bluuebunny/crossref_metadata_2025 huggingface dataset:
In-situ SEM and EBSD investigation of the deformation behavior of extruded Mg-6Al-1Zn-1.1Sc alloy
Authors: Zhang Lei , Zhang Honggang , Wang Jinhui , Chen Lijia , Yuan Shuai , Jin Peipeng
Published: August 2023

The present study subjects the extruded Mg-6Al-1Zn-1.1Sc (wt%) alloy to reveal the deformation during in-situ tensile testing at room temperature by scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD). The results demonstrate that the parallel slip traces are increasingly observed on the surfaces of grains with increasing strains owing to the movement of dislocations inside the grains toward the sample surface, while microcracks are frequently observed at grain boundaries. The slip trace analysis indicate that many basal slips are activated during the deformation. The twinning behaviors of the extruded alloy during tensile testing are dominated by extension twinning. The orientation of grains is demonstrated to have a profound effect on their deformation, where grains with orientations deviating greatest from 〈0001〉//TD exhibit the highest dislocation density after deformation. This can be attributed to the fact that these oriented grains are prone to activate basal slip due to the large Schmid factor (SF). Similarly, the deformation of grains is also found to be highly dependent on their size, where the dislocation density of coarser grains increases more significantly than that of finer grains during deformation because coarser grains have greater space available for accommodating dislocations than finer grains.
Configurable calorimeter simulation for AI applications
Authors: Charkin-Gorbulin Anton , Cranmer Kyle , Di Bello Francesco Armando , Dreyer Etienne , Ganguly Sanmay , Gross Eilam , Heinrich Lukas , Kado Marumi , Kakati Nilotpal , Rieck Patrick , Santi Lorenzo , Tusoni Matteo
Published: August 2023

A configurable calorimeter simulation for AI (CoCoA) applications is presented, based on the Geant4 toolkit and interfaced with the Pythia event generator. This open-source project is aimed to support the development of machine learning algorithms in high energy physics that rely on realistic particle shower descriptions, such as reconstruction, fast simulation, and low-level analysis. Specifications such as the granularity and material of its nearly hermetic geometry are user-configurable. The tool is supplemented with simple event processing including topological clustering, jet algorithms, and a nearest-neighbors graph construction. Formatting is also provided to visualise events using the Phoenix event display software.
Alpaca single B cell interrogation and heavy-chain-only antibody discovery on an optofluidic platform
Authors: Shapiro Mariya B , Boucher Jacqueline , Brousseau Anna , Dehkharghani Amin , Gabriel Justin , Kamat Vishal , Patil Ketan , Gao Feng , Walker Jennifer , Kelly Ryan , Souders Colby A
Published: August 2023

In vivo VHH discovery approaches have been limited by the lack of methodologies for camelid B cell interrogation. Here, we report a novel application of the Beacon® optofluidic platform to the discovery of heavy-chain-only antibodies by screening alpaca B cells. Methods for alpaca B cell enrichment, culture, IgG2/3 detection, and sequencing were developed and used to discover target-specific VHH from an alpaca immunized with prostate-specific membrane antigen (PSMA) or a second target. PSMA-specific hits were expressed as VHH-Fc and characterized using label-free techniques. Anti-PSMA IgG2/3 titer plateaued on day 153, when on-Beacon IgG2/3 secretion and target binding rates peaked. Of 13 recombinantly expressed VHH-Fc, all but one bound with nanomolar affinity, and five were successfully humanized. Repertoire sequencing uncovered additional variants within the clonal lineages of the validated hits. The establishment of this workflow extends the powerful Beacon technology to enable rapid VHH discovery directly from natural camelid immune repertoires.
Application of the International Consensus Classification and World Health Organization 5th edition classification to a series of myeloid neoplasms
Authors: Chopra Saurav , Bailey Nathanael G
Published: August 2023

Objectives

Two new classifications of myeloid neoplasms have recently been published: the International Consensus Classification (ICC) and the 5th edition of the World Health Organization classification (WHO5). We sought to examine the real-world impact of dueling classifications on patient diagnoses.

Methods

Our institutional pathology database was searched, and 237 specimens with a diagnosis of myeloid neoplasia were randomly selected. For each case, a classification based on the WHO5 and the ICC was assigned. The WHO5 and ICC diagnoses were compared to determine their degree of concordance.

Results

After applying the WHO5 and ICC diagnostic criteria, 134 (56.5%) cases were classified as concordant, 63 (26.6%) cases had terminological differences, 37 (15.6%) cases had minor diagnostic discrepancies, and 3 (1.3%) cases had major diagnostic discrepancies. Cases with minor diagnostic discrepancies included 25 cases of myelodysplastic syndrome (MDS), 10 cases of acute myeloid leukemia (AML), and 2 cases of myeloid precursor lesions. Cases with major diagnostic discrepancies included 2 cases that were diagnosed as MDS, not otherwise specified (NOS), according to the ICC but classified as AML with NPM1 alteration and AML with RBM15::MRTFA according to the WHO5 and 1 case that was characterized as chronic myelomonocytic leukemia according to the ICC and as AML with NPM1 alteration according to the WHO5.

