bluuebunny/crossref_metadata_2025 huggingface dataset:
lncRNA MALAT1 participates in metformin inhibiting the proliferation of breast cancer cell
Authors: Huang Yongye , Zhou Ziyan , Zhang Jin , Hao Zhenzhen , He Yunhao , Wu Zihan , Song Yiquan , Yuan Kexun , Zheng Shanyu , Zhao Qi , Li Tianye , Wang Bing
Published: June 2021

In recent years, the repurposing of conventional and chemotherapeutic drugs is recognized as an alternative strategy for health care. The main purpose of this study is to strengthen the application of non‐oncological drug metformin on breast cancer treatment in the perspective of epigenetics. In the present study, metformin was found to inhibit cell proliferation, promote apoptosis and induce cell cycle arrest in breast cancer cells at a dose‐dependent manner. In addition, metformin treatment elevated acH3K9 abundance and decreased acH3K18 level. The expression of lncRNA MALAT1, HOTAIR, DICER1‐AS1, LINC01121 and TUG1 was up‐regulated by metformin treatment. In metformin‐treated cells, MALAT1 knock‐down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression. The expression of Beclin1, VDAC1, LC3‐II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock‐down. The reduced phosphorylation of c‐Myc was further decreased in the metformin‐treated cells in combination with MALAT1 knock‐down than metformin treatment alone. Taken together, these results provide a promising repurposed strategy for metformin on cancer treatment by modulating epigenetic modifiers.
Influence of pre‐treatments on the degradation kinetics of chlorophylls in morisa xak (Amaranthus caudatus) leaves after microwave drying
Authors: Nayak Prakash Kumar , Chandrasekar Chandra Mohan , Haque Anbarul , Kesavan Radha Krishnan
Published: June 2021

Drying is one of the complex processes, comprising parallel heat and mass transfer reactions. It extends the shelf life of perishable agricultural produces (like green leafy vegetables) by decreasing the level of water activity. In the present work, hot water and ultrasound pretreatments were conducted, prior to the dehydration of fresh morisa xak (Amaranthus caudatus) leaves by microwave drying for improving color stability. In order to assess the color degradation kinetics of chlorophyll, the impact of drying techniques on hunter color parameters (L*, a*, b*) and total color difference (TCD) has been evaluated. Thermal degradation of chlorophyll of the green leaves followed the first order kinetics and Arrhenius equation was employed to describe the temperature dependence of the reaction rate constant. From the study, the protective effect of ultra sound pretreatment on the color stability of morisa xak leaves prior to microwave drying can be observed.

Practical Applications

Morisa xak is popular and an important green leaves consumed by North Eastern Part of India. As it has high moisture content, morisa xak leaves has been prone to deterioration during post‐harvest storage. Microwave drying has been preferred over traditional hot air drying method due to its high drying rates and better drying quality. As chlorophyll is the main coloring pigment in green leaves, its deterioration is very common during drying. In the current investigation, different pre‐treatments (hot water and ultra sound) were applied to morisa xak leaves before microwave drying to improve the chlorophyll content. The results of the study indicated that the application of ultra sound pretreatment before microwave drying could be a promising technique in comparison with hot air drying method for drying of green leaves with minimum degradation in chlorophyll.
The impact of COVID‐19 on the social inclusion of older adults with an intellectual disability during the first wave of the pandemic in Ireland
Authors: McCausland D. , Luus R. , McCallion P. , Murphy E. , McCarron M.
Published: June 2021

Background

Social restrictions and service closures from COVID‐19 have negatively impacted social inclusion and well‐being for some people with intellectual disabilities (IDs).

Methods

The fourth wave of a national longitudinal study on ageing in people with ID in Ireland was interrupted during the COVID‐19 outbreak. Social inclusion data for pre‐existing participants interviewed before COVID‐19 (n = 444) were compared with data for pre‐existing participants interviewed during/after lockdown (n = 62).

Results

More people interviewed after lockdown reported frequent family contact. Significantly greater numbers in the post‐lockdown group reported access to and use of technology than the pre‐lockdown group. Technology use was higher among those living in grouped residences supported by services compared with individuals living independently or with family.

Conclusions

During the early stages of the COVID‐19 pandemic in Ireland, many older adults with ID stayed connected with family and reported rates of contact higher than were reported by others before COVID‐19. This connection may have been supported by a significant increase in technology use during the pandemic. However, uneven use of technology may disadvantage some including individuals living with family or independently. Given that COVID‐19 restrictions are likely to continue to restrict social opportunities, increased digital support may assist more people with ID to use technology to maintain their social connections.
Universal Health Care for the United States: A Primer for Health Care Providers
Authors: Alspaugh Amy , Lanshaw Nikki , Kriebs Jan , Van Hoover Cheri
Published: June 2021

The United States is one of a very few high‐income countries that does not guarantee every person the right to health care. Residents of the United States pay more out‐of‐pocket for increasingly worse outcomes. People of color, those who have lower incomes, and those who live in rural areas have less access to health care and are therefore at even greater risk for poor health. Universal health care, a term for various models of health care systems that provide care for every resident of a given country, will help move the United States toward higher quality, more affordable, and more equitable care. This article defines a reproductive justice and human rights foundation for universal health care, explores how health insurance has worked historically in the United States, identifies the economic reasons for implementing universal health care, and discusses international models that could be used domestically.
The Use of Integrase Strand Transfer Inhibitors to Treat HIV in Pregnancy
Authors: Nissim Oriel , Lazenby Gweneth B.
Published: June 2021

