bluuebunny/crossref_metadata_2025 huggingface dataset:
AGN-driven galactic outflows: comparing models to observations
Authors: Ishibashi W , Fabian A C , Arakawa N
Published: January 2021

The actual mechanism(s) powering galactic outflows in active galactic nuclei (AGNs) is still a matter of debate. At least two physical models have been considered in the literature: wind shocks and radiation pressure on dust. Here, we provide a first quantitative comparison of the AGN radiative feedback scenario with observations of galactic outflows. We directly compare our radiation pressure-driven shell models with the observational data from the most recent compilation of molecular outflows on galactic scales. We show that the observed dynamics and energetics of galactic outflows can be reproduced by AGN radiative feedback, with the inclusion of radiation trapping and/or luminosity evolution. The predicted scalings of the outflow energetics with AGN luminosity can also quantitatively account for the observational scaling relations. Furthermore, sources with both ultrafast and molecular outflow detections are found to be located in the ‘forbidden’ region of the NH–λ plane. Overall, an encouraging agreement is obtained over a wide range of AGN and host galaxy parameters. We discuss our results in the context of recent observational findings and numerical simulations. In conclusion, AGN radiative feedback is a promising mechanism for driving galactic outflows that should be considered, alongside wind feedback, in the interpretation of future observational data.
Current mechanisms of primordial follicle activation and new strategies for fertility preservation
Authors: Zhang Yan , Zhou Xiaomei , Zhu Ye , Wang Hanbin , Xu Juan , Su Yiping
Published: January 2021

Premature ovarian insufficiency (POI) is characterized by symptoms caused by ovarian dysfunction in patients aged <40 years. It is associated with a shortened reproductive lifespan. The only effective treatment for patients who are eager to become pregnant is IVF/Embryo Transfer (ET) using oocytes donated by young women. However, the use of the technique is constrained by the limited supply of oocytes and ethical issues. Some patients with POI still have some residual follicles in the ovarian cortex, which are not regulated by gonadotropin. These follicles are dormant. Therefore, activating dormant primordial follicles (PFs) to obtain high-quality oocytes for assisted reproductive technology may bring new hope for patients with POI. Therefore, this study aimed to explore the factors related to PF activation, such as the intercellular signaling network, the internal microenvironment of the ovary and the environment of the organism. In addition, we discussed new strategies for fertility preservation, such as in vitro activation and stem cell transplantation.
DAZAP2 acts as specifier of the p53 response to DNA damage
Authors: Liebl Magdalena C , Moehlenbrink Jutta , Becker Huong , Raddatz Günter , Abdeen Suhaib K , Aqeilan Rami I , Lyko Frank , Hofmann Thomas G
Published: January 2021

The DNA damage-responsive tumor suppressors p53 and HIPK2 are well established regulators of cell fate decision-making and regulate the cellular sensitivity to DNA-damaging drugs. Here, we identify Deleted in Azoospermia-associated protein 2 (DAZAP2), a small adaptor protein, as a novel regulator of HIPK2 and specifier of the DNA damage-induced p53 response. Knock-down or genetic deletion of DAZAP2 strongly potentiates cancer cell chemosensitivity both in cells and in vivo using a mouse tumour xenograft model. In unstressed cells, DAZAP2 stimulates HIPK2 polyubiquitination and degradation through interplay with the ubiquitin ligase SIAH1. Upon DNA damage, HIPK2 site-specifically phosphorylates DAZAP2, which terminates its HIPK2-degrading function and triggers its re-localization to the cell nucleus. Interestingly, nuclear DAZAP2 interacts with p53 and specifies target gene expression through modulating a defined subset of p53 target genes. Furthermore, our results suggest that DAZAP2 co-occupies p53 response elements to specify target gene expression. Collectively, our findings propose DAZAP2 as novel regulator of the DNA damage-induced p53 response that controls cancer cell chemosensitivity.
When “Peripheral” Becomes “Central”: Primary and Secondary Malignant Intracerebral Nerve Sheath Tumor: A Case Report and a Systematic Review
Authors: Rubino Franco , Eichberg Daniel G , Shah Ashish H , Luther Evan M , Lu Victor M , Saad Ali G , Kahn David , Komotar Ricardo J , Ivan Michael E
Published: January 2021

BACKGROUND

The intracerebral occurrence of malignant peripheral nerve sheath tumors (MPNSTs) is exceedingly rare, and despite aggressive treatments, local recurrence and poor prognosis are very frequent. Like other brain tumors, these tumors could be primary or secondary, making the term “peripheral” an imprecise term for a primary brain tumor.

OBJECTIVE

To analyze the reported cases of primary and secondary cerebral MPSNTs in terms of diagnosis, treatment, and overall survival. Additionally, we present a case of malignant intracerebral nerve sheath tumor (MINST) treated with radical surgery and radiotherapy.

METHODS

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, one database (PubMed) and crossed references were queried for MPNST with brain metastasis and primary MINSTs from 1971 to 2020. Data regarding demographic features, primary tumor site, risk factors, brain location of the lesion, treatment applied, and overall survival were extracted.

