bluuebunny/crossref_metadata_2025 huggingface dataset:
There is No Link Between Birth Weight and Developmental Dysplasia of the Hip
Authors: Hanratty Charlotte , Thyagarajan Balamurugan , Clarke Nicholas M. , Aarvold Alexander
Published: August 2021

Aims

Developmental Dysplasia of the Hip (DDH) has been linked to high birth weight and packaging disorders, though the evidence is limited. This has implications on screening strategies. The aim of this study was to establish whether birth weight was truly associated with the incidence of DDH.

Patients and Methods

This cohort study analysed the birth weights of all babies born at our institution over a 24 month period, between 01/01/2017 and 01/01/2019. Babies with DDH and those without DDH were compared. Babies were excluded if born before 38 weeks, had incomplete data or were a non-singleton pregnancy. Sub-analysis was performed for DDH severity (dysplastic versus subluxed/dislocated hips), breech presentation, gestational age, gender and ethnicity. Statistical analysis was performed using SPSS.

Results

There were 10,113 babies born at our institution during the selected timeframe, of which 884 were excluded for prematurity, 336 for being non-singleton and 19 for incomplete data. This left 8874 for analysis, of which 95 babies had confirmed DDH. Both the Non-DDH and DDH data sets had normal distribution (Shapiro-Wilkes, p = 0.308 and 0.629, respectively), with mean birth weights of 3477.7 g with DDH and 3492.8 g without DDH. No difference in birth weight was found (Independent T test, p = 0.789). Females had a lower birth weight than males (3293.1 g versus 3416.6 g (p < 0.001)) yet have a higher incidence of DDH (ratio 6:1 in this dataset). No significant difference was found between birth weights of females with and without DDH (p = 0.068), nor between males with and without DDH (p = 0.513). There were no significant differences in birth weights even when only displaced hips were analysed (p = 0.543), nor according to breech presentation (p = 0.8). Longer gestation babies weighed more (p < 0.00001), yet showed no increase in DDH incidence (p = 0.64).

Conclusion

This study discredits the belief that DDH may be related to higher birth weight, thus casting doubt on the link to DDH being a packaging problem in utero. This, therefore, allows future research to prioritise the investigation of alternative aetiologies.
Hue and cry for Fritillaria cirrhosa D.Don, a threatened medicinal plant in the Western Himalaya
Authors: Mathela Manisha , Kumar Amit , Sharma Monika , Goraya Gurinderjit Singh
Published: August 2021

The unique Himalayan ecosystems are repositories to the wild populations of diverse flora and fauna. The high value medicinal and aromatic plant species (MAPs) are an example of the same. Since time immemorial, these MAPs have been traditionally used by the local inhabitants and have eventually developed a high market value all over the world. Increasing market demand engenders over-extraction of species, unsustainable collection further catalyses decline in wild populations. The current communication raises high conservation concern on the rapid population decline ofFritillaria cirrhosaD.Don in the Western Himalaya. Harvested and traded with a new trade name i.e., ‘Jangli lehsun’ probably to disguise commonAlliumspecies, the species is facing tremendous decline in wild populations due to its illegal harvesting and trade in Himachal Pradesh. Further,F. cirrhosafaces threat due to unorganized, over-extraction, unsustainable and premature harvesting of the bulbs, coupled with illegal hidden markets functioning parallelly. Considering that this valuable species is under multiple threats being a medicinally important plant, priority should be given for its conservation through in-situ such as identification of medicinal plant conservation areas and ex-situ methods for its propagation and multiplication. Further, to ensure the long-term conservation ofFritillaria cirrhosa, prioritized conservation strategies such as strengthening of the Biodiversity Management Committees, capacity building through awareness programs for the key stakeholders and sustainable harvesting would be the practical solution.
Evaluating Observational Constraints on Intermodel Spread in Cloud, Temperature, and Humidity Feedbacks
Authors: He Haozhe , Kramer Ryan J. , Soden Brian J.
Published: August 2021

Uncertainty in climate feedbacks is the primary source of the spread in projected surface temperature responses to anthropogenic forcing. Cloud feedback persistently appears as the main source of disagreement in future projections while the combined lapse‐rate plus water vapor (LR + WV) feedback is a smaller (30%), but non‐trivial source of uncertainty in climate sensitivity. Here we attempt to observationally constrain the feedbacks in an effort to reduce their intermodel uncertainties. The observed interannual variation provides a useful constraint on the long‐term cloud feedback, as evidenced by the consistency of global‐mean values and regional contributions to the intermodel spread on both interannual and long‐term timescales. However, interannual variability does not serve to constrain the long‐term LR + WV feedback spread, which we find is dominated by the varying tropical relative humidity (RH) response to interhemispheric warming differences under clear‐sky conditions and the RH‐fixed LR feedback under all‐sky conditions.
Wetter Summers Mitigated Temperature Stress on Rocky Mountain Forests During the Last Interglacial Warm Period
Authors: Berkelhammer M. , Insel N. , Stefanescu I.
Published: August 2021

