bluuebunny/crossref_metadata_2025 huggingface dataset:
Perspective taking in the human brain: complementary evidence from neuroimaging studies with media-based naturalistic stimuli and artificial controlled paradigms
Authors: Jääskeläinen Iiro P. , Kosonogov Vladimir
Published: February 2023

Perception and interpretation of various types of events and information in life crucially depend on one’s perspective. A specific perspective can be explicitly adopted, for example, via instructing an experimental subject, implicitly viaa priori information given to subjects, and by subjects’ personality traits or cultural background. The neural basis of perspective taking has been addressed in a number of recent neuroimaging studies, some of which have used movies and narratives as media-based stimuli to pursue a holistic understanding of the phenomenon under ecologically valid conditions. Results across these studies suggest that the human brain flexibly adapts to support the information-processing needs of different perspectives, however, also that inferior temporal-occipital areas and posterior-medial parietal areas are engaged across different perspectives. These findings are complemented by studies that have investigated specific aspects of perspective taking with highly controlled experimental designs. They have disclosed involvement of the temporoparietal junction in visual perspective taking and the importance of the affective component of the pain matrix when empathizing with others’ pain. Identification with the protagonists also seems to matter, as dorsomedial vs. ventromedial prefrontal areas are recruited when the protagonist is dissimilar vs. similar to self. Finally, as a translational aspect, perspective taking can, under certain conditions, serve as an effective emotion regulation technique, wherein lateral and medial regions of the prefrontal cortex seem to support reappraisal processes. Together, findings from studies with media-based stimuli and more traditional paradigms complement each other to gain a comprehensive understanding of the neural basis of perspective taking.
Insights into the role of intracellular calcium signaling in the neurobiology of neurodevelopmental disorders
Authors: Klocke Benjamin , Krone Kylie , Tornes Jason , Moore Carter , Ott Hayden , Pitychoutis Pothitos M.
Published: February 2023

Calcium (Ca2+) comprises a critical ionic second messenger in the central nervous system that is under the control of a wide array of regulatory mechanisms, including organellar Ca2+ stores, membrane channels and pumps, and intracellular Ca2+-binding proteins. Not surprisingly, disturbances in Ca2+ homeostasis have been linked to neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. However, aberrations in Ca2+ homeostasis have also been implicated in neuropsychiatric disorders with a strong neurodevelopmental component including autism spectrum disorder (ASD) attention-deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). While plasma membrane Ca2+ channels and synaptic Ca2+-binding proteins have been extensively studied, increasing evidence suggests a prominent role for intracellular Ca2+ stores, such as the endoplasmic reticulum (ER), in aberrant neurodevelopment. In the context of the current mini-review, we discuss recent findings implicating critical intracellular Ca2+-handling regulators such as the sarco-ER Ca2+ ATPase 2 (SERCA2), ryanodine receptors (RyRs), inositol triphosphate receptors (IP3Rs), and parvalbumin (PVALB), in the emergence of ASD, SCZ, and ADHD.
Transcranial cortex-wide Ca2+ imaging for the functional mapping of cortical dynamics
Authors: Yamada Serika , Wang Yan , Monai Hiromu
Published: February 2023

Visualization and tracking of the information flow in the broader brain area are essential because nerve cells make a vast network in the brain. Fluorescence Ca2+ imaging is a simultaneous visualization of brain cell activities in a wide area. Instead of classical chemical indicators, developing various types of transgenic animals that express Ca2+-sensitive fluorescent proteins enables us to observe brain activities in living animals at a larger scale for a long time. Multiple kinds of literature have reported that transcranial imaging of such transgenic animals is practical for monitoring the wide-field information flow across the broad brain regions, although it has a lower spatial resolution. Notably, this technique is helpful for the initial evaluation of cortical function in disease models. This review will introduce fully intact transcranial macroscopic imaging and cortex-wide Ca2+ imaging as practical applications.
Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer’s disease
Authors: Zhou Yujuan , Wang Xu , Liu Yingying , Gu Yulu , Gu Renjun , Zhang Geng , Lin Qing
Published: February 2023

Alzheimer’s disease (AD) is a degenerative disease of the central nervous system, the most common type of dementia in old age, which causes progressive loss of cognitive functions such as thoughts, memory, reasoning, behavioral abilities and social skills, affecting the daily life of patients. The dentate gyrus of the hippocampus is a key area for learning and memory functions, and an important site of adult hippocampal neurogenesis (AHN) in normal mammals. AHN mainly consists of the proliferation, differentiation, survival and maturation of newborn neurons and occurs throughout adulthood, but the level of AHN decreases with age. In AD, the AHN will be affected to different degrees at different times, and its exact molecular mechanisms are increasingly elucidated. In this review, we summarize the changes of AHN in AD and its alteration mechanism, which will help lay the foundation for further research on the pathogenesis and diagnostic and therapeutic approaches of AD.
Adult-born neurons add flexibility to hippocampal memories
Authors: Fölsz Orsolya , Trouche Stéphanie , Croset Vincent
Published: February 2023

