bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing perceived effectiveness of career development efforts led by the women in American Medical Informatics Association Initiative
Authors: Wei Duo (Helen) , Kukhareva Polina V , Tao Donghua , Sordo Margarita , Pandita Deepti , Dua Prerna , Banerjee Imon , Abraham Joanna
Published: July 2022

Objective

We sought to ascertain perceived factors affecting women’s career development efforts in the American Medical Informatics Association (AMIA) and to provide recommendations for improvements.

Materials and Methods

Data were collected using a 27-item survey administered via the AMIA newsletter and other social channels. Survey questions comprised 3 demographics, 15 Likert-scale, and 9 open-ended items. Likert-scale responses were summarized across respondent ages, career stages, and career domains, and open-ended responses were thematically analyzed.

Results

We received survey responses from 109 AMIA women members. Our findings demonstrate that AMIA had made strides in promoting career development, and the most effective AMIA efforts included social events (83%), panel discussions (80%), and scientific sessions (79%). However, despite these efforts, women members perceived that gender-specific challenges persisted within AMIA, and recognized the need for increased networking opportunities (96%), raising awareness of gender-specific challenges (95%), and encouraging gender proportional representation in leadership (92%).

Discussion

International and national biomedical informatics professional communities have put forth efforts to address gender-specific issues in career development. Yet, our study identified that some of these, including the deep-rooted gender power hierarchy and bias, are still perceived as profound in AMIA.

Conclusion

Even though existing career development efforts for women are highly effective, important perceived gender-specific career development issues require further attention and investigation to improve existing AMIA activities.
Using Twitter data to understand public perceptions of approved versus off-label use for COVID-19-related medications
Authors: Hua Yining , Jiang Hang , Lin Shixu , Yang Jie , Plasek Joseph M , Bates David W , Zhou Li
Published: July 2022

Objective

Understanding public discourse on emergency use of unproven therapeutics is essential to monitor safe use and combat misinformation. We developed a natural language processing-based pipeline to understand public perceptions of and stances on coronavirus disease 2019 (COVID-19)-related drugs on Twitter across time.

Methods

This retrospective study included 609 189 US-based tweets between January 29, 2020 and November 30, 2021 on 4 drugs that gained wide public attention during the COVID-19 pandemic: (1) Hydroxychloroquine and Ivermectin, drug therapies with anecdotal evidence; and (2) Molnupiravir and Remdesivir, FDA-approved treatment options for eligible patients. Time-trend analysis was used to understand the popularity and related events. Content and demographic analyses were conducted to explore potential rationales of people’s stances on each drug.

Results

Time-trend analysis revealed that Hydroxychloroquine and Ivermectin received much more discussion than Molnupiravir and Remdesivir, particularly during COVID-19 surges. Hydroxychloroquine and Ivermectin were highly politicized, related to conspiracy theories, hearsay, celebrity effects, etc. The distribution of stance between the 2 major US political parties was significantly different (P < .001); Republicans were much more likely to support Hydroxychloroquine (+55%) and Ivermectin (+30%) than Democrats. People with healthcare backgrounds tended to oppose Hydroxychloroquine (+7%) more than the general population; in contrast, the general population was more likely to support Ivermectin (+14%).

Conclusion

Our study found that social media users with have different perceptions and stances on off-label versus FDA-authorized drug use across different stages of COVID-19, indicating that health systems, regulatory agencies, and policymakers should design tailored strategies to monitor and reduce misinformation for promoting safe drug use. Our analysis pipeline and stance detection models are made public at https://github.com/ningkko/COVID-drug.
Increasing vitamin D levels to improve fertilization rates in cattle
Authors: Peixoto de Souza Vanessa , Jensen Jared , Whitler William , Estill Charles T , Bishop Cecily V
Published: July 2022

Recently, interest in supplementing vitamin D (Vit D) to improve aspects of health, mainly in human fertility, has emerged. Still, supplementation of Vit D above the minimum required levels has yet to be explored in cattle despite evidence for Vit D receptors in reproductive tissues. The objective of this study was to establish if a dose–response relationship exists between Vit D exposure and success of in vitro production (IVP) of embryos and, if acute supplementation of Vit D improves pregnancy rates during timed artificial insemination (TAI) of dairy cows. Cumulus-oocyte complexes (COCs) were obtained from ovaries acquired from a local abattoir and cultured in five different IVP treatments from three separate collections (Control, 50, 100, 150, and 200 ng/mL of 1,25(OH)2D3; n = 20–30 COCs/group). In Experiment 2, dairy breed cows (n = 100) were synchronized for TAI with the PresynchOvsynch protocol. Cows received 150,000 IU of Vit D (n = 48) or castor oil as control (n = 53) along with gonadotropin-releasing hormone (GnRH) 24 h before TAI. Serum samples were collected before and 24 h after treatment. A small cohort of cows (n = 4) received the same treatments in two separate cycles and follicular fluid (FF) was collected after 24 h for calcidiol (25OHD) analyses. Increased concentrations of Vit D resulted in decreased rates of maturation of COC (150 and 200 ng/mL vs. control and 50 ng/mL; P = 0.01). Supplementation with 50 ng/mL resulted in greater numbers of early blastocyst and blastocyst stage embryos (P < 0.009). Pregnancy at first breeding did not differ (P = 0.13) between groups, but serum 25OHD increased in treated females after 24 h (P = 0.002). The FF 25OHD levels were reflective of serum levels, however, the observed increase in the treatment cycle (P = 0.04) was parallel to an overall increase in serum 25OHD during the entire second cycle, likely due to increased environmental sunlight exposure (March, control vs. May, treatment). A similar increase in the serum 25OHD in the lactating commercial herd maintained in covered housing was not observed, although experiments were conducted during a similar timeframe. This herd had levels of 25OHD near the low end of sufficiency according to National Research Council (NRC) guidelines. We conclude mild Vitamin D supplementation with concentrations at the higher end of NRC guidelines can improve maturation rates of recovered COCs. However, longer term supplementation may be needed to appreciate any benefits on fertility.
Exploring methods to summarize gut microbiota composition for microbiability estimation and phenotypic prediction in swine
Authors: He Yuqing , Tiezzi Francesco , Jiang Jicai , Howard Jeremy , Huang Yijian , Gray Kent , Choi Jung-Woo , Maltecca Christian
Published: July 2022