Recent droughts have highlighted concerns of how rising summer temperatures will increase tree mortality rates across the western United States. We analyzed subfossil wood samples from Colorado dating to the last interglacial to assess the response of two common conifers to a previous warm period. The trees experienced comparable growth rates and water use efficiency during the interglacial relative to modern despite evidence from model simulations of a 30% increase in evaporative demand during the peak of the growing season. High‐resolution isotopic analysis of the wood samples show an enrichment in the late season cellulosic O relative to modern samples, which we find was associated with increased reliance on summer rain. The data are consistent with model simulations showing the interglacial was associated with wetter summers across the western US. We propose enhanced summer rain during this period compensated for drought stress imposed by higher evaporative demand.
Seasonal Relationship Between Net Primary and Net Community Production in the Subtropical Gyres: Insights From Satellite and Argo Profiling Float Measurements
Authors: Yang Bo
Published: August 2021

The ratio between net community production (NCP) and net primary production (NPP) is a useful index of carbon export efficiency (e‐ratio). Seasonal variations of e‐ratio are poorly documented due to the lack of field measurements. In this study, the satellite‐based NPP and Argo‐Oxygen (O2) based NCP were used to determine e‐ratio in the subtropical gyres. Comparisons with long‐term field measurements at the Hawaii Ocean Time‐Series showed good agreement in annual mean and spring‐summer (April–July) e‐ratio. With the short‐term tracer (O2) the satellite‐Argo approach revealed significant seasonal variations in NCP and e‐ratio in the subtropical gyres of the North Pacific, North Atlantic, and South Pacific. The satellite‐Argo‐derived annual mean e‐ratio in all three Northern Hemisphere sites were close to those from the temperature‐based empirical model, but significantly lower in the South Pacific subtropical gyre where the sub‐annual NCP variations were stronger.
Intermodel Spread in the Impact of the Springtime Pacific Meridional Mode on Following‐Winter ENSO Tied to Simulation of the ITCZ in CMIP5/CMIP6
Authors: Zheng Yuqiong , Chen Wen , Chen Shangfeng
Published: August 2021

The Pacific meridional mode (PMM) is the leading air‐sea coupled mode over the subtropical northeastern Pacific and plays an important role in El Niño‐Southern Oscillation (ENSO) occurrence. This study examined the performances of CMIP5/CMIP6 models in simulating the PMM and its association with ENSO. CMIP6 offers improvements in capturing the spatial structure and seasonality of PMM compared to CMIP5, but still considerably underestimates the air‐sea coupling strength and coupling persistence time associated with the PMM. Additionally, large intermodel spread exists in the springtime PMM‐wintertime ENSO relationship across the CMIP models, which is attributable to bias in the simulation of ITCZ. Models with a stronger climatological ITCZ provide favorable backgrounds for PMM‐related sea surface temperature anomalies (SSTAs) to induce stronger atmospheric heating over the subtropical North Pacific. The enhanced air‐sea coupling favors PMM‐related SSTAs and atmospheric anomalies propagating southwestwards to the tropical central Pacific where they impact the following‐winter ENSO.
Comprehensive Observational Features for the Kuroshio Transport Decreasing Trend During a Recent Global Warming Hiatus
Authors: Liu Zhao‐Jun , Zhu Xiao‐Hua , Nakamura Hirohiko , Nishina Ayako , Wang Min , Zheng Hua
Published: August 2021

Linear trends in Kuroshio transport during a recent global warming hiatus (1998–2013) were evaluated using long‐term ferryboat ADCP (acoustic Doppler current profiler) data and tidal gauge data in the Tokara Strait south of Japan. The Kuroshio exhibited a remarkable weakening trend of approximately 0.05 Sv year−1 (1 Sv = 106 m3 s−1). The pycnocline in the weakened Kuroshio was relaxed and displayed shoaling at the offshore edge, which was attributed to vertical thermocline displacement rather than to water mass modification. Importantly, Kuroshio transport trends in the Tokara Strait were affected by sea surface height anomalies, which were driven by the combined effects of the clockwise baroclinic‐mode coastal trapped wave propagation along the southern coast of Japan and downstream Kuroshio advection in the East China Sea. Both features were induced by wind stress curl changes related to the global warming hiatus over the North Pacific.
Toward an Ice‐Free Mountain Range: Demise of Pyrenean Glaciers During 2011–2020
Authors: Vidaller I. , Revuelto J. , Izagirre E. , Rojas‐Heredia F. , Alonso‐González E. , Gascoin S. , René P. , Berthier E. , Rico I. , Moreno A. , Serrano E. , Serreta A. , López‐Moreno J. I.
Published: August 2021

Pyrenean glaciers are the largest in southern Europe. Their survival is threatened by climate change, highlighting the significance of their study. This research presents an assessment of changes in the glacierized area and thickness of Pyrenean glaciers from 2011 to 2020, using high‐resolution optical satellite, airborne lidar and UAV images. The total glacierized area has shrunk by 23.2% and thickness has decreased on average by 6.3 m. These two variables show no correlation for individual glaciers. Although climatic conditions do not vary much among glaciers, their evolution was heterogeneous during the study period. The smaller glaciers (<10 ha) show a higher variability in their area decrease and thickness loss whereas the four largest glaciers (>10 ha) have a more homogeneous response. This can be attributed to the generally larger influence of local topography on the response of the smaller Pyrenean glaciers. There is no sign of slowdown in glacier shrinkage respect to previous decades.
Dependence of Precipitation on Precipitable Water Vapor Over the Maritime Continent and Implications to the Madden‐Julian Oscillation
Authors: Chen Siyue , Wong Nathanael Z. , Ma Ding , Chan Pak Wah , Kuang Zhiming
Published: August 2021

