bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formalizing falsification for theories of consciousness across computational hierarchies
Authors: Hanson Jake R , Walker Sara I 
Published: August 2021

AbstractThe scientific study of consciousness is currently undergoing a critical transition in the form of a rapidly evolving scientific debate regarding whether or not currently proposed theories can be assessed for their scientific validity. At the forefront of this debate is Integrated Information Theory (IIT), widely regarded as the preeminent theory of consciousness because it quantified subjective experience in a scalar mathematical measure called Φ that is in principle measurable. Epistemological issues in the form of the “unfolding argument” have provided a concrete refutation of IIT by demonstrating how it permits functionally identical systems to have differences in their predicted consciousness. The implication is that IIT and any other proposed theory based on a physical system’s causal structure may already be falsified even in the absence of experimental refutation. However, so far many of these arguments surrounding the epistemological foundations of falsification arguments, such as the unfolding argument, are too abstract to determine the full scope of their implications. Here, we make these abstract arguments concrete, by providing a simple example of functionally equivalent machines realizable with table-top electronics that take the form of isomorphic digital circuits with and without feedback. This allows us to explicitly demonstrate the different levels of abstraction at which a theory of consciousness can be assessed. Within this computational hierarchy, we show how IIT is simultaneously falsified at the finite-state automaton level and unfalsifiable at the combinatorial-state automaton level. We use this example to illustrate a more general set of falsification criteria for theories of consciousness: to avoid being already falsified, or conversely unfalsifiable, scientific theories of consciousness must be invariant with respect to changes that leave the inference procedure fixed at a particular level in a computational hierarchy.
RBP differentiation contributes to selective transmissibility of OPT3 mRNAs
Authors: Lv Xinmin , Sun Yaqiang , Hao Pengbo , Zhang Cankui , Tian Ji , Fu Mengmeng , Xu Zhen , Wang Yi , Zhang Xinzhong , Xu Xuefeng , Wu Ting , Han Zhenhai 
Published: August 2021

Abstract
Long-distance mobile mRNAs play key roles in gene regulatory networks that control plant development and stress tolerance. However, the mechanisms underlying species-specific delivery of mRNA still need to be elucidated. Here, the use of grafts involving highly heterozygous apple (Malus) genotypes allowed us to demonstrate that apple (Malus domestica) oligopeptide transporter3 (MdOPT3) mRNA can be transported over a long distance, from the leaf to the root, to regulate iron uptake; however, the mRNA of Arabidopsis (Arabidopsis thaliana) oligopeptide transporter 3 (AtOPT3), the MdOPT3 homolog from A. thaliana, does not move from shoot to root. Reciprocal heterologous expression of the two types of mRNAs showed that the immobile AtOPT3 became mobile and moved from the shoot to the root in two woody species, Malus and Populus, while the mobile MdOPT3 became immobile in two herbaceous species, A. thaliana and tomato (Solanum lycopersicum). Furthermore, we demonstrated that the different transmissibility of OPT3 in A. thaliana and Malus might be caused by divergence in RNA-binding proteins between herbaceous and woody plants. This study provides insights into mechanisms underlying differences in mRNA mobility and validates the important physiological functions associated with this process.
CRISPR/Cas9 mutants of tomato MICRORNA164 genes uncover their functional specialization in development
Authors: Gupta Suresh Kumar , Vishwakarma Abhaypratap , Kenea Hawi Deressa , Galsurker Ortal , Cohen Hagai , Aharoni Asaph , Arazi Tzahi 
Published: August 2021

