bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromodulatory functions exerted by oxytocin on different populations of hippocampal neurons in rodents
Authors: Talpo Francesca , Spaiardi Paolo , Castagno Antonio Nicolas , Maniezzi Claudia , Raffin Francesca , Terribile Giulia , Sancini Giulio , Pisani Antonio , Biella Gerardo Rosario
Published: February 2023

Oxytocin (OT) is a neuropeptide widely known for its peripheral hormonal effects (i.e., parturition and lactation) and central neuromodulatory functions, related especially to social behavior and social, spatial, and episodic memory. The hippocampus is a key structure for these functions, it is innervated by oxytocinergic fibers, and contains OT receptors (OTRs). The hippocampal OTR distribution is not homogeneous among its subregions and types of neuronal cells, reflecting the specificity of oxytocin’s modulatory action. In this review, we describe the most recent discoveries in OT/OTR signaling in the hippocampus, focusing primarily on the electrophysiological oxytocinergic modulation of the OTR-expressing hippocampal neurons. We then look at the effect this modulation has on the balance of excitation/inhibition and synaptic plasticity in each hippocampal subregion. Additionally, we review OTR downstream signaling, which underlies the OT effects observed in different types of hippocampal neuron. Overall, this review comprehensively summarizes the advancements in unraveling the neuromodulatory functions exerted by OT on specific hippocampal networks.
Angiotensin II increases respiratory rhythmic activity in the preBötzinger complex without inducing astroglial calcium signaling
Authors: Tacke Charlotte , Bischoff Anne M. , Harb Ali , Vafadari Behnam , Hülsmann Swen
Published: February 2023

Angiotensin II (Ang II) is the primary modulator of the renin-angiotensin system and has been widely studied for its effect on the cardiovascular system. While a few studies have also indicated an involvement of Ang II in the regulation of breathing, very little is known in this regard and its effect on brainstem respiratory regions such as the preBötzinger complex (preBötC), the kernel for inspiratory rhythm generation, has not been investigated yet. This study reports that Ang II temporarily increases phrenic nerve activity in the working heart-brainstem preparation, indicating higher central respiratory drive. Previous studies have shown that the carotid body is involved in mediating this effect and we revealed that the preBötC also plays a part, using acute slices of the brainstem. It appears that Ang II is increasing the respiratory drive in an AT1R-dependent manner by optimizing the interaction of inhibitory and excitatory neurons of the preBötC. Thus, Ang II-mediated effects on the preBötC are potentially involved in dysregulating breathing in patients with acute lung injury.
Noise-modulated multistable synapses in a Wilson-Cowan-based model of plasticity
Authors: Lea-Carnall Caroline A. , Tanner Lisabel I. , Montemurro Marcelo A.
Published: February 2023

Frequency-dependent plasticity refers to changes in synaptic strength in response to different stimulation frequencies. Resonance is a factor known to be of importance in such frequency dependence, however, the role of neural noise in the process remains elusive. Considering the brain is an inherently noisy system, understanding its effects may prove beneficial in shaping therapeutic interventions based on non-invasive brain stimulation protocols. The Wilson-Cowan (WC) model is a well-established model to describe the average dynamics of neural populations and has been shown to exhibit bistability in the presence of noise. However, the important question of how the different stable regimes in the WC model can affect synaptic plasticity when cortical populations interact has not yet been addressed. Therefore, we investigated plasticity dynamics in a WC-based model of interacting neural populations coupled with activity-dependent synapses in which a periodic stimulation was applied in the presence of noise of controlled intensity. The results indicate that for a narrow range of the noise variance, synaptic strength can be optimized. In particular, there is a regime of noise intensity for which synaptic strength presents a triple-stable state. Regulating noise intensity affects the probability that the system chooses one of the stable states, thereby controlling plasticity. These results suggest that noise is a highly influential factor in determining the outcome of plasticity induced by stimulation.
Posterior division of ipsilateral C7 transfer to C5 for shoulder abduction limitation
Authors: Huang Xinying , You Zongqi , Xiang Yaoxian , Dai Junxi , Jiang Junjian
Published: February 2023

Background

Reparation of C5 by proximal selective ipsilateral C7 transfer has been reported for the treatment of neurogenic shoulder abduction limitation as an alternative to the reparation of the suprascapular nerve (SSN) and the axillary nerve (AXN) by distal nerve transfers. However, there is a lack of evidence to support either strategy leading to better outcomes based on long-term follow-up.

Objective

The purpose of the study was to investigate the safety and long-term outcomes of the posterior division of ipsilateral C7 (PDIC7) transfer to C5 in treating neurogenic shoulder abduction limitation.

Methods

A total of 27 cases with limited shoulder abduction caused by C5 injury (24 cases of trauma, 2 cases of neuritis, and 1 case of iatrogenic injury) underwent PDIC7 transfer to the C5 root. A total of 12 cases (11 cases of trauma and 1 case of neuritis) of C5 injury underwent spinal accessory nerve (SAN) transfer to SSN plus the triceps muscular branch of the radial nerve (TMBRN) transfer to AXN. The patients were followed up for at least 12 months for muscle strength and shoulder abduction range of motion (ROM).

Results

In cases that underwent PDIC7 transfer, the average shoulder abduction was 105.9° at the 12-month follow-up. In total, 26 of 27 patients recovered at least M3 (13 reached M4) (Medical Research Council Grading) of the deltoid. In cases that underwent SAN transfer to SSN plus TMBRN to AXN, the average shoulder abduction was 84.6° at the 12-month follow-up. In total, 11 of 12 patients recovered at least M3 (4 reached M4) of the deltoid.

