bluuebunny/crossref_metadata_2025 huggingface dataset:
Cascadia Burning: The historic, but not historically unprecedented, 2020 wildfires in the Pacific Northwest,USA
Authors: Reilly Matthew J. , Zuspan Aaron , Halofsky Joshua S. , Raymond Crystal , McEvoy Andy , Dye Alex W. , Donato Daniel C. , Kim John B. , Potter Brian E. , Walker Nathan , Davis Raymond J. , Dunn Christopher J. , Bell David M. , Gregory Matthew J. , Johnston James D. , Harvey Brian J. , Halofsky Jessica E. , Kerns Becky K.
Published: June 2022

Wildfires devastated communities in Oregon and Washington in September 2020, burning almost as much forest west of the Cascade Mountain crest (“the westside”) in 2 weeks (~340,000 ha) as in the previous five decades (~406,00 ha). Unlike dry forests of the interior western United States, temperate rain forests of the Pacific Northwest have experienced limited recent fire activity, and debates surrounding what drove the 2020 fires, and management strategies to adapt to similar future events, necessitate a scientific evaluation of the fires. We evaluate five questions regarding the 2020 Labor Day fires: (1) How do the 2020 fires compare with historical fires? (2) How did the roles of weather and antecedent climate differ geographically and from the recent past (1979–2019)? (3) How do fire size and severity compare to other recent fires (1985–2019), and how did forest management and prefire forest structure influence burn severity? (4) What impact will these fires have on westside landscapes? and (5) How can we adapt to similar fires in the future? Although 5 of the 2020 fires were much larger than any others in the recent past and burned ~10 times the area in high‐severity patches >10,000 ha, the 2020 fires were remarkably consistent with historical fires. Reports from the early 1900s, along with paleo‐ and dendro‐ecological records, indicate similar and potentially even larger wildfires over the past millennium, many of which shared similar seasonality (late August/early September), weather conditions, and even geographic locations. Consistent with the largest historical fires, strong east winds and anomalously dry conditions drove the rapid spread of high‐severity wildfire in 2020. We found minimal difference in burn severity among stand structural types related to previous management in the 2020 fires. Adaptation strategies for similar fires in the future could benefit by focusing on ignition prevention, fire suppression, and community preparedness, as opposed to fuel treatments that are unlikely to mitigate fire severity during extreme weather. While scientific uncertainties remain regarding the nature of infrequent, high‐severity fires in westside forests, particularly under climate change, adapting to their future occurrence will require different strategies than those in interior, dry forests.
Modeling metal forming of a magnesium alloy using an adapted material model
Authors: Wolf Alexander , Küsters Niklas , Bräunling Sven , Weck Daniel , Kittner Kristina , Gude Maik , Prahl Ulrich , Brosius Alexander
Published: June 2022

Modeling sheet metal forming of materials for lightweight construction requires an understanding of their plastic behavior in different loading directions. The presented work focuses on twin‐roll‐casted magnesium alloy AZ31. It is characterized by unique mechanical properties compared to other magnesium alloys due to the employed twin‐roll‐casting‐process. In general, magnesium alloys with their hexagonal closed‐packed structure possess a complex forming behavior including a deformation‐induced anisotropy evolution. In the context of a fast design approach, an adaptation of the Yield2000‐2d criteria usually used for body‐centered cubic or face‐centered cubic materials is tested. The goal is a simple, versatile material model which parameters are determined just by tensile tests with moderate testing effort. In the investigated model, the yield locus definition is modified by adding a term for the yield exponent evolution during the forming process. The modeling approach is presented and the necessary tests for material data acquisition and evaluation are described. After experimental identification of the model parameters, the material model is applied in a forming simulation. The investigation provides promising results matching well with experimental data. Thus, the application of this model in a fast design step is feasible, offering valuable data like deformed shape, process‐related material properties and induced stresses for further processing.
Soil Ecotoxicology Needs Robust Biomarkers: A Meta-Analysis Approach to Test the Robustness of Gene Expression-Based Biomarkers for Measuring Chemical Exposure Effects in Soil Invertebrates
Authors: Swart Elmer , Martell Ellie , Svendsen Claus , Spurgeon David J.
Published: June 2022

Gene expression-based biomarkers are regularly proposed as rapid, sensitive, and mechanistically informative tools to identify whether soil invertebrates experience adverse effects due to chemical exposure. However, before biomarkers could be deployed within diagnostic studies, systematic evidence of the robustness of such biomarkers to detect effects is needed. In our study, we present an approach for conducting a meta-analysis of the robustness of gene expression-based biomarkers in soil invertebrates. The approach was developed and trialed for two measurements of gene expression commonly proposed as biomarkers in soil ecotoxicology: earthworm metallothionein (MT) gene expression for metals and earthworm heat shock protein 70 (HSP70) gene expression for organic chemicals. We collected 294 unique gene expression data points from the literature and used linear mixed-effect models to assess concentration, exposure duration, and species effects on the quantified response. The meta-analysis showed that the expression of earthworm MT was strongly metal concentration dependent, stable over time and species independent. The metal concentration-dependent response was strongest for cadmium, indicating that this gene is a suitable biomarker for this metal. For copper, no clear concentration-dependent response of MT gene expression in earthworms was found, indicating MT is not a reliable biomarker for this metal. For HSP70, overall marginal up-regulation and lack of a concentration-dependent response indicated that this gene is not suitable as a biomarker for organic pollutant effects in earthworms. The present study demonstrates how meta-analysis can be used to assess the status of biomarkers. We encourage colleagues to apply this open-access approach to other biomarkers, as such quantitative assessment is a prerequisite to ensuring that the suitability and limitations of proposed biomarkers are known and stated. Environ Toxicol Chem 2022;41:2124–2138. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Methyltransferase 1 is required for nonhomologous end‐joining repair and renders hepatocellular carcinoma resistant to radiotherapy
Authors: Liao Junbin , Yi Yang , Yue Xin , Wu Xiaoxue , Zhu Meiyan , Chen Yong , Peng Sui , Kuang Ming , Lin Shuibin , Peng Zhenwei
Published: June 2022

