Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses.

Viral infections induce a conserved host response distinct from bacterial infections. We hypothesized that the conserved response is associated with disease severity and is distinct between patients with different outcomes. To test this, we integrated 4,780 blood transcriptome profiles from patients aged 0 to 90 years infected with one of 16 viruses, including SARS-CoV-2, Ebola, chikungunya, and influenza, across 34 cohorts from 18 countries, and single-cell RNA sequencing profiles of 702,970 immune cells from 289 samples across three cohorts. Severe viral infection was associated with increased hematopoiesis, myelopoiesis, and myeloid-derived suppressor cells. We identified protective and detrimental gene modules that defined distinct trajectories associated with mild versus severe outcomes. The interferon response was decoupled from the protective host response in patients with severe outcomes. These findings were consistent, irrespective of age and virus, and provide insights to accelerate the development of diagnostics and host-directed therapies to improve global pandemic preparedness.

Author Correction: Mapping the world's free-flowing rivers.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mapping the world's free-flowing rivers.

Free-flowing rivers (FFRs) support diverse, complex and dynamic ecosystems globally, providing important societal and economic services. Infrastructure development threatens the ecosystem processes, biodiversity and services that these rivers support. Here we assess the connectivity status of 12 million kilometres of rivers globally and identify those that remain free-flowing in their entire length. Only 37 per cent of rivers longer than 1,000 kilometres remain free-flowing over their entire length and 23 per cent flow uninterrupted to the ocean. Very long FFRs are largely restricted to remote regions of the Arctic and of the Amazon and Congo basins. In densely populated areas only few very long rivers remain free-flowing, such as the Irrawaddy and Salween. Dams and reservoirs and their up- and downstream propagation of fragmentation and flow regulation are the leading contributors to the loss of river connectivity. By applying a new method to quantify riverine connectivity and map FFRs, we provide a foundation for concerted global and national strategies to maintain or restore them.

DeepHost: phage host prediction with convolutional neural network.

Next-generation sequencing expands the known phage genomes rapidly. Unlike culture-based methods, the hosts of phages discovered from next-generation sequencing data remain uncharacterized. The high diversity of the phage genomes makes the host assignment task challenging. To solve the issue, we proposed a phage host prediction tool-DeepHost. To encode the phage genomes into matrices, we design a genome encoding method that applied various spaced $k$-mer pairs to tolerate sequence variations, including insertion, deletions, and mutations. DeepHost applies a convolutional neural network to predict host taxonomies. DeepHost achieves the prediction accuracy of 96.05% at the genus level (72 taxonomies) and 90.78% at the species level (118 taxonomies), which outperforms the existing phage host prediction tools by 10.16-30.48% and achieves comparable results to BLAST. For the genomes without hits in BLAST, DeepHost obtains the accuracy of 38.00% at the genus level and 26.47% at the species level, making it suitable for genomes of less homologous sequences with the existing datasets. DeepHost is alignment-free, and it is faster than BLAST, especially for large datasets. DeepHost is available at https://github.com/deepomicslab/DeepHost.

Terahertz manipulation of nonlinear optical response in topological material PtBi2.

The substantial nonlinear optical response observed in numerous topological materials renders them well-suited for optic and photonic applications, underscoring the critical need to devise effective strategies for manipulating their nonlinearity to enhance their versatility across different applications. In this Letter, we focus on the second-harmonic generation (SHG) response of the topological material PtBi2 under intense terahertz (THz) pulses and unveil the transient nonlinearity manipulated by a THz electric field. Our findings demonstrate that upon excitation of an intense THz pulse, there emerges a substantial enhancement in the SHG signal of PtBi2, which is predominantly attributed to the linear term involving the THz field, i.e., χ(2)χ(3)ETHz. We also clearly observe the transient change in the nonlinear coefficients, which could arise from the excitation of the bands with linear dispersion via the intense THz pulse. These findings bear significant implications for achieving ultrafast modulation of nonlinearity in topological materials, thereby opening avenues for advanced applications in this field.

Properties of Cosmic Deuterons Measured by the Alpha Magnetic Spectrometer.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above ∼13 GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

Natural disasters: a comprehensive study using EMDAT database 1995-2022.