Conclusion

Posterior division of ipsilateral C7 transfer is a one-stage, safe, and effective surgical procedure for patients with neurogenic shoulder abduction limitation.
Video-based marker-free tracking and multi-scale analysis of mouse locomotor activity and behavioral aspects in an open field arena: A perspective approach to the quantification of complex gait disturbances associated with Alzheimer's disease
Authors: Bogachev Mikhail , Sinitca Aleksandr , Grigarevichius Konstantin , Pyko Nikita , Lyanova Asya , Tsygankova Margarita , Davletshin Eldar , Petrov Konstantin , Ageeva Tatyana , Pyko Svetlana , Kaplun Dmitrii , Kayumov Airat , Mukhamedshina Yana
Published: February 2023

Introduction

Complex gait disturbances represent one of the prominent manifestations of various neurophysiological conditions, including widespread neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Therefore, instrumental measurement techniques and automatic computerized analysis appears essential for the differential diagnostics, as well as for the assessment of treatment effectiveness from experimental animal models to clinical settings.

Methods

Here we present a marker-free instrumental approach to the analysis of gait disturbances in animal models. Our approach is based on the analysis of video recordings obtained with a camera placed underneath an open field arena with transparent floor using the DeeperCut algorithm capable of online tracking of individual animal body parts, such as the snout, the paws and the tail. The extracted trajectories of animal body parts are next analyzed using an original computerized methodology that relies upon a generalized scalable model based on fractional Brownian motion with parameters identified by detrended partial cross-correlation analysis.

Results

We have shown that in a mouse model representative movement patterns are characterized by two asymptotic regimes characterized by integrated 1/f noise at small scales and nearly random displacements at large scales separated by a single crossover. More detailed analysis of gait disturbances revealed that the detrended cross-correlations between the movements of the snout, paws and tail relative to the animal body midpoint exhibit statistically significant discrepancies in the Alzheimer's disease mouse model compared to the control group at scales around the location of the crossover.

Discussion

We expect that the proposed approach, due to its universality, robustness and clear physical interpretation, is a promising direction for the design of applied analysis tools for the diagnostics of various gait disturbances and behavioral aspects in animal models. We further believe that the suggested mathematical models could be relevant as a complementary tool in clinical diagnostics of various neurophysiological conditions associated with movement disorders.
Exploring neurocognitive factors and brain activation in adult cochlear implant recipients associated with speech perception outcomes—A scoping review
Authors: Beckers Loes , Tromp Nikki , Philips Birgit , Mylanus Emmanuel , Huinck Wendy
Published: February 2023

Background

Cochlear implants (CIs) are considered an effective treatment for severe-to-profound sensorineural hearing loss. However, speech perception outcomes are highly variable among adult CI recipients. Top-down neurocognitive factors have been hypothesized to contribute to this variation that is currently only partly explained by biological and audiological factors. Studies investigating this, use varying methods and observe varying outcomes, and their relevance has yet to be evaluated in a review. Gathering and structuring this evidence in this scoping review provides a clear overview of where this research line currently stands, with the aim of guiding future research.

Objective

To understand to which extent different neurocognitive factors influence speech perception in adult CI users with a postlingual onset of hearing loss, by systematically reviewing the literature.

Methods

A systematic scoping review was performed according to the PRISMA guidelines. Studies investigating the influence of one or more neurocognitive factors on speech perception post-implantation were included. Word and sentence perception in quiet and noise were included as speech perception outcome metrics and six key neurocognitive domains, as defined by the DSM-5, were covered during the literature search (Protocol in open science registries: 10.17605/OSF.IO/Z3G7W of searches in June 2020, April 2022).

Results

From 5,668 retrieved articles, 54 articles were included and grouped into three categories using different measures to relate to speech perception outcomes: (1) Nineteen studies investigating brain activation, (2) Thirty-one investigating performance on cognitive tests, and (3) Eighteen investigating linguistic skills.

Conclusion

The use of cognitive functions, recruiting the frontal cortex, the use of visual cues, recruiting the occipital cortex, and the temporal cortex still available for language processing, are beneficial for adult CI users. Cognitive assessments indicate that performance on non-verbal intelligence tasks positively correlated with speech perception outcomes. Performance on auditory or visual working memory, learning, memory and vocabulary tasks were unrelated to speech perception outcomes and performance on the Stroop task not to word perception in quiet. However, there are still many uncertainties regarding the explanation of inconsistent results between papers and more comprehensive studies are needed e.g., including different assessment times, or combining neuroimaging and behavioral measures.

Systematic review registration

https://doi.org/10.17605/OSF.IO/Z3G7W.
Spatial localization during open-loop smooth pursuit
Authors: Dowiasch Stefan , Blanke Marius , Knöll Jonas , Bremmer Frank
Published: February 2023

Introduction

Numerous previous studies have shown that eye movements induce errors in the localization of briefly flashed stimuli. Remarkably, the error pattern is indicative of the underlying eye movement and the exact experimental condition. For smooth pursuit eye movements (SPEM) and the slow phase of the optokinetic nystagmus (OKN), perceived stimulus locations are shifted in the direction of the ongoing eye movement, with a hemifield asymmetry observed only during SPEM. During the slow phases of the optokinetic afternystagmus (OKAN), however, the error pattern can be described as a perceptual expansion of space. Different from SPEM and OKN, the OKAN is an open-loop eye movement.