Background and Aims:

Radiotherapy is an increasingly essential therapeutic strategy in the management of hepatocellular carcinoma (HCC). Nevertheless, resistance to radiotherapy is one of the primary obstacles to successful treatment outcomes. Hence, we aim to elucidate the mechanisms underlying radioresistance and identify reliable biotargets that would be inhibited to enhance the efficacy of radiotherapy in HCC.

Approach and Results:

From a label‐free quantitative proteome screening, we identified transfer RNA (tRNA; guanine‐N [7]‐) methyltransferase 1 (METTL1), a key enzyme for N7‐methylguanosine (m7G) tRNA modification, as an essential driver for HCC cells radioresistance. We reveal that METTL1 promotes DNA double‐strand break (DSB) repair and renders HCC cells resistant to ionizing radiation (IR) using loss‐of‐function and gain‐of‐function assays in vitro and in vivo. Mechanistically, METTL1‐mediated m7G tRNA modification selectively regulates the translation of DNA‐dependent protein kinase catalytic subunit or DNA ligase IV with higher frequencies of m7G‐related codons after IR treatment, thereby resulting in the enhancement of nonhomologous end‐joining (NHEJ)–mediated DNA DSB repair efficiency. Clinically, high METTL1 expression in tumor tissue is significantly correlated with poor prognosis in radiotherapy‐treated patients with HCC.

Conclusions:

Our findings show that METTL1 is a critical enhancer for HCC cell NHEJ‐based DNA repair following IR therapy. These findings give insight into the role of tRNA modification in messenger RNA translation control in HCC radioresistance.
Iron overload disorders
Authors: Hsu Christine C. , Senussi Nizar H. , Fertrin Kleber Y. , Kowdley Kris V.
Published: June 2022

Iron overload disorders represent a variety of conditions that lead to increased total body iron stores and resultant end‐organ damage. An elevated ferritin and transferrin‐iron saturation can be commonly encountered in the evaluation of elevated liver enzymes. Confirmatory homeostatic iron regulator (HFE) genetic testing for C282Y and H63D, mutations most encountered in hereditary hemochromatosis, should be pursued in evaluation of hyperferritinemia. Magnetic resonance imaging with quantitative assessment of iron content or liver biopsy (especially if liver disease is a cause of iron overload) should be used as appropriate. A secondary cause for iron overload should be considered if HFE genetic testing is negative for the C282Y homozygous or C282Y/H63D compound heterozygous mutations. Differential diagnosis of secondary iron overload includes hematologic disorders, iatrogenic causes, or chronic liver diseases. More common hematologic disorders include thalassemia syndromes, myelodysplastic syndrome, myelofibrosis, sideroblastic anemias, sickle cell disease, or pyruvate kinase deficiency. If iron overload has been excluded, evaluation for causes of hyperferritinemia should be pursued. Causes of hyperferritinemia include chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions, such as adult‐onset Still's disease or hemophagocytic lymphohistiocytosis. In this review, we describe the diagnostic testing of patients with suspected hereditary hemochromatosis, the evaluation of patients with elevated serum ferritin levels, and signs of secondary overload and treatment options for those with secondary iron overload.
Sentinel lymph node mapping in endometrial cancer: A comparison of main national and international guidelines
Authors: Dick Aharon , Perri Tamar , Kogan Liron , Brandt Benny , Meyer Raanan , Levin Gabriel
Published: June 2022

Objectives

To compare national and international guidelines regarding sentinel lymph node (SLN) mapping in endometrial cancer.

Methods

A descriptive comparative study of the National Comprehensive Cancer Network (NCCN), the Society of Gynecologic Oncology (SGO), the European Society of Gynecological Oncology (ESGO), the British Gynecological Cancer Society (BGCS), and the Japan Society of Gynecologic Oncology (JSGO) guidelines.

Results

There is a broad consensus that SLN mapping is an appropriate alternative to pelvic lymphadenectomy for uterine‐confined endometrioid endometrial cancer (five of five guidelines). It is broadly accepted that a full lymphadenectomy should be performed in case of failed SLN mapping (four of five guidelines), and that mapping with the fluorescent dye indocyanine green is superior to other methods (four of five guidelines). It is agreed that the cervix is the preferable site for dye injection (four of five guidelines), and pathology ultrastaging is advocated by most guidelines (three of five guidelines). Regarding high‐risk patients (i.e., high‐grade histology and non‐endometroid carcinomas), some guidelines accept (three of five), but others currently do not advocate (one of five guidelines), SLN mapping as a sole method for lymph node evaluation. There is no consensus regarding para‐aortic lymph node evaluation in pelvic SLN‐positive patients.

