bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative temperature and relative humidity changes recorded by the Lake Cuoqia in the southeastern Tibetan Plateau during the past 300 years
Authors: Yan Tianlong , Zhang Can , Zhang Haixia , Sun Xiaoshuang , Liu Yilan , Liu Ruikun , Zhang Wei , Zhao Cheng
Published: February 2023

High-elevation lakes on the Tibetan Plateau have the advantage of sensitive response to climate changes. Multiple proxy records in lake sediments can provide a large amount of extractable information for paleoclimate reconstructions and assessing the position of recent global warming within the context of natural climate variability. In this study, we reconstruct the climatic and environmental changes over the past 300 years from a remote alpine lake (Lake Cuoqia) in the southeastern Tibetan Plateau using multiple proxies including branched glycerol dialkyl glycerol tetraethers (brGDGTs), n-alkanes, elements, fatty acids and their hydrogen isotopes. Due to ice-cover nature of lake surface during winter, brGDGTs mainly reflect the variation in warm-season temperature from March to October, supported by nearby instrumental data. Our reconstructed high-resolution temperature showed a continuous cooling trend between 1700 and 1950 AD, followed by a rapid warming afterward, in parallel with other proxies such as n-alkanes and fatty acids in the same core, which is also consistent with previously published regional temperature records. The hydrogen isotope (δD) of fatty acids, similar to regional tree-ring δ18O, can record the history of atmospheric precipitation isotope and further indicate the variations of regional relative humidity. Our record exhibited a long-term decrease since 1700 AD, in accord with the decreasing lake level inferred from the ratio of Fe/Mn. The combined pattern of reconstructed temperature and relative humidity showed consistent changes before 1950 AD toward to a gradually cold-dry trend, whereas started to decouple afterward. Before 1950 AD, the declined temperature and relative humidity are mainly driven by insolation and thermal contrast between the Indian-Pacific Ocean and south Asian continent. After 1950 AD, decoupling of temperature and relative humidity may be related to the increased regional evaporation and human-induced emission of greenhouse gases and aerosol.
The effect of habitat transformation on a twig epiphytic orchid: Evidence from population dynamics
Authors: Ospina-Calderón Nhora Helena , Tremblay Raymond L. , Torres Alba Marina , Flanagan Nicola S.
Published: February 2023

The tropical Andean landscape has been dramatically transformed over the last century with remaining native forest limited to small fragments within a heterogeneous matrix of crops, cattle pastures, and urban environments. We aimed to explore the impact of habitat transformation on the population dynamics in an endemic twig epiphytic orchid located within the undisturbed forest and within modified matrix habitat in two regions with contrasting landscape structures: with a dominant shade coffee matrix and a dominant grassland matrix. Over 2 years, we surveyed 4,650 individuals of the Colombian endemic orchid, Rodriguezia granadensis. We undertook four post-breeding censuses in three sites in each region in both native forest and pasture sub-sites (12 sub-sites; 48 censuses in total), and constructed demographic transition matrices (n = 36). The transition probabilities were calculated using a Bayesian approach and population grow rates were evaluated using asymptotic models and elasticities using transient dynamics. Between regions, higher population growth rate and inertia (defined as the largest or smallest long-term population density with the same initial density distribution) was seen in the shade coffee-dominated landscape. Additionally, population growth rate and damping ratio was higher in forest compared with pasture, with lower convergence time for the forest subsites. These demographic patterns reveal the contrasting levels of population resilience of this orchid in different landscape structures with the more connected shade-coffee dominated landscape permitting some healthier populations with greater population growth and survival in forest than pasture. This study highlights that twig epiphyte colonization of isolated phorophytes in pastures should not be interpreted as a sign of a healthy population but as a temporal transitory period.
The IgH Eµ-MAR regions promote UNG-dependent error-prone repair to optimize somatic hypermutation
Authors: Martin Ophélie A. , Thomas Morgane , Marquet Marie , Bruzeau Charlotte , Garot Armand , Brousse Mylène , Bender Sébastien , Carrion Claire , Choi Jee Eun , Vuong Bao Q. , Gearhart Patricia J. , Maul Robert W. , Le Noir Sandrine , Pinaud Eric
Published: February 2023

Intoduction

Two scaffold/matrix attachment regions (5’- and 3’-MARsEµ) flank the intronic core enhancer (cEµ) within the immunoglobulin heavy chain locus (IgH). Besides their conservation in mice and humans, the physiological role of MARsEµ is still unclear and their involvement in somatic hypermutation (SHM) has never been deeply evaluated.

Methods

Our study analyzed SHM and its transcriptional control in a mouse model devoid of MARsEµ, further combined to relevant models deficient for base excision repair and mismatch repair.

Results

We observed an inverted substitution pattern in of MARsEµ-deficient animals: SHM being decreased upstream from cEµ and increased downstream of it. Strikingly, the SHM defect induced by MARsEµ-deletion was accompanied by an increase of sense transcription of the IgH V region, excluding a direct transcription-coupled effect. Interestingly, by breeding to DNA repair-deficient backgrounds, we showed that the SHM defect, observed upstream from cEµ in this model, was not due to a decrease in AID deamination but rather the consequence of a defect in base excision repair-associated unfaithful repair process.

