bluuebunny/crossref_metadata_2025 huggingface dataset:
Trade, Attitudes to Trade, and Trade Regulation
Authors: Howard-Johnston James
Published: August 2024

Despite the studied indifference of the governing classes, it is undeniable that manufacturing and commerce were important in the Roman empire in antiquity. Mercantile enterprise was programmed into Byzantium and the Aegean from the deep past and can be glimpsed in the dark centuries of defensive warfare. An important text, the Book of the Eparch, casts light on commercial activity in Constantinople in the tenth century and on the regulatory system—subtle, sensitive to the particularities of individual trades and the varying concerns of government. Textual and archaeological evidence reveals an active market in the Aegean and along the trade routes radiating out to the Khazar khaganate and its successors in the north, the Caliphate in the east, and the Latin west. Byzantium had a commercial and industrial sector which generated considerable wealth in the tenth–twelfth centuries.
TWAS-GKF: a novel method for causal gene identification in transcriptome-wide association studies with knockoff inference
Authors: Wang Anqi , Tian Peixin , Zhang Yan Dora
Published: August 2024

Motivation

Transcriptome-wide association study (TWAS) aims to identify trait-associated genes regulated by significant variants to explore the underlying biological mechanisms at a tissue-specific level. Despite the advancement of current TWAS methods to cover diverse traits, traditional approaches still face two main challenges: (i) the lack of methods that can guarantee finite-sample false discovery rate (FDR) control in identifying trait-associated genes; and (ii) the requirement for individual-level data, which is often inaccessible.

Results

To address this challenge, we propose a powerful knockoff inference method termed TWAS-GKF to identify candidate trait-associated genes with a guaranteed finite-sample FDR control. TWAS-GKF introduces the main idea of Ghostknockoff inference to generate knockoff variables using only summary statistics instead of individual-level data. In extensive studies, we demonstrate that TWAS-GKF successfully controls the finite-sample FDR under a pre-specified FDR level across all settings. We further apply TWAS-GKF to identify genes in brain cerebellum tissue from the Genotype-Tissue Expression (GTEx) v8 project associated with schizophrenia (SCZ) from the Psychiatric Genomics Consortium (PGC), and genes in liver tissue related to low-density lipoprotein cholesterol (LDL-C) from the UK Biobank, respectively. The results reveal that the majority of the identified genes are validated by Open Targets Validation Platform.

Availability and implementation

The R package TWAS.GKF is publicly available at https://github.com/AnqiWang2021/TWAS.GKF.
Increasing opportunities for breast-conserving therapy in multiple ipsilateral breast cancer: Dutch nationwide study
Authors: Heeling Eva , Volders José H , de Roos Wilfred K , van Eekeren Ramon R J P , van der Ploeg Iris M C , Vrancken Peeters Marie-Jeanne T F D
Published: August 2024

Introduction

An increasing number of breast cancer patients undergo breast-conserving surgery (BCS), but multiple ipsilateral breast cancer (MIBC) is still considered a relative contraindication for breast conservation. This study provides an update on trends in the surgical management for MIBC over a 10-year period.

Methods

Nationwide data from the Netherlands Cancer Registration of all patients diagnosed with breast cancer between 2011 and 2021 were analysed. The primary outcomes of this study were the incidence of MIBC and the trend in breast surgery type among patients between 2011 and 2021. Secondary outcomes were the positive resection margin rates in patients treated with BCS, the proportion of patients requiring re-excision and overall survival.

Results

In total, 114 433 patients (83%) with unifocal breast cancer and 23 932 patients (17%) with MIBC were identified. The incidence of MIBC was stable (17%) over the years. Overall BCS rates, both primary and after neoadjuvant chemotherapy, increased in MIBC from 29% in 2011 to 41% in 2021. Re-excision was performed in 1348 patients (n = 8455, 16%). The 5-year OS estimate for patients with MIBC treated with BCS was 93%. The pathological complete response (pCR) in MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy was 23%.