Methods

Visually guided smooth pursuit can be transformed into an open–loop eye movement by briefly blanking the pursuit target (gap). Here, we examined flash localization during open-loop pursuit and asked, whether localization is also prone to errors and whether these are similar to those found during SPEM or during OKAN. Human subjects tracked a pursuit target. In half of the trials, the target was extinguished for 300 ms (gap) during the steady–state, inducing open–loop pursuit. Flashes were presented during this gap or during steady–state (closed–loop) pursuit.

Results

In both conditions, perceived flash locations were shifted in the direction of the eye movement. The overall error pattern was very similar with error size being slightly smaller in the gap condition. The differences between errors in the open- and closed-loop conditions were largest in the central visual field and smallest in the periphery.

Discussion

We discuss the findings in light of the neural substrates driving the different forms of eye movements.
Superstorm Sandy exposure in utero is associated with neurobehavioral phenotypes and brain structure alterations in childhood: A machine learning approach
Authors: Demirci Gozde M. , DeIngeniis Donato , Wong Wai Man , Shereen A. Duke , Nomura Yoko , Tsai Chia-Ling
Published: February 2023

Introduction

Prenatal maternal stress (PNMS), including exposure to natural disasters, has been shown to serve as a risk factor for future child psychopathology and suboptimal brain development, particularly among brain regions shown to be sensitive to stress and trauma exposure. However, statistical approaches deployed in most studies are usually constrained by a limited number of variables for the sake of statistical power. Explainable machine learning, on the other hand, enables the study of high data dimension and offers novel insights into the prominent subset of behavioral phenotypes and brain regions most susceptible to PNMS. In the present study, we aimed to identify the most important child neurobehavioral and brain features associated with in utero exposure to Superstorm Sandy (SS).

Methods

By leveraging an explainable machine learning technique, the Shapley additive explanations method, we tested the marginal feature effect on SS exposures and examined the individual variable effects on disaster exposure.

Results

Results show that certain brain regions are especially sensitive to in utero exposure to SS. Specifically, in utero SS exposure was associated with larger gray matter volume (GMV) in the right caudate, right hippocampus, and left amygdala and smaller GMV in the right parahippocampal gyrus. Additionally, higher aggression scores at age 5 distinctly correlated with SS exposure.

Discussion

These findings suggest in utero SS exposure may be associated with greater aggression and suboptimal developmental alterations among various limbic and basal ganglia brain regions.
MicroRNAs in spinal cord injury: A narrative review
Authors: Zhang Chunjia , Talifu Zuliyaer , Xu Xin , Liu Wubo , Ke Han , Pan Yunzhu , Li Yan , Bai Fan , Jing Yingli , Li Zihan , Li Zehui , Yang Degang , Gao Feng , Du Liangjie , Li Jianjun , Yu Yan
Published: February 2023

Spinal cord injury (SCI) is a global medical problem with high disability and mortality rates. At present, the diagnosis and treatment of SCI are still lacking. Spinal cord injury has a complex etiology, lack of diagnostic methods, poor treatment effect and other problems, which lead to the difficulty of spinal cord regeneration and repair, and poor functional recovery. Recent studies have shown that gene expression plays an important role in the regulation of SCI repair. MicroRNAs (miRNAs) are non-coding RNA molecules that target mRNA expression in order to silence, translate, or interfere with protein synthesis. Secondary damage, such as oxidative stress, apoptosis, autophagy, and inflammation, occurs after SCI, and differentially expressed miRNAs contribute to these events. This article reviews the pathophysiological mechanism of miRNAs in secondary injury after SCI, focusing on the mechanism of miRNAs in secondary neuroinflammation after SCI, so as to provide new ideas and basis for the clinical diagnosis and treatment of miRNAs in SCI. The mechanisms of miRNAs in neurological diseases may also make them potential biomarkers and therapeutic targets for spinal cord injuries.
The relationship between fermentable carbohydrates and post-prandial bowel symptoms in patients with functional bowel disorders
Authors: MacIntosh Alice , Heenan Phoebe E. , Wright-McNaughton Morag , Frampton Chris , Skidmore Paula , Wall Catherine L. , Muir Jane , Talley Nicholas Joseph , Roy Nicole Clemence , Gearry Richard B.
Published: February 2023

Background and aims

A low fermentable oligosaccharide, disaccharide, monosaccharide, and polyols (FODMAP) diet alleviates symptoms of irritable bowel syndrome (IBS). We aimed to investigate the relationship between habitual FODMAP intake and post-prandial bowel symptoms in adults with IBS, functional diarrhoea (FD), or constipation (FD) (functional bowel disorders), and in healthy adults (controls).

Methods

292 participants (173 with functional bowel disorders and 119 controls) completed a food and symptom times diary. Estimated meal portion sizes were entered into the Monash FODMAP Calculator to analyse FODMAP content. Wilcoxon and ANOVA tests were used to investigate the relationship between FODMAP intake and post-prandial bowel symptoms.

