bluuebunny/crossref_metadata_2025 huggingface dataset:
Halorarius litoreus gen. nov., sp. nov., Halorarius halobius sp. nov., Haloglomus halophilum sp. nov., Haloglomus salinum sp. nov., and Natronomonas marina sp. nov., extremely halophilic archaea isolated from tidal flat and marine solar salt
Authors: Sun Ya-Ping , Wang Bei-Bei , Wu Zhang-Ping , Zheng Xi-Wen , Hou Jing , Cui Heng-Lin
Published: January 2023

Five novel halophilic archaeal strains, named BND22T, ZY10T, ZY41T, ZY58T, and ZY43T, were isolated from the coastal saline sediment of the intertidal zone located in Qingdao and the natural sea salt produced from Huanghua marine solar saltern, PRChina. These five strains demonstrated the typical morphology and growth characteristics of haloarchaea. The comparison of 16S rRNA gene revealed that strain BDN22T was associated with Salinirubellus salinus ZS-35-S2T (95.2% similarity), strain ZY10T was related to Halosegnis rubeus F17-44T (95.1% similarity), both strains ZY41T and ZY58T were closely related to Haloglomus irregulare F16-60T (98.1% and 98.2% similarities, respectively), and strain ZY43T was close to Natronomonas salina YPL13T (98.0% similarity). In addition to the 16S rRNA gene, the rpoB′ gene is undoubtedly another important molecular marker for the identification of halophilic archaea, and concatenated-conserved-protein phylogeny was widely used in archaeal classification in recent years. Phylogenetic and phylogenomic analyses based on rpoB′ genes and 122 concatenated archaeal protein genes showed that these haloarchaea construct three different clades and gathered together with the current members of Haloarculaceae. Strains BND22T and ZY10T formed two distinct clades separated from Salinirubellus salinus ZS-35-S2T and Halosegnis members, strains ZY41T and ZY58T clustered with Haloglomus irregulare F16-60T, and strain ZY43T gathered with the current members of Natronomonas. The ANI, DDH, and AAI values of these five strains against phylogenetic neighbours were no more than 91%, 45%, and 92%, respectively, far below the cut-off values for species delineation, supporting their placements in new taxa. Based on the phenotypic, chemotaxonomic, phylogenetic, and phylogenomic properties, these five strains represent five novel taxa of the family Haloarculaceae, Halorarius litoreus gen. nov., sp. nov. (type strain BND22T = CGMCC 1.18780T = JCM 34966T), Halorarius halobius sp. nov. (type strain ZY10T = CGMCC 1.17475T = JCM 34319T), Haloglomus halophilum sp. nov. (type strain ZY41T = CGMCC 1.17030T = JCM 34161T), Haloglomus salinum sp. nov. (type strain ZY58T = CGMCC 1.17216T = JCM 34163T), and Natronomonas marina sp. nov. (type strain ZY43T = CGMCC 1.17202T = JCM 34162T). This is the first report of description of a novel haloarchaeon isolated from a marine intertidal zone.
Hydration and durability of low-heat cementitious composites for dam concrete: Thermodynamic modeling and experiments
Authors: Zhang Juntao , Lv Tong
Published: January 2023

To demonstrate the superiority of dam concrete, a systematic study was conducted to examine the durability of low-heat cementitious composite (LHCC) that is composed of Portland cement (PC), fly ash (FA), and MgO expansive additive (MEA) with PC as the reference group. Through GEMS software, XRD, SEM, and EDS, the difference mechanism in durability between the two cementitious materials was revealed from the perspectives of phase evolution and microstructural characteristics. Water at 40 °C was adopted for curing in the study to match the long-term temperature field inside the concrete dam. According to the results of the RCM, accelerated carbonation, and rapid freeze–thaw cycle experiments, LHCC outperforms PC in durability. The hydration process of LHCC is simulated by inputting the reaction degree of each phase calculated using the MPK model into the GEMS software. The thermodynamic model output shows that portlandite first increases and then decreases as LHCC hydration proceeds, and C-S-H and stratlingite are supplemented in the later stage, which reflects the high performance of FA involved in hydration. In addition, hydrotalcite that is capable of chloride ion adsorption is increasingly generated with the consumption of brucite. As is clearly shown in the SEM images, there are denser space grids formed by overlapping C-S-H in LHCC with almost no capillary pores. Meanwhile, when combined with the results of EDS, it is strongly demonstrated that the FA in LHCC can be hydrated to produce dense fibrous C-S-H in large amounts, providing a basis for the positive development of durability.
Microbial community structure characteristics among different karst aquifer systems, and its potential role in modifying hydraulic properties of karst aquifers
Authors: Liang Zuobing , Li Shaoheng , Wang Zhuowei , Li Rui , Yang Zhigang , Chen Jianyao , Gao Lei , Sun Yuchuan
Published: January 2023

