bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision-Making in the Era of New Medical Technologies in Pediatric Hematology-Oncology: The Death of Palliative Care?
Authors: Fortin Sylvie , Le Gall Josiane , Richer Johanne , Payot Antoine , Duval Michel
Published: January 2021

Background:

Recent advances in immunology, genomics, and cellular therapy have opened numerous therapeutic possibilities in pediatric hematology-oncology, generating new hope in poor prognosis situations. How decisions are made when it comes to treatments and aims needs to be explored in this new technologic context. In particular, their impact on the gold standard of early referral to palliative care must be assessed.

Materials and Methods:

Stemming from an ethnographic study combining semistructured interviews and observations carried out in a hematopoietic stem cell transplant unit in a Montréal Pediatric Hospital, we discuss the decision-making process when a patient faces poor prognosis.

Results and Discussion:

Although health care providers individually envisioned that palliative care may be the best course of action for patients receiving emergent therapy, they remained collectively in the curative mode. The intricate relationship between science, hope, caregiver, and care receiver sustains this perspective even when (near) death is the probable outcome. When proven treatment fails, emerging therapeutic possibilities offer new hope that can delay the referral to the palliative care team.
A Comparison Between the Effect of Combined Chain Exercises Plus Kinesio Taping With Combined Chain Exercises Alone in Knee Osteoarthritis
Authors: Danazumi Musa Sani , Ibrahim Shehu Usman , Yakasai Abdulsalam Mohammed , Dermody Gordana , Bello Bashir , Kaka Bashir
Published: January 2021

Objective

This study aimed to examine the effect of Kinesio taping as an adjunct to combined chain exercises compared with combined chain exercises alone in the management of individuals with knee osteoarthritis.

Methods

A total of 60 (27 male, 33 female) individuals (age range = 50–71 yrs and mean age = 54.26 ± 8.83 yrs) diagnosed as having mild to moderate knee osteoarthritis (based on the Kellgren and Lawrence grade I―III classification) were randomly allocated into two groups with 30 participants each in the Kinesio taping + combined chain exercises and combined chain exercises groups. Participants in the Kinesio taping + combined chain exercises group received Kinesio taping plus combined chain exercises and those in the combined chain exercises group received only combined chain exercises. Each participant was assessed for pain, range of motion, functional mobility, and quality of life at baseline and after 8 wks of intervention. A mixed-design multivariate analysis of variance was used to analyze the treatment effect.

Results

No significant differences were observed in the baseline characteristics of participants in both groups. The result indicated that there was a significant time effect for all outcomes, with a significant interaction between time and intervention (P < 0.001). The Bonferroni post hoc analyses of time and intervention effects indicated that the Kinesio taping + combined chain exercises group improved significantly better than the combined chain exercises group in all outcomes, pain (mean = 2.01 [0.64] vs. 3.94 [1.12], F[df] = 5.466[1,58], P = 0.011), flexion range of motion (mean = 121.15 [2.07] vs. 104.28 [3.24], F[df] = 26.722[1,58], P < 0.001), functional mobility (mean = 19.47 [1.95] vs. 31.01 [2.39], F[df] = 29.436[1,58], P < 0.001), and quality of life (mean = 68.76 [3.19] vs. 45.62 [2.87], F[df] = 71.984[1,58], P < 0.001), after 8 wks of intervention.

Conclusions

The findings of this study concluded that Kinesio taping + combined chain exercises and combined chain exercises were both effective but Kinesio taping plus combined chain exercises was more effective in the management of individuals with knee osteoarthritis.

Trial Registration

Pan African Clinical Trial Registry: PACTR201810603949411.
Clinical outcome assessment in clinical trials of chronic pain treatments
Authors: Patel Kushang V. , Amtmann Dagmar , Jensen Mark P. , Smith Shannon M. , Veasley Christin , Turk Dennis C.
Published: January 2021

Clinical outcome assessments (COAs) measure outcomes that are meaningful to patients in clinical trials and are critical for determining whether a treatment is effective. The objectives of this study are to (1) describe the different types of COAs and provide an overview of key considerations for evaluating COAs, (2) review COAs and other outcome measures for chronic pain treatments that are recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) or other expert groups, and (3) review advances in understanding pain-related COAs that are relevant to clinical trials. The authors reviewed relevant articles, chapters, and guidance documents from the European Medicines Agency and U.S. Food and Drug Administration. Since the original core set of outcome measures were recommended by IMMPACT 14 years ago, several new advancements and publications relevant to the measurement or interpretation of COAs for chronic pain trials have emerged, presenting new research opportunities. Despite progress in the quality of measurement of several outcome domains for clinical trials of chronic pain, there remain some measurement challenges that require further methodological investigation.
Children Treated for Nonsyndromic Craniosynostosis Exhibit Average Adaptive Behavior Skills with Only Minor Shortcomings
Authors: Kljajić Marizela , Maltese Giovanni , Tarnow Peter , Sand Peter , Kölby Lars
Published: January 2021

Background:

Adaptive behavior skills are important when assessing cognitive functions related to daily life; however, few studies have assessed these skills in patients treated for nonsyndromic craniosynostosis. In this study, the authors assessed the adaptive behavior skills of children treated for craniosynostosis and examined whether their outcomes are related to surgical technique.