Discussion

Our study pointed out an unexpected “fence” function of MARsEµ regions in limiting the error-prone repair machinery to the variable region of Ig gene loci.
Macrophage: Key player in the pathogenesis of autoimmune diseases
Authors: Yang Shuang , Zhao Ming , Jia Sujie
Published: February 2023

The macrophage is an essential part of the innate immune system and also serves as the bridge between innate immunity and adaptive immune response. As the initiator and executor of the adaptive immune response, macrophage plays an important role in various physiological processes such as immune tolerance, fibrosis, inflammatory response, angiogenesis and phagocytosis of apoptotic cells. Consequently, macrophage dysfunction is a vital cause of the occurrence and development of autoimmune diseases. In this review, we mainly discuss the functions of macrophages in autoimmune diseases, especially in systemic lupus erythematosus (SLE), rheumatic arthritis (RA), systemic sclerosis (SSc) and type 1 diabetes (T1D), providing references for the treatment and prevention of autoimmune diseases.
The interaction between dietary fiber and gut microbiota, and its effect on pig intestinal health
Authors: Hu Ruiqi , Li Shuwei , Diao Hui , Huang Chongbo , Yan Jiayou , Wei Xiaolan , Zhou Mengjia , He Peng , Wang Tianwei , Fu Hongsen , Zhong Chengbo , Mao Chi , Wang Yongsheng , Kuang Shengyao , Tang Wenjie
Published: February 2023

Intestinal health is closely associated with overall animal health and performance and, consequently, influences the production efficiency and profit in feed and animal production systems. The gastrointestinal tract (GIT) is the main site of the nutrient digestive process and the largest immune organ in the host, and the gut microbiota colonizing the GIT plays a key role in maintaining intestinal health. Dietary fiber (DF) is a key factor in maintaining normal intestinal function. The biological functioning of DF is mainly achieved by microbial fermentation, which occurs mainly in the distal small and large intestine. Short-chain fatty acids (SCFAs), the main class of microbial fermentation metabolites, are the main energy supply for intestinal cells. SCFAs help to maintain normal intestinal function, induce immunomodulatory effects to prevent inflammation and microbial infection, and are vital for the maintenance of homeostasis. Moreover, because of its distinct characteristics (e.g. solubility), DF is able to alter the composition of the gut microbiota. Therefore, understanding the role that DF plays in modulating gut microbiota, and how it influences intestinal health, is essential. This review gives an overview of DF and its microbial fermentation process, and investigates the effect of DF on the alteration of gut microbiota composition in pigs. The effects of interaction between DF and the gut microbiota, particularly as they relate to SCFA production, on intestinal health are also illustrated.
Single-domain antibody delivery using an mRNA platform protects against lethal doses of botulinum neurotoxin A
Authors: Panova Eugenia A. , Kleymenov Denis A. , Shcheblyakov Dmitry V. , Bykonia Evgeniia N. , Mazunina Elena P. , Dzharullaeva Alina S. , Zolotar Anastasia N. , Derkaev Artem A. , Esmagambetov Ilias B. , Sorokin Ivan I. , Usachev Evgeny V. , Noskov Anatoly N. , Ivanov Igor A. , Zatsepin Timofei S. , Dmitriev Sergey E. , Gushchin Vladimir A. , Naroditsky Boris S. , Logunov Denis Y. , Gintsburg Alexander L.
Published: February 2023

Single-domain antibodies (sdAbs, VHHs, or nanobodies) are a promising tool for the treatment of both infectious and somatic diseases. Their small size greatly simplifies any genetic engineering manipulations. Such antibodies have the ability to bind hard-to-reach antigenic epitopes through long parts of the variable chains, the third complementarity-determining regions (CDR3s). VHH fusion with the canonical immunoglobulin Fc fragment allows the Fc-fusion single-domain antibodies (VHH-Fc) to significantly increase their neutralizing activity and serum half-life. Previously we have developed and characterized VHH-Fc specific to botulinum neurotoxin A (BoNT/A), that showed a 1000-fold higher protective activity than monomeric form when challenged with five times the lethal dose (5 LD50) of BoNT/A. During the COVID-19 pandemic, mRNA vaccines based on lipid nanoparticles (LNP) as a delivery system have become an important translational technology that has significantly accelerated the clinical introduction of mRNA platforms. We have developed an mRNA platform that provides long-term expression after both intramuscular and intravenous application. The platform has been extensively characterized using firefly luciferase (Fluc) as a reporter. An intramuscular administration of LNP-mRNA encoding VHH-Fc antibody made it possible to achieve its rapid expression in mice and resulted in 100% protection when challenged with up to 100 LD50 of BoNT/A. The presented approach for the delivery of sdAbs using mRNA technology greatly simplifies drug development for antibody therapy and can be used for emergency prophylaxis.
Dietary fiber alters immunity and intestinal barrier function of different breeds of growing pigs
Authors: Ding Sujuan , Cheng Yating , Azad Md. Abul Kalam , Dong Haibo , He Jun , Huang Pan , Kong Xiangfeng
Published: February 2023

Introduction

Dietary fiber (DF) regulates immune response and barrier function by interacting with epithelial cells and immune cells. However, the differences in the regulation of intestinal health of different pig breeds by DF remain obscure.

Methods

A total of 60 healthy pigs (20 pigs/breed) from Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) pigs (body weight = 11.00 ± 1.00 kg) were fed two different levels (low and high) of DF for 28 days to evaluate the differences in the modulation of intestinal immunity and barrier function by DF in different pig breeds.

