bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-talk between mitochondrial function, growth, and stress signalling pathways in plants
Authors: Welchen Elina , Canal María Victoria , Gras Diana E , Gonzalez Daniel H
Published: December 2020

Plant mitochondria harbour complex metabolic routes that are interconnected with those of other cell compartments, and changes in mitochondrial function remotely influence processes in different parts of the cell. This implies the existence of signals that convey information about mitochondrial function to the rest of the cell. Increasing evidence indicates that metabolic and redox signals are important for this process, but changes in ion fluxes, protein relocalization, and physical contacts with other organelles are probably also involved. Besides possible direct effects of these signalling molecules on cellular functions, changes in mitochondrial physiology also affect the activity of different signalling pathways that modulate plant growth and stress responses. As a consequence, mitochondria influence the responses to internal and external factors that modify the activity of these pathways and associated biological processes. Acting through the activity of hormonal signalling pathways, mitochondria may also exert remote control over distant organs or plant tissues. In addition, an intimate cross-talk of mitochondria with energy signalling pathways, such as those represented by TARGET OF RAPAMYCIN and SUCROSE NON-FERMENTING1-RELATED PROTEIN KINASE 1, can be envisaged. This review discusses available evidence on the role of mitochondria in shaping plant growth and stress responses through various signalling pathways.
Asteroseismology of luminous red giants with Kepler – II. Dependence of mass-loss on pulsations and radiation
Authors: Yu Jie , Hekker Saskia , Bedding Timothy R , Stello Dennis , Huber Daniel , Gizon Laurent , Khanna Shourya , Bi Shaolan
Published: December 2020

Mass-loss by red giants is an important process to understand the final stages of stellar evolution and the chemical enrichment of the interstellar medium. Mass-loss rates are thought to be controlled by pulsation-enhanced dust-driven outflows. Here, we investigate the relationships between mass-loss, pulsations, and radiation, using 3213 luminous Kepler red giants and 13 5000 ASAS–SN semiregulars and Miras. Mass-loss rates are traced by infrared colours using 2MASS and Wide-field Infrared Survey Explorer(WISE) and by observed-to-model WISE fluxes, and are also estimated using dust mass-loss rates from literature assuming a typical gas-to-dust mass ratio of 400. To specify the pulsations, we extract the period and height of the highest peak in the power spectrum of oscillation. Absolute magnitudes are obtained from the 2MASS Ks band and the Gaia DR2 parallaxes. Our results follow. (i) Substantial mass-loss sets in at pulsation periods above ∼60 and ∼100 d, corresponding to Asymptotic-Giant-Branch stars at the base of the period-luminosity sequences C′ and C. (ii) The mass-loss rate starts to rapidly increase in semiregulars for which the luminosity is just above the red-giant-branch tip and gradually plateaus to a level similar to that of Miras. (iii) The mass-loss rates in Miras do not depend on luminosity, consistent with pulsation-enhanced dust-driven winds. (iv) The accumulated mass-loss on the red giant branch consistent with asteroseismic predictions reduces the masses of red-clump stars by 6.3 per cent, less than the typical uncertainty on their asteroseismic masses. Thus mass-loss is currently not a limitation of stellar age estimates for galactic archaeology studies.
Fast and Robust Identity-by-Descent Inference with the Templated Positional Burrows–Wheeler Transform
Authors: Freyman William A , McManus Kimberly F , Shringarpure Suyash S , Jewett Ethan M , Bryc Katarzyna ,   The 23 and Me Research Team, Auton Adam
Published: December 2020

Estimating the genomic location and length of identical-by-descent (IBD) segments among individuals is a crucial step in many genetic analyses. However, the exponential growth in the size of biobank and direct-to-consumer genetic data sets makes accurate IBD inference a significant computational challenge. Here we present the templated positional Burrows–Wheeler transform (TPBWT) to make fast IBD estimates robust to genotype and phasing errors. Using haplotype data simulated over pedigrees with realistic genotyping and phasing errors, we show that the TPBWT outperforms other state-of-the-art IBD inference algorithms in terms of speed and accuracy. For each phase-aware method, we explore the false positive and false negative rates of inferring IBD by segment length and characterize the types of error commonly found. Our results highlight the fragility of most phased IBD inference methods; the accuracy of IBD estimates can be highly sensitive to the quality of haplotype phasing. Additionally, we compare the performance of the TPBWT against a widely used phase-free IBD inference approach that is robust to phasing errors. We introduce both in-sample and out-of-sample TPBWT-based IBD inference algorithms and demonstrate their computational efficiency on massive-scale data sets with millions of samples. Furthermore, we describe the binary file format for TPBWT-compressed haplotypes that results in fast and efficient out-of-sample IBD computes against very large cohort panels. Finally, we demonstrate the utility of the TPBWT in a brief empirical analysis, exploring geographic patterns of haplotype sharing within Mexico. Hierarchical clustering of IBD shared across regions within Mexico reveals geographically structured haplotype sharing and a strong signal of isolation by distance. Our software implementation of the TPBWT is freely available for noncommercial use in the code repository (https://github.com/23andMe/phasedibd, last accessed January 11, 2021).
Evidence for multi-copy Mega-NUMTsin the human genome
Authors: Lutz-Bonengel Sabine , Niederstätter Harald , Naue Jana , Koziel Rafal , Yang Fengtang , Sänger Timo , Huber Gabriela , Berger Cordula , Pflugradt René , Strobl Christina , Xavier Catarina , Volleth Marianne , Weiß Sandra Carina , Irwin Jodi A , Romsos Erica L , Vallone Peter M , Ratzinger Gudrun , Schmuth Matthias , Jansen-Dürr Pidder , Liehr Thomas , Lichter Peter , Parsons Thomas J , Pollak Stefan , Parson Walther
Published: December 2020

