bluuebunny/crossref_metadata_2025_split huggingface dataset:
GENES AFFECTING PRODUCTIVITY IN NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER
Authors: Watanabe Takao K , Ohnishi Seido 
Published: January 2021

ABSTRACT
Two hundred second chromosomes were extracted from a Japanese population in October of 1972, and the viabilities and productivities of homozygotes and heterozygotes from them were examined. Viability was measured by the Cy method and productivity by the number of progeny produced per female. The frequency of lethal-carrying chromosomes was 0.315. When the average heterozygote viability was standardized as 1.000, the average homozygote viability was 0.595 including the lethal lines, and 0.866 excluding them. The frequency of recessive sterile chromosomes among 131 non-lethal lines was 0.092 in females and 0.183 in males. There were two instances in which homozygosis for the second chromosome caused sterility in both sexes, which was close to the number expected (2.2) on a random basis of 0.092 × 0.183 × 131. When the average heterozygote productivity of 200 lines was standardized as 1.000, the average homozygote productivity was 0.532 including female steriles, and 0.584 excluding them. The ratio of detrimental load to lethal load was 0.383, while the ratio of partial sterility load to complete sterility load was 5.767. The average viability of lethal heterozygotes was slightly, but not significantly, lower than that of lethal-free heterozygotes, while the average productivity of lethal heterozygotes was significantly lower than that of lethal-free heterozygotes. There was a significant association of sterility in either sex with low viability of homozygotes. However, no statistically significant differences in viability and productivity were detected between sterile heterozygotes and non-sterile heterozygotes. The heterozygous effects of viability and productivity polygenes were examined by regressions of the heterozygotes on the sum of corresponding homozygotes. The regression coefficients were slightly positive for both viability and productivity if lethal and sterile chromosomes were excluded. The correlation between viability and productivity in homozygotes was significantly positive when sterile chromosomes were included, but the significance disappeared when the sterile chromosomes were excluded. In the heterozygotes there were no detectable correlations between them.
Adaptive learning algorithms to optimize mobile applications for behavioral health: guidelines for design decisions
Authors: Figueroa Caroline A , Aguilera Adrian , Chakraborty Bibhas , Modiri Arghavan , Aggarwal Jai , Deliu Nina , Sarkar Urmimala , Jay Williams Joseph , Lyles Courtney R 
Published: January 2021

AbstractObjectiveProviding behavioral health interventions via smartphones allows these interventions to be adapted to the changing behavior, preferences, and needs of individuals. This can be achieved through reinforcement learning (RL), a sub-area of machine learning. However, many challenges could affect the effectiveness of these algorithms in the real world. We provide guidelines for decision-making.Materials and MethodsUsing thematic analysis, we describe challenges, considerations, and solutions for algorithm design decisions in a collaboration between health services researchers, clinicians, and data scientists. We use the design process of an RL algorithm for a mobile health study “DIAMANTE” for increasing physical activity in underserved patients with diabetes and depression. Over the 1.5-year project, we kept track of the research process using collaborative cloud Google Documents, Whatsapp messenger, and video teleconferencing. We discussed, categorized, and coded critical challenges. We grouped challenges to create thematic topic process domains.ResultsNine challenges emerged, which we divided into 3 major themes: 1. Choosing the model for decision-making, including appropriate contextual and reward variables; 2. Data handling/collection, such as how to deal with missing or incorrect data in real-time; 3. Weighing the algorithm performance vs effectiveness/implementation in real-world settings.ConclusionThe creation of effective behavioral health interventions does not depend only on final algorithm performance. Many decisions in the real world are necessary to formulate the design of problem parameters to which an algorithm is applied. Researchers must document and evaulate these considerations and decisions before and during the intervention period, to increase transparency, accountability, and reproducibility.Trial Registrationclinicaltrials.gov, NCT03490253.
Multivariable Manipulation of Spectrophotometric Data with Genetic Algorithm Selection for Novel Quantitative Resolution of Five Antiviral Drugs in Their Pharmaceutical Products
Authors: Essam Hebatallah M , Morsi Amani M , El-Zeiny Mohammed B 
Published: January 2021

