bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenicity of two doses of BNT162b2 and mRNA‐1273 vaccines for solid cancer patients on treatment with or without a previous SARS‐CoV‐2 infection
Authors: La Verde Nicla , Riva Agostino , Cona Maria Silvia , Gabrieli Arianna , Cattaneo Monica , Fasola Cinzia , Lipari Giuseppe , De Stradis Claudia , Favorito Valentina , Lombardi Stocchetti Benedetta , Chizzoniti Davide , Covizzi Alice , Rulli Eliana , Galli Francesca , Ruggieri Lorenzo , Gambaro Anna , Ferrario Sabrina , Dalu Davide , Tarkowski Maciej S.
Published: September 2022

Previous studies on the immunogenicity of SARS‐CoV‐2 mRNA vaccines showed a reduced seroconversion in cancer patients. The aim of our study is to evaluate the immunogenicity of two doses of mRNA vaccines in solid cancer patients with or without a previous exposure to the virus. This is a single‐institution, prospective, nonrandomized study. Patients in active treatment and a control cohort of healthy people received two doses of BNT162b2 (Comirnaty, BioNTech/Pfizer, The United States) or mRNA‐1273 (Spikevax, Moderna). Vaccine was administered before starting anticancer therapy or on the first day of the treatment cycle. SARS‐CoV‐2 antibody levels against S1, RBD (to evaluate vaccine response) and N proteins (to evaluate previous infection) were measured in plasma before the first dose and 30 days after the second one. From January to June 2021, 195 consecutive cancer patients and 20 healthy controls were enrolled. Thirty‐one cancer patients had a previous exposure to SARS‐CoV‐2. Cancer patients previously exposed to the virus had significantly higher median levels of anti‐S1 and anti‐RBD IgG, compared to healthy controls (P = .0349) and to cancer patients without a previous infection (P < .001). Vaccine type (anti‐S1: P < .0001; anti‐RBD: P = .0045), comorbidities (anti‐S1: P = .0274; anti‐RBD: P = .0048) and the use of G‐CSF (anti‐S1: P = .0151) negatively affected the antibody response. Conversely, previous exposure to SARS‐CoV‐2 significantly enhanced the response to vaccination (anti‐S1: P < .0001; anti‐RBD: P = .0026). Vaccine immunogenicity in cancer patients with a previous exposure to SARS‐CoV‐2 seems comparable to that of healthy subjects. On the other hand, clinical variables of immune frailty negatively affect humoral immune response to vaccination.
Audit report information improvement and earnings management
Authors: Sai Qian , Li Yanxi , Liu Yanwen , Zhao Heng , Ouyang Shanshan
Published: September 2022

Increasing the disclosure of key audit matters (KAMs) has been an important change in audit reports in recent years. After the implementation of this policy, what changes have taken place in the behaviour of auditors after the implementation of this policy? What impact has it had on the audit report? A series of problems deserve systematic analysis and empirical testing. This paper examines the relationship between the communication of KAMs and earnings management. We examined quasi‐natural experimental data shaped by new auditing standards issued by the Ministry of Finance of China on 23 December 2016. The new auditing standards have been implemented in phases for the listed companies. We find that (1) communicating KAMs in audit reports restrains the auditor's motivational reasoning behaviour by triggering rationality constraints and improves the auditor's professional scepticism, thus improving audit quality and significantly reducing the company's accrued earnings management level. (2) The influence of communicating KAMs on earnings management is more significant for sampled firms with high external financing dependence and low marketization, revealing its supplementary role in the existing corporate governance mechanism. The findings of this paper enrich existing research on KAMs and supplement important empirical evidence from the Chinese market for assessing the effects of audit reporting reforms worldwide.
Solvent types used for the preparation of hydrogels determine their mechanical properties and influence cell viability through gelatine and calcium ions release
Authors: Rosińska Karolina , Bartniak Mateusz , Wierzbicka Adrianna , Sobczyk‐Guzenda Anna , Bociaga Dorota
Published: September 2022

Alginate‐gelatin hydrogels are the most commonly used materials for 3D bioprinting. Their printability depends on their properties, and these derive from the way they are prepared and their very composition. Therefore, the aim of the study was to investigate the type of solvent (deionized water, phosphate buffer, and culture medium) and contents of gelatin in the composition of hydrogel (2% wt/vol alginate, 6% and 9% wt/vol of gelatin) on their biological, physicochemical, and mechanical properties, as well as printability and the ability of cells to proliferate in the printed structures. The results obtained revealed that all the manufactured hydrogel materials are biocompatible. The use of deionized water as a solvent results in the highest degree of cross‐linking of hydrogels, thus obtaining a polymer with the highest rigidity. Moreover, an increase in gelatin content leads to an increase in the Young's modulus value, irrespectively of the solvent in which the hydrogels were prepared. Based on the chemical structure, it is more reasonable to use a culture medium for bioink preparation due to free NH and NH2 groups being present, which are ligands for cell attachment and their proliferation. For the selected material (2A9GM), the printability and high viability of the cells after printing were confirmed. In this case, the concentration of the cross‐linking agent influences gelatin amount release and calcium ions release, and these two processes determine the change in the viability of the cells encapsulated in the bioink.
Denosumab for Prevention of Acute Onset Immobilization-Induced Alterations of Bone Turnover: A Randomized Controlled Trial
Authors: Wadiura Lisa Irina , Butylina Maria , Reinprecht Andrea , Aretin Marie-Bernadette , Mischkulnig Mario , Gleiss Andreas , Pietschmann Peter , Kerschan-Schindl Katharina
Published: September 2022

