Sources of performance variability in deep learning-based polyp detection.

PURPOSE: Validation metrics are a key prerequisite for the reliable tracking of scientific progress and for deciding on the potential clinical translation of methods. While recent initiatives aim to develop comprehensive theoretical frameworks for understanding metric-related pitfalls in image analysis problems, there is a lack of experimental evidence on the concrete effects of common and rare pitfalls on specific applications. We address this gap in the literature in the context of colon cancer screening. METHODS: Our contribution is twofold. Firstly, we present the winning solution of the Endoscopy Computer Vision Challenge on colon cancer detection, conducted in conjunction with the IEEE International Symposium on Biomedical Imaging 2022. Secondly, we demonstrate the sensitivity of commonly used metrics to a range of hyperparameters as well as the consequences of poor metric choices. RESULTS: Based on comprehensive validation studies performed with patient data from six clinical centers, we found all commonly applied object detection metrics to be subject to high inter-center variability. Furthermore, our results clearly demonstrate that the adaptation of standard hyperparameters used in the computer vision community does not generally lead to the clinically most plausible results. Finally, we present localization criteria that correspond well to clinical relevance. CONCLUSION: We conclude from our study that (1) performance results in polyp detection are highly sensitive to various design choices, (2) common metric configurations do not reflect the clinical need and rely on suboptimal hyperparameters and (3) comparison of performance across datasets can be largely misleading. Our work could be a first step towards reconsidering common validation strategies in deep learning-based colonoscopy and beyond.

Study of the effect of photon self-absorption on the detection efficiency of HPGe detector in measurements of an activated uranium sample.

The photon self-absorption effect of uranium on the full-energy peak (FEP) efficiency calibration of high purity germanium (HPGe) detector was studied as a function of energy using an activated uranium sample has a thickness of 1 mm. The absolute efficiencies of the detector were obtained with the use of gamma standard sources and gamma rays of radionuclides created by irradiating the uranium sample with secondary neutrons. The measurements were carried out with the use of a Planar HPGe detector. MCNP simulation code was used to verify the experimental results. The comparison of the empirical results with the simulation results showed a good agreement. To interpret the efficiencies, the reaction rates were calculated using two methods: (1) - the use of the efficiency curve from the standard sources combined with the self-absorption correction of the uranium material and (2) - the use of the efficiency curve obtained from gamma rays in the sample.

Correction: Recombinant Lloviu virus as a tool to study viral replication and host responses.

[This corrects the article DOI: 10.1371/journal.ppat.1010268.].

Recombinant Lloviu virus as a tool to study viral replication and host responses.

Next generation sequencing has revealed the presence of numerous RNA viruses in animal reservoir hosts, including many closely related to known human pathogens. Despite their zoonotic potential, most of these viruses remain understudied due to not yet being cultured. While reverse genetic systems can facilitate virus rescue, this is often hindered by missing viral genome ends. A prime example is Lloviu virus (LLOV), an uncultured filovirus that is closely related to the highly pathogenic Ebola virus. Using minigenome systems, we complemented the missing LLOV genomic ends and identified cis-acting elements required for LLOV replication that were lacking in the published sequence. We leveraged these data to generate recombinant full-length LLOV clones and rescue infectious virus. Similar to other filoviruses, recombinant LLOV (rLLOV) forms filamentous virions and induces the formation of characteristic inclusions in the cytoplasm of the infected cells, as shown by electron microscopy. Known target cells of Ebola virus, including macrophages and hepatocytes, are permissive to rLLOV infection, suggesting that humans could be potential hosts. However, inflammatory responses in human macrophages, a hallmark of Ebola virus disease, are not induced by rLLOV. Additional tropism testing identified pneumocytes as capable of robust rLLOV and Ebola virus infection. We also used rLLOV to test antivirals targeting multiple facets of the replication cycle. Rescue of uncultured viruses of pathogenic concern represents a valuable tool in our arsenal for pandemic preparedness.

Stroke Thrombectomy in Patients with COVID-19: Initial Experience in 13 Cases.

We performed a retrospective review in both comprehensive stroke units of a region affected early by the coronavirus disease 2019 (COVID-19) pandemic, between March 1 and April 26, 2020, including patients with COVID-19 who underwent mechanical thrombectomy for ischemic stroke. We identified 13 cases, representing 38.2% of 34 thrombectomies performed during this period. We observed increased mortality and a high incidence of thrombotic complications during hospitalization. Given the high rate of infected patients, systematic use of full personal protection measures seems justified.

