bluuebunny/crossref_metadata_2025 huggingface dataset:
Interlocking detachable coil embolization for giant tandem bronchial aneurysms
Authors: Chen Yingjie , Qin Wei , Zhu Ziyang , Wang Xiaojiang , Yu Wei , Li Fajiu , Li Chenghong
Published: December 2021

Rationale:

Bronchial artery aneurysm (BAA) is a rare disease that can be life-threatening if it ruptures. Tandem connections of multiple aneurysms are even rarer and more challenging to manage.

Patient concerns:

A 46-year-old woman presented to the hospital with intermittent hemoptysis for a week. A bronchial artery computed tomographic angiography scan revealed 2 BAAs associated with bronchial artery-to-pulmonary artery fistulas in the left lung. Three-dimensional CT reconstruction showed 2 bronchial aneurysms in tandem and 1 aneurysm adjacent to the descending aorta.

Diagnoses:

Giant tandem bronchial aneurysms were confirmed using computerized tomographic angiography.

Interventions:

Nine interlocking detachable coils and 11 standard pushable coils were introduced into aneurysms for embolization.

Outcomes:

There was no episodes of hemoptysis. CT angiography indicated that the coils were closely knit and in their proper position 1 month later; at follow-up, the patient had no adverse effects and no recurrence of hemoptysis.

Lessons:

BAA is a rare disease that can be life-threatening if it ruptures. It should be treated aggressively to determine the presence of symptoms.
Quality assessment of conventional and traditional oriental medicine clinical practice guidelines for knee osteoarthritis using AGREE II instrument
Authors: Kim Jun-Yeon , Kim Jung-Hyun , Goo Bon-Hyuk , Park Yeon-Cheol , Seo Byung-Kwan , Baek Yong-Hyeon
Published: December 2021

Introduction:

Knee osteoarthritis is a degenerative disease and its prevalence tends to increase. Clinical practice guidelines (CPGs) are evidence-based recommendations for treatment that help policymakers, practitioners, and patients make more appropriate and efficient decisions during the course of management. This study aimed to evaluate the quality of knee osteoarthritis CPGs using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.

Method:

The retrieval engines and websites were utilized from January 2010 to December 2020. The search words were “Clinical practice guideline” OR “Critical practice guideline” OR “guideline∗” AND “Osteoarthritis.” The quality of the CPGs was independently examined by four appraisers using the AGREE II instrument. Consequently, the selected CPGs were graded as Classes A, B, and C according to the level of recommendation.

Result:

In this study, 13 CPGs for knee osteoarthritis were selected and evaluated qualitatively using the AGREE II instrument. The overall quality percentage score was as follows: clarity of presentation, 72.6%, scope and purpose, 62.6%, rigor of development, 54.2%, stakeholder investment, 50.5%, editorial independence, 46.5%, applicability, 22.5%.

Conclusion:

Auxiliary materials for the treatment process of knee OA should be supplemented in future revised versions for quality improvement of knee OA CPGs. Also, more evidence should be accumulated to support the recommendation of traditional oriental medical treatments in the clinical field. From the perspective of integrative medicine, along with conventional pharmacological treatment, exercise, weight loss, and acupuncture can be combined together in clinical situations.
Efficacy of greater occipital nerve block for pain relief in patients with postdural puncture headache
Authors: Chang Ying-Jen , Hung Kuo-Chuan , Chen I-Wen , Kuo Chi-Lin , Teng I-Chia , Lin Ming-Chung , Yew Ming , Liao Shu-Wei , Wu Chung-Yi , Yu Chia-Hung , Lan Kuo-Mao , Sun Cheuk-Kwan
Published: December 2021

Background:

This study aimed at assessing the therapeutic effectiveness of greater occipital nerve block (GONB) against postdural puncture headache (PDPH).

Methods:

Studies investigating analgesic effects of GONB against PDPH in adults were retrieved from the MEDLINE, EMBASE, Google scholar, and Cochrane central databases from their inception dates to May, 2021. Pain score at postprocedural 24 hours was the primary endpoint, while secondary endpoints were pain score at postprocedural 1 hour and 12 hours as well as the risk of intervention failure.

Results:

Of the 7 studies (randomized controlled trials [RCTs], n = 4; non-RCTs, n = 3) that recruited 275 patients, 2 investigated female patients undergoing cesarean section and the other 5 were conducted in both obstetric and nonobstetric settings. Pooled results showed a lower mean pain score at 24 hours (i.e., primary outcome) (mean difference [MD] = –2.66, 95%: CI: –3.98 to –1.33, P < .001; I
2 = 97%, 6 studies), 1 hour (MD = –4.23, 95% confidence interval [CI]: –5.08 to –3.37, P < .00001; I
2 = 86%, 5 studies), and 6 hours (MD = –2.78, 95% CI: –4.99 to –0.57, P = .01; I
2 = 98%, 4 studies) in patients with GONB compared to those without. Trial sequential analysis supported the robustness of evidence at postprocedural 24 hours. The use of GONB also decreased the risk of intervention failure (relative ratio [RR] = 0.4, 95% CI: 0.19 to 0.82, P = .01; I
2 = 96%, 6 studies, 277 patients).

