bluuebunny/crossref_metadata_2025 huggingface dataset:
Auxetic incisions with alternating slit shapes: a promising technique for enhancing synthetic skin grafts expansion
Authors: Gupta Vivek , Chanda Arnab
Published: July 2023

Split thickness skin grafts are widely used in treating burn injuries. To date, with limited availability of donor skin and minimal expansions offered by conventional skin grafting, it is challenging to cover large and severe burns. In this study, novel synthetic skin grafts with alternating slit (AS) shaped cut patterns were developed and tested to evaluate the expansion potentials offered by auxetic or negative Poisson’s ratio structures in skin grafting. A range of auxetic incision patterns were designed with varying unit cell dimensions, and these were projected onto skin using 3D printing. The mechanical properties and digital image correlation of the created synthetic skin grafts were used to determine stress, effective Poisson’s ratio, meshing ratio (MR), and generated strains for strain loadings of up to 150%. The AS graft simulant with equal slit lengths and low slit spacings exhibited the maximum negative Poisson’s effect, expansion, and Mr Expansions were inversely related with the spacing between slits. The lowest value for the MR and highest stress was observed with high spacing, high horizontal slit length, and low vertical slit length. The expansions were highly sensitive to the applied strain, with low strains exhibiting high auxeticity. Such an extensive experimental investigation of the expansion potentials and stress estimations of skin grafts with varying AS dimensional parameters have not been conducted previously. The findings would be crucial for advancing research on mitigation of large burn injuries using high expansion skin grafts.
Green building rating systems: A critical comparison between LOTUS, LEED, and Green Mark
Authors: Doan Dat Tien , Tran Hung Van , Aigwi Itohan Esther , Naismith Nicola , Ghaffarianhoseini Amirhosein , Ghaffarianhoseini Ali
Published: July 2023

Despite being established in Vietnam for over a decade, LOTUS has not achieved the same popularity as other international green building rating systems (GBRS), such as LEED and Singapore’s Green Mark (GM). Consequently, concerns about its effectiveness persist. This study employed a systematic literature review to compare and analyse the effectiveness of LOTUS against LEED and GM rating systems. The findings revealed that LEED was the most widely adopted GBRS in Vietnam. While the primary criteria identified across all three systems were energy, water, materials, and indoor environment, the critical aspect of sustainability was environmental. Although GM placed a greater emphasis on sustainability and climate-responsive design, LEED and LOTUS prioritised site location. These results suggest that the late introduction and complexities surrounding the initial versions of LOTUS significantly contributed to its limited popularity in Vietnam. To enhance its effectiveness, this study recommends that the Vietnam Green Building Council (VGBC) increase its engagement with green building researchers and construction stakeholders both within and outside Vietnam, with the aim of simplifying its approach. A more user-friendly and streamlined version of LOTUS will likely encourage adoption by Vietnamese construction practitioners, thereby raising awareness of green building practices in Vietnam.
Neural-prior stochastic block model
Authors: Duranthon O , Zdeborová L
Published: July 2023

The stochastic block model (SBM) is widely studied as a benchmark for graph clustering aka community detection. In practice, graph data often come with node attributes that bear additional information about the communities. Previous works modeled such data by considering that the node attributes are generated from the node community memberships. In this work, motivated by a recent surge of works in signal processing using deep neural networks as priors, we propose to model the communities as being determined by the node attributes rather than the opposite. We define the corresponding model; we call it the neural-prior SBM. We propose an algorithm, stemming from statistical physics, based on a combination of belief propagation and approximate message passing. We analyze the performance of the algorithm as well as the Bayes-optimal performance. We identify detectability and exact recovery phase transitions, as well as an algorithmically hard region. The proposed model and algorithm can be used as a benchmark for both theory and algorithms. To illustrate this, we compare the optimal performances to the performance of simple graph neural networks.
Quantum information diode based on a magnonic crystal
Authors: Shukla Rohit K , Chotorlishvili Levan , Vijayan Vipin , Verma Harshit , Ernst Arthur , Parkin Stuart S P , Mishra Sunil K
Published: July 2023

Exploiting the effect of nonreciprocal magnons in a system with no inversion symmetry, we propose a concept of a quantum information diode (QID), i.e. a device rectifying the amount of quantum information transmitted in the opposite directions. We control the asymmetric left and right quantum information currents through an applied external electric field and quantify it through the left and right out-of-time-ordered correlation. To enhance the efficiency of the QID, we utilize a magnonic crystal. We excite magnons of different frequencies and let them propagate in opposite directions. Nonreciprocal magnons propagating in opposite directions have different dispersion relations. Magnons propagating in one direction match resonant conditions and scatter on gate magnons. Therefore, magnon flux in one direction is damped in the magnonic crystal leading to an asymmetric transport of quantum information in the QID. A QID can be fabricated from an yttrium iron garnet film. This is an experimentally feasible concept and implies certain conditions: low temperature and small deviation from the equilibrium to exclude effects of phonons and magnon interactions. We show that rectification of the flaw of quantum information can be controlled efficiently by an external electric field and magnetoelectric effects.
The 𝑚=2 amplituhedron and the hypersimplex: Signs, clusters, tilings, Eulerian numbers
Authors: Parisi Matteo , Sherman-Bennett Melissa , Williams Lauren
Published: July 2023

