bluuebunny/crossref_metadata_2025 huggingface dataset:
Making the case for Africa and the democratic republic of the Congo as the global rare earth element supply leaders
Authors: Gibson Pandwe Aletha
Published: June 2023

The initiative to electrify and decarbonize economies over the next two decades, particularly in the energy and transportation sectors, is going to cause a significant increase in demand for critical rare earth elements , Rare earth elements have already proved themselves highly useful, contributing to many everyday items including batteries, electric vehicles, computer components, photovoltaic panels, and turbines to name a few examples. The number of countries outside of the United States that currently source and provide these critical elements is limited, posing implications for the security and continuity of the global and national supply chain and specifically to the national security of the US. This article is a mini review of the existing literature with recommendations for partnerships. It discusses potential stress points in the current supply chain of REEs and explores the feasibility of expanded American partnerships with Africa and the Democratic Republic of the Congo specifically to address opportunities to strengthen the security and transparency of the global supply chain of REEs. In Africa, REEs are concentrated in countries like South Africa, Madagascar, Malawi, Kenya, Namibia, the DRC, Mozambique, Tanzania, Zambia, and Burundi. These countries have significant quantities of neodymium, praseodymium, and dysprosium among other REEs that are required in the numerous technological items (including green technologies) that are manufactured today. The framework for extracting the elements from those countries requires specific attention to ensure the preservation of natural assets that are key to global health.
Spatio-temporal variation of water requirement and meteorological impact factors of maize Shaanxi, China
Authors: Duan Jingjing , Zhao Jing , Sun Geyao , Gao Feng
Published: June 2023

To quantitatively reveal the characteristics of the spatial and temporal distribution and the influencing factors of the maize water requirement in Shaanxi Province, the Penman-Monteith model and path analysis were used to systematically analyze the interannual variation and spatial distribution of the maize water requirement at different growth stages in three climatic zones in Shaanxi Province. And the relationship between the water requirement and meteorological factors based on daily meteorological data in Shaanxi Province for the past 60 years. The results showed that the maize water requirement during the whole growth period decreased from 1960 to 1989, with a rate of change of −2.08 mm/a, increased from 1989 to 2019, with a rate of change of 0.38 mm/a, and decreased from 1960 to 2019, with a rate of change of −0.46 mm/a. The water requirement of maize decreases from north to south during the whole reproductive period. That of seedling and male stage are more in the Guanzhong, followed by the north and the least in the south. The water requirement of maize at jointing stage increased from north to south. And the water requirement distribution is more in the north, followed by the south and the least in the Guanzhong area during the maturity period. The average temperature and the duration of the sunshine are the key factors that affect maize water requirement in Shaanxi Province, and have an increasing effect on water requirement, wind speed has an increasing effect on water requirement but is not obvious, water vapor pressure and relative humidity have an inhibiting effect on water requirement. For spring maize, the promoting effect of the duration of the sunshine on maize water requirement was gradually strengthened from north to south. The promoting effect of mean temperature and wind speed decreased gradually. The inhibitory effect of water vapor pressure and relative humidity decreases continuously. This study can provide a scientific basis for the management of irrigation quota in maize growing areas under similar cropping conditions.
Human brains have shrunk: the questions are when and why
Authors: DeSilva Jeremy , Fannin Luke , Cheney Isabelle , Claxton Alexander , Ilieş Iulian , Kittelberger Jessica , Stibel Jeff , Traniello James
Published: June 2023

Human brain reduction from the Late Pleistocene/Holocene to the modern day is a longstanding anthropological observation documented with numerous lines of independent evidence. In a recent study (DeSilva et al., 2021; Front. Ecol. Evol.), we analyzed a large compilation of fossil and recent human crania and determined that this reduction was surprisingly recent, occurring rapidly within the past 5,000 to 3,000 years of human history. We attributed such a change as a consequence of population growth and cooperative intelligence and drew parallels with similar evolutionary trends in eusocial insects, such as ants. In a reply to our study, Villmoare and Grabowski (2022; Front. Ecol. Evol.) reassessed our findings using portions of our dataset and were unable to detect any reduction in brain volume during this time frame. In this paper, responding to Villmoare and Grabowski’s critique, we reaffirm recent human brain size reduction in the Holocene, and encourage our colleagues to continue to investigate both the timing and causes of brain size reduction in humans in the past 10,000 years.
Blood analytes of hawksbill sea turtles (Eretmochelys imbricata) from Florida waters: reference intervals and size-relevant correlations
Authors: Stacy Nicole I. , Perrault Justin R. , Wood Lawrence D.
Published: June 2023

