bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and outcomes of COVID-19 in patients with HIV: a multicentre research network study
Authors: Hadi Yousaf B. , Naqvi Syeda F.Z. , Kupec Justin T. , Sarwari Arif R.
Published: August 2020

Objective:

We studied clinical outcomes of COVID-19 infection in patients living with HIV (PLH) in comparison to non-HIV population.

Design:

Analysis of a multicentre research network TriNETX was performed including patients more than 10 years of age diagnosed with COVID-19.

Methods:

Outcomes in COVID-19 positive patients with concurrent HIV (PLH) were compared with a propensity-matched cohort of patients without HIV (non-PLH).

Results:

Fifty thousand one hundred and sixty-seven patients with COVID-19 were identified (49,763 non-PLH, 404 PLH). PLH were more likely to be men, African–American, obese and have concurrent hypertension, diabetes, chronic kidney disease and nicotine dependence compared with non-PLH cohort (all P values <0.05). We performed 1 : 1 matching for BMI, diabetes, hypertension, chronic lung diseases, chronic kidney disease, race, history of nicotine dependence and sex. In unmatched analysis, PLH had higher mortality at 30 days [risk ratio 1.55, 95% confidence interval (95% CI): 1.01–2.39] and were more likely to need inpatient services (risk ratio 1.83, 95% CI: 1.496–2.24). After propensity score matching, no difference in mortality was noted (risk ratio 1.33, 95% CI: 0.69–2.57). A higher proportion of PLH group needed inpatient services (19.31 vs. 11.39%, risk ratio 1.696, 95% CI: 1.21–2.38). Mean C-reactive protein, ferritin, erythrocyte sedimentation rate and lactate dehydrogenase levels after COVID-19 diagnosis were not statistically different and mortality was not different for PLH with a history of antiretroviral treatment.

Conclusion:

Crude COVID-19 mortality is higher in PLH; however, propensity-matched analyses revealed no difference in outcomes, showing that higher mortality is driven by higher burden of comorbidities. Early diagnosis and intensive surveillance are needed to prevent a ‘Syndemic’ of diseases in this vulnerable cohort.
Tomoelastography for Measurement of Tumor Volume Related to Tissue Stiffness in Pancreatic Ductal Adenocarcinomas
Authors: Marticorena Garcia Stephan R. , Zhu Liang , Gültekin Emin , Schmuck Rosa , Burkhardt Christian , Bahra Marcus , Geisel Dominik , Shahryari Mehrgan , Braun Jürgen , Hamm Bernd , Jin Zheng-yu , Sack Ingolf , Guo Jing
Published: August 2020

Objectives

Estimations of tumor volume and boundary in pancreatic ductal adenocarcinoma (PDAC) are crucial for surgery planning. The aim of the study is to evaluate tomoelastography for detection of PDAC and quantification of PDAC volume based on tissue stiffness.

Materials and Methods

From March 2018 to December 2019, a total of 102 participants (30 healthy participants and 72 patients with histologically proven PDAC) were prospectively enrolled in a multicenter study. Multifrequency magnetic resonance elastography was combined with tomoelastography postprocessing to generate maps of shear wave speed (SWS) depicting highly resolved anatomical details of tissue stiffness. Subregional analysis of pancreatic head, body, and tail and reproducibility tests were performed in healthy participants, whereas tumorous (PDAC-T) and nontumorous (PDAC-NT) pancreatic tissue analysis was conducted in patients. In all patients, tumor volumes measured by computed tomography (CT) were compared with SWS-derived volumes. In addition, in 32 patients, tumor sizes were evaluated by macroscopy after resection.

Results

Tumor volumes were quantified in 99% and 87% of all cases with tomoelastography and CT, respectively. Pancreatic SWS was highly reproducible (repeatability coefficient = 0.12) and did not vary regionally or with patient age, sex, or body mass index (all P > 0.08). Shear wave speed was higher in PDAC-T (2.08 ± 0.38 m/s) than in healthy (1.25 ± 0.09 m/s; P < 0.001) and PDAC-NT (1.28 ± 0.14 m/s; P < 0.001) participants. A threshold of 1.47 m/s separated PDAC-T from healthy volunteers (area under the curve = 1.0, sensitivity = 100%, specificity = 100%), while 1.49 m/s separated PDAC-T from PDAC-NT with high accuracy (area under the curve = 0.99, sensitivity = 90%, specificity = 100%). Tomoelastography-derived tumor volume correlated with CT volume (r = 0.91, P < 0.001) and ex vivo tumor volume (r = 0.66, P < 0.001).

Conclusions

Tomoelastography provides a quantitative imaging marker for tissue stiffness depicting PDAC boundaries and separates PDAC from unaffected pancreatic tissue.
Can a Novel Deep Neural Network Improve the Computer-Aided Detection of Solid Pulmonary Nodules and the Rate of False-Positive Findings in Comparison to an Established Machine Learning Computer-Aided Detection?
Authors: Perl Regine Mariette , Grimmer Rainer , Hepp Tobias , Horger Marius Stefan
Published: August 2020

Objective

The aim of this study was to compare the performance of 2 approved computer-aided detection (CAD) systems for detection of pulmonary solid nodules (PSNs) in an oncologic cohort. The first CAD system is based on a conventional machine learning approach (VD10F), and the other is based on a deep 3D convolutional neural network (CNN) CAD software (VD20A).