For pregnant women with HIV, antiretroviral therapy (ART) plays a key role in prevention of perinatal transmission. Newer antiretroviral regimens now contain integrase strand transfer inhibitors, which have been found to rapidly suppress HIV viral load in nonpregnant women; however, there are limited data for use in pregnancy. Here, we present the case of a pregnant woman with well‐controlled HIV on a well‐tolerated prepregnancy regimen of bictegravir, emtricitabine, and tenofovir alafenamide. As there are limited safety data on bictegravir in pregnancy, this ART regimen was changed to a preferred regimen for pregnancy. In the second trimester, because of adverse effects from the new ART regimen and after a risk‐benefit discussion, the patient restarted the original regimen. She was able to maintain viral suppression until giving birth.
Postoperative morbidity and mortality after surgical resection of small bowel neuroendocrine neoplasms: A systematic review and meta‐analysis
Authors: Kaçmaz Enes , Chen Jeffrey W. , Tanis Pieter J. , Nieveen van Dijkum Els J. M. , Engelsman Anton F.
Published: June 2021

Although small bowel resection is generally considered a low risk gastrointestinal procedure, this might not be true for small bowel neuroendocrine neoplasms (SB‐NEN) as a result of potential central mesenteric involvement. We aimed to determine the reported morbidity and mortality after resection of SB‐NEN in the literature and assess the effect of hospital volume on postoperative morbidity and mortality. A systematic review was performed by searching MEDLINE and Embase in March 2021. All studies reporting morbidity and/or mortality after SB‐NEN resection were included. Pooled proportions of overall morbidity (Clavien‐Dindo I‐IV), severe morbidity (Clavien‐Dindo III‐IV), 30‐day mortality, 90‐day mortality and in‐hospital mortality were calculated, as well as the association with hospital volume (high volume defined as the fourth quartile). Thirteen studies were included, with a total of 1087 patients. Pooled proportions revealed an overall morbidity of 13% (95% confidence interval [CI] = 7%‐24%, I2 = 90%), severe morbidity of 7% (95% CI = 4%‐14%, I2 = 70%), 30‐day mortality of 2% (95% CI = 1%‐3%, I2 = 0%), 90‐day mortality of2% (95% CI = 2%‐4%, I2 = 35%) and in‐hospital mortality of 1% (95% CI = 0%‐2%, I2 = 0%). An annual hospital volume of nine or more resections was associated with lower overall and severe morbidity compared to lower volume: 10% vs 15% and 4% vs 9%, respectively. Thirty‐day mortality was similar (2% vs 1%) and 90‐day mortality was higher in high‐volume hospitals: 4% vs 1%. This systematic review with meta‐analyses showed severe morbidity of 7% and low mortality rates after resection of SB‐NEN. The currently available literature suggests a certain impact of hospital volume on postoperative outcomes, although heterogeneity among the included studies constrains interpretation.
A TOR1AIP1 variant segregating with an early onset limb girdle myasthenia—Support for the role of LAP1 in NMJ function and disease
Authors: Malfatti Edoardo , Catchpool Tara , Nouioua Sonia , Sihem Hellal , Fournier Emmanuel , Carlier Robert Y. , Cardone Nastasia , Davis Mark R. , Laing Nigel G. , Sternberg Damien , Ravenscroft Gianina
Published: June 2021

Rare pathogenic variants in TOR1AIP1 (OMIM 614512), coding the inner nuclear membrane protein lamin‐associated protein 1 (LAP1), have been associated with a spectrum of disorders including limb girdle muscular dystrophy with cardiac involvement and a severe multisystem phenotype. Recently, Cossins et al reported two siblings with limb girdle muscular dystrophy and impaired transmission of the neuromuscular synapse, demonstrating that defective LAP1 may lead to a congenital myasthenic syndrome. Herein, we describe the association of TOR1AIP1 deficiency with congenital myasthenic syndrome in three siblings.
Silicon drives the evolution of complex crystal morphology in calcifying algae
Authors: Mock Thomas
Published: June 2021

This article is a Commentary on Langer et al. (2021), 231: 1845–1857.
Linking xylem network failure with leaf tissue death
Authors: Brodribb Timothy , Brodersen Craig R. , Carriqui Marc , Tonet Vanessa , Rodriguez Dominguez Celia , McAdam Scott
Published: June 2021

Global warming is expected to dramatically accelerate forest mortality as temperature and drought intensity increase. Predicting the magnitude of this impact urgently requires an understanding of the process connecting atmospheric drying to plant tissue damage. Recent episodes of forest mortality worldwide have been widely attributed to dry conditions causing acute damage to plant vascular systems. Under this scenario vascular embolisms produced by water stress are thought to cause plant death, yet this hypothetical trajectory has never been empirically demonstrated.

Here we provide foundational evidence connecting failure in the vascular network of leaves with tissue damage caused during water stress.

We observe a catastrophic sequence initiated by water column breakage under tension in leaf veins which severs local leaf tissue water supply, immediately causing acute cellular dehydration and irreversible damage.