INTRODUCTION: The frequency, intensity, and geographical reach of natural disasters, fueled in part by factors such as climate change, population growth, and urbanization, have undeniably been escalating concerns around the world. DESIGN AND METHODS: This is a retrospective analysis of natural disasters recorded in the Emergency Events Database from 1995 to 2022. RESULTS: Between 1995 and 2022, 11,360 natural disasters occurred, with a mean of 398 per year. Asia experienced the most disasters (4390) and the highest number of casualties (918,198). Hydrological disasters were the most common subgroup (4969), while geophysical disasters led in terms of deaths (770,644). Biological disasters caused the most injuries (2544), particularly in Africa. CONCLUSION: Recognizing the historical impacts of the various subtypes of natural disasters may help different regions better risk analyze and mitigate the unique risks associated with such events.

[Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma].

Objective: To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma. Methods: The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model. Results: Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome (HR=8.50,95% CI: 1.679-8.328,P=0.001), serum albumin (HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy (HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions: Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

[Effect of changes in posterior tibial slope on the mid-term clinical outcomes of Oxford unicompartmental knee arthroplasty].

Objective: To investigate the impact of changes in the posterior tibial slope (PTS) in Oxford unicompartmental knee arthroplasty (OUKA) on the mid-term clinical outcomes of postoperative patients. Methods: This study was a follow-up study. The data of 135 patients (150 knees) who underwent OUKA at the China-Japan Friendship Hospital from January 2012 to January 2013 were analyzed retrospectively. The patients were followed-up for at least ten years. According to the changes in PTS of the medial tibial plateau before and after surgery, patients were divided into three groups: group A (PTS decreased by more than 5°), group B (PTS changed by 5° or less), and group C (PTS increased by more than 5°). The Knee Society Clinical Score (KSS-C), Knee Society Functional Score (KSS-F), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), and knee range of motion (ROM) among the three groups were compared at the last follow-up. Results: Prior to the final follow-up assessment, six patients expired, and an additional nine patients were lost to follow-up. A total of 120 patients (135 knees) were enrolled in this study (30 males and 90 females). The mean age was (66.29±8.62) years, and the follow-up time was (10.54±0.72) years. Group A consisted of 32 patients (34 knees), group B comprised 77 patients (90 knees), and group C included 11 patients (11 knees). One knee in group A suffered prosthesis loosening, and two knees in group C experienced postoperative bearing dislocation, one knee encountered bearing fragmentation. The incidence of postoperative complications differed significantly among the three groups (P<0.05). The preoperative OKS was (33.91±6.59) points, KSS-F was (43.46±8.99) points, KSS-C was (41.05±5.70) points and ROM was 115.23°±13.53°; after the surgery, they changed to (18.82±7.01) points, (81.51±7.34) points, (82.64±7.94) points, and 119.07°±8.62°, respectively, and all the differences were statistically significant (all P<0.001). In terms of postoperative outcomes, group A had an OKS of (21.44±8.46) points and a FJS of (63.83±11.40) points, group B had an OKS of (17.07±5.81) points and a FJS of (70.49±12.45) points, group C had an OKS of (25.09±5.07) points and a FJS score of (59.48±10.09) points; the differences among the three groups were all statistically significant (all P<0.05), but there were no significant differences in the postoperative KSS scores and ROM among the three groups (all P>0.05). Conclusions: After OUKA, better mid-term clinical outcomes are achieved when ΔPTS is<5°. Although the recommended central value for PTS in OUKA is 7° according to Oxford, it should be individualized, and it is recommended to consider the preoperative angle, with a change of less than 5° before and after surgery.

[Application of EXODUS system combined with allosteric DNA nanoswitches in the detection of miR-107 among plasma exosomes of Parkinson's disease patients].

This study aimed to achieve rapid detection of Parkinson's disease (PD) plasma exosome miR-107. A case-control design was used to collect ten Parkinson's disease and ten healthy control plasma samples from the Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from December 2023 to January 2024. Exosome detection via the ultrafast-isolation system (EXODUS) was used to isolate plasma exosomes. The nanoparticle tracking analysis technology and electron microscopy were used to identify exosome particle size and morphology. The Qiagen miRNeasy Micro Kit was used to extract RNA. The microRNA-activated conditional looping of engineered switches (miRacles) was used to detect miR-107, and the relative expression was analyzed by agarose gel electrophoresis. Thermo Fisher RevertAid RT Reverse Transcription Kit was used to perform reverse transcription of RNA, and real-time PCR was used to detect miR-107. The independent samples t-test was used for comparison between groups. EXODUS system completed the isolation of exosomes from 500 µl plasma within 1.5 hours. The exosome concentration (mean±SD) was (4.82±2.02)×1010 particles/ml in the control group and (5.08±2.34)×1010 particles/ml in the PD group. There was no significant difference in exosome concentration between PD patients and healthy controls (t=-0.168, P=0.872). The morphology of exosomes was confirmed by electron microscopy. The miRacles nanoswitch could detect fM-level miR-107 and also effectively distinguish miR-107 from its family members, including miR-15a and miR-16. Agarose gel electrophoresis showed that the mean±SD of relative grey value content was 1.00±0.26 in the control group and 1.86±0.21 in the PD group. The miR-107 in the PD group was significantly higher than that in the control (t=-8.143, P<0.001), which was consistent with the result of real-time PCR. EXODUS combined with miRacles could achieve rapid, non-enzymatic and cheap detection of plasma exosomal miR-107 in PD patients.