Conclusion:

Our results suggested a therapeutic effect of greater occipital nerve block against postdural puncture headache up to postprocedural 24 hours. Further large-scale studies are warranted to evaluate its therapeutic benefit beyond the acute stage.
Comparative Study of Acute Anogenital Injury Between Consensual and Nonconsensual Postmenarche Adolescents
Authors: Suttipasit Papanu , Sinlapamongkolkul Phakatip , Wongwittayapanich Surachet
Published: December 2021

In Thailand, sexual activity involving those under the legal age of consent may be legally and medically problematic, even if it is consensual. Thus, differentiating anogenital injury characteristics that occur during consensual versus nonconsensual acts with adolescent female subjects could aid legal advocates and improve health care and social support for these patients. Our study included postmenarche female patients having acute anogenital injuries after consensual and nonconsensual penetration. We found that nonconsenting patients had more cases of anogenital injury than consenting (69.8% vs 55.5%), with at least 1 abrasion, contusion, laceration, labia major or minor injury, and external or internal site injury. Both consensual and nonconsensual cases had the same common sites for injury type, reflecting the same injury mechanism; prior sexual intercourse was a significant protective factor against some anogenital injury prevalence, types, and sites for both groups. Adolescents forced into nonconsensual acts had more nonanogenital injuries. Looking at factors such as age, prior sexual activity history, and use of condom and/or contraceptive pills, it is very clear that early sexual education, particularly around consent, is critically needed in Thailand for the best interests of adolescents and children so that they and/or their guardians can access the health and legal resources required.
Characterizing Financial Sustainability of Sexually Transmitted Disease Clinics Through Insurance Billing Practices
Authors: Pearson William S. , Chan Philip A. , Cramer Ryan , Gift Thomas L.
Published: December 2021

Context:

Sexually transmitted infections (STIs) continue to increase in the United States. Publicly funded sexually transmitted disease (STD) clinics provide important safety net services for communities at greater risk for STIs. However, creating financially sustainable models of STI care remains a challenge.

Objective:

Characterization of clinic insurance billing practices and patient willingness to use insurance.

Design:

Cross-sectional survey assessment of clinic administrators and patients.

Setting:

Twenty-six STD clinics and 4138 patients attending these clinics in high STD morbidity metropolitan statistical areas in the United States.

Participants:

Clinic administrators and patients of these clinics.

Intervention:

Survey assessment.

Main Outcome Measure:

Insurance billing practices of STD clinics and patient insurance status and willingness to use their insurance.

Results:

Fifteen percent of clinics (4/26) indicated that they billed only Medicaid, 58% (15/26) billed both Medicaid and private insurance, 27% (7/26) did not bill for any health insurance, and none (0%) billed only private health insurance companies. Of 4138 patients surveyed, just more than one-half of patients (52.6%) were covered by some form of health insurance. More than one-half (57.2%) of all patients covered by health insurance indicated that they would be willing to use their health insurance for that visit. After adjusting for patient demographics and clinic characteristics, the patients covered by government insurance were 3 times as likely (odds ratio: 3.16; 95% confidence interval, 2.44-4.10) than patients covered by private insurance to be willing to use their insurance for their visit.

Conclusion:

Opportunities exist for sustainable STI services through the enhancement of billing practices in STD clinics. The STD clinics provide care to large numbers of individuals who are both insured and who are willing to use their insurance for their care. As Medicaid expansion continues across the country, efforts focused on improving reimbursement rates for Medicaid may improve financial sustainability of STD clinics.
Omeprazole Increases Survival Through the Inhibition of Inflammatory Mediaters in Two Rat Sepsis Models
Authors: Kotsuka Masaya , Hashimoto Yuki , Nakatake Richi , Okuyama Tetsuya , Hatta Masahiko , Yoshida Terufumi , Okumura Tadayoshi , Nishizawa Mikio , Kaibori Masaki , Sekimoto Mitsugu
Published: December 2021

Background:

Omeprazole (OMZ) is a proton pump inhibitor that is used to reduce gastric acid secretion, but little is known about its possible liver protective effects. This study investigated whether OMZ has beneficial effects in rat septic models of LPS-induced liver injury after D-galactosamine (GalN) treatment and 70% hepatectomy (PH), and to determine the mechanisms of OMZ in an in vitro model of liver injury.

Methods:

In the in vivo models, the effects of OMZ were examined 1 h before treatments in both models on survival, nuclear factor (NF)-κB activation, histopathological analysis, and proinflammatory mediator expression in the liver and serum. In the in vitro model, primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of OMZ. The influence of OMZ on nitric oxide (NO) product and inducible NO synthase (iNOS) induction and on the associated signaling pathway was analyzed.

Results:

OMZ increased survival and decreased tumor necrosis factor-alpha, iNOS, cytokine-induced neutrophil chemoattractant 1, IL-6, and IL-1β mRNA expression, and increased IL-10 mRNA expression in the livers of both GaIN/LPS- and PH/LPS-treated rats. Necrosis and apoptosis were inhibited by OMZ in GaIN/LPS rats, but OMZ had no effects on necrosis in PH/LPS rats. OMZ inhibited iNOS induction partially through suppression of NF-κB signaling in hepatocytes.

