bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterozygous KCNH2 variant phenotyping using Flp-In HEK293 and high-throughput automated patch clamp electrophysiology
Authors: Ng Chai-Ann , Farr Jessica , Young Paul , Windley Monique J , Perry Matthew D , Hill Adam P , Vandenberg Jamie I
Published: March 2021

KCNH2 is one of the 59 medically actionable genes recommended by the American College of Medical Genetics for reporting of incidental findings from clinical genomic sequencing. However, half of the reported KCNH2 variants in the ClinVar database are classified as variants of uncertain significance. In the absence of strong clinical phenotypes, there is a need for functional phenotyping to help decipher the significance of variants identified incidentally. Here, we report detailed methods for assessing the molecular phenotype of any KCNH2 missense variant. The key components of the assay include quick and cost-effective generation of a bi-cistronic vector to co-express Wild-type (WT) and any KCNH2 variant allele, generation of stable Flp-In HEK293 cell lines and high-throughput automated patch clamp electrophysiology analysis of channel function. Stable cell lines take 3–4 weeks to produce and can be generated in bulk, which will then allow up to 30 variants to be phenotyped per week after 48 h of channel expression. This high-throughput functional genomics assay will enable a much more rapid assessment of the extent of loss of function of any KCNH2 variant.
Practical model to identify liver transplant recipients at low risk of postoperative haemorrhage, bile leakage and ascites
Authors: Hobeika C , Cauchy F , Weiss E , Chopinet S , Sepulveda A , Dondero F , Khoy-Ear L , Grigoresco B , Dokmak S , Durand F , Le Roy B , Paugam-Burtz C , Soubrane O
Published: March 2021

Background

This study aimed to identify a subgroup of recipients at low risk of haemorrhage, bile leakage and ascites following liver transplantation (LT).

Methods

Factors associated with significant postoperative ascites (more than 10 ml/kg on postoperative day 5), bile leakage and haemorrhage after LT were identified using three separate multivariable analyses in patients who had LT in 2010–2019. A model predicting the absence of all three outcomes was created and validated internally using bootstrap procedure.

Results

Overall, 944 recipients underwent LT. Rates of ascites, bile leakage and haemorrhage were 34.9, 7.7 and 6.0 per cent respectively. The 90-day mortality rate was 7.0 per cent. Partial liver graft (relative risk (RR) 1.31; P = 0.021), intraoperative ascites (more than 10 ml/kg suctioned after laparotomy) (RR 2.05; P = 0.001), malnutrition (RR 1.27; P = 0.006), portal vein thrombosis (RR 1.56; P = 0.024) and intraoperative blood loss greater than 1000 ml (RR 1.39; P = 0.003) were independently associated with postoperative ascites and/or bile leak and/or haemorrhage, and were introduced in the model. The model was well calibrated and predicted the absence of all three outcomes with an area under the curve of 0.76 (P = 0.001). Of the 944 patients, 218 (23.1 per cent) fulfilled the five criteria of the model, and 9.6 per cent experienced postoperative ascites (RR 0.22; P = 0.001), 1.8 per cent haemorrhage (RR 0.21; P = 0.033), 4.1 per cent bile leak (RR 0.54; P = 0.048), 40.4 per cent severe complications (RR 0.70; P = 0.001) and 1.4 per cent 90-day mortality (RR 0.13; P = 0.004).

Conclusion

A practical model has been provided to identify patients at low risk of ascites, bile leakage and haemorrhage after LT; these patients could potentially qualify for inclusion in non-abdominal drainage protocols.
Predictive value of Altmetric score on citation rates and bibliometric impact
Authors: Robinson D B T , Powell A G M T , Waterman J , Hopkins L , James O P , Egan R J , Lewis W G
Published: March 2021

Background

Bibliometric and Altmetric analyses provide different perspectives regarding research impact. This study aimed to determine whether Altmetric score was associated with citation rate independent of established bibliometrics.

Methods

Citations related to a previous cohort of 100 most cited articles in surgery were collected and a 3-year interval citation gain calculated. Citation count, citation rate index, Altmetric score, 5-year impact factor, and Oxford Centre for Evidence-Based Medicine levels were used to estimate citation rate prospect.

Results

The median interval citation gain was 161 (i.q.r. 83–281); 74 and 62 articles had an increase in citation rate index (median increase 2.8 (i.q.r. –0.1 to 7.7)) and Altmetric score (median increase 3 (0–4)) respectively. Receiver operating characteristic (ROC) curve analysis revealed that citation rate index (area under the curve (AUC) 0.86, 95 per cent c.i. 0.79 to 0.93; P < 0.001) and Altmetric score (AUC 0.65, 0.55 to 0.76; P = 0.008) were associated with higher interval citation gain. An Altmetric score critical threshold of 2 or more was associated with a better interval citation gain when dichotomized at the interval citation gain median (odds ratio (OR) 4.94, 95 per cent c.i. 1.99 to 12.26; P = 0.001) or upper quartile (OR 4.13, 1.60 to 10.66; P = 0.003). Multivariable analysis revealed only citation rate index to be independently associated with interval citation gain when dichotomized at the median (OR 18.22, 6.70 to 49.55; P < 0.001) or upper quartile (OR 19.30, 4.23 to 88.15; P < 0.001).

