bluuebunny/crossref_metadata_2025 huggingface dataset:
Terahertz dielectric spectroscopy of human brain gliomas and intact tissues ex vivo: double-Debye and double-overdamped-oscillator models of dielectric response
Authors: Gavdush A. A. , Chernomyrdin N. V. , Komandin G. A. , Dolganova I. N. , Nikitin P. V. , Musina G. R. , Katyba G. M. , Kucheryavenko A. S. , Reshetov I. V. , Potapov A. A. , Tuchin V. V. , Zaytsev K. I.
Published: November 2020

Terahertz (THz) technology offers novel opportunities in the intraoperative neurodiagnosis. Recently, the significant progress was achieved in the study of brain gliomas and intact tissues, highlighting a potential for THz technology in the intraoperative delineation of tumor margins. However, a lack of physical models describing the THz dielectric permittivity of healthy and pathological brain tissues restrains the further progress in this field. In the present work, the ex vivo THz dielectric response of human brain tissues was analyzed using relaxation models of complex dielectric permittivity. Dielectric response of tissues was parametrized by a pair of the Debye relaxators and a pair of the overdamped-oscillators – namely, the double-Debye (DD) and double-overdamped-oscillator (DO) models. Both models accurately reproduce the experimental curves for the intact tissues and the WHO Grades I–IV gliomas. While the DD model is more common for THz biophotonics, the DO model is more physically rigorous, since it satisfies the sum rule. In this way, the DO model and the sum rule were, then, applied to estimate the content of water in intact tissues and gliomas ex vivo. The observed results agreed well with the earlier-reported data, justifying water as a main endogenous label of brain tumors in the THz range. The developed models can be used to describe completely the THz-wave – human brain tissues interactions in the frameworks of classical electrodynamics, being quite important for further research and developments in THz neurodiagnosis of tumors.
Hyperspectral microscopy combined with DAPI staining for the identification of hepatic carcinoma cells
Authors: Liu Kunxing , Lin Sifan , Zhu Siqi , Chen Yao , Yin Hao , Li Zhen , Chen Zhenqiang
Published: November 2020

In this study, the DAPI staining is firstly reported for use in the identification of hepatic carcinoma cells based on hyperspectral microscopy. Nuclei in cancer cells usually contain more aneuploidies than that in normal cells, leading to the change of DNA content. Here, we stain hepatic carcinoma tissues and normal hepatic tissues with 4’,6-diamidino-2-phenylindole (DAPI) which is sensitive to the DNA content as a fluorochrome binds to DNA. Consequently, the difference in DNA content between hepatic carcinoma cells and normal hepatic cells can be identified by the fluorescent spectral characteristics. Harnessing the hyperspectral microscopy, we find that the fluorescent properties of these two kinds of cells are different not only in the intensity but also in the spectral shape. These properties are exploited to train a support vector machine (SVM) model for classifying cells. The results show that the sensitivity and specificity for the identification of 1000 hepatic carcinoma samples are 99.3% and 99.1%, respectively.
Spectral characterization of photon-pair sources via classical sum-frequency generation
Authors: Kaneda Fumihiro , Oikawa Jo , Yabuno Masahiro , China Fumihiro , Miki Shigehito , Terai Hirotaka , Mitsumori Yasuyoshi , Edamatsu Keiichi
Published: November 2020

Tailoring spectral properties of photon pairs is of great importance for optical quantum information and measurement applications. High-resolution spectral measurement is a key technique for engineering spectral properties of photons, making them ideal for various quantum applications. Here we demonstrate spectral measurements and optimization of frequency-entangled photon pairs produced via spontaneous parametric downconversion (SPDC), utilizing frequency-resolved sum-frequency generation (SFG), the reverse process of SPDC. A joint phase-matching spectrum of a nonlinear crystal around 1580 nm is captured with a 40 pm resolution and a > 40 dB signal-to-noise ratio, which is significantly improved compared to traditional frequency-resolved coincidence measurements. Moreover, our scheme is applicable to collinear degenerate sources whose characterization is difficult with previously demonstrated stimulated difference frequency generation (DFG). We also illustrate that the observed phase-matching function is useful for finding an optimal pump spectrum to maximize the spectral indistinguishability of SPDC photons. We expect that our precise spectral characterization technique will be useful tool for characterizing and tailoring SPDC sources for a wide range of optical quantum applications.
Ultra-compact and broadband silicon polarizer employing a nanohole array structure
Authors: He Yu , Zhang Yong , Zhang Ruihuan , Sun Lu , Su Yikai
Published: November 2020

An ultra-compact and broadband transverse magnetic (TM)-pass polarizer is experimentally demonstrated using a photonic crystal nanohole structure. By engineering the period of the circular holes, the fundamental transverse electric mode is suppressed due to the bandgap of the nanohole array, while the

mode propagates with a negligible insertion loss. Simulation results predict that the bandwidth of the device can reach 245 nm with a 33 dB polarization extinction ratio (PER). In the experiment, an insertion loss

for the

mode and a PER over 20.8 dB are demonstrated in a 70 nm wavelength range from 1520 to 1590 nm, mainly limited by the grating couplers used for fiber-to-chip coupling. The fabricated device is compact with a total length of 7.21 µm.
Investigation of anisotropic thermal lens effect in a dual-polarized Nd:YLF laser
Authors: Chen Chi-Wen , Fang Yu-Han , Cho Chun-Yu , Liang Hsing-Chih
Published: November 2020