Conclusion

Guidelines for SLN mapping are comparable with regards to surgical technique, ultrastaging, and management in case of failed mapping. Nevertheless, some variations exist regarding the management of high‐grade histology and positive pelvic lymph nodes.
Interactive effects of high temperature and pesticide exposure on oxidative status, apoptosis, and renin expression in kidney of goldfish: Molecular and cellular mechanisms of widespread kidney damage and renin attenuation
Authors: Lacy Brittney , Rahman Md Saydur
Published: June 2022

One of many noteworthy consequences of increasing societal reliance on pesticides is their predominance in aquatic environments. These pernicious chemicals interact with high temperatures from global climate change, heat waves, and natural variations to create unstable environments that negatively impact organisms' health. To understand these conditions, we examined the dose‐dependent effects of environmentally relevant pesticide mixtures (metolachlor, linuron, isoproturon, tebuconazole, aclonifen, atrazine, pendimethalin, and azinphos‐methyl) combined with elevated temperatures (22 control vs. 32°C for 4‐week exposure) on renin, dinitrophenyl protein (DNP, an indicator of reactive oxygen species, ROS), 3‐nitrotyrosine protein (NTP, an indicator of reactive nitrogen species, RNS), superoxidase dismutase (SOD, an antioxidant), and catalase (CAT, an antioxidant) expressions in the kidneys of goldfish (Carassius auratus). Histopathological analysis showed widespread damage to kidney tissues in high temperature and pesticide co‐exposure groups, including rupture of the epithelial layer, hemorrhaging, and degeneration of tubular epithelium. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemical analyses demonstrated significant declines in renin receptor‐like mRNA and protein expressions in kidney tissues under combined exposure to high temperature and pesticides compared with controls; conversely, expression of DNP, NTP, SOD, and CAT increased in kidney tissues under the same conditions. Apoptotic cells were also increased in co‐exposure groups as assessed by in situ terminal deoxynucleotidyl transferase dUTP nick labeling (TUNEL) assay. The enhanced apoptosis in kidneys of heat and pesticides co‐exposed fish was associated with increased caspase‐3 (a protease enzyme) mRNA levels. Our results demonstrated that high temperature and pesticides induced oxidative/nitrative stress (i.e., ROS/RNS), damaged tissues, increased cellular apoptosis, and suppressed renin expression in kidneys of goldfish.
Longitudinal Associations of High-Volume and Vigorous-Intensity Exercise With Hip Fracture Risk in Men
Authors: Korhonen Marko T. , Kujala Urho M. , Kettunen Jyrki , Korhonen Olga V. , Kaprio Jaakko , Sarna Seppo , Törmäkangas Timo
Published: June 2022

Maintenance of vigorous exercise habits from young to old age is considered protective against hip fractures, but data on fracture risk in lifelong vigorous exercisers are lacking. This longitudinal cohort study examined the hazard of hip fractures in 1844 male former athletes and 1216 population controls and in relation to exercise volume and intensity in later years. Incident hip fractures after age 50 years were identified from hospital discharge register from 1972 to 2015. Exercise and covariate information was obtained from questionnaires administered in 1985, 1995, 2001, and 2008. Analyses were conducted using extended proportional hazards regression model for time-dependent exposures and effects. During the mean ± SD follow-up of 21.6 ± 10.3 years, 62 (3.4%) athletes and 38 (3.1%) controls sustained a hip fracture. Adjusted hazard ratio (HR) indicated no statistically significant difference between athletes and controls (0.84; 95% confidence interval [CI], 0.55–1.29). In subgroup analyses, adjusted HRs for athletes with recent high (≥15 metabolic equivalent hours [MET-h]/week) and low (<15 MET-h/week) exercise volume were 0.83 (95% CI, 0.46–1.48) and 1.04 (95% CI, 0.57–1.87), respectively, compared with controls. The adjusted HR was not statistically significant between athletes with low-intensity exercise (<6 METs) and controls (1.08; 95% CI, 0.62–1.85). Athletes engaging in vigorous-intensity exercise (≥6 METs at least 75 minutes/week) had initially 77% lower hazard rate (adjusted HR 0.23; 95% CI, 0.06–0.86) than controls. However, the HR was time-dependent (adjusted HR 1.04; 95% CI, 1.01–1.07); by age 75 years the HRs for the athletes with vigorous-intensity exercise reached the level of the controls, but after 85 years the HRs for these athletes increased approximately 1.3-fold annually relative to the controls. In conclusion, these data suggest that continuation of vigorous-intensity exercise is associated with lower HR of hip fracture up to old age. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Zingiberene exerts chemopreventive activity against 7,12‐dimethylbenz(a)anthracene‐induced breast cancer in Sprague‐Dawley rats
Authors: Seshadri Vidya Devanathadesikan , Oyouni Atif Abdulwahab A. , Bawazir Waleed M. , Alsagaby Suliman A. , Alsharif Khalaf F. , Albrakati Ashraf , Al‐Amer Osama M.
Published: June 2022