The microbial composition resemblance among individuals in a group can be summarized in a square covariance matrix and fitted in linear models. We investigated eight approaches to create the matrix that quantified the resemblance between animals based on the gut microbiota composition. We aimed to compare the performance of different methods in estimating trait microbiability and predicting growth and body composition traits in three pig breeds. This study included 651 purebred boars from either breed: Duroc (n = 205), Landrace (n = 226), and Large White (n = 220). Growth and body composition traits, including body weight (BW), ultrasound backfat thickness (BF), ultrasound loin depth (LD), and ultrasound intramuscular fat (IMF) content, were measured on live animals at the market weight (156 ± 2.5 d of age). Rectal swabs were taken from each animal at 158 ± 4 d of age and subjected to 16S rRNA gene sequencing. Eight methods were used to create the microbial similarity matrices, including 4 kernel functions (Linear Kernel, LK; Polynomial Kernel, PK; Gaussian Kernel, GK; Arc-cosine Kernel with one hidden layer, AK1), 2 dissimilarity methods (Bray-Curtis, BC; Jaccard, JA), and 2 ordination methods (Metric Multidimensional Scaling, MDS; Detrended Correspondence analysis, DCA). Based on the matrix used, microbiability estimates ranged from 0.07 to 0.21 and 0.12 to 0.53 for Duroc, 0.03 to 0.21 and 0.05 to 0.44 for Landrace, and 0.02 to 0.24 and 0.05 to 0.52 for Large White pigs averaged over traits in the model with sire, pen, and microbiome, and model with the only microbiome, respectively. The GK, JA, BC, and AK1 obtained greater microbiability estimates than the remaining methods across traits and breeds. Predictions were made within each breed group using four-fold cross-validation based on the relatedness of sires in each breed group. The prediction accuracy ranged from 0.03 to 0.18 for BW, 0.08 to 0.31 for BF, 0.21 to 0.48 for LD, and 0.04 to 0.16 for IMF when averaged across breeds. The BC, MDS, LK, and JA achieved better accuracy than other methods in most predictions. Overall, the PK and DCA exhibited the worst performance compared to other microbiability estimation and prediction methods. The current study shows how alternative approaches summarized the resemblance of gut microbiota composition among animals and contributed this information to variance component estimation and phenotypic prediction in swine.
Circadian clocks and their integration with metabolic and reproductive systems: our current understanding and its application to the management of dairy cows
Authors: Casey Theresa M , Plaut Karen
Published: July 2022

The circadian system is an inbuilt timekeeping mechanism that tracks the 24-h day through the generation of circadian rhythms. Circadian rhythms enable animals to forecast and anticipate regular changes in their environment, and orchestrate biochemical, physiological and behavioral events so that the right process occurs at the right time. The 24 h rhythms generated by circadian clocks are integrated into homeostatic feedback loops and repair pathways. Metabolic and reproductive systems are highly integrated with the circadian timing system and demonstrate reciprocal regulation. Circadian clocks set the timing of circadian rhythms by gathering temporal information from external and internal signals to include light and nutrients. Exogenous and endogenous factors that function as inputs to the circadian clocks can disrupt their timing when applied at unusual and inappropriate times, and are referred to as chronodisruptors. Changes in the natural light-dark cycle perturb the circadian system. Other chronodisrupters include inappropriately timed food intake and physical activity and biological stress. Knowledge of the biology underlying circadian clock timing is critical to understanding how to maximize health and production efficiency of cattle. Here we review circadian clocks and their function in the regulation of metabolic and reproductive systems as well as the consequence of circadian disruption on mammary development and lactation with a particular focus on recent research findings from studies of dairy cows.
Bone Marrow Stem Cell-Exo-Derived TSG-6 Attenuates 1-Methyl-4-Phenylpyridinium+-Induced Neurotoxicity via the STAT3/miR-7/NEDD4/LRRK2 Axis
Authors: Huang Dezhi , Zhang Mingming , Tan Zhigang
Published: July 2022

