Screening Of Samples Research Articles

Patterns and determinants of cannabis use in youth visiting an urban emergency department in France

Background Cannabis use frequently starts during adolescence and young adulthood and can induce psychosocial and health consequences. Young people constitute hard-to-reach populations. Emergency departments could constitute a key care setting to identify cannabis use and its consequences among young people. Objectives To estimate the rate of cannabis use in the 16- to 25-year-old population visiting the emergency department for any reason and to assess the psychosocial factors associated with cannabis use. Methods This was a cross-sectional study among young people who attended the emergency department, over 5-months. Data were sociodemographic characteristics, self-administered questionnaires for problematic substance use screening, and urine drug screening samples. They were classified in the cannabis use (CU) group if they had a positive urine screen or reported cannabis use in the previous month. Characteristics of individuals in the CU and non-CU groups were compared. Results A total of 460 participants were included, of whom 105 were in the CU group. Cannabis users were more likely to be male (aOR = 1.85; [1.18–2.90]), to be unemployed (aOR = 1.77; [1.03–3.04]), to have a lower mental health status score (aOR = 0. 82; [0.75–0.90]), to report a history of sexual abuse (aOR = 2.99; [1.70–5.25]), and to have a positive AUDIT screen (aOR = 4.23; [2.61–6.86]). Conclusions The emergency department is a primary care setting for young people, which is conducive to screening for substance use. Cannabis users can be assessed and referred to adapt their treatment, given their lack of adherence to the traditional addictology care system.

The Early Benefits and Psychological Effects of Screening for Monoclonal Gammopathy of Undetermined Significance: Results of the Istopmm Study

Introduction: Multiple myeloma (MM) develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Recent evidence shows that initiating treatment at an asymptomatic stage improves outcomes in MM. However, a vast majority of MM patients are diagnosed at the point of symptomatic malignancy and never have the opportunity to receive early treatment. We aimed to evaluate systematic screening for MGUS as a way to significantly expand the availability of early treatment and improve overall outcomes. Despite the widespread use of cancer screening, the literature on the potential harms of screening, particularly psychological harms, is limited. Studies on the psychological effects of screening are therefore, urgently needed. The Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM) is a population-based screening study and randomized controlled trial (RCT) of follow-up strategies aimed at evaluating the potential benefits and harms of MGUS screening. Methods: All residents of Iceland born in 1975 or earlier were invited to participate of whom 80,759 individuals (54% of the eligible population) provided written informed consent for screening. Serum samples collected between 2016-2020 were screened by serum protein electrophoresis (SPEP) and free light-chain (FLC) assay. Those who had MGUS entered a RCT of follow-up strategies. Arm 1 was not notified; Arm 2 was followed according to guidelines; Arm 3 was followed according to a more intensive strategy. Participants who progressed were offered early treatment. Participants were followed to a diagnosis of MM, SMM, Waldenström's macroglobulinemia (WM), smoldering WM, chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL) with censoring at death. Progression rates were compared using the log-rank test. At registration, all participants were asked to answer the Patient Health Questionnaire 9 (PHQ-9), General Anxiety Disorder 7 (GAD-7), and the Satisfaction with Life Scale (SWLS), validated questionnaires that assess depression, anxiety, and satisfaction with life. These questionnaires were sent annually to all participants and two weeks after MGUS diagnosis to Arms 2 and 3. Scores for Arm 1 and Arms 2 and 3 combined were compared using a generalized estimating equations linear model to account for multiple and differential numbers of observations before and after MGUS diagnosis. Results: A total of 75,422 participants provided a serum sample for screening and 3,487 had previously unknown MGUS and entered the RCT. Over a median follow-up of 4-4.5 years (depending on the outcome of interest) a total of 33, 136, and 185 were diagnosed with MM, SMM, WM, SWM, CLL, or NHL in Arms 1, 2, and 3 (p<0.001), respectively (Figure). In total, 775 (65%) and 1,838 (72%) participants in Arm 1 and Arms 2 and 3 answered a total of 2,673 and 8,540 questionnaires respectively. PHQ-9 and GAD-7 scores were not higher and SWLS scores were not lower in those who were made aware of their MGUS status (Arms 2 and 3) either at MGUS diagnosis, one year after diagnosis, or at the end of follow-up. Thus, no negative psychological impact was observed. In fact, a small positive psychological impact of MGUS diagnosis was observed as demonstrated by lower scores on PHQ-9 and GAD-7. However, the effect sizes were small (Cohens' d range: 0.02-0.2) indicating no meaningful difference in psychological wellbeing between the groups (Table). Discussion: In this first, large population-based screening study for MGUS and subsequent RCT, we found that screening is feasible and leads to early diagnosis and treatment of MM and related disorders. Importantly, MGUS screening was not associated with any demonstrable psychological harm. This shows, for first time, that providing detailed and balanced information at diagnosis, and plans for follow-up can prevent psychological harm from the diagnosis of this precancerous condition, a finding which is of significance to the field of cancer screening in general. These findings are a major milestone towards establishing the role of MGUS screening. If they translate into the prevention of symptomatic malignancies and improvements in overall survival, screening for MGUS can produce a paradigm shift in the field of plasma cell disorders towards a future of early detection, early treatment, and prevention, and perhaps even a cure.

