bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative estimation of chemical microheterogeneity through the determination of fuzzy entropy
Authors: Gentili Pier Luigi , Perez-Mercader Juan
Published: August 2022

Chemical micro-heterogeneity is an attribute of all living systems and most of the soft and crystalline materials. Its characterization requires a plethora of techniques. This work proposes a strategy for quantifying the degree of chemical micro-heterogeneity. First of all, our approach needs the collection of time-evolving signals that can be fitted through poly-exponential functions. The best fit is determined through the Maximum Entropy Method. The pre-exponential terms of the poly-exponential fitting function are used to estimate Fuzzy Entropy. Related to the possibility of implementing Fuzzy sets through the micro-heterogeneity of chemical systems. Fuzzy Entropy becomes a quantitative estimation of the Fuzzy Information that can be processed through micro-heterogeneous chemical systems. We conclude that our definition of Fuzzy Entropy can be extended to other kinds of data, such as morphological and structural distributions, spectroscopic bands and chromatographic peaks. The chemical implementation of Fuzzy sets and Fuzzy logic will promote the development of Chemical Artificial Intelligence.
Systematic review of guidelines for the diagnosis and treatment of Clostridioides difficile infection
Authors: Gu Ting , Li Wen , Yang Li-Li , Yang Si-Min , He Qian , He Hai-Yu , Sun Da-Li
Published: August 2022

Objective

To systematically assess the current related methodological quality of guidelines for the diagnosis and treatment of Clostridioides difficile infection (CDI), revealing the heterogeneity and reasons for guideline recommendations for the diagnosis and treatment of CDI.

Methods

We searched electronic databases systematically between 2017 and 2021 to find the latest guidelines for the diagnosis and treatment of CDI. The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used for quality assessment of the included guidelines. The main recommendations for the diagnosis and treatment of CDI in the guidelines were extracted and evaluated for consistency, and the level of evidence supporting these recommendations was further extracted and analysed.

Results

Fourteen guidelines for the diagnosis and treatment of CDI were finally included in this study. There were four guidelines, BSG and HIS, ASCRS, IDSA AND SHEA, and NICE, with an overall score of more than 60%, which is worthy of clinical recommendation. Further analysis of the consistency of the main recommendations for the diagnosis and treatment of CDI in the guidelines showed that the recommendations differed among guidelines. There are no unified classification criteria for the severity of CDI in current studies; some recommendations for the diagnosis and treatment of CDI do not provide evidence to support the recommendations, most recommendations cite low levels of evidence, and there is a lack of high-quality research evidence.

Conclusion

The quality of guidelines for the diagnosis and treatment of CDI is uneven. Recommendations on the diagnosis and treatment of CDI have also varied in the guidelines for the past 5 years. Improvements of the aforementioned factors associated with causing heterogeneity would be a rational approach by guideline developers to further update guidelines for the diagnosis and treatment of CDI.
Composition and diverse differences of intestinal microbiota in ulcerative colitis patients
Authors: Zhu Siying , Han Muzhou , Liu Simao , Fan Liqiaona , Shi Haiyun , Li Peng
Published: August 2022

Objective

To explore the composition of the intestinal microbiota in ulcerative colitis (UC) patients and to identify differences in the microbiota between patients with active disease and those in remission.

Methods

Between September 2020 and June 2021, we enrolled into our study, and collected stool samples from, patients with active UC or in remission and healthy control subjects. The diagnosis of UC was based on clinical, endoscopic, radiological, and histological findings. The composition of the intestinal microbiota was determined by sequencing of the 16S rRNA V3–V4 region and by bioinformatic methods. The functional composition of the intestinal microbiota was predicted using PICRUSt 2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) software.

Results

We found that the intestinal flora was significantly less rich and diverse in UC patients than in healthy control subjects. Beta diversity analysis revealed notable differences in the intestinal flora compositions among the three groups, but there was no statistical difference in alpha diversity between UC patients with active disease and those in remission. At the phylum level, the relative abundances of Proteobacteria and Patescibacteria were significantly higher, and the relative abundances of Desulfobacterota and Verrucomicrobiota were lower, in UC patients with active disease than in the healthy control group. Higher levels of potential pathogens and lower levels of butyrate-producing bacteria were also detected in UC patients with active disease. Linear discriminant analysis Effect Size (LefSe) revealed that 71 bacterial taxa could serve as biomarkers, with 26 biomarkers at the genus level. In addition, network analysis showed that there was a positive correlation between Roseburia and Lachnospira. Functional predictions indicated that gene functions involving the metabolism of some substances, such as methane, lipopolysaccharide, geraniol, and ansamycins, were significantly different among the three groups.