Little is known about how microbial activity affects the hydraulic properties of karst aquifers. To explore the potential impacts of microbial activity on the hydraulic properties of karst aquifers, microbiological analysis, heat tracer, isotope (dissolved inorganic carbon isotope, δ13CDIC) and aqueous geochemical analyses were conducted at six monitoring wells in Northern Guangdong Province, China. Greater hydraulic conductivity corresponded to a low temperature gradient to an extent; the temperature gradient in karst groundwater aquifers can reflect the degree of dissolution. Higher HCO3− concentrations coupled with lower d-excess and pH values at B2 and B6 reflect potential microbial activity (e.g., Sulfuricurvum kujiense) causing carbonate dissolution. Microbial activity or the input of anthropogenic acids, as evidenced by significantly more positive δ13CDIC values, potentially affect carbonate dissolution in deep karst aquifers, which eventually alters hydraulic properties of karst aquifer. However, more direct evidence is needed to quantify the effects of microbial activity on carbonate dissolution in karst aquifers.
Neuromicrobiology, an emerging neurometabolic facet of the gut microbiome?
Authors: Miri Saba , Yeo JuDong , Abubaker Sarah , Hammami Riadh
Published: January 2023

The concept of the gut microbiome is emerging as a metabolic interactome influenced by diet, xenobiotics, genetics, and other environmental factors that affect the host’s absorption of nutrients, metabolism, and immune system. Beyond nutrient digestion and production, the gut microbiome also functions as personalized polypharmacy, where bioactive metabolites that our microbes excrete or conjugate may reach systemic circulation and impact all organs, including the brain. Appreciable evidence shows that gut microbiota produce diverse neuroactive metabolites, particularly neurotransmitters (and their precursors), stimulating the local nervous system (i.e., enteric and vagus nerves) and affecting brain function and cognition. Several studies have demonstrated correlations between the gut microbiome and the central nervous system sparking an exciting new research field, neuromicrobiology. Microbiome-targeted interventions are seen as promising adjunctive treatments (pre-, pro-, post-, and synbiotics), but the mechanisms underlying host-microbiome interactions have yet to be established, thus preventing informed evidence-based therapeutic applications. In this paper, we review the current state of knowledge for each of the major classes of microbial neuroactive metabolites, emphasizing their biological effects on the microbiome, gut environment, and brain. Also, we discuss the biosynthesis, absorption, and transport of gut microbiota-derived neuroactive metabolites to the brain and their implication in mental disorders.
KODAMA exploratory analysis in metabolic phenotyping
Authors: Zinga Maria Mgella , Abdel-Shafy Ebtesam , Melak Tadele , Vignoli Alessia , Piazza Silvano , Zerbini Luiz Fernando , Tenori Leonardo , Cacciatore Stefano
Published: January 2023

KODAMA is a valuable tool in metabolomics research to perform exploratory analysis. The advanced analytical technologies commonly used for metabolic phenotyping, mass spectrometry, and nuclear magnetic resonance spectroscopy push out a bunch of high-dimensional data. These complex datasets necessitate tailored statistical analysis able to highlight potentially interesting patterns from a noisy background. Hence, the visualization of metabolomics data for exploratory analysis revolves around dimensionality reduction. KODAMA excels at revealing local structures in high-dimensional data, such as metabolomics data. KODAMA has a high capacity to detect different underlying relationships in experimental datasets and correlate extracted features with accompanying metadata. Here, we describe the main application of KODAMA exploratory analysis in metabolomics research.
Alzheimer’s disease biomarkers in patients with obstructive sleep apnea hypopnea syndrome and effects of surgery: A prospective cohort study
Authors: Kong Weili , Zang Yi
Published: January 2023

Background

Obstructive sleep apnea hypopnea syndrome (OSAHS) may cause Alzheimer’s disease (AD), t-tau, p-tau, Aβ42, and Aβ40 are important elements in the process of AD, and changes in the levels of these biomarkers may affect the cognitive functioning of patients. Our objective was to investigate whether uvulopalatopharyngoplasty could reduce the plasma levels of AD biomarkers in OSAHS patients and the potential correlations of AD biomarkers with cognitive impairment and sleepiness, and explore the independent influencing factors of cognitive function.

Methods

Alzheimer’s disease biomarkers were measured in the plasma of 35 patients with severe OSAHS requiring surgical treatment and 16 healthy controls without OSAHS. The cognitive function and sleepiness of OSAHS patients was also evaluated. The case group was given uvulopalatopharyngoplasty and followed at the postoperative sixth month, the follow-up cases were 27, and plasma AD biomarker levels, cognitive function, and sleepiness were re-evaluated. The preoperative and postoperative AD biomarker levels OSAHS patients were compared with each other and those of the control group. Linear stepwise regression and lasso regression were used to explore the relationships of AD biomarkers with cognitive impairment and sleepiness.

Results

Significantly higher Aβ40, t-tau, p-tau in plasma were observed preoperatively in OSAHS patients comparing to controls (29.24 ± 32.52 vs. 13.18 ± 10.78, p = 0.049; 11.88 ± 7.05 vs. 7.64 ± 4.17, p = 0.037; 26.31 ± 14.41 vs. 17.34 ± 9.12, p = 0.027). The sixth month of postoperation, the plasma AD biomarkers (Aβ42, Aβ40, t-tau, p-tau) in plasma levels decreased significantly (0.23 ± 0.17 vs. 0.20 ± 0.16, p = 0.0001; 29.24 ± 32.52 vs. 23.52 ± 24.46, p = 0.0046; 11.88 ± 7.05 vs. 8.88 ± 6.21, p = 0.0001;26.31 ± 14.41 vs. 20.43 ± 10.50, p = 0.0001). A comparison of MMSE and ESS scores from before to after surgery revealed obvious differences (27.14 ± 1.65 vs. 29.07 ± 1.78, p = 0.0001; 11.91 ± 4.84 vs. 5.89 ± 2.83, p = 0.0001). Changes in cognitive function and sleepiness scores from before to after uvulopalatopharyngoplasty were significantly correlated with AD biomarkers. Body mass index and t-tau were potential influencing factors cognitive function.

