bluuebunny/crossref_metadata_2025 huggingface dataset:
The retaining β-Kdo glycosyltransferase WbbB uses a double-displacement mechanism with an intermediate adduct rearrangement step
Authors: Forrester Taylor J. B. , Ovchinnikova Olga G. , Li Zhixiong , Kitova Elena N. , Nothof Jeremy T. , Koizumi Akihiko , Klassen John S. , Lowary Todd L. , Whitfield Chris , Kimber Matthew S.
Published: October 2022

WbbB, a lipopolysaccharide O-antigen synthesis enzyme from Raoultella terrigena, contains an N-terminal glycosyltransferase domain with a highly modified architecture that adds a terminal β-Kdo (3-deoxy-d-manno-oct-2-ulosonic acid) residue to the O-antigen saccharide, with retention of stereochemistry. We show, using mass spectrometry, that WbbB forms a covalent adduct between the catalytic nucleophile, Asp232, and Kdo. We also determine X-ray structures for the CMP-β-Kdo donor complex, for Kdo-adducts with D232N and D232C WbbB variants, for a synthetic disaccharide acceptor complex, and for a ternary complex with both a Kdo-adduct and the acceptor. Together, these structures show that the enzyme-linked Asp232-Kdo adduct rotates to reposition the Kdo into a second sub-site, which then transfers Kdo to the acceptor. Retaining glycosyltransferases were thought to use only the front-side SNi substitution mechanism; here we show that retaining glycosyltransferases can also potentially use double-displacement mechanisms, but incorporating an additional catalytic subsite requires rearrangement of the protein’s architecture.
Molecular insights into the distinct signaling duration for the peptide-induced PTH1R activation
Authors: Zhai Xiuwen , Mao Chunyou , Shen Qingya , Zang Shaokun , Shen Dan-Dan , Zhang Huibing , Chen Zhaohong , Wang Gang , Zhang Changming , Zhang Yan , Liu Zhihong
Published: October 2022

The parathyroid hormone type 1 receptor (PTH1R), a class B1 G protein-coupled receptor, plays critical roles in bone turnover and Ca2+ homeostasis. Teriparatide (PTH) and Abaloparatide (ABL) are terms as long-acting and short-acting peptide, respectively, regarding their marked duration distinctions of the downstream signaling. However, the mechanistic details remain obscure. Here, we report the cryo-electron microscopy structures of PTH– and ABL–bound PTH1R-Gs complexes, adapting similar overall conformations yet with notable differences in the receptor ECD regions and the peptide C-terminal portions. 3D variability analysis and site-directed mutagenesis studies uncovered that PTH–bound PTH1R–Gs complexes display less motions and are more tolerant of mutations in affecting the receptor signaling than ABL–bound complexes. Furthermore, we combined the structural analysis and signaling assays to delineate the molecular basis of the differential signaling durations induced by these peptides. Our study deepens the mechanistic understanding of ligand-mediated prolonged or transient signaling.
Neuromelanin and T2*-MRI for the assessment of genetically at-risk, prodromal, and symptomatic Parkinson’s disease
Authors: Ben Bashat Dafna , Thaler Avner , Lerman Shacham Hedva , Even-Sapir Einat , Hutchison Matthew , Evans Karleyton C. , Orr-Urterger Avi , Cedarbaum Jesse M. , Droby Amgad , Giladi Nir , Mirelman Anat , Artzi Moran
Published: October 2022

MRI was suggested as a promising method for the diagnosis and assessment of Parkinson’s Disease (PD). We aimed to assess the sensitivity of neuromelanin-MRI and T2* with radiomics analysis for detecting PD, identifying individuals at risk, and evaluating genotype-related differences. Patients with PD and non-manifesting (NM) participants [NM-carriers (NMC) and NM-non-carriers (NMNC)], underwent MRI and DAT-SPECT. Imaging-based metrics included 48 neuromelanin and T2* radiomics features and DAT-SPECT specific-binding-ratios (SBR), were extracted from several brain regions. Imaging values were assessed for their correlations with age, differences between groups, and correlations with the MDS-likelihood-ratio (LR) score. Several machine learning classifiers were evaluated for group classification. A total of 127 participants were included: 46 patients with PD (62.3 ± 10.0 years) [15:LRRK2-PD, 16:GBA-PD, and 15:idiopathic-PD (iPD)], 47 NMC (51.5 ± 8.3 years) [24:LRRK2-NMC and 23:GBA-NMC], and 34 NMNC (53.5 ± 10.6 years). No significant correlations were detected between imaging parameters and age. Thirteen MRI-based parameters and radiomics features demonstrated significant differences between PD and NMNC groups. Support-Vector-Machine (SVM) classifier achieved the highest performance (AUC = 0.77). Significant correlations were detected between LR scores and two radiomic features. The classifier successfully identified two out of three NMC who converted to PD. Genotype-related differences were detected based on radiomic features. SBR values showed high sensitivity in all analyses. In conclusion, neuromelanin and T2* MRI demonstrated differences between groups and can be used for the assessment of individuals at-risk in cases when DAT-SPECT can’t be performed. Combining neuromelanin and T2*-MRI provides insights into the pathophysiology underlying PD, and suggests that iron accumulation precedes neuromelanin depletion during the prodromal phase.
CMTM4 is a subunit of the IL-17 receptor and mediates autoimmune pathology
Authors: Knizkova Daniela , Pribikova Michaela , Draberova Helena , Semberova Tereza , Trivic Tijana , Synackova Alzbeta , Ujevic Andrea , Stefanovic Jana , Drobek Ales , Huranova Martina , Niederlova Veronika , Tsyklauri Oksana , Neuwirth Ales , Tureckova Jolana , Stepanek Ondrej , Draber Peter
Published: October 2022

