bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOTSPOT: hierarchical host prediction for assembled plasmid contigs with transformer
Authors: Ji Yongxin , Shang Jiayu , Tang Xubo , Sun Yanni 
Published: April 2023

Abstract

Motivation
As prevalent extrachromosomal replicons in many bacteria, plasmids play an essential role in their hosts’ evolution and adaptation. The host range of a plasmid refers to the taxonomic range of bacteria in which it can replicate and thrive. Understanding host ranges of plasmids sheds light on studying the roles of plasmids in bacterial evolution and adaptation. Metagenomic sequencing has become a major means to obtain new plasmids and derive their hosts. However, host prediction for assembled plasmid contigs still needs to tackle several challenges: different sequence compositions and copy numbers between plasmids and the hosts, high diversity in plasmids, and limited plasmid annotations. Existing tools have not yet achieved an ideal tradeoff between sensitivity and precision on metagenomic assembled contigs.

Results
In this work, we construct a hierarchical classification tool named HOTSPOT, whose backbone is a phylogenetic tree of the bacterial hosts from phylum to species. By incorporating the state-of-the-art language model, Transformer, in each node’s taxon classifier, the top-down tree search achieves an accurate host taxonomy prediction for the input plasmid contigs. We rigorously tested HOTSPOT on multiple datasets, including RefSeq complete plasmids, artificial contigs, simulated metagenomic data, mock metagenomic data, the Hi-C dataset, and the CAMI2 marine dataset. All experiments show that HOTSPOT outperforms other popular methods.

Availability and implementation
The source code of HOTSPOT is available via: https://github.com/Orin-beep/HOTSPOT
DIGGER-Bac: prediction of seed regions for high-fidelity construction of synthetic small RNAs in bacteria
Authors: Philipp Niklas , Brinkmann Cedric K , Georg Jens , Schindler Daniel , Berghoff Bork A 
Published: April 2023

Summary
Synthetic small RNAs (sRNAs) are gaining increasing attention in the field of synthetic biology and bioengineering for efficient post-transcriptional regulation of gene expression. However, the optimal design of synthetic sRNAs is challenging because alterations may impair functions or off-target effects can arise. Here, we introduce DIGGER-Bac, a toolbox for Design and Identification of seed regions for Golden Gate assembly and Expression of synthetic sRNAs in Bacteria. The SEEDling tool predicts optimal sRNA seed regions in combination with user-defined sRNA scaffolds for efficient regulation of specified mRNA targets. Results are passed on to the G-GArden tool, which assists with primer design for high-fidelity Golden Gate assembly of the desired synthetic sRNA constructs.
Smoking is a predictor of complications in all types of surgery: a machine learning-based big data study
Authors: Gräsbeck Helene L , Reito Aleksi R P , Ekroos Heikki J , Aakko Juhani A , Hölsä Olivia , Vasankari Tuula M 
Published: April 2023

Abstract

Background
Machine learning algorithms are promising tools for smoking status classification in big patient data sets. Smoking is a risk factor for postoperative complications in major surgery. Whether this applies to all surgery is unknown. The aims of this retrospective cohort study were to develop a machine learning algorithm for clinical record-based smoking status classification and to determine whether smoking and former smoking predict complications in all surgery types.

Methods
All surgeries performed in a Finnish hospital district from 1 January 2015 to 31 December 2019 were analysed. Exclusion criteria were age below 16 years, unknown smoking status, and unknown ASA class. A machine learning algorithm was developed for smoking status classification. The primary outcome was 90-day overall postoperative complications in all surgeries. Secondary outcomes were 90-day overall complications in specialties with over 10 000 surgeries and critical complications in all surgeries.

Results
The machine learning algorithm had precisions of 0.958 for current smokers, 0.974 for ex-smokers, and 0.95 for never-smokers. The sample included 158 638 surgeries. In adjusted logistic regression analyses, smokers had increased odds of overall complications (odds ratio 1.17; 95 per cent c.i. 1.14 to 1.20) and critical complications (odds ratio 1.21; 95 per cent c.i. 1.14 to 1.29). Corresponding odds ratios of ex-smokers were 1.09 (95 per cent c.i. 1.06 to 1.13) and 1.09 (95 per cent c.i. 1.02 to 1.17). Smokers had increased odds of overall complications in all specialties with over 10 000 surgeries. ASA class was the most important complication predictor.

