bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants
Authors: Hellström William , Hortensius Lisa M. , Löfqvist Chatarina , Hellgren Gunnel , Tataranno Maria Luisa , Ley David , Benders Manon J.N.L. , Hellström Ann , Björkman–Burtscher Isabella M. , Heckemann Rolf A. , Sävman Karin 
Published: June 2022

Abstract
Background
Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term.

Material/methods
Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)−1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age.

Results
In total, 49 infants (median [range] GA 25.4 [22.9–27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, β = 0.90), white matter (p = 0.007, β = 0.33), cortical gray matter (p = 0.002, β = 0.43), deep gray matter (p = 0.008, β = 0.05), and cerebellar (p = 0.006, β = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors.

Conclusions
Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants.

Impact

High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants.

IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood.

Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).
Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells
Authors: Zhang Wenbo , Ross P. Joel , Ellis James , Salter Michael W. 
Published: June 2022

AbstractNMDA receptors (NMDARs), a prominent subtype of glutamatergic receptors, are implicated in the pathogenesis and development of neuropsychiatric disorders such as epilepsy, intellectual disability, autism spectrum disorder, and schizophrenia, and are therefore a potential therapeutic target in treating these disorders. Neurons derived from induced pluripotent stem cells (iPSCs) have provided the opportunity to investigate human NMDARs in their native environment. In this review, we describe the expression, function, and regulation of NMDARs in human iPSC-derived neurons and discuss approaches for utilizing human neurons for identifying potential drugs that target NMDARs in the treatment of neuropsychiatric disorders. A challenge in studying NMDARs in human iPSC-derived neurons is a predominance of those receptors containing the GluN2B subunit and low synaptic expression, suggesting a relatively immature phenotype of these neurons and delayed development of functional NMDARs. We outline potential approaches for improving neuronal maturation of human iPSC-derived neurons and accelerating the functional expression of NMDARs. Acceleration of functional expression of NMDARs in human iPSC-derived neurons will improve the modeling of neuropsychiatric disorders and facilitate the discovery and development of novel therapeutics targeting NMDARs for the treatment of these disorders.
Resistance to targeted therapies: delving into FLT3 and IDH
Authors: Desikan Sai Prasad , Daver Naval , DiNardo Courtney , Kadia Tapan , Konopleva Marina , Ravandi Farhad 
Published: June 2022

AbstractRecent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance.
Modest volcanic SO2 emissions from the Indonesian archipelago
Authors: Bani Philipson , Oppenheimer Clive , Tsanev Vitchko , Scaillet Bruno , Primulyana Sofyan , Saing Ugan Boyson , Alfianti Hilma , Marlia Mita 
Published: June 2022

AbstractIndonesia hosts the largest number of active volcanoes, several of which are renowned for climate-changing historical eruptions. This pedigree might suggest a substantial fraction of global volcanic sulfur emissions from Indonesia and are intrinsically driven by sulfur-rich magmas. However, a paucity of observations has hampered evaluation of these points—many volcanoes have hitherto not been subject to emissions measurements. Here we report new gas measurements from Indonesian volcanoes. The combined SO2 output amounts to 1.15 ± 0.48 Tg/yr. We estimate an additional time-averaged SO2 yield of 0.12-0.54 Tg/yr for explosive eruptions, indicating a total SO2 inventory of 1.27-1.69 Tg/yr for Indonesian. This is comparatively modest—individual volcanoes such as Etna have sustained higher fluxes. To understand this paradox, we compare the geodynamic, petrologic, magma dynamical and shallow magmatic-hydrothermal processes that influence the sulfur transfer to the atmosphere. Results reinforce the idea that sulfur-rich eruptions reflect long-term accumulation of volatiles in the reservoirs.
Mechanism of glycogen synthase inactivation and interaction with glycogenin
Authors: Marr Laura , Biswas Dipsikha , Daly Leonard A. , Browning Christopher , Vial Sarah C. M. , Maskell Daniel P. , Hudson Catherine , Bertrand Jay A. , Pollard John , Ranson Neil A. , Khatter Heena , Eyers Claire E. , Sakamoto Kei , Zeqiraj Elton 
Published: June 2022