Mezigdomide Treatment in Relapsed-Refractory Myeloma Patients Shifts Bone Marrow NK and T Cell Populations from Exhaustion to Activation

Background The effect of immunomodulatory drugs (IMiDs) and novel cereblon E3 ligase modulators (CELMoDs) on the tumour microenviroment (TME) of multiple myeloma (MM) patients remains poorly understood. A recent multi-center phase 1/2 trial (CC-92480-MM-001) of CELMoD Mezigdomide (MEZI) demonstrated clinical response in triple-class refractory, heavily pre-treated MM patients (Richardson et al, EHA abstracts 2020). Here, we report results from high dimensional mass cytometry immune profiling of baseline and treatment samples from relapsed-refractory MM (RRMM) patients to understand the effect of MEZI on the bone marrow (BM) TME. In addition, we analyze baseline samples to evaluate BM immune phenotypes that may correlate with response to MEZI. Methods We identified 45 RRMM patients with paired bone marrow aspirate samples pre- (screening) and post- (cycle 2 onwards) MEZI treatment, and 32 additional patients with isolated screening samples. Of the 45 patients, 39 received a dose of 0.8-1.0mg daily for 14 or 21 days of a 28-day cycle, 6 received 0.2-0.6mg on varying schedules as part of the trial design. CD138-negative BM mononuclear cells were isolated from these patients and profiled at single-cell resolution using a previously described 39-marker TME CyTOF-panel (van Oekelen, ASH 2021). Both manual hierarchical gating and unsupervised computational workflows were used for CyTOF data analysis. Around 5 million total cells were analyzed and over 100 immune populations. Samples with <2500 total events were excluded for quality-control. Population frequencies used for comparison are reported as median percentage of the parent population. Statistical comparisons between groups were assessed using the Wilcoxon test. Results Upon MEZI treatment, both adaptive and innate BM immune compartments demonstrated a significant increase in activated populations and marked reduction in exhausted/senescent populations (Figure 1A). Total NK and NKT populations expanded on MEZI (p<0.01 for both). Both CD4 and CD8 T cell populations shifted towards an effector phenotype with significant increases in effector memory (CCR7-CD45RA-) populations (p<0.001 for both) and concurrent reductions of and naïve (p<0.001), central memory (p<0.01 for CD4, NS for CD8) and TEMRA populations (p<0.001). HLADR-expressing CD4, CD8 and NKT populations significantly increased on MEZI (p<0.001 for all) as did ICOS-expressing CD4 (p<0.01), NK (p<0.001) and NKT cells (p<0.05). Senescent NK, NKT, CD4 and CD8 populations expressing KLRG1 decreased on MEZI treatment (p<0.01 for all) and CD57 positive CD8 and NKT cell populations also reduced (p<0.05). CD8, NK and NKT cells expressing the inhibitory checkpoint molecule TIGIT, showed a near 3-fold reduction of on treatment (p<0.001 for all). Although PD1-positive populations did not change on MEZI, PD1/TIGIT double-positive CD4 and CD8 populations showed significant reduction (p<0.05 for both). A dose-dependent reduction of TIGIT-expressing CD8 and NKT populations was seen at higher doses of MEZI (p<0.05 for both), suggesting a direct effect of MEZI on the BM TME. We further correlated depth-of-response with baseline immune composition in 77 patients (Figure 1B). Patients with progression of disease (n=9) on MEZI, when compared to all other patients (n=68), were found to have higher frequencies of PD1 (p<0.05) and TIGIT (p<0.001) positive, as well as dual PD1 and TIGIT positive (p<0.001), CD8 and NKT populations. Number of prior lines (median = 6) and type of MM therapy prior to MEZI did not significantly affect baseline PD1 or TIGIT positive populations. Conclusion MEZI treatment leads to significant activation of adaptive and innate BM immune populations with concurrent reduction of exhausted and senescent populations. These findings are concordant with prior observations of IMiD-mediated immune-stimulation. Patients progressing through MEZI had higher levels of immune checkpoint expression at baseline, which may be helpful for patient selection for this novel CELMoD. These results also suggest that MEZI may be useful in combination with other agents for increasing immune activation and reducing immune exhaustion. Further analyses comparing the effect of different CELMoDs on the BM TME are ongoing.

