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  1. [Gene cloning and sequencing of chicken anemia virus(CAV) isolated from Harbin]
    He C, Ding N, Li J, Li Y
    Wei Sheng Wu Xue Bao, 2002 Aug;42(4):436-41.
    PMID: 12557549
    A Chicken anemia virus has been isolated from a chicken flock in Harbin of China. The genome of the ivrus was cloned through polymerase chain reaction(PCR) and sequence of the genome was analyzed. The cycle genome is made of 2298 base pairs including three overlapping open reading frames(vp1, vp2, vp3) and a regulative region. Comparing sequence of the genome through BLAST in GenBank, this sequence exhibits 96.9% identity with other genome of CA Vs and least. Multiple alignment of this genome of this virus, 26p4, strain isolated in Germany, strain isolated in Malaysia and Cux-1 found that this sequence exhibits 98.2% (42/2298), 98.2% (42/2298), 96.9% (72/2298) and 97.5% (60/2319) identify with them, respectively. A new CAV strain was isolated and it has better identify with CAV isolated in Europe countries than is Asia country Malaysia. Multiple alignment of VP1, VP2, VP3 of 26p4, strain isolated in Germany, strain isolated in Malaysia, Cux-1 and strain isolated in Harbin of China found the VP2 the most conservative.
  2. Fulltext The role of ubiquitous metal ions in degradation of microplastics in hot-compressed water
    Vo TP, Rintala J, Dai L, Oh WD, He C
    Water Res, 2023 Oct 15;245:120672.
    PMID: 37783176 DOI: 10.1016/j.watres.2023.120672
    Hydrothermal processing (HTP) is an efficient thermochemical technology to achieve sound treatment and resource recovery of sewage sludge (SS) in hot-compressed subcritical water. However, microplastics (MPs) and heavy metals can be problematic impurities for high-quality nutrients recovery from SS. This study initiated hydrothermal degradation of representative MPs (i.e., polyethylene (PE), polyamide (PA), polypropylene (PP)) under varied temperatures (180-300 °C) to understand the effect of four ubiquitous metal ions (i.e., Fe3+, Al3+, Cu2+, Zn2+) on MPs degradation. It was found that weight loss of all MPs in metallic reaction media was almost four times of that in water media, indicating the catalytic role of metal ions in HTP. Especially, PA degradation at 300 °C was promoted by Fe3+ and Al3+ with remarkable weight loss higher than 95% and 92%, respectively, which was ca. 160 °C lower than that in pyrolysis. Nevertheless, PE and PP were more recalcitrant polymers to be degraded under identical condition. Although higher temperature thermal hydrolysis reaction induced severe chain scission of polymers to reinforce degradation of MPs, Fe3+ and Al3+ ions demonstrated the most remarkable catalytic depolymerization of MPs via enhanced free radical dissociation rather than hydrolysis. Pyrolysis gas chromatography-mass spectrometry (Py GC-MS) was further complementarily applied with GC-MS to reveal HTP of MPs to secondary MPs and nanoplastics. This fundamental study highlights the crucial role of ubiquitous metal ions in MPs degradation in hot-compressed water. HTP could be an energy-efficient technology for effective treatment of MPs in SS with abundant Fe3+ and Al3+, which will benefit sustainable recovery of cleaner nutrients in hydrochar and value-added chemicals or monomers from MPs.
  3. Effect of metal doping (Me = Zn, Cu, Co, Mn) on the performance of bismuth ferrite as peroxymonosulfate activator for ciprofloxacin removal
    Koo PL, Choong ZY, He C, Bao Y, Jaafar NF, Oh WD
    Chemosphere, 2023 Mar;318:137915.
    PMID: 36702411 DOI: 10.1016/j.chemosphere.2023.137915
    In this study, a facile hydrothermal method was employed to prepare Me-doped Bi2Fe4O9 (Me = Zn, Cu, Co, and Mn) as peroxymonosulfate (PMS) activator for ciprofloxacin (CIP) degradation. The characteristics of the Me-doped bismuth ferrites were investigated using various characterization instruments including SEM, TEM, FTIR and porosimeter indicating that the Me-doped Bi2Fe4O9 with nanosheet-like square orthorhombic structure was successfully obtained. The catalytic activity of various Me-doped Bi2Fe4O9 was compared and the results indicated that the Cu-doped Bi2Fe4O9 at 0.08 wt.% (denoted as BFCuO-0.08) possessed the greatest catalytic activity (kapp = 0.085 min-1) over other Me-doped Bi2Fe4O9 under the same condition. The synergistic interaction between Cu, Fe and oxygen vacancies are the key factors which enhanced the performance of Me-doped Bi2Fe4O9. The effects of catalyst loading, PMS dosage, and pH on CIP degradation were also investigated indicating that the performance increased with increasing catalyst loading, PMS dosage, and pH. Meanwhile, the dominant reactive oxygen species was identified using the chemical scavengers with SO4•-, •OH, and 1O2 playing a major role in CIP degradation. The performance of BFCuO-0.08 deteriorated in real water matrix (tap water, river water and secondary effluent) due to the presence of various water matrix species. Nevertheless, the BFCuO-0.08 catalyst possessed remarkable stability and can be reused for at least four successive cycles with >70% of CIP degradation efficiency indicating that it is a promising catalyst for antibiotics removal.