Breast cancer is the primary cause of cancer‐related death in females, wherein increased mortality of breast cancer patients is recorded worldwide. Zingiberene is a monocyclic sesquiterpene from the ginger plant and has many pharmacological benefits. In this exploration, we assessed the anticancer actions of Zingiberene against the 7,12‐dimethylbenz(a)anthracene (DMBA)‐stimulated mammary carcinogenesis in rats and MDA‐MB‐231 cells. Breast cancer was induced in the Female Sprague‐Dawley rats through the 25 mg/kg of DMBA in 0.5 ml of corn oil and then treated with 20 and 40 mg/kg of Zingiberene, respectively. The body weight of animals and tumor volume was measured. Hematological parameters, transaminases, lipid profile, lipid peroxidation, and antioxidants status were scrutinized using standard techniques. The estrogen receptor‐α and inflammatory markers were inspected by using respective assay kits. Histological damage scores were determined. In vitro experiments were conducted to scrutinize Zingiberene's effect on cell viability and apoptotic cell death in MDA‐MB‐231 cells. Zingiberene substantially modulated the DMBA‐stimulated physiological and hematological changes and decreased the transaminases, and lipid peroxidation in the DMBA‐stimulated animals. Zingiberene also elevated the antioxidant level and suppressed the inflammatory markers. Histological study revealed the protective effects of Zingiberene. The viability of MDA‐MB‐231 cells was noticeably diminished by the Zingiberene, thus inducing apoptotic cell death. Overall, our findings reliably proved the anticancer potential of Zingiberene against the DMBA‐stimulated mammary tumorigenesis, and it could be a promising chemotherapeutic agent.
Magnetic exchange interactions in binuclear and tetranuclear iron(III) complexes described by spin‐flip DFT and Heisenberg effective Hamiltonians
Authors: Kotaru Saikiran , Kähler Sven , Alessio Maristella , Krylov Anna I.
Published: June 2022

Low‐energy spectra of single‐molecule magnets (SMMs) are often described by Heisenberg Hamiltonians. Within this formalism, exchange interactions between magnetic centers determine the ground‐state multiplicity and energy separation between the ground and excited states. In this contribution, we extract exchange coupling constants (J) for a set of iron (III) binuclear and tetranuclear complexes from all‐electron calculations using non‐collinear spin‐flip time‐dependent density functional theory (NC‐SF‐TDDFT). For 12 binuclear complexes with J‐values ranging from −6 to −132 cm−1, our benchmark calculations using the short‐range hybrid ωPBEh functional and 6‐31G(d,p) basis set agree well with the experimentally derived values (mean absolute error of 4.7 cm−1). For the tetranuclear SMMs, the computed J constants are within 6 cm−1 from the experimentally derived values. We explore the range of applicability of the Heisenberg model by analyzing bonding patterns in these Fe(III) complexes using natural orbitals (NO), their occupations, and the number of effectively unpaired electrons. The results illustrate the efficiency of the spin‐flip protocol for computing the exchange couplings and the utility of the NO analysis in assessing the validity of effective spin Hamiltonians.
Quantification of anthocyanins in blueberries (Vaccinium spp.) by modified QuEChERS and liquid chromatography‐mass spectrometry
Authors: Yang Lun‐Chi , Hsu Shih‐Hsin , Meng Yun‐Yu , Chen Sung‐Fang
Published: June 2022

Anthocyanins are among the most extensively investigated class of bioflavonoids in plant and fruit products due to their widespread presence in nature and their antioxidant activity. A method based on a modified quick, easy, cheap, effective, rugged, and safe method (QuEChERS) was developed for the determination of six common types of anthocyanins in blueberries using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The QuEChERS procedure was optimized in the dispersive solid‐phase extraction (d‐SPE) for obtaining the targeted anthocyanins. This method provided the quantitative ranges between 2.5 and 1,000 μg L−1 (R2 > 0.9974) for the target analytes with satisfactory recoveries and precisions. The developed method was successfully applied to the analysis of anthocyanins in blueberries from different countries and the total anthocyanins concentrations were in the range from 926.5 to 2074.6 μg kg−1. This proposed method provided an efficient and sensitive approach for the qualitative and quantitative determination of the common anthocyanins in blueberry samples.
Mast cell‐derived exosomal miR‐181a‐5p modulated trophoblast cell viability, migration, and invasion via YY1/MMP‐9 axis
Authors: Wang Yinfen , Chen Aner
Published: June 2022

Background

Mast cells regulate the process of preeclampsia (PE). Since we previously identified mast cells specifically expressing miR‐181a‐5p in the placenta of PE patients, it is plausible to examine the effect and mechanism of mast cell‐derived exosomal miR‐181a‐5p on trophoblast cells.

Methods

The miR‐181a‐5p and YY1 levels were determined by quantitative real‐time reverse transcription‐polymerase chain reaction. Exosomes were identified by transmission electron microscopy, Western blot, and PKH‐26 labeling. Mast cells or trophoblast cell malignant phenotype were detected using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, wound healing, and Transwell assays. Quantification of YY1 and metastasis‐related proteins was performed using Western blot. TargetScan, JASPAR, dual‐luciferase reporter genes, and chromatin immunoprecipitation were exploited to verify the relationship between miR‐181a‐5p, YY1, and MMP‐9.

Results

MiR‐181a‐5p was overexpressed in mast cells of PE patients. Overexpressed miR‐181a‐5p restrained mast cell viability. Mast cell exosomes were successfully isolated, containing high expressions of CD63 and HSP70 and low expression of Calnexin and could be transported to the cytoplasm of trophoblast cells. Mast cell exosomes attenuated the viability, migration, and invasion of HTR‐8/SVneo cells, inhibited YY1, N‐cadherin, Vimentin, and MMP‐9 protein expressions, and promoted E‐cadherin protein expression. The effect of exosomes was enhanced by miR‐181a‐5p mimic but was reversed by miR‐181a‐5p inhibitor. MiR‐181a‐5p targeted YY1 which bound to the MMP‐9 promoter. Overexpressed YY1 in HTR‐8/SVneo cells accelerated the malignant phenotype of the cells and reversed the regulatory effects of exosomal miR‐181a‐5p.