Conclusion

The breast conservation rate in MIBC has increased over the last decade. In addition, 23% of MIBC patients treated with neoadjuvant chemotherapy followed by mastectomy achieved a pCR. This suggests increasing opportunities for even more BCS in MIBC.
CoinFA: an efficient coin mixing scheme with flexible amounts
Authors: Yang Xin , Zeng Peng , Raymond Choo Kim-Kwang , Li Chengju , Yang Yanzhao
Published: August 2024

Coin mixing is an efficient anonymization technology of cryptocurrency used to eliminate the linkability of transaction parties by hiding their addresses in an anonymous set. However, a common weakness with most existing coin mixing schemes is that the amount of mixed coins must be the same for all requests within a mixing cycle, otherwise it is easy for an attacker to restore the linkability of transaction parties. In this paper, we design a stage-payable puzzle solution mechanism, named CoinFA, which reverses the control of the requesting amounts to the users for flexible mixing amounts. In our design, the payee (with an output address) first requests a puzzle from the mixers and the latter are the only ones who know the solution of the puzzle. If the payee solves the puzzle successfully, he can be rewarded with the corresponding Bitcoins. The payer (allowed to have multiple input addresses) then requests the solution by paying in installments. We achieve better security by weakening the rights of the involved third parties, while the hierarchical structure allows our solution to have better efficiency and robustness. We perform a security analysis on CoinFA based on the standard Rivest-Shamir-Adleman (RSA) assumption and Elliptic Curve Digital Signature Algorithm unforgeability. We also analyze the performance of CoinFA by comparing it with two related schemes, and the results show that our CoinFA scheme has a greater advantage when the mixing amount is relatively small.
Prevalence of Sexual Dysfunction in Inflammatory Bowel Disease: Systematic Review and Meta-analysis
Authors: Nardone Olga Maria , Calabrese Giulio , Bertin Luisa , Ford Alexander C , Castiglione Fabiana , Zingone Fabiana , Savarino Edoardo , Barberio Brigida
Published: August 2024

Background and Aims

Patients with inflammatory bowel disease (IBD) may experience symptoms of sexual dysfunction (SD). However, the magnitude of this problem remains uncertain. Therefore, we performed a systematic review and meta-analysis to assess the prevalence of SD in adult patients with IBD.

Methods

MEDLINE, EMBASE, and EMBASE Classic (from inception to April 9, 2024) were searched to identify observational studies reporting the prevalence of SD in adult patients with IBD based on validated screening instruments. Data were extracted, and pooled prevalence (PP), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated.

Results

Of 1017 citations evaluated, 18 articles fulfilled the eligibility criteria, containing 2694 patients with IBD recruited from 13 different countries. The PP of SD in IBD patients was 50.6% (95% CI, 40.8%-60.5%; I2 = 96.3%) with an OR = 2.94 (95% CI, 1.99%-4.35%, I2 = 73.4) compared to healthy controls. When we considered ulcerative colitis (UC) or Crohn’s disease (CD) separately, the PP of SD was 64.8% (95% CI, 45.1%-82.1%; I2 = 88.8%) in patients with UC and 58.3% (95% CI, 36.0%-79.0%; I2 = 95.3%) in patients with CD. In the subgroup analysis based on sex, the PP of SD was higher in females with IBD than in males (62.7% vs 34.0%; OR = 3.99, 95% CI, 2.80%-5.68%; I2 = 61.7%). Furthermore, the PP of SD was higher in patients with active disease than in patients with inactive disease (75.1% vs 34.2%; OR = 9.65, 95% CI, 1.02%-91.33%, I2 = 95.5%).

Conclusions

We demonstrated high prevalence of SD in IBD patients, especially in women. Encouraging gastroenterologists to screen for, and treat, these disorders with a holistic approach might improve quality of life of patients with IBD.
Epidemiology and clinical correlates of hidradenitis suppurativa in primary care in Italy
Authors: Lapi Francesco , Marconi Ettore , Casoli Lucia , Tedeschi Andrea , Giomi Barbara , Cricelli Claudio
Published: August 2024

Background

Hidradenitis suppurativa (HS) is a persistent skin disorder that is characterized by painful lesions or pus-filled lumps, mostly occurring in areas where the skin flexes. It is a disfiguring condition that significantly reduces the quality of life of those affected. Developing new, effective treatments for HS is crucial, but it is important that it be recognized and diagnosed early, especially in primary care settings.

Objectives

To assess the epidemiology and clinical correlates of HS in a primary care setting. The study utilized the Italian Health Search Database (HSD). A case-control design was adopted to investigate the clinical correlates of HS. Cases were classified as either “definite” or “probable” using an operational algorithm. Up to 10 controls were matched to each case based on factors such as calendar period, age, sex, and duration of follow-up.

Results

Cumulative prevalence of HS increased from 0.06% in 2002 to 0.46% in 2021. When only “definite” cases were considered, the prevalence was almost 10 times lower (0%–0.02%). Several clinical correlates were found to be positively associated with HS, including obesity, dyslipidemia, hypertension, autoimmune/inflammatory diseases, and depression.

