bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility of Onchocerciasis Elimination Using a “Test-and-not-treat” Strategy in Loa loa Co-endemic Areas
Authors: Blok David J , Kamgno Joseph , Pion Sebastien D , Nana-Djeunga Hugues C , Niamsi-Emalio Yannick , Chesnais Cedric B , Mackenzie Charles D , Klion Amy D , Fletcher Daniel A , Nutman Thomas B , de Vlas Sake J , Boussinesq Michel , Stolk Wilma A
Published: December 2020

Background

Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe, but is associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration.

Methods

We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated precontrol mf prevalence levels from 2% to 40%. The impact of TaNT was simulated under varying levels of participation, systematic nonparticipation, and exclusion from ivermectin resulting from high L loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%.

Results

In areas with 30% to 40% precontrol mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic nonparticipation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than 6 months.

Conclusions

Our model predicts that onchocerciasis can be eliminated using TaNT in L loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.
Heterogeneity of diabetes as a risk factor for major adverse cardiovascular events in anticoagulated patients with atrial fibrillation: an analysis of the ARISTOTLE trial
Authors: De Caterina Raffaele , Patti Giuseppe , Westerbergh Johan , Horowitz John , Ezekowitz Justin A , Lewis Basil S , Lopes Renato D , McMurray John J V , Atar Dan , Bahit M Cecilia , Keltai Matyas , López-Sendón José L , Ruzyllo Witold , Granger Christopher B , Alexander John H , Wallentin Lars
Published: December 2020

Aims

Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial.

Methods and results

Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62–2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90–1.94); for insulin-treated diabetes: 2.34 (1.43–3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86–166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88–1.42); for insulin-treated diabetes 1.85 (1.36–2.53), interaction P = 0.001.

Conclusion

In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.
Dental age, agenesis, and morphological anomalies in individuals with Van der Woude syndrome and isolated cleft palate
Authors: Awadh Wael , Pegelow Marie , Heliövaara Arja , Rice David P
Published: December 2020

Objectives

To analyse the differences between dental age and chronological age and dental anomalies in individuals with Van der Woude syndrome (VWS) and compare with non-syndromic cleft palate (NSCP) and non-cleft controls.

Materials and methods

In total, 204 oral panoramic radiographs (118 girls and 86 boys) consisting of 51 VWS patients (age x̅ = 8.17 ± 1.34 years), 51 NSCP patients (age x̅ = 8.09 ± 1.41 years), and 102 normative non-cleft children (age x̅ = 8.62 ± 1.24 years) were collected. Dental stages were assessed by the Demirjian method, with the local dental maturity index as reference. Dental anomalies including agenesis were investigated. Statistical differences were determined by One-way ANOVA and regression. Repeatability was calculated by an intra-class correlation test and 95% confidence interval.

Results

The difference between dental age and chronological age of the VWS group (0.12 years) and the NSCP group (0.09 years) was significantly lower than the non-cleft group (0.40 years) (P = 0.002). There was no significant difference between the VWS and NSCP groups (P = 0.885). Hypodontia was more prevalent in both the VWS group (37.25%, P = 0.0001) and the NSCP group (19.60%, P = 0.035) compared with the non-cleft group (5.88%). The odds for hypodontia in the VWS group were approximately double compared with the NSCP group. In VWS patients, the most commonly missing teeth were the permanent second premolars and the maxillary permanent laterals incisors. Peg-shaped teeth had a prevalence of 13.70% in VWS patients.

Conclusions

In VWS and NSCP patients compared with non-cleft children, the difference in dental age compared with chronological age decreased. Hypodontia occurs at a high prevalence in VWS and NSCP patients compared with non-cleft children.
Positional, Mobility, and Reference Effects: How Does Social Class Affect Life Satisfaction in Europe?
Authors: Kaiser Caspar , Trinh Nhat An
Published: December 2020

In this study, we analyse the effects of social class on life satisfaction. We develop a theoretical framework that shows how social class affects life satisfaction through five different pathways. Informed by this framework, we estimate the direct effects of class destination and class origin, the effect of own intergenerational class mobility, as well as the effects of others’ class position and mobility. To do so, we utilize European Social Survey waves 1 to 5 (2002–2010) and obtain information on life satisfaction as well as destination and origin class for about 80,000 respondents in 32 European countries. We find (i) class destination consistently and strongly structures life satisfaction across Europe, (ii) own class mobility has a significant impact on life satisfaction in Eastern Europe, as does (iii) the class mobility of others. The last finding points to the hitherto neglected importance of reference effects when considering the impact of social class on life satisfaction.
Automatic reconstruction of the left atrium activation from sparse intracardiac contact recordings by inverse estimate of fibre structure and anisotropic conduction in a patient-specific model
Authors: Lubrecht Jolijn M , Grandits Thomas , Gharaviri Ali , Schotten Ulrich , Pock Thomas , Plank Gernot , Krause Rolf , Auricchio Angelo , Conte Giulio , Pezzuto Simone
Published: December 2020

Aims

Electric conduction in the atria is direction-dependent, being faster in fibre direction, and possibly heterogeneous due to structural remodelling. Intracardiac recordings of atrial activation may convey such information, but only with high-quality data. The aim of this study was to apply a patient-specific approach to enable such assessment even when data are scarce, noisy, and incomplete.