Conclusion

Citation rate index and Altmetric score appear to be important predictors of interval citation gain, and better at predicting future citations than the historical and established impact factor and Oxford Centre for Evidence-Based Medicine quality descriptors.
Systematic approach towards reliable estimation of abdominal aortic aneurysm size by ultrasound imaging and CT
Authors: Tomee S M , Meijer C A , Kies D A , le Cessie S , Wasser M N J M , Golledge J , Hamming J F , Lindeman J H N
Published: March 2021

Background

The management of abdominal aortic aneurysm (AAA) is fully dictated by AAA size, but there are no uniform measurement guidelines, and systematic differences exist between ultrasound- and CT-based size estimation. The aim of this study was to devise a uniform ultrasound acquisition and measurement protocol, and to test whether harmonization of ultrasound and CT readings is feasible.

Methods

A literature review was undertaken to evaluate evidence for ultrasound-based measurement of AAA. A protocol for measuring AAA was then developed, and intraobserver and interobserver reproducibility was tested. Finally, agreement between ultrasound readings and CT-based AAA diameters was evaluated. This was an observational study of patients with a small AAA who participated in two pharmaceutical intervention trials.

Results

Based on a literature review, an ultrasound acquisition and reading protocol was devised. Evaluation of the protocol showed an intraobserver repeatability of 1.6 mm (2s.d.) and an interobserver intraclass correlation coefficient (ICC) of 0.97. Comparison of protocolled ultrasound readings and local CT readings indicated a good correlation (r = 0.81), but a systematic +4.1-mm difference for CT. Harmonized size readings for ultrasound imaging and CT increased the correlation (r = 0.91) and reduced the systematic difference to +1.8 mm by CT. Interobserver reproducibility of protocolized CT measurements showed an ICC of 0.94 for the inner-to-inner method and 0.96 for the outer-to-outer method.

Conclusion

The absence of harmonized size acquisition and reading guidelines results in overtreatment and undertreatment of patients with AAA. This can be avoided by the implementation of standardized ultrasound acquisition and a harmonized reading protocol for ultrasound- and CT-based readings.
Economic assessment of starting robot-assisted laparoscopic inguinal hernia repair in a single-centre retrospective comparative study: the EASTER study
Authors: Muysoms F , Vierstraete M , Nachtergaele F , Van Garsse S , Pletinckx P , Ramaswamy A
Published: March 2021

Background

There has been a rapid adoption of robot-assisted laparoscopic inguinal hernia repair in the USA, despite a lack of proven clinical advantage and higher material cost. No studies have been published regarding the cost and outcome of robotic inguinal hernia surgery in a European Union setting.

Methods

A retrospective comparative study was performed on the early outcome and costs related to laparoscopic inguinal hernia repair, with either conventional or robot-assisted surgery.

Results

The study analysed 676 patients undergoing laparoscopic inguinal hernia repair (272 conventional and 404 robotic repairs). Conventional laparoscopic and robotic repair groups were comparable in terms of duration of surgery (57.6 versus 56.2 min respectively; P = 0.224), intraoperative complication rate (1.1 versus 1.2 per cent; P = 0.990), in-hospital complication rate (4.4 versus 4.5 per cent; P = 0.230) and readmission rate (3.3 versus 1.2 per cent; P = 0.095). There was a significant difference in hospital stay in favour of the robotic approach (P = 0.014), with more patients treated on an outpatient basis in the robotic group (59.2 per cent versus 70.0 per cent for conventional repair). At 4-week follow-up, equal numbers of seromas or haematomas were recorded in the conventional laparoscopic and robotic groups (13.3 versus 15.7 per cent respectively; P = 0.431), but significantly more umbilical wound infections were seen in the conventional group (3.0 per cent versus 0 per cent in the robotic group; P = 0.001). Robotic inguinal hernia repair was significantly more expensive overall, with a mean cost of €2612 versus €1963 for the conventional laparoscopic approach (mean difference €649; P < 0.001).

Conclusion

Robot-assisted laparoscopic inguinal hernia repair was significantly more expensive than conventional laparoscopy. More patients were treated as outpatients in the robotic group. Postoperative complications were infrequent and mild.
Eye contact and sociability data suggests that Australian dingoes were never domesticated
Authors: Ballard J William O , Gardner Chloe , Ellem Lucille , Yadav Sonu , Kemp Richard I
Published: March 2021

