bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepSom: a CNN-based approach to somatic variant calling in WGS samples without a matched normal
Authors: Vilov Sergey , Heinig Matthias
Published: January 2023

Motivation

Somatic mutations are usually called by analyzing the DNA sequence of a tumor sample in conjunction with a matched normal. However, a matched normal is not always available, for instance, in retrospective analysis or diagnostic settings. For such cases, tumor-only somatic variant calling tools need to be designed. Previously proposed approaches demonstrate inferior performance on whole-genome sequencing (WGS) samples.

Results

We present the convolutional neural network-based approach called DeepSom for detecting somatic single nucleotide polymorphism and short insertion and deletion variants in tumor WGS samples without a matched normal. We validate DeepSom by reporting its performance on five different cancer datasets. We also demonstrate that on WGS samples DeepSom outperforms previously proposed methods for tumor-only somatic variant calling.

Availability and implementation

DeepSom is available as a GitHub repository at https://github.com/heiniglab/DeepSom.

Supplementary information

Supplementary data are available at Bioinformatics online.
MacFrag: segmenting large-scale molecules to obtain diverse fragments with high qualities
Authors: Diao Yanyan , Hu Feng , Shen Zihao , Li Honglin
Published: January 2023

Construction of high-quality fragment libraries by segmenting organic compounds is an important part of the drug discovery paradigm. This article presents a new method, MacFrag, for efficient molecule fragmentation. MacFrag utilized a modified version of BRICS rules to break chemical bonds and introduced an efficient subgraphs extraction algorithm for rapid enumeration of the fragment space. The evaluation results with ChEMBL dataset exhibited that MacFrag was overall faster than BRICS implemented in RDKit and modified molBLOCKS. Meanwhile, the fragments acquired through MacFrag were more compliant with the ‘Rule of Three’.

Availability and implementation

https://github.com/yydiao1025/MacFrag.

Supplementary information

Supplementary data are available at Bioinformatics online.
SAMStat 2: quality control for next generation sequencing data
Authors: Lassmann Timo
Published: January 2023

Motivation

SAMStat is an efficient program to extract quality control metrics from fastq and SAM/BAM files. A distinguishing feature is that it displays sequence composition, base quality composition and mapping error profiles split by mapping quality. This allows users to rapidly identify reasons for poor mapping including the presence of untrimmed adapters or poor sequencing quality at individual read positions.

Results

Here, we present a major update to SAMStat. The new version now supports paired-end and long-read data. Quality control plots are drawn using the ploty javascript library.

Availability and implementation

The source code of SAMStat and code to reproduce the results are found here: https://github.com/timolassmann/samstat.
PDBench: evaluating computational methods for protein-sequence design
Authors: Castorina Leonardo V , Petrenas Rokas , Subr Kartic , Wood Christopher W
Published: January 2023

Ever increasing amounts of protein structure data, combined with advances in machine learning, have led to the rapid proliferation of methods available for protein-sequence design. In order to utilize a design method effectively, it is important to understand the nuances of its performance and how it varies by design target. Here, we present PDBench, a set of proteins and a number of standard tests for assessing the performance of sequence-design methods. PDBench aims to maximize the structural diversity of the benchmark, compared with previous benchmarking sets, in order to provide useful biological insight into the behaviour of sequence-design methods, which is essential for evaluating their performance and practical utility. We believe that these tools are useful for guiding the development of novel sequence design algorithms and will enable users to choose a method that best suits their design target.

Availability and implementation

https://github.com/wells-wood-research/PDBench

Supplementary information

Supplementary data are available at Bioinformatics online.
Mapache: a flexible pipeline to map ancient DNA
Authors: Neuenschwander Samuel , Cruz Dávalos Diana I , Anchieri Lucas , Sousa da Mota Bárbara , Bozzi Davide , Rubinacci Simone , Delaneau Olivier , Rasmussen Simon , Malaspinas Anna-Sapfo
Published: January 2023

We introduce mapache, a flexible, robust and scalable pipeline to map, quantify and impute ancient and present-day DNA in a reproducible way. Mapache is implemented in the workflow manager Snakemake and is optimized for low-space consumption, allowing to efficiently (re)map large datasets—such as reference panels and multiple extracts and libraries per sample — to one or several genomes. Mapache can easily be customized or combined with other Snakemake tools.

Availability and implementation

Mapache is freely available on GitHub (https://github.com/sneuensc/mapache). An extensive manual is provided at https://github.com/sneuensc/mapache/wiki.

Supplementary information

Supplementary data are available at Bioinformatics online.
The association between atopic dermatitis, cognitive function and school performance in children and young adults
Authors: Vittrup Ida , Andersen Yuki M F , Skov Lone , Wu Jashin J , Agner Tove , Thomsen Simon F   , Egeberg Alexander , Thyssen Jacob P
Published: January 2023

Background

Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school.

Objectives

To examine the association between hospital-managed paediatric AD, school performance and cognitive function.

Methods

In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription.

