bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the mitochondrial phylogenetic landscape of Thailand reveals complex admixture and demographic dynamics
Authors: Jaisamut Kitipong , Pitiwararom Rachtipan , Sukawutthiya Poonyapat , Sathirapatya Tikumphorn , Noh Hasnee , Worrapitirungsi Wikanda , Vongpaisarnsin Kornkiat
Published: November 2023

The evolutionary dynamics of mitochondrial DNA within the Thai population were comprehensively explored with a specific focus on the influence of South Asian admixture. A total of 166 samples were collected through randomized sampling, ensuring a diverse representation. Our findings unveil substantial genetic and haplogroup diversity within the Thai population. We have identified 164 haplotypes categorized into 97 haplogroups, with a notable inclusion of 20 novel haplogroups. The distribution of haplogroups exhibited variations across different populations and countries. The central Thai population displayed a high diversity of haplogroups from both the M and N clades. Maternal lineage affinities were discerned between several Mainland Southeast Asia (MSEA) and South Asian populations, implying ancestral genetic connections and a substantial influence of South Asian women in establishing these relationships. f4-statistics indicates the presence of a Tibeto-Burman genetic component within the Mon population from Thailand. New findings demonstrate two phases of population expansion occurring 22,000–26,000 and 2500–3800 years ago, coinciding with the Last Glacial Maximum, and Neolithic demographic transition, respectively. This research significantly enhances our understanding of the maternal genetic history of Thailand and MSEA, emphasizing the influence of South Asian admixture. Moreover, it underscores the critical role of prior information, such as mutation rates, within the Bayesian framework for accurate estimation of coalescence times and inferring demographic history.
Different cultivation systems and foliar application of calcium nanoparticles affect the growth and physiological characteristics of pennyroyal (Mentha pulegium L.)
Authors: Roosta Hamid Reza , Samadi Arman , Bikdeloo Mahdi
Published: November 2023

The aim of this study was to investigate the impact of different cultivation systems (soil cultivation, hydroponic cultivation in greenhouse conditions, and hydroponic vertical cultivation in plant factory under different LED lights) and foliar spraying of nano calcium carbonate on pennyroyal plants. Nano calcium carbonate was applied to the plants at a 7-day interval, three times, one month after planting. Results showed that the greenhouse cultivation system with calcium carbonate foliar spraying produced the highest amount of shoot and root fresh mass in plants. Additionally, foliar spraying of calcium carbonate increased internode length and leaf area in various cultivation systems. Comparing the effects of different light spectrums revealed that red light increased internode length while decreasing leaf length, leaf area, and plant carotenoids. Blue light, on the other hand, increased the leaf area and root length of the plants. The hydroponic greenhouse cultivation system produced plants with the highest levels of chlorophyll, carotenoids, and phenolic compounds. White light-treated plants had less iron and calcium than those exposed to other light spectrums. In conclusion, pennyroyal plants grown in greenhouses or fields had better growth than those grown in plant factories under different light spectrums. Furthermore, the calcium foliar application improved the physiological and biochemical properties of the plants in all the studied systems.
Binding interactions of hydrophobically-modified flavonols with β-glucosidase: fluorescence spectroscopy and molecular modelling study
Authors: Chepeleva Liudmyla V. , Demidov Oleksii O. , Snizhko Arsenii D. , Tarasenko Dmytro O. , Chumak Andrii Y. , Kolomoitsev Oleksii O. , Kotliar Volodymyr M. , Gladkov Eugene S. , Kyrychenko Alexander , Roshal Alexander D.
Published: November 2023

Binding interactions of fluorescent flavonols with the β-glucosidase enzyme are studied using fluorescence spectroscopy in combination with molecular docking and molecular dynamics simulations.
Decentralized collaborative optimal scheduling for EV charging stations based on multi‐agent reinforcement learning
Authors: Li Hang , Han Bei , Li Guojie , Wang Keyou , Xu Jin , Khan Muhammad Waseem
Published: November 2023

Charging behaviours of electric vehicles (EVs) exhibit substantial randomness, making accurate prediction or modelling challenging. Furthermore, as the number of EVs continues to increase, charging stations are diversifying their offerings to accommodate distinct charging characteristics, addressing a wide spectrum of EV charging needs. Previous research mostly focused on the randomness of EVs while neglecting the heterogeneity in charging infrastructure. Therefore, this paper introduces a decentralized collaborative optimal method for EV charging stations, taking into account the varying facility types and the power limitations. First, a decentralized collaborative framework is proposed. The energy boundary model and the average laxity of EVs contribute to transforming the optimization problem into a Markov Decision Process (MDP) with uncertain transitions. Then, multi‐agent deep deterministic policy gradient multi‐individuals (MADDPG‐MI) algorithm is developed to train several heterogeneous agents presenting different types of charging facilities. Each agent makes decisions for multiple homogenous charging piles. Numerous simulation studies validate that the proposed method can effectively reduce charging costs and manages in scenarios involving either homogeneous or multiple heterogeneous charging facilities. Moreover, the MADDPG‐MI algorithm demonstrates performance consistency among multiple decision‐making units while consuming lower training resources offering enhanced scalability.
A visual faulty feeder detection method for power distribution network based on spatial image generation and deep learning
Authors: Guo Wei , Shi Yuntao
Published: November 2023

