bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted delivery of maytansine to liver cancer cells via galactose-modified supramolecular two-dimensional glycomaterial
Authors: Xie Hai-Na , Chen Yu-Yuan , Zhu Guo-Biao , Han Hai-Hao , Hu Xi-Le , Pan Zhi-Qiang , Zang Yi , Xie Dong-Hao , He Xiao-Peng , Li Jia , James Tony D.
Published: March 2022

A two-dimensional (2D) glycomaterial for targeted delivery of maytansine to liver cancer cells was developed.
A healable, recyclable and thermochromic epoxy resin for thermally responsive smart windows
Authors: Huang Qi-Sheng , Zhao Pei-Chen , Lai Jian-Cheng , Zhang Xiao-Peng , Li Cheng-Hui
Published: March 2022

An epoxy resin modified by coordination between Ni2+and imidazole/hydroxyl groups show high mechanical strength and thermal healing/recycling/reprocessing/thermochromic behavior, and might be useful in the field of thermally-responsive smart windows.
Cascade Michael/aldol/rearrangement between phenacylmalononitriles and maleimides: highly diastereoselective access to functionalized bicyclic cyclopentenes containing a CN-substituted all-carbon quaternary center
Authors: Gao Li , Li Gaihui , Li Xiaokang , Zhang Guoshun , Zhang Min , Li Qingshan , Ban Shurong
Published: March 2022

A highly diastereoselective approach towards the synthesis of quaternary center-containing cyclopentenes was developed. The tandem Michael/aldol/rearrangement processes occurred under mild reaction conditions.
Polymer mechanochemistry for the release of small cargoes
Authors: Shen Hang , Cao Yunzheng , Lv Miaojiang , Sheng Qinxin , Zhang Zhengbiao
Published: March 2022

We review the recent progress on polymer mechanochemistry that releases small cargoes, followed by our perspectives on future developments.
Combining the most suitable energetic tetrazole and triazole moieties: synthesis and characterization of 5-(1-hydroxy-3-nitro-1,2,4-triazol-5-yl)-1-hydroxy-tetrazole and its nitrogen-rich ionic derivatives
Authors: Bauer Lukas , Benz Maximilian , Klapötke Thomas M. , Pignot Cedric , Stierstorfer Jörg
Published: March 2022

The combination of 1-hydroxy-tetrazole and 1-hydroxy-1,2,4-triazole produces a new bisheterocyclic moiety, which is characterized and derivatized extensively. We tried to combine the positive advantages of the TKX-50 and MAD-X1 backbone with this new building block.
F127-assisted preparation of FeCo nanoalloys encapsulated in nitrogen-doped carbon for efficient oxygen reduction reaction
Authors: Zhao Jianbo , Bing Wanzhen , Yuan Haifeng , Yang Weichuang , Li Xiaomeng , Zhang Meng , Han Lifeng , Jia Xiaodong , Chen Shanyong
Published: March 2022

A novel F127-assisted ZIF-67 pyrolysis strategy to construct FeCo nanoalloys encapsulated in nitrogen-doped carbon for efficient oxygen reduction reaction was reported.
Feasability of An Eccentric Isokinetic Protocol to Induce Trunk
Muscle Damage: A Pilot Study
Authors: Engel Tilman , Schraplau Anne , Wochatz Monique , Kopinski Stephan , Sonnenburg Dominik , Schomoeller Anne , Risch Lucie , Kaplick Hannes , Mayer Frank
Published: March 2022

Eccentric exercise is discussed as a treatment option for clinical populations,
but specific responses in terms of muscle damage and systemic inflammation after
repeated loading of large muscle groups have not been conclusively
characterized. Therefore, this study tested the feasibility of an isokinetic
protocol for repeated maximum eccentric loading of the trunk muscles. Nine
asymptomatic participants (5 f/4 m;
34±6 yrs; 175±13 cm; 76±17 kg)
performed three isokinetic 2-minute all-out trunk strength tests (1x concentric
(CON), 2x eccentric (ECC1, ECC2), 2 weeks apart; flexion/extension,
60°/s, ROM 55°). Outcomes were peak torque, torque
decline, total work, and indicators of muscle damage and inflammation (over
168 h). Statistics were done using the Friedman test (Dunn’s
post-test). For ECC1 and ECC2, peak torque and total work were increased and
torque decline reduced compared to CON. Repeated ECC bouts yielded unaltered
torque and work outcomes. Muscle damage markers were highest after ECC1
(soreness 48 h, creatine kinase 72 h; p<0.05). Their
overall responses (area under the curve) were abolished post-ECC2 compared to
post-ECC1 (p<0.05). Interleukin-6 was higher post-ECC1 than CON, and
attenuated post-ECC2 (p>0.05). Interleukin-10 and tumor necrosis
factor-α were not detectable. All markers showed high inter-individual
variability. The protocol was feasible to induce muscle damage indicators after
exercising a large muscle group, but the pilot results indicated only weak
systemic inflammatory responses in asymptomatic adults.
Analysis of the Results of Sonographic Screening Examinations According to the Maternity Guidelines Before and After the Introduction of the Extended Basic Screening (IIb Screening) in Hesse
Authors: Schmand Christine , Misselwitz Björn , Hudel Helge , Bedei Ivonne , Wolter Aline , Schenk Johanna , Keil Corinna , Köhler Siegmund , Axt-Fliedner Roland
Published: March 2022

Aim of the Study The aim of the study is to examine the detection rates of malformations before and after the introduction of extended basic screening in Hesse by the Federal Joint Committee (Gemeinsamer Bundesausschuss, GQH) on July 1, 2013.

