bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Implications for Exercise at Altitude Among Individuals With Cardiovascular Disease
Authors: Cornwell William K. , Baggish Aaron L. , Bhatta Yadav Kumar Deo , Brosnan Maria Joan , Dehnert Christoph , Guseh J. Sawalla , Hammer Debra , Levine Benjamin D. , Parati Gianfranco , Wolfel Eugene E. ,   the American Heart Association Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; and Council on Arteriosclerosis, Thrombosis and Vascular Biology
Published: September 2021

An increasing number of individuals travel to mountainous environments for work and pleasure. However, oxygen availability declines at altitude, and hypoxic environments place unique stressors on the cardiovascular system. These stressors may be exacerbated by exercise at altitude, because exercise increases oxygen demand in an environment that is already relatively oxygen deplete compared with sea‐level conditions. Furthermore, the prevalence of cardiovascular disease, as well as diseases such as hypertension, heart failure, and lung disease, is high among individuals living in the United States. As such, patients who are at risk of or who have established cardiovascular disease may be at an increased risk of adverse events when sojourning to these mountainous locations. However, these risks may be minimized by appropriate pretravel assessments and planning through shared decision‐making between patients and their managing clinicians. This American Heart Association scientific statement provides a concise, yet comprehensive overview of the physiologic responses to exercise in hypoxic locations, as well as important considerations for minimizing the risk of adverse cardiovascular events during mountainous excursions.
Thrombolysis in Mild Stroke
Authors: Asdaghi Negar , Romano Jose G. , Gardener Hannah , Campo-Bustillo Iszet , Purdon Barbara , Khan Yosef M. , Gulati Deepak , Broderick Joseph P. , Schwamm Lee H. , Smith Eric E. , Saver Jeffrey L. , Sacco Ralph , Khatri Pooja ,   on behalf of MaRISS and PRISMS Collaborators and Investigators†
Published: September 2021

Background and Purpose:

Mild ischemic stroke patients enrolled in randomized controlled trials of thrombolysis may have a different symptom severity distribution than those treated in routine clinical practice.

Methods:

We compared the distribution of the National Institutes of Health Stroke Scale (NIHSS) scores, neurological symptoms/severity among patients enrolled in the PRISMS (Potential of r-tPA for Ischemic Strokes With Mild Symptoms) randomized controlled trial to those with NIHSS score ≤5 enrolled in the prospective MaRISS (Mild and Rapidly Improving Stroke Study) registry using global
P
values from χ
2
analyses.

Results:

Among 1736 participants in MaRISS, 972 (56%) were treated with alteplase and 764 (44%) were not. These participants were compared with 313 patients randomized in PRISMS. The median NIHSS scores were 3 (2–4) in MaRISS alteplase-treated, 1 (1–3) in MaRISS non–alteplase-treated, and 2 (1–3) in PRISMS. The percentage with an NIHSS score of 0 to 2 was 36.3%, 73.3%, and 65.2% in the 3 groups, respectively (
P
<0.0001). The proportion of patients with a dominant neurological syndrome (≥1 NIHSS item score of ≥2) was higher in MaRISS alteplase-treated (32%) compared with MaRISS nonalteplase-treated (13.8%) and PRISMS (8.6%;
P
<0.0001).

Conclusions:

Patients randomized in PRISMS had comparable deficit and syndromic severity to patients not treated with alteplase in the MaRISS registry and lesser severity than patients treated with alteplase in MaRISS. The PRISMS trial cohort is representative of mild patients who do not receive alteplase in current broad clinical practice.
Reanalyses and a High-Resolution Model Fail to Capture the “High Tail” of CAPE Distributions
Authors: Wang Ziwei , Franke James A. , Luo Zhenqi , Moyer Elisabeth J.
Published: September 2021

Convective available potential energy (CAPE) is of strong interest in climate modeling because of its role in both severe weather and in model construction. Extreme levels of CAPE (>2000 J kg−1) are associated with high-impact weather events, and CAPE is widely used in convective parameterizations to help determine the strength and timing of convection. However, to date few studies have systematically evaluated CAPE biases in models in a climatological context, and none have addressed bias in the high tail of CAPE distributions. This work compares CAPE distributions in ~200 000 summertime proximity soundings from four sources: the observational radiosonde network [Integrated Global Radiosonde Archive (IGRA)], 0.125° reanalyses (ERA-Interim and ERA5), and a 4-km convection-permitting regional WRF simulation driven by ERA-Interim. Both reanalyses and the WRF Model consistently show too-narrow distributions of CAPE, with the high tail (>90th percentile) systematically biased low by up to 10% in surface-based CAPE and even more in alternate CAPE definitions. This “missing tail” corresponds to the most impacts-relevant conditions. CAPE bias in all datasets is driven by surface temperature and humidity: reanalyses and the WRF Model underpredict observed cases of extreme heat and moisture. These results suggest that reducing inaccuracies in land surface and boundary layer models is critical for accurately reproducing CAPE.
Variability of Tropical Cyclone Landfalls in China
Authors: Shan Kaiyue , Yu Xiping
Published: September 2021