The anisotropic thermal lens effect of a dual-polarization Nd:YLF laser is experimentally investigated by measuring the transverse beat frequency between

T
E
M

0
,
0

and

T
E
M

1
,
0

modes in the self-pulsing operation, and focal lengths of thermal lensing for both polarizations can be accurately determined. The focal length of the thermal lens for

π

polarization was observed to be negative and varies from

−

1.1

to

−

0.5

m

for the absorbed pump power increasing from 1.7 to 3.8 W. For

σ

polarization, the focal length of the thermal lens was determined to be positive and varies from 1.2 to 0.9 m for the absorbed pump power increasing from 8.4 to 10.9 W. The sensitivity factors of the thermal lens for both polarizations were evaluated to be

M
π

=
−

0.54

m

−
1

/

W

and

M
σ

=

0.1

m

−
1

/

W

, respectively.
Meta-objective with sub-micrometer resolution for microendoscopes
Authors: Liu Yan , Yu Qing-Yun , Chen Ze-Ming , Qiu Hao-Yang , Chen Rui , Jiang Shao-Ji , He Xin-Tao , Zhao Fu-Li , Dong Jian-Wen
Published: November 2020

Microendoscopes are vital for disease detection and clinical diagnosis. The essential issue for microendoscopes is to achieve minimally invasive and high-resolution observations of soft tissue structures inside deep body cavities. Obviously, the microscope objective is a must with the capabilities of both high lateral resolution in a wide field of view (FOV) and miniaturization in size. Here, we propose a meta-objective, i.e., microscope objective based on cascaded metalenses. The two metalenses, with the optical diameters of 400 μm and 180 μm, respectively, are mounted on both sides of a 500-μm-thick silica film. Sub-micrometer lateral resolution reaches as high as 775 nm in such a naked meta-objective, with monochromatic aberration correction in a 125 μm full FOV and near diffraction limit imaging. Combined with a fiber bundle microscope system, the single cell contour of biological tissue (e.g., water lily leaf) can be clearly observed, compared to the indistinguishable features in other conventional lens-based fiber bundle systems, such as plano–convex and gradient refractive index (GRIN) cases.
Direct generation of watt-level yellow Dy3+-doped fiber laser
Authors: Zou Jinhai , Li Tianran , Dou Yanbo , Li Jin , Chen Nan , Bu Yikun , Luo Zhengqian
Published: November 2020

Yellow lasers (

∼
565
–
590
  
nm

) are of tremendous interest in biomedicine, astronomy, spectroscopy, and display technology. So far, yellow lasers still have relied heavily on nonlinear frequency conversion of near-infrared lasers, precluding compact and low-cost yellow laser systems. Here, we address the challenge through demonstrating, for the first time, to the best of our knowledge, watt-level high-power yellow laser generation directly from a compact fiber laser. The yellow fiber laser simply consists of a

Dy

3
+

-doped ZBLAN fiber as gain medium, a fiber end-facet mirror with high reflectivity at yellow and a 450-nm diode laser as the pump source. We comprehensively investigated the dependence of the yellow laser performance on the output coupler reflectivity and the gain fiber length and demonstrated that the yellow fiber laser with an output coupler reflectivity of 4% and a gain fiber length of

∼
1.8
  
m

yields a maximum efficiency of 33.6%. A maximum output power of 1.12 W at 575 nm was achieved at a pump power of 4.20 W. This work demonstrated the power scaling of yellow

Dy

3
+

-doped ZBLAN fiber lasers, showing their promise for applications in ophthalmology, astronomical exploration, and high-resolution spectroscopy.
Inferring a network from dynamical signals at its nodes
Authors: Weistuch Corey , Agozzino Luca , Mujica-Parodi Lilianne R. , Dill Ken A.
Published: November 2020

We give an approximate solution to the difficult inverse problem of inferring the topology of an unknown network from given time-dependent signals at the nodes. For example, we measure signals from individual neurons in the brain, and infer how they are inter-connected. We use Maximum Caliber as an inference principle. The combinatorial challenge of high-dimensional data is handled using two different approximations to the pairwise couplings. We show two proofs of principle: in a nonlinear genetic toggle switch circuit, and in a toy neural network.
Inference of mutability landscapes of tumors from single cell sequencing data
Authors: Tsyvina Viachaslau , Zelikovsky Alex , Snir Sagi , Skums Pavel
Published: November 2020

One of the hallmarks of cancer is the extremely high mutability and genetic instability of tumor cells. Inherent heterogeneity of intra-tumor populations manifests itself in high variability of clone instability rates. Analogously to fitness landscapes, the instability rates of clonal populations form their mutability landscapes. Here, we present MULAN (MUtability LANdscape inference), a maximum-likelihood computational framework for inference of mutation rates of individual cancer subclones using single-cell sequencing data. It utilizes the partial information about the orders of mutation events provided by cancer mutation trees and extends it by inferring full evolutionary history and mutability landscape of a tumor. Evaluation of mutation rates on the level of subclones rather than individual genes allows to capture the effects of genomic interactions and epistasis. We estimate the accuracy of our approach and demonstrate that it can be used to study the evolution of genetic instability and infer tumor evolutionary history from experimental data. MULAN is available athttps://github.com/compbel/MULAN.
An exact method for quantifying the reliability of end-of-epidemic declarations in real time
Authors: Parag Kris V. , Donnelly Christl A. , Jha Rahul , Thompson Robin N.
Published: November 2020