Results

In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference −0.29 [95% confidence interval (CI) −0.45 to −0.13, P < 0.001], difference −0.26 (95% CI −0.42 to −0.10, P = 0.0016) and difference −0.30 (95% CI −0.49 to −0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference −0.60 (95% CI −0.87 to −0.32, P < 0.001).

Conclusions

AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.
Past climate changes and geographical barriers: the evolutionary history of a subtropical highland grassland species of Solanaceae,Petunia altiplana
Authors: Soares Luana S , Fagundes Nelson J R , Freitas Loreta B
Published: January 2023

Climate changes and associated glacial and interglacial cycles during the Quaternary strongly influenced the evolutionary history of countless number of species. Subtropical highland grasslands (SHG) in southern South America constitute a distinct vegetation type with high diversity and endemism rates. The most recent common ancestor of the genus Petunia (Solanaceae) originated in lowland grasslands, and some lineages secondarily migrated to SHG. Here, we describe the evolutionary history of an SHG species, P. altiplana, distributed throughout a wide area in a river-fragmented landscape. We used plastid and nuclear markers to evaluate the role of the Pelotas River and Quaternary climate cycles over the genetic structure and historical demography of this species based on a phylogeographical approach. We found moderate population expansions during the last 25 kyr, with a more recent (c. 1.6 kya) divergence between two groups of populations from opposite river margins, possibly caused by the expansion of the Araucaria Forest along the river valley, effectively isolating distinct grassland patches.
Auditory stimulation and deep learning predict awakening from coma after cardiac arrest
Authors: Aellen Florence M , Alnes Sigurd L , Loosli Fabian , Rossetti Andrea O , Zubler Frédéric , De Lucia Marzia , Tzovara Athina
Published: January 2023

Assessing the integrity of neural functions in coma after cardiac arrest remains an open challenge. Prognostication of coma outcome relies mainly on visual expert scoring of physiological signals, which is prone to subjectivity and leaves a considerable number of patients in a ‘grey zone’, with uncertain prognosis. Quantitative analysis of EEG responses to auditory stimuli can provide a window into neural functions in coma and information about patients’ chances of awakening. However, responses to standardized auditory stimulation are far from being used in a clinical routine due to heterogeneous and cumbersome protocols. Here, we hypothesize that convolutional neural networks can assist in extracting interpretable patterns of EEG responses to auditory stimuli during the first day of coma that are predictive of patients’ chances of awakening and survival at 3 months. We used convolutional neural networks (CNNs) to model single-trial EEG responses to auditory stimuli in the first day of coma, under standardized sedation and targeted temperature management, in a multicentre and multiprotocol patient cohort and predict outcome at 3 months. The use of CNNs resulted in a positive predictive power for predicting awakening of 0.83 ± 0.04 and 0.81 ± 0.06 and an area under the curve in predicting outcome of 0.69 ± 0.05 and 0.70 ± 0.05, for patients undergoing therapeutic hypothermia and normothermia, respectively. These results also persisted in a subset of patients that were in a clinical ‘grey zone’. The network’s confidence in predicting outcome was based on interpretable features: it strongly correlated to the neural synchrony and complexity of EEG responses and was modulated by independent clinical evaluations, such as the EEG reactivity, background burst-suppression or motor responses. Our results highlight the strong potential of interpretable deep learning algorithms in combination with auditory stimulation to improve prognostication of coma outcome.
Rehabilitation enhances epothilone-induced locomotor recovery after spinal cord injury
Authors: Griffin Jarred M , Hingorani Jai Prakash Sonia , Bockemühl Till , Benner Jessica M , Schaffran Barbara , Moreno-Manzano Victoria , Büschges Ansgar , Bradke Frank
Published: January 2023