Methods:

The Adaptive Behavior Assessment System, 2nd Edition, parent report was used for children (age, 7 to 16 years) treated for sagittal (n = 41), metopic (n = 24), and other rare synostoses (n = 8). Background data, including intelligence quotient, were controlled for confounders.

Results:

All evaluated children treated for craniosynostosis were estimated as lower in all aspects of adaptive behavior skills (full-scale, conceptual, social, and practical composites; effect size, 0.36 to 0.44) as compared with norms. The sagittal group showed shortcomings in social composite (effect size, 0.48) and subscales measuring self-care and self-direction, although no difference was observed between spring-assisted surgery and pi-plasty regarding outcomes of adaptive behavior skills. In addition, children treated for metopic synostosis showed results indicating shortcomings with adaptive behavior according to the full-scale, conceptual, and social composites (effect size, 0.53 to 0.61) relative to norms. Furthermore, attrition analysis revealed no significant differences between responders (rate, 80.2 percent) and nonresponders.

Conclusion:

These results found that children treated for craniosynostosis display average adaptive behavior skills, and that the two surgical techniques used to treat sagittal synostosis did not differ in their behavioral outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
High Superficial Musculoaponeurotic System Lamellar Facelift Under Local Anesthesia
Authors: Ors Safvet
Published: January 2021

Purpose:

Patients, nowadays, prefer easy, low-risk, day-case procedures under local anesthesia for facial rejuvenation. Therefore, they favor facelift operations applied under local anesthesia.

Materials and Methods:

A total of 160 patients who underwent high superficial musculoaponeurotic system (SMAS) lamellar facelift under local anesthesia between 2010 and 2020 were included in this study. Patients operated under general anesthesia were excluded from this study. High SMAS lamellar facelift under local anesthesia was performed in all patients, consisting of 145 women and 15 men without any additional disease aged between 38 and 65 years. About 140 of these patients underwent primary facelift, whereas 20 of them had undergone SMAS plication more than 10 years ago. Lidocaine was used as a local anesthetic and the patients were not sedated. The duration of the operation was 80 minutes on average. The patients were left to rest for 1 hour after the operation and then sent home until their follow-up every other day for the first week.

Results:

This study shows that high SMAS facelift operations for the mid-face can easily be performed under local anesthesia under operating room conditions without sedation. However, an important point to keep in mind is that although the results of this surgery satisfy the patients, the outcomes do not entirely match the expectations from total face and neck lift performed under general anesthesia. High SMAS facelift with local anesthesia should be considered as an alternative for patients who do not want to undergo general anesthesia or who are at risk of undergoing general anesthesia. Especially during the COVID-19 pandemic, local anesthesia was considered much safer for the patients.

Level of evidence: Level V
SAVE 2.0: Identifying and strengthening resident leadership skills through simulation based team training
Authors: Onufer Emily Jean , Andrade Erin , Caldwell Katharine E. , Cullinan Darren , Vallar Kelly , Turnbull Isaiah R. , Schuerer Douglas , Wise Paul E. , Klingensmith Mary E. , Punch LJ
Published: January 2021

BACKGROUND

The “Surgery for Abdomino-thoracic ViolencE (SAVE)” animate lab engages surgical residents in the management of penetrating injuries in a team setting. Senior residents, representing postgraduate year (PGY) 3–5, assume the role of team leader and facilitate the junior residents, PGY1–2, in operative management of simulated penetrating wounds. Residents completed five scenarios with increasing level of difficulty within set time limits. Senior residents were evaluated on their team’s ability to “SAVE” their patient within the time allotted, as well as their communication and leadership skills.

METHODS

General, vascular, urology, and plastic surgery residents (n = 79) were divided into 25 teams of three to four residents by “resident scores” (R scores, the sum of the team members’ PGY) to create balanced teams with comparable years of clinical experience. Residents completed assessments of their senior resident’s leadership ability and style.

RESULTS

Evaluation of a resident’s desired learning style changed across PGY with junior residents preferring more hands-on guidance compared with senior residents preferring only verbal correction. Resident leadership evaluations demonstrated that team leaders of varied resident years achieved the highest scores. Greater differences in the mismatch between autonomy provided to and desired by junior residents correlated to greater junior resident discomfort in expressing their opinion, confidence, and leadership ratings of senior residents. However, greater autonomy mismatch also correlated to more rapid time to task completion.

CONCLUSION

Different from our expectations, clinical experience alone did not define team leader success. Leadership is a powerful influence on the outcome of team performance and may be a skill, which can transcend overall clinical experience. A match between desired and provided resident autonomy and team cohesion may demonstrate a stronger effect on team success in stressful operative situations, such as trauma resuscitation. Enhancement of leadership skills early in residency training may represent an important focus for trauma surgery education.
Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of Antibody-mediated Rejection
Authors: Hu Robert W. , Korutla Laxminarayana , Reddy Sanjana , Harmon Joey , Zielinski Patrick D. , Bueker Alex , Molina Maria , Romano Connie , Margulies Ken , McLean Rhondalyn , Lal Priti , Vallabhajosyula Prashanth
Published: January 2021

Background.