Although most neurons are generated embryonically, neurogenesis is maintained at low rates in specific brain areas throughout adulthood, including the dentate gyrus of the mammalian hippocampus. Episodic-like memories encoded in the hippocampus require the dentate gyrus to decorrelate similar experiences by generating distinct neuronal representations from overlapping inputs (pattern separation). Adult-born neurons integrating into the dentate gyrus circuit compete with resident mature cells for neuronal inputs and outputs, and recruit inhibitory circuits to limit hippocampal activity. They display transient hyperexcitability and hyperplasticity during maturation, making them more likely to be recruited by any given experience. Behavioral evidence suggests that adult-born neurons support pattern separation in the rodent dentate gyrus during encoding, and they have been proposed to provide a temporal stamp to memories encoded in close succession. The constant addition of neurons gradually degrades old connections, promoting generalization and ultimately forgetting of remote memories in the hippocampus. This makes space for new memories, preventing saturation and interference. Overall, a small population of adult-born neurons appears to make a unique contribution to hippocampal information encoding and removal. Although several inconsistencies regarding the functional relevance of neurogenesis remain, in this review we argue that immature neurons confer a unique form of transience on the dentate gyrus that complements synaptic plasticity to help animals flexibly adapt to changing environments.
Comparison of oncological outcomes in elderly early-stage cervical cancer patients treated with radical surgery or radiotherapy: A real-world retrospective study with propensity score matching
Authors: Gu Yu , Cheng Hongyan , Cang Wei , Chen Lihua , Yang Junjun , Xiang Yang
Published: February 2023

Objective

To compare the oncological outcomes of radical surgery and radical radiotherapy in elderly (over 65 years) patients with early-stage cervical cancer (IB-IIA).

Methods

Elderly patients with stage IB-IIA cervical cancer treated at Peking Union Medical College Hospital from January 2000 to December 2020 were retrospectively reviewed. All patients were divided into the radiotherapy group (RT group) and the operation group (OP group) according to their primary intervention. Propensity score matching (PSM) analysis was performed to balance the biases. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and adverse effects.

Results

A total of 116 patients were eligible for the study (47 in the RT group, and 69 in the OP group), and after PSM, 82 patients were suitable for further analysis (37 in the RT group, and 45 in the OP group). In the real-world setting, it was found that compared with radiotherapy, operation was more frequently selected for elderly cervical cancer patients with adenocarcinoma (P < 0.001) and IB1 stage cancer (P < 0.001). The 5-year PFS rates between the RT and OP groups were not significant (82.3% vs. 73.6%, P = 0.659), and the 5-year OS rate of the OP group was significantly better than that in the RT group (100% vs. 76.3%, P = 0.039), especially in patients with squamous cell carcinoma (P = 0.029) and tumor size of 2~4 cm with G2 differentiation (P = 0.046). There was no significant difference in PFS between the two groups (P = 0.659). In the multivariate analysis, compared with operation, radical radiotherapy was an independent risk factor of OS (hazard ratio = 4.970, 95% CI, 1.023~24.140, P = 0.047). No difference was observed in adverse effects between the RT and OP groups (P = 0.154) and in ≥grade 3 adverse effects (P = 0.852).

Conclusion

The study found that surgery was more frequently selected for elderly cervical cancer patients with adenocarcinoma and IB1 stage cancer in the real-world setting. After PSM to balance the biases, it showed that compared with radiotherapy, surgery could improve the OS of elderly early-stage cervical cancer patients and was an independent protective factor of OS in elderly early-stage cervical cancer patients.
Diagnostic value of tumor-associated autoantibodies panel in combination with traditional tumor markers for lung cancer
Authors: Xu Yu , Zhang Wenjing , Xia Tingting , Liu Yuliang , Bi Zhoukui , Guo Liang , Xie Weijia , Xiang Ying , Xu Zhi , Yu Zubin , Li Yafei , Bai Li
Published: February 2023

Introduction

The diagnostic value of 7 tumor-associated autoantibodies (AABs) including p53, PGP9.5, SOX2, GAGE7, GBU4-5, MEGEA1, and CAGE for the detection of lung cancer has shown inconsistency in several studies. This study aimed to confirm the diagnostic value of 7AABs and to explore whether the diagnostic value would be improved by combining them with 7 traditional tumor-associated antigens (CEA, NSE, CA125, SCC, CA15-3, pro-GRP, and CYFRA21-1) in clinical settings.

Methods

The plasma levels of 7-AABs were detected by enzyme-linked immunosorbent assay (ELISA) in 533 lung cancer cases and 454 controls. The 7 tumor antigens (7-TAs) were measured by Electrochemiluminescence immunoassay with Cobas 6000 (Roche, Basel, Switzerland).