Conclusions

This study confirms that a majority of cases are classified similarly using the 2 systems. Given the overall similarity of the systems, future harmonization of the classifications should be pursued to avoid confusion and multiple diagnoses.
The Association of Personal Neglect with Motor, Activities of Daily Living, and Participation Outcomes after Stroke: A Systematic Review
Authors: Embrechts Elissa , Loureiro-Chaves Renata , Nijboer Tanja C W , Lafosse Christophe , Truijen Steven , Saeys Wim
Published: August 2023

Despite its potential clinical impact, the association of personal neglect (PN) with motor, activities of daily living (ADL), and participation outcomes after stroke is not well-understood. This first-ever systematic review on the topic therefore evaluates this association, taking into account suggested subtypes of PN, including body representation neglect, somatosensory neglect, motor neglect, and premotor neglect. A systematic literature search was conducted on February 17, 2023 in PubMed, Web of Science, Scopus, PubPsych, and PsycArticles databases. The study adheres to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses, and its protocol was registered on PROSPERO (CRD42020187460). Eleven observational studies were included, gathering 1,400 individuals after stroke (429 showed PN). Results show that individuals with body representation neglect after stroke have significantly decreased movement control and motor strength, lower functional mobility, and ADL independency compared with those without body representation neglect after stroke. Individuals with motor neglect after stroke showed worse motor function and spasticity than to those without motor neglect after stroke. Nonspecified PN (i.e., PN evaluated with an outcome measure that does not allow subcategorization) was related to worse lateropulsion with pushing, longer length of stay and greater odds of being discharged to somewhere other than home. No study evaluated somatosensory and premotor neglect. This review highlights the limited research in this area and emphasizes the need for a more comprehensive PN assessment. However, currently available assessment tools show limited ability to accurately diagnose PN subtypes and future research should prioritize the development of comprehensive diagnostic test batteries.
Using Therapeutic Photography in Social Work—An Interpretive Phenomenological Analysis of the Dynamics within a Group Programme
Authors: Gibson Neil
Published: August 2023

Therapeutic photography is the practice of using photography in order to explore issues and reach defined outcomes with people who use services. It has been deemed to be an accessible tool which can have a positive impact on self-esteem, self-efficacy and empowerment. Using interpretive phenomenological analysis, this research analyses observations and focus group feedback from a group of participants receiving support from a third-sector organisation for mental health issues. Specifically, the data were analysed to look at how a therapeutic photography programme contributed to group dynamics, exploration and outcomes. Three inter-related super-ordinate themes were identified, these being (1) exposing the self; (2) searching; and (3) developing the self. These themes centred around the identity of the participants as they explored their photographs and associated narratives. The results suggest that the medium of photography contributes to enhanced self-disclosure and social bonding through the familiarity of engaging with photographs. The photographs also enable participants to feel in control of the information shared, facilitating the level of exploration and personal learning around identity and roles and could be beneficial in social work with groups where these outcomes are sought.
Intersectional hybrids of Carex remota with C. otrubae and C. vulpina (Cyperaceae) in Europe
Authors: Koopman Jacob , Więcław Helena , Cembrowska-Lech Danuta
Published: August 2023

Carex vulpina and C. otrubae are closely related and morphologically similar species that hybridize with C. remota. The spontaneous appearance of hybrids can cause difficulties in the taxonomic treatment of this group. Morphological separation of the examined species and hybrids had been tested using discriminant function analysis (DFA). We have also analysed the effect of DNA barcoding on hybrid identification from the perspective of machine learning approach (MLA). Hybrids were investigated in terms of three barcodes sequence (ITS, matK, rbcL) by means of the BLOG and WEKA (MLA). Our results provide the first insights into the morphological and genetic relationships between the studied species and their hybrids. Morphological analysis showed traits useful in the identification of hybrids, i.e. dark brown usually fibrous basal sheaths and a dorsally split beak in Carex remota × C. vulpina (inherited from C. vulpina), distinctly separated spikes, and a long bract in C. otrubae × C. remota (inherited from C. remota). Phylogenetic analysis also indicated a close relationship of Carex remota × C. vulpina with C. vulpina and C. otrubae × C. remota with C. remota. Moreover, we have presented here nomenclatural notes on the hybrids and typified the names Carex × crepinii [C. otrubae × C. remota] and Carex × kernii [Carex remota × C. vulpina].
On Their Sovereign’s Secret Service: Special Envoys Detained while in Transit
Authors: Martha Rutsel Silvestre J , De Vriese Kit
Published: August 2023

The case of Mr. Saab, a Venezuelan ad hoc diplomat, raises numerous issues beyond codified international law. The issues discussed in this article are a vivid reminder of the importance of customary international law, and that its principles should not be held to have been tacitly dispensed with by any treaty in the absence of any words making clear an intention to do so. Indeed, whilst important portions of the law of diplomatic relations, including ad hoc diplomacy through special missions, are codified in the Vienna Convention on Diplomatic Relations (VCDR) and the Convention on Special Missions (Special Missions Convention), important aspects of ad hoc diplomacy remains governed by customary international law—as confirmed by the preambles of these treaties. The VCDR and the Special Missions Convention, whether collectively or separately, do not cover all issues relating to diplomacy. In this article, an attempt is made to how these issues should have been addressed in Mr. Saab’s case if the executive and judicial branches of the Government of Cabo Verde had kept this in mind.
Chromosome-level genome of butterflyfish unveils genomic features of unique colour patterns and morphological traits
Authors: Zhang Suyu , Song Yue , Liu Meiru , Yuan Zengbao , Zhang Mengqi , Zhang He , Seim Inge , Fan Guangyi , Liu Shanshan , Liu Xin
Published: August 2023