In the case of a single‐phase grounding fault in the distribution network, the transient zero‐sequence current (TZSC) tends to be non‐linear and non‐stationary. The faulty line selection is relatively difficult. The distributed power access further brings many difficulties to faulty line selection. This work proposes a novel method of faulty line selection using spatial image generation and deep learning. At first, the optimal smooth denoising model can be used to smooth the zero‐sequence current for each line, reducing the external environment electromagnetic interference. Then, the treated zero‐sequence current is mapped into the colorful floral hoop image by using symmetrized Hilbert transform pattern (SHTP). The SHTP transforms the one‐dimensional time domain signal into the two‐dimensional space domain image, enhancing invisible information and obtaining more abundant feature information. Finally, the deep features of the SHTP floral hoop image are extracted by means of deep learning method. In order to improve the faulty line selection universality, a mixed sample library containing three different topologies is established, including the 10 kV radial distribution network, IEEE‐13 node model, IEEE‐34 node model and StarSim platform. The comparisons show that the proposed method has a more noticeable visualization effect on fault features, higher classification precision rate, and better anti‐noise performance.
Correlated random walk and noise suppression in detecting electric fields
Authors: Wan Fei , Lu Li-Hua , Li You-Quan
Published: November 2023

Detecting a weak electric field in a strong noisy background is always an interesting but hard task. We investigate the collective effects of charged Brownian particles in the presence of a weak electric field together with a strong noisy background field by numerical simulation. We show that the pattern formed by snapshots touched by the Brownian particles on one boundary surface can manifest the direction of an applied weak electric field but will be spoiled if there exists a strong noisy background. Moreover, we find that the influence of noise can be suppressed effectively if the correlations caused by the inter-particle electric interaction are taken into account. This work is expected to provide a new angle of view: correlated random walk plays a constructive role in noise suppression.
Characteristics of stochastic solutions for the chiral NLSE through Brownian motion process
Authors: Alkhidhr Hanan A.
Published: November 2023

In this work, we produce some new stochastic chiral solitons for the chiral nonlinear Schrödinger equation through Brownian motion process. Specifically, we use the unified approach to produce these soliton solutions. These solutions are so important in quantum mechanics, optical fiber communication, heat transfer, applications of energy, etc. These solutions behave in qualitatively distinct structural ways, based on physical coefficients parameters and the noise parameter. The results of the solitary structures of this system agree well with the properties of the nonlinear Schrödinger systems used to investigate dispersive modes and higher-order chiral systems. We introduce some plots for the deterministic and stochastic cases in order to show the behavior of waves in both cases. Namely, we used Matlab 18 to create comprehensive configurations to highlight the physical dynamical description of the solutions as well as provide further information. The dominance of the noise term in all wave conversion, growth, and damping of envelopes and shocks has been verified. Finally, our analysis can be outspread to several equations arising in natural science.
Rigidity percolation in a random tensegrity via analytic graph theory
Authors: Stephenson William , Sudhakar Vishal , McInerney James , Czajkowski Michael , Rocklin D. Zeb
Published: November 2023

Functional structures from across the engineered and biological world combine rigid elements such as bones and columns with flexible ones such as cables, fibers, and membranes. These structures are known loosely as tensegrities, since these cable-like elements have the highly nonlinear property of supporting only extensile tension. Marginally rigid systems are of particular interest because the number of structural constraints permits both flexible deformation and the support of external loads. We present a model system in which tensegrity elements are added at random to a regular backbone. This system can be solved analytically via a directed graph theory, revealing a mechanical critical point generalizing that of Maxwell. We show that even the addition of a few cable-like elements fundamentally modifies the nature of this transition point, as well as the later transition to a fully rigid structure. Moreover, the tensegrity network displays a collective avalanche behavior, in which the addition of a single cable leads to the elimination of multiple floppy modes, a phenomenon that becomes dominant at the transition point. These phenomena have implications for systems with nonlinear mechanical constraints, from biopolymer networks to soft robots to jammed packings to origami sheets.
Hyperbolic Actions and 2nd Bounded Cohomology of Subgroups of 𝖮𝗎𝗍(𝖥_{𝗇})
Authors: Handel Michael , Mosher Lee
Published: November 2023

In this two part work we prove that for every finitely generated subgroup

Γ
>

O
u
t

(

F
n

)

\Gamma >{\mathsf {Out}}(F_n)

, either

Γ
\Gamma

is virtually abelian or

H
b
2

(
Γ
;

R

)

H^2_b(\Gamma ;{\mathbb {R}})

contains a vector space embedding of

ℓ
1

\ell ^1

. The method uses actions on hyperbolic spaces. In Part I we focus on the case of infinite lamination subgroups

Γ
\Gamma

—those for which the set of all attracting laminations of all elements of

Γ
\Gamma

is an infinite set—using actions on free splitting complexes of free groups. In Part II we focus on finite lamination subgroups