The reported decreasing trend of the annual tropical cyclone (TC) landfalls in southern China and increasing trend in southeastern China in recent decades are confirmed to be an abrupt shift occurring at the end of the twentieth century, based on a statistical analysis. The opposite trends in the two adjacent regions are often considered to be a result of tropical cyclone landfalls in southern China being deflected northward. However, it is demonstrated in this study that they are phenomenally independent. In fact, the abrupt decrease of TC landfalls in southern China occurs as a result of an abrupt decrease of the westward events in the postpeak season (October–December), which in turn is a consequence of a significant decrease of the TC genesis frequency in the southeastern part of the western North Pacific (WNP) Ocean basin. On the other hand, the abrupt increase of TC landfalls in southeastern China occurs because of an abrupt increase of the northwest events in the peak season (July–September), as the consequence of a statistically westward shift of TC genesis. The relevant variations of TC genesis are shown to be mainly caused by decreased relative vorticity and increased vertical wind shear, which, however, are intrinsically related to the accelerated zonal atmospheric circulation driven by a La Niña–like sea surface warming pattern over the WNP that developed after the end of twentieth century.
Global trends in downward surface solar radiation from spatial interpolated ground observations during 1961-2019
Authors: Yuan Menghan , Leirvik Thomas , Wild Martin
Published: September 2021

Downward surface solar radiation (SSR) is a crucial component of the Global Energy Balance, affecting temperature and the hydrological cycle profoundly, and it provides crucial information about climate change. Many studies have examined SSR trends, however they are often concentrated on specific regions due to limited spatial coverage of ground based observation stations. To overcome this spatial limitation, this study performs a spatial interpolation based on a machine learning method, Random Forest, to interpolate monthly SSR anomalies using a number of climatic variables (various temperature indices, cloud coverage, etc.), time point indicators (years and months of SSR observations), and geographical characteristics of locations (latitudes, longitudes, etc). The predictors that provide the largest explanatory power for interannual variability arediurnal temperature rangeandcloud coverage. The output of the spatial interpolation is a 0:5° ×0:5° monthly gridded dataset of SSR anomalies with complete land coverage over the period 1961-2019, which is used afterwards in a comprehensive trend analysis fori)each continent separately, andii)the entire globe.

The continental level analysis reveals the major contributors to the global dimming and brightening. In particular, the global dimming before the 1980s is primarily dominated by negative trends in Asia and North America, while Europe and Oceania have been the two largest contributors to the brightening after 1982 and up until 2019.
An energy budget framework to understand mechanisms of land–ocean warming contrast induced by increasing greenhouse gases Part I: Near-equilibrium state
Authors: Toda Masaki , Watanabe Masahiro , Yoshimori Masakazu
Published: September 2021

Modeling studies have shown that surface air temperature (SAT) increase in response to an increase in the atmospheric CO2 concentration is larger over land than over ocean. This so-called land–ocean warming contrast, φ, defined as the land–mean SAT change divided by the ocean-mean SAT change, is a striking feature of global warming. Small heat capacity over land is unlikely the sole cause because the land-ocean warming contrast is found in the equilibrium state of CO2 doubling experiments.

Several different mechanisms have been proposed to explain the land–ocean warming contrast, but the comprehensive understanding has not yet been obtained. In Part I of this study, we propose a framework to diagnose φ based on energy budgets at the top of atmosphere and for the atmosphere, which enables the decomposition of contributions from effective radiative forcing (ERF), climate feedback, heat capacity, and atmospheric energy transport anomaly to φ. Using this framework, we analyzed the SAT response to an abrupt CO2 quadrupling using 15 Coupled Model Intercomparison Project Phase 6 (CMIP6) Earth system models. In the near-equilibrium state (years 121-150), φ is 1.49 ± 0.11, which is primarily induced by the land–ocean difference in ERF and heat capacity. We found that contributions from ERF, feedback, and energy transport anomaly tend to cancel each other, leading to a small inter-model spread of φ compared to the large spread of individual components. In the equilibrium state without heat capacity contribution, ERF and energy transport anomaly are the major contributors to φ, which shows a weak negative correlation with the equilibrium climate sensitivity.
Toward All-Sky Assimilation of Microwave Temperature Sounding Channels in Environment Canada’s Global Deterministic Weather Prediction System
Authors: Shahabadi Maziar Bani , Buehner Mark
Published: September 2021

The all-sky assimilation of radiances from microwave instruments is developed in the 4D-EnVar analysis system at Environment and Climate Change Canada (ECCC). Assimilation of cloud-affected radiances from Advanced Microwave Sounding Unit-A (AMSU-A) temperature sounding channels 4 and 5 for non-precipitating scenes over the ocean surface is the focus of this study. Cloud-affected radiances are discarded in the ECCC operational data assimilation system due to the limitations of forecast model physics, radiative transfer models, and the strong nonlinearity of the observation operator. In addition to using symmetric estimate of innovation standard deviation for quality control, a state-dependent observation error inflation is employed at the analysis stage. The background-state clouds are scaled by a factor of 0.5 to compensate for a systematic overestimation by the forecast model before being used in the observation operator. The changes in the fit of the background state to observations show mixed results. The number of AMSU-A channels 4 and 5 assimilated observations in the all-sky experiment is 5%–12% higher than in the operational system. The all-sky approach improves temperature analysis when verified against ECMWF operational analysis in the areas where the extra cloud-affected observations were assimilated. Statistically significant reductions in error standard deviation by 1%–4% for the analysis and forecasts of temperature, specific humidity, and horizontal wind speed up to maximum 4 days were achieved in the all-sky experiment in the lower troposphere. These improvements result mainly from the use of cloud information for computing the observation-minus-background departures. The operational implementation of all-sky assimilation is planned for the fall of 2021.
Philosophical cosmology and religious polemic: The “worship of creation” in the writings of Philo of Alexandria and the Wisdom of Solomon
Authors: Wasserman Emma
Published: September 2021