We derive and validate a novel and analytic method for estimating the probability that an epidemic has been eliminated (i.e. that no future local cases will emerge) in real time. When this probability crosses 0.95 an outbreak can be declared over with 95% confidence. Our method is easy to compute, only requires knowledge of the incidence curve and the serial interval distribution, and evaluates the statistical lifetime of the outbreak of interest. Using this approach, we show how the time-varying under-reporting of infected cases will artificially inflate the inferred probability of elimination, leading to premature (false-positive) end-of-epidemic declarations. Contrastingly, we prove that incorrectly identifying imported cases as local will deceptively decrease this probability, resulting in delayed (false-negative) declarations. Failing to sustain intensive surveillance during the later phases of an epidemic can therefore substantially mislead policymakers on when it is safe to remove travel bans or relax quarantine and social distancing advisories. World Health Organisation guidelines recommend fixed (though disease-specific) waiting times for end-of-epidemic declarations that cannot accommodate these variations. Consequently, there is an unequivocal need for more active and specialised metrics for reliably identifying the conclusion of an epidemic.
A context-dependent bifurcation in the Pointed transcriptional effector network contributes specificity and robustness to retinal cell fate acquisition
Authors: Wu Chudong , Boisclair Lachance Jean-François , Ludwig Michael Z. , Rebay Ilaria
Published: November 2020

Spatiotemporally precise and robust cell fate transitions, which depend on specific signaling cues, are fundamental to the development of appropriately patterned tissues. The fidelity and precision with which photoreceptor fates are recruited in the Drosophila eye exemplifies these principles. The fly eye consists of a highly ordered array of ~750 ommatidia, each of which contains eight distinct photoreceptors, R1-R8, specified sequentially in a precise spatial pattern. Recruitment of R1-R7 fates requires reiterative receptor tyrosine kinase / mitogen activated protein kinase (MAPK) signaling mediated by the transcriptional effector Pointed (Pnt). However the overall signaling levels experienced by R2-R5 cells are distinct from those experienced by R1, R6 and R7. A relay mechanism between two Pnt isoforms initiated by MAPK activation directs the universal transcriptional response. Here we ask how the generic Pnt response is tailored to these two rounds of photoreceptor fate transitions. We find that during R2-R5 specification PntP2 is coexpressed with a closely related but previously uncharacterized isoform, PntP3. Using CRISPR/Cas9-generated isoform specific null alleles we show that under otherwise wild type conditions, R2-R5 fate specification is robust to loss of either PntP2 or PntP3, and that the two activatepntP1redundantly; however under conditions of reduced MAPK activity, both are required. Mechanistically, our data suggest that intrinsic activity differences between PntP2 and PntP3, combined with positive and unexpected negative transcriptional auto- and cross-regulation, buffer first-round fates against conditions of compromised RTK signaling. In contrast, in a mechanism that may be adaptive to the stronger signaling environment used to specify R1, R6 and R7 fates, the Pnt network resets to a simpler topology in which PntP2 uniquely activatespntP1and auto-activates its own transcription. We propose that differences in expression patterns, transcriptional activities and regulatory interactions between Pnt isoforms together facilitate context-appropriate cell fate specification in different signaling environments.
Population genomic evidence that human and animal infections in Africa come from the same populations of Dracunculus medinensis
Authors: Durrant Caroline , Thiele Elizabeth A. , Holroyd Nancy , Doyle Stephen R. , Sallé Guillaume , Tracey Alan , Sankaranarayanan Geetha , Lotkowska Magda E. , Bennett Hayley M. , Huckvale Thomas , Abdellah Zahra , Tchindebet Ouakou , Wossen Mesfin , Logora Makoy Samuel Yibi , Coulibaly Cheick Oumar , Weiss Adam , Schulte-Hostedde Albrecht I. , Foster Jeremy M. , Cleveland Christopher A. , Yabsley Michael J. , Ruiz-Tiben Ernesto , Berriman Matthew , Eberhard Mark L. , Cotton James A.
Published: November 2020

Background

Guinea worm–Dracunculus medinensis–was historically one of the major parasites of humans and has been known since antiquity. Now, Guinea worm is on the brink of eradication, as efforts to interrupt transmission have reduced the annual burden of disease from millions of infections per year in the 1980s to only 54 human cases reported globally in 2019. Despite the enormous success of eradication efforts to date, one complication has arisen. Over the last few years, hundreds of dogs have been found infected with this previously apparently anthroponotic parasite, almost all in Chad. Moreover, the relative numbers of infections in humans and dogs suggests that dogs are currently the principal reservoir on infection and key to maintaining transmission in that country.

Principal findings

In an effort to shed light on this peculiar epidemiology of Guinea worm in Chad, we have sequenced and compared the genomes of worms from dog, human and other animal infections. Confirming previous work with other molecular markers, we show that all of these worms areD.medinensis, and that the same population of worms are causing both infections, can confirm the suspected transmission between host species and detect signs of a population bottleneck due to the eradication efforts. The diversity of worms in Chad appears to exclude the possibility that there were no, or very few, worms present in the country during a 10-year absence of reported cases.