Methods and Materials

Nine hundred sixty-seven patients with a total of 2451 PSNs were retrospectively evaluated using the 2 different CAD systems. All patients had thin-slice chest computed tomography (0.6 mm) using 100 kV and 100 mAs and a high-resolution kernel (I50f). The CAD images generated by VD10F were transferred to the PACS for evaluation. The images generated by VD20A were evaluated using a Web browser–based viewer. Finally, a senior radiologist who was blinded for the CAD results examined the thin-slice images of every patient (ground truth).

Results

A total of 2451 PSNs were detected by the senior radiologist. CAD-VD10F detected 1401 true-positive, 143 false-negative, 565 false-positive (FP), and 342 true-negative PSNs, resulting in sensitivity of 90.7%, specificity of 37.7%, positive predictive value of 0.71, and negative predictive value of 0.70. CAD-VD20A detected 1381 true-positive, 163 false-negative, 337 FP, and 570 true-negative PSNs, resulting in sensitivity of 89.4%, specificity of 62.8%, positive predictive value of 0.80, and negative predictive value 0.77, respectively. The rate of FP per scan was 0.6 for CAD-VD10F and 0.3 for CAD-VD20A.

Conclusions

The new deep learning–based CAD software (VD20A) shows similar sensitivity with the conventional CAD software (VD10F), but a significantly higher specificity.
Hope Springs Eternal: Insights Into the Durability of Springs to Provide Long-Term Correction of the Scaphocephalic Head Shape
Authors: Shakir Sameer , Humphries Laura S. , Kalmar Christopher L. , Bartlett Scott P. , Swanson Jordan W. , Taylor Jesse A.
Published: August 2020

Spring-mediated cranial vault expansion (SMC) has become a primary treatment modality at our institution to correct scaphocephalic head shape in the setting of isolated sagittal craniosynostosis (CS). Spring-mediated cranioplasty is associated with minimal procedural morbidity and reliable clinical efficacy, although long-term outcomes are not well elucidated. Herein we describe our institutional experience and lessons learned with SMC. We hypothesize that SMC performed in young infants offers durable scaphocephalic correction as measured by cephalic index (CI) at the 1, 3, and 5-year postoperative timepoints.

Patients with isolated sagittal CS who underwent SMC at our institution during an 8-year period were retrospectively studied. The primary outcome measure was long-term head shape determined by CI at the 1, 3, and 5-year postoperative timepoints. Secondary outcomes included patient and spring factors associated with change in CI, including age and spring force. All statistical tests were 2-tailed with P < 0.05 denoting significance.

In total, 88 patients underwent SMC at a median age of 3.3 months with a median preoperative CI 69 (interquartile range: [66, 71]). The postoperative CI increased to 73 [71, 76] at postoperative day 1. At 1 month, the CI increased by 8.6 to 77 (P < 0.0001) and appeared to reach a plateau at 3 months (76, [74, 78]) without further improvement (P < 0.10). At 5 years, CI remained stable without relapse (76, [75, 81], demonstrating an 8.9 increase from preoperative CI. Age at time of spring placement and change in CI were inversely related (P < 0.005). Total spring force directly correlated with increased change in postoperative CI at the 6-month postoperative timepoint (P < 0.02).

In summary, SMC offers durable correction of scaphocephaly as measured by CI for patients with isolated sagittal CS at the 5-year postoperative timepoint. The cranial expansion observed 1-month post-spring implantation may serve as a proxy for long-term CI.
A Novel Sand Dollar and Staves Technique for Unilateral Lambdoid Craniosynostosis
Authors: Abu-Ghname Amjed , Masoumy Mohamad , Basagaoglu Berkay , Dempsey Robert F. , Dauser Robert C. , Maricevich Renata S.
Published: August 2020

Background:

Unilateral lambdoid synostosis (ULS) is the rarest form of craniosynostosis. Due to the associated cranio-caudal shift seen in ULS, surgical correction is technically challenging from a morphological standpoint. Herein, the authors present a novel “Sand-Dollar and Staves” technique for the repair of ULS.

Methods:

A zigzag coronal incision is performed, and an anteriorly-based pericranial flaps are elevated. Prefabricated cutting guides are placed and the calvarium is marked. To treat the flattening on the ipsilateral side, a wedged suturectomy is performed with additional barrel staves. A large circle centered over the bulging on the contralateral side is cut out above the open lambdoid suture. This piece is barrel staved in a radial fashion, leaving the center intact and creating a Sand-Dollar appearance. This disk is then flattened and trimmed. The modified Sand-Dollar is fixed using an absorbable plating system. While gentle pressure is applied to the Sand-Dollar piece as it is being secured, the ipsilateral side demonstrates compensatory filling. Results are evaluated using the Whitaker Classification.

Results:

Four patients underwent surgical correction with this technique. The procedure was performed at mean age of 11.7 months. The mean operative time was 2.5 hours. Intraoperative blood loss was 50 to 100 ml. Total hospitalization time was 2 to 3 days. No post-operative complications were encountered. Whitaker scores ranged from 1 to 1.5. The mean follow-up was 10 months.

Conclusion:

The Sand-Dollar and Staves procedure is a novel, single-stage approach for the management of ULS with decreased operative time, blood loss, and hospital stay with satisfactory aesthetic outcomes.
Biomarkers in amyotrophic lateral sclerosis: a review of new developments
Authors: Verber Nick , Shaw Pamela J.
Published: August 2020

Purpose of review

This review draws together the most recent findings in ALS biomarker research from biochemical, imaging and neurophysiology techniques.

