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Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.
Methods
By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.
Results
A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.
Conclusions
Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.
Participants and Methods:
64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.
Results:
Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.
Conclusions:
LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.
As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.
This study was a systematic review to investigate the progression of untreated obstructive sleep apnoea in order to evaluate whether mild obstructive sleep apnoea should be treated from the standpoint of disease progression.
Method
The database search study outcomes that were collected included Apnea Hypopnea Index and Respiratory Disturbance Index. A meta-analysis of obstructive sleep apnoea severity over time intervals was performed.
Results
A total of 17 longitudinal studies and 1 randomised, controlled trial were included for review. For patients with mild obstructive sleep apnoea, mean pre-study and post-study Apnea Hypopnea Index was 5.21 and 8.03, respectively, over a median interval of 53.1 months. In patients with moderate to severe obstructive sleep apnoea, mean pre-study and post-study Apnea Hypopnea Index was 28.9 and 30.3, respectively, over a median interval of 57.8 months. Predictors for disease progression in mild obstructive sleep apnoea are patients aged less than 60 years and those with a baseline body mass index less than 25.
Conclusion
Mild obstructive sleep apnoea progression is observed, but it does not appear to reach any clinically significant progression to moderate or severe obstructive sleep apnoea.
In this paper, sliding panels are used to increase the bending stiffness of the classic corrugated flexible skin, and the corresponding application procedure for aircraft structures is developed. After the conceptual design of the corrugated flexible skin with sliding panels is proposed, the analytical models to calculate the equivalent tensile and bending properties are investigated. At the same time, its flexibility in the corrugation direction and the load-bearing capacity (is proportional to the bending stiffness) in the direction perpendicular to corrugation are studied by numerical simulation and experiment. The application procedure is established based on geometric analysis and strain definition, and according to this procedure, the corrugated flexible skin with sliding panels is applied to the drooping leading edge to eliminate the gap on the upper skin. The results show that the corrugated flexible skin with sliding panels has more bending stiffness than the classic corrugated flexible skin in the direction perpendicular to corrugation while maintaining the deform ability in the corrugation direction, and the application procedure is effective and can be applied to other parts of the aircraft structure.
Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks.
Objectives
To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population.
Methods
RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years.
Results
A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses.
Conclusions
RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
The spatio-temporal variation of leaf chlorophyll content is an important crop phenotypic trait that is of great significance for evaluating crop productivity. This study used a soil-plant analysis development (SPAD) chlorophyll meter for non-destructive monitoring of leaf chlorophyll dynamics to characterize the patterns of spatio-temporal variation in the nutritional status of maize (Zea mays L.) leaves under three nitrogen treatments in two cultivars. The results showed that nitrogen levels could affect the maximum leaf SPAD reading (SPADmax) and the duration of high SPAD reading. A rational model was used to measure the changes in SPAD readings over time in single leaves. This model was suitable for predicting the dynamics of the nutrient status for each leaf position under different nitrogen treatments, and model parameter values were position dependent. SPADmax at each leaf decreased with the reduction of nitrogen supply. Leaves at different positions in both cultivars responded differently to higher nitrogen rates. Lower leaves (8th–10th positions) were more sensitive than the other leaves in response to nitrogen. Monitoring the SPAD reading dynamic of lower leaves could accurately characterize and assess the nitrogen supply in plants. The lower leaves in nitrogen-deficient plants had a shorter duration of high SPAD readings compared to nitrogen-sufficient plants; this physiological mechanism should be studied further. In summary, the spatio-temporal variation of plant nitrogen status in maize was analysed to determine critical leaf positions for potentially assisting in the identification of appropriate agronomic management practices, such as the adjustment of nitrogen rates in late fertilization.
To study the effectiveness of unilateral cochlear implantation, binaural-bimodal hearing devices, and bilateral cochlear implantation in children with inner-ear malformation.
Methods
This study comprised 261 patients who were allocated to inner-ear malformation or control groups. Twenty-four months after surgery, aided sound-field thresholds were tested, and the Meaningful Auditory Integration Scale, Infant-Toddler Meaningful Auditory Integration Scale, Meaningful Use of Speech Scale, Categories of Auditory Performance scale and Speech Intelligibility Rating test were completed.