Interleukin-17A (IL-17A) is a key mediator of protective immunity to yeast and bacterial infections but also drives the pathogenesis of several autoimmune diseases, such as psoriasis or psoriatic arthritis. Here we show that the tetra-transmembrane protein CMTM4 is a subunit of the IL-17 receptor (IL-17R). CMTM4 constitutively associated with IL-17R subunit C to mediate its stability, glycosylation and plasma membrane localization. Both mouse and human cell lines deficient in CMTM4 were largely unresponsive to IL-17A, due to their inability to assemble the IL-17R signaling complex. Accordingly, CMTM4-deficient mice had a severe defect in the recruitment of immune cells following IL-17A administration and were largely resistant to experimental psoriasis, but not to experimental autoimmune encephalomyelitis. Collectively, our data identified CMTM4 as an essential component of IL-17R and a potential therapeutic target for treating IL-17-mediated autoimmune diseases.
A ten-year (2009–2018) database of cancer mortality rates in Italy
Authors: Cazzolla Gatti Roberto , Di Paola Arianna , Monaco Alfonso , Velichevskaya Alena , Amoroso Nicola , Bellotti Roberto
Published: October 2022

In Italy, approximately 400.000 new cases of malignant tumors are recorded every year. The average of annual deaths caused by tumors, according to the Italian Cancer Registers, is about 3.5 deaths and about 2.5 per 1,000 men and women respectively, for a total of about 3 deaths every 1,000 people. Long-term (at least a decade) and spatially detailed data (up to the municipality scale) are neither easily accessible nor fully available for public consultation by the citizens, scientists, research groups, and associations. Therefore, here we present a ten-year (2009–2018) database on cancer mortality rates (in the form of Standardized Mortality Ratios, SMR) for 23 cancer macro-types in Italy on municipal, provincial, and regional scales. We aim to make easily accessible a comprehensive, ready-to-use, and openly accessible source of data on the most updated status of cancer mortality in Italy for local and national stakeholders, researchers, and policymakers and to provide researchers with ready-to-use data to perform specific studies.
A data set of distributed global population and water withdrawal from 1960 to 2020
Authors: Yan Denghua , Zhang Xin , Qin Tianling , Li Chenhao , Zhang Jianyun , Wang Hao , Weng Baisha , Wang Kun , Liu Shanshan , Li Xiangnan , Yang Yuheng , Li Weizhi , Lv Zhenyu , Wang Jianwei , Li Meng , He Shan , Liu Fang , Bi Wuxia , Xu Ting , Shi Xiaoqing , Man Zihao , Sun Congwu , Liu Meiyu , Wang Mengke , Huang Yinghou , Long Haoyu , Niu Yongzhen , Dorjsuren Batsuren , Gedefaw Mohammed , Li Yizhe , Tian Zihao , Mu Shizhou , Wang Wenyu , Zhou Xiaoxiang
Published: October 2022

Population and water withdrawal data sets are currently faced with difficulties in collecting, processing and verifying multi-source time series, and the spatial distribution characteristics of long series are also relatively lacking. Time series is the basic guarantee for the accuracy of data sets, and the production of long series spatial distribution is a realistic requirement to expand the application scope of data sets. Through the time-consuming and laborious basic processing work, this research focuses on the population and water intake time series, and interpolates and extends them to specific land uses to ensure the accuracy of the time series and the demand of spatially distributed data sets. This research provides a set of population density and water intensity products from 1960 to 2020 distributed to the administrative units or the corresponding regions. The data set fills the gaps in the multi-year data set for the accuracy of population density and the intensity of water withdrawal.
Development and cross-national investigation of a model explaining participation in WHO-recommended and placebo behaviours to prevent COVID-19 infection
Authors: Kłosowska Joanna , Bajcar Elżbieta A. , Bieniek Helena , Brączyk Justyna , Joshanloo Mohsen , Mattarozzi Katia , Bagnis Arianna , Pontén Moa , Lalouni Maria , Geers Andrew L. , Clemens Kelly S. , Park Joonha , Choi Gahee , Choi Yun-Kyeung , Jung Wookyoung , Son Eunjung , Yoon Hyae Young , Bąbel Przemysław
Published: October 2022

