bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Determination of Voriconazole and Its Voriconazole N-Oxide Metabolite in Human Urine by Liquid Chromatography/Tandem Mass Spectrometry
Authors: Yu Yong , Yang Yu-Qing , Zeng Nv-Jin , Zhang Hong-Wen , Sun Lu-Ning , Wang Yong-Qing
Published: November 2021

A convenient and sensitive liquid chromatography–tandem mass spectrometry method was established to simultaneously quantify voriconazole (VRZ) and its metabolite, voriconazole N-oxide (VNO), in human urine. Voriconazole-d3 and voriconazole-d3 N-oxide were used as isotopic internal standards. Samples were processed by protein precipitation and separated using a ZORBAX SB-Aq column (1.8 μm, 2.1 × 50 mm). Mass spectrometry was performed using an API 4000 mass spectrometry by positive electrospray ionization. The flow rate was 0.6 mL/min. Gradient elution was performed with methanol and 0.1% formic acid as the organic and water phase, respectively. The VRZ and VNO calibration curves ranged from 20.0 to 7200 ng/mL in human urine. The specificity, matrix effect, extraction recovery, intra/inter-run precision, accuracy and stability were validated for both VRZ and VNO in human urine. The developed method was used to study urinary excretion after intravenous injection of 4 mg/kg VRZ in healthy Chinese subjects.
DCMP: database of cancer mutant protein domains
Authors: Emerson Isaac Arnold , Chitluri Kiran Kumar
Published: November 2021

Protein domains are functional and structural units of proteins. They are responsible for a particular function that contributes to protein’s overall role. Because of this essential role, the majority of the genetic variants occur in the domains. In this study, the somatic mutations across 21 cancer types were mapped to the individual protein domains. To map the mutations to the domains, we employed the whole human proteome to predict the domains in each protein sequence and recognized about 149 668 domains. A novel Perl-API program was developed to convert the protein domain positions into genomic positions, and users can freely access them through GitHub. We determined the distribution of protein domains across 23 chromosomes with the help of these genomic positions. Interestingly, chromosome 19 has more number of protein domains in comparison with other chromosomes. Then, we mapped the cancer mutations to all the protein domains. Around 46–65% of mutations were mapped to their corresponding protein domains, and significantly mutated domains for all the cancer types were determined using the local false discovery ratio (locfdr). The chromosome positions for all the protein domains can be verified using the cross-reference ensemble database.

Database URL:http://dcmp.vit.ac.in/
Transcatheter aortic valve replacement in mixed aortic valve disease: a systematic review and meta-analysis
Authors: Guddeti Raviteja R , Gill Gauravpal S , Garcia-Garcia Hector M , Alla Venkata Mahesh
Published: November 2021

Background

Utilization of transcatheter aortic valve replacement (TAVR) has expanded from high-risk patients to intermediate- and select low-risk candidates with severe aortic stenosis (AS). TAVR is currently not indicated for patients with aortic insufficiency, and its outcomes in mixed aortic valve disease (MAVD) are unclear.

Methods

A systematic search of PubMed, Medline, CINHAL, and Cochrane databases was performed to identify studies comparing TAVR outcomes in patients with AS vs. MAVD. Primary outcomes included 30-day and late all-cause mortality, and paravalvular regurgitation (PVR). Secondary outcomes were major bleeding, vascular complications, device implantation success, permanent pacemaker, and stroke. Pooled odds ratios (OR) and 95% confidence intervals (CIs) were calculated using Der Simonian-Laird random-effects model.

Results

Six observational studies with 58 879 patients were included in the analysis. There was no significant difference in 30-day all-cause mortality [OR 1.03 (95% CI 0.92–1.15); P = 0.63], however, MAVD group had higher odds of moderate-to-severe PVR [1.81 (1.41–2.31); P < 0.01]. MAVD patients had lower odds of device implantation success [0.60 (0.40–0.91); P = 0.02] while other secondary outcomes were similar in the two groups.

Conclusions

TAVR in MAVD is associated with increased odds of paravalvular regurgitation and lower odds of device implantation success when compared to severe aortic stenosis.
A Domain Based Approach to Semantic Lexicon Expansion
Authors: Prentice Sheryl , Rayson Paul , Knight Jo , El-Haj Mahmoud , Elstein Solly
Published: November 2021

Current approaches to the expansion of semantic lexicons for corpus annotation are somewhat ad hoc in nature and do not generally offer a systematic means of identifying areas for development within one’s lexicon. The present paper sets forward a domain based approach to semantic lexicon expansion, targeting UCREL’s Semantic Analysis System (USAS). First, an updated version of the lexicon is compared to representative corpora to ascertain areas of underrepresentation in a novel method which we call K-FLUX analysis. Second, an example set of underrepresented types are targeted for development using domain specific corpora. Collectively, the results show that some corpora are more successful than others in supplementing the existing USAS lexicon. The paper discusses the various factors that should be borne in mind when utilising the proposed method before concluding with how findings might inform future developments of the lexicon, and crucially, the semantic system on which it is based.
Assessment of water, sanitation and hygiene practices for prevention and control of COVID-19 in Kenya
Authors: Mwai J , Nyole D , Abdi M , Ahmed I , Mutai J , Kaduka L , Ndemwa P , Omogi J
Published: November 2021

Background

Safely managed water, sanitation and hygiene (WASH) services are an essential part of preventing and protecting human health during infectious disease outbreaks, including the current coronavirus disease 2019 (COVID-19) pandemic. Additionally, adherence to COVID-19 measures, including washing hands using soap and proper waste disposal, no doubt can improve containment of the virus.