Dogs were the first animal to become domesticated by humans, and they represent a classic model system for unraveling the processes of domestication. We compare Australian dingo eye contact and socialization with Basenji and German Shepherd dog (GSD) breeds. Australian dingoes arrived in Australia 5,000–8,000 BP, and there is debate whether they were domesticated before their arrival. The Basenji represents a primitive breed that diverged from the remaining breeds early in the domestication process, while GSDs are a breed dog selected from existing domestic dogs in the late 1800s. We conducted a 4-phase study with unfamiliar and familiar investigators either sitting passively or actively calling each canid. We found 75% of dingoes made eye contact in each phase. In contrast, 86% of Basenjis and 96% of GSDs made eye contact. Dingoes also exhibited shorter eye-gaze duration than breed dogs and did not respond to their name being called actively. Sociability, quantified as a canid coming within 1 m of the experimenter, was lowest for dingoes and highest for GSDs. For sociability duration, dingoes spent less time within 1 m of the experimenter than either breed dog. When compared with previous studies, these data show that the dingo is behaviorally intermediate between wild wolves and Basenji dogs and suggest that it was not domesticated before it arrived in Australia. However, it remains possible that the accumulation of mutations since colonization has obscured historical behaviors, and dingoes now exist in a feralized retamed cycle. Additional morphological and genetic data are required to resolve this conundrum.
Effectiveness of music therapy for autism spectrum disorder, dementia, depression, insomnia and schizophrenia: update of systematic reviews
Authors: Gassner Lucia , Geretsegger Monika , Mayer-Ferbas Julia
Published: March 2021

Background

Music therapy (MT) aims at maintaining, restoring and furthering physical/emotional/mental health. This review assesses effectiveness of MT and its methods for autism spectrum disorder (ASD), dementia, depression, insomnia and schizophrenia.

Methods

A search for systematic reviews and health technology assessment reports was conducted and yielded 139 hits. Given the large amount, we focused on five frequent diagnostic groups with available Cochrane reviews. A second search was conducted in four databases. Two authors independently performed study selection, data extraction and assessed methodological quality. Only trials with moderate/low risk of bias (RoB) were selected.

Results

Ten randomized controlled trials (1.248 participants) met inclusion criteria. For schizophrenia, no studies with low/moderate RoB were found; therefore, updating was not possible. The Cochrane authors stated that quality of life (QoL), social functioning, global/mental state improved for schizophrenia, but not global functioning. For ASD, MT improved behaviour, social communication, brain connectivity and parent–child relationship. For depression, mood was enhanced, and for insomnia, sleep quality, stress, anxiety, total sleep time, disease severity and psychological QoL improved. MT positively affected mood, neuropsychiatric behaviour, apathy, communication and physical functions for dementia; behavioural/psychological symptoms improved only in severe, and memory and verbal fluency only in mild Alzheimer’s disease. Cognition improved for dementia in one of four studies. Both active (playing music) and receptive (listening to music) methods were used for dementia, whereas for ASD and depression, active methods were applied. For insomnia, only receptive methods were used.

Conclusion

These findings provide evidence that MT helps patients improving their physical/psychosocial health. More research investigating long-term effects is needed.
FGFR/Heartless and Smog interact synergistically to negatively regulate Fog mediated G-protein coupled receptor signaling in the Drosophila nervous system
Authors: Shweta Kumari , Basargekar Anagha , Ratnaparkhi Anuradha
Published: March 2021

Folded gastrulation (Fog) is a secreted ligand that signals through the G-protein-coupled receptors Mist and Smog and the G-protein Concertina to activate downstream effectors to elicit cell-shape change during gastrulation. In the embryonic central nervous system (CNS), Fog has roles in axon guidance and glial morphogenesis. However, the elements of the pathway as well as mechanisms required for transducing the signal in this context have not been determined. We find that while Concertina is essential for Fog signaling, Mist is dispensable and Smog, surprisingly, functions as a negative regulator of the pathway in the CNS. Interestingly Heartless, a fibroblast growth factor receptor, also functions as a negative regulator. Furthermore, both Heartless and Smog interact in a synergistic manner to regulate Fog signaling. Our results thus identify Heartless and Smog as part of a common regulatory pathway that functions to restrict Fog signaling in the embryonic CNS and highlights the context-specific role for Fog receptors during development.
The Genome of the Margined White Butterfly (Pieris macdunnoughii): Sex Chromosome Insights and the Power of Polishing with PoolSeq Data
Authors: Steward Rachel A , Okamura Yu , Boggs Carol L , Vogel Heiko , Wheat Christopher W
Published: March 2021

We report a chromosome-level assembly for Pieris macdunnoughii, a North American butterfly whose involvement in an evolutionary trap imposed by an invasive Eurasian mustard has made it an emerging model system for studying maladaptation in plant–insect interactions. Assembled using nearly 100× coverage of Oxford Nanopore long reads, the contig-level assembly comprised 106 contigs totaling 316,549,294 bases, with an N50 of 5.2 Mb. We polished the assembly with PoolSeq Illumina short-read data, demonstrating for the first time the comparable performance of individual and pooled short reads as polishing data sets. Extensive synteny between the reported contig-level assembly and a published, chromosome-level assembly of the European butterfly Pieris napi allowed us to generate a pseudochromosomal assembly of 47 contigs, placing 91.1% of our 317 Mb genome into a chromosomal framework. Additionally, we found support for a Z chromosome arrangement in P. napi, showing that the fusion event leading to this rearrangement predates the split between European and North American lineages of Pieris butterflies. This genome assembly and its functional annotation lay the groundwork for future research into the genetic basis of adaptive and maladaptive egg-laying behavior by P. macdunnoughii, contributing to our understanding of the susceptibility and responses of insects to evolutionary traps.
Antioxidants Associated With Oncogenic Human Papillomavirus Infection in Women
Authors: Lin Hui-Yi , Fu Qiufan , Kao Yu-Hsiang , Tseng Tung-sung , Reiss Krzysztof , Cameron Jennifer E , Ronis Martin J , Su Joseph , Nair Navya , Chang Hsiao-Man , Hagensee Michael E
Published: March 2021