Recent findings

The potential of circulating RNA is highlighted, including new retrieval techniques. With ongoing genetic clinical trials, the need for pharmacodynamic biomarkers is essential. There is a strong case for neurofilament proteins being validated in ALS; their biomarker profile is discussed. Oxidative stress and neuroinflammation studies offer insight into disease mechanisms and offer good biomarker potential. Recent metabolic studies include investigation of lipid profiles, creatinine and ferritin. The potential of chitinase proteins as pharmacodynamic and prognostic biomarkers is highlighted. The role of tau and amyloidβ is debated, as evidenced by the articles presented here. Proteomic approaches provide unbiased discoveries of novel biomarkers, together with confirmation of previous findings. The use of imaging techniques is outlined to demonstrate selective atrophy, volume loss, muscle and tract involvement. In-vivo imaging is discussed with reference to histone deacetylase, oxidative stress, neuroinflammation and metabolic changes. New applications of electrophysiology demonstrate objective muscle biomarkers and brain network perturbations.

The biomarker research field continues to provide insight into the disease. Multicentre collaborations are needed to validate these promising recent findings.
Climate change mitigation potential of wetlands and the cost-effectiveness of their restoration
Authors: Taillardat Pierre , Thompson Benjamin S. , Garneau Michelle , Trottier Karelle , Friess Daniel A.
Published: August 2020

The cost-effective mitigation of climate change through nature-based carbon dioxide removal strategies has gained substantial policy attention. Inland and coastal wetlands (specifically boreal, temperate and tropical peatlands; tundra; floodplains; freshwater marshes; saltmarshes; and mangroves) are among the most efficient natural long-term carbon sinks. Yet, they also release methane (CH
4
) that can offset the carbon they sequester. Here, we conducted a meta-analysis on wetland carbon dynamics to (i) determine their impact on climate using different metrics and time horizons, (ii) investigate the cost-effectiveness of wetland restoration for climate change mitigation, and (iii) discuss their suitability for inclusion in climate policy as negative emission technologies. Depending on metrics, a wetland can simultaneously be a net carbon sink (i.e. boreal and temperate peatlands net ecosystem carbon budget = −28.1 ± 19.13 gC m
−2
y
−1
) but have a net warming effect on climate at the 100 years time-scale (i.e. boreal and temperate peatland sustained global warming potential = 298.2 ± 100.6 gCO
2
eq
−1
m
−2
y
−1
). This situation creates ambivalence regarding the effect of wetlands on global temperature. Moreover, our review reveals high heterogeneity among the (limited number of) studies that document wetland carbon budgets. We demonstrate that most coastal and inland wetlands have a net cooling effect as of today. This is explained by the limited CH
4
emissions that undisturbed coastal wetlands produce, and the long-term carbon sequestration performed by older inland wetlands as opposed to the short lifetime of CH
4
in the atmosphere. Analysis of wetland restoration costs relative to the amount of carbon they can sequester revealed that restoration is more cost-effective in coastal wetlands such as mangroves (US$1800 ton C
−1
) compared with inland wetlands (US$4200–49 200 ton C
−1
). We advise that for inland wetlands, priority should be given to conservation rather than restoration; while for coastal wetlands, both conservation and restoration may be effective techniques for climate change mitigation.
Rooting carbon dioxide removal research in the social sciences
Authors: Dowell Glen , Niederdeppe Jeff , Vanucchi Jamie , Dogan Timur , Donaghy Kieran , Jacobson Rory , Mahowald Natalie , Milstein Mark , Zelikova T. Jane
Published: August 2020

Reports from a variety of bodies have highlighted the role that carbon dioxide removal (CDR) technologies and practices must play in order to try to avoid the worst effects of anthropogenic climate change. Research into the feasibility of these technologies is primarily undertaken by scholars in the natural sciences, yet, as we argue in this commentary, there is great value in collaboration between these scholars and their colleagues in the social sciences. Spurred by this belief, in 2019, a university and a non-profit organization organized and hosted a workshop in Washington, DC, intended to bring natural and physical scientists, technology developers, policy professionals and social scientists together to explore how to better integrate social science knowledge into the field of CDR research. The workshop sought to build interdisciplinary collaborations across CDR topics, draft new social science research questions and integrate and exchange disciplinary-specific terminology. But a snowstorm kept many social scientists who had organized the conference from making the trip in person. The workshop went on without them and organizers did the best they could to include the team remotely, but in the age before daily video calls, remote participation was not as successful as organizers had hoped. And thus, a workshop that was supposed to focus on social science integration moved on, without many of the social scientists who organized the event. The social scientists in the room were supposed to form the dominant voice but with so many stuck in a snow storm, the balance of expertise shifted, as it often does when social scientists collaborate with natural and physical scientists. The outcomes of that workshop, lessons learned and opportunities missed, form the basis of this commentary, and they collectively indicate the barriers to integrating the natural, physical and social sciences on CDR. As the need for rapid, effective and successful CDR has only increased since that time, we argue that CDR researchers from across the spectrum must come together in ways that simultaneously address the technical, social, political, economic and cultural elements of CDR development, commercialization, adoption and diffusion if the academy is to have a material impact on climate change in the increasingly limited window we have to address it.
Behavioural frameworks to understand public perceptions of and risk response to carbon dioxide removal
Authors: Shrum Trisha R. , Markowitz Ezra , Buck Holly , Gregory Robin , van der Linden Sander , Attari Shahzeen Z. , Van Boven Leaf
Published: August 2020