Influence of type of dwelling on the prevalence of chronic respiratory diseases in Ho Chi Minh City, Viet Nam.

SETTING and OBJECTIVE: Exposure to pollutants is related to the type of dwelling inhabited. Besides tobacco smoke, indoor air pollution is a significant risk factor for chronic respiratory disease (CRD). The prevalence of CRD by type of dwelling was studied in Ho Chi Minh City, Viet Nam.DESIGN: A total of 1561 people living in four type of dwellings were enrolled. Information on respiratory health, lung function, dwelling characteristics and sources of indoor pollution was obtained using a symptom and demographics questionnaire and spirometry. The two main respiratory health outcomes were clinical chronic CRD (CCRD) and chronic obstructive respiratory disease (CORD) (forced expiratory volume in 1 sec/forced vital capacity <0.7). We used binary logistic regression adjusted for age, sex, time spent at home, smoking status, certain occupational exposures, previous tuberculosis, presence of pets, rats or cockroaches at home, wall dampness, biofuel use and use of airconditioning.RESULTS: The prevalence of CCRD (24.3%) and CORD (5.3%) in the type of dwellings studied were not similar (χ² P < 0.0001). CCRD and CORD prevalence was similar in tube houses and apartments. Compared to people living in apartments, those living in rental single rooms had a 46% higher risk of developing CCRD. The odds ratio of having CORD in people living in rental single rooms and in rural houses were respectively 4.64 (95%CI 1.97-10.5) and 2.99 (95%CI 1.21-7.37).CONCLUSION: Type of dwelling was associated with CCRD and CORD morbidity.

Two-step system consisting of novel vertical flow and free water surface constructed wetland for effective sewage treatment and reuse.

This study developed a unique system by combining the novel vertical flow (NVF) using expanded clay (ExC) and free flow surface constructed wetland (FWS) for dormitory sewage purification and reuse. The NVF tank consisted of filter layers of ExC, sandy soil, sand, and gravel. The FWS consisted of sandy soil substrate and was installed after the NVF. Colocasia esculenta and Dracaena sanderiana was planted in NVF and FWS, respectively. The treatment system was operated and tested for more than 21 weeks by increasing the hydraulic loading rate (HLR) from 0.02 m/d to 0.12 m/d. The results demonstrated that effluents in the system changed proportionally to the HLRs, except for nitrate nitrogen. Furthermore, the maximum removal efficiencies for TSS, BOD5, NH4-N, and Tcol were 76 ± 13%, 74 ± 11%, 90 ± 3%, and 59 ± 18% (0.37 ± 0.19 log10MPN/100 mL), respectively. At HLRs of 0.04-0.06 m/d, the treatment system satisfied the limits of agriculture irrigation.

Molecular epidemiology of noroviruses detected in Vietnamese children with acute gastroenteritis from 2012 to 2015.

Noroviruses, an important cause of diarrhoea in humans, are genetically diverse. The recent norovirus seasons recorded the emergence of new recombinants of the capsid and polymerase genotypes, with a global dominance of GII.Pe_GII.4 Sydney 2012 and GII.P17_GII.17 in Asian countries. However, the number of papers reporting the distribution of both polymerase and capsid genotypes circulating among children is scarce, with none from Vietnam. This study described both the polymerase and capsid genotypes of noroviruses circulating in Vietnamese children using stool specimens obtained under the World Health Organization rotavirus surveillance programme from 2012 to 2015. Of 350 specimens tested, noroviruses were detected in 90 (28 %) of 319 inpatient specimens and in 9 (29 %) of 31 outpatient specimens. The polymerase and capsid genotype combinations of GII.Pe_GII.4 Sydney 2012 and GII.P21_GII.3 were co-dominant (51 and 24 %, respectively), both of which were recombinants, contributing to a high proportion (87 %) of recombinants among circulating noroviruses. GII.4 variants evolved in the same fashion in Vietnam as in other countries, with amino acid substitutions in the putative variant-specific epitopes of the protruding domain. Unlike neighbouring countries where the predominance of GII.P17_GII.17 was reported, only one GII.P17_GII.17 strain was detected from an outpatient in 2015 in Vietnam. In conclusion, a substantial burden due to norovirus gastroenteritis hospitalizations among Vietnamese children was associated with circulating co-dominant GII.Pe_GII.4 Sydney 2012 and GII.P21_GII.3 strains. Continued surveillance is necessary to monitor infection caused by GII.4 variants and that of GII.P17_GII.17 noroviruses in paediatric patients in Vietnam.