To protect themselves from COVID-19, people follow the recommendations of the authorities, but they also resort to placebos. To stop the virus, it is important to understand the factors underlying both types of preventive behaviour. This study examined whether our model (developed based on the Health Belief Model and the Transactional Model of Stress) can explain participation in WHO-recommended and placebo actions during the pandemic. Model was tested on a sample of 3346 participants from Italy, Japan, Poland, Korea, Sweden, and the US. It was broadly supported: objective risk and cues to action showed both direct and indirect (through perceived threat) associations with preventive behaviours. Moreover, locus of control, decision balance, health anxiety and preventive coping moderated these relationships. Numerous differences were also found between countries. We conclude that beliefs about control over health and perceived benefits of actions are critical to the development of interventions to improve adherence to recommendations.
Reference genes for the developing mouse lung under consideration of biological, technical and experimental confounders
Authors: Shin H. , Morty R. E. , Sucre J. M. , Negretti N. M. , Markmann M. , Hossain H. , Krauss-Etschmann S. , Dehmel S. , Hilgendorff A.
Published: October 2022

For gene expression analysis, the raw data obtained from RT-qPCR are preferably normalized to reference genes, which should be constantly expressed regardless of experimental conditions. Selection of reference genes is particularly challenging for the developing lung because of the complex transcriptional and epigenetic regulation of genes during organ maturation and injury repair. To date, there are only limited experimental data addressing reliable reference genes for this biological circumstance. In this study, we evaluated reference genes for the lung in neonatal C57BL/6 mice under consideration of biological, technical and experimental conditions. For that, we thoroughly selected candidates from commonly used reference genes side-by-side with novel ones by analyzing publicly available microarray datasets. We performed RT-qPCR of the selected candidate genes and analyzed their expression variability using GeNorm and Normfinder. Cell-specific expression of the candidate genes was analyzed using our own single-cell RNA-sequencing data from the developing mouse lung. Depending on the investigated conditions, i.e., developmental stages, sex, RNA quality, experimental condition (hyperoxia) and cell types, distinct candidate genes demonstrated stable expression confirming their eligibility as reliable reference genes. Our results provide valuable information for the selection of proper reference genes in studies investigating the neonatal mouse lung.
Effect of pretransplant dialysis vintage on clinical outcomes in deceased donor kidney transplant
Authors: Lim Jeong-Hoon , Jeon Yena , Kim Deok Gie , Kim Yeong Hoon , Kim Joong Kyung , Yang Jaeseok , Kim Myoung Soo , Jung Hee-Yeon , Choi Ji-Young , Park Sun-Hee , Kim Chan-Duck , Kim Yong-Lim , Cho Jang-Hee ,   The Korean Organ Transplantation Registry Study Group, Kim Myoung Soo , Yang Jaeseok , Kong Jin Min , Kwon Oh Jung , Kim Deok Gie , Jung Cheol Woong , Kim Yeong Hoon , Kim Joong Kyung , Kim Chan-Duck , Min Ji Won , Lee Sik , Park Yeon Ho , Park Jae Berm , Park Jung Hwan , Park Jong-Won , Ban Tae Hyun , Song Sang Heon , Song Seung Hwan , Shin Ho Sik , Yang Chul Woo , Yoon Hye Eun , Lee Kang Wook , Lee Sang-Ho , Lee Su Hyung , Lee Yu Ho , Lee Jung Pyo , Lee Jeong-Hoon , Jeon Jin Seok , Jun Heungman , Jeong Kyung Hwan , Chung Ku Yong , Lee Jong Soo , Chae Dong-Wan , Choi Soo Jin Na , Shin Sung , Han Seungyeup , Huh Kyu Ha
Published: October 2022

The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio [aHR] 3.59; 95% confidence interval [CI] 1.69–7.63; P < 0.001; aHR 2.37; 95% CI 1.06–5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94–25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT.
Microbial community in resistant and susceptible Churra sheep infected by Teladorsagia circumcincta
Authors: Castilla Gómez de Agüero Verónica , Esteban-Blanco Cristina , Argüello Héctor , Valderas-García Elora , Andrés Sonia , Balaña-Fouce Rafael , Arranz Juan José , Gutiérrez-Gil Beatriz , Martínez-Valladares María
Published: October 2022

Gastrointestinal nematodes (GIN) are a major threat to health and welfare in small ruminants worldwide. Teladorsagia circumcincta is a nematode that inhabits the abomasum of sheep, especially in temperate regions, causing important economic losses. Given that T. circumcincta and microbiome share the same niche, interactions between them and the host are expected. Although it is known that within a sheep breed there are animals that are more resistant than others to infection by GIN, it is not known if the microbiome influences the phenotype of these animals. Under this condition, 12 sheep were classified according to their cumulative faecal egg count (cFEC) at the end of a first experimental infection, 6 as resistant group (RG) and 6 as susceptible group (SG) to T. circumcincta infection. Then, all sheep were experimentally infected with 70,000 L3 of T. circumcincta and at day 7 days post-infection were euthanized. At necropsy, gastric mucosa and gastric content from abomasum were collected to extract bacterial DNA and sequence V3-V4 region from 16S rRNA gene using Ilumina technology. After bioanalysis performed, results showed that α-diversity and β-diversity remained similar in both groups. However, resistant phenotype sheep showed a higher number of bacteria butyrate-fermenting species as Clostridium sensu stricto 1 (abundance in RG: 1.29% and in SG: 0.069%; p = 0.05), and Turicibacter (abundance in RG: 0.31% and in SG: 0.027%; p = 0.07) in gastric content but also Serratia spp in gastric mucosa (abundance in RG: 0.12% and in SG: 0.041%; p = 0.07). A trend towards a significant negative correlation between cFEC and Clostridium sensu stricto 1 abundance in gastric content was detected (r = − 0.537; p = 0.08). These data suggest that microbiome composition could be another factor associated with the development of the resistant phenotype modifying the interaction with the host and the in last instance affecting the individual risk of infection.
Epigallocatechin gallate (EGCG) alleviates vascular dysfunction in angiotensin II-infused hypertensive mice by modulating oxidative stress and eNOS
Authors: Mohd Sabri Nurul Aiza , Lee Siew-Keah , Murugan Dharmani Devi , Ling Wei Chih
Published: October 2022