The hypersimplexΔk+1,n\Delta _{k+1,n}is the image of the positive GrassmannianGrk+1,n≥0Gr^{\geq 0}_{k+1,n}under the moment map. It is a polytope of dimensionn−1n-1inRn\mathbb {R}^n. Meanwhile, the amplituhedronAn,k,2(Z)\mathcal {A}_{n,k,2}(Z)is the projection of the positive GrassmannianGrk,n≥0Gr^{\geq 0}_{k,n}into the GrassmannianGrk,k+2Gr_{k,k+2}under a mapZ~\tilde {Z}induced by a positive matrixZ∈Matn,k+2>0Z\in Mat_{n,k+2}^{>0}. Introduced in the context ofscattering amplitudes, it is not a polytope, and has full dimension2k2kinsideGrk,k+2Gr_{k,k+2}. Nevertheless, there seem to be remarkable connections between these two objects viaT-duality, as conjectured by Łukowski, Parisi, and Williams [Int. Math. Res. Not. (2023)]. In this paper we use ideas from oriented matroid theory, total positivity, and the geometry of the hypersimplex and positroid polytopes to obtain a deeper understanding of the amplituhedron. We show that the inequalities cutting outpositroid polytopes—images of positroid cells ofGrk+1,n≥0Gr^{\geq 0}_{k+1,n}under the moment map—translate into sign conditions characterizing the T-dualGrasstopes—images of positroid cells ofGrk,n≥0Gr^{\geq 0}_{k,n}underZ~\tilde {Z}. Moreover, we subdivide the amplituhedron intochambers, just as the hypersimplex can be subdivided into simplices, with both chambers and simplices enumerated by the Eulerian numbers. We use these properties to prove the main conjecture of Łukowski, Parisi, and Williams [Int. Math. Res. Not. (2023)]: a collection of positroid polytopes is a tiling of the hypersimplex if and only if the collection of T-dual Grasstopes is a tiling of the amplituhedronAn,k,2(Z)\mathcal {A}_{n,k,2}(Z)for allZZ. Moreover, we prove Arkani-Hamed–Thomas–Trnka’s conjectural sign-flip characterization ofAn,k,2\mathcal {A}_{n,k,2}, and Łukowski–Parisi–Spradlin–Volovich’s conjectures onm=2m=2cluster adjacencyand onpositroid tilesforAn,k,2\mathcal {A}_{n,k,2}(images of2k2k-dimensional positroid cells which map injectively intoAn,k,2\mathcal {A}_{n,k,2}). Finally, we introduce new cluster structures in the amplituhedron.
An oviduct glycan increases sperm lifespan by diminishing the production of ubiquinone and reactive oxygen species
Authors: Hughes Jennifer R , McMorrow Katie J , Bovin Nicolai , Miller David J
Published: July 2023

Sperm storage by females after mating for species-dependent periods is used widely among animals with internal fertilization to allow asynchrony between mating and ovulation. Many mammals store sperm in the lower oviduct where specific glycans on oviduct epithelial cells retain sperm to form a reservoir. Binding to oviduct cells suppresses sperm intracellular Ca2+ and increases sperm longevity. We investigated the mechanisms by which a specific oviduct glycan, 3-O-sulfated Lewis X trisaccharide (suLeX), prolongs the lifespan of porcine sperm. Using targeted metabolomics, we found that binding to suLeX diminishes the abundance of 4-hydroxybenzoic acid, the precursor to ubiquinone (also known as Coenzyme Q), 30 min after addition. Ubiquinone functions as an electron acceptor in the electron transport chain (ETC). 3-O-sulfated Lewis X trisaccharide also suppressed the formation of fumarate. A component of the citric acid cycle, fumarate is synthesized by succinate-coenzyme Q reductase, which employs ubiquinone and is also known as Complex II in the ETC. Consistent with the reduced activity of the ETC, the production of harmful reactive oxygen species (ROS) was diminished. The enhanced sperm lifespan in the oviduct may be because of suppressed ROS production because high ROS concentrations have toxic effects on sperm.
Intersectional Making of the ‘Sri Lankan Case’: The Racialization of Domestic Violence in the Swiss Police Force
Authors: Khazaei Faten
Published: July 2023

This article uses an intersectional lens to ethnographically analyze police treatment of domestic violence in Switzerland. The analysis suggests three interlinked explanatory factors to understand the differential treatment of domestic violence for white Swiss/European nationals on the one hand, and racialized non-European migrants on the other. These factors are (1) prevailing generalized representations of the racialization of violence against women in Switzerland, (2) the police professional logic used to categorize sections of the public, and (3) the specific police institutional memory of two emblematic cases of domestic violence involving families of Sri Lankan nationality. The article discusses the implications of this differential treatment not only for racialized non-Europeans but also for Swiss and white European women subjected to domestic violence.
A comparison of cardiovascular imaging practices in Africa, North America, and Europe: two faces of the same coin
Authors: Lakshmanan Suvasini , Mbanze Irina
Published: July 2023