Predicting an Underlying Clonal Plasma Cell Population in Light-Chain Monoclonal Gammopathy of Undetermined Significance Using Free Light-Chain Ratio

Introduction: The management of light-chain (LC) monoclonal gammopathy of undetermined significance (MGUS) presents inherent challenges as the key diagnostic factor - abnormal free-light chain (FLC) levels - only indirectly implies the presence of an underlying clonal cell population. Moreover, the lack of M protein, used in current risk-stratification models, necessitates a distinct approach for risk assessment in LC-MGUS. Using next-generation flow cytometry (NGF), we assessed clonal plasma cell presence in bone marrow (BM) samples from individuals with LC monoclonal gammopathies. This approach enabled us to evaluate the predictive value of FLC ratio for an underlying clonal plasma cell population in LC-MGUS and its prognostic implications. Aim: To evaluate the association between FLC ratio and the presence of clonal plasma cells in the BM of individuals with LC monoclonal gammopathies as well as the risk of progression. Methods: The study is a part of the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, a population-based screening study for multiple myeloma (MM) precursors and randomized trial of follow-up strategies. We included screened individuals with an abnormal FLC ratio (<0.26 or >1.65) and elevated involved LC (kappa ≥19.4 mg/L or lambda ≥26.3 mg/L) (Freelite, The Binding Site), with no detected M protein. Those with previously known MM or related disorders were excluded. NGF was used to determine clonal plasma cell presence in BM samples. Logistic regression was used to assess the relationship between FLC ratio (used as involved/uninvolved ratio throughout the study) and clonal plasma cell presence. Receiver operating characteristic (ROC) curve analysis was used to assess the predictive ability of FLC ratio for clonal plasma cell presence in LC-MGUS and to determine an optimal cutoff value. Kaplan-Meier analysis was used to assess time to progression to more advanced plasma cell disorder for LC-MGUS, stratified by the FLC ratio cutoff. A linear mixed-effects model was used to evaluate the change in FLC ratio (expressed as fold change relative to the screening sample) over time for those with FLC ratio below the cutoff at screening. Results: After screening 75,422 individuals, 1,965 with LC disease were included, with median age of 71 years (range of 42-100 years), and a median FLC ratio of 1.85. Most (95.4%) had involved FLC of type kappa. Clonal plasma cells were identified by NGF in 8/21 (38.1%) LC-MGUS, and all LC-smoldering MM (SMM) (n=21) and LC-MM (n=7) cases. A significant prediction of clonal plasma cell presence was found for FLC ratio (OR=6.47; p=0.012; n=49), supported by ROC curve analysis for LC-MGUS (AUC=0.94; n=21), identifying FLC ratio of 3.15 as optimal cutoff (92% sensitivity, 100% specificity). Of the 254 individuals randomized to active follow-up within the iStopMM study, baseline diagnosis distribution was 223 (87.8%) LC-MGUS, 22 (8.7%) LC-SMM, 7 (2.8%) LC-MM, 1 (0.4%) solitary plasmacytoma, and 1 (0.4%) chronic lymphocytic leukemia. Among these, 123 (representing 88% of the screened study cohort) had FLC ratio <3.15 at screening, thereof 122 (99.2%) with LC-MGUS and 1 (0.8%) with solitary plasmacytoma. No disease progression was observed for individuals with FLC ratio <3.15 (n=100) over a median follow-up of 46 months. Conversely, disease progression occurred in 13/97 (13.4%) LC-MGUS with ≥3.15 FLC ratio (9 to SMM, 3 to MM, and 1 to smoldering Waldenströms macroglobulinemia) during median follow-up of 42 months (p=0.00018 vs FLC ratio <3.15) (Figure). The linear mixed-effects model of 454 repeated FLC from 128 individuals with <3.15 FLC ratio at screening did not indicate significant change in FLC ratio over a median follow-up of 48 months. Conclusions: In this study, we utilized NGF to confirm an underlying clonal plasma cell population in BM of individuals with LC-MGUS and evaluate its association with involved/uninvolved FLC ratio. Clonal plasma cells were detected in a minority of LC-MGUS (38.1%), for which FLC ratio was found to be highly predictive. An FLC ratio cutoff of 3.15 optimally discriminated based on clonal plasma cell presence, and we found no evidence of progressive disease in LC-MGUS below this cutoff during follow-up. Altogether, the more stringent FLC ratio cutoff can assist in determining the likelihood of an underlying clonal plasma cell population in LC-MGUS and may, as such, help to guide the management of LC-MGUS.