Γ
\Gamma

and on the construction of useful new hyperbolic actions of those subgroups.
Race, Social Justice, and University Language Programs From an International Perspective
Authors: Gavari Starkie Elisa , Tenca Sidotti Paula
Published: November 2023

The democratization of university access made possible the arrival of new university students from different backgrounds. At this time access was opened to all individuals coming from all different backgrounds. The new student population had a strong impact on the university life. Some university professors complained that although some students were talented, they could not communicate in complex scenarios. The article will focus on the theoretical principles that inspired the democratic curriculum and the psychological approach that allowed new individual cognitive perspectives and a new vision of the university population. At this time the education principles by Freire and Dewey generated an impulse for democratic education. From this framework the article will analyze the research and educational principles that inspired the Writing Across Curriculums (WAC) movement and the supplementary Writing in the Disciplines (WID). Both programs were very successful and led to the establishment of the Writing Academic Centers that since then and until now guarantee a democratic university education. These centers have fostered WAC, which developed into WID. The need to address global classrooms has inspired Writing Across the Communities, which considers race and social justice within language programs. The university scientific approach is aligned with the international organization’s objectives for the 20th century.
Risky Sexual Behaviors: Trends Among Young People (10–24 Years) in Four East African Countries
Authors: Makumbi Fredrick E. , Nabukeera Sarah , Bukenya Justine N. , Sebina Kibira Simon Peter
Published: November 2023

The future of sub-Saharan Africa depends on the health of young people (10–24 years) who form about one-third of the region’s population. This large population of young people is a potential asset for social-economic development if appropriate investments and social empowerment can be provided. Despite the vast opportunities, young people are faced with enormous social, economic, and health challenges. Young people’s health increasingly remains important especially with the use and misuse of narcotics (drugs and alcohol) a key risk factor for risky sexual behaviors (RSBs).

RSBs are defined as behaviors that increase one’s risk of contracting sexually transmitted infections (STIs), including human immunodeficiency virus (HIV) and unintended pregnancies. RSBs include multiple sex partners, sex without a condom, alcohol use with sex, sex initiation before age 15, nonuse of modern contraceptives, and early marriage (before age 18 years).

RSBs are reportedly influenced by a number of factors including lack of access to accurate, customized HIV information and prevention services, socioeconomic reasons, lack of parental control, peer pressure, and lack of youth-friendly recreational facilities. The consequences or impact of RSB, especially among the adolescents and young people, include poor health (STIs including HIV/AIDS, unintended pregnancies, unsafe abortions, maternal deaths, and mental health such as psychological distress), and negative social and economic challenges (nonenrollment and nonretention in school and early child marriage).

Understanding the trends in RSBs can provide insights in how well available interventions and policies have minimized their consequences among adolescents, and lay a basis to further develop more innovative and effective strategies especially in low-income countries.
US-Lebanese Relations
Authors: Whalen Emily I.
Published: November 2023

Lebanon is a relatively minor country in US foreign relations, lacking any significant resources or symbolic importance for Washington. Yet the history of the Lebanese-US relationship is an illustrative example of the consequences of US foreign policy, highlighting the contours of the US role in the international system. The history of Lebanese–US relations falls into four eras. The first period was mostly driven by private individuals, while the second period saw Lebanon undergoing significant changes as the United States competed with the Soviet Union. In the third period, Lebanon’s devastating civil war served as a stage upon which the United States stepped into its role of global hegemon. Finally, during the early 21st century, relations between the United States and Lebanon have faltered, as Lebanon’s post–civil war political system tacks between crisis and paralysis.

Lebanon’s fate as a small nation in the US-led international system of the late 20th and early 21st centuries paints an evocative portrait of US power. To the extent that its relationship with the United States is generalizable, Lebanon serves as an illustration of the costs of maintaining a particular version of the global status quo. Despite its relative insignificance, Lebanon offers a valuable perspective on the impact of US foreign policy.
Evolution and prognostic value of left ventricular deformation and myocardial work parameters in transthyretin amyloid cardiomyopathy
Authors: Antonelli Jerome , Neveu Antoine , Kosmala Wojciech , L’Official Guillaume , Curtis Elizabeth , Oger Emmanuel , Donal Erwan
Published: November 2023

Aims

Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized condition. It remains challenging to estimate the extent of disease and the prognosis for most patients. Myocardial work is a sensitive echocardiographic approach that improves the characterization of myocardial damage. We investigate the parameters of myocardial deformation and work in ATTR-CM patients and their changes over time.

Methods and results

We analysed clinical, electrocardiographic, biological, and echocardiographic characteristics in 113 patients [median age 82 (77–85), 90.4% male] diagnosed with wild-type ATTR-CM based on international consensus at a single centre. We compared the data at baseline and 18-month follow-up. Thirty-four patients died and 12 were hospitalized for heart failure at a median follow-up of 935 days (interquartile range 691–1159 days). Left ventricular end-diastolic diameter, left atrial strain during reservoir phase (LASRES), left ventricular longitudinal strain, global work index (GWI), global constructive work significantly decreased from baseline to 18 months, while left ventricular wall thickness increased. Left ventricular ejection fraction, right ventricular free wall strain (FWS), global wasted work (GWW), and global work efficiency did not alter significantly. Strain parameters were identified as prognostic on baseline evaluation using a multivariate analysis: GWI, GWW, FWS, and LASRES. They were significantly associated with the risk of death and hospitalization for heart failure.