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. There are significant differences in the burden of cardiovascular disease and associated risk factors, across high-income countries and low- and middle-income countries. Cardiac imaging by echocardiography, cardiac computed tomography, cardiac magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography myocardial perfusion imaging are well-established non-invasive tests that aid in the diagnosis, risk stratification, and management of various cardiac diseases. However, there are significant inequalities in availability and access to imaging modalities in low- and middle-income countries attributed to financial constraints, disparities in healthcare and technical infrastructure. In the post-COVID-19 pandemic era, these disparities are exaggerated by the continued technological advancements driving innovations in the field of cardiovascular (CV) imaging in high-income countries, while there is an urgent need to provide sustainable access to diagnostic imaging for patients in economically strained healthcare systems in regions like Africa. This review aims to highlight the inequalities in the burden of cardiac disease, associated risk factors, and access to diagnostic CV imaging tests, while also exploring the need for sustainable solutions to implementing CV imaging all over the world.
Multi-omic analysis of mandibuloacral dysplasia type A patient iPSC-derived MSC senescence reveals miR-311 as a novel biomarker for MSC senescence
Authors: He Liangge , Liao Jinqi , Liu Zhen , Wang Ting , Zhou Yan , Wang Tianfu , Lei Baiying , Zhou Guangqian
Published: July 2023

Mandibuloacral dysplasia type A (MADA) is a rare genetic progeroid syndrome associated with lamin A/C (LMNA) mutations. Pathogenic mutations of LMNA result in nuclear structural abnormalities, mesenchymal tissue damage and progeria phenotypes. However, it remains elusive how LMNA mutations cause mesenchymal-derived cell senescence and disease development. Here, we established an in vitro senescence model using induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) from MADA patients with homozygous LMNA p.R527C mutation. When expanded to passage 13 in vitro, R527C iMSCs exhibited marked senescence and attenuation of stemness potential, accompanied by immunophenotypic changes. Transcriptome and proteome analysis revealed that cell cycle, DNA replication, cell adhesion and inflammation might play important roles in senescence. In-depth evaluation of changes in extracellular vesicle (EV) derived iMSCs during senescence revealed that R527C iMSC-EVs could promote surrounding cell senescence by carrying pro-senescence microRNAs (miRNAs), including a novel miRNA called miR-311, which can serve as a new indicator for detecting chronic and acute mesenchymal stem cell (MSC) senescence and play a role in promoting senescence. Overall, this study advanced our understanding of the impact of LMNA mutations on MSC senescence and provided novel insights into MADA therapy as well as the link between chronic inflammation and aging development.
Universal consistency of Wasserstein k-NN classifier: a negative and some positive results
Authors: Ponnoprat Donlapark
Published: July 2023

We study the $k$-nearest neighbour classifier ($k$-NN) of probability measures under the Wasserstein distance. We show that the $k$-NN classifier is not universally consistent on the space of measures supported in $(0,1)$. As any Euclidean ball contains a copy of $(0,1)$, one should not expect to obtain universal consistency without some restriction on the base metric space, or the Wasserstein space itself. To this end, via the notion of $\sigma $-finite metric dimension, we show that the $k$-NN classifier is universally consistent on spaces of discrete measures (and more generally, $\sigma $-finite uniformly discrete measures) with rational mass. In addition, by studying the geodesic structures of the Wasserstein spaces for $p=1$ and $p=2$, we show that the $k$-NN classifier is universally consistent on spaces of measures supported on a finite set, the space of Gaussian measures and spaces of measures with finite wavelet series densities.
Robotic-assisted total knee arthroplasty for extra-articular femur deformity correction
Authors: Alturki Abdullah A , Alshammari Nayf A , Albassam Abdulrahman L , Aljaafri Ziad A , Almugren Turki S
Published: July 2023

Femoral shaft fracture is one of the most common injuries encountered. However, improper management can lead to significant long-term complications, of which is malunion. Patients with femoral malunion are at increased risk of developing knee osteoarthritis, and if arthroplasty is indicated, these extra-articular deformities pose a challenge as corrective osteotomy and soft tissue release are also required. In such circumstances, robotic arm-assisted total knee arthroplasty (RATKA) might be an appropriate option. In this case, we present a 66-year-old woman who had previously suffered a femur shaft fracture, which was treated conservatively, and developed a varus malunion and severe knee osteoarthritis, and who was treated with RATKA.
Predicting functional consequences of SNPs on mRNA translation via machine learning
Authors: Li Zheyu , Chen Liang
Published: July 2023