Chaetodontidae, known as butterflyfishes, are typical fish in coral ecosystems, exhibiting remarkable interspecific differences including body colour patterns and feeding ecology. In this study, we report genomes of three butterflyfish species (Chelmon rostratus, Chaetodon trifasciatus and Chaetodon auriga) and a closely related species from the Pomacanthidae family, Centropyge bicolour, with an average genome size of 65,611 Mb. Chelmon rostratus, comprising 24 chromosomes assembled to the chromosome level, could be served as a reference genome for butterflyfish. By conducting a collinearity analysis between butterflyfishes and several fishes, we elucidated the specific and conserved genomic features of butterflyfish, with particular emphasis on novel genes arising from tandem duplications and their potential functions. In addition to the two melanocyte-specific tyr genes commonly found in fish, we found the gene tyrp3, a new tyrosinase-related proteins gene in the reef fish, including butterflyfish and clownfish, implicating their involvement in the pigmentation diversity of fish. Additionally, we observed a tandem duplication expansion of three copies of nell1 gene in C. rostratus genome, which likely contribute to its unique jaw development and distinctive morphology of its sharp mouth. These results provided valuable genomic resources for further investigations into the genetic diversity and evolutionary adaptations of reef fish.
Blind spot in endocarditis guidelines: Mycobacterium chimaera prosthetic valve endocarditis after cardiac surgery—a case series
Authors: Trauth Janina , Matt Ulrich , Kohl Thomas A , Niemann Stefan , Herold Susanne
Published: August 2023

Background

The recently published 2023 Duke-ISCVID Criteria for Infective Endocarditis for the first time consider mycobacteria (esp. Mycobacterium chimaera) as ‘typical’ microorganisms for prosthetic valve endocarditis (major criteria). This reflects the ongoing worldwide outbreak of M. chimaera prosthetic valve endocarditis.

Case summary

Our case series demonstrates a diagnostic pathway for mycobacterial endocarditis. Symptoms are unspecific, and standard microbiological testing does not result in identification of the causative agent (see Graphical Abstract); therefore patients require special microbiological and imaging diagnostics. One patient with early diagnosis and stringent antibiotic and surgical therapy survived. Two patients with disseminated infection at the time point of diagnosis had fatal outcomes.

Discussion

The diagnostic approach in our small retrospective case series is in line with the new modified Duke criteria and underlines the diagnostic gap in the previous definitions. Outcome of M. chimaera prosthetic valve endocarditis is related to timely diagnosis and anti-mycobacterial as well as surgical treatment. Non-tuberculous mycobacteria should be given more attention in future endocarditis guidelines.
The impact of malperfusion patterns in elderly patients undergoing surgery for acute type A aortic dissection
Authors: Pitts Leonard , Kofler Markus , Montagner Matteo , Heck Roland , Kurz Stephan D , Buz Semih , Falk Volkmar , Kempfert Jörg
Published: August 2023

OBJECTIVES

The aim of this study is to investigate the outcome of elderly patients with surgically treated acute type A aortic dissection (ATAAD) complicated by malperfusion.

METHODS

Patients ≥70 years old who underwent surgical treatment for ATAAD between January 2000 and December 2020 were enrolled in this study and stratified by their specific Penn Classification into 4 different subgroups, where Penn Abc was defined as multilevel malperfusion. Short- and long-term outcomes were investigated. Multivariable binary logistic regression was performed to identify risk factors for 1-year mortality.

RESULTS

Four hundred elderly patients underwent surgical treatment for ATAAD. A total of 204 (51%) patients had no evidence of malperfusion (Penn Aa), 106 (26.5%) had localized organic malperfusion (Penn Ab), 44 (11%) patients had systemic malperfusion (Penn Ac) and 46 (11.5%) suffered from multilevel malperfusion (Penn Abc). For the latter, in-hospital mortality was 70% (P < 0.001). Age (P < 0.006) and multilevel malperfusion (P < 0.001) were independent risk factors for 1-year mortality. Patients with multilevel malperfusion showed the worst 1-year survival (P < 0.001). In the case of Penn Aa, in-hospital mortality was 13% (P < 0.001).

CONCLUSIONS

Surgery may lead to satisfactory results in the absence of malperfusion, even in octogenarians. Elderly patients with multilevel malperfusion show very poor surgical outcome. In these patients, the decision for surgery should be taken with caution. Operation, if performed, should be carried out by experienced teams only.
Performance of DNA-based biomarkers for classification of adrenocortical carcinoma: a prognostic study
Authors: Lippert Juliane , Dischinger Ulrich , Appenzeller Silke , Prete Alessandro , Kircher Stefan , Skordilis Kassiani , Elhassan Yasir S , Altieri Barbara , Fassnacht Martin , Ronchi Cristina L
Published: August 2023

Objective

Adrenocortical carcinoma (ACC) is a rare aggressive malignancy with heterogeneous clinical outcomes. Recent studies proposed a combination of clinical/histopathological parameters (S-GRAS score) or molecular biomarkers (BMs) to improve prognostication. We performed a comparative analysis of DNA-based BMs by evaluating their added prognostic value to the S-GRAS score.

