bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of a CTNNB1‐associated metabolic prognostic model for hepatocellular carcinoma
Authors: Huo Junyu , Wu Liqun , Zang Yunjin
Published: December 2020

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy closely related to metabolic reprogramming. We investigated how CTNNB1 mutation regulates the HCC metabolic phenotype and thus affects the prognosis of HCC. We obtained the mRNA expression profiles and clinicopathological data from The Cancer Genome Atlas (TCGA), the International Cancer Genomics Consortium (ICGC) and the Gene Expression Omnibus database (GSE14520 and GSE116174). We conducted gene set enrichment analysis on HCC patients with and without mutant CTNNB1 through TCGA dataset. The Kaplan‐Meier analysis and univariate Cox regression analysis assisted in screening metabolic genes related to prognosis, and the prognosis model was constructed using the Lasso and multivariate Cox regression analysis. The prognostic model showed good prediction performance in both the training cohort (TCGA) and the validation cohorts (ICGC, GSE14520, GSE116174), and the high‐risk group presented obviously poorer overall survival compared with low‐risk group. Cox regression analysis indicated that the risk score can be used as an independent predictor for the overall survival of HCC. The immune infiltration in different risk groups was also evaluated in this study to explore underlying mechanisms. This study is also the first to describe an metabolic prognostic model associated with CTNNB1 mutations and could be implemented for determining the prognoses of individual patients in clinical practice.
Google search trends for itch in Europe: a retrospective longitudinal study
Authors: Pereira M.P. , Ziehfreund S. , Rueth M. , Ewering T. , Legat F.J. , Lambert J. , Elberling J. , Misery L. , Brenaut E. , Papadavid E. , Garcovich S. , Evers A.W.M. , Halvorsen J.A. , Szepietowski J.C. , Reich A. , Gonçalo M. , Lvov A. , Bobko S. , Serra‐Baldrich E. , Wallengren J. , Savk E. , Leslie T. , Ständer S. , Zink A. ,   the EADV Task Force Pruritus
Published: December 2020

Background

Itch is a common symptom in the general population. Affected individuals often do not seek medical consultation and rely on Internet searches to obtain information regarding their itch.

Objectives

The aim of this study was to attain insights into common concerns of the general population regarding itch can by analysing itch‐related Internet search behaviour.

Methods

Google AdWords Keyword Planner was used to assess search volumes for itch‐related terms in 15 European countries between September 2014 and August 2018. All identified keywords were qualitatively categorized. Itch‐related terms were descriptively analysed and are shown as number of searches/100 000 inhabitants.

Results

The search volume for the keyword ‘itch’ per 100 000 inhabitants was highest in Northern Europe, followed by Eastern, Central and Southern Europe. In 4/15 countries, itch was searched for more often in the autumn/winter months compared to in the spring/summer months. Most itch‐related terms were related to dermatological conditions such as inflammatory skin diseases (e.g. psoriasis, atopic dermatitis), allergic or immunologic conditions (e.g. urticaria), and infectious diseases or infestations (e.g. scabies). In terms of body location, genitoanal itch dominated the searches. Symptoms and signs related to itch, possible non‐dermatological aetiologies, and treatment options were also among the most searched terms.

Conclusions

These analyses provided for the first time insights into the search behaviour patterns related to itch across Europe. People from Northern and Eastern Europe are more likely to seek online information regarding itch. Causes for the itch, especially dermatological conditions, and genitoanal itch are the most important concerns for Internet users. This unconventional and inexpensive method identifies medical needs of people beyond the medical setting, including people who do not seek medical consultation. Accordingly, the data could be used to guide public health interventions and manage respective inhabitants’ medical needs.
Sexual selection on performance traits in an Australian lizard with alternative reproductive tactics
Authors: Noble Daniel W. A. , Kar Fonti , Nakagawa Shinichi , Keogh J. Scott , Whiting Martin J.
Published: December 2020

Sexual selection shapes the adaptive landscape in complex ways that lead to trait integration. Much of our understanding of selection comes from studies of morphological traits. However, few studies attempt to quantify the form and direction of selection on performance even though it is predicted to be a more direct target of selection in nature. We measured sexual selection on performance traits (bite force, sprint speed and endurance) in an Australian lizard, the Eastern water skink (Eulamprus quoyii). We first staged 123 contests between size‐matched males to investigate whether performance traits were important in determining contest outcome. In a second experiment, we established six breeding populations in large replicate semi‐natural enclosures to estimate whether performance traits predicted reproductive success. Our results show that none of the performance measures were important in predicting contest outcome and were not generally strong predictors of reproductive success. However, our analyses suggest a complex fitness landscape driven by males adopting different alternative reproductive tactics (ARTs). We provide a rare test of the role performance plays in sexual selection and highlight the need to test common assumptions regarding the link between maximal performance and fitness. Our results suggest that performance traits may not necessarily be direct targets of sexual selection, but rather indirect targets through their integration with morphological and/or behavioural traits, highlighting a need for more explicit tests of the predicted links between performance and fitness.
Cumulative evidence for reducing recurrence of colonic diverticular bleeding using endoscopic clipping versus band ligation: Systematic review and meta‐analysis
Authors: Nagata Naoyoshi , Niikura Ryota , Ishii Naoki , Kaise Mitsuru , Omata Fumio , Tominaga Naoyuki , Kitagawa Tomoyuki , Ikeya Takashi , Kobayashi Katsumasa , Furumoto Yohei , Narasaka Toshiaki , Iwata Eri , Sugimoto Mitsushige , Itoi Takao , Uemura Naomi , Kawai Takashi
Published: December 2020

Background and Aim

Either clipping or band ligation will become the most common endoscopic treatment for colonic diverticular bleeding (CDB). Rebleeding is a significant clinical outcome of CDB, but there is no cumulative evidence comparing reduction of short‐term and long‐term rebleeding between them. Thus, we conducted a systematic review and meta‐analysis to determine which endoscopic treatment is more effective to reduce recurrence of CDB.