Abstract
Plant MICRORNA164 (miR164) plays diverse regulatory functions by post-transcriptional repression of certain NAM/ATAF/CUC-domain transcription factors. However, the involvement of miR164 in fleshy fruit development and ripening remains poorly understood. Here, de novo prediction of tomato (Solanum lycopersicum) MIR164 genes identified four genes (SlMIR164a-d), of which SlMIR164d has an atypically long pre-miRNA. The roles of the fruit expressed SlMIR164a, b, and d were studied by analysis of their Clustered Regularly Interspaced Short Palindromic Repeats mutants. The slmir164bCR mutant plants exhibited shoot and flower abnormalities characteristic of ectopic boundary specification, whereas the shoot and flower development of slmir164aCR and slmir164dCR mutants were indistinguishable from wild-type. Strikingly, the knockout of SlMIR164a practically eliminated sly-miR164 from the developing and ripening fruit pericarp. The sly-miR164-deficient slmir164aCR fruits were smaller than the wild-type, due to reduced pericarp cell division and expansion, and displayed intense red color and matte, instead of glossy appearance, upon ripening. We found that the fruit skin phenotypes were associated with morphologically abnormal outer epidermis and thicker cuticle. Quantitation of sly-miR164 target transcripts in slmir164aCR ripening fruits demonstrated the upregulation of SlNAM3 and SlNAM2. Specific expression of their miR164-resistant versions in the pericarp resulted in the formation of extremely small fruits with abnormal epidermis, highlighting the importance of their negative regulation by sly-miR164a. Taken together, our results demonstrate that SlMIR164a and SlMIR164b play specialized roles in development: SlMIR164b is required for shoot and flower boundary specification, and SlMIR164a is required for fruit growth including the expansion of its outer epidermis, which determines the properties of the fruit skin.
Enzyme engineering and in vivo testing of a formate reduction pathway
Authors: Wang Jue , Anderson Karl , Yang Ellen , He Lian , Lidstrom Mary E 
Published: August 2021

Abstract
Formate is an attractive feedstock for sustainable microbial production of fuels and chemicals, but its potential is limited by the lack of efficient assimilation pathways. The reduction of formate to formaldehyde would allow efficient downstream assimilation, but no efficient enzymes are known for this transformation. To develop a 2-step formate reduction pathway, we screened natural variants of acyl-CoA synthetase (ACS) and acylating aldehyde dehydrogenase (ACDH) for activity on one-carbon substrates and identified active and highly expressed homologs of both enzymes. We then performed directed evolution, increasing ACDH-specific activity by 2.5-fold and ACS lysate activity by 5-fold. To test for the in vivo activity of our pathway, we expressed it in a methylotroph which can natively assimilate formaldehyde. Although the enzymes were active in cell extracts, we could not detect formate assimilation into biomass, indicating that further improvement will be required for formatotrophy. Our work provides a foundation for further development of a versatile pathway for formate assimilation.
The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein
Authors: Resende Paola Cristina , Naveca Felipe G , Lins Roberto D , Dezordi Filipe Zimmer , Ferraz Matheus V. F , Moreira Emerson G , Coêlho Danilo F , Motta Fernando Couto , Paixão Anna Carolina Dias , Appolinario Luciana , Lopes Renata Serrano , Mendonça Ana Carolina da Fonseca , da Rocha Alice Sampaio Barreto , Nascimento Valdinete , Souza Victor , Silva George , Nascimento Fernanda , Neto Lidio Gonçalves Lima , da Silva Fabiano Vieira , Riediger Irina , Debur Maria do Carmo , Leite Anderson Brandao , Mattos Tirza , da Costa Cristiano Fernandes , Pereira Felicidade Mota , dos Santos Cliomar Alves , Rovaris Darcita Buerger , Fernandes Sandra Bianchini , Abbud Adriano , Sacchi Claudio , Khouri Ricardo , Bernardes André Felipe Leal , Delatorre Edson , Gräf Tiago , Siqueira Marilda Mendonça , Bello Gonzalo , Wallau Gabriel L 
Published: August 2021

Abstract
Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141–144, ∆211, and ∆256–258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.
Relationship Between Umbilical Cord Gas Values and Neonatal Outcomes
Authors: Johnson Grace J. , Salmanian Bahram , Denning Stacie G. , Belfort Michael A. , Sundgren Nathan C. , Clark Steven L. 
Published: August 2021

OBJECTIVE:
To evaluate the relationship between umbilical artery cord gas values and fetal tolerance of labor, as reflected by Apgar score. We hypothesized the existence of wide biological variability in fetal tolerance of metabolic acidemia, which, if present, would weaken one fundamental assumption underlying the use of electronic fetal heart rate (FHR) monitoring.