The weakening of the Madden‐Julian Oscillation (MJO) as it propagates over the Maritime Continent (MC) is often referred to as the MC barrier. Here, we use 3‐hourly precipitable water vapor (PWV) data obtained from the Sumatran GPS Array and the ERA5 reanalysis to investigate the role played by the column moisture over the MC. Over Sumatra and the whole MC, we find a stronger dependence of precipitation on PWV over the ocean as compared to both inland and coastal regions. The MJO modulates the PWV over the ocean and over the MC by roughly the same amount, and the weaker precipitation variations over the MC between the MJO phases may be interpreted in terms of its weaker dependence on PWV over the MC. This different precipitation dependence on column moisture between the MC and the ocean may contribute to the MC barrier effect.
On the Stability of Talc in Subduction Zones: A Possible Control on the Maximum Depth of Decoupling Between the Subducting Plate and Mantle Wedge
Authors: Peacock Simon M. , Wang Kelin
Published: August 2021

Geophysical observations including surface heat flow data indicate the subducting slab becomes fully coupled to the overlying mantle wedge at ∼70–80 km depth. This maximum depth of decoupling (MDD) separates cool, stagnant forearc mantle from warmer, convecting mantle capable of generating arc magmas. Thermodynamic calculations demonstrate that talc is stable in H2O‐undersaturated parts of the mantle wedge where its stability is controlled by the pressure‐dependent, fluid‐absent reaction: talc + forsterite = antigorite + enstatite, which occurs at pressures ∼2–2.5 GPa (∼70–80 km depth) and temperatures <650°C. At shallower depths, H2O‐undersaturated portions of the basal mantle wedge contain talc, which experimental studies show dramatically weakens rocks. At greater depths, talc is restricted to silica‐rich portions of the mantle wedge. The common MDD in subduction zones may reflect the downdip transition from a talc‐present decoupled shear zone to a talc‐absent fully coupled interface along the base of the mantle wedge.
Longitudinal Variation in the Thermospheric Superrotation: CHAMP Observation and TIE‐GCM Simulation
Authors: Wang Hui , Lühr H. , Zhang K. D.
Published: August 2021

By means of 4 years of Challenging Minisatellite Payload (CHAMP) zonal wind observations and a Thermosphere‐Ionosphere Electrodynamics General Circulation Model simulation, longitudinal and seasonal variations of thermospheric superrotation at magnetic equator are investigated first. The superrotation shows four‐ and three‐peaked longitudinal patterns in March and September equinoxes, and a two‐peaked variation during solstices. The superrotation is stronger in December than in June solstice, and stronger in March than in September equinox. The mean correlation between the zonal variation of superrotation and nighttime eastward wind is about 0.8, while it is 0.6 with daytime westward zonal wind. The interaction between the neutral wind and geomagnetic field plays a more important role in the superrotation, rather than the F‐region electron density. The lower atmospheric tides tend to suppress the superrotation, but contribute to the longitudinal patterns of the superrotation. The viscous force is also important for the longitudinal modulation of the superrotation.
Thermospheric Traveling Atmospheric Disturbances in Austral Winter From GOCE and CHAMP
Authors: Xu Shuang , Vadas Sharon L. , Yue Jia
Published: August 2021

In this study, we analyze the thermospheric density data provided by the Gravity Field and Steady‐State Ocean Circulation Explorer during June–August 2010–2013 at ∼260 km altitude and the Challenging Minisatellite Payload during June–August 2004–2007 at ∼370 km altitude to study high latitude traveling atmospheric disturbances (TADs) in austral winter. We extract the TADs along the satellite tracks from the density for varying Kp, and linearly extrapolate the TAD distribution to Kp = 0; we call these the geomagnetic “quiet time” results here. We find that the quiet time spatial distribution of TADs depends on the spatial scale (along‐track horizontal wavelength ) and altitude. At z ∼ 260 km, TADs with  ≤ 330 km are seen mainly around and slightly downstream of the Southern Andes‐Antarctic region, while TADs with  > 800 km are distributed fairly evenly around the geographic South pole at latitudes ≥60°S. At z ∼ 370 km, TADs with  ≤ 330 km are relatively weak and are distributed fairly evenly over Antarctica, while TADs with  > 330 km make up a bipolar distribution. For the latter, the larger size lobe is centered at ∼60°S, and is located around, downstream and somewhat upstream of the Andes/Antarctic Peninsula, while the smaller lobe is located over the Antarctic continent at 90°–150°E. We also find that the TAD morphology for Kp ≥ 2 and  > 330 km depends strongly on geomagnetic activity, likely due to auroral activity, with greatly enhanced TAD amplitudes with increasing Kp.
Therapeutic targeting of both dihydroorotate dehydrogenase and nucleoside transport in MYCN-amplified neuroblastoma
Authors: Yu Yajie , Ding Jane , Zhu Shunqin , Alptekin Ahmet , Dong Zheng , Yan Chunhong , Zha Yunhong , Ding Han-Fei
Published: August 2021

