bluuebunny/crossref_metadata_2025 huggingface dataset:
An fMRI study of visual geometric shapes processing
Authors: Wei Liuqing , Li Xueying , Huang Lina , Liu Yuansheng , Hu Luming , Shen Wenbin , Ding Qingguo , Liang Pei
Published: March 2023

Cross-modal correspondence has been consistently evidenced between shapes and other sensory attributes. Especially, the curvature of shapes may arouse the affective account, which may contribute to understanding the mechanism of cross-modal integration. Hence, the current study used the functional magnetic resonance imaging (fMRI) technique to examine brain activity’s specificity when people view circular and angular shapes. The circular shapes consisted of a circle and an ellipse, while the angular shapes consisted of a triangle and a star. Results show that the brain areas activated by circular shapes mainly involved the sub-occipital lobe, fusiform gyrus, sub and middle occipital gyrus, and cerebellar VI. The brain areas activated by angular shapes mainly involve the cuneus, middle occipital gyrus, lingual gyrus, and calcarine gyrus. The brain activation patterns of circular shapes did not differ significantly from those of angular shapes. Such a null finding was unexpected when previous cross-modal correspondence of shape curvature was considered. The different brain regions detected by circular and angular shapes and the potential explanations were discussed in the paper.
Exogenous L-lactate administration in rat hippocampus increases expression of key regulators of mitochondrial biogenesis and antioxidant defense
Authors: Akter Mastura , Ma Haiying , Hasan Mahadi , Karim Anwarul , Zhu Xiaowei , Zhang Liang , Li Ying
Published: March 2023

L-lactate plays a critical role in learning and memory. Studies in rats showed that administration of exogenous L-lactate into the anterior cingulate cortex and hippocampus (HPC) improved decision-making and enhanced long-term memory formation, respectively. Although the molecular mechanisms by which L-lactate confers its beneficial effect are an active area of investigations, one recent study found that L-lactate supplementation results in a mild reactive oxygen species burst and induction of pro-survival pathways. To further investigate the molecular changes induced by L-lactate, we injected rats with either L-lactate or artificial CSF bilaterally into the dorsal HPC and collected the HPC after 60 minutes for mass spectrometry. We identified increased levels of several proteins that include SIRT3, KIF5B, OXR1, PYGM, and ATG7 in the HPC of the L-lactate treated rats. SIRT3 (Sirtuin 3) is a key regulator of mitochondrial functions and homeostasis and protects cells against oxidative stress. Further experiments identified increased expression of the key regulator of mitochondrial biogenesis (PGC-1α) and mitochondrial proteins (ATPB, Cyt-c) as well as increased mitochondrial DNA (mtDNA) copy number in the HPC of L-lactate treated rats. OXR1 (Oxidation resistance protein 1) is known to maintain mitochondrial stability. It mitigates the deleterious effects of oxidative damage in neurons by inducing a resistance response against oxidative stress. Together, our study suggests that L-lactate can induce expression of key regulators of mitochondrial biogenesis and antioxidant defense. These findings create new research avenues to explore their contribution to the L-lactate’s beneficial effect in cognitive functions as these cellular responses might enable neurons to generate more ATP to meet energy demand of neuronal activity and synaptic plasticity as well as attenuate the associated oxidative stress.
Breadfruit (Artocarpus altilis): Processing, nutritional quality, and food applications
Authors: Mehta Kervyn Ajay , Quek Yu Chin Rina , Henry Christiani Jeyakumar
Published: March 2023

Breadfruit is an underutilized but highly nutritive crop containing complex carbohydrates while being low in fat. It is also a good source of essential amino acids (leucine, isoleucine, and valine). With a better understanding of breadfruit’s morphology, its potential as a global solution to food security has been gaining popularity. Breadfruit has been forecasted to have a larger amount of suitable cultivable land area compared to major crops such as rice and wheat, making its cultivation more desirable. Due to its highly perishable nature, good post-harvesting and post-processing practices are essential to extend the shelf life of breadfruit for global transportation and consumption. This paper aims to provide a comprehensive review on various processing methods of flour and starch, nutritional significance and new food applications of this novel food staple. In this review, the effects of the different processing and post-processing methods of breadfruit flour and starch have been described, and the nutritional composition and application of breadfruit flour as an ingredient replacer in various food applications have been discussed. It is vital to understand the processing and post-processing methods of breadfruit flour to enhance its shelf-life, physicochemical and functional properties. Furthermore, a compilation of novel food applications has been done to promote its use in the food industry. In conclusion, breadfruit flour and starch are highly versatile for use in numerous food products with added health benefits.
Exploiting embryonic niche conditions to grow Wilms tumor blastema in culture
Authors: Wojcik Heather M. , Lovvorn Harold N. , Hollingshead Melinda , Pierce Janene , Stotler Howard , Murphy Andrew J. , Borgel Suzanne , Phelps Hannah M. , Correa Hernan , Perantoni Alan O.
Published: March 2023