AbstractBackgroundIn many real-world situations there are many components in a mixture that produce an enormous amount of information.ObjectiveThe main task is to build up balanced models that convert these data into meaningful information to deal with. Hence, different chemometric models were applied for the analysis of data obtained from a mixture containing sofosbuvir, ledipasvir, velpatasvir, daclatasvir, and valacyclovir that were recently used internationally for their antiviral activity.MethodsPartial Least Squares, Spectral Residual Augmented Classical Least Squares, and Concentration Residual Augmented Classical Least Squares designs were applied with and without variable selection procedure [Genetic Algorithm (GA)]. The methods were used for the quantitative analysis of the drugs in laboratory prepared mixtures and real market sample through handling the UV spectral data.ResultsRobust models were obtained by applying GA. The proposed methods were found to be rapid, simple, and required no preliminary separation steps.ConclusionThese models can be used on a routine basis in quality control laboratories or factories giving competitor results to those obtained by the reported methods.HighlightsThe proposed models offer a powerful analytical alternative for laboratories that consider economic strategies in their requirements.
Fast autooxidation of a bis-histidyl-ligated globin from the anhydrobiotic tardigrade, Ramazzottius varieornatus, by molecular oxygen
Authors: Kobayashi Kazuo , Kim JeeEun , Fukuda Yohta , Kozawa Takahiro , Inoue Tsuyoshi 
Published: January 2021

Abstract
Tardigrades, a phylum of meiofaunal organisms, exhibit extraordinary tolerance to various environmental conditions, including extreme temperatures (−273 to 151°C) and exposure to ionizing radiation. Proteins from anhydrobiotic tardigrades with homology to known proteins from other organisms are new potential targets for structural genomics. Recently, we reported spectroscopic and structural characterization of a hexacoordinated haemoglobin (Kumaglobin [Kgb]) found in an anhydrobiotic tardigrade. In the absence of its exogenous ligand, Kgb displays hexacoordination with distal and proximal histidines. In this work, we analysed binding of the molecular oxygen ligand following reduction of haem in Kgb using a pulse radiolysis technique. Radiolytically generated hydrated electrons (eaq−) reduced the haem iron of Kgb within 20 µs. Subsequently, ferrous haem reacted with O2 to form a ferrous-dioxygen intermediate with a second-order rate constant of 3.0 × 106 M−1 s−1. The intermediate was rapidly (within 0.1 s) autooxidized to the ferric form. Redox potential measurements revealed an Eʹ0 of −400 mV (vs. standard hydrogen electrode) in the ferric/ferrous couple. Our results suggest that Kgb may serve as a physiological generator of O2▪− via redox signalling and/or electron transfer.
Site-specific differences in survival among upper and lower tract urothelial carcinoma patients treated with radical surgery
Authors: Anno Tadatsugu , Kikuchi Eiji , Shigeta Keisuke , Ogihara Koichiro , Watanabe Keitaro , Yanai Yoshinori , Takamatsu Kimiharu , Hasegawa Shintaro , Masuda Takeshi , Oyama Masafumi , Mizuno Ryuichi , Oya Mototsugu 
Published: January 2021

Abstract

Background
It currently remains unclear whether the location of primary tumours affects the clinical outcomes of patients with locally advanced urothelial carcinoma in the urinary tract. The aim of the present study was to compare prognostic differences between bladder urothelial carcinoma and upper tract urothelial carcinoma, particularly pT3 or higher tumours.

Methods
In total, 307 patients with pT3 or higher urothelial carcinoma without distant metastasis who underwent radical cystectomy for bladder urothelial carcinoma (N = 127, 41.4%) or radical nephroureterectomy for upper tract urothelial carcinoma (N = 180, 58.6%) at Keio University Hospital and three affiliated hospitals between 1994 and 2017 were enrolled. Oncological outcomes were compared between bladder urothelial carcinoma and upper tract urothelial carcinoma using Cox regression analysis.