  4. Fulltext Sustainable utilization of Sedum plumbizincicola as superior hydrochar for efficient nutrients recovery
    Zhang R, Zhang Y, Goei R, Oh WD, Zhang Z, He C
    J Environ Manage, 2023 Oct 15;344:118441.
    PMID: 37379626 DOI: 10.1016/j.jenvman.2023.118441
    To realize sound disposal of hyperaccumulator harvested from phytoremediation, hydrothermal carbonization (HTC) has been employed to obtain superior hydrochar adsorbents for removal of phosphate and ammonium from water body. A series of hydrochars have been prepared under tuned HTC conditions to tailor hydrochar with desired properties. Generally, increased temperature and prolonged reaction time facilitated acidic oxygen functional groups on hydrochars, thereby improving adsorption capacity of hydrochar. In single solute system, a superior hydrochar, derived from HTC under 260 °C for 2 h, achieved a maximum phosphate and ammonium adsorption capacity of 52.46 mg/g and 27.56 mg/g at 45 °C, respectively. In binary system, synergistic adsorption was observed only in lower solute concentration, whereas competitive adsorption occurred under higher solute concentration. Characterization and adsorption kinetics suggested chemisorption may dominate the adsorption process, thus the adsorption capacity could be improved by tuning pHpzc of hydrochar. This study firstly demonstrates the sustainable utilization of hyperaccumulators into nutrients-enriched hydrochar as fertilizer for in-situ phytoremediation of contaminated sites with minimized environmental risks towards circular economy.
  5. Recent advances in catalyst design, performance, and challenges of metal-heteroatom-co-doped biochar as peroxymonosulfate activator for environmental remediation
    Manickavasagam G, He C, Lin KA, Saaid M, Oh WD
    Environ Res, 2024 Apr 16;252(Pt 2):118919.
    PMID: 38631468 DOI: 10.1016/j.envres.2024.118919
    The escalation of global water pollution due to emerging pollutants has gained significant attention. To address this issue, catalytic peroxymonosulfate (PMS) activation technology has emerged as a promising treatment approach for effectively decontaminating a wide range of pollutants. Recently, modified biochar has become an increasingly attractive as PMS activator. Metal-heteroatom-co-doped biochar (MH-BC) has emerged as a promising catalyst that can provide enhanced performance over heteroatom-doped and metal-doped biochar due to the synergism between metal and heteroatom in promoting PMS activation. Therefore, this review aims to discuss the fabrication pathways (i.e., internal vs external doping and pre-vs post-modification) and key parameters (i.e., source of precursors, synthesis methods, and synthesis conditions) affecting the performance of MH-BC as PMS activator. Subsequently, an overview of all the possible PMS activation pathways by MH-BC is provided. Subsequently, Also, the detection, identification, and quantification of several reactive species (such as, •OH, SO4•-, O2•-, 1O2, and high valent oxo species) generated in the catalytic PMS system by MH-BC are also evaluated. Lastly, the underlying challenges associated with poor stability, the lack of understanding regarding the interaction between metal and heteroatom during PMS activation and quantification of radicals in multi-ROS system are also deliberated.
  6. Fulltext Emergence and adaptive evolution of Nipah virus
    Li K, Yan S, Wang N, He W, Guan H, He C, et al.
    Transbound Emerg Dis, 2020 Jan;67(1):121-132.
    PMID: 31408582 DOI: 10.1111/tbed.13330
    Since its first emergence in 1998 in Malaysia, Nipah virus (NiV) has become a great threat to domestic animals and humans. Sporadic outbreaks associated with human-to-human transmission caused hundreds of human fatalities. Here, we collected all available NiV sequences and combined phylogenetics, molecular selection, structural biology and receptor analysis to study the emergence and adaptive evolution of NiV. NiV can be divided into two main lineages including the Bangladesh and Malaysia lineages. We formly confirmed a significant association with geography which is probably the result of long-term evolution of NiV in local bat population. The two NiV lineages differ in many amino acids; one change in the fusion protein might be involved in its activation via binding to the G protein. We also identified adaptive and positively selected sites in many viral proteins. In the receptor-binding G protein, we found that sites 384, 386 and especially 498 of G protein might modulate receptor-binding affinity and thus contribute to the host jump from bats to humans via the adaption to bind the human ephrin-B2 receptor. We also found that site 1645 in the connector domain of L was positive selected and involved in adaptive evolution; this site might add methyl groups to the cap structure present at the 5'-end of the RNA and thus modulate its activity. This study provides insight to assist the design of early detection methods for NiV to assess its epidemic potential in humans.