Metabolic reprogramming is an integral part of the growth-promoting program driven by the MYC family of oncogenes. However, this reprogramming also imposes metabolic dependencies that could be exploited therapeutically. Here we report that the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is an attractive therapeutic target for MYCN-amplified neuroblastoma, a childhood cancer with poor prognosis. Gene expression profiling and metabolomic analysis reveal that MYCN promotes pyrimidine nucleotide production by transcriptional upregulation of DHODH and other enzymes of the pyrimidine-synthesis pathway. Genetic and pharmacological inhibition of DHODH suppresses the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines. Furthermore, we obtain evidence suggesting that serum uridine is a key factor in determining the efficacy of therapeutic agents that target DHODH. In the presence of physiological concentrations of uridine, neuroblastoma cell lines are highly resistant to DHODH inhibition. This uridine-dependent resistance to DHODH inhibitors can be abrogated by dipyridamole, an FDA-approved drug that blocks nucleoside transport. Importantly, dipyridamole synergizes with DHODH inhibition to suppress neuroblastoma growth in animal models. These findings suggest that a combination of targeting DHODH and nucleoside transport is a promising strategy to overcome intrinsic resistance to DHODH-based cancer therapeutics.
Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy
Authors: Grote Beverborg Niels , Später Daniela , Knöll Ralph , Hidalgo Alejandro , Yeh Steve T. , Elbeck Zaher , Silljé Herman H. W. , Eijgenraam Tim R. , Siga Humam , Zurek Magdalena , Palmér Malin , Pehrsson Susanne , Albery Tamsin , Bomer Nils , Hoes Martijn F. , Boogerd Cornelis J. , Frisk Michael , van Rooij Eva , Damle Sagar , Louch William E. , Wang Qing-Dong , Fritsche-Danielson Regina , Chien Kenneth R. , Hansson Kenny M. , Mullick Adam E. , de Boer Rudolf A. , van der Meer Peter
Published: August 2021

Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca2+ handling is a key feature of HF pathophysiology. Restoring the Ca2+ regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp−/−), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF.
Neighboring Pd single atoms surpass isolated single atoms for selective hydrodehalogenation catalysis
Authors: Chu Chiheng , Huang Dahong , Gupta Srishti , Weon Seunghyun , Niu Junfeng , Stavitski Eli , Muhich Christopher , Kim Jae-Hong
Published: August 2021

Single atom catalysts have been found to exhibit superior selectivity over nanoparticulate catalysts for catalytic reactions such as hydrogenation due to their single-site nature. However, improved selectively is often accompanied by loss of activity and slow kinetics. Here we demonstrate that neighboring Pd single atom catalysts retain the high selectivity merit of sparsely isolated single atom catalysts, while the cooperative interactions between neighboring atoms greatly enhance the activity for hydrogenation of carbon-halogen bonds. Experimental results and computational calculations suggest that neighboring Pd atoms work in synergy to lower the energy of key meta-stable reactions steps, i.e., initial water desorption and final hydrogenated product desorption. The placement of neighboring Pd atoms also contribute to nearly exclusive hydrogenation of carbon-chlorine bond without altering any other bonds in organohalogens. The promising hydrogenation performance achieved by neighboring single atoms sheds light on a new approach for manipulating the activity and selectivity of single atom catalysts that are increasingly studied in multiple applications.
Extreme sea levels at different global warming levels
Authors: Tebaldi Claudia , Ranasinghe Roshanka , Vousdoukas Michalis , Rasmussen D. J. , Vega-Westhoff Ben , Kirezci Ebru , Kopp Robert E. , Sriver Ryan , Mentaschi Lorenzo
Published: August 2021

The Paris agreement focused global climate mitigation policy on limiting global warming to 1.5 or 2 °C above pre-industrial levels. Consequently, projections of hazards and risk are increasingly framed in terms of global warming levels rather than emission scenarios. Here, we use a multimethod approach to describe changes in extreme sea levels driven by changes in mean sea level associated with a wide range of global warming levels, from 1.5 to 5 °C, and for a large number of locations, providing uniform coverage over most of the world’s coastlines. We estimate that by 2100 ~50% of the 7,000+ locations considered will experience the present-day 100-yr extreme-sea-level event at least once a year, even under 1.5 °C of warming, and often well before the end of the century. The tropics appear more sensitive than the Northern high latitudes, where some locations do not see this frequency change even for the highest global warming levels.
Population-based study on birth outcomes among women with hypertensive disorders of pregnancy and gestational diabetes mellitus
Authors: Lin Ya-Wen , Lin Ming-Hung , Pai Lee-Wen , Fang Jen-Wei , Mou Chih-Hsin , Sung Fung-Chang , Tzeng Ya-Ling
Published: August 2021