This article treats Hellenistic Jewish literature that ridicules the alleged worship of the elements, the heavens, the heavenly bodies, or other “parts” of the cosmos, especially as developed in the writings of Philo of Alexandria and Ps-Solomon. It is argued that such claims constitute a distinctive sub-type of religious polemic that draws on and adapts from Platonic and Stoic traditions of cosmology. Such polemics are most clearly developed in Philo’s treatises and in chapter 13 of the Wisdom of Solomon, but they also appear in more abbreviated form in the fragments of Philo of Byblos and Aristobulus. I suggest that these traditions of invective may bear on the interpretation of Rom 1:19–23, but only in an indirect way.
The Extra Costs Associated With Living With a Disability in the United States
Authors: Morris Zachary A. , McGarity Stephen V. , Goodman Nanette , Zaidi Asghar
Published: September 2021

People with disabilities encounter many financial expenses that those without disabilities do not incur. In this article, we provide estimates of the extra costs associated with living with a disability in the United States. Drawing on four nationally representative surveys, we estimate that a household containing an adult with a work disability requires, on average, 29% more income (or an additional $18,322 a year for a household at the median income level) to obtain the same standard of living as a comparable household without a member with a disability. Single adults with disabilities are estimated to have higher costs than those with disabilities who are married, and adults with cognitive impairments are estimated to have higher costs compared to those with other kinds of impairments. We further calculate the federal poverty rate for households that include adults with disabilities adjusted for the direct additional costs of disability. The rate rises from 24% to 35% after adjusting for the extra costs of disability, which would result in an estimated 2.2 million more people with disabilities counted as poor. This suggests that the official poverty measure in the United States substantially underestimates the degree of deprivation experienced by people with disabilities.
In Vitro Evaluation of Anti-Lung Cancer and Anti-COVID-19 Effects using Fermented Black Color Ginseng Extract
Authors: Han Yaxi , Yang Dong-Uk , Huo Yue , Pu Jianyu , Lee Seung-Jin , Yang Deok-Chun , Kang Se Chan
Published: September 2021

Ginseng is known as the “king” of herbal plants and has been used widely in Asia for centuries. Ginseng contains active saponins, including protopanaxadiols, protopanaxatriols, and other compounds. There are many methods for processing ginseng, such as steaming, fermentation, expansion, and conversion of active compounds, which can improve its biological activity. In this study, we investigated the cytotoxic and oxidative effects of fermented black color ginseng (FBCG), black ginseng (BG), and white ginseng (WG) on a human lung carcinoma cell line (A549). Moreover, we found that treatment with FBCG induced oxidative stress in the A549 cell line and increases the apoptosis percentage; these effects were linked to the stimulation of the caspase 3/mitogen-activated protein kinase (caspase 3/MAPK) pathway. We also evaluated the anti-coronavirus disease-2019 (COVID-19) effect of FBCG on a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Vero E6 cell line. Our results suggest that FBCG not only inhibits the replication of this strain of virus in the cell but also reduces the number of viral RNA (vRNA) copies in the extracellular environment. Taken together, these data show that FBCG has both potential anti-lung cancer and anti-COVID-19 effects.
A Blueprint for Scaling Tutoring and Mentoring Across Public Schools
Authors: Kraft Matthew A. , Falken Grace T.
Published: September 2021

In this thought experiment, we explore how to make access to individualized instruction and academic mentoring more equitable by taking tutoring to scale as a permanent feature of the U.S. public education system. We first synthesize the tutoring and mentoring literature and characterize the landscape of existing tutoring programs. We then outline a blueprint for integrating federally funded and locally delivered tutoring into the school day. High school students would serve as tutors/mentors in elementary schools via an elective class, college students in middle schools via federal work-study, and 2- and 4-year college graduates in high schools via AmeriCorps. We envision an incremental, demand-driven expansion process with priority given to high-needs schools. Our blueprint highlights a range of design tradeoffs, implementation challenges, and program costs. We estimate that targeted approaches to scaling school-wide tutoring nationally, such as focusing on K–8 Title I schools, would cost between $5 and $16 billion annually.
Aggressive B-cell lymphoma cases with 11q aberration patterns indicate a spectrum beyond Burkitt-like lymphoma
Authors: Gebauer Niklas , Witte Hanno M. , Merz Hartmut , Oschlies Ilske , Klapper Wolfram , Caliebe Almuth , Tharun Lars , Spielmann Malte , von Bubnoff Nikolas , Feller Alfred C. , Murga Penas Eva M.
Published: September 2021