Effect of the stiffness of bone substitutes on the biomechanical behaviour of femur for core decompression.

Core decompression is the most common procedure for treatment of the early stages of osteonecrosis of the femoral head. The purpose of this study was to compare the biomechanical performance of four different bone graft substitutes combined with core decompression. Subject-specific finite element models generated from computed tomography (CT) scan data were used for a comprehensive analysis. Two different contact conditions were simulated representing states of osseointegration at the interface. Our results showed that the use of a low-stiffness bone substitute did not increase the risk of femoral fracture in the early postoperative phase, but resulted in less micromotion and interfacial stresses than high-stiffness bone substitutes.

Micro-scale finite element modeling of ultrasound propagation in aluminum trabecular bone-mimicking phantoms: A comparison between numerical simulation and experimental results.

The present study investigated the accuracy of micro-scale finite element modeling for simulating broadband ultrasound propagation in water-saturated trabecular bone-mimicking phantoms. To this end, five commercially manufactured aluminum foam samples as trabecular bone-mimicking phantoms were utilized for ultrasonic immersion through-transmission experiments. Based on micro-computed tomography images of the same physical samples, three-dimensional high-resolution computational samples were generated to be implemented in the micro-scale finite element models. The finite element models employed the standard Galerkin finite element method (FEM) in time domain to simulate the ultrasonic experiments. The numerical simulations did not include energy dissipative mechanisms of ultrasonic attenuation; however, they expectedly simulated reflection, refraction, scattering, and wave mode conversion. The accuracy of the finite element simulations were evaluated by comparing the simulated ultrasonic attenuation and velocity with the experimental data. The maximum and the average relative errors between the experimental and simulated attenuation coefficients in the frequency range of 0.6-1.4 MHz were 17% and 6% respectively. Moreover, the simulations closely predicted the time-of-flight based velocities and the phase velocities of ultrasound with maximum relative errors of 20 m/s and 11 m/s respectively. The results of this study strongly suggest that micro-scale finite element modeling can effectively simulate broadband ultrasound propagation in water-saturated trabecular bone-mimicking structures.

Abrupt emergence and predominance in Vietnam of rotavirus A strains possessing a bovine-like G8 on a DS-1-like background.

An apparently single rotavirus A strain possessing a genotype constellation of G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 abruptly emerged, caused diarrhoea in children requiring hospitalisation, and increased to reach 27 % of strains detected during the first half of 2015 in Vietnam.

The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients.

BACKGROUND: Psychological factors are known to significantly modulate itch in patients suffering from chronic itch. Itch is also highly susceptible to both placebo and nocebo (negative placebo) effects. Brain activity likely supports nocebo-induced itch, but is currently unknown. METHODS: We collected functional MRI (fMRI) data from atopic dermatitis (AD) patients, in a within-subject design, and contrast brain response to nocebo saline understood to be allergen vs open-label saline control. Exploratory analyses compared results to real allergen itch response and placebo responsiveness, evaluated in the same patients. RESULTS: Nocebo saline produced greater itch than open saline control (P < 0.01). Compared to open saline, nocebo saline demonstrated greater fMRI response in caudate, dorsolateral prefrontal cortex (dlPFC), and intraparietal sulcus (iPS) - brain regions important for cognitive executive and motivational processing. Exploratory analyses found that subjects with greater dlPFC and caudate activation to nocebo-induced itch also demonstrated greater dlPFC and caudate activation, respectively, for real allergen itch. Subjects reporting greater nocebo-induced itch also demonstrated greater placebo reduction of allergen-evoked itch, suggesting increased generalized modulation of itch perception. CONCLUSIONS: Our study demonstrates the capacity of nocebo saline to mimic both the sensory and neural effects of real allergens and provides an insight to the brain mechanisms supporting nocebo-induced itch in AD, thus aiding our understanding of the role that expectations and other psychological factors play in modulating itch perception in chronic itch patients.

Remote effects of lower limb ischemia-reperfusion: impaired lung, unchanged liver, and stimulated kidney oxidative capacities.