Introduction

Wilms Tumor (WT), or nephroblastoma, is the most common pediatric kidney cancer. Most WTs display a “favorable” triphasic histology, in which the tumor is comprised of blastemal, stromal, and epithelial cell types. Blastemal predominance after neoadjuvant chemotherapy or diffuse anaplasia (“unfavorable” histology; 5-8%) portend a worse prognosis. Blastema likely provide the putative cancer stem cells (CSCs), which retain molecular and histologic features characteristic of nephron progenitor cells (NPCs), within WTs. NPCs arise in the metanephric mesenchyme (MM) and populate the cap mesenchyme (CM) in the developing kidney. WT blastemal cells, like NPCs, similarly express markers, SIX2 and CITED1. Tumor xenotransplantation is currently the only dependable method to propagate tumor tissue for research or therapeutic screening, since efforts to culture tumors in vitro as monolayers have invariably failed. Therefore, a critical need exists to propagate WT stem cells rapidly and efficiently for high-throughput, real-time drug screening.

Methods

Previously, our lab developed niche conditions that support the propagation of murine NPCs in culture. Applying similar conditions to WTs, we assessed our ability to maintain key NPC "stemness" markers, SIX2, NCAM, and YAP1, and CSC marker ALDHI in cells from five distinct untreated patient tumors.

Results

Accordingly, our culture conditions maintained the expression of these markers in cultured WT cells through multiple passages of rapidly dividing cells.

Discussion

These findings suggest that our culture conditions sustain the WT blastemal population, as previously shown for normal NPCs. As a result, we have developed new WT cell lines and a multi-passage in vitro model for studying the blastemal lineage/CSCs in WTs. Furthermore, this system supports growth of heterogeneous WT cells, upon which potential drug therapies could be tested for efficacy and resistance.
Ultrasound features for prediction of long-term outcomes of women with primary breast cancer <20 mm
Authors: Shao Sihui , Yao Minghua , Li Chunxiao , Li Xin , Wang Jianfeng , Chen Jing , Zheng Yi , Wu Rong
Published: March 2023

Background

Some women die despite the favorable prognosis of small breast cancers. Breast ultrasound features may reflect pathological and biological characteristics of a breast tumor. This study aimed to explore whether ultrasound features could identify small breast cancers with poor outcomes.

Methods

This retrospective study examined confirmed breast cancers with a size of <20 mm diagnosed in our hospital between 02/2008 and 08/2019. Clinicopathological and ultrasound features were compared between alive and deceased breast cancer patients. Survival was analyzed using the Kaplan-Meier curves. Multivariable Cox proportional hazards models were used to examine the factors associated with breast cancer-specific survival (BCSS) and disease-free survival (DFS).

Results

Among the 790 patients, the median follow-up was 3.5 years. The deceased group showed higher frequencies of spiculated (36.7% vs. 11.2%, P<0.001), anti-parallel orientation (43.3% vs. 15.4%, P<0.001), and spiculated morphology combined with anti-parallel orientation (30.0% vs. 2.4%, P<0.001). Among 27 patients with spiculated morphology and anti-parallel orientation, nine cancer-specific deaths and 11 recurrences occurred, for a 5-year BCSS of 77.8% and DFS of 66.7%, while 21 breast-cancer deaths and 41 recurrences occurred among the remaining patients with higher 5-year BCSS (97.8%, P<0.001) and DFS (95.4%, P<0.001). Spiculated and anti-parallel orientation (HR=7.45, 95%CI: 3.26-17.00; HR=6.42, 95%CI: 3.19-12.93), age ≥55 years (HR=5.94, 95%CI: 2.24-15.72; HR=1.98, 95%CI: 1.11-3.54), and lymph nodes metastasis (HR=3.99, 95%CI: 1.89-8.43; HR=2.99, 95%CI: 1.71-5.23) were independently associated with poor BCSS and DFS.

Conclusions

Spiculated and anti-parallel orientation at ultrasound are associated with poor BCSS and DFS in patients with primary breast cancer <20 mm.
Association of serum metabolome profile with the risk of breast cancer in participants of the HUNT2 study
Authors: Mrowiec Katarzyna , Kurczyk Agata , Jelonek Karol , Debik Julia , Giskeødegård Guro F. , Bathen Tone F. , Widłak Piotr
Published: March 2023

Background

The serum metabolome is a potential source of molecular biomarkers associated with the risk of breast cancer. Here we aimed to analyze metabolites present in pre-diagnostic serum samples collected from healthy women participating in the Norwegian Trøndelag Health Study (HUNT2 study) for whom long-term information about developing breast cancer was available.

Methods

Women participating in the HUNT2 study who developed breast cancer within a 15-year follow-up period (BC cases) and age-matched women who stayed breast cancer-free were selected (n=453 case-control pairs). Using a high-resolution mass spectrometry approach 284 compounds were quantitatively analyzed, including 30 amino acids and biogenic amines, hexoses, and 253 lipids (acylcarnitines, glycerides, phosphatidylcholines, sphingolipids, and cholesteryl esters).