Assessments of health variables in wild animal populations have evolved into important tools for characterizing spatiotemporal population trends and fitness, effects of stressors, diseases, and ecosystem health. Blood as a sample matrix can be obtained fairly non-invasively in the field, with preservation and sample processing techniques that allow for readily available routine and advanced diagnostic testing of blood. For wild-caught hawksbill sea turtles (Eretmochelys imbricata) foraging in southeastern Florida, USA, the objectives of this study were to (1) establish reference intervals for hematological and 24 plasma biochemical analytes, (2) determine length-and body condition-specific relationships with blood analytes, and (3) determine how water temperature influenced plasma biochemical analytes. Reference intervals were established for clinically normal juvenile (n = 26) and subadult (n = 39) hawksbills, with descriptive data reported for adult turtles (n = 3). Although subadults (mainly captured at Palm Beach County) were heavier and larger with greater body depth, juveniles (mainly captured at Monroe County) had a higher body condition index. Positive length-specific correlations were identified for packed cell volume, eosinophils, aspartate aminotransferase, phosphorus, cholesterol, glutamate dehydrogenase, total protein, albumin, and globulins, with negative correlations including alkaline phosphatase, creatine kinase, calcium, calcium to phosphorus ratio, and glucose. Subadults had less frequent morphological features of red blood cell regeneration compared to juveniles. These findings provide insight into life-stage class differences regarding hematopoiesis, antigenic stimulation, somatic growth, dietary shifts, nutritional status, osmoregulation, metabolism, physical activity or stress levels, and possible habitat differences. Life-stage class is the likely driver for the observed blood analyte differences, in addition to influences from water temperature. The data herein offer baseline information for a snapshot in time for critically endangered hawksbills inhabiting the Florida reef system and for answering individual-and population-relevant questions of relevance to conservation and population management.
Assessment of hydrological connectivity characteristics of riparian zones and their correlation with root–soil composites at different bank heights of a first-class river in China
Authors: Yang Qihong , Zhang Chaobo , Liu Xiaoguang , Yao Shiming , Huang Renyong
Published: June 2023

Under the combined effects of topography and vegetation, hydrological connectivity characteristics of riverbank slopes become complex and unclear, which limit the utilization and protection of riparian zones. To quantify the hydrological connectivity in root–soil composites, we conducted dyeing and tracing experiments in a high elevation plot and a low elevation plot on the bank of the Fenhe River. Soil and root properties and hydrological connectivity indexes in the plots were measured and analyzed. The results showed that the soil dyeing area ratio was approximate 1 in the soil depth of 0–5 cm and then decreased to 0.1 from 5 cm to 25 cm. The dyeing area ratio, maximum dyed depth, length index, peak value and non-uniformity coefficient of the high plot (Pc2) were 27%, 26%, 5%, 40% and 45% greater than those of the low plot (Pc1). The index of hydrological connectivity (IHC) of Pc2 was 7%, 44% and 71% greater than Pc1 in the soil depths 0–10 cm, 10–20 cm and 20–30 cm respectively. There was no significant correlation between the IHC and the physical properties of the soil at different depths, and the soil hydrological connectivity was closely related to the plant roots with diameter less than 1mm. The study primarily explored the characteristics of hydrological connectivity in root–soil composites. The results provide a scientific basis for exploring hydrological connectivity of riparian zones, which can support future riparian zone protection and restoration efforts in similar regions.
Prioritization of nasal polyp-associated genes by integrating GWAS and eQTL summary data
Authors: Yoshikawa Masahiro , Asaba Kensuke , Nakayama Tomohiro
Published: June 2023

Background: Nasal polyps (NP) are benign inflammatory growths of nasal and paranasal sinus mucosa that can substantially impair patients’ quality of life by various symptoms such as nasal obstruction, insomnia, and anosmia. NP often relapse even after surgical treatment, and the curative therapy would be challenging without understanding the underlying mechanisms. Genome wide association studies (GWASs) on NP have been conducted; however, few genes that are causally associated with NP have been identified.

Methods: We aimed to prioritize NP associated genes for functional follow-up studies using the summary data-based Mendelian Randomization (SMR) and Bayesian colocalization (COLOC) methods to integrate the summary-level data of the GWAS on NP and the expression quantitative trait locus (eQTL) study in blood. We utilized the GWAS data including 5,554 NP cases and 258,553 controls with 34 genome-wide significant loci from the FinnGen consortium (data freeze 8) and the eQTL data from 31,684 participants of predominantly European ancestry from the eQTLGen consortium.

Results: The SMR analysis identified several genes including TNFRSF18, CTSK, and IRF1 that were associated with NP due to not linkage but pleiotropy or causality. The COLOC analysis strongly suggested that these genes and the trait of NP were affected by shared causal variants, and thus were colocalized. An enrichment analysis by Metascape suggested that these genes might be involved in the biological process of cellular response to cytokine stimulus.

Conclusion: We could prioritize several NP associated genes including TNFRSF18, CTSK, and IRF1 for follow-up functional studies in future to elucidate the underlying disease mechanisms.
Genome editing of human embryos for research purposes: Japanese lay and expert attitudes
Authors: Akatsuka Kyoko , Hatta Taichi , Sawai Tsutomu , Fujita Misao
Published: June 2023

Background: Multiple surveys of the general public and experts on human genome editing have been conducted. However, many focused only on editing in clinical applications, with few regarding its use for basic research. Given that genome editing for research purposes is indispensable for the realization of clinical genome editing, understanding lay attitudes toward genome editing in research, particularly using human embryos, which is likely to provoke ethical concerns, is helpful for future societal discussion.