METHODS:
We conducted a retrospective cohort study of term, singleton, nonanomalous fetuses delivered in our institution between March 2012 and July 2020. Universally obtained umbilical cord gas values and Apgar scores were extracted. We calculated Spearman correlation coefficients and receiver operating characteristic curves for various levels of umbilical artery pH, base excess, and Apgar scores.

RESULTS:
We analyzed data from 29,787 deliveries. The statistical correlation between umbilical artery pH and base excess and both 1- and 5-minute Apgar scores was weak or nonexistent in all pH range subgroups (range 0.064–0.213). Receiver operating characteristic curve analysis suggested umbilical artery pH value of 7.22 yields the best discrimination for prediction of a severely depressed newborn (5-minute Apgar score less than 4), but sensitivity and specificity for this predictive value remains poor to moderate.

CONCLUSION:
The use of electronic FHR monitoring is predicated on a documented relationship between FHR patterns and umbilical artery pH, and an assumed correlation between pH and fetal outcomes, reflecting fetal tolerance of labor and delivery. Our data demonstrate a weak-to-absent correlation between metabolic acidemia and even short-term fetal condition, thus significantly weakening this latter assumption. No amount of future modification of FHR pattern interpretation to better predict newborn pH is likely to lead to improved newborn outcomes, given this weakness in a fundamental assumption on which FHR monitoring is based.
Patient Experiences of Telemedicine in Spine Care
Authors: Lightsey Harry M. , Yeung Caleb M. , Bernstein David N. , Sumathipala Marissa G. , Chen Antonia F. , Schoenfeld Andrew J. , Makhni Melvin C. 
Published: August 2021

Study Design.
Survey-based study.

Objective.
We performed a mixed methods study involving patients using telemedicine for spine care. We sought to understand factors influencing the utilization and evaluation of this modality.

Summary of Background Data.
Telemedicine has been integrated into routine spine care; its long-term viability will depend not only on optimizing its safety, efficiency, and cost-effectiveness, but also on understanding patient valuation of its benefits and limitations.

Methods.
We used a clinical registry to identify spine patients seen virtually by providers at our tertiary academic medical center between March and September of 2020. We distributed an online survey that queried patients’ experiences with telemedicine. We performed statistical analyses of Likert-scale questions and a thematic analysis of free-form responses. Sociodemographic data were abstracted and analyzed.

Results.
Overall, we evaluated 139 patient surveys. High levels of patient-rated care and patient-rated experience were observed for both in-person and telemedicine visits; however, in-person visits were rated significantly higher in both respects (9.3/10 vs. 8.7/10 for patient-rated care, P < 0.001; 9.0/10 vs. 8.4/10 for patient-rated experience, P = 0.006). A preference for in-person first-time visits was observed which was not maintained for follow up appointments. Both patient and clinical factors influenced perceptions of telemedicine. Thematic analysis of free-form responses provided by 113 patients (81%) generated favorable, unfavorable, and reflective themes, each further contextualized by subthemes. Responders were not significantly different from nonresponders across sociodemographic characteristics.

Conclusion.
Our quantitative and qualitative findings yield insight into the patient experience of telemedicine in spine care. A preference for in-person visits was notable, particularly for new patient evaluations. This preference was not maintained for follow-up care. Patients acknowledged the benefits of telemedicine and reflected on its effective integration with in-person care. These results may guide best practices to improve access and patient satisfaction in the future.