Results
Significantly higher rates of male patients, smokers, neoadjuvant chemotherapy, lymph node involvement and lymphovascular invasion were observed in the bladder urothelial carcinoma group. The incidence of regional lymph node or local recurrence was higher in patients with bladder urothelial carcinoma than in those with upper tract urothelial carcinoma, while that of lung metastasis was lower. In all patients, bladder urothelial carcinoma was independently associated with disease recurrence (hazard ratio (HR) 1.504, P = 0.035) in addition to neoadjuvant chemotherapy and lymphovascular invasion. Bladder urothelial carcinoma was also independently associated with cancer death (HR = 1.998, P = 0.002) as well as lymphovascular invasion. Following the exclusion of patients who received neoadjuvant chemotherapy, bladder urothelial carcinoma remained an independent risk factor for disease recurrence and cancer death (HR = 1.702, P = 0.010 and HR = 1.888, P = 0.013, respectively).

Conclusions
Bladder urothelial carcinoma may follow worse prognosis compared to upper tract urothelial carcinoma, particularly that with a high pathological stage.
Management and Outcomes in Children with Third-Generation Cephalosporin-Resistant Urinary Tract Infections
Authors: Wang Marie E , Greenhow Tara L , Lee Vivian , Beck Jimmy , Bendel-Stenzel Michael , Hames Nicole , McDaniel Corrie E , King Erin E , Sherry Whitney , Parmar Deepika , Patrizi Sara T , Srinivas Nivedita , Schroeder Alan R 
Published: January 2021

Abstract

Background
Third-generation cephalosporin-resistant urinary tract infections (UTIs) often have limited oral antibiotic options with some children receiving prolonged parenteral courses. Our objectives were to determine predictors of long parenteral therapy and the association between parenteral therapy duration and UTI relapse in children with third-generation cephalosporin-resistant UTIs.

Methods
We conducted a multisite retrospective cohort study of children &lt;18 years presenting to acute care at 5 children’s hospitals and a large managed care organization from 2012 to 2017 with a third-generation cephalosporin-resistant UTI from Escherichia coli or Klebsiella spp. Long parenteral therapy was ≥3 days and short/no parenteral therapy was 0–2 days of concordant parenteral antibiotics. Discordant therapy was antibiotics to which the pathogen was non-susceptible. Relapse was a UTI from the same organism within 30 days.

Results
Of the 482 children included, 81% were female and the median age was 3.3 years (interquartile range: 0.8-8). Fifty-four children (11.2%) received long parenteral therapy (median duration: 7 days). Predictors of long parenteral therapy included age &lt;2 months (adjusted odds ratio [aOR] 67.3; 95% confidence interval [CI]: 16.4-275.7), limited oral antibiotic options (aOR 5.9; 95% CI: 2.8-12.3), and genitourinary abnormalities (aOR 5.4; 95% CI: 1.8-15.9). UTI relapse occurred in 1 of the 54 (1.9%) children treated with long parenteral therapy and in 6 of the 428 (1.5%) children treated with short/no parenteral therapy (P = .57). Of the 105 children treated exclusively with discordant antibiotics, 3 (2.9%, 95% CI: 0.6%-8.1%) experienced UTI relapse.

Conclusions
Long parenteral therapy was associated with age &lt;2 months, limited oral antibiotic options, and genitourinary abnormalities. UTI relapse was rare and not associated with duration of parenteral therapy. For UTIs with limited oral options, further research is needed on the effectiveness of continued discordant therapy.
A systems-level gene regulatory network model for Plasmodium falciparum
Authors: Neal Maxwell L , Wei Ling , Peterson Eliza , Arrieta-Ortiz Mario L , Danziger Samuel A , Baliga Nitin S , Kaushansky Alexis , Aitchison John D 
Published: January 2021