Methods: An online survey was conducted with Japanese laypeople and researchers to ascertain their views regarding human genome editing for research purposes. Participants were queried about their acceptance as a function of the target of genome editing (germ cells, surplus IVF embryos, research embryos, somatic cells); then, those who answered “acceptable depending on the purpose” were asked about their acceptance in the context of specific research purposes of genome editing. Participants were also asked about their expectations and concerns regarding human genome editing.

Results: Replies were obtained from 4,424 laypeople and 98 researchers. Approximately 28.2–36.9% of the laypeople exhibited strong resistance to genome editing for research purposes regardless of their applications. In contrast, 25.5% of the researchers demonstrated resistance only to genome editing in research embryos; this percentage was substantially higher than those concerning the other three targets (5.1–9.2%). Approximately 50.4–63.4% of laypeople who answered “acceptable depending on the purpose” approved germline genome editing for disease research; however, only 39.3–42.8% approved genome editing in basic research to obtain biological knowledge. In contrast, the researchers displayed a lower degree of acceptance of germline genome editing for research purposes related to chronic diseases (60.9–66.7%) than for other research purposes (73.6–90.8%). Analysis of responses concerning expectations and concerns indicated that laypeople who would not accept genome editing of human embryos did not necessarily worry about “instrumentalization of the embryo.” They also had substantially low expectations for recognized advantages of genome editing, including “advances in science” and “reduction of intractable diseases,” compared with other groups of respondents.

Conclusion: The assumptions shared among experts in conventional bioethical debates and policy discussions on human genome editing are not self-evident to laypeople.
Ultrarapid and high-resolution HLA class I typing using transposase-based nanopore sequencing applied in pharmacogenetic testing
Authors: Anukul Nampeung , Jenjaroenpun Piroon , Sirikul Chonticha , Wankaew Natnicha , Nimsamer Pattaraporn , Roothumnong Ekkapong , Pithukpakorn Manop , Leetrakool Nipapan , Wongsurawat Thidathip
Published: June 2023

Nanopore sequencing has been examined as a method for rapid and high-resolution human leukocyte antigen (HLA) typing in recent years. We aimed to apply ultrarapid nanopore-based HLA typing for HLA class I alleles associated with drug hypersensitivity, including HLA-A*31:01, HLA-B*15:02, and HLA-C*08:01. Most studies have used the Oxford Nanopore Ligation Sequencing kit for HLA typing, which requires several enzymatic reactions and remains relatively expensive, even when the samples are multiplexed. Here, we used the Oxford Nanopore Rapid Barcoding kit, which is transposase-based, with library preparation taking less than 1 h of hands-on time and requiring minimal reagents. Twenty DNA samples were genotyped for HLA-A, -B, and -C; 11 samples were from individuals of different ethnicity and nine were from Thai individuals. Two primer sets, a commercial set and a published set, were used to amplify the HLA-A, -B, and -C genes. HLA-typing tools that used different algorithms were applied and compared. We found that without using several third-party reagents, the transposase-based method reduced the hands-on time from approximately 9 h to 4 h, making this a viable approach for obtaining same-day results from 2 to 24 samples. However, an imbalance in the PCR amplification of different haplotypes could affect the accuracy of typing results. This work demonstrates the ability of transposase-based sequencing to report 3-field HLA alleles and its potential for race- and population-independent testing at considerably decreased time and cost.
Association of the rs1990760, rs3747517, and rs10930046 polymorphisms in the IFIH1 gene with susceptibility to autoimmune diseases: a meta-analysis
Authors: Xiao Zilin , Luo Shuoming , Zhou Yuemin , Pang Haipeng , Yin Wenfeng , Qin Jiabi , Xie Zhiguo , Zhou Zhiguang
Published: June 2023

Objective

Interferon induced with helicase C domain 1 (IFIH1) single-nucleotide polymorphisms (SNP) rs1990760, rs3747517, and rs10930046 have been shown to be closely related to the risk of autoimmune diseases. The aim of this study was firstly to examine the association of the rs1990760 with type 1 diabetes (T1D) in a Chinese population. Secondly, to assess the association of SNP rs1990760, rs3747517, and rs10930046 with autoimmune diseases susceptibility.

Methods

A total of 1,273 T1D patients and 1,010 healthy control subjects in a Chinese population were enrolled in this case-control study. Subsequently, we performed a meta-analysis on the association of the SNP rs1990760, rs3747517, and rs10930046 in the IFIH1 gene with susceptibility to autoimmune diseases. The random and fixed genetic effects models were used to evaluate the association and the effect sizes, including odds ratios (OR) and 95% confidence intervals (CI). Stratification analyses based on ethnicity and the type of autoimmune diseases were performed.