Background

Human papillomavirus (HPV) infection is a major cause of cervical cancer. Studies showed the onset of HPV carcinogenesis may be induced by oxidative stress affecting the host immune system. The association between antioxidants and oncogenic HPV remains unclear. In this study, we aim to identify antioxidants associated with vaginal HPV infection in women.

Methods

The associations between the 15 antioxidants and vaginal HPV infection status (no, low-risk [LR], and high-risk [HR] HPV) were evaluated using 11 070 women who participated in the 2003–2016 National Health and Nutrition Examination Survey (NHANES).

Results

We identified serum albumin and 4 dietary antioxidants (vitamin A, B2, E, and folate) inversely associated with HR-HPV infection. Women with a low level of albumin (≤39 g/L) have a significantly higher risk of HR-HPV (odds ratio [OR] = 1.4, P = .009 vs >44 g/L). A Nutritional Antioxidant Score (NAS) was developed based on these 4 dietary antioxidants. The women with the lowest quartile NAS had a higher chance of HR-HPV (OR = 1.3, P = .030) and LR-HPV (OR = 1.4, P = .002) compared with the women with the highest quartile NAS.

Conclusions

We identified 5 antioxidants negatively associated with vaginal HR-HPV infection in women. Our findings provide valuable insights into understanding antioxidants’ impact on HPV carcinogenesis.
Content of antenatal care and perception about services provided by primary hospitals in Nepal: a convergent mixed methods study
Authors: Acharya Yubraj , James Nigel , Thapa Rita , Naz Saman , Shrestha Rishav , Tamang Suresh
Published: March 2021

Background

Nepal has made significant strides in maternal and neonatal mortality over the last three decades. However, poor quality of care can threaten the gains, as maternal and newborn services are particularly sensitive to quality of care. Our study aimed to understand current gaps in the process and the outcome dimensions of the quality of antenatal care (ANC), particularly at the sub-national level. We assessed these dimensions of the quality of ANC in 17 primary, public hospitals across Nepal. We also assessed the variation in the ANC process across the patients’ socio-economic gradient.

Methods

We used a convergent mixed methods approach, whereby we triangulated qualitative and quantitative data. In the quantitative component, we observed interactions between providers (17 hospitals from all 7 provinces) and 198 women seeking ANC and recorded the tasks the providers performed, using the Service Provision Assessments protocol available from the Demographic and Health Survey program. The main outcome variable was the number of tasks performed by the provider during an ANC consultation. The tasks ranged from identifying potential signs of danger to providing counseling. We analyzed the resulting data descriptively and assessed the relationship between the number of tasks performed and users’ characteristics. In the qualitative component, we synthesized users’ and providers’ narratives on perceptions of the overall quality of care obtained through focus group discussions and in-depth interviews.

Results

Out of the 59 tasks recommended by the World Health Organization, providers performed only 22 tasks (37.3%) on average. The number of tasks performed varied significantly across provinces, with users in province 3 receiving significantly higher quality care than those in other provinces. Educated women were treated better than those with no education. Users and providers agreed that the overall quality of care was inadequate, although providers mentioned that the current quality was the best they could provide given the constraints they faced.

Conclusion

The quality of ANC in Nepal’s primary hospitals is poor and inequitable across education and geographic gradients. While current efforts, such as the provision of 24/7 birthing centers, can mitigate gaps in service availability, additional equipment, infrastructure and human resources will be needed to improve quality. Providers also need additional training focused on treating patients from different backgrounds equally. Our study also points to the need for additional research, both to document the quality of care more objectively and to establish key determinants of quality to inform policy.
Extragalactic H i 21-cm absorption line observations with the Five-hundred-meter Aperture Spherical radio Telescope
Authors: Zhang Bo , Zhu Ming , Wu Zhong-Zu , Yu Qing-Zheng , Jiang Peng , Yue You-Ling , Huang Meng-Lin , Hao Qiao-Li
Published: March 2021