Method This is a retrospective, mainly exploratory data analysis of quality assurance data from the Office for Quality Assurance in Hesse (GQH). The data was collected in the period from January 1, 2010 to December 31, 2016 in the obstetric departments of the Hessian hospitals using documentation forms. The classification and evaluation of the diagnoses is based on ICD-10-GM-2019.

Results At least one malformation is present in 0.7% of the cases. With a share of 30.0%, most of the congenital malformations are from the musculoskeletal system. 12.2% of the malformations come from the facial cleft, closely followed by malformations of the circulatory system with 11.3%. The highest prenatal detection rate (PDR) is found in congenital malformations of the nervous system at 56.8%. The lowest PDR is found in those of the genital organs with 2.1%. The PDR of cardiovascular malformations is 32.9%. Overall, a PDR of 25.2% is achieved. There was no change in the number of prenatal malformation diagnoses after the introduction of extended basic ultrasound. The distribution of malformation diagnoses not detected prenatally to the organ systems also has not changed after the introduction.

Conclusion The introduction of extended basic ultrasound did not bring the desired improvement with regard to the PDR in Hesse. Alternative approaches should be considered.
Transporter-mediated Natural Product-Drug Interactions
Authors: Bi Yajuan , Wang Xue , Ding Hui , He Feng , Han Lifeng , Zhang Youcai
Published: March 2022

The increasing use of natural products in clinical practice has raised great concerns about the potential natural product-drug interactions (NDIs). Drug transporters mediate the
transmembrane passage of a broad range of drugs, and thus are important determinants for drug pharmacokinetics and pharmacodynamics. Generally, transporters can be divided into ATP binding
cassette (ABC) family and solute carrier (SLC) family. Numerous natural products have been identified as inhibitors, substrates, inducers, and/or activators of drug transporters. This review
article aims to provide a comprehensive summary of the recent progress on the research of NDIs, focusing on the main drug transporters, such as P-glycoprotein (P-gp), breast cancer
resistance protein (BCRP), organic anion transporter 1 and 3 (OAT1/OAT3), organic anion-transporting polypeptide 1B1 and 1B3 (OATP1B1/OATP1B3), organic cation transporter 2 (OCT2), multidrug
and toxin extrusion protein 1 and 2-K (MATE1/MATE2-K). Additionally, the challenges and strategies of studying NDIs are also discussed.
On the Need to Revitalize Descriptive Epidemiology
Authors: Fox Matthew P , Murray Eleanor J , Lesko Catherine R , Sealy-Jefferson Shawnita
Published: March 2022

Nearly every introductory epidemiology course begins with a focus on person, place, and time, the key components of descriptive epidemiology. And yet in our experience, introductory epidemiology courses were the last time we spent any significant amount of training time focused on descriptive epidemiology. This gave us the impression that descriptive epidemiology does not suffer from bias and is less impactful than causal epidemiology. Descriptive epidemiology may also suffer from a lack of prestige in academia and may be more difficult to fund. We believe this does a disservice to the field and slows progress towards goals of improving population health and ensuring equity in health. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and subsequent coronavirus disease 2019 pandemic have highlighted the importance of descriptive epidemiology in responding to serious public health crises. In this commentary, we make the case for renewed focus on the importance of descriptive epidemiology in the epidemiology curriculum using SARS-CoV-2 as a motivating example. The framework for error we use in etiological research can be applied in descriptive research to focus on both systematic and random error. We use the current pandemic to illustrate differences between causal and descriptive epidemiology and areas where descriptive epidemiology can have an important impact.
Blood Pressure Goals in Acute Stroke
Authors: Guo Qian-Hui , Liu Chu-Hao , Wang Ji-Guang
Published: March 2022

Antihypertensive treatment is highly effective in both primary and secondary prevention of stroke. However, current guideline recommendations on the blood pressure goals in acute stroke are clinically empirical and generally conservative. Antihypertensive treatment is only recommended for severe hypertension. Several recent observational studies showed that the relationship between blood pressure and unfavorable clinical outcomes was probably positive in acute hemorrhagic stroke but J- or U-shaped in acute ischemic stroke with undetermined nadir blood pressure. The results of randomized controlled trials are promising for blood pressure management in hemorrhagic stroke but less so in ischemic stroke. A systolic blood pressure goal of 140 mm Hg is probably appropriate for acute hemorrhagic stroke. The blood pressure goal in acute ischemic stroke, however, is uncertain, and probably depends on the time window of treatment and the use of revascularization therapy. Further research is required to investigate the potential benefit of antihypertensive treatment in acute stroke, especially with regard to the possible reduction of blood pressure variability and more intensive blood pressure lowering in the acute and subacute phases of a stroke, respectively.
Upper Facial Anastomoses Between the External and Internal Carotid Vascular Territories – A 3D Computed Tomographic Investigation
Authors: Li Zhen-Hao , Alfertshofer Michael , Hong Wei-Jin , Li Xin-Rui , Zhang You-Liang , Moellhoff Nicholas , Frank Konstantin , Luo Sheng-Kang , Cotofana Sebastian
Published: March 2022