Results

Age was a major confounding factor responsible for a large heterogeneity in the dataset, hence age-defined subgroups were analyzed separately. The largest number of metabolites whose serum levels differentiated BC cases and controls (82 compounds) were observed in the subgroup of younger women (<45 years old). Noteworthy, increased levels of glycerides, phosphatidylcholines, and sphingolipids were associated with reduced risk of cancer in younger and middle-aged women (≤64 years old). On the other hand, increased levels of serum lipids were associated with an enhanced risk of breast cancer in older women (>64 years old). Moreover, several metabolites could be detected whose serum levels were different between BC cases diagnosed earlier (<5 years) and later (>10 years) after sample collecting, yet these compounds were also correlated with the age of participants. Current results were coherent with the results of the NMR-based metabolomics study performed in the cohort of HUNT2 participants, where increased serum levels of VLDL subfractions were associated with reduced risk of breast cancer in premenopausal women.

Conclusions

Changes in metabolite levels detected in pre-diagnostic serum samples, which reflected an impaired lipid and amino acid metabolism, were associated with long-term risk of breast cancer in an age-dependent manner.
Somatic mutation detection and KRAS amplification in testicular germ cell tumors
Authors: Cabral Eduardo R. M. , Pacanhella Marilia F. , Lengert Andre V. H. , Reis Mariana B. dos , Leal Leticia F. , Lima Marcos A. de , Silva Aline L. V. da , Pinto Icaro A. , Reis Rui M. , Pinto Mariana T. , Cárcano Flavio M.
Published: March 2023

Background

Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center.

Materials and methods

A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan–Meier method and log-rank test.

Results

KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable.

Conclusion

Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.
Pathologic complete response to chemoimmunotherapy of an advanced gastric cancer patient with high PD-L1 expression, dMMR, and unique gut microbiota composition: A case report
Authors: Jiang Hongpeng , Wang Junyun , Deng Wei
Published: March 2023

Background

Advanced gastric cancer (AGC) is a malignant disease with limited therapeutic options and a poor prognosis. Recently, immune checkpoint inhibitors (ICIs), represented by inhibitors of programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), have emerged as a potential gastric cancer (GC) therapy.

Case presentation

This case study aimed to reveal the tumor response to neoadjuvant chemotherapy combined with camrelizumab in a patient with AGC based on the characteristics of the clinical pathology, genomics variation, and gut microbiome. Samples from a 59-year-old male patient diagnosed with locally advanced unresectable GC (cT4bN2M0, high grade) presenting PD-L1-positive, deficient mismatch repair (dMMR), and highly specific gut microbiota enrichment were subjected to target region sequencing, metagenomic sequencing, and immunohistochemistry staining. The patient received neoadjuvant therapy, including camrelizumab, apatinib, S-1, and abraxane, which eventually promoted dramatic tumor shrinkage without serious adverse effects and allowed subsequent radical gastrectomy and lymphadenectomy. Finally, the patient achieved pathologic complete response (pCR), and the recurrence-free survival time was 19 months at the last follow-up in April 2021.

Conclusions

The patient with PD-L1-positive, dMMR, and a highly specific gut microbiota enrichment exhibited a pCR to neoadjuvant chemoimmunotherapy.
Case report: Subacute transverse myelitis with gait preservation secondary to Lyme disease and a review of the literature
Authors: Colot Charlotte , Adler Catherine , Mignon Céline , De Leucio Alessandro , Jissendi Patrice , Fonteyne Jean , Aeby Alec
Published: March 2023

Subacute presentation with gait preservation is rare in the initial presentation of transverse myelitis (TM) in children. Lyme TM is poorly described in the literature. Here, we present the case of a 10-year-old boy who presented with neck pain with irradiation in the upper limbs for 13 days, accompanied by a right latero-torticollis. Magnetic resonance imaging (MRI) of the spine showed a hypersignal in the centromedullary T2 weighted image (WI) between C1 and C7, which was suggestive of cervical TM. A lumbar puncture revealed pleocytosis and proteinorachia. The test results ofBorreliaIgG in the blood and intrathecal IgG synthesis were positive, confirming the diagnosis of TM secondary to Lyme disease. The patient was treated with high doses of steroids and antibiotics, following which he recovered completely. After a review of the clinical features of the eight previously published pediatric cases, we can conclude that Lyme TM usually has a subacute clinical presentation and is frequently limited to the cervical spine with pure sensory symptoms and gait preservation. Moreover, acute and chronic sphincter dysfunction is rare, and recovery is usually complete.
Acori Tatarinowii Rhizoma: A comprehensive review of its chemical composition, pharmacology, pharmacokinetics and toxicity
Authors: Wen Jianxia , Yang Yi , Hao Junjie
Published: March 2023