Results

The positive rate of 7-AABs in the lung cancer group (64.00%) was significantly higher than that of healthy controls (47.90%). The 7-AABs panel was able to discriminate lung cancer from controls with a specificity of 51.50%. After combining the 7-AABs with 7-TAs, the sensitivity showed a significantly enhancement compared with 7AABs panel alone (92.09% vs 63.21%). In patients with resectable lung cancer, the combination of 7-AABs and 7-TAs improved the sensitivity from 63.52% to 97.42%

Discussion

In conclusion, our study found that the diagnostic value of 7-AABs was enhanced when combined with 7-TAs. This combined panel could be used as promising biomarker to detect resectable lung cancer in clinical settings.
MicroRNAs as potential biomarkers and therapeutic targets in age-related macular degeneration
Authors: Cruz-Aguilar Marisa , Groman-Lupa Sergio , Jiménez-Martínez María C.
Published: February 2023

Age-related macular degeneration (AMD) involves degenerative and neovascular alteration in the macular region of the retina resulting in central vision loss. AMD can be classified into dry (dAMD) and wet AMD (wAMD). There is no established treatment for dAMD, and therapies available for wAMD have limited success. Diagnosis in early AMD stages is difficult due to the absence of clinical symptoms. Currently, imaging tests are used in the diagnosis of AMD, but cannot predict the clinical course. The clinical limitations to establishing a diagnosis of AMD have led to exploration for innovative and more sensitive tests to support the diagnosis and prognosis of the disease. MicroRNAs (miRNAs) are small single-stranded non-coding RNA molecules that negatively regulate genes by post-transcriptional gene silencing. Because these molecules are dysregulated in various processes implicated in the pathogenesis of AMD, they could contribute to the early detection of the disease and monitoring of its progression. Studies of miRNA profiling have indicated several miRNAs as potential diagnostic biomarkers of AMD, but no approved biomarker is available at present for early AMD detection. Thus, understanding the function of miRNAs in AMD and their use as potential biomarkers may lead to future advances in diagnosis and treatment. Here we present a brief review of some of the miRNAs involved in regulating pathological processes associated with AMD and discuss several candidate miRNAs proposed as biomarkers or therapeutic targets for AMD.
Case Report: A novel PHOX2B p.Ala248_Ala266dup variant causing congenital central hypoventilation syndrome
Authors: Artamonova Irina N. , Zlotina Anna M. , Ismagilova Olga R. , Levko Tatyana A. , Kolbina Natalia Yu , Bryzzhin Aleksandr V. , Smorodin Andrey P. , Borodin Alexandr V. , Mamaeva Ekaterina A. , Sukhotskaya Anna A. , Kagantsov Ilya M. , Malysheva Daria A. , Vasichkina Elena S. , Pervunina Tatiana M. , Petrova Natalia A.
Published: February 2023

Introduction

Congenital central hypoventilation syndrome (CCHS) is a rare disease characterized by central alveolar hypoventilation and impaired autonomic regulation, caused by pathogenic variants of PHOX2B gene. More than 90% of patients have a polyalanine repeat mutation (PARM) in the heterozygous state, characterized by the expansion of GCN repeats and an increase in the number of alanine repeats, so that genotypes 20/24–20/33 are formed (the normal genotype is 20/20). The remaining 10% of patients harbor non-PARMs.

Case description

We present a clinical case of a girl with a novel PHOX2B heterozygous genetic variant in the exon 3: NM_003924.4: c.735_791dup, p.Ala248_Ala266dup. The duplication includes 16 GCN (alanine) repeats and 3 adjacent amino acids. Both clinically healthy parents demonstrated a normal PHOX2B sequence. In addition, the girl has a variant of unknown significance in RYR1 gene and a variant of unknown significance in NKX2-5 gene. The child's phenotype is quite special. She needs ventilation during sleep, and has Hirschsprung's disease type I, arteriovenous malformation S4 of the left lung, ventricular and atrium septal defects, coronary right ventricular fistula, hemodynamically nonsignificant, episodes of sick sinus and atrioventricular dissociation with bradycardia, divergent alternating strabismus, and oculus uterque (both eyes) (OU) retinal angiopathy. Two episodes of hypoglycemic seizures were also registered. Severe pulmonary hypertension resolved after appropriate ventilation adjustment. Diagnostic odyssey was quite dramatic.

Conclusion

Detection of a novel PHOX2B variant expands the understanding of molecular mechanisms of CCHS and genotype–phenotype correlations.
Successful weaning from the invasive respiratory support after nusinersen treatment in a child with SMA type 1: A case report
Authors: Pan Meiling , Shi Jun , Miao Hongjun , Zhang Qin
Published: February 2023

Background

Spinal muscular atrophy (SMA) is an autosomal recessive disease, which can be classified into 4 types according to the symptom onset age and the highest physical developmental milestone. Among them, type 1 SMA is the most severe form that affects infants younger than 6 months. Permanent assisted ventilation is usually needed for infants with type 1 SMA before the age of 2 years due to the rapid progression of disease. Nusinersen can improve the motor function of SMA patients, but its effect on respiratory function varies. In the present study, we reported a case of child with type 1 SMA who was successfully weaned from the invasive respiratory support after nusinersen treatment.

Case presentation

A girl aged 6 years and 5 months was admitted for SMA in the Children’s Hospital of Nanjing Medical University for 18 times. She received the first administration of nusinersen in November 2020 at the age of 5 years and 1 month. At the age of 6 years and 1 month following 6 loading doses, we tried to wean the child from the invasive ventilation for non-invasive respiratory support using a nasal mask. At present, the patient shows oxygen saturation (SpO2) above 95% without ventilator support during the daytime, and no signs of dyspnea. A non-invasive home ventilator was used at nighttime for the sake of safety. The CHOP INTEND score increased by 11 points from the first loading dose to the sixth. She can now move her limbs against gravity, take in food orally and perform partial vocal function.