Conclusions:

OMZ inhibited the induction of several inflammatory mediators, resulting in the prevention of LPS-induced liver injury after GalN liver failure and PH, although OMZ showed different doses and mechanisms in the two models.
The experience of remote recruitment for Essential Coaching for Every Mother during the coronavirus disease 2019 pandemic
Authors: Dol Justine , Murphy Gail Tomblin , McMillan Douglas , Aston Megan , Campbell-Yeo Marsha
Published: December 2021

Introduction and aims:

Due to physical distancing recommendations because of the COVID-19 pandemic, recruitment approaches for perinatal research needed to shift from in-person to remote. The purpose of this study is to describe the recruitment and retention of women for an mHealth intervention study for Essential Coaching for Every Mother.

Methods:

Three methods were used for recruitment: social media, posters in hospital, and media outreach. First time mothers were eligible for enrollment antenatally (37+ weeks) and postnatally (<3 weeks). Eligibility screening occurred remotely via text message. Outcomes were days to recruit 75 participants, eligibility vs. ineligibility rates, dropout and exclusion reasons, survey completion rates, perinatal timing of enrollment, and recruitment sources.

Results:

Recruitment ran from 15 July to 19 September 2020 (67 days) with 200 potential participants screened and 88 enrolled. It took 50 days to enroll 75 participants. Women recruited antenatally were more likely to receive all intervention messages (68 vs. 19%) and miss fewer messages (6.4 vs. 13.8) than women enrolled postnatally. Participants heard about the study through family/friends (31%), news (20%), Facebook groups/ads (30%), posters (12%), or other (7%).

Conclusion:

Antenatal recruitment resulted in participants enrolling earlier and receiving more messages. Remote recruitment was a feasible way to recruit, with word of mouth and media outreach being most successful, followed by Facebook.
ICTV Virus Taxonomy Profile: Retroviridae 2021
Authors: Coffin John , Blomberg Jonas , Fan Hung , Gifford Robert , Hatziioannou Theodora , Lindemann Dirk , Mayer Jens , Stoye Jonathan , Tristem Michael , Johnson Welkin ,   ICTV Report Consortium
Published: December 2021

Viruses in the family Retroviridae are found in a wide variety of vertebrate hosts. Enveloped virions are 80–100 nm in diameter with an inner core containing the viral genome and replicative enzymes. Core morphology is often characteristic for viruses within the same genus. Replication involves reverse transcription and integration into host cell DNA, resulting in a provirus. Integration into germline cells can result in a heritable provirus known as an endogenous retrovirus. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Retroviridae, which is available at ictv.global/report/retroviridae.
vRhyme enables binning of viral genomes from metagenomes
Authors: Kieft Kristopher , Adams Alyssa , Salamzade Rauf , Kalan Lindsay , Anantharaman Karthik
Published: December 2021

Genome binning has been essential for characterization of bacteria, archaea, and even eukaryotes from metagenomes. Yet, no approach exists for viruses. We developed vRhyme, a fast and precise software for construction of viral metagenome-assembled genomes (vMAGs). vRhyme utilizes single- or multi-sample coverage effect size comparisons between scaffolds and employs supervised machine learning to identity nucleotide feature similarities, which are compiled into iterations of weighted networks and refined bins. Using simulated viromes, we displayed superior performance of vRhyme compared to available binning tools in constructing more complete and uncontaminated vMAGs. When applied to 10,601 viral scaffolds from human skin, vRhyme advanced our understanding of resident viruses, highlighted by identification of a Herelleviridae vMAG comprised of 22 scaffolds, and another vMAG encoding a nitrate reductase metabolic gene, representing near-complete genomes post-binning. vRhyme will enable a convention of binning uncultivated viral genomes and has the potential to transform metagenome-based viral ecology.
Prior exposure to microcystin alters host gut resistome and is associated with dysregulated immune homeostasis in translatable mouse models
Authors: Saha Punnag , Bose Dipro , Stebliankin Vitalii , Cickovski Trevor , Seth Ratanesh K. , Porter Dwayne E. , Brooks Bryan W. , Mathee Kalai , Narasimhan Giri , Colwell Rita , Scott Geoff I. , Chatterjee Saurabh
Published: December 2021

The increased propensity of harmful algal blooms (HABs) and exposure from HABs-cyanotoxin causes human toxicity. It has been associated with the progression of several diseases that encompass the liver, kidneys, and immune system. Recently, a strong association of cyano-HAB toxicity with the altered host gut microbiome has been shown. We tested the hypothesis that prior exposure to cyanotoxin microcystin may alter the microbiome and induce microbiome-host-resistome crosstalk. Using both wild-type and humanized mice, we show that the mice exposed to microcystin had an altered microbiome signature that harbored antimicrobial resistance genes. Host resistome phenotypes such as mefA, msrD, mel, ant6, and tet40 increased in diversity and relative abundance following microcystin exposure. Interestingly, the increased abundance of these genes was traced to resistance to common antibiotics such as tetracycline, macrolides, glycopeptide, and aminoglycosides, crucial for modern-day treatment for several diseases. Increased abundance of these genes was positively associated with increased expression of PD1, a T-cell homeostasis marker, and pleiotropic inflammatory cytokine IL-6 with a concomitant negative association with immunosurveillance markers IL7 and TLR2. Microcystin exposure also caused decreased TLR2, TLR4, and REG3G expressions, increased immunosenescence, and higher systemic levels of IL-6 in both wild-type and humanized mice. In conclusion, the results show a first-ever characterization of the host resistome of microcystin exposure and its connection to host immune status and antibiotic resistance. The results may be crucial for understanding the ability of exposed subjects to fight future bacterial infections and the progression of the debilitating disease in hospital settings.
Non-toxigenic Vibrio cholerae challenge strains for evaluating vaccine efficacy and inferring mechanisms of protection
Authors: Fakoya Bolutife , Hullahalli Karthik , Rubin Daniel H. F. , Leitner Deborah R. , Chilengi Roma , Sack David A. , Waldor Matthew K.
Published: December 2021