Design and methods

A total of 194 formalin-fixed, paraffin-embedded (FFPE) ACC samples were analysed, including a retrospective training cohort (n = 107) and a prospective validation cohort (n = 87). Targeted DNA sequencing and pyrosequencing were used to detect somatic single-nucleotide variations in ACC-specific genes and methylation in the promoter region of paired box 5 (PAX5). The European Network for the Study of Adrenocortical Tumors (ENSAT) tumour stage, age, symptoms at presentation, resection status, and Ki-67 were combined to calculate S-GRAS. Endpoints were overall (OS), progression-free (PFS), and disease-free survival (DFS). Prognostic role was evaluated by multivariable survival analysis and their performance compared by Harrell's concordance index (C index).

Results

In training cohort, an independent prognostic role was confirmed at multivariate analysis for two DNA-based BMs: alterations in Wnt/β-catenin and Rb/p53 pathways and hypermethylated PAX5 (both P< .05 for PFS and DFS, hazard ratio [HR] 1.47-2.33). These were combined to S-GRAS to obtain a combined (COMBI) score. At comparative analysis, the best discriminative prognostic model was COMBI score in both cohorts for all endpoints, followed by S-GRAS score (C index for OS 0.724 and 0.765, PFS 0.717 and 0.670, and DFS 0.699 and 0.644, respectively).

Conclusions

Targeted DNA-based BM evaluated on routinely available FFPE samples improves prognostication of ACC beyond routinely available clinical and histopathological parameters. This approach may help to better individualise patient's management.
Fish biogeography and hybridization: do contemporary distributions predict introgression history?
Authors: Waters Jonathan M , Campbell Ciaran S M , Dutoit Ludovic
Published: August 2023

Freshwater ecosystems frequently house diverse assemblages of closely related fish taxa, which can be particularly prone to hybridization and introgression. While extensive introgression may be expected among biogeographically proximate lineages, recent analyses imply that contemporary distributions do not always accurately predict hybridization history. Here, we use the ABBA–BABA approach to test biogeographic hypotheses regarding the extent of hybridization in the recent evolution of New Zealand’s species-rich freshwater Galaxias vulgaris fish complex. Genome-wide comparisons reveal significant increases in introgression associated with increasing geographic overlap of taxa. The estimator DP, which assesses the net proportion of a genome originating from introgression, shows a particularly strong relationship with biogeographic overlap (R2 = .43; p = .005). Our analyses nevertheless reveal surprisingly substantial signatures of introgression among taxa that currently have disjunct distributions within drainages (e.g., separate subcatchments). These “anomalies” imply that current biogeography is not always an accurate predictor of introgression history. Our study suggests that both modern and ancient biogeographic shifts, including recent anthropogenic range fragmentation and tectonically driven riven capture events, have influenced introgression histories in this dynamic freshwater fish radiation.
Fabric controls fault stability in serpentinite gouges
Authors: Pozzi G , Collettini C , Scuderi M M , Tesei T , Marone C , Amodio A , Cocco M
Published: August 2023

Serpentinites are polymineralic rocks distributed almost ubiquitously across the globe in active tectonic regions. Magnetite-rich serpentinites are found in the low-strain domains of serpentinite shear zones, which act as potential sites of nucleation of unstable slip. To assess the potential of earthquake nucleation in these materials, we investigate the link between mechanical properties and fabric of these rocks through a suite of laboratory shear experiments. Our experiments were done at room temperature and cover a range of normal stress and slip velocity from 25 to 100 MPa and 0.3 to 300 µm s−1, respectively. We show that magnetite-rich serpentinites are ideal materials since they display strong sensitivity to the loading rate and are susceptible to nucleation of unstable slip, especially at low forcing slip velocities. We also aim at the integration of mechanical and microstructural results to describe the underlying mechanisms that produce the macroscopic behaviour. We show that mineralogical composition and mineral structure dictates the coexistence of two deformation mechanisms leading to stable and unstable slip. The weakness of phyllosilicates allows for creep during the interseismic phase of the laboratory seismic cycle while favouring the restoration of a load-bearing granular framework, responsible of the nucleation of unstable events. During dynamic slip, fault zone shear fabric determines the mode of slip, producing either asymmetric or Gaussian slip time functions for either fast or slow events. We report rate/state friction parameters and integrate our mechanical data with microstructural observations to shed light on the mechanisms dictating the complexity of laboratory earthquakes. We show that mineralogical and fabric heterogeneities control fault slip behaviour.
Effectiveness and Safety Profile of Budesonide Maintenance in Microscopic Colitis: A Systematic Review and Meta-Analysis
Authors: Tome June , Tariq Raseen , Hassett Leslie C , Khanna Sahil , Pardi Darrell S
Published: August 2023

Background

Microscopic colitis (MC) is a common cause of chronic diarrhea. Randomized controlled trials (RCTs) have demonstrated the efficacy of budesonide treatment for MC. However, relapse is frequent after discontinuation of budesonide, and data on maintenance therapy are limited. We performed a systematic review and meta-analysis evaluating these outcomes in clinical trials and real-world settings.