RESULTS

A total of 55 patients were selected (including the reported case): 29 patients were secondary brain MPNST and 26 patients were primary MINST. The mean age was 41.8 ± 22 and 31.2 ± 23 yr, respectively. All brain metastases of MPNST (100%) had a primary tumor elsewhere in the body at the time of diagnosis. The overall survival was significantly shorter in patients with a secondary brain MPNST compared to MINST (P = .002).

CONCLUSION

We present a comprehensive analysis of every reported primary and secondary intracerebral MPNST. The prognosis in terms of survival is worst in the last one despite aggressive treatment. The lack of a primary MPNST in screening tests is sufficient to confirm a MINST at time of diagnosis.
Performance of Unobserved Self-Collected Nasal Swabs for Detection of SARS-CoV-2 by RT-PCR Utilizing a Remote Specimen Collection Strategy
Authors: Kagan Ron M , Rogers Amy A , Borillo Gwynngelle A , Clarke Nigel J , Marlowe Elizabeth M
Published: January 2021

Background

The use of a remote specimen collection strategy employing a kit designed for unobserved self-collection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) can decrease the use of personal protective equipment (PPE) and exposure risk. To assess the impact of unobserved specimen self-collection on test performance, we examined results from a SARS-CoV-2 qualitative RT-PCR test for self-collected specimens from participants in a return-to-work screening program and assessed the impact of a pooled testing strategy in this cohort.

Methods

Self-collected anterior nasal swabs from employee return-to-work programs were tested using the Quest Diagnostics Emergency Use Authorization SARS-CoV-2 RT-PCR. The cycle threshold (Ct) values for the N1 and N3 N-gene targets and a human RNase P (RP) gene control target were tabulated. For comparison, we utilized Ct values from a cohort of health care provider–collected specimens from patients with and without coronavirus disease 2019 symptoms.

Results

Among 47 923 participants, 1.8% were positive. RP failed to amplify for 13/115 435 (0.011%) specimens. The median (interquartile range) Cts were 32.7 (25.0–35.7) for N1 and 31.3 (23.8–34.2) for N3. Median Ct values in the self-collected cohort were significantly higher than those of symptomatic but not asymptomatic patients. Based on Ct values, pooled testing with 4 specimens would have yielded inconclusive results in 67/1268 (5.2%) specimens but only a single false-negative result.

Conclusions

Unobserved self-collection of nasal swabs provides adequate sampling for SARS-CoV-2 RT-PCR testing. These findings alleviate concerns of increased false negatives in this context. Specimen pooling could be used for this population, as the likelihood of false-negative results is very low when using a sensitive, dual-target methodology.
What Do Dreams Do?
Authors: Llewellyn Sue
Published: January 2021

What is a dream? It’s a complex, non-obvious pattern derived from your experience. But you haven’t actually experienced it. Strange. Revealing complex, hidden patterns makes dreams odd. Dreams associate elements of different experiences to make something new: a pattern you didn’t know was there until you dreamt it. Patterns are discernible forms in the way something happens or is done. Some patterns are easy to spot, being certain and obvious: night follows day. Patterns in human/animal experiences are less obvious because, first, the patterned elements appear at different times or places and, second, the pattern exhibits tendencies not certainties. Spotting such patterns depends on non-obvious associations. If prompted with ‘sea’, while awake, your logical brain makes obvious associations, ‘beach’ or ‘boat’, with a seaside pattern i.e. beach-boat-seaside. But after awakening from dreaming, when your brain is still tuned to non-obvious associations, ‘sick’ may come to mind. A less obvious element of sea experiences. You tend to seasickness when it’s rough. But you also get sick if you eat shellfish, have a migraine, or travel in cars—but only if you read. Sea–rough–car–read–shellfish–migraine. Visualizing these non-obvious associations between elements of different experiences becomes dream-like. Dreaming brains evolved to identify non-obvious associations. Across evolutionary time, you didn’t want to get sick. Survival depended on being well enough to anticipate the non-obvious patterns of predators and human competitors, while securing access to food and water. Making associations drives many, if not all, brain functions. Dream associations support memory, emotional stability, creativity, unconscious decision-making, and prediction, while also contributing to mental illness. This book explains how.
Eleven biosynthetic genes explain the majority of natural variation in carotenoid levels in maize grain
Authors: Diepenbrock Christine H , Ilut Daniel C , Magallanes-Lundback Maria , Kandianis Catherine B , Lipka Alexander E , Bradbury Peter J , Holland James B , Hamilton John P , Wooldridge Edmund , Vaillancourt Brieanne , Góngora-Castillo Elsa , Wallace Jason G , Cepela Jason , Mateos-Hernandez Maria , Owens Brenda F , Tiede Tyler , Buckler Edward S , Rocheford Torbert , Buell C Robin , Gore Michael A , DellaPenna Dean
Published: January 2021