Methods

A comprehensive search of the databases PubMed/MEDLINE and Embase was performed through December 2019. Main outcomes were early and late rebleeding rates, defined as bleeding within 30 days and 1 year of endoscopic therapy for CDB. Initial hemostasis, need for transcatheter arterial embolization, or surgery were also assessed. Overall pooled estimates were calculated.

Results

Sixteen studies fulfilled the eligibility criteria, and a total of 790 participants were included. The pooled prevalence of early rebleeding was significantly lower for band ligation than clipping (0.08 vs 0.19; heterogeneity test, P = 0.012). The pooled prevalence of late rebleeding was significantly lower for band ligation than clipping (0.09 vs 0.29; heterogeneity test, P = 0.024). No significant difference of initial hemostasis rate was noted between the two groups. Pooled prevalence of need for transcatheter arterial embolization or surgery was significantly lower for band ligation than clipping (0.01 vs 0.02; heterogeneity test, P = 0.031). There were two cases with colonic diverticulitis due to band ligation but none in clipping.

Conclusion

Band ligation therapy was more effective compared with clipping to reduce recurrence of colonic diverticular hemorrhage over short‐term and long‐term durations.
A case of nasal septal perforation caused by bevacizumab for advanced cervical cancer
Authors: Taira Yusuke , Shimoji Yuko , Nakasone Tadaharu , Arakaki Yoshihisa , Nakamoto Tomoko , Kudaka Wataru , Aoki Yoichi
Published: December 2020

Nasal septal perforation caused by bevacizumab is rarely reported in other cancers such as ovarian cancer and breast cancer, but it has not been reported in cervical cancer. A 48‐year‐old woman with a medical history of chronic allergic rhinitis was diagnosed stage 4B (T2bN1M0) cervical cancer and paclitaxel and carboplatin along with bevacizumab (triweekly) were administered. After eight courses of chemotherapy, nasal septal perforation was noted. The possibility of nasal septal perforation by bevacizumab was considered by excluding other causes. We report the first case of nasal septal perforation caused by bevacizumab for advanced cervical cancer.
A New Species of Freshwater Algae Nephrochlamys yushanlensis sp. nov. (Selenastraceae, Sphaeropleales) and Its Lipid Accumulation during Nitrogen and Phosphorus Starvation
Authors: Maltsev Yevhen , Maltseva Irina , Maltseva Svetlana , Kociolek John Patrick , Kulikovskiy Maxim
Published: December 2020

The new species Nephrochlamys yushanlensis sp. nov. is described from a freshwater plankton sample. A comparison of morphology, 18S rDNA gene and ITS2 sequences, and fatty acid profiles showed that the novel strain represents a new lineage within the genus Nephrochlamys. For the first time with a member of the Selenastraceae, experiments with phosphate and nitrate deprivation were conducted to evaluate changes in biomass, lipid and triacylglycerol (TAGs) accumulation, and composition of fatty acids. Biomass dry weight under simultaneous nitrogen and phosphorus depletion was 1.73 g · L−1, which is significantly lower than the 2.41 g · L−1 observed in the control. All conditions of nutrient restriction significantly increased the lipid content in comparison with the control. The largest increase in the total lipid content, reaching 58.64% DW per cell at the end of cultivation, occurred with nitrogen deficiency. Significant increases in TAGs content (to 23.69% and 21.74%, respectively) occurred in phosphorus‐ and nitrogen‐depleted conditions in comparison to the control (16.90%). Oleic (49.8–64.1%), palmitic (21.1–22.7%), and linoleic (8.6–10.3%) acids were the dominant fatty acids when cultured on standard BBM medium, as well as with the shortage of nutrients. Phosphorus deprivation as well as absence of both nitrogen and phosphorus led to the appearance of FAMEs α‐linolenic (1.5–4.1%) and stearidonic (1.0–1.8%) acids. In general, FAME profiles revealed that the relative percentage of saturated and monounsaturated fatty acids increased (88.9% of total fatty acids) in nitrogen‐depletion conditions, suggesting this strain may be suitable for biodiesel production.
Governing complex linguistic diversity in Barcelona, Luxembourg and Riga
Authors: Kraus Peter A , Climent‐Ferrando Vicent , Frank Melanie , Garcia Núria
Published: December 2020

Contemporary migration has entailed the emergence of new forms of multilingualism in many European cities. The article uses the concept of complex diversity to analyse this dynamic. The concept points at settings where historical forms of multilingualism and more recent patterns of linguistic heterogeneity interact in ways that lead to particularly rich cultural configurations. The authors assess how local authorities deal with multilingualism in three cities that represent ‘most complex’ cases of diversity politics: Barcelona, Luxembourg and Riga. The focus is on policies related to public communication and on the approaches adopted to promote social and political inclusion in ever more multilingual urban environments. In normative terms, the article concludes that political responses to complex diversity should aim both at overcoming linguistic status inequalities based on historical structures of domination and at creating common spaces of communication for diverse citizens.
Mast seeding: the devil (and the delight) is in the detail
Authors: Kelly Dave
Published: December 2020

This article is a Commentary on Bogdziewicz et al. (2021), 229: 2357–2364.
Andrographolide‐loaded solid lipid nanoparticles enhance anti‐cancer activity against head and neck cancer and precancerous cells
Authors: Li Hongquan , Qu Xingzhou , Qian Wenhao , Song Yang , Wang Changhong , Liu Wei
Published: December 2020

Background

Increasing evidence indicates that andrographolide (ADG) exhibits anti‐cancer activity against various cancer cell lines. However, its high hydrophobicity and poor bioavailability restrict its clinical application as a chemopreventative agent. Previously, we have shown that ADG‐loaded solid lipid nanoparticles (SLNs) significantly enhanced the bioavailability and anti‐hyperlipidemic activity of ADG.