Conclusions

This study found that correct diagnoses of HS were made, as demonstrated by the expected relationship with clinical correlates. These associations were consistent when probable cases were included in the analysis. This evidence could serve as a foundation for proposing a decision support system for general practitioners to help identify HS in individuals with certain coexisting conditions.
New perspectives in hepatocellular carcinoma surveillance after hepatitis C virus eradication
Authors: Pan Calvin Q , Park Andrew J , Park James S
Published: August 2024

Achieving a sustained virologic response (SVR) through direct-acting antivirals for hepatitis C virus (HCV) infection significantly reduces the long-term risk of hepatocellular carcinoma (HCC), particularly in patients with advanced fibrosis (F3) or cirrhosis (F4). However, despite this improvement, the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate. This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively, especially at advanced fibrosis (F3), and the unclear cost-effectiveness, modality, frequency, and duration of HCC surveillance in individuals with SVR but without cirrhosis. These factors contribute to significant variations in surveillance guidelines recommended by different professional societies. Therefore, there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians. This review article evaluates the existing data, addresses ongoing controversies, and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.
De Novo Genome Assemblies From Two Indigenous Americans from Arizona Identify New Polymorphisms in Non-Reference Sequences
Authors: Köroğlu Çiğdem , Chen Peng , Traurig Michael , Altok Serdar , Bogardus Clifton , Baier Leslie J
Published: August 2024

There is a collective push to diversify human genetic studies by including underrepresented populations. However, analyzing DNA sequence reads involves the initial step of aligning the reads to the GRCh38/hg38 reference genome which is inadequate for non-European ancestries. In this study, using long-read sequencing technology, we constructed de novo genome assemblies from two indigenous Americans from Arizona (IAZ). Each assembly included ∼17 Mb of DNA sequence not present [nonreference sequence (NRS)] in hg38, which consists mostly of repeat elements. Forty NRSs totaling 240 kb were uniquely anchored to the hg38 primary assembly generating a modified hg38-NRS reference genome. DNA sequence alignment and variant calling were then conducted with whole-genome sequencing (WGS) sequencing data from 387 IAZ using both the hg38 and modified hg38-NRS reference maps. Variant calling with the hg38-NRS map identified ∼50,000 single-nucleotide variants present in at least 5% of the WGS samples which were not detected with the hg38 reference map. We also directly assessed the NRSs positioned within genes. Seventeen NRSs anchored to regions including an identical 187 bp NRS found in both de novo assemblies. The NRS is located in HCN2 79 bp downstream of Exon 3 and contains several putative transcriptional regulatory elements. Genotyping of the HCN2-NRS revealed that the insertion is enriched in IAZ (minor allele frequency = 0.45) compared to other reference populations tested. This study shows that inclusion of population-specific NRSs can dramatically change the variant profile in an underrepresented ethnic groups and thereby lead to the discovery of previously missed common variations.
Microplastic Leachate Negatively Affects Fertilization in the Coral Montipora capitata
Authors: Wilkins Keiko W , Yew Joanne Y , Seeley Meredith , Richmond Robert H
Published: August 2024

Synopsis

Microplastic pollution is an emerging stressor of concern to coral reef ecosystems, which are already threatened by additional global and local level anthropogenic stressors. The effects of ingesting microplastics alone on corals have been well studied, but the effects of the chemical composition of these particles have been understudied. Many microplastic-associated chemicals are endocrine disrupters potentially posing a threat to organismal reproduction. Therefore, the goal of this study was to determine if differences exist between the effects of microplastics themselves and microplastic leachate on Montipora capitata fertilization due to changes in fatty acid quantity and composition. Assays were conducted two years in a row which exposed M. capitata gamete bundles to either one of four types of recently manufactured, virgin microspheres (nylon, polypropylene, high-density polyethylene, or low-density polyethylene) at three concentrations (50, 100, or 200 particles/L) or microplastic leachates, presumably including plastic additives from these microspheres. Gamete fertilization was not impacted by microplastic particles themselves, but some of the microplastic leachate treatments with the same polymer type significantly reduced fertilization rates for M. capitata. Additionally, a total of 17 fatty acids were seen in both years, but neither fatty acid quantity nor composition correlated with observed declines in fertilization. Instead, fertilization and fatty acid data independently varied by concentration and polymer type, likely due to the presence of different chemicals. This study is the first to directly test the toxicity of microplastic leachate to coral reproduction. These findings show that microplastic-associated chemicals are an important stressor affecting successful coral fertilization and fatty acid quantity and composition and provide evidence for the negative effects of microplastic leachate to coral reproduction. Thus, plastic additives could pose an additional threat to coral replenishment and persistence in coral reef ecosystems.
New findings on the genetic basis of feathered legs in chickens: association of CUBN gene mutations with feathered-leg phenotype
Authors: Huang Lan , Guo Qixin , Sun Jialuo , Wang Zhixiu , Jiang Yong , Chang Guobin , Bai Hao
Published: August 2024