Conclusion

Multi-chamber strain assessment may improve the surveillance of patients with ATTR-CM, and myocardial work parameters may improve clinical risk stratification in this population.
The prevalence and significance of the EIF2AK4 variants in the patients with pulmonary arterial hypertension
Authors: Momoi M , Hiraide T , Shinya Y , Sato K , Inami T , Fukuda K , Kataoka M
Published: November 2023

Background

Eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) has been reported to be the causative gene of pulmonary veno-occlusive disease (PVOD).[1] Although some patients with pulmonary arterial hypertension (PAH) also carry the EIF2AK4 variants, its importance remains unclear.

Purpose

The purpose of this study was to evaluate the prevalence and significance of EIF2AK4 variants in patients with PAH.

Methods

The whole exome sequencing were performed in total 162 patients with idiopathic or heritable PAH. The clinical data including the high-resolution CT scanning, pulmonary function test, laboratory data at diagnosis, and therapeutic response to pulmonary vasodilator were evaluated.

Results

We identified the heterozygous variants of EIF2AK4 in 6 (3.7%) patients. Among them, 2 patients also had bone morphogenetic protein receptor type 2 (BMPR2) variants which were defined as pathogenic by American College of Medical Genetics and Genomics classification. The other 4 patients did not have known PAH associated gene variants. Although the typical findings of PVOD such as interlobular septal thickening and enlarged mediastinal lymph nodes, were not identified by the CT scanning, the median percent diffusing capacity for carbon monoxide of patients with EIF2AK4 heterozygous variants was reduced to 45.6%. In addition, 4 of 6 patients received prostacyclin injection therapy because oral combination therapy was ineffective, and 2 patients died. Moreover, none of the 6 patients reached mean pulmonary arterial pressure≤30 mmHg despite the combination therapy. We also identified homozygous EIF2AK4 variants in 2 patients with PAH. They did not have the known causative variants of PAH. CT scanning at diagnosis did not detect any characteristic of PVOD in either of the two patients. Although the pulmonary vasodilator was initiated without induction of pulmonary edema, one patient was refractory to the therapy.

Conclusions

The genetic analysis is crucial for accurate diagnosis even in patients diagnosed with PAH because heterozygous or homozygous variants in EIF2AK4 could be involved in the disease pathology.
Retrospective analysis of confirmed cases of pulmonary veno-occlusive disease: a single tertiary referral center study
Authors: Gonzalez Bonilla H M , Frantz R P , Cajigas H R , Borlaug B A , Bratt A , Krowka M J , Dubrock H M , Reddy Y N V , Kane G C , Anand V
Published: November 2023

Background

Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension that primarily results in intimal fibrosis of the pulmonary venules and veins, the venous lesions are often associated with changes in interlobular septa, lung parenchyma, and pulmonary arterioles and arteries.

Purpose

We sought to study the clinical characteristics of patients with confirmed PVOD at a single large referral center.

Methods

We retrospectively reviewed data from a total of 675 patients with pulmonary hypertension (identified by ICD codes or search of text) from 2017 and 2022 from a database obtained from electronic medical records at our institution. Patients with group 2 pulmonary hypertension were excluded. Only 29 cases were confirmed by histology or genetic testing.

Results

Out of the 29 patients confirmed with PVOD, 28 (96.5%) had a characteristic histology (lung biopsy (55.1%), explanted lung for transplant (27.5%) and autopsy (13.7%)) and 1 (3.4%) had a positive genetic test for EIF2AK4 biallelic mutation. The age at diagnosis was 53±16 years, 14 (48.2%) were men, 2 (6.8%) had systemic scleroderma, 2 (6.8%) had psoriasis, 2 (6.8%) were exposed to cytotoxic agents, 16 (55.1%) were smokers and 2 (6.8%) had a family history of pulmonary hypertension. All patients had computed tomography of the chest but only 12 (41.3%) had all 3 typical features found in PVOD (ground glass opacities, interlobular septal thickening, and lymphadenopathy). The most common feature was interlobular septal thickening in 26 (89.6%), followed by ground glass opacities present in 25 (86.2%) and lymphadenopathy in 12 (41.3%) of the patients. At diagnosis, mean pulmonary artery pressure was 45±15 mmHg and pulmonary vascular resistance was 9±6 WU. The median DLCO was 41 (34-58) %. On echocardiogram, 14 (48.2%) had severely enlarged right ventricle (RV), RV function was ≥moderately reduced in 17 (58.6%), RV systolic pressure was 63±20 mmHg and 6 (20.6%) had pericardial effusion. Out of 21 (72.4%) patients who received pulmonary vasodilators, 4 (13.7%) received single agent. 10 (34.4%) received 2 agents, 6 (20.6%) 3 agents, and 1 (3.4%) received 4 agents. 35.7% of these treated patients reported an improvement or initial worsening of symptoms with subsequent improvement afterwards. 18 (62%) patients with PVOD died, 12 (41.3%) had a lung transplant and 6 (20.6%) were still alive without the transplant until the day data was collected. Mean duration from diagnosis to death and lung transplantation was 446 ± 405 days and 274±479 days respectively.