Conclusion

Obstructive sleep apnea hypopnea syndrome can increase plasma AD biomarkers levels. Uvulopalatopharyngoplasty can improve patients’ cognition and sleepiness, and the mechanism may be related to changes in plasma AD biomarkers. Higher AHI and higher t-tau level were identified as independent risk factors for cognitive decline.
Integration of amyloid-β oligomerization tendency as a plasma biomarker in Alzheimer's disease diagnosis
Authors: Pyun Jung-Min , Youn Young Chul , Park Young Ho , Kim SangYun
Published: January 2023

Introduction

There has been significant development in blood-based biomarkers targeting amyloidopathy of Alzheimer's disease (AD). However, the guidelines for integrating such biomarkers into AD diagnosis are still inadequate. Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ) as a plasma biomarker detecting oligomerization tendency is available in the clinical practice.

Main text

We suggest how to interpret the results of plasma biomarker for amyloidopathy using MDS-OAβ with neuropsychological test, brain magnetic resonance imaging (MRI), and amyloid PET for AD diagnosis. Combination of each test result differentiates various stages of AD, other neurodegenerative diseases, or cognitive impairment due to the causes other than neurodegeneration.

Discussion

A systematic interpretation strategy could support accurate diagnosis and staging of AD. Moreover, comprehensive use of biomarkers that target amyloidopathy such as amyloid PET on brain amyloid plaque and MDS-OAβ on amyloid-β oligomerization tendency can complement to gain advanced insights on amyloid-β dynamics in AD.
Case report: SCN4A p.R1135H gene variant in combination with thyrotoxicosis causing hypokalemic periodic paralysis
Authors: Zhang Zhi , Xiao Banghui
Published: January 2023

Hypokalemic periodic paralysis (HPP) is a heterogeneous group of diseases characterized by intermittent episodes of delayed paralysis of skeletal muscle with episodes of hypokalemia, caused by variants in CACNA1S or SCN4A genes, or secondary to thyrotoxicosis, Sjogren syndrome, primary aldosteronism, etc. HPP may be the only presentation in Andersen–Tawil syndrome in which the majority of cases are caused by pathogenic variants in the KCNJ2 gene. We present a case of a 29-year-old male with hypokalemic periodic paralysis. The patient began to experience recurrent weakness of the extremities at the age of 26, which was effectively treated with potassium supplementation. He had recently developed dry mouth, palpitations, weight loss, and even dyspnea, with a serum potassium level as low as 1.59 mmol/L. The results of auxiliary examinations showed Graves' disease, and genetic testing indicated a missense variant, NM_000334.4 (SCN4A):c.3404G>A (p.R1135H). He did not experience periodic paralysis during follow-up after lifestyle guidance and treatment of thyrotoxicosis with radioactive iodine. It is a rare case of SCN4A p.R1135H gene variant combined with hyperthyroidism resulting in HPP with respiratory muscle paralysis to raise awareness of the disease and avoid misdiagnosis and missed diagnosis.
Inhibitory synapse dysfunction and epileptic susceptibility associated with KIF2A deletion in cortical interneurons
Authors: Ruiz-Reig Nuria , García-Sánchez Dario , Schakman Olivier , Gailly Philippe , Tissir Fadel
Published: January 2023

Malformation of cortical development (MCD) is a family of neurodevelopmental disorders, which usually manifest with intellectual disability and early-life epileptic seizures. Mutations in genes encoding microtubules (MT) and MT-associated proteins are one of the most frequent causes of MCD in humans. KIF2A is an atypical kinesin that depolymerizes MT in ATP-dependent manner and regulates MT dynamics. In humans, single de novo mutations in KIF2A are associated with MCD with epileptic seizures, posterior pachygyria, microcephaly, and partial agenesis of corpus callosum. In this study, we conditionally ablated KIF2A in forebrain inhibitory neurons and assessed its role in development and function of inhibitory cortical circuits. We report that adult mice with specific deletion of KIF2A in GABAergic interneurons display abnormal behavior and increased susceptibility to epilepsy. KIF2A is essential for tangential migration of cortical interneurons, their positioning in the cerebral cortex, and for formation of inhibitory synapses in vivo. Our results shed light on how KIF2A deregulation triggers functional alterations in neuronal circuitries and contributes to epilepsy.
Kinetics of cone specific G-protein signaling in avian photoreceptor cells
Authors: Yee Chad , Görtemaker Katharina , Wellpott Rieke , Koch Karl-Wilhelm
Published: January 2023

Cone photoreceptor cells of night-migratory songbirds seem to process the primary steps of two different senses, vision and magnetoreception. The molecular basis of phototransduction is a prototypical G protein-coupled receptor pathway starting with the photoexcitation of rhodopsin or cone opsin thereby activating a heterotrimeric G protein named transducin. This interaction is well understood in vertebrate rod cells, but parameter describing protein–protein interactions of cone specific proteins are rare and not available for migratory birds. European robin is a model organism for studying the orientation of birds in the earth magnetic field. Recent findings showed a link between the putative magnetoreceptor cryptochrome 4a and the cone specific G-protein of European robin. In the present work, we investigated the interaction of European robin cone specific G protein and cytoplasmic regions of long wavelength opsin. We identified the second loop in opsin connecting transmembrane regions three and four as a critical binding interface. Surface plasmon resonance studies using a synthetic peptide representing the second cytoplasmic loop and purified G protein α-subunit showed a high affinity interaction with a KD value of 21 nM. Truncation of the G protein α-subunit at the C-terminus by six amino acids slightly decreased the affinity. Our results suggest that binding of the G protein to cryptochrome can compete with the interaction of G protein and non-photoexcited long wavelength opsin. Thus, the parallel presence of two different sensory pathways in bird cone photoreceptors is reasonable under dark-adapted conditions or during illumination with short wavelengths.
Comparison and recommendation of dietary patterns based on nutrients for Eastern and Western patients with inflammatory bowel disease
Authors: Hou Yue , Wang Sai-Feng , Zhou Ke , Dai Shi-Xue
Published: January 2023