Chickens are the most thoroughly domesticated vertebrate species, and after long-continued natural and artificial selection, they now show rich phenotypic diversity. In particular, feathered legs present in domestic chickens are a characteristic that is carefully selected by advanced breeders. Previous studies have identified the key mutations responsible for feathered legs on chromosomes 13 and 15; however, not all chickens can be easily distinguished based on these two markers. In this study, whole-genome resequencing of 29 Bamaxiaogu chickens (BXCs) yielded 12,201,978 valid single-nucleotide polymorphisms (SNPs) and 2,792,426 valid insertions and deletions (InDels). Population structure analysis based on SNPs revealed that the test samples came from the same natural population. Based on these findings, we used an SNP- and InDel-based genome-wide association study (GWAS) to investigate the genetic basis of feathered legs in chickens. GWAS results revealed that 2 SNPs located in the introns of cubilin (CUBN; SNP1, chr2:19885382T>A) and recombinant Ras suppressor protein 1 (RSU1) genes (SNP2, chr2:20002551G>A), as well as an InDel (InDel1, chr2:19884383TG>T) on CUBN, were all significantly associated with the presence of feathered legs. Diagnostic testing demonstrated that SNP1 effectively differentiated between chickens with feathered legs and those with clean legs (leg without feathers) within the BXC population and may thus be considered an effective marker of feathered legs in BXC. In contrast, other loci did not show the same discriminatory power. This study not only presents a new variant of feathered legs but also provides valuable novel insights into the underlying mechanisms of variation in the feathered-legs trait among chickens.
Examining imidacloprid behaviorally resistant house flies (Musca domestica L.) (Diptera: Muscidae) for neonicotinoid cross-resistance
Authors: Torres Jaqueline N , Hubbard Caleb B , Murillo Amy C
Published: August 2024

The house fly (Musca domestica L.) is a ubiquitous fly species commonly associated with confined animal and urban waste storage facilities. It is known for its pestiferous nature and ability to mechanically vector numerous disease-causing pathogens. Effective control of adult house fly populations has traditionally relied upon insecticidal food baits; however, due to the overuse of insecticides, resistance has proven to yield many insecticidal baits and chemical classes less effective. Imidacloprid, the most widely used neonicotinoid, has been formulated and commonly used in house fly baits for over 2 decades. However, widespread evidence of physiological and behavioral resistance to imidacloprid has been documented. While previous studies have investigated the mechanisms of behavioral resistance to imidacloprid in the house fly, it remains unclear whether behavioral resistance is specific to imidacloprid or if behavioral cross-resistance exists to other compounds within the neonicotinoid class of insecticides. The current study used no-choice and choice-feeding bioassays to examine a lab-selected imidacloprid behaviorally resistant house fly colony for cross-resistance to other insecticides in the neonicotinoid chemical class. All flies exhibited high mortality (97–100%) in no-choice assays, even when exposed to imidacloprid, indicating physiological susceptibility to all tested neonicotinoids. House flies exhibited high mortality (98–100%) in choice assays when exposed to all neonicotinoid insecticides tested besides imidacloprid. These results confirm that imidacloprid behavioral resistance is specific to the compound imidacloprid and that alternative neonicotinoids remain viable options for control. Our study showed no evidence of behavioral cross-resistance to other compounds in the neonicotinoid class.
Where There’s Hope, There’s Life
: On the Importance of Hope in Health Care
Authors: Clarke Steve , Oakley Justin
Published: August 2024

It is widely supposed that it is important to ensure that patients undergoing medical procedures hope that their treatments will be successful. But why is hope so important, if indeed it is? After examining the answers currently on offer in the literature, we identify a hitherto unrecognized reason for supposing that it is important that patients possess hope for a successful treatment, which draws on prospect theory, Kahneman and Tversky’s hugely influential descriptive theory about decision-making in situations of risk and uncertainty. We also consider some concerns about patient consent and the potential manipulation of patients that are raised by our account.
A rare case of chicken wishbone in Meckel’s diverticulum causing partial perforation and diverticulitis
Authors: Mamukadze Irada , Park Sean , Flessland Olivia , Moberg Libby , Jentz Amy
Published: August 2024