Results

TB and XB pigs had higher plasma Eos level, Eos%, and Lym% but lower Neu level compared with the DR pigs when fed low DF (LDF). The TB and XB pigs had higher plasma Eos, MCV, and MCH levels and Eos% while lower Neu% compared with the DR pigs when fed high DF (HDF). HDF decreased IgA, IgG, IgM, and sIgA concentrations in the ileum of TB and XB pigs compared with the DR pigs, while the plasma IgG and IgM concentrations of TB pigs were higher than those of the DR pigs. Moreover, compared with the DR pigs, HDF decreased the levels of IL-1β, IL-17, and TGF-β in the plasma, and IL-1β, IL-2, IL-6, IL-10, IL-17, IFN-γ, TGF-β, and TNF-α in the ileum of TB and XB pigs. However, HDF did not affect the mRNA expression of cytokines in the ileum of TB, XB, and DR pigs, while HDF increased the TRAF6 expression of TB pigs compared with the DR pigs. In addition, HDF increased the Claudin abundance of TB and DR pigs compared with the pigs feeding with LDF. Moreover, in the LDF and HDF groups, the XB pigs had higher protein abundances of Claudin and ZO-1 compared with the TB and DR pigs.

Conclusions

DF regulated the TB and DR pigs’ plasma immune cells, the XB pigs showed enhanced barrier function, and the DR pigs had increased ileal inflammation, which indicates that Chinese indigenous pigs are more DF tolerant than the DR pigs.
Donor selection for adoptive immunotherapy with NK cells in AML patients: Comparison between analysis of lytic NK cell clones and phenotypical identification of alloreactive NK cell repertoire
Authors: Meazza Raffaella , Ruggeri Loredana , Guolo Fabio , Minetto Paola , Canevali Paolo , Loiacono Fabrizio , Ciardelli Sara , Bo Alessandra , Luchetti Silvia , Serio Alberto , Zannoni Letizia , Retière Christelle , Colomar-Carando Natalia , Parisi Sarah , Curti Antonio , Lemoli Roberto M. , Pende Daniela
Published: February 2023

Natural killer (NK) cell-based adoptive immunotherapy in leukemia patients is an emerging field of interest based on clinical evidence of efficacy and safety. Elderly acute myeloid leukemia (AML) patients have been successfully treated with NK cells from HLA-haploidentical donors, especially when high amounts of alloreactive NK cells were infused. The aim of this study was comparing two approaches to define the size of alloreactive NK cells in haploidentical donors for AML patients recruited in two clinical trials with the acronym “NK-AML” (NCT03955848), and “MRD-NK”. The standard methodology was based on the frequency of NK cell clones capable of lysing the related patient-derived cells. The alternative approach consisted of the phenotypic identification of freshly derived NK cells expressing, as inhibitory receptors, only the inhibitory KIR(s) specific for the mismatched KIR-Ligand(s) (HLA-C1, HLA-C2, HLA-Bw4). However, in KIR2DS2+ donors and HLA-C1+ patients, the unavailability of reagents staining only the inhibitory counterpart (KIR2DL2/L3) may lead to an underestimated identification of the alloreactive NK cell subset. Conversely, in the case of HLA-C1 mismatch, the alloreactive NK cell subset could be overestimated due to the ability of KIR2DL2/L3 to recognize with low-affinity also HLA-C2. Especially in this context, the additional exclusion of LIR1-expressing cells might be relevant to refine the size of the alloreactive NK cell subset. We could also associate degranulation assays, using as effector cells IL-2 activated donor peripheral blood mononuclear cells (PBMC) or NK cells upon co-culture with the related patient target cells. The donor alloreactive NK cell subset always displayed the highest functional activity, confirming its identification accuracy by flow cytometry. Despite the phenotypic limitations and considering the proposed corrective actions, a good correlation was shown by the comparison of the two investigated approaches. In addition, the characterization of receptor expression on a fraction of NK cell clones revealed expected but also few unexpected patterns. Thus, in most instances, the quantification of phenotypically defined alloreactive NK cells from PBMC can provide data similar to the analysis of lytic clones, with several advantages, such as a shorter time to achieve the results and, perhaps, higher reproducibility/feasibility in many laboratories.
MgO NPs catalyzed the synthesis of novel pyridin-3-yl-pyrimidin-2-yl-aminophenyl-amide derivatives and evaluation of pharmacokinetic profiles and biological activity
Authors: Gani Ibtihal Haitham , Al-Obaidi Zaid
Published: February 2023