Conclusion

The richness and diversity of the intestinal microbiota differed significantly among the three groups. Richness describes the state of being rich in number of intestinal bacteria, whereas diversity is the number of different species of intestinal bacteria. Different bacterial taxa could be used as biomarkers, expanding our understanding of the relationship between the intestinal microbiota microenvironment and UC in the future.
Influences of tropical monsoon and El Niño Southern Oscillations on surface chlorophyll-a variability in the Gulf of Thailand
Authors: Leenawarat Dudsadee , Luang-on Jutarak , Buranapratheprat Anukul , Ishizaka Joji
Published: August 2022

This study investigated the seasonal variability of surface chlorophyll-a (chl-a) and the influence of the El Niño Southern Oscillation (ENSO) related to environmental parameters in the Gulf of Thailand (GoT). Monthly chl-a data from MODIS from 2002 to 2020 as well as sea surface temperature (SST), wind, precipitation, and river discharge were used in this analysis. Results from seasonal climatology and Empirical Orthogonal Function (EOF) described high chl-a concentration areas along the western to the southern coasts and near Ca Mau Cape during the northeast monsoon (NEM), and the upper GoT (UGoT), eastern coast, and the GoT mouth during the southwest monsoon (SWM), while low chl-a took place during the non-monsoon (NON). The GoT was divided into six areas based on the EOFs of chl-a, and then the correlation between chl-a variability and environmental parameters was also examined. The results suggested that chl-a in coastal and offshore areas were controlled by different mechanisms. Chl-a in coastal areas responded to precipitation and river discharge as well as the shoreward wind; meanwhile, chl-a in offshore areas correlated with SST and wind magnitude indicating the importance of water mixing and upwelling. The fluctuation of chl-a in each season related to ENSO was captured by EOF based on the seasonal anomaly. The influence of ENSO was strong during NEM and NON but minimal during SWM. El Niño/La Niña generally caused low/high precipitation and high/low SST. Moreover, El Niño/La Niña caused anomalously weak/strong wind during NEM contrary to during NON. Anomalous high/low chl-a were observed in shallow regions during El Niño/La Niña corresponding to strong/weak wind in NON. Abnormal wind under ENSO also created the shifting in the high chl-a area near Ca Mau Cape. These results have improved our understanding of monsoons and ENSO variabilities as the crucial drivers of changes in the tropical marine ecosystem in both seasonal and interannual time scales.
Quantification of CO2 removal in a large-scale enhanced weathering field trial on an oil palm plantation in Sabah, Malaysia
Authors: Larkin Christina S. , Andrews M. Grace , Pearce Christopher R. , Yeong Kok L. , Beerling David J. , Bellamy Joshua , Benedick Suzan , Freckleton Robert P. , Goring-Harford Heather , Sadekar Satyam , James Rachael H.
Published: August 2022

Modeling studies show that large-scale deployment of enhanced rock weathering on croplands has the potential to reduce levels of atmospheric carbon dioxide by the end of the century. There is, however, a pressing need to verify model predictions through long-term field trials. Here we report results from the first 3 years of an ongoing enhanced weathering field trial, carried out on an oil palm plantation in Sabah, Malaysia. Crushed silicate rock was applied to three hydrologically isolated catchments, and three adjacent (paired) reference catchments were left untreated. The drawdown of atmospheric CO2 was quantified via the export of alkalinity in stream waters and changes in soil carbonate content. The amended and reference catchments were found to have a similar extent of CO2 drawdown via alkalinity export [respectively, 3.8 ± 0.8 (1 SD) and 3.7 ± 0.6 (1 SD) tCO2 ha−1] when all catchments were averaged over the study period (October 2018 to July 2021). However, differences were observed between the different catchment pairs (plots): two of the plots displayed a similar extent of CO2 removal for both the amended and reference catchments, but the third amended catchment had a higher extent of CO2 removal of ~1 tCO2 ha−1 relative to its adjacent reference catchment. The difference in CO2 removal rates determined for this plot can likely be attributed to increased weathering of silicate minerals in the amended catchment. Soil carbonate concentrations were on average <0.2 wt% CaCO3, but we report a small increase of ~0.03 wt% CaCO3 in the top 30 cm of soil in the amended soils relative to the reference catchments. The magnitude of CO2 drawdown via alkalinity export determined for these agricultural catchments is around an order of magnitude higher than in natural forested catchments in Sabah and similar to that of basaltic catchments. We show that these high weathering rates are primarily driven by weathering of carbonate fertilizers. The data presented from this field trial provide vital contextual information on the real-world efficacy and practicalities associated with the implementation of enhanced weathering for atmospheric CO2 removal that will help to inform further trials as well as wider-scale deployment.
Bridge to nowhere: A retrospective single-center study on patients using chronic intravenous inotropic support as bridge therapy who do not receive surgical therapy
Authors: Rao Anirudh , Singh Manavotam , Maini Mansi , Anderson Kelley M. , Crowell Nancy A. , Henderson Paul R. , Gholami Sherry S. , Sheikh Farooq H. , Najjar Samer S. , Groninger Hunter
Published: August 2022

Background

Many patients with advanced heart failure (HF) are administered chronic intravenous inotropic support (CIIS) as bridge to surgical therapy; some ultimately never receive surgery. We aimed to describe reasons patients “crossover” from CIIS as bridge therapy to palliative therapy, and compare end-of-life outcomes to patients initiated on CIIS as palliative therapy.

Methods

Single-institution, retrospective cohort study of patients on CIIS as bridge or palliative therapy between 2010 and 2016; data obtained through review of health records and multi-disciplinary selection meeting minutes, was analyzed using descriptive and inferential statistics.