Meckel’s diverticulum (MD), a rare congenital abnormality, can lead to issues like diverticulitis and bleeding. Foreign bodies in MD are even rarer, causing vague symptoms and perforation, requiring urgent surgery. This case report highlights a patient with a foreign body in MD, focusing on clinical presentation and management. A 55-year-old male presented with abdominal pain, nausea, and vomiting. Computed tomography scan revealed a foreign body perforating the small bowel. Exploratory laparotomy found a partially perforated MD with a foreign body. Diverticulectomy was performed, and the patient recovered, discharged the next day. Foreign bodies in MD are exceedingly rare and can cause inflammation, infection, and perforation, mimicking appendicitis. Diagnosis is challenging due to nonspecific symptoms, with imaging and clinical evaluation crucial. Surgical intervention, like diverticulectomy, is primary. Early diagnosis and prompt surgery are critical in managing MD complicated by foreign bodies, ensuring favorable outcomes. This report underscores symptom recognition and effective management strategies.
Challenges in diagnosis and management of invasive ductal carcinoma in axillary ectopic breast tissue: a case study
Authors: Suliman Alsadig , Osman MagdAlden , Ali Siddig , Hussein Sara , Osman Reem Mohamed , Tageldin Enas , Ali Lobna E
Published: August 2024

Ectopic breast tissue (EBT) is breast tissue located outside the normal anatomic boundaries of the breasts, developing due to incomplete embryological regression of the mammary ridges. EBT can develop anywhere along the milk line, with the axilla being the most common site. While generally benign, EBT can undergo malignant transformation. This case report discusses a 24-year-old female with locally advanced invasive ductal carcinoma in the axillary EBT, highlighting its clinical presentation, diagnostic process, and management in a resource-limited setting. The patient underwent wide local excision and axillary lymph node dissection followed by adjuvant chemotherapy and radiotherapy, achieving a favorable short-term outcome. This case underscores the importance of considering EBT in differential diagnosis of axillary masses and the need for tailored treatment strategies in such settings.
Spin evolution of neutron stars in transient low-mass X-ray binaries
Authors: Cui Zhe , Li Xiang-Dong
Published: August 2024

Millisecond pulsar + helium white dwarf (MSP + He WD) binaries are thought to have descended from neutron star low-mass X-ray binaries (NS LMXBs). The NSs accreted from the progenitors of the WDs and their spin periods were accordingly accelerated to the equilibrium periods of order milliseconds. Thus, the initial spin periods of the ‘recycled’ NSs are critically determined by the average mass transfer rate in the LMXB phase. However, the standard picture neglects the possible spin-down of the NSs when the donor star decouples from its Roche lobe at the end of the mass transfer, as well as the transient behaviour of most LMXBs. Both imply more complicated spin evolution during the recycling process. In this work, we perform detailed calculations of the formation of MSP + He WD binaries. We take into account three magnetic braking (MB) prescriptions proposed in the literature, and examine the effects of both persistent and transient accretion. We find that the spin periods are not sensitively dependent on the efficiency of MB, but are considerably influenced by the accretion mode. In comparison with persistent accretion, transient accretion leads to shorter and longer spin periods of the NSs in narrow and wide systems, respectively. This may help account for the measured spin periods of MSPs in wide binaries, which seem to be longer than predicted by the persistent accretion model.
Comparing Gaia, NED, and SIMBAD source classifications in nearby galaxies
Authors: Hales J , Barmby P
Published: August 2024

Gaia Data Release 3 (DR3) provides the first classifications for the sources in Gaia’s all-sky database. Most Gaia sources are stars in the Milky Way, but DR3 also contains many sources that belong to nearby galaxies, as well as background galaxies and quasars. In this work, we compare the Gaia classifications from the Discrete Source Classifier (CU8-DSC) module to the more detailed and heterogeneous classifications in NED (NASA Extragalactic Database) and/or SIMBAD (Set of Identifications, Measurements and Bibliography for Astronomical Data) for sources with sky positions within twice the Holmberg radius of nearby galaxies. Matching these catalogues gives approximately $3.2\times 10^5$ unique Gaia matches for $4\times 10^5$ sources over 1040 galaxies (excluding some large Local Group galaxies) in the Local Volume Galaxy catalogue. Matched sources contain a lower fraction of Gaia-classified stars and higher fractions of galaxies and quasars ($\sim 95$ per cent, 2 per cent, and 2 per cent, respectively) than DR3 overall. Considering NED (SIMBAD) classifications as truth values, the balanced accuracy of Gaia classification is 0.80 (0.83): the most common disagreements are literature-classified galaxies Gaia-classified as stars and literature-classified stars Gaia-classified as quasars. Purity (P) and completeness (C) metrics show that agreement between Gaia classification and NED/SIMBAD classification is best for stars ($P\, \mathrm{ and}\, C\sim 0.9$), and decreases for quasars ($P\lt 0.3$ and $0.7\lt C\lt 0.8$), galaxies ($0.7\lt P\lt 0.8$ and $0.3\lt C\lt 0.6$), white dwarfs ($0.04\lt P\lt 0.6$ and $C\sim 0.6$), and binary stars ($P\, \mathrm{ and}\, C\lt 0.1$). NED or SIMBAD sources classified only by detection wavelength are most often Gaia-classified as stars, while non-stellar components of galaxies appear in all Gaia classes.
Adult outcomes of childhood kidney replacement therapy in Europe from 2008 to 2019: an ERA Registry study
Authors: Montez de Sousa Iris R , Bonthuis Marjolein , Kramer Anneke , Ordoñez Flor Angel , de la Cerda Ojeda Francisco , Rydell Helena , Helve Jaakko , Groothoff Jaap W , Hommel Kristine , Buchwinkler Lukas , Segelmark Mårten , Arici Mustafa , Palsson Runolfur , Bell Samira , Trujillo-Alemán Sara , Bakkaloglu Sevcan A , Sørensen Søren S , Vila Anna , Ortiz Alberto , Stel Vianda S , Jager Kitty J
Published: August 2024