Conclusion
Machine learning algorithms are feasible for smoking status classification in big surgical data sets. Current and former smoking predict complications in all surgery types.
Cholinergic system correlates of postural control changes in Parkinson’s disease freezers
Authors: Roytman Stiven , Paalanen Rebecca , Griggs Alexis , David Simon , Pongmala Chatkaew , Koeppe Robert A , Scott Peter J H , Marusic Uros , Kanel Prabesh , Bohnen Nicolaas I 
Published: April 2023

Abstract
Postural instability and freezing of gait are the most debilitating dopamine-refractory motor impairments in advanced stages of Parkinson’s disease because of increased risk of falls and poorer quality of life. Recent findings suggest an inability to efficaciously utilize vestibular information during static posturography among people with Parkinson’s disease who exhibit freezing of gait, with associated changes in cholinergic system integrity as assessed by vesicular acetylcholine transporter PET. There is a lack of adequate understanding of how postural control varies as a function of available sensory information in patients with Parkinson’s disease with freezing of gait. The goal of this cross-sectional study was to examine cerebral cholinergic system changes that associate with inter-sensory postural control processing features as assessed by dynamic computerized posturography and acetylcholinesterase PET.
Seventy-five participants with Parkinson’s disease, 16 of whom exhibited freezing of gait, underwent computerized posturography on the NeuroCom© Equitest sensory organization test platform, striatal dopamine, and acetylcholinesterase PET scanning. Findings demonstrated that patients with Parkinson’s disease with freezing of gait have greater difficulty maintaining balance in the absence of reliable proprioceptive cues as compared to those without freezing of gait [β = 0.28 (0.021, 0.54), P = 0.034], an effect that was independent of disease severity [β = 0.16 (0.062, 0.26), P &lt; 0.01] and age [β = 0.092 (−0.005, 0.19), P = 0.062]. Exploratory voxel-based analysis revealed an association between postural control and right hemispheric cholinergic network related to visual-vestibular integration and self-motion perception. High anti-cholinergic burden predicted postural control impairment in a manner dependent on right hemispheric cortical cholinergic integrity [β = 0.34 (0.065, 0.61), P &lt; 0.01].
Our findings advance the perspective that cortical cholinergic system might play a role in supporting postural control after nigro-striatal dopaminergic losses in Parkinson’s disease. Failure of cortex-dependent visual-vestibular integration may impair detection of postural instability in absence of reliable proprioceptive cues. Better understanding of how the cholinergic system plays a role in this process may augur novel treatments and therapeutic interventions to ameliorate debilitating symptoms in patients with advanced Parkinson’s disease.
SARM1 deletion delays cerebellar but not spinal cord degeneration in an enhanced mouse model of SPG7 deficiency
Authors: Montoro-Gámez Carolina , Nolte Hendrik , Molinié Thibaut , Evangelista Giovanna , Tröder Simon E , Barth Esther , Popovic Milica , Trifunovic Aleksandra , Zevnik Branko , Langer Thomas , Rugarli Elena I 
Published: April 2023

Abstract
Hereditary spastic paraplegia is a neurological condition characterized by predominant axonal degeneration in long spinal tracts, leading to weakness and spasticity in the lower limbs. The nicotinamide adenine dinucleotide (NAD+)-consuming enzyme SARM1 has emerged as a key executioner of axonal degeneration upon nerve transection and in some neuropathies. An increase in the nicotinamide mononucleotide/NAD+ ratio activates SARM1, causing catastrophic NAD+ depletion and axonal degeneration. However, the role of SARM1 in the pathogenesis of hereditary spastic paraplegia has not been investigated.
Here, we report an enhanced mouse model for hereditary spastic paraplegia caused by mutations in SPG7. The eSpg7 knockout mouse carries a deletion in both Spg7 and Afg3l1, a redundant homologue expressed in mice but not in humans. The eSpg7 knockout mice recapitulate the phenotypic features of human patients, showing progressive symptoms of spastic-ataxia and degeneration of axons in the spinal cord as well as the cerebellum. We show that the lack of SPG7 rewires the mitochondrial proteome in both tissues, leading to an early onset decrease in mito-ribosomal subunits and a remodelling of mitochondrial solute carriers and transporters.
To interrogate mechanisms leading to axonal degeneration in this mouse model, we explored the involvement of SARM1. Deletion of SARM1 delays the appearance of ataxic signs, rescues mitochondrial swelling and axonal degeneration of cerebellar granule cells and dampens neuroinflammation in the cerebellum. The loss of SARM1 also prevents endoplasmic reticulum abnormalities in long spinal cord axons, but does not halt the degeneration of these axons. Our data thus reveal a neuron-specific interplay between SARM1 and mitochondrial dysfunction caused by lack of SPG7 in hereditary spastic paraplegia.
Palatability profile in spontaneously hypertensive rats
Authors: Pereira Emilson Donizete , De Luca Laurival A , Menani José Vanderlei , Andrade Carina Aparecida Fabrício 
Published: April 2023