Endomyocardial biopsy remains the gold standard for distinguishing types of immunologic injury—acute versus antibody-mediated rejection (AMR). Exosomes are tissue-specific extracellular microvesicles released by many cell types, including transplanted heart. Circulating transplant heart exosomes express donor-specific human leukocyte antigen (HLA) I molecules. As AMR is mediated by antibodies to donor HLAs, we proposed that complement deposition that occurs with AMR at tissue level would also occur on circulating donor heart exosomes.

Methods.

Plasma exosomes in 4 patients were isolated by column chromatography and ultracentrifugation. Donor heart exosomes were purified using anti-donor HLA I antibody beads and complement C4d protein expression was assessed in this subset as marker for AMR.

Results.

Three patients had no rejection episodes. Circulating donor heart exosomes showed troponin protein and mRNA expression at all follow-up time points. One patient developed AMR on day 14 endomyocardial biopsy that was treated with rituximab, IVIG/plasmapheresis. Time-specific detection of C4d protein was seen in donor heart exosome subset in this patient, which resolved with treatment. C4d was not seen in other 3 patients’ donor exosomes.

Conclusions.

Anti-donor HLA I specificity enables characterization of circulating donor heart exosomes in the clinical setting. Further characterization may open the window to noninvasively diagnose rejection type, such as AMR.
Rejection-associated Mitochondrial Impairment After Heart Transplantation
Authors: Romero Erick , Chang Eleanor , Tabak Esteban , Pinheiro Diego , Tallaj Jose , Litovsky Silvio , Keating Brendan , Deng Mario , Cadeiras Martin
Published: January 2021

Background.

Mitochondrial dysfunction is associated with poor allograft prognosis. Mitochondrial-related gene expression (GE) in endomyocardial biopsies (EMBs) could be useful as a nonimmune functional marker of rejection. We hypothesize that acute cardiac allograft rejection is associated with decreased mitochondrial-related GE in EMBs.

Methods.

We collected 64 routines or clinically indicated EMB from 47 patients after heart transplant. The EMBs were subjected to mRNA sequencing. We conducted weighted gene coexpression network analysis to construct module-derived eigengenes. The modules were assessed by gene ontology enrichment and hub gene analysis. Modules were correlated with the EMBs following the International Society of Heart and Lung Transplantation histology-based criteria and a classification based on GE alone; we also correlated with clinical parameters.

Results.

The modules enriched with mitochondria-related and immune-response genes showed the strongest correlation to the clinical traits. Compared with the no-rejection samples, rejection samples had a decreased activity of mitochondrial-related genes and an increased activity of immune-response genes. Biologic processes and hub genes in the mitochondria-related modules were primarily involved with energy generation, substrate metabolism, and regulation of oxidative stress. Compared with International Society of Heart and Lung Transplantation criteria, GE-based classification had stronger correlation to the weighted gene coexpression network analysis–derived functional modules. The brain natriuretic peptide level, ImmuKnow, and Allomap scores had negative relationships with the expression of mitochondria-related modules and positive relationships with immune-response modules.

Conclusions.

During acute cardiac allograft rejection, there was a decreased activity of mitochondrial-related genes, related to an increased activity of immune-response genes, and depressed allograft function manifested by brain natriuretic peptide elevation. This suggests a rejection-associated mitochondrial impairment.
Prevalence of Mild Cognitive Impairment in the Lothian Birth Cohort 1936
Authors: Welstead Miles , Luciano Michelle , Muniz-Terrera Graciela , Taylor Adele M. , Russ Tom C.
Published: January 2021

Background:

The Lothian Birth Cohort 1936 (LBC1936) is a highly phenotyped longitudinal study of cognitive and brain ageing. Given its substantial clinical importance, we derived an indicator of mild cognitive impairment (MCI) and amnestic and nonamnestic subtypes at 3 time points.

Methods:

MCI status was derived at 3 waves of the LBC1936 at ages 76 (n=567), 79 (n=441), and 82 years (n=341). A general MCI category was derived as well as amnestic MCI (aMCI) and nonamnestic MCI (naMCI). A comparison was made between MCI derivations using normative data from the LBC1936 cohort versus the general UK population.

Results:

MCI rates showed a proportional increase at each wave between 76 and 82 years from 15% to 18%. Rates of MCI subtypes also showed a proportional increase over time: aMCI 4% to 6%; naMCI 12% to 16%. Higher rates of MCI were found when using the LBC1936 normative data to derive MCI classification rather than UK-wide norms.