Results

IFIH1 SNP rs1990760 was not associated with a significant risk of T1D in the Chinese population in the case-control study. A total of 35 studies including 70,966 patients and 124,509 controls were identified and included in the meta-analysis. The results displayed significant associations between IFIH1 rs1990760 A allele and rs3747517 C allele and autoimmune diseases risk (OR=1.09, 95% CI: 1.01~1.17; OR=1.24, 95% CI: 1.15~1.25, respectively). Stratified analysis indicated a significant association rs1990760 and rs3747517 with autoimmune diseases risk in the Caucasian population (OR=1.11, 95% CI: 1.02~1.20, OR=1.29, 95% CI: 1.18~1.41, respectively).

Conclusions

This study revealed no association between IFIH1 SNP rs1990760 and T1D in Chinese. Furthermore, the meta-analysis indicated that rs1990760 and rs3747517 polymorphisms, confer susceptibility to autoimmune diseases, especially in the Caucasian population.
Intrathymic somatotropic circuitry: consequences upon thymus involution
Authors: Reis Maria Danielma dos Santos , Veneziani Luciana Peixoto , Porto Felipe Lima , Lins Marvin Paulo , Mendes-da-Cruz Daniella Arêas , Savino Wilson
Published: June 2023

Growth hormone (GH) is a classic pituitary-derived hormone crucial to body growth and metabolism. In the pituitary gland, GH production is stimulated by GH-releasing hormone and inhibited by somatostatin. GH secretion can also be induced by other peptides, such as ghrelin, which interacts with receptors present in somatotropic cells. It is well established that GH acts directly on target cells or indirectly by stimulating the production of insulin-like growth factors (IGFs), particularly IGF-1. Notably, such somatotropic circuitry is also involved in the development and function of immune cells and organs, including the thymus. Interestingly, GH, IGF-1, ghrelin, and somatostatin are expressed in the thymus in the lymphoid and microenvironmental compartments, where they stimulate the secretion of soluble factors and extracellular matrix molecules involved in the general process of intrathymic T-cell development. Clinical trials in which GH was used to treat immunocompromised patients successfully recovered thymic function. Additionally, there is evidence that the reduction in the function of the somatotropic axis is associated with age-related thymus atrophy. Treatment with GH, IGF-1 or ghrelin can restore thymopoiesis of old animals, thus in keeping with a clinical study showing that treatment with GH, associated with metformin and dehydroepiandrosterone, could induce thymus regeneration in healthy aged individuals. In conclusion, the molecules of the somatotrophic axis can be envisioned as potential therapeutic targets for thymus regeneration in age-related or pathological thymus involution.
Distinct subtypes of endometriosis identified based on stromal-immune microenvironment and gene expression: implications for hormone therapy
Authors: Wang Yuning , Chen Yun , Xiao Yinping , Ruan Jingyao , Tian Qi , Cheng Qi , Chang Kaikai , Yi Xiaofang
Published: June 2023

Background

Endometriosis (EMs) is a chronic inflammatory condition that is highly heterogeneous. Current clinical staging fails to accurately predict drug responses and prognosis. In this study, we aimed to reveal the heterogeneity of ectopic lesions and investigate the possible underlying mechanisms using transcriptomic data and clinical information.

Methods

The EMs microarray dataset GSE141549 was obtained from the Gene Expression Omnibus database. Unsupervised hierarchical clustering was performed to identify EMs subtypes, which was followed by the functional enrichment analysis and estimation of immune infiltrates. Subtype-associated gene signatures were identified and further validated in other independent datasets, including GSE25628, E-MTAB-694, and GSE23339. Additionally, tissue microarrays (TMAs) were generated from premenopausal patients with EMs to investigate the potential clinical implications of the two identified subtypes.

Results

The unsupervised clustering analysis revealed that ectopic EMs lesions can be classified into two distinct subtypes: stroma-enriched (S1) and immune-enriched (S2). The functional analysis revealed that S1 correlated with fibroblast activation and extracellular matrix remodeling in the ectopic milieu, whereas S2 was characterized by the upregulation of immune pathways and a higher positive correlation with the immunotherapy response. Moreover, we identified a subtype signature composed of FHL1 and SORBS1, and constructed a subtype diagnostic model. Based on the cohort data from the TMAs, we found that S2 was strongly associated with the failure of/intolerance to hormone therapy.

Conclusions

This study identified two distinct subtypes that are varyingly associated with hormone resistance, stroma-immunity, and molecular features, thereby highlighting the importance of this stromal-immune heterogeneity in identifying EMs subtypes and providing novel insights into future personalized hormone-free therapy in EMs.
Orchestrated regulation of immune inflammation with cell therapy in pediatric acute liver injury
Authors: Duan Mingyue , Liu Xiaoguai , Yang Ying , Zhang Yanmin , Wu Rongqian , Lv Yi , Lei Hong
Published: June 2023