The maternal mode of mitochondrial DNA (mtDNA) inheritance is central to human genetics. Recently, evidence for bi-parental inheritance of mtDNA was claimed for individuals of three pedigrees that suffered mitochondrial disorders. We sequenced mtDNA using both direct Sanger and Massively Parallel Sequencing in several tissues of eleven maternally related and other affiliated healthy individuals of a family pedigree and observed mixed mitotypes in eight individuals. Cells without nuclear DNA, i.e. thrombocytes and hair shafts, only showed the mitotype of haplogroup (hg) V. Skin biopsies were prepared to generate ρ° cells void of mtDNA, sequencing of which resulted in a hg U4c1 mitotype. The position of the Mega-NUMT sequence was determined by fluorescence in situ hybridization and two different quantitative PCR assays were used to determine the number of contributing mtDNA copies. Thus, evidence for the presence of repetitive, full mitogenome Mega-NUMTs matching haplogroup U4c1 in various tissues of eight maternally related individuals was provided. Multi-copy Mega-NUMTs mimic mixtures of mtDNA that cannot be experimentally avoided and thus may appear in diverse fields of mtDNA research and diagnostics. We demonstrate that hair shaft mtDNA sequencing provides a simple but reliable approach to exclude NUMTs as source of misleading results.
The MDM2 inducible promoter folds into four-tetrad antiparallel G-quadruplexes targetable to fight malignant liposarcoma
Authors: Lago Sara , Nadai Matteo , Ruggiero Emanuela , Tassinari Martina , Marušič Maja , Tosoni Beatrice , Frasson Ilaria , Cernilogar Filippo M , Pirota Valentina , Doria Filippo , Plavec Janez , Schotta Gunnar , Richter Sara N
Published: December 2020

Well-differentiated liposarcoma (WDLPS) is a malignant neoplasia hard to diagnose and treat. Its main molecular signature is amplification of the MDM2-containing genomic region. The MDM2 oncogene is the master regulator of p53: its overexpression enhances p53 degradation and inhibits apoptosis, leading to the tumoral phenotype. Here, we show that the MDM2 inducible promoter G-rich region folds into stable G-quadruplexes both in vitro and in vivo and it is specifically recognized by cellular helicases. Cell treatment with G-quadruplex-ligands reduces MDM2 expression and p53 degradation, thus stimulating cancer cell cycle arrest and apoptosis. Structural characterization of the MDM2 G-quadruplex revealed an extraordinarily stable, unique four-tetrad antiparallel dynamic conformation, amenable to selective targeting. These data indicate the feasibility of an out-of-the-box G-quadruplex-targeting approach to defeat WDLPS and all tumours where restoration of wild-type p53 is sought. They also point to G-quadruplex-dependent genomic instability as possible cause of MDM2 expansion and WDLPS tumorigenesis.
Proportionate mortality study of unionized maintenance of way railroad workers
Authors: Goldsmith D F , Barlet G
Published: December 2020

Background

Railroad maintenance of way (MOW) workers are exposed to many workplace hazards, including diesel fuel and exhaust, ballast (silica) dust, asbestos, solvents, herbicides, welding fumes, heavy rolling equipment, vibration and extreme weather.

Aims

Due to the number of excess deaths we found in a companion standardized mortality ratio (SMR) study for union members <65 years, we hypothesized that these workers may have elevated mortality risks among all ages for many chronic conditions.

Methods

Proportionate mortality ratios (PMRs) were calculated for 37 661 male MOW workers ages 20 and older who were members of the Brotherhood of Maintenance of Way Employes Division (BMWED). A data set was submitted to the National Death Index (NDI) to identify decedents and to determine cause of death for workers who died between 1979 and 2014. The CDC WONDER database was used to determine expected mortality for US males.

Results

For certain diseases and cancers the SMR and PMR findings have parallel mortality excesses. Examples include septicaemia and anaemia; diabetes; chronic obstructive pulmonary disease (COPD); nephritis; and transportation accidents. Among cancers, we found excess oesophageal, stomach, colorectal, lung, prostate, kidney and in situ cancers. Two excess SMR findings were not replicated in the PMR assessment—Alzheimer’s and Parkinson’s disease.

Conclusions

The PMR findings suggest that some of the mortality excesses from the SMR study are elevated, which adds support to their being consistently raised among BMWED members. The shared excess causes of death in the PMR and SMR studies should be focused on for future prevention and surveillance activities.
Family Policy as a Power Source of Political Stability: The Experience of Kazakhstan
Authors: Iskakova Zhuldyzay , Kalashnikova Natalya , Onychko Marina , Salikzhanov Rinat , Smagambet Bayan , Otar Elmira , Abetova Zeinep
Published: December 2020

This article is based on an analysis of the results of a survey conducted among 106 experts in the field of family policy in Kazakhstan in March 2020. The study results provided an expert assessment of family policy effectiveness in Kazakhstan and civil society’s role in it. The results show that experts assess the effectiveness of the civil sector in implementing the national family policy above the state: the level of efficiency is two times higher, and the level of knowledge and competencies is three times higher. In this regard, the government should interact more intensively with non-governmental organizations.
Phylogenomics, Origin, and Diversification of Anthozoans (Phylum Cnidaria)
Authors: McFadden Catherine S , Quattrini Andrea M , Brugler Mercer R , Cowman Peter F , Dueñas Luisa F , Kitahara Marcelo V , Paz-García David A , Reimer James D , Rodríguez Estefanía
Published: December 2020