To evaluate birth outcomes in women with hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), we used insurance data of Taiwan to evaluate 11 adverse neonatal outcomes of infants born to women with HDP (N = 7775) and with both HDP and GDM (HDP/GDM) (N = 1946), comparing to women with neither disorder (N = 19,442), matched by age. The impacts of preeclampsia/eclampsia were also evaluated. Results showed that Caesarean section delivery was near 1.7-fold greater in the HDP/GDM and HDP groups than in comparisons. The preterm delivery rates were more than threefold greater in HDP/GDM group and HDP group than in comparisons with adjusted odds ratios (aORs) of 4.84 (95% confidence interval (CI) 4.34–5.40) and 3.92 (95% CI 3.65–4.21), respectively, followed by jaundice (aORs 2.95 (95% CI 2.63–3.33) and 1.90 (95% CI 1.76–2.06)), and small gestation age (SGA) (aORs 6.57 (95% CI 5.56–7.75) and 5.81 (95% CI 5.15–6.55)). Incidence rates of birth trauma, patent ductus arteriosus, atrial septal defect, respiratory distress syndrome, and neonatal hypoglycemia were also higher in the HDP/GDM and HDP groups than in the comparison group. Most adverse outcomes increased further in women with preeclampsia or eclampsia. In conclusion, women with HDP are at elevated risks of adverse neonatal outcomes. Risks of most adverse outcomes increase further for women with both HDP and GDM. Preeclampsia or eclampsia may also contribute to these outcomes to higher risk levels. Every pregnant woman with these conditions deserves specialized prenatal care.
RETRACTED ARTICLE: Day-ahead electricity price forecasting using WPT, VMI, LSSVM-based self adaptive fuzzy kernel and modified HBMO algorithm
Authors: Syah Rahmad , Rezaei Mohammad , Elveny Marischa , Majidi Nezhad Meysam , Ramdan Dadan , Nesaht Mehdi , Davarpanah Afshin
Published: August 2021

Due to focal liberality in electricity market projection, researchers try to suggest powerful and successful price forecasting algorithms. Since, the accurate information of future makes best way for market participants so as to increases their profit using bidding strategies, here suggests an algorithm for electricity price anticipation. To cover this goal, separate an algorithm into three steps, namely; pre-processing, learning and tuning. The pre-processing part consists of Wavelet Packet Transform (WPT) to analyze price signal to high and low frequency subseries and Variational Mutual Information (VMI) to select valuable input data in order to helps the learning part and decreases the computation burden. Owing to the learning part, a new Least squares support vector machine based self-adaptive fuzzy kernel (LSSVM-SFK) is proposed to extract best map pattern from input data. A new modified HBMO is introduced to optimally set LSSVM-SFK variables such as bias, weight, etc. To improve the performances of HBMO, two modifications are proposed that has high stability in HBMO. Suggested forecasting algorithm is examined on electricity markets that has acceptable efficiency than other models.
Bioclimatic and anthropogenic variables shape the occurrence of Batrachochytrium dendrobatidis over a large latitudinal gradient
Authors: Alvarado-Rybak Mario , Lepe-Lopez Manuel , Peñafiel-Ricaurte Alexandra , Valenzuela-Sánchez Andrés , Valdivia Catalina , Mardones Fernando O. , Bacigalupe Leonardo D. , Puschendorf Robert , Cunningham Andrew A. , Azat Claudio
Published: August 2021

Amphibian chytridiomycosis, caused by the fungusBatrachochytrium dendrobatidis(Bd), has caused the greatest known loss of biodiversity due to an infectious disease. We usedBdinfection data from quantitative real-time PCR (qPCR) assays of amphibian skin swabs collected across Chile during 2008–2018 to modelBdoccurrence with the aim to determine bioclimatic and anthropogenic variables associated withBdinfection. Also, we usedBdpresence/absence records to identify geographicalBdhigh-risk areas and compareBdprevalence and infection loads between amphibian families, ecoregions, and host ecology. Data comprised 4155Bd-specific qPCR assays from 162 locations across a latitudinal gradient of 3700 km (18º to 51ºS). Results showed a significant clustering ofBdassociated with urban centres and anthropogenically highly disturbed ecosystems in central-south Chile. BothBdprevalence andBdinfection loads were higher in aquatic than terrestrial amphibian species. Our model indicated positive associations ofBdprevalence with altitude, temperature, precipitation and human-modified landscapes. Also, we found that macroscale drivers, such as land use change and climate, shape the occurrence ofBdat the landscape level. Our study provides with new evidence that can improve the effectiveness of strategies to mitigate biodiversity loss due to amphibian chytridiomycosis.
AEG-1 silencing attenuates M2-polarization of glioma-associated microglia/macrophages and sensitizes glioma cells to temozolomide
Authors: Li Jing , Sun Yuchen , Sun Xuanzi , Zhao Xu , Ma Yuan , Wang Yuzhu , Zhang Xiaozhi
Published: August 2021