Microtubule stabilization through epothilones is a promising preclinical therapy for functional recovery following spinal cord injury that stimulates axon regeneration, reduces growth-inhibitory molecule deposition and promotes functional improvements. Rehabilitation therapy is the only clinically validated approach to promote functional improvements following spinal cord injury. However, whether microtubule stabilization can augment the beneficial effects of rehabilitation therapy or act in concert with it to further promote repair remains unknown. Here, we investigated the pharmacokinetic, histological and functional efficacies of epothilone D, epothilone B and ixabepilone alone or in combination with rehabilitation following a moderate contusive spinal cord injury. Pharmacokinetic analysis revealed that ixabepilone only weakly crossed the blood–brain barrier and was subsequently excluded from further investigations. In contrast, epothilones B and D rapidly distributed to CNS compartments displaying similar profiles after either subcutaneous or intraperitoneal injections. Following injury and subcutaneous administration of epothilone B or D, rats were subjected to 7 weeks of sequential bipedal and quadrupedal training. For all outcome measures, epothilone B was efficacious compared with epothilone D. Specifically, epothilone B decreased fibrotic scaring which was associated with a retention of fibronectin localized to perivascular cells in sections distal to the lesion. This corresponded to a decreased number of cells present within the intralesional space, resulting in less axons within the lesion. Instead, epothilone B increased serotonergic fibre regeneration and vesicular glutamate transporter 1 expression caudal to the lesion, which was not affected by rehabilitation. Multiparametric behavioural analyses consisting of open-field locomotor scoring, horizontal ladder, catwalk gait analysis and hindlimb kinematics revealed that rehabilitation and epothilone B both improved several aspects of locomotion. Specifically, rehabilitation improved open-field locomotor and ladder scores, as well as improving the gait parameters of limb coupling, limb support, stride length and limb speed; epothilone B improved these same gait parameters but also hindlimb kinematic profiles. Functional improvements by epothilone B and rehabilitation acted complementarily on gait parameters leading to an enhanced recovery in the combination group. As a result, principal component analysis of gait showed the greatest improvement in the epothilone B plus rehabilitation group. Thus, these results support the combination of epothilone B with rehabilitation in a clinical setting.
Machine learning for prediction of all-cause mortality after transcatheter aortic valve implantation
Authors: Kwiecinski Jacek , Dabrowski Maciej , Nombela-Franco Luis , Grodecki Kajetan , Pieszko Konrad , Chmielak Zbigniew , Pylko Anna , Hennessey Breda , Kalinczuk Lukasz , Tirado-Conte Gabriela , Rymuza Bartosz , Kochman Janusz , Opolski Maksymilian P , Huczek Zenon , Dweck Marc R , Dey Damini , Jimenez-Quevedo Pilar , Slomka Piotr , Witkowski Adam
Published: January 2023

Aims

Prediction of adverse events in mid-term follow-up after transcatheter aortic valve implantation (TAVI) is challenging. We sought to develop and validate a machine learning model for prediction of 1-year all-cause mortality in patients who underwent TAVI and were discharged following the index procedure.

Methods and results

The model was developed on data of patients who underwent TAVI at a high-volume centre between January 2013 and March 2019. Machine learning by extreme gradient boosting was trained and tested with repeated 10-fold hold-out testing using 34 pre- and 25 peri-procedural clinical variables. External validation was performed on unseen data from two other independent high-volume TAVI centres. Six hundred four patients (43% men, 81 ± 5 years old, EuroSCORE II 4.8 [3.0–6.3]%) in the derivation and 823 patients (46% men, 82 ± 5 years old, EuroSCORE II 4.7 [2.9–6.0]%) in the validation cohort underwent TAVI and were discharged home following the index procedure. Over the 12 months of follow-up, 68 (11%) and 95 (12%) subjects died in the derivation and validation cohorts, respectively. In external validation, the machine learning model had an area under the receiver-operator curve of 0.82 (0.78–0.87) for prediction of 1-year all-cause mortality following hospital discharge after TAVI, which was superior to pre- and peri-procedural clinical variables including age 0.52 (0.46–0.59) and the EuroSCORE II 0.57 (0.51–0.64), P < 0.001 for a difference.

Conclusion

Machine learning based on readily available clinical data allows accurate prediction of 1-year all-cause mortality following a successful TAVI.
Decoupling of height growth and drought or pest resistance tradeoffs is revealed through multiple common-garden experiments of lodgepole pine
Authors: Liu Yang , Erbilgin Nadir , Cappa Eduardo Pablo , Chen Charles , Ratcliffe Blaise , Wei Xiaojing , Klutsch Jennifer G , Ullah Aziz , Azcona Jaime Sebastian , Thomas Barb R , El-Kassaby Yousry A
Published: January 2023

The environment could alter growth and resistance tradeoffs in plants by affecting the ratio of resource allocation to various competing traits. Yet, how and why functional tradeoffs change over time and space is poorly understood particularly in long-lived conifer species. By establishing four common-garden test sites for five lodgepole pine populations in western Canada, combined with genomic sequencing, we revealed the decoupling pattern and genetic underpinnings of tradeoffs between height growth, drought resistance based on δ13C and dendrochronology, and metrics of pest resistance based on pest suitability ratings. Height and δ13C correlation displayed a gradient change in magnitude and/or direction along warm-to-cold test sites. All cold test sites across populations showed a positive height and δ13C relationship. However, we did not observe such a clinal correlation pattern between height or δ13C and pest suitability. Further, we found that the study populations exhibiting functional tradeoffs or synergies to various degrees in test sites were driven by non-adaptive evolutionary processes rather than adaptive evolution or plasticity. Finally, we found positive genetic relationships between height and drought or pest resistance metrics and probed five loci showing potential genetic tradeoffs between northernmost and the other populations. Our findings have implications for deciphering the ecological, evolutionary, and genetic bases of the decoupling of functional tradeoffs due to environmental change.
Can we ignore trait-dependent colonization and diversification in island biogeography?
Authors: Xie Shu , Valente Luis , Etienne Rampal S
Published: January 2023