Human challenge studies are instrumental for testing cholera vaccines, but these studies use outdated strains and require inpatient facilities. Here, we created next-generation isogenic Ogawa and Inaba V. cholerae challenge strains (ZChol strains) derived from a contemporary Zambian clinical isolate representative of current dominant pandemic V. cholerae. To minimize the risk of severe diarrhea these strains were rendered non-toxigenic, since antibody responses which limit V. cholerae colonization are the primary mechanism of immune protection. These strains did not cause diarrhea in infant mice and proved to accurately gauge reduction in intestinal colonization mediated by effective vaccination. They are also valuable as targets for measuring vibriocidal antibody responses. Using barcoded ZChol strains, we discovered that vaccination tightens the infection bottleneck without restricting pathogen expansion in vivo. ZChol strains have the potential to enhance the safety, relevance, and scope of future cholera vaccine challenge studies and be valuable reagents for studies of immunity to cholera.
Characterization of sequence determinants of enhancer function using natural genetic variation
Authors: Yang Marty G. , Ling Emi , Cowley Christopher J. , Greenberg Michael E. , Vierbuchen Thomas
Published: December 2021

Sequence variation in enhancers, a class of cis-regulatory elements that control cell type-specific gene transcription, contributes significantly to phenotypic variation within human populations. Enhancers are short DNA sequences (∼200 bp) composed of multiple binding sites (4-10 bp) for transcription factors (TFs). The transcriptional regulatory activity of an enhancer is encoded by the type, number, and distribution of TF binding sites that it contains. However, the sequence determinants of TF binding to enhancers and the relationship between TF binding and enhancer activity are complex, and thus it remains difficult to predict the effect of any given sequence variant on enhancer function. Here, we generate allele-specific maps of TF binding and enhancer activity in fibroblasts from a panel of F1 hybrid mice that have a high frequency of sequence variants. We identified thousands of enhancers that exhibit differences in TF binding and/or activity between alleles and use these data to define features of sequence variants that are most likely to impact enhancer function. Our data demonstrate a critical role for AP-1 TFs at many fibroblast enhancers, reveal a hierarchical relationship between AP-1 and TEAD TF binding at enhancers, and delineate the nature of sequence variants that contribute to AP-1 TF binding. These data represent one of the most comprehensive assessments to date of the impact of sequence variation on enhancer function in chromatin, with implications for identifying functional cis-regulatory variation in human populations.
2FAST2Q: A general-purpose sequence search and counting program for FASTQ files
Authors: Bravo Afonso M. , Typas Athanasios , Veening Jan-Willem
Published: December 2021

The increasingly widespread use of next generation sequencing protocols has brought the need for the development of user-friendly raw data processing tools. Here, we present 2FAST2Q, a versatile and intuitive standalone program capable of extracting and counting feature occurrences in FASTQ files. 2FAST2Q can be used in any experimental setup that requires feature extraction from raw reads, being able to quickly handle mismatch alignments, nucleotide wise Phred score filtering, custom read trimming, and sequence searching within a single program. Using published CRISPRi datasets in whichEscherichia coliandMycobacterium tuberculosisgene essentiality, as well as host-cell sensitivity towards SARS-CoV2 infectivity were tested, we demonstrate that 2FAST2Q efficiently recapitulates the output in read counts per provided feature as with traditional pipelines. Moreover, we show how different FASTQ read filtering parameters impact downstream analysis, and suggest a default usage protocol. 2FAST2Q has a familiar user interface and uses a custom sequence mismatch search algorithm, taking advantage of Python’s numba module JIT runtime speeds. It is thus easier to use and faster than currently available tools, efficiently processing large CRISPRi-Seq or random-barcode sequencing datasets on any up-to-date laptop. 2FAST2Q is available as an executable file for all current operating systems without installation and as a Python3 module on the PyPI repository (available athttps://veeninglab.com/2fast2q). We expect that 2FAST2Q will not only be useful for people working in microbiology but also for other fields in which amplicon sequencing data is generated.
Microcin MccI47 selectively inhibits enteric bacteria and reduces carbapenem-resistant Klebsiella pneumoniae colonization in vivo when administered via an engineered live biotherapeutic
Authors: Mortzfeld Benedikt M. , Palmer Jacob D. , Bhattarai Shakti K. , Dupre Haley L. , Mercado-Lubo Regino , Silby Mark W. , Bang Corinna , McCormick Beth A. , Bucci Vanni
Published: December 2021

Background

The gastrointestinal (GI) tract is the reservoir for multidrug-resistant (MDR) pathogens, specifically carbapenem-resistant (CR) Klebsiella pneumoniae and other Enterobacteriaceae, which often lead to the spread of antimicrobial resistance genes, severe extraintestinal infections, and lethal outcomes. Selective GI decolonization has been proposed as a new strategy for preventing transmission to other body sites and minimizing spreading to susceptible individuals.