Anthozoan cnidarians (corals and sea anemones) include some of the world’s most important foundation species, capable of building massive reef complexes that support entire ecosystems. Although previous molecular phylogenetic analyses have revealed widespread homoplasy of the morphological characters traditionally used to define orders and families of anthozoans, analyses using mitochondrial genes or rDNA have failed to resolve many key nodes in the phylogeny. With a fully resolved, time-calibrated phylogeny for 234 species constructed from hundreds of ultraconserved elements and exon loci, we explore the evolutionary origins of the major clades of Anthozoa and some of their salient morphological features. The phylogeny supports reciprocally monophyletic Hexacorallia and Octocorallia, with Ceriantharia as the earliest diverging hexacorals; two reciprocally monophyletic clades of Octocorallia; and monophyly of all hexacoral orders with the exception of the enigmatic sea anemone Relicanthus daphneae. Divergence dating analyses place Anthozoa in the Cryogenian to Tonian periods (648–894 Ma), older than has been suggested by previous studies. Ancestral state reconstructions indicate that the ancestral anthozoan was a solitary polyp that had bilateral symmetry and lacked a skeleton. Colonial growth forms and the ability to precipitate calcium carbonate evolved in the Ediacaran (578 Ma) and Cambrian (503 Ma) respectively; these hallmarks of reef-building species have subsequently arisen multiple times independently in different orders. Anthozoans formed associations with photosymbionts by the Devonian (383 Ma), and photosymbioses have been gained and lost repeatedly in all orders. Together, these results have profound implications for the interpretation of the Precambrian environment and the early evolution of metazoans.[Bilateral symmetry; coloniality; coral; early metazoans; exon capture; Hexacorallia; Octocorallia photosymbiosis; sea anemone; ultraconserved elements.]
Surgery in mycetoma-endemic villages: unique experience
Authors: Mohamed El Samani Wadaa , Bakhiet Sahar Mubarak , El Nour Mustafa , Suliman Suliman Hussein , El Amin Hajo Mohamed , Fahal Ahmed Hassan
Published: December 2020

In this communication, the Mycetoma Research Center (MRC), University of Khartoum, WHO Collaborating Center on Mycetoma, shares its experience in field surgery for mycetoma. The surgery was conducted in two mycetoma-endemic villages in Sennar and the White Nile States in collaboration with local health authorities, local community leaders, activists and civil society associations. In these villages, the local health centres were renovated and operating theatres were established. The medical and health missions’ team was established at the MRC. The team conducted 15 missions over the period 2013–2020 and 1200 mycetoma patients received surgical treatment. These included wide local excisions, minor amputations and debridement that were conducted under spinal or ketamine analgesia. The missions adopted a community holistic management approach, which included medical and surgical treatment, health education sessions, village hygiene improvement and socio-economic support. The latter offered the mycetoma amputees artificial prosthesis and financial support. All these services were provided free of charge. This holistic approach proved to be effective for early case detection and management, optimal treatment outcome and favourable disease prognosis. During the study period, the number of patients with massive lesions and the amputation rate decreased and this reduced the medical and socio-economic disease burdens on patients and families. This treatment approach needs the collaboration of all stakeholders for sustainability and quality improvement.
Central Visual Field Sensitivity With and Without Background Light Given to the Nontested Fellow Eye in Glaucoma Patients
Authors: Mine Izumi , Shoji Takuhei , Kumagai Tomoyuki , Yoshikawa Yuji , Kosaka Akane , Shinoda Kei
Published: December 2020

Precis:

This study showed the difference of monocular visual sensitivity between with and without background light given to the nontested fellow eyes in glaucoma patients. Monocular sensitivity measurements of the worse eyes with fellow eye’s background light conditions should carefully be considered when assessing the impact of functional impairment in glaucoma patients.

Purpose:

The purpose of this study was to investigate the difference between monocular sensitivities measured with and without background light given to the nontested fellow eye in glaucoma patients using a new perimeter named “imo.”

Methods:

In this cross-sectional study, we examined 102 eyes of 51 patients (mean age, 65.1±14.9 y) with open-angle glaucoma who were affected with at least 1 significant point in the central 10 degrees. We conducted a routine ophthalmic examination and visual field testing using the Humphrey Field Analyzer 24-2 and 10-2 programs. The eyes were assigned to “better” and “worse” categories based on the visual acuity and central visual thresholding. Subsequently, we compared the central visual sensitivities with and without background light given to the nontested fellow eye.

Results:

The mean sensitivity (MS) in the central 5 points of the visual field of the worse eyes was better when measured with background light than without background light (P=0.037) given to the nontested fellow eye. No significant difference was seen among the MS in the visual field of the better eyes. After dividing the patients into low (n=25) and high sensitivity (n=26) groups, only the low sensitivity group in worse eyes had higher MS with background light than without background light (P<0.05) given to the nontested fellow eye.