Acute liver injury (ALI) in children, which commonly leads to acute liver failure (ALF) with the need for liver transplantation, is a devastating life-threatening condition. As the orchestrated regulation of immune hemostasis in the liver is essential for resolving excess inflammation and promoting liver repair in a timely manner, in this study we focused on the immune inflammation and regulation with the functional involvement of both innate and adaptive immune cells in acute liver injury progression. In the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, it was also important to incorporate insights from the immunological perspective for the hepatic involvement with SARS-CoV-2 infection, as well as the acute severe hepatitis of unknown origin in children since it was first reported in March 2022. Furthermore, molecular crosstalk between immune cells concerning the roles of damage-associated molecular patterns (DAMPs) in triggering immune responses through different signaling pathways plays an essential role in the process of liver injury. In addition, we also focused on DAMPs such as high mobility group box 1 (HMGB1) and cold-inducible RNA-binding protein (CIRP), as well as on macrophage mitochondrial DNA-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in liver injury. Our review also highlighted novel therapeutic approaches targeting molecular and cellular crosstalk and cell-based therapy, providing a future outlook for the treatment of acute liver injury.
The diverse effects of transforming growth factor-β and SMAD signaling pathways during the CTL response
Authors: Chandiran Karthik , Cauley Linda S.
Published: June 2023

Cytotoxic T lymphocytes (CTLs) play an important role in defense against infections with intracellular pathogens and anti-tumor immunity. Efficient migration is required to locate and destroy infected cells in different regions of the body. CTLs accomplish this task by differentiating into specialized subsets of effector and memory CD8 T cells that traffic to different tissues. Transforming growth factor-beta (TGFβ) belongs to a large family of growth factors that elicit diverse cellular responses via canonical and non-canonical signaling pathways. Canonical SMAD-dependent signaling pathways are required to coordinate changes in homing receptor expression as CTLs traffic between different tissues. In this review, we discuss the various ways that TGFβ and SMAD-dependent signaling pathways shape the cellular immune response and transcriptional programming of newly activated CTLs. As protective immunity requires access to the circulation, emphasis is placed on cellular processes that are required for cell-migration through the vasculature.
Targeted immune activation in pediatric solid tumors: opportunities to complement local control approaches
Authors: Vonderhaar Emily P. , Dwinell Michael B. , Craig Brian T.
Published: June 2023

Surgery or radiation therapy is nearly universally applied for pediatric solid tumors. In many cases, in diverse tumor types, distant metastatic disease is present and evades surgery or radiation. The systemic host response to these local control modalities may lead to a suppression of antitumor immunity, with potential negative impact on the clinical outcomes for patients in this scenario. Emerging evidence suggests that the perioperative immune responses to surgery or radiation can be modulated therapeutically to preserve anti-tumor immunity, with the added benefit of preventing these local control approaches from serving as pro-tumorigenic stimuli. To realize the potential benefit of therapeutic modulation of the systemic response to surgery or radiation on distant disease that evades these modalities, a detailed knowledge of the tumor-specific immunology as well as the immune responses to surgery and radiation is imperative. In this Review we highlight the current understanding of the tumor immune microenvironment for the most common peripheral pediatric solid tumors, the immune responses to surgery and radiation, and current evidence that supports the potential use of immune activating agents in the perioperative window. Finally, we define existing knowledge gaps that limit the current translational potential of modulating perioperative immunity to achieve effective anti-tumor outcomes.
Planning sentence production in aphasia: evidence from structural priming and eye-tracking
Authors: van Boxtel Willem S. , Cox Briana N. , Keen Austin , Lee Jiyeon
Published: June 2023

Background

Grammatical encoding is impaired in many persons with aphasia (PWA), resulting in deficits in sentence production accuracies and underlying planning processes. However, relatively little is known on how these grammatical encoding deficits can be mediated in PWA. This study aimed to facilitate off-line (accuracy) and real-time (eye fixations) encoding of passive sentences through implicit structural priming, a tendency to better process a current sentence because of its grammatical similarity to a previously experienced (prime) sentence.

Method

Sixteen PWA and Sixteen age-matched controls completed an eyetracking-while-speaking task, where they described a target transitive picture preceded by a comprehension prime involving either an active or passive form. We measured immediate and cumulative priming effects on proportions of passives produced for the target pictures and proportions of eye fixations made to the theme actor in the target scene before speech onset of the sentence production.

Results and conclusion

Both PWA and controls produced cumulatively more passives as the experiment progressed despite an absence of immediate priming effects in PWA. Both groups also showed cumulative changes in the pre-speech eye fixations associated with passive productions, with this cumulative priming effect greater for the PWA group. These findings suggest that structural priming results in gradual adaptation of the grammatical encoding processes of PWA and that structural priming may be used as a treatment component for improving grammatical deficits in aphasia.
Influencing factors associated with high myopia in Chinese college students
Authors: Zhang Weiran , Hou Xiaoyun , Li Chang , Wang Sennan , Liu Nianen , Zhang Yan , Li Zhiqing
Published: June 2023

Background

High myopia (HM) may elicit irreversible pathological changes in the fundus and severely impair visual quality, thereby becoming a major public health issue in China. However, the influencing factors associated with HM remain unknown in Chinese college students, whose visual quality is crucial to country development.