Results

Here, we purify the to-date uncharacterized class IIb microcin I47 (MccI47) and demonstrate potent inhibition of numerous Enterobacteriaceae, including multidrug-resistant clinical isolates, in vitro at concentrations resembling those of commonly prescribed antibiotics. We then genetically modify the probiotic bacterium Escherichia coli Nissle 1917 (EcN) to produce MccI47 from a stable multicopy plasmid by using MccI47 toxin production in a counterselection mechanism to engineer one of the native EcN plasmids, which renders provisions for inducible expression and plasmid selection unnecessary. We then test the clinical relevance of the MccI47-producing engineered EcN in a murine CR K. pneumoniae colonization model and demonstrate significant MccI47-dependent reduction of CR K. pneumoniae abundance after seven days of daily oral live biotherapeutic administration without disruption of the resident microbiota.

Conclusions

This study provides the first demonstration of MccI47 as a potent antimicrobial against certain Enterobacteriaceae, and its ability to significantly reduce the abundance of CR K. pneumoniae in a preclinical animal model, when delivered from an engineered live biotherapeutic product. This study serves as the foundational step towards the use of engineered live biotherapeutic products aimed at the selective removal of MDR pathogens from the GI tract
Comprehensive transcriptional profiling and mouse phenotyping reveals dispensable role for adipose tissue selective long noncoding RNA Gm15551
Authors: Engelhard Christoph Andreas , Huang Chien , Khani Sajjad , Kasparek Petr , Prochazka Jan , Rozman Jan , Reguera David Pajuelo , Sedlacek Radislav , Kornfeld Jan-Wilhelm
Published: December 2021

1

Cold and nutrient activated brown adipose tissue (BAT) is capable of increasing systemic energy expenditure via uncoupled respiration and secretion of endocrine factors thereby protecting mice against diet-induced obesity and improving insulin response and glucose tolerance in men. Long non-coding RNAs (lncRNAs) have recently been identified as fine tuning regulators of cellular function. While certain lncRNAs have been functionally characterised in adipose tissue, their overall contribution in the activation of BAT remains elusive. We identified lncRNAs correlating to inter-scapular brown adipose tissue (iBAT) function in high fat diet (HFD) and cold stressed mice. We focused on Gm15551 which has an adipose tissue specific expression profile, is highly upregulated during adipogenesis and downregulated by β-adrenergic activation in mature adipocytes. Albeit we performed comprehensive transcriptional and adipocyte physiology profiling in vitro and in vivo, we could not detect an effect of gain or loss of function of Gm15551.
The acquisition of clinically relevant amoxicillin resistance in Streptococcus pneumoniae requires ordered horizontal gene transfer of four loci
Authors: Gibson Paddy S. , Bexkens Evan , Zuber Sylvia , Cowley Lauren A. , Veening Jan-Willem
Published: December 2021

Understanding how antimicrobial resistance spreads is critical for optimal application of new treatments. In the naturally competent human pathogen Streptococcus pneumoniae, resistance to β-lactam antibiotics is mediated by recombination events in genes encoding the target proteins, resulting in reduced drug binding affinity. However, for the front-line antibiotic amoxicillin, the exact mechanism of resistance still needs to be elucidated. Through successive rounds of transformation with genomic DNA from a clinically resistant isolate, we followed amoxicillin resistance development. Using whole genome sequencing, we showed that multiple recombination events occurred at different loci during one round of transformation. We found examples of non-contiguous recombination, and demonstrated that this could occur either through multiple D-loop formation from one donor DNA molecule, or by the integration of multiple DNA fragments. We also show that the final minimum inhibitory concentration (MIC) differs depending on recipient genome, explained by differences in the extent of recombination at key loci. Finally, through back transformations of mutant alleles and fluorescently labelled penicillin (bocillin-FL) binding assays, we confirm that pbp1a, pbp2b, pbp2x, and murM are the main resistance determinants for amoxicillin resistance, and that the order of allele uptake is important for successful resistance evolution. We conclude that recombination events are complex, and that this complexity contributes to the highly diverse genotypes of amoxicillin-resistant pneumococcal isolates.
Extent of Molecular Chaperone Association Might Determine Fates of Membraneless Organelles during Aging in C. elegans
Authors: Mukherjee Pritam , Panda Prajnadipta , Kasturi Prasad
Published: December 2021

Proteome imbalance can lead to protein misfolding and aggregation which is associated with pathologies. Protein aggregation can also be an active, organized process and can be exploited by cells as a survival strategy. In adverse conditions, it is beneficial to deposit the proteins in a condensate rather degrading and resynthesizing. Membraneless organelles (MLOs) are biological condensates formed through liquid–liquid phase separation (LLPS), involving cellular components such as nucleic acids and proteins. LLPS is a regulated process, which when perturbed, can undergo a transition from a physiological liquid condensate to pathological solid-like protein aggregates.