Acori Tatarinowii Rhizoma (ATR, Shi Chang Pu in Chinese), a natural product with multiple targets in various diseases. This review provides the comprehensive summary of the chemical composition, pharmacological effects, pharmacokinetics parameters and toxicity of ATR. The results indicated that ATR possesses a wide spectrum of chemical composition, including volatile oil, terpenoids, organic acids, flavonoids, amino acids, lignin, carbohydrates and so on. Accumulating evidence from various studies has shown that ATR exerts a wide range of pharmacological properties, including protecting nerve cells, alleviating learning and memory impairment, anti-ischemic, anti-myocardial ischemia, anti-arrhythmic, anti-tumor, anti-bacterial, and anti-oxidant activities. Currently, ATR is widely used in the central nervous system, cardiovascular system, gastrointestinal digestive system, respiratory system in China, and for the treatment of epilepsy, depression, amnesia, consciousness, anxiety, insomnia, aphasia, tinnitus, cancers, dementia, stroke, skin diseases, and other complex diseases. Pharmacokinetic studies indicated that β-asarone, α-asarone, cis-methylisoeugenol, and asarylaldehyde, the active components of ATR, were absorbed slowly after oral administration of ATR. Moreover, toxicity studies have suggested that ATR has no carcinogenic, teratogenic and mutagenic toxicity. Nevertheless, long term or high-dose toxicity testing in animals to explore the acute and chronic toxicity of acori Tatarinowii Rhizoma is still lacking. In view of good pharmacological activities, ATR is expected to be a potential drug candidate for the treatment of Alzheimer’s disease, depression, or ulcerative colitis. However, further studies are needed to elucidate its chemical composition, pharmacological effects, molecular mechanisms and targets, improve its oral bioavailability, and clarify its potential toxicity.
Sex-related differences in the efficacy of Baclofen enantiomers on self-administered alcohol in a binge drinking pattern and dopamine release in the core of the nucleus accumbens
Authors: Jeanblanc Jérôme , Sauton Pierre , Houdant Charles , Fernandez Rodriguez Sandra , de Sousa Sofia Vilelas , Jeanblanc Virginie , Bodeau Sandra , Labat Laurence , Soichot Marion , Vorspan Florence , Naassila Mickael
Published: March 2023

Introduction: Clinical studies on the effectiveness of Baclofen in alcohol use disorder (AUD) yielded mixed results possibly because of differential effects of the enantiomers and sex-related differences. Here we examined the effect of the different Baclofen enantiomers on alcohol intake and on evoked dopamine release in the core of the nucleus accumbens (NAcc) in male and female Long Evans rats.

Methods: Rats were trained to chronically self-administer 20% alcohol solution in daily binge drinking sessions and were treated with the different forms of Baclofen [RS(±), R(+) and S(−)]. The effects on the evoked dopamine release within the core of the nucleus accumbens were measured in brain slices from the same animals and the alcohol naïve animals using the fast scan cyclic voltammetry technique.

Results: RS(±)-Baclofen reduced alcohol intake regardless of sex but more females were non-responders to the treatment. R(+)-Baclofen also reduced alcohol intake regardless of sex but females were less sensitive than males. S(−)-Baclofen did not have any effect on average but in some individuals, especially in the females, it did increase alcohol intake by at least 100%. There were no sex differences in Baclofen pharmacokinetic but a strong negative correlation was found in females with a paradoxical effect of increased alcohol intake with higher blood Baclofen concentration. Chronic alcohol intake reduced the sensitivity to the effect of Baclofen on evoked dopamine release and S(−)-Baclofen increased dopamine release specifically in females.

Discussion: Our results demonstrate a sex-dependent effect of the different forms of Baclofen with no or negative effects (meaning an increase in alcohol self-administration) in subgroup of females that could be linked to a differential effect on dopamine release and should warrant future clinical studies on alcohol use disorder pharmacotherapy that will deeply analyze sex difference.
Characterization of ligand-induced thermal stability of the human organic cation transporter 2 (OCT2)
Authors: Maane Max , Xiu Fangrui , Bellstedt Peter , Kullak-Ublick Gerd A. , Visentin Michele
Published: March 2023

Introduction: The human organic cation transporter 2 (OCT2) is involved in the transport of endogenous quaternary amines and positively charged drugs across the basolateral membrane of proximal tubular cells. In the absence of a structure, the progress in unraveling the molecular basis of OCT2 substrate specificity is hampered by the unique complexity of OCT2 binding pocket, which seemingly contains multiple allosteric binding sites for different substrates. Here, we used the thermal shift assay (TSA) to better understand the thermodynamics governing OCT2 binding to different ligands.

Methods: Molecular modelling and in silico docking of different ligands revealed two distinct binding sites at OCT2 outer part of the cleft. The predicted interactions were assessed by cis-inhibition assay using [3H]1-methyl-4-phenylpyridinium ([3H]MPP+) as a model substrate, or by measuring the uptake of radiolabeled ligands in intact cells. Crude membranes from HEK293 cells harboring human OCT2 (OCT2-HEK293) were solubilized in n-Dodecyl-β-D-Maltopyranoside (DDM), incubated with the ligand, heated over a temperature gradient, and then pelleted to remove heat-induced aggregates. The OCT2 in the supernatant was detected by western blot.

Results: Among the compounds tested, cis-inhibition and TSA assays showed partly overlapping results. Gentamicin and methotrexate (MTX) did not inhibit [3H]MPP+ uptake but significantly increased the thermal stabilization of OCT2. Conversely, amiloride completely inhibited [3H]MPP+ uptake but did not affect OCT2 thermal stabilization. [3H]MTX intracellular level was significantly higher in OCT2-HEK293 cells than in wild type cells. The magnitude of the thermal shift (ΔTm) did not provide information on the binding. Ligands with similar affinity showed markedly different ΔTm, indicating different enthalpic and entropic contributions for similar binding affinities. The ΔTm positively correlated with ligand molecular weight/chemical complexity, which typically has high entropic costs, suggesting that large ΔTm reflect a larger displacement of bound water molecules.