Results

IBS participants experienced more post-prandial bowel symptoms compared to participants with other functional bowel disorders or controls. Meals associated with abdominal pain contained on average increased excess fructose (0.31 g vs. 0.18 g, p < 0.05), sorbitol (0.27 g vs. 0.10 g, p < 0.01), and total FODMAP (3.46 g vs. 2.96 g, p < 0.05) compared to meals not associated with pain. Abdominal swelling was associated with increased sorbitol (0.33 g vs. 0.11 g, p < 0.01), and total FODMAP (3.26 g vs. 3.02 g, p < 0.05) consumption. Abdominal bloating was associated with increased galacto oligosaccharide consumption (0.18 g vs. 0.14 g, p < 0.05).

Conclusion

These findings support the role of FODMAP in post-prandial bowel symptom onset, however, the amount and type of FODMAP triggering symptoms vary between individuals. Future research should investigate the relationship between the effect of individual FODMAP consumption on post-prandial bowel symptoms for each subtype, the interaction of FODMAP with differing functional bowel disorders and whether longitudinally symptoms and dietary intake are stable.
Body mass index, C-reactive protein, and pancreatic cancer: A Mendelian randomization analysis to investigate causal pathways
Authors: Li Zhenqi , Jin Liquan , Xia Lu , Li Xiangzhi , Guan Yunfei , He Hongyang
Published: February 2023

Aim

To explore whether C-reactive protein (CRP) mediates the risk of body mass index (BMI) in pancreatic cancer (PC) and calculate the mediate proportion of CRP in this possible mechanism.

Methods

Based on two-sample Mendelian randomization (TSMR), a two-step Mendelian randomization (TM) model was conducted to determine whether CRP was a mediator of the causal relationship between BMI and PC. The multivariable Mendelian randomization (MVMR) study was designed for mediating analysis and to calculate the mediating proportion mediated by CRP.

Results

BMI has a positive causal relationship with PC (n = 393 SNPs, OR = 1.484, 95% CI: 1.021–2.157, p< 0.05). BMI has a positive causal relationship with CRP (n = 179 SNPs, OR = 1.393, 95% CI: 1.320–1.469, p< 0.05). CRP has a positive causal relationship with PC (n = 54 SNPs, OR = 1.348, 95% CI: 1.004–1.809, p< 0.05). After adjusting CRP, BMI has no causal relationship with PC (n = 334 SNPs, OR = 1.341, 95% CI: 0.884–2.037, p< 0.05). After adjusting BMI, there was still a positive causal relationship between CRP and PC (n = 334 SNPs, OR = 1.441, 95% CI: 1.064–1.950, p< 0.05). The mediating effect of CRP was 29%.

Conclusions

In clinical practice, while actively advocating for weight loss among obese patients, we should focus on chronic inflammation levels in obese patients as well. In addition, anti-inflammatory dietary patterns and appropriate physical activity are important in preventing PC.
Antibody-removal therapies for de novo DSA in pediatric intestinal recipients: Why, when, and how? A single-center experience
Authors: Lasa-Lázaro María , Ramos-Boluda Esther , Mancebo Esther , Castro-Panete María José , González-Sacristán Rocío , Serradilla Javier , Andrés-Moreno Ane Miren , Hernández-Oliveros Francisco , Paz-Artal Estela , Talayero Paloma
Published: February 2023

Background

Donor-specific anti-HLA antibodies (DSA) impact negatively on the outcome of intestinal grafts. Although the use of antibody-removal therapies (ART) is becoming more frequent in the last few years, issues regarding their timing and effectiveness remain under discussion.

Methods

In the present study, we report our experience with eight ART procedures (based on plasmapheresis, intravenous immunoglobulin, and rituximab) in eight pediatric intestinal and multivisceral transplants with de novo DSA (dnDSA).

Results

ART were performed when dnDSA appeared in two contexts: (1) concomitant with rejection (acute or chronic) or (2) without rejection or any other clinical symptom. Complete DSA removal was observed in seven out of eight patients, showing an effectiveness of 88%. In the group treated for dnDSA without clinical symptoms, the success rate was 100%, with complete DSA removal and without rejection afterward. A shorter time between DSA detection and ART performance appeared as a significant factor for the success of the therapy (p = 0.0002). DSA against HLA-A and DQ alleles were the most resistant to ART, whereas anti-DR DSA were the most sensitive. In addition, the 8-year allograft survival rate in recipients undergoing ART was similar to that in those without DSA, being significantly lower in non-treated DSA-positive recipients (p = 0.013).

Conclusion

The results confirm the effectiveness of ART in terms of DSA removal and allograft survival and encourage its early use even in the absence of clinical symptoms.
MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease
Authors: Weinheimer Oliver , Konietzke Philip , Wagner Willi L. , Weber Dorothea , Newman Beverly , Galbán Craig J. , Kauczor Hans-Ulrich , Mall Marcus A. , Robinson Terry E. , Wielpütz Mark O.
Published: February 2023

Objectives

Quantitative computed tomography (QCT) offers some promising markers to quantify cystic fibrosis (CF)-lung disease. Air trapping may precede irreversible bronchiectasis; therefore, the temporal interdependencies of functional and structural lung disease need to be further investigated. We aim to quantify airway dimensions and air trapping on chest CT of school-age children with mild CF-lung disease over two years.

Methods

Fully-automatic software analyzed 144 serial spirometer-controlled chest CT scans of 36 children (median 12.1 (10.2–13.8) years) with mild CF-lung disease (median ppFEV1 98.5 (90.8–103.3) %) at baseline, 3, 12 and 24 months. The airway wall percentage (WP5–10), bronchiectasis index (BEI), as well as severe air trapping (A3) were calculated for the total lung and separately for all lobes. Mixed linear models were calculated, considering the lobar distribution of WP5–10, BEI and A3 cross-sectionally and longitudinally.