Abstract
Many of the gene regulatory processes of Plasmodium falciparum, the deadliest malaria parasite, remain poorly understood. To develop a comprehensive guide for exploring this organism's gene regulatory network, we generated a systems-level model of P. falciparum gene regulation using a well-validated, machine-learning approach for predicting interactions between transcription regulators and their targets. The resulting network accurately predicts expression levels of transcriptionally coherent gene regulatory programs in independent transcriptomic data sets from parasites collected by different research groups in diverse laboratory and field settings. Thus, our results indicate that our gene regulatory model has predictive power and utility as a hypothesis-generating tool for illuminating clinically relevant gene regulatory mechanisms within P. falciparum. Using the set of regulatory programs we identified, we also investigated correlates of artemisinin resistance based on gene expression coherence. We report that resistance is associated with incoherent expression across many regulatory programs, including those controlling genes associated with erythrocyte-host engagement. These results suggest that parasite populations with reduced artemisinin sensitivity are more transcriptionally heterogenous. This pattern is consistent with a model where the parasite utilizes bet-hedging strategies to diversify the population, rendering a subpopulation more able to navigate drug treatment.
LIG1 syndrome mutations remodel a cooperative network of ligand binding interactions to compromise ligation efficiency
Authors: Jurkiw Thomas J , Tumbale Percy P , Schellenberg Matthew J , Cunningham-Rundles Charlotte , Williams R Scott , O’Brien Patrick J 
Published: January 2021

Abstract
Human DNA ligase I (LIG1) is the main replicative ligase and it also seals DNA breaks to complete DNA repair and recombination pathways. Immune compromised patients harbor hypomorphic LIG1 alleles encoding substitutions of conserved arginine residues, R771W and R641L, that compromise LIG1 activity through poorly defined mechanisms. To understand the molecular basis of LIG1 syndrome mutations, we determined high resolution X-ray structures and performed systematic biochemical characterization of LIG1 mutants using steady-state and pre-steady state kinetic approaches. Our results unveil a cooperative network of plastic DNA-LIG1 interactions that connect DNA substrate engagement with productive binding of Mg2+ cofactors for catalysis. LIG1 syndrome mutations destabilize this network, compromising Mg2+ binding affinity, decreasing ligation efficiency, and leading to elevated abortive ligation that may underlie the disease pathology. These findings provide novel insights into the fundamental mechanism by which DNA ligases engage with a nicked DNA substrate, and they suggest that disease pathology of LIG1 syndrome could be modulated by Mg2+ levels.
A benchmark and an algorithm for detecting germline transposon insertions and measuring de novo transposon insertion frequencies
Authors: Yu Tianxiong , Huang Xiao , Dou Shengqian , Tang Xiaolu , Luo Shiqi , Theurkauf William E , Lu Jian , Weng Zhiping 
Published: January 2021

Abstract
Transposons are genomic parasites, and their new insertions can cause instability and spur the evolution of their host genomes. Rapid accumulation of short-read whole-genome sequencing data provides a great opportunity for studying new transposon insertions and their impacts on the host genome. Although many algorithms are available for detecting transposon insertions, the task remains challenging and existing tools are not designed for identifying de novo insertions. Here, we present a new benchmark fly dataset based on PacBio long-read sequencing and a new method TEMP2 for detecting germline insertions and measuring de novo ‘singleton’ insertion frequencies in eukaryotic genomes. TEMP2 achieves high sensitivity and precision for detecting germline insertions when compared with existing tools using both simulated data in fly and experimental data in fly and human. Furthermore, TEMP2 can accurately assess the frequencies of de novo transposon insertions even with high levels of chimeric reads in simulated datasets; such chimeric reads often occur during the construction of short-read sequencing libraries. By applying TEMP2 to published data on hybrid dysgenic flies inflicted by de-repressed P-elements, we confirmed the continuous new insertions of P-elements in dysgenic offspring before they regain piRNAs for P-element repression. TEMP2 is freely available at Github: https://github.com/weng-lab/TEMP2.
Dietary sodium intake does not alter renal potassium handling and blood pressure in healthy young males
Authors: Pechère-Bertschi Antoinette , Olivier Valérie , Burnier Michel , Udwan Khalil , de Seigneux Sophie , Ponte Belén , Maillard Marc , Martin Pierre-Yves , Feraille Eric 
Published: January 2021

Abstract

Background
The effects of sodium (Na+) intakes on renal handling of potassium (K+) are insufficiently studied.