Remote organ impairments are frequent and increase patient morbidity and mortality after lower limb ischemia-reperfusion (IR). We challenged the hypothesis that lower limb IR might also impair lung, renal, and liver mitochondrial respiration. Two-hour tourniquet-induced ischemia was performed on both hindlimbs, followed by a two-hour reperfusion period in C57BL6 mice. Lungs, liver and kidneys maximal mitochondrial respiration (V(max)), complexes II, III, and IV activity (V(succ)), and complex IV activity (V(TMPD)) were analyzed on isolated mitochondria. Lower limb IR decreased significantly lung V(max) (29.4 ± 3.3 versus 24 ± 3.7 µmol O2/min/g dry weight, resp.; P = 0.042) and tended to reduce V(succ) and V(TMPD). IR did not modify liver but increased kidneys mitochondrial respiration (79.5 ± 19.9 versus 108.6 ± 21.4, P = 0.035, and 126 ± 13.4 versus 142.4 ± 10.4 µmol O2/min/g dry weight for V(max) and V(succ), resp.). Kidneys mitochondrial coupling was increased after IR (6.5 ± 1.3 versus 8.8 ± 1.1, P = 0.008). There were no histological changes in liver and kidneys. Thus, lung mitochondrial dysfunction appears as a new early marker of hindlimb IR injuries in mice. Further studies will be useful to determine whether enhanced kidneys mitochondrial function allows postponing kidney impairment in lower limb IR setting.

Alterations of insulin-like growth factor-1 receptor gene copy number and protein expression are common in non-small cell lung cancer.

AIMS: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase membrane receptor involved in tumourigenesis that may be a potential therapeutic target. We aimed to investigate the incidence and prognostic significance of alterations in IGF1R copy number, and IGF1R protein expression in resected primary non-small cell lung cancer (NSCLC), and lymph node metastases. METHODS: IGF1R gene copy number status was evaluated by chromogenic silver in situ hybridisation and IGF1R protein expression was evaluated by immunohistochemistry in tissue microarray sections from a retrospective cohort of 309 surgically resected NSCLCs and results were compared with clinicopathological features, including EGFR and KRAS mutational status and patient survival. RESULTS: IGF1R gene copy number status was positive (high polysomy or amplification) in 29.2% of NSCLC, and 12.1% exhibited IGF1R gene amplification. High IGF1R expression was found in 28.3%. There was a modest correlation between IGF1R gene copy number and protein expression (r=0.2, p<0.05). Alterations of IGF1R gene copy number and protein expression in primary tumours were significantly associated with alterations in lymph node metastases (p<0.01). High IGF1R gene copy number and protein expression was significantly higher in squamous cell carcinomas (SCC) compared with other subtypes of NSCLC (p<0.05). There were no other associations between IGF1R status and other clinicopathological features including patient age, gender, smoking status, tumour size, stage, grade, EGFR or KRAS mutational status or overall survival. CONCLUSIONS: High IGF1R gene copy number and protein overexpression are frequent in NSCLC, particularly in SCCs, but they are not prognostically relevant.

Experimental and computational studies on the femoral fracture risk for advanced core decompression.

BACKGROUND: Two questions are often addressed by orthopedists relating to core decompression procedure: 1) Is the core decompression procedure associated with a considerable lack of structural support of the bone? and 2) Is there an optimal region for the surgical entrance point for which the fracture risk would be lowest? As bioresorbable bone substitutes become more and more common and core decompression has been described in combination with them, the current study takes this into account. METHODS: Finite element model of a femur treated by core decompression with bone substitute was simulated and analyzed. In-vitro compression testing of femora was used to confirm finite element results. FINDINGS: The results showed that for core decompression with standard drilling in combination with artificial bone substitute refilling, daily activities (normal walking and walking downstairs) are not risky for femoral fracture. The femoral fracture risk increased successively when the entrance point is located further distal. The critical value of the deviation of the entrance point to a more distal part is about 20mm. INTERPRETATION: The study findings demonstrate that optimal entrance point should locate on the proximal subtrochanteric region in order to reduce the subtrochanteric fracture risk. Furthermore the consistent results of finite element and in-vitro testing imply that the simulations are sufficient.

The first identification of rotavirus B from children and adults with acute diarrhoea in kathmandu, Nepal.

Rotavirus B (RVB) in the genus Rotavirus of the family Reoviridae is known to be a cause of acute gastroenteritis among children and adults in parts of Asia including China, India, Bangladesh and Myanmar. In a 15-month surveillance programme between March 2007 and May 2008, 3,080 stool specimens were collected from children and adults with acute gastroenteritis in an infectious disease hospital in Kathmandu, Nepal. In 25 (0.8%) specimens RVB was detected, for the first time in Nepal, by the use of polyacrylamide gel electrophoresis followed by confirmation with reverse-transcription PCR and sequencing. The strains detected in this study had very similar electropherotypes, and their VP7 sequences were almost identical and phylogenetically belonged to the Indo-Bangladeshi lineage which was distinct from the Chinese lineage. Thus, this study showed the circulation of RVB strains belonging to the Indo-Bangladeshi lineage in a broader region than previously documented, suggesting that this phylogenetic divide corresponded to the geographic divide created by the Himalayan Mountains. Further studies may be warranted to identify and characterize the RVB strains in northern Vietnam which is adjacent to southern China with a long and less mountainous border.