By highlighting the primacy of vascular network failure in the death of leaves exposed to drought or evaporative stress our results provide a strong mechanistic foundation upon which models of plant damage in response to dehydration can be confidently structured.
Tree water uptake enhances nitrogen acquisition in a fertilized boreal forest – but not under nitrogen‐poor conditions
Authors: Henriksson Nils , Lim Hyungwoo , Marshall John , Franklin Oskar , McMurtrie Ross E. , Lutter Reimo , Magh Ruth , Lundmark Tomas , Näsholm Torgny
Published: June 2021

Understanding how plant water uptake interacts with acquisition of soil nitrogen (N) and other nutrients is fundamental for predicting plant responses to a changing environment, but it is an area where models disagree.

We present a novel isotopic labelling approach which reveals spatial patterns of water and N uptake, and their interaction, by trees. The stable isotopes15N and2H were applied to a small area of the forest floor in stands with high and low soil N availability. Uptake by surrounding trees was measured. The sensitivity of N acquisition to water uptake was quantified by statistical modelling.

Trees in the high‐N stand acquired twice as much15N as in the low‐N stand and around half of their N uptake was dependent on water uptake (2H enrichment). By contrast, in the low‐N stand there was no positive effect of water uptake on N uptake.

We conclude that tree N acquisition was only marginally dependent on water flux toward the root surface under low‐N conditions whereas under high‐N conditions, the water‐associated N uptake was substantial. The results suggest a fundamental shift in N acquisition strategy under high‐N conditions.
A partially sex‐reversed giant kelp sheds light into the mechanisms of sexual differentiation in a UV sexual system
Authors: Müller Dieter G. , Gaschet Enora , Godfroy Olivier , Gueno Josselin , Cossard Guillaume , Kunert Maritta , Peters Akira F. , Westermeier Renato , Boland Wilhelm , Cock J. Mark , Lipinska Agnieszka P. , Coelho Susana M.
Published: June 2021

In UV sexual systems, sex is determined during the haploid phase of the life cycle and males have a V chromosome whereas females have a U chromosome. Previous work in the brown alga Ectocarpus revealed that the V chromosome has a dominant role in male sex determination and suggested that the female developmental programme may occur by ‘default’.

Here, we describe the identification of a genetically male giant kelp strain presenting phenotypic features typical of a female, despite lacking the U‐specific region. The conversion to the female developmental programme is however incomplete, because gametes of this feminized male are unable to produce the sperm‐attracting pheromone lamoxirene. We identify the transcriptomic patterns underlying the male and female specific developmental programmes, and show that the phenotypic feminization is associated with both feminization and de‐masculinization of gene expression patterns. Importantly, the feminization phenotype was associated with dramatic downregulation of two V‐specific genes including a candidate male‐determining gene.

Our results reveal the transcriptional changes associated with sexual differentiation in a UV system, and contribute to disentangling the role of sex‐linked and autosomal gene expression in the initiation of sex‐specific developmental programmes.

Overall, the data presented here imply that the U‐specific region is not required to initiate the female developmental programme, but is critical to produce fully functional eggs, arguing against the idea that female is the ‘default’ sex in this species.
Grow and Advance through Intentional Networking: A pilot program to foster connections within the Women's Empowerment and Leadership Initiative in the Society for Pediatric Anesthesia
Authors: Margolis Rebecca D. , Berenstain Laura K. , Janosy Norah , Yanofsky Samuel , Tackett Sean , Schwartz Jamie McElrath , Lee Jennifer K. , Deutsch Nina , Sinskey Jina L.
Published: June 2021

Background

The Women's Empowerment and Leadership Initiative in the Society for Pediatric Anesthesia was established to support women's efforts to achieve promotion, leadership positions, and equity in pediatric anesthesiology through coaching, mentoring, sponsorship, and networking. Career advancement relies on the establishment of mentoring relationships within institutions and at regional and national levels. Prior to the SARS‐CoV‐2 (COVID‐19) pandemic, networking was primarily conducted at large national meetings.

Aims

When national meetings were canceled by the COVID‐19 pandemic, the Women's Empowerment and Leadership Initiative sought to reduce networking barriers by creating a pilot program called “Grow and Advance through Intentional Networking” (GAIN).

Materials & Methods

Monthly 1‐h virtual GAIN sessions were developed based on topics requested by the Women's Empowerment and Leadership Initiative members. Faculty facilitated psychologically safe small‐group discussions to maximize engagement.

Results

We present an overview of our pilot GAIN program, which has been well received by the Women's Empowerment and Leadership Initiative members and met with continuous demand for more sessions.

Discussion

Professional networking is critical for career advancement and for developing and maintaining a sense of community and well‐being. Early‐ and mid‐career physicians depend on these relationships to facilitate academic productivity and promotion.

