As one of the major approaches in combating the COVID-19 pandemics, the availability of specific and reliable assays for the SARS-CoV-2 viral genome and its proteins is essential to identify the ...infection in suspected populations, make diagnoses in symptomatic or asymptomatic individuals, and determine clearance of the virus after the infection. For these purposes, use of the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) for detection of the viral nucleic acid remains the most valuable in terms of its specificity, fast turn-around, high-throughput capacity, and reliability. It is critical to update the sequences of primers and probes to ensure the detection of newly emerged variants. Various assays for increased levels of IgG or IgM antibodies are available for detecting ongoing or past infection, vaccination responses, and persistence and for identifying high titers of neutralizing antibodies in recovered individuals. Viral genome sequencing is increasingly used for tracing infectious sources, monitoring mutations, and subtype classification and is less valuable in diagnosis because of its capacity and high cost. Nanopore target sequencing with portable options is available for a quick process for sequencing data. Emerging CRISPR-Cas-based assays, such as SHERLOCK and AIOD-CRISPR, for viral genome detection may offer options for prompt and point-of-care detection. Moreover, aptamer-based probes may be multifaceted for developing portable and high-throughput assays with fluorescent or chemiluminescent probes for viral proteins. In conclusion, assays are available for viral genome and protein detection, and the selection of specific assays depends on the purposes of prevention, diagnosis and pandemic control, or monitoring of vaccination efficacy.
During the COVID-19 pandemics, sensitive and reliable assays for SARS-CoV-2 detection are essential for screening the population, identifying asymptomatic individuals, making diagnoses, monitoring treatment responses, and determining viral clearance. This review summarizes the principles, advantages, disadvantages, and specific applications of currently available assays for detection of the viral nucleotide, genome or proteins, as well as host antibody responses, and provide overall guidelines for selection of optimal assays for specific usage.
Abstract
The supernova remnant (SNR) 30 Dor B is associated with the H
ii
region ionized by the OB association LH99. The complex interstellar environment has made it difficult to study the physical ...structure of this SNR. We have used Hubble Space Telescope H
α
images to identify SNR shocks and deep Chandra X-ray observations to detect faint diffuse emission. We find that 30 Dor B hosts three zones with very different X-ray surface brightnesses and nebular kinematics that are characteristic of SNRs in different interstellar environments and/or evolutionary stages. The ASKAP 888 MHz map of 30 Dor B shows counterparts to all X-ray emission features except the faint halo. The ASKAP 888 and 1420 MHz observations are used to produce a spectral index map, but its interpretation is complicated by the background thermal emission and the pulsar PSR J0537−6910's flat spectral index. The stellar population in the vicinity of 30 Dor B indicates a continuous star formation in the past 8–10 Myr. The observed very massive stars in LH99 cannot be coeval with the progenitor of 30 Dor B’s pulsar. Adopting the pulsar’s spin-down timescale, 5000 yr, as the age of the SNR, the X-ray shell would be expanding at ∼4000 km s
−1
and the post-shock temperature would be 1–2 orders of magnitude higher than that indicated by the X-ray spectra. Thus, the bright central region of 30 Dor B and the X-ray shell requires two separate SN events, and the faint diffuse X-ray halo perhaps other older SN events.