Conclusion

PVOD is a rare and lethal cause of pulmonary hypertension. When suspected, a trial of medical therapy should be initiated carefully. The evaluation for lung transplant should be considered early given its high mortality.
Of mice and men: transcriptome-based clustering reveals molecular heterogeneity among mouse atherosclerosis models and partially reflects the diversity of human plaques
Authors: Brouwer E , Michal M , Pasterkamp G
Published: November 2023

Background

Mice are frequently used as model organisms to study atherosclerosis, but many treatments effective in mice do not successfully translate to humans. In a recent study, we clustered 654 human plaques based on transcriptomic data and described the categorisation into five distinct plaque types. We now hypothesise that the reasons for the failures of translating results from mouse models can be partially explained by the fact that mouse models do not reflect all the phenotypic variability we observe in human plaques.

Methods

We used transcriptomic data from the aortic samples (from arch to mid abdomen) of 102 different strains of inbred mice (n = 366). Those mice are F1 progenies from the Hybrid Mouse Diversity Panel (HMDP) crossed with C57BL/6J carrying dominant ApoE-Leiden and CETP transgenes. The gene expression data were normalised and batch effect was removed and clustered by a shared nearest neighbour modularity optimization-based clustering algorithm. Differential gene expression between the clusters was performed to reveal the difference in the biology of the clusters. The clusters were linked to physiological measurements and correlated to human transcriptomic-based plaque clusters.

Results

Transcriptional profiles of atherosclerotic lesions in mice could be categorised into four distinct clusters with specific gene expression fingerprints. The different clusters have a different activity for some pathways, including smooth muscle cell related pathways and metabolic pathways. Comparison with human clusters revealed that most mice strains (n = 287, 78%) correlated best with human plaque type #3 which is enriched in both inflammatory and fibrosis-related genes. This cluster represents about 20% of all human lesions but was found to be associated with severe cardiovascular events. A few mouse strains showed the highest correlations with two other human plaque types (e.g. BUB/Bnj for plaque type #1 and LG/J for plaque type #4), while the human plaque types #0 and #2 were much less reflected in analysed mouse models. Interestingly inflammatory pathways, important drivers in differentiating human clusters, only showed minor differences through all mice clusters.

Conclusions

Transcriptomic profiling of atherosclerotic lesions reveals that mice associate only partly with the human plaque phenotypes. The best associations were observed with those human plaques that correlate with a more severe clinical phenotype. The existence of different types of lesions observed in humans should be taken into account when choosing a mouse model to study atherosclerosis.
Dynamics of indicators of central hemodynamics and arterial wall rigidity during the background of combination therapy with amlodipine/ valsartan in patients with arterial hypertension
Authors: Yuldasheva A , Abdullaeva G J , Khamidullaeva G A , Masharipov S H M , Ibragimova I A
Published: November 2023

Aim

Assess the impact of antihypertensive therapy of the double fixed combination of amlodipine/valsartan on the parameters of central hemodynamics and elastic properties of arteries in patients with arterial hypertension.

Materials and methods

During the 3-month follow-up period, 30 patients with arterial hypertension were examined at our cardiology center. Women - 53.3%, men - 46.7%. The average age of the respondents was 54.7±11.3 years. The average duration of AH was 9.5±7.1 years. Patients with previously uncontrolled hypertension were prescribed combination therapy with the inclusion of amlodipine/valsartan, if necessary, the dose was titrated every 2 weeks. All patients initially and 3 months later underwent applanation tonometry using the SphygmoCor device. Central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), central pulse pressure (cPP), aortic augmentation (AA), augmentation index (AIx), pulse wave velocity (PWV) were measured, resulting in a conclusion about the state of arterial stiffness . Results are presented as M±SD.

Results

An analysis of the dynamics of central hemodynamic parameters and vascular stiffness during 3-month combination therapy with amlodipine/valsartan showed a significant decrease in such indicators as cSBP, cDAP, CPD, AA, as well as pulse wave velocity. Thus, the cSBP index initially amounted to 155.2±22.6 mm Hg. and in dynamics - 131.6±18.3 mm Hg. (p<0.001); the cDAP index was 84.2±12.7 mm Hg. vs. 78.4±8.2 mm Hg respectively (p<0.02); the CPP index was 71.0±19.8 mm Hg. vs. 53.2±18.1 mm Hg. respectively (p<0.001); the AA index was 18.3±16.5 mm Hg. vs. 11.9±6.3 mm Hg. respectively (p<0.02); PWV was 9.9±2.7 m/s versus 8.2±2.7 m/s, respectively (p<0.001).

