bluuebunny/crossref_metadata_2025 huggingface dataset:
A transcriptome-wide association study identifies susceptibility genes for Parkinson’s disease
Authors: Yao Shi , Zhang Xi , Zou Shu-Cheng , Zhu Yong , Li Bo , Kuang Wei-Ping , Guo Yan , Li Xiao-Song , Li Liang , Wang Xiao-Ye
Published: September 2021

Genome-wide association study (GWAS) has seen great strides in revealing initial insights into the genetic architecture of Parkinson’s disease (PD). Since GWAS signals often reside in non-coding regions, relatively few of the associations have implicated specific biological mechanisms. Here, we aimed to integrate the GWAS results with large-scale expression quantitative trait loci (eQTL) in 13 brain tissues to identify candidate causal genes for PD. We conducted a transcriptome-wide association study (TWAS) for PD using the summary statistics of over 480,000 individuals from the most recent PD GWAS. We identified 18 genes significantly associated with PD after Bonferroni corrections. The most significant gene, LRRC37A2, was associated with PD in all 13 brain tissues, such as in the hypothalamus (P = 6.12 × 10−22) and nucleus accumbens basal ganglia (P = 5.62 × 10−21). We also identified eight conditionally independent genes, including four new genes at known PD loci: CD38, LRRC37A2, RNF40, and ZSWIM7. Through conditional analyses, we demonstrated that several of the GWAS significant signals on PD could be driven by genetically regulated gene expression. The most significant TWAS gene LRRC37A2 accounts for 0.855 of the GWAS signal at its loci, and ZSWIM7 accounts for all the GWAS signals at its loci. We further identified several phenotypes previously associated with PD by querying the single nucleotide polymorphisms (SNPs) in the final model of the identified genes in phenome databases. In conclusion, we prioritized genes that are likely to affect PD by using a TWAS approach and identified phenotypes associated with PD.
3D integration and measurement of a semiconductor double quantum dot with a high-impedance TiN resonator
Authors: Holman Nathan , Rosenberg D. , Yost D. , Yoder J. L. , Das R. , Oliver William D. , McDermott R. , Eriksson M. A.
Published: September 2021

One major challenge to scaling quantum dot qubits is the dense wiring requirements, making it difficult to envision fabricating large 2D arrays of nearest-neighbor-coupled qubits necessary for error correction. We describe a method to ameliorate this issue by spacing out the qubits using superconducting resonators facilitated by 3D integration. To prove the viability of this approach, we use integration to couple an off-chip high-impedance TiN resonator to a double quantum dot in a Si/SiGe heterostructure. Using the resonator as a dispersive gate sensor, we tune the device down to the single electron regime with an SNR = 5.36. Characterizing the individual systems shows 3D integration can be done while maintaining low-charge noise for the quantum dots and high-quality factors for the superconducting resonator (single photon QL = 2.14 × 104 with Qi ≈ 3 × 105), necessary for readout and high-fidelity two-qubit gates.
Comparative effects of alive and pasteurized Akkermansia muciniphila on normal diet-fed mice
Authors: Ashrafian Fatemeh , Keshavarz Azizi Raftar Shahrbanoo , Shahryari Arefeh , Behrouzi Ava , Yaghoubfar Rezvan , Lari Arezou , Moradi Hamid Reza , Khatami Shohreh , Omrani Mir Davood , Vaziri Farzam , Masotti Andrea , Siadat Seyed Davar
Published: September 2021

Recently, Akkermansia muciniphila an anaerobic member of the gut microbiota, has been proposed as a next-generation probiotic. The aim of this study was evaluation of the effect of alive and pasteurized A. muciniphila on health status, intestinal integrity, immune response, lipid metabolism, and gut microbial composition in normal-diet fed mice as well as direct effects of the bacterium on Caco-2 cell line. A total of 30 mice were distributed into three different groups, control, alive, and pasteurized A. muciniphila-treated group. After acclimation, control and treatment groups were administrated with PBS and 109 CFU/200µL of bacterial suspension for 5 weeks, respectively. Besides, Caco-2 separately exposed to alive, pasteurized A. muciniphila and PBS for 24 h. The results showed that administration of A. muciniphila leads to reduction in body, liver, and white adipose weight. Histology data revealed both treatments had no adverse effects in colon, liver, and adipose tissues as well as induced better gut structure. Moreover, biochemical parameters and inflammatory biomarkers in plasma demonstrated that pasteurized A. muciniphila had more pronounce effect. Furthermore, alive A. muciniphia had better effects on the modulation of gene expression related to fatty acid synthesis, energy homeostasis, and immune response in the liver; meanwhile, these effects in the adipose was more in the pasteurized A. muciniphila administration. More importantly, the improvement of gut health by enhancing strengthen intestinal integrity and maintaining immune homeostasis was seen in both treatments; notably, pasteurized A. muciniphila had more effective. Similarly, treatment with the pasteurized form more effectively upregulated tight junction and regulated immune response-related genes in Caco-2 cell line. Both treatments triggered the improvement of microbiota communities, particularly the alive form. Therefore, both forms of A. muciniphila could modulate lipid and immune homeostasis, improved some gut microbiota, and promoted the overall health, while all these effects were dominantly observed in pasteurized form. In conclusion, pasteurized A. muciniphila can be considered as new medical supplement to maintain health state and prevent diseases in normal mice through different mechanisms.
Hypersensitivity in teeth affected by molar-incisor hypomineralization (MIH)
Authors: Linner Thomas , Khazaei Yeganeh , Bücher Katharina , Pfisterer Jan , Hickel Reinhard , Kühnisch Jan
Published: September 2021