Methods and results

Contact intracardiac recordings in the left atrium from nine patients who underwent ablation therapy were collected before pulmonary veins isolation and retrospectively included in the study. The Personalized Inverse Eikonal Model from cardiac Electro-Anatomical Maps (PIEMAP), previously developed, has been used to reconstruct the conductivity tensor from sparse recordings of the activation. Regional fibre direction and conduction velocity were estimated from the fitted conductivity tensor and extensively cross-validated by clustered and sparse data removal. Electrical conductivity was successfully reconstructed in all patients. Cross-validation with respect to the measurements was excellent in seven patients (Pearson correlation r > 0.93) and modest in two patients (r = 0.62 and r = 0.74). Bland–Altman analysis showed a neglectable bias with respect to the measurements and the limit-of-agreement at –22.2 and 23.0 ms. Conduction velocity in the fibre direction was 82 ± 25 cm/s, whereas cross-fibre velocity was 46 ± 7 cm/s. Anisotropic ratio was 1.91±0.16. No significant inter-patient variability was observed. Personalized Inverse Eikonal model from cardiac Electro-Anatomical Maps correctly predicted activation times in late regions in all patients (r = 0.88) and was robust to a sparser dataset (r = 0.95).

Conclusion

Personalized Inverse Eikonal model from cardiac Electro-Anatomical Maps offers a novel approach to extrapolate the activation in unmapped regions and to assess conduction properties of the atria. It could be seamlessly integrated into existing electro-anatomic mapping systems. Personalized Inverse Eikonal model from cardiac Electro-Anatomical Maps also enables personalization of cardiac electrophysiology models.
The geometry of signal space: a case study of direct mapping between seismic signals and event distribution
Authors: Harris David B , Dodge Douglas A
Published: December 2020

Under favourable circumstances, seismic waveforms corresponding to an ensemble of events related by a common, spatially distributed process collectively exhibit a regular, signal-space geometry. When events in the ensemble have a common, or nearly common, source mechanism, this geometry is a distorted image of the distribution of events in the source region. The signal-space image can be visualized using a relatively simple waveform alignment and projection operation. Ensemble waveform correlation measurements can be inverted to estimate the distribution of the events in the source region, up to an arbitrary rotation, reflection and scaling, with residual distortion. We demonstrate these concepts with synthetic waveforms and with observations of long-wall mining induced seismicity for which substantial ground truth information is available. Our experience with these data has implications for location, correlation detection and machine learning and possible application to studies of repeating events in induced, volcanic and glacial seismicity. Our results place limits on the widely held assumption that waveform correlation is a useful measure of event separation. We suggest that the constraints on event separation need to be evaluated in the context of a population of related events, whose waveforms sample the signal space image of the source region. A better indicator of event separation is the length of the shortest path in signal space along the image.
Merlin cooperates with neurofibromin and Spred1 to suppress the Ras–Erk pathway
Authors: Cui Yan , Ma Lin , Schacke Stephan , Yin Jiani C , Hsueh Yi-Ping , Jin Hongchuan , Morrison Helen
Published: December 2020

The Ras–Erk pathway is frequently overactivated in human tumors. Neurofibromatosis types 1 and 2 (NF1, NF2) are characterized by multiple tumors of Schwann cell origin. The NF1 tumor suppressor neurofibromin is a principal Ras-GAP accelerating Ras inactivation, whereas the NF2 tumor suppressor merlin is a scaffold protein coordinating multiple signaling pathways. We have previously reported that merlin interacts with Ras and p120RasGAP. Here, we show that merlin can also interact with the neurofibromin/Spred1 complex via merlin-binding sites present on both proteins. Further, merlin can directly bind to the Ras-binding domain (RBD) and the kinase domain (KiD) of Raf1. As the third component of the neurofibromin/Spred1 complex, merlin cannot increase the Ras-GAP activity; rather, it blocks Ras binding to Raf1 by functioning as a ‘selective Ras barrier’. Merlin-deficient Schwann cells require the Ras–Erk pathway activity for proliferation. Accordingly, suppression of the Ras–Erk pathway likely contributes to merlin’s tumor suppressor activity. Taken together, our results, and studies by others, support targeting or co-targeting of this pathway as a therapy for NF2 inactivation-related tumors.
Association of Serum 25-Hydroxyvitamin D With Prevalence, Incidence, and Clearance of Vaginal HPV Infection in Young Women
Authors: El-Zein Mariam , Khosrow-Khavar Farzin , Burchell Ann N , Tellier Pierre-Paul , Eintracht Shaun , McNamara Elizabeth , Coutlée Francois , Franco Eduardo L ,   for the HITCH study group, Rodrigues Allita , Kelsall Gail , Dumais Suzanne , Morykon Natalia , Rocamora Amelia , Slavtcheva Nathalie , Moravan Veronika , Wissing Michel , Roger Michel
Published: December 2020

Background

We assessed the association between serum 25-hydroxyvitamin D levels and genital human papillomavirus (HPV) prevalence, incidence, and clearance among female participants in the HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) Cohort Study.