Glioma is the most frequent primary malignancy in the brain; temozolomide (TMZ) is the first-line chemotherapeutic agent used to combat this tumor. We showed here that astrocyte elevated gene-1 (AEG-1) was overexpressed in glioma tissues and associated with a worse subtype and a poor prognosis. CCK-8 proliferation assays and clone formation experiments presented that AEG-1 knockdown sensitizes glioma cells to TMZ. The γH2AX foci formation assays indicated that AEG-1 silencing promotes TMZ-induced DNA damage in glioma cells. Glioma-associated microglia/macrophages (GAMs), the largest subpopulation infiltrating glioma, play important roles in the tumor microenvironment. Bioinformatics analyses and functional studies demonstrated that AEG-1 silencing decreased M2-polarization of HMC3 microglia and the secretion of tumor supportive cytokines IL-6 and TGF-β1. The expression of AEG-1 was positively associated with M2 markers in glioma tissues varified by IHC staining. Based on the results of Affymetrix microarray and GSEA analyses, Western blot and Co-Immunoprecipitation assays were conducted to show that AEG-1 activates Wnt/β-catenin signaling by directly interacting with GSK-3β. The co-localization of AEG-1 and GSK-3β in the cytoplasm of glioma cells was detected through immunofluorescence staining. This study raises the possibility that targeting AEG-1 might improve the efficiency of chemotherapy and reduce immunosuppressive M2 GAMs in glioma.
Variability of high-sensitivity cardiac troponin T and I in asymptomatic patients receiving hemodialysis
Authors: Wongcharoen Wanwarang , Chombandit Teetad , Phrommintikul Arintaya , Noppakun Kajohnsak
Published: August 2021

Variation of high-sensitivity cardiac troponin I and T (hs-cTn) during hemodialysis has been observed. Observational studies demonstrated the increased incidence of adverse cardiovascular events after long compared to short interdialytic intervals. Therefore, we aimed to compare variation of hs-cTnI and hs-cTnT before and after hemodialysis and between short and long interdialytic intervals. We enrolled 200 asymptomatic patients receiving regular hemodialysis. The hs-cTnI and hs-cTnT levels were measured before and after hemodialysis on the day after short and long interdialytic intervals. Mean age was 62.3 ± 14.8 years (Male 55.5%). Prevalence of increased hs-cTnI and hs-cTnT was 34.5% and 99.0%, respectively. The median ± interquartile range of hs-cTnT increased significantly after hemodialysis during short and long interdialytic intervals. However, hs-cTnI level did not increase after hemodialysis during short and long intervals. We found that levels of hs-cTnI and T did not differ between short interdialytic and long interdialytic intervals. We demonstrated higher prevalence of elevated hs-cTnT in patients with regular hemodialysis compared to hs-cTnI. The rise of hs-cTnT was observed immediately after hemodialysis but no significant change of hs-cTnI was noted. Accordingly, hs-cTnI may be preferable as a diagnostic marker in patients with suspected acute myocardial infarction than hs-cTnT.
Temporal analysis shows relaxed genetic erosion following improved stocking practices in a subarctic transnational brown trout population
Authors: Klütsch Cornelya F. C. , Maduna Simo N. , Polikarpova Natalia , Forfang Kristin , Beddari Benedicte , Gjelland Karl Øystein , Aspholm Paul Eric , Amundsen Per-Arne , Hagen Snorre B.
Published: August 2021

Maintaining standing genetic variation is a challenge in human-dominated landscapes. We used genetic (i.e., 16 short tandem repeats) and morphological (i.e., length and weight) measurements of 593 contemporary and historical brown trout (Salmo trutta) samples to study fine-scale and short-term impacts of different management practices. These had changed from traditional breeding practices, using the same broodstock for several years, to modern breeding practices, including annual broodstock replacement, in the transnational subarctic Pasvik River. Using population genetic structure analyses (i.e., Bayesian assignment tests, DAPCs, and PCAs), four historical genetic clusters (E2001A-D), likely representing family lineages resulting from different crosses, were found in zone E. These groups were characterized by consistently lower genetic diversity, higher within-group relatedness, lower effective population size, and significantly smaller body size than contemporary stocked (E2001E) and wild fish (E2001F). However, even current breeding practices are insufficient to prevent genetic diversity loss and morphological changes as demonstrated by on average smaller body sizes and recent genetic bottleneck signatures in the modern breeding stock compared to wild fish. Conservation management must evaluate breeding protocols for stocking programs and assess if these can preserve remaining natural genetic diversity and morphology in brown trout for long-term preservation of freshwater fauna.
Protocatechuic acid attenuates isoproterenol-induced cardiac hypertrophy via downregulation of ROCK1–Sp1–PKCγ axis
Authors: Bai Liyan , Kee Hae Jin , Han Xiongyi , Zhao Tingwei , Kee Seung-Jung , Jeong Myung Ho
Published: August 2021

Cardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (Nppa, Nppb, and Myh7), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKCγ both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKCγ decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKCγ increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKCγ expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1/Sp1/PKCγ axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.
Tumor location and type affect local recurrence and joint damage in tenosynovial giant cell tumor: a multi-center study
Authors: Ota Takehiro , Nishida Yoshihiro , Ikuta Kunihiro , Tsukushi Satoshi , Yamada Kenji , Kozawa Eiji , Urakawa Hiroshi , Imagama Shiro
Published: August 2021