Background

Facial regions with a high risk for causing injection-related visual comprise are dual-supply vascular areas such as the nose, glabella, and forehead. These regions have in common that they receive arterial blood supply both by branches of the internal (ICA) and the external carotid artery (ECA).

Objective

The authors sought to investigate the anastomotic pathways between ICA and ECA branches in the upper face.

Methods

Postmortem computed tomographic angiographic scans of n = 38 Chinese non-embalmed hemifaces (25 males, 13 females; mean age, 37.79 [11.8] years; mean BMI, 21.90 [2.3] kg/m2) were conducted. Data analysis relied on the calculation of depth, distances, and pathways of forehead and temporal arteries to investigate the number of anastomotic connections, the connecting branches, and the layer of connection between ICA and ECA territories.

Results

Between ICA and ECA territories, only 1 connection in 57.9%, 2 connections in 31.6%, 3 connections in 5.3%, and 4 and 5 connections in 2.6% each were identified. A superficial connection was observed in 15.8% whereas in 84.2% the anastomotic connection was identified to be both superficial and deep.

Conclusions

Adverse events following facial minimally invasive soft-tissue filler injections for aesthetic purposes are not frequent but devastating if they occur. Anatomic knowledge as presented in this study can help to increase awareness of 3-dimensional vascular anastomotic pathways and identify safer injection zones and safer fascial planes. Evidence-based injection techniques should be followed, and safety aspects should be placed over the aesthetic outcome.
PacRAT: a program to improve barcode-variant mapping from PacBio long reads using multiple sequence alignment
Authors: Yeh Chiann-Ling C , Amorosi Clara J , Showman Soyeon , Dunham Maitreya J
Published: March 2022

Use of PacBio sequencing for characterizing barcoded libraries of genetic variants is on the rise. However, current approaches in resolving PacBio sequencing artifacts can result in a high number of incorrectly identified or unusable reads. Here, we developed a PacBio Read Alignment Tool (PacRAT) that improves the accuracy of barcode-variant mapping through several steps of read alignment and consensus calling. To quantify the performance of our approach, we simulated PacBio reads from eight variant libraries of various lengths and showed that PacRAT improves the accuracy in pairing barcodes and variants across these libraries. Analysis of real (non-simulated) libraries also showed an increase in the number of reads that can be used for downstream analyses when using PacRAT.

Availability and implementation

PacRAT is written in Python and is freely available (https://github.com/dunhamlab/PacRAT).

Supplementary information

Supplemental data are available at Bioinformatics online.
EDClust: an EM–MM hybrid method for cell clustering in multiple-subject single-cell RNA sequencing
Authors: Wei Xin , Li Ziyi , Ji Hongkai , Wu Hao
Published: March 2022

Motivation

Single-cell RNA sequencing (scRNA-seq) has revolutionized biological research by enabling the measurement of transcriptomic profiles at the single-cell level. With the increasing application of scRNA-seq in larger-scale studies, the problem of appropriately clustering cells emerges when the scRNA-seq data are from multiple subjects. One challenge is the subject-specific variation; systematic heterogeneity from multiple subjects may have a significant impact on clustering accuracy. Existing methods seeking to address such effects suffer from several limitations.

Results

We develop a novel statistical method, EDClust, for multi-subject scRNA-seq cell clustering. EDClust models the sequence read counts by a mixture of Dirichlet-multinomial distributions and explicitly accounts for cell-type heterogeneity, subject heterogeneity and clustering uncertainty. An EM-MM hybrid algorithm is derived for maximizing the data likelihood and clustering the cells. We perform a series of simulation studies to evaluate the proposed method and demonstrate the outstanding performance of EDClust. Comprehensive benchmarking on four real scRNA-seq datasets with various tissue types and species demonstrates the substantial accuracy improvement of EDClust compared to existing methods.

Availability and implementation

The R package is freely available at https://github.com/weix21/EDClust.