Methods

We genotyped HPV DNA in vaginal samples and quantified baseline serum 25-hydroxyvitamin D levels using Roche’s Linear Array and Total vitamin D assay, respectively. We used logistic and Cox proportional hazards models, respectively, to estimate adjusted odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

There was no association between vitamin D levels (every 10-ng/mL increase) at baseline and HPV prevalence (OR, 0.88; 95% CI, .73–1.03) or incidence (HR, 0.88; 95% CI, .73–1.06), but we observed a modest negative association with HPV clearance (HR, 0.76; 95% CI, .60–.96). Vitamin D levels <30 ng/mL, compared with those ≥30 ng/mL, were not associated with HPV prevalence (OR, 0.98; 95% CI, .57–1.69) or incidence (HR, .87; 95% CI, .50–1.43), but they were associated with a marginally significant increased clearance (OR, 2.14; 95% CI, .99–4.64). We observed consistent results with restricted cubic spline modeling of vitamin D levels and clinically defined categories. HPV type-specific analyses accounting for multiple HPV infections per participant showed no association between vitamin D levels and all study outcomes.

Conclusions

This study provided no evidence of an association between low vitamin D levels and increased HPV prevalence, acquisition, or clearance.
Will the COVID-19 pandemic transform infection prevention and control in surgery? Seeking leverage points for organizational learning
Authors: Toccafondi Giulio , Di Marzo Francesco , Sartelli Massimo , Sujan Mark , Smyth Molly , Bowie Paul , Cardi Martina , Cardi Maurizio
Published: December 2020

Background

In response to the coronavirus disease of 2019 (COVID-19) pandemic, healthcare systems worldwide have stepped up their infection prevention and control efforts in order to reduce the spread of the infection. Behaviours, such as hand hygiene, screening and cohorting of patients, and the appropriate use of antibiotics have long been recommended in surgery, but their implementation has often been patchy.

Methods

The current crisis presents an opportunity to learn about how to improve infection prevention and control and surveillance (IPCS) behaviours. The improvements made were mainly informal, quick and stemming from the frontline rather than originating from formal organizational structures.

The adaptations made and the expertise acquired have the potential for triggering deeper learning and to create enduring improvements in the routine identification and management of infections relating to surgery.

Results

This paper aims to illustrate how adopting a human factors and ergonomics perspective can provide insights into how clinical work systems have been adapted and reconfigured in order to keep patients and staff safe.

Conclusion

For achieving sustainable change in IPCS practices in surgery during COVID-19 and beyond we need to enhance organizational learning potentials.
Comparative genomics of ESBL-producingEscherichia coli(ESBL-Ec) reveals a similar distribution of the 10 most prevalent ESBL-Ec clones and ESBL genes among human community faecal and extra-intestinal infection isolates in the Netherlands (2014–17)
Authors: Verschuuren T D , van Hout D , Arredondo-Alonso S , Fluit A C , Reuland E A , Top J , Schürch A C , Bosch T , Bonten M J M , Kluytmans J A J W , Willems R J L
Published: December 2020

Introduction

The human gut microbiota is an important reservoir of ESBL-producing Escherichia coli (ESBL-Ec). Community surveillance studies of ESBL-Ec to monitor circulating clones and ESBL genes are logistically challenging and costly.

Objectives

To evaluate if isolates obtained in routine clinical practice can be used as an alternative to monitor the distribution of clones and ESBL genes circulating in the community.

Methods

WGS was performed on 451 Dutch ESBL-Ec isolates (2014–17), including 162 community faeces and 289 urine and blood isolates. We compared proportions of 10 most frequently identified STs, PopPUNK-based sequence clusters (SCs) and ESBL gene subtypes and the degree of similarity using Czekanowski’s proportional similarity index (PSI).

Results

Nine out of 10 most prevalent STs and SCs and 8/10 most prevalent ESBL genes in clinical ESBL-Ec were also the most common types in community faeces. The proportions of ST131 (39% versus 23%) and SC131 (40% versus 25%) were higher in clinical isolates than in community faeces (P < 0.01). Within ST131, H30Rx (C2) subclade was more prevalent among clinical isolates (55% versus 26%, P < 0.01). The proportion of ESBL gene blaCTX-M-1 was lower in clinical isolates (5% versus 18%, P < 0.01). Czekanowski’s PSI confirmed that the differences in ESBL-Ec from community faeces and clinical isolates were limited.