Conclusion

Programs like the Women's Empowerment and Leadership Initiative GAIN are critical for advancing our specialty and supporting the well‐being of pediatric anesthesiologists. GAIN addresses barriers to professional networking, including during the COVID‐19 pandemic.
Spinozan Doxasticism About Delusions
Authors: Bongiorno Federico
Published: June 2021

The Spinozan theory of belief fixation holds that mentally representing truth‐apt propositions leads to immediately believing them. In this paper, I explore how the theory fares as a defence of doxasticism about delusions (the view that they are beliefs). Doxasticism has been criticised on the grounds that delusions typically do not abide by rational standards that we expect beliefs to conform to. If belief fixation is Spinozan, I argue, these deviations from rationality are not just compatible with, but supportive of, their status as beliefs.
Adventitious roots support population expansion of the invasive plant Mikania micrantha Kunth
Authors: Shen Shicai , Xu Gaofeng , Li Diyu , Yang Shaosong , Jin Guimei , Liu Shufang , Clements David Roy , Chen Aidong , Zhang Fudou , Wen Lila , Tao Qiong , Zhang Shuiying , Yang Jiazhen
Published: June 2021

Mikania micrantha Kunth is a serious invasive alien plant characterized by the formation of an adventitious root system in its prostrate growth form. Unlike the initial roots from seed germination, adventitious roots gradually appear above the stem and branch nodes. Little is known about adventitious roots play on plant growth and population expansion of M. micrantha. We hypothesized that adventitious roots provide an advantage for plant growth and nutrient availability. To test this hypothesis, plant growth, physiology, and nutrition characteristics of M. micrantha were measured under four soil surface conditions allowing various plant parts to touch the soil to stimulate variable adventitious root formation. The results showed that the biomass, stem length, branch number, and adventitious root biomass of M. micrantha were significantly increased (P < 0.05) with increasing nodes bearing adventitious roots. As the number of nodes with adventitious roots increased, the net photosynthetic rate, antioxidant enzyme activities like superoxide dismutase, catalase, peroxidase, and malondialdehyde, chlorophyll content, and plant nutrient contents (N, P, and K) of M. micrantha were increased (P < 0.05), with higher values in main stem leaves than in those of branch leaves. The concentrations of soil organic matter, total N, total P, total K, available N, available P, and available K were greater (P < 0.05) in initial soil (CK) than in treatment soil (with M. micrantha) and were significantly reduced by adventitious roots. Our study was the first to show that plant growth, physiology and nutrition status of M. micrantha were strongly promoted by adventitious roots in the prostrate growth form.
Federal Regulation and Mortality in the 50 States
Authors: Broughel James , Chambers Dustin
Published: June 2021

Previous research speculates that some regulations are counterproductive in the sense that they increase (rather than decrease) mortality risk. However, few empirical studies have measured the extent to which this phenomenon holds across the regulatory system as a whole. Using a novel U.S. state panel data set spanning the period 2000–2014, we estimate the effect of U.S. federal regulation on state‐level mortality. We find that a 1% increase in federal regulation of state economies is associated with an increase in an index of state mortality of between 0.53% and 1.35%. These findings are robust to the form of mortality measure, choice of covariates, and the inclusion/exclusion of various regions, states, and industries. We also provide an update of the “cost‐per‐life saved cutoff,” which is the counterproductive risk threshold for expenditures. We find that expenditures in excess of $38.6 million (2019 dollars) per life saved can be expected to increase mortality risk. This article fills an important gap in the empirical literature and boosts the credibility of mortality risk analysis, whereby public policymakers weigh both the expected lives saved and lost due to a proposed regulation or other policy.
HLA‐A homozygosis is associated with susceptibility to COVID‐19
Authors: De Marco Renato , Faria Tathyane C. , Mine Karina L. , Cristelli Marina , Medina‐Pestana José O. , Tedesco‐Silva Hélio , Gerbase‐DeLima Maria
Published: June 2021

The purpose of this single center retrospective study was to investigate the relationship between HLA and ABO polymorphisms and COVID‐19 susceptibility and severity in kidney transplant recipients. It included 720 recipients who had COVID‐19 and 1680 controls composed by recipients in follow‐up who did not contact the transplantation center for COVID‐19 symptoms, up to the moment of their inclusion in the study. HLA‐A, ‐B, and ‐DRB1 allele groups and ABO frequencies were compared between recipients with COVID‐19 (all cases, or separately mild/moderate and severe disease) and controls. The HLA association study was conducted in two case–control series and only associations that showed a p‐value <0.05 in both series were considered. No HLA association regarding COVID‐19 occurrence or severity met this criterion. Homozygosity at HLA‐A locus was associated with COVID‐19 susceptibility (odds ratio 1.4) but not severity. Blood groups A and O were associated with susceptibility and resistance to COVID‐19, respectively. COVID‐19 severity was associated only with older age and cardiac disease, in a multivariate analysis. We conclude that an influence of HLA on COVID‐19 susceptibility is supported by the association with homozygosity at HLA‐A locus but that there is no evidence for a role of any particular HLA‐A, ‐B, or ‐DRB1 polymorphism. Thus, we suggest that what matters is the overall capability of an individual's HLA molecules to present SARS‐CoV‐2 peptides to T cells, a factor that might have a great influence on the breadth of the immune response.
Which Attitudes for the Fitting Attitude Analysis of Value?
Authors: Deonna Julien A. , Teroni Fabrice
Published: June 2021