Conclusions

This work reinforces the importance of adequate surveillance of both human and dog populations in the Guinea worm eradication campaign and suggests that control programs aiming to interrupt disease transmission should stay aware of the possible emergence of unusual epidemiology as pathogens approach elimination.
SARS-CoV-2 lineage B.6 was the major contributor to early pandemic transmission in Malaysia
Authors: Chong Yoong Min , Sam I-Ching , Chong Jennifer , Kahar Bador Maria , Ponnampalavanar Sasheela , Syed Omar Sharifah Faridah , Kamarulzaman Adeeba , Munusamy Vijayan , Wong Chee Kuan , Jamaluddin Fadhil Hadi , Chan Yoke Fun
Published: November 2020

Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia’s second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays.

Clinical Trial Registration: COVID-19 paper.
Knowledge of health workers on snakes and snakebite management and treatment seeking behavior of snakebite victims in Bhutan
Authors: Sapkota Sunil , Pandey Deb P. , Dhakal Guru P. , Gurung Dhan B.
Published: November 2020

Background

Published information on snakebite is rare in Bhutan although remarkably higher number of snakebites and associated deaths are reported from other South Asian countries.

Aims and methodology

Structured questionnaire was used to collect knowledge of health workers in snakebite management and health seeking behavior of snakebite victims as observed by health workers. Study was conducted in purposively sampled 10 Dzongkhags (district level administrative units) with higher incidence of snakebites.

Result

Heath workers scored 27–91% (with an average of 63%, SD = 14) for 52 questions related to snake identification and snakebite management. Among 118 health workers interviewed, 23% had adequate knowledge on snakes and snakebite management while 77% had inadequate knowledge. Among 32 Doctors, 63% of them scored above or equal to 75%. Health workers from Sarpang scored higher (76%, SD = 11) than those from other Dzongkhags. Snakebite victim's visit to local (traditional) healers prior to seeking medical help from hospital was observed by 75 (63%) health workers. Fifty one percent of health workers observed patients treated with local methods such as the use of black stone called Jhhar Mauro (believed to absorb snake venom), application of honey, rubbing of green herbal paste made up of Khenpa Shing (Artemisia myriantha Wallich ex Besser var. paleocephala [Pamp] Ling) and consumption of fluid made up of Neem leaf (Azadirachta indica Juss). Use of tight tourniquet as a first aid to snakebite was observed by 80% of the health workers.

Conclusion

Health workers lack confidence in snakebite management. Snakebite victims are likely to suffer from harmful local practices and traditional beliefs on local treatment practices. Empowering health workers with adequate knowledge on snakebite management and making locals aware in pre-hospital care of snakebites are needed to improve the pre- and in-hospital management of snakebite in Bhutan.
Early impairment of myocardial deformation assessed by regional speckle-tracking echocardiography in the indeterminate form of Chagas disease without fibrosis detected by cardiac magnetic resonance
Authors: Romano Minna Moreira Dias , Moreira Henrique Turin , Marin-Neto José Antônio , Baccelli Priscila Elias , Alenezi Fawaz , Klem Igor , Maciel Benedito Carlos , Kisslo Joseph , Schmidt André , Velazquez Eric J.
Published: November 2020

Chagas disease (CD) will account for 200,000 cardiovascular deaths worldwide over the next 5 years. Early detection of chronic Chagas cardiomyopathy (CCC) is a challenge. We aimed to test if speckle-tracking echocardiography (STE) can detect incipient myocardial damage in CD. METHODS: Among 325 individuals with positive serological tests, 25 (age 55±12yrs) were selected to compose the group with indeterminate form of Chagas disease (IFCD), based on stringent criteria of being asymptomatic and with normal EKG/X-ray studies. This group was compared with a group of 20 patients with CCC (55±11yrs) and a group of 20 non-infected matched control (NC) subjects (48±10yrs). CD patients and NC were submitted to STE and CD patients were submitted to cardiac magnetic resonance (CMR) with late gadolinium administration to detect cardiac fibrosis by the late enhancement technique. Global longitudinal strain (GLS), circumferential (GCS) and radial strain (GRS) were defined as the average of segments measured from three apical view (GLS) and short axis views (GRS and GCS). Regional left ventricular (LV) longitudinal strain (Reg LS) was measured from each of the 17 segments. Twist was measured as systolic peak difference between basal and apical rotation and indexed to LV length to express torsion. RESULTS: STE global indices (GLS, GCS, twist and torsion) were reduced in CCC vs NC (GLS: -14±6.3% vs -19.3±1.6%, p = 0.001; GCS: -13.6±5.2% vs -17.3 ±2.8%; p = 0.008; twist: 8±7° vs 14±7°, p = 0.01 and torsion: 0.96±1°/cm vs 1.9±1°/cm, p = 0.005), but showed no differences in IFCD vs NC. RegLS was reduced in IFCD vs NC in four LV segments: basal-inferior (-16.3±3.3% vs -18.6±2.2%, p = 0.013), basal inferoseptal (-13.1±3.4 vs -15.2±2.7, p = 0.019), mid-inferoseptal (-17.7±3.2 vs -19.4±2, p = 0.032) and mid-inferolateral (-15.2±3.5 vs -17.8±2.8, p = 0.014). These abnormalities in RegLS occurred in the absence of myocardial fibrosis detectable with CMR in nearly 92% of subjects with IFCD, while myocardial fibrosis was present in 65% with CCC. CONCLUSION: RegLS detects early regional impairment of myocardial strain that is independent from fibrosis in IFCD subjects.
Evaluation of the sensitivity and specificity of GST-tagged recombinant antigens 2B2t, Ag5t and DIPOL in ELISA for the diagnosis and follow up of patients with cystic echinococcosis
Authors: Sánchez-Ovejero Carlos , Akdur Eylem , Manzano-Román Raúl , Hernández-González Ana , González-Sánchez María , Becerro-Recio David , González-Miguel Javier , Akhan Okan , Cretu Carmen M. , Vutova Kamenna , Tamarozzi Francesca , Mariconti Mara , Brunetti Enrico , Vola Ambra , Fabiani Massimo , Casulli Adriano , Siles-Lucas Mar
Published: November 2020