To understand how the MLO-associated proteins (MLO-APs) behave during aging, we performed a comparative meta-analysis with age related proteome of C. elegans. We found that the MLO-APs are highly abundant throughout the lifespan. Interestingly, they are aggregating more in long-lived mutant worms compared to the age matched wildtype worms. GO term analysis revealed that the cell cycle and embryonic development are among the top enriched processes in addition to RNP components in insoluble proteome. Considering antagonistic pleotropic nature of these developmental genes and post mitotic status of C. elegans, we assume that these proteins phase transit during post development. As the organism ages, these MLO-APs either mature to become more insoluble or dissolve in uncontrolled manner. However, in the long-lived daf-2 mutant worms, the MLOs may attain protective states due to extended availability and association of molecular chaperones.
Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment
Authors: Navarro Alexandra P. , Cheeseman Iain M.
Published: December 2021

The kinetochore is a macromolecular structure that is required to ensure proper chromosome segregation during each cell division. The kinetochore is assembled upon a platform of the 16-subunit Constitutive Centromere Associated Network (CCAN), which is present at centromeres throughout the cell cycle. The nature and regulation of CCAN assembly, interactions, and dynamics required to facilitate changing centromere properties and requirements remain to be fully elucidated. The CENP-LN CCAN sub-complex displays a unique cell cycle-dependent localization behavior, peaking in S phase. Here, we demonstrate that phosphorylation of CENP-L and CENP-N controls CENP-LN complex formation and localization in a cell cycle-dependent manner. Mimicking constitutive phosphorylation of either CENP-L or CENP-N or simultaneously preventing phosphorylation of both proteins prevents CENP-LN localization and disrupts chromosome segregation. Together, our work suggests that cycles of phosphorylation and dephosphorylation are critical for CENP-LN complex recruitment and dynamics at centromeres to enable cell cycle-dependent CCAN reorganization.
Evidence for widespread cytoplasmic structuring into mesoscopic condensates
Authors: Keber Felix C. , Nguyen Thao , Brangwynne Clifford P. , Wühr Martin
Published: December 2021

Eukaryotic cytoplasm organizes itself via both membrane-bound organelles and membrane-less biomolecular condensates (BMCs). Known BMCs exhibit liquid-like properties and are typically visualized on the scale of ~1 μm. They have been studied mostly by microscopy, examining select individual proteins. Here, we investigate the global organization of native cytoplasm with quantitative proteomics, using differential pressure filtration, size exclusion, and dilution experiments. These assays reveal that BMCs form throughout the cytosplasm, predominantly at the mesoscale of ~100 nm. Our data indicate that at least 18% of the proteome is organized via such mesoscale BMCs, suggesting that cells widely employ dynamic liquid-like clustering to organize their cytoplasm, at surprisingly small length scales.
The measurement properties and acceptability of a new parent-infant bonding tool (‘Me and My Baby’) designed for use in a universal healthcare setting in the UK
Authors: Bywater T. , Dunn A. , Endacott C. , Smith K. , Tiffin P. A , Blower S. , Price M.
Published: December 2021

NICE guidelines acknowledge the importance of the parent-infant relationship for child development but highlight the need for further research to establish reliable tools for assessment, particularly for parents of children under one year.

This study explores the acceptability and psychometric properties of a co-developed tool, ‘Me and My Baby’ (MaMB).

Study design

A cross-sectional design was applied. The MaMB was administered universally (in two sites) with mothers during routine 6–8-week Health Visitor contacts. The sample comprised 467 mothers (434 MaMB completers and 33 ‘non-completers’). Dimensionality of instrument responses were evaluated via exploratory and confirmatory ordinal factor analyses. Item response modelling was conducted via a Rasch calibration to evaluate how the tool conformed to principles of ‘fundamental measurement’. Tool acceptability was evaluated via completion rates and comparing ‘completers’ and ‘non-completers’ demographic differences on age, parity, ethnicity, and English as an additional language. Free-text comments were summarised. Data sharing agreements and data management were compliant with the General Data Protection Regulation, and University of York data management policies.

Results

High completion rates suggested the MaMB was acceptable. Psychometric analyses showed the response data to be an excellent fit to a unidimensional confirmatory factor analytic model. All items loaded statistically significantly and substantially (>0.4) on a single underlying factor (latent variable). The item response modelling showed that most MaMB items fitted the Rasch model. Item reliability was high (0.94) yet the test yielded little information on each respondent, as highlighted by the ‘person separation index’ of 0.1 (=>2.0 is required to reliably discriminate between two groups).

Conclusions and next steps

MaMB reliably measures a single construct, likely to be infant bonding. However, further validation work is needed, preferably with ‘enriched population samples’ to include higher-need/risk families. The MaMB tool may benefit from reduced response categories (from four to three) and some modest item wording amendments. Following further validation and reliability appraisal the MaMB may ultimately be used with fathers/other primary caregivers and be potentially useful in research, universal health settings as part of a referral pathway, and clinical practice, to identify dyads in need of additional support/interventions.
A comprehensive systematic review and meta-analysis of the global data involving 61,532 cancer patients with SARS-CoV-2 infection
Authors: Khoury Emma , Nevitt Sarah , Madsen William Rohde , Turtle Lance , Davies Gerry , Palmieri Carlo
Published: December 2021

Background

SARS-CoV-2 have been shown to be associated with more severe disease and death in cancer patient. A systematic review and meta-analysis was conducted to determine the risk by age, tumour type and treatment of infection with SARS-CoV-2 in cancer patients.

Methods

Systematic review by searching PubMed, Web of Science, and Scopus for articles published in English up to June 14, 2021 of SARS-CoV-2 infection in >10 patients with malignant disease. Outcomes included factors in patients with malignant disease that may predict a poor outcome from COVID-19 compared to patients without malignant disease, including patient demographics, tumour subtype and cancer treatments. A meta-analysis was performed using random effects model.