We present a pilot study of extragalactic H i 21-cm absorption lines using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). We observed five continuum sources with H i absorption features first identified in the 40 per cent data release of the Arecibo Legacy Fast Arecibo L-Band Feed Array (ALFA) Survey (ALFALFA), including two systems later detected by the Westerbork Synthesis Radio Telescope (WSRT). Most of our observations were carried out during the FAST commissioning phase, and we have tested different observing modes, as well as data reduction methods, to produce the best spectra. Our observations successfully confirmed the existence of H i absorption lines in all these systems, including two sources that were marginally detected by ALFALFA. We fitted the H i profiles with single or double of Gaussian functions, and calculated the H i column densities of each source. The H i absorption profiles obtained by FAST show much higher spectral resolution and higher SNR ratio than the existing data in the literature, thus demonstrating the power of FAST in revealing detailed structures of H i absorption lines. Our pilot observations and tests have enabled us to develop a strategy to search for H i absorption sources using the data from the FAST extragalactic H i survey, which is one of the key projects undertaken at FAST. We expect that over 1500 extragalactic H i absorbing systems could be detected with survey data, based on sensitivity level that we achieved in pilot observations.
Application of a new X-ray reflection model to V1223 Sagittarii
Authors: Hayashi Takayuki , Kitaguchi Takao , Ishida Manabu
Published: March 2021

In intermediate polars (IPs), the intrinsic thermal emissions from white dwarfs (WDs) have typically been studied. Few reports have analysed X-ray reflections from WDs. We recently developed an elaborate IP-reflection spectral model. Herein, we report the first application of a reflection model with an IP thermal model to the spectra of the brightest typical IP V1223 Sagittarii observed by the Suzaku and Nuclear Spectroscopic Telescope Array satellites. The model reasonably reproduces the spectra within the range of 5–78 keV and estimates the WD mass as 0.92 ± 0.02 M⊙. The WD mass estimated by the proposed model is consistent with that measured using an active galactic nucleus reflection model and a partial covering absorption model. However, the choice of incorrect parameter values, such as an unsuitable fitting energy band and an incorrect metal abundance, was found to introduce systematic errors (e.g. ≲0.2 M⊙ in the WD mass) in the WD mass measurement. Our spin-phase-resolved analysis resulted in discoveries regarding the modulations of the equivalent width of the fluorescent iron K α line and the angle between the post-shock accretion column and the line of sight (viewing angle). The viewing angle anticorrelates approximately with the X-ray flux and has average and semi-amplitude values of 55° and 7°, respectively, which points towards two WD spin axis angles from the line of sight of 55° and 7°, respectively. Both estimated spin axis angles are different from the reported system inclination of 24°.
Local government competition and regional innovation efficiency: From the perspective of China-style fiscal federalism
Authors: Zhao Chen , Feng Feng , Chen Yuee , Li Xingteng
Published: March 2021

Through data envelope analysis, this article finds that the innovation efficiency of China’s three regions is shrinking. From the perspective of Chinese fiscal federalism, we try to study the influence of two forms of local government competition (vertical competition and horizontal competition) on regional innovation efficiency. We find that both fiscal decentralization and competition among local governments effectively promote regional innovation efficiency, while there is no effective interaction mechanism between them. The attitude of local governments toward scientific and technological (S&T) activities also directly affects the efficiency of regional innovation. From the top of policy design, in order to establish a national innovation system and improve innovation efficiency, appropriate fiscal autonomy should be granted to local governments. Suggestions include that local governments should strengthen S&T activities and cooperate with each other, which is an important S&T policy guidance for central government in the future.
Multisystem Inflammatory Syndrome in a Child with Scrub Typhus and Macrophage Activation Syndrome
Authors: Gupta Aman , Gill Arpinder
Published: March 2021

Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C) and macrophage activation syndrome (MAS) have been speculated as three distinct phenotypes of hyperinflammation seen in children during coronavirus disease (COVID-19) pandemic. KD has been reported in association with dengue, scrub typhus and leptospirosis. COVID-19 and dengue coinfection has also been described. However, MIS-C with concomitant infection has rarely been reported. We report an adolescent girl with clinical and laboratory parameters of MIS-C resembling KD with positive serology for scrub typhus at presentation. Clinical manifestations resolved and laboratory parameters improved with IVIG, azithromycin and corticosteroids. However, she developed fever recurrence with thrombocytopenia, elevated inflammatory markers, hypofibrinogenemia and hypertriglyceridemia which were consistent with MAS. With the emergence of MIS-C and increase in the number of such cases being reported throughout world, physicians should be aware of different phenotypes of hyperinflammation associated with COVID-19 and the possibility of coexistence of MIS-C with other infections.

LAY SUMMARY

Clinical and laboratory parameters of multisystem inflammatory syndrome in children (MIS-C) mimic Kawasaki disease (KD). KD has been described in association with dengue, scrub typhus and leptospirosis. However, MIS-C with concomitant infection has rarely been reported in literature. A 14-year-old-girl presented with fever and rash with history of redness of eyes, lips and tongue. Investigations showed anemia, lymphopenia, thrombocytosis with elevated erythrocyte sedimentation rate, C-reactive protein, pro-brain natriuretic peptide, Interleukin-6, ferritin and d-dimer. Scrub typhus immunoglobulin M was positive. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) level was also elevated. A diagnosis of MIS-C with concomitant scrub typhus was proffered. Child received azithromycin, intravenous immunoglobulin and methylprednisolone. After an afebrile period of 2.5 days, child developed unremitting fever and rash. Repeat investigations showed anemia, worsening lymphopenia, thrombocytopenia, transaminitis, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia which were consistent with a diagnosis of macrophage activation syndrome (MAS). KD, MIS-C and MAS represent three distinct phenotypes of hyperinflammation seen in children during coronavirus disease pandemic. Several tropical infections may mimic or coexist with MIS-C which can be a diagnostic challenge for the treating physician. Identification of coexistence or differentiation between the two conditions is important in countries with high incidence of tropical infections to guide appropriate investigations and treatment.
The First Genomic Resources for Phymatotrichopsis omnivora, a Soilborne Pezizomycete Pathogen with a Broad Host Range
Authors: Mattupalli Chakradhar , Shiller Jason B. , Kankanala Prasanna , Krom Nick , Marek Stephen M. , Mysore Kirankumar S. , Young Carolyn A.
Published: March 2021