The adoption of carbon dioxide removal (CDR) technologies at a scale sufficient to draw down carbon emissions will require both individual and collective decisions that happen over time in different locations to enable a massive scale-up. Members of the public and other decision-makers have not yet formed strong attitudes, beliefs and preferences about most of the individual CDR technologies or taken positions on policy mechanisms and tax-payer support for CDR. Much of the current discourse among scientists, policy analysts and policy-makers about CDR implicitly assumes that decision-makers will exhibit unbiased, rational behaviour that weighs the costs and benefits of CDR. In this paper, we review behavioural decision theory and discuss how public reactions to CDR will be different from and more complex than that implied by rational choice theory. Given that people do not form attitudes and opinions in a vacuum, we outline how fundamental social normative principles shape important intergroup, intragroup and social network processes that influence support for or opposition to CDR technologies. We also point to key insights that may help stakeholders craft public outreach strategies that anticipate the nuances of how people evaluate the risks and benefits of CDR approaches. Finally, we outline critical research questions to understand the behavioural components of CDR to plan for an emerging public response.
The future of carbon dioxide removal must be transdisciplinary
Authors: Zelikova Tamara Jane
Published: August 2020

Carbon dioxide removal (CDR) represents a suite of pathways to remove carbon dioxide from the atmosphere and mitigate climate change. The importance of CDR has expanded in recent years as emission reductions are not at pace to meet climate goals. This CDR-themed issue brings together diverse perspectives in order to identify opportunities to integrate across CDR disciplines, create a more holistic research agenda and inform how CDR is deployed. The individual papers within the issue discuss engineered and nature-based CDR approaches as well as the broader social and behavioural dimensions of CDR development and deployment. Here, I summarize the main take-aways from these individual papers and present a path for integrating key lessons across disciplines to ensure CDR is scaled equitably and sustainably to deliver on its climate mitigation promise.
Agromyces humi sp. nov., actinobacterium isolated from farm soil
Authors: Lee Jae-Chan , Whang Kyung-Sook
Published: August 2020

A Gram-stain-positive actinobacterial strain, designated ANK073T, was isolated from rhizosphere soil sampled at a spinach farming field in Shinan, Republic of Korea. Cells of strain ANK073T were found to be aerobic, non-motile, non-spore-forming rods which could grow at 20–40 °C (optimum, 30 °C), at pH 6.0–10.0 (optimum, pH 6.5–7.5) and at salinities of 0–4 % (w/v) NaCl (optimum, 0 % NaCl). The 16S rRNA gene sequence analysis showed that strain ANK073T belongs to the genus

Agromyces

with high sequence similarities to

Agromyces humatus

CD5T (98.8 %),

Agromyces tardus

SJ-23T (98.5 %) and

Agromyces iriomotensis

IY07-20T (98.4 %). The phylogenetic analysis indicated that strain ANK073T formed a distinct phyletic line in the genus

Agromyces

and the results of DNA–DNA relatedness and phylogenomic analysis based on whole genome sequences demonstrated that strain ANK073T could be separated from its closest relatives in the genus

Agromyces

. The strain contained 2,4-diaminobutylic acid, glycine, d-glutamic acid and d-alanine in the peptidoglycan. The predominant menaquinones were identified as MK-12 and MK-11, and the major fatty acids were anteiso-C17 : 0, anteiso-C15 : 
0 and iso-C15:0. The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The G+C content of the genome was determined to be 70.2 mol%. On the basis of its phenotypic and chemotaxonomic properties and the results of phylogenetic and phylogenomic analyses, strain ANK073T is considered to represent a novel species in the genus

Agromyces

, for which the name Agromyces humi sp. nov. is proposed. The type strain is ANK073T (=KACC 18683T=NBRC 111825T).
Patent prospects and trends in post-harvest management technology of
fresh agricultural products
Authors: Choi Ji Weon , Kim Su Yeon , Lim Sooyeon , Choi Hyunjin , Yang Haejo , Shin Il Sheob
Published: August 2020

To predict the best direction for post-harvest management technology of fresh
agricultural products, the growth potential of patents was evaluated using 1,517
valid patents from 1998 to 2017 for four countries (Korea, China, Japan, and
United States) and the European Union. A patent portfolio (PP) index was used to
evaluate the technological growth of the collected patents. Patent increase (PI)
and patent sharing (PS) indices were used to evaluate the emerging trends in
technology. A technology cycle time (TCT) model based on the PI, PS, and market
power (MP) indices was used to compare the growth potential of each category.
The PP index indicated that post-harvest management technology is in a growth
stage; both the PI and PS indices showed that storage technology has high
development potential, whereas packaging technology has low development
potential owing to a low rate of increase. A multi-layer TCT model predicted
that post-harvest management technology has high growth potential because the PI
was 168.8%, the ratio of PS was 36.6%, and the MP increased
111.3%. Our results indicate that post-harvest management technologies
have high growth potential, although patent applications decreased in some
countries early in the study period. This study is important to establish the
future strategy for extending the exportation of fresh agricultural products in
Korea.
Effect of commercial carbohydrases on the hesperetin and narigenin
contents of citrus fruits
Authors: Shin Kwang-Seup , Chang Hyeon-Jun , Lee Jeung-Hee
Published: August 2020