Objectives

We aimed to investigate whether ADG‐SLN enhanced the bioavailability and anti‐cancer efficacy of ADG in the human immortalized oral epithelial (HIOEC), precancerous leukoplakia (Leuk1), HN6, and HN30 cells that represented an in vitro model of stepwise head and neck squamous cell carcinoma development.

Results

The 50% inhibitive concentration (IC50) of ADG‐SLN was significantly lower than that of free ADG against HIOEC, Leuk1, and HN6 and HN30 cells. Moreover, ADG‐SLN was more effective than free ADG in promoting cell cycle arrest and apoptosis. Importantly, intracellular absorption of ADG was significantly higher in HN6 cells treated with ADG‐SLN compared with free ADG‐treated cells.

Conclusions

Our preliminary study demonstrates that ADG‐SLN exhibits superior inhibitory activity against head and neck cancer and precancerous cells compared with free ADG. This effect is due to the higher efficiency of cellular uptake and intracellular absorption by ADG‐SLN.
Power profiles of centre–distance multifocal soft contact lenses
Authors: Nti Augustine N , Ritchey Eric R , Berntsen David A
Published: December 2020

Purpose

Centre‐distance multifocal contact lenses (MFCLs) for myopia control are thought to slow myopia progression by providing both clear foveal vision and myopic defocus. Characterising the power profile of lenses is important to understanding their possible effects on retinal defocus when worn. The power profiles of three commercially available MFCLs were determined.

Methods

Three centre‐distance MFCL designs were studied: Biofinity Multifocal D +2.50 add (comfilcon A), Proclear Multifocal D +2.50 add (omafilcon A), and NaturalVue Multifocal (etafilcon A). Two lenses each in power from −1.00D to −6.00D in 1D steps were stored in ISO 18369‐3:2017 standard phosphate buffered saline for 24 h. Optical power profiles were measured in a wet cell with the SHSOphthalmic profiler accounting for centre thickness and manufacturer‐reported material refractive index. Sagittal power maps from the SHSOphthalmic were exported, and custom MATLAB code was used to generate power profiles by averaging along the vertical and horizontal meridians. One‐way anova with Tukey’s HSD post‐hoc t‐tests were used to analyse maximum add power by lens design.

Results

Plus power increased out from the lens centre for all three MFCLs. Power profiles of Biofinity D and Proclear D MFCLs show three distinct areas within the optic zone; the distance zone (from lens centre to about 1.6 mm radius), intermediate zone (about 1.6 mm radius to 2.1 mm) and near zone (about 2 mm radius to 4 mm). For NaturalVue MFCLs, plus power starts increasing almost immediately from the lens centre, reaching maximum measured mean plus power at a radius of 2.7 mm. From 2.7 mm to 3.0 mm, there was a decrease in plus power, which was then generally maintained out to the optic zone edge. Across all lens powers, maximum add power was highest with the NaturalVue MFCL (+3.32 ± 0.44D), then Proclear D (+1.84 ± 0.28D) and Biofinity D (+1.47 ± 0.34D) MFCLs (all p < 0.04). Add power peaked at different locations for different lens powers and designs.

Conclusions

Power profiles of MFCLs vary based on lens design and power. These power profiles are consistent with reported myopic and hyperopic changes in peripheral refraction with MFCLs and provide some explanation for reported differences in peripheral refraction with these MFCLs. Further work is needed to determine whether these power profile differences influence myopia progression.
Anesthesia management for ENT surgery in a child with X‐linked pyruvate kinase deficiency
Authors: Hau Vickie , Bonilla‐Velez Juliana , Low Daniel
Published: December 2020

Pyruvate dehydrogenase complex deficiency (PDCD) is a rare X‐linked disorder that affects glucose metabolism. There are several case reports describing the anesthetic management of patients with PDCD. This is the first case report to describe the anesthetic management of a PDCD patient requiring spontaneous ventilation using dexmedetomidine and ketamine.
Differential localization of flavonoid glucosides in an aquatic plant implicates different functions under abiotic stress
Authors: Böttner Laura , Grabe Veit , Gablenz Saskia , Böhme Niklas , Appenroth Klaus J. , Gershenzon Jonathan , Huber Meret
Published: December 2020