In this study, novel pyridin-3-yl-pyrimidin-2-yl-aminophenyl-amide derivatives using two methods, namely, using trimethylamine as a classical method and using magnesium oxide nanoparticles, were synthesized. Biological activities of the derivatives such as inhibitors of receptor tyrosine kinase, pharmacokinetics profiles, anticancer activity against lung cancer, antibacterial and antifungal activity against specialized aquatic bacterial species, Gram-positive and Gram-negative species, and fungal species, and antioxidant activity were evaluated. The structures of synthetic derivatives were confirmed using FT-IR, 1H-NMR, and 13C-NMR spectra and elemental analysis. The results showed that these compounds possess more cytotoxic activity than the reference drug (i.e., imatinib). Furthermore, compound IIB gives ten-fold lower IC50 values (0.229 μM) than imatinib (2.479 μM) when tested against (A549) lung cancer cell lines employing MTT assay. To investigate antibacterial and antifungal activities, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) parameters were evaluated, and derivative IIC showed the highest activity (MIC 16–128 μg/mL), which can be attributed to its structure. In addition, the antibacterial and antifungal properties of the derivatives were higher than some drugs. The antioxidant property of the derivatives was studied by using the DPPH (2,2-diphenylpicrylhydrazyl) method, and the results showed that the evaluated IC50 value was close to the IC50 value of ascorbic acid (4.45–4.83 μg/mL).
Multiaxial compressive strength of hybrid fiber reinforced concrete: A unified empirical model
Authors: Li Jian , Hong Jian , Liu Shiyao , Zhou Yuzai , Meng Kuan
Published: February 2023

In engineering design, the strength analysis of concrete structures heavily depends on the compressive strength of hybrid fiber reinforced concrete (HFRC), which also has an impact on the stability and safety of the structure. The objective of this study is to develop a unified empirical model that can quickly estimate the compressive strength of hybrid fiber reinforced concrete under multiaxial compression. To measure the multiaxial compressive strength of hybrid fiber reinforced concrete, 108 cylindrical specimens and 225 cubic specimens were designed for conventional and true triaxial testing, respectively. Two typical stress paths, i.e., proportional loading and constant restraint loading, were employed to simulate the multiaxial compressive strength of hybrid fiber reinforced concrete, and stress ratio- and confinement pressure-dependent formulas were proposed to calculate the strength correspondingly. Based on the validation against the available test results, it has been demonstrated that the empirical model can effectively predict the axial strength of hybrid fiber reinforced concrete. The test findings reveal that the constraint pressure considerably affects the compressive strength of concrete, and steel fiber can further improve these capabilities significantly.
Exercise sustains motor function in Parkinson's disease: Evidence from 109 randomized controlled trials on over 4,600 patients
Authors: Zhang Meiqi , Li Fang , Wang Dongyu , Ba Xiaohong , Liu Zhan
Published: February 2023

Physical exercise has been widely identified as a supplementary therapy for Parkinson's disease (PD). Evaluating changes in motor function over long-term periods of exercise and comparing efficacy of various exercise types will enable a better understanding of the effects of exercise on PD. In the current study, a total of 109 studies that covered 14 types of exercise were included in the analyses, enrolling 4,631 PD patients. The results of meta-regression revealed that chronic exercise delays the progression of PD motor symptoms, mobility, and balance decline deterioration, whereas for the non-exercise PD groups, motor function progressively decline. Results from network meta-analyses suggest that dancing is the optimal exercise for general motor symptoms of PD. Furthermore, Nordic walking is the most efficient exercise to mobility and balance performance. The results from network meta-analyses also suggest that Qigong may have specific benefit in improving hand function. The findings of the current study provide further evidence that chronic exercise preserves the progression of motor function decline in PD and suggest that dancing, yoga, multimodal training, Nordic walking, aquatic training, exercise gaming, and Qigong are effective PD exercises.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=276264, identifier: CRD42021276264.
Estradiol decreases the excitability of RA projection neurons in adult male zebra finches
Authors: Zhang Yutao , Sun Yalun , Wu Yanran , Sun Wei , Zhang Kun , Meng Wei , Wang Songhua
Published: February 2023

Zebra finches are essential animal models for studying learned vocal signals. The robust nucleus of the arcopallium (RA) plays an important role in regulating singing behavior. Our previous study showed that castration inhibited the electrophysiological activity of RA projection neurons (PNs) in male zebra finches, demonstrating that testosterone modulates the excitability of RA PNs. Testosterone can be converted into estradiol (E2) in the brain through aromatase; however, the physiological functions of E2 in RA are still unknown. This study aimed to investigate the electrophysiological activities of E2 on the RA PNs of male zebra finches through patch-clamp recording. E2 rapidly decreased the rate of evoked and spontaneous action potentials (APs) of RA PNs, hyperpolarized the resting membrane potential, and decreased the membrane input resistance. Moreover, the G-protein–coupled membrane-bound estrogen receptor (GPER) agonist G1 decreased both the evoked and spontaneous APs of RA PNs. Furthermore, the GPER antagonist G15 had no effect on the evoked and spontaneous APs of RA PNs; E2 and G15 together also had no effect on the evoked and spontaneous APs of RA PNs. These findings suggested that E2 rapidly decreased the excitability of RA PNs and its binding to GPER suppressed the excitability of RA PNs. These pieces of evidence helped us fully understand the principle of E2 signal mediation via its receptors to modulate the excitability of RA PNs in songbirds.
Steroid treatment response to post SARS-CoV-2 PANS symptoms: Case series
Authors: Berloffa Stefano , Salvati Andrea , Pantalone Gloria , Falcioni Ludovica , Rizzi Micaela M. , Naldini Francesca , Masi Gabriele , Gagliano Antonella
Published: February 2023

Background

Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by a wide spectrum of symptoms, including the onset of obsessive-compulsive disorder and/or severely restricted food intake, associated with emotional symptoms, behavioral symptoms, developmental regression, and somatic symptoms. Among the possible triggering agents, infectious agents have been extensively explored. More recently, sporadic case reports describe a possible association between PANS and SARS-CoV-2 infection but data on clinical presentation and treatment are still scarce.