Bone marrow mesenchymal stem cell-derived exosome (BMSCs-Exo)-derived TNF-stimulated gene-6 (TSG-6) has anti-inflammatory and antioxidative stress-related properties that may be beneficial in the treatment of Parkinson disease (PD) patients. To elucidate the mechanisms involved, we analyzed the effects of BMSCs-Exo-derived TSG-6 on in vitro models of PD induced with 1-methyl-4-phenylpyridinium (MPP+). TSG-6 was abundant in BMSCs-Exo and it attenuated MPP+-induced neurotoxicity. Moreover, BMSCs-Exo reversed the MPP+-induced toxicity accelerated by neural precursor cells expressed developmentally downregulated 4 (NEDD4) knockdown or miR-7 mimics. Further analysis indicated that NEDD4 combined with leucine-rich repeat kinase 2 (LRRK2) to accelerate ubiquitin degradation of LRRK2. Signal transducer and activator of transcription 3 (STAT3) bound to the miR-7 promoter and miR-7 targeted NEDD4. These data indicate that BMSCs-Exo-derived TSG-6 attenuated neurotoxicity via the STAT3-miR-7-NEDD4 axis. Our results define the specific mechanisms for BMSCs-Exo-derived TSG-6 regulation of MPP+-induced neurotoxicity that are relevant to understanding PD pathogenesis and developing therapies for PD patients.
Diabetes-Related Worries and Coping Among Youth and Young Adults With Type 1 Diabetes
Authors: Taraban Lindsay , Wasserman Rachel , Cao Viena T , Eshtehardi Sahar S , Anderson Barbara J , Thompson Debbe , Marrero David G , Hilliard Marisa E
Published: July 2022

Objective

Although mood and anxiety symptoms are common in youth with type 1 diabetes (T1D), little research has described their worries across developmental stages or the strategies they use to cope with these worries. This secondary data analysis aimed to describe and characterize common T1D-related worries and coping strategies from middle childhood through young adulthood.

Methods

Twenty-three youth (9 children, 7 adolescents, and 7 young adults) completed semistructured qualitative interviews about health-related quality of life. We coded interview transcripts using thematic analysis to generate common themes of diabetes-related worries and coping strategies.

Results

Participants’ worries fell into four major themes: Managing Blood Glucose, Self-Efficacy for Diabetes Management, Interpersonal Relationships, and Lifestyle Impact, and eight youth denied having diabetes-related worries. Coping strategies fell into the three major themes: Attempts to Change Source of Worry, Attempts to Change Reactions to Worry, and Attempts to Orient Away from the Worry.

Conclusions

Youths’ worries about various aspects of living with and feeling able to self-manage diabetes are important to consider across pediatric development as they can impact youths’ participation in daily activities and future plans. By adolescence, youth report longer-term worries about the health and lifestyle implications of diabetes. Youths’ reported coping strategies are generally consistent with existing coping frameworks, though our data suggest some possible refinements. Social support emerged as an important coping strategy for all age groups. Thus, interventions supporting youth in building and strengthening their social networks may be particularly beneficial in helping youth cope with their diabetes-related worries across development.
Individual Differences in Germ Spreading Behaviors Among Children With Attention-Deficit/Hyperactivity Disorder: The Role of Executive Functioning
Authors: Hernandez Melissa L , Spiegel Jamie A , Coxe Stefany , Dick Anthony S , Graziano Paulo A
Published: July 2022

Objective

Infectious diseases, such as coronavirus disease 2019 (COVID-19), are commonly transmitted by respiratory droplets and contact with contaminated surfaces. Individuals with attention-deficit/hyperactivity disorder (ADHD) are more likely to be infected with COVID-19 and experience more hospitalizations than individuals without ADHD. The current study investigated the role of ADHD symptomatology and executive functioning (EF) in germ spreading behavior frequency among young children with and without ADHD and parenting responses to these behaviors.

Methods

Participants included 53 children diagnosed with ADHD and 47 typically developing (TD) children between the ages of 4–5 years (76% male; Mage = 4.62; 86% Hispanic/Latinx). Parents and teachers reported on children’s ADHD symptomatology and children completed three EF tasks. Germ spreading behavior frequency (direct contact of hand to face and toy in mouth) and parenting responses (verbal and nonverbal behaviors) were observed during a 5-min parent–child play situation.

Results

Negative binomial regression analyses indicated that both ADHD diagnostic status and poor metacognition predicted both higher rates of toy to mouth (β = 1.94, p < .001; β = 0.03, p = .004) and face touching frequency (β = 0.60, p = .03; β = 0.03, p = .004), respectively. Additionally, poor attention and worse cognitive flexibility only predicted higher rates of toy to mouth frequency (β = 0.09, p < .001; β = −0.04, p = .001), respectively.