Phymatotrichopsis omnivora is a destructive plant pathogen causing root rot disease of alfalfa, cotton, pecan, grape, and many other important dicotyledonous species. A member of the family Rhizinaceae, in the class Pezizomycetes, P. omnivora is a soilborne ascomycete fungus that is difficult to maintain in culture, currently genetically intractable, and for which there are no publicly available genomic resources. We have generated draft genome sequences of four P. omnivora isolates obtained from cotton and alfalfa, growing in Texas and Oklahoma. These genome sequences will provide new insights into the biology of the fungus, including the factors responsible for its broad host range and pathogenicity.
Variation in UV-Mediated Damage Recovery Among Pseudoidium neolycopersici Isolates: Possible Mechanisms
Authors: Pathak Ranjana , Suthaparan Aruppillai
Published: March 2021

The cryptochrome/photolyase family (CPF) consists of a diversified class of flavoproteins that are evolutionarily related. Although their domain architecture is highly conserved, they perform entirely different physiological functions. Previous studies have confirmed the presence of a functional photolyase in Pseudoidium neolycopersici, which repairs UV-C-induced DNA damage by using near UV-A/blue light as an energy source. Similar doses of UV-C treatment followed by incubation with dark or blue light was tested on conidia germination of five isolates of P. neolycopersici collected from different regions of Norway and the Netherlands. The results showed variations in the effect of UV on germination and germination recovery under blue light incubation after UV treatment. Evolutionary studies confirmed that P. neolycopersici photolyase is highly conserved among different isolates of P. neolycopersici and among different species. All CPF members have a core domain consisting of an identical cofactor, flavin adenine dinucleotide (FAD), and an additional photoantenna chromophore. An amino acid sequence analysis demonstrated that CPF members have highly conserved C terminals compared with their N terminals, because FAD binds in the C-terminal region. When compared with other CPF members, varying lengths of N and C terminals were noticed in P. neolycopersici photolyase and putative cryptochrome, respectively. Further research using comparative genomics targeting pyrimidine base composition, the role of regulatory elements, including promotor architecture, and the characterization of optical properties of native photolyase among isolates may help to explain the differences in the biological responses of conidia germination of P. neolycopersici treated with UV.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Organoids as a new model system to study neural tube defects
Authors: Wu Yu , Peng Sisi , Finnell Richard H. , Zheng Yufang
Published: March 2021

The neural tube is the first critically important structure that develops in the embryo. It serves as the primordium of the central nervous system; therefore, the proper formation of the neural tube is essential to the developing organism. Neural tube defects (NTDs) are severe congenital defects caused by failed neural tube closure during early embryogenesis. The pathogenesis of NTDs is complicated and still not fully understood even after decades of research. While it is an ethically impossible proposition to investigate the in vivo formation process of the neural tube in human embryos, a newly developed technology involving the creation of neural tube organoids serves as an excellent model system with which to study human neural tube formation and the occurrence of NTDs. Herein we reviewed the recent literature on the process of neural tube formation, the progress of NTDs investigations, and particularly the exciting potential to use neural tube organoids to model the cellular and molecular mechanisms underlying the etiology of NTDs.
Thromboelastography Parameters and Platelet Count on Admission to the ICU and the Development of Venous Thromboembolism in Patients With Coronavirus Disease 2019
Authors: Marvi Tanya K. , Stubblefield William B. , Tillman Benjamin F. , Tenforde Mark W. , Feldstein Leora R. , Patel Manish M. , Self Wesley H. , Grijalva Carlos G. , Rice Todd W.
Published: March 2021

Objectives:

Determine if thromboelastography parameters and platelet count on the day of ICU admission are associated with the development of venous thromboembolism in patients with coronavirus disease 2019.

Design:

Prospective, observational cohort study.

Setting:

Tertiary-care, academic medical center in Nashville, TN.

Patients:

Patients with coronavirus disease 2019 pneumonia and acute respiratory failure admitted to the adult ICU without venous thromboembolism at the time of ICU admission.

Intervention:

None.