The recent characterization of a group of non-MYC rearranged aggressive B-cell lymphomas, resembling Burkitt lymphoma (BL), characteristically harboring a telomeric 11q loss or combined 11q proximal gains/loss pattern has led to the introduction of the provisional entity of Burkitt-like lymphoma with 11q aberration (BLL-11q). Prompted by the discovery of a telomeric 11q loss in an HIV+ high-grade B-cell lymphoma patient, we investigated an extended cohort of aggressive B-cell lymphomas, enriched for cases with histopathological features intermediate between DLBCL and BL, including double- and triple-hit lymphomas (n = 47), for 11q loss/combined 11q proximal gains/loss pattern by fluorescence in situ hybridization. We provide first evidence that 11q aberrations can be found in both BLL in the context of an underlying HIV infection as well as in high-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements. We therefore propose that the clinicopathological spectrum of malignancies carrying this aberration may be broader than previously assumed.
Structuring of plant communities across agricultural landscape mosaics: the importance of connectivity and the scale of effect
Authors: McLeish Michael , Peláez Adrián , Pagán Israel , Gavilán Rosario , Fraile Aurora , García-Arenal Fernando
Published: September 2021

Background

Plant communities of fragmented agricultural landscapes, are subject to patch isolation and scale-dependent effects. Variation in configuration, composition, and distance from one another affect biological processes of disturbance, productivity, and the movement ecology of species. However, connectivity and spatial structuring among these diverse communities are rarely considered together in the investigation of biological processes. Spatially optimised predictor variables that are based on informed measures of connectivity among communities, offer a solution to untangling multiple processes that drive biodiversity.

Results

To address the gap between theory and practice, a novel spatial optimisation method that incorporates hypotheses of community connectivity, was used to estimate the scale of effect of biotic and abiotic factors that distinguish plant communities. We tested: (1) whether different hypotheses of connectivity among sites was important to measuring diversity and environmental variation among plant communities; and (2) whether spatially optimised variables of species relative abundance and the abiotic environment among communities were consistent with diversity parameters in distinguishing four habitat types; namely Crop, Edge, Oak, and Wasteland. The global estimates of spatial autocorrelation, which did not consider environmental variation among sites, indicated significant positive autocorrelation under four hypotheses of landscape connectivity. The spatially optimised approach indicated significant positive and negative autocorrelation of species relative abundance at fine and broad scales, which depended on the measure of connectivity and environmental variation among sites.

Conclusions

These findings showed that variation in community diversity parameters does not necessarily correspond to underlying spatial structuring of species relative abundance. The technique used to generate spatially-optimised predictors is extendible to incorporate multiple variables of interest along with a priori hypotheses of landscape connectivity. Spatially-optimised variables with appropriate definitions of connectivity might be better than diversity parameters in explaining functional differences among communities.
De novo transcriptome analysis provides insights into formation of in vitro adventitious root from leaf explants of Arnebia euchroma
Authors: Devi Jyoti , Kaur Ekjot , Swarnkar Mohit Kumar , Acharya Vishal , Bhushan Shashi
Published: September 2021

Background

Adventitious root formation is considered a major developmental step during the propagation of difficult to root plants, especially in horticultural crops. Recently, adventitious roots induced through plant tissue culture methods have also been used for production of phytochemicals such as flavonoids, anthocyanins and anthraquinones. It is rather well understood which horticultural species will easily form adventitious roots, but the factors affecting this process at molecular level or regulating the induction process in in vitro conditions are far less known. The present study was conducted to identify transcripts involved in in vitro induction and formation of adventitious roots using Arnebia euchroma leaves at different time points (intact leaf (control), 3 h, 12 h, 24 h, 3 d, 7 d, 10 d and 15 d). A. euchroma is an endangered medicinal Himalayan herb whose root contains red naphthoquinone pigments. These phytoconstituents are widely used as an herbal ingredient in Asian traditional medicine as well as natural colouring agent in food and cosmetics.

Results

A total of 137.93 to 293.76 million raw reads were generated and assembled to 54,587 transcripts with average length of 1512.27 bps and N50 of 2193 bps, respectively. In addition, 50,107 differentially expressed genes were identified and found to be involved in plant hormone signal transduction, cell wall modification and wound induced mitogen activated protein kinase signalling. The data exhibited dominance of auxin responsive (AUXIN RESPONSE FACTOR8, IAA13, GRETCHEN HAGEN3.1) and sucrose translocation (BETA-31 FRUCTOFURANOSIDASE and MONOSACCHARIDE-SENSING protein1) genes during induction phase. In the initiation phase, the expression of LATERAL ORGAN BOUNDARIES DOMAIN16, EXPANSIN-B15, ENDOGLUCANASE25 and LEUCINE-rich repeat EXTENSION-like proteins was increased. During the expression phase, the same transcripts, with exception of LATERAL ORGAN BOUNDARIES DOMAIN16 were identified. Overall, the transcriptomic analysis revealed a similar patterns of genes, however, their expression level varied in subsequent phases of in vitro adventitious root formation in A. euchroma.

Conclusion

The results presented here will be helpful in understanding key regulators of in vitro adventitious root development in Arnebia species, which may be deployed in the future for phytochemical production at a commercial scale.
Genome-wide identification and characterization of bZIP transcription factors and their expression profile under abiotic stresses in Chinese pear (Pyrus bretschneideri)
Authors: Manzoor Muhammad Aamir , Manzoor Muhammad Mudassar , Li Guohui , Abdullah Muhammad , Han Wang , Wenlong Han , Shakoor Awais , Riaz Muhammad Waheed , Rehman Shamsur , Cai Yongping
Published: September 2021

Background

In plants, basic leucine zipper transcription factors (TFs) play important roles in multiple biological processes such as anthesis, fruit growth & development and stress responses. However, systematic investigation and characterization of bZIP-TFs remain unclear in Chinese white pear. Chinese white pear is a fruit crop that has important nutritional and medicinal values.