Results
Aided sound-field thresholds were significantly better for bilateral cochlear implantation patients than for unilateral cochlear implantation or binaural-bimodal hearing device patients. There was no significant difference in Meaningful Auditory Integration Scale, Infant-Toddler Meaningful Auditory Integration Scale, or Categories of Auditory Performance scores among the three groups. The binaural-bimodal hearing device patients outperformed unilateral cochlear implantation patients on both Meaningful Use of Speech Scale and Speech Intelligibility Rating scores. No statistical difference was observed between the two subgroups.
Conclusion
Children who received bilateral cochlear implants have the best auditory awareness in a quiet environment. Children with binaural-bimodal hearing devices have better voice control and verbal skills than unilateral cochlear implantation patients, and people are more likely to understand them. Children with inner-ear malformations benefit from cochlear implantation.
Background: The goal of the study was to assess responder rates at various times after initiating atogepant treatment. Methods: A 12-week phase 3 trial evaluated the safety, efficacy, and tolerability of atogepant for preventive treatment of migraine (ADVANCE; NCT03777059) in adult participants with a ≥1-year history of migraine, experiencing 4-14 migraine days/month. Participants were randomized to atogepant 10, 30, or 60mg, or placebo once daily. These analyses evaluated ≥25%, ≥50%, ≥75%, and 100% reductions in mean monthly migraine days (MMDs) across 12 weeks and each 4-week interval. Adverse events (AEs) in ≥5% of participants are reported. Results: The efficacy analysis population included 873 participants: placebo: n=214; atogepant: 10mg: n=214; 30mg: n=223; 60mg: n=222. Atogepant-treated participants were more likely to experience a ≥50% reduction in the 3-month mean MMDs (56-61% vs 29% with placebo; P<0.0001). The proportions of participants experiencing ≥25%, ≥50%, ≥75%, and 100% reductions in mean MMDs significantly increased during each 4-week interval (≥50% reduction: 48-71% vs 27-47% with placebo). The most common AEs for atogepant were constipation (6.9-7.7%) and nausea (4.4-6.1%). Conclusions: Once-daily atogepant 10, 30, and 60mg significantly increased responder rates at all thresholds with approximately 60% achieving a ≥50% reduction in mean MMDs at 12 weeks.
The extent of the reduction of maize (Zea mays L.) kernel moisture content through drying is closely related to field temperature (or accumulated temperature; AT) following maturation. In 2017 and 2018, we selected eight maize hybrids that are widely planted in Northeastern China to construct kernel drying prediction models for each hybrid based on kernel drying dynamics. In the traditional harvest scenario using the optimal sowing date (OSD), maize kernels underwent drying from 4th September to 5th October, with variation coefficients of 1.0–1.9. However, with a latest sowing date (LSD), drying occurred from 14th September to 31st October, with variation coefficients of 1.3–3.0. In the changed harvest scenario, the drying time of maize sown on the OSD condition was from 12th September to 9th November with variation coefficients of 1.3–3.0, while maize sown on the LSD had drying dates of 26th September to 28th October with variation coefficients of 1.5–3.6. In the future harvest scenario, the Fengken 139 (FK139) and Jingnongke 728 (JNK728) hybrids finished drying on 20th October and 8th November, respectively, when sown on the OSD and had variation coefficients of 2.7–2.8. Therefore, the maize kernel drying time was gradually delayed and was associated with an increased demand for AT ⩾ 0°C late in the growing season. Furthermore, we observed variation among different growing seasons likely due to differences in weather patterns, and that sowing dates impact variations in drying times to a greater extent than harvest scenarios.
This study investigated the audiometric and sound localisation results in patients with conductive hearing loss after bilateral Bonebridge implantation.
Method
Eight patients with congenital microtia and atresia supplied with bilateral Bonebridge devices were enrolled in this study. Hearing tests and sound localisation were tested under unaided, unilateral and bilateral aided conditions.
Results
Mean functional gain was higher with a bilateral fitting than with a unilateral fitting, especially at 1.0–4.0 kHz (p < 0.05, both). The improvement in speech reception threshold in noise with a bilateral fitting was a 2.3 dB higher signal-to-noise ratio compared with unilateral fitting (p < 0.05). Bilateral fitting had better sound localisation than unilateral fitting (p <0.001). Four participants who attended follow up showed improved sound localisation ability after one year.