Results

Of 246 patients discharged on CIIS as bridge therapy, 37 (16%) (male n = 28, 76%; African American n = 22, 60%) ultimately never received surgery. 67 matched patients on CIIS as palliative therapy were included for analysis (male n = 47, 70%; African American n = 47, 70%). The most common reasons for “crossover” from CIIS as bridge therapy to palliative therapy were frailty (n = 10, 27%), cardiac arrest (n = 5, 13.5%), and progressive non-cardiac illnesses (n = 6, 16.2%). A similar percentage of patients in the bridge (n = 28, 76%) and palliative (n = 48, 72%) groups died outside the hospital (P=0.66); however, fewer bridge patients received hospice care compared to the palliative group (35% vs 69%, P < 0.001). Comparing patients who died in the hospital, bridge patients (n = 9; 100%) were more likely to die in the intensive care unit than palliative patients (n = 8; 42%) (P < 0.001).

Conclusion

Patients on CIIS as bridge therapy who do not ultimately receive surgical therapy “crossover” to palliative intention due to frailty, or development of or identification of serious illnesses. Nevertheless, these “bridge to nowhere” patients are less likely to receive palliative care or hospice and more likely to die in the intensive care unit than patients on CIIS as palliative therapy.
Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study
Authors: Zhang Yuxuan , Zhang Xinyi , Chen Delong , Lu Jia , Gong Qinyan , Fang Jiacheng , Jiang Jun
Published: August 2022

Background

Observational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.

Methods

Two-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10−8) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10−5). Summary-level statistics for CVDs, including coronary artery disease (CAD), myocardial infarction, heart failure, atrial fibrillation, stroke and its subtypes were collected. The ME estimation was performed using the inverse-variance weighted and Wald ratio methods. Sensitivity analysis was performed using the weighted median, MR-Egger, leave-one-out analysis, MR pleiotropy residual sum and outlier and MR Steiger.

Results

Based on the locus-wide significance level, genetically predicted genus Oxalobacter was positively associated with the risk of CAD (odds ratio (OR) = 1.06, 95% confidence interval (CI), 1.03 – 1.10, P = 1.67 × 10−4), family Clostridiaceae_1 was negatively correlated with stroke risk (OR = 0.83,95% CI, 0.75–0.93, P = 7.76 × 10−4) and ischemic stroke risk (OR = 0.823,95% CI, 0.74–0.92, P = 4.15 × 10−4). There was no causal relationship between other genetically predicted gut microbiome components and CVDs risk. Based on the genome-wide statistical significance threshold, the results showed that the gut microbiome had no causal relationship with CVDs risk.

Conclusion

Our findings reveal that there are beneficial or adverse causal effects of gut microbiome components on CVDs risk and provide novel insights into strategies for the prevention and management of CVDs through the gut microbiome.
Spatial variability and post-depositional diffusion of stable isotopes in high accumulation regions of East Antarctica
Authors: Mahalinganathan Kanthanathan , Thamban Meloth , Ejaz Tariq , Srivastava Rohit , Redkar B. L. , Laluraj C. M.
Published: August 2022

Stable isotopes of Antarcticice cores are used extensively in reconstructing the past climate. Variations in snow accumulation patterns and post-depositional processes such as changes in isotope ratios due to diffusion may complicate these records. We analyzed the spatio-temporal variations of snow accumulation, stable isotopic composition, and factors controlling their distribution along two transects in the Dronning Maud Land (DML) and Princess Elizabeth Land (PEL) regions of East Antarctica. The δ18O and δD variations are dominantly influenced by snow accumulation in the DML region and temperature in the PEL region. To evaluate the extent of diffusion in isotope records, the isotope record of an ice core (IND-33) drilled after 5 years close to the DML transect was compared with the snow isotope records. A quantitative comparison of the snow core δ18O records with that of the ice core revealed signal attenuation ranging between 55 and 70%. Using a firn diffusion model, we estimated a diffusion length of 6 cm in IND-33 over 5 years. Our study revealed that while isotope diffusion exists even in high accumulation sites of coastal Antarctica, it does not significantly impact the dating and paleoclimatic interpretation of isotope records, unlike in low accumulation areas.
Site-specific seismic hazard and risk potential of Bengal Basin with emphasis on holistic seismic hazard microzonation and its structural impact assessment in the cities of Dhanbad and Mymensingh
Authors: Nath Sankar Kumar , Biswas Arpita , Srivastava Anand , Sengupta Arnab , Ghatak Chitralekha , Madan Jyothula
Published: August 2022