Tooth hypersensitivity is a common symptom in patients with molar-incisor hypomineralization (MIH). Therefore, this clinical study aimed to assess potential associations between patient- and tooth-related variables and the intensity of hypersensitivity in MIH-affected permanent teeth compared to healthy controls. Fifty-seven MIH patients and 20 healthy adolescents with a total of 350 MIH-affected and 193 healthy teeth were included in this study. The intensity of hypersensitivity was measured after cold air stimulation using the Schiff Cold Air Sensitivity Scale (SCASS) by the dentist and visual analogue scale (VAS) by the patient. Tooth hypersensitivity was low in non-MIH teeth (97.9% of the group had zero SCASS and VAS values). In contrast, MIH-affected teeth with demarcated opacities and atypical restorations had moderate SCASS and VAS values, whereas teeth with enamel breakdown were mostly linked to severe hypersensitivity. The logistic regression model confirmed a significantly lower level of hypersensitivity in MIH patients aged ≥ 8 years (OR 0.06, 95% CI 0.01–0.50, p = 0.009) and higher levels in molar teeth (OR 5.49, 95% CI 1.42–21.27, p = 0.014) and teeth with enamel disintegration (OR 4.61, 95% CI 1.68–12.63, p = 0.003). These results indicate that MIH-related tooth hypersensitivity seems to be present in disintegrated molars immediately after tooth eruption.
Endomicroscopy of the human cochlea using a micro-optical coherence tomography catheter
Authors: Iyer Janani S. , Yin Biwei , Stankovic Konstantina M. , Tearney Guillermo J.
Published: September 2021

Sensorineural hearing loss (SNHL) is one of the most profound public health concerns of the modern era, affecting 466 million people today, and projected to affect 900 million by the year 2050. Advances in both diagnostics and therapeutics for SNHL have been impeded by the human cochlea’s inaccessibility for in vivo imaging, resulting from its extremely small size, convoluted coiled configuration, fragility, and deep encasement in dense bone. Here, we develop and demonstrate the ability of a sub-millimeter-diameter, flexible endoscopic probe interfaced with a micro-optical coherence tomography (μOCT) imaging system to enable micron-scale imaging of the inner ear’s sensory epithelium in cadaveric human inner ears.
Numerical modelling and experimental verification of thermal effects in living cells exposed to high-power pulses of THz radiation
Authors: Sitnikov D. S. , Pronkin A. A. , Ilina I. V. , Revkova V. A. , Konoplyannikov M. A. , Kalsin V. A. , Baklaushev V. P.
Published: September 2021

Exposure of cells or biological tissues to high-power pulses of terahertz (THz) radiation leads to changes in a variety of intracellular processes. However, the role of heating effects due to strong absorption of THz radiation by water molecules still stays unclear. In this study, we performed numerical modelling in order to estimate the thermal impact on water of a single THz pulse as well as a series of THz pulses. A finite-element (FE) model that provides numerical solutions for the heat conduction equation is employed to compute the temperature increase. A simple expression for temperature estimation in the center of the spot of THz radiation is presented for given frequency and fluence of the THz pulse. It has been demonstrated that thermal effect is determined by either the average power of radiation or by the fluence of a single THz pulse depending on pulse repetition rate. Human dermal fibroblasts have been exposed to THz pulses (with an energy of $$15\,\upmu \hbox {J}$$

15

μ
J

and repetition rate of 100 Hz) to estimate the thermal effect. Analysis of heat shock proteins expression has demonstrated no statistically significant difference ($$p < 0.05$$

p
<
0.05

) between control and experimental groups after 3 h of irradiation.
A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles
Authors: Gimenez Alba Marina , Salman Ahmed M. , Marques Rodolfo F. , López-Camacho César , Harrison Kate , Kim Young Chan , Janse Chris J. , Soares Irene S. , Reyes-Sandoval Arturo
Published: September 2021