[Long-term prophylactic therapy combined with on-demand therapy for the control of hereditary angioedema--Comment on the 2021 edition of the international WAO/EAACI guideline for the management of hereditary angioedema].

The 2021 edition of the international World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) guideline for the management of hereditary angioedema (HAE) is mainly based on high-quality randomized controlled trials. It provides clinical classification for HAE and offers graded recommendations for on-demand therapy, short-term prophylactic therapy, and long-term prophylactic therapy. Additionally, it provides management strategies for people with different HAE types. This article focused on the interpretation of short-term, long-term prophylactic therapy and on-demand therapy for HAE, supplemented with the latest clinical evidence, aiming to provide references for the long-term management of HAE.

[Several key and difficult issues related to the grading of urothelial carcinoma of urinary bladder].

Grading and staging are the most important prognostic factors for both non-invasive and invasive urothelial carcinomas, and are also one of the most common difficulties encountered by pathologists in the daily diagnostic practice of urothelial carcinoma. Recently, the International Society of Urological Pathology organized a survey and questionnaire conference on various issues related to the diagnosis, grading, and staging of urothelial carcinoma, and ultimately formed a series of consensus opinions. This article briefly summarizes the consensus opinions of this series, and combines them with the current pathological diagnosis status of urothelial carcinoma in China. It briefly comments on how to apply this series of consensus opinions in the daily diagnostic practice of pathologists, deeply understand relevant diagnostic problems, and carry out relevant clinical pathological research to further solve problems.

[Pituitary Crooke cell neuroendocrine tumor of adrenocorticotropic hormone differentiation-specific transcription factor lineage: a clinicopathological analysis of six cases].

Objective: To investigate the clinicopathological features of Crooke cell tumor of adrenocorticotropic hormone differentiation specific transcription factor (TPIT, also known as transcription factor 19, TBX19) lineage neuroendocrine tumors. Methods: Six cases of Crooke cell tumor diagnosed at the First Affiliated Hospital of University of Science and Technology of China, Hefei, China from October 2019 to October 2023 were collected. The clinical and pathological features of these cases were analyzed. Results: Among the six cases, one was male and five were female, with ages ranging from 26 to 75 years, and an average age of 44 years. All tumors occurred within the sella turcica. Clinical presentations included visual impairment in two cases, menstrual disorders in one case, Cushing's syndrome in one case, headache in one case, and one asymptomatic case discovered during a physical examination. Preoperative serum analyses revealed elevated levels of cortisol and adrenocorticotropic hormones in two cases, elevated cortisol in two cases, elevated adrenocorticotropic hormone in one case, and one case with a mild increase in prolactin due to the pituitary stalk effect. Magnetic resonance imaging revealed uneven enhancement of masses with maximum diameters ranging from 1.7 to 3.2 cm, all identified as macroadenomas. Microscopically, tumor cells exhibited irregular polygonal shapes, solid sheets, or pseudo-papillary arrangements around blood vessels. The cell nuclei were eccentric or centrally located, varying in size, with abundant cytoplasm. Some tumor cells showed perinuclear halo. Immunohistochemistry demonstrated diffuse strong positivity for TPIT in five cases, focal weak positivity for TPIT in one case, diffuse strong positivity for adrenocorticotropic hormone in all cases, and faint staining around the nuclei in a few cells. CK8/18 showed a strong positive ring pattern in more than 50% of tumor cells, focal weak positive expression of p53, and the Ki-67 positive index ranged 1%-5%. Periodic acid-Schiff staining revealed positive cytoplasm and negative perinuclear areas. Conclusions: Crooke cell tumor is a rare type of pituitary neuroendocrine tumors. Its pathological characteristics include a distinctive perinuclear clear zone and immunohistochemical markers, such as CK8/18 exhibiting a ring or halo pattern. This entity represents a high-risk subtype among pituitary neuroendocrine tumors, displaying a high risk of invasion and a propensity for recurrence. Accurate diagnosis is crucial for the postoperative follow-up and multimodal treatment planning.