Background

Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients’ characteristics, treatment history, and graft and patient survival, to report their 5-year prognosis and expected remaining lifetime.

Methods

Data on KRT patients reaching their 18th birthday in 2008–19 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years old. Kaplan–Meier and Cox proportional hazards regression were used for patient and graft survival analyses.

Results

In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0–4 years) and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% [95% confidence interval (CI) 96.2–97.5]. Dialysis patients had a higher risk of death than kidney transplant recipients [adjusted hazard ratio 5.44 (95% CI 3.34–8.86)]. Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for 18-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively.

Conclusion

Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population, yet having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis.
Thermally drawn multi-material fibers: from fundamental research to industrial applications
Authors: Chen Xin , Meng Yan , Laperrousaz Stella , Banerjee Hritwick , Song Jinwon , Sorin Fabien
Published: August 2024

Thermally drawn fiber devices, with their complex micro- to nanoscale architectures, hold great promises not only for scientific research but also for scalable industrial applications in soft smart systems.
Effects of Vitamin D Supplementation and Baseline Vitamin D Status on Acute Respiratory Infections and Cathelicidin: A Randomized Controlled Trial
Authors: Laaksi Akseli , Kyröläinen Heikki , Pihlajamäki Harri , Vaara Jani P , Luukkaala Tiina , Laaksi Ilkka
Published: August 2024

Background

Vitamin D supplementation may lower the risk of acute respiratory infection (ARI), and the effects may be mediated through the induction of cathelicidin production.

Objective

To study the effect of vitamin D supplementation on ARI and cathelicidin concentration in a randomized controlled trial (RCT) and to study the associations between baseline serum 25 hydroxyvitamin D (25(OH)D) and ARIs and cathelicidin concentrations in a 14-week follow-up study.

Methods

In the RCT study, the participants were randomized into 2 groups to receive either 20 µg of vitamin D3 or an identical placebo daily. Blood samples were obtained 3 times, at the beginning (study week 0), mid-term (study week 6), and at the end of the study period (study week 14). The follow-up study had 412 voluntary young men from 2 different locations and seasons (January and July). The primary outcomes were the number of ARIs diagnosed and the number of days off because of ARI.

Results

In the RCT, vitamin D supplementation had no effect on ARI or days off because of ARI. However, regardless of the group, vitamin D insufficiency (<50 nmol/L) was associated with increased ARI. In the 14-week follow-up study, insufficient serum 25(OH)D at baseline was also associated with increased risk of ARI (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2–3.7) and also days-off duty (OR, 2.3; 95% CI, 1.3–4.0) and was inversely associated with cathelicidin concentration (OR, 0.49; 95% CI, .24–.99).

Conclusions

Sufficient serum 25(OH)D may be preventive against acute respiratory infection and the preventive effect could be mediated through the induction of cathelicidin production.