Epigallocatechin gallate (EGCG) has been shown to have antihypertensive activity. However, the role of epigallocatechin gallate (EGCG) in improving vascular function via modulation of endothelial nitric oxide synthase (eNOS) in hypertensive subjects is not well researched. Angiotensin II-infused hypertensive mice (8–10 weeks old) received EGCG (50 mg/kg/day) for 14 days via oral gavage. The arterial systolic blood pressure (SBP) was measured using the tail-cuff method every three days. At the end of the treatment, the vascular reactivity of the isolated aortae was studied using wire myographs. The level of nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and tetrahydrobiopterine (BH4) were determined using assay kits while the presence of proteins (NOS, p-eNOS and NOx-2) were determined using by Western blotting. In vivo treatment with EGCG for 14 days significantly attenuated the increase in SBP, alleviated the vascular dysfunction, increased the vascular cGMP and BH4 level as well as the expression of p-eNOS and decreased elevated ROS level and NOx-2 protein in angiotensin II-infused hypertensive mice. Collectively, treatment with EGCG in hypertensive mice exerts a blood pressure lowering effect which is partly attributed to the improvement in the vascular function due to its ability to reduce vascular oxidative stress in the aortic tissue leading to a decrease in eNOS uncoupling thus increasing NO bioavailability.
Determining the optical properties of solar cells using low cost scanners
Authors: Juhl Mattias Klaus , Veettil Binesh Puthen , Scardera Giuseppe , Payne David Neil Roger
Published: October 2022

This paper investigates the use of consumer flatbed scanners for the use of monitoring solar cell precursors. Two types of scanners are investigated a contact image scanner and scanners with more conventional optical setups. The contact image sensor is found to be more suitable as it does not require additional flat field calibration. The scanners’ ability to monitor variation in sample texture was investigated by monitoring the reflection of multi-crystalline and mono-crystalline textured wafers. For a baseline, a comparison was made to a high-end tool used in industry. Both good qualitative agreement and statistical correlation were achieved between the scanner and industry tool for the isotropic multi-crystalline wafers.
Urban ecosystem drives genetic diversity in feral honey bee
Authors: Patenković Aleksandra , Tanasković Marija , Erić Pavle , Erić Katarina , Mihajlović Milica , Stanisavljević Ljubiša , Davidović Slobodan
Published: October 2022

Urbanization can change biodiversity in both directions, positive and negative, and despite the rising global trend of urban beekeeping, little is known about the impact of urbanization on the genetic diversity of honey bees. We investigate how urbanization affects the genetic variability of feral and managed honey bee colonies that are spread throughout the entire city, even in highly urban areas, through genetic analysis of 82 worker bees. We found convincing evidence of high genetic differentiation between these two groups. Additionally, by comparing city samples with 241 samples from 46 apiaries in rural parts of the country, variations in mitochondrial tRNAleu-cox2 intergenic region and microsatellite loci indicated that feral colonies have distinct patterns of genetic diversity. These results, with evidence that feral honey bees find niches within highly modified and human-dominated urban landscapes, lead us to conclude that urbanization is a driver of the genetic diversity of feral honey bees in the city.
Mangroves provide blue carbon ecological value at a low freshwater cost
Authors: Krauss Ken W. , Lovelock Catherine E. , Chen Luzhen , Berger Uta , Ball Marilyn C. , Reef Ruth , Peters Ronny , Bowen Hannah , Vovides Alejandra G. , Ward Eric J. , Wimmler Marie-Christin , Carr Joel , Bunting Pete , Duberstein Jamie A.
Published: October 2022

“Blue carbon” wetland vegetation has a limited freshwater requirement. One type, mangroves, utilizes less freshwater during transpiration than adjacent terrestrial ecoregions, equating to only 43% (average) to 57% (potential) of evapotranspiration ($$ET$$

ET

). Here, we demonstrate that comparative consumptive water use by mangrove vegetation is as much as 2905 kL H2O ha−1 year−1 less than adjacent ecoregions with $${E}_{c}$$

E
c

-to-$$ET$$

ET

ratios of 47–70%. Lower porewater salinity would, however, increase mangrove $${E}_{c}$$

E
c

-to-$$ET$$

ET

ratios by affecting leaf-, tree-, and stand-level eco-physiological controls on transpiration. Restricted water use is also additive to other ecosystem services provided by mangroves, such as high carbon sequestration, coastal protection and support of biodiversity within estuarine and marine environments. Low freshwater demand enables mangroves to sustain ecological values of connected estuarine ecosystems with future reductions in freshwater while not competing with the freshwater needs of humans. Conservative water use may also be a characteristic of other emergent blue carbon wetlands.
Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation
Authors: Ribeiro Filipa , Romão Vasco C. , Rosa Sara , Jesus Kátia , Água-Doce Ana , Barreira Sofia C. , Martins Patrícia , da Silva Susana Lopes , Nobre Ema , Bugalho Maria João , Fonseca Válter R. , Eurico Fonseca João , Graca Luis
Published: October 2022