A Novel Approach on the Sensitivity of Preserved Plasmodium falciparum Positive RDT kits for the Molecular Detection of Pfmdr 1 and Pfcrt Genes in Pregnant Women

Storing blood samples for molecular screening have become increasingly difficult due to unstable electricity and high cost of generators fuels. Samples often deteriorate giving false negative upon molecular analysis. This research was aimed at determining the sensitivity of preserved Plasmodium falciparum positive RDT kits for the molecular detection of Pfmdr 1 and Pfcrt genes among pregnant women in From February 2020 to May 2020, Sokoto, Nigeria. 200 pregnant patients who visited the hospital for ANC had their blood samples taken, and a questionnaire was given out. To detect Plasmodium falciparum, RDT kits tailored to its monoclonal antibody were utilized. P. falciparum positive Rapid Diagnostic Test Kits were air tightened with nylon and silica-preserved for three months in a closed cabinet. The preserved positive samples were utilized to extract DNA, and the Pfmdr1 and Pfcrt genes' existence was then checked using a PCR procedure. 4 samples tested positive for both genes, suggesting a 21.05 % prevalence, according to the results of the inquiry into the Pfcrt and Pfmdr1 genes. This study has revealed the sensitivity of preserved RDT kits (with silica) for DNA extraction. Researchers and molecular laboratories should be preserving positive RDT kits meant for DNA extraction and other molecular analysis as it is much easier to preserve and there is no cost involved.

Acceptability of decentralizing childhood tuberculosis diagnosis in low-income countries with high tuberculosis incidence: Experiences and perceptions from health care workers in Sub-Saharan Africa and South-East Asia.

Decentralizing childhood tuberculosis services, including diagnosis, is now recommended by the WHO and could contribute to increasing tuberculosis detection in high burden countries. However, implementing microbiological tests and clinical evaluation could be challenging for health care workers (HCWs) in Primary Health Centers (PHCs) and even District Hospitals (DHs). We sought to assess the acceptability of decentralizing a comprehensive childhood tuberculosis diagnosis package from HCWs' perspective. We conducted implementation research nested within the TB-Speed Decentralization study. HCWs from two health districts of Cambodia, Cameroon, Côte d'Ivoire, Mozambique, Sierra Leone, and Uganda implemented systematic screening, nasopharyngeal aspirates (NPA) and stool sample collection with molecular testing, clinical evaluation and chest X-ray (CXR) interpretation. We investigated their experiences and perceptions in delivering the diagnostic package components in 2020-21 using individual semi-structured interviews. We conducted thematic analysis, supported by the Theoretical Framework of Acceptability. HCWs (n = 130, 55% female, median age 36 years, 53% nurses, 72% PHC-based) perceived that systematic screening, although increasing workload, was beneficial as it improved childhood tuberculosis awareness. Most HCWs shared satisfaction and confidence in performing NPA, despite procedure duration, need to involve parents/colleagues and discomfort for children. HCWs shared positive attitudes towards stool sample-collection but were frustrated by delayed stool collection associated with cultural practices, transport and distance challenges. Molecular testing, conducted by nurses or laboratory technicians, was perceived as providing quality results, contributing to diagnosis. Clinical evaluation and diagnosis raised self-efficacy issues and need for continuous training and clinical mentoring. HCWs valued CXR, however complained that technical and logistical problems limited access to digital reports. Referral from PHC to DH was experienced as burdensome. HCWs at DH and PHC-levels perceived and experienced decentralized childhood tuberculosis diagnosis as acceptable. Implementation however could be hampered by feasibility issues, and calls for innovative referral mechanisms for patients, samples and CXR.

Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions.

Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy.

Gestation-suppressed serum TSH levels during early pregnancy are not associated with altered maternal and neonatal outcomes.

The aim of the study was to investigate the impact of suppressed serum TSH levels (sTSH) during early pregnancy on maternal and neonatal outcomes. In this single-centre, retrospective cohort study 1081 women were screened at 11.8 ± 2.4 weeks of pregnancy for TSH, free T4 (FT4) and TPOAb. Exclusion criteria were twin- and assisted- reproduction pregnancies, women with TSH levels >3.74 mIU/L, severe hyperthyroidism, treated for thyroid dysfunction before or after screening and gestational blood sampling <6 or >16 weeks of pregnancy. The prevalence of adverse pregnancy outcomes was compared between the study group sTSH (TSH: < 0.06 mIU/L; n = 36) and euthyroid controls (TSH: 0.06-3.74 mIU/L; n = 1045), and the impact of sTSH on pregnancy outcomes verified in logistic regression analyses. Median (IQR) serum TSH level in women with sTSH was 0.03 (0.03-0.03) vs 1.25 (0.81-1.82) mIU/L in controls and FT4 levels 18.0 (14.4-20.3) vs 14.2 (12.9-15.4) pmol/L; both P < 0.001. None of the women with sTSH had thyrotropin receptor antibodies. Compared with controls, the prevalence of TPOAb positivity (TAI) was comparable between groups (5.6% vs 6.6%; P = 0.803). The prevalence of maternal and neonatal pregnancy outcomes was comparable between the study and control group. The logistic regression analyses with corrections for TAI, FT4 and demographic parameters confirmed the absence of an association between sTSH, and the following outcomes: iron deficient anaemia (aORs (95% CI)): 1.41 (0.64-2.99); P = 0.385, gestational diabetes: 1.19 (0.44-2.88); P = 0.713, preterm birth: 1.57 (0.23-6.22);P = 0.574 and low Apgar-1' score: 0.71 (0.11-2.67); P = 0.657. Suppressed serum TSH levels during the first to early second trimester of pregnancy were not associated with altered maternal or neonatal outcomes.