Methods

A systematic search was performed on October 31, 2022, of Medline, Embase, Cochrane, and Scopus. Case series, case-control, cohort studies, and RCTs of adults with MC were included. Data were pooled using random effects models to calculate weighted pooled estimates and 95% confidence intervals. Heterogeneity was assessed using the I2 statistic.

Results

We included 35 studies (11 RCTs, 24 observational studies) with 1657 MC patients treated with budesonide induction and 146 for maintenance. The overall pooled clinical remission rate with budesonide treatment was similar between RCTs and observational studies. The pooled remission rate with budesonide maintenance therapy was 84% (95% CI, 0.60-1.00; I2 = 91%). After budesonide discontinuation, the pooled relapse rate was 53% (95% CI, 0.42-0.63; I2 = 76%). On maintenance therapy, no differences were noted in adverse events (eg, metabolic bone disease, hypertension, hyperglycemia, cataracts/glaucoma) in those on budesonide vs placebo or other noncorticosteroid medications for MC (P = .9).

Conclusions

Budesonide is an effective maintenance treatment for MC. There is a high risk of recurrence after budesonide discontinuation, but long-term use at the lowest effective dose appears to be relatively safe and have limited adverse effects.
Applying the ‘Ceased Circumstances’ Cessation Clause: More Politics than Law?
Authors: Cole Georgia
Published: August 2023

Drawing on a detailed history of the ‘ceased circumstances’ cessation clause that was invoked for Eritrean refugees in 2002, this article highlights why the starting point for any analysis of the application of article 1C(5) of the 1951 Convention relating to the Status of Refugees must focus as much on politics as on law. This is not only because of the impossibility of insulating States and the United Nations High Commissioner for Refugees (UNHCR) from the political pressures that surround any determination of ‘ceased circumstances’ in a particular country, but also because the very standards on which such a determination rests are inherently relational, circumstantial, and political. Despite guidelines on the application of the clause promoting an ‘objective and verifiable’ approach, they rest on assessments of a ‘functioning’ government and ‘effective’ protection, of acceptable standards of human rights, and of the ‘best interests’ of refugees, all of which are geographically and historically contingent. The article thus argues that focusing on the legal standards that ostensibly underpin any invocation of article 1C(5) may perpetuate the fallacy that these standards can ever be objectively determined and, in focusing attention on how to better clarify these thresholds and conditions, this approach may, in certain instances, divert attention from confronting the political pressures that govern the application of the clause.
Effective Density for Inhomogeneous Quadratic Forms II: Fixed Forms and Generic Shifts
Authors: Ghosh Anish , Kelmer Dubi , Yu Shucheng
Published: August 2023

We establish effective versions of Oppenheim’s conjecture for generic inhomogeneous quadratic forms. We prove such results for fixed quadratic forms and generic shifts. Our results complement our previous paper [13] where we considered generic forms and fixed shifts. In this paper, we use ergodic theorems and in particular we establish a strong spectral gap with effective bounds for some representations of orthogonal groups, which do not possess Kazhdan’s property $(T)$.
Collagen microgel to simulate the adipocyte microenvironment for in vitro research on obesity
Authors: Moreno-Castellanos Natalia , Cuartas-Gómez Elías , Vargas-Ceballos Oscar
Published: August 2023

Obesity is linked to adipose tissue dysfunction, a dynamic endocrine organ. Two-dimensional cultures present technical hurdles hampering their ability to follow individual or cell groups for metabolic disease research. Three-dimensional type I collagen microgels with embedded adipocytes have not been thoroughly investigated to evaluate adipogenic maintenance as instrument for studying metabolic disorders. We aimed to develop a novel tunable Col-I microgel simulating the adipocyte microenvironment to maintain differentiated cells with only insulin as in vitro model for obesity research. Adipocytes were cultured and encapsulated in collagen microgels at different concentrations (2, 3 and 4 mg/mL). Collagen microgels at 3 and 4 mg/mL were more stable after 8 days of culture. However, cell viability and metabolic activity were maintained at 2 and 3 mg/mL, respectively. Cell morphology, lipid mobilization and adipogenic gene expression demonstrated the maintenance of adipocyte phenotype in an in vitro microenvironment. We demonstrated the adequate stability and biocompatibility of the collagen microgel at 3 mg/mL. Cell and molecular analysis confirmed that adipocyte phenotype is maintained over time in the absence of adipogenic factors. These findings will help better understand and open new avenues for research on adipocyte metabolism and obesity.

Insight box In the context of adipose tissue dysfunction research, new struggles have arisen owing to the difficulty of cellular maintenance in 2D cultures. Herein, we sought a novel approach using a 3D type I collagen-based biomaterial to adipocyte culture with only insulin. This component was tailored as a microgel in different concentrations to support the growth and survival of adipocytes. We demonstrate that adipocyte phenotype is maintained and key adipogenesis regulators and markers are over time. The cumulative results unveil the practical advantage of this microgel platform as an in vitro model to study adipocyte dysfunction and obesity.
Exposure of Salmonella enterica serovar 1,4,[5],12:i:- to benzalkonium chloride leads to acquired resistance to this disinfectant and antibiotics
Authors: Yang Mingzhe , Dong Qingli , Niu Hongmei , Li Jiaming , Lin Zijie , Aslam Muhammad Zohaib , Wang Xiang , Li Zhuosi , Liu Yangtai , Ma Yue , Qin Xiaojie
Published: August 2023

Aims

Disinfectants such as benzalkonium chloride (BC), extensively used in animal farms and food-processing industries, contribute to the development of adaptive and cross-resistance in foodborne pathogens, posing a serious threat to food safety and human health. The purpose of this study is to explore whether continuous exposure of Salmonella enterica serovar 1,4,[5],12:i:- (S. 1,4,[5],12:i:-) to sublethal concentrations of BC could result in acquired resistance to this agent and other environmental stresses (e.g. antibiotics, heat, and acid).