Conclusion

Mast cell‐derived exosomal miR‐181a‐5p modulates HTR‐8/SVneo cell viability, migration, and invasion via YY1/MMP‐9.
Treatment barriers and gender‐based perceptions: Establishing gender‐based treatment specialty facilities as a strategy to motivate South African young women to seek treatment for substance use disorders
Authors: Nyashanu Tichaenzana , Zirima Herbert
Published: June 2022

South Africa alongside other low‐middle‐income countries have been some of the hardest hit by the substance use scourge. The study sought to identify and measure treatment barriers among young adults (18–29 years) living with substance use disorders, and then examine the role of gender in the perception of treatment barriers, with a view to establish gender‐based treatment specialty facilities as a strategy to promote treatment seeking among young South African women. Quantitative method was used for this study, employing simple random sampling. Exploratory factor analysis and independent samples t‐tests were used as statistical measures. The identified treatment barriers were found to have a larger effect on females than males. Women were considered less likely to utilise treatment services compared to males. Health promotion practitioners and policymakers can alleviate the situation by establishing gender‐based treatment facilities. that respond better to women's needs.
RNF144B stimulates the proliferation and inhibits the apoptosis of human spermatogonial stem cells via the FCER2/NOTCH2/HES1 pathway and its abnormality is associated with azoospermia
Authors: Du Li , Chen Wei , Li Chunyun , Cui Yinghong , He Zuping
Published: June 2022

Studies on gene regulation and signaling transduction pathways of human spermatogonial stem cells (SSCs) are of the utmost significance for unveiling molecular mechanisms underlying human spermatogenesis and gene therapy of male infertility. We have demonstrated, for the first time, that RNF144B stimulated cell proliferation and inhibited the apoptosis of human SSCs. The target of RNF144B was identified as FCER2 by RNA sequencing. We revealed that RNF144B interacted with FCER2 by immunoprecipitation. Consistently, overexpression of FCER2 reversed the phenotype of proliferation and apoptosis of human SSCs caused by RNF144B knockdown. Interestingly, FCER2 pulled down N2ICD (NOTCH2 intracellular domain), while N2ICD could bind to FCER2 in human SSCs. The levels of NOTCH2, FCER2, HES1, and HEY1 were reduced by RNF144B siRNA in human SSCs. Significantly, RNF144B was expressed at a lower level in nonobstructive azoospermia (NOA) patients than in the obstructive azoospermia (OA) patients with normal spermatogenesis, and 52 patients with heterozygous mutations of RNF144B were detected in 1,000 NOA patients. These results implicate that RNF144B promotes the proliferation of human SSCs and suppresses their apoptosis via the FCER2/NOTCH2/HES1 pathway and that the abnormality of RNF144B is associated with spermatogenesis failure. This study thus provides novel molecular mechanisms regulating the fate determinations of human SSCs, and it offers new biomarkers for the diagnosis and treatment of male infertility.
Gut microbial characteristics in poor appetite and undernutrition: a cohort of older adults and microbiota transfer in germ‐free mice
Authors: Fluitman Kristina S. , Davids Mark , Olofsson Louise E. , Wijdeveld Madelief , Tremaroli Valentina , Keijser Bart J.F. , Visser Marjolein , Bäckhed Fredrik , Nieuwdorp Max , IJzerman Richard G.
Published: June 2022

Background

Older adults are particularly prone to the development of poor appetite and undernutrition. Possibly, this is partly due to the aged gut microbiota. We aimed to evaluate the gut microbiota in relation to both poor appetite and undernutrition in community‐dwelling older adults. Furthermore, we studied the causal effects of the microbiota on body weight and body composition by transferring faecal microbiota from cohort participants into germ‐free mice.

Methods

First, we conducted a cross‐sectional cohort study of 358 well‐phenotyped Dutch community‐dwelling older adults from the Longitudinal Aging Study Amsterdam. Data collection included body measurements, a faecal and blood sample, as well as extensive questionnaires on appetite, dietary intake, and nutritional status. Appetite was assessed by the Council of Nutrition Appetite Questionnaire (CNAQ) and undernutrition was defined by either a low body mass index (BMI) (BMI < 20 kg/m2 if <70 years or BMI < 22 kg/m2 if ≥70 years) or >5% body weight loss averaged over the last 2 years. Gut microbiota composition was determined with 16S rRNA sequencing. Next, we transferred faecal microbiota from 12 cohort participants with and without low BMI or recent weight loss into a total of 41 germ‐free mice to study the potential causal effects of the gut microbiota on host BMI and body composition.

Results

The mean age (range) of our cohort was 73 (65–93); 58.4% was male. Seventy‐seven participants were undernourished and 21 participants had poor appetite (CNAQ < 28). A lower abundance of the genus Blautia was associated with undernutrition (log2 fold change = −0.57, Benjamini–Hochberg‐adjusted P = 0.008), whereas higher abundances of taxa from Lachnospiraceae, Ruminococcaceae UCG‐002, Parabacteroides merdae, and Dorea formicigenerans were associated with poor appetite. Furthermore, participants with poor appetite or undernutrition had reduced levels of faecal acetate (P = 0.006 and 0.026, respectively). Finally, there was a trend for the mice that received faecal microbiota from older adults with low BMI to weigh 1.26 g less after 3 weeks (P = 0.086) and have 6.13% more lean mass (in % body weight, P = 0.067) than the mice that received faecal microbiota from older adults without low BMI or recent weight loss.