Methods

We describe a case series (10 children) with acute onset or relapse of PANS symptoms after SARS-CoV-2 infection. Standardized measures (CBCL, CPRS, C-GAS, CGI-S, Y-BOCS, PANSS, and YGTSS) were used to describe the clinical picture. The efficacy of a pulse treatment with steroids for three consecutive months was assessed.

Results

Our data suggest that the clinical presentation of the COVID-19-triggered PANS is largely similar to that reported in typical PANS, including acute onset, with OCD and/or eating disorders, and associated symptoms. Our data suggest that treatment with corticosteroids may be beneficial for both global clinical severity and global functioning. No serious adverse effects were observed. Both OCD symptoms and tics consistently improved. Among psychiatric symptoms, affective and oppositional symptoms appeared more sensitive to the steroid treatment than the other symptoms.

Conclusion

Our study confirms that COVID-19 infection in children and adolescents could trigger acute-onset neuropsychiatric symptoms. Thus, in children and adolescents with COVID-19, a specific neuropsychiatric follow-up should be routinely included. Even if a small sample size and a follow-up with only two points (baseline and endpoint, after 8 weeks) limit the conclusions, it seems that steroid treatment in the acute phase may be beneficial and well tolerated.
White matter hyperintensities in cholinergic pathways are associated with dementia severity in e4 carriers but not in non-carriers
Authors: Yu Ming-Chun , Chuang Yi-Fang , Wu Shu-Ching , Ho Cheng-Feng , Liu Yi-Chien , Chou Chia-Ju
Published: February 2023

Background and objectives

Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways.

Methods

From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating—Sum of Boxes (CDR-SB).

Results

After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group.

Conclusions

Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.
Using spontaneous eye blink-related brain activity to investigate cognitive load during mobile map-assisted navigation
Authors: Cheng Bingjie , Lin Enru , Wunderlich Anna , Gramann Klaus , Fabrikant Sara I.
Published: February 2023

The continuous assessment of pedestrians’ cognitive load during a naturalistic mobile map-assisted navigation task is challenging because of limited experimental control over stimulus presentation, human-map-interactions, and other participant responses. To overcome this challenge, the present study takes advantage of navigators’ spontaneous eye blinks during navigation to serve as event markers in continuously recorded electroencephalography (EEG) data to assess cognitive load in a mobile map-assisted navigation task. We examined if and how displaying different numbers of landmarks (3 vs. 5 vs. 7) on mobile maps along a given route would influence navigators’ cognitive load during navigation in virtual urban environments. Cognitive load was assessed by the peak amplitudes of the blink-related fronto-central N2 and parieto-occipital P3. Our results show increased parieto-occipital P3 amplitude indicating higher cognitive load in the 7-landmark condition, compared to showing 3 or 5 landmarks. Our prior research already demonstrated that participants acquire more spatial knowledge in the 5- and 7-landmark conditions compared to the 3-landmark condition. Together with the current study, we find that showing 5 landmarks, compared to 3 or 7 landmarks, improved spatial learning without overtaxing cognitive load during navigation in different urban environments. Our findings also indicate a possible cognitive load spillover effect during map-assisted wayfinding whereby cognitive load during map viewing might have affected cognitive load during goal-directed locomotion in the environment or vice versa. Our research demonstrates that users’ cognitive load and spatial learning should be considered together when designing the display of future navigation aids and that navigators’ eye blinks can serve as useful event makers to parse continuous human brain dynamics reflecting cognitive load in naturalistic settings.
Dose and time-dependence of acute intermittent theta-burst stimulation on hippocampus-dependent memory in parkinsonian rats
Authors: Wang Yixuan , Liu Jian , Hui Yanping , Wu Zhongheng , Wang Ling , Wu Xiang , Bai Yihua , Zhang Qiaojun , Li Libo
Published: February 2023

Background

The treatment options for cognitive impairments in Parkinson’s disease (PD) are limited. Repetitive transcranial magnetic stimulation has been applied in various neurological diseases. However, the effect of intermittent theta-burst stimulation (iTBS) as a more developed repetitive transcranial magnetic stimulation paradigm on cognitive dysfunction in PD remains largely unclear.

Objective

Our aim was to explore the effect of acute iTBS on hippocampus-dependent memory in PD and the mechanism underlying it.

Methods

Different blocks of iTBS protocols were applied to unilateral 6-hydroxidopamine-induced parkinsonian rats followed by the behavioral, electrophysiological and immunohistochemical analyses. The object-place recognition and hole-board test were used to assess hippocampus-dependent memory.

Results

Sham-iTBS and 1 block-iTBS (300 stimuli) didn’t alter hippocampus-dependent memory, hippocampal theta rhythm and the density of c-Fos- and parvalbumin-positive neurons in the hippocampus and medial septum. 3 block-iTBS (900 stimuli) alleviated 6-hydroxidopamine-induced memory impairments, and increased the density of hippocampal c-Fos-positive neurons at 80 min post-stimulation but not 30 min compared to sham-iTBS. Interestingly, 3 block-iTBS first decreased and then increased normalized theta power during a period of 2 h following stimulation. Moreover, 3 block-iTBS decreased the density of parvalbumin-positive neurons in the medial septum at 30 min post-stimulation compared to sham-iTBS.