Citrus fruits were treated with commercial carbohydrases to produce hydrolyzed
citrus with higher amounts of hesperetin and narigenin. The suitable enzymatic
reaction conditions were determined using standard hesperidin and naringin with
three carbohydrases (Viscozyme L > AMG 300L > Pectinex Ultra
Pulp), varying reaction buffer pH levels (5.0 > 4.0 > 6.0) and
reaction times (24 h > 2 h). Viscozyme L produced significantly higher
contents of hesperetin and narigenin than the other enzymes (p<0.05), and
the contents increased with reaction time. With Viscozyme L, higher contents of
hesperetin and narigenin (1.63 and 2.10 times) and higher total phenolic
contents (1.69 times) were produced in the hydrolyzed immature citrus relative
to those in the hydrolyzed mature citrus (p<0.05). In addition to the
minimum inhibitory concentration of the hydrolyzed immature citrus was lower
against Staphylococcus aureus than against Escherichia
coli. Thus, enzymatic hydrolysis with immature citrus appears to
produce much higher contents of hesperetin, narignenin and total phenolic
contents than with the mature citrus, and enzymatic hydrolysis could improve the
quality of citrus beverages. Hydrolyzed citrus would likely serve as a
functional food additive with high added value in the citrus processing
industry.
The effect of osmotic dehydration pretreatment with sweetenerson the
quality of dried aronia berries
Authors: Bae Suin , Choi Ji-Young , Lee Hyeon-Jeong , Kim Jiyoon , Moon Kwang-Deog
Published: August 2020

Aronia (Aronia melanocarpa) berries are rich in polyphenols.
However, they are extremely astringent, which reduces their commercial
viability. This study suggests a treatment method to produce more commercial
aronia products. In this method, the berries were pretreated with osmotic
dehydration and then dried with hot air or lyophilized to reduce their
astringency. Sucrose, glucose, and xylitol were used as the pretreatment
solutions. The products were prepared and grouped as follows: raw aronia (CON),
freeze-dried (FD), osmo-dehydrated using sucrose solution and freeze-dried
(FDS), osmo-dehydrated using glucose solution and freeze-dried (FDG),
osmo-dehydrated using xylitol solution and freeze-dried (FDX), hot-air-dried
(HD), osmo-dehydrated using sucrose solution and hot-air-dried (HDS),
osmo-dehydrated using glucose solution and hot-air-dried (HDG), and
osmo-dehydrated using xylitol solution and hot-air-dried (HDX). Water loss was
highest in aronia berries that were osmo-dehydrated using sucrose solution
(16.36%), followed by berries that were dehydrated using glucose solution
(14.26%), and those that were osmo-dehydrated using xylitol solution
(12.83%). Moisture contents and total soluble solid contents of the FD
products were 3.83-7.45% and 6,908.47 °Brix, respectively. FDS and
FDX showed relatively high phenolic compound contents and antioxidant
activities. FDG and FDS showed better texture and redness. FDS received the
highest score for sweetness (5.07) and overall preference (5.13). Hence, FDS
proved to be the most appropriate pretreatment, because it allows a better
control of the moisture content and maintenance of their appearance and texture,
with a relatively low reduction of their phenolic contents. Hence, it affords
better preservation efficiency to aronia products.
Antioxidant activity and immune-enhancing effect of aqueous leaf
Elaeagnus multiflora Thunb
Authors: Kim Mi Ri , Kim Young Uk , Im So Jeong , Jo A Ra , Lee Gyu Ok , Shin Ja Won , Kang Hu Won , Choi Hak Joon , Lee Seul Gi , Kim Cho Een , Lee Hak Sung , Kim Jaeyong , Choi Chul Yung
Published: August 2020

In this study, we aimed to investigate the antioxidant and immunopotentiating
effects of leaves of cherry elaeagnus (Elaeagnus multiflora,
Em). The leaf, stem, and root of Em have been used in Kampo medicine. There are
data on the therapeutic effects of Em fruit, but no information on its leaves.
We thus investigated the antioxidant and immunopotentiating effects of Em leaf
extract. Balb/c mouse spleen cells were treated with
concanavalin A and hot aqueous Em leaf extract (50, 100, and 200 μg/mL),
and the effects on spleen cell proliferation and the secretion of interleukin
(IL)-2, IL-4, and IL-10 were evaluated. A concentration-dependent increase in
the secretion of IL-2 and IL-4 cytokines was observed, with concentrations of
1.86 pg/mL of IL-2 and 37.63 pg/mL of IL-4 when cells were treated with 200
μg/mL of the extract. Natural killer (NK) cell activity was determined
based on a co-culture of spleen cells and Yac-1 cells. NK activity gradually
increased in a concentration-dependent manne. Further,
2,2-diphenyl-1-picrylhydrazyl radical scavenging activity was 58.5% and
2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging
activity was 78.2% with an extract concentration of 200 μg/mL. The
high antioxidant activity of the hot water extract of Em leaves suggests their
potential therapeutic value and warrants further studies.
COVID-19 Infection Among Healthcare Workers in a National Healthcare System: the Qatar Experience
Authors: Alajmi Jameela , Jeremijenko Andrew M. , Abraham Joji C. , Ishaq Moza , Concepcion Elli G. , Butt Adeel A. , Abou-Samra Abdul-Badi
Published: August 2020