Conclusions

This study demonstrates several associations of the gut microbiota with both poor appetite and undernutrition in older adults. Moreover, it is the first to explore a causal relation between the aged gut microbiota and body weight and body composition in the host. Possibly, microbiota‐manipulating strategies will benefit older adults prone to undernutrition.
The role of ABCB1 gene polymorphisms in steroid‐resistant nephrotic syndrome: Evidence from a meta‐analysis of steroid‐receiving patients
Authors: Aziz Md. Abdul , Islam Mohammad Safiqul
Published: June 2022

Previous studies in nephrotic syndrome have shown that three common variants in the ABCB1 gene, including rs1128503, rs2032582, and rs1045642, change the expression and activity of ABCB1, which may be responsible for the drug resistance. However, as a result of the inconclusive outcomes of these studies, we performed a meta‐analysis to validate the association between ABCB1 polymorphisms and the susceptibility of steroid‐resistant nephrotic syndrome (SRNS). The association was evaluated by calculating the odds ratio (OR) and 95% confidence interval. A total of 12 studies containing 1,463 subjects (514 steroid‐resistant and 949 steroid‐sensitive) were included. Single nucleotide polymorphism rs1128503 showed a significant association with SRNS (p < 0.05) only in the allele model (OR = 1.40) in Africans. A statistically significant association was found for rs2032582 in codominant 2, dominant, recessive, and allele models (OR = 1.85, 1.52, 1.38, and 1.34, respectively). Subgroup analysis revealed that rs2032582 showed a significant correlation with SRNS in codominant 1, 2, dominant, over‐dominant, and allele models in Africans (OR = 3.22, 3.52, 3.29, 1.74, and 1.83, respectively). In the case of rs1045642, codominant 1 (OR = 0.72) and recessive models (OR = 1.34) revealed a significant correlation with SRNS. Again, codominant 1 (OR = 0.58), dominant (OR = 0.69), and over‐dominant models (OR = 0.62) showed a protective effect in Asians. Haplotype analysis showed that the TGC haplotype is associated with a 1.83, 1.77, and 2.17 times significant correlation in overall, Asian, and African populations, respectively. By contrast, the CGC haplotype showed a 0.69 and 0.57 times lower association in the overall and African populations, respectively. The CTC haplotype also showed a 1.79 times enhanced susceptibility for SRNS in the overall population. Our study suggests that ABCB1 polymorphisms are associated with SRNS development, especially in Africans and Asians.
Improving ART initiation among men who use HIV self‐testing in Malawi: a qualitative study
Authors: Hubbard Julie A. , Mphande Misheck , Phiri Khumbo , Balakasi Kelvin , Hoffman Risa M. , Daniels Joseph , Choko Augustine , Coates Thomas J. , Dovel Kathryn
Published: June 2022

Introduction

HIV self‐testing (HIVST) increases HIV testing uptake among men; however, the linkage to antiretroviral therapy (ART) among HIVST users is low. Innovative strategies for ART initiation are needed, yet little is known about the unique barriers to care experienced by male HIVST users, and what ART‐related interventions men desire.

Methods

We conducted semi‐structured in‐depth interviews with cisgender men (≥15 years) in Malawi who tested HIV positive using HIVST between 2018 and 2020, as well as interviews with their female partners (≥15 years) who distributed the HIVST kits. Medical records from seven facilities were used to identify respondents. We included men who received HIVST from a health facility (primary distribution) and from sexual partners (secondary distribution). Interview guides focused on unique barriers to ART initiation following HIVST and desired interventions to improve linkage and initiation. Interviews were audio recorded, translated and transcribed to English, and analysed using constant comparison methods in Atlas.ti v.8.4. Themes were compared by HIVST distribution strategy. Data were collected between 2019 and 2020.

Results

Twenty‐seven respondents were interviewed: eight male/female dyads (16 respondents), eight men without a female partner and three women who represented men who did not participate in the study. Among the 19 men represented (16 men interviewed in person, three represented by secondary report from female partners), seven received HIVST through primary distribution, 12 through secondary distribution. Six men never initiated ART (all secondary HIVST distribution). Barriers to ART initiation centred on the absence of healthcare workers at the time of diagnosis and included lack of external motivation for linkage to care (men had to motivate themselves) and lack of counselling before and after testing (leaving ART‐related fears and misconceptions unaddressed)––the latter was especially true for secondary HIVST distribution. Desired interventions were similar across distribution strategies and included ongoing peer mentorship for normalizing treatment adherence, counselling messages tailored to men, outside‐facility services for convenience and privacy, and facility navigation to help men understand how to navigate ART clinics.

Conclusions

Male HIVST users face unique challenges to ART initiation, especially those receiving HIVST through secondary distribution. Male‐tailored interventions are desired by men and may help overcome barriers to care.
Patient characteristics associated with conversion from negative to positive severe acute respiratory syndrome coronavirus‐2 polymerase chain reaction test results: Implications for clinical false‐negativity from a single‐center: A case‐control study
Authors: Atluri Vidya L. , Stalter Randy M. , McGuffin Sarah A. , Johnson Luke , Healy Bailey , Benesch Hailey A. , Lan Kristine , Marsland Paula , Pottinger Paul , Patel Rena C.
Published: June 2022

Background

Accurate diagnosis of coronavirus disease 2019 is essential to limiting transmission within healthcare settings. The aim of this study was to identify patient demographic and clinical characteristics that could impact the clinical sensitivity of the nasopharyngeal severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV2) reverse transcription polymerase chain reaction (RT‐PCR) test.