Clinical Trial Registry number: NCT05014048. https://clinicaltrials.gov/study/NCT05014048?term=NCT05014048&rank=1
“Let Us… Take Our Places in Public Affairs:” Black Women’s Political Activism in the Pacific Northwest, 1870–1920
Authors: Cobbins-Modica Quin’Nita
Published: August 2024

African American women in the Pacific Northwest played a significant role in local and national political campaigns before the ratification of the Nineteenth Amendment. Despite being a marginal population, they helped secure women’s voting rights and created a network of gendered partisan clubs and organizations throughout the region’s urban localities. Collectively, they sought to protect fundamental civil and human rights, expand women’s freedoms, and improve the lives of African Americans. By 1918, their organizing power and leadership within the Republican Party gave rise to the historic campaign of Alice S. Presto, the first documented Black woman to run for elective office in the United States. This article examines the early activism of western Black women and the ways they wielded their electoral and political influence to help shape the concepts of freedom and progressive politics in the American West.
Optimizing transcriptome-based synthetic lethality predictions to improve precision oncology in early-stage breast cancer: BC-SELECT
Authors: Kim Yewon , Nagy Matthew , Pollard Rebecca , Rajagopal Padma Sheila
Published: August 2024

Patients with early-stage triple-negative (TNBC) or HER2-positive (HER2+) breast cancer do not have tools to predict response before treatment. Pathologic complete response (pCR) is a proxy that still requires neoadjuvant treatment. BC-SELECT is a clinically focused computational tool that leverages genetic interactions, such as synthetic lethality (SL) or rescue (SR), to predict treatment response from gene expression data. BC-SELECT builds on existing related tools (SELECT, ENLIGHT) to navigate competing treatment options.

BC-SELECT involves two main steps: (1) a “gene pair identification” step that identifies clinically relevant partner genes usingin vivoandin vitrodatasets for a drug target, and (2) “training/parameter tuning” using early-stage breast cancer clinical trials to develop predicted response scores to treatment. We evaluated BC-SELECT’s ability to predict responders to trastuzumab, poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy by training on three trials including 86 patients and validating on nine trials including 722 patients.

BC-SELECT significantly predicted treatment response in 6/9 early-stage trials, including in all PARP inhibitors (ROC-AUCs 0.6-0.8; Odds Ratio (OR): 1.9-3.5) and immunotherapy (ROC-AUCs 0.7-0.8; OR: 3.2-7.1). BC-SELECT distinguished between responders and non-responders in 8/9 trials (FDR-corrected Wilcoxon rank-sum test p-value <0.1). BC-SELECT outperformed SELECT and ENLIGHT in predicting immunotherapy response. Specificity was comparable across subtypes, with HER2+ 0.64, TNBC 0.66, and hormone-receptor positive (HR+) 0.76.

There are no standard-of-care pre-treatment predictors of response in TNBC and HER2+ breast cancer. Our findings position BC-SELECT as an eventual decision-support tool to prioritize treatments approved for patients with early-stage breast cancer.

STATEMENT OF SIGNIFICANCE

BC-SELECT is a clinically focused computational tool that leverages genetic interactions, such as synthetic lethality, to predict treatment response from gene expression data for PARP inhibitors and immunotherapy in early-stage breast cancer.
Learning and embodied decisions in active inference
Authors: Priorelli Matteo , Stoianov Ivilin Peev , Pezzulo Giovanni
Published: August 2024

Biological organisms constantly face the necessity to act timely in dynamic environments and balance choice accuracy against the risk of missing valid opportunities. As formalized by embodied decision models, this might require brain architectures wherein decision-making and motor control interact reciprocally, in stark contrast to traditional models that view them as serial processes. Previous studies have assessed that embodied decision dynamics emerge naturally under active inference – a computational paradigm that considers action and perception as subject to the same imperative of free energy minimization. In particular, agents can infer their targets by using their own movements (and not only external sensations) as evidence, i.e., viaself-evidencing. Such models have shown that under appropriate conditions, action-generated feedback can stabilize and improve decision processes. However, how adaptation of internal models to environmental contingencies influences embodied decisions is yet to be addressed. To shed light on this challenge, in this study we systematically investigate the learning dynamics of an embodied model of decision-making during atwo-alternative forced choicetask, using a hybrid (discrete and continuous) active inference framework. Our results show that active inference agents can adapt to embodied contexts by learning various statistical regularities of the task – namely, prior preferences for the correct target, cue validity, and response strategies that prioritize faster or slower (but more accurate) decisions. Crucially, these results illustrate the efficacy of learning discrete preferences and strategies using sensorimotor feedback from continuous dynamics.
Three Open Questions in Polygenic Score Portability
Authors: Wang Joyce Y. , Lin Neeka , Zietz Michael , Mares Jason , Narasimhan Vagheesh M. , Rathouz Paul J. , Harpak Arbel
Published: August 2024

