlated with diet. Finally, by considering how transverse sections to the beak centreline evolve with distance from the tip, we show that a simple geometry-driven growth law termed ‘modified mean curvature flow’ captures the beak shapes of Darwin’s finches and Hawaiian honeycreepers. A surprising consequence of the simple growth law is that beak shapes that are not allowed based on the developmental programme of the beak are also not observed in nature, suggesting a link between evolutionary morphology and development in terms of growth-driven developmental constraints.
The relative impact of parental and current environment on plant transcriptomes depends on type of stress and genotype
Authors: Earley Timothy S. , Feiner Nathalie , Alvarez Mariano F. , Coolon Joseph D. , Sultan Sonia E.
Published: September 2023

Through developmental plasticity, an individual organism integrates influences from its immediate environment with those due to the environment of its parents. While both effects on phenotypes are well documented, their relative impact has been little studied in natural systems, especially at the level of gene expression. We examined this issue in four genotypes of the annual plant
Persicaria maculosa
by varying two key resources—light and soil moisture—in both generations. Transcriptomic analyses showed that the relative effects of parent and offspring environment on gene expression (i.e. the number of differentially expressed transcripts, DETs) varied both for the two types of resource stress and among genotypes. For light, immediate environment induced more DETs than parental environment for all genotypes, although the precise proportion of parental versus immediate DETs varied among genotypes. By contrast, the relative effect of soil moisture varied dramatically among genotypes, from 8-fold more DETs due to parental than immediate conditions to 10-fold fewer. These findings provide evidence at the transcriptomic level that the relative impacts of parental and immediate environment on the developing organism may depend on the environmental factor and vary strongly among genotypes, providing potential for the interplay of these developmental influences to evolve.
Sufficiency and necessity of big data capabilities for decision performance in the public sector
Authors: Talib Sarah , Papastathopoulo Avraam , Ahmad Syed Zamberi
Published: September 2023

Purpose

This study aims to examine the necessity effects of big data analytics capabilities (BDAC) on decision-making performance (DMP), particularly in the public sector.

Design/methodology/approach

The authors used the combined methods of partial least square structural equation modeling (PLS-SEM) and necessary condition analysis (NCA) to test the hypothesized relationships.

Findings

The findings show that the presence of all three BDAC (infrastructure, management and personnel) is significant and necessary to achieve higher levels of DMP. Specifically, the results revealed big data management capabilities to be of higher necessity to achieve the highest possible DMP. The findings provide public-sector practitioners with insights to support the development of their BDAC.

Originality/value

Time-sensitive domains such as the public sector require insight and quality decision-making to create public value and achieve competitive advantage. This study examined BDAC in light of the combined methods of (PLS-SEM) and NCA to test the hypothesized relationships in the public sector context.
Hinduja Global Solutions Limited: rewarding the shareholders
Authors: Dhamija Sanjay , Bhatia Shikha
Published: September 2023

Learning outcomes

After working through the case and assignment questions, the learning outcomes of this study are to understand the dividend policy of a company; compare different types of dividends that a company may give; assess the impact of stock splits and the issue of bonus shares (stock dividends); compare cash dividend and buy-backs as methods of cash distribution to shareholders; evaluate the methods of cash distribution that may be appropriate for the company; and assess the trade-off between long-term value creation and shareholder expectations.

Case overview/synopsis

This case study presents the dilemma faced by Partha DeSarkar, the executive director and global CEO of Hinduja Global Solutions (HGS) Limited, a leading business process management (BPM) company. The company would have surplus cash of about US$1.2bn from the selling of its health-care service businesses. The company planned to invest a part of this cashflow into the company’s future growth, with some of it distributed among its shareholders. This case study provides an excellent opportunity for students to determine the best method for rewarding the shareholders. It allows students to compare various cash distribution methods. Students can examine in detail the process involved, the quantum of distribution, tax implications, financial implications, fundraising flexibility and valuation impact of available options.

Complexity academic level

This case study is best suited for senior undergraduate- and graduate-level business school students in courses focusing on corporate finance, financial management, strategic management and investment banking.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS: 1 Accounting and Finance
Transformative research and education in Living Labs using the SDGs as a compass
Authors: Heijmans Annelies , Eweg Rik
Published: September 2023

Purpose

This study aims to investigate how Living Labs of Van Hall Larenstein UAS perform as sustainability-oriented, transdisciplinary learning environments. It shows how the sustainable development goals (SDGs) can be used as a compass and debates the sustainability impact of applied research.

Design/methodology/approach

A case study approach was adopted, including a literature review, scoping visits, online workshops and peer-to-peer inter-vision/learning, using the SDGs as a compass and framework for analysis.

Findings

Most Living Labs use a “silo-approach” on the SDGs and are designed from a technological-expert perspective. This results in blind spots, particularly on SDGs related to reducing socio-economic inequality and just institutions. Debating unsustainable systems, cultures and practices is avoided. To contribute to sustainability transitions, universities need to invest in developing transformative capacity. This refers to SDG-transition competences such as collaborative communication, constructively engaging with diversity and conflicts, discussing values, norms and ethics and encouraging reflexivity.

Research limitations/implications

Mainly lecturer-researchers were involved in the study. COVID-19 travel restrictions hindered the research at the grassroots level in India and Indonesia.

Originality/value

The study revealed the importance of creating Living Labs as safe and brave inter- and transdisciplinary learning environments to practice reflexivity: encouraging students, researchers and stakeholders to look at sustainability issues from plural perspectives and questioning unsustainable practices, which combined lead to changing perceptions, practices and relations and a deeper understanding of how change happens. The SDGs as a compass method supports reflexivity among stakeholders and in redirecting strategies towards a sustainable future.
Exploration of student sex work in the North East of England
Authors: Haskins Mollie , Osu Tinisha , Carr Michelle
Published: September 2023

Purpose

This paper aims to explore the prevalence, motivations and support for student sex work within North East higher education institutions. With limited existing research in this area, this study fills a crucial gap in understanding student sex work in the UK and its specific manifestation in the North East region.

Design/methodology/approach

To achieve its objectives, this study adopted an exploratory, cross-sectional design conducted entirely online due to the Covid-19 pandemic. A mixed-methodology approach was used, inspired by previous research, gathering quantitative data through a semi-structured questionnaire and qualitative data through open-ended survey questions.

Findings

The study revealed that 11.4% of students engaged in sex work, primarily in indirect and online-based forms. lesbian, gay, bisexual and transgender (LGBTQ)+ students were more likely to participate in sex work compared to heterosexual students. Financial difficulties and lifestyle preferences were identified as significant motivations for student sex work.

Research limitations/implications

A limitation of the study was the lack of diversity in the sample, with predominantly young, white, heterosexual and cis-gender females, potentially neglecting other demographics' struggles. Future research should include larger and more diverse samples to ensure representative findings.

Practical implications

The research highlights the need for greater awareness and support for student sex workers within North East universities. Policies and services should consider the unique challenges faced by LGBTQ+ student sex workers to reduce stigma and potential dangers.

Social implications

Understanding the prevalence of student sex work sheds light on the need to challenge societal assumptions and stigmas surrounding sex work, particularly concerning gender and sexuality.

Originality/value

This study breaks new ground by providing novel insights into an understudied research area – the prevalence of student sex work in North East England. The findings lay the foundation for future research and can inform policies and support systems to improve the safety and well-being of student sex workers. Furthermore, the study contributes to broader discussions on gender, sexuality and sex work in academic settings.