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus sensu lato. Diagnosis and monitoring of CE rely primarily on imaging while serology is used as a confirmatory test. However, imaging is not always conclusive and currently available serological assays have suboptimal sensitivity and specificity, lack standardization, and are not useful for patients´ follow-up. Seroassays for CE are usually based on hydatid fluid (HF), a complex, variable antigenic mixture, and cross-reactivity exists especially with alveolar echinococcosis. Recombinant proteins based on immunogenic antigens most abundant in HF, such as AgB1, AgB2 and Ag5, have been used to overcome these limitations. None of them so far showed potential to replace HF; however, their performance have been largely tested on a limited number of samples, and comparison of different antigens using the same cohort has been rarely performed. The combination of several immunogenic epitopes in a single recombinant protein could enhance test sensitivity. For the diagnosis and follow-up of patients with CE, we compared the performance of the crude HF, previously described recombinant 2B2t antigen, and GST-tagged version of 2B2t, and novel designed recombinants (GST-Ag5t and the GST-DIPOL chimera containing AgB1, AgBB2 and Ag5 epitopes) by IgG-ELISA format. Samples belong to a retrospective cohort of 253 well-characterized patients with CE, previously described for the evaluation of the 2B2t antigen, 92 patients with alveolar echinococcosis, and 82 healthy donors. The reference standard for CE diagnosis was the presence of a CE lesion as diagnosed by ultrasonography. The highest sensitivity was obtained with HF [86.7%, 95% confidence interval (CI): 81.2–91.0], followed by GST-2B2t (70.0%, 95% CI: 63.1–76.2), 2B2t (65.5%, 95% CI: 58.5–72.0), GST-Ag5t (64.5%, 95% CI: 57.5–71.1) and GST-DIPOL (63.1%, 95% CI: 56.0–69.7). The GST-2B2t had the best specificity (95.8%, 95% CI: 88.3–99.1) and the lowest cross-reactivity (38.7%, 95% CI: 27.6–50.6). Good response to treatment also correlated to negative test results in the GST-2B2t ELISA. While none of the tested recombinant antigen appears suitable to replace HF for the diagnosis of CE, GST-2B2t should be further explored as a confirmation test, based on its high specificity and low cross-reactivity, and for the follow-up after treatment in those patients with positive serology for this antigen.
Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests
Authors: Silva Anjana , Hlusicka Jiri , Siribaddana Nipuna , Waiddyanatha Subodha , Pilapitiya Senaka , Weerawansa Prasanna , Lokunarangoda Niroshan , Thalgaspitiya Sujeewa , Siribaddana Sisira , Isbister Geoffrey K.
Published: November 2020

Delays in treatment seeking and antivenom administration remain problematic for snake envenoming. We aimed to describe the treatment seeking pattern and delays in admission to hospital and administration of antivenom in a cohort of authenticated snakebite patients. Adults (> 16 years), who presented with a confirmed snakebite from August 2013 to October 2014 were recruited from Anuradhapura Hospital. Demographic data, information on the circumstances of the bite, first aid, health-seeking behaviour, hospital admission, clinical features, outcomes and antivenom treatment were documented prospectively. There were 742 snakebite patients [median age: 40 years (IQR:27–51; males: 476 (64%)]. One hundred and five (14%) patients intentionally delayed treatment by a median of 45min (IQR:20-120min). Antivenom was administered a median of 230min (IQR:180–360min) post-bite, which didn’t differ between directly admitted and transferred patients; 21 (8%) receiving antivenom within 2h and 141 (55%) within 4h of the bite. However, transferred patients received antivenom sooner after admission to Anuradhapura hospital than those directly admitted (60min [IQR:30-120min] versus 120min [IQR:52-265min; p<0.0001]). A significantly greater proportion of transferred patients had features of systemic envenoming on admission compared to those directly admitted (166/212 [78%] versus 5/43 [12%]; p<0.0001), and had positive clotting tests on admission (123/212 [58%] versus 10/43 [23%]; p<0.0001). Sri Lankan snakebite patients present early to hospital, but there remains a delay until antivenom administration. This delay reflects a delay in the appearance of observable or measurable features of envenoming and a lack of reliable early diagnostic tests. Improved early antivenom treatment will require reliable, rapid diagnostics for systemic envenoming.
Transmission competence of a new mesonivirus, Yichang virus, in mosquitoes and its interference with representative flaviviruses
Authors: Ye Guoguo , Wang Yujuan , Liu Xiaoyun , Dong Qiannan , Cai Quanxin , Yuan Zhiming , Xia Han
Published: November 2020