Metabolic bone disease is a devastating condition in critically ill patients admitted to an intensive care unit (ICU). We investigated the effects of early administration of the antiresorptive drug denosumab on bone metabolism in previously healthy patients. Fourteen patients with severe intracerebral or subarachnoid hemorrhage were included in a phase 2 trial. Within 72 hours after ICU admission, they were randomized in a 1:1 ratio to receive denosumab 60 mg or placebo subcutaneously. The primary endpoint was group differences in the percentage change of C-terminal telopeptide of type 1 collagen (CTX-1) levels in serum from denosumab/placebo application to 4 weeks thereafter. Changes in serum levels of bone formation markers and urinary calcium excretion were secondary outcome parameters. Regarding serum levels of CTX-1, changes over time averaged −0.45 ng/mL (95% confidence interval [CI] −0.72, −0.18) for the denosumab group and 0.29 ng/mL (95% CI −0.01, 0.58) for the placebo group. The primary endpoint, the group difference in changes between baseline and secondary measurement, adjusted for baseline serum levels and baseline neurological status, averaged −0.74 ng/mL (95% CI −1.14, −0.34; p = 0.002). The group difference in changes between baseline and secondary osteocalcin measurement averaged −5.60 ng/mL (95% CI −11.2, −0.04; p = 0.049). The group difference in averaged change between baseline and secondary measurement of 24-hour urine calcium excretion was significant (−1.77 mmol/L [95% CI −3.48, −0.06; p = 0.044]). No adverse events could be attributed to the study medication. The investigation proved that a single application of denosumab early after admission to an ICU prevents acute immobilization-associated increase in bone resorption among previously healthy individuals. © 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).
Exposure of aluminium to C6 glioma cells modulates molecular and functional neurotoxic markers
Authors: Dey Mangaldeep , Singh Rakesh Kumar
Published: September 2022

The risk of aluminium exposure to humans is very high as it may get into the human body through excessive dietary contaminants, inhalation of fine particulate matter, or through parenteral routes as a vaccine adjuvant and so forth. The increased level of aluminium in brain tissue has been shown to be associated with several neurodegenerative and neurotoxic adverse effects, including AD. However, the exact mechanism of aluminium‐induced neurotoxicity is still unclear. Therefore, our study aimed to investigate the mechanism of neurotoxic and neurodegenerative effects through in vitro exposure of aluminium in rat glioma C6 cell line. The findings of our study have indicated that aluminium chloride exposure may lead to alteration in acetylcholine levels, increased oxidative imbalance and induction of molecular structural and functional markers of neuronal inflammation. This study also demonstrated that aluminium exposure may lead to the induction of caspase‐3 along with apoptotic cell death and a significant increase in amyloid‐beta and hyperphosphorylated tau levels in C6 cells. Thus, this study may provide a mechanistic understanding of the regulation of neuroinflammatory and neurodegenerative biomarkers due to aluminium exposure.
Serious disease risk among patients with unexpected weight loss: a matched cohort of over 70 000 primary care presentations
Authors: Withrow Diana R. , Oke Jason , Friedemann Smith Claire , Hobbs Richard , Nicholson Brian D.
Published: September 2022

Background

Unexpected weight loss (UWL) in patients consulting in primary care presents dilemmas for management because of the broad differential diagnoses associated with UWL. Research on the risks of serious disease among patients with UWL to date has largely taken place in secondary care, limiting generalizability to primary care patients. In this study, we use a large matched cohort study to estimate the risks of 12 serious diseases among patients presenting to primary care with UWL where this was recorded, stratified by age and sex, in order to inform a rational clinical approach to patients presenting with UWL.

Methods

This was a retrospective matched cohort study using electronic health records (EHRs) from the UK Clinical Practice Research Datalink (CPRD). Each patient with UWL (ascertained from EHR coding) was matched to five patients without UWL and followed until the earliest of a diagnosis of the serious disease, date of death, exit from the CPRD database, or end of the study. Observed absolute risks of the 12 serious diseases were estimated as probabilities, and hazard ratios (HRs) were estimated with Cox proportional hazards models.

Results

Between 2000 and 2012, 70 193 patients in CPRD had at least one record of UWL and were matched with 295 579 patients without UWL. Patients with UWL had significantly higher risk of nearly all serious diseases examined compared with patients without. HRs ranged from 1.43 for congestive heart failure [95% confidence interval (CI): 1.27–1.62] to 9.70 for malabsorption (95% CI: 6.81–13.82). The absolute risks of any given serious disease were relatively low (<6% after 1 year). The magnitude and rank order of absolute risks varied by age and sex. Depression was the most common diagnosis among women aged <80 with UWL (3.74% of women aged <60 and 2.46% of women aged 60–79), whereas diabetes was the most common in men <60 with UWL (2.96%) and cancer was the most common in men aged 60 and over with UWL (3.79% of men aged 60–70 and 5.28% of men aged ≥80).