The functional impact of single nucleotide polymorphisms (SNPs) on translation has yet to be considered when prioritizing disease-causing SNPs from genome-wide association studies (GWAS). Here we apply machine learning models to genome-wide ribosome profiling data to predict SNP function by forecasting ribosome collisions during mRNA translation. SNPs causing remarkable ribosome occupancy changes are named RibOc-SNPs (Ribosome-Occupancy-SNPs). We found that disease-related SNPs tend to cause notable changes in ribosome occupancy, suggesting translational regulation as an essential pathogenesis step. Nucleotide conversions, such as ‘G → T’, ‘T → G’ and ‘C → A’, are enriched in RibOc-SNPs, with the most significant impact on ribosome occupancy, while ‘A → G’ (or ‘A→ I’ RNA editing) and ‘G → A’ are less deterministic. Among amino acid conversions, ‘Glu → stop (codon)’ shows the most significant enrichment in RibOc-SNPs. Interestingly, there is selection pressure on stop codons with a lower collision likelihood. RibOc-SNPs are enriched at the 5′-coding sequence regions, implying hot spots of translation initiation regulation. Strikingly, ∼22.1% of the RibOc-SNPs lead to opposite changes in ribosome occupancy on alternative transcript isoforms, suggesting that SNPs can amplify the differences between splicing isoforms by oppositely regulating their translation efficiency.
Structure–function analysis of an ancient TsaD–TsaC–SUA5–TcdA modular enzyme reveals a prototype of tRNA t6A and ct6A synthetases
Authors: Jin Mengqi , Zhang Zelin , Yu Zhijiang , Chen Wei , Wang Xiaolei , Lei Dongsheng , Zhang Wenhua
Published: July 2023

N 6-threonylcarbamoyladenosine (t6A) is a post-transcriptional modification found uniquely at position 37 of tRNAs that decipher ANN-codons in the three domains of life. tRNA t6A plays a pivotal role in promoting translational fidelity and maintaining protein homeostasis. The biosynthesis of tRNA t6A requires members from two evolutionarily conserved protein families TsaC/Sua5 and TsaD/Kae1/Qri7, and a varying number of auxiliary proteins. Furthermore, tRNA t6A is modified into a cyclic hydantoin form of t6A (ct6A) by TcdA in bacteria. In this work, we have identified a TsaD–TsaC–SUA5–TcdA modular protein (TsaN) from Pandoraviruses and determined a 3.2 Å resolution cryo-EM structure of P. salinus TsaN. The four domains of TsaN share strong structural similarities with TsaD/Kae1/Qri7 proteins, TsaC/Sua5 proteins, and Escherichia coli TcdA. TsaN catalyzes the formation of threonylcarbamoyladenylate (TC-AMP) using L-threonine, HCO3− and ATP, but does not participate further in tRNA t6A biosynthesis. We report for the first time that TsaN catalyzes a tRNA-independent threonylcarbamoyl modification of adenosine phosphates, leading to t6ADP and t6ATP. Moreover, TsaN is also active in catalyzing tRNA-independent conversion of t6A nucleoside to ct6A. Our results imply that TsaN from Pandoraviruses might be a prototype of the tRNA t6A- and ct6A-modifying enzymes in some cellular organisms.
The Threat of Anti-Theism: What is at Stake in the Axiology of God?
Authors: Ballard Brian Scott
Published: July 2023

Would God's existence be a good thing for us? According to anti-theism, the answer is No. Probably, many theists will want to reject anti-theism. But it isn’t obvious why. After all, whether p is good for us is logically independent from whether p is true. So anti-theism seems entirely compatible with theism. In this essay, however, I argue this seeming compatibility is mistaken. If anti-theism is true, then the theism of most practicing believers is false. And if I am right about this, then anti-theism presents a serious challenge to traditional theistic belief, notably theistic belief anchored in the Bible.
Interventions to Enhance Nursing Student Compliance With Infection Control: A Systematic Review
Authors: Alanazi Salwa Jadid , Haas Tanya , Scafide Katherine N.
Published: July 2023

AIM

The purpose of this review was to identify effective strategies for improving infection control practices among prelicensure nursing students.

BACKGROUND

Infection control practices are fundamental skills taught to prelicensure nursing students. The most effective teaching strategy to support infection control behaviors has yet to be determined.

METHOD

A systematic search of peer-reviewed English literature published before October 2021 was conducted in three databases, followed by critical appraisal. Outcomes included either observed or self-reported infection control behaviors.

RESULTS

Twelve eligible studies met inclusion criteria for qualitative synthesis. Studies with integrated simulation or multimodal interventions generally achieved higher infection control compliance than those with greater emphasis on traditional education. The appraisal noted intervention/instrument heterogeneity and limited control.

CONCLUSION

Didactic infection control education should be supplemented with other modalities, but further controlled studies are needed to identify which specific approach is most effective.
Nonoperative Management of Achilles Tendon Ruptures
Authors: King Brandon William , Andrews Erickson George
Published: July 2023

Acute Achilles tendon ruptures are an increasingly common injury. Although operative fixation continues to be dominant in the United States, a growing body of literature supports nonoperative management. Although the specifics of functional rehabilitation vary, many studies support this management approach. Continued controversies include the type of castor orthosis used, acceptable gap size, need for ultrasound evaluation, time to initiation of weight bearing, time to initiation of motion, duration of orthosis, length of treatment, and use of heel wedges in shoes once the orthosis is discontinued.