Flavonoids may mediate UV protection in plants either by screening of harmful radiation or by minimizing the resulting oxidative stress. To help distinguish between these alternatives, more precise knowledge of flavonoid distribution is needed. We used confocal laser scanning microscopy (cLSM) with the “emission fingerprinting” feature to study the cellular and subcellular distribution of flavonoid glucosides in the giant duckweed (Spirodela polyrhiza), and investigated the fitness effects of these compounds under natural UV radiation and copper sulphate addition (oxidative stress) using common garden experiments indoors and outdoors. cLSM “emission fingerprinting” allowed us to individually visualize the major dihydroxylated B‐ring‐substituted flavonoids, luteolin 7‐O‐glucoside and luteolin 8‐C‐glucoside, in cross‐sections of the photosynthetic organs. While luteolin 8‐C‐glucoside accumulated mostly in the vacuoles and chloroplasts of mesophyll cells, luteolin 7‐O‐glucoside was predominantly found in the vacuoles of epidermal cells. In congruence with its cellular distribution, the mesophyll‐associated luteolin 8‐C‐glucoside increased plant fitness under copper sulphate addition but not under natural UV light treatment, whereas the epidermis‐associated luteolin 7‐O‐glucoside tended to increase fitness under both stresses across chemically diverse genotypes. Taken together, we demonstrate that individual flavonoid glucosides have distinct cellular and subcellular locations and promote duckweed fitness under different abiotic stresses.
Evolving Science and Practice of Risk Assessment
Authors: von Stackelberg Katherine , Williams Pamela R.D.
Published: December 2020

Managing public health risks from environmental contaminants has historically relied on a risk assessment process defined by the regulatory context in which these risks are assessed. Risk assessment guidance follows a straightforward, chemical‐by‐chemical approach to inform regulatory decisions around the question “what is the risk‐based concentration protective of human and ecological health outcomes?” Here we briefly summarize regulatory risk assessment in the context of innovative risk assessment approaches based on an evolving understanding of the underlying scientific disciplines that support risk analysis more broadly. We discuss scientific versus regulatory tensions in the application of these approaches for future risk assessments, and challenges in translating our improved understanding of the underlying scientific complexity to the regulatory landscape to better inform decision making that extends beyond conventional regulatory mandates.
Phaseolus vulgaris MIR1511 genotypic variations differentially regulate plant tolerance to aluminum toxicity
Authors: Ángel Martín‐Rodríguez Jose , Ariani Andrea , Leija Alfonso , Elizondo Armando , Fuentes Sara I. , Ramirez Mario , Gepts Paul , Hernández Georgina , Formey Damien
Published: December 2020

The common‐bean (Phaseolus vulgaris), a widely consumed legume, originated in Mesoamerica and expanded to South America, resulting in the development of two geographically distinct gene pools. Poor soil condition, including metal toxicity, are often constraints to common‐bean crop production. Several P. vulgaris miRNAs, including miR1511, respond to metal toxicity. The MIR1511 gene sequence from the two P. vulgaris model sequenced genotypes revealed that, as opposed to BAT93 (Mesoamerican), the G19833 (Andean) accession displays a 58‐bp deletion, comprising the mature and star miR1511 sequences. Genotyping‐By‐Sequencing data analysis from 87 non‐admixed Phaseolus genotypes, comprising different Phaseolus species and P. vulgaris populations, revealed that all the P. vulgaris Andean genotypes and part of the Mesoamerican (MW1) genotypes analyzed displayed a truncated MIR1511 gene. The geographic origin of genotypes with a complete versus truncated MIR1511 showed a distinct distribution. The P. vulgaris ALS3 (Aluminum Sensitive Protein 3) gene, known to be important for aluminum detoxification in several plants, was experimentally validated as the miR1511 target. Roots from BAT93 plants showed decreased miR1511 and increased ALS3 transcript levels at early stages under aluminum toxicity (AlT), while G19833 plants, lacking mature miR1511, showed higher and earlier ALS3 response. Root architecture analyses evidenced higher tolerance of G19833 plants to AlT. However, G19833 plants engineered for miR1511 overexpression showed lower ALS3 transcript level and increased sensitivity to AlT. Absence of miR1511 in Andean genotypes, resulting in a diminished ALS3 transcript degradation, appears to be an evolutionary advantage to high Al levels in soils with increased drought conditions.
Association between renal failure and red blood cell alloimmunization among newly transfused patients
Authors: Oud Josine A. , Evers Dorothea , Middelburg Rutger A. , de Vooght Karen M. K. , van de Kerkhof Daan , Visser Otto , Péquériaux Nathalie C.V. , Hudig Francisca , van der Bom Johanna G. , Zwaginga Jaap Jan
Published: December 2020

Background

Renal failure and renal replacement therapy (RRT) affect the immune system and could therefore modulate red blood cell (RBC) alloimmunization after transfusion.

Study Design and Methods

We performed a nationwide multicenter case‐control study within a source population of newly transfused patients between 2005 and 2015. Using conditional multivariate logistic regression, we compared first‐time transfusion‐induced RBC alloantibody formers (N = 505) with two nonalloimmunized recipients with similar transfusion burden (N = 1010).

Results

Renal failure was observed in 17% of the control and 13% of the case patients. A total of 41% of the control patients and 34% of case patients underwent acute RRT. Renal failure without RRT was associated with lower alloimmunization risks after blood transfusion (moderate renal failure: adjusted relative rate [RR], 0.82 [95% confidence interval (CI), 0.67‐1.01]); severe renal failure, adjusted RR, 0.76 [95% CI, 0.55‐1.05]). With severe renal failure patients mainly receiving RRT, the lowest alloimmunization risk was found in particularly these patients [adjusted RR 0.48 (95% CI 0.39‐0.58)]. This was similar for patients receiving RRT for acute or chronic renal failure (adjusted RR, 0.59 [95% CI, 0.46‐0.75]); and adjusted RR, 0.62 [95% CI 0.45‐0.88], respectively).