Conclusions

This analysis provides new evidence to patients and clinicians about the risks of serious disease among patients presenting with UWL in primary care. Depending on age and sex, the results suggest that workup for UWL should include screening for diabetes, thyroid dysfunction, depression, and dementia. If performed in a timely manner, this workup could be used to triage patients eligible for cancer pathway referral.
Effect of cerium on the production of reactive oxygen species in the root of Arabidopsis thaliana: An in vitro study
Authors: Lyu Keliang , Lyu Zhiwen , Zhang Xinran , Hao Donghao , Yang Zhonghuang , Liu Yumeng , Liu Dongwu , Wang Xue
Published: September 2022

In the current study, the effect of trivalent cerium (Ce3+) on the production of reactive oxygen species (ROS) was investigated in the root of Arabidopsis thaliana by an in vitro study. The roots of A. thaliana were exposed with 0, 1, and 5 μmol/L Ce3+ for 12 h in vitro. It was found that the level of H2O2, O2.−, and ·OH was enhanced by 5 μmol/L Ce3+, but reduced by 1 μmol/L Ce3+. The activities of peroxidase (POD), catalase (CAT), and superoxidase dismutase (SOD) were enhanced by 1 μmol/L Ce3+, but reduced by 5 μmol/L Ce3+. Moreover, we used a laser‐scanning confocal microscopy to detect the changes of ROS in the root cells of A. thaliana by using a fluorochrome 2′,7′‐dichlorofluorescein diacetate (H2DCF‐DA). It showed that the level of ROS was declined in the root cells treated by 1 μmol/L Ce3+, but the oscillation of ROS was found in the root cells treated with 5 μmol/L Ce3+. In addition, REEs affect the uptake of mineral elements, which may be related to the oxidative stress in the cells of roots. In all, the data of our study indicated that the appropriate concentration of Ce3+ exhibited an anti‐oxidation property and improved the defense system in the root cells of A. thaliana.
The effects of an online decision aid to support the reproductive decision‐making process of genetically at risk couples—A pilot study
Authors: Severijns Yil , Heijmans Maartje W. F. , de Die‐Smulders Christine E. M. , Bijlsma Emilia K. , Corsten‐Janssen Nicole , Joosten Sara J. R. , van Kuijk Sander M. J. , Lichtenbelt Klaske D. , Ottenheim Cecile P. E. , Stuurman Kyra E. , Tan‐Sindhunata Gita M. B. , de Vries Hein , van Osch Liesbeth A. D. M.
Published: September 2022

Couples at risk of transmitting a genetic disease to their offspring may experience doubts about their reproductive options. This study examines the effects of an online decision aid (DA) on the (joint) reproductive decision‐making process of couples (not pregnant at time of inclusion) at risk of transmitting a genetic disease to their offspring. The primary outcome is decisional conflict, and secondary outcomes are knowledge, realistic expectations, deliberation, joint informed decision‐making, and decisional self‐efficacy. These outcomes were measured with a pretest–posttest design: before use (T0), after use (T1), and 2 weeks after use (T2) of the decision aid (DA). Usability of the DA was assessed at T1. Paired sample t‐tests were used to compute differences between baseline and subsequent measurements. The comparisons of T0‐T1 and T0‐T2 indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline decisional conflict scores. Furthermore, use of the DA led to increased knowledge, improved realistic expectations, and increased levels of deliberation, with higher increase in participants with low baseline scores. Decision self‐efficacy only improved for participants with lower baseline scores. Participants indicated that the information in the DA was comprehensible and clearly organized. These first results indicate that this online DA is an appropriate tool to support couples at risk of transmitting a genetic disease and a desire to have (a) child(ren) in their reproductive decision‐making process.
A note on minor antichains of uncountable graphs
Authors: Pitz Max
Published: September 2022

A simplified construction is presented for Komjáth's result that for every uncountable cardinal , there are graphs of size none of them being a minor of another.
Skin cancer in essential thrombocythaemia and polycythaemia vera patients treated with hydroxycarbamide
Authors: Mathur Abhinav , Edman Joakim , Liang Livia , Scott Neil W. , Watson Henry G.
Published: September 2022

Hydroxycarbamide (HC) is used as a cytoreductive treatment in myeloproliferative neoplasms (MPN). Observational studies have raised the possibility that HC contributes to the development of secondary malignancies, including skin tumours in MPN patients. In this retrospective observational study, we report a single‐centre experience of 324 HC‐treated MPN patients with long‐term follow‐up, compared to 47 MPN patients not on HC. Thirty‐three patients (10.2%) (HC) versus one patient (2.1%) (no HC) developed skin tumours during follow‐up (Hazard ratios [HR] 5.70, 95% confidence intervals 0.66–48.09, p = 0.112). However, male gender, age at MPN diagnosis, type of MPN (polycythaemia rubra vera) and previous history of skin cancer were prognostic variables associated with development of skin cancer.
A new aberrantly spliced BCR‐ABL1 transcript variant (e13a1) identified in routine monitoring using different quantitative reverse transcription polymerase chain reaction techniques in a patient with chronic myeloid leukemia
Authors: Naumann Nicole , Bross‐Bach Ulrike , Seifarth Wolfgang , Fabarius Alice , Hofmann Wolf‐Karsten , Saußele Susanne , Spiess Birgit
Published: September 2022

Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) of BCR‐ABL1 transcript level is an essential part of routine disease monitoring in patients with chronic myeloid leukemia. One patient sample (e13a2 transcript detected by nested PCR) attracted attention by revealing an aberrantly spliced BCR‐ABL1 transcript variant e13a1. The last 38 base pairs (bp) of BCR exon 13 were replaced by a 37 bp insertion of the ABL1 intron 1–2/exon 1 sequence. The rare aberrant BCR‐ABL1 fusion transcript can cause discrepancies in molecular diagnostics. This scenario highlights the importance of an individual characterization of the BCR‐ABL1 fusion sequence in case of unclear qRT‐PCR results.
Protein profiling by reverse phase protein array (RPPA) in classical hairy cell leukemia (HCL) and HCL‐variant
Authors: Hoff Fieke W. , Griffen Ti'ara L. , Qiu Yihua , Kornblau Steven M.
Published: September 2022

Classical hairy cell leukemia (HCL‐c) and HCL variant (HCL‐v) are recognized as separate entities with HCL‐v having significantly shorter overall survival. Proteomic studies, shown to be prognostic in various forms of leukemia, have not been performed in HCL. We performed reverse phase protein array‐based protein profiling with 384 antibodies in HCL‐c (n = 12), HCL‐v (n = 4), and normal B‐cells (n = 5) samples. While HCL could be distinguished from normal based on unsupervised hierarchical clustering, overlap in protein expression patterns was seen between HCL‐c and HCL‐v, with ∼10% of the proteins being differentially expressed, suggesting potential therapeutic targets.
Exploring the impact of population density on journey‐to‐crime in cases of stranger sexual assault and stranger homicide
Authors: Almond Louise , McManus Michelle , Hankey Natasha , Trevett Naomi , Mee Richard
Published: September 2022

The purpose of this research is to further understanding of how environmental factors impact on the distance an offender travels from their home to their crime scene ‐ the so called ‘journey‐to‐crime’ (JTC.). Currently, Geographic Profilers rely on relatively generic JTC research to form inferences about the likely distance travelled by an offender, and may be missing the opportunity to make a more bespoke assessment which takes these factors into account. 1186 cases of female stranger sexual assault (Study 1) and 124 cases of stranger homicide (Study 2) were analysed. Euclidean measurement of distance was provided from the offender's recorded home to 3 crime site locations: (1) the initial contact with victim, (2) the assault/murder, and (3) the victim release/body disposal. Each crime site location was coded according to: (a) population density and (b) urban or rural. Initial analysis examined the median distance travelled from an offender's residence to the three different crime site locations. Significant findings for stranger sexual assaults indicated that the initial contact location was significantly further from an offender's residence compared to the sexual assault and victim release location. This was not replicated for stranger homicide offences. Both sexual assault and homicide cases revealed that the distance travelled to the ‘initial approach’ location did not differ according to population density, or whether the location was urban or rural. Regarding ‘sexual assault’ locations, offenders were found to travel significantly further from their home to attack their victim in low population density and rural areas. Results showed that both sexual assault and homicide offenders travelled significantly further from their home to the ‘victim release/body disposal’ site in low population density areas and rural areas. These findings have important, practical applications for investigations, allowing Geographic Profilers to provide more bespoke inferences about an offender's journey to crime.
Synthesis of novel thiosemicarbazone derivatives and investigation of their dual AChE and MAO‐B inhibitor effects
Authors: Uytun Ayşe Nur , Osmaniye Derya , Sağlık Begüm Nurpelin , Levent Serkan , Ozkay Yusuf , Kaplancıklı Zafer Asım
Published: September 2022

In this study, 15 thiosemicarbazone derivatives were synthesized. Analysis of the obtained compounds was performed by means of 1H‐NMR, 13C‐NMR and high resolution mass spectroscopy (HRMS) spectroscopic methods. The inhibition effect of the obtained compounds on cholinesterase and monoaminoxidase (MAO) enzymes were investigated with in vitro methods. None of the compounds showed significant activity on the butyrylcholinesterase enzyme. On the other hand, compounds 3b, 3c, 3e, 3k, 3l, 3m, 3n and 3o displayed significant activity on acetylcholinesterase (AChE) while compounds 3f, 3i, 3k, 3l, 3m, 3n, 3o also showed remarkable effects on monoamine oxidase‐B (MAO‐B) enzymes. For the selected compounds, docking studies were performed and the enzyme active site and binding modes were determined. It was revealed that the strongest interaction with AChE and MAO‐B enzyme active sites was observed with the compound 3k. Another important factor in the treatment of diseases affecting the central nervous system such as Alzheimer's is the ability of the compounds to cross the blood‐brain barrier (BBB). Additionally, the agents planned for the treatment of these diseases must also pass the blood‐brain barrier. Therefore, in silico BBB penetration properties of active compounds were investigated.
Simultaneous Acquisition of Diffusion Tensor and Dynamic Diffusion MRI
Authors: Gangolli Mihika , Wang Wen‐Tung , Gai Neville D. , Pham Dzung L. , Butman John A.
Published: September 2022

Background

Dynamic diffusion magnetic resonance imaging (ddMRI) metrics can assess transient microstructural alterations in tissue diffusivity but requires additional scan time hindering its clinical application.

Purpose

To determine whether a diffusion gradient table can simultaneously acquire data to estimate dynamic and diffusion tensor imaging (DTI) metrics.

Study Type

Prospective.