Conclusions

We reported a child with type 1 SMA who was successfully weaned from the 2-years invasive ventilation after 6 loading doses, and now only need non-invasive ventilation 12 h per day. It is suggested that even a late nusinersen treatment can improve respiratory and motor function in SMA patients, and wean them from mechanical ventilation, thus improve the quality of life and reduce the medical cost.
Gut-Brain cross talk: The pathogenesis of neurodevelopmental impairment in necrotizing enterocolitis
Authors: Manohar Krishna , Mesfin Fikir M. , Liu Jianyun , Shelley W. Christopher , Brokaw John P. , Markel Troy A.
Published: February 2023

Necrotizing enterocolitis (NEC) is a devastating condition of multi-factorial origin that affects the intestine of premature infants and results in high morbidity and mortality. Infants that survive contend with several long-term sequelae including neurodevelopmental impairment (NDI)—which encompasses cognitive and psychosocial deficits as well as motor, vision, and hearing impairment. Alterations in the gut-brain axis (GBA) homeostasis have been implicated in the pathogenesis of NEC and the development of NDI. The crosstalk along the GBA suggests that microbial dysbiosis and subsequent bowel injury can initiate systemic inflammation which is followed by pathogenic signaling cascades with multiple pathways that ultimately lead to the brain. These signals reach the brain and activate an inflammatory cascade in the brain resulting in white matter injury, impaired myelination, delayed head growth, and eventual downstream NDI. The purpose of this review is to summarize the NDI seen in NEC, discuss what is known about the GBA, explore the relationship between the GBA and perinatal brain injury in the setting of NEC, and finally, highlight the existing research into possible therapies to help prevent these deleterious outcomes.
YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosis via aberrant glycolysis associated with EGFR/PKM2/HIF-1α pathway
Authors: Li Xin , Ma Tian-Kui , Wang Min , Zhang Xiao-Dan , Liu Tian-Yan , Liu Yue , Huang Zhao-Hui , Zhu Yong-Hong , Zhang Shuang , Yin Li , Xu Yan-Yan , Ding Hong , Liu Cong , Shi Hang , Fan Qiu-Ling
Published: February 2023

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD.

Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis.

Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis.

Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.
Natural product-based bioactive agents in combination attenuate neuroinflammation in a tri-culture model
Authors: Liu Yang , Chang Dennis , Liu Tianqing , Zhou Xian
Published: February 2023

Introduction: Neuroinflammation is an important pathological event contributing to the onset and progression of neurodegenerative diseases. The hyperactivation of microglia triggers the release of excessive proinflammatory mediators that lead to the leaky blood-brain barrier and impaired neuronal survival. Andrographolide (AN), baicalein (BA) and 6-shogaol (6-SG) possess anti-neuroinflammatory properties through diverse mechanisms of action. The present study aims to investigate the effects of the pair-combinations of these bioactive compounds in attenuating neuroinflammation.

Methods: A tri-culture model with microglial N11 cells, microvascular endothelial MVEC(B3) cells, and neuroblastoma N2A cells was established in a transwell system. AN, BA and 6-SG used alone (25 µM) or in pair-wised combinations (12.5 + 12.5 µM) were subjected to the tri-culture system. Upon the stimulation of lipopolysaccharides (LPS) at 1 μg/mL, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) levels were determined by ELISA assays. Immunofluorescence staining was applied to investigate the nuclear translocation of nuclear factor kappa B p65 (NF-κB p65) on N11 cells, expressions of protein zonula occludens-1 (ZO-1) on MVEC cells and phosphorylated tau (p-tau) on N2A cells, respectively. The endothelial barrier permeability of MVEC cells was assessed by the Evans blue dye, and the resistance from the endothelial barrier was measured by transepithelial/endothelial electrical resistance (TEER) value. Neuronal survival of N2A cells was determined by Alamar blue and MTT assays.

Results: Combinations of AN-SG and BA-SG synergistically lowered the TNF and IL-6 levels in LPS-induced N11 cells. Remarkably, the combined anti-neuroinflammatory effects of AN-SG and BA-SG remained significantly greater compared to their individual components at the same concentration level. The molecular mechanism of the attenuated neuroinflammation was likely to be mediated by downregulation of NF-κB p65 translocation (p < 0.0001 vs. LPS stimulation) in N11 cells. In the MVEC cells, both AN-SG and BA-SG restored TEER values, ZO-1 expression and reduced permeability. Furthermore, AN-SG and BA-SG significantly improved neuronal survival and reduced expressions of p-tau on N2A cells.