Results

In this study, 62 bZIP genes were comprehensively identified from Chinese Pear, and 54 genes were distributed among 17 chromosomes. Frequent whole-genome duplication (WGD) and dispersed duplication (DSD) were the major driving forces underlying the bZIP gene family in Chinese white pear. bZIP-TFs are classified into 13 subfamilies according to the phylogenetic tree. Subsequently, purifying selection plays an important role in the evolution process of PbbZIPs. Synteny analysis of bZIP genes revealed that 196 orthologous gene pairs were identified between Pyrus bretschneideri, Fragaria vesca, Prunus mume, and Prunus persica. Moreover, cis-elements that respond to various stresses and hormones were found on the promoter regions of PbbZIP, which were induced by stimuli. Gene structure (intron/exon) and different compositions of motifs revealed that functional divergence among subfamilies. Expression pattern of PbbZIP genes differential expressed under hormonal treatment abscisic acid, salicylic acid, and methyl jasmonate  in pear fruits by real-time qRT-PCR.

Conclusions

Collectively, a systematic analysis of gene structure, motif composition, subcellular localization, synteny analysis, and calculation of synonymous (Ks) and non-synonymous (Ka) was performed in Chinese white pear. Sixty-two bZIP-TFs in Chinese pear were identified, and their expression profiles were comprehensively analyzed under ABA, SA, and MeJa hormones, which respond to multiple abiotic stresses and fruit growth and development. PbbZIP gene occurred through Whole-genome duplication and dispersed duplication events. These results provide a basic framework for further elucidating the biological function characterizations under multiple developmental stages and abiotic stress responses.
Incidence and survival analyses for occult lung cancer between 2004 and 2015: a population-based study
Authors: Wu Lei-Lei , Li Chong-Wu , Lin Wei-Kang , Qiu Li-Hong , Xie Dong
Published: September 2021

Background

This study aimed to investigate the incidence and long-term survival outcomes of occult lung cancer between 2004 and 2015.

Methods

A total of 2958 patients were diagnosed with occult lung cancer in the 305,054 patients with lung cancer. The entire cohort was used to calculate the crude incidence rate. Eligible 52,472 patients (T1-xN0M0, including 2353 occult lung cancers) were selected from the entire cohort to perform survival analyses after translating T classification according to the 8th TNM staging system. Cancer-specific survival curves for different T classifications were presented.

Results

The crude incidence rate of occult lung cancer was 1.00 per 100 patients, and it was reduced between 2004 and 2015 [1.4 per 100 persons in 2004; 0.6 per 100 persons in 2015; adjusted risk ratio = 0.437, 95% confidence interval (CI) 0.363–0.527]. In the survival analysis, there were 2206 death events in the 2353 occult lung cancers. The results of the multivariable analysis revealed that the prognoses with occult lung cancer were similar to patients with stage T3N0M0 (adjusted hazard ratio = 1.054, 95% CI 0.986–1.127, p = 0.121). Adjusted survival curves presented the same results. In addition, adjusted for other confounders, female, age ≤ 72 years, surgical treatment, radiotherapy, adenocarcinoma, and non-squamous and non-adenocarcinoma non-small cell carcinoma were independent protective prognostic factors (all p < 0.05).

Conclusions

Occult lung cancer was uncommon. However, the cancer-specific survival of occult lung cancer was poor, therefore, we should put the assessment of its prognoses on the agenda. Timely surgical treatment and radiotherapy could improve survival outcomes for those patients. Besides, we still need more research to confirm those findings.
Uev1A promotes breast cancer cell migration by up-regulating CT45A expression via the AKT pathway
Authors: Niu Tong , Wu Zhaojia , Xiao Wei
Published: September 2021

Background

UEV1A encodes a ubiquitin-E2 variant closely associated with tumorigenesis and metastasis, but its underlying mechanism in promoting metastasis remains to be investigated.

Methods

In this study, we experimentally manipulated UEV1A and CT45A gene expression and monitored their effects on cancer-related gene expression, cell migration and the signal transduction cascade.

Results

It was found that UEV1A overexpression induces CT45A family gene expression in breast cancer cells. Indeed, ectopic expression of UEV1A was sufficient to induce CT45A and its downstream genes involved in tumorigenesis, epithelial-mesenchymal transition (EMT), stemness and metastasis, and to promote cell migration and EMT signaling. Consistently, depletion of CT45A abolished the above effects, indicating that CT45A is a critical downstream effector of Uev1A. The Uev1A-induced cell migration and EMT signaling was dependent on AKT but independent of NF-κB, indicating that CT45A acts downstream of the AKT pathway.