The Bengal Basin located in the eastern part of the Indian subcontinent at the conjunction of the Eurasian, Indian, and Indo-Burma plates with two progressing deformation fronts viz. the Himalayas and the Indo-Burmese orogenic belts is one of the largest fluvio-deltaic to shallow marine sedimentary basin covered by alluvial plains of Holocene deposits extending from the Himalayas to the Bay of Bengal over thick younger alluvium comprising shallow layers of silt, clay, and sand that can have disastrous consequences due to site-specific ground motion amplification and liquefaction effects. The basin surrounded by Shillong and Assam plateaus in the Northeast is in the active tectonofabric of major active faults and lineaments triggering many devastating earthquakes in the past implicating the MM Intensity of VIII–XI in the near-source region causing widespread damage and destruction in the basin, thus bringing in the essence of assessing surface level seismic hazard and the risk imposed on the basin. Consideration of seismicity patterns, fault networks, and similarity in focal mechanisms yielded 49 areal seismogenic sources and additional active tectonic features in the 0–25 km, 25–70 km, and 70–180 km hypocentral depth ranges, which along with 14 ground motion prediction equations that include site-specific next generation spectral attenuation models pertaining to Northeast India, East-Central Himalaya, and Bengal Basin tectonic provinces yielded probabilistic peak ground acceleration (PGA) at engineering bedrock in the range of 0.08–0.58 g. Both the geophysical and geotechnical investigations at 6,000 sites provided effective shear wave velocity distribution in the range of 113–948 m/s on the geographical information system, thus classifying the basin into 11 site classes with “None” to “Severe” liquefaction hazard potential. A systematic non-linear/equivalent linear site response analysis and its spectral convolution with firm rock peak ground acceleration yielded surface-consistent hazard in the range of 0.09–1.17 g, thus opening up the issue of risk assessment and holistic seismic hazard microzonation of all the cities in the basin and their structural impact assessment using the SELENA-based capacity spectrum method on FEMA and BMTPC-regulated 11 model building types in the damage states of “none,” “slight,” “moderate,” “extensive,” and “complete” for all of those, however, in-depth studies carried out for Mymensingh and Dhanbad have been presented.
Living coralligenous as geo-historical structure built by coralline algae
Authors: Basso Daniela , Bracchi Valentina Alice , Bazzicalupo Pietro , Martini Marco , Maspero Francesco , Bavestrello Giorgio
Published: August 2022

The most important reef of the Mediterranean is the Coralligène (Coralligenous = C), including several types of calcareous algal-invertebrate build-ups growing in normal open marine conditions. We analyzed and compared two C samples from the Ligurian Sea developed in different environmental settings: 1) off Portofino on a rocky cliff, at a depth of about 40 m and 2) in front of Bogliasco, on a sub-horizontal substrate at a depth of 10 m. The maximum AMS radiocarbon dating provided an older age for Bogliasco (about 5 ka BP) than for Portofino (about 3.6 ka BP), and the mean accumulation rate of the Portofino build-up (about 80 µm y−1) was found to be higher than the one in Bogliasco (about 65 µm y−1). The different sides of each build-up showed a remarkable heterogeneity in the dominant cover by living organisms, and the comparison between the two build-ups highlighted an evident diversity in their taxonomic composition and structure, although crustose coralline algae (CCA) are the dominant framework builder and major autogenic ecosystem engineers at both localities, in the present as in the past millennia. Other major components of the structure are bryozoans and serpulids, and an important role is played by sediment filling. In Bogliasco, extreme climate events and major peaks of fine matrix and terrigenous grains are observed, lithologically related to the drainage basin of the Poggio creek and associated with charophyte occurrence and reduced CCA abundance. The occurrence of the rareSporolithon ptychoideswas observed both in Portofino at about 750 BCE and in Bogliasco. TheseSporolithonphases are likely related to warm and humid spells punctuating the Holocene climate fluctuations in the Ligurian Sea. Because coralline algae are confirmed to be the most important habitat engineer of the Mediterranean reefs, they deserve more attention in the framework of any monitoring initiative aimed at C management and conservation.
Subseasonal forecasts of precipitation over maritime continent in boreal summer and the sources of predictability
Authors: Lyu Yang , Zhu Shoupeng , Zhi Xiefei , Dong Fu , Zhu Chengying , Ji Luying , Fan Yi
Published: August 2022

In this study, subseasonal precipitation forecast skills over Maritime Continent in boreal summer are investigated for the ECMWF and CMA models involved in the S2S Project. Results indicate that the ECMWF model shows generally superior forecast performances than CMA, which is characterized by lower errors and higher correlations compared with the observations. Meanwhile, ECMWF tends to produce wet biases with increasing lead times, while the mean errors of CMA are revealed to be approximately constant throughout lead times of 2–4 weeks over most areas. Besides, the temporal correlations between model outputs and observations obviously decrease with growing lead times, with a high-low distribution presented from north to south. In addition, the roles of large-scale drivers like ENSO and BSISO in modulating subseasonal precipitation forecast skills are also assessed in the models. Both ECMWF and CMA can reasonably capture the ENSO related precipitation anomalies for all lead times, while their capabilities of capturing BSISO related precipitation anomalies decrease with growing lead times, which is more obvious in CMA. The enhanced subseasonal precipitation forecast skills mainly respond to the BSISO associated precipitation variability. For most MC areas such as southern Indochina, western Indonesia, Philippines and the eastern ocean, the forecast skills of both ECMWF and CMA can be improved to a great extent by enhancing the capture of BSISO related precipitation anomalies, with the temporal correlations for both ECMWF and CMA increased by about 0.15 for lead times of 3–4 weeks. It provides an opportunity window for the models to improve precipitation forecasts on the subseasonal timescale.
Representative sampling method for laboratory testing on shear strength of rock joints
Authors: Wang Changshuo , Yong Rui , Du Shigui , Luo Zhanyou , Huang Chuxia , Ye Jun
Published: August 2022