Discussion: In conclusion, TSA might represent a viable approach to expand our knowledge on OCT2 binding descriptors.
Maternal opioids age-dependently impair neonatal respiratory control networks
Authors: Beyeler Sarah A. , Naidoo Robyn , Morrison Nina R. , McDonald Emilee A. , Albarrán David , Huxtable Adrianne G.
Published: March 2023

Infants exposed to opioids in utero are an increasing clinical population and these infants are often diagnosed with Neonatal Abstinence Syndrome (NAS). Infants with NAS have diverse negative health consequences, including respiratory distress. However, many factors contribute to NAS, confounding the ability to understand how maternal opioids directly impact the neonatal respiratory system. Breathing is controlled centrally by respiratory networks in the brainstem and spinal cord, but the impact of maternal opioids on developing perinatal respiratory networks has not been studied. Using progressively more isolated respiratory network circuitry, we tested the hypothesis that maternal opioids directly impair neonatal central respiratory control networks. Fictive respiratory-related motor activity from isolated central respiratory networks was age-dependently impaired in neonates after maternal opioids within more complete respiratory networks (brainstem and spinal cords), but unaffected in more isolated networks (medullary slices containing the preBötzinger Complex). These deficits were due, in part, to lingering opioids within neonatal respiratory control networks immediately after birth and involved lasting impairments to respiratory pattern. Since opioids are routinely given to infants with NAS to curb withdrawal symptoms and our previous work demonstrated acute blunting of opioid-induced respiratory depression in neonatal breathing, we further tested the responses of isolated networks to exogenous opioids. Isolated respiratory control networks also demonstrated age-dependent blunted responses to exogenous opioids that correlated with changes in opioid receptor expression within a primary respiratory rhythm generating region, the preBötzinger Complex. Thus, maternal opioids age-dependently impair neonatal central respiratory control and responses to exogenous opioids, suggesting central respiratory impairments contribute to neonatal breathing destabilization after maternal opioids and likely contribute to respiratory distress in infants with NAS. These studies represent a significant advancement of our understanding of the complex effects of maternal opioids, even late in gestation, contributing to neonatal breathing deficits, necessary first steps in developing novel therapeutics to support breathing in infants with NAS.
Shrub encroachment alters plant trait response to nitrogen addition in a semi-arid grassland
Authors: Li Dan , Liu Yanshu , Yang Xiaohui , Zhang Xiao , Shi Zhongjie
Published: March 2023

Encroachment of shrubs over large regions of arid and semi-arid grassland can affect grassland traits and growth under a background of increasing nitrogen (N) deposition. However, the effects of N input rates on species traits and the growth of shrubs on grasslands remain unclear. We examined the effects of six different N addition rates on the traits of Leymus chinensis in an Inner Mongolia grassland encroached by the leguminous shrub, Caragana microphylla. We randomly selected 20 healthy L. chinensis tillers within shrubs and 20 tillers between shrubs in each plot, measuring the plant height, number of leaves, leaf area, leaf N concentration per unit mass (LNCmass), and aboveground biomass. Our results showed that N addition significantly enhanced the LNCmass of L. chinensis. The aboveground biomass, heights, LNCmass, leaf area, and leaf number of plants within the shrubs were higher than those between shrubs. For L. chinensis growing between shrubs, the LNCmass and leaf area increased with N addition rates, leaf number and plant height had binomial linear relationships to N addition rates. However, the number of leaves, leaf areas and heights of plants within shrubs did not vary under various N addition rates. Structural Equation Modelling revealed N addition had an indirect effect on the leaf dry mass through the accumulation of LNCmass. These results indicate that the response of dominant species to N addition could be regulated by shrub encroachment and provide new insights into management of shrub encroached grassland in the context of N deposition.
Alternative splicing in ABA signaling during seed germination
Authors: Sybilska Ewa , Daszkowska-Golec Agata
Published: March 2023

Seed germination is an essential step in a plant’s life cycle. It is controlled by complex physiological, biochemical, and molecular mechanisms and external factors. Alternative splicing (AS) is a co-transcriptional mechanism that regulates gene expression and produces multiple mRNA variants from a single gene to modulate transcriptome diversity. However, little is known about the effect of AS on the function of generated protein isoforms. The latest reports indicate that alternative splicing (AS), the relevant mechanism controlling gene expression, plays a significant role in abscisic acid (ABA) signaling. In this review, we present the current state of the art about the identified AS regulators and the ABA-related changes in AS during seed germination. We show how they are connected with the ABA signaling and the seed germination process. We also discuss changes in the structure of the generated AS isoforms and their impact on the functionality of the generated proteins. Also, we point out that the advances in sequencing technology allow for a better explanation of the role of AS in gene regulation by more accurate detection of AS events and identification of full-length splicing isoforms.
Relationship of insight to neurocognitive function and risk of recurrence in depression: A naturalistic follow-up study
Authors: Wang Min , Liu Qiong , Yang Xiao , Dou Yikai , Wang Yu , Zhang Zijian , Luo Ruiqing , Ma Yangrui , Wang Qiang , Li Tao , Ma Xiaohong
Published: March 2023

Introduction

Major depressive disorder (MDD) is a highly recurrent mental illness accompanied by impairment of neurocognitive function. Lack of insight may affect patients’ motivation to seek treatment, resulting in poor clinical outcomes. This study explores the relationship of insight to neurocognitive function and the risk of recurrence of depressive episodes in patients with MDD.