Abstract
The spontaneously hypertensive rats (SHRs) have enhanced palatability for NaCl taste as measured by the increased number of hedonic versus aversive responses to intraoral infusion (1 mL/1 min) of 0.3 M NaCl, in a taste reactivity test in euhydrated condition or after 24 h of water deprivation + 2 h of partial rehydration (WD-PR). SHRs also ingested more sucrose than normotensive rats, without differences in quinine hydrochloride intake. Here, we investigated the palatability of SHRs (n = 8–10) and normotensive Holtzman rats (n = 8–10) to sucrose and quinine sulphate infused intraorally in the same conditions that NaCl palatability was increased in SHRs. SHRs had similar number of hedonic responses to 2% sucrose in euhydrated condition (95 ± 19) or after WD-PR (142 ± 25), responses increased when compared with normotensive rats in euhydrated condition (13 ± 3) or after WD-PR (21 ± 6). SHRs also showed increased number of aversive responses to 1.4 mM quinine sulphate compared with normotensive rats, whether in euhydrated condition (86 ± 6, vs. normotensive: 54 ± 7) or after WD-PR (89 ± 9, vs. normotensive: 40 ± 9). The results suggest that similar to NaCl taste, sweet taste responses are increased in SHRs and resistant to challenges in bodily fluid balance. They also showed a more intense aversive response in SHRs to bitter taste compared with normotensives. This suggests that the enhanced response of SHRs to taste rewards does not correspond to a decreased response to a typical aversive taste.
The ERA Registry Annual Report 2020: a summary
Authors: Astley Megan E , Boenink Rianne , Abd ElHafeez Samar , Trujillo-Alemán Sara , Arribas Federico , Åsberg Anders , Beckerman Pazit , Bell Samira , Bouzas-Caamaño María Encarnación , Farnés Jordi Comas , Galvão Ana Amélia , Gjorgjievski Nikola , Kelmendi Vjollca Godanci , Guidotti Rebecca , Helve Jaakko , Idrizi Alma , Indriðason Ólafur S , Ioannou Kyriakos , Kerschbaum Julia , Komissarov Kirill , Castro de la Nuez Pablo , Lassalle Mathilde , Nordio Maurizio , Arévalo Olga Lucía Rodríguez , Santiuste Carmen , Seyahi Nurhan , Roblero María Fernanda Slon , Steenkamp Retha , ten Dam Marc A G J , Zakharova Elena V , Ziginskiene Edita , Bonthuis Marjolein , Stel Vianda S , Ortiz Alberto , Jager Kitty J , Kramer Anneke 
Published: April 2023

ABSTRACT

Background
The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with ESKD. This paper is a summary of the ERA Registry Annual Report 2020, also including comparisons among primary renal disease (PRD) groups.

Methods
Data were collected from 52 national and regional registries from 34 European countries and countries bordering the Mediterranean Sea: 35 registries from 18 countries providing individual level data and 17 registries from 17 countries providing aggregated data. Using this data, KRT incidence and prevalence, kidney transplantation rates, expected remaining lifetimes and survival probabilities were calculated.