The direct shear test is commonly used to determine the shear strength of rock joints. The measured shear strength, however, varies greatly with specimen positions due to the heterogeneity of rock joints. As a result, selecting specimens that represent the overall properties of rock joints is usually difficult. This paper aims to investigate the heterogeneity of rock joints and propose a new sampling method for selecting representative specimens. The roughness and shear strength variations of specimens taken from different positions of a natural rock joint were analyzed, and it was discovered that the heterogeneity of rock joint roughness is responsible for the heterogeneity of shear strength. The limitations of the traditional sampling method based on visual judgment were extensively investigated, revealing that shear strength parameters acquired by the traditional method contain large coefficient of variation (COV) values. To acquire trustworthy shear strength parameters, we proposed a representative sampling method based on the maximum likelihood estimation of the overall properties of rock joints. The number of determined representative specimens increases with the increase of normal stress. Representative specimens determined under low normal stresses can likewise exhibit the overall properties of the rock joint when subjected to high normal stresses. The Mohr-Coulomb and a nonlinear criterion were used to validate the derived representative specimens, demonstrating that the proposed method can produce reliable shear strength parameters and shear strength envelopes. Particularly, the determined representative specimens could derive shear strength parameters with relative errors less than 10% and COV values less than 0.1. The proposed method provides a quantitative and reliable tool for determining representative specimens to obtain reliable shear strength of rock joints.
GPCR heteromers: An overview of their classification, function and physiological relevance
Authors: Dale Natasha C. , Johnstone Elizabeth K. M. , Pfleger Kevin D. G.
Published: August 2022

G protein-coupled receptors (GPCRs) are capable of interacting to form higher order structures such as homomers and heteromers. Heteromerisation in particular has implications for receptor function, with research showing receptors can attain unique expression, ligand binding, signalling and intracellular trafficking upon heteromerisation. As such, GPCR heteromers represent novel drug targets with extensive therapeutic potential. Changes to ligand affinity, efficacy and G protein coupling have all been described, with alterations to these pharmacological aspects now well accepted as common traits for heteromeric complexes. Changes in internalisation and trafficking kinetics, as well as β-arrestin interactions are also becoming more apparent, however, few studies to date have explicitly looked at the implications these factors have upon the signalling profile of a heteromer. Development of ligands to target GPCR heteromers both experimentally and therapeutically has been mostly concentrated on bivalent ligands due to difficulties in identifying and developing heteromer-specific ligands. Improving our understanding of the pharmacology and physiology of GPCR heteromers will enable further development of heteromer-specific ligands with potential to provide therapeutics with increased efficacy and decreased side effects.
The burden of vitamin D deficiency in household members of children presenting with symptomatic vitamin D deficiency
Authors: Uday Suma , Högler Wolfgang
Published: August 2022

Background

Micronutrient deficiencies are common among household/family members due to shared lifestyle and dietary habits. The extent of biochemical abnormalities in household members of children presenting with symptomatic vitamin D deficiency remains unknown.

Aim

Investigate the prevalence of vitamin D deficiency and biochemical osteomalacia in the mothers and siblings of children presenting with symptomatic vitamin D deficiency.

Methods

All mothers and sibling of children referred to a single tertiary endocrine centre between January 2018 and December 2021, with symptomatic vitamin D deficiency were investigated prospectively for vitamin D deficiency [defined as 25 hydroxyvitamin D (25OHD) < 30nmol/L] and biochemical osteomalacia [vitamin D deficiency and elevated alkaline phosphatase (ALP) and/or parathormone (PTH)] as per clinical guidelines.

Reults

Ninety-seven family members (68 siblings and 29 mothers) of 29 index cases (median age 1.7 years, 55.5% male) were investigated. The majority (65.5%, n=19) were of Asian ethnic background. The mean (SD) 25OHD levels of the index, maternal and sibling cohorts were 15 (10), 15 (7) and 20 (10) nmol/L respectively. Vitamin D deficiency was noted in 93% of the maternal and 79% of the sibling cohorts. Biochemical osteomalacia was present in 72% of the maternal and 79% of the sibling cohorts. Mothers of infants had significantly lower mean 25OHD levels compared to mothers of older children [11 (n=12) vs 18 nmol/L (n=17) respectively, p=0.006)], most of whom were symptomatic (66.6%, n=8/12). None of the mothers had hypocalcaemia. Among the 10% (n=7) of the siblings with hypocalcaemia, 86% (n=6/7) had concurrent dietary calcium deficiency and 71.4% (n= 5/7) reported symptoms in retrospect. Hypocalcaemic siblings had significantly lower 25OHD (7 vs 15 nmol/L, p<0.001), higher PTH (175 vs 58 ng/L, p<0.001) and ALP (846 vs 318 IU/L, p<0.001), respectively compared to normocalcaemic siblings.