The application of state-dependent speciation and extinction models to phylogenetic trees has shown an important role for traits in diversification. However, this role remains comparatively unexplored on islands, which can include multiple independent clades resulting from different colonization events. To explore whether assuming no dependence on traits leads to bias in inference on island dynamics, we extend an island biodiversity model, DAISIE (Dynamic Assembly of Islands through Speciation, Immigration, and Extinction) to include trait-dependent diversification simulations, and evaluate the robustness of the inference model which ignores this trait-dependence. Our results indicate that when the differences between colonization, extinction, and speciation rates between trait states are moderate, the model shows negligible error for a variety of island diversity metrics, suggesting that island diversity dynamics can be accurately estimated without the need to explicitly model trait dependence. We conclude that for many biologically realistic scenarios with trait-dependent diversification and colonization, this simple trait-less inference model is informative and robust to trait effects on colonization, speciation, and extinction. Nonetheless, our new simulation model may provide a useful tool for studying patterns of trait variation.
A forensic case of hydranencephaly in a preterm neonate fully documented by postmortem imaging techniques
Authors: Egger Coraline , Dédouit Fabrice , Schrag Bettina , Hanquinet Sylviane , Fracasso Tony
Published: January 2023

The authors present a medico-legal autopsy case of hydranencephaly in a male preterm newborn, fully documented by postmortem unenhanced and enhanced imaging techniques (postmortem computed tomography and postmortem magnetic resonance imaging). Hydranencephaly is a congenital anomaly of the central nervous system, consisting in almost complete absence of the cerebral hemispheres and replacement of the cerebral parenchyma by cerebrospinal fluid, rarely encountered in forensic medical practice. A premature baby was born during the supposed 22nd and 24th week of pregnancy in the context of a denial of pregnancy without any follow-up. The newborn died a few hours after birth and medico-legal investigations were requested to determine the cause of death and exclude the intervention of a third person in the lethal process. The external examination revealed neither traumatic nor malformative lesions. Postmortem imaging investigations were typical of hydranencephaly, and conventional medico-legal autopsy, neuropathological examination, and histological examination confirmed a massive necrotic-haemorrhagic hydranencephaly. This case represents in itself an association of out-of-the-ordinary elements making it worthy of interest.

Key Points
A combinatorial DNA assembly approach to biosynthesis ofN-linked glycans inE. coli
Authors: Passmore Ian J , Faulds-Pain Alexandra , Abouelhadid Sherif , Harrison Mark A , Hall Catherine L , Hitchen Paul , Dell Anne , Heap John T , Wren Brendan W
Published: January 2023

Glycoengineering of recombinant glycans and glycoconjugates is a rapidly evolving field. However, the production and exploitation of glycans has lagged behind that of proteins and nucleic acids. Biosynthetic glycoconjugate production requires the coordinated cooperation of three key components within a bacterial cell: a substrate protein, a coupling oligosaccharyltransferase, and a glycan biosynthesis locus. While the acceptor protein and oligosaccharyltransferase are the products of single genes, the glycan is a product of a multigene metabolic pathway. Typically, the glycan biosynthesis locus is cloned and transferred en bloc from the native organism to a suitable Escherichia coli strain. However, gene expression within these pathways has been optimized by natural selection in the native host and is unlikely to be optimal for heterologous production in an unrelated organism. In recent years, synthetic biology has addressed the challenges in heterologous expression of multigene systems by deconstructing these pathways and rebuilding them from the bottom up. The use of DNA assembly methods allows the convenient assembly of such pathways by combining defined parts with the requisite coding sequences in a single step. In this study, we apply combinatorial assembly to the heterologous biosynthesis of the Campylobacter jejuni  N-glycosylation (pgl) pathway in E. coli. We engineered reconstructed biosynthesis clusters that faithfully reproduced the C. jejuni heptasaccharide glycan. Furthermore, following a single round of combinatorial assembly and screening, we identified pathway clones that outperform glycan and glycoconjugate production of the native unmodified pgl cluster. This platform offers a flexible method for optimal engineering of glycan structures in E. coli.
Sustained Diet-Induced Remission in Pediatric Crohn’s Disease Is Associated With Kynurenine and Serotonin Pathways
Authors: Ghiboub Mohammed , Boneh Rotem Sigall , Sovran Bruno , Wine Eytan , Lefèvre Antoine , Emond Patrick , Verburgt Charlotte M , Benninga Marc A , de Jonge Wouter J , Van Limbergen Johan E
Published: January 2023

Background

Both the Crohn’s disease exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) can induce remission in mild-to-moderate pediatric Crohn’s disease and are associated with a marked decrease in fecal kynurenine levels. This suggests a link between clinical outcome of dietary therapy and changes in tryptophan metabolism pathways. Here, we characterize the changes in several fecal tryptophan metabolites induced by CDED+PEN or EEN and their association with remission.

Methods

A total of 21 tryptophan metabolites were quantified in fecal samples from a 12-week prospective randomized trial with CDED+PEN or EEN for induction of remission in mild to moderate pediatric Crohn’s disease. Tryptophan metabolites at week 0 (W0), W6, and W12 of 73 samples were quantitatively measured by liquid chromatography coupled with triple quadrupole mass spectrometry, and data were analyzed according to clinical groups of baselines (W0), induced remission at W6, no remission, sustained remission at W12, and nonsustained remission.