Results
A general population of 654.9 million people was covered by the ERA Registry in 2020. The overall incidence of KRT was 128 per million population (p.m.p.). In incident KRT patients, 54% were older than 65 years, 63% were men and the most common PRD was diabetes mellitus (21%). Regarding initial treatment modality in incident patients, 85% received haemodialysis (HD), 11% received peritoneal dialysis (PD) and 4% received a pre-emptive kidney transplant. On 31 December 2020, the prevalence of KRT was 931 p.m.p. In prevalent patients, 45% were older than 65 years, 60% were men and glomerulonephritis was the most common PRD (18%). Of these patients, 58% were on HD, 5% on PD and 37% were living with a kidney transplant. The overall kidney transplantation rate in 2020 was 28 p.m.p., with a majority of kidney grafts from deceased donors (71%). The unadjusted 5-year survival, based on incident dialysis patient from 2011–15, was 41.8%. For patients having received a deceased donor transplant, the unadjusted 5-year survival probability was 86.2% and for patients having received a living donor transplant it was 94.4%. When comparing data by PRD group, differences were found regarding the distribution of age groups, sex and treatment modality received.
Pharmacological strategies to manage hyperkalaemia: out with the old, in with the new? Not so fast…
Authors: Carrero Juan Jesus , Sood Manish M , Gonzalez-Ortiz Ailema , Clase Catherine M 
Published: April 2023

ABSTRACT
Since the 1950s, sodium polystyrene sulphonate (SPS) has been the dominant cation exchange agent prescribed for hyperkalaemia. Clinicians have had plenty of time to learn of SPS's advantages and limitations. The demands of drug regulatory agencies regarding the incorporation of medications into the market were not so stringent then as they are today, and the efficacy and safety of SPS have been questioned. In recent years, two novel cation exchangers, patiromer and sodium zirconium cyclosilicate, have received (or are in the process of receiving) regulatory approval in multiple jurisdictions globally, after scrutiny of carefully conducted trials regarding their short-term and mid-term efficacy. In this debate, we defend the view that all three agents are likely to have similar efficacy. Harms are much better understood for SPS than for newer agents, but currently there are no data to suggest that novel agents are safer than SPS. Drug choices need to consider costs, access and numbers-needed-to-treat to prevent clinically important events; for potassium exchangers, we need trials directly examining clinically important events.
The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison
Authors: Evans Marie , Dai Lu , Avesani Carla Maria , Kublickiene Karolina , Stenvinkel Peter 
Published: April 2023

ABSTRACT
The profile of gut microbiota can vary according to host genetic and dietary characteristics, and be influenced by disease state and environmental stressors. The uremic dysbiosis results in a loss of biodiversity and overgrowth of microorganisms that may cause elevation of metabolic solutes such as trimethylamine N-oxide (TMAO), inducing pathogenic effects on its host. In patients with chronic kidney disease (CKD), TMAO levels are elevated because of a decreased clearance and an increased production from the uremic gut dysbiosis with a disrupted intestinal barrier and elevated enzymatic hepatic activity. Dietary precursors of TMAO are abundant in animal-derived foods such as red meat, egg yolk and other full-fat dietary products. TMAO is also found naturally in fish and certain types of seafood, with the TMAO content highly variable according to the depth of the sea where the fish is caught, as well as processing and storage. Although evidence points towards TMAO as being an important link to vascular damage and adverse cardiovascular outcomes, the evidence in CKD patients has not been consistent. In this review we discuss the potential dietary sources of TMAO and its actions on the intestinal microbiome as an explanation for the divergent results. We further highlight the potential of a healthy diet as one feasible therapeutic opportunity to prevent gut dysbiosis and reduce uremic toxin levels in patients with CKD.
εγ-Thalassemia, a New Hemoglobinopathy Category
Authors: Oliveira Jennifer L , Thompson Christineil H , Saravanaperumal Siva Arumugam , Koganti Tejaswi , Jenkinson Garrett , Hein Molly S , Kohorst Mira A , Hasadsri Linda , Nguyen Phuong L , Matern Dietrich , Kipp Benjamin R , Klee Eric W , Wieben Eric D , Hoyer James D , Rangan Aruna 
Published: April 2023

Abstract

Background
Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely disparate phenotypes, including variable degrees of microcytic anemia and Hb F levels. When present, increased Hb A2 is used as a surrogate marker for β-thalassemia. Notably, ϵγδβ-thalassemias lack the essential regulatory locus control region (LCR) and cause severe transient perinatal anemia but normal newborn screen (NBS) results and Hb A2 levels. Herein, we report a novel deletion of the ϵ, Aγ, Gγ, and ψβ loci with intact LCR, δ-, and β-regions in 2 women and newborn twins.