Conclusions

In view of the substantial morbidity uncovered in household/family members of children diagnosed with symptomatic vitamin D deficiency, we recommend universal supplementation of all risk groups. Biochemical testing and treatment is indicated to replenish stores only in those at highest risk such as mothers of infants, individuals with concurrent dietary calcium deficiency and those with clinical symptoms.
Androgen receptor in breast cancer: The “5W” questions
Authors: Ravaioli Sara , Maltoni Roberta , Pasculli Barbara , Parrella Paola , Giudetti Anna Maria , Vergara Daniele , Tumedei Maria Maddalena , Pirini Francesca , Bravaccini Sara
Published: August 2022

Androgen receptor (AR) is expressed in 60-70% of breast cancers (BCs) and the availability of anti-AR compounds, currently used for treating prostate cancer, paves the way to tackle specifically AR-positive BC patients. The prognostic and predictive role of AR in BC is a matter of debate, since the results from clinical trials are not striking, probably due to both technical and biological reasons. In this review, we aimed to highlight WHAT is AR, describing its structure and functions, WHAT to test and HOW to detect AR, WHERE AR should be tested (on primary tumor or metastasis) and WHY studying this fascinating hormone receptor, exploring and debating on its prognostic and predictive role. We considered AR and its ratio with other hormone receptors, analyzing also studies including patients with ductal carcinoma in situ and with early and advanced BC, as well. We also emphasized the effects that both other hormone receptors and the newly emerging androgen-inducible non coding RNAs may have on AR function in BC pathology and the putative implementation in the clinical setting. Moreover, we pointed out the latest results by clinical trials and we speculated about the use of anti-AR therapies in BC clinical practice.
A feasibility study of SMART reactor power performance optimizations-part 1: Steady-state and burn-up analysis
Authors: Zhong Yiming , Norman Paul , Wu Wenbin
Published: August 2022

SMART is an integral small pressurized water nuclear reactor design with a rated power output of 100 MWe from 330 MWth, but it needs a higher power output for the United Kingdom energy market. This study applies Monte Carlo code OpenMC to build a full-core model and innovatively adjust the simulation coefficients to approach the reactor operating conditions. The analysis results point out the reasonable optimization’s technical direction. The model’s sensitivity to ENDF and JEFF nuclear data libraries and spatial division is tested and verified. Then it performs a series of simulations to obtain the core’s neutronic parameters, such as neutron energy and spatial distributions, effective neutron multiplication factor keff and its variation versus depletion. The analysis found that the initially designed core’s keff is 1.22906, and the temperature reactivity defect is 11612 pcm. In 1129 full-power operating days, the keff will decrease to 0.99126, and the reactor depletes 8.524 × 1026235U atoms. However, the outermost fuel assemblies’ 235U depletion rate is lower than 45% in this extended refuelling cycle, and their ending enrichment is higher than 2.4%. That means the fuel economy of the original design’s two-batch refuelling scheme core layout is insufficient. Improving the thermal neutron fluence in these assemblies may optimize the SMART power performance effectively.
Combining real-time fluorescence spectroscopy and flow cytometry to reveal new insights in DOC and cell characterization of drinking water
Authors: Schuster Jonas , Huber Johanna , Stumme Jakob , Grieb Anissa , Ernst Mathias
Published: August 2022

Sudden changes in drinking water quality can cause harmful consequences for end users. Thus, real-time monitoring of drinking water quality can allow early warning and provide crucial gains for securing safe water distribution. This study investigated the advantages of simultaneous real-time measuring of flow cytometry and fluorescence spectroscopy. A contamination event was investigated in a laboratory-scale analysis by spiking drinking water samples with organic nutrients. Flow cytometric data were analyzed by creating fingerprints based on differentiation into high and low nucleic acid cells (HNA/LNA). The detailed characterization of these data showed that an increase in HNA cells indicated an increase in the bacterial growth potential even before actual TCC increases. The fluorescence data was decomposed via the PARAFAC method to reveal seven fluorescent components. Three aromatic protein-like components were associated with the microbiological condition of the drinking water cells; namely, Components 4 (λEx = 279 nm, λEm = 351 nm), 6 (λEx = 279 nm, λEm = 332 nm), and 7 (λEx = 276 nm, λEm = 302 nm). Component 6 was identified as a possible organic variable for appropriate monitoring of TCC, whereas Components 4 and 7 were identified as organic compounds representing nutrients for organisms present in drinking water. Overall, combining both methods for real-time monitoring can be a powerful tool to guarantee drinking water quality.
Spatial-temporal changes of NDVI in the three northeast provinces and its dual response to climate change and human activities
Authors: Wu Rina , Wang Yan , Liu Buyun , Li Xueming
Published: August 2022