Methods

This is a cross-sectional observational study. Two thousand three hundred and fifteen undergraduate and graduate students were initially recruited from various majors in 3 universities in Tianjin, China. Under the principle of voluntary participation and informed consent, simple random sampling was conducted in the recruited subjects while maintaining balanced number of subjects from each major. After screening with inclusion and exclusion criteria, 96 undergraduate and graduate students (186 eyes) were finally included and divided into non-HM and HM groups. The eyes of subjects were examined by optical coherence tomography angiography (OCTA) for vessel density and structure thickness at the macula and optic disc, and the subjects were surveyed by an itemized questionnaire on lifestyles and study habits.

Results

The OCTA and questionnaire results revealed 10 factors, including hemodynamic and anatomic parameters and lifestyle metrics, with statistical significance between the non-HM and HM groups. Receiver operating characteristic curve analysis showed that vessel density of the inner retina at the macula, vessel density of the radial peripapillary capillary at the optic disc, smartphone usage time, continuous near work time, and sleeping after midnight had superior values of area under the curve (AUC > 0.700). Therefore, these 5 factors were selected for univariant and multivariant logistic regression analyses. A prediction model comprising the 5 influencing factors had an AUC of 0.940 and 95% CI of 0.908–0.972.

Conclusion

This study for the first time identified the vessel density of the inner retina at the macula, the vessel density of the radial peripapillary capillary at the optic disc, smartphone usage time, continuous near work time, and sleeping after midnight as influencing factors associated with HM in Chinese college students. A prediction model comprising the 5 influencing factors was proposed for calculating likelihood of a Chinese college student developing HM, based on which lifestyle improvement and medical intervention might be recommended.
The impact of loneliness on quality of life in people with Parkinson’s disease: results from the Survey of Health, Ageing and Retirement in Europe
Authors: Prell Tino , Schönenberg Aline , Heimrich Konstantin G.
Published: June 2023

Background

Loneliness is a growing issue for public health in an aging society. However, there is a lack of research on loneliness in people with Parkinson’s disease (PwPD).

Methods

We analyzed cross-sectional and longitudinal data from wave 5 (N = 559 PwPD) and 6 (N = 442 PwPD) from the Survey of Health, Ageing and Retirement in Europe (SHARE). Loneliness was assessed using the three-item version of the Revised UCLA Loneliness Scale. Descriptive statistics, group comparisons, multiple linear regressions, and generalized estimating equation analysis were performed to explore loneliness prevalence, its relationship with other factors, and its impact on Quality of Life (QoL) in PwPD.

Results

Depending on the used cut-off, the prevalence of loneliness in PwPD ranged from 24.1 to 53.8%. These prevalences were higher compared to people without PD. Loneliness was mainly linked to decreased functional abilities, weaker grip strength, more symptoms of depression, and country of residence. Loneliness was also associated with current QoL and predicts future QoL in PwPD, highlighting its impact on well-being.

Conclusion

Addressing loneliness could potentially improve QoL for PwPD, making it a modifiable risk factor that clinicians and policy-makers should consider.
Macrophages promote Fibrinogenesis during kidney injury
Authors: Oh Hanna , Kwon Ohbin , Kong Min Jung , Park Kwon Moo , Baek Jea-Hyun
Published: June 2023

Macrophages (Mø) are widely considered fundamental in the development of kidney fibrosis since Mø accumulation commonly aggravates kidney fibrosis, while Mø depletion mitigates it. Although many studies have aimed to elucidate Mø-dependent mechanisms linked to kidney fibrosis and have suggested various mechanisms, the proposed roles have been mostly passive, indirect, and non-unique to Mø. Therefore, the molecular mechanism of how Mø directly promote kidney fibrosis is not fully understood. Recent evidence suggests that Mø produce coagulation factors under diverse pathologic conditions. Notably, coagulation factors mediate fibrinogenesis and contribute to fibrosis. Thus, we hypothesized that kidney Mø express coagulation factors that contribute to the provisional matrix formation during acute kidney injury (AKI). To test our hypothesis, we probed for Mø-derived coagulation factors after kidney injury and uncovered that both infiltrating and kidney-resident Mø produce non-redundant coagulation factors in AKI and chronic kidney disease (CKD). We also identified F13a1, which catalyzes the final step of the coagulation cascade, as the most strongly upregulated coagulation factor in murine and human kidney Mø during AKI and CKD. Our in vitro experiments revealed that the upregulation of coagulation factors in Mø occurs in a Ca2 + −dependent manner. Taken together, our study demonstrates that kidney Mø populations express key coagulation factors following local injury, suggesting a novel effector mechanism of Mø contributing to kidney fibrosis.
Does postcholecystectomy increase the risk of colorectal cancer?
Authors: Dong Zhenyu , Shi Ruixian , Li Pengda , Song Xiaobiao , Dong Fan , Zhu Jianmin , Wu Riga , Liang Zhi , Du Mingyue , Wang Jijun , Yang Zhigang
Published: June 2023