Subjects

Seven healthy subjects, 39 epilepsy patients (15 female, 31 male, age ± 15).

Field Strength/Sequence

Two‐dimensional diffusion MRI (b = 1000 s/mm2) at a field strength of 3 T. Sessions in healthy subjects—standard ddMRI (30 directions), standard DTI (15 and 30 directions), and nested cubes scans (15 and 30 directions). Sessions in epilepsy patients—two 30 direction (standard ddMRI, 10 nested cubes) or two 15 direction scans (standard DTI, 5 nested cubes).

Assessment

Fifteen direction DTI was repeated twice for within‐session test–retest measurements in healthy subjects. Bland–Altman analysis computed bias and limits of agreement for DTI metrics using test–retest scans and standard 15 direction vs. 5 nested cubes scans. Intraclass correlation (ICC) analysis compared tensor metrics between 15 direction DTI scans (standard vs. 5 nested cubes) and the coefficients of variation (CoV) of trace and apparent diffusion coefficient (ADC) between 30 direction ddMRI scans (standard vs. 10 nested cubes).

Statistical Tests

Bland–Altman and ICC analysis using a P‐value of 0.05 for statistical significance.

Results

Correlations of mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were strong and significant in gray (ICC > 0.95) and white matter (ICC > 0.95) between standard vs. nested cubes DTI acquisitions. Correlation of white matter fractional anisotropy was also strong (ICC > 0.95) and significant. ICCs of the CoV of dynamic ADC measured using repeated cubes and nested cubes acquisitions were modest (ICC >0.60), but significant in gray matter.

Conclusion

A nested cubes diffusion gradient table produces tensor‐based and dynamic diffusion measurements in a single acquisition.

Level of Evidence

2

Technical Efficacy

Stage 1
Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS‐CoV‐2 variants
Authors: Wang Qiong , Ye Sheng‐Bao , Zhou Zhi‐Jian , Li Jin‐Yan , Lv Ji‐Zhou , Hu Bodan , Yuan Shuofeng , Qiu Ye , Ge Xing‐Yi
Published: September 2022

Increasing evidence supports inter‐species transmission of SARS‐CoV‐2 variants from humans to domestic or wild animals during the ongoing COVID‐19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS‐CoV‐2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS‐CoV‐2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, to evaluate the impact of S mutations, we tested 27 pseudoviruses of SARS‐CoV‐2 carrying different spike mutants by infecting Hela cells expressing different angiotensin‐converting enzyme 2 (ACE2) orthologs from 20 animals. Of these 27 pseudoviruses, 20 bear single mutation and the other 7 were cloned from emerging SARS‐CoV‐2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429), and Mu (B.1.621). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS‐CoV‐2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS‐CoV‐2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammal ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS‐CoV‐2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS‐CoV‐2 variants with these two mutations.
Differences in incidence and fatality of COVID‐19 by SARS‐CoV‐2 Omicron variant versus Delta variant in relation to vaccine coverage: A world‐wide review
Authors: Wang Chao , Liu Bei , Zhang Sihui , Huang Ninghua , Zhao Tianshuo , Lu Qing‐Bin , Cui Fuqiang
Published: September 2022

We aim to evaluate the evolution differences in the incidence and case fatality rate (CFR) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta and Omicron variants. The average incidence and CFRs were described between different countries. A gamma generalized linear mixed model (GLMM) was used to compare the CFRs of Delta and Omicron variants based on vaccination coverage. Totally, 50 countries were included for analyses. The incidence of coronavirus disease 2019 (COVID‐19) ranged from 0.16/100,000 to 82.95/100,000 during the Delta period and 0.03/100,000 to 440.88/100,000 during the Omicron period. The median CFRs were 8.56 (interquartile range [IQR]: 4.76–18.39) during the Delta period and 3.04 (IQR: 1.87–7.48) during the Omicron period, respectively. A total of 47 out of 50 countries showed decreased CFRs of the Omicron variant with the rate ratio ranging from 0.02 (95% confidence interval [CI]: 0.01–0.03) (in Cambodia) to 0.97 (95% CI: 0.87–1.08) (in Ireland). Gamma GLMM analysis showed that the decreased CFR was largely a result of the decreased pathogenicity of Omicron besides the increased vaccination coverage. The Omicron variant shows a higher incidence but a lower CFR around the world as a whole, which is mainly a result of the decreased pathogenicity by SARS‐CoV‐2's mutation, while the vaccination against SARS‐CoV‐2 still acts as a valuable measure in preventing people from death.
Enterovirus‐71 utilizes small extracellular vesicles to cross the blood–brain barrier for infecting the central nervous system via transcytosis
Authors: Gu Jiaqi , Zhao Yuxue , Wu Jing , Chen Yiwen , Yin Yiqian , Jia Xiaonan , Mao Lingxiang
Published: September 2022

Background

Central nervous system (CNS) infections caused by Enterovirus 71 (EV71) pose a serious threat to children, causing severe neurogenic complications and even fatality in some patients. However, the pathogenesis of EV71 infections in the CNS remains unclear.