Advances in technology have greatly stimulated the understanding of insect-specific viruses (ISVs). Unfortunately, most of these findings are based on sequencing technology, and laboratory data are scarce on the transmission dynamics of ISVs in nature and the potential effects of these viruses on arboviruses. Mesonivirus is a class of ISVs with a wide geographical distribution. Recently, our laboratory reported the isolation of a novel strain of mesonivirus, Yichang virus (YCV), from Culex mosquitoes, China. In this study, the experimental infection of YCV by the oral route for adult and larvae mosquitoes, and the vertical transmission has been conducted, which suggests that YCV could adopt a mixed-mode transmission. Controlled experiments showed that the infectivity of YCV depends on the mosquito species, virus dose, and infection route. The proliferation curve and tissue distribution of YCV in Cx. quinquefasciatus and Ae. albopictus showed that YCV is more susceptible to Ae. albopictus and is located in the midgut. Furthermore, we also assessed the interference of YCV with flaviviruses both in vitro and in vivo. YCV significantly inhibited the proliferation of DENV-2 and ZIKV, in cell culture, and reduced transmission rate of DENV-2 in Ae. albopictus. Our work provides insights into the transmission of ISVs in different mosquito species during ontogeny and their potential ability to interact with mosquito-borne viruses.
Mitigating seafloor disturbance of bottom trawl fisheries for North Sea sole Solea solea by replacing mechanical with electrical stimulation
Authors: Rijnsdorp A. D. , Depestele J. , Eigaard O. R. , Hintzen N. T. , Ivanovic A. , Molenaar P. , O’Neill F. G. , Polet H. , Poos J. J. , van Kooten T.
Published: November 2020

Ecosystem effects of bottom trawl fisheries are of major concern. Although it is prohibited to catch fish using electricity in European Union waters, a number of beam trawlers obtained a derogation and switched to pulse trawling to explore the potential to reduce impacts. Here we analyse whether using electrical rather than mechanical stimulation results in an overall reduction in physical disturbance of the seafloor in the beam-trawl fishery for soleSolea solea. We extend and apply a recently developed assessment framework to the Dutch beam-trawl fleet and show that the switch to pulse trawling substantially reduced benthic impacts when exploiting the total allowable catch of sole in the North Sea. Using Vessel Monitoring by Satellite and logbook data from 2009 to 2017, we estimate that the trawling footprint decreased by 23%, the precautionary impact indicator of the benthic community decreased by 39%, the impact on median longevity of the benthic community decreased by 20%, the impact on benthic biomass decreased by 61%, and the amount of sediment mobilised decreased by 39%. The decrease in impact is due to the replacement of tickler chains by electrode arrays, a lower towing speed and higher catch efficiency for sole. The effort and benthic physical disturbance of the beam-trawl fishery targeting plaicePleuronectes platessain the central North Sea increased with the recovery of the plaice stock. Our study illustrates the utility of a standardized methodological framework to assess the differences in time trends and physical disturbance between gears.
Stimulation of the human mitochondrial transporter ABCB10 by zinc-mesoporphrin
Authors: Martinez Melissa , Fendley Gregory A. , Saxberg Alexandra D. , Zoghbi Maria E.
Published: November 2020

Heme biosynthesis occurs through a series of reactions that take place within the cytoplasm and mitochondria, so intermediates need to move across these cellular compartments. However, the specific membrane transport mechanisms involved in the process are not yet identified. The ATP-binding cassette protein ABCB10 is essential for normal heme production, as knocking down this transporter in mice is embryonically lethal and accompanied by severe anemia plus oxidative damage. The role of ABCB10 is unknown, but given its location in the inner mitochondrial membrane, it has been proposed as a candidate to export either an early heme precursor or heme. Alternatively, ABCB10 might transport a molecule important for protection against oxidative damage. To help discern between these possibilities, we decided to study the effect of heme analogs, precursors, and antioxidant peptides on purified human ABCB10. Since substrate binding increases the ATP hydrolysis rate of ABC transporters, we have determined the ability of these molecules to activate purified ABCB10 reconstituted in lipid nanodiscs using ATPase measurements. Under our experimental conditions, we found that the only heme analog increasing ABCB10 ATPase activity was Zinc-mesoporphyrin. This activation of almost seventy percent was specific for ABCB10, as the ATPase activity of a negative control bacterial ABC transporter was not affected. The activation was also observed in cysteine-less ABCB10, suggesting that Zinc-mesoporphyrin’s effect did not require binding to typical heme regulatory motifs. Furthermore, our data indicate that ABCB10 was not directly activated by neither the early heme precursor delta-aminolevulinic acid nor glutathione, downsizing their relevance as putative substrates for this transporter. Although additional studies are needed to determine the physiological substrate of ABCB10, our findings reveal Zinc-mesoporphyrin as the first tool compound to directly modulate ABCB10 activity and raise the possibility that some actions of Zinc-mesoporphyrin in cellular and animal studies could be mediated by ABCB10.
Changes in cAMP effector predominance are associated with increased oxytocin receptor expression in twin but not infection-associated or idiopathic preterm labour
Authors: Yulia Angela , Varley Alice J. , Singh Natasha , Lei Kaiyu , Tribe Rachel , Johnson Mark R.
Published: November 2020