Methods

Demographic, clinical variables, and neurocognitive function measured with Intra-Extra Dimensional Set Shift (IED) from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were collected from 277 patients with MDD. Among them, 141 participants completed a follow-up visit within 1–5 years. Insight was measured using the 17-item Hamilton Depression Rating Scale (HAM-D). To explore the factors associated with recurrence, binary logistic regression models were used.

Results

Patients with MDD, without insight, had significantly higher total and factor scores (anxiety/somatization, weight, retardation, and sleep) on the HAM-D and worse performance in the neurocognition task, compared to those with insight. Furthermore, binary logistic regression revealed that insight and retardation can predict recurrence.

Conclusion

Lack of insight is associated with recurrence and impaired cognitive flexibility in patients with MDD.
Downregulation of cyclic adenosine monophosphate levels in leukocytes of hibernating captive black bears is similar to reported cyclic adenosine monophosphate findings in major depressive disorder
Authors: Tsiouris John A. , Flory Michael
Published: March 2023

Introduction

Cyclic adenosine monophosphate (cAMP) levels in the lymphoblasts and leukocytes of patients with major depressive disorder (MDD) have been reported to be downregulated compared to in controls. cAMP is a derivative of adenosine triphosphate (ATP), and low ATP turnover has been reported in the state of hypometabolism associated with human MDD and with mammalian hibernation due to suppression of mitochondrial metabolism. Similarities have been noted between many state-dependent neurobiological changes associated with MDD in humans and with mammalian hibernation.

Methods

To compare cAMP levels between human MDD and mammalian hibernation and to investigate whether cAMP downregulation is another state-dependent neurobiological finding, we measured cAMP concentrations in lysed leukocytes, plasma, and serum in serial blood specimens from nine female captive black bears (Ursus americanus; CBBs), and cortisol levels in serum from 10 CBBs.

Results

Cortisol levels were significantly higher during hibernation in CBBs, confirming previous findings in hibernating black bears and similar to findings in humans with MDD. cAMP levels were significantly lower during hibernation versus active states (pre-hibernation and exit from hibernation) and were similar to the cAMP downregulation reported in MDD patients versus euthymic patients or controls. cAMP level changes during the different states (hibernation, pre-hibernation, active) confirm their state-dependent status.

Discussion

These findings are similar to the neurobiological findings associated with the hypometabolism (metabolic depression) observed during mammalian hibernation and reported during MDD. A sudden increase in cAMP levels was observed before entrance into pre-hibernation and during exit from hibernation. Further investigation is suggested into the possible role of elevated cAMP levels in initiation of the chain reaction of changes in gene expression, proteins, and enzymes leading to the suppression of mitochondrial metabolism and to low ATP turnover. This process leads to hypometabolism, the old adaptive mechanism that is used by organisms for energy preservation and is associated with both mammalian hibernation and human MDD.
Hyperfocus symptom and internet addiction in individuals with attention-deficit/hyperactivity disorder trait
Authors: Ishii Sayuri , Takagi Shunsuke , Kobayashi Nanase , Jitoku Daisuke , Sugihara Genichi , Takahashi Hidehiko
Published: March 2023

Background

Hyperfocus symptom is the intense concentration on a certain object. It is a common but often overlooked symptom in those with attention-deficit/hyperactivity disorder (ADHD). Hyperfocus disrupts attention control and results in a focus on inappropriate behaviors. It allows individuals to focus on internet use and make them use internet excessively. This excessive internet use can lead to an addiction. This study investigated the status of IA and hyperfocus, the mediation effect of hyperfocus in relation to IA, and the relationship between ADHD subtypes and hyperfocus in those with ADHD symptoms.

Methods

This web-based cross-sectional study included 3,500 Japanese adults who completed internet-based questionnaires, which included the Adult ADHD Self-Report Scale (ASRS), Internet Addiction Test (IAT), and Hyperfocus Scale (HFS) to assess ADHD symptoms, internet dependence, and hyperfocus symptoms, respectively. The mediating role of HFS in the relationship between ASRS and IAT was assessed by mediation analysis. To analyze the relationship between hyperfocus symptoms and ADHD subtypes, we compared the correlation of HFS with the Inattention and Hyperactive Scores of ASRS.

Results

ADHD traits were associated with higher IAT scores (p < 0.001) and higher HFS scores (p < 0.001). Mediation analysis and bootstrap testing showed that HFS significantly mediated the association between ASRS and IAT. Analyses of ADHD subtypes demonstrated that HFS was significantly correlated with the Inattention (R = 0.597, p < 0.001) and Hyperactive (R = 0.523, p < 0.001) Scores. The correlation between HFS and the Inattention Score was significantly higher than that between HFS and the Hyperactive Score (p < 0.001).