Methods

A cross-sectional survey was conducted in Kilifi and Mombasa Counties in Kenya. A total of 612 quantitative data were collected using a mobile data collection tool Open Data Kit. Parametric and non-parametric tests were used to examine factors associated with WASH practices and control of COVID-19 in Kenya.

Results

More than half of the respondents were from Kilifi, 431 (70.4%) were female and the mean age was 38.2±14.8 y. Households in Kilifi were most likely not to have enough water, while Mombasa households were more likely to pay for water. Sanitation coverage was 47.6%, with more than half sharing sanitation facilities. Sharing of latrines was significantly associated with county and income level. Accessing soap was worse compared with the month prior to the survey, only 3.9% had their garbage collected by formal service providers and only 17% reported wearing any protective gear while handling waste at home.

Conclusions

Water is disproportionately available in the two counties, with low sanitation coverage. There is low knowledge on hand washing and inadequate waste disposal services.
Inference-based correction of multi-site height and weight measurement data in the All of Us research program
Authors: Khan Mirza S , Carroll Robert J
Published: November 2021

Objective

Measurement and data entry of height and weight values are error prone. Aggregation of medical record data from multiple sites creates new challenges prompting the need to identify and correct errant values. We sought to characterize and correct issues with height and weight measurement values within the All of Us (AoU) Research Program.

Materials and Methods

Using the AoU Researcher Workbench, we assessed site-level measurement value distributions to infer unit types. We also used plausibility checks with exceptions for conditions with possible outlier values, eg obesity, and assessed for excess deviation within individual participant’s records.

Results

15.8% of height and 22.4% of weight values had missing unit type information.

Discussion

We identified several measurement unit related issues: the use of different units of measure within and between sites, missing units, and incorrect labeling of units. Failure to account for these in patient data repositories may lead to erroneous study results and conclusions.

Conclusion

Discrepancies in height and weight measurement data may arise from missing or mislabeled units. Using site- and participant-level analyses while accounting for outlier value-associated clinical conditions, we can infer measurement units and apply corrections. These methods are adaptable and expandable within AoU and other data repositories.
Relationship of tissue dimensions and three captive bolt placements on cadaver heads from mature swine (Sus scrofa domesticus) > 200 kg body weight
Authors: Anderson Karly N , Allen Kaysie J , Baysinger Angela , Benjamin Madonna , Berger Jennifer , Claus James R , Greco Brian J , Massie Emily A , O’Brien Brett , Ramirez Alejandro , Rendahl Aaron K , Reyes Arquimides A , Zhitnitskiy Perle E , Vogel Kurt D
Published: November 2021

Three penetrating captive bolt (PCB) placements were tested on cadaver heads from swine with estimated body weight (BW) >200 kg (sows = 232.9 ± 4.1 kg; boars = 229.3 ± 2.6 kg). The objectives were to determine tissue depth, cross-sectional brain area, visible brain damage (BD), regions of BD, and bolt–brain contact; and determine relationships between external head dimensions and tissue depth at each placement. A Jarvis PAS-Type P 0.25R PCB with a Long Stunning Rod Nosepiece Assembly and 3.5 g power loads was used at the following placements on heads from 111 sows and 46 boars after storage at 2 to 4 °C for ~62 h before treatment: FRONTAL (F)—3.5 cm superior to the optic orbits at midline, TEMPORAL (T)—at the depression posterior to the lateral canthus of the eye within the plane between the lateral canthus and the base of the ear, or BEHIND EAR (BE)—directly caudal to the pinna of the ear on the same plane as the eyes and targeting the middle of the opposite eye. For sows, the bolt path was in the plane of the brain for 42/42 (100%, 95% confidence interval [CI]: 91.6% to 100.0%) F heads, 39/40 (97.5%, 95% CI: 86.8% to 99.9%) T heads, and 34/39 (87.5%, 95% CI: 72.6% to 95.7%) BE heads; for the heads that could reliably be assessed for BD damage was detected in 25/26 (96.2%, 95% CI: 80.4% to 99.9%) F heads, 24/35 (68.6%, 95% CI: 50.7% to 83.2%) T heads, and 5/40 (12.5%, 95% CI: 4.2% to 26.8%) BE heads. For boars, the bolt path was in the plane of the brain for 17/17 (100.0%, 95% CI: 80.5% to 100.0%) F heads, 18/18 (100.0%, 95% CI: 81.5% to 100.0%) T heads, and 14/14 (100.0%, 95% CI: 76.8% to 100.0%) BE heads; damage was detected in 11/12 (91.7%, 95% CI: 61.5% to 99.8%) F heads, 2/15 (13.3%, 95% CI: 1.7% to 40.5%) T heads, and 7/14 (50.0%, 95% CI: 23.0% to 77.0%) BE heads. Tissue depth was reported as mean ± standard error followed by 95% one-sided upper reference limit (URL). For sows, total tissue thickness was different (P < 0.05) between placements (F: 52.7 ± 1.0 mm, URL: 64.1 mm; T: 69.8 ± 1.4 mm, URL: 83.9 mm; BE: 89.3 ± 1.5 mm, URL: 103.4 mm). In boars, total tissue thickness was different (P < 0.05) between placements (F: 41.2 ± 2.1 mm, URL: 56.3 mm; T: 73.2 ± 1.5 mm, URL: 83.4 mm; BE: 90.9 ± 3.5 mm, URL: 113.5 mm). For swine > 200 kg BW, F placement may be more effective than T or BE due to less soft tissue thickness, which may reduce concussive force. The brain was within the plane of bolt travel for 100% of F heads with BD for 96.2% and 91.7% of F sow and boar heads, respectively.
Successful laparoscopic extraction of trichobezoar due to Rapunzel syndrome: first reported case in Kuwait
Authors: Al-Mulla Ahmad E , Altabeekh Ali , Al-Jafar Ahmad , Dashti Shaimaa
Published: November 2021