Results

WP5–10 remained stable (P = 0.248), and BEI changed from 0.41 (0.28–0.7) to 0.54 (0.36–0.88) (P = 0.156) and A3 from 2.26% to 4.35% (P = 0.086) showing variability over two years. ppFEV1 was also stable (P = 0.276). A robust mixed linear model showed a cross-sectional, regional association between WP5–10 and A3 at each timepoint (P < 0.001). Further, BEI showed no cross-sectional, but another mixed model showed short-term longitudinal interdependencies with air trapping (P = 0.003).

Conclusions

Robust linear/beta mixed models can still reveal interdependencies in medical data with high variability that remain hidden with simpler statistical methods. We could demonstrate cross-sectional, regional interdependencies between wall thickening and air trapping. Further, we show short-term regional interdependencies between air trapping and an increase in bronchiectasis. The data indicate that regional air trapping may precede the development of bronchiectasis. Quantitative CT may capture subtle disease progression and identify regional and temporal interdependencies of distinct manifestations of CF-lung disease.
Case report: Savolitinib induced severe adverse reactions resembling septic shock in an HIV-1–positive patient with advanced non-small cell lung cancer
Authors: Xiong Ye , Cao Qing , Guo Yongzheng , Liu Xiang , Zhu Xueling , Dai Bohao , Zhu Biao
Published: February 2023

Savolitinib, a small-molecule inhibitor of the receptor tyrosine kinase mesenchymal-epithelial transition (MET) factor, was approved for the treatment of non-small cell lung cancer (NSCLC) by the China National Medical Products Administration in June 2021. Its safety for NSCLC treatment has been confirmed in several prospective cohort studies. Herein, we report a rare case of shock, a serious adverse event, after treatment with savolitinib in an HIV-1–positive patient with advanced NSCLC. A 38-year-old man with an 8-year history of HIV-1 positivity was diagnosed with NSCLC 5 years ago; the lung cancer recurred after surgical resection. Despite chemotherapy, immunotherapy, and targeted therapy, tumor progression continued. He received savolitinib because of MET amplification. In the first 2 weeks of savolitinib use, he developed a mild rash on his trunk. In the following month, he was hospitalized for fever and circulatory shock thrice after taking savolitinib 400 mg. He had no urticaria or eosinophilia. During the three hospitalizations, he was negative for pathogens. His condition gradually improved after treatment with antibiotics, steroids, and vasopressors. Attention should be paid to the occurrence of septic shock-like presentations when using savolitinib in HIV-1 patients with NSCLC.
Clofazimine for the treatment of tuberculosis
Authors: Stadler Jacob A. M. , Maartens Gary , Meintjes Graeme , Wasserman Sean
Published: February 2023

Shorter (6–9 months), fully oral regimens containing new and repurposed drugs are now the first-choice option for the treatment of drug-resistant tuberculosis (DR-TB). Clofazimine, long used in the treatment of leprosy, is one such repurposed drug that has become a cornerstone of DR-TB treatment and ongoing trials are exploring novel, shorter clofazimine-containing regimens for drug-resistant as well as drug-susceptible tuberculosis. Clofazimine’s repurposing was informed by evidence of potent activity against DR-TB strains in vitro and in mice and a treatment-shortening effect in DR-TB patients as part of a multidrug regimen. Clofazimine entered clinical use in the 1950s without the rigorous safety and pharmacokinetic evaluation which is part of modern drug development and current dosing is not evidence-based. Recent studies have begun to characterize clofazimine’s exposure-response relationship for safety and efficacy in populations with TB. Despite being better tolerated than some other second-line TB drugs, the extent and impact of adverse effects including skin discolouration and cardiotoxicity are not well understood and together with emergent resistance, may undermine clofazimine use in DR-TB programmes. Furthermore, clofazimine’s precise mechanism of action is not well established, as is the genetic basis of clofazimine resistance. In this narrative review, we present an overview of the evidence base underpinning the use and limitations of clofazimine as an antituberculosis drug and discuss advances in the understanding of clofazimine pharmacokinetics, toxicity, and resistance. The unusual pharmacokinetic properties of clofazimine and how these relate to its putative mechanism of action, antituberculosis activity, dosing considerations and adverse effects are highlighted. Finally, we discuss the development of novel riminophenazine analogues as antituberculosis drugs.
Pharmacological screening of silibinin for antischizophrenic activity along with its acute toxicity evaluation in experimental animals
Authors: Ain Qurat Ul , Saleem Uzma , Ahmad Bashir , Khalid Iqra
Published: February 2023