Supplementary information

Supplementary data are available at Bioinformatics online.
Maternal body mass index is associated with an altered immunological profile at 28 weeks of gestation
Authors: Rees April , Richards Oliver , Allen-Kormylo Anastasia , Jones Nicholas , Thornton Catherine A
Published: March 2022

Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surrounding obesity and the maternal immune system. The objective of this study was to consider if immunological changes in pregnancy are influenced by maternal obesity. Peripheral blood was collected from fasted GDM-negative pregnant women at 26–28 weeks of gestation. Analysis was done using immunoassay, flow cytometry, bioenergetics analysis, and cell culture. The plasma profile was significantly altered with increasing BMI, specifically leptin (r = 0.7635), MCP-1 (r = 0.3024), and IL-6 (r = 0.4985). Circulating leukocyte populations were also affected with changes in the relative abundance of intermediate monocytes (r = –0.2394), CD4:CD8 T-cell ratios (r = 0.2789), and NKT cells (r = –0.2842). Monocytes analysed in more detail revealed elevated CCR2 expression and decreased mitochondrial content with increased BMI. However, LPS-stimulated cytokine production and bioenergetic profile of PBMCs were not affected by maternal BMI. The Th profile skews towards Th17 with increasing BMI; Th2 (r = –0.3202) and Th9 (r = –0.3205) cells were diminished in maternal obesity, and CytoStim™-stimulation exacerbates IL-6 (r = 0.4166), IL-17A (r = 0.2753), IL-17F (r = 0.2973), and IL-22 (r = 0.2257) production with BMI, while decreasing IL-4 (r = –0.2806). Maternal obesity during pregnancy creates an inflammatory microenvironment. Successful pregnancy requires Th2-biased responses yet increasing maternal BMI favours a Th17 response that could be detrimental to pregnancy. Further research should investigate key populations of cells identified here to further understand the immunological challenges that beset pregnant women with obesity.
Crustal thickness and Poisson's ratios in eastern China estimated jointly by receiver function and gravity data
Authors: Tang Hanhan , Guo Lianghui , Chen Guojiang , Huang Zhangrong , Fang Yuan
Published: March 2022

Crustal thickness and Poisson's ratio have played significant roles in determining the crustal structure, compositions and deformation. We improved the algorithm for joint estimation by receiver function and gravity data on the optimization of initial model, sediment-correction, as well as estimation of associated density parameter, and utilized it to estimate the crustal thickness and Poisson's ratios in eastern China. The uncertainty analyses verified the reliability of our model. Our results demonstrate that the crustal thickness in eastern China increases gradually from east (about 26.6 km) to west (about 62.4 km) with an NNE-trending gradient zone along the line of Great Khingan-Taihang-Wuling Orogenic belt. The crustal Poisson's ratios in eastern China, ranging from 0.19 to 0.31, reflect the characteristics of different tectonic blocks. Low crustal Poisson's ratios are mainly presented along the sutural and orogenic belts between tectonic blocks. Low Poisson's ratio associated with the Central Asian Orogenic Belt accretionary wedge suggests that it extends further east than previously thought, beneath the Songliao Basin (between the city line of Sonid Right Banner-Linxi-Tongliao-Jilin-Wangqing and Bayan-Huade-Chifeng-Liaoyuan-Helong). After reducing the influence of the sediment, banded-like high-Poisson's ratios show up in Sichuan Basin and Ordos Basin. Combined with the magnetic data and petrophysical properties, we speculate it to be the intrusions of intermediate-basic rocks in the basement. High Poisson's ratios presented in the northern Songliao Basin may be related to multistage magmatic intrusions and eruptions since Meso-Cenozoic. High Poisson's ratios in Panxi rift are related to magmatic activities caused by mantle plumes.
Soviet Publications of Holocaust Diaries in the 1960s: Anne Frank and Masha Rolnikaite
Authors: Estraikh Gennady
Published: March 2022

A strict ban on organized Jewish activities apart from those of a limited number of religious bodies, coupled with the state monopoly on all publishing, simplified the Soviet Union’s control over Holocaust-related publication. The appearance of any such work was an idiosyncratic event, associated with concurrent political and cultural contexts and official agendas. The relatively liberal climate of the first post-Stalinist decade raised the possibility of such events. Soviet publication of both the diary of Anne Frank and Masha Rolnikaite’s I Must Tell reflected in part foreign policy considerations, but each played a rather different role in the Soviet cultural sphere. Anne Frank’s diary—not reprinted for three decades—would be referred to as, and possibly read only as, an important anti-fascist narrative with distant relevance to wartime events in the Soviet Union. Masha Rolnikaite (Rolnik), a survivor of the Vilnius ghetto, would become a widely published belletrist “Soviet Anne Frank.”
Safety and Benefits of Intraoperative Enteral Nutrition in Critically Ill Pediatric Burn Patients: A Systematic Review and Pooled Analysis
Authors: Hudson Alexandra S , Morzycki Alexander D , Wong Joshua
Published: March 2022