Conclusion

Our findings suggest that hyperfocus may play an important role in addictive behavior in ADHD as a manifestation of attentional control malfunction.
First-line Immuno-chemotherapy for extensive-stage small-cell lung cancer: A network meta-analysis and cost-effectiveness analysis
Authors: Zhu Youwen , Liu Kun , Yang Qiuping , Zeng Manting , Peng Libo
Published: March 2023

Introduction

Many randomized controlled trials have indicated that immuno-chemotherapy could generate clinical benefits, though the cost of immuno-chemotherapy was so prohibitive and the options were varied. This investigation aimed at evaluating effectiveness, safety, and cost-effectiveness for immuno-chemotherapy as a first-line therapeutic option for ES-SCLC patients.

Methods

Multiple scientific literature repositories were searched for clinical studies where immuno-chemotherapy was regarded as the first-line treatment for ES-SCLC, which were published in English between Jan 1, 2000, and Nov 30, 2021. This study conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based upon US-resident payer perspectives. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated through NMA. In addition, costings, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost–benefit ratio (ICER) were estimated by CEA.

Results

We identified 200 relevant search records, of which four randomized controlled trials (RCTs) (2,793 patients) were included. NMA demonstrated that the effect of atezolizumab plus chemotherapy was ranked at a more elevated position in comparison to other immuno-chemotherapy options and chemotherapy alone, within the general population. The influence of atezolizumab plus chemotherapy and durvalumab plus chemotherapy was ranked higher within populations experiencing non-brain metastases (NBMs) andbrain metastases (BMs), respectively. The CEA revealed that the ICERs of immuno-chemotherapy over chemotherapyalone were higher than the willingness-to-pay (WTP) threshold of $150,000/QALY in any population. However, treatment with atezolizumab plus chemotherapy and durvalumab plus chemotherapy were more favorable health advantages than other immuno-chemotherapy regimens and chemotherapy alone, and the results were 1.02 QALYs and 0.89 QALYs within overall populations and populations with BMs, respectively.

Conclusion

The NMA and cost-effectiveness investigation demonstrated that atezolizumab plus chemotherapy could be an optimal first-line therapeutic option for ES-SCLC when compared with other immuno-chemotherapy regimens. Durvalumab plus chemotherapy is likely to be the most favorable first-line therapeutic option for ES-SCLC with BMs.
Accelerated aging in people experiencing homelessness: A rapid review of frailty prevalence and determinants
Authors: Mantell Rhys , Hwang Ye In Jane , Radford Kylie , Perkovic Silvija , Cullen Patricia , Withall Adrienne
Published: March 2023

Introduction

Older people experiencing homelessness (PEH) are a rapidly growing population at risk of accelerated aging and the early onset of geriatric conditions. One construct that shows promise in predicting age-related decline is frailty. Better understanding the rates and causes of frailty in PEH may improve understanding of its antecedents, thereby facilitating more targeted health and aged care service interventions. The aim of this study was to conduct a rapid review on the prevalence and determinants of frailty in adult PEH.

Methods

We conducted a rapid review of primary research papers studying PEH and frailty or frailty-related concepts.

Results

Fourteen studies were included, which indicate that frailty presents earlier and at higher rates in PEH than community-dwelling cohorts. A notable difficulty for many aging PEH was early-onset cognitive impairment which was associated with a range of negative functional outcomes. Another recurrent theme was the negative impact that drug and alcohol use and dependence can have on the health of PEH. Further, psychosocial and structural determinants such as loneliness, living in an impoverished neighborhood and being female had statistically significant associations with frailty and functional decline in PEH.

Discussion and implications

PEH in their 40s and 50s can be frail and experience geriatric conditions, including cognitive impairment. Factors that have important relationships to frailty and functional decline in PEH include cognitive deficits, drug and alcohol dependence and loneliness, as well as upstream determinants such as gender and ethnicity. More targeted data and research on these factors, including cohort studies to better investigate their potentially causal effects, is important for researchers and practitioners assessing and treating frailty in PEH, particularly those interested in early intervention and prevention.

Prospero registration ID

CRD42022292549.
Rupture, repair, the loss and re-construction of identity: Seeking support in situations of adolescent-to-parent violence and abuse
Authors: Rutter Nikki
Published: March 2023