Methods

We conducted a retrospective, matched case‐control study of patients who underwent repeated nasopharyngeal SARS‐CoV2 RT‐PCR testing at a tertiary care academic medical center between March 1 and July 23, 2020. The primary endpoint was conversion from negative to positive PCR status within 14 days. We conducted conditional logistic regression modeling to assess the associations between demographic and clinical features and conversion to test positivity.

Results

Of 51,116 patients with conclusive SARS‐CoV2 nasopharyngeal RT‐PCR results, 97 patients converted from negative to positive within 14 days. We matched those patients 1:2 to 194 controls by initial test date. In multivariate analysis, clinical suspicion for a respiratory infection (adjusted odds ratio [aOR] 20.9, 95% confidence interval [CI]: 3.1–141.2) and lack of pulmonary imaging (aOR 4.7, 95% CI: 1.03–21.8) were associated with conversion, while a lower burden of comorbidities trended toward an increased odds of conversion (aOR 2.2, 95% CI: 0.9–5.3).

Conclusions

Symptoms consistent with a respiratory infection, especially in relatively healthy individuals, should raise concerns about a clinical false‐negative result. We have identified several characteristics that should be considered when creating institutional infection prevention guidelines in the absence of more definitive data and should be included in future studies.
Simulation and projection of climate extremes in China by multiple Coupled Model Intercomparison Project Phase 6 models
Authors: Wei Linxiao , Xin Xiaoge , Li Qilin , Wu Yao , Tang Hongyu , Li Yonghua , Yang Baogang
Published: June 2022

This study evaluates the ability of 23 climate models from phase 6 of the Coupled Model Intercomparison Project (CMIP6) in simulating extreme climate events over China. The multimodel ensemble (MME) performs better than most individual models in reproducing the climatological mean distribution of all extreme indices. The MME can reproduce well the climatological mean distributions of five extreme climate indices over China, including annual total precipitation (PTOT), maximum consecutive 5‐day precipitation (RX5), simple daily intensity (SDII), maximum daily maximum temperature (TXX), and minimum daily minimum temperature (TNN), with Taylor skill scores exceeding 0.7. SDII and TXX are the most skilful precipitation and temperature extreme indices simulated by the MME, respectively. The MME has relatively lower skill in simulating the climatological mean distribution of warm days (TX90P) and cold nights (TN10P) over China. Future projections of these extreme climate indices by the end of the 21st century are explored with the MME under the SSP1‐2.6, SSP2‐4.5, and SSP5‐8.5 scenarios. The PTOT and RX5 in northwestern China are all projected to increase by more than 30% under SSP5‐8.5. R20 is projected to increase by 4–5 days over southeastern China under SSP5‐8.5. There are fewer (more) consecutive dry days over north China (south China), with a change of 5 days under SSP5‐8.5. The extreme temperature indices, including TX90P, TXX, and TNN, all increase with time and higher SSP scenarios. The three indices increase by 40–55%, 4–6°C, and 4–7°C under SSP5‐8.5 over east China, respectively. The TN10P decreases by more than 6% over east China. The changes in these extreme indices under SSP1‐2.6 and SSP2‐4.5 are similar to those under SSP5‐8.5 but with a smaller magnitude. Large uncertainties still exist in the future projections, especially under the high SSP scenarios.
From proof‐of‐concept to proof‐of‐value: Approaching third‐party data to operational workflows of national meteorological services
Authors: Garcia‐Marti Irene , Overeem Aart , Noteboom Jan Willem , de Vos Lotte , de Haij Marijn , Whan Kirien
Published: June 2022

National meteorological services (NMS) are limited by practical and financial boundaries in the number of official meteorological measurements that it can collect. This means that large regions are often unobserved. These gaps can be filled by novel data sources, including measurements from personal weather stations that are owned and operated by amateur citizen scientists, or opportunistic sensing from devices that are not designed to measure meteorological variables, like commercial microwave links (radio connections between mobile phone towers). These types of data are known as “third‐party data” (3PD) as they are not owned or operated by NMS or research institutes (e.g., university, government department). Demonstration of the quality and value of these novel data sources is an active area of research. NMS, like the Royal Netherlands Meteorological Institute (KNMI), are faced with some unique challenges when it comes to transferring research to operations. KNMI is in the early stages of developing an operational pipeline for 3PD. We outline some use cases where we have demonstrated the quality of 3PD. We discuss our experiences with some of these challenges that can occur when transferring between proof‐of‐concepts on 3PD developed in research settings into real operational workflows providing valuable services. Hence, in this work we introduce our third‐party data life cycle, in which we provide an integral overview of this transitioning process considering business and social aspects, technical feasibility assessments, the importance of quality control, and aspects related to data integration and alignment with the existing official data sources. We also reflect on how these potential new applications could fit into KNMIs long‐term strategies and contribute to the high‐resolution weather forecast and early warning issuing. We hope that sharing these experiences will provide some general guidelines to organizations in need of providing new services stemming from 3PD and transform them into “daily business.”
Photoinduced effects of monochromatic visible light with different wavelengths on realgar
Authors: Wu Furong , Zhang Yongkang , Li Yan , Wang Yuhang , Ma Junjie , Wang Fengping
Published: June 2022