Burn injuries significantly increase a patient’s metabolic demand. Adequate nutrition is essential as an adjunct to recovery and reducing morbidity and mortality. In contrast to adults, this is especially important for pediatric patients who have limited reserves and are in a period of growth. Burn patients often require multiple anesthetic procedures that are accompanied by standard perioperative fasting periods that result in substantial nutritional interruptions. Continuous intraoperative feeding has been proposed as a solution, but there is no current consensus on its role and safety, particularly in the pediatric population. Thus, the goal of this study was to examine the safety and benefits of intraoperative nutrition in critically ill pediatric burn injured patients. A systematic review of MEDLINE, PubMed, Scopus, and Web of Science was conducted using the following terms: feeding or enteral or nutrition or fasting and adolescent or youth or pediatric or child or teen and burn or thermal injury or fire. The primary outcome was incidence of aspiration. Secondary outcomes included patient nutritional status (caloric deficit and weight), wound healing, days spent in the intensive care unit, ventilator days, pneumonia, number of surgeries, length of hospital stay, and mortality. Pooled analyses of binary outcomes were computed. Four studies consisting of 496 patients, met inclusion criteria. All studies were level IV evidence, but had high methodological quality. The median burn TBSA was 43.8% (interquartile range 33.4%–58.8%), with a median of 30% of patients having an inhalational injury. Patients underwent a median of 4.2 surgeries (interquartile range 1.8–7.4). Intraoperative feeding was conducted through nasoduodenal tubes. There were no aspiration events. Pooled analysis demonstrated that there were no differences in rates of aspiration, pneumonia, or wound infection (P > .05) between patients who were intraoperatively fed and those who were not. Those fed intraoperatively had significantly more surgeries, ventilator days, longer hospital stays, but lower mortality (P < .05). There was large heterogeneity in nutritional assessment methods. Intraoperatively fed patients had an average gain of 144.4 kcal/kg, 1.7 days of exclusive enteral nutrition (vs loss of −119.1 kcal/kg and −1.4 days), and a cumulative positive caloric balance of +2673 kcal ± 2147 (vs loss of −7899 kcal ± 3123) compared to those with interrupted feeding. Continuous intraoperative duodenal feeding during burn surgery appears to be safe in the pediatric burn population, with no reported episodes of aspiration. Uninterrupted feeding was also associated with weight maintenance and reduced caloric deficit. It may also have a survival benefit, as continuously fed patients needed more surgeries and intensive/hospital care, but had decreased mortality.
Quantitative Nodal Burden and Mortality Across Solid Cancers
Authors: Nguyen Anthony T , Luu Michael , Nguyen Vina P , Lu Diana J , Shiao Stephen L , Kamrava Mitchell , Atkins Katelyn M , Mita Alain C , Scher Kevin S , Spratt Daniel E , Faries Mark B , Daskivich Timothy J , Lin De-Chen , Chen Michelle M , Clair Jon Mallen-St , Sandler Howard M , Ho Allen S , Zumsteg Zachary S
Published: March 2022

Background

Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors.

Methods

We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses.

Results

Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites.

Conclusions

Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors.
Trichofolliculoma of the external auditory canal: a case report and review of the literature
Authors: Saleem Matthew I , Tham Tristan , Ponder Brent , Georgolios Alexandros
Published: March 2022

Trichofolliculoma is a rare tumor that arises from immature hair follicular tissue. In this report, we present the case of a 51-year-old man with a trichofolliculoma in the left external auditory canal. Uniquely, there was no prior trauma in this patient, despite previous trauma being hypothesized in the etiology of this tumor. The lesion was excised using microsurgical instruments and the tumor was closely adherent to the cartilage of the external auditory canal. Histopathology following excisional biopsy confirmed the diagnosis.
A simple pipeline for cell cycle kinetic studies in the root apical meristem
Authors: Pasternak Taras , Kircher Stefan , Pérez-Pérez José Manuel , Palme Klaus
Published: March 2022

Root system architecture ultimately depends on precise signaling between different cells and tissues in the root apical meristem (RAM) and integration with environmental cues. This study describes a simple pipeline to simultaneously determine cellular parameters, nucleus geometry, and cell cycle kinetics in the RAM. The method uses marker-free techniques for nucleus and cell boundary detection, and 5-ethynyl-2ʹ-deoxyuridine (EdU) staining for DNA replication quantification. Based on this approach, we characterized differences in cell volume, nucleus volume, and nucleus shape across different domains of the Arabidopsis RAM. We found that DNA replication patterns were cell layer and region dependent. G2 phase duration, which varied from 3.5 h in the pericycle to more than 4.5 h in the epidermis, was found to be associated with some features of nucleus geometry. Endocycle duration was determined as the time required to achieve 100% EdU-positive cells in the elongation zone and, as such, it was estimated to be in the region of 5 h for the epidermis and cortex. This experimental pipeline could be used to precisely map cell cycle duration in the RAM of mutants and in response to environmental stress in several plant species without the need for introgressing molecular cell cycle markers.
Foliar chlorophyll concentration modulates the degree of fungal exploitation in a rhizoctonia-associated orchid
Authors: Suetsugu Kenji , Matsubayashi Jun
Published: March 2022