Inflammatory bowel disease (IBD), a non-specific chronic idiopathic inflammatory condition of the digestive system, requires lifelong treatment in which drugs are the mainstay, along with surgery when necessary. In adjuvant therapies, the diet is considered to be an essential, controllable, and economical component. However, the majority of recent nutrition research has focused on the general effects of nutrients on IBD, with little attention given to the advantages and negative aspects of individual foods and dietary combinations. To cover these shortcomings, we surveyed the benefits and drawbacks of typical foods and their chemical compositions on intestinal pathophysiology by comparing nutrients existing in the foods in Eastern and Western countries. Moreover, for Eastern and Western patients with IBD, we innovatively propose a 3-step dietary recommendation based on modified customary eating habits, including lowering the triggering foods, modifying dietary advice to control disease progression, and improving surgery prognosis.
The impact of Ramadan intermittent fasting on anthropometric measurements and body composition: Evidence from LORANS study and a meta-analysis
Authors: Al-Jafar Rami , Wahyuni Nisa Sri , Belhaj Karim , Ersi Mohammad Hamed , Boroghani Zahra , Alreshidi Amer , Alkhalaf Zahra , Elliott Paul , Tsilidis Konstantinos K. , Dehghan Abbas
Published: January 2023

Background

Although the effect of Ramadan intermittent fasting (RIF) on anthropometry and body composition has been questioned, none of the previous studies tried to explain the reported changes in these parameters. Also, systematic reviews that investigated the topic were limited to healthy individuals or a specific disease group.

Methods

The London Ramadan Study (LORANS) is an observational study on health effects of RIF. We measured weight, waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio (WHR), basal metabolic rate (BMR), fat percentage (FP), free-fat mass (FFM), extremities predicted muscle mass, total body water (TBW), trunk FM, trunk FFM and trunk predicted muscle mass before and immediately after Ramadan. Using mixed-effects regression models, we investigated the effect of RIF with adjustment for potential confounders. We also conducted a meta-analysis of the results of LORANS with other studies that investigated the effect of RIF on anthropometry and body composition. The review protocol is registered with PROSPERO registry (CRD42020186532).

Results

We recruited 146 participants (Mean ± SD age = 43.3 ± 15 years). Immediately after Ramadan, compared with before Ramadan, the mean difference was−1.6 kg (P<0.01) in weight,−1.95cm (P<0.01) in WC,−2.86cm (P <0.01) in HC, −0.60 kg/m2 (P < 0.01) in BMI and −1.24 kg (P < 0.01) in FM. In the systematic review and meta-analysis, after screening 2,150 titles and abstracts, 66 studies comprising 7,611 participants were included. In the general population, RIF was followed by a reduction of 1.12 Kg in body weight (−1.89– −0.36, I2 = 0), 0.74 kg/m2 reduction in BMI (−0.96– −0.53, I2 = 0), 1.54cm reduction in WC (−2.37– −0.71, I2 = 0) and 1.76cm reduction in HC (−2.69– −0.83, I2 = 0). The effect of fasting on anthropometric and body composition parameters starts to manifest in the second week of Ramadan and starts to diminish 3 weeks after Ramadan.

Conclusion

RIF is associated with a reduction in body weight, BMI, WC, HC, FM, FP and TBW. Most of these reductions are partially attributed to reduced FM and TBW. The reductions in these parameters appear to reverse after Ramadan.
Prognostic analysis of breast cancer in Xinjiang based on Cox proportional hazards model and two−step cluster method
Authors: Wu Mengjuan , Zhao Ting , Zhang Qian , Zhang Tao , Wang Lei , Sun Gang
Published: January 2023

Objective

To examine the factors that affect the prognosis and survival of breast cancer patients who were diagnosed at the Affiliated Cancer Hospital of Xinjiang Medical University between 2015 and 2021, forecast the overall survival (OS), and assess the clinicopathological traits and risk level of prognosis of patients in various subgroups.

Method

First, nomogram model was constructed using the Cox proportional hazards models to identify the independent prognostic factors of breast cancer patients. In order to assess the discrimination, calibration, and clinical utility of the model, additional tools such as the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA) were used. Finally, using two-step cluster analysis (TCA), the patients were grouped in accordance with the independent prognostic factors. Kaplan-Meier survival analysis was employed to compare prognostic risk among various subgroups.