Results

Reduction in components of the kynurenine pathway, such as kynurenine and quinolinic acid, were strongly associated with induced remission with both CDED+PEN and EEN, which were maintained in sustained remission. Specific serotonin pathway metabolites, such as melatonin, N-acetylserotonin, and 5-OH-tryptophan, were significantly increased in fecal samples from patients maintaining remission at W12 with both CDED+PEN and EEN. Importantly, in samples from patients failing to sustain remission, no changes were observed. Remission induction with EEN differs from CDED+PEN, particularly the moderate effects on indole pathway metabolites. The ratios of kynurenine and melatonin and quinolinic acid and melatonin perform well as markers for sustained remission.

Conclusions

The reduction in specific kynurenine pathway compounds and the increase in serotonin pathway compounds are associated with diet-induced and sustained remission. Further studies are warranted to assess causality and the association of these metabolites with specific diet and lifestyle factors, affecting sustained clinical remission.
Sovereign debt default and inequality
Authors: Apeti Ablam Estel
Published: January 2023

Based on a sample of 124 developing countries over the period 1980–2016, we find that default increases inequality. This result, which passes a series of robustness tests, is sensitive to the size of the debt in default, the duration of the default episode, the institutional quality, the level of development, and the type of default (on external or domestic debt) and may persist until 5 years after the end of the default episode. Besides, the declines in redistributive capacity characterized by lower taxes and subsidies and social spending are identified as channels through which default increases inequality in default countries vis-à-vis nondefault countries. Finally, additional results show that default also raises wealth inequality.
Thoracic endovascular aortic repair with collateral vessels from the femoral artery to Adamkiewicz’s artery
Authors: Noda Kazuki , Seike Yoshimasa , Nishii Tatsuya , Matsuda Hitoshi
Published: January 2023

Identification of the Adamkiewicz’s artery (AKA) prior to the operation is one of the spinal cord ischaemia preventive measures. A 75-year-old man presented with the rapid expansion of thoracic aortic aneurysm. Collateral vessels from the right common femoral artery to the AKA were observed on preoperative computed tomography angiography. The stent graft was successfully deployed through the contralateral side via a pararectal laparotomy to avoid collateral vessel injury supplying the AKA. This case highlights the significance of preoperative identification of collateral vessels to the AKA.
Rising Gold Prices but Lower Incomes for Gold Miners: Evidence on Market Imperfections from Burkina Faso during COVID-19
Authors: van der Merwe Antoinette , Brugger Fritz , Günther Isabel
Published: January 2023

Although artisanal gold mining is known for human rights violations and environmental degradation, it is an increasingly important economic activity in many African countries, with a high potential to alleviate poverty. Due to increased demand for gold investment during the COVID-19 pandemic, the monthly international gold price has increased by 20% from January to May 2020. To understand how the COVID-19 pandemic has influenced gold miners, we analyse a panel survey of about 170 artisanal gold miners interviewed 2 months before the first case of COVID-19 in Burkina Faso. Follow-up surveys were done early in the pandemic and about 1 year after baseline. Various pre-existing local market failures caused local gold prices to decrease by 20%–30% from January to May 2020, when international gold prices noticeably increased. Market failures include oligopsonistic market conditions on the mines, which worsened due to travel restrictions that disrupted trading routes, reduced local traders' liquidity and made it difficult for traders to reach mines. Moreover, we find that miners have very little knowledge of international gold prices, and due to insecurity and credit constraints, they are unable to wait for local prices to recover. Once travel restrictions were lifted, the local gold price recovered close to the global gold price. To make local markets more competitive and ensure that miners benefit from rising international gold prices, governments could broadcast world gold prices on local radio, increase trading opportunities and provide access to credits for miners.
Utilization of feather keratin waste to antioxidant and migration-enhancer peptides byBacillus licheniformis8-4
Authors: Pei Xiao-Dong , Li Fan , Gao Tian-Tian , Su Lin-Ying , Yu Fu-Tian , Shi Ping , Liu Chen-Xing , Wang Cheng-Hua
Published: January 2023

Aims

Feathers are keratin-rich byproducts of poultry processing, but those are often frequently abandoned as garbage and thus polluting the environment. Therefore, the study focused on the efficient biodegradation, bioactivity, and high-value application of feather keratin.

Methods and results

Feather-degrading bacteria were identified, and the degradation properties were characterized. DPPH (1,1-Diphenyl-2-picrylhydrazyl radical) and ABTS (2,2′-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid))radical scavenging assays, cytotoxicity assays, intracellular reactive oxygen scavenging assays, and cell migration assays were used to examine the biological activities of the feather keratin hydrolysis peptides (FKHPs). The results showed that we screened a feather-degrading strain of Bacillus licheniformis 8-4, which achieved complete degradation of 2% (w/v) feathers within 48 h. Notably, the feather fermentation broth was particularly high in FKHPs, which exhibited good DPPH and ABTS radical scavenging ability. Further studies revealed that FKHPs had both the ability to scavenge H2O2-induced ROS from HaCat cells and the ability to promote HaCat cell migration, while remaining non-toxic.