Some green orchids obtain carbon from both mycobionts and photosynthesis at the adult stage. Intriguingly, these orchids can produce albino and, in rare cases, variegated phenotypes. Here, we studied a Platanthera hondoensis population with green, variegated, and albino individuals. Although its closely related Platanthera species are usually associated with non-ectomycorrhizal rhizoctonias, and several studies have failed to find evidence of trophic plasticity in rhizoctonia-associated orchids, variegated and albino P. hondoensis must possess a higher fungal dependency than green P. hondoensis. Therefore, we investigated whether (i) P. hondoensis is associated with non-ectomycorrhizal rhizoctonias and (ii) the degree of mycoheterotrophy (using 13C abundance as a proxy) correlates with the foliar chlorophyll concentration. High-throughput DNA sequencing revealed that all P. hondoensis phenotypes were dominantly associated with a rhizoctonia from Ceratobasidiaceae belonging to a clade distinct from recognized ectomycorrhizal clades. Regression analysis revealed a positive linear relationship between foliar chlorophyll concentration and the degree of mycoheterotrophy. This study strongly suggests that rhizoctonia-associated P. hondoensis can dynamically adjust fungal exploitation in response to photosynthetic carbon levels. Since rhizoctonia is the most common orchid mycorrhizal partner, trophic plasticity may be a widespread adaptive trait in green orchids.
Pathogenic Homozygous Mutations in the DBT Gene (c.1174A>C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier
Authors: Alijanpour Morteza , Jazayeri Omid , Soleimani Amiri Shima , Brosens Erwin
Published: March 2022

Objective

Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns.

Methods

Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients.

Results

We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A > C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A > G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A > C), lead to terminate these various interpretations of c.1150 A > G variant.

Conclusion

Our study introduced c.1150 A > G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.
Influenza Vaccine Booster Stimulates Antibody Response in Beta Thalassemia Major Patients
Authors: Sheikh Maryam , Ahmadi-Vasmehjani Abbas , Atashzar Mohammad Reza , Karbalaie Niya Mohammad Hadi , Ebrahimian Arefeh , Baharlou Rasoul
Published: March 2022

The aim of this study was to evaluate antibody response against influenza vaccine in beta thalassemia major patients from Iran. Thirty beta thalassemia major patients were enrolled and divided into three groups: single dose (group 1), double dose (group 2), and control (group 3). Seroconversion, seroprotection, and geometric mean titer (GMT) assays were performed through hemagglutination inhibition (HI) on days 0, 14, and 60. Based on the results, the level of antibody titer was increased in group 2. Two weeks after vaccination, seroconversion rate was about 20% and 30% in groups 1 and 2. Sixty days after vaccination, the seroconversion rate was around 70% and GMT showed a more than 2-fold increase in group 2. Based on the results, the immunogenicity of double dose vaccination against influenza infection appears to be higher than the single dose vaccine in beta thalassemia major patients, and thus it is recommended to use two doses of vaccine, especially in splenectomized patients who are more sensitive than others.
In Search of Carl Czerny’s Schemata: Listening to Early Nineteenth-Century Improvisation
Authors: Rabinovitch Gilad
Published: March 2022

This article analyzes Carl Czerny’s exemplars for fantasizing in Systematische Anleitung zum Fantasieren auf dem Pianoforte (1829). I argue that a musical prototype combining scale-degree schemata (Meyer 1980, Gjerdingen 2007) and sentential features (Caplin 1998) emerges as an implicit knowledge structure in several of Czerny’s notated musical examples that demonstrate how to react to a given theme for improvisation. Through an examination of notated fantasies recommended by Czerny as models for extemporizing, I propose a beginning-of-fantasy prototype, which allows us to discern improvisatory qualities in Beethoven’s notated “artworks” such as the Tempest sonata, the Appassionata, and others.
Blood exosomes-based targeted delivery of cPLA2 siRNA and metformin to modulate glioblastoma energy metabolism for tailoring personalized therapy
Authors: Zhan Qi , Yi Kaikai , Cui Xiaoteng , Li Xueping , Yang Shixue , Wang Qixue , Fang Chuan , Tan Yanli , Li Lijie , Xu Can , Yuan Xubo , Kang Chunsheng
Published: March 2022

Background

Targeting glioblastoma (GBM) energy metabolism through multiple metabolic pathways has emerged as an effective therapeutic approach. Dual inhibition of phospholipid and mitochondrial metabolism with cytoplasmic phospholipase A2 (cPLA2) knockdown and metformin treatment could be a potential strategy. However, the strategic prerequisite is to explore a carrier capable of co-delivering the therapeutic combination to cross the blood-brain barrier (BBB) and preferentially accumulate at the GBM site.

Methods

Blood exosomes (Exos) were selected as the combination delivery carriers. The cellular uptake of Exos and the therapeutic effects of the combination strategy were evaluated in primary GBM cells. In vivo GBM-targeted delivery efficiency and anti-GBM efficacy were tested in a patient-derived xenograft (PDX) model.

Results

Here, we showed that the Exos-mediated cPLA2 siRNA/metformin combined strategy could regulate GBM energy metabolism for personalized treatment. Genomic analysis and experiments showed that polymerase 1 and transcript release factor (PTRF, a biomarker of GBM) positively regulated the uptake of Exos by GBM cells, confirming the feasibility of the delivery strategy. Further, Exos could co-load cPLA2 siRNA (sicPLA2) and metformin and co-deliver them across the BBB and into GBM tissue. The mitochondrial energy metabolism of GBM was impaired with this combination treatment (Exos-Met/sicPLA2). In the PDX GBM model, systemic administration of Exos-Met/sicPLA2 reduced tumor growth and prolonged survival.