[Comparison and analysis of ophthalmic resources and service ability in Shanxi Province in 2014 and 2021].

Objective: To compare and analyze the ophthalmic resources and service ability in Shanxi Province in 2014 and 2021, and to provide reference for the development planning of ophthalmology and eye care. Methods: In this cross-sectional study, a questionnaire survey was conducted among all ophthalmic institutions registered in the health administrative department in 11 cities of Shanxi Province by the end of 2014 and 2021 by using the National Ophthalmology Competency Resource Questionnaire (compiled by the Medical Administration and Hospital Authority of the National Health and Wellness Commission). The basic situations of ophthalmic institutions in 2014 and 2021, as well as the human resources, ophthalmic equipment configuration, technology and medical service capabilities, were recorded and compared. The chi-square test was used for statistical analysis. Results: A total of 270 questionnaires for 2014 were collected from 270 ophthalmic institutions, and 292 questionnaires for 2021 from 292 ophthalmic institutions. The institution categories in 2014 (197 general hospitals, 31 eye hospitals and 42 others) were statistically different from those in 2021 (182 general hospitals, 45 eye hospitals and 65 others) (P<0.05). The proportion of doctors with senior titles in ophthalmic institutions increased from 25.5% (346/1 358) in 2014 to 41.7% (580/1 391) in 2021, the proportion of senior technicians increased from 9.4% (14/148) to 25.3% (110/435), the proportion of doctors with junior titles decreased from 42.1% (572/1 358) to 26.5% (369/1 391), and the proportion of junior technicians decreased from 45.3% (67/148) to 39.1% (170/435). There was a significant difference in the distribution of professional titles between doctors and technicians in ophthalmic institutions (P<0.05). The number of doctors (130 to 28), nurses (152 to 50), technicians (33 to 11) and full-time optometrists (44 to 12) in the first-class ophthalmic institutions decreased, the increase of equipment with the ophthalmic A-ultrasound scan system, fundus camera and coherent optical tomography system (35.1%, 28.9% and 25.4%; P<0.05) ranked the top three, and the increase of performing the phacoemulsification procedure, intraocular lens implantation, intravitreal injection and iris surgery (30.2%, 24.7% and 20.7%; P<0.05) ranked the top three in 2021 as compared to 2014. Conclusions: The resources and service ability of ophthalmology in Shanxi Province developed in 2021 in comparison with 2014. However, there were some problems, such as changes in the type and structure of eye institutions, unreasonable proportions of professional titles, insufficient human resources in primary ophthalmic institutions, and slow improvement in the allocation of ophthalmology equipment and technical capabilities.

[Analysis of factors affecting the progression of visual field defects in patients with myopia and primary open-angle glaucoma].