Conclusions

The effective feather-degrading ability of B. licheniformis 8-4 allowed for the fermentation of feather medium to yield active peptides that were both antioxidants and cell-migration enhancers.
Feeding aSaccharomyces cerevisiaefermentation product before and during a feed restriction challenge on milk production, plasma biomarkers, and immune function in Holstein cows
Authors: Coleman Danielle N , Jiang Qianming , Lopes Matheus G , Ritt Luciano , Liang Yusheng , Aboragah Ahmad , Trevisi Erminio , Yoon Ilkyu , Loor Juan J
Published: January 2023

Periods of decreased feed intake may disrupt function of the intestinal barrier. Feeding NutriTek® (NTK; Diamond V, Cedar Rapids, IA), a postbiotic from S. cerevisiae fermentation (SCFP), improved health and supported anti-inflammatory functions. We investigated the effects of feeding NTK to cows before and during a period of feed restriction (FR) designed to model periods of intestinal barrier dysfunction. In total, 16 multiparous cows (97.1 ± 7.6 DIM; n = 8/group) were fed a control diet (CON) or CON plus 19 g/d NTK for 9 wk (Phase 1; P1) and then were subjected to an FR challenge for 5 d, during which they were fed 40% of their ad libitum intake from the 7 d prior to FR. Milk yield (MY) and DMI were collected daily. During FR, milk was collected daily for composition, blood daily to measure plasma biomarkers and to measure monocyte and neutrophil phagocytosis and oxidative burst on d 1, 3, and 5. Data were analyzed using a mixed model in SAS 9.4. All data were subjected to repeated measures ANOVA. Dietary treatment (TRT), Day, and their interaction (TRT × Day) were considered as fixed effects and cow as the random effect. For analysis of P1, data collected during a 7-d adaptation phase were used as a covariate. During P1, NTK cows tended to have greater DMI and had greater fat, ECM and FCM yields, and feed efficiency (ECM/DMI and FCM/DMI). Protein yield tended to be greater in NTK compared with CON cows. A tendency for greater monocyte phagocytosis was detected with NTK. However, during FR, feeding NTK led to lower MY and lactose yield and tended to lower solids percentage. While NTK cows tended to have reduced neutrophil oxidative burst than CON cows during FR (NTK: 26.20%, CON: 36.93%), there was no difference in phagocytosis (NTK: 7.92%, CON: 6.31%). Plasma biomarkers of energy metabolism, liver function, inflammation, and oxidative stress during the FR period did not differ. Overall, results suggested that feeding NTK increased the yield of FCM, ECM, feed efficiency and milk components prior to FR.
Soluble corn fiber, resistant corn starch, and protected butyrate effects on performance, gastrointestinal volatile fatty acids, and apparent total-tract digestibility of calcium and phosphorus in nursery pigs
Authors: Kerr Brian J , Pearce Sarah C , Ramirez Shelby M , Schweer Wesley P , Gabler Nicholas K
Published: January 2023

An experiment was conducted to determine how feeding calcium (Ca)-deficient diet would affect gastrointestinal pH and volatile fatty acids (VFAs), Ca digestibility, bone mineral density (BMD), and performance in nursery pigs; and if supplementation of nondigestible oligosaccharides would affect these same parameters. In total, 240 weaned pigs (BW = 7.1 kg) were placed into 80 pens with 3 pigs/pen. The eight dietary treatments consisted of: 1) positive control (PC, 0.83% total Ca), 2) negative control (NC, 0.50% total Ca), 3 and 4) NC + 5% or 7.5% soluble corn fiber (SCF), 5 and 6) NC + 5% or 7.5% resistant corn starch (rCS), 7 and 8) NC + 0.25% or 0.50% fat-protected butyrate (pBRT). Pigs were ad libitum fed the dietary treatments for 21 d to determine average daily gain (ADG), average daily feed intake (ADFI) and gain:feed ratio (GF) with a fecal sample collected from each pen to determine Ca digestibility using acid insoluble ash as the dietary marker, with 1 pig/pen euthanized on d 21 for collection of ileal and colon contents and the left humerus. Pigs fed the NC diet had a lower colonic pH compared with pigs fed the PC (P = 0.06) but no effect on total VFA was observed (P > 0.10). Pigs fed diets containing SCF and rCS had lower colonic pH and total VFA compared to pigs fed the NC diet (P ≤ 0.05). Pigs fed diets containing pBRT had greater colonic total VFA compared to pigs fed the NC diet (P ≤ 0.07), but no difference in colonic pH was observed (P > 0.10). Pigs fed the NC diet had a greater Ca digestibility compared to pigs fed the PC (P ≤ 0.01), with no treatment to the NC having any effect on Ca digestibility compared to pigs fed the NC (P > 0.10). There was no effect of dietary Ca level on BMD and no overall addition of feeding SCF, rCS, or pBRT on BMD compared to pigs fed the NC (P > 0.10). There was no impact on pig ADG, ADFI, or GF by reducing dietary Ca by 40% (i.e., pigs fed the NC) compared to pigs fed the PC (P > 0.10). Relative to pigs fed the NC, there was no overall effect of SCF, rCS, or pBRT on ADG, ADFI, or GF (P > 0.10). In conclusion, feeding young pigs a Ca-deficient diet reduced colonic pH, increased digestibility of Ca, but had no impact on bone mineralization or overall pig performance. Supplementation of nondigestible oligosaccharides pr protected butyrate had either no effect or an inconsistent effect on colonic pH, Ca, or PHOS digestibility, bone mineralization, or overall pig performance.
Effect of physically effective neutral detergent fiber and undigested neutral detergent fiber on eating behavior, ruminal fermentation and motility, barrier function, blood metabolites, and total tract digestibility in finishing cattle
Authors: Pereira Murillo Ceola Stefano , Beauchemin Karen A , McAllister Tim A , Yang Wenzhu Z , Wood Katharine M , Penner Gregory Brent
Published: January 2023