Level of Evidence:

Level I.
Development of Quality Measures for Inpatient Diabetes Care and Education Specialists: A Call to Action
Authors: Klinkner Gwen , Bak Leigh , Clements Jennifer N. , Gonzales Eva H.
Published: July 2023

Diabetes and hyperglycemia are associated with an increased risk of in-hospital complications that lead to longer lengths of stay, increased morbidity, higher mortality, and risk of readmission. Diabetes care and education specialists (DCESs) working in hospital settings are uniquely prepared and credentialed to serve as content experts to facilitate change and implement processes and programs to improve glycemic-related outcomes. A recent survey of DCESs explored the topic of productivity and clinical metrics. Outcomes highlighted the need to better evaluate the impact and value of inpatient DCESs, advocate for the role, and to expand diabetes care and education teams to optimize outcomes. The purpose of this article was to recommend strategies and metrics that can be used to quantify the work of inpatient DCESs and describe how such metrics can help to show the value of the inpatient DCES and assist in making a business case for the role.
Management of Patients After Treatment of Severe Alcohol-associated Hepatitis
Authors: Shetty Akshay , Ibrahim Brittney , Eskander Benjamin , Saab Sammy
Published: July 2023

Alcohol-associated liver disease is the leading indication for hospitalization among patients with chronic liver disease. Rates of hospitalization for alcohol-associated hepatitis have been rising over the last 2 decades. Patients with alcohol-associated hepatitis carry significant morbidity and mortality, but there is a lack of standardized postdischarge management strategies to care for this challenging group of patients. Patients warrant management of not only their liver disease but also their alcohol use disorder. In this review, we will discuss outpatient management strategies for patients who were recently hospitalized and discharged for alcohol-associated hepatitis. We will discuss short management of their liver disease, long-term follow-up, and review-available treatment options for alcohol use disorder and challenges associated with pursuing treatment for alcohol use disorder.
Microneedling in the relief of pain in arthritis: a brief review
Authors: Chen Kexin , Mao Xiaowei , YU Mingming , Zhou Weijiao , Shang Shaomei
Published: July 2023

Pain is the main symptom of arthritis. Microneedling is a new method of transdermal drug delivery that relives the pain in arthritis according to the mechanisms of pain in arthritis. This paper provides a review of the mechanisms of pain in arthritis and the use of different types of microneedles (MNs) in pain relief in arthritis. The mechanism of pain in arthritis is primarily a joint tissue lesion that causes the release of inflammatory factors by pro-inflammatory cells, resulting in pain. MNs can carry various drugs to reduce inflammatory factors, cartilage destruction and thus the symptom of pain. MNs can be classified into five types, which are solid MNs, hollow MNs, coated MNs, dissolving MNs, and swelling MNs. Among them, dissolving MNs and swelling MNs have better prospects for application in long-term management of pain in arthritis due to the biosafety of their materials and its convenience brought by the sustained-release design.
Palliative sedation: autonomy, suffering, and euthanasia
Authors: Colburn Ben , Johnston Bridget
Published: July 2023

Purpose of review

This contemporary and novel review of palliative sedation explores some of the distinctive ethical problems associated with that intervention. It is timely in light of recent reviews of palliative care guidelines on the topic and given the current public debates around the related but distinct practice of euthanasia.

Recent findings

The main themes discussed are patient autonomy, the nature of suffering and how to alleviate it, and the relationship between palliative sedation and euthanasia.

First, palliative sedation poses a significant problem for patient autonomy, both in terms of securing informed consent and in terms of the ongoing effect on individual well-being. Second, as an intervention to alleviate suffering, it is appropriate only in limited cases and counterproductive in others, for example, where an individual values their ongoing psychological or social agency more than the relief of pain or negative experience. Third, people’s ethical views about palliative sedation are often coloured by their understanding of the legal and moral status of assisted dying and euthanasia; this is unhelpful and occludes the interesting and urgent ethical questions raised by palliative sedation as a distinct end-of-life intervention.
Relationships Between Urinary and Nonurinary Symptoms in Treatment-Seeking Women in LURN
Authors: Smith Abigail R. , Mansfield Sarah A. , Bradley Catherine S. , Kenton Kimberly S. , Helmuth Margaret E. , Cameron Anne P. , Kirkali Ziya , Bretschneider C. Emi , Andreev Victor , Sarma Aruna , Lane Giulia , Collins Sarah A. , Cella David , Lai H. Henry , Harte Steven E. , Griffith James W. ,   the LURN Study Group
Published: July 2023

Importance

Physical health and psychological health represent modifiable factors in the causal pathway of lower urinary tract symptoms (LUTS).

Objectives

Understand the relationship between physical and psychological factors and LUTS over time.

Study Design

Adult women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network observational cohort study completed the LUTS Tool and Pelvic Floor Distress Inventory, including urinary (Urinary Distress Inventory), prolapse (Pelvic Organ Prolapse Distress Inventory), and colorectal anal (Colorectal-Anal Distress Inventory) subscales at baseline, 3 months, and 12 months. Physical functioning, depression, and sleep disturbance were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires; relationships were assessed using multivariable linear mixed models.