Result

T-stage, N-stage, M-stage, molecular subtyping, type of operation, and involvement in postoperative chemotherapy were identified as the independent prognostic factors. The nomogram was subsequently constructed and confirmed. The area under the ROC curve used to predict 1-, 3-, 5- and 7-year OS were 0.848, 0.820, 0.813, and 0.791 in the training group and 0.970, 0.898, 0.863, and 0.798 in the validation group, respectively. The calibration curves of both groups were relatively near to the 45° reference line. And the DCA curve further demonstrated that the nomogram has a higher clinical utility. Furthermore, using the TCA, the patients were divided into two subgroups. Additionally, the two groups’ survival curves were substantially different. In particular, in the group with the worse prognosis (the majority of patients did not undergo surgical therapy or postoperative chemotherapy treatment), the T-, N-, and M-stage were more prevalent in the advanced, and the total points were likewise distributed in the high score side.

Conclusion

For the survival and prognosis of breast cancer patients in Xinjiang, the nomogram constructed in this paper has a good prediction value, and the clustering results further demonstrated that the selected factors were important. This conclusion can give a scientific basis for tailored treatment and is conducive to the formulation of focused treatment regimens for patients in practical practice.
Efficacy and safety of a novel 450 nm blue diode laser versus plasmakinetic electrocautery for the transurethral resection of non-muscle invasive bladder cancer: The protocol and result of a multicenter randomized controlled trial
Authors: Wu Kaijie , Jiang Dali , Zhang Lianhua , Jiang Shuai , Lin Tianhai , Luo Yi , Fan Jinhai , Yang Tao , Chen Haige , Zhang Peng , Wang Xinghuan , Wei Qiang , Guo Jianming , Huang Yiran , He Dalin
Published: January 2023

Objectives

To be the first to apply a novel 450 nm blue diode laser in transurethral resection of bladder tumor (TURBt) to treat patients with non-muscle invasive bladder cancer (NMIBC) and evaluate its efficacy and safety during the preoperative period compared to the conventional plasmakinetic electrocautery.

Materials and Methods

Randomized controlled trial (RCT) in five medical centers was designed as a non-inferiority study and conducted from October 2018 to December 2019. Patients with NMIBC were randomized to the blue laser or plasmakinetic electrocautery group for TURBt. As the first study to evaluate this novel blue laser device, the primary outcome was the effective resection rate of bladder tumors, including effective dissection and hemostasis. The secondary outcomes were the perioperative records, including surgical time, postoperative indwelling catheter time, hospital stay length, blood loss, reoperation rate, wound healing and adverse events.

Results

A total of 174 patients were randomized to either the blue laser group (85 patients) or plasmakinetic electrocautery group (89 patients). There was no statistical significance in the clinical features of bladder tumors, including tumor site, number and maximum lesion size. Both the blue laser and plasmakinetic electrocautery could effectively dissect all visible bladder tumors. The surgical time for patients in the blue laser group was longer (p=0.001), but their blood loss was less than that of patients in the control group (p=0.003). There were no differences in the postoperative indwelling catheter time, hospital stay length, reoperation rate or other adverse events. However, the patients undergoing TURBt with the blue laser showed a faster wound healing at 3 months after operation.

Conclusion

The novel blue laser could be effectively and safely used for TURBt in patients with NMIBC, and this method was not inferior to plasmakinetic electrocautery during the perioperative period. However, TURBt with the blue laser may provide the benefit to reduce preoperative blood loss and accelerate postoperative wound healing. Moreover, longer follow-up to confirm recurrence-free survival benefit was required.
Glioblastoma and the search for non-hypothesis driven combination therapeutics in academia
Authors: Johanssen Timothy , McVeigh Laura , Erridge Sara , Higgins Geoffrey , Straehla Joelle , Frame Margaret , Aittokallio Tero , Carragher Neil O. , Ebner Daniel
Published: January 2023

Glioblastoma (GBM) remains a cancer of high unmet clinical need. Current standard of care for GBM, consisting of maximal surgical resection, followed by ionisation radiation (IR) plus concomitant and adjuvant temozolomide (TMZ), provides less than 15-month survival benefit. Efforts by conventional drug discovery to improve overall survival have failed to overcome challenges presented by inherent tumor heterogeneity, therapeutic resistance attributed to GBM stem cells, and tumor niches supporting self-renewal. In this review we describe the steps academic researchers are taking to address these limitations in high throughput screening programs to identify novel GBM combinatorial targets. We detail how they are implementing more physiologically relevant phenotypic assays which better recapitulate key areas of disease biology coupled with more focussed libraries of small compounds, such as drug repurposing, target discovery, pharmacologically active and novel, more comprehensive anti-cancer target-annotated compound libraries. Herein, we discuss the rationale for current GBM combination trials and the need for more systematic and transparent strategies for identification, validation and prioritisation of combinations that lead to clinical trials. Finally, we make specific recommendations to the preclinical, small compound screening paradigm that could increase the likelihood of identifying tractable, combinatorial, small molecule inhibitors and better drug targets specific to GBM.
Risk of second primary cancer among breast cancer patients: A systematic review and meta-analysis
Authors: Parhizgar Parynaz , Bahadori Monfared Ayad , Mohseny Maryam , Keramatinia Aliasghar , Hashemi Nazari Seyed Saeed , Rahman Syed Azizur , Al Marzouqi Amina , Al-Yateem Nabeel , Mosavi Jarrahi Alireza
Published: January 2023

Objectives

The aim of this study was to estimate the extra risk of second primary cancer among breast cancer patients.