With the increasing number of cholecystectomy and the high proportion of colorectal cancer in malignant tumors, the question of whether cholecystectomy is a risk factor for colorectal disease has been widely concerned. After reviewing the literature at home and abroad, the authors will summarize the research progress of the correlation between the occurrence of colorectal tumors after cholecystectomy, in order to provide help for the prevention and treatment of colorectal tumors.
Insilico generation of novel ligands for the inhibition of SARS-CoV-2 main protease (3CLpro) using deep learning
Authors: Prabhakaran Prejwal , Hebbani Ananda Vardhan , Menon Soumya V. , Paital Biswaranjan , Murmu Sneha , Kumar Sunil , Singh Mahender Kumar , Sahoo Dipak Kumar , Desai Padma Priya Dharmavaram
Published: June 2023

The recent emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease (COVID-19) has become a global public health crisis, and a crucial need exists for rapid identification and development of novel therapeutic interventions. In this study, a recurrent neural network (RNN) is trained and optimized to produce novel ligands that could serve as potential inhibitors to the SARS-CoV-2 viral protease: 3 chymotrypsin-like protease (3CLpro). Structure-based virtual screening was performed through molecular docking, ADMET profiling, and predictions of various molecular properties were done to evaluate the toxicity and drug-likeness of the generated novel ligands. The properties of the generated ligands were also compared with current drugs under various phases of clinical trials to assess the efficacy of the novel ligands. Twenty novel ligands were selected that exhibited good drug-likeness properties, with most ligands conforming to Lipinski’s rule of 5, high binding affinity (highest binding affinity: −9.4 kcal/mol), and promising ADMET profile. Additionally, the generated ligands complexed with 3CLpro were found to be stable based on the results of molecular dynamics simulation studies conducted over a 100 ns period. Overall, the findings offer a promising avenue for the rapid identification and development of effective therapeutic interventions to treat COVID-19.
Pseudomonas spp. can help plants face climate change
Authors: Zboralski Antoine , Filion Martin
Published: June 2023

Climate change is increasingly affecting agriculture through droughts, high salinity in soils, heatwaves, and floodings, which put intense pressure on crops. This results in yield losses, leading to food insecurity in the most affected regions. Multiple plant-beneficial bacteria belonging to the genus Pseudomonas have been shown to improve plant tolerance to these stresses. Various mechanisms are involved, including alteration of the plant ethylene levels, direct phytohormone production, emission of volatile organic compounds, reinforcement of the root apoplast barriers, and exopolysaccharide biosynthesis. In this review, we summarize the effects of climate change-induced stresses on plants and detail the mechanisms used by plant-beneficial Pseudomonas strains to alleviate them. Recommendations are made to promote targeted research on the stress-alleviating potential of these bacteria.
Fixation and staining methods for macroscopical investigation of the brain
Authors: Nardi Leonardo , Schmeisser Michael J. , Schumann Sven
Published: June 2023

The proper preservation of human brain tissue is an indispensable requirement for post-mortem investigations. Neuroanatomical teaching, neuropathological examination, neurosurgical training, basic and clinical neuroscientific research are some of the possible downstream applications of brain specimens and, although much apart from one another, proper tissue fixation and preservation is a common denominator to all of them. In this review, the most relevant procedures to fixate brain tissue are described. In situ and immersion fixation approaches have been so far the most widespread ways to deliver the fixatives inside the skull. Although most of them rely on the use of formalin, alternative fixative solutions containing lower amounts of this compound mixed with other preservative agents, have been attempted. The combination of fixation and freezing paved the way for fiber dissection, particularly relevant for the neurosurgical practice and clinical neuroscience. Moreover, special techniques have been developed in neuropathology to tackle extraordinary problems, such as the examination of highly infective specimens, as in the case of the Creutzfeldt-Jakob encephalopathy, or fetal brains. Fixation is a fundamental prerequisite for further staining of brain specimens. Although several staining techniques have been developed for the microscopical investigation of the central nervous system, numerous approaches are also available for staining macroscopic brain specimens. They are mostly relevant for neuroanatomical and neuropathological teaching and can be divided in white and gray matter staining techniques. Altogether, brain fixation and staining techniques are rooted in the origins of neuroscience and continue to arouse interest in both preclinical and clinical neuroscientists also nowadays.
Rhythmic oscillations in the midbrain dopaminergic nuclei in mice
Authors: Oberto Virginie J. , Matsumoto Jumpei , Pompili Marco N. , Todorova Ralitsa , Papaleo Francesco , Nishijo Hisao , Venance Laurent , Vandecasteele Marie , Wiener Sidney I.
Published: June 2023

Introduction

Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates.

Methods

We recorded from optogenetically identified dopaminergic sites in four mice training in operant olfactory and visual discrimination tasks.

Results

Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1–2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals.