Conclusions:

Monocular sensitivities measured with background light given to the nontested fellow eye were higher than those without background light in the worse eye group of glaucoma patients. Monocular MS measurements of the worse eyes with fellow eye’s background light conditions and their related indices should thus carefully be considered when assessing the impact of functional impairment in glaucoma patients.
1H NMR-based dynamic metabolomics delineates the therapeutic effects of Shenfu injection on laparoscopic hysterectomy
Authors: Wang Xue , Wang Kai , Wang Huan , Li Xiangkui , Feng Jinzhou , Chen Qian
Published: December 2020

To explore the effect and mechanism of Shenfu Injection on serum metabolomics in laparoscopic hysterectomy.

1.5 mL/kg Shenfu injection was added to inject 200 mL of normal saline after the patients who entered the standard were admitted to the operating room. NMR metabolomics were performed at each time point before anesthesia (T0), immediately after pneumoperitoneum (T1), and at the end of surgery (T2).

Multivariate trajectory analysis showed that SFI treatment could make laparoscopic hysterectomy interfere with the recovery of plasma metabolites to normal metabolic state, with a time-dependent trend. In addition, the key metabolic changes of laparoscopic hysterectomy at different stages of SFI treatment involve energy metabolism, oxidative stress response, amino acid metabolism, and pyruvate metabolism. Especially, the important role of SFI in the treatment of laparoscopic hysterectomy is antioxidant capacity. The results show that SFI can be used as a potential drug for laparoscopic hysterectomy.

The current findings provided, for the first time, sound evidence of the protective effects of SFI on laparoscopic hysterectomy from both biochemical and metabolomics perspectives. The mechanisms of SFI could be related to regulating amino acid metabolism, pyruvate metabolism, and energy metabolism. The present study lays an important foundation for further research and for the broad clinical application of SFI.
Bayesian network analysis of open, laparoscopic, and robot-assisted radical cystectomy for bladder cancer
Authors: Dong Lin , Qin Yu , Ya Lu , Liang Cao , Tinghui Hu , Pinlin He , Jin Yang , Youliang Wang , Shu Cui , Tao Wu
Published: December 2020

Background:

We have performed the direct and network meta-analysis to evaluate the safety and efficacy of robot-assisted (RARC) versus laparoscopic (LRC) versus open radical cystectomy (ORC) for bladder cancer (BCa).

Methods:

A systematic search of PubMed, Cochrane Library, and Embase was performed up until Dec 20, 2019. Outcome indexes include oncologic outcomes (the recurrence rate, mortality), pathologic outcomes (lymph node yield (LNY), positive lymph node (PLN), positive surgical margins (PSM)), perioperative outcomes (operating time (OP), estimated blood loss (EBL), blood transfusion rate, the length of hospital stay (LOS) and the time to regular diet) and postoperative 90-day complications.

Results:

We have analyzed 6 RCTs, 23 prospective studies, and 25 retrospective studies (54 articles: 6382 patients). On one hand, the direct meta-analysis shows RARC is better than LRC or ORC. On the other hand, the clinical effects of the recurrence rate, Morbidity, PSM, LNY, PLN, and postoperative 90-day complications of RARC, LRC and ORC are all no statistical significance by network meta-analysis. Moreover, the probability rank shows that the comprehensive rank of RARC is better than LRC or ORC. The clinical effects of OP, EBL, LOS, blood transfusion rate and the time to regular diet are all statistical significance by network meta-analysis. There are ORC > LRC > RARC in the EBL ranking. Patients with RARC exhibited a decrease of LOS compared to those with LRC or ORC. Patients with RARC exhibited a decrease in blood transfusion rate and the time to regular diet compared to those with ORC. Patients with ORC exhibited an increase of OP compared to those with RARC or LRC. The heterogeneity tests of most studies are < 50%. Most studies have no publication bias and the quality of the selected studies is good.

Conclusion:

The direct meta-analysis and network meta-analysis suggest that RARC is better than LRC or ORC according to comprehensive analysis. However, we need a large sample size and more high-quality studies to verify and improve in the further.
Ovarian Inflammation Mass Mimicking Recurrent Rectal Cancer 17 Years After Surgery
Authors: Shen Guohua , Kuang Anren
Published: December 2020

A 58-year-old woman diagnosed with rectal cancer received surgery and chemotherapy 17 years ago, and since then, she has been tumor-free. However, 1 month ago, she complained of progressive abdominal and pelvic pain. MRI scans revealed a soft-tissue ovarian mass with heterogeneous signals in the right pelvis, showing obvious enhancement after contrast injection. On PET/CT images, the lesion presented with intense FDG accumulation. Above imaging findings raised the possibility of tumor recurrence, and thus exploratory laparotomy was performed. Pathological results confirmed the diagnosis of active inflammation with fibrous tissue hyperplasia.
Impact of Cardiac Risk Factors in the Postsurgical Outcomes of Patients With Cleft Lip
Authors: Goodenough Christopher J. , Anderson Kathryn T. , Cepeda Alfredo , Smith Kari E. , Hanfland Robert A. , Wadhwa Nitin , Teichgraeber John F. , Greives Matthew R.
Published: December 2020

Congenital cardiac comorbidities represent a potentially elevated risk for complications in patients undergoing cleft lip repair. National databases, such as the National Surgical Quality Improvement Program Pediatric (NSQIP-P) allow for analysis of large national datasets to assess these risks and potential complications. The aim of this study is to assess the risk of complications in patients undergoing cleft lip repair with congenital cardiac co-morbidities using the NSQIP-P.

The 2012 to 2014 NSQIP-P databases were queried for patients undergoing cleft lip repair. Data abstracted for analysis included demographic, clinical, and outcomes data. Patients with cleft lip were stratified based on the presence or absence of congenital cardiac comorbidities. Univariate analysis and step-wise, forward logistic regression were performed to compare these groups.