  7. Fulltext [Key processes and progress in phytomining of nickel contaminated soils: a review]
    Geng K, Sun S, Huang Z, Huang C, Wu C, Deng T, et al.
    Sheng Wu Gong Cheng Xue Bao, 2020 Mar 25;36(3):436-449.
    PMID: 32237538 DOI: 10.13345/j.cjb.200023
    Phytomining technology cultivates hyperaccumulator plants on heavy metal contaminated soils, followed by biomass harvesting and incineration to recover valuable metals, offering an opportunity for resource recycling and soil remediation. Large areas of ultramafic soils, naturally rich in nickel (Ni), are present in numerous places around the world. As an environmentally friendly and cost-effective soil remediation technology, phytomining has a broad application prospect in such areas and thus has attracted great attention from global researchers. The key processes of phytomining include: (1) high-selectivity response of hyperaccumulator plants to Ni the underlying mechanisms involved in the rhizosphere; (2) underlying mechanisms of high-efficiency uptake and translocation of Ni in hyperaccumulators; and (3) resource recycling of high-added value Ni products from the Ni-rich bio-ore of hyperaccumulators. In recent 30 years, phytomining practices have successfully carried out in United States, Albania and Malaysia. However, the research and application of this technology in China are still in the fledging stage. This paper reviews the key processes and research progress of phytomining, and points out the bottleneck, to provide theoretical basis and technical guidance for phytomining.
  8. H3PO4 activation mediated the iron phase transformation and enhanced the removal of bisphenol A on iron carbide-loaded activated biochar
    Zhao N, Liu K, He C, Zhao D, Zhu L, Zhao C, et al.
    Environ Pollut, 2022 Feb 05;300:118965.
    PMID: 35134429 DOI: 10.1016/j.envpol.2022.118965
    Zero valent iron-loaded biochar (Fe0-BC) has shown promise for the removal of various organic pollutants, but is restricted by reduced specific surface area, low utilization efficiency and limited production of reactive oxygen species (ROS). In this study, iron carbide-loaded activated biochar (Fe3C-AB) with a high surface area was synthesized through the pyrolysis of H3PO4 activated biochar with Fe(NO3)3, tested for removing bisphenol A (BPA) and elucidated the adsorption and degradation mechanisms. As a result, H3PO4 activated biochar was beneficial for the transformation of Fe0 to Fe3C. Fe3C-AB exhibited a significantly higher removal rate and removal capacity for BPA than that of Fe0-BC within a wide pH range of 5.0-11.0, and its performance was maintained even under extremely high salinity and different water sources. Moreover, X-ray photoelectron spectra and density functional theory calculations confirmed that hydrogen bonds were formed between the COOH groups and BPA. 1O2 was the major reactive species, constituting 37.0% of the removal efficiency in the degradation of BPA by Fe3C-AB. Density functional reactivity theory showed that degradation pathway 2 of BPA was preferentially attacked by ROS. Thus, Fe3C-AB with low cost and excellent recycling performance could be an alternative candidate for the efficient removal of contaminants.
  9. The organism fate of inland freshwater system under micro-/nano-plastic pollution: A review of past decade
    Liang J, Xiong S, He C, Song Z, Yang S, Ma D, et al.
    Aquat Toxicol, 2023 Dec;265:106774.
    PMID: 38000134 DOI: 10.1016/j.aquatox.2023.106774
    Micro- and nano-plastics (MPs/NPs) are characterized by their small size and extensive surface area, making them global environmental pollutants with adverse effects on organisms at various levels, including organs, cells, and molecules. Freshwater organisms, such as microalgae, emerging plants, zooplankton, benthic species, and fish, experience varying impacts from MPs/NPs, which are prevalent in both terrestrial and aquatic inland environments. MPs/NPs significantly impact plant physiological processes, including photosynthesis, antioxidant response, energy metabolism, and nitrogen removal. Extended exposure and ingestion to MPs/NPs might cause metabolic and behavioral deviations in zooplankton, posing an extinction risk. Upon exposure to MPs/NPs, both benthic organisms and fish display behavioral and metabolic disturbances, due to oxidative stress, neural toxicity, intestinal damage, and metabolic changes. Results from laboratory and field investigations have confirmed that MPs/NPs can be transported across multiple