Level of Evidence: 4
HBsAg Loss Due to Tenofovir Treatment for HBV Reactivation Following DAAs Therapy in One Patient with HBV-HCV Coinfection
Authors: He Dan-Dan , Li Wei-Zhe , Huang Shuo , Zhang Li-Ping , Li Jing-Jing , Zeng Zhao-Hai , Yu Zu-Jiang , Zeng Qing-Lei 
Published: August 2021

Abstract
Hepatitis B virus (HBV) reactivation induced by administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported in previous studies, the subsequent clinical outcomes varied from no symptom to liver failure or death, however, the timing of anti-HBV treatment is controversial. We report the clinical HBV reactivation in a 51 years old female fibrotic patient with chronic HBV-HCV infection during the paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) therapy. Her baseline HCV RNA, HBV DNA, alanine aminotransferase (ALT), and liver stiffness measurement levels were 5,560,000 IU/mL, <15 IU/mL, 48 U/L, and 11.8 kPa, respectively. At 8 weeks of PrOD treatment, her HCV RNA, HBV DNA, and ALT levels were <15 IU/mL, 2,880,000 IU/mL, and 837 U/L, respectively, and clinical reactivation was diagnosed. Meanwhile, tenofovir was immediately used for anti-HBV treatment. Fortunately, HBV DNA and ALT were undetectable and normalized after 16 weeks of anti-HBV therapy, and unexpectedly, hepatitis B surface antigen loss occurred at 80 weeks of anti-HBV treatment. This study may extend our understanding of the timing of anti-HBV therapy to prevent potential HBV reactivation during DAAs treatment in HBV-HCV coinfected patients, and proper initiation timing may lead to functional cure of chronic HBV infection.
Hepatic Steatosis in Infancy: The Beginning of Pediatric Nonalcoholic Fatty Liver Disease?
Authors: McNelis Kera , Yodoshi Toshifumi , Divanovic Senad , Gandhi Chandrashekhar , Kim Jae H. , Anton Christopher G. , Trout Andrew T. , Mouzaki Marialena 
Published: August 2021

Objectives:
Nonalcoholic fatty liver disease is clinically silent and the age of its onset is unknown. Fatty liver can occur as early as in utero in the context of an unfavorable maternal metabolic environment. Our objective was to determine the prevalence of hepatic steatosis in a cohort of previously healthy infants less than 3 months of age.

Methods:
Retrospective study of all abdominal computed tomography (CT) scans performed from 2009 to 2019 for the investigation of trauma. Two independent reviewers applied published criteria to determine the presence of hepatic steatosis. Descriptive statistics were used. The groups with and without steatosis were compared using Wilcoxon-Mann Whitney or Fisher exact test.

Results:
Of 119 CT scans available in infants younger than 3 months of age, 65 were performed in previously healthy infants for the investigation of trauma. The included population was predominantly male, non-Hispanic, with a median age of 60 days (interquartile range, 34–73 d). Depending on the criteria used, 23% or 26% of infants had evidence of fatty liver. The prevalence of maternal obesity and/or diabetes was 11% (of the 65 pregnancies) but there was no significant difference in maternal risk factors between infants with and without evidence of steatosis.

Conclusions:
Findings suggest CT evidence of hepatic steatosis in up to a quarter of otherwise healthy infants ≤3 months of age. This may represent early manifestation of pediatric nonalcoholic fatty liver disease. The natural history and pathophysiology of this condition need to be studied to determine optimal detection, prevention and early intervention strategies.
Efficacy of an opioid-sparing analgesic protocol in pain control after less invasive cranial neurosurgery
Authors: Ahmad Shahjehan , Khanna Ryan , Onyewuenyi Alvin Chidozie , Panos Nicholas , Breslin Rory , Sani Sepehr 
Published: August 2021

Abstract

Introduction:
Opioid overuse in postoperative patients is a worrisome trend, and potential alternatives exist which warrant investigation. Nonsteroidal anti-inflammatory drug use in treating postoperative cranial surgery pain has been hampered by concern for inadequate pain control and increased risk of hemorrhagic complications. A safe and effective alternative to opioid-based pain management is critical to improving postoperative care.