Discussion: The AN-SG and BA-SG combinations showed greater anti-neuroinflammatory potential than those used alone in mono- and tri-cultured N11 cells, thereby further protecting endothelial tight junction and neuronal survival. Taken together, AN-SG and BA-SG may provide improved anti-neuroinflammatory and neuroprotective activities.
Manhattan Project 1940s research on the prompt fission neutron spectrum
Authors: Chadwick Mark B. , Capote Roberto
Published: February 2023

We describe how the prompt fission neutron spectrum (PFNS) was determined for the Manhattan Project at Los Alamos. Early work before World War II at American and British universities is described, together with theoretical work by Feather at Cambridge and Bethe at Los Alamos. As the Manhattan Project was being planned in 1942, two experiments on natural uranium were commissioned that proved to be influential: 1) An integral experiment at Chicago by Christy and Manley that accurately determined the average PFNS spectrum energy, 2.2 ± 0.2 MeV; 2) Bloch and Staub’s Stanford cyclotron measurement of the PFNS spectrum, which obtained an average energy of 1.70 ± 0.34 MeV. These two papers, previously unavailable outside of Los Alamos, are reproduced in the Supplementary Appendix. From these data, at the beginning of the project in 1943 Serber estimated an average 235U PFNS energy of 2 MeV, and indeed this agrees with today’s best estimate. The challenges facing the scientists involved both the availability of only very small samples of enriched uranium and plutonium targets, and fast neutron detection technologies. During the project, 235U and 239Pu PFNS were measured by Nicodemus and Staub. These also proved to be quite accurate and gave an average spectrum energy of 2 MeV for 235U. [This is not reproduced in the Appendix because it was published after the war in Physical Review 89, 1288 (1953)]. New methods were developed to enable more accurate measurements, and this paper describes how the PFNS was determined surprisingly well by 1945. We end by describing the post-war measurements in the 50s, including the PFNS data used by Ford and Wheeler in their simulations in 1951, the Bonner 1952 data, the seminal 1952 Watt paper with a new empirical parametrization of the PFNS, and the accurate PFNS measurement undertaken at Los Alamos by Cranberg et al. in 1956. We compare the measurements with our best understanding today as embodied in the Evaluated Nuclear Data File ENDF/B-VIII.0. Some images from historical documents in our Los Alamos National Security Research Center (NSRC) archives are shown.
Using carpet plots to analyze blood transit times in the brain during hypercapnic challenge magnetic resonance imaging
Authors: Fitzgerald Bradley , Yao Jinxia Fiona , Hocke Lia M. , Frederick Blaise deB. , van Niftrik Christiaan Hendrik Bas , Tong Yunjie
Published: February 2023

Blood arrival time and blood transit time are useful metrics in characterizing hemodynamic behaviors in the brain. Functional magnetic resonance imaging in combination with a hypercapnic challenge has been proposed as a non-invasive imaging tool to determine blood arrival time and replace dynamic susceptibility contrast (DSC) magnetic resonance imaging, a current gold-standard imaging tool with the downsides of invasiveness and limited repeatability. Using a hypercapnic challenge, blood arrival times can be computed by cross-correlating the administered CO2 signal with the fMRI signal, which increases during elevated CO2 due to vasodilation. However, whole-brain transit times derived from this method can be significantly longer than the known cerebral transit time for healthy subjects (nearing 20 s vs. the expected 5–6 s). To address this unrealistic measurement, we here propose a novel carpet plot-based method to compute improved blood transit times derived from hypercapnic blood oxygen level dependent fMRI, demonstrating that the method reduces estimated blood transit times to an average of 5.32 s. We also investigate the use of hypercapnic fMRI with cross-correlation to compute the venous blood arrival times in healthy subjects and compare the computed delay maps with DSC-MRI time to peak maps using the structural similarity index measure (SSIM). The strongest delay differences between the two methods, indicated by low structural similarity index measure, were found in areas of deep white matter and the periventricular region. SSIM measures throughout the remainder of the brain reflected a similar arrival sequence derived from the two methods despite the exaggerated spread of voxel delays computed using CO2 fMRI.
A HD-Zip I transcription factor from physic nut, JcHDZ21, confers sensitive to salinity in transgenic Arabidopsis
Authors: Tang Yuehui , Peng Jingrui , Lin Jin , Zhang Miaomiao , Tian Yun , Shang Yaqian , Chen Shuying , Bao Xinxin , Wang Qiyuan
Published: February 2023

HD-Zip is a plant-specific transcription factor that plays an important regulatory role in plant growth and stress response. However, there have been few reports on the functions of members of the physic nut HD-Zip gene family. In this study, we cloned a HD-Zip I family gene from physic nut by RT-PCR, and named JcHDZ21. Expression pattern analysis showed that JcHDZ21 gene had the highest expression in physic nut seeds, and salt stress inhibited the expression of JcHDZ21 gene. Subcellular localization and transcriptional activity analysis showed that JcHDZ21 protein is localized in the nucleus and has transcriptional activation activity. Salt stress results indicated that JcHDZ21 transgenic plants were smaller and had more severe leaf yellowing compared to those of the wild type. Physiological indicators showed that transgenic plants had higher electrical conductivity and MDA content, and lower proline and betaine content compared with wild-type plants under salt stress. In addition, the expression of abiotic stress-related genes in JcHDZ21 transgenic plants was significantly lower than that in wild type under salt stress. Our results showed that ectopic expression of JcHDZ21 increased the sensitivity of transgenic Arabidopsis to salt stress. This study provides a theoretical basis for the future application of JcHDZ21 gene in the breeding of physic nut stress-tolerant varieties.
An improved reference genome for Trifolium subterraneum L. provides insight into molecular diversity and intra-specific phylogeny
Authors: Shirasawa Kenta , Moraga Roger , Ghelfi Andrea , Hirakawa Hideki , Nagasaki Hideki , Ghamkhar Kioumars , Barrett Brent A. , Griffiths Andrew G. , Isobe Sachiko N.
Published: February 2023