Results

Of 545 women enrolled, 472 had follow-up. Median age was 57 years; 61% and 78% reported stress urinary incontinence and overactive bladder, respectively; and 81% reported obstructive symptoms. The PROMIS depression scores were positively associated with all urinary outcomes (range, 2.5- to 4.8-unit increase per 10-unit increase in depression score; P < 0.01 for all). Higher sleep disturbance scores were associated with higher urgency, obstruction, LUTS Total Severity, Urinary Distress Inventory, and Pelvic Floor Distress Inventory (1.9- to 3.4-point increase per 10-unit increase, all P < 0.02). Better physical functioning was associated with less severe urinary symptoms except stress urinary incontinence (2.3- to 5.2-point decrease per 10-unit increase, all P < 0.01). All symptoms decreased over time; however, no association was detected between baseline PROMIS scores and trajectories of LUTS over time.

Conclusions

Nonurologic factors demonstrated small to medium cross-sectional associations with urinary symptom domains, but no significant association was detected with changes in LUTS. Further work is needed to determine whether interventions targeting nonurologic factors reduce LUTS in women.
A Tale of Two Cities: Policing and Firearm Homicides in Boston and Philadelphia
Authors: Hatchimonji Justin S. , Bakillah Emna , Hynes Allyson M. , Torres Cristano M. , Sanchez Sabrina E. , Seamon Mark J. , Scantling Dane R.
Published: July 2023

Background

Recent political movements have raised questions about the effectiveness of police funding, but the impact of law enforcement budgets on firearm violence is unknown. We hypothesized that department funding and measures of police activity would be associated with decreased shootings and firearm homicides (FH) in two major cities with different police funding patterns.

Methods

We collected data from these sources: district attorney’s offices, police departments, Federal Bureau of Investigation Uniform Crime Reporting program, the Centers for Disease Control, the Annual Survey of Public Employment & Payroll, and the American Community Survey. Data included demographics, police department budgets, number of officers, homicide clearance rates, firearms recovered, shootings, and FH, 2015-2020. Totals were normalized to population and number of shootings. We used panel linear regression to measure associations between policing variables, shootings and FH while adjusting for covariates.

Results

FH significantly increased in Philadelphia. In Boston the trend was less clear, though there was an increase in 2020. Police budget normalized to shootings trended towards a decrease in Philadelphia and an increase in Boston. The number of firearms recovered annually appeared to increase in Boston but peaked mid-study in Philadelphia. In multivariable analyses, police budget was associated with neither shootings nor FH. However, increased firearm recovery was associated with lower shooting (β = -.0004, p = 0.022) and FH (β = -.00005, p = 0.004) rates.

Conclusion

Philadelphia and Boston demonstrated differences in police funding, 2015-2020. While budget is not associated with shootings or FH, firearm recovery is, suggesting that removal of firearms from circulation remains key. The impact this has on vulnerable populations requires further investigation.

Level of Evidence

III, retrospective cross-sectional
An efficient method for high molecular weight bacterial DNA extraction suitable for shotgun metagenomics from skin swabs
Authors: Serghiou Iliana R. , Baker Dave , Evans Rhiannon , Dalby Matthew J. , Kiu Raymond , Trampari Eleftheria , Phillips Sarah , Watt Rachel , Atkinson Thomas , Murphy Barry , Hall Lindsay J. , Webber Mark A.
Published: July 2023

The human skin microbiome represents a variety of complex microbial ecosystems that play a key role in host health. Molecular methods to study these communities have been developed but have been largely limited to low-throughput quantification and short amplicon-based sequencing, providing limited functional information about the communities present. Shotgun metagenomic sequencing has emerged as a preferred method for microbiome studies as it provides more comprehensive information about the species/strains present in a niche and the genes they encode. However, the relatively low bacterial biomass of skin, in comparison to other areas such as the gut microbiome, makes obtaining sufficient DNA for shotgun metagenomic sequencing challenging. Here we describe an optimised high-throughput method for extraction of high molecular weight DNA suitable for shotgun metagenomic sequencing. We validated the performance of the extraction method, and analysis pipeline on skin swabs collected from both adults and babies. The pipeline effectively characterised the bacterial skin microbiota with a cost and throughput suitable for larger longitudinal sets of samples. Application of this method will allow greater insights into community compositions and functional capabilities of the skin microbiome.
Bio-optical signatures ofinsituphotosymbionts predict bleaching severity prior to thermal stress in the Caribbean coral speciesAcropora palmata
Authors: Hoadley Kenneth D. , Lowry Sean , McQuagge Audrey , Dalessandri Shannon , Lockridge Grant , Karabelas Eleftherios , Klepac Courtney , Kenkel Carly , Muller Erinn M.
Published: July 2023