This study evaluated the effects of physically effective neutral detergent fiber (peNDF) and undigested neutral detergent fiber (uNDF) on eating behavior, ruminal fermentation and motility, barrier function, blood metabolites, and total tract nutrient digestibility for finishing cattle. Six Simmental heifers (668 ± 28.4 kg BW) were used in a replicated 3 × 3 Latin square (21 d periods) balanced for carry-over effects. Treatments included a control (CON; Table 1) with no forage peNDF and minimal uNDF (peNDF: 0.0%, and uNDF: 4.88 ± 0.01; 95.15% barley grain, 4.51% vitamin and mineral supplement, and 0.34% urea on a DM basis). Pelleted wheat straw (PELL) was included at 10% of dietary DM by replacing barley grain to provide added uNDF but no forage peNDF (peNDF: 0.00%, and uNDF: 6.78 ± 0.02%). Finally, chopped wheat straw (STR) was included as a replacement for pelleted wheat straw to provide forage peNDF and uNDF (peNDF: 1.74 ± 0.06%, and uNDF: 6.86 ± 0.03%). Dry matter intake was not affected (P = 0.93) by treatments. Cattle fed CON spent less time ruminating (P = 0.010) and had less meals/d (P = 0.035) when compared with cattle fed STR, with those fed PELL being intermediate but not different from other treatments. Cattle fed CON had lesser ruminal pH (P = 0.020), and a greater duration that pH was < 5.5 (P = 0.020) as compared to cattle fed STR, with those fed PELL being intermediate but not different. Cattle fed CON and PELL had greater total short-chain fatty acid concentration (P = 0.003) and molar proportion of propionate (P < 0.001) when compared with cattle fed STR. Cattle fed STR had greater (P = 0.010) total ruminal pool size when compared with cattle fed CON and PELL. Cattle fed CON had greater (P = 0.043) duration between ruminal contractions when compared with cattle fed STR, with those fed PELL being intermediate. Cattle fed CON had greater serum amyloid A (P = 0.003) and haptoglobin (P < 0.001) concentration when compared with the other treatments. Cattle fed CON had greater dry matter (P < 0.001) digestibility when compared with the other treatments. In conclusion, inclusion of PELL and STR impacted eating behavior, but only STR affected ruminal fermentation, ruminal motility, systemic inflammation, and total tract nutrient digestibility in finishing cattle. These results are interpreted to suggest that the combination of peNDF and uNDF may be better than uNDF alone to adequately capture biological effects of NDF in high-concentrate diets.
Platforms and Global Governance: Globalization on Steroids
Authors: Trachtman Joel P
Published: January 2023

Platforms constitute a novel context for social interaction. Physical distance makes little to no difference to interaction, and so the frequency and intensity of cross-territorial border interaction grow dramatically. This growth in interaction will be globalization on steroids. Platforms increase both collision among national rules (jurisdictional collision) and collision at the international level among functional rules (fragmentation). Revised normative and organizational tools will be needed to manage the increased globalization and fragmentation resulting from the rise of platform commerce. These tools may include modifications and extensions of existing rules of trade law, but they will embrace other areas of regulation in a much more nuanced manner than has been necessary until now. The existing fragmentation or ‘siloed’ nature of our international trade and regulatory systems will need to be modified—lateralized—to allow a more coherent approach.
International Taxation, Globalization, and the Economic Digital Divide
Authors: Avi-Yonah Reuven
Published: January 2023