Conclusions:

We found that MCI and aMCI rates in the LBC1936 were consistent with previous research. However, naMCI rates were higher than expected. Future LBC1936 research should assess the predictive factors associated with MCI prevalence to validate previous findings and identify novel risk factors.
The efficacy and safety in attention deficit hyperactivity disorder of second-generation antipsychotics and other medications for hyperactivity in children and adolescents with autism: a meta-analysis
Authors: Wang Fang , Wen Fang , Yu Liping , Yan Junjuan , Liu Jingran , Li Ying , Cui Yonghua
Published: January 2021

Children and adolescents with ASD also have co-occurrence of attention deficit hyperactivity disorder (ADHD) symptoms. ADHD symptoms, especially hyperactivity, greatly increased the severity of autism symptoms. This study concentrated on two widely-used medications: the second generation of antipsychotics (SGAs) and ADHD medication, aiming to conduct a meta-analysis about their effect on hyperactivity, so it would offer some evidence for clinical medication choice. The Medline, Embase, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure databases were searched from inception to July 2019 for studies exploring the use of SGAs and ADHD medications in autistic children and adolescents. Double-blind, randomized controlled trials that reported hyperactivity as an outcome were included in the study. A total of thirteen trials with 712 participants were included in our meta-analysis. For SGAs, the standardized mean difference (SMD) of hyperactivity subscale in Aberrant behavior checklist scale or conners rating scales was 0.59, 95% confidence interval (CI): 0.23–0.96, I2 = 74%, Q = 15.34, P < 0.01. For ADHD medications, SMD was −0.66, with 95% CI: −0.99 to 0.33, I2 = 53%, Q = 15.02, P = 0.04. As for adverse events, in the SGAs group, somnolence had the largest effect size, risk ratio = 5.62, 95% CI: 3.20– 9.87 (I2 = 0%, Q = 2.45, P = 0.65). In ADHD group, the side effect of decreased appetite showed the largest effect size (risk ratio = 2.63, 95% CI = 0.99–7.01, I2 = 65.7%, Q = 11.66, P = 0.02). Both ADHD medications and SGAs were effective in dealing with hyperactivity in children and adolescents with autism but were shown to increase the risk of decreased appetite, somnolence, headache and nausea or vomiting. The clinical use of these medications should carefully weigh the benefits and risks.
Rule of thumb in human intelligence for assessing the COVID-19 outbreak in Japan
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi
Published: January 2021

Background

The COVID-19 outbreak in Japan exhibited its third peak at the end of 2020. Mathematical modelling and developed AI cannot explain several peaks in a single year.

Object

This study was conducted to evaluate a rule of thumb for prediction from past wave experiences.

Method

We rescaled the number of newly infected patients as 100% at the peak and checked similarities among waves. Then we extrapolated the courses of the third and later waves.

Results

Results show some similarity around the second and the third waves. Based on this similarity, we expected the bottom of the third wave will show 2131 newly positive patients including asymptomatic patients at around the end of February, 2021.

Discussion and Conclusion

We can infer the course of the third wave from similarity with the second wave. Mathematical modelling has been unable to do it, even when AI was used for prediction. Performance of the rule of thumb used with human intelligence might be superior to that of AI under these circumstances.
The landscape of alternative polyadenylation in single cells of the developing mouse embryo
Authors: Agarwal Vikram , Lopez-Darwin Sereno , Kelley David R. , Shendure Jay
Published: January 2021

3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examined a dataset comprising ∼2 million cells spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RBP dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.
Quantifying cell transitions inC. eleganswith data-fitted landscape models
Authors: Camacho-Aguilar Elena , Warmflash Aryeh , Rand David A.
Published: January 2021

Increasing interest has emerged in new mathematical approaches that simplify the study of complex differentiation processes by formalizing Waddington’s landscape metaphor. However, a rational method to build these landscape models remains an open problem. Building on pioneering work byCorson and Siggia(2012, 2017) we study vulval development inC. elegansby developing a framework based on Catastrophe Theory (CT) and approximate Bayesian computation (ABC) to build data-fitted landscape models. We first identify the candidate qualitative landscapes, and then use CT to build the simplest model consistent with the data, which we quantitatively fit using ABC. The resulting model suggests that the underlying mechanism is a quantifiable two-step decision controlled by EGF and Notch-Delta signals, where a non-vulval/vulval decision is followed by a bistable transition to the two vulval states. This new model fits a broad set of data and makes several novel predictions.
Evolution of recombination landscapes in diverging populations of bread wheat
Authors: Danguy des Déserts Alice , Bouchet Sophie , Sourdille Pierre , Servin Bertrand
Published: January 2021

Reciprocal exchanges of DNA (crossovers) that occur during meiosis are mandatory to ensure the production of fertile gametes in sexually reproducing species. They also contribute to shuffle parental alleles into new combinations thereby fuelling genetic variation and evolution. However, due to biological constraints, the recombination landscape is highly heterogenous along the genome which limits the range of allelic combinations and the adaptability of populations. An approach to better understand the constraints on the recombination process is to study how it evolved in the past. In this work we tackled this question by constructing recombination profiles in four diverging bread wheat (Triticum aestivum L.) populations established from 371 landraces genotyped at 200,062 SNPs. We used linkage disequilibrium (LD) patterns to estimate in each population the past distribution of recombination along the genome and characterize its fine-scale heterogeneity. At the megabase scale, recombination rates derived from LD patterns were consistent with family-based estimates obtained from a population of 406 recombinant inbred lines. Among the four populations, recombination landscapes were significantly positively correlated between each other and shared a statistically significant proportion of highly recombinant intervals. However, this comparison also highlighted that the similarity in recombination landscapes between populations was significantly decreasing with their genetic differentiation in most regions of the genome. This observation was found to be robust to SNP ascertainment and demography and suggests a relatively rapid evolution of factors determining the fine-scale localization of recombination in bread wheat.
Brain Connectivity meets Reservoir Computing
Authors: Damicelli Fabrizio , Hilgetag Claus C. , Goulas Alexandros
Published: January 2021

The connectivity of Artificial Neural Networks (ANNs) is different from the one observed in Biological Neural Networks (BNNs). Can the wiring of actual brains help improve ANNs architectures? Can we learn from ANNs about what network features support computation in the brain when solving a task?