Conclusions

Our findings demonstrated that Exos-based combined delivery of sicPLA2 and metformin selectively targeted the GBM energy metabolism to achieve antitumor effects, showing its potential as a personalized therapy for GBM patients.
Secondhand Aerosol Exposure From Heated Tobacco Products and Its Socioeconomic Inequalities in Japan: The JASTIS Study 2017–2020
Authors: Tamada Yudai , Takeuchi Kenji , Okawa Sumiyo , Tabuchi Takahiro
Published: March 2022

Introduction

The growing use of heated tobacco products (HTPs) has raised concerns about secondhand aerosol (SHA) from HTPs, but few studies have been reported on it. This study aimed to investigate the trends in SHA exposure and their socioeconomic inequalities in Japan.

Methods

The prevalence of SHA exposure from 2017 to 2020 was estimated using longitudinal internet survey data of 5221 participants, aged 20–69 years in 2017 (baseline), with adjustments using inverse probability weighting for “being a participant in an internet survey”. Multivariable modified Poisson regression models were applied to examine the association between socioeconomic status (ie, educational attainment and equivalent income) at baseline and SHA exposure in 2020 with adjustments for sex and age.

Results

The estimated prevalence of SHA exposure has consistently increased from 4.5% in 2017 to 10.8% in 2020. Lower educational attainment was associated with a higher risk of SHA exposure (p for trend = 0.010). The covariate-adjusted risks of SHA exposure in participants with a low-education and middle-education level were 1.57 and 1.34 times higher, respectively, than in those with a high-education level. However, significant differences in risks of SHA exposure between participants with low-, middle-, and high-income levels were not observed. Meanwhile, participants with a low-education and middle-education level also had 1.87 and 1.61 times higher risks of secondhand smoke (SHS) exposure from combustible cigarettes than those with a high-education level, respectively.

Conclusions

Our study revealed a rapid increase in SHA exposure and the existence of educational inequalities in both SHA and SHS exposure.

Implications

Using longitudinal internet cohort survey data, we found that the prevalence of exposure to secondhand aerosol (SHA) from heated tobacco products (HTPs) rapidly increased to 10.8% in 2020 in Japan. Furthermore, people with lower educational attainment were at higher risk of SHA exposure, suggesting that extensive educational interventions may be necessary to inform the public that although emissions from HTPs contain significantly lesser amounts of harmful and potentially harmful constituents and these compounds than cigarette smoke, they are not harmless and still entail risks, and its long-term effects are unknown. Therefore, future extensive monitoring of SHA exposure is needed.
The Incidence of Ocular Complications in Candidemic Patients and Implications for the Practice of Routine  Eye Exams
Authors: Hillenbrand Molly , Mendy Angelico , Patel Kavya , Wilkinson Racheal , Liao Siyun , Robertson Jamie , Apewokin Senu
Published: March 2022

Background

Ocular candidiasis is a known complication of candidemia. Given the poor ocular penetration of echinocandins, there is some concern that the increasing use of echinocandins may portend an increased incidence of ophthalmic complications. We examined the changing trends in antifungal prescribing patterns and the incidence of ophthalmic complications after candidemia.

Methods

Patients with blood cultures positive for Candida species between January 2014 and June 2020 who underwent screening fundoscopic examination by an ophthalmologist were analyzed. The χ2 analysis was used to compare antifungal prescriptions and ocular exam findings before and after 2016. Trend analysis was also performed to assess temporal changes in prescribing practices and eye exam findings.

Results

There were 226 candidemia cases during the study period, 129 (57.1%) of which underwent screening eye exams. From 2014 to 2015, 24 of 37 (64.5%) patients received eye-penetrating antifungals compared to 36 of 92 (39.1%) from 2016 to 2020 (P = .008). Overall, 30 of 129 (23.3%) patients had abnormal eye exams with the prevalence of abnormal findings being 7 of 37 (18.9%) before 2016 compared to 23 of 92 (25%, P = .46) thereafter. A trend analysis revealed an increase in abnormal eye findings over the study period (P = .008). Of the 30 patients who had abnormal eye exams, 9 (30%) had a change in systemic antifungal therapy from echinocandins to eye-penetrating antifungals. Echinocandin use was associated with abnormal eye findings.