Abstract

According to the fitting attitude (FA) analysis of value concepts, to conceive of an object as having a given value is to conceive of it as being such that a certain evaluative attitude taken towards it would be fitting. Among the challenges that this analysis has to face, two are especially pressing. The first is a psychological challenge: the FA analysis must call upon attitudes that shed light on our value concepts while not presupposing the mastery of these concepts. The second challenge is normative: the FA analysis must account for the fittingness of the relevant attitudes in terms of a kind of normativity intimately related to these attitudes, but again without presupposing the mastery of the relevant value concepts. In this paper, we show that real progress is possible if we pay close attention to the nature of the attitudes recruited by the analysis. More specifically, we claim that an FA analysis that appeals to emotions conceived as evaluative attitudes — as opposed to, for instance, evaluative judgements or evaluative perceptions — has the best prospects of meeting the two challenges and of putting the FA analysis on a strong footing.
The evolution of the phenylpropanoid pathway entailed pronounced radiations and divergences of enzyme families
Authors: de Vries Sophie , Fürst‐Jansen Janine M. R. , Irisarri Iker , Dhabalia Ashok Amra , Ischebeck Till , Feussner Kirstin , Abreu Ilka N , Petersen Maike , Feussner Ivo , de Vries Jan
Published: June 2021

Land plants constantly respond to fluctuations in their environment. Part of their response is the production of a diverse repertoire of specialized metabolites. One of the foremost sources for metabolites relevant to environmental responses is the phenylpropanoid pathway, which was long thought to be a land‐plant‐specific adaptation shaped by selective forces in the terrestrial habitat. Recent data have, however, revealed that streptophyte algae, the algal relatives of land plants, have candidates for the genetic toolkit for phenylpropanoid biosynthesis and produce phenylpropanoid‐derived metabolites. Using phylogenetic and sequence analyses, we here show that the enzyme families that orchestrate pivotal steps in phenylpropanoid biosynthesis have independently undergone pronounced radiations and divergence in multiple lineages of major groups of land plants; sister to many of these radiated gene families are streptophyte algal candidates for these enzymes. These radiations suggest a high evolutionary versatility in the enzyme families involved in the phenylpropanoid‐derived metabolism across embryophytes. We suggest that this versatility likely translates into functional divergence, and may explain the key to one of the defining traits of embryophytes: a rich specialized metabolism.
Reliability of Manually Segmenting T1ρ Magnetic Resonance Sequences of Talar Articular Cartilage
Authors: Song Kyeongtak , Kosik Kyle B. , Gribble Phillip A. , Wikstrom Erik A.
Published: June 2021

Context: Quantifying early posttraumatic ankle osteoarthritis pathogenesis using compositional magnetic resonance (MR) imaging sequences is becoming more common. These MR sequences are often manually segmented to isolate the cartilage of interest before cartilage compositional values (eg, T1ρ or T2) are quantified. However, limited information is available regarding the reliability and reproducibility of manual segmentation for the entire talar dome. Objective: The purpose of this study was to determine the intraobserver and interobserver reliability of manually segmenting T1ρ MR sequences of the entire talar dome and 4 subregions of interest. Design: Descriptive observational study. Setting: Laboratory. Patients or Other Participants: Ten uninjured healthy individuals (4M and 6F: 21.40 [3.03] y, 170.00 [7.93] cm, 71.03 [14.97] kg) participated. Intervention: None. Main Outcome Measures: Two investigators manually segmented 10 T1ρ ankle MR sequences using ITK-SNAP software to calculate T1ρ mean relaxation times and cartilage volumes. Each observer repeated the segmentation twice, with segmentations separated by 1 month. Intraobserver and interobserver reliability was determined using intraclass correlation coefficients (ICCs) with 95% confidence intervals and root mean square coefficient of variations (RMSCVs). Results: For T1ρ relaxation time, intraobserver (ICC = .994–.997, RMSCV = 1.31%–1.51%) and interobserver reliability (ICC = .990, RMSCV = 2.36%) was excellent for the overall talar dome. Excellent intraobserver (ICC = .975–.980, RMSCV = 3.88%–4.59%) and excellent interobserver reliability (ICC = .970, RMSCV = 5.13%) was noted for overall talar cartilage volume. Conclusions: The results demonstrate that manual segmentation of the entire talar dome from a T1ρ MR is reliable and repeatable.
Role of nucleosomal cores and histone H1 in regulation of transcription by RNA polymerase II
Authors: Laybourn PJ , Kadonaga JT
Published: June 2021

The relation between chromatin structure and transcriptional activity was examined by in vitro transcription analysis of chromatin reconstituted in the absence or presence of histone H1. To maintain well-defined template DNA, purified components were used in the reconstitution of chromatin. Reconstitution of nucleosomal cores to an average density of 1 nucleosome per 200 base pairs of DNA resulted in a mild reduction of basal RNA polymerase II transcription to 25 to 50 percent of that obtained with naked DNA templates. This nucleosome-mediated repression was due to nucleosomal cores located at the RNA start site and could not be counteracted by the sequence-specific transcription activators Sp1 and GAL4-VP16. When H1 was incorporated into the chromatin at 0.5 to 1.0 molecule per nucleosome (200 base pairs of DNA), RNA synthesis was reduced to 1 to 4 percent of that observed with chromatin containing only nucleosomal cores, and this H1-mediated repression could be counteracted by the addition of Sp1 or GAL4-VP16 (antirepression). With naked DNA templates, transcription was increased by a factor of 3 and 8 by Sp1 and GAL4-VP-16, respectively (true activation). With H1-repressed chromatin templates, however, the magnitude of transcriptional activation mediated by Sp1 and GAL4-VP16 was 90 and more than 200 times higher, respectively, because of the combined effects of true activation and antirepression. The data provide direct biochemical evidence that support and clarify previously proposed models in which there is depletion or reconfiguration of nucleosomal cores and histone H1 at the promoter regions of active genes.
Defining protective responses to pathogens: cytokine profiles in leprosy lesions
Authors: Yamamura M , Uyemura K , Deans RJ , Weinberg K , Rea TH , Bloom BR , Modlin RL
Published: June 2021