One of the most promising strategies for the management of plastic waste is microbial biodegradation, but efficient degraders for many types of plastics are still lacking, including those for ...polystyrene (PS). Genomics has emerged as a powerful tool for mining environmental microbes that may have the ability to degrade different types of plastics. In this study, we use 16S rRNA sequencing to analyze the microbiomes for multiple PS samples collected from sites with different vegetation in Taiwan to reveal potential common properties between species that exhibit growth advantages on PS surfaces. Phylum enrichment analysis identified Cyanobacteria and Deinococcus-Thermus as being the most over-represented groups on PS, and both phyla include species known to reside in extreme environments and could encode unique enzymes that grant them properties suitable for colonization on PS surfaces. Investigation of functional enrichment using reference genomes of PS-enriched species highlighted carbon metabolic pathways, especially those related to hydrocarbon degradation. This is corroborated by the finding that genes encoding long-chain alkane hydroxylases such as AlmA are more prevalent in the genomes of PS-associated bacteria. Our analyses illustrate how plastic in the environment support the colonization by different microbes compared to surrounding soil. In addition, our results point to the possibility that alkane hydroxylases could confer growth advantages of microbes on PS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Leprosy, caused by Mycobacterium leprae, affects over 200,000 people annually worldwide and remains endemic in the ethnically diverse, mountainous and underdeveloped southwestern provinces of China. ...Delayed diagnosis of leprosy persists in China, thus, additional knowledge to support early diagnosis, especially early diagnosis of paucibacillary (PB) patients, based on the host immune responses induced by specific M. leprae antigens is needed. The current study aimed to investigate leprosy patients and controls in Southwest China by comparing supernatants after stimulation with specific M. leprae antigens in an overnight whole-blood assay (WBA) to determine whether host markers induced by specific M. leprae antigens improve the diagnosis or discrimination of PB patients with leprosy.
Leprosy patients 13 multibacillary (MB) patients and 7 PB patients and nonleprosy controls 21 healthy household contacts (HHCs), 20 endemic controls (ECs) and 19 tuberculosis (TB) patients were enrolled in this study. The supernatant levels of ten host markers stimulated by specific M. leprae antigens were evaluated by overnight WBA and multiplex Luminex assays. The diagnostic value in PB patients and ECs and the discriminatory value between PB patients and HHCs or TB patients were evaluated by receiver operator characteristics (ROC) analysis. ML2044-stimulated CXCL8/IL-8 achieved the highest sensitivity of 100%, with a specificity of 73.68%, for PB diagnosis. Compared to single markers, a 3-marker combination model that included ML2044-induced CXCL8/IL-8, CCL4/MIP-1 beta, and IL-6 improved the diagnostic specificity to 94.7% for PB patients. ML2044-stimulated IL-4 and CXCL8/IL-8 achieved the highest sensitivity (85.71% and 100%) and the highest specificity (95.24% and 84.21%) for discriminating PB patients from HHCs and TB patients, respectively.
Our findings suggest that the host markers induced by specific M. leprae antigens in an overnight WBA increase diagnostic and discriminatory value in PB patients with leprosy, with a particularly strong association with interleukin 8.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate antigen-specific immune responses for leprosy diagnosis in a hyperendemic area in China.
Eighty-three leprosy patients and 161 non-leprosy controls were enrolled from Hani-yi Autonomous ...Prefecture of Honghe, Yunnan Province, China. Leprosy patients were divided into multibacillary (MB, n = 38), paucibacillary (PB, n = 23), and post-multi-drug therapy (MDT, n = 22) groups. Controls were divided into the following groups: healthy household contacts (HHC, n = 119), tuberculosis (TB, n = 11), and endemic controls (EC, n = 31). The NDO-LID Rapid Test, M. leprae antigen-specific ELISA and antigen-specific IFN-γ secretion in a whole blood assay (WBA) were used to evaluate these subjects.