Subterranean clover (Trifolium subterraneum L., Ts) is a geocarpic, self-fertile annual forage legume with a compact diploid genome (n = x = 8, 544 Mb/1C). Its resilience and climate adaptivity have made it an economically important species in Mediterranean and temperate zones. Using the cultivar Daliak, we generated higher resolution sequence data, created a new genome assembly TSUd_3.0, and conducted molecular diversity analysis for copy number variant (CNV) and single-nucleotide polymorphism (SNP) among 36 cultivars. TSUd_3.0 substantively improves prior genome assemblies with new Hi-C and long-read sequence data, covering 531 Mb, containing 41,979 annotated genes and generating a 94.4% BUSCO score. Comparative genomic analysis among select members of the tribe Trifolieae indicated TSUd 3.0 corrects six assembly-error inversion/duplications and confirmed phylogenetic relationships. Its synteny with T. pratense, T. repens, Medicago truncatula and Lotus japonicus genomes were assessed, with the more distantly related T. repens and M. truncatula showing higher levels of co-linearity with Ts than between Ts and its close relative T. pratense. Resequencing of 36 cultivars discovered 7,789,537 SNPs subsequently used for genomic diversity assessment and sequence-based clustering. Heterozygosity estimates ranged from 1% to 21% within the 36 cultivars and may be influenced by admixture. Phylogenetic analysis supported subspecific genetic structure, although it indicates four or five groups, rather than the three recognized subspecies. Furthermore, there were incidences where cultivars characterized as belonging to a particular subspecies clustered with another subspecies when using genomic data. These outcomes suggest that further investigation of Ts sub-specific classification using molecular and morpho-physiological data is needed to clarify these relationships. This upgraded reference genome, complemented with comprehensive sequence diversity analysis of 36 cultivars, provides a platform for future gene functional analysis of key traits, and genome-based breeding strategies for climate adaptation and agronomic performance. Pangenome analysis, more in-depth intra-specific phylogenomic analysis using the Ts core collection, and functional genetic and genomic studies are needed to further augment knowledge of Trifolium genomes.
Assessment of trunk microtensiometer as a novel biosensor to continuously monitor plant water status in nectarine trees
Authors: Conesa María R. , Conejero Wenceslao , Vera Juan , Ruiz-Sánchez Ma Carmen
Published: February 2023

The objective of this work was to validate the trunk water potential (Ψtrunk), using emerged microtensiometer devices, as a potential biosensor to ascertain plant water status in field-grown nectarine trees. During the summer of 2022, trees were subjected to different irrigation protocols based on maximum allowed depletion (MAD), automatically managed by real-time soil water content values measured by capacitance probes. Three percentages of depletion of available soil water (α) were imposed: (i) α=10% (MAD=27.5%); (ii) α=50% (MAD=21.5%); and (iii) α=100%, no-irrigation until Ψstem reached -2.0 MPa. Thereafter, irrigation was recovered to the maximum water requirement of the crop. Seasonal and diurnal patterns of indicators of water status in the soil-plant-atmosphere continuum (SPAC) were characterised, including air and soil water potentials, pressure chamber-derived stem (Ψstem) and leaf (Ψleaf) water potentials, and leaf gas exchange, together with Ψtrunk. Continuous measurements of Ψtrunk served as a promising indicator to determine plant water status. There was a strong linear relationship between Ψtrunkvs. Ψstem (R2 = 0.86, p<0.001), while it was not significant between Ψtrunkvs. Ψleaf (R2 = 0.37, p>0.05). A mean gradient of 0.3 and 1.8 MPa was observed between Ψtrunkvs.Ψstem and Ψleaf, respectively. In addition, Ψtrunk was the best matched to the soil matric potential. The main finding of this work points to the potential use of trunk microtensiometer as a valuable biosensor for monitoring the water status of nectarine trees. Also, trunk water potential agreed with the automated soil-based irrigation protocols implemented.
Effect of transcranial direct current stimulation on postpartum depression: A study protocol for a randomized controlled trial
Authors: Sun Weiming , Kang Xizhen , Dong Xiangli , Zeng Zijian , Zou Qing , Su Meixiang , Zhang Ke , Liu Guanxiu , Yu Guohua
Published: February 2023