Conclusion

These findings are indicative of a weakened humoral response in acute as well as chronic renal failure, which appeared to be most pronounced when treated with RRT. Future research should focus on how renal failure and RRT mechanistically modulate RBC alloimmunization.
Cold storage of platelets in platelet additive solution maintains mitochondrial integrity by limiting initiation of apoptosis‐mediated pathways
Authors: Reddoch‐Cardenas Kristin M. , Peltier Grant C. , Chance Tiffani C. , Nair Prajeeda M. , Meledeo Michael A. , Ramasubramanian Anand K. , Cap Andrew P. , Bynum James A.
Published: December 2020

Background

Cold storage of platelets in plasma maintains hemostatic function and is an attractive alternative to room temperature platelets (RTPs). We have recently shown that functional differences between cold‐stored platelets (CSPs) and RTPs after 5‐day storage are associated with mitochondrial respiration and that CSPs in platelet (PLT) additive solution (PAS) can maintain hemostatic function for at least 15 days.

Study Design and Methods

This study tested the hypothesis that cold storage in PAS preserves mitochondrial integrity by reducing PLT apoptosis. CSPs and RTPs in plasma or PAS were stored and assayed for up to 15 days for mitochondrial function and integrity, mitochondrial‐associated mRNA transcript expression, apoptotic proteins, and apoptotic flow cytometry metrics.

Results

CSP preserved mitochondria‐associated mRNA comparable to baseline levels, improved mitochondrial respiration, and minimized depolarization to Day 15. Additionally, CSPs had minimal induction of caspases, preservation of plasma membrane integrity, and low expression of pro‐apoptotic Bax. Storage in PAS appeared to be protective for RTPs in some parameters and enhanced the effects of CSPs.

Conclusion

Mitochondrial function and molecular analyses defined CSP priming as distinctly different from the well‐documented RTP storage lesion. While current blood bank storage at room temperature is limited to 5 to 7 days, refrigeration and storage in PAS for up to 15 days may represent an opportunity to enhance inventories and access to PLT hemostatic support for bleeding patients.
Printing for Protection
Authors: Sethi Chitra
Published: December 2020

After seeing a number of projects trying to help frontline workers, Josef Průša decided to produce face shields with both 3D printed and laser-cut plastic components.
Guarding the Gate
Authors: Winters Jeffrey
Published: December 2020

To keep symptomatic workers from infecting entire businesses, employers are resorting to temperature screenings in the front lobby. Mechanical engineer Howard Horn realized it would be faster and safer for building owners to automate the process.
Characterization of vapor draw vessel performance for low-volatility solid precursor delivery
Authors: Maslar James E. , Kimes William A. , Sperling Brent A. , Kanjolia Ravindra K.
Published: December 2020

Low volatility precursors are widely utilized in chemical vapor deposition (CVD) and atomic layer deposition (ALD) processes. Compared to gases and high volatility liquid precursors, delivery of low volatility liquid and solid precursors can be problematic, with solid precursors being particularly so. To investigate some of these delivery issues, the performance of a vapor draw vessel was characterized for the delivery of pentakis(dimethylamido) tantalum (PDMAT), a low-volatility solid precursor at preferable delivery temperatures, for reduced-pressure cyclical CVD and ALD processes. Vessel characterization involved determining (1) a source efficiency as a function of process conditions and (2) the degree of PDMAT decomposition as a function of temperature and vessel idle time. The PDMAT partial pressure, flow rate, and mass per injection used to determine the source efficiency were determined from measurements obtained using a custom-designed non-dispersive infrared gas analyzer. For a series of injections after an idle/purge sufficiently long to saturate the vessel head space, the source efficiency decreased from a maximum slightly less than unity for the first injection until a consistent value was reached that was approximately one half to one third of the maximum value. A comparable trend was observed for mass delivered per injection. For the conditions used in this investigation, the source efficiency decreased when the injection time was increased to longer than 1 s, when pressure was decreased, and when the carrier gas flow rate was increased. Although the corresponding mass per injection increased with these changes, the increase in mass was less than that predicted had the carrier gas been saturated. The source efficiency did not depend strongly on temperature and only moderately on vessel idle durations (4–16 s). The degree of PDMAT decomposition was evaluated by measuring the partial pressure of dimethylamine (the primary PDMAT decomposition product under the conditions of this investigation) using the same gas analyzer. For a given idle time, the amount of dimethylamine delivered more than doubled as vessel temperature was increased from 68 to 78 °C.
Protein condensates as aging Maxwell fluids
Authors: Jawerth Louise , Fischer-Friedrich Elisabeth , Saha Suropriya , Wang Jie , Franzmann Titus , Zhang Xiaojie , Sachweh Jenny , Ruer Martine , Ijavi Mahdiye , Saha Shambaditya , Mahamid Julia , Hyman Anthony A. , Jülicher Frank
Published: December 2020

Rheology of aging protein condensates

Protein condensates that form by undergoing liquid-liquid phase separation will show changes in their rheological properties with time, a process known as aging. Jawerth
et al.
used laser tweezer–based active and microbead-based passive rheology to characterize the time-dependent material properties of protein condensates (see the Perspective by Zhang). They found that condensate aging is not gelation of the condensates, but rather a changing viscoelastic Maxwell liquid with a viscosity that strongly increases with age, whereas the elastic modulus stays the same.