Autoantibodies are produced within germinal centers (GC), in a process regulated by interactions between B, T follicular helper (Tfh), and T follicular regulatory (Tfr) cells. The GC dysregulation in human autoimmunity has been inferred from circulating cells, albeit with conflicting results due to diverse experimental approaches. We applied a consistent approach to compare circulating Tfr and Tfh subsets in patients with different autoimmune diseases. We recruited 97 participants, including 72 patients with Hashimoto’s thyroiditis (HT, n = 18), rheumatoid arthritis (RA, n = 16), or systemic lupus erythematosus (SLE, n = 32), and 31 matched healthy donors (HD). We found that the frequency of circulating T follicular subsets differed across diseases. Patients with HT had an increased frequency of blood Tfh cells (p = 0.0215) and a reduced Tfr/Tfh ratio (p = 0.0338) when compared with HD. This was not observed in patients with systemic autoimmune rheumatic diseases (RA, SLE), who had a reduction in both Tfh (p = 0.0494 and p = 0.0392, respectively) and Tfr (p = 0.0003 and p = 0.0001, respectively) cells, resulting in an unchanged Tfr/Tfh ratio. Activated PD-1+ICOS+Tfh and CD4+PD-1+CXCR5–Tph cells were raised only in patients with SLE (p = 0.0022 and p = 0.0054), without association with disease activity. Our data suggest that GC dysregulation, assessed by T follicular subsets, is not uniform in human autoimmunity. Specific patterns of dysregulation may become potential biomarkers for disease and patient stratification.
Transcriptional targets of senataxin and E2 promoter binding factors are associated with neuro-degenerative pathways during increased autophagic flux
Authors: Casey Aaron E. , Liu Wenjun , Hein Leanne K. , Sargeant Timothy J. , Pederson Stephen M. , Mäkinen Ville-Petteri
Published: October 2022

Autophagy is an intracellular recycling process that degrades harmful molecules and enables survival during starvation, with implications for diseases including dementia, cancer and atherosclerosis. Previous studies demonstrate how a limited number of transcription factors (TFs) can increase autophagy. However, this knowledge has not resulted in translation into therapy, thus, to gain understanding of more suitable targets, we utilized a systems biology approach. We induced autophagy by amino acid starvation and mTOR inhibition in HeLa, HEK 293 and SH-SY5Y cells and measured temporal gene expression using RNA-seq. We observed 456 differentially expressed genes due to starvation and 285 genes due to mTOR inhibition (PFDR < 0.05 in every cell line). Pathway analyses implicated Alzheimer’s and Parkinson’s diseases (PFDR ≤ 0.024 in SH-SY5Y and HeLa) and amyotrophic lateral sclerosis (ALS, PFDR < 0.05 in mTOR inhibition experiments). Differential expression of the Senataxin (SETX) target gene set was predicted to activate multiple neurodegenerative pathways (PFDR ≤ 0.04). In the SH-SY5Y cells of neuronal origin, the E2F transcription family was predicted to activate Alzheimer’s disease pathway (PFDR ≤ 0.0065). These exploratory analyses suggest that SETX and E2F may mediate transcriptional regulation of autophagy and further investigations into their possible role in neuro-degeneration are warranted.
Interim FDG-PET/CT for therapy monitoring and prognostication in Hodgkin’s Lymphoma
Authors: Al-Ibraheem Akram , Anwer Farah , Juweid Malik E. , Shagera Qaid Ahmed , Khalaf Aysar N. , Obeidat Shahed , Mansour Areen , Ma’koseh Mohammad , Halahleh Khalid , Jaradat Imad , Almasri Nidal , Mansour Asem
Published: October 2022

The aim of the study was to assess the predictive value of interim FDG-PET/CT (iPET) in patients with Hodgkin’s lymphoma (HL) treated with Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. A total of 245 consecutive patients with de novo HL between 12/2013 and 12/2017 were evaluated retrospectively. All patients were treated with upfront ABVD, performed PET/CT scans at baseline, after 2 cycles (interim PET, iPET2) or 4 cycles (iPET4) and at the end of therapy, and followed up for at least 6 months after therapy. The response status on iPET was defined according to the standard five-point Deauville scores (DS) as follows: complete metabolic response (CMR, DS 1–3) and non-complete metabolic response (nCMR) (DS 4 and 5). End-of-treatment (EoT) response was assessed by FDG-PET/CT and if needed biopsy confirmation of PET-positive findings. The association between iPET and EoT response was investigated using logistic regression analysis. Survival analysis was performed using the Cox regression hazard model and Kaplan–Meier methods. Sixty-nine patients underwent iPET-2 and 176 iPET-4. No association was found between the timing of iPET and iPET response status (P-value = 0.71). Two hundred and one patients (82%) had iPET-CMR and 44 (18%) iPET -nCMR. iPET was strongly associated with EoT response status: 194/201 (96 .5%) of iPET-CMR had a complete response at the EoT while only 21/44 (47.7%) of patients with iPET-nCMR presented a complete response at EoT (P-value < 0.0001). The median follow-up was 32 months (range 6–81). Patients with iPET-CMR presented a better outcome with 91% 3 y event-free-survival (EFS) and 95% 3 y overall survival (OS) than those with iPET-nCMR (41 and 86%, respectively, P-value < 0.0001). In multivariable analyses, iPET retained an independent prognostic factor of EFS and OS (P-value < 0.0001 and P-value = 0.002, respectively). iPET is highly predictive of outcome of HL patients treated with ABVD and allows to tailor therapy to the individual patient.
Gene signature of m6A RNA regulators in diagnosis, prognosis, treatment, and immune microenvironment for cervical cancer
Authors: Wang Shizhi , Ding Bo , Wang Shiyuan , Yan Wenjing , Xia Qianqian , Meng Dan , Xie Shuqian , Shen Siyuan , Yu Bingjia , Liu Haohan , Hu Jing , Zhang Xing
Published: October 2022