Conclusion
Patients demonstrated better hearing threshold, speech reception thresholds in noise and directional hearing with bilateral Bonebridge devices than with a unilateral Bonebridge device. Sound localisation ability with bilateral Bonebridge devices can be improved through long-term training.
A new near-infrared direct acceleration mechanism driven by Laguerre–Gaussian laser is proposed to stably accelerate and concentrate electron slice both in longitudinal and transversal directions in vacuum. Three-dimensional simulations show that a 2-μm circularly polarized ${\mathrm{LG}}_p^l$ (p = 0, l = 1, σz = −1) laser can directly manipulate attosecond electron slices in additional dimensions (angular directions) and give them annular structures and angular momentums. These annular vortex attosecond electron slices are expected to have some novel applications such as in the collimation of antiprotons in conventional linear accelerators, edge-enhancement electron imaging, structured X-ray generation, and analysis and manipulation of nanomaterials.
Glutamine synthetase (GS) and glutamate synthase (GOGAT) play a central role in plant nitrogen (N) metabolism. In order to study the effect of powdery mildew (Blumeria graminis f. sp. tritici, Bgt) on N metabolism, field experiments were carried out to evaluate GS and GOGAT activity, GS expression and grain protein content (GPC) in susceptible (Xi'nong 979) and resistant (Zhengmai 103) wheat cultivars under three treatments. The three treatments were no inoculation (CK), inoculated once with Bgt (MP) and inoculated nine times with Bgt (HP). For Xi'nong 979, the activities of GS and GOGAT in grains as well as GS activity in flag leaves increased at 10–15 days after anthesis (DAA), and decreased significantly at 15 or 20–30 DAA in HP and MP. However, GS activity in grains decreased from 20 DAA, which was later than that of flag leaves (15 DAA). At the same time, GS expression in grains was up-regulated at early stage, with GS1 at 10 DAA and GS2 at 15 DAA, followed by a continuous down-regulation. This result indicated that GS and GOGAT activity as well as GS expression were inhibited by powdery mildew, indicating that N metabolism in grains was inhibited at 20–30 DAA. The current study also found out that the yield of the susceptible cultivar decreased significantly, while its GPC increased obviously in HP. It was shown that the increase of GPC was not due to the enhancement of N metabolism, but due to the passive increase caused by yield reduction.
The characteristic traits of maize (Zea mays L.) leaves affect light interception and photosynthesis. Measurement or estimation of individual leaf area has been described using discontinuous equations or bell-shaped functions. However, new maize hybrids show different canopy architecture, such as leaf angle in modern maize which is more upright and ear leaf and adjacent leaves which are longer than older hybrids. The original equations and their parameters, which have been used for older maize hybrids and grown at low plant densities, will not accurately represent modern hybrids. Therefore, the aim of this paper was to develop a new empirical equation that captures vertical leaf distribution. To characterize the vertical leaf profile, we conducted a field experiment in Jilin province, Northeast China from 2015 to 2018. Our new equation for the vertical distribution of leaf profile describes leaf length, width or leaf area as a function of leaf rank, using parameters for the maximum value for leaf length, width or area, the leaf rank at which the maximum value is obtained, and the width of the curve. It thus involves one parameter less than the previously used equations. By analysing the characteristics of this new equation, we identified four key leaf ranks (4, 8, 14 and 20) for which leaf parameter values need to be quantified in order to have a good estimation of leaf length, width and area. Together, the method of leaf area estimation proposed here adds versatility for use in modern maize hybrids and simplifies the field measurements by using the four key leaf ranks to estimate vertical leaf distribution in maize canopy instead of all leaf ranks.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
We study the evolution of unidirectional water waves from a randomly forced input condition with uncorrelated Fourier components. We examine the kurtosis of the linearised free surface as a convenient proxy for the probability of a rogue wave. We repeat the laboratory experiments of Onorato et al. (Phys. Rev. E, vol. 70, 2004, 067302), both experimentally and numerically, and extend the parameter space in our numerical simulations. We consider numerical simulations based on the modified nonlinear Schrödinger equation and the fully nonlinear water wave equations, which are in good agreement. For low steepness, existing analytical models based on the nonlinear Schrödinger equation (NLS) are found to be accurate. For cases which are steep or have very narrow bandwidths, these analytical models over-predict the rate at which excess kurtosis develops. In these steep cases, the kurtosis in both our experiments and numerical simulations peaks before returning to an equilibrium level. Such transient maxima are not predicted by NLS-based analytical models. Above a certain threshold of steepness, the steady-state value of kurtosis is primarily dependent on the spectral bandwidth. We also examine how the average shape of extreme events is modified by nonlinearity over the evolution distance, showing significant asymmetry during the initial evolution, which is greatly reduced once the spectrum has reached equilibrium. The locations of the maxima in asymmetry coincide approximately with the locations of the maxima in kurtosis.