Silibinin (SIL), a flavolignan extracted from the medicinal plant “silybum marianum (milk thistle)”, has traditionally been used to treat liver disease. This phytochemical has displayed neuroprotective properties, its activity against schizophrenia is not elucidated. The present study was designed to evaluate the antipsychotic potential of silibinin and probe its toxic potential. The acute oral toxicity study was assessed as per OECD 425 guidelines. Animals were divided into two groups of female rats (n = 6): one group served as the normal control and the other group received a 2,000 mg/kg dose of SIL. We also evaluated the antipsychotic potential of SIL. To this end, animals were divided into six groups (n = 10) of mice for both the preventive and curative protocols. Group I (CMC 1 mL/kg) served as the normal control and received CMC 1 mL/kg; group II was the diseased group treated with ketamine (10 mg/kg) i.p; group III was the standard group treated with clozapine 1 mg/kg; groups IV, V, and VI served as the treatment groups, receiving SIL 50, 100, and 200 mg/kg, respectively, orally for both protocols. Improvement in positive symptoms of the disease was evaluated by stereotypy and hyperlocomotion, while negative symptoms (behavioral despair) were determined by a forced swim test and a tail suspension test in the mice models. The results suggested that the LD50 of SIL was greater than 2,000 mg/kg. Moreover, SIL prevented and reversed ketamine-induced increase in stereotypy (p < 0.001) and behavioral despair in the forced swim and tail suspension tests (p < 0.001). Taken together, the findings suggest that silibinin is a safe drug with low toxicity which demonstrates significant antipsychotic activity against the positive and negative symptoms of schizophrenia.
High-power Er:Y2O3 ceramic laser with an optical vortex beam output at ∼ 2.7 μm
Authors: Ding Manman , Wang Jun , Wang Fei , Shen Deyuan , Tang Dingyuan , Zhu Heyuan
Published: February 2023

We report on the direct generation of the high-power optical vortices at ∼2.7 μm from an Er:Y2O3 ceramic laser end-pumped by an annular pump beam using a simple capillary fiber-based pump beam conditioning scheme. Taking advantage of the thermal gradient on the gain medium and mode matching between the pump and oscillating modes, vortex beams with a controllable topological charge order of l = 1 and l = 2 were successfully achieved. The laser yields 4.65 W of output power at an absorbed power of 19.8 W, corresponding to a slope efficiency of 25.9% with respect to the absorbed pump power. Adaptable beam profiles from a shallow crater-shape to quasi-top-hat intensity patterns were directly produced by actively defining the gain distribution in the ceramic, generating 4-W shallow crater-shape beams and 3.9-W quasi-top-hat beams, corresponding to a slope efficiency of 22.0% and 22.7%, respectively. Such optical vortices and tailored spatial intensity profiles in the 3-µm spectral region will enable novel applications, such as super-resolution molecular spectroscopy and material processing.
Performance analysis of SMI filter for antenna array receiver in pulse interference environment
Authors: Wang Jie , Ou Gang , Liu Wenxiang , Lu Zukun , Yin Haibo
Published: February 2023

This paper analyzes the performance of sample matrix inversion (SMI) filter used by antenna array receivers in pulse interference environment. Firstly, from the perspective of comparison, it is proved that the theoretical optimal signal to interference noise ratio (SINR) of SMI filter under pulse interference is the same with that under continuous interferences. Then the convergence characteristics of SMI filter under pulse interference are deduced, and the relationship between the convergence speed and length of training samples and duty of interferences is given. Finally, the results of signal simulation are consistent with those of numerical analysis, which verifies the correctness of theoretical analysis. The results show that the convergence speed of SMI filter decreases under pulse interference, and the SMI filter needs more training samples to suppress the pulse interference effectively.
A bibliometric review of 35 years of studies about preeclampsia
Authors: Akbari Razieh , Hantoushzadeh Sedigheh , Panahi Zahra , Bahonar Sajedeh , Ghaemi Marjan
Published: February 2023

The purpose of this study is to investigate preeclampsia. It used the visualization tools of CiteSpace, VOSviewer, Gunnmap, Bibliometrix®, and Carrot2 to analyze 3,754 preeclampsia studies from 1985 to 2020 in Obstetrics and Gynecology areas. Carrot2 was used to explain each cluster in extra detail. The results found that there is an increasing trend in many publications related to preeclampsia from 1985 to 2020. The number of studies on preeclampsia has increased significantly in the last century. Analysis of the keywords found a strong relationship with preeclampsia concepts and keywords classified into five categories. Co-citation analysis was also performed which was classified into six categories. Reading the article offers important to support not only to grind the context of preeclampsia challenges but also to design a new trend in this field. The number of studies on preeclampsia has substantially improved over the decades ago. The findings of documents published from 1985 to 2020 showed three stages in research on this subject: 1985 to 1997 (a seeding stage), 1997–2005 (rapid growth stage), and 2005 onwards (development stage).
Develop a preliminary core germplasm with the novel polymorphism EST-SSRs derived from three transcriptomes of colored calla lily (Zantedeschia hybrida)
Authors: Wang Yi , Yang Tuo , Wang Xue , Sun Xuan , Liu Hongyan , Wang Di , Wang Huanxiao , Zhang Guojun , Li Yanbing , Wang Xian , Wei Zunzheng
Published: February 2023

The development of high-throughput sequencing technology has made it possible to develop molecular markers such as EST-SSR from transcriptome sequences in non-model plants such as bulbous flowers. However, the EST-SSR markers that have been developed are weakly validated and low polymorphic due to the short read size and poor quality of the assembled sequences. This study therefore used the CandiSSR pipeline to identify 550 potential polymorphic SSR loci among 487 homologous unigenes based on the transcriptomic sequences of three varieties of colored calla lily, and 460 of these loci with appropriate flanking sequences were suitable for primer pairs design. A further validation with 200 randomly selected EST-SSRs demonstrated an increase of more than 30% and 100% in amplification validity and polymorphism, respectively, in comparison with our previous study. In addition, since most of the current varieties of colored calla lily are hybridized from a few species, which have low genetic diversity, we subsequently identified primary core germplasm for 160 colored calla lily accessions using the aforementioned 40 polymorphic EST-SSRs. It was concluded that the core germplasm containing 42 accessions derived from the M strategy incorporated into the software Power Core was the most representative of all 160 original germplasm, as evidenced by the preservation of 100% of the EST-SSR variation, with a higher level of genetic diversity and heterogeneity (Nei = 0.40, I = 0.66, PIC = 0.43). This study provides a practical example of polymorphism EST-SSR markers developed from multiple transcriptomes for non-model plants. A future breeding program for colored calla lily will also benefit from the core germplasm defined by those molecular markers.
OsPSTOL but not TaPSTOL can play a role in nutrient use efficiency and works through conserved pathways in both wheat and rice
Authors: Milner Matthew J. , Bowden Sarah , Craze Melanie , Wallington Emma J.
Published: February 2023