Methods

An in vitro blood–brain barrier (BBB) model was constructed by coculturing brain microvascular endothelial cells (BMECs) and astrocytes in transwell inserts for simulating CNS infections. EV71 virions and small extracellular vesicles (sEVs) derived from EV71‐infected cells (EV71‐sEVs) were isolated from the cell culture supernatant by density gradient centrifugation. The BBB model was separately infected with EV71 virions and EV71‐sEVs. The mechanism of crossing the BBB was determined by inhibiting the different endocytic modes. A murine model of EV71 infection was constructed for confirming the results of in vitro experiments.

Results

The EV71‐sEVs containing viral components were endocytosed by BMECs and released on the abluminal side of the BBB model, where they infected the astrocytes without disrupting the BBB in the early stages of infection. The integrity of the tight junctions (TJs) between BMECs was breached via downregulation of PI3K/Akt signaling in the late stages of infection.

Conclusions

EV71 utilized the circulating sEVs for infecting the CNS by crossing the BBB.
Whole‐genome sequencing of SARS‐CoV‐2: Comparison of target capture and amplicon single molecule real‐time sequencing protocols
Authors: Nicot Florence , Trémeaux Pauline , Latour Justine , Jeanne Nicolas , Ranger Noémie , Raymond Stéphanie , Dimeglio Chloé , Salin Gérald , Donnadieu Cécile , Izopet Jacques
Published: September 2022

Fast, accurate sequencing methods are needed to identify new variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) genome. Single‐molecule real‐time (SMRT) Pacific Biosciences (PacBio) provides long, highly accurate sequences by circular consensus reads. This study compares the performance of a target capture SMRT PacBio protocol for whole‐genome sequencing (WGS) of SARS‐CoV‐2 to that of an amplicon PacBio SMRT sequencing protocol. The median genome coverage was higher (p < 0.05) with the target capture protocol (99.3% [interquartile range, IQR: 96.3–99.5]) than with the amplicon protocol (99.3% [IQR: 69.9–99.3]). The clades of 65 samples determined with both protocols were 100% concordant. After adjusting for Ct values, S gene coverage was higher with the target capture protocol than with the amplicon protocol. After stratification on Ct values, higher S gene coverage with the target capture protocol was observed only for samples with Ct > 17 (p < 0.01). PacBio SMRT sequencing protocols appear to be suitable for WGS, genotyping, and detecting mutations of SARS‐CoV‐2.
Machine learning using convolutional neural networks for SERS analysis of biomarkers in medical diagnostics
Authors: Li Joy Qiaoyi , Dukes Priya Vohra , Lee Walter , Sarkis Michael , Vo‐Dinh Tuan
Published: September 2022

Surface‐enhanced Raman spectroscopy (SERS) has wide diagnostic applications because of narrow spectral features that allow multiplexed analysis. Machine learning (ML) has been used for non‐dye‐labeled SERS spectra but has not been applied to SERS dye‐labeled materials with known spectral shapes. Here, we compare the performances of spectral decomposition, support vector regression, random forest regression, partial least squares regression, and convolutional neural network (CNN) for SERS “spectral unmixing” from a multiplexed mixture of 7 SERS‐active “nanorattles” loaded with different dyes for mRNA biomarker detection. We showed that CNN most accurately determined relative contributions of each distinct dye‐loaded nanorattle. CNN and comparative models were then used to analyze SERS spectra from a singleplexed, point‐of‐care assay detecting an mRNA biomarker for head and neck cancer in 20 samples. The CNN, trained on simulated multiplexed data, determined the correct dye contributions from the singleplex assay with RMSElabel = 6.42 × 10−2. These results demonstrate the potential of CNN‐based ML to advance SERS‐based diagnostics.
Current trends in nonoperative management for rectal adenocarcinoma: An unequal playing field?
Authors: Lee Katherine C. , Zhao Beiqun , Pianka Kurt , Liu Shanglei , Eisenstein Samuel , Ramamoorthy Sonia , Lopez Nicole E.
Published: September 2022

Background and Objectives

Increasing evidence suggests patient‐oriented benefits of nonoperative management (NOM) for rectal cancer. However, vigilant surveillance requires excellent access to care. We sought to examine patient, socioeconomic, and facility‐level factors associated with NOM over time.

Methods

Using the National Cancer Database (2006–2017), we examined patients with Stage II–III rectal adenocarcinoma, who received neoadjuvant chemoradiation and received NOM versus surgery. Factors associated with NOM were assessed using multivariable logistic regression with backward stepwise selection.

Results

There were 59,196 surgical and 8520 NOM patients identified. NOM use increased from 12.9% to 15.9% between 2006 and 2017. Patients who were Black (adjusted odds ratio [aOR]: 1.36, 95% confidence interval [CI]: 1.26–1.47), treated at community cancer centers (aOR: 1.22, 95% CI: 1.12–1.30), without insurance (aOR: 1.87, 95% CI: 1.68–2.09), and with less education (aOR: 1.53, 95% CI: 1.42–1.65) exhibited higher odds of NOM. Patients treated at high‐volume centers (aOR: 0.79, 95% CI: 0.74–0.84) and those who traveled >25.6 miles for care (aOR: 0.59, 95% CI: 0.55–0.64) had lower odds of NOM.