The past decade has witnessed the creation of a new international tax regime. The original international tax regime was created a century ago by the League of Nations. Until the 1980s, it functioned reasonably well and prevented most instances of double taxation and double non-taxation by allocating cross-border income between home and host jurisdictions based on a compromise reached in 1923. However, since the advent of globalization in the 1980s and digitalization in the 1990s, the original international tax regime ceased to function as intended. The main problems were the increased mobility of capital related to increased intangibility and digitalization, together with a relaxation of capital controls and increased tax competition. These developments posed a problem for countries that wished to leave their borders open to reap the benefits of globalization and to engage in tax competition to attract investment. The outcome was a significant fall in tax revenues that threatened the social safety net of the modern welfare state. The trilemma of open borders, tax competition, and satisfying voters’ demand for social insurance culminated in the financial crisis of 2008–09, where many countries were forced to implement austerity measures at the same time that parliamentary hearings, leaks, and media reports revealed that rich individuals and large corporations were paying very little tax on cross-border income. The results over the past decade have been the creation of a new international tax regime designed to curb both tax evasion by the rich and tax competition among countries seeking to attract business activity within their borders by granting various preferential tax provisions to multinational enterprises. The key question going forward is how the new international tax regime will deal with international (in)equity, i.e. the economic digital divide. In what follows, I will first discuss the decline of the original international tax regime from 1980 to 2009, then the creation of the new international tax regime from 2010 on, and finally the implications of the new international tax regime for the economic digital divide.
Advances in fluorescence microscopy for orthohantavirus research
Authors: Menke Laura , Sperber Hannah S , Aji Amit Koikkarah , Chiantia Salvatore , Schwarzer Roland , Sieben Christian
Published: January 2023

Orthohantaviruses are important zoonotic pathogens responsible for a considerable disease burden globally. Partly due to our incomplete understanding of orthohantavirus replication, there is currently no effective antiviral treatment available. Recently, novel microscopy techniques and cutting-edge, automated image analysis algorithms have emerged, enabling to study cellular, subcellular and even molecular processes in unprecedented detail and depth. To date, fluorescence light microscopy allows us to visualize viral and cellular components and macromolecular complexes in live cells, which in turn enables the study of specific steps of the viral replication cycle such as particle entry or protein trafficking at high temporal and spatial resolution. In this review, we highlight how fluorescence microscopy has provided new insights and improved our understanding of orthohantavirus biology. We discuss technical challenges such as studying live infected cells, give alternatives with recombinant protein expression and highlight future opportunities, for example, the application of super-resolution microscopy techniques, which has shown great potential in studies of different cellular processes and viral pathogens.
Development of temporal series 4D-STEM and application to relaxation time measurement
Authors: Nakazawa Katsuaki , Mitsuishi Kazutaka
Published: January 2023

Diffraction patterns contain useful information about the materials. Recent developments in four-dimensional scanning transmission electron microscopy and the acquisition of the spatial distribution of diffraction patterns have produced significant results. The acquisition of a temporal series of diffractions is achieved for a stationary beam. However, the acquisition of spatiotemporal distribution of diffraction patterns has only been established under limited conditions. In this study, we developed a simple method that enables the recording of the spatiotemporal distribution of diffraction patterns and applied it to the relaxation time measurement that is robust to sample drift.
Advancing rapid cycle research in cancer care delivery: a National Cancer Institute workshop report
Authors: Norton Wynne E , Kennedy Amy E , Mittman Brian S , Parry Gareth , Srinivasan Shobha , Tonorezos Emily , Vanderpool Robin C , Jacobsen Paul B
Published: January 2023

Generating actionable research findings quickly and efficiently is critical for improving the delivery of cancer-related care and outcomes. To address this issue, the National Cancer Institute convened subject matter experts, researchers, clinicians, and patients for a 2-day virtual meeting in February 2022. The purpose of this meeting was to identify how rapid cycle interventional research methods can be used to generate findings useful in improving routine clinical practice. The meeting yielded an initial conceptualization of rapid cycle interventional research as being comprised of 6 key elements: use of iterative study designs; reliance on proximal primary outcomes; early and continued engagement with community and clinical partners; use of existing data sources to measure primary outcomes; facilitative features of the study setting and context; and consideration of appropriate rigor relative to intended use of findings. The meeting also identified the types of study designs that can be leveraged to conduct rapid cycle interventional research and provided examples of these; considered this approach from the perspective of key partners; described the clinical and data infrastructure, research resources, and key collaborations needed to support this work; identified research topics best addressed using this approach; and considered needed methodological advances. The National Cancer Institute is committed to exploring opportunities to encourage further development and application of this research approach as a means for better promoting improvements in the delivery of cancer-related care.
The development and validation of a measure of moral intuition salience for children and adolescents: The Moral Intuitions and Development Scale
Authors: Cingel Drew P , Krcmar Marina , Marple Catherine , Snyder Allyson L
Published: January 2023

In this article, we create and validate a measure of moral intuition salience developmentally appropriate for use among children and adolescents. This measure allows researchers to apply moral foundations theory and the model of intuitive morality and exemplars to child and adolescent moral development and media use, an important addition to the literature, as to date, this theory and its measurement have generally only been used among college-aged and adult participants. Following five pilot tests (total N = 713) that demonstrated face, concurrent, and predictive validity of our measure among young adults, we present validation data from 8- to 17-year-olds (N = 577), demonstrating the developmental nature of these moral intuitions and linking them with media use. This measure can be used to understand how children’s moral intuition salience relates to their media and content choices, as well as how media relates to the moral intuitions most salient to the child.