The NDO-LID Rapid Test achieved higher positive response rates in MB than in PB patients94.7%(36/38) vs 65.2%(15/23), and these rates were higher than those observed by ELISA using anti-LID-192.1%(35/38) vs 52.2%(12/23), anti-NDO-LID92.1%(35/38) vs 47.8% (11/23), and anti-ND-O-BSA89.5%(34/38) vs 60.9%(14/23). However, the NDO-LID Rapid Test also showed a higher positive response rate in the EC group (33.3%,10/31), which was higher than the rates observed for anti-NDO-LID (12.9%,4/31) and anti-ND-O-BSA (16.1%,5/31). M. leprae antigen-specific ELISA demonstrated relatively high specificity (86.84-97.37%) but low sensitivity (15.97-72.73%) in discriminating between leprosy patients and non-leprosy controls by ROC curve analysis. In contrast, M. leprae antigen-specific IFN-γ secretion detection achieved higher positive response rates in PB than in MB patients (positive ratio of MB vs PB: 40% vs 56% for LID-1, 28.6% vs 47.8% for ML89, 31.4% vs 60.7% for ML2044, and 31.4 vs 47.8% for ML2028) and could distinguish MB from EC when stimulated with ML89(AUC = 0.6664) and PB fromTB when stimulated with ML2044 and ML2028(AUC = 0.7549 and 0.7372, respectively).
The NDO-LID Rapid Test and M. leprae antigen-specific ELISA are useful tools to assist in the diagnosis of leprosy patients, especially MB patients, although the former had higher sensitivity but lower specificity than the latter. M. leprae antigen-specific IFN-γ release assessed by WBA has diagnostic value for distinguishing PB from TB but not for distinguishing PB from HHC or EC. Screening novel M. leprae-specific antigens, combining different M. leprae antigens and a multi-cytokine analyte model may be needed for more effective diagnosis of leprosy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We aimed to identify an unique host transcriptional signature in peripheral blood mononuclear cells (PBMCs) in response to
antigens to distinguish between patients with leprosy and non-leprosy ...controls for early diagnosis of the disease. Sixteen individuals were enrolled in the discovery cohort eight patients with leprosy, comprising four multibacillary (MB) and four paucibacillary (PB); and eight non-leprosy controls, comprising four healthy house contacts (HHCs) and four endemic controls (ECs). The differences in the transcriptome response of PBMCs to
sonicate antigen were evaluated between leprosy patients and non-leprosy controls, and 12 differentially expressed genes (
,
,
,
,
,
,
,
,
,
, and
) were identified. The accuracy of the 12 differentially expressed genes was further validated for the diagnosis of leprosy using real-time quantitative PCR in 82 individuals (13 MB, 10 PB, 37 HHCs, and 22 ECs) in the validation cohort. We found that a 5 gene signature set
,
,
,
and
had a suitable performance in discriminating leprosy from ECs. In addition, elevated expression of
,
,
and
was associated with MB diagnosis compared with ECs, whereas increased expression of
,
,
and
was found to be useful biomarkers for PB diagnosis from ECs. Moreover, we found decreased expression of
among leprosy patients could distinguish leprosy from HHCs, whereas higher expression of
among MB than PB could distinguish different leprosy patients. In conclusion, among the 12 candidate host genes identified, a three gene signature
, and
showed the best performance in distinguishing leprosy patients from healthy controls. These findings may have implications for developing a rapid blood-based test for early diagnosis of leprosy.
Background
The thoracic radiotherapy (TRT) target volume for limited‐stage small‐cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective ...randomized trial on the TRT target volume before and after induction chemotherapy are presented.
Methods
After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved‐field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded.
Results
The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow‐up of 54.1 months (range, 19.9‐165.0 months) in survivors, the 3‐year local/regional progression‐free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was −7.3% (95% CI, −18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5‐year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out‐of‐field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy.
Conclusions
TRT could be limited to the postchemotherapy tumor volume, and involved‐field radiotherapy could be routinely applied for limited‐stage SCLC.
This is the only phase 3 study on thoracic radiotherapy target volumes for limited‐stage small‐cell lung cancer using modern radiotherapy facilities. Radiation dosimetric and pathologic analyses are also performed to interpret the clinical findings.