Science
, this issue p.
1317
; see also p.
1271
Poverty, depression, and anxiety: Causal evidence and mechanisms
Authors: Ridley Matthew , Rao Gautam , Schilbach Frank , Patel Vikram
Published: December 2020

Taxing mental health

Mental equilibrium is essential for an economically productive life in both industrialized and developing countries. Accumulating evidence shows that mental ill-health and poverty tend to be traveling partners, but which is the cause? Ridley
et al.
reviewed the literature on natural and controlled economic experiments involving individuals living in poverty. The authors sought to resolve the mechanisms whereby poverty triggers mental illness and how mental illness compounds poverty. Their results reveal the benefits of cash support and of low-cost therapeutic interventions for those suffering from mental illness under poverty.

Science
, this issue p.
eaay0214
Indian monsoon derailed by a North Atlantic wavetrain
Authors: Borah P. J. , Venugopal V. , Sukhatme J. , Muddebihal P. , Goswami B. N.
Published: December 2020

Season of the drought

The Indian monsoon is a critical source of water for hundreds of millions of people, and when it fails to deliver its normal quantity of rain, enormous human, economic, and ecological costs can be incurred. Monsoon droughts are not always seasonal, however. Borah
et al.
found that nearly half of all monsoonal droughts were subseasonal and characterized by a steep decline in late-season rainfall. Moreover, this type of subseasonal drought appears to be related to a distinct cold anomaly in the North Atlantic Ocean, raising the possibility that monsoon droughts may be more predictable.

Science
, this issue p.
1335
Genetic interaction mapping informs integrative structure determination of protein complexes
Authors: Braberg Hannes , Echeverria Ignacia , Bohn Stefan , Cimermancic Peter , Shiver Anthony , Alexander Richard , Xu Jiewei , Shales Michael , Dronamraju Raghuvar , Jiang Shuangying , Dwivedi Gajendradhar , Bogdanoff Derek , Chaung Kaitlin K. , Hüttenhain Ruth , Wang Shuyi , Mavor David , Pellarin Riccardo , Schneidman Dina , Bader Joel S. , Fraser James S. , Morris John , Haber James E. , Strahl Brian D. , Gross Carol A. , Dai Junbiao , Boeke Jef D. , Sali Andrej , Krogan Nevan J.
Published: December 2020

From phenotype to structure

Much insight has come from structures of macromolecular complexes determined by methods such as crystallography or cryo–electron microscopy. However, looking at transient complexes remains challenging, as does determining structures in the context of the cellular environment. Braberg
et al.
used an integrative approach in which they mapped the phenotypic profiles of a comprehensive set of mutants in a protein complex in the context of gene deletions or environmental perturbations (see the Perspective by Wang). By associating the similarity between phenotypic profiles with the distance between residues, they determined structures for the yeast histone H3-H4 complex, subunits Rpb1-Rpb2 of yeast RNA polymerase II, and subunits RpoB-RpoC of bacterial RNA polymerase. Comparison with known structures shows that the accuracy is comparable to structures determined based on chemical cross-links.

Science
, this issue p.
eaaz4910
; see also p.
1269
The evolution of a tropical biodiversity hotspot
Authors: Harvey Michael G. , Bravo Gustavo A. , Claramunt Santiago , Cuervo Andrés M. , Derryberry Graham E. , Battilana Jaqueline , Seeholzer Glenn F. , McKay Jessica Shearer , O’Meara Brian C. , Faircloth Brant C. , Edwards Scott V. , Pérez-Emán Jorge , Moyle Robert G. , Sheldon Frederick H. , Aleixo Alexandre , Smith Brian Tilston , Chesser R. Terry , Silveira Luís Fábio , Cracraft Joel , Brumfield Robb T. , Derryberry Elizabeth P.
Published: December 2020

Diversity does not drive speciation

The role of the environment in the origin of new species has long been debated. Harvey
et al.
examined the evolutionary history and species diversity of suboscine birds in the tropics (see the Perspective by Morlon). Contrary to expectations that the tropics have higher rates of speciation, the authors observed that higher and more constant speciation rates occur in harsh environments relative to the tropics. Thus, for this group of birds, diversification in temperate to Arctic regions followed by the movement and retention of species in the tropics results in their higher local levels of species diversity.

Science
, this issue p.
1343
; see also p.
1268
Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites
Authors: Veenvliet Jesse V. , Bolondi Adriano , Kretzmer Helene , Haut Leah , Scholze-Wittler Manuela , Schifferl Dennis , Koch Frederic , Guignard Léo , Kumar Abhishek Sampath , Pustet Milena , Heimann Simon , Buschow René , Wittler Lars , Timmermann Bernd , Meissner Alexander , Herrmann Bernhard G.
Published: December 2020

Trunk formation in a dish

Building mammalian embryos from self-organizing stem cells in culture would accelerate the investigation of morphogenetic and differentiation processes that shape the body plan. Veenvliet
et al.
report a method for generating embryonic trunk-like structures (TLSs) with a neural tube, somites, and gut by embedding mouse embryonic stem cell aggregates in an extracellular matrix surrogate. Live imaging and comparative single-cell transcriptomics indicate that TLS formation is analogous to mouse development. TLSs therefore provide a scalable, tractable, and accessible high-throughput platform for decoding mammalian embryogenesis at a high level of resolution.