DNA Methylation Testing for Endometrial Cancer Detection in Urine, Cervicovaginal Self-Samples and Cervical Scrapes

ABSTRACT Endometrial cancer is the sixth most common cancer in women globally and has a rising incidence, accounting for 417,000 new diagnoses and more than 97,000 deaths in 2020. Early detection is critical because of a poor advanced-stage prognosis and high relapse risk. Postmenopausal bleeding precedes endometrial cancer in 90% of cases, yet only 5% to 10% of patients with this symptom have an underlying malignancy. Recent cytology research has demonstrated endometrial cancer cells in vaginal samples, suggesting urine and cervicovaginal self-samples may allow convenient and minimally invasive screening. In addition, screening samples for DNA methylation in tumor suppressor genes can increase testing efficacy of triaging patients with postmenopausal bleeding as it does not require intact tumor cells. This study aimed to evaluate the diagnostic performance of endometrial cancer detection using DNA methylation analysis in paired urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. Paired samples from participants of the SOLUTION1 study with endometrial cancer were collected between October 2016 and August 2020. A complete urine void and cervicovaginal self-sample was collected at home, whereas the cervical scrape was taken by a clinician in the operating room before surgery. Each patient had a paired urine, cervicovaginal self-sample, and clinician-taken cervical scrape available for methylation analysis. Controls were collected from the Urine Controls (URIC) biobank and Dutch national cervical cancer screening program. Promoter hypermethylation of the ADCYAP1, BHLHE22, CDH13, CDO1, GALR1, GHSR, HAND2, SST, and ZIC1 genes was tested using quantitative methylation-specific polymerase chain reaction. Optimal 3-marker combinations were determined for each sample type using multivariable logistic regression analysis, and diagnostic performances of each marker and 3-marker panels were assessed by leave-one-out cross validation. A total of 103 endometrial cancer patients were included in this study, with 317 unpaired samples of control women. Methylation levels of all markers were significantly higher in all 3 sample types of endometrial cancer patients compared with healthy control women. In urine, the non–cross-validated area under the curve of the DNA methylation markers ranged between 0.61 and 0.93, in cervicovaginal self-samples between 0.62 and 0.91, and in clinician-taken cervical scrapes between 0.61 and 0.95. Most markers (7/9) showed the highest performance in urine, with the remaining 2 showing best performance in clinician-taken cervical scrapes. The optimal 3-marker combination panels showed area under the curve values of 0.95 (05% confidence interval [CI], 0.92–0.98) for urine, 0.94 (95% CI, 0.90–0.97) for cervicovaginal self-samples, and 0.97 (95% CI, 0.96–0.99) for clinician-taken cervical scrapes. The sensitivity and specificity of the optimal urine testing panel were both 90%, were 89% sensitivity and 92% specificity for cervicovaginal self-samples, and were 93% sensitivity and 90% specificity for clinician-taken cervical scrapes. The leave-one-out cross-validation analysis revealed virtually equal performances in marker panels for each of the 3 testing modalities. The results of this study demonstrate high diagnostic potential of DNA methylation testing in minimally and noninvasive samples for endometrial cancer detection, emphasizing the potential for patient-friendly home-based sample collection.

Is the Earnings Quality of Family Businesses Better Than Non-family Businesses?

Objective - This study aims to prove whether the earnings quality of family businesses is better than non-family businesses to address two conflicting theories regarding the quality of family business earnings: agency theory and socioemotional wealth theory. Methodology/Technique –. This research uses a regression model to examine the influence of family business/non-family business characteristics on earnings quality. To obtain robust results, this research measures earnings quality using 5 measurement proxies, including measurements of available opportunities for earnings management, earnings management practices, earnings persistence, earnings restatement, and investor responsiveness to earnings quality. The screening sample was carried out on firms listed on the Indonesia Stock Exchange (IDX) for the period 2016–2020, resulting in 932 research observations. Findings - Overall, this research proves that FB earnings quality is better than NFB earnings quality. The results of this study extend the implementation of socioemotional wealth theory in explaining the characteristics of FB, in which the characteristics of FB and non-FB have an impact on earnings quality. Novelty - Financial statement analysts can utilize the results of this study in interpreting earnings quality based on the characteristics of FB and NFB. Type of Paper: Empirical JEL Classification: M41, M49. Keywords: Earnings Quality, Family Business (FB), Non-family Business (NFB), Socioemotional Wealth Theory Reference to this paper should be referred to as follows: Purba, G.K; Surya, A.N; Joshi, P.L; Tyagi, A. (2023). Is the Earnings Quality of Family Businesses Better Than Non-family Businesses?, Acc. Fin. Review, 8(2), 36 – 53. https://doi.org/10.35609/afr.2023.8.2(1)

Expressive Language Profiles in a Clinical Screening Sample of Mandarin-Speaking Preschool Children With Autism Spectrum Disorder.