Osteochondral destruction and a high recurrence rate after surgery are major concerns that make difficult the treatment course of tenosynovial giant cell tumor. The aims of this study were to elucidate rates of postoperative local recurrence and osteochondral destruction, as correlated with various demographic factors. Eighty surgically treated patients with intra-articular tumors (knee: 49, ankle and foot: 12, hip: 10, others: 9) were included in this study. Factors including age, disease type (diffuse/localized), location, existence of osteochondral destruction were correlated with local recurrence or development/progression of osteochondral destruction. The 5-year local recurrence free survival rate was 71.4%. Diffuse type (n = 59, localized: n = 21) (P = 0.023) and knee location (P = 0.002) were independent risk factors for local recurrence. Diffuse type (P = 0.009) was a significant risk factor, and knee location (P = 0.001) was a negative factor for osteochondral destruction at the initial examination. Progression of osteochondral destruction was observed more often in cases with local recurrence (P = 0.040) and findings of osteochondral destruction at the initial examination (P = 0.029). Diffuse type is a factor that should be noted for both local recurrence and osteochondral destruction, while local recurrence occurs but osteochondral destruction is less observed in the knee.
Spatiotemporal effects on dung beetle activities in island forests-home garden matrix in a tropical village landscape
Authors: Asha G. , Manoj K. , Megha P. P. , Sinu Palatty Allesh
Published: August 2021

Insects in seasonal tropics experience a wide range of temperatures along seasons, habitats, and a day. Therefore, the thermal tolerance of the insects can be a major driver for their habitat preference, temporal patterns of activity, and formation of communities. We examined the dung beetle communities of eleven pairs of neighboring open (home gardens) and closed habitats (sacred groves) during dry and wet seasons and diel periods (day and night) to understand the dung beetle activities along a spatiotemporal gradient constituted by the sacred groves—home garden matrix on a tropical village landscape. We tested the following hypotheses: (i) closed habitats have greater activities of dung beetles over open habitats; (ii) the diurnal communities of dung beetles are different from the nocturnal communities; and (iii) the diurnal-nocturnal activities of dung beetles could be predicted by the habitat and season. We considered abundance, richness, total biomass, and Shannon diversity of overall beetles, abundance of different functional groups, and species composition in communities as the quantitative measures in the predictive statistical models. In total, 2727 dung beetles belonging to 38 species, ten genera, and three functional groups were collected. The open habitat supported more number of dung beetles (N = 2318) than the closed habitat (N = 409). The diurnal communities were different from nocturnal communities, particularly in open habitat, where the temperature was different between day and night. The dominant species of the diurnal communities of open habitat hardly used the closed habitat in any context including dry–wet seasons, but the nocturnal communities of the open habitat were closer to the communities of closed habitat. The diel period and habitat predicted the abundance activity of functional groups; season was a poor predictor of dung beetle activities. Given that the species composition has turned over across habitats, and the closed habitat supported remarkably lesser number of beetles than the open habitats, the closed habitat is unlikely to be a thermal refuge for the open habitat species in village landscapes that have island forests, such as sacred groves, and home gardens form a matrix.
Partitioning of gene expression among zebrafish photoreceptor subtypes
Authors: Ogawa Yohey , Corbo Joseph C.
Published: August 2021

Vertebrate photoreceptors are categorized into two broad classes, rods and cones, responsible for dim- and bright-light vision, respectively. While many molecular features that distinguish rods and cones are known, gene expression differences among cone subtypes remain poorly understood. Teleost fishes are renowned for the diversity of their photoreceptor systems. Here, we used single-cell RNA-seq to profile adult photoreceptors in zebrafish, a teleost. We found that in addition to the four canonical zebrafish cone types, there exist subpopulations of green and red cones (previously shown to be located in the ventral retina) that express red-shifted opsin paralogs (opn1mw4 or opn1lw1) as well as a unique combination of cone phototransduction genes. Furthermore, the expression of many paralogous phototransduction genes is partitioned among cone subtypes, analogous to the partitioning of the phototransduction paralogs between rods and cones seen across vertebrates. The partitioned cone-gene pairs arose via the teleost-specific whole-genome duplication or later clade-specific gene duplications. We also discovered that cone subtypes express distinct transcriptional regulators, including many factors not previously implicated in photoreceptor development or differentiation. Overall, our work suggests that partitioning of paralogous gene expression via the action of differentially expressed transcriptional regulators enables diversification of cone subtypes in teleosts.
Genomic comparisons and phylogenetic analysis of mastitis-related staphylococci with a focus on adhesion, biofilm, and related regulatory genes
Authors: Pizauro Lucas José Luduverio , de Almeida Camila Chioda , Silva Saura Rodrigues , MacInnes Janet I. , Kropinski Andrew M. , Zafalon Luiz Francisco , de Avila Fernando Antônio , de Mello Varani Alessandro
Published: August 2021