Conclusions

Young children with ADHD are at high risk for spreading germs via putting toys in their mouth and touching their face. Particularly, high levels of inattention and poor EF appear to be associated with higher rates of germ spreading behaviors.
The role of carotenoids as a source of retrograde signals: impact on plant development and stress responses
Authors: Sierra Julio , McQuinn Ryan P , Leon Patricia
Published: July 2022

Communication from plastids to the nucleus via retrograde signal cascades is essential to modulate nuclear gene expression, impacting plant development and environmental responses. Recently, a new class of plastid retrograde signals has emerged, consisting of acyclic and cyclic carotenoids and/or their degradation products, apocarotenoids. Although the biochemical identity of many of the apocarotenoid signals is still under current investigation, the examples described herein demonstrate the central roles that these carotenoid-derived signals play in ensuring plant development and survival. We present recent advances in the discovery of apocarotenoid signals and their role in various plant developmental transitions and environmental stress responses. Moreover, we highlight the emerging data exposing the highly complex signal transduction pathways underlying plastid to nucleus apocarotenoid retrograde signaling cascades. Altogether, this review summarizes the central role of the carotenoid pathway as a major source of retrograde signals in plants.
Incidental Discovery of a Patient with the Bombay Phenotype
Authors: Jacobs Jeremy W , Horstman Erin , Gisriel Savanah D , Tormey Christopher A , Sostin Nataliya
Published: July 2022

Bombay phenotype, an exceptionally rare blood type in individuals outside of Southeast Asia, occurs in approximately 1 in 1,000,000 individuals in Europe. This blood phenotype is characterized by the absence of the H antigen on red blood cells (RBCs) and in secretions. As the H antigen is the structure on which the ABO system is built, individuals lacking this antigen are unable to produce A or B antigens and appear as type O on routine ABO phenotyping. H deficiency does not cause ill effect; however, these individuals produce an anti-H alloantibody capable of causing severe acute hemolytic transfusion reactions when exposed to RBCs that express the H antigen. In this case study, we highlight the incidental discovery of a patient with Bombay phenotype in a North American hospital system, expected test results, the immunologic and genetic basis underlying the Bombay and para-Bombay phenotypes, and methods to ensure availability of compatible blood.
The redshift evolution of extragalactic magnetic fields
Authors: Pomakov V P , O’Sullivan S P , Brüggen M , Vazza F , Carretti E , Heald G H , Horellou C , Shimwell T , Shulevski A , Vernstrom T
Published: July 2022

Faraday rotation studies of distant radio sources can constrain the evolution and the origin of cosmic magnetism. We use data from the LOFAR Two-Metre Sky Survey: Data Release 2 (LoTSS DR2) to study the dependence of the Faraday rotation measure (RM) on redshift. By focusing on radio sources that are close in terms of their projection on the sky, but physically unrelated (‘random pairs’), we measure the RM difference, ΔRM, between the two sources. Thus, we isolate the extragalactic contribution to ΔRM from other contributions. We present a statistical analysis of the resulting sample of random pairs and find a median absolute RM difference |ΔRM| =(1.79 ± 0.09) ${\rm rad\, m}^{-2}$, with |ΔRM| uncorrelated both with respect to the redshift difference of the pair and the redshift of the nearer source, and a median excess of random pairs over physical pairs of (1.65 ± 0.10) ${\rm rad\, m}^{-2}$. We seek to reproduce this result with Monte Carlo simulations assuming a non-vanishing seed cosmological magnetic field and a redshift evolution of the comoving magnetic field strength that varies as (1 + z)−γ. We find the best-fitting results B0 ≡ Bcomoving(z = 0) ≲ (2.0 ± 0.2) nG and γ ≲ 4.5 ± 0.2 that we conservatively quote as upper limits due to an unmodelled but non-vanishing contribution of local environments to the RM difference. A comparison with cosmological simulations shows our results to be incompatible with primordial magnetogenesis scenarios with uniform seed fields of order nG.
Constraints on the magnetic field structure in accreting compact objects from aperiodic variability
Authors: Mönkkönen Juhani , Tsygankov Sergey S , Mushtukov Alexander A , Doroshenko Victor , Suleimanov Valery F , Poutanen Juri
Published: July 2022

We investigate the aperiodic variability for a relatively large sample of accreting neutron stars and intermediate polars, focusing on the properties of the characteristic break commonly observed in power spectra of accreting objects. In particular, we investigate the relation of the break frequency and the magnetic field strength, both of which are connected to the size of the magnetosphere. We find that for the majority of objects in our sample the measured break frequency values indeed agree with estimated inner radii of the accretion disc, which allows to use observed break frequencies to independently assess the magnetic field strength and structure in accreting compact objects. As a special case, we focus on Hercules X-1 which is a persistent, medium-luminosity X-ray pulsar accreting from its low-mass companion. In the literature, it has been suggested that the complex pulse profiles, the spin-up behaviour and the luminosity-correlation of the cyclotron energy seen in Her X-1 can be explained with a complex magnetic field structure of the neutron star. Here, we connect the measured break frequency to the magnetospheric radius and show that the magnetic field strength derived assuming a dipole configuration is nearly an order of magnitude smaller than the magnetic field strength corresponding to the cyclotron energy. Accordingly, this discrepancy can be explained with the magnetic field having strong multipole components. The multipolar structure would also increase the accreting area on the neutron star surface, explaining why the critical luminosity for accretion column formation is puzzlingly high in this source.
Luminosity distribution of Type II supernova progenitors
Authors: Rodríguez Ósmar
Published: July 2022