Conclusion

The results indicate that multiple blocks of iTBS elicit dose and time-dependent effects on hippocampus-dependent memory in PD, which may be attributed to changes in c-Fos expression and the power of theta rhythm in the hippocampus.
Modulation of neuronal excitability by binge alcohol drinking
Authors: Gimenez-Gomez Pablo , Le Timmy , Martin Gilles E.
Published: February 2023

Drug use poses a serious threat to health systems throughout the world. The number of consumers rises every year being alcohol the drug of abuse most consumed causing 3 million deaths (5.3% of all deaths) worldwide and 132.6 million disability-adjusted life years. In this review, we present an up-to-date summary about what is known regarding the global impact of binge alcohol drinking on brains and how it affects the development of cognitive functions, as well as the various preclinical models used to probe its effects on the neurobiology of the brain. This will be followed by a detailed report on the state of our current knowledge of the molecular and cellular mechanisms underlying the effects of binge drinking on neuronal excitability and synaptic plasticity, with an emphasis on brain regions of the meso-cortico limbic neurocircuitry.
Functional foods and dietary supplements in the management of non-alcoholic fatty liver disease: A systematic review and meta-analysis
Authors: Wang Lei-lei , Zhang Pian-hong , Yan Hui-hui
Published: February 2023

Objective

In this systematic review and meta-analysis, we aimed to clarify the overall effects of functional foods and dietary supplements in non-alcoholic fatty liver disease (NAFLD) patients.

Methods

Randomized controlled trials (RCTs) published in PubMed, ISI Web of Science, Cochrane library, and Embase from January 1, 2000 to January 31, 2022 were systematically searched to assess the effects of functional foods and dietary supplements in patients with NAFLD. The primary outcomes were liver-related measures, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic fibrosis and steatosis, while the secondary outcomes included body mass index (BMI), waist circumference (WC), triacylglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). These indexes were all continuous variables, so the mean difference (MD) was used for calculating the effect size. Random-effects or fixed-effects models were used to estimate the mean difference (MD). The risk of bias in all studies was assessed with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions.

Results

Twenty-nine articles investigating functional foods and dietary supplements [antioxidants (phytonutrients and coenzyme Q10) = 18, probiotics/symbiotic/prebiotic = 6, fatty acids = 3, vitamin D = 1, and whole grain = 1] met the eligibility criteria. Our results showed that antioxidants could significantly reduce WC (MD: −1.28 cm; 95% CI: −1.58, −0.99, P < 0.05), ALT (MD: −7.65 IU/L; 95% CI: −11.14, −4.16, P < 0.001), AST (MD: −4.26 IU/L; 95% CI: −5.76, −2.76, P < 0.001), and LDL-C (MD: −0.24 mg/dL; 95% CI: −0.46, −0.02, P < 0.05) increased in patients with NAFLD but had no effect on BMI, TG, and TC. Probiotic/symbiotic/prebiotic supplementation could decrease BMI (MD: −0.57 kg/m2; 95% CI: −0.72, −0.42, P < 0.05), ALT (MD: −3.96 IU/L; 95% CI: −5.24, −2.69, P < 0.001), and AST (MD: −2.76; 95% CI: −3.97, −1.56, P < 0.0001) levels but did not have beneficial effects on serum lipid levels compared to the control group. Moreover, the efficacy of fatty acids for treating NAFLD was full of discrepancies. Additionally, vitamin D had no significant effect on BMI, liver transaminase, and serum lipids, while whole grain could reduce ALT and AST but did not affect serum lipid levels.

Conclusion

The current study suggests that antioxidant and probiotic/symbiotic/prebiotic supplements may be a promising regimen for NAFLD patients. However, the usage of fatty acids, vitamin D, and whole grain in clinical treatment is uncertain. Further exploration of the efficacy ranks of functional foods and dietary supplements is needed to provide a reliable basis for clinical application.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier: CRD42022351763.
Network pharmacology-based analysis of Resinacein S against non-alcoholic fatty liver disease by modulating lipid metabolism
Authors: Mao Fei-Fei , Gao Shan-Shan , Huang Yan-Jie , Zhou Nian , Feng Jin-Kai , Liu Zong-Han , Zhang Yu-Qing , Yuan Lu-Yun , Wei Gang , Cheng Shu-Qun
Published: February 2023

Background

Ganoderma lucidum is reportedly the best source of traditional natural bioactive constituents. Ganoderma triterpenoids (GTs) have been verified as an alternative adjuvant for treating leukemia, cancer, hepatitis and diabetes. One of the major triterpenoids, Resinacein S, has been found to regulate lipid metabolism and mitochondrial biogenesis. Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that has become a major public health problem. Given the regulatory effects on lipid metabolism of Resinacein S, we sought to explore potential protective effects against NAFLD.

Methods

Resinacein S was extracted and isolated from G. lucidum. And mice were fed with high fat diet with or without Resinacein S to detect hepatic steatosis. According to Network Pharmacology and RNA-seq, we analyzed the hub genes of Resinacein S against NAFLD disease.

Results

Our results can be summarized as follows: (1) The structure of Resinacein S was elucidated using NMR and MS methods. (2) Resinacein S treatment could significantly attenuate high-fat diet (HFD)-induced hepatic steatosis and hepatic lipid accumulation in mouse. (3) GO terms, KEGG pathways and the PPI network of Resinacein S induced Differentially Expressed Genes (DEGs) demonstrated the key target genes of Resinacein S against NAFLD. (4) The hub proteins in PPI network analysis could be used for NAFLD diagnosis and treatment as drug targets.