Methods and Results

BC tolerance increased in all tested strains after exposure to gradually increasing concentrations of BC, with increases in minimum inhibitory concentrations between two and sixfold. The survival rate of BC-adapted strains was significantly (P < 0.05) higher than that of their wild-type (non-adapted) counterparts in lethal concentrations of BC. In addition, significant reductions (P < 0.05) in zeta potential were observed in BC-adapted strains compared to wild-type ones, indicating that a reduction in cell surface charge was a cause of adaptative resistance. More importantly, two BC-adapted strains exhibited increased antibiotic resistance to levofloxacin, ceftazidime, and tigecycline, while gene mutations (gyrA, parC) and antibiotic efflux-related genes (acrB, mdsA, mdsB) were detected by genomic sequencing analysis. Moreover, the tolerance of BC-adapted strains to heat (50, 55, and 60°C) and acid (pH 2.0, 2.5) was strain-dependent and condition-dependent.

Conclusions

Repeated exposure to sublethal concentrations of BC could result in the emergence of BC- and antibiotic-resistant S. 1,4,[5],12:i:- strains.
Diet production and utilization of corn fermented protein compared to traditional yeast in healthy adult cats
Authors: Kilburn-Kappeler Logan R , Paulk Chad B , Aldrich Charles G
Published: August 2023

The inclusion of yeast in pet food can provide health benefits and increase palatability. Corn fermented protein is a co-product from ethanol production which contains approximately 20% to 25% yeast. The objective of this study was to determine the effects of the yeast in CFP on diet production and utilization when fed to healthy adult cats. The four experimental diets included a control with 15% soybean meal (CON) and diets containing either 3.5% brewer’s dried yeast (BDY), 2.5% brewer’s dried yeast plus 17.5% distillers dried grains with solubles (BDY+DDGS), or 17.5% corn fermented protein (CFP). All treatments except CON were formulated to contain 3.5% yeast. Experimental diets were fed to adult cats (n = 11) in an incomplete 4 × 4 replicated Latin square design. Cats were adapted to diet for 9 d followed by a 5-d total fecal collection. Titanium dioxide (0.4%) was added to all diets as an external marker to estimate digestibility. Data were analyzed using a mixed model in SAS (version 9.4, SAS Institute, Inc., Cary, NC) with treatment as a fixed effect and cat and period as random effects. Preconditioner discharge temperature was greater (P < 0.05) for CON and BDY (average, 96 °C) compared to BDY + DDGS and CFP (average, 91 °C). Extruder screw speed, die temperature, kibble toughness, and kibble hardness were greatest (P < 0.05) for CFP. The bulk density of BDY + DDGS at 392 g/L was greater (P < 0.05) than BDY and CFP (average, 342 g/L). The sectional expansion index of kibble for CFP was greater (P < 0.05) than BDY + DDGS and smaller (P < 0.05) than CON but similar to BDY. Fecal output was greatest (P < 0.05) for cats fed BDY + DDGS. Nutrient digestibility was lowest (P < 0.05) for BDY + DDGS. The concentrations of short-chain and branched-chain fatty acids in fecal samples were not altered (P > 0.05) by dietary treatment. Cats had no preference (P > 0.05) when comparing CON to BDY or BDY + DDGS. However, cats consumed significantly less CFP compared to CON. The significant differences for bulk density, fecal output, and nutrient digestibility among dietary treatments are likely due to a greater fiber effect of DDGS compared to CFP. Therefore, the yeast component in CFP may provide greater kibble expansion and nutrient utilization compared to DDGS when fed to cats.
Small molecule inducers of actinobacteria natural product biosynthesis
Authors: Alwali Amir Y , Parkinson Elizabeth I
Published: August 2023

Actinobacteria are a large and diverse group of bacteria that are known to produce a wide range of secondary metabolites, many of which have important biological activities, including antibiotics, anti-cancer agents, and immunosuppressants. The biosynthesis of these compounds is often highly regulated with many natural products (NPs) being produced at very low levels in laboratory settings. Environmental factors, such as small molecule elicitors, can induce the production of secondary metabolites. Specifically, they can increase titers of known NPs as well as enabling discovery of novel NPs typically produced at undetectable levels. These elicitors can be NPs, including antibiotics or hormones, or synthetic compounds. In recent years, there has been a growing interest in the use of small molecule elicitors to induce the production of secondary metabolites from actinobacteria, especially for the discovery of NPs from “silent” biosynthetic gene clusters. This review aims to highlight classes of molecules that induce secondary metabolite production in actinobacteria and to describe the potential mechanisms of induction.