Methods and materials

This is a systematic review. A comprehensive search of literature was performed in PubMed, Web of Science, Cochrane library, and Scopus. The search included all published studies up to October 2022. This systematic review included studies published in the English language that reported the risk of second primary non-breast cancer [i.e., standardized incidence ratio (SIR)] among breast cancer patients older than 15 years. After evaluating the methodological quality of the selected studies, SIRs were pooled with consideration of heterogeneity among studies. The estimates were pooled by age and time since the diagnosis of primary breast cancer for both sexes (male and female). Age was categorized based on before 50 years and after 50 years, and time was categorized as duration of less than and more than 10 years, respectively.

Results

From 2,484 articles, 30 articles were eligible for inclusion in the systematic review and meta-analysis. The studies varied in terms of population, number of cases, study design, setting, and year of implementation of the research. The estimated SIR for men and women was 1.28 (95% CI: 1.18, 1.38) and 1.27 (95% CI: 1.15, 1.39), respectively. Women diagnosed with breast cancer before menopause [SIR: 1.52 (95% CI: 1.34, 1.71) vs. 1.21 (95% CI: 1.08, 1.34)] as well as women after 10 years since their breast cancer diagnosis [1.33 (95% CI: 1.22, 1.431) vs. 1.24 (95% CI: 1.10, 1.37)] were at a higher risk of developing second primary cancer. Among men, while there were no differences in risk based on age, with the increase of time, the risk of second primary cancer was reduced [SIR: 1.22 (95% CI: 1.12, 1.33) vs. 1.00 (95% CI: 0.79, 1.22)].

Conclusion

There is an extra risk of second primary cancer among breast cancer patients. The extra risk should be considered for further screening and preventive measures among this population.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336062, identifier (CRD42022336062).
Identification of KIT and BRAF mutations in thyroid tissue using next-generation sequencing in an Ecuadorian patient: A case report
Authors: Cadena-Ullauri Santiago , Paz-Cruz Elius , Tamayo-Trujillo Rafael , Guevara-Ramírez Patricia , Ruiz-Pozo Viviana , Solis-Pazmino Paola , Garcia Cristhian , Godoy Richard , Lincango-Naranjo Eddy , Zambrano Ana Karina
Published: January 2023

Background

The incidence of thyroid cancer has increased worldwide. Ecuador presents the highest incidence among Latin American countries and the second around the world. Genetic alteration is the driving force for thyroid tumorigenesis and progression. The change from valine (V) to glutamic acid (E) at codon 600 of the BRAF gene (BRAFVal600Glu) is the most commonly reported mutation in thyroid cancer. Moreover, the BRAF mutation is not the only mutation that has been correlated with TC. For instance, mutations and overexpression of the KIT gene has been associated with different types of cancer, including lung and colon cancer, and neuroblastoma.

Case presentation

A woman in her early fifties, self-identified as mestizo, from Otavalo, Imbabura-Ecuador had no systemic diseases and denied allergies, but she had a family history of a benign thyroid nodule. Physical examination revealed a thyroid gland enlargement. The fine-needle aspiration biopsy indicated papillary thyroid cancer. The patient underwent a successful total thyroidectomy with an excellent recovery and no additional treatments after surgery. Using Next-Generation sequencing a heterozygous mutation in the BRAF gene, causing an amino acid change Val600Glu was identified. Similarly, in the KIT gene, a heterozygous mutation resulting in an amino acid change Leu678Phe was detected. Moreover, an ancestry analysis was performed, and the results showed 3.1% African, 20.9% European, and 76% Native American ancestry.

Conclusions

This report represents the genetic characteristics of papillary thyroid cancer in an Ecuadorian woman with a mainly Native American ethnic component. Further studies of pathological variants are needed to determine if the combined demographic and molecular profiles are useful to develop targeted treatments focused on the Ecuadorian population.
Deciphering an isolated lung phenotype of NKX2-1 frameshift pathogenic variant
Authors: Delestrain Céline , Aissat Abdel , Nattes Elodie , Gibertini Isabelle , Lacroze Valérie , Simon Stéphanie , Decrouy Xavier , de Becdelièvre Alix , Fanen Pascale , Epaud Ralph
Published: January 2023

Background

to perform a functional analysis of a new NK2 homeobox 1 (NKX2-1) variant (c.85_86del denominated NKX2-1DEL) identified in a family presenting with isolated respiratory disease, in comparison to another frameshift variant (c.254dup denominated NKX2-1DUP) identified in a subject with classical brain-lung-thyroid syndrome.

Methods

pathogenic variants were introduced into the pcDNA3-1(+)-wt-TTF1 plasmid. The proteins obtained were analyzed by western blot assay. Subcellular localization was assessed by confocal microscopy in A549 and Nthy cells. Transactivation of SFTPA, SFTPB, SFTPC, and ABCA3 promoters was assessed in A549 cells. Thyroglobulin promoter activity was measured with the paired box gene 8 (PAX8) cofactor in Nthy cells.

Results

The two sequence variants were predicted to produce aberrant proteins identical from the 86th amino acid, with deletion of their functional homeodomain, including the nuclear localization signal. However, 3D conformation prediction of the conformation prediction of the mutant protein assumed the presence of a nuclear localization signal, a bipartite sequence, confirmed by confocal microscopy showing both mutant proteins localized in the nucleus and cytoplasm. Transcriptional activity with SFTPA, SFTPB, SFTPC, ABCA3 and thyroglobulin promoters was significantly decreased with both variants. However, with NKX2-1DEL, thyroglobulin transcriptional activity was maintained with the addition of PAX8.