trophic levels. Moreover, MPs/NPs-induced alterations in zooplankton populations can impede energy transfer, leading to food scarcity for filter-feeding fish, larvae of benthic organism and fish, thus jeopardizing aquatic ecosystems. Furthermore, MPs/NPs can harm the nervous systems of aquatic organisms, influencing their feeding patterns, circadian rhythms, and mobility. Such behavioral alterations might also introduce unforeseen ecological risks. This comprehensive review aims to explore the consequences of MPs/NPs on freshwater organisms and their interconnected food webs. The investigation encompasses various aspects, including behavioral changes, alterations in physiology, impacts on metabolism, transgenerational effects, and the disruption of energy transfer within the ecosystem. This review elucidated the physiological and biochemical toxicity of MPs/NPs on freshwater organisms, and the ensuing risks to inland aquatic ecosystems.
  10. Predictors of job burnout among Chinese nurses: a systematic review based on big data analysis
    Xia M, Wang J, Bi D, He C, Mao H, Liu X, et al.
    Biotechnol Genet Eng Rev, 2023 Jan 22.
    PMID: 36683283 DOI: 10.1080/02648725.2023.2168910
    Job burnout is an occupational hazard induced by prolonged exposure to excessive work-related stress -a state of physical or emotional exhaustion that also involves a sense of reduced accomplishment and loss of personal identity. Knowledge jobs involve many health-promoting features, but stress and burnout may be caused by the rapid increase in the knowledge intensity of work, new job demands, and emerging new professional subcultures emphasizing the excessive commitment to work. Although there are studies on job burnout and predictors among nurses worldwide, evidence specific to Chinese nurses is lacking. The purpose of this review is to synthesize current research on predictors related to burnout affecting Chinese nurses. We searched the Chinese databases including National Knowledge Infrastructure (CNKI), WanFang, China Science and Technology Journal Database, and Chinese Biological Medical Database (CBM); and international databases including Cochrane Library, PubMed, EMBASE, and Web of Science published up to 30th August 2022. The 125 studies identified assessed a range of predictors of job burnout. The results showed good working relationships and internally controlled individuals were found to be predictive of job burnout. Moreover, numerous predictors produced contradictory data. There are still challenges with how to systematically operationalize such a complicated phenomenon to effectively prevent or reduce job burnout.
  11. Genomic bacterial load associated with bacterial genotypes and clinical characteristics in patients with scrub typhus in Hainan Island, Southern China
    Wang G, Fu R, Zhang L, Xue L, Al-Mahdi AY, Xie X, et al.
    PLoS Negl Trop Dis, 2023 Apr 21;17(4):e0011243.
    PMID: 37083859 DOI: 10.1371/journal.pntd.0011243
    Scrub typhus, caused by mite-borne Orientia tsutsugamushi (O. tsutsugamushi), is a major febrile disease in the Asia-Pacific region. The DNA load of O. tsutsugamushi in the blood was previously found to be significantly higher in patients with fatal disease than those with non-fatal disease and correlated with the duration of illness, presence of eschar, and hepatic enzyme levels. In this prospective observation study, we analyzed the association of bacterial DNA load with clinical features, disease severity, and genotype using real-time PCR targeting the 56 kDa TSA gene of O. tsutsugamushi in the blood samples of 117 surviving patients with scrub typhus who had not received appropriate antibiotic treatment. The median O. tsutsugamushi DNA load was 3.11×103 copies/mL (range, 44 to 3.3×106 copies/mL). The severity of patients was categorized as mild, moderate, and severe based on the number of dysfunctional organs, and no significant difference in O. tsutsugamushi DNA load was found among these groups. Patients infected with the Karp group showed a significantly higher O. tsutsugamushi DNA load than those in the Gilliam (P 
  12. Comparison of the accuracy of the 7-item HADS Depression subscale and 14-item total HADS for screening for major depression: A systematic review and individual participant data meta-analysis
    Wu Y, Levis B, Daray FM, Ioannidis JPA, Patten SB, Cuijpers P, et al.
    Psychol Assess, 2023 Feb;35(2):95-114.
    PMID: 36689386 DOI: 10.1037/pas0001181
    The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
  13. Fulltext The Accuracy of the Patient Health Questionnaire-9 Algorithm for Screening to Detect Major Depression: An Individual Participant Data Meta-Analysis
    He C, Levis B, Riehm KE, Saadat N, Levis AW, Azar M, et al.
    Psychother Psychosom, 2020;89(1):25-37.
    PMID: 31593971 DOI: 10.1159/000502294
    BACKGROUND: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results.