The identification of bleaching tolerant traits among individual corals is a major focus for many restoration and conservation initiatives but often relies on large scale or high-throughput experimental manipulations which may not be accessible to many front-line restoration practitioners. Here we evaluate a machine learning technique to generate a predictive model which estimates bleaching severity using non-destructive chlorophyll-a fluorescence photophysiological metrics measured with a low-cost and open access bio-optical tool. First, a four-week long thermal bleaching experiment was performed on 156 genotypes ofAcropora palmataat a land-based restoration facility. Resulting bleaching responses (percent change in Fv/Fm or Absorbance) significantly differed across the four distinct phenotypes generated via a photophysiology-based dendrogram, indicating strong concordance between fluorescence-based photophysiological metrics and future bleaching severity. Next, these correlations were used to train and then test a Random Forest algorithm-based model using a bootstrap resampling technique. Correlation between predicted and actual bleaching responses in test corals was significant (p <0.0001) and increased with the number of corals used in model training (Peak average R2values of 0.42 and 0.33 for Fv/Fm and absorbance, respectively). Strong concordance between photophysiology-based phenotypes and future bleaching severity may provide a highly scalable means for assessing reef corals.
Corticosterone exposure causes long-term changes in DNA methylation, physiology, and breeding decisions in a wild bird
Authors: Taff Conor C. , McNew Sabrina M. , Campagna Leonardo , Vitousek Maren N.
Published: July 2023

When facing challenges, vertebrates activate an evolutionarily conserved hormonal stress response that can dramatically alter behavior and physiology. Although this response can be costly, conceptual models suggest that it can also recalibrate the stress response system, priming more effective responses to future challenges. Little is known about whether this process occurs in wild animals, particularly in adulthood, and if so, how information about prior experience with stressors is encoded. One potential mechanism is hormonally-mediated changes to DNA methylation. We simulated the spikes in corticosterone that accompany an acute stress response using non-invasive dosing in female tree swallows (Tachycineta bicolor) and monitored the phenotypic effects one year later, and DNA methylation both shortly after treatment and a full year later. The year after treatment, experimental females had stronger negative feedback and initiated breeding earlier – traits that are associated with stress resilience and reproductive performance in our population – and higher baseline corticosterone. We also found that natural variation in stress-induced corticosterone predicted patterns of DNA methylation, including methylation of the MC2R gene, which encodes the adrenocorticotropic hormone receptor. Finally, corticosterone treatment causally influenced methylation on short (1-2 weeks) and long (1 year) time scales; however, many of these changes did not have clear links to functional regulation of the stress response. Taken together, our results are consistent with corticosterone-induced priming of future stress resilience, and support DNA methylation as a potential mechanism. Uncovering the mechanisms linking experience with the response to future challenges has implications for understanding the drivers of stress resilience.

SIGNIFICANCE

A stress response to an environmental challenge can preserve an individual’s fitness and may even prime them to survive similar challenges in the future. What mechanisms underlie priming is unclear, but epigenetic alterations to stress-related genes are one possibility. We experimentally tested whether increasing corticosterone in free-living swallows had lasting phenotypic or epigenetic effects. A year after treatment, females who received corticosterone had altered stress physiology and bred earlier than control birds, traits that are associated with higher fitness. Treatment also altered DNA methylation and methylation of the MC2R gene was correlated with stress physiology. This study adds to a growing body of literature suggesting that epigenetic changes are key to animals’ response to a changing environment.
Cell-penetrating peptides stimulate protein transport on the Twin-arginine translocation pathway
Authors: McNeilage Robert , Ganesan Iniyan , Keilman Johnathan , Theg Steven M.
Published: July 2023

The Tat pathway is essential for photosynthetic protein transport across plant thylakoid membranes and is also ubiquitous throughout prokaryotes and archaea. The Tat pathway is unique amongst protein translocation pathways as it specializes in transporting folded proteins driven by a proton motive force. Mechanistic details of the actual translocation step (s) of the pathway remain elusive. Here, we show that membrane thinning stimulates Tat transport and, conversely, membrane strengthening abolishes Tat transport. We draw parallels from the Tat transport mechanism to that of cell penetrating peptides and propose that the Tat pore could be toroidal in shape and lined by lipids, as in those formed by cell penetrating peptides.

Significance Statement

Protein translocation across membranes is a significant cellular activity in both prokaryotes and eukaryotes. The Tat pathway for protein translocation operates in bacteria, archaea, chloroplasts, and plant mitochondria. Its mechanism of action has been difficult to decipher, but recent evidence suggests it does not use a conical proteinaceous transport channel. Instead, it has been suggested to translocate proteins through lipid-lined toroidal pores set up by membrane thinning. This work supports that hypothesis by showing that membrane-thinning cell-penetrating peptides stimulate the Tat pathway in both chloroplasts and bacterial plasma membranes, and that membrane stabilization blocks the pathway. We believe this is the most direct evidence to date of the toroidal pore mechanism operating in the Tat pathway.
Inhibition of an immunometabolic axis of mTORC1 activation extends mammalian healthspan
Authors: Widjaja Anissa A. , Lim Wei-Wen , Viswanathan Sivakumar , Chothani Sonia , Corden Ben , Goh Joyce Wei Ting , Tan Jessie , Pua Chee Jian , Lim Radiance , Singh Brijesh K. , Cibi Dasan Mary , Weber Susanne , Lim Sze Yun , Adami Eleonora , George Benjamin L. , Sweeney Mark , Xie Chen , Tripathi Madhulika , Withers Dominic J , Hübner Norbert , Schafer Sebastian , Ho Lena , Gil Jesus , Carling David , Cook Stuart A.
Published: July 2023