Rapunzel syndrome is a rare condition typically found in young female patients with mental or psychiatric disorders. It manifests as a large trichobezoar extending beyond the pylorus into the small intestine and leads to various adverse conditions. Early diagnosis and prompt management are crucial to avoiding complications. These bezoars are extracted endoscopically, laparoscopically and via open surgery (most common). In this current report, we discuss a successful laparoscopic extraction of a trichobezoar in a 12-year-old girl with acute abdominal pain due to small-bowel obstruction. We describe our technique compared with others’ techniques and include a literature review on this topic.
The proteome of developing barley anthers during meiotic prophase I
Authors: Lewandowska Dominika , Orr Jamie , Schreiber Miriam , Colas Isabelle , Ramsay Luke , Zhang Runxuan , Waugh Robbie
Published: November 2021

Flowering plants reproduce sexually by combining a haploid male and female gametophyte during fertilization. Male gametophytes are localized in the anthers, each containing reproductive (meiocyte) and non-reproductive tissue necessary for anther development and maturation. Meiosis, where chromosomes pair and exchange their genetic material during a process called recombination, is one of the most important and sensitive stages in breeding, ensuring genetic diversity. Most anther development studies have focused on transcript variation, but very few have been correlated with protein abundance. Taking advantage of a recently published barley anther transcriptomic (BAnTr) dataset and a newly developed sensitive mass spectrometry-based approach to analyse the barley anther proteome, we conducted high-resolution mass spectrometry analysis of barley anthers, collected at six time points and representing their development from pre-meiosis to metaphase. Each time point was carefully staged using immunocytology, providing a robust and accurate staging mirroring our previous BAnTr dataset. We identified >6100 non-redundant proteins including 82 known and putative meiotic proteins. Although the protein abundance was relatively stable throughout prophase I, we were able to quantify the dynamic variation of 336 proteins. We present the first quantitative comparative proteomics study of barley anther development during meiotic prophase I when the important process of homologous recombination is taking place.
Phosphorylation of ribosomal protein S6 differentially affects mRNA translation based on ORF length
Authors: Bohlen Jonathan , Roiuk Mykola , Teleman Aurelio A
Published: November 2021

Phosphorylation of Ribosomal Protein S6 (RPS6) was the first post-translational modification of the ribosome to be identified and is a commonly-used readout for mTORC1 activity. Although the cellular and organismal functions of RPS6 phosphorylation are known, the molecular consequences of RPS6 phosphorylation on translation are less well understood. Here we use selective ribosome footprinting to analyze the location of ribosomes containing phosphorylated RPS6 on endogenous mRNAs in cells. We find that RPS6 becomes progressively dephosphorylated on ribosomes as they translate an mRNA. As a consequence, average RPS6 phosphorylation is higher on mRNAs with short coding sequences (CDSs) compared to mRNAs with long CDSs. We test whether RPS6 phosphorylation differentially affects mRNA translation based on CDS length by genetic removal of RPS6 phosphorylation. We find that RPS6 phosphorylation promotes translation of mRNAs with short CDSs more strongly than mRNAs with long CDSs. Interestingly, RPS6 phosphorylation does not promote translation of mRNAs with 5′ TOP motifs despite their short CDS lengths, suggesting they are translated via a different mode. In sum this provides a dynamic view of RPS6 phosphorylation on ribosomes as they translate mRNAs and the functional consequence on translation.
The SARS-CoV-2 RNA polymerase is a viral RNA capping enzyme
Authors: Walker Alexander P , Fan Haitian , Keown Jeremy R , Knight Michael L , Grimes Jonathan M , Fodor Ervin
Published: November 2021

SARS-CoV-2 is a positive-sense RNA virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic, which continues to cause significant morbidity, mortality and economic strain. SARS-CoV-2 can cause severe respiratory disease and death in humans, highlighting the need for effective antiviral therapies. The RNA synthesis machinery of SARS-CoV-2 is an ideal drug target and consists of non-structural protein 12 (nsp12), which is directly responsible for RNA synthesis, and numerous co-factors involved in RNA proofreading and 5′ capping of viral RNAs. The formation of the 5′ 7-methylguanosine (m7G) cap structure is known to require a guanylyltransferase (GTase) as well as a 5′ triphosphatase and methyltransferases; however, the mechanism of SARS-CoV-2 RNA capping remains poorly understood. Here we find that SARS-CoV-2 nsp12 is involved in viral RNA capping as a GTase, carrying out the addition of a GTP nucleotide to the 5′ end of viral RNA via a 5′ to 5′ triphosphate linkage. We further show that the nsp12 NiRAN (nidovirus RdRp-associated nucleotidyltransferase) domain performs this reaction, and can be inhibited by remdesivir triphosphate, the active form of the antiviral drug remdesivir. These findings improve understanding of coronavirus RNA synthesis and highlight a new target for novel or repurposed antiviral drugs against SARS-CoV-2.
Taiji-reprogram: a framework to uncover cell-type specific regulators and predict cellular reprogramming cocktails
Authors: Wang Jun , Liu Cong , Chen Yue , Wang Wei
Published: November 2021