Realgar is a well‐known light‐sensitive material. Under illumination, realgar is oxidized into arsenolite and uzonite, and uzonite generates pararealgar. To further study the effect of light with different wavelengths on realgar, herein, the light‐induced reaction of realgar under irradiation of four monochromatic visible lights, red light (628.0–648.0 nm), amber light (585.4–604.6 nm), green light (506.0–544.0 nm), and blue light (428.9–447.1 nm), have been studied by confocal Raman, X‐ray diffraction, and ultraviolet–visible absorption spectroscopy. The results of Raman spectra show that the photoinduced effect of different monochromatic lights on realgar is different. Realgar is stable under red light but is sensitive to other visible lights like amber, green, and blue light. The light‐induced reaction of realgar is the fastest under the green light. The effect of the blue light on realgar is complicated. Pararealgar, as the light‐induced product of realgar, transforms into uzonite under the blue light, which is discussed based on the bandgap of pararealgar calculated using the density functional theory method.
Effect of Plasticization on Stretching Stability of Poly(Vinyl Alcohol) Films: A Case Study Using Glycerol and Water
Authors: Fu Zhen‐zhen , Yao Yi‐hang , Guo Sheng‐jie , Wang Ke , Zhang Qin , Fu Qiang
Published: June 2022

Adding small molecular plasticizers is the most common route to tailor the stretchability of poly(vinyl alcohol) (PVA). However, how the plasticization along with the nature of the plasticizer governs the structural homogeneity during stretching remains an open question to answer. Herein, two representative plasticizers, glycerol (GLY) and water, are chosen to endow the PVA films with ductility. It is found that large strain cavitations cause obvious stress whitening in the PVA/H2O films; on the contrary, most of the PVA/GLY films maintain transparent undergoing tensile deformation. Through a combination of experimental inspections and molecular dynamic simulation, it is revealed that partial water molecules that behave as free water will aggregate into microdomains, which serve as mechanical defects responsible for yielding voids. Whereas, the GLY plasticizer homogeneously disperses at a molecular level and interacts with PVA chains through strong hydrogen bonds. More interestingly, it is illustrated that the dispersion and bound states of plasticizers are closely related to the mechanical character of the plasticized PVA films. These findings offer new insight into the working mechanism of plasticization on the structural stability during stretching, and guide the design of PVA/plasticizer system to obtain excellent comprehensive mechanics.
Using the Analytic Hierarchy Process method to develop two efficiency indicators for the Food Acquisition Program – Milk modality
Authors: Neves Josemir Araújo , Rangel Adriano Henrique do Nascimento , Neto Manoel Pereira , Matos Marta Maria Souza , Silva Rita de Cássia de Andrade , Novaes Luciano Patto , Urbano Stela Antas , Paulino Hideljundes Macedo
Published: June 2022

This work describes the process of building two indicators in order to measure the efficiency of the Food Acquisition Program – Milk modality (PAA‐Milk) in the States which implement it. The Analytic Hierarchy Process (AHP) methodology was used to develop the first indicator, while the Principal Component Analysis was used as a tool for cutting and simplifying the structure of the first indicator to obtain the second indicator. The results demonstrate the great potential of the AHP tool together with the statistical tools to develop indicators to diagnose and monitor public policies in Brazil. The states of Alagoas, Paraíba, and Ceará presented the best efficiency in the performance of the Program, while Bahia and Pernambuco presented the worst results.
The Impact of Type 2 Diabetes in Parkinson's Disease
Authors: Athauda Dilan , Evans James , Wernick Anna , Virdi Gurvir , Choi Minee L. , Lawton Michael , Vijiaratnam Nirosen , Girges Christine , Ben‐Shlomo Yoav , Ismail Khalida , Morris Huw , Grosset Donald , Foltynie Thomas , Gandhi Sonia
Published: June 2022

Background

Type 2 diabetes (T2DM) is an established risk factor for developing Parkinson's disease (PD), but its effect on disease progression is not well understood.

Objective

The aim of this study was to investigate the influence of T2DM on aspects of disease progression in PD.

Methods

We analyzed data from the Tracking Parkinson's study to examine the effects of comorbid T2DM on PD progression and quality of life by comparing symptom severity scores assessing a range of motor and nonmotor symptoms.

Results

We identified 167 (8.7%) patients with PD and T2DM (PD + T2DM) and 1763 (91.3%) patients with PD without T2DM (PD). After controlling for confounders, patients with T2DM had more severe motor symptoms, as assessed by Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III (25.8 [0.9] vs. 22.5 [0.3] P = 0.002), and nonmotor symptoms, as assessed by Non‐Motor Symptoms Scale total (38.4 [2.5] vs. 31.8 [0.7] P < 0.001), and were significantly more likely to report loss of independence (odds ratio, 2.08; 95% confidence interval [CI]: 1.34–3.25; P = 0.001) and depression (odds ratio, 1.62; CI: 1.10–2.39; P = 0.015). Furthermore, over time, patients with T2DM had significantly faster motor symptom progression (P = 0.012), developed worse mood symptoms (P = 0.041), and were more likely to develop substantial gait impairment (hazard ratio, 1.55; CI: 1.07–2.23; P = 0.020) and mild cognitive impairment (hazard ratio, 1.7; CI: 1.24–2.51; P = 0.002) compared with the PD group.

Conclusions

In the largest study to date, T2DM is associated with faster disease progression in Parkinson's, highlighting an interaction between these two diseases. Because it is a potentially modifiable metabolic state, with multiple peripheral and central targets for intervention, it may represent a target for alleviating parkinsonian symptoms and slowing progression to disability and dementia. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society