Nationally, between 2012 and 2014, 2126 patients underwent cleft lip repair, 227 with cardiac disease, and 1899 without cardiac disease. Weights were similar between the groups at the time of surgery, though patients with cardiac comorbidities were older. Postoperatively, cardiac disease patients were more likely to experience an adverse event. Specifically, they were more likely to experience reintubation, reoperation, longer length of stay, and death. Rates of surgical site infection and dehiscence were not different between the groups.

This study demonstrates that cleft lip repair in patients with congenital heart defects is safe. However, patients undergoing cleft lip repair with comorbid congenital cardiac disease were more likely to experience adverse events. Cardiac patients require special preoperative evaluation before repair of their cleft lip, but do not appear to experience worse wound-related outcomes.
Use of Keystone Flaps in Consideration of the Facial Aesthetic Subunit Concept as an Alternative Reconstructive Option for Nasal Defect Coverage
Authors: Lee Hyun Gun , Kong Yu Taek , Kim Kyu Nam
Published: December 2020

Nasal defect coverage has some challenging aspects for plastic surgeons because of the midfacial location of the nose and the relationship between convexities and concavities of nasal subunits. The authors described our experience with performing keystone flap (KF) nasal reconstruction in accordance with the facial aesthetic subunit concept and demonstrated the expanding versatility of KFs in nasal reconstruction. Between January 2017 and February 2020, 15 patients (average age, 72.07 ± 13.00 years, range: 38–88 years) underwent KF reconstruction for nasal defects. We performed KF reconstruction in accordance with the facial aesthetic subunit concept. Data, including the defect causes and locations, defect sizes, flap sites and sizes, types of KFs, flap survival, complications, and follow-up period for each patient were reviewed retrospectively. Cosmetic outcomes were evaluated by independent plastic surgeons and patients through satisfactory postoperative surveys. Sixteen defects occurred in 15 patients. The defect sizes ranged from 0.8 × 1 cm to 2.5 × 3 cm. The flap sizes ranged from 1.5 × 3.5 cm to 4 × 6 cm. All defects were successfully covered with KFs from adjacent subunits. All flaps survived without any postoperative complications. At the mean follow-up period of 8.33 ± 2.92 months, the objective cosmetic outcomes were rated favorably, and the average subjective patient satisfaction score was 7.93 ± 1.28 on a scale of 1 to 10. We suggest that using KF reconstruction in consideration of the facial aesthetic subunit concept can be a promising alternative modality for covering nasal defects with outstanding aesthetic outcomes.
Flumazenil for Successful Seizure Induction With Electroconvulsive Therapy: Case Report and Literature Review
Authors: Uchinuma Niina , Yasuda Kazuyuki , Iwata Yusuke , Hirata Takashi , Uemura Takuji , Tamaoki Toshio , Suzuki Takefumi
Published: December 2020

Objective

Electroconvulsive therapy (ECT) is indicated for various psychiatric situations that are difficult to manage otherwise and may be regarded as a last resort but seizure induction is sometimes difficult, resulting in inadequate trials and futile outcomes.

Method

We report on a 72-year-old female patient with bipolar depression whose seizure induction with ECT was challenging but the use of flumazenil was deemed effective to obtain remission in the end. We also provide a literature review on this topic.

Results

Seizure induction was managed with the use of flumazenil, a selective GABA-A receptor antagonist to neutralize the effects of benzodiazepine hypnotics, together with decreasing the amount of anesthesia, increasing the pulse width, and adding chlorpromazine. A PubMed search with keywords of flumazenil and ECT yielded only 14 hits (December 2020) and found some indication that flumazenil might be of use for this purpose even in the absence of benzodiazepines, although evidence base has remained very limited.

Conclusions

Flumazenil, an antidote of benzodiazepines, may be effective regardless of whether benzodiazepines are in use. Because inefficient ECT is clinically problematic, more studies are necessary to investigate the effectiveness of flumazenil for successful seizure induction with ECT.
Modelling of COVID-19 vaccination strategies and herd immunity, in scenarios of limited and full vaccine supply in NSW, Australia
Authors: MacIntyre C Raina , Costantino Valentina , Trent Mallory
Published: December 2020

Several vaccines for SARS-CoV-2 are expected to be available in Australia in 2021. Initial supply is likely to be limited, and will require a judicious vaccination strategy until supply is unrestricted. If vaccines have efficacy as post-exposure prophylaxis (PEP) in contacts, this provides more policy options. We used a deterministic mathematical model of epidemic response with limited supply (age-targeted or ring vaccination) and mass vaccination for the State of New South Wales (NSW) in Australia. For targeted vaccination, the effectiveness of vaccinating health workers, young people and older adults was compared. For mass vaccination, we tested varying vaccine efficacy (VE) and distribution capacities. With a limited vaccine stockpile of 1 million doses in NSW, if there is efficacy as PEP, the most efficient way to control COVID-19 will be ring vaccination, however at least 90% of contacts per case needs to be traced and vaccinated. Health worker vaccination is required for health system resilience. Age based strategies with restricted doses make minimal impact on the epidemic, but vaccinating older people prevents more deaths. Herd immunity can only be achieved with mass vaccination. With 90% VE, herd immunity can be achieved by vaccinating 66% of the population. A vaccine with less than 70% VE cannot achieve herd immunity and will result in ongoing risk of outbreaks. For mass vaccination, distributing at least 60,000 doses per day is required to achieve control. Slower rates of vaccination will result in the population living with COVID-19 longer, and higher cases and deaths.
Clinicopathological Evaluation of Dry eyes and Ocular surface in Newly diagnosed patients of Hyperthyroidism and Hypothyroidism and its Comparison to Healthy Subjects
Authors: Paharia Nidhi , Agrawal Nikhil , Agrawal Shruti
Published: December 2020

Purpose

To evaluate tear function test, corneal surface disorder in recently diagnosed hyperthyroid and hypothyroid patients and to compare results with healthy subjects.