The study was conducted at Hamad Medical Corporation in Qatar, a national healthcare system with 14 hospitals and over 28,000 employees. A total of 16,912 staff members were tested for SARS-CoV-2 between March 10 and June 24, 2020 with 1,799 (10.6%) testing positive. Nurses and midwives had the highest number of infections (33.2% of all infected HCWs) followed by non-clinical support service staff (31.3%), administrative staff (14.6%), allied health professionals (12.7%), physicians (5.2% and other clinical support staff (2.9%). Among 671 infected HCW surveyed by the infection prevention and control team immediately after the positive COVID-19 test was reported, exposure to a family member or roommate with confirmed infection each were reported by 9.5%. Two-thirds of the infected HCWs were symptomatic with fever (34.6%), cough (32.2%) and sore throat (15.8%) being the most commonly reported symptoms. Among the survey respondents, 78 (11.6%) were hospitalized, 9 (1.3%) required supplemental oxygen, 4 (0.6%) were admitted to the intensive care unit) and 2 (0.3%) required mechanical ventilation. There were no deaths. To understand the transmission dynamics and impact of facility designation as COVID-19 or non-COVID-19 facility, we conducted a focused follow-up telephone survey on 393 COVID-19 positive HCW 1-6 weeks after diagnosis. Only 5% of respondents reported acquiring the virus from working at a COVID-19 designated facility while the remaining 95% reported working at a non-COVID-19 facility and acquired the infection from accidental exposure to a colleague (45%) or to a patient (29%). Among infected HCW at COVID-19 designated facilities, 82% reported used full PPE at all times while 68% of infected HCW at non-COVID-19 facilities reported using PPE as directed.
In vivo structural MRI-based atlas of human thalamic nuclei
Authors: Saranathan Manojkumar , Iglehart Charles , Monti Martin , Tourdias Thomas , Rutt Brian
Published: August 2020

Thalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are very few digital MRI thalamic atlases and they have been constructed using a small number of post-mortem brains. The goal of this work is the development of a structural thalamic atlas at high spatial resolution based on manual segmentation of 20 subjects that include healthy subjects and patients with multiple-sclerosis. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available.
Neural Mechanisms of Acceptance and Commitment Therapy for Chronic Pain: A Network-Based fMRI Approach
Authors: Aytur Semra A. , Ray Kimberly L. , Meier Sarah K. , Campbell Jenna , Gendron Barry , Waller Noah , Robin Donald A.
Published: August 2020

Over 100 million Americans suffer from chronic pain (CP), which causes more disability than any other medical condition in the U.S. at a cost of $560-$635 billion per year (IOM, 2011). Opioid analgesics are frequently used to treat CP. However, long term use of opioids can cause brain changes such as opioid-induced hyperalgesia that, over time, increase pain sensation. Also, opioids fail to treat complex psychological factors that worsen pain-related disability, including beliefs about and emotional responses to pain. Cognitive behavioral therapy (CBT) can be efficacious for CP. However, CBT generally does not focus on important factors needed for long-term functional improvement, including attainment of personal goals and the psychological flexibility to choose responses to pain.

Acceptance and Commitment Therapy (ACT) has been recognized as an effective, non-pharmacologic treatment for a variety of CP conditions. However, little is known about the neurologic mechanisms underlying ACT. We conducted an ACT intervention in women (n=9) with chronic musculoskeletal pain. Functional magnetic resonance imaging (fMRI) data were collected pre- and post-ACT, and changes in functional connectivity (FC) were measured using Network-Based Statistics (NBS). Behavioral outcomes were measured using validated assessments such as the Acceptance & Action Questionnaire (AAQ-II), the Chronic Pain Acceptance Questionnaire (CPAQ), the Center for Epidemiologic Studies Depression Scale (CES-D), and the NIH Toolbox Neuro-QoL™ (Quality of Life in Neurological Disorders) scales.

Results suggest that, following the four-week ACT intervention, participants exhibited reductions in brain activation within and between key networks including self-reflection (default mode, DMN), emotion (salience, SN), and cognitive control (frontal parietal, FPN). These changes in connectivity strength were correlated with changes in behavioral outcomes including decreased depression and pain interference, and increased participation in social roles. This study is one of the first to demonstrate that improved function across the DMN, SN, and FPN may drive the positive outcomes associated with ACT. This study contributes to the emerging evidence supporting the use of neurophysiological indices to characterize treatment effects of alternative and complementary mind-body therapies.

Perspective

This article identifies neural mechanisms that may mediate behavioral changes associated with Acceptance and Commitment Therapy (ACT) in persons with chronic musculoskeletal pain. This information could potentially help clinicians to determine which mind-body therapies may benefit specific patients as part of an integrative pain management approach.
Deciphering the state of immune silence in fatal COVID-19 patients
Authors: Bost Pierre , De Sanctis Francesco , Canè Stefania , Ugel Stefano , Donadello Katia , Castellucci Monica , Eyal David , Fiore Alessandra , Anselmi Cristina , Barouni Roza Maria , Trovato Rosalinda , Caligola Simone , Lamolinara Alessia , Iezzi Manuela , Facciotti Federica , Mazzariol Anna Rita , Gibellini Davide , De Nardo Pasquale , Tacconelli Evelina , Gottin Leonardo , Polati Enrico , Schwikowski Benno , Amit Ido , Bronte Vincenzo
Published: August 2020