Continuing studies imply that m6A RNA modification is involved in the development of cervical cancer (CC), but lack strong support on recurrence and diagnosis prediction. In this research, a comprehensive analysis of 33 m6A regulators was performed to fulfill them. Here, we performed diagnostic and prognosis models and identified key regulators, respectively. Then the CC patients were separated into two clusters in accordance with 33 regulators, and participants in the cluster 1 had a worse prognosis. Subsequently, the m6AScore was calculated to quantify the m6A modification pattern based on regulators and we found that patients in cluster 1 had higher m6AScore. Afterwards, immune microenvironment, cell infiltration, escape analyses and tumor burden mutation analyses were executed, and results showed that m6AScore was correlated with them, but to a limited extent. Interestingly, HLAs and immune checkpoint expression, and immunophenoscore in patients with high-m6AScores were significantly lower than those in the low-m6AScore group. These suggested the m6AScores might be used to predict the feasibility of immunotherapy in patients. Results provided a distinctive perspective on m6A modification and theoretical basis for CC diagnosis, prognosis, clinical treatment strategies, and potential mechanism exploration.
A machine learning approach to explore predictors of graft detachment following posterior lamellar keratoplasty: a nationwide registry study
Authors: Muijzer M. B. , Hoven C. M. W. , Frank L. E. , Vink G. , Wisse R. P. L. ,   The Netherlands Corneal Transplant Network (NCTN), Bartels Marjolijn C. , Cheng Yanny Y. , Dhooge Mario R. P. , Dickman Mor , van Dooren Bart T. H. , Eggink Cathrien A. , Geerards Annette J. M. , van Goor Tom A. , Lapid-Gortzak Ruth , van Luijk Chantal M. , van der Meulen Ivanka J. , Nieuwendaal Carla P. , Nuijts Rudy M. M. A. , Nobacht Siamak , Oahalou Abdulkarim , van Oosterhout Emile C. A. A. , Remeijer Lies , van Rooij Jeroen , Santana Nathalie T. Y. , Stoutenbeek Remco , Tang Mei L. , Vaessen Thijs , Visser Nienke , Wijdh Robert H. J. , Wisse Robert P. L.
Published: October 2022

Machine learning can be used to explore the complex multifactorial patterns underlying postsurgical graft detachment after endothelial corneal transplantation surgery and to evaluate the marginal effect of various practice pattern modulations. We included all posterior lamellar keratoplasty procedures recorded in the Dutch Cornea Transplant Registry from 2015 through 2018 and collected the center-specific practice patterns using a questionnaire. All available data regarding the donor, recipient, surgery, and practice pattern, were coded into 91 factors that might be associated with the occurrence of a graft detachment. In this research, we used three machine learning methods; a regularized logistic regression (lasso), classification tree analysis (CTA), and random forest classification (RFC), to select the most predictive subset of variables for graft detachment. A total of 3647 transplants were included in our analysis and the overall prevalence of graft detachment was 9.9%. In an independent test set the area under the curve for the lasso, CTA, and RFC was 0.70, 0.65, and 0.72, respectively. Identified risk factors included: a Descemet membrane endothelial keratoplasty procedure, prior graft failure, and the use of sulfur hexafluoride gas. Factors with a reduced risk included: performing combined procedures, using pre-cut donor tissue, and a pre-operative laser iridotomy. These results can help surgeons to review their practice patterns and generate hypotheses for empirical research regarding the origins of graft detachments.
The distance distribution of human microRNAs in MirGeneDB database
Authors: Wang Hsiuying
Published: October 2022