Setting/Venue

Mahatma Gandhi Medical College, Jaipur, Rajasthan, India

Methods

Cross sectional analytical study. 30 recently diagnosed (within 3 months of diagnosis) patients of hyperthyroidism and hypothyroidism each and 30 healthy age matched controls were included. All patients and controls underwent assessment of proptosis, Palpebral fissure-height (PFH), tear function test (OSDI questionnaire, Schirmer’s test and Tear Break-up-time (TBUT) and Impression Cytology for ocular surface assessment. These parameters were compared between cases and controls. Standard statistical analysis was used.

Results

Mean Proptosis and PFH showed no significant difference among groups (P value =0.071). Mean value of OSDI was 42.33+22.67, 41.15+16.03 and 29.33+6.84 in hyperthyroid, hypothyroid & Controls respectively, the difference being statistically significant (p=0.001).

Mean TBUT was 7.13+3.28 sec, 6.38+2.46 sec, and 11.15+2.39 sec in hyperthyroidism, hypothyroidism and controls respectively (p=0.001). Mean value of Schirmer tear test was 12.93+5.81mm, 13.30+4.44mm, and 17.55+7.35mm in hyperthyroidism, Hypothyroidism and controls respectively (p=0.001). 80% of patients in hyperthyroidism group had grade 2-3 squamous metaplasia as compared to 70% in hypothyroidism patients and 24.4% in controls, signifying ocular surface damage (p<0.05).

Conclusions

Mean PFH and proptosis did not differ between three groups. However, increased OSDI score, decreased Schirmer’s test value, decreased TBUT and grade 2-3 squamous metaplasia in patients of thyroid dysfunction suggests presence of dry eyes. Despite no clinically visible signs of thyroid ophthalmopathy, there is ocular surface damage right from the early stages of thyroid dysfunction. This is attributable to evaporative mechanism as well as ocular surface inflammation and hyperosmolarity of tear film.
Cohort profile: The Westlake BioBank for Chinese (WBBC) pilot cohort: a prospective study for the late adolescence
Authors: Zhu Xiao-Wei , Liu Ke-Qi , Wang Ping-Yu , Liu Jun-Quan , Chen Jin-Yang , Xu Xue-Jin , Xu Jin-Jian , Qiu Mo-Chang , Sun Yi , Liu Chun , Bai Wei-Yang , Zhao Pian-Pian , Xia Jiangwei , Gai Si-Rui , Guan Peng-Lin , Qian Yu , Cong Pei-Kuan , Xie Shu-Yang , Wang Bin , Zheng Hou-Feng
Published: December 2020

Purpose

The Westlake BioBank for Chinese (WBBC) pilot cohort is a population-based prospective study with its major purpose to better understand the effect of genetic and environmental factors on growth and development from adolescents to adults. The dataset comprises a wide range of demographics, anthropometric measures, physical activity, sleep quality, age at menarche and bone mineral density.

Participants

A total of 14,726 participants (4,751 males and 9975 females) aged 14 to 25 years were recruited and the baseline survey was carried out from 2017 to 2019. The pilot cohort contains rich range of information regarding of demographics, anthropometric measurements, blood pressure and heart rate, lifestyle and sleep patterns, biological, clinical and health outcomes.

Findings to date

There were most of the participants were Chinese Han ethnic (97.78%), and more than 60% of them were originally from rural areas. For anthropometry measurements, the mean height and weight were 172.92 cm and 65.81 kg for men, and 160.13 cm and 52.85 kg for women; the mean waist, hip and thigh circumference were 75.51cm, 90.75cm and 51.56 cm in men, and 71.67cm, 89.75cm and 51.68 among women. Results indicated that the prevalence of underweight in female was much higher than male, but the prevalence of overweight and obesity in female was lower than male. The mean of serum 25(OH)D level in the 14,726 young participants was 22.39 ng/ml, and male had higher level of serum 25(OH)D than female, overall, 33.47% of the participants had vitamin D deficiency and even more participants suffered from vitamin D insufficiency (58.17%). The proportion of deficiency in women was much higher than that in men (41.83 vs. 16.35%).