Vitamin A deficiency remains prevalent in parts of Asia, Latin America, and sub-Saharan Africa where maize (Zea mays) is a food staple. Extensive natural variation exists for carotenoids in maize grain. Here, to understand its genetic basis, we conducted a joint linkage and genome-wide association study of the US maize nested association mapping panel. Eleven of the 44 detected quantitative trait loci (QTL) were resolved to individual genes. Six of these were correlated expression and effect QTL (ceeQTL), showing strong correlations between RNA-seq expression abundances and QTL allelic effect estimates across six stages of grain development. These six ceeQTL also had the largest percentage of phenotypic variance explained, and in major part comprised the three to five loci capturing the bulk of genetic variation for each trait. Most of these ceeQTL had strongly correlated QTL allelic effect estimates across multiple traits. These findings provide an in-depth genome-level understanding of the genetic and molecular control of carotenoids in plants. In addition, these findings provide a roadmap to accelerate breeding for provitamin A and other priority carotenoid traits in maize grain that should be readily extendable to other cereals.
Pain and Poverty: Disparities by Poverty Level in the Experience of Pain-Related Interference
Authors: Keralis Jessica M
Published: January 2021

Objective

To assess the relationship between poverty and pain-related interference.

Subjects

Data on a sample of 108,259 adults aged 18 and older from the Household Component of the Medical Expenditure Panel Survey (MEPS) from 2013 to 2017 were analyzed.

Methods

I assess the odds of reporting any pain-related interference, as well as increasing levels of pain-related interference, using binary and ordinal logistic regression, respectively.

Results

After controlling for covariates, the analysis showed a significant association between poverty and pain-related interference, with more severe levels of poverty associated with increased odds of reporting any pain-related interference as well as increased levels of pain-related interference. However, Hispanics were less likely to report any pain-related interference overall, and more severe levels of poverty were associated with decreased odds of reporting pain among Hispanics.

Conclusions

Policy makers should regard poverty as a social determinant of health, taking poverty and socioeconomic status into consideration when designing health policies.
Do You Know that I Know that You Know…? Higher-Order Beliefs in Survey Data
Authors: Coibion Olivier , Gorodnichenko Yuriy , Kumar Saten , Ryngaert Jane
Published: January 2021

We implement a new survey of firms, focusing on their higher-order macroeconomic expectations. The survey provides a novel set of stylized facts regarding the relationship between first-order and higher-order expectations of economic agents, including how they adjust their beliefs in response to a variety of information treatments. We show how these facts can be used to calibrate key parameters of noisy-information models with infinite regress as well as to test predictions made by this class of models. We also consider a range of extensions to the basic noisy-information model that can potentially better reconcile theory and empirics. Although some extensions like level-k thinking are unsuccessful, incorporating heterogeneous long-run priors can address the empirical shortcomings of the basic noisy-information model.
The value of telephone consultations during COVID-19 pandemic. An observational study
Authors: Martos-Pérez F , Martín-Escalante M D , Olalla-Sierra J , Prada-Pardal J L , García-de-Lucas M D , González-Vega R , Jiménez-Puente A , García-Alegría J
Published: January 2021

Background

Many Spanish hospitals converted scheduled in-person visits to telephone visits during the COVID-19 lockdown. There is scarce information about the performance of those visits.

Aim

To compare telephone visits during the COVID-19 lockdown period with previous in-person visits.

Design

Retrospective descriptive study.

Methods

Telephone visits from 15 March to 31 May 2020 were compared with in-person visits during the same period in 2019.

Main measures

The proportions of both groups were compared in term of failure to contact patient, requested diagnostic tests/referrals, discharges, admissions and emergency visits within 30–60 days. A sample of patients, and all participating physicians completed surveys. Z-score test was used (statistical significance P<0.05).

Results

A total of 5602 telephone visits were conducted. In comparison to in-person visits, telephone visits showed higher rates of visit compliance (95.9% vs. 85.2%, P<0.001) and discharges (22.12% vs. 11.82%; P<0.001), and lower number of ancillary tests and referrals. During the 30- and 60-day periods following the telephone visit, a reduction of 52% and 47% in the combined number of emergency department visits and hospital admissions was observed compared to in-person visits (P<0.01). Of the 120 patients surveyed, 95% were satisfied/very satisfied with the telephone visits. Of the 26 physicians, 84.6% considered telephone visits were useful to prioritize patients.

Conclusions

During health emergencies, previously scheduled outpatient in-person visits can be converted to telephone visits, reducing absenteeism, increasing the rate of discharges and reducing ancillary tests and referrals without increasing the rate of hospital admissions or emergency department visits.
Patient perceptions of health-related quality of life in giant cell arteritis: international development of a disease-specific patient-reported outcome measure
Authors: Robson Joanna C , Almeida Celia , Dawson Jill , Bromhead Alison , Dures Emma , Guly Catherine , Hoon Elizabeth , Mackie Sarah , Ndosi Mwidimi , Pauling John , Hill Catherine
Published: January 2021

Objectives

GCA is a large vessel vasculitis (LVV) presenting with headache, jaw claudication, musculoskeletal and visual involvement. Current treatment is glucocorticoids and anti-IL-6 tocilizumab in refractory disease. The objective of this study was to explore the impact of GCA and its treatment on people’s health-related quality of life (HRQoL), to inform the development of a disease-specific patient-reported outcome measure (PROM) for use in clinical trials and practice.