Results

81 studies were included, totalling 61,532 cancer patients. Haematological malignancies comprised 22.1% (9,672 of 43,676) of cases. Relative risk (RR) of mortality when age and sex matched was 1.69 (95% CI, 1.46-1.95; p<0.001; I2=51%). RR of mortality, versus non-cancer patients, was associated with decreasing age (exp(b)0.96; 95% CI, 0.922–0.994; p=0.028) but not male sex (exp(b)1.89; 95% CI, 0.222–6.366; p=0.83). RR of mortality in those with haematological malignancies versus non-cancer control was 1.81 (95% CI, 1.53-2.95; I2=0.0%). Compared to other cancers, increased risk of death was seen for lung (RR 1.68, 95% CI, 1.45-1.94; p<0.001), genitourinary (RR 1.11; 95% CI, 1.00-1.24; p=0.059) and haematological malignancies (RR 1.42; 95% CI, 1.31-1.54; p<0.001). Breast (RR 0.51; 95% CI, 0.36-0.71; p<0.001) and gynaecological cancers (RR 0.76; 95% CI, 0.62-0.93; p=0.009) had lower risk of death. Receipt of chemotherapy had greatest overall pooled mortality risk of 30% (95% CI, 25-36%; I2=86.97%) and endocrine therapy the lowest at 11% (95% CI, 6-16%; I2=70.7%).

Conclusions

Cancer patients, particularly younger cancer patients, appear at increased risk of mortality from COVID-19 compared to non-cancer patients. Differences in outcomes were seen based on tumour types and treatment.

Highlights

-

To our knowledge this is the largest review and meta-analysis of COVID-19 in cancer patients with insights into tumour types and therapies.

-

In unadjusted analysis cancer doubles the risk of COVID-19 related mortality. This decreased when adjusted for age and sex.

-

Younger cancer patients have the highest risk of mortality when compared to non-cancer COVID-19 patient of a similar age.

-

Patients with lung, genitourinary and haematological malignancies are at increased risk of mortality, breast and gynaecological cancers are at lower risk.

-

Patients on chemotherapy have the highest pooled mortality risk with those on endocrine therapy the lowest.
Knowledge, Attitude and Practices towards COVID 19 pandemic among homeless street young adults in Lusaka, Zambia – A Mixed Methods Approach
Authors: Samuyachi K. , Sampa M. , Zambwe M. , Chipimo P.J.
Published: December 2021

Objective

To determine the knowledge, attitude and practices towards COVID-19 among homeless street young adults in Lusaka district, Zambia.

Methods

A total of 89 young street adults aged between 16-35 years were sampled. A concurrent mixed methods approach was used, Structured questionnaires and focused group discussion, to achieve the objectives. STATA 13 was used to produce Descriptive statistics while thematic analysis was used to analyze the qualitative data.

Results

Majority of the survey participants were male 67(78%), 55(62%) were single while 53(59%) had attained a Primary School Education. The majority of the participants received the COVID-19 information through the radio (61%). Only 44 (49%)% had adequate knowledge on Covid-19 of whom 70 (78.6%) had a positive attitude towards COVID-19. However, the 65(73%) had a low risk perception of contracting the disease. Further, 66 (74.2%) had a positive attitude towards the effectiveness of precautionary behaviors and measures. The finding also revealed that only 3(3.3%) had good practice towards the Covid-19 preventative measures overall with (SD:0).

Conclusion

Knowledge and attitudes towards COVID-19 were quite high among homeless street adults. However, their good practices were alarmingly low. Specific strategies for them being a vulnerable group are required.
The early-stage comprehensive costs of routine PrEP implementation and scale-up in Zambia
Authors: Hendrickson Cheryl , Long Lawrence C , van Rensburg Craig , Claassen Cassidy W , Njelesani Mwansa , Moyo Crispin , Mulenga Lloyd , O’Bra Heidi , Russell Colin A , Nichols Brooke E
Published: December 2021

Introduction

Pre-exposure prophylaxis (PrEP) is effective at preventing HIV infection, but PrEP cost-effectiveness is sensitive to PrEP implementation and program costs. Preliminary studies indicate that, in addition to direct delivery cost, PrEP provision requires substantial demand creation and user support to encourage PrEP initiation and persistence. We estimated the cost of providing PrEP in Zambia through different PrEP delivery models.

Methods

Taking a guidelines-based approach for visits, labs and drugs assuming fidelity to the expanded 2018 Zambian PrEP guidelines, we estimated the annual cost of providing PrEP per client for five delivery models: one focused on key populations (men-who-have-sex-with-men (MSM) and female sex workers (FSW), one on adolescent girls and young women (AGYW), and three integrated programs (operated within the HIV counselling and testing service at primary healthcare centres). Program start-up, provider, and user support costs were based on program expenditure data and number of PrEP sites and clients in 2018. PrEP clinic visit costs were based on micro-costing at two PrEP delivery sites (in 2018 USD).