I present progenitor luminosities (L) for a sample of 112 Type II supernovae (SNe II), computed directly from progenitor photometry and the bolometric correction technique, or indirectly from empirical correlations between progenitor luminosity and [${\rm O\, \small {I}}$] λλ6300, 6364 line luminosity at 350 d since explosion, 56Ni mass, or absolute V-band magnitude at 50 d since explosion. To calibrate these correlations, I use 12 SNe II with progenitor luminosities measured from progenitor photometry. I find that the correlations mentioned above are strong and statistically significant, and allow to estimate progenitor luminosities to a precision between 20 and 24 per cent. I correct the SN sample for selection bias and define a subsample of 112 SNe II with progenitor luminosities between log (L/L⊙) = 4.6 dex, corresponding to the completeness limit of the corrected sample, and the maximum observed progenitor luminosity of log (L/L⊙) = 5.091 dex. The luminosity distribution for this subsample is statistically consistent with those for red supergiants (RSGs) in LMC, SMC, M31, and M33 with 4.6 ≤ log (L/L⊙) ≤ 5.091. This supports that SN II progenitors correspond to RSGs. The conspicuous absence of SN II progenitors with log (L/L⊙) > 5.1 dex with respect to what is observed in RSG luminosity distributions, known as the RSG problem, is significant at a $5.2\pm 0.5\, \sigma$ level.
A combinatorial system to examine the enzymatic repair of multiply damaged DNA substrates
Authors: Hsu Chia Wei , Conrad James W , Sowers Mark L , Baljinnyam Tuvshintugs , Herring Jason L , Hackfeld Linda C , Hatch Sandra S , Sowers Lawrence C
Published: July 2022

DNA damage drives genetic mutations that underlie the development of cancer in humans. Multiple pathways have been described in mammalian cells which can repair this damage. However, most work to date has focused upon single lesions in DNA. We present here a combinatorial system which allows assembly of duplexes containing single or multiple types of damage by ligating together six oligonucleotides containing damaged or modified bases. The combinatorial system has dual fluorescent labels allowing examination of both strands simultaneously, in order to study interactions or competition between different DNA repair pathways. Using this system, we demonstrate how repair of oxidative damage in one DNA strand can convert a mispaired T:G deamination intermediate into a T:A mutation. We also demonstrate that slow repair of a T:G mispair, relative to a U:G mispair, by the human methyl-binding domain 4 DNA glycosylase provides a competitive advantage to competing repair pathways, and could explain why CpG dinucleotides are hotspots for C to T mutations in human tumors. Data is also presented that suggests repair of closely spaced lesions in opposing strands can be repaired by a combination of short and long-patch base excision repair and simultaneous repair of multiply damage sites can potentially lead to lethal double strand breaks.
Molecular insights into the interaction of CAG trinucleotide RNA repeats with nucleolin and its implication in polyglutamine diseases
Authors: An Ying , Chen Zhefan S , Chan Ho Yin Edwin , Ngo Jacky Chi Ki
Published: July 2022

Polyglutamine (polyQ) diseases are a type of inherited neurodegenerative disorders caused by cytosine–adenine–guanine (CAG) trinucleotide expansion within the coding region of the disease-associated genes. We previously demonstrated that a pathogenic interaction between expanded CAG RNA and the nucleolin (NCL) protein triggers the nucleolar stress and neuronal cell death in polyQ diseases. However, mechanisms behind the molecular interaction remain unknown. Here, we report a 1.45 Å crystal structure of the r(CAG)5 oligo that comprises a full A′-form helical turn with widened grooves. Based on this structure, we simulated a model of r(CAG)5 RNA complexed with the RNA recognition motif 2 (RRM2) of NCL and identified NCL residues that are critical for its binding to CAG RNA. Combined with in vitro and in vivo site-directed mutagenesis studies, our model reveals that CAG RNA binds to NCL sites that are not important for other cellular functions like gene expression and rRNA synthesis regulation, indicating that toxic CAG RNA interferes with NCL functions by sequestering it. Accordingly, an NCL mutant that is aberrant in CAG RNA-binding could rescue RNA-induced cytotoxicity effectively. Taken together, our study provides new molecular insights into the pathogenic mechanism of polyQ diseases mediated by NCL–CAG RNA interaction.
StrainXpress: strain aware metagenome assembly from short reads
Authors: Kang Xiongbin , Luo Xiao , Schönhuth Alexander
Published: July 2022

Next-generation sequencing–based metagenomics has enabled to identify microorganisms in characteristic habitats without the need for lengthy cultivation. Importantly, clinically relevant phenomena such as resistance to medication, virulence or interactions with the environment can vary already within species. Therefore, a major current challenge is to reconstruct individual genomes from the sequencing reads at the level of strains, and not just the level of species. However, strains of one species can differ only by minor amounts of variants, which makes it difficult to distinguish them. Despite considerable recent progress, related approaches have remained fragmentary so far. Here, we present StrainXpress, as a comprehensive solution to the problem of strain aware metagenome assembly from next-generation sequencing reads. In experiments, StrainXpress reconstructs strain-specific genomes from metagenomes that involve up to >1000 strains and proves to successfully deal with poorly covered strains. The amount of reconstructed strain-specific sequence exceeds that of the current state-of-the-art approaches by on average 26.75% across all data sets (first quartile: 18.51%, median: 26.60%, third quartile: 35.05%).
The conundrum of the complex relationship between acute kidney injury and cardiac arrhythmias
Authors: Genovesi Simonetta , Regolisti Giuseppe , Burlacu Alexandru , Covic Adrian , Combe Christian , Mitra Sandip , Basile Carlo ,   The EuDial Working Group of ERA, Bartolucci Chiara
Published: July 2022