Methods

Participants from the UK and Australia, with biopsy- or imaging-confirmed GCA, were interviewed to identify salient aspects of HRQoL in relation to GCA and its treatment. Purposive sampling included a range of demographic and disease features (cranial, LVV-GCA and visual involvement). Inductive analysis identified individual themes of importance, then domains. Candidate questionnaire items were developed from the individual themes, refined by piloting, cognitive interviews and a linguistic translatability assessment.

Results

Thirty-six interviews were conducted to saturation with participants with GCA from the UK (25) and Australia (11). Mean age was 74 years, 23 (63.9%) were female, 13 (36.1%) had visual loss and 5 (13.9%) had LVV-GCA. Thirty-nine individual themes within five domains were identified: physical symptoms; activity of daily living and function; participation; psychological impact; and impact on sense of self and perception of health. Sixty-nine candidate items were developed from individual themes; piloting and refinement resulted in a 40-item draft questionnaire.

Conclusion

This international qualitative study underpins the development of candidate items for a disease-specific PROM for GCA. The draft questionnaire is now ready for psychometric testing.
Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity
Authors: Qin Hua , Keenan Brendan T , Mazzotti Diego R , Vaquerizo-Villar Fernando , Kraemer Jan F , Wessel Niels , Tufik Sergio , Bittencourt Lia , Cistulli Peter A , de Chazal Philip , Sutherland Kate , Singh Bhajan , Pack Allan I , Chen Ning-Hung , Fietze Ingo , Gislason Thorarinn , Holfinger Steven , Magalang Ulysses J , Penzel Thomas
Published: January 2021

Study Objectives

Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample.

Methods

1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates.

Results

Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009).

Conclusions

Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients.

Clinical Trial Information: 

A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00003966
The assessment of parents’ knowledge, attitudes and concerns about febrile seizures in children at tertiary hospitals in Rwanda—a descriptive study
Authors: Hakizimana, MBBS, MMed Onesphore , Kalimba, MBBS, MMed Edgar , Arnold, MD Linda , Cartledge, MBChB Peter
Published: January 2021

Background

Febrile seizures (FSs) are the most common seizure disorder in childhood. No previous research has been performed to assess caregiver attitudes, knowledge and concerns of FSs in Rwanda or East Africa.

Objectives

This study sought to assess knowledge, attitudes and concerns regarding FS among caregivers of children presenting to tertiary hospitals in Rwanda using a previously validated questionnaire. The secondary objective was to assess the reliability of a translated version of the Huang Febrile Seizures Questionnaire (HFSQ).

Methods

A multi-centre observational study was conducted at four tertiary teaching hospitals in Rwanda. The admitting doctor determined that children met the definition of FSs. A translated version, of a validated questionnaire, the HFSQ, employing yes/no and five-point Likert questions, was used for this study, after minor adjustments.

Results

Eighty-six caregivers were recruited. Caregivers had low levels of pre-existing knowledge regarding FSs. The most significant caregiver concern was that ‘siblings will have FSs too’(mean = 3.62 ± 0.7). Caregivers felt that children with FSs do not need more attention and care and that FSs can be outgrown (mean = 3.4 ± 1.0).

Discussion

The findings support the need for locally relevant educational materials to be shared with caregivers after a FS event. The HFSQ is a good quality tool for assessing parental knowledge and concerns and has the potential to be used in clinical practice as a benchmarking tool for education.
Fermentation: An Unreliable Seed Treatment for Bacterial Fruit Blotch of Watermelon
Authors: Ge Yixin , Luo Lan , Xia Liming , Luo Xue , Bi Hongkai , Gong Hanxiao , Tian Yanli , Walcott Ron R. , Hu Baishi
Published: January 2021

Acidovorax citrulli is a seedborne pathogen that causes bacterial fruit blotch (BFB), a global threat to watermelon production. Treating watermelon seeds to eliminate A. citrulli is a critical component of BFB management, and several strategies have been evaluated to mitigate the impact of the disease. In China, watermelon seed producers routinely incubate seeds in watermelon juice (fermentation) to reduce the risk of seed infection by A. citrulli and seedling transmission of BFB. However, there has been limited effort to evaluate the efficacy of fermentation in mitigating A. citrulli seed infection. The current study showed that fermented watermelon fruit juice could inhibit A. citrulli population growth and demonstrated that the low pH conditions, not the temperature dynamic, generated during fermentation might play a major role in A. citrulli growth inhibition and could induce the viable but nonculturable (VBNC) state in A. citrulli. We developed an effective method that was based on propidium monoazide PCR to detect viable A. citrulli cells under low pH conditions or in fermented watermelon fruit juice. We also provided evidence that VBNC A. citrulli cells induced by fermented watermelon fruit juice could not be resuscitated and did not retain their virulence on watermelon seedlings. However, VBNC A. citrulli cells could be resuscitated in Luria–Bertani medium. Based on these observations, we conclude that fermentation in watermelon fruit juice may not be an effective seed treatment for BFB because it may increase the seed infection by A. citrulli.
Case Management on the Front Lines of COVID-19
Authors: Baker Michelle , Nelson Sheila , Krsnak Jean
Published: January 2021

Purpose:

Since the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disease known as COVID-19, case management has emerged as a critical intervention in the treatment of cases, particularly for patients with severe symptoms and medical complications. In addition, case managers have been on the front lines of the response across the health care spectrum to reduce risks of contagion, including among health care workers. The purpose of this article is to discuss the case management response, highlighting the importance of individual care plans to provide access to the right care and treatment at the right time to address both the consequences of the disease and patient comorbidities.