This cross-sectional study aimed to depict expressive language profiles and clarify lexical-grammatical interrelationships in Mandarin-speaking preschoolers with autism spectrum disorder (ASD) during the administration of the simplified Chinese Psychoeducational Profile-Third Edition screening. We collected naturalistic language samples from 81 (74 boys, seven girls) 2- to 7-year-old (Mage = 55.6 months, SD = 15.17) Mandarin-speaking children with ASD in clinician-child interactions. The child participants were divided into five age subgroups with 12-month intervals according to their chronological age. Computer-assisted part-of-speech tagging, constituency analysis, and dependency analysis addressed the developmental trajectories of early lexical and grammatical growth in each age subgroup. Significant within-ASD differences were observed in content words, function words, and lexical categories. Nouns and verbs were the predominant lexical categories, while noun types overwhelmed verb types in children over 3 years old. The grammatical development of 5- to 6-year-old Mandarin-speaking children with ASD was better than that of 3- to 4-year-old children. The trends of syntactic structures, grammatical relations, and grammatical complexity in each age group were similar. Mandarin-speaking preschoolers with ASD produce more lexicons with increasing age. They preserve the noun bias as a universal mechanism in early lexical learning. Moreover, their developmental trajectories of grammatical growth were comparable in each age subgroup. In addition, their lexicons and grammar were synchronically developed during early language acquisition.

Automated Deep Learning Artificial Intelligence Tool for Spleen Segmentation on CT: Defining Volume-Based Thresholds for Splenomegaly.

BACKGROUND: Splenomegaly has historically been assessed on imaging using potentially inaccurate linear measurements. Prior work tested a deep-learning artificial intelligence (AI) tool that automatically segments the spleen to determine splenic volume. OBJECTIVE: To apply the deep-learning AI tool in a large screening population to establish volume-based splenomegaly thresholds. METHODS: This retrospective study included a primary (screening) sample of 8901 patients (mean age, 56±10 years; 4235 men, 4666 women) who underwent CT colonoscopy (n=7736) or renal-donor CT (n=1165) from April 2004 to January 2017, and a secondary sample of 104 patients (mean age, 56±8 years; 62 men, 42 women) with end-stage liver disease (ESLD) who underwent pre-liver transplant CT from January 2011 to May 2013. The automated deep-learning AI tool was used for spleen segmentation, to determine splenic volumes. Two radiologists independently reviewed a subset of segmentations. Weight-based volume thresholds for splenomegaly were derived using regression analysis. Performance of linear measurements was assessed. Frequency of splenomegaly using weight-based volumetric thresholds in the secondary sample was determined. RESULTS: In the primary sample, both observers confirmed splenectomy in 20 patients with automated splenic volume of zero; confirmed incomplete splenic coverage in 28 patients with a tool output error; and confirmed adequate segmentation in 21 patients with low (<50 cc) volume, 49 patients with high (>600 cc) volume, and 200 additional randomly selected patients. In 8853 patients included in analysis of splenic volumes (i.e., excluding zero or error values), the mean automated splenic volume was 216±100 ml. Weight-based volumetric threshold (in milliliters) for splenomegaly was defined as 3.0*(weight[kg])+127; for weight >125 kg, splenomegaly threshold was constant (503 ml). Sensitivity and specificity for volume-defined splenomegaly were 13% and 100% at true-craniocaudal length of 13 cm, and 78% and 88% for maximum-3D length of 13 cm. In the secondary sample, both observers identified segmentation failure in one patient. Mean automated splenic volume in the 103 remaining patients was 796±457 ml; 84% (87/103) of patients met the weight-based volume-defined splenomegaly threshold. CONCLUSION: We derived a weight-based volumetric threshold for splenomegaly using an automated AI-based tool. CLINICAL IMPACT: The AI tool could facilitate large-scale opportunistic screening for splenomegaly.

Clonal expansion and rapid characterization of Klebsiella pneumoniae ST1788, an otherwise uncommon strain spreading in Wales, UK.