Cellular reprogramming is a promising technology to develop disease models and cell-based therapies. Identification of the key regulators defining the cell type specificity is pivotal to devising reprogramming cocktails for successful cell conversion but remains a great challenge. Here, we present a systems biology approach called Taiji-reprogram to efficiently uncover transcription factor (TF) combinations for conversion between 154 diverse cell types or tissues. This method integrates the transcriptomic and epigenomic data to construct cell-type specific genetic networks and assess the global importance of TFs in the network. Comparative analysis across cell types revealed TFs that are specifically important in a particular cell type and often tightly associated with cell-type specific functions. A systematic search of TFs with differential importance in the source and target cell types uncovered TF combinations for desired cell conversion. We have shown that Taiji-reprogram outperformed the existing methods to better recover the TFs in the experimentally validated reprogramming cocktails. This work not only provides a comprehensive catalog of TFs defining cell specialization but also suggests TF combinations for direct cell conversion.
PATIENT DOSES IN WHOLE-BODY PET/CT EXAMINATIONS IN THE LARGEST TERTIARY HOSPITAL IN GREECE
Authors: Tzampazidou E , Fotina A A , Chatonidis V , Tsalafoutas I A , Datseris I E , Samartzis A
Published: November 2021

The purpose of this study was to determine the patient radiation dose in combined whole-body positron emission tomography/computed tomography (PET/CT) examinations performed in the largest tertiary hospital in Greece. Computed tomography dose index (CTDIvol), dose length product (DLP), weight, height and administered activity of 2-[18F] fluoro-2-deoxy-D-glucose values for PET/CT examinations were recorded in a sample of 1014 randomly selected patients. The mean (±standard deviation) and median (interquartile) CTDIvol values were equal to 5.5 ± 2.4 and 4.8 (2.5) mGy, respectively. The respective DLP values were 483.3 ± 212.4 and 426 (234.6) mGy·cm. For the administered activity, mean and median were equal to 363.9 ± 68.3 and 361.6 (85.6) MBq. The mean administered activity per body weight was 4.8 ± 0.6 and the median 4.8 (0.6) MBq/kg. The results of this survey are within the range of values reported in the literature and can be used as a standard of reference until national diagnostic reference levels are established for whole-body PET/CT procedures.
Maternal dopamine encodes affective signals of human infants
Authors: Zeevi Lior , Irani Merav , Catana Ciprian , Feldman Barrett Lisa , Atzil Shir
Published: November 2021

Mothers are highly responsive to their offspring. In non-human mammals, mothers secrete dopamine in the nucleus accumbens (NAcc) in response to their pups. Yet, it is still unknown which aspect of the offspring behavior elicits dopaminergic responses in mothers. Here, we tested whether infants’ affective signals elicit dopaminergic responses in the NAcc of human mothers. First, we conducted a behavioral analysis on videos of infants’ free play and quantified the affective signals infants spontaneously communicated. Then, we presented the same videos to mothers during a magnetic resonance-positron emission tomography scan. We traced the binding of [11C]raclopride to free D2/3-type receptors to assess maternal dopaminergic responses during the infant videos. When mothers observed videos with many infant signals during the scan, they had less [11C]raclopride binding in the right NAcc. Less [11C]raclopride binding indicates that less D2/3 receptors were free, possibly due to increased endogenous dopamine responses to infants’ affective signals. We conclude that NAcc D2/3 receptors are involved in maternal responsiveness to affective signals of human infants. D2/3 receptors have been associated with maternal responsiveness in nonhuman animals. This evidence supports a similar mechanism in humans and specifies infant-behaviors that activate the maternal dopaminergic system, with implications for social neuroscience, development and psychopathology.
Splitting of RNA-dependent RNA polymerase is common in Narnaviridae: Identification of a type II divided RdRp from deep-sea fungal isolates
Authors: Chiba Yuto , Oiki Sayoko , Zhao Yanjie , Nagano Yuriko , Urayama Syun-ichi , Hagiwara Daisuke
Published: November 2021

Until recently, it was accepted that RNA-dependent RNA polymerase (RdRp) is the only essential gene for non-retro RNA viruses and is encoded by a single open reading frame (ORF) in their genomes. However, divided RdRps that are coded by two ORFs were discovered in fungal RNA viruses in a few independent reports. This discovery showed higher plasticity of viral RdRp than was expected. Among these divided RdRps, the division site was common; specifically, the first part of the RdRp contains motifs F, A, and B, whereas the latter part possesses motifs C and D. These RdRps are designated as type I divided RdRp and have been limited to viruses in a specific clade of Narnaviridae. In this study, to further understand the plasticity of RdRp, we explored viruses from deep sea–derived fungal strains as an untapped resource with a focus on Aspergillus section Versicolores. Seven strains were found to be infected by a total of 13 viruses, and the viral RNA genomes were determined by fragmented and primer-ligated double-stranded RNA sequencing technology. Among them, six strains belong to Narnaviridae. One of the strains, Aspergillus tennesseensis narnavirus 1, which infects an Aspergillus tennesseensis, has a divided RdRp with a new division site (referred to as type II divided RdRp). A couple of sequences for possible type II divided RdRps were also detected in public metagenomic data sets. Our findings reveal that different types of divisions in RdRp are present in the virosphere, and two types of RdRp splitting occurred independently within Narnaviridae.
Bursaphelenchus xylophilus: An Important Pathogenic Factor of Pine Wilt Disease and Its Relationship with Bursaphelenchus mucronatus
Authors: Li Yu-Long , Fan Chang-Ji , Jiang Xiao-Hui , Tian Xing-Yi , Han Zheng-Min
Published: November 2021