Primary Practice Settings:

The COVID-19 response spans the full continuum of health and human services, including acute care, subacute care, workers' compensation (especially catastrophic case management), home health, primary care, and community-based care.

Implications for Case Management Practice:

From the earliest days of the pandemic, case managers have assumed an important role on the front lines of the medical response to COVID-19, ensuring that procedures are in place for managing a range of patients: those who were symptomatic but able to self-isolate and care for themselves at home; those who had serious symptoms and needed to be hospitalized; and those who were asymptomatic and needed to be educated about the importance of self-isolating. Across the care spectrum, individualized responses to the clinical and psychosocial needs of patients with COVID-19 in acute care, subacute care, home health, and other outpatient settings have been guided by the well-established case management process of screening, assessing, planning, implementing, following up, transitioning, and evaluating. In addition, professional case managers are guided by values such as advocacy, ensuring access to the right care and treatment at the right time; autonomy, respecting the right to self-determination; and justice, promoting fairness and equity in access to resources and treatment. The value of justice also addresses the sobering reality that people from racial and ethnic minority groups are at an increased risk of getting sick and dying from COVID-19. Going forward, case management will continue to play a major role in supporting patients with COVID-19, in both inpatient and outpatient settings, with telephonic follow-up and greater use of telehealth.
Cognitive Errors in Pediatric Emergency Medicine
Authors: Scarfone Richard J. , Nagler Joshua
Published: January 2021

Fundamental to the practice of pediatric emergency medicine is making timely and accurate diagnoses. However, studies have shown errors in this process are common. A number of factors in the emergency department environment as well as identifiable errant patterns of thinking can contribute to such challenges. Cognitive psychologists have described 2 types of thinking: system 1 (fast) relies primarily on intuition and pattern recognition, whereas system 2 (slow) is more deliberative and analytical. Reviewing how these 2 styles of thinking are applied in clinical practice provides a framework for understanding specific cognitive errors. This article uses illustrative examples to introduce many of these common errors, providing context for how and why they occur. In addition, a practical approach to reducing the risk of such errors is offered.
Cyberlindnera sylvatica sp. nov., a yeast species isolated from forest habitats
Authors: Brysch-Herzberg Michael , Dlauchy Dénes , Seidel Martin , Péter Gábor
Published: January 2021

Five yeast strains isolated from forest habitats in Hungary and Germany were characterized phenotypically and by sequencing of the D1/D2 domain of the large subunit rRNA gene and the ITS1-5.8S-ITS2 (ITS) region of the rRNA gene. The strains have identical D1/D2 domain and ITS region sequences. By sequence comparisons, Candida mycetangii and Candida maritima were identified as the closest relatives among the currently recognized yeast species. The DNA sequences of the investigated strains differ by 1.2 % (six substitutions) in the D1/D2 domain and by 3.5 % (12 substitutions and eight indels) in the ITS region from the type strain of C. mycetangii (CBS 8675T) while by 1.2 % (six substitutions and one indel) in the D1/D2 domain and by 7 % (32 substitutions and seven indels) in the ITS region from the type strain of C. maritima (CBS 5107T). Because the intraspecies heterogeneity seems to be very low and the distance to the most closely related species is above the commonly expected level for intraspecies variability Cyberlindnera sylvatica sp. nov. (holotype, CBS 16335T; isotype, NCAIM Y.02233T; MycoBank no., MB 835268) is proposed to accommodate the above-noted five yeast strains. Phenotypically the novel species can be distinguished from C. mycetangii and C. maritima by the formation of ascospores. Cyberlindnera sylvatica forms one or two hat-shaped ascospores per ascus on many different media as well as well-developed pseudohyphae and true hyphae. Additionally, we propose the transfer of three anamorphic members of the Cyberlindnera americana sub-clade to the genus Cyberlindnera as the following new taxonomic combinations Cyberlindnera maritima f.a., comb. nov., Cyberlindnera mycetangii f.a., comb. nov. and Cyberlindnera nakhonratchasimensis f.a., comb. nov.
Genetic and biological characterization of Newcastle disease viruses circulating in Bangladesh during 2010–2017: further genetic diversification of class II genotype XIII in Southcentral Asia
Authors: Nooruzzaman Mohammed , Mumu Tanjin Tamanna , Kabiraj Congriev Kumar , Hasnat Azmary , Rahman Md Mijanur , Chowdhury Emdadul Haque , Dimitrov Kiril M. , Islam Mohammad Rafiqul
Published: January 2021