ANNs’ architectures are carefully engineered and have crucial importance in many recent performance improvements. On the other hand, BNNs’ exhibit complex emergent connectivity patterns. At the individual level, BNNs connectivity results from brain development and plasticity processes, while at the species level, adaptive reconfigurations during evolution also play a major role shaping connectivity.

Ubiquitous features of brain connectivity have been identified in recent years, but their role in the brain’s ability to perform concrete computations remains poorly understood. Computational neuroscience studies reveal the influence of specific brain connectivity features only on abstract dynamical properties, although the implications of real brain networks topologies on machine learning or cognitive tasks have been barely explored.

Here we present a cross-species study with a hybrid approach integrating real brain connectomes and Bio-Echo State Networks, which we use to solve concrete memory tasks, allowing us to probe the potential computational implications of real brain connectivity patterns on task solving.

We find results consistent across species and tasks, showing that biologically inspired networks perform as well as classical echo state networks, provided a minimum level of randomness and diversity of connections is allowed. We also present a framework,bio2art, to map and scale up real connectomes that can be integrated into recurrent ANNs. This approach also allows us to show the crucial importance of the diversity of interareal connectivity patterns, stressing the importance of stochastic processes determining neural networks connectivity in general.
A duplicated copy of the meiotic geneZIP4preserves up to 50% pollen viability and grain number in polyploid wheat
Authors: Alabdullah Abdul Kader , Moore Graham , Martín Azahara C.
Published: January 2021

Although most flowering plants are polyploid, little is known of how the meiotic process evolved to stabilise and preserve polyploid fertility. On wheat polyploidisation, the major meiotic geneZIP4on chromosome 3B duplicated onto 5B and subsequently diverged. This 5B meiotic gene copy (TaZIP4-B2) was recently shown to promote homologous pairing, synapsis and crossover, and suppress homoeologous crossover. We therefore suspected that these stabilising effects on meiosis could be important for the preservation of wheat polyploid fertility.

A CRISPRTazip4-B2mutant was exploited to assess the contribution of the 5B duplicatedZIP4copy in maintaining pollen viability and grain setting.

Analysis demonstrated abnormalities in 56% of meiocytes in theTazip4-B2mutant, with micronuclei in 50% of tetrads, reduced size in 48% of pollen grains and a near 50% reduction in grain number. Further studies showed that most of the reduced grain number resulted from pollination with less viable pollen, suggesting that the stabilising effect ofTaZIP4-B2on meiosis has a greater consequence in subsequent male, rather than female gametogenesis.

These studies reveal the extraordinary value of the wheat chromosome 5BTaZIP4-B2duplication to agriculture and human nutrition. Future studies should assess whether differentTaZIP4-B2alleles exhibit variable effects on meiotic stabilisation and/or resistance to temperature change.
Exploring the natural origins of SARS-CoV-2 in the light of recombination
Authors: Lytras Spyros , Hughes Joseph , Martin Darren , de Klerk Arné , Lourens Rentia , Kosakovsky Pond Sergei L , Xia Wei , Jiang Xiaowei , Robertson David L
Published: January 2021

The lack of an identifiable intermediate host species for the proximal animal ancestor of SARS-CoV-2, and the large geographical distance between Wuhan and where the closest evolutionary related coronaviruses circulating in horseshoe bats (Sarbecoviruses) have been identified, is fuelling speculation on the natural origins of SARS-CoV-2. We have comprehensively analysed phylogenetic relations between SARS-CoV-2, and the related bat and pangolin Sarbecoviruses sampled so far. Determining the likely recombination events reveals a highly reticulate evolutionary history within this group of coronaviruses. Clustering of the inferred recombination events is non-random with evidence that Spike, the main target for humoral immunity, is beside a recombination hotspot likely driving antigenic shift in the ancestry of bat Sarbecoviruses. Coupled with the geographic ranges of their hosts and the sampling locations, across southern China, and into Southeast Asia, we confirm horseshoe bats, Rhinolophus, are the likely SARS-CoV-2 progenitor reservoir species. By tracing the recombinant sequence patterns, we conclude that there has been relatively recent geographic movement and co-circulation of these viruses’ ancestors, extending across their bat host ranges in China and Southeast Asia over the last 100 years or so. We confirm that a direct proximal ancestor to SARS-CoV-2 is yet to be sampled, since the closest relative shared a common ancestor with SARS-CoV-2 approximately 40 years ago. Our analysis highlights the need for more wildlife sampling to (i) pinpoint the exact origins of SARS-CoV-2’s animal progenitor, and (ii) survey the extent of the diversity in the related Sarbecoviruses’ phylogeny that present high risk for future spillover.