Conclusions

Distributions of the 10 most prevalent clones and ESBL genes from ESBL-Ec community gut colonization and extra-intestinal infection overlapped in majority, indicating that isolates from routine clinical practice could be used to monitor ESBL-Ec clones and ESBL genes in the community.
Validation and Optimization of qPCR Method for Identification of Actaea racemosa (Black Cohosh) NHPs
Authors: Shanmughanandhan Jeevitha , Shanmughanandhan Dhivya , Ragupathy Subramanyam , Henry, Thomas A , Newmaster Steven G
Published: December 2020

Background

Actaea racemosa (black cohosh) herbal dietary supplements are commonly used to treat menopausal symptoms in women. However, there is a considerable risk of contamination of A. racemosa herbal products in the natural health product (NHP) industry, impacting potential efficacy. Authentication of A. racemosa products is challenging because of the standard, multi-part analytical chemistry methods that may be too costly and not appropriate for both raw and finished products.

Objective

In this paper, we discuss developing and validating quick alternative biotechnology methods to authenticate A. racemosa herbal dietary supplements, based on the use of a species-specific hydrolysis PCR probe assay.

Methods

A qPCR-based species-specific hydrolysis probe assay was designed, validated, and optimized for precisely identifying the species of interest using the following analytical validation criteria: (1) specificity (accuracy) in determining the target species ingredient, while not identifying other non-target species; (2) sensitivity in detecting the smallest amount of the target material; and (3) reliability (repeatability and reproducibility) in detecting the target species in raw materials on a real-time PCR platform.

Results

The results show that the species-specific hydrolysis probe assay was successfully developed for the raw materials and powders of A. racemosa. The specificity of the test was 100% to the target species. The efficiency of the assay was observed to be 99%, and the reliability of the assay was 100% for the raw/starting and powder materials.

Conclusion

The method developed in this study can be used to authenticate and perform qualitative analysis of A. racemosa supplements.
Structural studies of reelin N-terminal region provides insights into a unique structural arrangement and functional multimerization
Authors: Nagae Masamichi , Suzuki Kei , Yasui Norihisa , Nogi Terukazu , Kohno Takao , Hattori Mitsuharu , Takagi Junichi
Published: December 2020

The large, secreted glycoprotein reelin regulates embryonic brain development as well as adult brain functions. Although reelin binds to its receptors via its central part, the N-terminal region directs multimer formation and is critical for efficient signal transduction. In fact, the inhibitory antibody CR-50 interacts with the N-terminal region and prevents higher-order multimerization and signalling. Reelin is a multidomain protein in which the central part is composed of eight characteristic repeats, named reelin repeats, each of which is further divided by insertion of a epidermal growth factor (EGF) module into two subrepeats. In contrast, the N-terminal region shows unique ‘irregular’ domain architecture since it comprises three consecutive subrepeats without the intervening EGF module. Here, we determined the crystal structure of the murine reelin fragment named RX-R1 including the irregular region and the first reelin repeat at 2.0-Å resolution. The overall structure of RX-R1 has a branched Y-shaped form. Interestingly, two incomplete subrepeats cooperatively form one entire subrepeat structure, though an additional subrepeat is inserted between them. We further reveal that Arg335 of RX-R1 is crucial for binding CR-50. A possible self-association mechanism via the N-terminal region is proposed based on our results.
Impacts of Different Winter Storage Conditions on the Physiology of Diutinus Honey Bees (Hymenoptera: Apidae)
Authors: Hopkins Brandon K , Chakrabarti Priyadarshini , Lucas Hannah M , Sagili Ramesh R , Sheppard Walter S
Published: December 2020

Global decline in insect pollinators, especially bees, have resulted in extensive research into understanding the various causative factors and formulating mitigative strategies. For commercial beekeepers in the United States, overwintering honey bee colony losses are significant, requiring tactics to overwinter bees in conditions designed to minimize such losses. This is especially important as overwintered honey bees are responsible for colony expansion each spring, and overwintered bees must survive in sufficient numbers to nurse the spring brood and forage until the new ‘replacement’ workers become fully functional. In this study, we examined the physiology of overwintered (diutinus) bees following various overwintering storage conditions. Important physiological markers, i.e., head proteins and abdominal lipid contents were higher in honey bees that overwintered in controlled indoor storage facilities, compared with bees held outdoors through the winter months. Our findings provide new insights into the physiology of honey bees overwintered in indoor and outdoor environments and have implications for improved beekeeping management.
Central Adiposity and Subsequent Risk of Breast Cancer by Menopause Status
Authors: Houghton Serena C , Eliassen Heather , Tamimi Rulla M , Willett Walter C , Rosner Bernard A , Hankinson Susan E
Published: December 2020

Background

Increased body mass index (BMI) is associated with higher postmenopausal breast cancer risk and lower premenopausal breast cancer risk. Less is known about the central adiposity-breast cancer risk association, particularly for tumor subtypes.