AbstractGlycogen is the major glucose reserve in eukaryotes, and defects in glycogen metabolism and structure lead to disease. Glycogenesis involves interaction of glycogenin (GN) with glycogen synthase (GS), where GS is activated by glucose-6-phosphate (G6P) and inactivated by phosphorylation. We describe the 2.6 Å resolution cryo-EM structure of phosphorylated human GS revealing an autoinhibited GS tetramer flanked by two GN dimers. Phosphorylated N- and C-termini from two GS protomers converge near the G6P-binding pocket and buttress against GS regulatory helices. This keeps GS in an inactive conformation mediated by phospho-Ser641 interactions with a composite “arginine cradle”. Structure-guided mutagenesis perturbing interactions with phosphorylated tails led to increased basal/unstimulated GS activity. We propose that multivalent phosphorylation supports GS autoinhibition through interactions from a dynamic “spike” region, allowing a tuneable rheostat for regulating GS activity. This work therefore provides insights into glycogen synthesis regulation and facilitates studies of glycogen-related diseases.
Identification of genes associated with human-canine communication in canine evolution
Authors: Tonoike Akiko , Otaki Ken-ichi , Terauchi Go , Ogawa Misato , Katayama Maki , Sakata Hikari , Miyasako Fumina , Mogi Kazutaka , Kikusui Takefumi , Nagasawa Miho 
Published: June 2022

AbstractThe dog (Canis familiaris) was the first domesticated animal and hundreds of breeds exist today. During domestication, dogs experienced strong selection for temperament, behaviour, and cognitive ability. However, the genetic basis of these abilities is not well-understood. We focused on ancient dog breeds to investigate breed-related differences in social cognitive abilities. In a problem-solving task, ancient breeds showed a lower tendency to look back at humans than other European breeds. In a two-way object choice task, they showed no differences in correct response rate or ability to read human communicative gestures. We examined gene polymorphisms in oxytocin, oxytocin receptor, melanocortin 2 receptor, and a Williams–Beuren syndrome-related gene (WBSCR17), as candidate genes of dog domestication. The single-nucleotide polymorphisms on melanocortin 2 receptor were related to both tasks, while other polymorphisms were associated with the unsolvable task. This indicates that glucocorticoid functions are involved in the cognitive skills acquired during dog domestication.
Elevated plasma level of the glycolysis byproduct methylglyoxal on admission is an independent biomarker of mortality in ICU COVID-19 patients
Authors: Alomar Fadhel A. , Alshakhs Marai N. , Abohelaika Salah , Almarzouk Hassan M. , Almualim Mohammed , Al-Ali Amein K. , Al-Muhanna Fahad , Alomar Mohammed F. , Alhaddad Mousa J. , Almulaify Mohammed S. , Alessa Faisal S. , Alsalman Ahmed S. , Alaswad Ahmed , Bidasee Sean R. , Alsaad Hassan A. , Alali Rudaynah A. , AlSheikh Mona H. , Akhtar Mohammed S. , Al Mohaini Mohammed , Alsalman Abdulkhaliq J. , Alturaifi Hussain , Bidasee Keshore R. 
Published: June 2022

AbstractBiomarkers to identify ICU COVID-19 patients at high risk for mortality are urgently needed for therapeutic care and management. Here we found plasma levels of the glycolysis byproduct methylglyoxal (MG) were 4.4-fold higher in ICU patients upon admission that later died (n = 33), and 1.7-fold higher in ICU patients that survived (n = 32),compared to uninfected controls (n = 30). The increased MG in patients that died correlated inversely with the levels of the MG-degrading enzyme glyoxalase-1 (r2 = − 0.50), and its co-factor glutathione (r2 = − 0.63), and positively with monocytes (r2 = 0.29). The inflammation markers, SSAO (r2 = 0.52), TNF-α (r2 = 0.41), IL-1β (r2 = 0.25), CRP (r2 = 0.26) also correlated positively with MG. Logistic regression analysis provides evidence of a significant relationship between the elevated MG upon admission into ICU and death (P < 0.0001), with 42% of the death variability explained. From these data we conclude that elevated plasma MG on admission is a novel independent biomarker that predicts mortality in ICU COVID-19 patients.
Equivalent magnetic circuit method of estimating iron losses in induction motor spindles
Authors: Lü Lang , Xiong Wanli , Hu Can 
Published: June 2022