Newcastle disease virus (NDV) is endemic in Bangladesh and is a major threat to commercial poultry operations. While complete fusion (F) genes are recommended for molecular characterization and classification of NDV isolates, heretofore, only partial F gene data have been available for Bangladeshi NDVs. To this end, we obtained the full-length F gene coding sequences of 11 representative NDVs isolated in Bangladesh between 2010 and 2017. In addition, one of the viruses (MK934289/chicken/Bangladesh/C161/2010) was used in an experimental infection of chickens to establish the viral pathotype and study gross and microscopic lesions. Phylogenetic analysis provided evidence that all studied Bangladeshi isolates belong to genotype XIII.2 of class II NDVs. Six of the viruses were isolated between 2010 and 2017 and grouped together with isolates from neighbouring India during 2013–2016. Another four Bangladeshi isolates (2010–2016) formed a separate monophyletic branch within XIII.2 and showed high nucleotide distance from the isolates from India and the other six Bangladeshi viruses within the sub-genotype; however, none of these groups fulfils all classification criteria to be named as a separate sub-genotype. The eleventh Bangladeshi virus studied here (C162) was genetically more distant from the remaining isolates. It out-grouped the viruses from sub-genotypes XIII.2.1 and XIII.2.2 and showed more than 9.5 % nucleotide distance from all genotype XIII sub-genotypes. This isolate may represent an NDV variant that is evolving independently from the other viruses in the region. The experimental infection in chickens revealed that the tested isolate (C161) is a velogenic viscerotropic virus. Massive haemorrhages, congestion and necrosis in different visceral organs, and lymphoid depletion in lymphoid tissues, typical for infection with velogenic NDV, were observed. Our findings demonstrate the endemic circulation of sub-genotype XIII.2 in Southcentral Asia and further genetic diversification of these viruses in Bangladesh and neighbouring India. This constant evolution of the viruses may lead to the establishment of new genetic groups in the region. Additional historical and prospective virus and surveillance data from the region and neighbouring countries will allow a more detailed epidemiological inference.
Distinctive features of SARS-CoV-2-specific T cells predict recovery from severe COVID-19
Authors: Neidleman Jason , Luo Xiaoyu , George Ashley F. , McGregor Matthew , Yang Junkai , Yun Cassandra , Murray Victoria , Gill Gurjot , Greene Warner C. , Vasquez Joshua , Lee Sulggi , Ghosn Eliver , Lynch Kara , Roan Nadia R.
Published: January 2021

Although T cells are likely players in SARS-CoV-2 immunity, little is known about the phenotypic features of SARS-CoV-2-specific T cells associated with recovery from severe COVID-19. We analyzed T cells from longitudinal specimens of 34 COVID-19 patients with severities ranging from mild (outpatient) to critical culminating in death. Relative to patients that succumbed, individuals that recovered from severe COVID-19 harbored elevated and increasing numbers of SARS-CoV-2-specific T cells capable of homeostatic proliferation. In contrast, fatal COVID-19 displayed elevated numbers of SARS-CoV-2-specific regulatory T cells and a time-dependent escalation in activated bystander CXCR4+ T cells. Together with the demonstration of increased proportions of inflammatory CXCR4+ T cells in the lungs of severe COVID-19 patients, these results support a model whereby lung-homing T cells activated through bystander effects contribute to immunopathology, while a robust, non-suppressive SARS-CoV-2-specific T cell response limits pathogenesis and promotes recovery from severe COVID-19.

Graphical Abstract

HIGHLIGHTS

Dysfunctional spike-specific T cells are characteristic of severe COVID-19

Spike-specific CD127+ Th1 cells are increased in survivors of severe COVID-19

Spike-specific Tregs and IL6+ CD8+ T cells are increased in fatal COVID-19

Escalation of activated lung-homing CXCR4+ T cells associates with fatal COVID-19

BRIEF SUMMARY

By conducting CyTOF on total and SARS-CoV-2-specific T cells from longitudinal specimens spanning the entire spectrum of COVID-19 diseases, Neidleman et al. demonstrate that spike-specific Th1 cells capable of IL7-dependent homeostatic proliferation predict survival from severe COVID-19, while Tregs and IL6+ CD8+ T cells recognizing spike predict fatal outcome. Fatal COVID-19 is characterized by escalating activation of bystander CXCR4+ T cells in the lungs. Boosting SARS-CoV-2-specific CD4+ T effector responses while diminishing CXCR4-mediated homing may help recovery from severe disease.
A Hybrid Machine Learning Framework for Enhancing the Prediction Power in Large Scale Population Studies: The ATHLOS Project
Authors: Barmpas Petros , Tasoulis Sotiris , Vrahatis Aristidis G. , Prina Matthew , Ayuso-Mateos José Luis , Bickenbach Jerome , Bayes Ivet , Bobak Martin , Félix Caballero Francisco , Chatterji Somnath , Egea-Cortés Laia , García-Esquinas Esther , Leonardi Matilde , Koskinen Seppo , Koupil Ilona , Pająk Andrzej , Prince Martin , Sanderson Warren , Scherbov Sergei , Tamosiunas Abdonas , Galas Aleksander , Haro Josep Maria , Sanchez-Niubo Albert , Plagianakos Vassilis , Panagiotakos Demosthenes
Published: January 2021