There is a large demand to reduce inputs for current crop production, particularly phosphate and nitrogen inputs which are the two most frequently added supplements to agricultural production. Gene characterization is often limited to the native species from which it was identified, but may offer benefits to other species. To understand if the rice gene Phosphate Starvation Tolerance 1 (PSTOL) OsPSTOL, a gene identified from rice which improves tolerance to low P growth conditions, might improve performance and provide the same benefit in wheat, OsPSTOL was transformed into wheat and expressed from a constitutive promoter. The ability of OsPSTOL to improve nutrient acquisition under low phosphate or low nitrogen was evaluated. Here we show that OsPSTOL works through a conserved pathway in wheat and rice to improve yields under both low phosphate and low nitrogen. This increase is yield is mainly driven by improved uptake from the soil driving increased biomass and ultimately increased seed number, but does not change the concentration of N in the straw or grain. Overexpression of OsPSTOL in wheat modifies N regulated genes to aid in this uptake whereas the putative homolog TaPSTOL does not suggesting that expression of OsPSTOL in wheat can help to improve yields under low input agriculture.
Identification of QTLs and critical genes related to sugarcane mosaic disease resistance
Authors: Lu Guilong , Wang Zhoutao , Pan Yong-Bao , Wu Qibin , Cheng Wei , Xu Fu , Dai Shunbin , Li Boyu , Que Youxiong , Xu Liping
Published: February 2023

Mosaic viral diseases affect sugarcane productivity worldwide. Mining disease resistance-associated molecular markers or genes is a key component of disease resistance breeding programs. In the present study, 285 F1 progeny were produced from a cross between Yuetang 93-159, a moderately resistant variety, and ROC22, a highly susceptible variety. The mosaic disease symptoms of these progenies, with ROC22 as the control, were surveyed by natural infection under 11 different environmental conditions in the field and by artificial infections with a mixed sugarcane mosaic virus (SCMV) and sorghum mosaic virus (SrMV) inoculum. Analysis of consolidated survey data enabled the identification of 29 immune, 55 highly resistant, 70 moderately resistant, 62 susceptible, and 40 highly susceptible progenies. The disease response data and a high-quality SNP genetic map were used in quantitative trait locus (QTL) mapping. The results showed that the correlation coefficients (0.26~0.91) between mosaic disease resistance and test environments were significant (p< 0.001), and that mosaic disease resistance was a highly heritable quantitative trait (H2 = 0.85). Seven mosaic resistance QTLs were located to the SNP genetic map, each QTL accounted for 3.57% ~ 17.10% of the phenotypic variation explained (PVE). Furthermore, 110 pathogen response genes and 69 transcription factors were identified in the QTLs interval. The expression levels of nine genes (Soffic.07G0015370-1P, Soffic.09G0015410-2T, Soffic.09G0016460-1T, Soffic.09G0016460-1P, Soffic.09G0017080-3C, Soffic.09G0018730-3P, Soffic.09G0018730-3C, Soffic.09G0019920-3C and Soffic.03G0019710-2C) were significantly different between resistant and susceptible progenies, indicating their key roles in sugarcane resistance to SCMV and SrMV infection. The seven QTLs and nine genes can provide a certain scientific reference to help sugarcane breeders develop varieties resistant to mosaic diseases.
Increasing precipitation during first half of growing season enhances ecosystem water use efficiency in a semiarid grassland
Authors: Zhang Jiayang , Yang Zhongling , Qiao Daiyu , Su Lei
Published: February 2023

Precipitation amount and seasonality can profoundly impact ecosystem carbon (C) and water fluxes. Water use efficiency (WUE), which measures the amount of C assimilation relative to the amount of water loss, is an important metric linking ecosystem C and water cycles. However, how increasing precipitation at different points in the growing season affects ecosystem WUE remains unclear. A manipulative experiment simulating increasing first half (FP+) and/or second half (SP+) of growing-season precipitation was conducted for 4 years (2015-2018) in a temperate steppe in the Mongolian Plateau. Gross ecosystem productivity (GEP) and evapotranspiration (ET) were measured to figure out ecosystem WUE (WUE = GEP/ET). Across the four years, FP+ showed no considerable impact on ecosystem WUE or its two components, GEP and ET, whereas SP+ stimulated GEP but showed little impact on ET, causing a positive response of WUE to FP+. The increased WUE was mainly due to higher soil water content that maintained high aboveground plant growth and community cover while ET was stable during the second half of growing season. These results illustrate that second half of growing-season precipitation is more important in regulating ecosystem productivity in semiarid grasslands and highlight how precipitation seasonality affects ecosystem productivity in the temperate steppe ecosystem.
Photosynthetic activity and metabolic profiling of bread wheat cultivars contrasting in drought tolerance
Authors: Ghaffar Abdul , Hussain Nadeem , Ajaj Rahaf , Shahin Suzan Marwan , Bano Hussan , Javed Muhammad , Khalid Ayesha , Yasmin Memoona , Shah Kausar Hussain , Zaheer Muhammad , Iqbal Muhammad , Zafar Zafar Ullah , Athar Habib-ur-Rehman
Published: February 2023