Malaria is a highly prevalent parasitic disease in regions with tropical and subtropical climates worldwide. Among the species of Plasmodium causing human malaria, P. vivax is the second most prevalent and the most geographically widespread species. A major target of a pre-erythrocytic vaccine is the P. vivax circumsporozoite protein (PvCSP). In previous studies, we fused two recombinant proteins representing three allelic variants of PvCSP (VK210, VK247 and P. vivax-like) to the mumps virus nucleocapsid protein to enhance immune responses against PvCSP. The objective of the present study was to evaluate the protective efficacy of these recombinants in mice challenged with transgenic P. berghei parasites expressing PvCSP allelic variants. Formulations containing Poly (I:C) or Montanide ISA720 as adjuvants elicited high and long-lasting IgG antibody titers specific to each PvCSP allelic variant. Immunized mice were challenged with two existing chimeric P. berghei parasite lines expressing PvCSP-VK210 and PvCSP-VK247. We also developed a novel chimeric line expressing the third allelic variant, PvCSP-P. vivax-like, as a new murine immunization-challenge model. Our formulations conferred partial protection (significant delay in the time to reach 1% parasitemia) against challenge with the three chimeric parasites. Our results provide insights into the development of a vaccine targeting multiple strains of P. vivax.
Monitoring the response of volcanic CO2 emissions to changes in the Los Humeros hydrothermal system
Authors: Jentsch Anna , Duesing Walter , Jolie Egbert , Zimmer Martin
Published: September 2021

Carbon dioxide is the most abundant, non-condensable gas in volcanic systems, released into the atmosphere through either diffuse or advective fluid flow. The emission of substantial amounts of CO2at Earth’s surface is not only controlled by volcanic plumes during periods of eruptive activity or fumaroles, but also by soil degassing along permeable structures in the subsurface. Monitoring of these processes is of utmost importance for volcanic hazard analyses, and is also relevant for managing geothermal resources. Fluid-bearing faults are key elements of economic value for geothermal power generation. Here, we describe for the first time how sensitively and quickly natural gas emissions react to changes within a deep hydrothermal system due to geothermal fluid reinjection. For this purpose, we deployed an automated, multi-chamber CO2flux monitoring system within the damage zone of a deep-rooted major normal fault in the Los Humeros Volcanic Complex (LHVC) in Mexico and recorded data over a period of five months. After removing the atmospheric effects on variations in CO2flux, we calculated correlation coefficients between residual CO2emissions and reinjection rates, identifying an inverse correlation of ρ = − 0.51 to − 0.66. Our results indicate that gas emissions respond to changes in reinjection rates within 24 h, proving an active hydraulic communication between the hydrothermal system and Earth’s surface. This finding is a promising indication not only for geothermal reservoir monitoring but also for advanced long-term volcanic risk analysis. Response times allow for estimation of fluid migration velocities, which is a key constraint for conceptual and numerical modelling of fluid flow in fracture-dominated systems.
Anthraquinolone and quinolizine derivatives as an alley of future treatment for COVID-19: an in silico machine learning hypothesis
Authors: Samarth Nikhil , Kabra Ritika , Singh Shailza
Published: September 2021

Coronavirus disease 2019 (Covid-19), caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has come to the fore in Wuhan, China in December 2019 and has been spreading expeditiously all over the world due to its high transmissibility and pathogenicity. From the outbreak of COVID-19, many efforts are being made to find a way to fight this pandemic. More than 300 clinical trials are ongoing to investigate the potential therapeutic option for preventing/treating COVID-19. Considering the critical role of SARS-CoV-2 main protease (Mpro) in pathogenesis being primarily involved in polyprotein processing and virus maturation, it makes SARS-CoV-2 main protease (Mpro) as an attractive and promising antiviral target. Thus, in our study, we focused on SARS-CoV-2 main protease (Mpro), used machine learning algorithms and virtually screened small derivatives of anthraquinolone and quinolizine from PubChem that may act as potential inhibitor. Prioritisation of cavity atoms obtained through pharmacophore mapping and other physicochemical descriptors of the derivatives helped mapped important chemical features for ligand binding interaction and also for synergistic studies with molecular docking. Subsequently, these studies outcome were supported through simulation trajectories that further proved anthraquinolone and quinolizine derivatives as potential small molecules to be tested experimentally in treating COVID-19 patients.
El Niño Modoki can be mostly predicted more than 10 years ahead of time
Authors: Liang X. San , Xu Fen , Rong Yineng , Zhang Renhe , Tang Xu , Zhang Feng
Published: September 2021

The 2014–2015 “Monster”/“Super” El Niño failed to be predicted one year earlier due to the growing importance of a new type of El Niño, El Niño Modoki, which reportedly has much lower forecast skill with the classical models. In this study, we show that, so far as of today, this new El Niño actually can be mostly predicted at a lead time of more than 10 years. This is achieved through tracing the predictability source with an information flow-based causality analysis, which has been rigorously established from first principles during the past 16 years (e.g., Liang in Phys Rev E 94:052201, 2016). We show that the information flowing from the solar activity 45 years ago to the sea surface temperature results in a causal structure resembling the El Niño Modoki mode. Based on this, a multidimensional system is constructed out of the sunspot number series with time delays of 22–50 years. The first 25 principal components are then taken as the predictors to fulfill the prediction, which through causal AI based on the Liang–Kleeman information flow reproduces rather accurately the events thus far 12 years in advance.
Refrigeration of eggs influences the virulence of Salmonella Typhimurium
Authors: Khan Samiullah , McWhorter Andrea R. , Moyle Talia S. , Chousalkar Kapil K.
Published: September 2021