Pine wilt disease is the most devastating pine disease caused by Bursaphelenchus xylophilus. Bursaphelenchus mucronatus is morphologically similar to B. xylophilus and geographically overlaps in its distribution. Although interspecific hybridization of the two nematodes has been performed in vitro, the dynamic regularity of hybrid formation and its risk in forests has not been well evaluated. In this study, a hybrid of B. xylophilus and Bursaphelenchus mucronatus mucronatus was identified in the laboratory and fields by molecular markers. The heterozygosity of ITS-5.8S loci for identification was unstable in the hybrid population, and the allele inherited from B. m. mucronatus was lost over several generations. We also provided evidence that hybrids existed in some new epidemic areas, while old epidemic areas were usually dominated by B. xylophilus. Hybrids could be generated when B. m. mucronatus was invaded by B. xylophilus, and the pathogenicity of the hybrids was similar to that of B. xylophilus. These findings may improve the understanding of the natural hybridization between B. xylophilus and B. m. mucronatus and pathogenic variation in pine wilt disease, providing new insights for future studies on disease detection, transmission, and quarantine.
Endoscopic High-speed Curettage and Bone Grafting of Unicameral Bone Cyst in Young Children: A Case Report
Authors: Megremis Panos K. , Megremis Orestis P.
Published: November 2021

Curettage and bone grafting are the most effective methods used in the treatment of unicameral and aneurysmal bone cysts. Endoscopic curettage and bone grafting are minimally invasive methods for the treatment of these bone cysts. We report a case report of a unicameral bone cyst of the calcaneus in a 9-year-old girl treated successfully with endoscopic high-speed curettage and bone grafting. Complete healing of the unicameral bone cyst of the calcaneus, according to the Modified Neer’s Classification Scale, was achieved 4.5 months postoperatively. Complete healing without recurrence, in 5 years follow-up, was evident. Endoscopic high-speed curettage allows a precise, thorough, and aggressive resection of the cyst’s tumor tissue, which is the key to successful and complete healing of the cysts. For the successful endoscopic bone cyst curettage, radiographic control guidance is necessary to avoid growth plate damage.

Level of Evidence: Diagnostic Level IV—therapeutic study. See Instructions for Authors for a complete description of levels of evidence.
Circular RNA circPDSS1 promotes osteosarcoma progression by sponging miR-502-3p and miR-4436a
Authors: Tang Shaolong , Tang Xinhai , Jin Zhengping , Liu Chao , Huang Qinghua , Wang Laijie , Diaty Diarra Mohamed , Ye Zhaoming
Published: November 2021

Osteosarcoma (OS) is a highly aggressive bone cancer. Patients with OS frequently develop drug resistance in clinical treatment, and the prognosis has not been improved significantly. There is an urgent need to identify novel markers and therapeutic targets. In this study, we focused on the highly expressed noncoding circular RNA circPDSS1 in OS, and studied its functional roles and downstream targets in OS cells by CCK-8, clone formation assay, transwell assays. Additionally, we performed luciferase reporter assay, RNA pull-down experiment and qRT-PCR to validate the micoRNA targets of circPDSS1. The involvement of circPDSS1 in tumorigenesis was also investigated in mouse xenografts model. The expression of circPDSS1 was significantly upregulated in OS tissues and cell lines. Patients with high circPDSS1 expression were associated with poorer progression-free survival (PFS) and overall survival (OS) as compared to those with low circPDSS1 expression. CircPDSS1 knockdown significantly inhibited the viability, clone formation ability and invasion ability of OS cells, and induced cell apoptosis, which were associated with the upregulation of proapoptotic proteins and the impairment of prosurvival signaling. Molecular mechanism study further demonstrated that circPDSS1 modulates OS cell functions by regulating the expression of miR-502-3p and miR-4436a. Our data suggest that circPDSS1 acts as a molecular sponge of miR-502-3p and miR-4436a regulates the proliferation and invasion of OS cells and promote the malignant progression of OS.
Racial Differences in Survival Among Advanced-stage Non–small-Cell Lung Cancer Patients Who Received Immunotherapy: An Analysis of the US National Cancer Database (NCDB)
Authors: Gupta Anjali , Zhang Dongyu , Braithwaite Dejana , Karanth Shama D. , Tailor Tina D. , Clarke Jeffrey M. , Akinyemiju Tomi
Published: November 2021