The ATHLOS cohort is composed of several harmonized datasets of international cohorts related to health and aging. The healthy aging scale has been constructed based on a selection of particular variables from 16 individual studies. In this paper, we consider a selection of additional variables found in ATHLOS and investigate their utilization for predicting the healthy aging. For this purpose motivated by the dataset’s volume and diversity we focus our attention upon the clustering for prediction scheme, where unsupervised learning is utilized to enhance prediction power, showing the predictive utility of exploiting structure in the data by clustering. We show that imposed computation bottlenecks can be surpassed when using appropriate hierarchical clustering within a clustering for ensemble classification scheme while retaining prediction benefits. We propose a complete methodology which is evaluated against baseline methods and the original concept. The results are very encouraging suggesting further developments in this direction along with applications in tasks with similar characteristics. A strait-forward open source implementation is provided for the R project.
The Forgotten Tract of Vision in Multiple Sclerosis: Vertical Occipital Fasciculus, Its Integrity, and Visuospatial Memory
Authors: Abdoalizadeh AmirHussein , Mohammadi Soheil , Aarabi Mohammad Hadi
Published: January 2021

Background

Visual disturbances are a common disease manifestation and a major patient complaint in Multiple Sclerosis (MS) due to lesions damaging white matter tracts involved in vision. Vertical Occipital Fasciculus (VOF) connects ventral and dorsal visual streams and was neglected for more than a century. It has recently become under focus in brain-related disorders. Thus, its role in the visual dysfunction in MS needs to be clarified.

Objective

Evaluate the integrity of bilateral VOFs in MS and its association with clinical and visual evaluations.

Methods

56 relapsing-remitting MS (RRMS) and 25 healthy controls (HC) were recruited. We acquired MS Functional Composite, Expanded Disability Status Scale (EDSS), and Brief Visuospatial Memory Test – Revised (BVMT-R), and structural and diffusion MRI scans. After VOF tractography, its integrity markers were statistically tested for between-group differences and clinical and visual tests associations.

Results

RRMS patients had lower fiber integrity in bilateral VOFs compared to HC. Lower integrity of bilateral VOFs was associated with poor clinical outcomes, higher visual score in EDSS, and lower total immediate and delayed recall in BVMT-R.

Conclusion

VOF damage is seen in RRMS and is associated with visual symptoms and visuospatial learning impairments.
BNP facilitates NMB-mediated histaminergic itch via NPRC-NMBR crosstalk
Authors: Meng Qing-Tao , Liu Xian-Yu , Liu Xue-Ting , Barry Devin M. , Jin Hua , Sun Yu , Yang Qianyi , Wan Li , Jin Jin-Hua , Shen Kai-Feng , Munanairi Admire , Kim Ray , Yin Jun , Tao Ailin , Chen Zhou-Feng
Published: January 2021

B-type natriuretic peptide (BNP) binds to its two cognate receptors NPRA and NPRC, encoded byNpr1andNpr3, respectively, with equal potency and both are expressed in the spinal cord. Moreover, natriuretic peptides (NP) signal through the inhibitory cGMP pathway, raising the question of how BNP may transmit itch information. We report thatNpr3is highly restricted to laminae I-II of the dorsal horn, and partially overlaps with neuromedin B receptor (NMBR) that encodes histaminergic itch. Functional studies indicate that NPRC is required for itch evoked by histamine but not chloroquine (CQ), a nonhistaminergic pruritogen. Importantly, BNP significantly facilitates scratching behaviors mediated by NMB, but not gastrin releasing peptide (GRP) that encodes nonhistaminergic itch. Consistently, BNP evoked Ca2+response in NMBR/NPRC HEK 293 cells and BNP-saporin that ablated bothNpr1andNpr3neurons impaired histamine-, but not CQ-evoked, itch. These results reveal a previously unknown mechanism by which BNP changes its inhibitory mode of action to the facilitation of itch through a novel NPRC-NMBR cross-talk. Our studies suggest that neuropeptides encode histaminergic and nonhistaminergic itch not only through distinct modes but also in synergy.
Commensal bacterial-derived retinoic acid primes host defense to intestinal infection
Authors: Woo Vivienne , Eshleman Emily M. , Whitt Jordan , Hashimoto-Hill Seika , Wu Shu-en , Engleman Laura , Rice Taylor , Karns Rebekah , Vallance Bruce A. , Alenghat Theresa
Published: January 2021