Salmonella Typhimurium is a human pathogen associated with eggs and egg-derived products. In Australia, it is recommended that eggs should be refrigerated to prevent condensation that can enhance bacterial penetration across the eggshell. Except for the United States, the guidelines on egg refrigeration are not prescriptive. In the current study, in-vitro and in-vivo experiments were conducted to understand the role of egg storage temperatures (refrigerated vs ambient) on bacterial load and the virulence genes expression of Salmonella Typhimurium. The in-vitro egg study showed that the load of Salmonella Typhimurium significantly increased in yolk and albumen stored at 25 °C. The gene expression study showed that ompR, misL, pefA, spvA, shdA, bapA, and csgB were significantly up-regulated in the egg yolk stored at 5 °C and 25 °C for 96 h; however, an in-vivo study revealed that mice infected with egg yolk stored at 25 °C, developed salmonellosis from day 3 post-infection (p.i.). Mice fed with inoculated egg yolk, albumen, or eggshell wash stored at refrigerated temperature did not show signs of salmonellosis during the period of the experiment. Data obtained in this study highlighted the importance of egg refrigeration in terms of improving product safety.
Experimental estimation of the longitudinal component of a highly focused electromagnetic field
Authors: Maluenda David , Aviñoá Marcos , Ahmadi Kavan , Martínez-Herrero Rosario , Carnicer Artur
Published: September 2021

The detection of the longitudinal component of a highly focused electromagnetic beam is not a simple task. Although in recent years several methods have been reported in the literature, this measure is still not routinely performed. This paper describes a method that allows us to estimate and visualize the longitudinal component of the field in a relatively simple way. First, we measure the transverse components of the focused field in several planes normal to the optical axis. Then, we determine the complex amplitude of the two transverse field components: the phase is obtained using a phase recovery algorithm, while the phase difference between the two components is determined from the Stokes parameters. Finally, the longitudinal component is estimated using the Gauss’s theorem. Experimental results show an excellent agreement with theoretical predictions.
Prognostic prediction by hypermetabolism varies depending on the nutritional status in early amyotrophic lateral sclerosis
Authors: Nakamura Ryutaro , Kurihara Mika , Ogawa Nobuhiro , Kitamura Akihiro , Yamakawa Isamu , Bamba Shigeki , Sanada Mitsuru , Sasaki Masaya , Urushitani Makoto
Published: September 2021

To examine whether hypermetabolism could predict the prognosis of early amyotrophic lateral sclerosis (ALS) patients with differing nutritional profiles. This single-center, retrospective study examined the prognosis of ALS patients with hypermetabolism in relation to their nutritional status at hospitalization. The metabolic state was estimated by the ratio of measured resting energy expenditure (mREE) to lean soft tissue mass (LSTM) (mREE/LSTM), wherein patients with ratios ≥ 38 were defined as hypermetabolic. Malnutrition was defined as %ideal body weight < 0.9. Forty-eight patients were enrolled in this study. The hypermetabolic group had shorter survival in the normal-weight group but more prolonged survival in the malnutrition group. Multiplication of nutritional and metabolic factors, such as [(body mass index (BMI) − 19.8) × (mREE/LSTM − 38)], designated as BMI-muscle metabolism index (BMM index), successfully predicted the prognosis in the group with a high BMM index (≥ 1), which showed shorter survival and a faster rate of weight loss and functional decline. Multivariate analysis using the Cox model showed high BMM index was an independent poor prognostic factor (hazard ratio: 4.05; p = 0.025). Prognostic prediction by hypermetabolism varies depending on the nutritional status in ALS, and the BMM index is a consistent prognostic factor.
Continuous warming shift greening towards browning in the Southeast and Northwest High Mountain Asia
Authors: Liu Yongchang , Li Zhi , Chen Yaning
Published: September 2021

Remote sensing and ground vegetation observation data show that climate warming promotes global vegetation greening, and the increase in air temperature in High Mountain Asia (HMA) is more than twice the global average. Under such a drastic warming in climate, how have the vegetation dynamics in HMA changed? In this study, we use the Normalized Difference Vegetation Index (NDVI) from 1982 to 2015 to evaluate the latest changes in vegetation dynamics in HMA and their climate-driving mechanisms. The results show that over the past 30 years, HMA has generally followed a “warm-wet” trend, with temperatures charting a continuous rise. During 1982–1998 precipitation increased (1.16 mm yr−1), but depicted to reverse since 1998 (− 2.73 mm yr−1). Meanwhile, the NDVI in HMA increased (0.012 per decade) prior to 1998, after which the trend reversed and declined (− 0.005 per decade). The main reason for the browning of HMA vegetation is the dual effects of warming and precipitation changes. As mentioned, the increase in air temperature in HMA exceeds the global average. The increase of water vapor pressure deficit caused by global warming accelerates the loss and consumption of surface water, and also aggravates the soil water deficit. That is to say, the abnormal increase of land evapotranspiration far exceeds the precipitation, and the regional water shortage increases. Climate change is the primary factor driving these vegetation and water dynamics, with the largest proportion reaching 41.9%.
Space-fractional quantum heat engine based on level degeneracy
Authors: Aydiner Ekrem
Published: September 2021