Discussion

These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.
Novel loss of function mutation in TUBA1A gene compromises tubulin stability and proteostasis causing spastic paraplegia and ataxia
Authors: Zocchi Riccardo , Bellacchio Emanuele , Piccione Michela , Scardigli Raffaella , D’Oria Valentina , Petrini Stefania , Baranano Kristin , Bertini Enrico , Sferra Antonella
Published: June 2023

Microtubules are dynamic cytoskeletal structures involved in several cellular functions, such as intracellular trafficking, cell division and motility. More than other cell types, neurons rely on the proper functioning of microtubules to conduct their activities and achieve complex morphologies. Pathogenic variants in genes encoding for α and β-tubulins, the structural subunits of microtubules, give rise to a wide class of neurological disorders collectively known as “tubulinopathies” and mainly involving a wide and overlapping range of brain malformations resulting from defective neuronal proliferation, migration, differentiation and axon guidance. Although tubulin mutations have been classically linked to neurodevelopmental defects, growing evidence demonstrates that perturbations of tubulin functions and activities may also drive neurodegeneration. In this study, we causally link the previously unreported missense mutation p.I384N in TUBA1A, one of the neuron-specific α-tubulin isotype I, to a neurodegenerative disorder characterized by progressive spastic paraplegia and ataxia. We demonstrate that, in contrast to the p.R402H substitution, which is one of the most recurrent TUBA1A pathogenic variants associated to lissencephaly, the present mutation impairs TUBA1A stability, reducing the abundance of TUBA1A available in the cell and preventing its incorporation into microtubules. We also show that the isoleucine at position 384 is an amino acid residue, which is critical for α-tubulin stability, since the introduction of the p.I384N substitution in three different tubulin paralogs reduces their protein level and assembly into microtubules, increasing their propensity to aggregation. Moreover, we demonstrate that the inhibition of the proteasome degradative systems increases the protein levels of TUBA1A mutant, promoting the formation of tubulin aggregates that, as their size increases, coalesce into inclusions that precipitate within the insoluble cellular fraction. Overall, our data describe a novel pathogenic effect of p.I384N mutation that differs from the previously described substitutions in TUBA1A, and expand both phenotypic and mutational spectrum related to this gene.
What have we learned from a case of convalescent plasma treatment in a two-time kidney transplant recipient COVID-19 patient? A case report from the perspective of viral load evolution and immune response
Authors: Aldunate Fabian , Fajardo Alvaro , Ibañez Natalia , Rammauro Florencia , Daghero Hellen , Arce Rodrigo , Ferla Diego , Pereira-Gomez Marianoel , Salazar Cecilia , Iraola Gregorio , Pritsch Otto , Hurtado Javier , Tenzi Jordan , Bollati-Fogolín Mariela , Bianchi Sergio , Nin Nicolas , Moratorio Gonzalo , Moreno Pilar
Published: June 2023

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, can have a wide range of clinical manifestations, ranging from asymptomatic disease to potentially life-threatening complications. Convalescent plasma therapy has been proposed as an effective alternative for the treatment of severe cases. The aim of this study was to follow a two-time renal transplant patient with severe COVID-19 treated with convalescent plasma over time from an immunologic and virologic perspective. A 42-year-old female patient, who was a two-time kidney transplant recipient, was hospitalized with COVID-19. Due to worsening respiratory symptoms, she was admitted to the intensive care unit, where she received two doses of convalescent plasma. We analyzed the dynamics of viral load in nasopharyngeal swab, saliva, and tracheal aspirate samples, before and after convalescent plasma transfusion. The levels of pro-inflammatory cytokines and antibody titers were also measured in serum samples. A significant decrease in viral load was observed after treatment in the saliva and nasopharyngeal swab samples, and a slight decrease was observed in tracheal aspirate samples. In addition, we found evidence of an increase in antibody titers after transfusion, accompanied by a decrease in the levels of several cytokines responsible for cytokine storm.
Advances in dynamic visual acuity test research
Authors: Chen Ganggang , Zhang Jin , Qiao Qi , Zhou Liyuan , Li Ying , Yang Jie , Wu Jiaxin , Huangfu Hui
Published: June 2023

The dynamic visual acuity test (DVAT) is a functional evaluation tool for the impairment and compensation of the vestibular system, which could reflect the Vestibulo-ocular reflex (VOR) function. We present an overview of DVAT research, displaying recent advances in test methods, application, and influencing factors; and discussing the clinical value of DVAT to provide a reference for clinical application. There are two primary types of DVAT: dynamic-object DVAT and static-object DVAT. For the latter, in addition to the traditional bedside DVAT, there are numerous other approaches, including Computerized DVAT (cDVAT), DVAT on a treadmill, DVAT on a rotary, head thrust DVA (htDVA) and functional head impulse testing (fHIT), gaze shift dynamic visual acuity with walking (gsDVA), translational dynamic visual acuity test (tDVAT), pediatric DVAT. The results of DAVT are affected by subject [occupation, static visual acuity (SVA), age, eyeglass lenses], testing methods, caffeine, and alcohol. DVAT has numerous clinical applications, such as screening for vestibular impairment, assessing vestibular rehabilitation, predicting fall risk, and evaluating ophthalmology-related disorders, vestibular disorders, and central system disorders.