Family violence is associated with life-long implications including increased vulnerability to poor mental and physical health, and increased risk of repeat victimization. When children or adolescents are the ones instigating the harm, mothers experience the compounding issues of violence, mother-blame, and stigma. In comparison to other forms of family violence, how mothers understand and interpret their experiences of adolescent-to-parent violence and abuse (APVA) is underexplored, particularly in relation to what it means for them at the emotional and individual level, and how this impacts their sense of self, and their mothering and professional identities. This brief research report uses an interpretive phenomenological approach utilising hermeneutics to explore how six mothers made-meaning of their lives and identity when their parenting journey was disrupted by APVA. Help-seeking behaviours were often met with denial, avoidance, and parent-blame from professionals, unless they were familiar with the mother through her professional identity first. Neurodivergences of the adolescents were reported, including mental illness, autism, pathological demand avoidance, and foetal alcohol spectrum disorder. and as no mother reported successful engagement with social care, youth justice, or mental health services when help-seeking, they needed to reimagine their parenting role, or hit crisis, before accessing appropriate support. Mothers could have been supported earlier if critical incidents were identified by services, and support and/or interventions provided earlier, when mothers first engaged in help-seeking behaviours.
Barriers and facilitators to implementing a new regulation restricting antimicrobial use in dairy production in Québec, Canada: A qualitative study
Authors: Millar Nikky , Dufour Simon , Lardé Hélène , Roy Jean-Philippe , Belloc Catherine , Francoz David , Paradis Marie-Ève , Archambault Marie , Fairbrother John Morris , Aenishaenslin Cécile
Published: March 2023

With the emergence of antimicrobial resistance (AMR), many countries are implementing restrictive regulations to reduce antimicrobial use (AMU) in animal production. Although these measures are effective at the national level, their implementation may generate challenges for producers and veterinarians. The objective of this study was to explore the barriers and facilitators of implementing a new regulation restricting the use of antimicrobials of very high importance for human health in the dairy production sector in the province of Québec, Canada. Individual interviews were conducted with fifteen veterinarians and twenty-seven dairy producers. Thematic analysis was performed based on the COM-B model of behavior change (capability-opportunity-motivation-behavior). Our results indicated that the lack of availability of alternative treatments, the long delays related to diagnostic tests and the fear of economic consequences were major barriers to the implementation of the regulation. A small number of producers also perceived that the regulation negatively impacted the health and wellbeing of their animals. Additionally, participants acknowledged the importance of early education and training to better understand the purpose of the regulation and increase its acceptability. Lastly, most participants reported that they had not only reduced their use of antimicrobials of very high importance for human health following the regulation, but they had also increased preventive practices on their farm. This study reveals that the implementation of restrictive regulations to reduce AMU in animal production can lead to multiple challenges in practice. Our results highlight the need for better communication and training of producers and veterinarians before and during the implementation of similar regulations in the future and underline the importance of measuring the direct and indirect impacts of those regulations on productivity and on animal health and wellbeing.
Fault Detection and Localisation of a Three-Phase Inverter with Permanent Magnet Synchronous Motor Load Using a Convolutional Neural Network
Authors: Łuczak Dominik , Brock Stefan , Siembab Krzysztof
Published: March 2023

Fault-tolerant control of a three-phase inverter can be achieved by performing a hardware reconfiguration of the six-switch and three-phase (6S3P) topology to the four-switch and three-phase (4S3P) topology after detection and localisation of the faulty phase. Together with hardware reconfiguration, the SVPWM algorithm must be appropriately modified to handle the new 4S3P topology. The presented study focuses on diagnosing three-phase faults in two steps: fault detection and localisation. Fault detection is needed to recognise the healthy or unhealthy state of the inverter. The binary state recognition problem can be solved by preparing a feature vector that is calculated from phase currents (ia, ib, and ic) in the time and frequency domains. After the fault diagnosis system recognises the unhealthy state, it investigates the signals to localise which phase of the inverter is faulty. The multiclass classification was solved by a transformation of the three-phase currents into a single RGB image and by training a convolutional neural network. The proposed methodology for the diagnosis of three-phase inverters was tested based on a simulation model representing a laboratory test bench. After the learning process, fault detection was possible based on a 128-sample window (corresponding to a time of 0.64 ms) with an accuracy of 99 percent. In the next step, the localisation of selected individual faults was performed on the basis of a 256-sample window (corresponding to a time of 1.28 ms) with an accuracy of 100 percent.
Evaluating the Combined Effects of Water and Fertilizer Coupling Schemes on Pear Vegetative Growth and Quality in North China
Authors: Liu Yanan , Bai Meijian , Li Yinong , Zhang Baozhong , Wu Xianbing , Shi Yuan , Liu Hairuo
Published: March 2023

Unreasonable fertilizer and irrigation applications and dosages in orchards in northern China result in poor vegetative growth and fruit quality. To reveal the combined effect of water and fertilizer coupling on vegetative growth and fruit quality, this study used pear as a field experiment material, considering: (1) irrigation lower limits (55%, 65%, 75%θf, θf is field capacity) and (2) nitrogen fertilizer application (162, 324, 486 kg·ha−1). Nine coupling schemes and a control treatment (C) were set up in the orthogonal combination. The results showed that, under the higher irrigation rate and nitrogen dose, the spring shoot length, base diameter, and leaves relative chlorophyll content values were increased by 36.77%, 31.86% and 12.91%, respectively. The response of each coupling scheme was different. However, selected water and nitrogen coupling schemes improved the fruit quality. The evaluation results indicated that medium irrigation and high fertilizer scheme were optimal. In conclusion, integrating the vegetative growth and fruit quality, it is recommended that the water and fertilizer coupling scheme for pear in the northern China is as follows: a lower irrigation limit of 65%θf and a nitrogen fertilizer amount of 486.00 kg·ha−1.