In order to examine the work and efficiency of the space-fractional quantum heat engine, we consider a model of the space-fractional quantum heat engine which has a Stirling-like cycle with a single particle under infinite potential well as an example. We numerically compute the work and efficiency for various fractional exponents. We show the work and the efficiency of the engine depending on the length of the potential well and fractional exponent of the engine. Furthermore, we show that fractional exponent plays a substantial role in the operating range of the quantum heat engine. Thus, we conclude that the fractional parameter can be used as a tuning parameter to obtain positive work and efficiency for the large size of the quantum heat engine. Additionally, the numerical results and model imply that the size of the engine can be enlarged in the nano-scale by using fractional deformations. As a result, in this study, we have not only shown that fractional deformations in space play an important role on the work and efficiency of the quantum heat engines but also introduced the concept of fractional quantum heat engines to the literature.
Native soil amendments combined with commercial arbuscular mycorrhizal fungi increase biomass of Panicum amarum
Authors: Luecke Noah C. , Mejia Austin J. , Crawford Kerri M.
Published: September 2021

Coastal dune restorations often fail because of poorly performing plants. The addition of beneficial microbes can improve plant performance, though it is unclear if the source of microbes matters. Here, we tested how native soil amendments and commercially available arbuscular mycorrhizal (AM) fungi influenced performance of Panicum amarum, a dominant grass on Texas coastal dunes. In a greenhouse experiment, we manipulated the identity of native soil amendments (from P. amarum, Uniola paniculata, or unvegetated areas), the presence of soil microbes in the native soil amendments (live or sterile), and the presence of the commercial AM fungi (present or absent). Native soils from vegetated areas contained 149% more AM fungal spores than unvegetated areas. The commercial AM fungi, when combined with previously vegetated native soils, increased aboveground biomass of P. amarum by 26%. Effects on belowground biomass were weaker, although the addition of any microbes decreased the root:shoot ratio. The origin of native soil amendments can influence restoration outcomes. In this case soil from areas with vegetation outperformed soil from areas without vegetation. Combining native soils with commercial AM fungi may provide a strategy for increasing plant performance while also maintaining other ecosystem functions provided by native microbes.
Assessing outcomes of ear molding therapy by health care providers and convolutional neural network
Authors: Hallac Rami R. , Jackson Sarah A. , Grant Jessica , Fisher Kaylyn , Scheiwe Sarah , Wetz Elizabeth , Perez Jeyna , Lee Jeon , Chitta Krishna , Seaward James R. , Kane Alex A.
Published: September 2021

Ear molding therapy is a nonsurgical technique to correct certain congenital auricular deformities. While the advantages of nonsurgical treatments over otoplasty are well-described, few studies have assessed aesthetic outcomes. In this study, we compared assessments of outcomes of ear molding therapy for 283 ears by experienced healthcare providers and a previously developed deep learning CNN model. 2D photographs of ears were obtained as a standard of care in our onsite photography studio. Physician assistants (PAs) rated the photographs using a 5-point Likert scale ranging from 1(poor) to 5(excellent) and the CNN assessment was categorical, classifying each photo as either “normal” or “deformed”. On average, the PAs classified 75.6% of photographs as good to excellent outcomes (scores 4 and 5). Similarly, the CNN classified 75.3% of the photographs as normal. The inter-rater agreement between the PAs ranged between 72 and 81%, while there was a 69.6% agreement between the machine model and the inter-rater majority agreement between at least two PAs (i.e., when at least two PAs gave a simultaneous score < 4 or ≥ 4). This study shows that noninvasive ear molding therapy has excellent outcomes in general. In addition, it indicates that with further training and validation, machine learning techniques, like CNN, have the capability to accurately mimic provider assessment while removing the subjectivity of human evaluation making it a robust tool for ear deformity identification and outcome evaluation.
From decimeter-scale elevated ionic conductivity regions in the cloud to lightning initiation
Authors: Iudin D. I. , Rakov V. A. , Syssoev A. A. , Bulatov A. A. , Hayakawa M.
Published: September 2021