Science
, this issue p.
eaba4937
Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients
Authors: Baruch Erez N. , Youngster Ilan , Ben-Betzalel Guy , Ortenberg Rona , Lahat Adi , Katz Lior , Adler Katerina , Dick-Necula Daniela , Raskin Stephen , Bloch Naamah , Rotin Daniil , Anafi Liat , Avivi Camila , Melnichenko Jenny , Steinberg-Silman Yael , Mamtani Ronac , Harati Hagit , Asher Nethanel , Shapira-Frommer Ronnie , Brosh-Nissimov Tal , Eshet Yael , Ben-Simon Shira , Ziv Oren , Khan Md Abdul Wadud , Amit Moran , Ajami Nadim J. , Barshack Iris , Schachter Jacob , Wargo Jennifer A. , Koren Omry , Markel Gal , Boursi Ben
Published: December 2020

New fecal microbiota for cancer patients

The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch
et al.
and Davar
et al.
report first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) can affect how metastatic melanoma patients respond to anti–PD-1 immunotherapy (see the Perspective by Woelk and Snyder). Both studies observed evidence of clinical benefit in a subset of treated patients. This included increased abundance of taxa previously shown to be associated with response to anti–PD-1, increased CD8
+
T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells, which are involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients.

Science
, this issue p.
602
, p.
595
; see also p.
573
CiBER-seq dissects genetic networks by quantitative CRISPRi profiling of expression phenotypes
Authors: Muller Ryan , Meacham Zuriah A. , Ferguson Lucas , Ingolia Nicholas T.
Published: December 2020

CiBER-seq dissects genetic networks

Cells integrate environmental signals and internal states to dynamically control gene expression. Muller
et al.
developed a technique to dissect this cellular logic by linking targeted, genome-wide genetic perturbations with a deep-sequencing readout that quantitatively measured the expression phenotype induced by each perturbation. The method, dubbed CiBER-seq, was able to recapitulate known regulatory pathways linking protein synthesis with nutrient availability in budding yeast cells. Unexpectedly, the authors found that the cellular logic also appears to consider protein production machinery in this decision. By uncovering additional facets of this deeply conserved pathway, the findings demonstrate the utility of comprehensive and quantitative CiBER-seq profiling in mapping the gene networks underlying cellular decisions.

Science
, this issue p.
eabb9662
A transmissible cancer shifts from emergence to endemism in Tasmanian devils
Authors: Patton Austin H. , Lawrance Matthew F. , Margres Mark J. , Kozakiewicz Christopher P. , Hamede Rodrigo , Ruiz-Aravena Manuel , Hamilton David G. , Comte Sebastien , Ricci Lauren E. , Taylor Robyn L. , Stadler Tanja , Leaché Adam , McCallum Hamish , Jones Menna E. , Hohenlohe Paul A. , Storfer Andrew
Published: December 2020

Emergence to endemism

The emergence of a devastating transmissible facial cancer among Tasmanian devils over the past few decades has caused substantial concern for their future because these animals are already threatened by a regional distribution and other stressors. Little is known about the overall history and trajectory of this disease. Patton
et al.
used an epidemiological phylodynamic approach to reveal the pattern of disease emergence and spread. They found that low Tasmanian devil densities appear to be contributing to slower disease growth and spread, which is good news for Tasmanian devil persistence and suggests that care should be taken when considering options for increasing devil populations.

Science
, this issue p.
eabb9772
Network-based screen in iPSC-derived cells reveals therapeutic candidate for heart valve disease
Authors: Theodoris Christina V. , Zhou Ping , Liu Lei , Zhang Yu , Nishino Tomohiro , Huang Yu , Kostina Aleksandra , Ranade Sanjeev S. , Gifford Casey A. , Uspenskiy Vladimir , Malashicheva Anna , Ding Sheng , Srivastava Deepak
Published: December 2020

Machine learning for medicine

Small-molecule screens aimed at identifying therapeutic candidates traditionally search for molecules that affect one to several outputs at most, limiting discovery of true disease-modifying drugs. Theodoris
et al.
developed a machine-learning approach to identify small molecules that broadly correct gene networks dysregulated in a human induced pluripotent stem cell disease model of a common form of heart disease involving the aortic valve. Gene network correction by the most efficacious therapeutic candidate generalized to primary aortic valve cells derived from more than 20 patients with sporadic aortic valve disease and prevented aortic valve disease in vivo in a mouse model.

Science
, this issue p.
eabd0724
Southern Ocean upwelling, Earth’s obliquity, and glacial-interglacial atmospheric CO
2
change
Authors: Ai Xuyuan E. , Studer Anja S. , Sigman Daniel M. , Martínez-García Alfredo , Fripiat François , Thöle Lena M. , Michel Elisabeth , Gottschalk Julia , Arnold Laura , Moretti Simone , Schmitt Mareike , Oleynik Sergey , Jaccard Samuel L. , Haug Gerald H.
Published: December 2020

Controlling atmospheric carbon dioxide

The atmospheric concentration of carbon dioxide (CO
2
) has varied substantially over the past million years in tandem with the glacial cycle. Although it is widely agreed that upwelling of Southern Ocean water is a key factor, the finer details about what caused these CO
2
variations are of great importance for understanding climate. Ai
et al.
identified three modes of change in Southern Ocean upwelling, adding a third to two previously recognized ones. This new mode can help explain better the relative timing of the glacial and CO
2
cycles.