AbstractThe iron losses in the motor of motorized spindles have a significant effect on their heat generation, thermal deformation, and machining accuracy. The equivalent magnetic circuit (EMC) method for estimating iron losses in the spindle motor is proposed, where the magnetic flux density distribution of any cross section inside the spindle motor is assumed as a uniform one. A mechanical loss separation method of no load running combined with a sudden loss of power supply is also proposed. The EMC method is verified by prototype experiment and a different analysis method comparison. The EMC does not need to solve complex electromagnetic fields, and to do 2D or 3D eddy current analysis and the corresponding post-processing. There is only need to perform a simple magnetic circuit calculation. Therefore, it can realize a fast analysis and prediction. The proposed mechanical loss separation method requires only one prototype during a whole testing process. There is no need for any other same prototype and a coupling device. It is simpler, and can eliminate the braking torque and electromagnetic losses of the spindle motor.
Simple and practical methods for utilizing parylene C film based on vertical deposition and laser patterning
Authors: Sim Jee Hoon , Chae Hyeonwook , Kim Su-Bon , Yoo Seunghyup 
Published: June 2022

AbstractWe propose two novel methods to effectively utilize parylene C films. First, we demonstrate a vertical deposition method capable of depositing a parylene C film of the same thickness on both sides of a sample. Through this method, we have formed parylene C films with a thickness of 4 μm on both sides of the sample with a thickness deviation of less than 2.5%. Further optical verification indicates that parylene C films formed by this method have a very uniform thickness distribution on each side of the surfaces. Second, we propose a debris-tolerant laser patterning method as a mask-less means to fabricate self-supporting ultrathin parylene C films. This method does not involve any photolithography and entails a simple and rapid process that can be performed using only a few materials with excellent biocompatibility. It is demonstrated that patterned parylene C films exhibit a high degree of surface uniformity and have various geometrical shapes so that they can be used for substrates of highly flexible and/or stretchable devices. Finally, we use both of the proposed methods to fabricate flexible, stretchable, and waterproof-packaged bifacial blue LED modules to illustrate their potential in emerging applications that would benefit from such versatile form factors.
Pharmacist-led antimicrobial stewardship programme in a small hospital without infectious diseases physicians
Authors: Cantudo-Cuenca María Rosa , Jiménez-Morales Alberto , Martínez-de la Plata Juan Enrique 
Published: June 2022

AbstractPharmacists may be tasked to lead antibiotic stewardship programmes (ASP) implementation in small hospitals in absence of infectious diseases (ID) physicians. The objectives are to evaluate the effectiveness of a pharmacist-led ASP in a hospital without ID physician support, with special focus on indicators of the hospital use of antimicrobial agents based on consumption and asess the potential clinical and economic impact of pharmacist interventions (PIs) through the CLEO tool. A prospective quasi-experimental study to implement an ASP in a 194-bed hospital. We evaluated changes in antimicrobial use measured as mean defined daily doses per 1000 patient-days (AUD) for intervention versus preintervention period. A total of 847 antimicrobial PIs were proposed, being 88.3% accepted. Discontinuation due to excessive duration was the most frequently performed PI (23.4%). Most of PIs was classified as major or moderate clinical impact, 41.7% and 37.8% respectively. The global consumption of antimicrobial was reduced from 907.1 to 693.8 AUD, with a signifcant drop in carbapenems and quinolones. Direct expenditure of antibiotics decreased significantly. Pharmacist-led ASP has being effective in reducing consumption of antibiotics. In the absence of ID physician´s support and oversight, pharmacists could lead the improvement of the use of antimicrobials.
Osteoprotegerin and MTHFR gene variations in rheumatoid arthritis: association with disease susceptibility and markers of subclinical atherosclerosis
Authors: Arida Aikaterini , Nezos Adrianos , Papadaki Ioanna , Sfikakis Petros P. , Mavragani Clio P. 
Published: June 2022