Future plans

WBBC is designed as a prospective cohort study and provides a unique and rich data set analyzing health trajectories of Chinese adolescents to young adults.
Antibody responses to endemic coronaviruses modulate COVID-19 convalescent plasma functionality
Authors: Morgenlander William , Henson Stephanie , Monaco Daniel , Chen Athena , Littlefield Kirsten , Bloch Evan M. , Fujimura Eric , Ruczinski Ingo , Crowley Andrew R. , Natarajan Harini , Butler Savannah E. , Weiner Joshua A. , Li Mamie Z. , Bonny Tania S. , Benner Sarah E. , Balagopal Ashwin , Sullivan David , Shoham Shmuel , Quinn Thomas C. , Eshleman Susan , Casadevall Arturo , Redd Andrew D. , Laeyendecker Oliver , Ackerman Margaret E. , Pekosz Andrew , Elledge Stephen J. , Robinson Matthew , Tobian Aaron A.R. , Larman H. Benjamin
Published: December 2020

COVID-19 convalescent plasma, particularly plasma with high-titer SARS-CoV-2 (CoV2) antibodies, has been successfully used for treatment of COVID-19. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the four endemic human coronavirus (HCoV) genomes in 126 COVID-19 convalescent plasma donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies to SARS-CoV-2. We also found that plasma preferentially reactive to the CoV2 receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a two-peptide serosignature that identifies plasma donations with high anti-S titer but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting therapeutic plasma with desired functionalities.
Effect of daily periodic human movement on dengue dynamics: the case of the 2010 outbreak in Hermosillo, Mexico
Authors: Tocto-Erazo Mayra R. , Olmos-Liceaga Daniel , Montoya José A.
Published: December 2020

The human movement plays an important rol in the spread of infectious diseases. On an urban scale, people move daily to workplaces, schools, among others. Here, we are interested in exploring the effect of the daily local stay on the variations of some characteristics of dengue dynamics such as the transmission rates and local basic reproductive numbers. For this, we use a two-patch mathematical model that explicitly considers that daily mobility of people and real data from the 2010 dengue outbreak in Hermosillo, Mexico. Based on a preliminary cluster analysis, we divide the city into two regions, the south and north sides, which determine each patch of the model. We use a Bayesian approach to estimate the transmission rates and local basic reproductive numbers of some urban mobility scenarios where residents of each patch spend daily the 100% (no human movement between patches), 75% and 50% of their day at their place of residence. For the north side, estimates of transmission rates do not vary and it is more likely that the local basic reproductive number to be greater than one for all three different scenarios. On the contrary, tranmission rates of the south side have more weight in lower values when consider the human movement between patches compared to the uncoupled case. In fact, local basic reproductive numbers less than 1 are not negligible for the south side. If information about commuting is known, this work might be useful to obtain better estimates of some contagion local properties of a patch, such as the basic reproductive number.
Non-invasive prenatal testing of fetal aneuploidies using a new method based on digital droplet PCR and cell free fetal DNA
Authors: Haidong Wang , Zhijie Yang , Picchiassi Elena , Tarquini Federica , Coata Giuliana , You Wang , Youxiang Wang , Yu Chen , Di Renzo Gian Carlo
Published: December 2020

Background

Current next generation sequencing (NGS) and microarray based Non-Invasive Prenatal Tests (NIPT), used for the detection of common fetal trisomies, are still expensive, time consuming and need to be performed in centralized laboratories. To improve NIPT in clinical routine practice as universal prenatal screening, we have developed a digital droplet PCR (ddPCR) based assay called iSAFE NIPT using cell free fetal DNA (cffDNA) for detection of fetal trisomies 13, 18 and 21 in a single reaction with advantage of high diagnostic accuracy and reduced cost.

Materials and Methods

We first used artificial DNA samples to evaluate analytical sensitivity and specificity of the iSAFE NIPT. Next, we analysed 269 plasma samples for the clinical validation of iSAFE NIPT. Fifty-eight of these, including five trisomies 21, two trisomies 18 and one trisomy 13 were utilised to establish the assay cut-off values based on ratios between chromosome counts. The remaining 211 plasma samples, including 10 trisomies 21, were analysed to evaluate iSAFE NIPT clinical performance.

Results

iSAFE NIPT achieved a 100% analytical sensitivity (95% CI 94.9-100% trisomy 21; 79.4-100% trisomy 18; 73.5-100% trisomy 13) and 100% specificity (95% CI 96.3-100% trisomy 21; 97.6-100% trisomy 18; 97.6-100% trisomy 13). It also achieved a 100% clinical sensitivity and specificity for trisomy 21 detection in the 211 clinical samples (95% CI for sensitivity is 69.1-100%, and 95% CI for specificity is 98.2-100%).

Conclusions

The iSAFE NIPT is a highly multiplexed ddPCR based assay for detection of fetal trisomies from maternal blood. Based on clinical validation, the iSAFE NIPT has high diagnostic sensitivity and specificity. It can be decentralized in routine clinical laboratories, is fast, easy to use and economical comparing to current NIPT.
Human papillomavirus (HPV) infection and vaccination: a cross-sectional study of college students’ knowledge, awareness, and attitudes in Villanova, PA
Authors: Goldfarb Jennifer A. , Comber Joseph D.
Published: December 2020