Conclusion

Resinacein S can significantly change the lipid metabolism in liver cells and yield a protective effect against steatosis and liver injury. Intersected proteins between NAFLD related genes and Resinacein S-induced DEGs, especially the hub protein in PPI network analysis, can be used to characterize targets of Resinacein S against NAFLD.
Impact of vitamin D on the prognosis after spinal cord injury: A systematic review
Authors: Wang Lei , Gan Jinlu , Wu Jingnan , Zhou Yingchun , Lei Deqiang
Published: February 2023

Vitamin D (VitD) insufficiency is a worldwide health problem and affects billions of people. Spinal cord injury (SCI) patients seem more susceptible to developing suboptimal levels of VitD. However, the literature regarding its impact on the prognosis of SCI is limited. Thus, in this review, we systematically investigated the published studies via a combination of keywords associated with SCI and VitD in four medical databases (Medline, Embase, Scopus, and Web of Science). All included studies were analyzed, and selected clinical data on the prevalence of VitD insufficiency (serum 25-hydroxyvitamin D < 30 ng/ml) and deficiency (serum 25-hydroxyvitamin D < 20 ng/ml) were collected for further meta-analysis via random effects. Through literature review, a total of 35 studies were eligible and included. The meta-analysis of VitD status (13 studies, 1,962 patients) indicated high prevalence of insufficiency (81.6% [75.7, 87.5]) and deficiency (52.5% [38.1, 66.9]) after SCI. Besides, low levels of VitD were reported to be associated with a higher risk of skeletal diseases, venous thromboembolism, psychoneurological syndromes, and chest illness after injury. Existing literature suggested that supplemental therapy might act as an adjuvant treatment to facilitate post-injury rehabilitation. Non-human experimental studies highlighted the neuroprotective effect of VitD, which was associated with enhancing axonal and neuronal survival, suppressing neuroinflammation, and modulating autophagy. Therefore, the current evidence suggests that the prevalence of VitD insufficiency is high in the SCI population, and low-level VitD may impair functional restoration after SCI. VitD supplemental treatment may have potential benefits to accelerate rehabilitation in mechanistically related processes after SCI. However, due to the limitation of the available evidence, more well-designed randomized controlled trials and mechanism experimental research are still needed to validate its therapeutic effect, elucidate its neuroprotective mechanism, and develop novel treatments.
Comprehensive genomic profiling: Does timing matter?
Authors: Thapa Bicky , Ahmed Gulrayz , Szabo Aniko , Kamgar Mandana , Kilari Deepak , Mehdi Maahum , Menon Smitha , Daniel Sherin , Thompson Jonathan , Thomas James , George Ben
Published: February 2023

Purpose

There is variability in utilization of Comprehensive Genomic Profiling (CGP) in most of the metastatic solid tumors (MST). We evaluated the CGP utilization patterns and its impact on outcomes at an academic tertiary center.

Patients and Methods

Institutional database was reviewed for CGP data in adult patients with MST between 01/2012 – 04/2020. Patients were categorized based on interval between CGP and metastatic diagnosis; 3 tertiles of distribution (T1-earliest to the diagnosis, T3-furthest), and pre-mets (CGP performed prior to diagnosis of metastasis). Overall survival (OS) was estimated from the time of metastatic diagnosis with left truncation at the time of CGP. Cox regression model was used to estimate the impact of timing of CGP on survival.

Results

Among 1,358 patients, 710 were female, 1,109 Caucasian, 186 Afro-Americans, and 36 Hispanic. The common histologies were lung cancer (254; 19%), colorectal cancer (203; 15%), gynecologic cancers (121; 8.9%), and pancreatic cancer (106; 7.8%). Time interval between diagnosis of metastatic disease and CGP was not statistically significantly different based on sex, race and ethnicity after adjusting for histologic diagnoses with 2 exceptions - Hispanics with lung cancer had delayed CGP compared to non-Hispanics (p =0.019) and females with pancreas cancer had delayed CGP compared to males (p =0.025). Lung cancer, gastro-esophageal cancer and gynecologic malignancies had better survival if they had CGP performed during the first tertile after metastatic diagnosis.

Conclusion

CGP utilization across cancer types was equitable irrespective of sex, race and ethnicity. Early CGP after metastatic diagnosis might have effect on treatment delivery and clinical outcomes in cancer type with more actionable targets.
Integrated multi-dimensional deep neural network model improves prognosis prediction of advanced NSCLC patients receiving bevacizumab
Authors: Li Butuo , Yang Linlin , Jiang Chao , Yao Yueyuan , Li Haoqian , Cheng Shuping , Zou Bing , Fan Bingjie , Wang Linlin
Published: February 2023

Background

The addition of bevacizumab was found to be associated with prolonged survival whether in combination with chemotherapy, tyrosine kinase inhibitors or immune checkpoint inhibitors in the treatment landscape of advanced non-small cell lung cancer (NSCLC) patients. However, the biomarkers for efficacy of bevacizumab were still largely unknown. This study aimed to develop a deep learning model to provide individual assessment of survival in advanced NSCLC patients receiving bevacizumab.