Highlights

The origin of SARS-CoV-2 can be traced to horseshoe bats, genus Rhinolophus, with ranges in both China and Southeast Asia.

The closest known relatives of SARS-CoV-2 exhibit frequent transmission among their Rhinolophus host species.

Sarbecoviruses have undergone extensive recombination throughout their evolutionary history.

Accounting for the mosaic patterns of these recombinants is important when inferring relatedness to SARS-CoV-2.

Breakpoint patterns are consistent with recombination hotspots in the coronavirus genome, particularly upstream of the pike open reading frame with a coldspot in S1.
Crystal structures of three copper(II)–2,2′-bipyridine (bpy) compounds, [Cu(bpy)2(H2O)][SiF6]·4H2O, [Cu(bpy)2(TaF6)2] and [Cu(bpy)3][TaF6]2 and a related coordination polymer, [Cu(bpy)(H2O)2SnF6]
n
Authors: Nisbet Matthew L. , Hiralal Emily , Poeppelmeier Kenneth R.
Published: January 2021

We report the hydrothermal syntheses and crystal structures of aquabis(2,2′-bipyridine-κ2
N,N′)copper(II) hexafluoridosilicate tetrahydrate, [Cu(bpy)2(H2O)][SiF6]·4H2O (bpy is 2,2′-bipyridine, C10H8N2), (I), bis(2,2′-bipyridine-3κ2
N,N′)-di-μ-fluorido-1:3κ2
F:F;2:3κ2
F:F-decafluorido-1κ5
F,2κ5
F-ditantalum(V)copper(II), [Cu(bpy)2(TaF6)2], (II), tris(2,2′-bipyridine-κ2
N,N′)copper(II) bis[hexafluoridotantalate(V)], [Cu(bpy)3][TaF6]2, (III), and catena-poly[[diaqua(2,2′-bipyridine-κ2
N,N′)copper(II)]-μ-fluorido-tetrafluoridotin-μ-fluorido], [Cu(bpy)(H2O)2SnF6]
n
, (IV). Compounds (I), (II) and (III) contain locally chiral copper coordination complexes with C
2, D
2, and D
3 symmetry, respectively. The extended structures of (I) and (IV) are consolidated by O—H...F and O—H...O hydrogen bonds. The structure of (III) was found to be a merohedral (racemic) twin.
Working mechanism and experimental study of electromagnetic measurement while drilling systems based on a relay station
Authors: Lu Chunhua , Wang Rongjing , Zhao Huibin , Zhang Tao
Published: January 2021

Electromagnetic measurement while drilling systems transmit downhole data via an information channel composed of a drill string and formation; the formation has a strong attenuation effect on the signal. Signal attenuation during electromagnetic wave transmission through the formation limits the well depth at which this technique can be applied. This paper discusses several commonly used methods to improve the depth at which electromagnetic measurement while drilling applications can be conducted, including turbine power supplies, adaptive power outputs and transmitting antenna extensions. Based on both theory and practice, the characteristics of these methods are analysed, and a relay station‐infused electromagnetic measurement while drilling system is proposed. The relay station‐infused electromagnetic measurement while drilling system consists of a downhole instrument assembly, a relay station and a ground receiver assembly. The repeater receives the electromagnetic wave signal from the underground transmitter and, after amplification, decoding and other processing, re‐encodes the signal and forwards it to the ground receiver at different frequencies, so as to increase the underground electromagnetic wave signal relay transmission. The design of the relay station module is introduced in detail, and the influencing factors and rules of signal transmission are analysed. Signal transmission experiments show that the electromagnetic measurement while drilling system based on a relay station can reliably represent the relay of signals and can thus be used in deeper wells.
Effects of 38 years of wildfires on tree density in the Blue Mountains, Australia
Authors: Rahmani Simin , Price Owen
Published: January 2021

Forests are vital for biodiversity, carbon storage and ecosystem services, but can be potentially threatened by fires. Given the significance of forests and fire in a changing climate, research into the long‐term effects of fire on forests plays an important role in understanding the global carbon cycle by the forests functioning as a large terrestrial carbon sink or source. In this study, we used aerial photography from 1975 and 2013 to count the change in the number of trees in 560 dry sclerophyll plots (40 × 40m) in the Blue Mountains of Australia. We analysed the relationship between the number of fires and severe fires in that period on the change in numbers of trees. We found that the average response was an increase of 1 tree per plot over 38 years. The number of fires had a small positive effect on tree numbers; plots with 2 or 3 severe fires had 1 and 2 extra trees, respectively, than those without fire. One exception was a severe fire in 2001 that did not show this positive effect, probably because it corresponded with extensive drought. Our findings suggest that number of forest canopy trees is resilient to the number of fires and number of severe fires.
Widespread dieback in a foundation species on a sub‐Antarctic World Heritage Island: Fine‐scale patterns and likely drivers
Authors: Dickson Catherine R. , Baker David J. , Bergstrom Dana M. , Brookes Rowan H. , Whinam Jennie , McGeoch Melodie A.
Published: January 2021