Conclusions

Based on previous reports and observations in this study, we propose that the Ubc13-Uev1A complex activates AKT through K63-linked polyubiquitination, which leads to enhanced CT45A expression, stimulated cell migration and EMT signaling in breast cells. Since similar effects were also observed in a colorectal cancer cell line, the Ubc13/Uev1A-AKT-CT45A axis may also promote tumorigenesis and metastasis in other tissues.
Application of CD54 in diagnosing bone marrow involvement by using flow cytometry in patients with diffuse large B-cell lymphoma
Authors: Wang Wei , Li Yan , Rivera Rivera Xavier , Zhao Linjun , Mei Di , Hu Wenqing , Jiang Bin
Published: September 2021

Background

Flow cytometry plays a key role in detecting bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL). To improve its detection sensitivity, we need to explore novel markers. In this study, we detected the expression CD54 on lymphoma cells in BM specimens from DLBCL patients and clarified its diagnostic significance in BM involvement by DLBCL.

Methods

We collected BM specimens from 76 patients with DLBCL (germinal center B-cell (GCB) = 25, non-GCB = 51) and 10 control patients without lymphoma. We detected and compared the expression of CD54 on lymphoma cells and normal mature B cells by using 10-color panels.

Results

Normal plasma cells expressed a higher level of CD54 as compared with hematogones (p < 0.05) and normal mature B cells (p < 0.05). Among 76 patients, 23 of them (GCB = 12, non-GCB = 11) had BM involvement. Lymphoma B cells from 12 cases (GBC = 4, non-GCB = 8) expressed a higher level of CD54 compared to normal mature B cells (p < 0.05). Additionally, lymphoma cells of the non-GCB subtype frequently expressed a higher level of CD54 in comparison to the GCB subtype (p < 0.05). And the high expression of CD54 was not related to plasmacytoid differentiation.

Conclusion

Aberrant expression of CD54 on lymphoma cells is frequently seen in patients’ BM specimens involved by DLBCL, especially in the non-GCB subtype. CD54 could be used as a new marker to gate on lymphoma cells and improve the detection sensitivity of BM involvement in patients with DLBCL.
The diagnostic trajectory in autism and intellectual disability in Quebec: pathways and parents’ perspective
Authors: Rivard Mélina , Patrick Coulombe , Mello Catherine , Morin Diane , Morin Marjorie
Published: September 2021

Background

This paper aimed to describe the diagnostic service trajectory of families of children with autism or intellectual disability in the province of Québec and identify predictors of parents’ perceptions of its quality.

Methods

The Evaluation of the services Trajectory in Autism by Parents instrument was completed by 259 parents at an assessment clinic. Children’s clinical records were also examined.

Results

On average 26 months elapsed between their first concerns and their child’s diagnosis, a period during which few (25%) received support. Parents’ evaluations were generally positive but were lower for the accessibility of the pre-assessment phase and the flexibility of the assessment process. Longer delays and a greater number of professionals consulted were associated with lower quality ratings. Some language-, immigration status-, and income-related differences in families’ appraisals were noted.

Conclusion

The diagnostic trajectory for neurodevelopmental disorders within public services in Québec presents some efficiency and accessibility challenges. Possible improvements are proposed to facilitate screening and to support families throughout this phase of their trajectory.
Pharmacies in informal settlements: a retrospective, cross-sectional household and health facility survey in four countries
Authors:   Improving Health in Slums Collaborative, Bakibinga Pauline , Kabaria Caroline , Kasiira Ziraba , Kibe Peter , Kyobutungi Catherine , Mbaya Nelson , Mberu Blessing , Mohammed Shukri , Njeri Anne , Azam Iqbal , Iqbal Romaina , Nazish Ahsana , Rizvi Narijis , Shifat Ahmed Syed A. K. , Choudhury Nazratun , Alam Ornob , Khan Afreen Zaman , Rahman Omar , Yusuf Rita , Odubanjo Doyin , Ayobola Motunrayo , Fayehun Olufunke , Omigbodun Akinyinka , Osuh Mary , Owoaje Eme , Taiwo Olalekan , Lilford Richard J. , Sartori Jo , Watson Samuel I. , Diggle Peter J. , Aujla Navneet , Chen Yen-Fu , Gill Paramjit , Griffiths Frances , Harris Bronwyn , Madan Jason , Muir Helen , Oyebode Oyinlola , Pitidis Vangelis , de Albuquerque João Porto , Smith Simon , Taylor Celia , Ulbrich Philip , Uthman Olalekan A. , Wilson Ria , Yeboah Godwin , Watson Sam
Published: September 2021

Background

Slums or informal settlements characterize most large cities in LMIC. Previous evidence suggests pharmacies may be the most frequently used source of primary care in LMICs but that pharmacy services are of variable quality. However, evidence on pharmacy use and availability is very limited for slum populations.

Methods

We conducted household, individual, and healthcare provider surveys and qualitative observations on pharmacies and pharmacy use in seven slum sites in four countries (Nigeria, Kenya, Pakistan, and Bangladesh). All pharmacies and up to 1200 households in each site were sampled. Adults and children were surveyed about their use of healthcare services and pharmacies were observed and their services, equipment, and stock documented.

Results

We completed 7692 household and 7451 individual adults, 2633 individual child surveys, and 157 surveys of pharmacies located within the seven sites. Visit rates to pharmacies and drug sellers varied from 0.1 (Nigeria) to 3.0 (Bangladesh) visits per person-year, almost all of which were for new conditions. We found highly variable conditions in what constituted a “pharmacy” across the sites and most pharmacies did not employ a qualified pharmacist. Analgesics and antibiotics were widely available but other categories of medications, particularly those for chronic illness were often not available anywhere. The majority of pharmacies lacked basic equipment such as a thermometer and weighing scales.