Methods

We used prospective waist (WC) and hip circumference (HC) measures in the Nurses’ Health Studies. We examined associations of WC, HC, and waist-to-hip ratio (WHR) with breast cancer independent of BMI, by menopausal status. Cox proportional hazards models estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for breast cancer risk factors, with and without BMI.

Results

Adjusting for BMI, WC and HC were not associated, and WHR was positively associated with premenopausal breast cancer risk (WHR, quintile 5 vs 1: HRQ5vQ1, BMI-adjusted = 1.27, 95% CI = 1.04 to 1.54; Ptrend = .01), particularly for estrogen receptor-negative (ER-) and progesterone receptor-negative (PR-) and basal-like breast cancers. Premenopausal WC, HC, and WHR were not associated with postmenopausal breast cancer risk, with or without BMI adjustment. Postmenopausal WC, HC, and WHR were each positively associated with postmenopausal breast cancer (eg, WC HRQ5vsQ1 = 1.59, 95% CI = 1.36 to 1.86); after adjustment for BMI, only WC remained statistically significant (HRQ5vsQ1, BMI-adjusted = 1.38, 95% CI = 1.15 to 1.64; Ptrend = .002). In postmenopausal women, associations were stronger among never-users of hormone therapy and for ER+/PR+ breast cancers.

Conclusions

Central adiposity was positively associated with pre- and postmenopausal breast cancers independent of BMI. This suggests that mechanisms other than estrogen may also play a role in the relationship between central adiposity and breast cancer. Maintaining a healthy waist circumference may decrease pre- and postmenopausal breast cancer risk.
Oral Health Status and Dental Treatment Needs in Syrian Refugee Children in Zaatari Camp
Authors: Salim Nesreen A , Shaini Firas J , Sartawi Samiha , Al-Shboul Bashar
Published: December 2020

The Syrian crisis has resulted in a devastating impact on refugees’ oral health and data on their oral health is lacking. To explore oral health and dental needs of Syrian refugee children, a cross-sectional study of 484 children was conducted. Caries prevalence, DMFT, SiC, and oral hygiene indices were recorded. Caries prevalence was 96.1%, with mean dmft/DMFT scores of 3.65/1.15, SiC scores were 6.64/2.56, and Hygiene Index was 1.13. Decay was the main component of dmft/DMFT (89%-88%). Most common complaint was pain (98.3%) with 88% of the children do not brush/brush occasionally. Pearson’s correlation displayed a strong association between dental caries and age (P ≤ 0.01), where caries in permanent dentition increases and in deciduous dentition decreases. Syrian refugees showed poor oral health, high caries prevalence, high unmet dental needs, and poor oral hygiene practices, which indicates lack of dental care services, and warranting urgent prevention to reduce the burden of oral disease of this population.
Achondroplasia—First Report from India of a Rare FGFR3 Gene Variant
Authors: Chaudhry Chakshu , G Prabakaran , Srivastava Priyanka , Das Reena , Kaur Jasbir , Panigrahi Inusha , Kaur Anupriya
Published: December 2020

The clinical manifestations of FGFR3 sequence variations can vary from mild unnoticed short stature to neonatal lethal dwarfism and can be causative of phenotypes including achondroplasia, hypochondroplasia, and thanatophoric dysplasia. Clinical data describe an 11 month old girl with restricted growth and preserved intellect. She had rhizomelic short stature with peculiar facies but no Acanthosis nigricans. In view of the absence of the hotspot mutation c.1138 G>A/G>C (p.Gly380Arg), complete gene sequencing was done that revealed a rare sequence variation, NM_000142.4:c.1043C>G (p.Ser348Cys) in FGFR3. This sequence variation has not been reported from India so far. This report emphasizes the benefit of sequencing the whole gene in individuals who are negative for hotspot mutation of achondroplasia with strong clinical suspicion.
Singing Cato: Poetic Grammar and Moral Citation in Medieval Latin Song
Authors: Caldwell Mary Channen
Published: December 2020

Widely acknowledged as emerging from clerical, monastic, and pedagogical communities, the poetry of medieval Latin song was informed by the vocabulary, grammar, and rhetoric emanating from these spheres of knowledge and practice. I argue for the specific manifestation of these spheres through grammatical citation, a practice in which noun and verb paradigms poetically shape Latin songs. Specifically, grammatical paradigms structure select songs by declining or conjugating strophic incipits systematically throughout the poem. Grammatical citationality in Latin songs, whose poetry otherwise chiefly explores festive, religious topics, serves as a signal of their implicitly disciplinary and didactic function. With grammar operating as an emblem of correct, moral behaviour, these devotional songs exemplified morally and spiritually upright Christian behaviour for singers and listeners. A capstone to this sung didacticism is the thirteenth-century Cum animadverterem, a conductus uniquely linking grammatical citation with a quotation from Cato’s Distichs, a famed medieval textbook of moral learning.
cosmic birth: efficient Bayesian inference of the evolving cosmic web from galaxy surveys
Authors: Kitaura Francisco-Shu , Ata Metin , Rodríguez-Torres Sergio A , Hernández-Sánchez Mónica , Balaguera-Antolínez A , Yepes Gustavo
Published: December 2020