Use of the bootstrap and permutation methods for a more robust variable importance in the projection metric for partial least squares regression.

Bio-pharmaceutical manufacturing is a multifaceted and complex process wherein the manufacture of a single batch hundreds of processing variables and raw materials are monitored. In these processes, identifying the candidate variables responsible for any changes in process performance can prove to be extremely challenging. Within this context, partial least squares (PLS) has proven to be an important tool in helping determine the root cause for changes in biological performance, such as cellular growth or viral propagation. In spite of the positive impact PLS has had in helping understand bio-pharmaceutical process data, the high variability in measured response (Y) and predictor variables (X), and weak relationship between X and Y, has at times made root cause determination for process changes difficult. Our goal is to demonstrate how the use of bootstrapping, in conjunction with permutation tests, can provide avenues for improving the selection of variables responsible for manufacturing process changes via the variable importance in the projection (PLS-VIP) statistic. Although applied uniquely to the PLS-VIP in this article, the generality of the aforementioned methods can be used to improve other variable selection methods, in addition to increasing confidence around other estimates obtained from a PLS model.

Evidence for Genetic Reassortment between Human Rotaviruses by Full Genome Sequencing of G3P[4] and G2P[4] Strains Co-circulating in India.

Rotavirus A causes severe diarrhoea in infants and young children worldwide. Many unusual combinations of G and P genotypes have been observed in rotaviruses circulating in developing countries. Mixed infection of a single individual with more than one strain is a mechanism by which genetic reassortants are formed with unusual G and P combinations. However, few studies have provided direct evidence for the formation of such unusual strains as a result of co-infection of co-circulating strains. Here, we used full-genome sequencing to re-analyze a G3P[4] strain (107E1B) and a G2P[4] strain (116E3D) detected in India in 1993 and showed that 107E1B had virtually an identical nucleotide sequence with 116E3D, except the VP7 gene. Phylogenetic analysis revealed that the 107E1B VP7 gene was of typical human rotavirus origin, with a 99.3% nucleotide sequence identity with another Indian G3 VP7 gene. Thus, this study provided robust evidence for the formation of the G3P[4] strain through genetic reassortment in which a G2P[4] strain with a typical DS-1 genogroup background acquired the VP7 gene from a co-circulating G3 human rotavirus strain. This study established a basis on which to facilitate full genome sequence analysis of an increasing number of G3P[4] strains in China and elsewhere in the world.

Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: global distribution of genogroups, genotypes and GII.4 variants.

Noroviruses are a leading cause of epidemic and sporadic acute gastroenteritis worldwide. The development of sensitive molecular diagnostic techniques has revolutionized our understanding of norovirus epidemiology over the past two decades, but norovirus strain types associated with sporadic gastroenteritis remain poorly described. Therefore, we conducted a systematic review of studies performed after 2000 to clarify the genotypic distribution of noroviruses in children (≤18 years of age) with sporadic acute gastroenteritis. Genogroup GII norovirus was the most prevalent, accounting for 96% of all sporadic infections. GII.4 was the most prevalent genotype, accounting for 70% of the capsid genotypes and 60% of the polymerase genotypes, followed by the capsid genotype GII.3 (16%) and the polymerase genotype GII.b (14%). The most common ORF1/ORF2 inter-genotype recombinants were GII.b, GII.12, and GII.4 polymerase genotypes combined with the capsid genotype GII.3, accounting for 19% of all genotyped strains. The distribution of GII.4 variants over the last decade was dominated by successive circulation of GII.4/2002, GII.4/2004, GII.4/2006b, and GII.4/2008 with GII.4/2006b continuing to date. Genotypes GII.4 and GII.3 have predominated in children during the past decade; this is most notable in the global emergence of GII.4 variant noroviruses. As the burden of rotavirus disease decreases following the introduction of childhood immunization programs, the relative importance of norovirus in the etiology of acute childhood gastroenteritis will likely increase. In order for a successful norovirus vaccine to be developed, it should provide immunity against strains with capsid genotypes GII.4 and GII.3.

Finite element modelling of stapled colorectal end-to-end anastomosis: advantages of variable height stapler design.

The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.