A multidrug-resistant strain of Klebsiella pneumoniae (Kp) sequence type (ST) 1788, an otherwise uncommon ST worldwide, was isolated from 65 patients at 11 hospitals and 11 general practices across South and West Wales, UK, between February 2019 and November 2021. A collection of 97 Kp ST1788 isolates (including 94 from Wales) was analysed to investigate the diversity and spread across Wales and to identify molecular marker(s) to aid development of a strain-specific real-time PCR. Whole genome sequencing (WGS) was performed with Illumina technology and the data were used to perform phylogenetic analyses. Pan-genome analysis of further Kp genome collections was used to identify an ST1788-specific gene target; a real-time PCR was then validated against a panel of 314 strains and 218 broth-enriched screening samples. Low genomic diversity was demonstrated amongst the 94 isolates from Wales. Evidence of spread within and across healthcare facilities was found. A yersiniabactin locus and the KL2 capsular locus were identified in 85/94 (90.4 %) and 94/94 (100 %) genomes respectively; bla SHV-232, bla TEM-1, bla CTX-M-15 and bla OXA-1 were simultaneously carried by 86/94 (91.5 %) isolates; 4/94 (4.3 %) isolates also carried bla OXA-48 carbapenemase. Aminoglycoside and fluoroquinolone resistance markers were found in 94/94 (100 %) and 86/94 (91.5 %) isolates respectively. The ST1788-specific real-time PCR was 100 % sensitive and specific. Our analyses demonstrated recent clonal expansion and spread of Kp ST1788 in the community and across healthcare facilities in South and West Wales with isolates carrying well-defined antimicrobial resistance and virulence markers. An ST1788-specific marker was also identified, enabling rapid and reliable preliminary characterization of isolates by real-time PCR. This study confirms the utility of WGS in investigating novel strains and in aiding proactive implementation of molecular tools to assist infection control specialists.

FUNDC2, a mitochondrial outer membrane protein, mediates triple-negative breast cancer progression via the AKT/GSK3β/GLI1 pathway.

Triple-negative breast cancer (TNBC) lacks effective therapeutic targets and has a poor prognosis, easy recurrence and metastasis. It is urgent and important to explore TNBC treatment targets. Through mass spectrometry combined with qRT-PCR validation in luminal A cells and TNBC cells, high-content screening and clinical sample analysis, FUNDC2 was discovered as a novel target. The function of the outer mitochondrial membrane protein FUNDC2 in breast cancer is still unclear. In this study, we find that FUNDC2 expression in TNBC tissues is significantly higher than that in luminal subtype breast cancer tissues. FUNDC2 silencing in TNBC cells significantly reduces cell proliferation, migration and invasion. As demonstrated in vivo using subcutaneous tumor xenografts in mice, FUNDC2 suppression significantly inhibits tumor growth. The underlying mechanism might be mediated by inactivating its downstream signal AKT/GSK3β and GLI1, a key factor of the Hedgehog signaling pathway. Therefore, FUNDC2 may promote TNBC progression and provide a therapeutic target for treating TNBC.

Performance of a Handheld MicroNIR Instrument for Determining Protein Levels in Sorghum Grain Samples.

Near infrared (NIR) spectroscopy is widely used for evaluating quality traits of cereal grains. For evaluating protein content of intact sorghum grains, parallel NIR calibrations were developed using an established benchtop instrumentation (Perten DA-7250) as a baseline to test the efficacy of an adaptive handheld instrument (VIAVI MicroNIR OnSite-W). Spectra were collected from 59 grain samples using both instruments at the same time. Cross-validated calibration models were validated with 33 test samples. The selected calibration model for DA-7250 with a coefficient of determination (R2) = 0.98 and a root mean square error of cross validation (RMSECV) = 0.41% predicted the protein content of a test set with R2 = 0.94, root mean square error of prediction (RMSEP) = 0.52% with a ratio of performance to deviation (RPD) of 4.13. The selected model for the MicroNIR with R2 = 0.95 and RMSECV = 0.62% predicted the protein content of the test set with R2 = 0.87, RMSEP = 0.76% with an RPD of 2.74. In comparison, the performance of the DA-7250 was better than the MicroNIR, however, the performance of the MicroNIR was also acceptable for screening intact sorghum grain protein levels. Therefore, the MicroNIR instrument may be used as a potential tool for screening sorghum samples where benchtop instruments are not appropriate such as for screening samples in the field or as a less expensive option compared with benchtop instruments.

Trends in Antibiotic-Resistant Bacteria Isolated from Screening Clinical Samples in a Tertiary Care Hospital over the 2018-2022 Period.

To assess the putative impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria recovered from routine screening samples and, more globally, the trends in time to first positive screening sample and carriage duration of those bacteria in patients admitted to a tertiary hospital, data from laboratory results were retrospectively mined over the 2018-2022 period. No significant differences could be found in the number of positive patients or MDR isolates per year, time to positive screening, or carriage duration. Extended-spectrum beta-lactamase producers were dominant throughout the studied period but their relative proportion decreased over time as well as that of meticillin-resistant Staphylococcus aureus. Meanwhile, carbapenemase-producing enterobacteria (CPE) proportion increased. Among the 212 CPE isolates, Klebsiella pneumoniae and Escherichia coli were the more frequent species but, beginning in 2020, a significant rise in Enterobacter cloacae complex and Citrobacter freundii occurred. OXA48 was identified as the leading carbapenemase and, in 2020, a peak in VIM-producing enterobacteria linked to an outbreak of E. cloacae complex during the COVID-19 pandemic was singled out. Finally, a worrisome rise in isolates producing multiple carbapenemases (NDM/VIM and mostly NDM/OXA48) was highlighted, especially in 2022, which could lead to therapeutic dead-ends if their dissemination is not controlled.