Lung cancer is the most common cause of cancer death among men and women in the United States, with significant racial disparities in survival. It is unclear whether these disparities persist upon equal utilization of immunotherapy. The purpose of this study was to evaluate the association between race and all-cause mortality among non–small-cell lung cancer (NSCLC) patients who received immunotherapy. We obtained data from the 2016 National Cancer Database on patients diagnosed with advanced-stage (III–IV) NSCLC from 2015 to 2016. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) by race/ethnicity. A total of 2940 patients were included. Non-Hispanic (NH)-Black patients had a lower risk of death relative to NH-White patients (HR: 0.85; 95% CI: 0.73, 0.98) after adjusting for sociodemographic, clinical, and treatment factors. Formal tests of interaction evaluating race with Charlson-Deyo comorbidity score and race with area-level median income were nonsignificant. However, in stratified analyses, NH-Black versus NH-White patients had a lower risk of death in models adjusted for sociodemographic factors among those with at least 1 comorbidity (HR: 0.75; 95% CI: 0.57, 0.97), and those living in regions within the 2 lowest quartiles of median income (HR: 0.82; 95% CI: 0.68, 0.99). Among advanced-stage NSCLC patients who received immunotherapy, NH-Black patients experienced higher survival compared with NH-White patients. We urge the implementation of policies and interventions that seek to equalize access to care as a means of addressing differences in overall NSCLC survival by race.
Development of a Novel Tear Lipid Test Strip
Authors: Li Qian , Jiao Shu-Jie , Wang Yue-Qi , Xie Hua-Tao , Zhang Ming-Chang
Published: November 2021

Purpose:

The unifying characteristic of dry eye is the loss of tear film homeostasis, and the tear lipid layer is a key component for maintaining film stability. The detection of tear lipid is of great significance for the diagnosis of dry eye. In this study, we explored a new test strip for the detection of tear lipid.

Methods:

The tear lipid test strip was prepared by coating the strip material with hydrophobic nano-silica. We tested its physical properties with iodine vapor chromogenic and cobalt chloride test methods. Its biosafety was evaluated by an ocular irritation test in rabbits. Finally, we established a rabbit meibomian gland dysfunction model and measured both eyes with the tear lipid test strip at the first, third, seventh, 14th, 16th, and 21st day after surgery.

Results:

The tear lipid test strip had fine lipophilicity and hydrophobicity. It can extract lipid from tear, and the tear lipid can be quantified by measuring the length of lipid infiltration. In the ocular irritation test, the test strip had no obvious eye irritation. The length of lipid infiltration between experimental and control rabbit eyes began to show statistical difference since the third day after surgery.

Conclusions:

The novel tear lipid test strip has great lipophilicity, hydrophobicity, and biological safety. It might be effectively applied in diagnosis of dry eye.
Outcomes of Descemet Membrane Endothelial Keratoplasty Using Cornea From Elderly Donors Aged 80 Years and Older: In the Aftermath of Current Donor Shortage
Authors: Basak Samar K. , Basak Soham , Gajendragadkar Nidhi
Published: November 2021

Purpose:

The purpose of this study was to report the outcomes of Descemet membrane endothelial keratoplasty (DMEK) using corneas from elderly donors aged 80 years and older.

Methods:

Eighty eyes of 78 patients who underwent DMEK-only or DMEK combined with cataract extraction (triple-DMEK) with surgeon-prepared graft between April 2016 and March 2020 were reviewed. Corrected distance visual acuity, endothelial cell density (ECD), and endothelial cell loss after 6 months, 1 year, and 2 years were analyzed.

Results:

The mean donor age was 83.6 ± 3.7 years (range: 80–100 years), and the mean donor ECD was 2889 ± 177 cells/mm2 (range: 2604–3460 cells/mm2). The mean recipient age was 67.2 ± 6.9 years (range: 60–89 years), and the mean follow-up was 21 ± 11 months (range: 6–52 months). The mean corrected distance visual acuity improved from a preoperative value of 1.36 ± 0.67 logarithm of the minimum angle of resolution to 0.22 ± 0.18 at 6 months (n = 75), 0.21 ± 0.2 at 1 year (n = 64), and 0.23 ± 0.3 logarithm of the minimum angle of resolution at 2 years (n = 41), respectively (P < 0.001). In 72 eyes (96%), the graft remained transparent until the last follow-up visit. The mean postoperative ECD was 2073 ±336 (n = 75), 1951 ± 379 (n = 65), and 1807 ± 431 cells/mm2 (n = 41) at 6 months, 1 year, and 2 years, respectively. Five eyes (6.7%) had donor detachments of which 4 required rebubbling. Two grafts failed after 1 year, and 2 eyes (2.6%) had graft rejection, of which 1 eye was reverted successfully by medical management.

Conclusions:

Cornea from elderly donors aged 80 years and older with good selection criteria may be considered for DMEK with successful outcomes. For India and other countries with unmet tissue needs, every best single cornea counts.
PACK Cross-Linking as Adjuvant Therapy Improves Clinical Outcomes in Culture-Confirmed Bacterial Keratitis
Authors: Achiron Asaf , Elhaddad Omar , Regev Tamir , Krakauer Yonit , Tsumi Erez , Hafezi Farhad , Knyazer Boris
Published: November 2021

Purpose:

We recently showed the positive clinical effects of combining accelerated corneal cross-linking (PACK-CXL) with antibiotic treatment in patients with presumed bacterial keratitis. In this study, we compare the impacts of a combined PACK-CXL/standard antibiotic treatment (PACK-ABX group) with standard antibiotic treatment alone (ABX group) in patients with culture-confirmed bacterial keratitis.

Methods:

We reviewed patients with moderate and severe bacterial keratitis and confirmed bacterial cultures. Clinical outcomes were compared for standard antibiotic treatment alone, before the initiation of PACK-CXL, and after adjuvant use of PACK-CXL.