Science
, this issue p.
1348
Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events
Authors: Lemieux Jacob E. , Siddle Katherine J. , Shaw Bennett M. , Loreth Christine , Schaffner Stephen F. , Gladden-Young Adrianne , Adams Gordon , Fink Timelia , Tomkins-Tinch Christopher H. , Krasilnikova Lydia A. , DeRuff Katherine C. , Rudy Melissa , Bauer Matthew R. , Lagerborg Kim A. , Normandin Erica , Chapman Sinéad B. , Reilly Steven K. , Anahtar Melis N. , Lin Aaron E. , Carter Amber , Myhrvold Cameron , Kemball Molly E. , Chaluvadi Sushma , Cusick Caroline , Flowers Katelyn , Neumann Anna , Cerrato Felecia , Farhat Maha , Slater Damien , Harris Jason B. , Branda John A. , Hooper David , Gaeta Jessie M. , Baggett Travis P. , O’Connell James , Gnirke Andreas , Lieberman Tami D. , Philippakis Anthony , Burns Meagan , Brown Catherine M. , Luban Jeremy , Ryan Edward T. , Turbett Sarah E. , LaRocque Regina C. , Hanage William P. , Gallagher Glen R. , Madoff Lawrence C. , Smole Sandra , Pierce Virginia M. , Rosenberg Eric , Sabeti Pardis C. , Park Daniel J. , MacInnis Bronwyn L.
Published: December 2020

Phylogenetics of superspreading

One important characteristic of coronavirus epidemiology is the occurrence of superspreading events. These are marked by a disproportionate number of cases originating from often-times asymptomatic individuals. Using a rich sequence dataset from the early stages of the Boston outbreak, Lemieuxet al.identified superspreading events in specific settings and analyzed them phylogenetically (see the Perspective by Alizon). Using ancestral trait inference, the authors identified several importation events, further investigated the context and contribution of particular superspreading events to the establishment of local and wider SARS-CoV-2 transmission, and used viral phylogenies to describe sustained transmission.

Science, this issue p.eabe3261; see also p.574
The glassiness of hardening protein droplets
Authors: Zhang Huaiying
Published: December 2020

Protein condensates can age to form glasses that increase in viscosity but retain elasticity
Isolation and Characterization of Rhizophydiales (Chytridiomycota), Obligate Parasites of Planktothrix agardhii in a Laurentian Great Lakes Embayment
Authors: McKindles Katelyn M. , Jorge Alejandro N. , McKay R. Michael , Davis Timothy W. , Bullerjahn George S.
Published: December 2020

Whereas many studies have focused on the factors contributing to the establishment and persistence of cyanobacterial harmful algal blooms (cHABs), few studies have examined bloom pathogenesis. Chytrid fungi infect cyanobacteria and stimulate food web interactions through manipulation of previously hard-to-digest filaments and the release of nutrients to support heterotrophic microbes.
Xpert MTB/XDR: a 10-Color Reflex Assay Suitable for Point-of-Care Settings To Detect Isoniazid, Fluoroquinolone, and Second-Line-Injectable-Drug Resistance Directly from Mycobacterium tuberculosis-Positive Sputum
Authors: Cao Yuan , Parmar Heta , Gaur Rajiv L. , Lieu Deanna , Raghunath Shobana , Via Nova , Battaglia Simone , Cirillo Daniela M. , Denkinger Claudia , Georghiou Sophia , Kwiatkowski Robert , Persing David , Alland David , Chakravorty Soumitesh
Published: December 2020

We describe the design, development, analytical performance, and a limited clinical evaluation of the 10-color Xpert MTB/XDR assay (CE-IVD only, not for sale in the United States). This assay is intended as a reflex test to detect resistance to isoniazid (INH), fluoroquinolones (FLQ), ethionamide (ETH), and second-line injectable drugs (SLIDs) in unprocessed sputum samples and concentrated sputum sediments which are positive for
Mycobacterium tuberculosis
.
Expression of HIV-1 Intron-Containing RNA in Microglia Induces Inflammatory Responses
Authors: Akiyama Hisashi , Jalloh Sallieu , Park Seonmi , Lei Maohua , Mostoslavsky Gustavo , Gummuluru Suryaram
Published: December 2020

Although peripheral viremia can be effectively suppressed with the advent of highly active antiretroviral therapy, a significant portion of HIV
+
individuals still suffer from neurocognitive disorders. Despite suppressive therapy, HIV persists in various tissues, including the central nervous system (CNS), leading to chronic inflammation, the chief driver of neurocognitive disorders.
Quantifying the competing influences of lithology and throw rate on bedrock river incision
Authors: Kent E. , Whittaker A.C. , Boulton S.J. , Alçiçek M.C.
Published: December 2020

River incision in upland areas is controlled by prevailing climatic and tectonic regimes, which are increasingly well described, and the nature of the bedrock lithology, which is still poorly constrained. Here, we calculated downstream variations in stream power and bedrock strength for six rivers crossing a normal fault in western Turkey, to derive new constraints on bedrock erodibility as function of rock type. These rivers were selected because they exhibit knick zones representing a transient response to an increase in throw rate, driven by fault linkage. Field measures of rock mass strength showed that the metamorphic units (gneisses and schists) in the catchments are ∼2 times harder than the sedimentary lithologies. Stream power increases downstream in all rivers, reaching a maxima upstream of the fault within the metamorphic bedrock but declining markedly where softer sedimentary rocks are encountered. We demonstrate a positive correlation between throw rate and stream power in the metamorphic rocks, characteristic of rivers obeying a detachment-limited model of erosion. We estimated bedrock erodibility in the metamorphic rocks as kb = 2.2–6.3 × 10−14 m s2 kg−1; in contrast, bedrock erodibility values were 5–30 times larger in the sedimentary units, with kb = 1.2–15 × 10−13 m s2 kg−1. However, in the sedimentary units, stream power does not scale predictably with fault throw rate, and we evaluated the extent to which the friable nature of the outcropping clastic bedrock alters the long-term erosional dynamics of the rivers. This study places new constraints on bedrock erodibilities upstream of active faults and demonstrates that the strength and characteristics of underlying bedrock exert a fundamental influence on river behavior.