We previously reported that at term pregnancy, a decline in myometrial protein kinase A (PKA) activity leads to an exchange protein activated by cyclic AMP (Epac1)-dependent increase in oxytocin receptor (OTR) expression, promoting the onset of labour. Here, we studied the changes in the cyclic adenosine monophosphate (cAMP) effector system present in different phenotypes of preterm labour (PTL). Myometrial biopsies obtained from women with phenotypically distinct forms of PTL and the levels of PKA and OTR were examined.

Although we found similar changes in the cAMP effector pathway in all forms of PTL, only in the case of twin PTL (T-PTL) was myometrial OTR levels increased in association with these results. Although there were several changes in the mRNA levels of components of the cAMP synthetic pathway, the total myometrial cAMP levels did not change with the onset of any subtype of PTL. With regards to the expression of cAMP-responsive genes, we found that the mRNA levels of 4 of the 5 cAMP-down-regulated genes were increased in T-PTL, similar to our findings in term labour.

These data signify that although changes in the cAMP effector system were common to all forms of PTL, only in T-PTL were OTR levels increased. Similarly, the mRNA levels of cAMP-repressed genes were only increased in T-PTL supporting the concept that the decline in PKA levels influences myometrial function driving the onset of T-PTL.
Genetic and reproductive consequences of consanguineous marriage in Bangladesh
Authors: Anwar Saeed , Taslem Mourosi Jarin , Arafat Yasir , Hosen Mohammad Jakir
Published: November 2020

Introduction

This study aimed to assess the prevalence, sociodemographic factors, reproductive consequences, and heritable disease burdens associated with consanguineous marriage (CM) in Bangladesh.

Methods

A total of 7,312 families, including 3,694 CM-families, were recruited from 102 locales of 58 districts of Bangladesh. Using a standard questionnaire, we collected medical history and background sociodemographic data of these families. Family history was assessed by pedigree analysis. Fertility, mortality, secondary sex ratio, selection intensity, lethal equivalents were measured using standard methods.

Results

The mean prevalence of CM in our studied population was 6.64%. Gross fertility was higher among CM families, as compared to the non-CM families (p < 0.05). The rate of under-5 child (U5) mortality was significantly higher among CM families (16.6%) in comparison with the non-CM families (5.8%) (p < 0.01). We observed a persuasive rise of abortion/miscarriage and U5 mortality rates with the increasing level of inbreeding. The value of lethal equivalents per gamete found elevated for autosomal inheritances as compared to sex-linked inheritance. CM was associated with the incidence of several single-gene and multifactorial diseases, and congenital malformations, including bronchial asthma, hearing defect, heart diseases, sickle cell anemia (p < 0.05). The general attitude and perception toward CM were rather indifferent, and very few people were concerned about its genetic burden.

Conclusion

This study highlights the harmful consequences of CM on reproductive behavior and the incidence of hereditary conditions. It essences the need for genetic counseling from premarital to postnatal levels in Bangladesh.
The complete mitochondrial genome of a cold seep gastropod Phymorhynchus buccinoides (Neogastropoda: Conoidea: Raphitomidae)
Authors: Du Lvpei , Cai Shanya , Liu Jun , Liu Ruoyu , Zhang Haibin
Published: November 2020

Phymorhynchus is a genus of deep-sea snails that are most distributed in hydrothermal vent or cold seep environments. In this study, we presented the complete mitochondrial genome of P. buccinoides, a cold seep snail from the South China Sea. It is the first mitochondrial genome of a cold seep member of the superfamily Conoidea. The mitochondrial genome is 15,764 bp in length, and contains 13 protein-coding genes (PCGs), 2 rRNA genes, and 22 tRNA genes. These genes are encoded on the positive strand, except for 8 tRNA genes that are encoded on the negative strand. The start codon ATG and 3 types of stop codons, TAA, TAG and the truncated termination codon T, are used in the 13 PCGs. All 13 PCGs in the 26 species of Conoidea share the same gene order, while several tRNA genes have been translocated. Phylogenetic analysis revealed that P. buccinoides clustered with Typhlosyrinx sp., Eubela sp., and Phymorhynchus sp., forming the Raphitomidae clade, with high support values. Positive selection analysis showed that a residue located in atp6 (18 S) was identified as the positively selected site with high posterior probabilities, suggesting potential adaption to the cold seep environment. Overall, our data will provide a useful resource on the evolutionary adaptation of cold seep snails for future studies.
Study on SARS-CoV-2 transmission and the effects of control measures in China
Authors: Zhang Bo , Zhou Hongwei , Zhou Fang
Published: November 2020

Objective

To reconstruct the transmission trajectory of SARS-CoV-2 and analyze the effects of control measures in China.

Methods

Python 3.7.1 was used to write a SEIR class to model the epidemic procedure and proportional estimation method to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A testing capacity limitation factor for medical resources was imposed to model the number of infected but not quarantined individuals. Baidu migration data were used to assess the number of infected individuals who migrated from Wuhan to other areas.