Soybean meal is rich in soybean isoflavones, which exhibit antioxidant, anti-inflammatory, antiviral and anticancer functions in humans and animals. This study was conducted to investigate the effects of soybean isoflavones on the growth performance, intestinal morphology and antioxidative properties in pigs. A total of 72 weaned piglets (7.45 ± 0.13 kg; 36 males and 36 females) were allocated into three treatments and fed corn-soybean meal (C-SBM), corn-soy protein concentrate (C-SPC) or C-SPC supplemented with equal levels of the isoflavones found in the C-SBM diet (C-SPC + ISF) for a 72-day trial. Each treatment had six replicates and four piglets per replicate, half male and half female. On day 42, one male pig from each replicate was selected and euthanized to collect intestinal samples. The results showed that compared to pigs fed the C-SPC diet, pigs fed the C-SBM and C-SPC + ISF diets had higher BW on day 72 (P < 0.05); pigs fed the C-SBM diet had significantly higher average daily gain (ADG) during days 14 to 28 (P < 0.05), with C-SPC + ISF being intermediate; pigs fed the C-SBM diet tended to have higher ADG during days 42 to 72 (P = 0.063), while pigs fed the C-SPC + ISF diet had significantly higher ADG during days 42 to 72 (P < 0.05). Moreover, compared to pigs fed the C-SPC diet, pigs fed the C-SBM diet tended to have greater villus height (P = 0.092), while pigs fed the C-SPC + ISF diet had significantly greater villus height (P < 0.05); pigs fed the C-SBM and C-SPC + ISF diets had significantly increased villus height-to-crypt depth ratio (P < 0.05). Compared with the C-SPC diet, dietary C-SPC + ISF tended to increase plasma superoxide dismutase activity on days 28 (P = 0.085) and 42 (P = 0.075) and reduce plasma malondialdehyde (MDA) content on day 42 (P = 0.089), as well as significantly decreased jejunal mucosa MDA content on day 42 (P < 0.05). However, no significant difference in the expression of tight junction genes among the three groups was found (P > 0.05). In conclusion, our results suggest that a long-term exposure to soybean isoflavones enhances the growth performance, protects the intestinal morphology and improves the antioxidative properties in pigs.
Porphyromonas gingivalis has been linked to the development and progression of oesophageal squamous cell carcinoma (ESCC), and is considered to be a high-risk factor for ESCC. Currently, the commonly used methods for P. gingivalis detection are culture or DNA extraction-based, which are either time and labour intensive especially for high-throughput applications. We aimed to establish and evaluate a rapid and sensitive direct quantitative polymerase chain reaction (qPCR) protocol for the detection of P. gingivalis without DNA extraction which is suitable for large-scale epidemiological studies. Paired gingival swab samples from 192 subjects undergoing general medical examinations were analysed using two direct and one extraction-based qPCR assays for P. gingivalis. Tris-EDTA buffer-based direct qPCR (TE-direct qPCR), lysis-based direct qPCR (lysis-direct qPCR) and DNA extraction-based qPCR (kit-qPCR) were used, respectively, in 192, 132 and 60 of these samples for quantification of P. gingivalis. The sensitivity and specificity of TE-direct qPCR was 95.24% and 100% compared with lysis-direct qPCR, which was 100% and 97.30% when compared with kit-qPCR; TE-direct qPCR had an almost perfect agreement with lysis-direct qPCR (κ = 0.954) and kit-qPCR (κ = 0.965). Moreover, the assay time used for TE-direct qPCR was 1.5 h. In conclusion, the TE-direct qPCR assay is a simple and efficient method for the quantification of oral P. gingivalis and showed high sensitivity and specificity compared with routine qPCR.