Conclusions

According to the results of 3-month combination therapy, indicators of central hemodynamics and the state of elastic properties of arteries are significantly improved, which is potentially associated with a decrease in the risk of developing cardiovascular complications in patients with hypertension.
Inhibition of cutaneous heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice
Authors: Qu Yaxuan , Sun Xiaoying , Wei Ningning , Wang KeWei
Published: November 2023

Ultraviolet B (UVB) radiation causes skin injury by trigging excessive calcium influx and signaling cascades in the skin keratinocytes. The heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 (TRPV3) channels robustly expressed in the keratinocytes play an important role in skin barrier formation and wound healing. Here, we report that inhibition of cutaneous TRPV3 alleviates UVB radiation‐induced skin lesions. In mouse models of ear swelling and dorsal skin injury induced by a single exposure of weak UVB radiation, TRPV3 genes and proteins were upregulated in quantitative real‐time PCR and Western blot assays. In accompany with TRPV3 upregulations, the expressions of proinflammatory cytokines tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) were also increased. Knockout of the TRPV3 gene alleviates UVB‐induced ear swelling and dorsal skin inflammation. Furthermore, topical applications of two selective TRPV3 inhibitors, osthole and verbascoside, resulted in a dose‐dependent attenuation of skin inflammation and lesions. Taken together, our findings demonstrate the causative role of overactive TRPV3 channel function in the development of UVB‐induced skin injury. Therefore, topical inhibition of TRPV3 may hold potential therapy or prevention of UVB radiation‐induced skin injury.
Quantitative Impact of Coil Misalignment and Misplacement in Transcranial Magnetic Stimulation
Authors: Koehler Max , Kammer Thomas , Goetz Stefan M.
Published: November 2023

Introduction

Targeting in transcranial magnetic stimulation (TMS) involves the accurate placement and positioning of the stimulation coil on the head of a subject or patient. In clinical and research applications, this placement is even done manually and/or with fixed coil holders that do not compensate for motion and drift of the head. The placement involves six degrees of freedom (DOF; three position DOF: 1× contact and 2× head location; three rotational DOF: 2× alignment and 1× electric field direction/orientation), which challenge operators. This procedure is—even with an experienced user—prone to positioning errors, which can result in low treatment efficacy or high stimulation strength due to overestimating the resting motor threshold (RMT). Whereas the position and field orientation are at least widely appreciated, the coil–head alignment and its impact are often not even known. Errors involve constant errors, drift (both leading to bias and inter-individual variability), and particularly fluctuations (causing intra-individual variability).

Objective

We demonstrate the impact of positioning error on cortical field strength to get a better understanding of the importance of accurate positioning and compare as well as quantify the impact of position vs. alignment errors.

Methods

We simulated the impact in a realistic head anatomy to quantify various levels of position errors and misalignment, rolling-off the coil from the target.

Results

Position and alignment errors shift the focus of the electric field and reduce the electric field in the actual target. A misalignment of 10° can exceed the loss of stimulation strength in the target associated with a shift of 10 mm, corresponding to threshold stimulation leading to no detectable electromyographic response anymore. Misalignment in the direction of the handle (pitch), with which many operators appear to struggle most, reduces the field in the actual target faster than left–right roll.

Conclusion

This work highlights the importance of the coil–head alignment for intra- and interindividual variability.
Omics-assisted systematic exploration of the intricate regulatory network of guvermectin biosynthesis centered by the cluster-situated regulator GvmR inStreptomyces
Authors: Shi Haoran , Wang Jiabin , Li Shanshan , Liu Chongxi , Dong Zhuoxu , Wang Xiangjing , Zhang Yanyan , Xiang Wensheng
Published: November 2023

Guvermectin, produced byStreptomycesbacteria, is a purine nucleoside natural product recently registered as a new biopesticide to boost rice yield. Despite its importance, the regulatory network governing guvermectin biosynthesis remains largely unknown, severely impeding industrial-scale production and widespread application in rice production. Here, we investigated the diverse regulatory mechanisms employed by the cluster-situated regulatory gene,gvmR, in controlling guvermectin production from the perspective of widespread disturbance of gene expression at genome scale. GvmR activates the expression of guvermectin cluster by binding to thegvmR,gvmAandO1promoters. Additionally, GvmR binds to the promoter ofscnR1, a previously unidentified and highly conserved regulator inStreptomyces.scnR1overexpression significantly suppressed guvermectin production by regulating the guvermectin cluster through binding to the same promoters as GvmR. Transcriptomic analysis revealed that GvmR extensively influences the expression of numerous genes located outside the guvermectin cluster, including the precursor supply (purine biosynthesis) and energy synthesis (oxidative phosphorylation) pathway genes, as well as 252 transcriptional regulatory genes. By genetic screening from 48 of these 252 regulatory genes, we identified additional five highly conserved genes that impact guvermectin production, suggesting a functional interplay between GvmR and highly conserved regulators in coordinating guvermectin production. These findings enrich our knowledge of the regulatory network governing guvermectin biosynthesis and offer a broadly applicable approach for investigating the molecular regulation of natural product biosynthesis and their high-titer production.
A comprehensive characterization of blood group antigen variants in the Middle Eastern population genomes - Insights into genetic epidemiology
Authors: Rophina Mercy , Pandhare Kavita , Scaria Vinod
Published: November 2023