Results

Basic reproduction number, R0, was 3.6 before the city was lockdown on Jan 23, 2020. The actual infected number the model predicted was 4508 in Wuhan before Jan 23, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan), 3.4 (Hubei except Wuhan,) and 3.3 (China except Hubei) in stage 1 (from Dec 08, 2019 to Jan 22, 2020) to 0.67 (Wuhan), 0.59 (Hubei except Wuhan) and 0.63 (China except Hubei) respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073 (95% confidence interval, 41673 to 42475), 21342 (95% confidence interval, 21057 to 21629) and 13384 (95% confidence interval, 13158 to 13612) infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei), respectively.

Conclusion

A series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic should be under control in early April with very few new cases occasionally reported.
Transcriptome analysis of Curcuma wenyujin from Haikou and Wenzhou, and a comparison of the main constituents and related genes of Rhizoma Curcumae
Authors: Lu Lilan , Liu Peiwei , Yang Yanfang , Zhang Yuxiu , Wang Caixia , Feng Jian , Wei Jianhe
Published: November 2020

For more than a thousand years, Rhizoma Curcumae (known as E zhu), a Chinese herbal medicine, has been used to eradicate blood stasis and relieve aches. The plant Curcuma wenyujin, which is grown primarily in Wenzhou, China, is considered the best source of Rhizoma Curcumae. In this study, we sought to ascertain differences in transcript profiles of C. wenyujin grown in traditional (Wenzhou) and recently established (Haikou) production areas based on Illumina and RNA (RNA-seq) sequencing. We also examined differences in the main components of the volatile oil terpene; curcumin, polysaccharide, and starch constituents and related genes in the corresponding pathways, in C. wenyujin cultivated in the two production areas. We accordingly found that the essential oil (2.05%), curcumin (1.46%), and polysaccharide (8.90%) content in Wenzhou rhizomes was higher than that in the rhizomes of plants from Haikou (1.60%, 0.91%, and 6.15%, respectively). In contrast, the starch content of Wenzhou rhizomes (17.0%) was lower than that of Haikou rhizomes (23.8%). Furthermore, we detected significant differences in the oil components of Haikou and Wenzhou rhizomes, with curzerene (32.34%), curdione (21.35%), and germacrene B (9.39%) being the primary components of the essential oil derived from Wenzhou rhizomes, and curzerene (20.13%), curdione (14.73%), and cineole (9.76%) being the main constituents in Haikou rhizomes. Transcriptome and qPCR analyses revealed considerable differences in gene expression between Wenzhou and Haikou rhizomes. The expression of terpene, curcumin, and polysaccharide pathway-related genes in Wenzhou rhizomes was significantly up-regulated, whereas the expression of starch-associated genes was significantly down-regulated, compared with those in Haikou rhizomes. Difference in the content of terpene, curcumin, polysaccharides, and starch in rhizomes from the two production areas could be explained in terms of differences in expression of the related genes.
Impact of progressive resistance training on CT quantified muscle and adipose tissue compartments in pancreatic cancer patients
Authors: Wochner Raoul , Clauss Dorothea , Nattenmüller Johanna , Tjaden Christine , Bruckner Thomas , Kauczor Hans-Ulrich , Hackert Thilo , Wiskemann Joachim , Steindorf Karen
Published: November 2020

Objectives

Loss of body weight is often seen in pancreatic cancer and also predicts poor prognosis. Thus, maintaining muscle mass is an essential treatment goal. The primary aim was to investigate whether progressive resistance training impacts muscle and adipose tissue compartments. Furthermore, the effect of body composition on overall survival (OS) was investigated.

Methods

In the randomized SUPPORT-study, 65 patients were assigned to 6-month resistance training (2x/week) or a usual care control group. As secondary endpoint, muscle strength of the upper and lower extremities was assessed before and after the intervention period. Routine CT scans were assessed on lumbar L3/4 level for quantification of total-fat-area, visceral-fat-area, subcutaneous-fat-area, intramuscular-fat-area, visceral-to-subcutaneous fat ratio (VFR), muscle-area (MA), muscle-density and skeletal-muscle-index (SMI). OS data were retrieved.

Results

Of 65 patients, 53 had suitable CT scans at baseline and 28 completed the intervention period with suitable CT scans. There were no significant effects observed of resistance training on body composition (p>0.05; effect sizes ω2p <0.02). Significant moderate to high correlations were found between MA and muscle strength parameters (r = 0.57–0.85; p<0.001). High VFR at baseline was a predictor of poor OS (VFR≥1.3 vs. <1.3; median OS 14.6 vs. 45.3 months; p = 0.012). Loss of muscle mass was also a predictor of poor OS (loss vs. gain of SMI; median OS 24.6 vs. 50.8 months; p = 0.049).

Conclusion

There is anabolic potential in patients with resectable pancreatic cancer. A progressive resistance training may help patients to maintain their muscle mass and avoid muscle depletion. CT-quantified muscle mass at the level of L3/4 showed a good correlation to muscle strength. Therefore, maintaining muscle mass and muscle strength through structured resistance training could help patients to maintain their physical functioning. A high VFR at baseline and a high loss of muscle mass are predictors of poor OS. Registered on ClinicalTrials.gov (NCT01977066).