Interactions between the microbiota and mammalian host are essential for effective defense against pathogenic infection; however, the microbial-derived cues that mediate this beneficial relationship remain unclear. Here, we find that the intestinal epithelial cell (IEC)-associated commensal bacteria, Segmented Filamentous Bacteria (SFB), promotes early protection against the bacterial pathogen,Citrobacter rodentium, independently of CD4+T cells. Global analyses demonstrated that SFB induced histone modifications in IECs at sites enriched for the retinoic acid receptor (RAR) motif. Interestingly, SFB-colonized mice exhibited greater expression of RAR targets during infection relative to germ-free mice, suggesting SFB may enhance defense through retinoic acid (RA) signaling. Consistent with this, supplementing germ-free mice with RA decreased pathogen levels. Further, mice with impaired RA-responsiveness in IECs displayed increased susceptibility toC. rodentiuminfection. RA was elevated in the intestine of mice colonized with SFB, indicating that the presence of commensal bacteria can modulate intestinal RA levels. However, this regulation by SFB was not dependent on mammalian RA production. Sequence analyses suggested that RA-generating enzymes are expressed by a subset of commensal bacteria. Remarkably, RA was produced by intestinal bacteria including SFB, and inhibiting RA signaling blocked SFB-induced protection againstC. rodentiuminfection. These data collectively reveal RA as an unexpected microbiota-derived metabolite that primes innate intestinal defense and suggests that pre- and probiotic approaches to elevate RA could prevent or combat pathogenic infection.
USP47 regulates a 53BP1-based complex function in DNA DSB repair
Authors: Sadideen Doraid T. , Chen Baowei , Basili Manal , Hromas Robert , Shaheen Montaser
Published: January 2021

53BP1 is a key DNA repair protein that regulates double strand break (DSB) repair pathway choice. It assembles a complex, whose loss reverses BRCA1 deficient cells sensitivity to PARP1 inhibitors potentially by antagonizing DSB end resection. 53BP1 is critical for immunoglobulin heavy chain class switch recombination (CSR), that is mediated by the generation and repair of DSBs. Here we identify a deubiquitylase, USP47, as a 53BP1 associated protein that regulates its function in these processes. USP47 loss results in 53BP1 protein instability in a proteasome dependent manner and in reduced 53BP1 ionizing radiation induced foci (IRIF). Like 53BP1, USP47 depletion results in enhanced homologous recombination repair, and defective immunoglobulin CSR. It is also required for resistance to DNA damaging agents. We identify a complex of 53BP1, USP47, Fen1, and Recql1 that regulates a microhomology mediated end joining (MMEJ), a repair pathway that is involved in CSR. Altogether, our findings implicate USP47 in DNA DSB repair at least through regulating a novel 53BP1 associated complex.
AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa
Authors: Xue Yunlu , Wang Sean K. , Rana Parimal , West Emma R. , Hong Christin M. , Feng Helian , Wu David M. , Cepko Constance L.
Published: January 2021

Retinitis pigmentosa (RP) is an inherited retinal disease, affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a gene-agnostic therapy, we screened ≈20 genes for their ability to prolong cone photoreceptor survivalin vivo. Here, we report an adeno-associated virus (AAV) vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A Txnip allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb), and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.
Astrocytic VMAT2 in the developing prefrontal cortex is required for normal grooming behavior in mice
Authors: Petrelli Francesco , Zehnder Tamara , Pucci Luca , Cali Corrado , Bondiolotti Bianca Maria , Perez Alicia Molinero , Dallerac Glenn , Déglon Nicole , Giros Bruno , Magara Fulvio , Magrassi Lorenzo , Mothet Jean-Pierre , Simmler Linda , Bezzi Paola
Published: January 2021

Astrocytes control synaptic activity by modulating peri-synaptic concentrations of ion and neurotransmitters including dopamine and, as such, can be critically involved in the modulation of some aspect of mammalian behavior. Here we report that genetic mouse model with a reduced medial prefrontal cortex (mPFC) dopamine levels, arising from astrocyte-specific conditional deletion of vesicular monoamine transporter 2 (VMAT2; aVMTA2cKO mice) shows excessive grooming and anxiety-like behaviour. The VMAT2cKO mice also develop a synaptic pathology, expressed through increased relative AMPA vs. NMDA receptor currents in synapses of the dorsal striatum receiving inputs from the mPFC. Importantly, behavioural and synaptic phenotypes are prevented by reexpression of mPFC VMAT2, showing that the deficits are driven by mPFC astrocytes. By analysing human tissue samples, we found that VMAT2 is expressed in human mPFC astrocytes, corroborating the potential translational relevance of our observations in mice. Our study shows that impairments of the astrocytic-control of dopamine in the mPFC has a profound impact on circuit function and behaviours, which resemble symptoms of anxiety disorders and obsessive compulsive disorder (OCD).
The emergence of cooperation by evolutionary generalization
Authors: Geoffroy Félix , André Jean-Baptiste
Published: January 2021

In principle, any cooperative behaviour can be evolutionarily stable as long as it is incentivized by a reward from the beneficiary, a mechanism that has been called reciprocal cooperation. However, what makes this mechanism so powerful also has an evolutionary downside. Reciprocal cooperation faces a chicken-and-egg problem of the same kind as communication: it requires two functions to evolve at the same time –cooperation and response to cooperation. As a result, it can only emerge if one side first evolves for another reason, and is then recycled into a reciprocal function. Developping an evolutionary model in which we make use of machine learning techniques, we show that this occurs if the fact to cooperate and reward others’ cooperation become general abilities that extend beyond the set of contexts for which they have initially been selected. Drawing on an evolutionary analogy with the concept of generalization, we identify the conditions necessary for this to happen. This allows us to understand the peculiar distribution of reciprocal cooperation in the wild, virtually absent in most species –or limited to situations where individuals have partially overlapping interests, but pervasive in the human species