Objective:
The objective of this retrospective study was to determine whether an NSAID-based opioid-sparing pain management protocol (OSP) is effective in analgesic control of less invasive cranial surgery patients at 6-, 12-, and 24-hour postoperatively. Secondary aims included investigating differences in hemorrhagic complications.

Methods:
Five hundred sixty-six consecutive patients who underwent cranial surgery before and after implementation of the celecoxib-based OSP were eligible. Propensity score matching was used to match patients in each cohort.

Results:
The opioid-sparing cohort had lower pain scores at 6 hours (3.45 vs 4.19, P = 0.036), 12 hours (3.21 vs 4.00, P = 0.006), and 24 hours (2.90 vs 3.59, P = 0.010). Rates of postoperative hemorrhage were not significantly different (5% intervention vs 8% control, P = 0.527). The opioid-sparing pain management protocol provided comparable or better pain control in the first 24 hours after less invasive cranial surgery. Hemorrhage rates did not change with the use of an NSAID-based OSP.

Conclusion:
An effective alternative to the current standard opioid-based pain management is feasible for less invasive cranial surgery. Determinations of hemorrhage risk and more complex cranial surgery will require larger prospective randomized trials.
Public attitudes towards COVID-19 vaccination in children: A qualitative study
Authors: Williams Simon N 
Published: August 2021

AbstractBackgroundCOVID-19 vaccinations in children remains controversial. In the UK, as of August 2021, they have not been approved, except in a few limited circumstances. To date, little qualitative research exists to explain the reasons and nuances behind public attitudes on this issue.MethodsQualitative group and one-to-one online interviews were conducted with a diverse sample of 24 adults to explore their views on the issue of COVID-19 vaccination in children.ResultsCOVID-19 vaccination in children was framed as a complex problem (a “minefield”). Six themes emerged to explain participants views: (1) Uncertainty over whether children can catch, transmit or be severely harmed by COVID-19; (2) Lower risk tolerance for unknown longer-term effects of the vaccine in children; (3) Association of the vaccine program with government’s handling of the pandemic; (4) Local social norms as a driver of hesitancy; (5) Vaccinating children as a way to protect vulnerable adults; (6) Children’s vaccination as parental choice.ConclusionsPublic attitudes to COVID-19 vaccination in children are likely to be met with more hesitancy compared to adult vaccinations. Public health communications will need to combat this hesitancy if vaccine uptake for children is to be pursued as a public health policy.
COVID-ONE-humoral immune: The One-stop Database for COVID-19-specific Antibody Responses and Clinical Parameters
Authors: Xu Zhaowei , Li Yang , Lei Qing , Huang Likun , Lai Dan-yun , Guo Shu-juan , Jiang He-wei , Hou Hongyan , Zheng Yun-xiao , Wang Xue-ning , Wu Jiaoxiang , Ma Ming-liang , Zhang Bo , Chen Hong , Yu Caizheng , Xue Jun-biao , Zhang Hai-nan , Qi Huan , Yu Siqi , Lin Mingxi , Zhang Yandi , Lin Xiaosong , Yao Zongjie , Sheng Huiming , Sun Ziyong , Wang Feng , Fan Xionglin , Tao Sheng-ce 
Published: August 2021

AbstractCoronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2, varies with regard to symptoms and mortality rates among populations. Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19. However, differences in immune responses and clinical features among COVID-19 patients remain largely unknown. Here, we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters (COVID-ONE humoral immune). COVID-ONE humoral immunity is based on a dataset that contains the IgG/IgM responses to 21 of 28 known SARS-CoV-2 proteins and 197 spike protein peptides against 2,360 COVID-19 samples collected from 783 patients. In addition, 96 clinical parameters for the 2,360 samples and information for the 783 patients are integrated into the database. Furthermore, COVID-ONE humoral immune provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups. A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters. After the “START” button is clicked, one can readily obtain a comprehensive analysis report for further interpretation. COVID-ONE-humoral immune is freely available at www.COVID-ONE.cn.