Under anthropogenic climate change, emerging diseases and pathogens are increasingly prevalent in high latitude and altitude regions that were previously protected by cold winter temperatures. Ongoing island‐wide dieback of a foundation species, the cushion plant Azorella macquariensis, on World Heritage listed Macquarie Island provides the first sub‐Antarctic example. To better understand the island‐wide progression of cushion dieback and its drivers, we established and quantified plant condition classes and measured microclimate across 62 sites. We then tested whether the drivers of cushion dieback were associated with (i) water stress: represented by vapour pressure deficit, wind exposure and gravel content, (ii) pathogen virulence: using freezing days and extreme humidity as empirically supported surrogates, or (iii) both. There was a strong north‐south progression in cushion condition, with dieback most active in the centre of the island and advanced in the north. Dieback was most extensive at sites with fewer freezing days and high humidity. Natural southern refugia were explained by the significantly colder temperatures, associated with a north‐south temperature gradient. It is expected that under current climate change trajectories, where Macquarie is likely to continue to become warmer and wetter, cushion dieback will remain pervasive, expanding most slowly in the south and potentially outpacing recovery. We emphasise the need for increased awareness to prevent the establishment of pathogens into and across the landscapes of newly susceptible high latitude and altitude regions. Areas of high conservation significance need to be prioritised for management, to prevent further landscape‐scale change under current climate trajectories.
Lack of general associations between intertidal assemblages and rock hardness
Authors: Janetzki Nathan , Benkendorff Kirsten , Fairweather Peter G.
Published: January 2021

Different assemblages of intertidal biota may be associated with the hardness of the rock type that comprises the seashore. However, very few published studies have investigated mobile and sessile assemblage differences between hardness classes. To remedy this, we investigated the physical attributes and biotic assemblages of 12 rock platforms across two bioregions, encompassing seven rock types categorised into either the soft (≤4 using Moh’s scale of scratch hardness) or hard (>4 on Moh’s scale) classes. Rock types from the soft versus hard classes differed physically, but the biotic assemblages showed few general differences between hardness classes. Instead, most biotic differences associated with rock hardness were specific to just one of the marine bioregions sampled, not both. Hardness‐related assemblage differences were only weakly‐to‐moderately correlated with hardness differences in mineralogy or microhabitat density. The detection of bioregion‐specific hardness differences for intertidal assemblages, rather than general hardness class trends, indicate that the type of rock comprising the seashore in each bioregion may be more strongly associated with the biotic patterns identified than hardness per se.
Elastase and exacerbation of neutrophil innate immunity are involved in multi‐visceral manifestations of COVID‐19
Authors: Guéant Jean‐Louis , Guéant‐Rodriguez Rosa‐Maria , Fromonot Julien , Oussalah Abderrahim , Louis Huguette , Chery Celine , Gette Mickael , Gleye Stanislas , Callet Jonas , Raso Jeremie , Blanchecotte François , Lacolley Patrick , Guieu Régis , Regnault Véronique
Published: January 2021

Background

Many arguments suggest that neutrophils could play a prominent role in COVID‐19. However, the role of key components of neutrophil innate immunity in severe forms of COVID‐19 has deserved insufficient attention. We aimed to evaluate the involvement of neutrophil elastase, histone‐DNA, and DNases in systemic and multi‐organ manifestations of COVID‐19.

Methods

We performed a multicenter study of markers of neutrophil innate immunity in 155 cases consecutively recruited in a screening center, local hospitals, and two regional university hospitals. The cases were evaluated according to clinical and biological markers of severity and multi‐organ manifestations and compared to 35 healthy controls.

Results

Blood neutrophil elastase, histone‐DNA, myeloperoxidase‐DNA, and free dsDNA were dramatically increased, and DNase activity was decreased by 10‐fold, compared with controls. Neutrophil elastase and histone‐DNA were associated with intensive care admission, body temperature, lung damage, and markers of cardiovascular outcomes, renal failure, and increased interleukin‐6 (IL‐6), IL‐8, and CXCR2. Neutrophil elastase was an independent predictor of the computed tomography score of COVID‐19 lung damage and the number of affected organs, in multivariate analyses. The increased blood concentrations of NE and neutrophil extracellular traps were related to exacerbation of neutrophil stimulation through IL‐8 and CXCR2 increased concentrations and increased serum DAMPs, and to impaired degradation of NETs as a consequence of the dramatic decrease in blood DNase activity.

Conclusion

Our results point out the key role of neutrophil innate immunity exacerbation in COVID‐19. Neutrophil elastase and DNase could be potential biomarkers and therapeutic targets of severe systemic manifestations of COVID‐19.
Increased risk of dementia in hypothyroidism: A Danish nationwide register‐based study
Authors: Thvilum Marianne , Brandt Frans , Lillevang‐Johansen Mads , Folkestad Lars , Brix Thomas H. , Hegedüs Laszlo
Published: January 2021

Objective

Globally, the prevalence of individuals with dementia is increasing, and identification of risk factors is of paramount interest. Using population‐based registers, we evaluated whether hypothyroidism is a risk factor for dementia.