One-Sentence Summary

This review describes chemical elicitors of actinobacteria natural products described to date and the proposed mechanisms of induction.
Off-host survival of Dermacentor variabilis (Acari: Ixodidae) adults near their northern distributional limit in Saskatchewan, Canada
Authors: Yunik Matthew E M , Diyes Chulantha P , Chilton Neil B
Published: August 2023

Dermacentor variabilis (Say) is expanding its range northwards in Saskatchewan and Manitoba (Canada). Knowledge of the relative ability of different life cycle stages to survive off-host over winter is important for assessing the potential for further range expansion and risk of pathogen transmission. In the present study, the off-host survival of D. variabilis adults was determined in outdoor terraria within a field plot close to Lizard Lake Community Pasture (LLCP) situated near the northern distributional limit in Saskatchewan. Only a small proportion (7%) of adult ticks in this relatively recently established population survived from mid-summer to late winter. Off-host survival had declined further to <4% by mid-spring. A significantly greater proportion of female ticks (6%) survived from mid-summer to mid-spring than did male ticks (1%). The supercooling points (SCPs), the temperature below 0 °C when body fluids spontaneously freeze, of the 17 ticks that survived through to mid-spring did not differ significantly from the SCPs of questing ticks in the previous summer, suggesting adult D. variabilis do not undergo cold hardening during winter diapause. The off-host survival of D. variabilis adults near LLCP was also much lower than that previously reported for adults from Sandy Hook in Manitoba, a population that has been established for decades. This finding suggests that there is geographical variation in the ability of D. variabilis in southern Canada to survive from mid-summer to the subsequent spring. However, the ecological and genetic factors influencing the survival of northern populations of D. variabilis requires further investigation.
Abnormal phosphorylation of protein tyrosine in neurodegenerative diseases
Authors: Shu Lijuan , Du Chunfu , Zuo Yunxia
Published: August 2023

Neurodegenerative diseases, including Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and multiple sclerosis, are chronic disorders of the CNS that are characterized by progressive neuronal dysfunction. These diseases have diverse clinical and pathological features and their pathogenetic mechanisms are not yet fully understood. Currently, widely accepted hypotheses include the accumulation of misfolded proteins, oxidative stress from reactive oxygen species, mitochondrial dysfunction, DNA damage, neurotrophin dysfunction, and neuroinflammatory processes. In the CNS of patients with neurodegenerative diseases, a variety of abnormally phosphorylated proteins play important roles in pathological processes such as neuroinflammation and intracellular accumulation of β-amyloid plaques and tau. In recent years, the roles of abnormal tyrosine phosphorylation of intracellular signaling molecules regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) in neurodegenerative diseases have attracted increasing attention. Here, we summarize the roles of signaling pathways related to protein tyrosine phosphorylation in the pathogenesis of neurodegenerative diseases and the progress of therapeutic studies targeting PTKs and PTPs that provide theoretical support for future studies on therapeutic strategies for these devastating and important neurodegenerative diseases.
Durable Anti-Vi IgG and IgA Antibody Responses in 15-Month-Old Children Vaccinated With Typhoid Conjugate Vaccine in Burkina Faso
Authors: Ouedraogo Alphonse , Diarra Amidou , Nébié Issa , Barry Nouhoun , Kabore Jean Moise , Tiono Alfred B , Datta Shrimati , Liang Yuanyuan , Mayo Ifayet , Oshinsky Jennifer J , Tracy J Kathleen , Girmay Tsion , Pasetti Marcela F , Jamka Leslie P , Neuzil Kathleen M , Sirima Sodiomon B , Laurens Matthew B
Published: August 2023

We assessed anti-Vi IgG/IgA responses to typhoid conjugate vaccine (TCV) in children enrolled in a double-blind randomized controlled, phase 2 trial in Burkina Faso. Anti-Vi IgG seroconversion and anti-Vi IgA titers were higher in TCV than control recipients at 30–35 months post-vaccination. TCV induces durable immunity in Burkinabe children vaccinated at 15 months.
Maxway CRT: improving the robustness of the model-X inference
Authors: Li Shuangning , Liu Molei
Published: August 2023

The model-X conditional randomisation test (CRT) is a flexible and powerful testing procedure for testing the hypothesis X⫫Y∣Z. However, it requires perfect knowledge of X∣Z and may lose its validity when there is an error in modelling X∣Z. This problem is even more severe when Z is of high dimensionality. In response to this, we propose the Maxway CRT, which learns the distribution of Y∣Z and uses it to calibrate the resampling distribution of X to gain robustness to the error in modelling X. We prove that the type-I error inflation of the Maxway CRT can be controlled by the learning error for a low-dimensional adjusting model plus the product of learning errors for X∣Z and Y∣Z, interpreted as an ‘almost doubly robust’ property. Based on this, we develop implementing algorithms of the Maxway CRT in practical scenarios including (surrogate-assisted) semi-supervised learning (SA-SSL) and transfer learning (TL). Through simulations, we demonstrate that the Maxway CRT achieves significantly better type-I error control than existing model-X inference approaches while preserving similar powers. Finally, we apply our methodology to two real examples of SA-SSL and TL.
Using Auxiliary Marginal Distributions in Imputations for Nonresponse while Accounting for Survey Weights, with Application to Estimating Voter Turnout
Authors: Tang Jiurui , Hillygus D Sunshine , Reiter Jerome P
Published: August 2023