Objective: To investigate the factors affecting the progression of visual field defects in patients with myopia and primary open-angle glaucoma (POAG), and to clarify whether the factors vary in patients with different degrees of myopia. Method: An ambispective cohort study was conducted among patients diagnosed with myopia and POAG from the glaucoma outpatient department at the Zhongshan Ophthalmic Center of Sun Yat-sen University between January 2006 and January 2024. Based on the criteria of functional visual field progression, patients were divided into the progression group and non-progression group, and further divided into the low to moderate myopia subgroup and high myopia subgroup according to the degree of myopia. The patient age, gender, type of glaucoma (high tension glaucoma and normal tension glaucoma), spherical equivalent refraction, best corrected visual acuity (BCVA, recorded as the logarithm of the minimum angle of resolution), intraocular pressure (IOP), central corneal thickness, baseline visual field, history of ophthalmic surgery (corneal refractive surgery and glaucoma surgery), and number of anti-glaucoma medications were summarized. The generalized estimation equation was used for comparison between groups, and the Cox proportional hazards model was used to analyze the factors affecting the progression of visual field defects. Results: A total of 182 eyes from 106 patients were included in this study. There were 57 eyes in the progression group and 125 eyes in the non-progression group. Compared with the non-progression group, the progression group had the older age [43 (29, 53) years old], worse BCVA [0.05 (0.00, 0.17)], greater IOP fluctuation [1.8 (1.3, 2.9)mmHg(1 mmHg=0.133 kPa)], more common baseline central defects [52.6%(30/57)], higher visual field pattern standard deviations [8.92 (5.32, 12.00)dB], lower visual field index [77% (67%, 88%)], and more anti-glaucoma medications [35.1% (20/57) patients used three medications] (all P<0.05). The Cox proportional hazards models showed that the baseline moderate visual field defects [hazard ratio (HR)=2.33, 95% confidence interval (CI): 1.25 to 4.36, P=0.008], baseline central defects (HR=2.09, 95%CI: 1.11 to 3.93, P=0.022), older age (Model A, HR=1.03, 95%CI: 1.00 to 1.05, P=0.017; Model B, HR=1.02, 95%CI: 1.00 to 1.05, P=0.019), and greater IOP fluctuation (Model A, HR=1.54, 95%CI: 1.32 to 1.81, P<0.001; Model B, HR=1.49, 95%CI: 1.26 to 1.75, P<0.001) were risk factors for visual field progression. In the low to moderate myopia subgroup, the increased risk of progression was associated with baseline central defects (HR=5.74, 95%CI: 1.72 to 19.20, P=0.005), worse BCVA (Model A, HR=15.80, 95%CI: 2.07 to 121.00, P=0.008; Model B, HR=12.50, 95%CI: 2.65 to 58.70, P=0.001), and older age (Model A, HR=1.05, 95%CI: 1.02 to 1.08, P=0.002; Model B, HR=1.07, 95%CI: 1.03 to 1.11, P<0.001). In the high myopia subgroup, the increased risk of progression was associated with baseline moderate visual field defects (HR=2.35, 95%CI: 1.12 to 4.92, P=0.024) and greater IOP fluctuation (Model A, HR=1.50, 95%CI: 1.24 to 1.82, P<0.001; Model B, HR=1.52, 95%CI: 1.26 to 1.83, P<0.001). Conclusions: Age, IOP fluctuation, baseline moderate visual field defects, and baseline central defects were the factors affecting the progression of visual field defects in patients with myopia and POAG. There were differences in the influencing factors of visual field progression in patients with different degrees of myopia.

Temporal Structures in Positron Spectra and Charge-Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

Temporal Structures in Electron Spectra and Charge Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0×10^{8} electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6σ at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.

Properties of Cosmic-Ray Sulfur and Determination of the Composition of Primary Cosmic-Ray Carbon, Neon, Magnesium, and Sulfur: Ten-Year Results from the Alpha Magnetic Spectrometer.

We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38×10^{6} sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

Gadoxetic acid in hepatocellular carcinoma and liver metastases: pearls and pitfalls.

Gadoxetic disodium (Primovist) is a hepatocyte-specific magnetic resonance imaging (MRI) contrast agent with increasing popularity with its unique dual dynamic and excretory properties in focal liver lesion detection and characterisation. In-depth knowledge of its diagnostic utility and pitfalls in hepatocellular carcinoma (HCC) and liver metastases is crucial in facilitating clinical management. The current article reviews the pearls and pitfalls in these aspects with highlights from the latest research evidence. Pearls for common usage of Primovist in HCC includes detection of precursor cancer lesions in cirrhotic patients. Hepatobiliary phase hypointensity precedes arterial phase hyperenhancement (APHE) in hepatocarcinogenesis. Hepatobiliary phase hypointense nodules without APHE can represent early or progressed hepatocellular carcinoma (HCC) and high-grade dysplastic nodules. In addition, Primovist is useful to differentiate HCC from pseudolesions. Pitfalls in diagnosing HCC include transient tachypnoea in the arterial phase, rare hepatobiliary phase hyperintense HCC, and decompensated liver cirrhosis compromising image quality. Primovist is currently the most sensitive technique in diagnosing liver metastases before curative hepatic resection. Other patterns of enhancement of liver metastases, "disappearing" liver metastases are important pitfalls. Radiologists should be aware of the diagnostic utility, limitations, and potential pitfalls for the common usage of hepatobiliary specific contrast agent in liver MRI.

Low-noise φ-OTDR employing nonlinear optical preamplification for distributed acoustic sensing.

A phase sensitive optical time domain reflectometry sensing scheme employing a two-stage nonlinear optical preamplification system is proposed to reduce the blind spot effect in Rayleigh scattering by improving the optical power distribution and to enhance the resolution at locations of low-backscatter intensity measurements, providing a higher signal-to-noise ratio for distributed acoustic measurements; the developed system has been tested in-laboratory and on in-field monitoring of a survey well in Cottessen, The Netherlands. The characterization shows strain noise levels below 1 nɛ for a 10 kHz sampling rate.