The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin-4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production.
Anti-SARS-CoV-2 Antibody Levels Measured by the AdviseDx SARS-CoV-2 Assay Are Concordant with Previously Available Serologic Assays but Are Not Fully Predictive of Sterilizing Immunity
Authors: Bradley Benjamin T. , Bryan Andrew , Fink Susan L. , Goecker Erin A. , Roychoudhury Pavitra , Huang Meei-Li , Zhu Haiying , Chaudhary Anu , Madarampalli Bhanupriya , Lu Joyce Y. C. , Strand Kathy , Whimbey Estella , Bryson-Cahn Chloe , Schippers Adrienne , Mani Nandita S. , Pepper Gregory , Jerome Keith R. , Morishima Chihiro , Coombs Robert W. , Wener Mark , Cohen Seth , Greninger Alexander L.
Published: June 2021

With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative antispike serological testing will likely become increasingly important. Here, we investigated the performance characteristics of the recently FDA-authorized semiquantitative antispike AdviseDx SARS-CoV-2 IgG II assay compared to the FDA-authorized antinucleocapsid Abbott Architect SARS-CoV-2 IgG, Roche Elecsys anti-SARS-CoV-2-S, EuroImmun anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA), and GenScript surrogate virus neutralization assays and examined the humoral response associated with vaccination, natural protection, and breakthrough infection.
Complete Genome Sequence of Streptococcus mutans 27-3, an Active Extracellular Membrane Vesicle Producer
Authors: Huang Xiaochang , Merritt Justin , Wen Zezhang Tom
Published: June 2021

Here, we report the complete genome sequence of
Streptococcus mutans
27-3. Isolated from a caries-active patient, 27-3 produces significantly more extracellular membrane vesicles than the commonly used laboratory strain UA159. This study provides useful information for comparative genomic analysis and better understanding of regulation of vesiculogenesis in this bacterium.
Alpine relief limited by glacial occupation time
Authors: Salcher Bernhard , Prasicek Günther , Baumann Sebastian , Kober Florian
Published: June 2021

Glaciers exert a major control on the shape of mountain topography. They tend to reduce relief above and scour troughs below the equilibrium line altitude (ELA). While many studies report this dichotomy, relief-limiting effects are controversial due to difficulties in quantifying key factors such as the initial topography, the timing of glacial occupancy, or rock uplift counteracting glacial erosion. Consequently, effectivity and degree of glacial erosion remain ambiguous. In geologically and climatically well-investigated parts of the European Central Alps, our calculation of glacial occupation time (GOT) from Quaternary ELA variations allows the quantification of gradual topographic modifications generated by the cumulative impact of cirque erosion over the Quaternary. We show that under low uplift, relief is effectively limited by glacial and periglacial headwall retreat, leading to a decline in topographic relief as GOT increases. Conversely, higher uplift rates seem to induce more persistent valley glaciation, triggering a positive feedback loop in which steep slopes are protected against erosion and relief increases.
How fast do submarine fans grow? Insights from the Quaternary Golo fans, offshore Corsica
Authors: Sweet Michael L. , Gaillot Gwladys T. , Rittenour Tammy M. , Love Kathrine , Blum Michael D.
Published: June 2021

High-resolution seismic, core, and chronological data from the Quaternary Golo deep-sea fans, offshore Corsica, France, give new insights into rates of submarine fan growth. Average vertical deposition rates for units that represent the Late Pleistocene glacial periods are 0.1–0.5 m/k.y. Glacial-age deposits are sand rich; in contrast, post-glacial deposits lack a significant sand fraction and are dominated by carbonate-rich mud. As a result, seismically constrained volumetric rates of deposition for glacial periods with low sea level and a subaerially exposed shelf are ∼0.23 km3/k.y., 2×–5× higher than rates during interglacials when sea level is high, the shelf is submerged, and sand is trapped in shallow-marine environments. At millennial time scales, variations in deposition rate reflect climate-driven sea-level changes, autogenic avulsion of river channels that extend across the shelf during low sea level, and autogenic avulsion of submarine channels that shift the locus of deposition laterally. Short-term deposition rates range from 8.6 m/k.y. at proximal portions of submarine fans to 0.4 m/k.y. along the distal fringe. Our data show that submarine fans can be dynamic environments with formation and evolution of levee-confined channels and lobe complexes in 103–104 yr, comparable to the time scales needed to form fluvial channel belts and delta lobes.
Contrasting northern and southern European winter climate trends during the Last Interglacial
Authors: Salonen J. Sakari , Sánchez-Goñi Maria Fernanda , Renssen Hans , Plikk Anna
Published: June 2021