Conclusions

Vulnerable groups who traditionally have difficulty accessing comprehensive cancer care were more likely to receive NOM, suggesting that healthcare disparities may be driving utilization. More research is needed to understand NOM decision‐making in rectal cancer treatment.
Estimating roe deer density using motion‐sensitive cameras in Switzerland
Authors: Hinojo Amael , Christe Philippe , Moreno Inès , Hofmeister Robin J. , Dandliker Gottlieb , Zimmermann Fridolin
Published: September 2022

Wildlife conservation and management need accurate methods for population survey and monitoring. Absolute counts of roe deer populations (Capreolus capreolus) are not possible, but the rapid advancement of motion‐sensitive camera technologies and new analytical approaches might potentially lead to more precise estimates at lower costs compared to traditional survey methods. We applied spatially explicit photographic capture–recapture models (SCR) in the Lake Geneva basin, Switzerland, from 25 April to 20 September 2018 to estimate roe deer densities in a pilot survey. We investigated the effect of survey duration and camera density on male roe deer density estimates to select the sampling design that produced density estimates with sufficient accuracy and precision at lower costs (i.e., material, fieldwork, data processing, and analyses). Males could be identified based on their antlers, which allowed us to apply SCR to estimate their density. Because females could not be identified individually, we inferred the overall roe deer density (adult and sub‐adult roe deer) based on the sex ratio estimated from motion‐sensitive camera photos. According to the results of sub‐sampling simulations and by taking into account the financial costs associated with fieldwork and analyses, we conclude that 20 motion‐sensitive cameras set over 20 nights (i.e., the 20/20 method) is a good compromise to provide reliable estimates of male roe deer density. Furthermore, studies estimating overall roe deer density using SCR and sex ratio estimates should be conducted from mid‐August to the end of October just after rutting season and the peak of yearling dispersal, when the movement rates of males and females, and hence their detection probabilities, are similar and when males are still carrying their antlers. This approach was successfully applied in 4 selected study areas with contrasting roe deer management regimes, resulting in overall roe deer density estimates ranging from 3.9 ± 1.3 (SE) deer/km2 forest to 22.5 ± 6.1 deer/km2 forest. Our study provides a valuable and cost‐effective approach using photographic SCR methodology and sex ratio information to calculate roe deer density estimates that can be used in management measures such as defining hunting quotas.
Exploring synergies between India's climate change and land degradation targets: Lessons from the Glasgow Climate COP
Authors: Dhyani Shalini , Santhanam Harini , Dasgupta Rajarshi , Bhaskar Dhanya , Murthy Indu K. , Singh Kripal
Published: September 2022

Land degradation, extending over 96 million hectares is a primary ecological issue for India that has resulted in catastrophic biodiversity loss and exacerbated extreme weather occurrences. One of the major sources of land degradation is large‐scale coal mining to realize country's expanding energy demands. By 2050 climate change and land degradation, will result in US$1730 billion loss for India. Climate COP in Glasgow, 2021 was a watershed event to confront broader climate change challenges. India made one of the boldest pledges to pursue the road of climate justice, protect the most vulnerable, and committed to achieving net‐zero emissions by 2070. This means gradually phasing down coal, reducing emissions and mainstreaming renewable sources. Given the prospect of five challenging but attainable targets, we examine India's readiness and the ramifications of these targets on land degradation reduction. Indian government is continuously increasing strategic support for improved mine closure and mine void restoration while, ensuring that land restoration supports ‘green’ job creation for poverty alleviation. While there is focus on investing significant amounts of national funding to address land degradation, international and private finances can enable to accomplish the larger goals. To enhance the effectiveness of the promises, we propose embedding diverse knowledge systems including indigenous knowledge systems and capabilities by formulating policies that incentivize environmental restoration, people‐centric, climate sensitive strategies, convergence between different government departments as well as schemes, and mainstreaming of systems thinking as a social transformation approach for achieving coupled Climate and Land Degradation Neutrality targets by 2030 and 2070.
Remote‐sensing‐based monitoring the dynamics of Kyagar Glacial Lake in the upstream section of Yarkant River, north Karakoram
Authors: Luo Yunyi , Liu Qiao , Zhong Yan , Han Wang
Published: September 2022

Long‐term monitoring of ice‐dammed lakes is important for understanding the process of lake storage, development, and glacial outburst flood (GLOF). Based on remote sensing observations for the period 1972–2020, we obtained what is so far the most detailed reconstruction of the filling and draining of Kyagar Lake, a typical annually ice‐dammed lake in the north Karakoram. We show that annually repeated lake fillings‐drainings were detected by satellite observations during two periods: 1996–2009 and 2015–2020, while between 2009 and 2015 no obvious cycle occurred. These two intermitted periods with regular annual revival of lake outburst were likely related to the long‐term cycle of glacier surge dynamics, namely two remarkable surge‐induced terminus accelerations during 1995–1997 and 2014–2016. Following each surge, the maximum lake areas decreased by about 33% from 1996 to 2009 and by about 88% from 2015 to 2020. Combined with climatic warming and the thinning of the ice‐dam, the storage capacity of Kyagar Lake will likely continue to decrease in the future, and the risk of lake outburst flood thus becomes lower. Repeated drainage following filling exacerbates the depletion of mass at the glacier terminal, leading to the cessation of storage and creating the conditions for the next glacial surge to occur, creating a long‐term iteration of the surge process. Considering the uncertainty and intensified climate changes, it suggests that a close monitoring of the glacial lake development and glacier dynamics would be still important.
Impacts of grass planting density and components on overland flow hydraulics and soil loss
Authors: Fu Yu , Wang Dichen , Sun Wenping , Guo Mingming
Published: September 2022