In this work, we represent the lightning initiation scenario as a sequence of two transitions of discharge activity to progressively larger spatial scales: the first one is from small-scale avalanches to intermediate-scale streamers; and the second one is from streamers to the lightning seed. We postulate the existence of ion production centers in the cloud, whose occurrence is caused by electric field bursts accompanying hydrometeor collisions (or near collisions) in the turbulent thundercloud environment. When a new ion production center is created inside (fully or partially) the residual ion spot left behind by a previously established center, there is a cumulative effect in the increasing of ion concentration. As a result, the essentially non-conducting thundercloud becomes seeded by elevated ion-conductivity regions (EICRs) with spatial extent of 0.1–1 m and a lifetime of 1–10 s. The electric field on the surface of an EICR (due to its conductivity being at least 4 orders of magnitude higher than ambient) is a factor of 3 or more higher than ambient. For a maximum ambient electric field of 100 kV/m typically measured in thunderclouds, such field enhancement is sufficient for initiation of positive streamers and their propagation over distances of the order of decimeters, and this will be happening naturally, without any external agents (e.g., superenergetic cosmic ray particles) or extraordinary in-cloud conditions, such as very high potential differences or very large hydrometeors. Provided that each EICR generates at least one streamer during its lifetime, the streamers will form a 3D network, some parts of which will contain hot channel segments created via the cumulative heating and/or thermal-ionizational instability. These hot channel segments will polarize, interact with each other, and cluster, forming longer conducting structures in the cloud. When the ambient potential difference bridged by such a conducting structure exceeds 3 MV, we assume that the lightning seed, capable of self-sustained bidirectional extension, is formed.
A body shape index is associated with endothelial dysfunction in both men and women
Authors: Kajikawa Masato , Maruhashi Tatsuya , Kishimoto Shinji , Yamaji Takayuki , Harada Takahiro , Hashimoto Yu , Han Yiming , Mizobuchi Aya , Aoki Gaku , Yoshimura Kenichi , Chayama Kazuaki , Goto Chikara , Yusoff Farina Mohamad , Nakashima Ayumu , Higashi Yukihito
Published: September 2021

A body shape index (ABSI) was proposed for estimation of abdominal adiposity. ABSI has been reported to have associations with cardiovascular risk factors and cardiovascular events. However, there is no information on the association between ABSI and endothelial function. We examined cross-sectional associations of ABSI with endothelial function in 8823 subjects (6773 men and 2050 women). Subjects with a lower quartile of flow-mediated vasodilation (FMD) were defined as subjects having endothelial dysfunction. Pearson’s correlation coefficient analysis revealed that ABSI was negatively correlated with FMD (men, r = − 0.23, P = 0.003; women, r = − 0.32, P < 0.001). The areas under the curves of ABSI and body mass index to predict endothelial dysfunction were 0.64 (95% confidence interval [CI] 0.62–0.65) and 0.58 (95% CI 0.57–0.60) in men, and 0.68 (95% CI 0.66–0.71) and 0.59 (95% CI 0.56–0.61) in women, respectively. The cutoff values of ABSI for predicting subjects with endothelial dysfunction were 0.0796 (sensitivity, 55.2%; specificity, 65.5%) in men and 0.0823 (sensitivity, 56.2%; specificity, 73.4%) in women. Multivariate analysis revealed that an ABSI value higher than the cutoff value remained an independent predictor of endothelial dysfunction in both sexes. The results of our study suggest that ABSI calculation should be performed for evaluation of risk of cardiovascular events in both men and women.

Clinical trial registration information URL for Clinical Trial: https://www.umin.ac.jp/ctr/index.htm; Registration Number for Clinical Trial: UMIN000012952 (01/05/2010).
Regulation of low-density lipoprotein receptor expression in triple negative breast cancer by EGFR-MAPK signaling
Authors: Scully Tiffany , Kase Nathan , Gallagher Emily J. , LeRoith Derek
Published: September 2021

Expression of the low-density lipoprotein receptor (LDLR) has been shown to play a critical role in hypercholesterolemia-associated breast cancer growth and is associated with shorter recurrence-free survival in human breast cancer studies. We sought to identify how circulating LDL cholesterol and tumor LDLR might accelerate oncogenic processes by determining whether increased LDLR expression and cholesterol uptake are associated with the activation of the epidermal growth factor receptor (EGFR) signaling pathway in triple negative breast cancer (TNBC) cell lines. EGF stimulation of MDA-MB-468 (MDA468) cells activated p44/42MAPK (MAPK), increased expression of LDLR, and fluorescent LDL cholesterol uptake. However, stimulation of MDA-MB-231 (MDA231) cells with EGF did not lead to increased expression of LDLR despite inducing phosphorylation of EGFR. Inhibition of MAPK using UO126 in MDA231 cells reduced LDLR expression, and in MDA468 cells, UO126 impaired the LDLR increase in response to EGF. MDA468 cells exposed to the transcription inhibitor, Actinomycin, prior to treatment with EGF showed reduced degradation of LDLR mRNA compared to vehicle-treated cells. Our results suggest that the EGF-associated increase in LDLR protein expression is cell line-specific. The common pathway regulating LDLR expression was MAPK in both TNBC cell lines.
Effects of gender, age, experience, and practice on driver reaction and acceptance of traffic jam chauffeur systems
Authors: Muslim Husam , Itoh Makoto , Liang Cho Kiu , Antona-Makoshi Jacobo , Uchida Nobuyuki
Published: September 2021