Measurements and Main Results:

The primary outcome was development of venous thromboembolism during the index hospitalization. Venous thromboembolism was defined by clinical imaging or autopsy, demonstrating deep vein thrombosis or pulmonary embolism. Forty consecutive critically ill adults with laboratory-confirmed coronavirus disease 2019 were enrolled; 37 (92.5%) were hypercoagulable by at least one thromboelastography parameter at the time of ICU admission and 12 (30%) met the primary outcome of venous thromboembolism during the index hospitalization. Patients who developed venous thromboembolism had decreased measures of clotting (maximum amplitude, alpha angle, shear elastic modulus parameter, and clotting index) on ICU admission thromboelastography compared with patients who did not develop venous thromboembolism (p < 0.05 for all measures). For each individual thromboelastography parameter used to dichotomize patients as hypercoagulable, the rate of venous thromboembolism was not higher in those identified as hypercoagulable; in fact, the venous thromboembolism rate was higher in patients who were not hypercoagulable by thromboelastography for maximum amplitude (p = 0.04) and alpha angle (p = 0.001). Platelet count was positively correlated with maximum amplitude, alpha angle, G parameter, and clotting index, and significantly lower in patients who developed venous thromboembolism than those who did not (median 186 vs 278 103/μL, p = 0.046). Venous thromboembolism was associated with inhospital mortality (odds ratio, 6.3; 95% CI, 1.4–29; p = 0.02).

Conclusions:

Our data do not support the use of thromboelastography to risk stratify critically ill adults with coronavirus disease 2019 for the development of venous thromboembolism or to guide decisions about anticoagulation. Lower platelet count on ICU admission, which may reflect platelet aggregation, was associated with venous thromboembolism.
Opening of BKCa channels causes migraine attacks: a new downstream target for the treatment of migraine
Authors: Al-Karagholi Mohammad Al-Mahdi , Ghanizada Hashmat , Waldorff Nielsen Cherie Amalie , Skandarioon Camilla , Snellman Josefin , Lopez-Lopez Cristina , Hansen Jakob Møller , Ashina Messoud
Published: March 2021

Migraine is a common and frequently disabling neurological disorder, but the initiating migraine mechanisms are still poorly understood. Potassium channel opening may cause migraine, and we therefore examined the migraine-inducing effect of MaxiPost, a large (big)-conductance calcium-activated potassium (BKCa) channel opener, on migraine induction and cephalic vasodilation in individuals with migraine. Twenty-six patients with migraine without aura were randomly allocated to receive an infusion of MaxiPost or placebo on 2 study days separated by at least 1 week. The primary endpoint was the difference in incidence of migraine attacks after MaxiPost compared with placebo. The secondary endpoints were the difference in incidence of headaches and the difference in area under the curve for headache intensity scores (0-12 hours), for middle cerebral artery blood flow velocity (VMCA) (0-2 hours), and for superficial temporal artery and radial artery diameter. Twenty-two patients completed the study. Twenty-one of 22 (95%) developed migraine attacks after MaxiPost compared with none after placebo (P< 0.0001); the difference of incidence is 95% (95% confidence interval 86%-100%). The incidence of headache over the 12-hour observation period was higher after MaxiPost day (n = 22) than after placebo (n = 7) (P< 0.0001). We found a significant increase of VMCAand superficial temporal and radial arteries' diameter. Because BKCachannel opening initiates migraine attacks, we suggest that BKCachannel blockers could be potential candidates for novel antimigraine drugs.
A thermal nociceptive patch in the S2 cortex of nonhuman primates: a combined functional magnetic resonance imaging and electrophysiology study
Authors: Ye Xiang , Yang Pai-Feng , Liu Qing , Dillenburger Barbara D. , Friedman Robert M. , Chen Li Min
Published: March 2021

Human functional magnetic resonance imaging (fMRI) and behavioral studies have established the roles of cortical areas along the Sylvian fissure in sensing subjective pain. Yet, little is known about how sensory aspects of painful information are represented and processed by neurons in these regions and how their electrophysiological activities are related to fMRI signals. The current study aims to partially address this critical knowledge gap by performing fMRI-guided microelectrode mapping and recording studies in the homologous region of the parietal operculum in squirrel monkeys under light anesthesia. In each animal studied (n = 8), we detected mesoscale mini-networks for heat nociception in cortical regions around the lateral sulcus. Within the network, we discovered a ∼1.5 × 1.5-mm2-sized cortical patch that solely contained heat nociceptive neurons that aligned with the heat fMRI activation locus. These neurons responded slowly to thermal (heat and cold) nociceptive stimuli exclusively, continued firing for several seconds after the succession of stimulation, and exhibited multidigit receptive fields and high spontaneous firing rates. Similar to the fMRI responses, increasing temperatures in the nociceptive range led to a nonlinear increase in firing rates. The finding of a clustering of heat nociceptive neurons provides novel insights into the unique functional organization of thermal nociception in the S2 subregion of the primate brain. With fMRI, it supports the existence of a modality-preferred heat nociceptive patch that is spatially separated and intermingled with touch patches containing neurons with comparable receptive fields and the presence of functionally distinct mini-networks in primate opercular cortex.
Addressing Health Equity and Social Determinants of Health Through Healthy People 2030
Authors: Gómez Cynthia A. , Kleinman Dushanka V. , Pronk Nico , Wrenn Gordon Glenda L. , Ochiai Emmeline , Blakey Carter , Johnson Ayanna , Brewer Karen H.
Published: March 2021