Methods
Capillary electrophoresis (CE), high-performance liquid chromatography (HPLC), DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), gap-polymerase chain reaction (gap-PCR), and long-read sequencing (LRS) were performed.

Results
NBS showed an Hb A &gt; Hb F pattern for both twins. At 20 months, Hb A2 was increased similarly to that in the mother and an unrelated woman. Unexplained microcytosis was absent and the twins lacked severe neonatal anemia. MLPA, LRS, and gap-PCR confirmed a 32 599 base pair deletion of ϵ (HBE1) through ψβ (HBBP1) loci.

Conclusions
This deletion represents a hemoglobinopathy category with a distinct phenotype that has not been previously described, an ϵγ-thalassemia. Both the NBS Hb A &gt; F pattern and the subsequent increased Hb A2 without microcytosis are unusual. A similar deletion should be considered when this pattern is encountered and appropriate test methods selected for detection. Knowledge of the clinical impact of this new category will improve genetic counselling, with distinction from the severe transient anemia associated with ϵγδβ-thalassemia.
How To Bind A TPM’s Attestation Keys With Its Endorsement Key
Authors: Chen Liqun , El Kassem Nada , Newton Christopher J P 
Published: April 2023

Abstract
A trusted platform module is identified by its endorsement key, while it uses an attestation key to provide attestation services, for example, signing a set of platform configuration registers, providing a timestamp or certifying another of its keys. This paper addresses the problem of how a certificate authority binds the endorsement and attestation keys together. This is necessary for the authority to be able to reliably certify the attestation key. This key binding also enables the authority to revoke the attestation key should the endorsement key be compromised. We study all of the existing solutions and show that they either do not solve the problem or cannot be implemented with a real trusted platform module (or both). We propose a new solution which addresses this problem. We develop a security model for our solution and provide a rigorous security proof under this model. We have also implemented the solution using a real trusted platform module, and our implementation results show that this solution is feasible and efficient.
Decreasing Proof Size of BLS Scheme
Authors: Fang Dong , Huang Guifang , Wang Mengfan , Hu Lei 
Published: April 2023

Abstract
Bootle et al. in CRYPTO 2019 proposed a zero knowledge proof for an $\mathrm{ISIS}_{m,n,q,\beta }$ instance $A\vec{s} = \vec{u} \bmod q$ with $\|\vec{s}\|_{\infty }\leq \beta $ (BLS scheme). It was implemented by transforming the instance into the form $A^{\prime }\vec{s}^{\prime } =\vec{u}\bmod q$, where the coefficients of $\vec{s}^{\prime}$ are in $\{0,1,2\}$, and proved the latter in an exact way. With the concrete parameters $m=1024,n=2048,\beta =1,q\approx 2^{32}$, their proof is of length 384.03KB. In this paper, we decrease the proof size of BLS scheme by two techniques. The first one takes effect on some special parameters. For these parameters, using the binary basic set instead of the ternary one results in a shorter proof. The second one deals with the repetition of the lower half in BLS scheme. Observing that what the lower half proves is of form $\mathbf{B}\vec{\mathbf{r}}=\vec{\mathbf{t}}$ with a short vector $\vec{\mathbf{r}}$ of polynomials, a variant of parallel repetition can be used to shorten the proof size. Combining these two techniques together, the proof size of the above-mentioned instance can be reduced to 220.01KB, only 57.3$\%$ of BLS scheme.
Graph model selection by edge probability prequential inference
Authors: Duvivier Louis , Cazabet Rémy , Robardet Céline 
Published: April 2023

AbstractGraphs are widely used for describing systems made of many interacting components and for understanding the structure of their interactions. Various statistical models exist, which describe this structure as the result of a combination of constraints and randomness. In this article, we introduce edge probability prequential inference, a new approach to perform model selection, which relies on probability distributions on edge ensembles. From a theoretical point of view, we show that this methodology provides a more consistent ground for statistical inference with respect to existing techniques, due to the fact that it relies on multiple realizations of the random variable. It also provides better guarantees against overfitting, by making it possible to lower the number of parameters of the model below the number of observations. Experimentally, we illustrate the benefits of this methodology in two situations: to infer the partition of a stochastic blockmodel and to identify the most relevant model for a given graph between the stochastic blockmodel and the configuration model.