We present cosmic birth (COSMological Initial Conditions from Bayesian Inference Reconstructions with THeoretical models): an algorithm to reconstruct the primordial and evolved cosmic density fields from galaxy surveys on the light-cone. The displacement and peculiar velocity fields are obtained from forward modelling at different redshift snapshots given some initial cosmic density field within a Gibbs-sampling scheme. This allows us to map galaxies, observed in a light-cone, to a single high redshift and hereby provide tracers and the corresponding survey completeness in Lagrangian space including tetrahedral tessellation mapping. These Lagrangian tracers in turn permit us to efficiently obtain the primordial density field, making the cosmic birth code general to any structure formation model. Our tests are restricted for the time being to augmented Lagrangian perturbation theory. We show how to robustly compute the non-linear Lagrangian bias from clustering measurements in a numerical way, enabling us to get unbiased dark matter field reconstructions at initial cosmic times. We also show that we can accurately recover the information of the dark matter field from the galaxy distribution based on a detailed simulation. Novel key ingredients to this approach are a higher order Hamiltonian-sampling technique and a non-diagonal Hamiltonian mass matrix. This technique could be used to study the Eulerian galaxy bias from galaxy surveys and could become an ideal baryon acoustic reconstruction technique. In summary, this method represents a general reconstruction technique, including in a self-consistent way a survey mask, non-linear and non-local bias, and redshift-space distortions, with an efficiency about 10 times superior to previous comparable methods.
The Ophiuchus DIsc Survey Employing ALMA (ODISEA) – III. The evolution of substructures in massive discs at 3–5 au resolution
Authors: Cieza Lucas A , González-Ruilova Camilo , Hales Antonio S , Pinilla Paola , Ruíz-Rodríguez Dary , Zurlo Alice , Casassus Simón , Pérez Sebastián , Cánovas Hector , Arce-Tord Carla , Flock Mario , Kurtovic Nicolas , Marino Sebastian , Nogueira Pedro H , Perez Laura , Price Daniel J , Principe David A , Williams Jonathan P
Published: December 2020

We present 1.3 mm continuum ALMA long-baseline observations at 3–5 au resolution of 10 of the brightest discs from the Ophiuchus DIsc Survey Employing ALMA (ODISEA) project. We identify a total of 26 narrow rings and gaps distributed in 8 sources and 3 discs with small dust cavities (r <10 au). We find that two discs around embedded protostars lack the clear gaps and rings that are ubiquitous in more evolved sources with Class II SEDs. Our sample includes five objects with previously known large dust cavities (r >20 au). We find that the 1.3 mm radial profiles of these objects are in good agreement with those produced by numerical simulations of dust evolution and planet–disc interactions, which predict the accumulation of mm-sized grains at the edges of planet-induced cavities. Our long-baseline observations resulted in the largest sample of discs observed at ∼3–5 au resolution in any given star-forming region (15 objects when combined with Ophiuchus objects in the DSHARP Large Program) and allow for a demographic study of the brightest $\sim\! 5{{\ \rm per\ cent}}$ of the discs in Ophiuchus (i.e. the most likely formation sites of giant planets in the cloud). We use this unique sample to propose an evolutionary sequence and discuss a scenario in which the substructures observed in massive protoplanetary discs are mainly the result of planet formation and dust evolution. If this scenario is correct, the detailed study of disc substructures might provide a window to investigate a population of planets that remains mostly undetectable by other techniques.
Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice
Authors: Han F , Dong M Z , Lei W L , Xu Z L , Gao F , Schatten H , Wang Z B , Sun X F , Sun Q Y
Published: December 2020

Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and ‘9 + 2’ flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.
Heritable pattern of oxidized DNA base repair coincides with pre-targeting of repair complexes to open chromatin
Authors: Bacolla Albino , Sengupta Shiladitya , Ye Zu , Yang Chunying , Mitra Joy , De-Paula Ruth B , Hegde Muralidhar L , Ahmed Zamal , Mort Matthew , Cooper David N , Mitra Sankar , Tainer John A
Published: December 2020