The evolution of Healthy People reflects growing awareness of health inequities over the life course. Each decade, the initiative has gained understanding of how the nation can achieve health and well-being. To inform Healthy People 2030's visionary goal of achieving health equity in the coming decade, the Secretary's Advisory Committee on National Health Promotion and Disease Prevention Objectives for 2030 (Secretary's Advisory Committee) provided the US Department of Health and Human Services with guidance on key terms, frameworks, and measurement for health equity. Conditions in the environments in which people are born, live, learn, work, play, worship, and age influence health and well-being outcomes, functioning, and quality-of-life outcomes and risks and are mostly responsible for health inequities. No single individual, organization, community, or sector has sole ownership, accountability, or capacity to sustain the health and well-being of an entire population. The COVID-19 pandemic in the United States highlights underlying inequities and disparities in health and health care across segments of the population. Contributing factors that were known prior to the pandemic have led to major discrepancies in rates of infection and death. To reduce health disparities and advance health equity, systems approaches—designed to shift interconnected aspects of public health problems—are needed.
Improving Throughput for Mid-acuity Patients in the Pediatric Emergency Department
Authors: Payne Asha S. , Brown Kathleen M. , Berkowitz Deena , Pettinichi Jeanne , Schultz Theresa Ryan , Thomas Anthony , Chamberlain James M. , Morrison Sephora N.
Published: March 2021

Purpose:

Visits to pediatric emergency departments (EDs) are increasing, leading to overcrowding, prolonged patient wait times, and negative patient experiences. In our system, these prolonged wait times and negative experiences notably impact mid-acuity patients. As such, we sought to decrease their time-to-first-provider from 92 to 60 minutes.

Methods:

After identifying inefficiencies in patient arrival, triage, and assessment, we redesigned our physical space and implemented a new triage process. Further, we deployed a new multidisciplinary front-end team consisting of a physician, nurses, and ED tech specialists to create and implement an initial management plan. Time-to-first-provider for mid-acuity patients was the main outcome measure. We examined ED length of stay (LOS) as a balancing measure. Post hoc, we measured time-to-first-nursing assessment and the proportion of high-acuity patients seen within 20 minutes as additional measures of the impact of these interventions on our system. All analyses were measured using statistical process control charts.

Results:

During high patient volumes, we decreased the time-to-first-provider to 70 minutes, but exceeded our goal during low patient volumes (41 minutes). We observed a 5% decrease in LOS during both high and low patient volumes (5% and 8%, respectively). There was a 60% increase in the time-to-first-nursing assessment.

Conclusions:

A new front-end process resulted in improved time-to-first-provider and LOS. The new process was associated with longer times for nursing assessments but did not negatively impact the rapid physician assessment of higher acuity patients.
Effects of hypoxia on the thermal physiology of a high-elevation lizard: implications for upslope-shifting species
Authors: Jiang Zhong-Wen , Ma Liang , Mi Chun-Rong , Du Wei-Guo
Published: March 2021

Montane reptiles are predicted to move to higher elevations in response to climate warming. However, whether upwards-shifting reptiles will be physiologically constrained by hypoxia at higher elevations remains unknown. We investigated the effects of hypoxic conditions on preferred body temperatures (T
pref
) and thermal tolerance capacity of a montane lizard (
Phrynocephalus vlangalii
) from two populations on the Qinghai–Tibet Plateau. Lizards from 2600 m a.s.l. were exposed to O
2
levels mimicking those at 2600 m (control) and 3600 m (hypoxia treatment). Lizards from 3600 m a.s.l. were exposed to O
2
levels mimicking those at 3600 m (control) and 4600 m (hypoxia treatment). The T
pref
did not differ between the control and hypoxia treatments in lizards from 2600 m. However, lizards from 3600 m selected lower body temperatures when exposed to the hypoxia treatment mimicking the O
2
level at 4600 m. Additionally, the hypoxia treatment induced lower critical thermal minimum (CT
min
) in lizards from both populations, but did not affect the critical thermal maximum (CT
max
) in either population. Our results imply that upwards-shifting reptiles may be constrained by hypoxia if a decrease in T
pref
reduces thermally dependent fitness traits, despite no observed effect on their heat tolerance.
Integrating social and cognitive aspects of belief dynamics: towards a unifying framework
Authors: Galesic Mirta , Olsson Henrik , Dalege Jonas , van der Does Tamara , Stein Daniel L.
Published: March 2021

Belief change and spread have been studied in many disciplines—from psychology, sociology, economics and philosophy, to biology, computer science and statistical physics—but we still do not have a firm grasp on why some beliefs change more easily and spread faster than others. To fully capture the complex social-cognitive system that gives rise to belief dynamics, we first review insights about structural components and processes of belief dynamics studied within different disciplines. We then outline a unifying quantitative framework that enables theoretical and empirical comparisons of different belief dynamic models. This framework uses a statistical physics formalism, grounded in cognitive and social theory, as well as empirical observations. We show how this framework can be used to integrate extant knowledge and develop a more comprehensive understanding of belief dynamics.