Mastitis is a common and costly disease on dairy farms, commonly caused by Staphylococcus spp. though the various species are associated with different clinical outcomes. In the current study, we performed genomic analyses to determine the prevalence of adhesion, biofilm, and related regulatory genes in 478 staphylococcal species isolated from clinical and subclinical mastitis cases deposited in public databases. The most prevalent adhesin genes (ebpS, atl, pls, sasH and sasF) were found in both clinical and subclinical isolates. However, the ebpS gene was absent in subclinical isolates of Staphylococcus arlettae, S. succinus, S. sciuri, S. equorun, S. galinarum, and S. saprophyticus. In contrast, the coa, eap, emp, efb, and vWbp genes were present more frequently in clinical (vs. subclincal) mastitis isolates and were highly correlated with the presence of the biofim operon (icaABCD) and its transcriptional regulator, icaR. Co-phylogenetic analyses suggested that many of these adhesins, biofilm, and associated regulatory genes could have been horizontally disseminated between clinical and subclinical isolates. Our results further suggest that several adhesins, biofilm, and related regulatory genes, which have been overlooked in previous studies, may be of use for virulence profiling of mastitis-related Staphylococcus strains or as potential targets for vaccine development.
Deep learning from HE slides predicts the clinical benefit from adjuvant chemotherapy in hormone receptor-positive breast cancer patients
Authors: Cho Soo Youn , Lee Jeong Hoon , Ryu Jai Min , Lee Jeong Eon , Cho Eun Yoon , Ahn Chang Ho , Paeng Kyunghyun , Yoo Inwan , Ock Chan-Young , Song Sang Yong
Published: August 2021

We hypothesized that a deep-learning algorithm using HE images might be capable of predicting the benefits of adjuvant chemotherapy in cancer patients. HE slides were retrospectively collected from 1343 de-identified breast cancer patients at the Samsung Medical Center and used to develop the Lunit SCOPE algorithm. Lunit SCOPE was trained to predict the recurrence using the 21-gene assay (Oncotype DX) and histological parameters. The risk prediction model predicted the Oncotype DX score > 25 and the recurrence survival of the prognosis validation cohort and TCGA cohorts. The most important predictive variable was the mitotic cells in the cancer epithelium. Of the 363 patients who did not receive adjuvant therapy, 104 predicted high risk had a significantly lower survival rate. The top-300 genes highly correlated with the predicted risk were enriched for cell cycle, nuclear division, and cell division. From the Oncotype DX genes, the predicted risk was positively correlated with proliferation-associated genes and negatively correlated with prognostic genes from the estrogen category. An integrative analysis using Lunit SCOPE predicted the risk of cancer recurrence and the early-stage hormone receptor-positive breast cancer patients who would benefit from adjuvant chemotherapy.
Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems
Authors: Wouters Kristiaan , Cento Alessia S. , Gaens Katrien H. , Teunissen Margee , Scheijen Jean L. J. M. , Barutta Federica , Chiazza Fausto , Collotta Debora , Aragno Manuela , Gruden Gabriella , Collino Massimo , Schalkwijk Casper G. , Mastrocola Raffaella
Published: August 2021

Advanced glycation endproducts (AGEs) are involved in several diseases, including NAFLD and NASH. RAGE is the main receptor mediating the pro-inflammatory signalling induced by AGEs. Therefore, targeting of RAGE has been proposed for prevention of chronic inflammatory diseases. However, the role of RAGE in the development of NAFLD and NASH remains poorly understood. We thus aimed to analyse the effect of obesity on AGEs accumulation, AGE-receptors and AGE-detoxification, and whether the absence of RAGE might improve hepatosteatosis and inflammation, by comparing the liver of lean control, obese (LeptrDb−/−) and obese RAGE-deficient (RAGE−/− LeptrDb−/−) mice. Obesity induced AGEs accumulation and RAGE expression with hepatosteatosis and inflammation in LeptrDb−/−, compared to lean controls. Despite the genetic deletion of RAGE in the LeptrDb−/− mice, high levels of intrahepatic AGEs were maintained accompanied by decreased expression of the protective AGE-receptor-1, impaired AGE-detoxifying system glyoxalase-1, and increased expression of the alternative AGE-receptor galectin-3. We also found sustained hepatosteatosis and inflammation as determined by persistent activation of the lipogenic SREBP1c and proinflammatory NLRP3 signalling pathways. Thus, RAGE targeting is not effective in the prevention of NAFLD in conditions of obesity, likely due to the direct liver specific crosstalk of RAGE with other AGE-receptors and AGE-detoxifying systems.
A genetic screen for Drosophila social isolation mutants and analysis of sex pistol
Authors: Eddison Mark
Published: August 2021

Prolonged periods of forced social isolation is detrimental to well-being, yet we know little about which genes regulate susceptibility to its effects. In the fruit fly,Drosophila melanogaster,social isolation induces stark changes in behavior including increased aggression, locomotor activity, and resistance to ethanol sedation. To identify genes regulating sensitivity to isolation, I screened a collection of sixteen hundred P-element insertion lines for mutants with abnormal levels of all three isolation-induced behaviors. The screen identified three mutants whose affected genes are likely central to regulating the effects of isolation in flies. One mutant,sex pistol(sxp), became extremely aggressive and resistant to ethanol sedation when socially isolated.sxpalso had a high level of male–male courtship. The mutation insxpreduced the expression of two minor isoforms of the actin regulatorhts(adducin),as well as mildly reducing expression ofCalpA, a calcium-dependent protease. As a consequence, sxpalso had increased expression of the insulin-like peptide,dILP5. Analysis of the social behavior ofsxpsuggests that these minorhtsisoforms function to limit isolation-induced aggression, while chronically high levels ofdILP5increase male–male courtship.