This study conducted a driving simulation experiment to compare four automated driving systems (ADS) designs during lane change demanding traffic situations on highways while accounting for the drivers’ gender, age, experience, and practice. A lane-change maneuver was required when the automated vehicle approaches traffic congestion on the left-hand lane. ADS-1 can only reduce the speed to synchronize with the congestion. ADS-2 reduces the speed and issues an optional request to intervene, advising the driver to change lanes manually. ADS-3 offers to overtake the congestion autonomously if the driver approves it. ADS-4 overtakes the congestion autonomously without the driver’s approval. Results of drivers’ reaction, acceptance, and trust indicated that differences between ADS designs increase when considering the combined effect of drivers’ demographic factors more than the individual effect of each factor. However, the more ADS seems to have driver-like capacities, the more impact of demographic factors is expected. While preliminary, these findings may help us understand how ADS users’ behavior can differ based on the interaction between human demographic factors and system design.
Perioperative rifaximin is not associated with enhanced functional and volumetric recovery after major liver resection
Authors: Bednarsch Jan , Czigany Zoltan , Loosen Sven H. , Heij Lara , Ruckgaber Lorenz , Maes Henning , Krause Jan-Pit , Reen Matthias , Toteva Beata , Vosdellen Theresa , Bruners Philipp , Lang Sven Arke , Ulmer Tom Florian , Roderburg Christoph , Luedde Tom , Neumann Ulf Peter
Published: September 2021

The objective of this randomized controlled trial (RCT) was to assess the impact of rifaximin on the course of liver function, liver regeneration and volumetric recovery in patients undergoing major hepatectomy. The ARROW trial was an investigator initiated, single-center, open-label, phase 3 RCT with two parallel treatment groups, conducted at our hepatobiliary center from 03/2016 to 07/2020. Patients undergoing major hepatectomy were eligible and randomly assigned 1:1 to receive oral rifaximin (550 mg twice daily for 7–10 or 14–21 days in case of portal vein embolization preoperatively and 7 days postoperatively) versus no intervention. Primary endpoint was the relative increase in postoperative liver function measured by LiMAx from postoperative day (POD) 4 to 7. Secondary endpoint were the course of liver function and liver volume during the study period as well as postoperative morbidity and mortality. Between 2016 and 2020, 45 patients were randomized and 35 patients (16 individuals in the rifaximin and 19 individuals in the control group) were eligible for per-protocol analysis. The study was prematurely terminated following interim analysis, due to the unlikelihood of reaching a significant primary endpoint. The median relative increase in liver function from POD 4 to POD 7 was 27% in the rifaximin group and 41% in the control group (p = 0.399). Further, no significant difference was found in terms of any other endpoints of functional liver- and volume regeneration or perioperative surgical complications following the application of rifaximin versus no intervention. Perioperative application of rifaximin has no effect on functional or volumetric regeneration after major hepatectomy (NCT02555293; EudraCT 2013-004644-28).
Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma
Authors: Hrudka Jan , Fišerová Hana , Jelínková Karolína , Matěj Radoslav , Waldauf Petr
Published: September 2021

Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.
Early activation of the cardiac CX3CL1/CX3CR1 axis delays β-adrenergic-induced heart failure
Authors: Flamant M. , Mougenot N. , Balse E. , Le Fèvre L. , Atassi F. , Gautier E. L. , Le Goff W. , Keck M. , Nadaud S. , Combadière C. , Boissonnas A. , Pavoine C.
Published: September 2021

We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early β-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF. Combining transcriptomic and secretomic approaches we characterized Mφ-enriched CD45+ cells from ECH hearts as CX3CL1- and TNFα-secreting cells. In-vivo experiments, using intramyocardial injection in ECH hearts of either Cx3cl1 or Cx3cr1 siRNA, or Cx3cr1−/− knockout mice, identified the CX3CL1/CX3CR1 axis as a protective pathway delaying transition to HF. In-vitro results showed that CX3CL1 not only enhanced ECH Mφ proliferation and expansion but also supported adult cardiomyocyte hypertrophy via a synergistic action with TNFα. Our data underscore the in-vivo transient protective role of the CX3CL1/CX3CR1 axis in ECH remodeling and suggest the participation of CX3CL1-secreting Mφ and their crosstalk with CX3CR1-expressing cardiomyocytes to delay HF.
Tumor budding correlates with tumor invasiveness and predicts worse survival in pT1 non-muscle-invasive bladder cancer
Authors: Eckstein Markus , Kimmel Charlotte , Bruendl Johannes , Weber Florian , Denzinger Stefan , Gierth Michael , Burger Maximilian , Hartmann Arndt , Otto Wolfgang , Breyer Johannes
Published: September 2021

Tumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p < 0.001) and extensive lamina propria invasion (p < 0.001). In Kaplan–Meier analysis, tumor budding was associated with significantly worse RFS (p = 0.005), PFS (p = 0.017) and CSS (p = 0.002). In patients who received BCG instillation therapy (n = 65), the absence of tumor budding was associated with improved RFS (p = 0.012), PFS (p = 0.011) and CSS (p = 0.022), with none of the patients suffering from progression or dying from the disease. Tumor budding is associated with a more aggressive and invasive stage of pT1 NMIBC and a worse outcome. This easy-to-assess parameter could help stratify patients into BCG therapy or early cystectomy treatment groups.
In-house reverse transcriptase polymerase chain reaction for detection of SARS-CoV-2 with increased sensitivity
Authors: Kalita Manash Jyoti , Dutta Kalpajit , Hazarika Gautam , Dutta Ridip , Kalita Simanta , Das Partha Pratim , Sarma Manash P. , Banu Sofia , Idris Md. Ghaznavi , Talukdar Anjan Jyoti , Dutta Sangitanjan , Sharma Ajanta , Medhi Subhash
Published: September 2021

As the COVID-19 infection continues to ravage the world, the advent of an efficient as well as the economization of the existing RT-PCR based detection assay essentially can become a blessing in these testing times and significantly help in the management of the pandemic. This study demonstrated an innovative and rapid corroboration of COVID-19 test based on innovative multiplex PCR. An assessment of optimal PCR conditions to simultaneously amplify the SARS-CoV-2 genes E, S and RdRp has been made by fast-conventional and HRM coupled multiplex real-time PCR using the same sets of primers. All variables of practical value were studied by amplifying known target-sequences from ten-fold dilutions of archived positive samples of COVID-19 disease. The multiplexing with newly designed E, S and RdRp primers have shown an efficient amplification of the target region of SARS-CoV-2. A distinct amplification was observed in 37 min using thermal cycler while it took 96 min in HRM coupled real time detection using SYBR green over a wide range of template concentrations. Our findings revealed decent concordance with other commercially available detection kits. This fast HRM coupled multiplex real-time PCR with SYBR green approach offers rapid and sensitive detection of SARS-CoV-2 in a cost-effective manner apart from the added advantage of primer compatibility for use in conventional multiplex PCR. The highly reproducible novel approach can propel extended applicability for developing sustainable commercial product besides providing relief to a resource limited setting.
Landscape genetics and the genetic legacy of Upper Paleolithic and Mesolithic hunter-gatherers in the modern Caucasus
Authors: Gavashelishvili Alexander , Yanchukov Alexey , Tarkhnishvili David , Murtskhvaladze Marine , Akhvlediani Irakli , Kazancı Ceren
Published: September 2021

This study clarifies the role of refugia and landscape permeability in the formation of the current genetic structure of peoples of the Caucasus. We report novel genome-wide data for modern individuals from the Caucasus, and analyze them together with available Paleolithic and Mesolithic individuals from Eurasia and Africa in order (1) to link the current and ancient genetic structures via landscape permeability, and (2) thus to identify movement paths between the ancient refugial populations and the Caucasus. The ancient genetic ancestry is best explained by landscape permeability implying that human movement is impeded by terrain ruggedness, swamps, glaciers and desert. Major refugial source populations for the modern Caucasus are those of the Caucasus, Anatolia, the Balkans and Siberia. In Rugged areas new genetic signatures take a long time to form, but once they do so, they remain for a long time. These areas act as time capsules harboring genetic signatures of ancient source populations and making it possible to help reconstruct human history based on patterns of variation today.
Spin structures of the ground states of four body bound systems with spin 3 cold atoms
Authors: Liu Y. M. , Bao C. G.
Published: September 2021

We consider the case that four spin-3 atoms are confined in an optical trap. The temperature is so low that the spatial degrees of freedom have been frozen. Exact numerical and analytical solutions for the spin-states have been both obtained. Two kinds of phase-diagrams for the ground states (g.s.) have been plotted. In general, the eigen-states with the total-spin S (a good quantum number) can be expanded in terms of a few basis-states $$f_{S,i}$$

f

S
,
i

. Let $$P_{f_{S,i}}^{\lambda }$$

P

f

S
,
i

λ

be the probability of a pair of spins coupled to $$\lambda =0, 2, 4$$

λ
=
0
,
2
,
4

, and 6 in the $$f_{S,i}$$

f

S
,
i

state. Obviously, when the strength $$g_{\lambda }$$

g
λ

of the $$\lambda $$
λ
-channel is more negative, the basis-state with the largest $$P_{f_{S,i}}^{\lambda }$$

P

f

S
,
i

λ

would be more preferred by the g.s.. When two strengths are more negative, the two basis-states with the two largest probabilities would be more important components. Thus, based on the probabilities, the spin-structures (described via the basis-states) can be understood. Furthermore, all the details in the phase-diagrams, say, the critical points of transition, can also be explained. Note that, for $$f_{S,i}$$

f

S
,
i

, $$P_{f_{S,i}}^{\lambda }$$

P

f

S
,
i

λ

is completely determined by symmetry. Thus, symmetry plays a very important role in determining the spin-structure of the g.s..