Human papillomaviruses are major causative agents of multiple cancers including cervical, penial, and oropharyngeal cancers. Almost all sexually active individuals are exposed to HPV in their lifetime and although not all HPV subtypes are capable of causing cancers, several high-risk subtypes widely circulate. Several HPV vaccines have been developed and successfully utilized to limit the spread of these viruses and reduce rates of associated cancers. Despite their success, HPV vaccination rates remain low. Studies estimate the highest prevalence of HPV in the United States is among college students. This makes college students an ideal target for interventions that promote HPV vaccination and prevention. To this end, we were interested in investigating the relationship between low HPV vaccine uptake and attitudes and awareness about HPV vaccination among college aged students. We designed a survey to assess knowledge and perception of HPV and HPV vaccination that could help pinpoint correlations between this knowledge and vaccination status. We find that more robust education focusing on the benefits of HPV vaccination could be utilized to improve vaccination rates.
Replication and cross-validation of T2D subtypes based on clinical variables: an IMI-RHAPSODY study
Authors: Slieker Roderick C , Donnelly Louise A , Fitipaldi Hugo , Bouland Gerard A , Giordano Giuseppe N. , Åkerlund Mikael , Gerl Mathias J. , Ahlqvist Emma , Ali Ashfaq , Dragan Iulian , Festa Andreas , Hansen Michael K. , Aly Dina Mansour , Kim Min , Kuznetsov Dmitry , Mehl Florence , Klose Christian , Simons Kai , Pavo Imre , Pullen Timothy J. , Suvitaival Tommi , Wretlind Asger , Rossing Peter , Lyssenko Valeriya , Quigley Cristina Legido , Groop Leif , Thorens Bernard , Franks Paul W , Ibberson Mark , Rutter Guy A , Beulens Joline WJ , ’t Hart Leen M , Pearson Ewan R
Published: December 2020

Aims/hypothesis

Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes (T2D). In the current study we replicate and cross-validate these T2D clusters in three large cohorts using readily measured variables in the clinic.

Methods

In this cross-sectional study, 15,940 individuals were clustered based on age, BMI, HbA1c, random or fasting C-peptide and HDL in three independent cohorts. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort’s cluster centres.

Results

Five distinct T2D clusters were identified and mapped back to the original four ANDIS clusters. Using C-peptide and HDL instead of HOMA-B and HOMA-S three of the clusters mapped with high sensitivity (80.6 – 90.7%) to the previously identified Severe Insulin Deficient (SIDD), Severe insulin resistant (SIRD) and Obese (MOD) clusters. The previously described ANDIS MARD cluster could be mapped to the two milder groups in our study – one characterised by high HDL, and the other having not any extreme characteristic (MDH cluster). When these two milder groups were combined they mapped well to the previously labelled MARD cluster (sensitivity 79.4%). In the cross-validation between cohorts, particularly the SIDD and MDH cluster cross-validated well with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity ranging from 36.1% to 92.3% where individuals shifted from SIRD to MD and vice versa.

Conclusions/interpretation

Clusters based on C-peptide instead of HOMA measures result in clusters that resemble those based on HOMA measures, especially for SIDD, SIRD and MOD. By adding HDL, the MARD cluster based upon HOMA measures resulted in the current clustering in two clusters with one cluster having high HDL levels. Cross-validation between cohorts showed generally a good resemblance between cohorts. Together, our results show that the clustering based on clinical variables readily measured in the clinic (age, HbA1c, HDL, BMI and C-peptide) results in informative clusters that are representative of the original ANDIS clusters and stable across cohorts.
Thermal stress accelerates Arabidopsis thaliana mutation rate
Authors: Belfield Eric J. , Brown Carly , Ding Zhong Jie , Chapman Lottie , Luo Mengqian , Hinde Eleanor , van Es Sam W. , Johnson Sophie , Ning Youzheng , Zheng Shao Jian , Mithani Aziz , Harberd Nicholas P.
Published: December 2020

Mutations are the source of both genetic diversity and mutational load. However, the effects of increasing environmental temperature on plant mutation rates and relative impact on specific mutational classes (e.g., insertion/deletion [indel] vs. single nucleotide variant [SNV]) are unknown. This topic is important because of the poorly defined effects of anthropogenic global temperature rise on biological systems. Here, we show the impact of temperature increase on Arabidopsis thaliana mutation, studying whole genome profiles of mutation accumulation (MA) lineages grown for 11 successive generations at 29°C. Whereas growth of A. thaliana at standard temperature (ST; 23°C) is associated with a mutation rate of 7 × 10−9 base substitutions per site per generation, growth at stressful high temperature (HT; 29°C) is highly mutagenic, increasing the mutation rate to 12 × 10−9. SNV frequency is approximately two- to threefold higher at HT than at ST, and HT-growth causes an ∼19- to 23-fold increase in indel frequency, resulting in a disproportionate increase in indels (vs. SNVs). Most HT-induced indels are 1–2 bp in size and particularly affect homopolymeric or dinucleotide A or T stretch regions of the genome. HT-induced indels occur disproportionately in nucleosome-free regions, suggesting that much HT-induced mutational damage occurs during cell-cycle phases when genomic DNA is packaged into nucleosomes. We conclude that stressful experimental temperature increases accelerate plant mutation rates and particularly accelerate the rate of indel mutation. Increasing environmental temperatures are thus likely to have significant mutagenic consequences for plants growing in the wild and may, in particular, add detrimentally to mutational load.
Genome-wide prediction of DNA mutation effect on nucleosome positions for yeast synthetic genomics
Authors: Routhier Etienne , Pierre Edgard , Khodabandelou Ghazaleh , Mozziconacci Julien
Published: December 2020

Genetically modified genomes are often used today in many areas of fundamental and applied research. In many studies, coding or noncoding regions are modified in order to change protein sequences or gene expression levels. Modifying one or several nucleotides in a genome can also lead to unexpected changes in the epigenetic regulation of genes. When designing a synthetic genome with many mutations, it would thus be very informative to be able to predict the effect of these mutations on chromatin. We develop here a deep learning approach that quantifies the effect of every possible single mutation on nucleosome positions on the full Saccharomyces cerevisiae genome. This type of annotation track can be used when designing a modified S. cerevisiae genome. We further highlight how this track can provide new insights on the sequence-dependent mechanisms that drive nucleosomes’ positions in vivo.