The rapid increase in population growth under changing climatic conditions causes drought stress, threatening world food security. The identification of physiological and biochemical traits acting as yield-limiting factors in diverse germplasm is pre-requisite for genetic improvement under water-deficit conditions. The major aim of the present study was the identification of drought-tolerant wheat cultivars with a novel source of drought tolerance from local wheat germplasm. The study was conducted to screen 40 local wheat cultivars against drought stress at different growth stages. Barani-83, Blue Silver, Pak-81, and Pasban-90 containing shoot and root fresh weight >60% of control and shoot and root dry weight >80% and 70% of control, respectively, P (% of control >80 in shoot and >88 in root), K+ (>85% of control), and quantum yield of PSII > 90% of control under polyethylene glycol (PEG)-induced drought stress at seedling stage can be considered as tolerant, while more reduction in these parameters make FSD-08, Lasani-08, Punjab-96, and Sahar-06 as drought-sensitive cultivars. FSD-08 and Lasani-08 could not maintain growth and yield due to protoplasmic dehydration, decreased turgidity, cell enlargement, and cell division due to drought treatment at adult growth stage. Stability of leaf chlorophyll content (<20% decrease) reflects photosynthetic efficiency of tolerant cultivars, while ~30 µmol/g fwt concentration of proline, 100%–200% increase in free amino acids, and ~50% increase in accumulation of soluble sugars were associated with maintaining leaf water status by osmotic adjustment. Raw OJIP chlorophyll fluorescence curves revealed a decrease in fluorescence at O, J, I, and P steps in sensitive genotypes FSD-08 and Lasani-08, showing greater damage to photosynthetic machinery and greater decrease in JIP test parameters, performance index (PIABS), maximum quantum yield (Fv/Fm) associated with increase in Vj, absorption (ABS/RC), and dissipation per reaction center (DIo/RC) while a decrease in electron transport per reaction center (ETo/RC). During the present study, differential modifications in morpho-physiological, biochemical, and photosynthetic attributes that alleviate the damaging effects of drought stress in locally grown wheat cultivars were analyzed. Selected tolerant cultivars could be explored in various breeding programs to produce new wheat genotypes with adaptive traits to withstand water stress.
Effect of intimacy and dyadic coping on psychological distress in pancreatic cancer patients and spousal caregivers
Authors: Li Jiarong , Liu Linglong , Chen Mingxia , Su Wang , Yao Tianying , Li Xiaoxuan
Published: February 2023

Aims

The aim of this study was to investigate the effect of intimacy and dyadic coping on anxiety and depression in patients with pancreatic cancer and their spousal caregivers.

Methods

This study conducted from October 2021 to June 2022, included 277 pancreatic cancer patients and their spousal caregivers. This research used actor-partner interdependence mediation model to explore the relationship of intimacy, dyadic coping, and psychological distress among pancreatic cancer patients and their spousal caregivers.

Results

The results of this study showed that there were two actor effects: the satisfaction of intimate relationship between pancreatic cancer patients and their spouse caregivers had a positive predictive effect on their dyadic coping (β = 1.787, p < 0.001) and (β = 1.587, p < 0.001). The dyadic coping of pancreatic cancer patients and their spouse caregivers had a negative predictive effect on their own anxiety and depression (β = −0.253, p < 0.001) and (β = −0.293, p < 0.001). The results of this study showed that there was a partner effect: intimate relationship satisfaction of pancreatic cancer patients had a positive predictive effect on dyadic coping of their spousal caregivers (β = 0.574, p < 0.05).

Conclusion

This study demonstrates the interdependence of pancreatic cancer patients and their spousal caregivers in coping with the disease. The healthy intimate relationship and effective dyadic coping styles are essential to alleviating disease pressure and lowering the psychological burden on cancer families.
Exploring the mechanism of empathy on lens language and linguistic landscape on movie-induced tourism: The moderating effect of cultural differences
Authors: Zeng Yanqin , Xu Ziqi , Chen Liang , Huang Yunxi
Published: February 2023

Since the development of film-induced tourism, scholars have increasingly shifted their attention to examining film-induced tourism from different perspectives. However, little research has been devoted to the underlying mechanisms by which audiences empathize with movie scenes. Current research believes that the lens language of movies is helpful for the communication between the movie and the audience. It not only helps the audience to shape the imagination of the movie scene, but also contributes to the construction of a virtual language landscape, and promotes the audience’s cognition of the movie scene. Bringing their emotions and self-expression into the story ultimately enhances the audience’s perception of where it was filmed. In exploring the framework of the transformation of empathy in lens language to landscape language, cultural differences are also proposed as the boundary conditions for the relationship between lens language and empathy. Structural equation modeling with PLS-SEM was employed to test the proposed hypotheses. The findings suggest that lens language positively predicts language landscape and empathy positively mediates the aforementioned relationship. Furthermore, the interaction term of cultural differences amplifies the relationship between lens language and empathy. Finally, we discuss theoretical and practical implications.