Postpartum depression (PPD) is a complex combination of physiological, emotional, and behavioral alterations associated with postpartum chemical, social, and psychological variations. It does harm to the relationship between family members that could potentially last for years. However, standard depression treatments are not ideal for PPD, and the outcomes of these treatments are debatable. Transcranial direct current stimulation (tDCS) is an emerging technology that could provide patients with PPD with a safe and non-pharmacological treatment. tDCS can relieve depression by directly stimulating the prefrontal cortex through the excitatory effect of the anode. It may also ease depression indirectly by promoting the production and release of the neurotransmitter GABA. The mechanism of tDCS makes it an ideal therapeutic approach to treat PPD, although it has not been widely used, and its effect has not been evaluated systematically and effectively. A double-blind, randomized controlled trial will be conducted involving 240 tDCS-naive patients with PPD, who will be randomly divided into two groups. One group will receive routine clinical treatment and care with active tDCS, and the other group will receive routine clinical treatment and care with sham tDCS. Each group of patients will receive a 3-week intervention during which they will receive 20 min of active or sham tDCS 6 days per week. The Montgomery–Åsberg Depression Rating Scale will be administered before the intervention as a baseline and on each weekend throughout the intervention phase. Before and after the intervention, the Perceived Stress Scale and the Positive and Negative Affect Schedule will be evaluated. Side effects and abnormal reactions will be recorded during each treatment. As antidepressants are banned in the study, the results will not be affected by drugs and will therefore be more accurate. Nonetheless, this experiment will be conducted in a single center as a small sample experiment. Therefore, future studies are required to confirm the effectiveness of tDCS in treating PPD.
Can vertical environmental regulation become a sharp weapon in China's green development process? The moderating role of pollution dividend
Authors: Du Sixuan , Pan Haiying , Meng Zuhan , Wang Ni , Ren Jiajia
Published: February 2023

Optimizing the vertical environmental regulation (VER) effect of the central government and reducing the negative execution motivation of local governments have become the priority points to accelerate the green development of China. Based on the spatial Durbin model, this paper not only examines the influence of VER on green development efficiency (GDE), but also discusses the moderating effect of politically and economically motivated pollution dividend (PPD and EPD) on the relationship between them. The research results are as follows: (1) VER has a U-shaped effect on local GDE, the green governance effect of which began to appear when VER was higher than 1.561. VER has an inverted N-shaped effect on adjacent GDE. When the VER intensity lies in (0.138, 3.012), it has a positive spatial spillover effect. (2) PPD weakens the local green governance effect of VER, while EPD positively moderates it. Both of them have no significant moderating effect on it in neighboring areas. (3) Cross-regional cooperative governance moderates the short-term weakness and pollution transfer of VER, and generally facilitates the positive moderating effect of PPD and EPD. In China's two major economic belts, VER, PPD and EPD also have different performances. This study proves the important influence of local inter-governmental competition and promotion tournament on the central environmental regulation for the first time, which is of great significance for optimizing the top-level design of the central government and implementing the governance responsibility of local governments.
Digital health in the era of COVID-19: Reshaping the next generation of healthcare
Authors: Getachew Emnet , Adebeta Tsegaye , Muzazu Seke G. Y. , Charlie Loveness , Said Bibie , Tesfahunei Hanna Amanuel , Wanjiru Catherine Lydiah , Acam Joan , Kajogoo Violet Dismas , Solomon Samrawit , Atim Mary Gorret , Manyazewal Tsegahun
Published: February 2023

COVID-19 is one of the most deadly diseases to have stricken us in recent decades. In the fight against this disease, governments and stakeholders require all the assistance they can get from various systems, including digital health interventions. Digital health technologies are supporting the tracking of the COVID-19 outbreak, diagnosing patients, expediting the process of finding potential medicines and vaccines, and disinfecting the environment, The establishment of electronic medical and health records, computerized clinical decision support systems, telemedicine, and mobile health have shown the potential to strengthen the healthcare system. Recently, these technologies have aided the health sector in a variety of ways, including prevention, early diagnosis, treatment adherence, medication safety, care coordination, documentation, data management, outbreak tracking, and pandemic surveillance. On the other hand, implementation of such technologies has questions of cost, compatibility with existing systems, disruption in patient-provider interactions, and sustainability, calling for more evidence on clinical utility and economic evaluations to help shape the next generation of healthcare. This paper argues how digital health interventions assist in the fight against COVID-19 and their opportunities, implications, and limitations.
Star-exoplanet interactions: A growing interdisciplinary field in heliophysics
Authors: Garcia-Sage K. , Farrish A. O. , Airapetian V. S. , Alexander D. , Cohen O. , Domagal-Goldman S. , Dong C. , Gronoff G. , Halford A. J. , Lazio J. , Luhmann J. G. , Schwieterman E. , Sciola A. , Segura A. , Toffoletto F. , Vievering J. , Ahmed Md Redyan , Bali K. , Rau G.
Published: February 2023

Traditionally, heliophysics is characterized as the study of the near-Earth space environment, where plasmas and neutral gases originating from the Earth, the Sun, and other solar system bodies interact in ways that are detectable only through in-situ or close-range (usually within ∼10 AU) remote sensing. As a result, heliophysics has data from the space environment around a handful of solar system objects, in particular the Sun and Earth. Comparatively, astrophysics has data from an extensive array of objects, but is more limited in temporal, spatial, and wavelength information from any individual object. Thus, our understanding of planetary space environments as a complex, multi-dimensional network of specific interacting systems may in the past have seemed to have little to do with the highly diverse space environments detected through astrophysical methods. Recent technological advances have begun to bridge this divide. Exoplanetary studies are opening up avenues to study planetary environments beyond our solar system, with missions like Kepler, TESS, and JWST, along with increasing capabilities of ground-based observations. At the same time, heliophysics studies are pushing beyond the boundaries of our heliosphere with Voyager, IBEX, and the future IMAP mission.