Design

Register‐based cohort study.

Patients and Methods

Risk of dementia was evaluated in two cohorts. The DNPR cohort comprises 111,565 hypothyroid patients, diagnosed between 1995 and 2012, and 446,260 euthyroid age‐ and sex‐matched individuals (median follow‐up 6.2 years). The OPENTHYRO cohort comprises 233,844 individuals with at least one measurement of serum thyrotropin (TSH) between 1995 and 2011, of whom 2,894 had hypothyroidism (median follow‐up 7.2 years). Primary outcome was dementia defined as an International Classification of Diseases 10 code, or prescription of medicine for dementia.

Results

In the DNPR cohort, risk of dementia was significantly increased in subjects with hypothyroidism (HR 1.22; 95% CI: 1.17–1.27), which attenuated after adjusting for pre‐existing comorbidity (HR 0.82; 95% CI: 0.79‐0.86). Stratification of age into ≤56 and >56 years showed an inverse relationship between age and risk of dementia (HR≤56 years. 2.03; 95% CI: 1.62–2.53 and HR>56 years. 1.00; 95% CI: 0.96–1.05). In the OPENTHYRO cohort, the risk of dementia was significantly increased for each 6 months of elevated TSH (HR 1.12; 95% CI: 1.07–1.16).

Conclusions

Hypothyroidism is associated with increased risk of dementia. The association is influenced by comorbidity and age. Every 6 months of elevated TSH increased the risk of dementia by 12%, suggesting that also the length of hypothyroidism influences the risk of dementia.
Vocal development in a large‐scale crosslinguistic corpus
Authors: Cychosz Margaret , Cristia Alejandrina , Bergelson Elika , Casillas Marisa , Baudet Gladys , Warlaumont Anne S. , Scaff Camila , Yankowitz Lisa , Seidl Amanda
Published: January 2021

This study evaluates whether early vocalizations develop in similar ways in children across diverse cultural contexts. We analyze data from daylong audio recordings of 49 children (1–36 months) from five different language/cultural backgrounds. Citizen scientists annotated these recordings to determine if child vocalizations contained canonical transitions or not (e.g., “ba” vs. “ee”). Results revealed that the proportion of clips reported to contain canonical transitions increased with age. Furthermore, this proportion exceeded 0.15 by around 7 months, replicating and extending previous findings on canonical vocalization development but using data from the natural environments of a culturally and linguistically diverse sample. This work explores how crowdsourcing can be used to annotate corpora, helping establish developmental milestones relevant to multiple languages and cultures. Lower inter‐annotator reliability on the crowdsourcing platform, relative to more traditional in‐lab expert annotators, means that a larger number of unique annotators and/or annotations are required, and that crowdsourcing may not be a suitable method for more fine‐grained annotation decisions. Audio clips used for this project are compiled into a large‐scale infant vocalization corpus that is available for other researchers to use in future work.
Endovascular treatment for basilar artery occlusion: A systematic review and meta‐analysis
Authors: Katsanos Aristeidis H. , Safouris Apostolos , Nikolakopoulos Stavros , Mavridis Dimitris , Goyal Nitin , Psychogios Marios N. , Magoufis Georgios , Krogias Christos , Catanese Luciana , Van Adel Brian , Raphaeli Guy , Sarraj Amrou , Themistocleous Marios , Kararizou Evangelia , Turc Guillaume , Arthur Adam , Alexandrov Andrei V. , Tsivgoulis Georgios
Published: January 2021

Background and purpose

Independent randomized controlled clinical trials (RCTs) have provided robust evidence for endovascular treatment (EVT) as the standard of care treatment for acute large vessel occlusions in the anterior circulation. We examined available studies specific to posterior cerebral circulation ischemic strokes to see if any conclusions can be drawn regarding EVT options.

Methods

We performed a systematic literature search to identify studies evaluating the safety and efficacy of EVT versus standard medical treatment for patients with acute basilar artery occlusion (BAO). We extracted data for outcomes of interest and presented associations between the two groups with the use of risk ratios (RRs) or odds ratios (ORs), with corresponding 95% confidence intervals (CIs). We used a random‐effects model to pool the effect estimates.

Results

We identified five studies (two RCTs, three observational cohorts) including a total of 1098 patients. Patients receiving EVT had a higher risk of symptomatic intracranial hemorrhage (sICH) compared to those receiving non‐interventional medical management (RR 5.42, 95% CI 2.74–10.71). Nonsignificant trends towards modified Rankin Scale (mRS) scores 0–2 (RR 1.02, 95% CI 0.74–1.41), mRS scores 0–3 (RR = 0.97, 95% CI 0.64–1.47), overall functional improvement (OR 0.93, 95% CI 0.57–1.51), and all‐cause mortality (RR 1.03, 95% CI 0.78–1.35) at 3 months were seen.

Conclusion

Although EVT increases the probability of sICH, the available data do not exclude the possibility of improved functional outcomes over standard therapy. As larger studies are challenged by the perceived lack of equipoise in this vulnerable patient population, results of ongoing RCTs are expected to provide substantial input for future meta‐analyses.