MicroRNAs (miRNAs) are small single-stranded non-coding RNAs around 22 nucleotide lengths found in organisms, playing an important role in cell differentiation, development, gene regulation, and apoptosis. The distance of disease miRNA biomarkers has been used to explore the association between various diseases as well as the association between virus and disease in the literature. To date, there have been no studies on deriving the distribution of the pairwise distance of human miRNAs. As the pairwise distance of miRNA biomarkers might be a useful tool in studying the disease association, in this paper, the distance distributions of human miRNAs were derived such that they could be used to measure the closeness between miRNAs. Two distance models were used to calculate the pairwise distances of 567 Homo sapiens miRNA genes accessed from the MirGeneDB database. These miRNA pairwise distances were fitted by the normal distribution, gamma distribution, empirical cumulative distribution, and the kernel density estimation method. This is the first study to provide the distance distribution of human miRNAs. The similarity of miRNA biomarkers for several diseases was examined using the derived distributions.
Adverse event profiles of microscopic colitis in the Japanese Adverse Drug Event Report (JADER) database
Authors: Yamashiro Kaito , Jouta Mika , Hosomi Kouichi , Yokoyama Satoshi , Ozaki Yuu , Hirata Atsushi , Ogata Fumihiko , Nakamura Takehiro , Tanei Shigeharu , Kawasaki Naohito
Published: October 2022

Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. “Colitis microscopic” (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.
Variation characteristics and the impact of urbanization of extreme precipitation in Shanghai
Authors: Mou Yali , Gao Xichao , Yang Zhiyong , Xu Tianyin , Feng Jie
Published: October 2022

With the rapid development of urbanization, the characteristics of extreme precipitation in urban areas have changed significantly. Revealing the spatial and temporal distribution of extreme precipitation under changing environment is the basis of scientific response to the urban flood. Trends of extreme precipitation at 95% and 99% thresholds in Shanghai and the influence of urbanization on them were analyzed. The results show that: (1) The precipitation threshold limit value for each site are 5.7 ~ 6.3 mm at 95% with a variation factor of 0.04, and 14.3 ~ 17.16 mm at 99% with a variation factor of 0.06. The precipitation thresholds under 99% conditions were more significantly different among stations. (2) The extreme precipitation at each site has been increasing over the past 50 years, and the growth rates of 95% and 99% extreme precipitation are 8.02~11.46%/10a and 7.11~16.86%/10a, respectively. The growth rate of extreme precipitation is significantly higher than that of average precipitation, while the extreme part of the precipitation probability distribution increases considerably. There is a strong variability in extreme precipitation in this region, while the 99% threshold precipitation varies more. (3) The extreme precipitation in Shanghai is significantly positively correlated with the urbanization of the area around the site. Urbanization has an increasing effect on regional extreme precipitation, with more extreme precipitation and greater growth rate in highly urbanized areas.
Compost from willow biomass (Salix viminalis L.) as a horticultural substrate alternative to peat in the production of vegetable transplants
Authors: Adamczewska-Sowińska Katarzyna , Sowiński Józef , Jamroz Elżbieta , Bekier Jakub
Published: October 2022

Willow (Salix viminalis L.) is a species well adapted to the environment conditions of central Europe. It is mainly cultivated for energy purposes as solid fuel. In this study, an evaluation of its suitability for other purposes was made using a 4-year old short rotation coppice (SRC) willow regrowth to produce chipped biomass which was composted. Four composting methods were used: without additives (WC), with the addition of nitrogen to narrow the C:N ratio (WN), with the addition of mycelium (WPG) and with the addition of mycelium and nitrogen (WPGN). A mixture of WC and WPGN composts was also prepared at 75:25% and 50:50% by volume. Composts, different proportion (25, 50 and 75%) of peat (SM) were evaluated for suitability as a substrate for tomato and cucumber transplant production. Tomato transplants produced in the medium were prepared from mixtures of willow composts (WPGN + WC(1) and WPGN + WC(2) and these mixtures with peat (WPGN + WC(1):SM and WPGN + WC(2):SM) were characterised as having the best parameters: plant height, lateral leaf span and number of leaves. Similarly, for cucumber transplants, better growth conditions than in peat substrate were obtained in the variant WPGN + WC(1) and WPGN + WC(1):SM. The addition of nitrogen to the composted biomass positively influenced the composting process. N concentration in the substrate was too high and toxic for the growth of tomato and cucumber transplants. At the end of the tomato and cucumber experiment, the nitrate content was 1510 and 2260 mg dm−3, respectively, in the WN substrate. Similarly, the high N–NO3− content in the composted willow substrate with the addition of nitrogen and mycelium did not promote the growth of tomato and cucumber. Based on this research at least 25% of the mass of the peat can be replaced by different willow composts without having an adverse impact on seedling growth and with some of the willow compost mixtures this could be as high as 50%.
A paleo-perspective on West Antarctic Ice Sheet retreat
Authors: Bart Philip J. , Kratochvil Matthew
Published: October 2022