Methods

All data were retrospectively collected from a cohort of 272 radiological and pathological proven advanced non-squamous NSCLC patients. A novel multi-dimensional deep neural network (DNN) models were trained based on clinicopathological, inflammatory and radiomics features using DeepSurv and N-MTLR algorithm. And concordance index (C-index) and bier score was used to demonstrate the discriminatory and predictive capacity of the model.

Results

The integration of clinicopathologic, inflammatory and radiomics features representation was performed using DeepSurv and N-MTLR with the C-index of 0.712 and 0.701 in testing cohort. And Cox proportional hazard (CPH) and random survival forest (RSF) models were also developed after data pre-processing and feature selection with the C-index of 0.665 and 0.679 respectively. DeepSurv prognostic model, indicated with best performance, was used for individual prognosis prediction. And patients divided in high-risk group were significantly associated with inferior PFS (median PFS: 5.4 vs 13.1 months, P<0.0001) and OS (median OS: 16.4 vs 21.3 months, P<0.0001).

Conclusions

The integration of clinicopathologic, inflammatory and radiomics features representation based on DeepSurv model exhibited superior predictive accuracy as non-invasive method to assist in patients counseling and guidance of optimal treatment strategies.
Impact of the COVID-19 pandemic on the digitization of routine pediatric practice in Spain: A nationwide survey study
Authors: Martín-Masot Rafael , Diaz-Martin Juan J. , Santamaría-Orleans Alicia , Navas-López Víctor Manuel
Published: February 2023

Introduction

The COVID-19 pandemic forced a change in the working dynamics of all healthcare professionals, leading to the sudden introduction of telemedicine. Although until that moment telemedicine applications had been described in the paediatric age, their use was anecdotal.

Objective

To analyse the experience of Spanish paediatricians after the forced digitization of consultations due to the pandemic.

Methods

A cross-sectional survey-type study was designed to obtain information from Spanish paediatricians about the changes that took place in the usual clinical practice.

Results

306 health professionals participated in the study Most of them agreed on the use of the internet and social networks during the pandemic, referring to mail or WhatsApp® as usual channels of communication with their patients' families. There was a great agreement among paediatricians that the evaluation of newborns after hospital discharge and establishing methodologies that allow childhood vaccination and the identification of subsidiary patients for face-to-face evaluation were necessary although the limitations of the lockdown. The idea that telephone and digital consultations have optimized the consultation time and that they will probably continue after the end of the pandemic was generally accepted. No changes in adherence to breastfeeding or the start of complementary feeding were referred to, but an increase in the duration of breastfeeding and the appearance of frequent hoaxes in social networks concerning infant feeding were found.

Conclusions

It is necessary to analyse the impact of telemedicine in paediatric consultations during the pandemic to evaluate its effectiveness and quality to maintain it in routine paediatric practice.
Intraoperative monitoring of cerebrovascular autoregulation in infants and toddlers receiving major elective surgery to determine the individually optimal blood pressure – a pilot study
Authors: Iller Maximilian , Neunhoeffer Felix , Heimann Lukas , Zipfel Julian , Schuhmann Martin U. , Scherer Simon , Dietzel Markus , Fuchs Joerg , Hofbeck Michael , Hieber Stefanie , Fideler Frank
Published: February 2023

Introduction

Inducing general anesthesia (GA) in children can considerably affect blood pressure, and the rate of severe critical events owing to this remains high. Cerebrovascular autoregulation (CAR) protects the brain against blood-flow-related injury. Impaired CAR may contribute to the risk of cerebral hypoxic–ischemic or hyperemic injury. However, blood pressure limits of autoregulation (LAR) in infants and children are unclear.

Materials and methods

In this pilot study CAR was monitored prospectively in 20 patients aged <4 years receiving elective surgery under GA. Cardiac- or neurosurgical procedures were excluded. The possibility of calculating the CAR index hemoglobin volume index (HVx), by correlating near-infrared-spectroscopy (NIRS)-derived relative cerebral tissue hemoglobin and invasive mean arterial blood pressure (MAP) was determined. Optimal MAP (MAPopt), LAR, and the proportion of time with a MAP outside LAR were determined.

Results

The mean patient age was 14 ± 10 months. MAPopt could be determined in 19 of 20 patients, with an average of 62 ± 12 mmHg. The required time for a first MAPopt depended on the extent of spontaneous MAP fluctuations. The actual MAP was outside the LAR in 30% ± 24% of the measuring time. MAPopt significantly differed among patients with similar demographics. The CAR range averaged 19 ± 6 mmHg. Using weight-adjusted blood pressure recommendations or regional cerebral tissue saturation, only a fraction of the phases with inadequate MAP could be identified.

Conclusion

Non-invasive CAR monitoring using NIRS-derived HVx in infants, toddlers, and children receiving elective surgery under GA was reliable and provided robust data in this pilot study. Using a CAR-driven approach, individual MAPopt could be determined intraoperatively. The intensity of blood pressure fluctuations influences the initial measuring time. MAPopt may differ considerably from recommendations in the literature, and the MAP range within LAR in children may be smaller than that in adults. The necessity of manual artifact elimination represents a limitation. Larger prospective and multicenter cohort studies are necessary to confirm the feasibility of CAR-driven MAP management in children receiving major surgery under GA and to enable an interventional trial design using MAPopt as a target.