Results:

A total of 47 eyes of 47 patients were included: 26 eyes in the PACK-ABX group and 21 eyes in the ABX group. Pathogens, baseline demographics (besides age), and clinical parameters were similar between the 2 groups. The PACK-ABX patients had better final uncorrected visual acuity [mean difference 0.57 Logarithm of the Minimum Angle of Resolution, 95% Confidence Interval (CI): 0.16–0.99, P = 0.07] and best-corrected visual acuity (mean difference 0.70 Logarithm of the Minimum Angle of Resolution, 95% CI: 0.23–1.16, P = 0.04), shorter reepithelialization time (mean difference 9.63 days, 95% CI: 3.14–16.12, P = 0.004), and reduced number of clinic visits (mean difference 4.8 meetings, 95% CI: 1.4–8.2, P = 0.007) and need for tectonic grafts (0 vs. 33.3%, P = 0.002). A multivariate analysis controlling for age, sex, ulcer size, and Gram stain showed that PACK-ABX treatment remained significantly associated with reepithelialization time (β = 14.5, P = 0.001).

Conclusions:

In our study, PACK-CXLs addition to the standard of care in cases of culture-proven bacterial keratitis had a positive effect on the final visual acuity and time to resolution, compared with the standard-of-care treatment.
Construction and Validation of a Predictive Nomogram Based on Ultrasound for Lymph Node Metastasis of Papillary Thyroid Carcinoma in the Cervical Central Region
Authors: Shen Haolin , Lv Guorong , Li Tingting , Wang Yuegui , Chen Keyue , Wang Kangjian , Li Ling , Zheng Xiaoyun , Yang Shuping
Published: November 2021

To establish and validate a nomogram for predicting lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) in the cervical central region. This retrospective study included 287 PTC patients with 309 nodules treated from December 2018 to May 2020 at our hospital. The cohort was divided randomly into a training set and a testing set according to a 7:3 ratio. The training set contained 216 nodules, and the testing set contained 93 nodules. The nomogram was developed using the training set, and the data of the testing set were used to validate the performance of nomogram. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The study showed multifocality, thyroid lesion size, and American College of Radiology Thyroid Imaging, Reporting and Data System (TI-RADS) score were significantly independently associated with LNM in the cervical central region. In the testing set, the calibration curve showed that the nomogram had good discrimination with a C-index of 0.775 (95% confidence interval, 0.680–0.869) and adequate calibration (P = 0.808). By decision curve analysis and clinical impact curve analysis, the nomogram was shown to have a satisfactory net benefit between thresholds of 0.40 and 0.75. The nomogram can be used for predicting LNM of PTC in the cervical central region and may provide valuable guidance for planning the surgical treatment of PTC patients.
CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
Authors: Crichton Emma S. , Zeng Shan , La Muraglia G. Michael , Badell I. Raul
Published: November 2021

Background.

Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necessary for germinal center (GC) and alloantibody formation. Perturbations in serum CXCL13 levels have been associated with humoral immune activity. Therefore, CXCL13 may correlate with the formation of HLA antibodies following transplantation.

Methods.

A murine skin graft model was utilized to define the production and kinetics of CXCL13 in response to alloantigen. Human Tfh:B-cell in vitro cocultures were performed to evaluate CXCL13 production by human lymphocytes, and serum from healthy controls and human transplant recipients with and without de novo DSA was tested for CXCL13.

Results.

CXCL13 was detectable in the blood of allografted mice and correlated with Tfh and GC B-cell responses. Greater CXCL13 expression was observed in the draining lymph nodes of allografted mice as compared with naïve or syngeneic graft recipients, and serum levels preceded the detection of DSA posttransplant. Similarly, productive human Tfh:B-cell interactions that led to plasmablast differentiation and IgG formation also exhibited CXCL13 expression. CXCL13 levels in human transplant recipients with de novo DSA were greater than in healthy controls and stable transplant patients and also correlated with the development of alloantibodies in a small cohort of serially monitored recipients.

Conclusions.

CXCL13 indicates GC alloreactivity and alloantibody formation and correlated with DSA formation in kidney transplant recipients, thereby introducing CXCL13 as a potential biomarker for HLA antibodies.
Modern perspectives on near-equilibrium analysis of Turing systems
Authors: Krause Andrew L. , Gaffney Eamonn A. , Maini Philip K. , Klika Václav
Published: November 2021

In the nearly seven decades since the publication of Alan Turing’s work on morphogenesis, enormous progress has been made in understanding both the mathematical and biological aspects of his proposed reaction–diffusion theory. Some of these developments were nascent in Turing’s paper, and others have been due to new insights from modern mathematical techniques, advances in numerical simulations and extensive biological experiments. Despite such progress, there are still important gaps between theory and experiment, with many examples of biological patterning where the underlying mechanisms are still unclear. Here, we review modern developments in the mathematical theory pioneered by Turing, showing how his approach has been generalized to a range of settings beyond the classical two-species reaction–diffusion framework, including evolving and complex manifolds, systems heterogeneous in space and time, and more general reaction-transport equations. While substantial progress has been made in understanding these more complicated models, there are many remaining challenges that we highlight throughout. We focus on the mathematical theory, and in particular linear stability analysis of ‘trivial’ base states. We emphasize important open questions in developing this theory further, and discuss obstacles in using these techniques to understand biological reality.