Conclusions

Pharmacies are locally and widely available to residents of slums. However, the conditions of the facilities and availability of medicines were poor and prices relatively high. Pharmacies may represent a large untapped resource to improving access to primary care for the urban poor.
Geospatial analysis and impact of targeted development of breast cancer care in The Gambia: a cross-sectional study
Authors: Sanyang Ousman , Lopez-Verdugo Fidel , Mali Meghan , Moustafa Moustafa , Nellermoe Jonathan , Sorensen Justin , Bittaye Mustapha , Njie Ramou , Singhateh Yankuba , Sambou Ngally Aboubacarr , Goldsmith Alison , Mohammed Nuredin I. , Brownson Kirstyn E. , Price Raymond R. , Sutherland Edward
Published: September 2021

Background

The Gambia has one of the lowest survival rates for breast cancer in Africa. Contributing factors are late presentation, delays within the healthcare system, and decreased availability of resources. We aimed to characterize the capacity and geographic location of healthcare facilities in the country and calculate the proportion of the population with access to breast cancer care.

Methods

A facility-based assessment tool was administered to secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia. GPS coordinates were obtained, and proximity of service availability and population analysis were performed. Distance thresholds of 10, 20, and 45 km were chosen to determine access to screening, pathologic diagnosis, and surgical management. An additional population analysis was performed to observe the potential impact of targeted development of resources for breast cancer care.

Results

All 102 secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia were included. Breast cancer screening is mainly performed through clinical breast examination and is available in 52 facilities. Seven facilities provide pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis, and surgical management is 72, 53, and 62%, respectively. A hypothetical targeted expansion of resources would increase the covered population to 95, 62, and 84%.

Conclusions

Almost half of the Gambian population does not have access to pathologic diagnosis and surgical management of breast cancer within the distance threshold utilized in the study. Mapping and population analysis can identify areas for targeted development of resources to increase access to breast cancer care.
Pathologic tau conformer ensembles induce dynamic, liquid-liquid phase separation events at the nuclear envelope
Authors: Kang Sang-Gyun , Han Zhuang Zhuang , Daude Nathalie , McNamara Emily , Wohlgemuth Serene , Molina-Porcel Laura , Safar Jiri G. , Mok Sue-Ann , Westaway David
Published: September 2021

Background

The microtubule-associated protein tau forms aggregates in different neurodegenerative diseases called tauopathies. Prior work has shown that a single P301L mutation in tau gene, MAPT, can promote alternative tau folding pathways that correlate with divergent clinical diagnoses. Using progressive chemical denaturation, some tau preparations from the brain featured complex transitions starting at low concentrations of guanidine hydrochloride (GdnHCl) denaturant, indicating an ensemble of differently folded tau species called conformers. On the other hand, brain samples with abundant, tangle-like pathology had simple GdnHCl unfolding profile resembling the profile of fibrillized recombinant tau and suggesting a unitary conformer composition. In studies here we sought to understand tau conformer progression and potential relationships with condensed liquid states, as well as associated perturbations in cell biological processes.

Results

As starting material, we used brain samples from P301L transgenic mice containing tau conformer ensembles that unfolded at low GdnHCl concentrations and with signatures resembling brain material from P301L subjects presenting with language or memory problems. We seeded reporter cells expressing a soluble form of 4 microtubule-binding repeat tau fused to GFP or YFP reporter moieties, resulting in redistribution of dispersed fluorescence signals into focal assemblies that could fuse together and move within processes between adjacent cells. Nuclear envelope fluorescent tau signals and small fluorescent inclusions behaved as a demixed liquid phase, indicative of liquid-liquid phase separation (LLPS); these droplets exhibited spherical morphology, fusion events and could recover from photobleaching. Moreover, juxtanuclear tau assemblies were associated with disrupted nuclear transport and reduced cell viability in a stable cell line. Staining for thioflavin S (ThS) became more prevalent as tau-derived inclusions attained cross-sectional area greater than 3 μm2, indicating (i) a bipartite composition, (ii) in vivo progression of tau conformers, and (iii) that a mass threshold applying to demixed condensates may drive liquid-solid transitions.

Conclusions

Tau conformer ensembles characterized by denaturation at low GdnHCl concentration templated the production of condensed droplets in living cells. These species exhibit dynamic changes and develop in vivo, and the larger ThS-positive assemblies may represent a waystation to arrive at intracellular fibrillar tau inclusions seen in end-stage genetic tauopathies.
Tuberculosis related disability: a systematic review and meta-analysis
Authors: Alene Kefyalew Addis , Wangdi Kinley , Colquhoun Samantha , Chani Kudakwashe , Islam Tauhid , Rahevar Kalpeshsinh , Morishita Fukushi , Byrne Anthony , Clark Justin , Viney Kerri
Published: September 2021

Background

The sustainable development goals aim to improve health for all by 2030. They incorporate ambitious goals regarding tuberculosis (TB), which may be a significant cause of disability, yet to be quantified. Therefore, we aimed to quantify the prevalence and types of TB-related disabilities.

Methods

We performed a systematic review of TB-related disabilities. The pooled prevalence of disabilities was calculated using the inverse variance heterogeneity model. The maps of the proportions of common types of disabilities by country income level were created.