At-Home Self-Collection of Urine or Vaginal Samples for Gonorrhea and Chlamydia Screening Among Young People Who Were Assigned Female at Birth

The U.S. has seen a rise in sexually transmitted infections; the need to increase access to screening is essential to reverse this trend, especially for vulnerable populations such as lesbian, gay, bisexual, and transgender/transsexual plus individuals, people of color, or those at a low SES. This study's primary objective is to assess preferences among people who were assigned female at birth for at-home self-collection for gonorrhea and chlamydia screening. This study aims to provide insight into the need for clinicians to adopt at-home self-collection of urine or vaginal samples to improve access to sexually transmitted infection screening. A recruitment mailer was distributed in September-October 2021. Inclusion criteria included established patients (seen within the last 3 years for clinical services either in person or through telemedicine) at a local urban federally qualified health center in the state of Wisconsin, assigned female at birth, aged 18-24 years, and speaking English language. Participants completed an anonymous online survey regarding their preferences, experiences, and likelihood of self-collecting either urine or vaginal samples for gonorrhea and chlamydia screening at home. Among the total participants (N=88), 69% (n=61) overall preferred home collection for screening with no significance based on age; lesbian, gay, bisexual, and transgender/transsexual plus status; and race and/or ethnicity. However, patients were less likely to prefer at-home self-collection screening if they had lower educational attainment (OR=0.25; 95% CI=0.08, 0.77; p<0.05), lacked insurance (OR=0.19; 95% CI=0.06, 0.67; p<0.05), or were unemployed (OR=0.28; 95% CI=0.08, 0.95; p<0.05). There is overall acceptability for at-home self-collection sexually transmitted infections screening (61 of 88=0.69; 95% CI=0.59, 0.79). Primary care clinics can expand needed screening by integrating such methods into workflows for established patients. Although this study showed that patients who are employed, attained a higher education level, and have their own insurance may prefer at-home self-collection, there is a need to focus on social determinants of health to decrease rising sexually transmitted infection rates in the U.S.

Prevalence of extended-spectrum β-lactamase and carbapenem-resistant Klebsiella pneumoniae in clinical samples.

To assess the prevalence of these resistant strains in the overall isolates of Klebsiella pneumoniae (K. pneumoniae) in hospital settings. This retrospective study was conducted from November 2020 to November 2021. The identification and antibiotic susceptibility testing were performed using standard laboratory methods according to the EUCAST standards. The detection of ESBL and carbapenemase production was performed using phenotypic methods such as E-test, combined-disk test with various inhibitors (ROSCO Diagnostica A/S), chromogenic medium for the detection of ESBL/carbapenemase-producing Enterobacteriaceae (CPE) isolates, and the VITEK 2 Compact system (BioMerieux). 944 isolates of K. pneumoniae were detected in various clinical specimens. Among these, ESBL-producing strains were detected in 349/944 (37%), whereas carbapenem- resistant strains in 188/944 (20%) of the isolates. The remaining isolates (407/944 [43%]) belonged to the wild type. ESBL isolates were the most common in wound swabs (138 [39.5%]), whereas CRKP isolates in screening samples (110 [58.5%]). The majority of ESBL isolates were detected in surgical departments (105 [30.1%]), whereas CRKP isolates in adult intensive care unit departments (79 [42.%]). Our results show an increasing frequency of CRKP strains. This presents a significant issue in terms of infection prevention and control in hospital settings.

Cervical sample-taking in the primary health service

In Norway, approximately 360000 cervical screening samples were taken in 2020, of which 11000 were registered as inadequate. We therefore wished to investigate doctors' knowledge of cervical sample-taking in the primary health service. An anonymous survey on cervical sample-taking was sent by email to around 4700 members of the Norwegian College of General Practice in September 2021. Of the 1039 doctors who responded to the survey, 820 (79%) reported that they always indicate the reason for taking the sample in the requisition form, and 898 (86%) reported that they avoid taking a sample during menstruation. Only one in three doctors (343) correctly indicated the location of the squamocolumnar junction in postmenopausal women. In response to a question aimed at users of the ThinPrep method, which is particularly sensitive to sampling errors, 426 out of 697 (61%) answered that they either avoid using a lubricant or use a water-based lubricant, while only 35% of the doctors responded that they stop taking the sample if bleeding occurs. The results show that although many doctors have satisfactory knowledge, a continuous focus on cervical sample-taking is essential. Correct sampling and knowledge of anatomical factors in postmenopausal women may be significant for reducing the number of inadequate samples.

Evaluation of the Performance of Self-sampling Versus Clinician-collected Sampling for Cervical Cancer Screening

Evaluation of the Performance of Self-sampling Versus Clinician-collected Sampling for Cervical Cancer Screening