Although abundant studies have confirmed the positive effect of vegetation on runoff and soil erosion reduction, few studies have clarified the effects of planting density and its components (aboveground parts and roots) on slope runoff and soil erosion mechanisms. A series of field experimental plots were constructed on two slopes (3°, 6°), including a bare land plot as the control, three grassed plots with three grass (Agropyron cristatum) planting densities of 20 cm × 20 cm, 15 cm × 15 cm, and 10 cm × 10 cm, and a plot without aboveground parts, to examine runoff and soil erosion process under simulated overland flow of 4, 8, 12, and 16 L min−1. The runoff regime was transformed from supercritical‐turbulent flow to subcritical‐laminar flow with increasing planting density. Grass significantly reduced the runoff rate (RR), velocity (V), shear stress (τ), stream power (ω), and soil loss rate (SLR), with average reductions of 38.6%, 56.6%, 76.5%, 87.6%, and 61.9%, respectively. The aboveground parts contributed 74.1% and 75.1% of the total reduction in RR and V, respectively, while the grass roots contributed to 84.9%, 89.7%, 84.9%, and 69.7% of the reductions in Reynolds number, τ, ω, and SLR, respectively. RR, V, τ, ω, and SLR were significantly affected by slope, inflow discharge, root density, and the ratio of grass stem area to plot area. The runoff–sediment relationship changed from positively exponential function to linear and power functions with the planting density increased. Grass significantly weakened the sensitivity of soil erosion by reducing soil erodibility and improving critical hydrodynamic triggering soil erosion. This study improved the understanding of grass controlling soil and water loss, and the plants with well‐developed roots and planting space of 10–15 cm are preferred to provide a scientific reference for revegetation strategy.
Anthropogenic land uses drive shifts in denitrification‐related microbiota in freshwater river ecosystems
Authors: Liu Xing , Pan Baozhu , Huang Zhenyu , Liu Xinyuan , He Haoran , Zhu Xinzheng
Published: September 2022

Microbiota play essential roles in nitrogen (N) cycling in freshwater river ecosystems. However, our understanding of microbial functional groups associated with N cycling (especially denitrification) in freshwater rivers under anthropogenic disturbance is still poor. Here, we studied the impacts of different land‐use types on denitrification‐related microbiota in the Weihe River, Hanjiang River, and their tributaries, in the Qinling Mountains, China. The major land‐use types in the three river areas were divided into natural (forest, shrub, grassland, and open water) and anthropogenic (agricultural and urbanized land) types. A landscape survey of microbiota in the river water and sediment was carried out with extensive sample sources based on deep 16S rRNA gene sequencing, which yielded operational taxonomic units for predicting functional groups. With increases in proportions of agricultural and urbanized land areas, electrical conductivity, total N, ammonium‐N, and nitrate‐N all increased in water samples. Conversely, microbial diversity exhibited a decreasing trend in water samples, whereas the relative abundance of denitrification‐related functional groups increased, with increases in the proportions of agricultural and urbanized land areas. The relative abundances of denitrification‐ and human‐related microbial functional groups in sediment samples were distinctively higher in Weihe River (mainly under agriculture and urbanization), when compared with those of Hanjiang River and Qinling tributaries (dominated by forests). The results indicate that anthropogenic land‐use types, such as agricultural and urbanized land, result in simple microbial community structure and stimulate microbe‐mediated denitrification in freshwater rivers.
Biogeography and ecological functions of root‐associated and soil fungi of Pinus sylvestris var. mongolica across different afforestation areas in desertified Northern China
Authors: Zhao Peishan , Gao Guanglei , Ding Guodong , Zhang Ying , Ren Yue , Wang Jiayuan
Published: September 2022

China has unquestionably led efforts to 'green' drylands, but an evaluation of the large‐scale effects of afforestation in desert ecosystems mediated by soil microorganisms is lacking. The ecological functions of fungi are closely related to soil and plant health. Therefore, there is a lively interest in revealing the biogeographic patterns of root‐associated (RAF) and soil fungal (SF) communities of Pinus sylvestris var. mongolica, a widespread evergreen tree endemic to Northern China. We revealed the community assembly of RAF and SF of natural forest and plantations in the Hulunbuir Desert, Horqin Desert, and Mu Us Desert and investigated fungal responses to geographical location, climate factors, soil properties, and stand age at regional and local scales. The results indicated that (1) SF was more diverse than RAF. For RAF, the diversity indices in the natural forest were significantly lower than those in plantations, and ectomycorrhizal fungi (50.37%) were the predominant functional guild in the natural forest. (2) At the local scale, SF, not RAF, is more sensitive to the impacts of soil properties. More than half of the differential genera were ectomycorrhizal and endophytic fungi, such as Acephala, Cadophora, Pustularia, and Trichoderma. (3) On the regional scale, precipitation and sunshine duration were the main influences on geographical differences in the fungal community composition. Geographical location directly and significantly influences RAF diversity and structure. The effect of climate factors on SF diversity was low, but it had a shaping effect on SF structure. Our results demonstrated that the fungal communities were geographically structured, a stable relationship was established between hosts and RAF, and soil nutrients had a significant impact on SF community composition. The ecological functions of fungi are important in evaluating afforestation efforts and maintaining stability in desert ecosystems.