Results

We included a total of 131 studies (217,475 patients) that were conducted in 49 countries. The most common type of disabilities were mental health disorders (23.1%), respiratory impairment (20.7%), musculoskeletal impairment (17.1%), hearing impairment (14.5%), visual impairment (9.8%), renal impairment (5.7%), and neurological impairment (1.6%). The prevalence of respiratory impairment (61.2%) and mental health disorders (42.0%) was highest in low-income countries while neurological impairment was highest in lower middle-income countries (25.6%). Drug-resistant TB was associated with respiratory (58.7%), neurological (37.2%), and hearing impairments (25.0%) and mental health disorders (26.0%), respectively.

Conclusions

TB-related disabilities were frequently reported. More uniform reporting tools for TB-related disability and further research to better quantify and mitigate it are urgently needed.

Prospero registration number

CRD42019147488
Sulfur, fresh cassava root and urea independently enhanced gas production, ruminal characteristics and in vitro degradability
Authors: Sumadong Phussorn , Cherdthong Anusorn , So Sarong , Wanapat Metha
Published: September 2021

Background

Total fresh cassava root (FCR) production was 275 million tonnes in 2018 which equals 61.1 % of the total production, and Thailand produced 10.7 % FCR of the total production. FCR is one of the main energy source for ruminant. The limitation of FCR utilization is due to the presence of hydrogen cyanide (HCN). The study aimed to evaluate the effect of sulfur, urea and FCR at various levels on in vitro gas production, ruminal fermentation and in vitro degradability. The study hypothesized that: (1) sulfur, urea and FCR have no interaction effect and (2) effect of FCR and urea is related to sulfur addition.

Results

The study aimed to elucidate the optimum level of elemental sulfur, fresh cassava root (FCR) and urea and their effect on in vitro gas production, ruminal fermentation, thiocyanate concentration, and in vitro degradability. A 3 × 2 × 4 in a completely randomized design were conducted. Factor A was level of sulfur at 0 %, 1 and 2 % of concentrate dry matter (DM), factor B was level of urea at 2 and 4 % of concentrate DM, and factor C was level of the FCR at 0, 200, 300 and 400 mg DM of the total substrate. The study found that elemental sulfur, urea and FCR had no interaction effect on the kinetics of in vitro gas, ruminal fermentation, HCN and in vitro degradability. Elemental sulfur supplementation (P < 0.05) significantly increased the in vitro gas produced from an insoluble fraction (b), in vitro DM degradability and either neutral detergent fiber (NDF) or acid detergent fiber (ADF) degradability and propionate (C3) concentration while decreased the ruminal HCN concentration. Urea levels showed a (P < 0.05) significant increase of the potential extent of in vitro gas production, ruminal ammonia nitrogen (NH3-N) and total volatile fatty acid (TVFA). Fresh cassava root supplementation (P < 0.05) significantly increased the in vitro gas produced from an immediate soluble fraction (a), in vitro gas produced from insoluble fraction, in vitro gas production rate constant, total VFA, C3 concentration and HCN while decreased ruminal pH, acetate and butyrate concentration. It could be concluded that 2 % elemental sulfur, 4 % urea and 300 mg FCR showed a greater effect on in vitro gas production, ruminal fermentation and HCN reduction.

Conclusions

The study found that elemental sulfur, urea, and FCR had no interaction effect on the kinetics of in vitro gas, total in vitro gas, ruminal fermentation, and HCN concentration. It could be concluded that 2 % elemental sulfur, 4 % urea, and 300 mg FCR showed a greater effect on in vitro gas production, ruminal fermentation, and HCN reduction.
Region-wise analysis of dairy cow movements in Japan
Authors: Murato Yoshinori , Hayama Yoko , Shimizu Yumiko , Sawai Kotaro , Yamaguchi Emi , Yamamoto Takehisa
Published: September 2021

Background

Animal movement is considered the most significant factor in the transmission of infectious diseases in livestock. A better understanding of its effects would help provide a more reliable estimation of the disease spread and help develop effective control measures. If the movement pattern is heterogeneous, its characteristics should be considered in epidemiological analyses, such as when using simulation models to obtain reliable outputs. In Japan, following the bovine spongiform encephalopathy epidemic, a traceability system for cattle was established in 2003, and the registration of all cattle movements in the national database began. This study is the first to analyze cattle movements in Japan. We examined regional and seasonal heterogeneity in dairy cow movements, which accounted for most Japanese breeding cattle.

Results

In the 14 years from April 2005 to March 2018, 4,577,709 between-farm movements of dairy cows were recorded, and the number of movements was counted by month and age for both inter- and intra-regional movements. As a result, two characteristic round-trip movements were observed: one was non-seasonal and inter-regional movements related to cattle-breeding ranches in Hokkaido (the northern region of Japan), which consists of the movement of cows around ages 6 to 8 and 21 to 23 months old. In addition, the seasonal movement of heifers for summer grazing within Hokkaido occurred in May and October at the peak ages of 13 to 14 and 19 to 20 months old, respectively. The observed heterogeneity seemed to reflect the suitability of raising the Holstein breed in Hokkaido and the shortage of supply of replacement heifers and available farming areas outside Hokkaido.

Conclusions

Understanding the patterns of dairy cow movements will help develop reliable infectious disease models and be beneficial for developing effective control measures against these diseases.