Background

The Middle Eastern population is characterized by increased prevalence of various Mendelian disorders owing to increased rates of consanguinity. Especially in disease conditions which require chronic transfusion support, it becomes important to know the blood group characteristics of potential donors to increase the likelihood of transfusion success. As there prevails a gap in knowledge about the population specific overall blood antigen profiles, this study seeks to utilize next generation sequencing datasets to unravel the comprehensive landscape of clinically significant minor blood group alleles in the middle eastern population.

Methods

This study utilizes the genetic variation data from a range of public datasets including the Greater Middle East Variome, the Qatar genome and exomes and the Iranome datasets to estimate the genotypic and phenotypic frequencies of blood group alleles in the Middle Easterners. The estimated frequencies were duly compared with major global populations to identify significant similarities or differences if any.

Results

A total of 77 unique ISBT approved blood group alleles were found commonly in all datasets. 8 variants (rs8176058, rs1058396, rs565898944, rs28362692, rs2071699, rs34783571, rs60322991 and rs57467915) belonging to KELL, KIDD, COLTON, H, JUNIOR and LANGEREIS blood groups were found clinically significant with previously reported evidence on transfusion complications. 730 variants were found to span exonic or splicing regions out of which 70 were predicted to be potentially deleterious by at least four computational tools.

Conclusions

This study serves first of its kind to extensively characterize the known and novel blood alleles in the Middle Easterners. A comprehensive user-friendly online resource namedalnasab -Alleles and antigens in Arab and Persian populations associated with blood groupswas also developed as a dependable reference for future transfusion research. The resource is accessible athttps://clingen.igib.res.in/alnasab/

Key points

Large scale Middle Eastern population sequencing datasets includingThe Greater Middle Eastern Variome, Genomes and exomes from Qatar and the Iranomedatasets were used in the study.

A total of2828exomes and88genomes were analyzed accounting for a total of

18717unique human blood group related variants.

2443exonic variants were extracted which systematically included1505non-synonymous variants,766synonymous variants,50stopgain variants and3stop loss variants.

Blood group associated variants identified in the study are provided as a comprehensive online repository -alnasab,Alleles and antigens in Arab and Persian populations associated with blood groups.The resource is accessible athttps://clingen.igib.res.in/alnasab/

Visual abstract
Two-dose “extended priming” immunization amplifies humoral immune responses by synchronizing vaccine delivery with the germinal center response
Authors: Bhagchandani Sachin H. , Yang Leerang , Maiorino Laura , Ben-Akiva Elana , Rodrigues Kristen A. , Romanov Anna , Suh Heikyung , Aung Aereas , Wu Shengwei , Wadhera Anika , Chakraborty Arup K. , Irvine Darrell J.
Published: November 2023

“Extended priming” immunization regimens that prolong exposure of the immune system to vaccines during the primary immune response have shown promise in enhancing humoral immune responses to a variety of subunit vaccines in preclinical models. We previously showed that escalating-dosing immunization (EDI), where a vaccine is dosed every other day in an increasing pattern over 2 weeks dramatically amplifies humoral immune responses. But such a dosing regimen is impractical for prophylactic vaccines. We hypothesized that simpler dosing regimens might replicate key elements of the immune response triggered by EDI. Here we explored “reduced ED” immunization regimens, assessing the impact of varying the number of injections, dose levels, and dosing intervals during EDI. Using a stabilized HIV Env trimer as a model antigen combined with a potent saponin adjuvant, we found that a two-shot extended-prime regimen consisting of immunization with 20% of a given vaccine dose followed by a second shot with the remaining 80% of the dose 7 days later resulted in increased total GC B cells, 5-10-fold increased frequencies of antigen-specific GC B cells, and 10-fold increases in serum antibody titers compared to single bolus immunization. Computational modeling of the GC response suggested that this enhanced response is mediated by antigen delivered in the second dose being captured more efficiently as immune complexes in follicles, predictions we verified experimentally. Our computational and experimental results also highlight how properly designed reduced ED protocols enhance activation and antigen loading of dendritic cells and activation of T helper cells to amplify humoral responses. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.
TR(acking) individuals down: exploring the effect of temporal resolution in resting-state functional MRI fingerprinting
Authors: Cassone Barbara , Saviola Francesca , Tambalo Stefano , Amico Enrico , Sarubbo Silvio , Van De Ville Dimitri , Jovicich Jorge
Published: November 2023