In many survey settings, population counts or percentages are available for some of the variables in the survey, for example, from censuses, administrative databases, or other high-quality surveys. We present a model-based approach to utilize such auxiliary marginal distributions in multiple imputation for unit and item nonresponse in complex surveys. In doing so, we ensure that the imputations produce design-based estimates that are plausible given the known margins. We introduce and utilize a hybrid missingness model comprising a pattern mixture model for unit nonresponse and selection models for item nonresponse. We also develop a computational strategy for estimating the parameters of and generating imputations with hybrid missingness models. We apply a hybrid missingness model to examine voter turnout by subgroups using the 2018 Current Population Survey for North Carolina. The hybrid missingness model also facilitates modeling measurement errors simultaneously with handling missing values. We illustrate this feature with the voter turnout application by examining how results change when we allow for overreporting, that is, individuals self-reporting that they voted when in fact they did not.
Large-scale preparation of yeast strains expressing condensates derived from a glycolytic enzyme via controlled dissolved oxygen levels under hypoxia
Authors: Murata Yuki , Hirayama Reina , Miura Natsuko , Kataoka Michihiko
Published: August 2023

Under hypoxia, Saccharomyces cerevisiae forms cytoplasmic condensates composed of proteins, including glycolytic enzymes, that are thought to regulate cellular metabolism. However, the hypoxic conditions required for condensate formation remain unclear. In this study, we developed a 300-mL-scale culture method to produce condensate-forming cells by precisely controlling the dissolved oxygen (DO) level in the media. Using enolase as a model, a foci formation rate of more than 50% was achieved at ∼0.1% DO, and the results showed that the DO level affected the foci formation rate. The foci formation rates of the previously reported foci-deficient strains and strains with single amino acid substitutions in the endogenous enolase were examined, and the effect of these amino acid substitutions on glucose consumption and ethanol and glycerol production under hypoxia was evaluated. The results of this study contribute to the investigation of the mechanisms that regulate biomacromolecular condensates under hypoxia.
Massive binary black holes from Population II and III stars
Authors: Costa Guglielmo , Mapelli Michela , Iorio Giuliano , Santoliquido Filippo , Escobar Gastón J , Klessen Ralf S , Bressan Alessandro
Published: August 2023

Population III stars, born from the primordial gas in the Universe, lose a negligible fraction of their mass via stellar winds and possibly follow a top-heavy mass function. Hence, they have often been regarded as the ideal progenitors of massive black holes (BHs), even above the pair instability mass gap. Here, we evolve a large set of Population III binary stars (metallicity Z = 10−11) with our population-synthesis code sevn, and compare them with Population II binary stars (Z = 10−4). In our models, the lower edge of the pair-instability mass gap corresponds to a BH mass of ≈86 (≈91) M⊙ for single Population III (II) stars. Overall, we find only mild differences between the properties of binary BHs (BBHs) born from Population III and II stars, especially if we adopt the same initial mass function and initial orbital properties. Most BBH mergers born from Population III and II stars have primary BH mass below the pair-instability gap, and the maximum secondary BH mass is <50 M⊙. Only up to ≈3.3 per cent (≈0.09 per cent) BBH mergers from Population III (II) progenitors have primary mass above the gap. Unlike metal-rich binary stars, the main formation channel of BBH mergers from Population III and II stars involves only stable mass transfer episodes in our fiducial model.
First-trimester occupational exposures and hypertensive disorders of pregnancy among US nurses
Authors: Agarwal I , Wang S , Stuart J , Strohmaier S , Schernhammer E , Rich-Edwards J , Kang J H
Published: August 2023

Background

Limited and conflicting data exist regarding the impact of first-trimester nursing occupational exposures on hypertensive disorders of pregnancy (HDP).

Aims

To investigate whether first-trimester night shift work, work hours and work-related activities are associated with HDP.

Methods

We conducted a cross-sectional analysis of 6610 women within the Nurses’ Health Study II. We used multiple logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of occupational exposures to HDP.

Results

Nine per cent of respondents reported an HDP in the index pregnancy (gestational hypertension: n = 354, 5%, preeclampsia: n = 222, 3%). First-trimester fixed or rotating night shift work was not significantly associated with gestational hypertension or preeclampsia compared to day shift work only. Compared to those working 21–40 h/week, working overtime (≥41 h/week) was not associated with gestational hypertension but was associated with 43% higher odds of preeclampsia (95% CI 1.02, 2.00). For part-time work (≤20 h/week), the OR was 0.76 (95% CI 0.56, 1.02) for gestational hypertension and 0.64 (95% CI 0.43, 0.97) for preeclampsia. The odds of preeclampsia were 3% higher per additional hour worked per week (95% CI 1.01–1.04). Compared to 0–4 h spent standing or walking per day, standing or walking ≥9 h daily was associated with 32% lower odds of gestational hypertension (95% CI 0.47, 0.99) but was not significantly associated with preeclampsia. Frequency of heavy lifting was not associated with either hypertensive disorder or pregnancy.

Conclusions

Among nurses, working overtime was associated with higher odds of preeclampsia.