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine levels, reduced urine output or both. Death may occur in 16–49% of patients admitted to an intensive care unit with severe AKI. Complex arrhythmias are a potentially serious complication in AKI patients with pre-existing or AKI-induced heart damage and myocardial dysfunction, with fluid overload, especially electrolyte and acid–base disorders, representing the pathogenetic mechanisms of arrhythmogenesis. Cardiac arrhythmias, in turn, increase the risk of poor renal outcomes, including AKI. Arrhythmic risk in AKI patients receiving kidney replacement treatment may be reduced by modifying dialysis/replacement fluid composition. The most common arrhythmia observed in AKI patients is atrial fibrillation. Severe hyperkalaemia, sometimes combined with hypocalcaemia, causes severe bradyarrhythmias in this clinical setting. Although the likelihood of life-threatening ventricular arrhythmias is reportedly low, the combination of cardiac ischaemia and specific electrolyte or acid–base abnormalities may increase this risk, particularly in AKI patients who require kidney replacement treatment.

The purpose of this review is to summarize the available epidemiological, pathophysiological and prognostic evidence aiming to clarify the complex relationships between AKI and cardiac arrhythmias.
Lineage-specific positive selection on ACE2 contributes to the genetic susceptibility of COVID-19
Authors: Pan Yuwen , Liu Panhong , Wang Fang , Wu Peng , Cheng Fanjun , Jin Xin , Xu Shuhua
Published: July 2022

The Angiotensin-Converting Enzyme-2 (ACE2) gene, located on Xp22.2, attracts a great deal of attention because the protein it encodes is believed to be the functional cellular receptor for the new coronavirus (SARS-CoV-2). However, recent studies are controversial, especially concerning the intrinsic link between ACE2 diversity and COVID-19 susceptibility. Here, we conduct a population genetic study on ACE2 in 6354 individuals representing 210 present-day populations and 5329 individuals of ancient or archaic groups. We dissected the genetic architecture of ACE2 and identified two major haplogroups (hg) in East Asians, i.e. ACE2-hg1 (43%) and ACE2-hg2 (53%), while other populations harbor more diverse ACE2-hgs. Accordingly, there was a significant loss of ACE2 common variations in East Asians in contrast to the X-chromosome-wide and genome-wide patterns. Notably, association analysis between ACE2-hgs and COVID-19 severity in 1229 Han Chinese individuals with various levels of COVID-19 severity showed a higher risk of ACE2-hg1 (odds ratio = 1.56, P < 0.01) and a lower risk of ACE2-hg2 (odds ratio = 0.65, P < 0.01). Interestingly, ACE2-hg1 is in strong linkage disequilibrium with rs1849863-C, which is an assumed risk factor of elevated plasma ACE2 level and is related to a higher risk of COVID-19 severity, hospitalization and infection. Strikingly, remarkable signatures of positive selection were detected, especially on ACE2-hg2, and were traced back to 100 000 years ago (but rose to a strong level during the Bronze Age, 5000∼3000 years ago, in East Asians). The selection pressures could have stemmed from multiple sources, but pre-COVID-19 viral epidemics and pandemics might have been potential driving forces, which consequently contributed to the genetic susceptibility to COVID-19 within and between populations.
A Missed Opportunity: Extragenital Screening for Gonorrhea and Chlamydia Sexually Transmitted Infections in People With HIV in a Southeastern Ryan White HIV/AIDS Program Clinic Setting
Authors: Geba Maria C , Powers Samuel , Williams Brooke , Dort Kathryn R , Rogawski McQuade Elizabeth T , McManus Kathleen A
Published: July 2022

Background

Guidelines recommend annual screening for gonorrhea/chlamydia in sexually active people with HIV at multiple sites (urogenital, oropharyngeal, rectal). In the first year of multisite screening at our Ryan White HIV/AIDS Program clinic, we studied (1) sexual history documentation rate, (2) sexually transmitted infection (STI) screening rate, (3) characteristics associated with STIs, and (4) the percentage of extragenital STIs that would have been missed without multisite screening.

Methods

Participants were ≥14 years old with ≥1 in-person medical visit at our clinic in 2019. Descriptive analyses were performed, and adjusting for number of sites tested, a log-binomial model was used to estimate the association between characteristics and STI diagnosis in men.

Results

In this cohort (n = 857), 21% had no sexual history recorded. Almost all STI diagnoses were among males (99.3%). Sixty-eight percent (253/375) received appropriate urogenital testing, 63% (85/134) received appropriate oropharyngeal testing, and 69% (72/105) received appropriate rectal testing. In male participants with ≥1 STI test (n = 347), Hispanic ethnicity and having a detectable HIV viral load were associated with an STI diagnosis. Of those diagnosed with an STI who had multisite testing, 96% (n = 25/26) were positive only at an extragenital site.