This article is part of the theme issue ‘Recent progress and open frontiers in Turing’s theory of morphogenesis’.
Healthcare professionals’ knowledge and practices towards hospital infections in surgical clinics
Authors: Galanis Petros , Kokkoliou Katerina , Vraka Irene , Konstantakopoulou Olympia , Siskou Olga , Bilali Angeliki , Kaitelidou Daphne
Published: November 2021

Background

Hospital-acquired infections are a major public health problem, as they increase hospitalization, cost, morbidity, mortality and antibiotic resistance.

Aim

To assess the level of knowledge and practices of health professionals about hospital infections in surgical clinics and investigate possible determinants that affects their compliance with international protocols for prevention and control of hospital infections.

Methods

A cross-sectional study with a convenience sample was conducted. Study population included 106 health professionals from medical and nursing staff in surgical clinics of a general hospital in Attica. Data collection was conducted during October and December 2019. We used the Healthcare-Associated Infections questionnaire to measure knowledge and practices of health professionals about hospital infections.

Results

The mean overall knowledge score for hospital infections was 59.4, indicating a moderate level of knowledge. The highest level of knowledge was about the safety of healthcare professionals, while the lowest level was about the source of hospital infections. The results of the multivariate linear regression showed that participants who were aware of the infection control program at their hospital and knew they had to wash their hands following the six steps of the hand hygiene protocol had a higher level of knowledge score regarding hospital infections. In contrast, participants who felt that their hospital was following a good infection control and prevention strategy had a lower level of knowledge. In addition, healthcare professionals who washed their hands before and after examining patients, after using medical equipment for patient care, throughout and after the end of the shift, and after removing disposable gloves had a higher level of knowledge for hospital infections.

Conclusions

The findings of the present study are consistent with the international literature on the existence of a moderate level of knowledge regarding international prevention guidelines. Compliance of healthcare professionals is essential to achieve universal, quality and safe healthcare and a safe working environment.
The effects of chronic consumption of lipid-rich and delipidated bovine dairy milk on brown adipose tissue volume in wild-type mice
Authors: D’Alonzo Zachary , Mamo John , Graneri Liam , Takechi Ryu , Lam Virginie
Published: November 2021

Brown adipose tissue (BAT) activation is associated with increased energy expenditure by inducing non-shivering thermogenesis. Ingestion of a milk fat globule membrane (MFGM) supplement and a high calorie diet are reported gateways into BAT activation. However, little is known about the effect of MFGM and high calorie diets on BAT volume. To gain insight into this, mice were maintained on a high fat (HF) or low-fat (LF) diet in conjunction with either full-cream (FC) or skim bovine dairy milk (BDM). After being maintained on their respective diets for 13 weeks, body composition, including BAT volume, was measured using X-ray microtomography. A high calorie diet resulted in an increase in BAT volume and mice consuming a HF diet in conjunction with FC BDM had significantly greater BAT volume than all other groups. Conversely, mice consuming a HF diet in addition to skim milk had lower BAT volume compared to the HF control. The data presented suggests that consumption of a high calorie diet in conjunction with FC BDM increases BAT volume in wild-type mice. This study may provide valuable insight into future studies investigating BAT volume and BAT activity in relation to environmental factors including diet.
Spacemake: processing and analysis of large-scale spatial transcriptomics data
Authors: Sztanka-Toth Tamas Ryszard , Jens Marvin , Karaiskos Nikos , Rajewsky Nikolaus
Published: November 2021

Spatial sequencing methods increasingly gain popularity within RNA biology studies. State-of-the-art techniques can read mRNA expression levels from tissue sections and at the same time register information about the original locations of the molecules in the tissue. The resulting datasets are processed and analyzed by accompanying software which, however, is incompatible across inputs from different technologies. Here, we present spacemake, a modular, robust and scalable spatial transcriptomics pipeline built in snakemake and python. Spacemake is designed to handle all major spatial transcriptomics datasets and can be readily configured to run on other technologies. It can process and analyze several samples in parallel, even if they stem from different experimental methods. Spacemake’s unified framework enables reproducible data processing from raw sequencing data to automatically generated downstream analysis reports. Moreover, spacemake is built with a modular design and offers additional functionality such as sample merging, saturation analysis and analysis of long-reads as separate modules. Moreover, spacemake employs novoSpaRc to integrate spatial and single-cell transcriptomics data, resulting in increased gene counts for the spatial dataset. Spacemake is open-source, extendable and can be readily integrated with existing computational workflows.
A combinatorial indexing strategy for epigenomic profiling of plant single cells
Authors: Tu Xiaoyu , Marand Alexandre P. , Schmitz Robert J. , Zhong Silin
Published: November 2021

Understanding how cis-regulatory elements facilitate gene expression is a key question in biology. Recent advances in single-cell genomics have led to the discovery of cell-specific chromatin landscapes that underlie transcription programs. However, the high equipment and reagent costs of commercial systems limit their applications for many laboratories. In this study, we profiled the Arabidopsis root single-cell epigenome using a combinatorial index and dual PCR barcode strategy without the need of any specialized equipment. We generated chromatin accessibility profiles for 13,576 Arabidopsis thaliana root nuclei with an average of 12,784 unique Tn5 integrations per cell and 85% of the Tn5 insertions localizing to discrete accessible chromatin regions. Comparison with data generated from a commercial microfluidic platform revealed that our method is capable of unbiased identification of cell type-specific chromatin accessibility with improved throughput, quality, and efficiency. We anticipate that by removing cost, instrument, and other technical obstacles, this combinatorial indexing method will be a valuable tool for routine investigation of single-cell epigenomes and usher new insight into plant growth, development and their interactions with the environment.