Methods
We assessed the effect of Na+ on renal K+ handling in 16 healthy males assigned to three 7-day periods on low salt diet [LSD, 3 g sodium chloride (NaCl)/day], normal salt diet (NSD, 6 g NaCl/day) and high salt diet (HSD, 15 g NaCl/day), with constant K+ intake. Contributions of distal NaCl co-transporter and epithelial Na+ channel in the collecting system on K+ and Na+ handling were assessed at steady state by acute response to 100 mg oral hydrochlorothiazide and with addition of 10 mg of amiloride to hydrochlorothiazide, respectively.

Results
Diurnal blood pressure slightly increased from 119.30 ± 7.95 mmHg under LSD to 123.00 ± 7.50 mmHg (P = 0.02) under HSD, while estimated glomerular filtration rate increased from 133.20 ± 34.68 mL/min under LSD to 187.00 ± 49.10 under HSD (P = 0.005). The 24-h K+ excretion remained stable on all Na+ intakes (66.28 ± 19.12 mmol/24 h under LSD; 55.91 ± 21.17 mmol/24 h under NSD; and 66.81 ± 20.72 under HSD, P = 0.9). The hydrochlorothiazide-induced natriuresis was the highest under HSD (30.22 ± 12.53 mmol/h) and the lowest under LSD (15.38 ± 8.94 mmol/h, P = 0.02). Hydrochlorothiazide increased kaliuresis and amiloride decreased kaliuresis similarly on all three diets.

Conclusions
Neither spontaneous nor diuretic-induced K+ excretion was influenced by Na+ intake in healthy male subjects. However, the respective contribution of the distal convoluted tubule and the collecting duct to renal Na+ handling was dependent on dietary Na+ intake.
Who on Earth Can Work from Home?
Authors: Garrote Sanchez Daniel , Gomez Parra Nicolas , Ozden Caglar , Rijkers Bob , Viollaz Mariana , Winkler Hernan 
Published: January 2021

AbstractThis paper reviews the emerging literature on which jobs can be performed from home and presents new estimates of the prevalence of such jobs based on the task content of occupations, their technology requirements and the availability of internet access by country and income groupings. Globally, one of every five jobs can be performed from home. In low-income countries, this ratio drops to one of every 26 jobs. Failing to account for internet access yields upward biased estimates of the resilience of poor countries, lagging regions, and poor workers. Since better paid workers are more likely to be able to work from home, COVID-19 is likely to exacerbate inequality, especially in richer countries where better paid and educated workers are insulated from the shock. The overall labor market burden of COVID-19 is bound to be larger in poor countries, where only a small share of workers can work from home and social protection systems are weaker. Across the globe, young, poorly educated workers and those on temporary contracts are least likely to be able to work from home and more vulnerable to the labor market shocks from COVID-19.
Site-Specific Conjugation of Cell Wall Polyrhamnose to Protein SpyAD Envisioning a Safe Universal Group A Streptococcal Vaccine
Authors: Gao Nina J. , Uchiyama Satoshi , Pill Lucy , Dahesh Samira , Olson Joshua , Bautista Leslie , Maroju Shilpa , Berges Aym , Liu Janet Z. , Zurich Raymond H. , van Sorge Nina M. , Fairman Jeff , Kapoor Neeraj , Nizet Victor 
Published: January 2021

Abstract
Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus (GAS) is a public health priority. The species defining group A cell wall carbohydrate (GAC, Lancefield antigen) can be engineered to remove its immunodominant N-acetylglucosamine (GlcNAc) side chain, implicated in provoking autoimmune cross-reactivity in rheumatic heart disease, leaving its polyrhamnose core (GACPR). Here we generate a novel protein conjugate of the GACPR and test the utility of this conjugate antigen in active immunization. Instead of conjugation to a standard carrier protein, we selected SpyAD, a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen. SpyAD was synthesized using the XpressTM cell-free protein expression system, incorporating a non-natural amino acid to which GACPR was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GACPR conjugates and avoid disruption of important T-cell and B-cell immunological epitopes. The conjugated SpyAD-GACPR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils. Active immunization of mice with a multivalent vaccine consisting of SpyAD-GACPR, together with candidate vaccine antigens streptolysin O and C5a peptidase, protected against GAS challenge in a systemic infection model and localized skin infection model, without evidence of cross reactivity to human heart or brain tissue epitopes. This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.