Conclusions

Prescription of eye-penetrating antifungals for candidemia has trended down since 2016. This was associated with a concomitant increase in abnormal findings on screening fundoscopy. Abnormal eye exams were not uncommon throughout our study period.
“Provide our basic needs or we go out”: the COVID-19 pandemic lockdown, inequality, and social policy in Ghana
Authors: Foli Rosina K , Ohemeng Frank L K
Published: March 2022

The effects of the coronavirus disease (COVID-19) pandemic cuts across every facet of a nation’s life. The near collapse of economies with the attendant job losses has brought forth the need for effective social policies, particularly in developing countries, that can serve citizens in dire need. Consequently, many of these countries have had to craft emergency social policies to help their citizens. Ghana is no exception. While measures to control the spread of the pandemic, such as lockdowns and restrictions on movement and gathering, were timely, they negatively impacted the poor, most of whom work in the informal sector and depend on daily survival activities such as buying and selling basic goods. As a result, some of the measures were ignored as people feared they would die from hunger rather than from the pandemic. Thus, governmental response to the pandemic was highlighted by policy layering and exposed the fragile social support systems in existence. The challenges of responding adequately to the pandemic underscore the importance of a transformative social welfare regime in ensuring the protection of citizens. This paper, based on desk research, explores the limitations of the existing social policy framework, which became manifest during the implementation of Ghana’s pandemic policies. Policy layering by government continues to weaken Ghana’s social welfare system, and this affected the official response with respect to the social issues that have emerged due to the pandemic.
Conditions of naturalness and fine-tuning for the type-I seesaw mechanism with four-zero texture
Authors: Yang Masaki J S
Published: March 2022

In this paper, we search for conditions under which the mass matrix of light neutrinos mν is not a result of large cancellations for the type-I seesaw mechanism with four-zero texture. For the Yukawa matrix of neutrinos Yν and heavy Majorana mass matrix MR, these conditions are written as $(Y_{\nu })_{i2} \propto (m_{\nu })_{i2} \Rightarrow (Y_{\nu })_{i2} \propto (M_{R})_{i2}$. We call them alignment conditions because they align certain rows or columns of the three neutrino mass matrices. If these conditions do not hold, the large mixing in mν is a result of fine-tuning due to the cancellation of several terms. Then they are required from the viewpoint of naturalness. They give an explanation of the seesaw invariance of four-zero texture, and place rough restrictions on flavor structures of neutrinos. Under these conditions, Yν must have a cascade hierarchy. For MR, the 12 submatrix has a similar hierarchy to Yν and mν. However, the 23 submatrix has a waterfall hierarchy without some fine-tuning. Therefore, it is likely that Yν and MR have qualitatively different flavor structures. Furthermore, since the conditions restrict CP phases of the matrix elements, they imply the existence of a universal generalized CP symmetry in the neutrino sector.
Timely sleep coupling: spindle-slow wave synchrony is linked to early amyloid-β burden and predicts memory decline
Authors: Chylinski Daphne , Van Egroo Maxime , Narbutas Justinas , Muto Vincenzo , Bahri Mohamed A. , Berthomier Christian , Salmon Eric , Bastin Christine , Phillips Christophe , Collette Fabienne , Maquet Pierre , Carrier Julie , Lina Jean Marc , Vandewalle Gilles
Published: March 2022

Sleep alteration is a hallmark of ageing and emerges as a risk factor for Alzheimer’s disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD processes is not fully established. Here, we investigated whether the coupling of spindles and slow waves is associated with early amyloid-beta (Aβ) brain burden, a hallmark of AD neuropathology, and cognitive change over 2 years in 100 healthy individuals in late-midlife (50-70y; 68 women). We found that, in contrast to other sleep metrics, earlier occurrence of spindles on slow-depolarisation slow waves is associated with higher medial prefrontal cortex Aβ burden (p=0.014, r2β*=0.06), and is predictive of greater longitudinal memory decline (p=0.032, r2β*=0.07). These findings unravel early links between sleep, AD-related processes and cognition and suggest that altered coupling of sleep microstructure elements, key to its mnesic function, contributes to poorer brain and cognitive trajectories in ageing.
Combining quadrat, rake and echosounding to estimate submerged aquatic vegetation biomass at the ecosystem scale
Authors: Botrel Morgan , Hudon Christiane , Biron Pascale M. , Maranger Roxane
Published: March 2022

Measuring freshwater submerged aquatic (SAV) biomass at large spatial scales is challenging and no single technique can cost effectively accomplish this while maintaining accuracy. We propose to combine and intercalibrate accurate quadrat-scuba diver technique, fast rake sampling and large scale echosounding. We found that the relationship between quadrat and rake biomass is moderately strong (R2 = 0.62, RMSECV = 2.19 g/m2) and varies with substrate type and SAV growth form. Rake biomass was also successfully estimated from biovolume10 and its error (R2 = 0.53, RMSECV = 5.95 g/m2), a biomass proxy derived from echosounding, at a resolution of 10 m radius from rake sampling point. However, the relationship was affected by SAV growth form, depth, acoustic data quality and wind conditions. Sequential application of calibrations yielded predictions in agreement with quadrat observations, but echosounding predictions underestimated biomass in shallow areas (< 1.5 m) while outperforming point estimation in deep areas (> 3 m). Whole-system biomass was more accurately estimated by calibrated echosounding than rake point surveys, owing to the large sample size and better representation of spatial heterogeneity of echosounding. We recommend developing as a one-time event a series of quadrat and rake calibration equations for each growth form and substrate type. Because the relationship between biovolume and biomass depends on SAV growth form, rake and echosounding calibration needs to be conducted frequently. With the two calibrations, rake can thus be used as a rapid ground truthing or in shallow areas where echosounding is inadequate.