Conclusion

These results provide novel insights into understanding the molecular mechanism of phenotypes associated with NKX2-1 pathogenic variants.
Effect of 0.02% and 0.01% atropine on ocular biometrics: A two-year clinical trial
Authors: Wang Ming , Cui Can , Yu Shi-Ao , Liang Ling-ling , Ma Jing-Xue , Fu Ai-Cun
Published: January 2023

Background

Several studies have shown that various concentrations of low-concentration atropine can reduce myopia progression and control axial elongation safely and efficiently in children. The aim of this study was to evaluate the effects of 0.02% and 0.01% atropine on ocular biometrics.

Methods

Cohort study. 138 and 142 children were randomized to use either 0.02% or 0.01% atropine eye drops, respectively. They wore single-vision (SV) spectacles, with one drop of atropine applied to both eyes nightly. Controls (N = 120) wore only SV spectacles. Ocular and corneal astigmatism were calculated using Thibos vector analysis and split into J0 and J45.

Results

The changes in cycloplegic spherical equivalent refraction (SER) and axial length (AL) were −0.81 ± 0.52D, −0.94 ± 0.59D, and −1.33 ± 0.72D; and 0.62 ± 0.29 mm, 0.72 ± 0.31 mm, and 0.89 ± 0.35 mm in the 0.02% and 0.01% atropine and control groups, respectively (all P < 0.05). Both anterior chamber depth (ACD) and ocular astigmatism (including J0) increased, and lens power decreased in the three groups (all P < 0.05). However, there were no differences in the changes in ACD, ocular astigmatism, and lens power among the three groups (all P > 0.05). Intraocular pressure (IOP), corneal curvature, ocular astigmatism J45, and corneal astigmatism (including J0 and J45) remained stable over time in the three groups (all P > 0.05). The contributions to SER progression from the changes in AL, lens and corneal power of the three groups were similar (P > 0.05). The contribution of AL change alone to the change in SER was 56.3%, 63.4% and 78.2% in the above corresponding three groups.

Conclusions

After 2 years, 0.02% and 0.01% atropine had no clinical effects on corneal and lens power, ocular and corneal astigmatism, ACD or IOP compared to the control group. 0.02% and 0.01% atropine helped to control myopia progression mainly by reducing AL elongation.
Perturbed autophagy intervenes systemic lupus erythematosus by active ingredients of traditional Chinese medicine
Authors: Tian Rui , Yuan Lin , Huang Yuan , Zhang Rui , Lyu Hao , Xiao Shuai , Guo Dong , Ali Declan William , Michalak Marek , Chen Xing-Zhen , Zhou Cefan , Tang Jingfeng
Published: January 2023

Systemic lupus erythematosus (SLE) is a common multisystem, multiorgan heterozygous autoimmune disease. The main pathological features of the disease are autoantibody production and immune complex deposition. Autophagy is an important mechanism to maintain cell homeostasis. Autophagy functional abnormalities lead to the accumulation of apoptosis and induce the autoantibodies that result in immune disorders. Therefore, improving autophagy may alleviate the development of SLE. For SLE, glucocorticoids or immunosuppressive agents are commonly used in clinical treatment, but long-term use of these drugs causes serious side effects in humans. Immunosuppressive agents are expensive. Traditional Chinese medicines (TCMs) are widely used for immune diseases due to their low toxicity and few side effects. Many recent studies found that TCM and its active ingredients affected the pathological development of SLE by regulating autophagy. This article explains how autophagy interferes with immune system homeostasis and participates in the occurrence and development of SLE. It also summarizes several studies on TCM-regulated autophagy intervention in SLE to generate new ideas for basic research, the development of novel medications, and the clinical treatment of SLE.
A second-order non-local model for granular flows
Authors: Kim Seongmin , Kamrin Ken
Published: January 2023

We determine a constitutive equation for developed three-dimensional granular flows based on a series of discrete element method simulations. In order to capture non-local phenomena, normal stress differences, and secondary flows, we extend a previously proposed granular temperature-sensitive rheological model by considering Rivlin-Ericksen tensors up to second order. Three model parameters are calibrated with the inertial number and a dimensionless granular temperature. We validate our model by running finite difference method simulations of inclined chute flows. The model successfully predicts the velocity and stress fields in this geometry, including secondary vortical flows that previous first-order models could not predict and slow creeping zones that local models miss. It simultaneously captures the non-trivial variation among diagonal components of the stress tensor throughout the domain.
G protein-coupled estrogen receptor 1 regulates renal endothelin-1 signaling system in a sex-specific manner
Authors: Guthrie Ginger L. , Almutlaq Rawan N. , Sugahara Sho , Butt Maryam K. , Brooks Craig R. , Pollock David M. , Gohar Eman Y.
Published: January 2023