The interdisciplinary field of star-exoplanet interactions is a critical, growing area of study that enriches heliophysics. A multidisciplinary approach to heliophysics enables us to better understand universal processes that operate in diverse environments, as well as the evolution of our solar system and extreme space weather. The expertise, data, theory, and modeling tools developed by heliophysicists are crucial in understanding the space environments of exoplanets, their host stars, and their potential habitability. The mutual benefit that heliophysics and exoplanetary studies offer each other depends on strong, continuing solar system-focused and Earth-focused heliophysics studies. The heliophysics discipline requires new targeted funding to support inter-divisional opportunities, including small multi-disciplinary research projects, large collaborative research teams, and observations targeting the heliophysics of planetary and exoplanet systems. Here we discuss areas of heliophysics-relevant exoplanetary research, observational opportunities and challenges, and ways to promote the inclusion of heliophysics within the wider exoplanetary community.
A machine learning-based model for the next 3-day geomagnetic index (Kp) forecast
Authors: Wang Jingjing , Luo Bingxian , Liu Siqing , Shi Liqin
Published: February 2023

The 3-day Kp forecast product is important and necessary for space weather forecasts. There is some essential information that can be obtained from the 3-day Kp forecast product, such as the start time of the geomagnetic storm, the maximum storm level, and the storm duration. In this study, we aimed to predict the next 3-day Kp index based on the previous Kp time series and SDO/AIA 193 Å images. We prepared datasets from May 2010 to December 2019 for training and datasets from January 2020 to October 2022 for testing. The similarity parameters of the previous and current geomagnetic conditions between the samples are calculated and analyzed. We assumed that the paired samples with high-similarity parameters of the previous and current geomagnetic conditions would also have high-similarity parameters of the next 3-day geomagnetic conditions. Based on the assumption, we selected the three best similarity parameters through the feature selection process and adopted the scalable tree boosting system (XGBoost) to develop a prediction model. It took the similarity parameters of the previous and current geomagnetic conditions as input and provided the best match sample from the training subset as a forecast. For the next 3-day non-storm (maximum Kp < 5) prediction period, our model reached an F1-score of 0.96. For the next 3-day storm (maximum Kp ≥ 5) prediction period, our model reached an F1-score of 0.82, a recall of 0.70, and a precision of 0.98.
Foodborne disease hazards and burden in Ethiopia: A systematic literature review, 1990–2019
Authors: Gazu Lina , Alonso Silvia , Mutua Florence , Roesel Kristina , Lindahl Johanna F. , Amenu Kebede , Maximiano Sousa Filipe , Ulrich Pattama , Guadu Tadesse , Dione Michel , Ilboudo Guy , Knight-Jones Theodore , Grace Delia
Published: February 2023

Background

Foodborne disease (FBD) affects millions of people each year, posing a health burden similar to malaria, tuberculosis or HIV. A recent World Bank study estimated the productivity losses alone attributed to unsafe food within Africa at $20 billion in 2016, and the cost of treating these illnesses at an additional $3.5 billion. Ethiopia faces multiple food safety challenges due to lack of infrastructure and basic pre-requisites for food safety such as clean water and environment, washing facilities, compounded by limited implementation of food safety regulations, and a lack of incentives for producers to improve food safety. A consolidation of our understanding and evidence of the source, nature and scale of FBD in Ethiopia is needed to inform policy and future research. We performed a Systematic Literature Review (SLR) of publications on FBD occurrence in Ethiopia including hazard presence and impact.

Method

The SLR followed Cochrane and PRISMA guidelines. We searched PubMed and CAB-Direct for relevant publications between 1990 and 2019 (inclusive). Observational studies and reviews were included. Two reviewers screened titles and abstracts, and retained publications were reviewed in full for quality and data extraction.

Result

In total 128 articles met the inclusion criteria. Most articles focused on the identification of biological hazards in food. High levels of microbial contamination in different food value chains were often found in the small,ad hoc, observational studies that dominated the literature. Raw milk (22/128, 17.0%) and raw beef (21/128, 16.4%) were the most studied food products. Foodborne (FB) parasites were often found at higher rates in food than bacterial and viral pathogens, possibly due to differences in ease of identification. High levels of bacterial contamination on the hands of food handlers were widely reported. There were no reports on the incidence of human FBDs or resulting health and economic impacts.

Conclusion

Our findings reflect existing concerns around food safety in Ethiopia. A lack of substantial, coordinated studies with robust methodologies means fundamental gaps remain in our knowledge of FBD in Ethiopia, particularly regarding FBD burden and impact. Greater investment in food safety is needed, with enhanced and coordinated research and interventions.