The Last Interglacial (LIG; 130–115 ka) is an important test bed for climate science as an instance of significantly warmer than preindustrial global temperatures. However, LIG climate patterns remain poorly resolved, especially for winter, affected by a suite of strong feedbacks such as changes in sea-ice cover in the high latitudes. We present a synthesis of winter temperature and precipitation proxy data from the Atlantic seaboard of Europe, spanning from southern Iberia to the Arctic. Our data reveal distinct, opposite latitudinal climate trends, including warming winters seen in the European Arctic while cooling and drying occurred in southwest Europe over the LIG. Climate model simulations for 130 and 120 ka suggest these contrasting climate patterns were affected by a shift toward an atmospheric circulation regime with an enhanced meridional pressure gradient and strengthened midlatitude westerlies, leading to a strong reduction in precipitation across southern Europe.
Supplemental Material: Emergent simplicity despite local complexity in eroding fluvial landscapes
Authors: Roberts Gareth G.
Published: June 2021

Movies S1 and S2 (showing examples of the time dependent behavior of the threshold model), and a simple mathematical explanation for how models of physical erosion can be simplified to few parameters.
Supplemental Material: First identification of a Cathaysian continental fragment beneath the Gagua Ridge, Philippine Sea, and its tectonic implications
Authors: Qian Sheng-Ping , al. et
Published: June 2021

Methods, supplemental figures, and supplemental tables
Supplemental Material: Nonclimatic and extrabasinal processes controlled pedogenesis in paleosols of the Paleocene Nacimiento Formation, New Mexico, USA
Authors: Hobbs Kevin M.
Published: June 2021

Geochemical data tables, X-Ray diffractograms from paleosol B horizon materials, and results of statistical analysis of pedotype and geochemical analysis data.
GUT-Monopole Searches by Means of Deep Underwater Baikal Neutrino Telescope
Authors: Gaponenko O. N.
Published: June 2021

The procedure for Grand Unified Theory (GUT) monopole searches by means of the NT200 Baikal neutrino detector is described. Event-selection and background-suppression algorithms are discussed in detail. Limits on the flux of slow monopoles are presented and are compared with theoretical predictions and with the results of other experiments.
Factors leading to neonatal mortality due to neonatal purpura fulminans through the lens of a child death review
Authors: Rana Kirtan , Gupta Atul , Sood Aditya , Gupta Madhu
Published: June 2021

A case of neonatal death due to neonatal purpura fulminans (NPF) was brought to community physicians’ notice by the auxiliary nurse midwife in her catchment area as part of the routine demographic health surveillance. The community physician then conducted the child death review in the community. The neonate was born out of consanguineous marriage (mother married to her first-degree maternal cousin) with spontaneous conception. This neonate was fourth in the birth order. The second-order and third-order births had also suffered from NPF and died. The baby was delivered in a tertiary care setting, and the paediatric surgeon planned debridement of the affected part on the third day of the birth, as per the mother. However, due to inadequate counselling regarding the procedure, mother left the hospital without seeking care against medical advice, and the child died at home.
SKAP2-BRAF fusion and response to an MEK inhibitor in a patient with metastatic melanoma resistant to immunotherapy
Authors: Chew Sonya Minmin , Lucas Mairi , Brady Michelle , Kelly Catherine Margaret
Published: June 2021

A woman in her 40s presented to the emergency department with headache and unintentional weight loss in September 2018. Investigations revealed a widely metastatic pan-negative melanoma of unknown primary. She had multiple lines of treatment including combination immunotherapy and chemotherapy. Next-generation sequencing identified an SKAP2-BRAF fusion protein, and she was commenced on an MEK inhibitor in September 2019 with a partial response seen on restaging scans after 6 weeks and a dramatic fall in her lactate dehydrogenase from 2248 IU/L to 576 IU/L. Unfortunately, the response was not maintained and she died from progression of her cancer in January 2020. SKAP2-BRAF fusions have a dimerisation domain that paradoxically activates the mitogen-activated protein kinase pathway, resulting in hyperproliferation if first-generation or second-generation BRAF inhibitors are used. Our knowledge is limited regarding the complex effects of targeted therapy in rare BRAF fusion proteins.
Dysphagia due to spontaneous hyperinflation of a swallowable intragastric balloon
Authors: Gaunt Elizabeth Ann , Fernandes Roland
Published: June 2021

A 49-year-old woman presented as an acute admission with persistent vomiting and an inability to tolerate both solids and liquids. Five weeks prior to the admission she had an Elipse swallowable intragastric balloon placed into her stomach as an aid to weight loss. This type of balloon stays inflated inside the stomach for 16 weeks before disintegrating and passing through the gastrointestinal tract. Observations and blood parameters were unremarkable but abdominal radiograph indicated that the balloon had undergone spontaneous hyperinflation—a rare complication. At gastroscopy, the balloon was found to fill the entire stomach volume causing dysphagia. The balloon was punctured endoscopically, contents suctioned and remnants retrieved through the gastroscope. The patient commenced oral intake the following day and was discharged home with no further symptoms at 12-week follow-up.
Photobacterium damselaesubsp.damselaebacteraemia in a patient with liver cirrhosis
Authors: Hayano Satoshi , Masaki Takayuki , Tadakuma Risako , Kashima Masayuki
Published: June 2021