    OBJECTIVE: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10.

    METHODS: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview.

    RESULTS: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88).

    CONCLUSIONS: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

  14. Probability of major depression diagnostic classification based on the SCID, CIDI and MINI diagnostic interviews controlling for Hospital Anxiety and Depression Scale - Depression subscale scores: An individual participant data meta-analysis of 73 primary studies
    Wu Y, Levis B, Sun Y, Krishnan A, He C, Riehm KE, et al.
    J Psychosom Res, 2020 02;129:109892.
    PMID: 31911325 DOI: 10.1016/j.jpsychores.2019.109892
    OBJECTIVE: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D).

    METHODS: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores.

    RESULTS: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)).

    CONCLUSION: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity.

  15. Fulltext Data-Driven Cutoff Selection for the Patient Health Questionnaire-9 Depression Screening Tool
    Levis B, Bhandari PM, Neupane D, Fan S, Sun Y, He C, et al.
    JAMA Netw Open, 2024 Nov 04;7(11):e2429630.
    PMID: 39576645 DOI: 10.1001/jamanetworkopen.2024.29630
    IMPORTANCE: Test accuracy studies often use small datasets to simultaneously select an optimal cutoff score that maximizes test accuracy and generate accuracy estimates.

    OBJECTIVE: To evaluate the degree to which using data-driven methods to simultaneously select an optimal Patient Health Questionnaire-9 (PHQ-9) cutoff score and estimate accuracy yields (1) optimal cutoff scores that differ from the population-level optimal cutoff score and (2) biased accuracy estimates.

    DESIGN, SETTING, AND PARTICIPANTS: This study used cross-sectional data from an existing individual participant data meta-analysis (IPDMA) database on PHQ-9 screening accuracy to represent a hypothetical population. Studies in the IPDMA database compared participant PHQ-9 scores with a major depression classification. From the IPDMA population, 1000 studies of 100, 200, 500, and 1000 participants each were resampled.

    MAIN OUTCOMES AND MEASURES: For the full IPDMA population and each simulated study, an optimal cutoff score was selected by maximizing the Youden index. Accuracy estimates for optimal cutoff scores in simulated studies were compared with accuracy in the full population.

    RESULTS: The IPDMA database included 100 primary studies with 44 503 participants (4541 [10%] cases of major depression). The population-level optimal cutoff score was 8 or higher. Optimal cutoff scores in simulated studies ranged from 2 or higher to 21 or higher in samples of 100 participants and 5 or higher to 11 or higher in samples of 1000 participants. The percentage of simulated studies that identified the true optimal cutoff score of 8 or higher was 17% for samples of 100 participants and 33% for samples of 1000 participants. Compared with estimates for a cutoff score of 8 or higher in the population, sensitivity was overestimated by 6.4 (95% CI, 5.7-7.1) percentage points in samples of 100 participants, 4.9 (95% CI, 4.3-5.5) percentage points in samples of 200 participants, 2.2 (95% CI, 1.8-2.6) percentage points in samples of 500 participants, and 1.8 (95% CI, 1.5-2.1) percentage points in samples of 1000 participants. Specificity was within 1 percentage point across sample sizes.

    CONCLUSIONS AND RELEVANCE: This study of cross-sectional data found that optimal cutoff scores and accuracy estimates differed substantially from population values when data-driven methods were used to simultaneously identify an optimal cutoff score and estimate accuracy. Users of diagnostic accuracy evidence should evaluate studies of accuracy with caution and ensure that cutoff score recommendations are based on adequately powered research or well-conducted meta-analyses.

  16. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
    Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  17. Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1
    Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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