Demographic studies reveal lower prevalence of hypertension among premenopausal females compared to age-matched males. The kidney plays a central role in the maintenance of sodium (Na+) homeostasis and consequently blood pressure. Renal endothelin-1 (ET-1) is a pro-natriuretic peptide that contributes to sex differences in blood pressure regulation and Na+ homeostasis. We recently showed that activation of renal medullary G protein-coupled estrogen receptor 1 (GPER1) promotes ET-1-dependent natriuresis in female, but not male, rats. We hypothesized that GPER1 upregulates the renal ET-1 signaling system in females, but not males. To test our hypothesis, we determined the effect of GPER1 deletion on ET-1 and its downstream effectors in the renal cortex, outer and inner medulla obtained from 12–16-week-old female and male mice. GPER1 knockout (KO) mice and wildtype (WT) littermates were implanted with telemetry transmitters for blood pressure assessment, and we used metabolic cages to determine urinary Na+ excretion. GPER1 deletion did not significantly affect 24-h mean arterial pressure (MAP) nor urinary Na+ excretion. However, GPER1 deletion decreased urinary ET-1 excretion in females but not males. Of note, female WT mice had greater urinary ET-1 excretion than male WT littermates, whereas no sex differences were observed in GPER1 KO mice. GPER1 deletion increased inner medullary ET-1 peptide content in both sexes but increased outer medullary ET-1 content in females only. Cortical ET-1 content increased in response to GPER1 deletion in both sexes. Furthermore, GPER1 deletion notably increased inner medullary ET receptor A (ETA) and decreased outer medullary ET receptor B (ETB) mRNA expression in male, but not female, mice. We conclude that GPER1 is required for greater ET-1 excretion in females. Our data suggest that GPER1 is an upstream regulator of renal medullary ET-1 production and ET receptor expression in a sex-specific manner. Overall, our study identifies the role of GPER1 as a sex-specific upstream regulator of the renal ET-1 system.
Cadmium toxicity in medicinal plants: An overview of the tolerance strategies, biotechnological and omics approaches to alleviate metal stress
Authors: Al-Khayri Jameel M. , Banadka Akshatha , Rashmi R , Nagella Praveen , Alessa Fatima M. , Almaghasla Mustafa I.
Published: January 2023

Medicinal plants, an important source of herbal medicine, are gaining more demand with the growing human needs in recent times. However, these medicinal plants have been recognized as one of the possible sources of heavy metal toxicity in humans as these medicinal plants are exposed to cadmium-rich soil and water because of extensive industrial and agricultural operations. Cadmium (Cd) is an extremely hazardous metal that has a deleterious impact on plant development and productivity. These plants uptake Cd by symplastic, apoplastic, or via specialized transporters such as HMA, MTPs, NRAMP, ZIP, and ZRT-IRT-like proteins. Cd exerts its effect by producing reactive oxygen species (ROS) and interfere with a range of metabolic and physiological pathways. Studies have shown that it has detrimental effects on various plant growth stages like germination, vegetative and reproductive stages by analyzing the anatomical, morphological and biochemical changes (changes in photosynthetic machinery and membrane permeability). Also, plants respond to Cd toxicity by using various enzymatic and non-enzymatic antioxidant systems. Furthermore, the ROS generated due to the heavy metal stress alters the genes that are actively involved in signal transduction. Thus, the biosynthetic pathway of the important secondary metabolite is altered thereby affecting the synthesis of secondary metabolites either by enhancing or suppressing the metabolite production. The present review discusses the abundance of Cd and its incorporation, accumulation and translocation by plants, phytotoxic implications, and morphological, physiological, biochemical and molecular responses of medicinal plants to Cd toxicity. It explains the Cd detoxification mechanisms exhibited by the medicinal plants and further discusses the omics and biotechnological strategies such as genetic engineering and gene editing CRISPR- Cas 9 approach to ameliorate the Cd stress.
Facilitating effects of the reductive soil disinfestation process combined with Paenibacillus sp. amendment on soil health and physiological properties of Momordica charantia
Authors: Liu Liangliang , Xie Yi , Zhong Xin , Deng Quanquan , Shao Qin , Cai Zucong , Huang Xinqi
Published: January 2023

Reductive soil disinfestation (RSD) is an anaerobic and facultative anaerobic microbial-mediated soil management process. The extent of improvement of diseased soil properties by RSD relative to comparable healthy soil is, however, not well characterized. Importantly, how to promote the colonization efficiency of these facultative anaerobic functional species to ensure soil and plant health remain unknown. Here, Fusarium wilt-diseased soil of Momordica charantia grown under a plastic-shed field (PS-CK) was used to conduct molasses-RSD (MO-RSD) along with Paenibacillus sp. (a model of facultative anaerobic species) (MOPA-RSD) treatment, and the soil from a nearby open-air paddy field was considered comparable healthy soil (OA-CK). Both RSD treatments significantly improved the properties of PS-CK soil, and the extent of improvement of soil pH, Fusarium oxysporum reduction efficiency (98.36%~99.56%), and microbial community and functional composition were higher than that achieved for OA-CK soil, which indicated that RSD-regulated most soil properties outperformed those of the comparable healthy soil. The disease incidence and ascorbic acid content of M. charantia in MO-RSD- and MOPA-RSD-treated soils were considerably decreased, while the weight and soluble protein contents were correspondingly increased, as compared to those of M. charantia in PS-CK soil. Specifically, the changes in these physiological properties of M. charantia in MOPA-RSD soil performed well than that in MO-RSD soil. The relative abundances of Cohnella, Effusibacillus, Rummeliibacillus, Oxobacter, Thermicanus, and Penicillium enriched in both RSD-treated soils were positively correlated with Paenibacillus and negatively correlated with F. oxysporum population and disease incidence (P < 0.05). Notably, the relative abundances of these potential probiotics were considerably higher in MOPA-RSD-treated soil than in MO-RSD alone-treated soil. These results show that the RSD process with inoculation of Paenibacillus sp. could promote the colonization of this species and simultaneously stimulate the proliferation of other probiotic consortia to further enhance soil health and plant disease resistance.