Photobacterium damselaesubsp.damselaeis a family ofVibrionaceaeand exists in the marine environment. The organism rarely causes soft-tissue infection in humans; moreover, most of the infected individuals have a history of fishing or exposure to brackish water. We experienced the case of a 63-year-old patient with a history of liver cirrhosis (Child-Pugh class B) who presented with a fever and swelling of the left leg with pain. His symptoms developed after fishing and eating raw fish with exposure of brackish water. He was diagnosed with cellulitis, andPhotobacterium damselaespp.damselaewas detected in blood culture. The patient was treated with ceftazidime and minocycline and he was discharged after recovery. We need to be aware that in immunocompromised patients with cellulitis exposed to brackish water, organisms other thanStaphylococciandStreptococcimay be the causative organisms.
Castleman’s disease masquerading as pancreatic neuroendocrine tumour
Authors: Gunda Deepika , Naughton Jack , Stevens Sean Gregory , Perini Marcos V
Published: June 2021

Castleman’s disease (CD) is a rare lymphoproliferative disorder. This case report, to the best of our knowledge, is the first report of CD simulating a pancreatic neuroendocrine tumour . The patient was a 58-year-old woman who initially presented with bilateral iritis and underwent investigation for possible systemic rheumatological disease. CT of the chest demonstrated an incidental finding of a well-demarcated retropancreatic mass. As the mass was found to enhance on DOTATATE (tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate) positron emission tomography, a diagnosis of pancreatic neuroendocrine tumour was made. The patient underwent an open distal pancreatectomy and splenectomy. Histopathological examination revealed the unexpected diagnosis of hyaline vascular CD of a lymph node posterior to the pancreas. After 2 years of follow-up, there is no evidence of disease recurrence.
Effect of the covid-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data
Authors: Woolf Steven H , Masters Ryan K , Aron Laudan Y
Published: June 2021

Objective

To estimate changes in life expectancy in 2010-18 and during the covid-19 pandemic in 2020 across population groups in the United States and to compare outcomes with peer nations.

Design

Simulations of provisional mortality data.

Setting

US and 16 other high income countries in 2010-18 and 2020, by sex, including an analysis of US outcomes by race and ethnicity.

Population

Data for the US and for 16 other high income countries from the National Center for Health Statistics and the Human Mortality Database, respectively.

Main outcome measures

Life expectancy at birth, and at ages 25 and 65, by sex, and, in the US only, by race and ethnicity. Analysis excluded 2019 because life table data were not available for many peer countries. Life expectancy in 2020 was estimated by simulating life tables from estimated age specific mortality rates in 2020 and allowing for 10% random error. Estimates for 2020 are reported as medians with fifth and 95th centiles.

Results

Between 2010 and 2018, the gap in life expectancy between the US and the peer country average increased from 1.88 years (78.66v80.54 years, respectively) to 3.05 years (78.74v81.78 years). Between 2018 and 2020, life expectancy in the US decreased by 1.87 years (to 76.87 years), 8.5 times the average decrease in peer countries (0.22 years), widening the gap to 4.69 years. Life expectancy in the US decreased disproportionately among racial and ethnic minority groups between 2018 and 2020, declining by 3.88, 3.25, and 1.36 years in Hispanic, non-Hispanic Black, and non-Hispanic White populations, respectively. In Hispanic and non-Hispanic Black populations, reductions in life expectancy were 18 and 15 times the average in peer countries, respectively. Progress since 2010 in reducing the gap in life expectancy in the US between Black and White people was erased in 2018-20; life expectancy in Black men reached its lowest level since 1998 (67.73 years), and the longstanding Hispanic life expectancy advantage almost disappeared.

Conclusions

The US had a much larger decrease in life expectancy between 2018 and 2020 than other high income nations, with pronounced losses among the Hispanic and non-Hispanic Black populations. A longstanding and widening US health disadvantage, high death rates in 2020, and continued inequitable effects on racial and ethnic minority groups are likely the products of longstanding policy choices and systemic racism.
Characteristics of oxygen concentration and the role of correction factor in real-time GI breath test
Authors: Lee Siu Man , Falconer Imogen H E , Madden Trudi , Laidler Peter O
Published: June 2021

Objective

A high quality end-expiratory breath sample is required for a reliable gastrointestinal breath test result. Oxygen (O2) concentration in the breath sample can be used as a quality marker. This study investigated the characteristics of O2concentration in the breath sample and the impact of using a correction factor in real-time breath measurement.

Design

This study includes two separate groups of patient data. Part 1 of the study analysed the patient’s ability to deliver end-expiratory breath samples over a 2-year period (n=564). Part 2 of the study analysed a separate group of patients (n=47) with additional data to investigate the O2characteristics and the role of correction factor in breath test.

Results

The results indicated 95.4% of 564 patients were able to achieve an O2concentration below 14% in their end-expiratory breath. Part 2 of the study revealed that the distribution of O2concentration was between 9.5% and 16.2%. Applying a correction factor to predict the end-expiratory H2and CH4values led to an average measurement error of −36.4% and −12.8%, respectively.

Conclusion

The majority of patients are able to deliver a high quality end-expiratory breath sample, regardless of age or gender. The correction factor algorithm is unreliable when predicting the end-expiratory result at 15% O2and it would have resulted in false negative result for 50% of the positive cases in this study. It has also indicated that the continuous O2measurement is essential to ensure breath sample quality by preventing secondary breathing during real-time breath collection.