Human genome stability requires efficient repair of oxidized bases, which is initiated via damage recognition and excision by NEIL1 and other base excision repair (BER) pathway DNA glycosylases (DGs). However, the biological mechanisms underlying detection of damaged bases among the million-fold excess of undamaged bases remain enigmatic. Indeed, mutation rates vary greatly within individual genomes, and lesion recognition by purified DGs in the chromatin context is inefficient. Employing super-resolution microscopy and co-immunoprecipitation assays, we find that acetylated NEIL1 (AcNEIL1), but not its non-acetylated form, is predominantly localized in the nucleus in association with epigenetic marks of uncondensed chromatin. Furthermore, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) revealed non-random AcNEIL1 binding near transcription start sites of weakly transcribed genes and along highly transcribed chromatin domains. Bioinformatic analyses revealed a striking correspondence between AcNEIL1 occupancy along the genome and mutation rates, with AcNEIL1-occupied sites exhibiting fewer mutations compared to AcNEIL1-free domains, both in cancer genomes and in population variation. Intriguingly, from the evolutionarily conserved unstructured domain that targets NEIL1 to open chromatin, its damage surveillance of highly oxidation-susceptible sites to preserve essential gene function and to limit instability and cancer likely originated ∼500 million years ago during the buildup of free atmospheric oxygen.
The nucleoid-associated protein IHF acts as a ‘transcriptional domainin’ protein coordinating the bacterial virulence traits with global transcription
Authors: Reverchon Sylvie , Meyer Sam , Forquet Raphaël , Hommais Florence , Muskhelishvili Georgi , Nasser William
Published: December 2020

Bacterial pathogenic growth requires a swift coordination of pathogenicity function with various kinds of environmental stress encountered in the course of host infection. Among the factors critical for bacterial adaptation are changes of DNA topology and binding effects of nucleoid-associated proteins transducing the environmental signals to the chromosome and coordinating the global transcriptional response to stress. In this study, we use the model phytopathogen Dickeya dadantii to analyse the organisation of transcription by the nucleoid-associated heterodimeric protein IHF. We inactivated the IHFα subunit of IHF thus precluding the IHFαβ heterodimer formation and determined both phenotypic effects of ihfA mutation on D. dadantii virulence and the transcriptional response under various conditions of growth. We show that ihfA mutation reorganises the genomic expression by modulating the distribution of chromosomal DNA supercoils at different length scales, thus affecting many virulence genes involved in both symptomatic and asymptomatic phases of infection, including those required for pectin catabolism. Altogether, we propose that IHF heterodimer is a ‘transcriptional domainin’ protein, the lack of which impairs the spatiotemporal organisation of transcriptional stress-response domains harbouring various virulence traits, thus abrogating the pathogenicity of D. dadantii.
Pathway-Based Reduction of Repeat Head Computed Tomography for Patients With Complicated Mild Traumatic Brain Injury: Implementation and Outcomes
Authors: Stippler Martina , Keith Stacey , Nelton Emmalin B , Parsons Charles S , Singleton Jennifer , Bilello Leslie A , Tibbles Carrie D , Davis Roger B , Edlow Jonathan A , Rosen Carlo L
Published: December 2020

BACKGROUND

Routine follow-up head imaging in complicated mild traumatic brain injury (cmTBI) patients has not been shown to alter treatment, improve outcomes, or identify patients in need of neurosurgical intervention. We developed a follow-up head computed tomography (CT) triage algorithm for cmTBI patients to decrease the number of routine follow-up head CT scans obtained in this population.

OBJECTIVE

To report our experience with protocol implications and patient outcome.

METHODS

Data on all cmTBI patients presenting from July 1, 2018 to June 31, 2019, to our level 1, tertiary, academic medical center were collected prospectively and analyzed retrospectively. Descriptive analysis was performed.

RESULTS

Of the 178 patients enrolled, 52 (29%) received a follow-up head CT. A total of 27 patients (15%) were scanned because of initial presentation and triaged to the group to receive a routine follow-up head CT. A total of 151 patients (85%) were triaged to the group without routine follow-up head CT scan. Protocol adherence was 89% with 17 violations.

CONCLUSION

Utilizing this protocol, we were able to safely decrease the use of routine follow-up head CT scans in cmTBI patients by 71% without any missed injuries or delayed surgery. Adoption of the protocol was high among all services managing TBI patients.
Nutritional and health factors affecting the bioavailability of calcium: a narrative review
Authors: Wawrzyniak Natalia , Suliburska Joanna
Published: December 2020

Calcium is responsible for the effectiveness of various processes, and its supply in the diet is necessary for the normal function of the human body. Apart from being an important component of the skeleton, calcium also helps maintain the structure of cell organelles and regulates intracellular and extracellular fluid homeostasis. This review presents the nutritional and health factors that affect the bioavailability of calcium. Physiological conditions and factors such as pregnancy, infancy, menopause, old age, hormones, growth factors associated with calcium metabolism, diseases limiting its absorption, and intestinal microbiota are distinguished among endogenous factors. Although the calcium supply in the body is genetically conditioned and specific to each person, its qualitative and quantitative composition can be modified by external factors. The exogenous factors include dietary modifications with particular nutrients and pharmacological treatment. Adequate calcium levels increase bone protection and prevent osteoporosis, a disease involving low mineral bone mass.
Impacts of the Great Recession on sport: evidence from English Football League attendance demand
Authors: Buraimo Babatunde , Migali Giuseppe , Simmons Rob
Published: December 2020