Geological records of ice sheet collapse can provide perspective on the ongoing retreat of grounded and floating ice. An abrupt retreat of the West Antarctic Ice Sheet (WAIS) that occurred during the early deglaciation is well recorded on the eastern Ross Sea continental shelf. There, an ice shelf breakup at 12.3 ± 0.6 cal. (calibrated) kyr BP caused accelerated ice-mass loss from the Bindschadler Ice Stream (BIS). The accelerated mass loss led to a significant negative mass balance that re-organized WAIS flow across the central and eastern Ross Sea. By ~ 11.5 ± 0.3 cal kyr BP, dynamic thinning of grounded ice triggered a retreat that opened a ~ 200-km grounding-line embayment on the Whales Deep Basin (WDB) middle continental shelf. Here, we reconstruct the pattern, duration and rate of retreat from a backstepping succession of small-scale grounding-zone ridges that formed on the embayment’s eastern flank. We used two end-member paleo-sediment fluxes, i.e., accumulation rates, to convert the cumulative sediment volumes of the ridge field to elapsed time for measured distances of grounding-line retreat. The end-members fluxes correspond to deposition rates for buttressed and unbuttressed ice stream flow. Both scenarios require sustained rapid retreat that exceeded several centuries. Grounding-line retreat is estimated to have averaged between ~ 100 ± 32 and ~ 700 ± 79 ma−1. The evidence favors the latter scenario because iceberg furrows that cross cut the ridges in deep water require weakly buttressed flow as the embayment opened. In comparison with the modern grounding-zone dynamics, this paleo-perspective provides confidence in model projections that a large-scale sustained contraction of grounded ice is underway in several Pacific-Ocean sectors of the WAIS.
Effects of application of horticultural soil amendments on decomposition, quantity, stabilisation and quality of soil carbon
Authors: Duddigan Sarah , Shaw Liz J. , Alexander Paul D. , Collins Chris D.
Published: October 2022

Application of organic soil amendments is commonplace in horticulture to improve soil fertility. Whether this practice can also augment the soil carbon (C) pool has been of increasing interest in recent years. We used a controlled field experiment that has received annual applications of six different horticultural soil amendments for seven consecutive years. Each amendment was examined in terms of its contribution to bulk C and the distribution of C between theoretical pools, as defined by physical fractionation. Physical fractionation was combined with 13C nuclear magnetic resonance spectroscopy with cross-polarization and magic angle spinning (CPMAS NMR) analysis. Results indicated that the difference in total C concentration between treatments resulted from an increase in unprotected, free, particulate organic matter (fOM), rather than an increase in soil organic matter being occluded in aggregates or in organo-mineral complexes, and that C persisted in the fOM fraction as a result of accumulation in the alkyl C region. Unlike fresh litter or plant residues, organic amendments have undergone decomposition during the composting process (or during formation in the case of peat), in the absence of mineral soil components. This ex situ decomposition (and possible stabilization through acquired recalcitrance) could reduce the opportunity to become physically or chemically protected through association with the soil mineral phase following addition to soil. Carbon:Nitrogen (C:N) of amendment material likely influenced the rate of amendment decomposition. In addition, C:N determines the decomposition of plant litter inputs, as determined by the tea bag index.
Gadolinium-doped fluorescent carbon quantum dots as MRI contrast agents and fluorescent probes
Authors: Molaei Mohammad Jafar
Published: October 2022

In this research passivated gadolinium-doped carbon quantum dots (Gd-doped CQDs) were synthesized from starch by a hydrothermal method. The X-ray diffraction (XRD) pattern of the Gd-doped CQDs showed the formation of highly amorphous carbon. The Fourier transform infrared spectroscopy (FTIR) results suggested that the CQDs are functionalized with C-N and N–H bonds. The synthesized CQDs with a size distribution of 2–8 nm have an absorption peak at 271 nm in UV–Visible spectroscopy (UV–Vis). The photoluminescence (PL) in CQDs was dependent on the excitation wavelength. The QY of the synthesized CQDs was calculated to be 13.2%. The Gd-doped CQDs exhibited sustained PL in ionic solutions with different ionic strengths and different temperatures up to 65 °C. Fluorescence imaging on mouse C34/connective tissue-L929 cells confirmed that Gd-doped CQDs could be well distributed over the cytoplasm. The magnetic resonance imaging (MRI) showed that the Gd-doped CQDs have extremely high longitudinal and transverse relaxivity values of as high as 218.28 mM−1 s−1 and 364.68 mM−1 s−1. The synthesized Gd-doped CQDs are promising candidates as multifunctional imaging probes and MRI contrast agents in biomedical diagnosis and brain mapping applications.
Effects of water extracts of Flaveria bidentis on the seed germination and seedling growth of three plants
Authors: Dai Lei , Wu Lili , Zhou Xiuren , Jian Zaiyou , Meng Li , Xu Guifang
Published: October 2022

To further explore the mechanism behind the allelopathic effects of Flaveria bidentis, we investigated the allelopathic effects of water extracts from Flaveria bidentis leaves on three plants, Shanghai green, barnyard grass and wheat. The results showed that the water extracts inhibited the germination potential, germination rate, seedling height, root length, chlorophyll content, fresh weight and dry weight of the three plants, and increasing the extract concentration further increased the inhibitory effect. The allelopathic effects of the water extracts from Flaveria bidentis leaves on the three receptor plants differed in strength from strong to weak as follows: Shanghai green > barnyard grass > wheat. Thus, wheat had strong resistance to the allelopathic effects of Flaveria bidentis and could be planted in area where Flaveria bidentis occurs. The effect of the water extract from Flaveria bidentis leaves on the seed germination and seedling growth of barnyard grass was obvious; thus, this extract could be used for the biological control of barnyard grass.
SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function
Authors: Dietrich Johannes W. , Dasgupta Riddhi , Anoop Shajith , Jebasingh Felix , Kurian Mathews E. , Inbakumari Mercy , Boehm Bernhard O. , Thomas Nihal
Published: October 2022

Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research.