Since the beginning of the SARS-CoV-2 pandemic, COVID-19 has appeared as a unique disease with unconventional tissue and systemic immune features. While COVID-19 severe forms share clinical and laboratory aspects with various pathologies such as hemophagocytic lymphohistiocytosis, sepsis or cytokine release syndrome, their exact nature remains unknown. This is severely impeding the ability to treat patients facing severe stages of the disease. To this aim, we performed an in-depth, single-cell RNA-seq analysis of more than 150.000 immune cells isolated from matched blood samples and broncho-alveolar lavage fluids of COVID-19 patients and healthy controls, and integrated it with clinical, immunological and functionalex vivodata. We unveiled an immune signature of disease severity that correlated with the accumulation of naïve lymphoid cells in the lung and an expansion and activation of myeloid cells in the periphery. Moreover, we demonstrated that myeloid-driven immune suppression is a hallmark of COVID-19 evolution and arginase 1 expression is significantly associated with monocyte immune regulatory features. Noteworthy, we found monocyte and neutro-phil immune suppression loss associated with fatal clinical outcome in severe patients. Additionally, our analysis discovered that the strongest association of the patients clinical outcome and immune phenotype is the lung T cell response. We found that patients with a robust CXCR6+ effector memory T cell response have better outcomes. This result is line with the rs11385942 COVID-19 risk allel, which is in proximity to the CXCR6 gene and suggest effector memory T cell are a primary feature in COVID-19 patients. By systemically quantifying the viral landscape in the lung of severe patients, we indeed identified Herpes-Simplex-Virus 1 (HSV-1) as a potential opportunistic virus in COVID-19 patients. Lastly, we observed an unexpectedly high SARS-CoV-2 viral load in an immuno-compromised patient, allowing us to study the SARS-CoV-2in-vivolife cycle. The development of myeloid dysfunctions and the impairment of lymphoid arm establish a condition of immune paralysis that supports secondary bacteria and virus infection and can progress to “immune silence” in patients facing death.
Risk of fomite-mediated transmission of SARS-CoV-2 in child daycares, schools, and offices: a modeling study
Authors: Kraay Alicia N.M. , Hayashi Michael A. L. , Berendes David M. , Sobolik Julia S. , Leon Juan S. , Lopman Benjamin A.
Published: August 2020

SARS-CoV-2 can persist on surfaces, suggesting that surface-based transmission might be important for this pathogen. We find that fomites may be a substantial source of risk, particularly in schools and child daycares. Combining surface cleaning and decontamination with strategies to reduce pathogen shedding on surfaces can help mitigate this risk.
Chemotactic Migration of Bacteria in Porous Media
Authors: Bhattacharjee T. , Amchin D. B. , Ott J. A. , Kratz F. , Datta S. S.
Published: August 2020

Chemotactic migration of bacteria—their ability to direct multicellular motion along chemical gradients—is central to processes in agriculture, the environment, and medicine. However, studies are typically performed in homogeneous media, despite the fact that many bacteria inhabit heterogeneous porous media such as soils, sediments, and biological gels. Here, we directly visualize the migration ofEscherichia colipopulations in 3D porous media. We find that pore-scale confinement is a strong regulator of chemotactic migration. Strikingly, cells use a different primary mechanism to direct their motion in confinement than in bulk liquid. Further, confinement markedly alters the dynamics and morphology of the migrating population—features that can be described by a continuum model, but only when standard motility parameters are substantially altered from their bulk liquid values. Our work thus provides a framework to predict and control the migration of bacteria, and active matter in general, in heterogeneous environments.

Statement of Significance

Typical studies of bacterial motility focus on cells in homogeneous media; however, many bacteria inhabit tight porous media such as soils, sediments, and biological gels. This paper demonstrates how confinement in a porous medium fundamentally alters the chemotactic migration ofEscherichia coli. We find that cells use a different primary mechanism to direct their motion in confinement than in bulk liquid. Further, confinement markedly alters the overall dynamics and morphology of a migrating population—features that can be described by a continuum model, but only when standard motility parameters are substantially altered from their bulk liquid values. This work thus provides a framework to predict and control the migration of bacteria, and active matter in general, in heterogeneous porous environments.
Autophagy is required for lipid homeostasis during dark-induced senescence in Arabidopsis
Authors: Barros Jessica A. S. , Magen Sahar , Lapidot-Cohen Taly , Rosental Leah , Brotman Yariv , Araújo Wagner L. , Avin-Wittenberg Tamar
Published: August 2020

Autophagy is an evolutionarily conserved mechanism that mediates the degradation of cytoplasmic components in eukaryotic cells. In plants, autophagy has been extensively associated with the recycling of proteins during carbon starvation conditions. Even though lipids constitute a significant energy reserve, our understanding of the function of autophagy in the management of cell lipid reserves and components remains fragmented. To further investigate the significance of autophagy in lipid metabolism, we performed an extensive lipidomic characterization of Arabidopsis (Arabidopsis thaliana) autophagy mutants (atg) submitted to dark-induced senescence conditions. Our results revealed an altered lipid profile inatgmutants, suggesting that autophagy affects the homeostasis of multiple lipid components under dark-induced senescence. The acute degradation of chloroplast lipids coupled with the differential accumulation of triacylglycerols (TAGs) and plastoglobuli indicates an alternative metabolic reprogramming towards lipid storage inatgmutants. The imbalance of lipid metabolism compromises the production of cytosolic lipid droplets and the regulation of peroxisomal lipid oxidation pathways inatgmutants.