This article investigates the impact of the 2007–9 Great Recession on attendance demand in the English Football League. We identify causal effects of variations in local unemployment rates on club matchday attendances using a difference-in-difference methodology applied to specific treatment and control group clubs categorized according to severity of local unemployment increase during the recession period. We find that treatment clubs in Tiers 3 and 4 suffered an attendance reduction of 10.5% purely through rising unemployment in local Travel to Work Areas containing clubs’ stadia after controlling for a large set of confounding influences. Smaller but still significant effects are found in alternative specifications, including the incorporation of Tier 2 clubs into the analysis.
Revisiting the Doctrine of Intertemporal Law
Authors: Wheatley Steven
Published: December 2020

There is a tension in the doctrine of intertemporal law outlined by Max Huber in the Island of Palmas case. The first branch demands that the legality of an act be judged by the law in force at the time the act occurs; the second that we take into account any change in the law over time. We see the problem in the 2019 Chagos Archipelago proceedings. The UK argued that the detachment of the Archipelago from Mauritius in 1965 was not unlawful, because it was not regarded as unlawful at the time. The International Court of Justice (ICJ) disagreed, deciding that the detachment was unlawful at that time, but it relied on the 1970 Declaration on Friendly Relations to confirm this conclusion. This article explains why the ICJ’s use of dynamic logic to reach its decision was correct—and what this tells us about the intertemporal doctrine.
A Novel Putative Microtubule-Associated Protein Is Involved in Arbuscule Development during Arbuscular Mycorrhiza Formation
Authors: Ho-Pl�garo Tania , Huertas Ra�l , Tamayo-Navarrete Mar�a I , Blancaflor Elison , Gavara Nuria , Garc�a-Garrido Jos� M
Published: December 2020

The formation of arbuscular mycorrhizal (AM) symbiosis requires plant root host cells to undergo major structural and functional reprogramming to house the highly branched AM fungal structure for the reciprocal exchange of nutrients. These morphological modifications are associated with cytoskeleton remodelling. However, molecular bases and the role of microtubules (MTs) and actin filament dynamics during AM formation are largely unknown. In this study, the tomato tsb (tomato similar to SB401) gene, belonging to a Solanaceae group of genes encoding MT-associated proteins (MAPs) for pollen development, was found to be highly expressed in root cells containing arbuscules. At earlier stages of mycorrhizal development, tsb overexpression enhanced the formation of highly developed and transcriptionally active arbuscules, while tsb silencing hampers the formation of mature arbuscules and represses arbuscule functionality. However, at later stages of mycorrhizal colonization, tsb overexpressing (OE) roots accumulate fully developed transcriptionally inactive arbuscules, suggesting that the collapse and turnover of arbuscules might be impaired by TSB accumulation. Imaging analysis of the MT cytoskeleton in cortex root cells OE tsb revealed that TSB is involved in MT bundling. Taken together, our results provide unprecedented insights into the role of novel MAP in MT rearrangements throughout the different stages of the arbuscule life cycle.
Finding a job after unemployment—education as a moderator of unemployment scarring in Norway and German-speaking Switzerland
Authors: Shi Lulu P , Di Stasio and Valentina
Published: December 2020

Using data collected with a factorial survey experiment in Norway and Switzerland, we analyze how employers react to unemployment spells when screening job applications. Our focus is on whether unemployment scarring varies depending on the applicants’ level of education and the duration and timing of the unemployment spell. We find unemployment scars of similar size in the two countries. Interestingly, education moderates the strength of unemployment scarring: in the Swiss context, graduates from vocational education and training (VET) programs are the most severely affected by unemployment, even years after regaining employment; this is not the case in Norway. We contribute to the unemployment scarring literature and to comparative scholarship on school-to-work transitions by exposing a trade-off of dual VET systems, which are known to provide a safety net from unemployment. Our findings show that these same systems can cause scars that are particularly long-lasting to VET graduates who fall into unemployment.
Cenote-Taker 2 democratizes virus discovery and sequence annotation
Authors: Tisza Michael J , Belford Anna K , Domínguez-Huerta Guillermo , Bolduc Benjamin , Buck Christopher B
Published: December 2020

Viruses, despite their great abundance and significance in biological systems, remain largely mysterious. Indeed, the vast majority of the perhaps hundreds of millions of viral species on the planet remain undiscovered. Additionally, many viruses deposited in central databases like GenBank and RefSeq are littered with genes annotated as ‘hypothetical protein’ or the equivalent. Cenote-Taker 2, a virus discovery and annotation tool available on command line and with a graphical user interface with free high-performance computation access, utilizes highly sensitive models of hallmark virus genes to discover familiar or divergent viral sequences from user-input contigs. Additionally, Cenote-Taker 2 uses a flexible set of modules to automatically annotate the sequence features of contigs, providing more gene information than comparable tools. The outputs include readable and interactive genome maps, virome summary tables, and files that can be directly submitted to GenBank. We expect Cenote-Taker 2 to facilitate virus discovery, annotation, and expansion of the known virome.