Conclusions

Screening rates were similar across all anatomical sites, indicating no obvious bias against extragenital testing. In males, STIs were more frequently diagnosed in people who identify as Hispanic and those with detectable viral loads, which may indicate more condomless sex in these populations. Based on infections detected exclusively at extragenital sites, our clinic likely underdiagnosed STIs before implementation of multisite screening.
Radiofrequency Neurotomy Does Not Cause Fatty Degeneration of the Lumbar Paraspinal Musculature in Patients with Chronic Lumbar Pain—A Retrospective 3D-Computer-Assisted MRI Analysis Using iSix Software
Authors: Oswald Katharina A C , Ekengele Venant , Hoppe Sven , Streitberger Konrad , Harnik Michael , Albers Christoph E
Published: July 2022

Objective

The present study aimed (1) to analyze the relative paraspinal autochthonous intramuscular fat volume before and after radiofrequency neurotomy (RFN) and (2) to compare it to the contralateral non-treated side.

Design

Retrospective cohort study.

Setting

Inselspital, University Hospital Bern, University of Bern.

Subjects

Twenty patients (59.60 ± 8.49 years; 55% female) with chronic low back pain, treated with RFN (L2/3—L5/S1) due to symptomatic facet joint syndrome (FCS) between 2008 and 2017 were included.

Methods

All patients received a magnetic resonance imaging (MRI) of the lumbar spine before and at a minimum of 6 months after RFN. The absolute (cm3) and relative (%) paraspinal muscle and fat volume was analyzed three-dimensionally on standard T2–MRI sequences using a newly developed software (iSix, Osiris plugin). Both sides were examined and allocated as treated or non-treated side.

Results

A total of 31 treated and 9 non-treated sides (Level L2/3–L5/S1) were examined. There were no differences in the relative paraspinal intramuscular fat volume before and at a median of 1.4 [0.9 – 2.6] years after RFN (P = .726). We found no differences in the relative fat volume between the treated and non-treated side before (P = .481) and after (P = .578) RFN.

Conclusions

Our study shows that there are no differences in the paraspinal muscle/fat distribution after RFN. RFN of the medial branches for FCS does not seem to cause fatty degeneration of the lumbar paraspinal muscles as a sign of iatrogenic muscle denervation.
Mitigating long queues and waiting times with service resetting
Authors: Bonomo Ofek Lauber , Pal Arnab , Reuveni Shlomi
Published: July 2022

What determines the average length of a queue, which stretches in front of a service station? The answer to this question clearly depends on the average rate at which jobs arrive at the queue and on the average rate of service. Somewhat less obvious is the fact that stochastic fluctuations in service and arrival times are also important, and that these are a major source of backlogs and delays. Strategies that could mitigate fluctuations-induced delays are, thus in high demand as queue structures appear in various natural and man-made systems. Here, we demonstrate that a simple service resetting mechanism can reverse the deleterious effects of large fluctuations in service times, thus turning a marked drawback into a favorable advantage. This happens when stochastic fluctuations are intrinsic to the server, and we show that service resetting can then dramatically cut down average queue lengths and waiting times. Remarkably, this strategy is also useful in extreme situations where the variance, and possibly even mean, of the service time diverge—as resetting can then prevent queues from “blowing up.” We illustrate these results on the M/G/1 queue in which service times are general and arrivals are assumed to be Markovian. However, the main results and conclusions coming from our analysis are not specific to this particular model system. Thus, the results presented herein can be carried over to other queueing systems: in telecommunications, via computing, and all the way to molecular queues that emerge in enzymatic and metabolic cycles of living organisms.
Sustained timber yield claims, considerations, and tradeoffs for selectively logged forests
Authors: Putz Francis E , Romero Claudia , Sist Plinio , Schwartz Gustavo , Thompson Ian , Roopsind Anand , Ruslandi  , Medjibe Vincent , Ellis Peter
Published: July 2022

What is meant by sustainability depends on what is sustained and at what level. Sustainable forest management, for example, requires maintenance of a variety of values not the least of which is sustained timber yields (STYs). For the 1 Bha of the world's forests subjected to selective or partial logging, failure to maintain yields can be hidden by regulatory requirements and questionable auditing practices such as increasing the number of commercial species with each harvest, reducing the minimum size at which trees can be harvested and accepting logs of lower quality. For assertions of STY to be credible, clarity is needed about all these issues, as well as about the associated ecological and economic tradeoffs. Lack of clarity about sustainability heightens risks of unsubstantiated claims and unseen losses. STY is possible but often requires cutting cycles that are longer and logging intensities that are lower than prescribed by law, as well as effective use of low-impact logging practices and application of silvicultural treatments to promote timber stock recovery. These departures from business-as-usual practices will lower profit margins but generally benefit biodiversity and ecosystem services.
Photoinduced isomerization sampling of retinal in bacteriorhodopsin
Authors: Ren Zhong
Published: July 2022