Results

The annual cost per PrEP client varied greatly by program type, from $394 (AGYW) to $760 in an integrated program. Cost differences were driven largely by volume (i.e. the number of clients initiated/model/site) which impacted the relative costs of program support and technical assistance assigned to each PrEP client. Direct service delivery costs, including staff and overheads, labs and monitoring, drugs and consumables ranged narrowly from $208-217/PrEP-user. Service delivery costs were a key component in the cost of PrEP, representing 36-65% of total costs. Reductions in service delivery costs per PrEP client are expected with further scale-up.

Conclusions

The results show that, even when integrated into full service delivery models, accessing vulnerable, marginalised populations at substantial risk of HIV infection is likely to cost more than previously estimated due to the programmatic costs involved in community sensitization and user support. Improved data on individual client resource usage (e.g. drugs, labs, visits) and outcomes (e.g. initiation, persistence) is required to get a better understanding of the true resource utilization, cost and expected outcomes and annual costs of different PrEP programs in Zambia.
Speech-driven Facial Animations Improve Speech-in-Noise Comprehension of Humans
Authors: Varano Enrico , Vougioukas Konstantinos , Ma Pingchuan , Petridis Stavros , Pantic Maja , Reichenbach Tobias
Published: December 2021

Understanding speech becomes a demanding task when the environment is noisy. Comprehension of speech in noise can be substantially improved by looking at the speaker’s face, and this audiovisual benefit is even more pronounced in people with hearing impairment. Recent advances in AI have allowed to synthesize photorealistic talking faces from a speech recording and a still image of a person’s face in an end-to-end manner. However, it has remained unknown whether such facial animations improve speech-in-noise comprehension. Here we consider facial animations produced by a recently introduced generative adversarial network (GAN), and show that humans cannot distinguish between the synthesized and the natural videos. Importantly, we then show that the end- to-end synthesized videos significantly aid humans in understanding speech in noise, although the natural facial motions yield a yet higher audiovisual benefit. We further find that an audiovisual speech recognizer benefits from the synthesized facial animations as well. Our results suggest that synthesizing facial motions from speech can be used to aid speech comprehension in difficult listening environments.
Song Richness Index: A measure to understand the diversity and repetition of notes in a birdsong
Authors: Sawant Suyash , Arvind Chiti , Joshi Viral , Robin V. V.
Published: December 2021

Birdsong plays an important role in mate attraction and territorial defense. Many birds, especially Passerines, produce varying sequences of multiple notes resulting in complex songs. Studying the diversity of notes within these songs can give insights into an individual’s reproductive fitness. We first looked at the previously described and commonly used diversity measures to understand the possible case-specific limitations. We then developed a new diversity measure-Song Richness Index (SRI). We compared SRI with three measures of diversity using all possible combinations of notes to understand the case-specific advantages and limitations of all approaches. Simulating all possible combinations gave us insights into how each diversity measure works in a real scenario. SRI showed an advantage over conventional measures of diversity like Note Diversity Index (NDI), Shannon’s Equitability (SH), and Simpson’s Diversity (SI), especially in the cases where songs are made up of only one type of repetitive note.
Visualizing translation dynamics at atomic detail inside a bacterial cell
Authors: Xue Liang , Lenz Swantje , Zimmermann-Kogadeeva Maria , Tegunov Dimitry , Cramer Patrick , Bork Peer , Rappsilber Juri , Mahamid Julia
Published: December 2021

Translation is the fundamental process of protein synthesis and is catalysed by the ribosome in all living cells. Here, we use cryo-electron tomography and sub-tomogram analysis to visualize the dynamics of translation inside the prokaryote Mycoplasma pneumoniae. We first obtain an in-cell atomic model for the M. pneumoniae ribosome that reveals distinct extensions of ribosomal proteins. Classification then resolves thirteen ribosome states that differ in conformation and composition and reflect intermediates during translation. Based on these states, we animate translation elongation and demonstrate how antibiotics reshape the translation landscape inside cells. During translation elongation, ribosomes often arrange in a defined manner to form polysomes. By mapping the intracellular three-dimensional organization of translating ribosomes, we show that their association into polysomes exerts a local coordination mechanism that is mediated by the ribosomal protein L9. Our work demonstrates the feasibility of visualizing molecular processes at atomic detail inside cells.
Chromosome remodelling by SMC/Condensin in B. subtilis is regulated by Soj/ParA during growth and sporulation
Authors: Roberts David M. , Anchimiuk Anna , Kloosterman Tomas G. , Murray Heath , Wu Ling Juan , Gruber Stephan , Errington Jeff
Published: December 2021

SMC complexes, loaded at ParB-parS sites, are key mediators of chromosome organization in bacteria. ParA/Soj proteins interact with ParB/Spo0J in a pathway involving ATP-dependent dimerization and DNA binding, leading to chromosome segregation and SMC loading. In Bacillus subtilis, ParA/Soj also regulates DNA replication initiation, and along with ParB/Spo0J is involved in cell cycle changes during endospore formation. The first morphological stage in sporulation is the formation of an elongated chromosome structure called an axial filament. We now show that a major redistribution of SMC complexes drives axial filament formation, in a process regulated by ParA/Soj. Unexpectedly, this regulation is dependent on monomeric forms of ParA/Soj that cannot bind DNA or hydrolyse ATP. These results reveal a new role for ParA/Soj proteins in the regulation of SMC dynamics in bacteria, and yet further complexity in the web of interactions involving chromosome replication, segregation, and organization, controlled by ParAB and SMC.