AbstractWe aimed to explore whether the rs2073618 variant (G1181C) of the osteoprotegerin (OPG) gene and the methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298AC) and rs1801133 (C677T) gene polymorphisms contribute to rheumatoid arthritis (RA) susceptibility and RA related subclinical atherosclerosis. Overall 283 RA patients and 595 healthy controls (HC) were genotyped for common variants of the OPG and MTHFR genes using PCR based assays. Clinical and laboratory parameters were recorded following thorough chart review. Surrogate markers of subclinical atherosclerosis (Carotid/Femoral intima media thickness/plaque formation) along with traditional risk factors for atherosclerosis were assessed in all RA patients and 280HC. Increased prevalence of the CC genotype of the rs2073618 variant was detected in RA patients vs HC (42.4% vs. 33%, p-value: 0.04). RA patients with high serum titers of rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibodies displayed increased prevalence of the CC genotype of the rs2073618 variant of the OPG gene compared to HC (48.6% and 47.5 vs 33.3%, p-values: 0.0029and 0.0077 respectively). Of interest, this genotype turned to be associated with higher carotid IMT scores (0.872 ± 0.264 vs 0.816 ± 0.284, p-value: 0.01) and marginally with higher rates of carotid plaque formation (66% vs 54.1%, p = 0.06). The MTHFR 1298CC genotype was more prevalent only in the anti-CCP positive group compared to HC, with no associations detected with markers of subclinical atherosclerosis, following adjustment for traditional cardiovascular (CVD) risk factors. Reduced rates of carotid/femoral plaque formation were detected among RA patients harboring the MTHFR TT genotype (52.4 vs 72.7, p-value: 0.009, respectively). This association remained significant following adjustment for classical CVD risk factors (OR [95% CI 0.364 [0.173–0.765], p-value: 0.008). Genetic variations of the osteoprotegerin and MTHFR genes seem to increase susceptibility for seropositive RA and potentially contribute to subclinical atherosclerosis linked to RA. Larger studies are needed to confirm these findings.
Influence of environmental factors on seed germination and seedling characteristics of perennial ryegrass (Lolium perenne L.)
Authors: Javaid Muhammad Mansoor , Mahmood Athar , Alshaya Dalal S. , AlKahtani Muneera D. F. , Waheed Hasnain , Wasaya Allah , Khan Sher Aslam , Naqve Maria , Haider Imran , Shahid Muhammad Adnan , Nadeem Muhammad Ather , Azmat Saira , Khan Bilal Ahmad , Balal Rashad Mukhtar , Attia Kotb A. , Fiaz Sajid 
Published: June 2022

AbstractInformation regarding the germination and seedling growth behavior of a potential weed species is an important tool to manage weeds without the use of agricultural chemicals that cause harmful effects on human health and the environment. A series of experiments were directed to investigate the influence of different environmental factors (temperature, pH, NaCl, moisture stress, and seed burial depth) on germination and seedling emergence of perennial ryegrass (Lolium perenne L.) under controlled conditions. Results suggested that 25 °C is the optimum temperature for maximum germination (95%) and seedling growth of perennial ryegrass, however, a quick decline was observed at 35 °C. Seed germination was unaffected by pH levels ranging from 5 to 10. The 92% seed germination was recorded where no salt stress was applied and germination was reduced by 87% at 250 mMNaCl concentration. Seed germination was unaffected by osmotic potential ranges from 0 to − 0.4 MPa thereafter declined and completely inhibited at − 0.8 or − 1.0 MPa. No seed emerged at the soil surface or a soil depth of 6 or 7 cm and 90% emergence occurred at 1 cmsoil depth. The germination and seedlings parameters like time to initial germination, mean germination time, time taken to 50% germination and germination index, root and shoot length, and fresh and dry weight of root and shoot are significantly affected with the environmental factors. The information obtained in this study will be helpful to develop better management strategies for germination and the emergence of perennial ryegrass in areas where it has the ability to rapidly colonize.
Designing of multi-epitope chimeric vaccine using immunoinformatic platform by targeting oncogenic strain HPV 16 and 18 against cervical cancer
Authors: Kumar Anoop , Sahu Utkarsha , Kumari Pratima , Dixit Anshuman , Khare Prashant 
Published: June 2022