Photoisomerization of retinoids inside a confined protein pocket represents a critical chemical event in many important biological processes from animal vision, nonvisual light effects, to bacterial light sensing and harvesting. Light-driven proton pumping in bacteriorhodopsin entails exquisite electronic and conformational reconfigurations during its photocycle. However, it has been a major challenge to delineate transient molecular events preceding and following the photoisomerization of the retinal from noisy electron density maps when varying populations of intermediates coexist and evolve as a function of time. Here, I report several distinct early photoproducts deconvoluted from the recently observed mixtures in time-resolved serial crystallography. This deconvolution substantially improves the quality of the electron density maps, hence demonstrates that the all-trans retinal undergoes extensive isomerization sampling before it proceeds to the productive 13-cis configuration. Upon light absorption, the chromophore attempts to perform trans-to-cis isomerization at every double bond together with the stalled anti-to-syn rotations at multiple single bonds along its polyene chain. Such isomerization sampling pushes all seven transmembrane helices to bend outward, resulting in a transient expansion of the retinal binding pocket, and later, a contraction due to recoiling. These ultrafast responses observed at the atomic resolution support that the productive photoreaction in bacteriorhodopsin is initiated by light-induced charge separation in the prosthetic chromophore yet governed by stereoselectivity of its protein pocket. The method of a numerical resolution of concurrent events from mixed observations is also generally applicable.
A potent tumor-selective ERK pathway inactivator with high therapeutic index
Authors: Zuo Zehua , Liu Jie , Sun Zhihao , Silverstein Rachel , Zou Meijuan , Finkel Toren , Bugge Thomas H , Leppla Stephen H , Liu Shihui
Published: July 2022

FDA-approved BRAF and MEK small molecule inhibitors have demonstrated some level of efficacy in patients with metastatic melanomas. However, these “targeted” therapeutics have a very low therapeutic index, since these agents affect normal cells, causing undesirable, even fatal, side effects. To address these significant drawbacks, here, we have reengineered the anthrax toxin-based protein delivery system to develop a potent, tumor-selective MEK inactivator. This toxin-based MEK inactivator exhibits potent activity against a wide range of solid tumors, with the highest activity seen when directed toward tumors containing the BRAFV600E mutation. We demonstrate that this reengineered MEK inactivator also exhibits an extremely high therapeutic index (>15), due to its in vitro and in vivo activity being strictly dependent on the expression of multiple tumor-associated factors including tumor-associated proteases matrix metalloproteinase, urokinase plasminogen activator, and anthrax toxin receptor capillary morphogenesis protein-2. Furthermore, we have improved the specificity of this MEK inactivator, restricting its enzymatic activity to only target the ERK pathway, thereby greatly diminishing off-target toxicity. Together, these data suggest that engineered bacterial toxins can be modified to have significant in vitro and in vivo therapeutic effects with high therapeutic index.
“The State is Coming”: The Emotional Content of State Formation through a Colombian Coca Substitution Program
Authors: Diamond Alex
Published: July 2022

How do states achieve popular recognition and symbolic power as “The State,” a collectively recognized entity that serves the common good? While classic work has described the state idea as produced by the actions of state officials, it is ultimately ordinary citizens who must recognize the state as such and consent to its rule. This article, based on 20 months of ethnographic research in a village that, after decades of armed group control, is a key site for the implementation of Colombia’s landmark peace deal, describes how the formation of the state’s symbolic power occurs (or not) through local emotions. I focus on a coca substitution program that has both stoked pre-existing local desires for the promise of the state as carrier of peace and progress and that has, largely because of its outsourcing to different contractors, failed to live up to its commitments, causing economic collapse and generating feelings of betrayal, mistrust, confusion, and impotence. I show how local feelings respond to the regional transformation state formation has caused, popular representations of the state, and their direct interactions with substitution program officials, including non-state actors. I argue that more than simply byproducts of state formation, these emotions are constitutive of the local imaginations of “The State” that are key to the state’s development of symbolic power. It is in the realm of everyday life and emotions, the interplay between local desires for state presence and the frustrations generated by their actual encounters with state power, that state rule is achieved—or not.
Aetiological Profile and Short-Term Neurological Outcome of Haemorrhagic Stroke in Children
Authors: Sharma Sunil , Suthar Renu , Dhawan Sumeet R , Ahuja Chirag Kamal , Bhatia Prateek , Baranwal Arun Kumar , Sankhyan Naveen
Published: July 2022

Background

Haemorrhagic stroke (HS) accounts for nearly half of the paediatric strokes. The aetiology of HS in childhood is not well defined in the Indian context.

Objectives

To study the aetiological profile and short-term neurological outcome of children with HS from North India.

Methods

In a prospective observational study, consecutive patients >28 days to <12 years of age admitted with a diagnosis of HS were enrolled. Demography, clinical, radiological details and investigations were recorded. Short-term outcomes were assessed at three months follow-up with the Paediatric Cerebral Performance Category scale and Paediatric Stroke Outcome Measure (PSOM).

Results

A total of 48 children with HS were enrolled. The median age was 6 months (1–58 months), and 33 (69%) were <2 years old. Vitamin K deficiency-related bleeding disorder (VKDB, 44%), central nervous system infections (19%), arteriovenous malformations (13%) and inherited coagulation disorders (8%) were the most common risk factors for HS. VKDB and inherited coagulation disorders were more frequent in children <2 years of age, and arteriovenous malformations were more frequent in children >2 years of age (p = 0.001). During hospitalization, 21 (44%) children died. Older age, low Glasgow coma score (<8) at admission and paediatric intracerebral haemorrhage score ≥2 were associated with mortality at discharge (p = <0.05). Among survivors, 15 (56%) children had neurological deficits (PSOM >0.5) at three month follow-up.

Conclusion

VKDB, inherited coagulation disorders, central nervous system infections and arteriovenous malformations were the most common risk factors for HS. VKDB is the single most important preventable risk factor for HS in infants.