Human ageing is associated with metabolic dysfunction, sarcopenia and frailty that taken together reduce healthspan. For age-associated diseases and lifespan, ERK, AMPK and mTORC1 represent critical pathways, across species1–7. Here we examined the hypothesis that IL11, recently shown to regulate ERK/mTORC1, is an inflammaging factor important for healthspan. As mice age, IL11 is progressively upregulated in liver, skeletal muscle, and fat to stimulate an ERK/AMPK/mTORC1 axis of cellular, tissue- and organismal-level ageing pathologies. In old mice, deletion ofIl11orIl11ra1protects against metabolic multi-morbidity, sarcopenia, and frailty. Administration of anti-IL11 therapy to elderly mice for six months reactivates an age-repressed program of white fat beiging, reverses metabolic dysfunction, restores muscle function, and reduces frailty. Across studies, inhibition of IL11 lowers epigenetic age, reduces telomere attrition, and preserves mitochondrial function. Towards clinical translation, we generated, humanised, and engineered a neutralising, high-affinity IL11 antibody. These studies identify IL11 as a key inflammaging factor and therapeutic target for mammalian healthspan.
An amino acid-resolution interactome for motile cilia illuminates the structure and function of ciliopathy protein complexes
Authors: McCafferty Caitlyn L. , Papoulas Ophelia , Lee Chanjae , Bui Khanh Huy , Taylor David W. , Marcotte Edward M. , Wallingford John B.
Published: July 2023

Motile cilia are ancient, evolutionarily conserved organelles whose dysfunction underlies motile ciliopathies, a broad class of human diseases. Motile cilia contain myriad different proteins that assemble into an array of distinct machines, so understanding the interactions and functional hierarchies among them presents an important challenge. Here, we defined the protein interactome of motile axonemes using cross-linking mass spectrometry (XL/MS) inTetrahymena thermophila. From over 19,000 XLs, we identified 4,757 unique amino acid interactions among 1,143 distinct proteins, providing both macromolecular and atomic-scale insights into diverse ciliary machines, including the Intraflagellar Transport system, axonemal dynein arms, radial spokes, the 96 nm ruler, and microtubule inner proteins, among others. Guided by this dataset, we used vertebrate multiciliated cells to reveal novel functional interactions among several poorly-defined human ciliopathy proteins. The dataset therefore provides a powerful resource for studying the basic biology of an ancient organelle and the molecular etiology of human genetic disease.

Highlights

Over 4,700 distinct amino-acid cross-links reveal the composition, structural organization, and conformational dynamics of proteins in motile ciliary axonemes.

Dense interaction networks are defined for tubulins, Intraflagellar Transport complexes, axonemal dyneins, radial spokes, the CCDC39/40 96nm molecular ruler, and other complexes.

These data reveal the placement of multiple adenylate kinases in the central apparatus and radial spokes of motile axonemes, a new microtubule-associated protein complex of CFAP58 and CCDC146, and insights into the activity of ciliopathy protein MAATS1/CFAP91.

The data also provide the first known molecular defect resulting from loss of the human ciliopathy protein ENKUR.
Extended Q-range small-angle neutron scattering to understand the morphology of proton-exchange membranes: the case of the functionalized syndiotactic-polystyrene model system
Authors: Schiavone Maria-Maddalena , Lamparelli David Hermann , Daniel Christophe , Golla Manuchar , Zhao Yue , Iwase Hiroki , Arima-Osonoi Hiroshi , Takata Shin-ichi , Szentmiklosi Laszlo , Maroti Boglarka , Allgaier Jürgen , Radulescu Aurel
Published: July 2023

Semi-crystalline polymers exhibit microphase separation into crystalline and amorphous domains characterized by multiple structural levels with sizes ranging from ångströms to hundreds of nanometres. The combination of small-angle (SANS) and wide-angle (WANS) neutron scattering on the same beamline enables reliable in situ characterization of such materials under application-relevant conditions, with the unique advantage of contrast variation by controlled labelling, allowing the structure of such multi-component systems to be resolved in detail. This paper reports a structural analysis performed on deuterated polymer membranes based on syndiotactic polystyrene (sPS) using an extended Q-range SANS and WANS combination, always with the same neutron scattering instrument, either a pinhole SANS diffractometer installed at a research reactor or a `small- and wide-angle' time-of-flight diffractometer installed at a neutron spallation source. sPS is a semi-crystalline material that becomes hydrophilic and proton conducting when suitable functionalization is achieved by thin film sulfonation, and can form various co-crystalline complexes (clathrates) with small organic molecules stored in the crystalline phase as guests in the vacancies between the polymer helices. Therefore, this material is interesting not only for its conducting properties but also for its versatility as a model system to evaluate the usefulness of extended Q-range neutron scattering in such studies. Variation of neutron contrast was achieved in the amorphous hydrophilic phase by using H2O or D2O to hydrate the membranes and in the crystalline phase by loading the clathrates with deuterated or protonated guest molecules. The experimental approach, the advantages and limitations of the two types of instrumentation used in such analyses, and the main results obtained with respect to the structural characterization of sulfonated sPS membranes under different hydration and temperature conditions are reported, and the potential of this method for similar structural studies on other semi-crystalline polymeric materials is discussed.