The chemokine CCL5 plays a potential role in the occurrence and development of colorectal cancer (CRC). Previous studies have shown that CCL5 directly acts on tumor cells to change tumor metastatic ...rates. In addition, CCL5 recruits immune cells and immunosuppressive cells into the tumor microenvironment (TME) and reshapes the TME to adapt to tumor growth or increase antitumor immune efficacy, depending on the type of secretory cells releasing CCL5, the cellular function of CCL5 recruitment, and the underlying mechanisms. However, at present, research on the role played by CCL5 in the occurrence and development of CRC is still limited, and whether CCL5 promotes the occurrence and development of CRC and its role remain controversial. This paper discusses the cells recruited by CCL5 in patients with CRC and the specific mechanism of this recruitment, as well as recent clinical studies of CCL5 in patients with CRC.
Key Messages
CCL5 plays dual roles in colorectal cancer progression.
CCL5 remodels the tumor microenvironment to adapt to colorectal cancer tumor growth by recruiting immunosuppressive cells or by direct action.
CCL5 inhibits colorectal cancer tumor growth by recruiting immune cells or by direct action.
Aims. The protoplanetary disk around HL Tau is the youngest candidate of planet formation known to date, and it is still embedded in a protostellar envelope with a size of thousands of au. In this ...work, we study the gas kinematics in the envelope and its possible influence on the embedded disk. Methods. We present our new ALMA cycle 3 observational results of HL Tau in the 13CO (2–1) and C18O (2–1) emission at resolutions of 0.̋8 (110 au), and we compare the observed velocity pattern with models of different types of gas motion. Results. The 13CO and C18O emission lines both show a central compact component with a size of 2″ (280 au) that traces the protoplanetary disk. The disk is clearly resolved and shows Keplerian motion, based on which, the protostellar mass of HL Tau is estimated to be 1.8 ± 0.3 M⊙, assuming the inclination angle of the disk to be 47° from the plane of the sky. The 13CO emission shows two arc structures with sizes of 1000–2000 au and masses of 3 × 10-3M⊙ connected to the central disk. One is blueshifted and stretches from the northeast to the northwest, and the other is redshifted and stretches from the southwest to the southeast. We find that simple kinematical models of infalling and (counter-)rotating flattened envelopes cannot fully explain the observed velocity patterns in the arc structures. The gas kinematics of the arc structures can be better explained with three-dimensional infalling or outflowing motions. Nevertheless, the observed velocity in the northwestern part of the blueshifted arc structure is ~60–70% higher than the expected free-fall velocity. We discuss two possible origins of the arc structures: (1) infalling flows externally compressed by an expanding shell driven by XZ Tau; and (2) outflowing gas clumps caused by gravitational instabilities in the protoplanetary disk around HL Tau.
Unhealthy gestational weight gain is a modifiable risk factor for adverse maternal and child health. Appropriate and effective intervention strategies that focus on behavioral change or maintenance ...are critical in weight management during pregnancy. Our aim was to uncover the influencing factors and psychosocial mechanisms of gestational weight control behavior, and to construct a behavioral model suitable for intervention based on Information-Motivation-Behavioral skills (IMB) model.
A sample of 559 pregnant women from a municipal maternal and child healthcare facility in Jiangsu Province, China was enrolled in this cross-sectional empirical study. Partial least square structural equation modelling was used to verify the hypothesized model, and post hoc analyses was used to test the effect of parity and pre-pregnancy BMI on the model.
The IMB model elements can predict gestational weight management (GWM) behavior well, with information being the most influential factor. As predicted, information affects GWM directly (β = 0.325, p < 0.05) and indirectly (β = 0.054, p < 0.05) through behavioral skills. Likewise, motivation has direct (β = 0.461, p < 0.05) effects on GWM, and has indirect (β = 0.071, p < 0.05) effects through behavioral skills. Behavioral skills have a direct impact (β = 0.154, p < 0.05). The model had a goodness of fit (GOF = 0.421) and was robust when tested in subgroups of different parity or pre-pregnancy BMI.
Findings from this study supported the predictions of the IMB model for GWM behavior, and identified its modifiable determinants. The tested behavior model for GWM can serve as a new validated intervention strategy in weight management among pregnant women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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