One-sentence summary

Autophagy is required for the mobilization of membrane lipid components and lipid droplet dynamics during extended darkness inArabidopsis.
Endocast and bony labyrinth of a stem gnathostome shed light on the earliest diversification of jawed vertebrates
Authors: Zhu You-an , Giles Sam , Young Gavin , Hu Yuzhi , Bazzi Mohamad , Ahlberg Per E. , Zhu Min , Lu Jing
Published: August 2020

Our understanding of the earliest evolution of jawed vertebrates depends on a credible phylogenetic assessment of the jawed stem gnathostomes collectively known as ‘placoderms’. However, their relationships, and even whether ‘placoderms’ represent a single radiation or a paraphyletic array, remain contentious. Here we describe the endocranial cavity and inner ear ofBrindabellaspis stensioi, commonly recovered as a taxon of uncertain affinity branching near the base of ‘placoderms’. While some features of its braincase and endocast resemble those of jawless vertebrates, its inner ear displays a repertoire of crown gnathostome characters. Both parsimony and Bayesian analyses suggest that established hypotheses of ‘placoderm’ relationships are unstable, with newly-revealed anatomy pointing to a potentially radical revision of early gnathostome evolution. Our results call into question the appropriateness of fusiform ‘placoderms’ as models of primitive gnathostome anatomy and raise questions of homology relating to key cranial features.

One Sentence Summary

The skull of a 400-million-year old fossil fish suggests that hypotheses of early jawed vertebrate relationships might have to be turned on their head.
Tutorial: Assessing metagenomics software with the CAMI benchmarking toolkit
Authors: Meyer Fernando , Lesker Till-Robin , Koslicki David , Fritz Adrian , Gurevich Alexey , Darling Aaron E. , Sczyrba Alexander , Bremges Andreas , McHardy Alice C.
Published: August 2020

Computational methods are key in microbiome research, and obtaining a quantitative and unbiased performance estimate is important for method developers and applied researchers. For meaningful comparisons between methods, to identify best practices, common use cases, and to reduce overhead in benchmarking, it is necessary to have standardized data sets, procedures, and metrics for evaluation. In this tutorial, we describe emerging standards in computational metaomics benchmarking derived and agreed upon by a larger community of researchers. Specifically, we outline recent efforts by the Critical Assessment of Metagenome Interpretation (CAMI) initiative, which supplies method developers and applied researchers with exhaustive quantitative data about software performance in realistic scenarios and organizes community-driven benchmarking challenges. We explain the most relevant evaluation metrics to assess metagenome assembly, binning, and profiling results, and provide step-by-step instructions on how to generate them. The instructions use simulated mouse gut metagenome data released in preparation for the second round of CAMI challenges and showcase the use of a repository of tool results for CAMI data sets. This tutorial will serve as a reference to the community and facilitate informative and reproducible benchmarking in microbiome research.
Single-cell lineage and transcriptome reconstruction of metastatic cancer reveals selection of aggressive hybrid EMT states
Authors: Simeonov Kamen P , Byrns China N , Clark Megan L , Norgard Robert J , Martin Beth , Stanger Ben Z , McKenna Aaron , Shendure Jay , Lengner Christopher J
Published: August 2020

Metastatic cancer remains largely incurable due to an incomplete understanding of how cancer cells disseminate throughout the body. However, tools for probing metastatic dissemination and associated molecular changes at high resolution are lacking. Here we present multiplexed, activatable, clonal, and subclonal GESTALT (macsGESTALT), an inducible lineage recorder with concurrent single cell readout of transcriptional and phylogenetic information. By integrating multiple copies of combined static barcodes and evolving CRISPR/Cas9 barcodes, macsGESTALT enables clonal tracing and subclonal phylogenetic reconstruction, respectively. High barcode editing and recovery rates produce deep lineage reconstructions, densely annotated with transcriptomic information. Applying macsGESTALT to a mouse model of metastatic pancreatic cancer, we reconstruct dissemination of tens-of-thousands of single cancer cells representing 95 clones and over 6,000 unique subclones across multiple distant sites, e.g. liver and lung metastases. Transcriptionally, cells exist along a continuum of epithelial-to-mesenchymal transition (EMT)in vivowith graded changes in associated signaling, metabolic, and regulatory processes. Lineage analysis reveals that from a majority of non-metastatic, highly epithelial clones, a single dominant clone that has progressed along EMT drives the majority of metastasis. Within this dominant clone a parallel process occurs, where a small number of aggressive subclones drive clonal outgrowth. By precisely mapping subclones along the EMT continuum, we find that size and dissemination gradually increase, peaking at late-hybrid EMT states but precipitously falling once subclones are highly mesenchymal. Late-hybrid EMT states are selected from a predominately epithelial ancestral pool, enabling rapid metastasis but also forcing extensive and continuous population bottlenecking. Notably, late-hybrid gene signatures are associated with decreased survival in human pancreatic cancer, while epithelial, early-hybrid, and highly mesenchymal states are not. Our findings illuminate features of metastasis and EMT with the potential for therapeutic exploitation. Ultimately, macsGESTALT provides a powerful, accessible tool for probing cancer and stem cell biologyin vivo.