AbstractCervical cancer is the most common gynaecological cancer and reaches an alarming stage. HPVs are considered the main causative agents for cervical cancer and other sexually transmitted infections across the globe. Currently, three prophylactic vaccines are available against HPV infections with no therapeutic values. Due to a lack of effective therapeutic and prophylactic measures, the HPV infection is spreading in an uncontrolled manner. Next-generation of vaccine is needed to have both prophylactic and therapeutic values against HPV. Here first time we have designed a multi-epitope chimeric vaccine using the most oncogenic strain HPV 16 and HPV 18 through an immunoinformatic approach. In this study, we have used the L1, E5, E6 and E7 oncoproteins from both HPV 16 and HPV 18 strains for epitope prediction. Our recombinant chimeric vaccine construct consists, selected helper and cytotoxic T cell epitopes. Our computational analysis suggests that this chimeric construct is highly stable, non-toxic and also capable of inducing both cell-mediated and humoral immune responses. Furthermore, in silico cloning of the multi-epitope chimeric vaccine construct was done and the stabilization of the vaccine construct is validated with molecular dynamics simulation studies. Finally, our results indicated that our construct could be used for an effective prophylactic and therapeutic vaccine against HPV.
Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in black South Africans: a cross-sectional study
Authors: Dlamini Siphiwe N. , Norris Shane A. , Mendham Amy E. , Mtintsilana Asanda , Ward Kate A. , Olsson Tommy , Goedecke Julia H. , Micklesfield Lisa K. 
Published: June 2022

AbstractAlthough appendicular skeletal muscle mass (ASM) and handgrip strength (HGS) are key components of sarcopenia, their underlying biological mechanisms remain poorly understood. We aimed to investigate associations of circulating biomarkers with ASM and HGS in middle-aged black South Africans. This study consisted of 934 black South Africans (469 men and 465 women, aged 41–72 years) from the Middle-aged Soweto cohort. Linear regression models were used to examine relationships between 182 biomarkers (measured with proximity extension assay) and dual-energy X-ray absorptiometry-measured ASM and dynamometer-measured HGS. Age, height, sex, smoking, alcohol, food insecurity, physical activity, visceral adipose tissue, HIV and menopausal status were included as confounders. Regression models showing sex-interactions were stratified by sex. The Benjamini–Hochberg false discovery rate (FDR) was used to control for multiple testing, and FDR-adjustedPvalues were reported. In the total sample, 10 biomarkers were associated with higher ASM and 29 with lower ASM (P < 0.05). Out of these 39 biomarkers, 8 were also associated with lower HGS (P < 0.05). MMP-7 was associated with lower HGS only (P = 0.011) in the total sample. Sex-interactions (P < 0.05) were identified for 52 biomarkers for ASM, and 6 for HGS. For men, LEP, MEPE and SCF were associated with higher ASM (P < 0.001, = 0.004, = 0.006, respectively), and MEPE and SCF were also associated with higher HGS (P = 0.001, 0.012, respectively). Also in men, 37 biomarkers were associated with lower ASM (P < 0.05), with none of these being associated with lower HGS. Furthermore, DLK-1 and MYOGLOBIN were associated with higher HGS only (P = 0.004, 0.006, respectively), while GAL-9 was associated with lower HGS only (P = 0.005), among men. For women, LEP, CD163, IL6, TNF-R1 and TNF-R2 were associated with higher ASM (P < 0.001, = 0.014, = 0.027, = 0.014, = 0.048, respectively), while IGFBP-2, CTRC and RAGE were associated with lower ASM (P = 0.043, 0.001, 0.014, respectively). No biomarker was associated with HGS in women. In conclusion, most biomarkers were associated with ASM and not HGS, and the associations of biomarkers with ASM and HGS displayed sex-specificity in middle-aged black South Africans. Proteomic studies should examine ASM and HGS individually. Future research should also consider sexual dimorphism in the pathophysiology of sarcopenia for development of sex-specific treatment and diagnostic methods.