As the most important ecological barrier in eastern China, the three northeast provinces have extraordinary ecological significance. Their geographical location and climatic conditions make the distribution pattern of vegetation unique. Among them, climate change and human activities are the main factors affecting the richness and complexity of vegetation, climate change dominates the overall pattern of vegetation distribution, and regional human intervention locally changes the growth state of vegetation. Therefore, based on NDVI data of vegetation, meteorological data and socio-economic data, statistical methods such as Sen’s slope estimator, Mann-Kendall trend test, center of gravity transfer model, Hurst index and coefficient of variation were adopted to analyze the spatio-temporal changes and future trends in vegetation coverage; The use of Geographic detector to understand the relationship between NDVI to climate change and human activities. The results suggested that: 1) The three northeast provinces of China experienced an overall increasing NDVI at a rate of 0.016%/year from 2001 to 2020. The NDVI shows intensive heterogeneity in space, exhibiting a landscape of high in the East, low in the west, high in the north and low in the south; 2) The results of geographic detectors show that the temporal and spatial distribution pattern of vegetation NDVI is mainly determined by ≥ 10°C accumulated temperature, ≥ 0°C accumulated temperature, annual average temperature and land use type. The interaction between factors presents a bi-variable enhancement and nonlinear enhancement, and human activity factors enhance the contribution of climate factors. 3) Future changes in NDVI indicated that the vegetation coverage showed a trend of “overall improvement and regional degradation” from 2001 to 2020, and showed reverse persistence. The degraded area of vegetation will be more than the improved area. The research results will help the three northeast provinces cope with global climate change, enrich the research on the vegetation in the three northeastern provinces, and provide a scientific basis for formulating appropriate regional ecological protection policies.
Multiple dimensions of niche specialization explain changes in species’ range area, occupancy, and population size
Authors: Di Cecco Grace J. , Hurlbert Allen H.
Published: August 2022

In response to environmental change, species may decrease or increase in population size across their range, expand or contract their range limits, or alter how sites are occupied within their existing range. Shifts in range limits and widespread changes in population size have been documented in birds especially in response to changes in climate. Range occupancy, or how patchily or continuously a species is distributed within their range, has been studied less in the context of anthropogenic changes but may be expected to decrease with range-wide population size if abundance-occupancy relationships are generally positive. Determining which properties of species are related to range expansion or contraction or increased range occupancy or decreased range occupancy is useful in developing an understanding of which species become “winners” or “losers” under global change. Species with broader climatic niches may be more likely to successfully expand to new sites as climate changes. Range occupancy can be related to habitat preferences of species, and habitat specialization may predict how species fill in sites within their range. To examine how species niche breadth may explain changes in species distributions, we modeled how changes in range-wide population size, range extent, and range occupancy from 1976 to 2016 were predicted by species’ climate, habitat, and diet niche breadth for 77 North American breeding bird species. We found that climate generalists were more likely to be increasing in range area, while species with declining population trends were likely to be contracting in range area and in occupancy within their range. Understanding how different dimensions of specialization relate to shifts in species distributions may improve predictions of which species are expected to benefit from or be vulnerable to anthropogenic change.
Clinical and Genetic Analysis of a Patient With Coexisting 17a-Hydroxylase/17,20-Lyase Deficiency and Moyamoya Disease
Authors: Huang Jiaming , Zhou Danli , Dong Nan , Ding Chenzhao , Liu Yan , Li Fangping
Published: August 2022

17a-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by pathogenic mutations in CYP17A1. Female patients present with hypertension, hypokalemia, and sexual infantilism while males present with sex development disorder. Moyamoya disease (MMD) is a chronic cerebrovascular disease that frequently results in intracranial ischemia or hemorrhage. The present study describes a case of 17OHD and MMD in a 27-year-old phenotypically female (46, XY) patient and discusses the clinical features and characteristics of her genetic defect. Clinical, hormonal, radiological, and genetic analyses were performed and blood samples were collected for whole-exome sequencing (WES). The results of the WES revealed a homozygous intronic mutation (c.297+2T>C) in CYP17A1, which led to combined 17a-hydroxylase/17,20-lyase deficiency, as well as novel variants in PCNT and CNOT3 that might lead to MMD. To our knowledge, this study is the first to describe 17OHD accompanied by MMD. While several cases have previously described patients with 17OHD with histories of cerebral hemorrhage or cerebral ischemia, a correlation in genetic levels between 17OHD and MMD was not found. The risk of cerebrovascular accidents should be considered in patients with 17OHD and hypertension. Cerebrovascular examination in patients with 17OHD may be beneficial for the prevention of life-threatening intracranial vascular disease.
Non-canonical DNA/RNA structures associated with the pathogenesis of Fragile X-associated tremor/ataxia syndrome and Fragile X syndrome
Authors: Yousuf Aadil , Ahmed Nadeem , Qurashi Abrar
Published: August 2022

Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X syndrome (FXS) are primary examples of fragile X-related disorders (FXDs) caused by abnormal expansion of CGG repeats above a certain threshold in the 5′-untranslated region of the fragile X mental retardation (FMR1) gene. Both diseases have distinct clinical manifestations and molecular pathogenesis. FXTAS is a late-adult-onset neurodegenerative disorder caused by a premutation (PM) allele (CGG expansion of 55–200 repeats), resulting in FMR1 gene hyperexpression. On the other hand, FXS is a neurodevelopmental disorder that results from a full mutation (FM) allele (CGG expansions of ≥200 repeats) leading to heterochromatization and transcriptional silencing of the FMR1 gene. The main challenge is to determine how CGG repeat expansion affects the fundamentally distinct nature of FMR1 expression in FM and PM ranges. Abnormal CGG repeat expansions form a variety of non-canonical DNA and RNA structures that can disrupt various cellular processes and cause distinct effects in PM and FM alleles. Here, we review these structures and how they are related to underlying mutations and disease pathology in FXS and FXTAS. Finally, as new CGG expansions within the genome have been identified, it will be interesting to determine their implications in disease pathology and treatment.
Genetic Characteristics and Variation Spectrum of USH2A-Related Retinitis Pigmentosa and Usher Syndrome
Authors: Li Wei , Jiang Xiao-Sen , Han Dong-Ming , Gao Jia-Yu , Yang Zheng-Tao , Jiang Li , Zhang Qian , Zhang Sheng-Hai , Gao Ya , Wu Ji-Hong , Li Jian-Kang
Published: August 2022

Purposes: We aimed to characterize the USH2A genotypic spectrum in a Chinese cohort and provide a detailed genetic profile for Chinese patients with USH2A-IRD.

Methods: We designed a retrospective study wherein a total of 1,334 patients diagnosed with IRD were included as a study cohort, namely 1,278 RP and 56 USH patients, as well as other types of IEDs patients and healthy family members as a control cohort. The genotype-phenotype correlation of all participants with USH2A variant was evaluated.

Results: Etiological mutations in USH2A, the most common cause of RP and USH, were found in 16.34% (n = 218) genetically solved IRD patients, with prevalences of 14.87% (190/1,278) and 50% (28/56). After bioinformatics and QC processing, 768 distinct USH2A variants were detected in all participants, including 136 disease-causing mutations present in 665 alleles, distributed in 5.81% of all participants. Of these 136 mutations, 43 were novel, nine were founder mutations, and two hot spot mutations with allele count ≥10. Furthermore, 38.5% (84/218) of genetically solved USH2A-IRD patients were caused by at least one of both c.2802T>G and c.8559–2 A>G mutations, and 36.9% and 69.6% of the alleles in the RP and USH groups were truncating, respectively.

Conclusion: USH2A-related East Asian-specific founder and hot spot mutations were the major causes for Chinese RP and USH patients. Our study systematically delineated the genotype spectrum of USH2A-IRD, enabled accurate genetic diagnosis, and provided East Asian and other ethnicities with baseline data of a Chinese origin, which would better serve genetic counseling and therapeutic targets selection.
In silico prediction of the animal susceptibility and virtual screening of natural compounds against SARS-CoV-2: Molecular dynamics simulation based analysis
Authors: Garg Priyanka , Vanamamalai Venkata Krishna , Jali Itishree , Sharma Shailesh
Published: August 2022

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. It has six open reading frames (orf1ab, orf3a, orf6, orf7a, orf8, and orf10), a spike protein, a membrane protein, an envelope small membrane protein, and a nucleocapsid protein, out of which, orf1ab is the largest ORF coding different important non-structural proteins. In this study, an effort was made to evaluate the susceptibility of different animals against SARS-CoV-2 by analyzing the interactions of Spike and ACE2 proteins of the animals and propose a list of potential natural compounds binding to orf1ab of SARS-CoV-2. Here, we analyzed structural interactions between spike proteins of SARS-CoV-2 and the ACE2 receptor of 16 different hosts. A simulation for 50 ns was performed on these complexes. Based on post-simulation analysis, Chelonia mydas was found to have a more stable complex, while Bubalus bubalis, Aquila chrysaetos chrysaetos, Crocodylus porosus, and Loxodonta africana were found to have the least stable complexes with more fluctuations than all other organisms. Apart from that, we performed domain assignment of orf1ab of SARS-CoV-2 and identified 14 distinct domains. Out of these, Domain 3 (DNA/RNA polymerases) was selected as a target, as it showed no similarities with host proteomes and was validated in silico. Then, the top 10 molecules were selected from the virtual screening of ∼1.8 lakh molecules from the ZINC database, based on binding energy, and validated for ADME and toxicological properties. Three molecules were selected and analyzed further. The structural analysis showed that these molecules were residing within the pocket of the receptor. Finally, a simulation for 200 ns was performed on complexes with three selected molecules. Based on post-simulation analysis (RMSD, RMSF, Rg, SASA, and energies), the molecule ZINC000103666966 was found as the most suitable inhibitory compound against Domain 3. As this is an in silico prediction, further experimental studies could unravel the potential of the proposed molecule against SARS-CoV-2.
Epigenetic manipulation to improve mouse SCNT embryonic development
Authors: Li Yamei , Sun Qiang
Published: August 2022

Cloned mammals can be achieved through somatic cell nuclear transfer (SCNT), which involves reprogramming of differentiated somatic cells into a totipotent state. However, low cloning efficiency hampers its application severely. Cloned embryos have the same DNA as donor somatic cells. Therefore, incomplete epigenetic reprogramming accounts for low development of cloned embryos. In this review, we describe recent epigenetic barriers in SCNT embryos and strategies to correct these epigenetic defects and avoid the occurrence of abnormalities in cloned animals.