Functional brain fingerprinting has emerged as an influential tool to quantify reliability in neuroimaging studies and to identify cognitive biomarkers in both healthy and clinical populations. Recent studies have revealed that brain fingerprints reside in the timescale-specific functional connectivity of particular brain regions. However, the impact of the acquisition’s temporal resolution on fingerprinting remains unclear. In this study, we examine for the first time the reliability of functional fingerprinting derived from resting-state functional MRI (rs-fMRI) with different whole-brain temporal resolutions (TR = 0.5, 0.7, 1, 2, and 3 s) in a cohort of 20 healthy volunteers. Our findings indicate that subject identifiability within a fixed TR is successful across different temporal resolutions, with the highest identifiability observed at TR 0.5 and 3 s. We discuss this observation in terms of protocol-specific effects of physiological noise aliasing. We further show that, irrespective of TR, associative brain areas make substantial contributions to subject identifiability, whereas sensory-motor regions become influential only when integrating data from different TRs. We conclude that functional connectivity fingerprinting derived from rs-fMRI holds significant potential for multicentric studies also employing protocols with different temporal resolutions. However, it remains crucial to consider fMRI signal’s sampling rate differences in subject identifiability between data samples, in order to improve reliability and generalizability of both whole-brain and specific functional networks’ results. These findings contribute to a better understanding of the practical application of functional connectivity fingerprinting, and its implications for future neuroimaging research.
Certain spatial prediction decreases the rhythm of attentional sampling
Authors: Huang Yih-Ning , Liang Wei-Kuang , Juan Chi-Hung
Published: November 2023

Recent studies demonstrate that behavioral performance during visual spatial attention fluctuates at theta (4-8 Hz) and alpha (8-16 Hz) frequencies, linked to phase amplitude coupling (PAC) of neural oscillations within the visual and attentional system. Moreover, previous research suggests that attentional sampling rhythms are task-dependent, evidenced by varying behavioral performance at different frequencies. To investigate the role of prior spatial prediction, we employed an adaptive discrimination task with variable cue-target onset asynchronies ranging from 300 ms to 1300 ms in steps of 20 ms, while manipulating spatial prediction via cue validity (100% & 50%), with concurrent Electroencephalography (EEG) recording. We applied adaptive data analytical methods, namely Holo-Hilbert Spectral Analysis (HHSA) and Holo-Hilbert Cross-frequency Phase Clustering (HHCFPC). Our findings indicate that response precision for near-threshold Landolt rings fluctuates at the theta- band (4 Hz) under certain predictions and at alpha & beta bands (15 & 19 Hz) with uncertain predictions. Furthermore, spatial prediction strengthens theta-alpha modulations at parietal- occipital areas, frontal theta phase and parietal-occipital alpha amplitude coupling, and within frontal theta phase/ alpha amplitude coupling. Notably, during the pre-target period, beta- modulated gamma oscillations in parietal-occipital areas predict response precision in spatially uncertain conditions, while frontal theta phase and parietal-occipital alpha amplitude coupling predict response precision in spatially certain conditions. In conclusion, our study not only strengthens the notion that the speed of periodic sampling in perception depends on the task at hand but also highlights the critical role of spatial prediction in attentional sampling rhythms.

Significance Statement

This study investigates the temporal dynamics of sustained spatial attention under varying certainty levels, employing behavioral and electrophysiological measures in an adaptive discrimination task. Unveiling the rhythmic nature of sustained attention, our findings showcase substantial effects of spatial certainty on attentional rhythms, witnessing an increased certainty that shifts these rhythms from beta to theta frequencies. Neural oscillations offer insights into the underlying mechanisms, revealing theta-alpha coupling and beta-gamma coupling within the visual system and frontal-parietal network. Significantly, our results challenge conventional notions of attentional rhythms, emphasizing the dynamic complexity of these processes. In a broader context, our study contributes to bridging the gap between task demands and periodic sampling rhythms, offering novel insights into attention allocation during complex tasks.
Cerebrospinal Fluid Flow Extends to Peripheral Nerves
Authors: Ligocki Alexander P. , Vinson Augustine V. , Yachnis Anthony T. , Dunn William A. , Smith Douglas E. , Scott Elizabeth A. , Alvarez-Castanon Jimena V. , Montalvo Daniel E. Baez , Frisone Olivia G. , Brown Gary A.J. , Pessa Joel E. , Scott Edward W.
Published: November 2023

Cerebrospinal fluid (CSF) is an aqueous solution responsible for nutrient delivery and waste removal for the central nervous system (CNS). The three-layer meningeal coverings of the CNS support CSF flow. Peripheral nerves have an analogous three-layer covering consisting of the epineurium, perineurium, and endoneurium. Peripheral axons, located in the inner endoneurium, are bathed in “endoneurial fluid” similar to CSF but of undefined origin. CSF flow in the peripheral nervous system has not been demonstrated. Here we show CSF flow extends beyond the CNS to peripheral nerves in a contiguous flowing system. Utilizing gold nanoparticles, we identified that CSF is continuous with the endoneurial fluid and reveal the endoneurial space as the likely site of CSF flow in the periphery. Nanogold distribution along entire peripheral nerves and within their axoplasm suggests CSF plays a role in nutrient delivery and waste clearance, fundamental aspects of peripheral nerve health and disease.

One Sentence Summary

Cerebrospinal fluid unites the nervous system by extending beyond the central nervous system into peripheral nerves.