A major obstacle hindering the broad adoption of polygenic scores (PGS) is their lack of “portability” to people that differ—in genetic ancestry or other characteristics—from the GWAS samples in which genetic effects were estimated. Here, we use the UK Biobank to measure the change in PGS prediction accuracy as a continuous function of individuals’ genome-wide genetic dissimilarity to the GWAS sample (“genetic distance”). Our results highlight three gaps in our understanding of PGS portability. First, prediction accuracy is extremely noisy at the individual level and not well predicted by genetic distance. In fact, variance in prediction accuracy is explained comparably well by socioeconomic measures. Second, trends of portability vary across traits. For several immunity-related traits, prediction accuracy drops near zero quickly even at intermediate levels of genetic distance. This quick drop may reflect GWAS associations being more ancestry-specific in immunity-related traits than in other traits. Third, we show that even qualitative trends of portability can depend on the measure of prediction accuracy used. For instance, for white blood cell count, a measure of prediction accuracy at the individual level (reduction in mean squared error) increases with genetic distance. Together, our results show that portability cannot be understood through global ancestry groupings alone. There are other, understudied factors influencing portability, such as the specifics of the evolution of the trait and its genetic architecture, social context, and the construction of the polygenic score. Addressing these gaps can aid in the development and application of PGS and inform more equitable genomic research.
Broad bandwidth photoacoustic imaging using a PVDF receiver array
Authors: Chandramoorthi Sowmiya , López-Marín Antonio , Beurskens Robert , van der Steen Antonius F.W. , van Soest Gijs
Published: August 2024

Photoacoustic (PA) signals are typically broadband, with a correlation between their frequency characteristics and source dimension. The transducers that are commonly used for PA acquisition are optimized for pulse-echo ultrasound imaging and are primarily based on inorganic piezoelectrics in ceramic, single-crystal, or composite form. These transducers are band-limited which limits their functionality as receivers for broadband PA signals. Custom broadband transducers are expensive and complex to manufacture. In this work, we propose to use a poly vinylidene difluoride (PVDF) based transducer for PA acquisition in combination with a commercial single-crystal linear array for pulse-echo acquisition. An 8-element PVDF array with 20dB onboard amplification was built in-house. The PVDF receiver is transparent to the pulse-echo ultrasound, and both transducers were positioned such that they image the same volume. The combined PA raw data from the PVDF and the linear array demonstrated the feasibility of achieving a broader overall reception bandwidth. This study establishes a foundation for a simpler acquisition system that enhances PA signal quality, co-registered with conventional ultrasound imaging, which may support the clinical adoption of PA imaging.
Natural variation in physical responses to waterlogging across climate-diverse pennycress accessions
Authors: Combs-Giroir Rachel , Lagergren John , Jacobson Daniel A. , Gschwend Andrea R.
Published: August 2024

Fluctuations in flooding and differences in hydrological gradients affect the geographic distribution of plant species across ecosystems, resulting in the presence of adaptive traits in populations that confer enhanced fitness in flooded environments. Many winter annual crops, such as pennycress (Thlaspi arvenseL.), are subjected to heavy precipitation events during their growing season, which are increasing in frequency due to climate change. Therefore, it is essential to identify pennycress accessions with natural variation in flooding resilience. In this study, we used climate modeling data to assess spring soil moisture levels in the geographic origins of 471 natural pennycress accessions. We selected 34 accessions with variations in predicted soil moisture to test survivability under prolonged waterlogging at the rosette stage. This identified variation in waterlogging tolerance, where six accessions had 0% survivability and nine accessions had 100% survivability. It took at least seven weeks for the first accessions to die under waterlogging, indicating that pennycress is hardy to prolonged waterlogging at the vegetative stage. Furthermore, we chose three “susceptible” and five “tolerant” accessions to waterlog for one week at the reproductive stage, the growth stage aligned with heavy spring rainfall. Six accessions had significantly reduced seed weight at maturity after recovery from waterlogging, and two accessions had minimal impacts on growth and seed yield after waterlogging. These two accessions can be used in future studies to explore adaptive traits, such as changes in root characteristics, as well as the genetic variation that contributes to pennycress waterlogging tolerance.
An Enzyme-Linked Immunosorbent Assay (ELISA)-based Activity Assay for AMP-Activated Protein Kinase (AMPK)
Authors: Nguyen Trezze P , Liu Yang
Published: August 2024

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism as well as other cellular processes. Efforts have been made to discover pharmacological modulators of AMPK activity because of their therapeutic potentials against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity, which represents an alternative in-house method to the traditional radioactive method as well as other techniques that require special reagents and commercial reagent kits.
Urinary Sodium Wasting and Disrupted Collecting Duct Function in Mice with dRTA-CausingSLC4A1Mutations
Authors: Mungara Priyanka , MacNaughton Kristina , Ullah AKM Shahid , Essuman Grace , Chelangarimiyandoab Forough , Mumtaz Rizwan , Hennings J. Christopher , Hübner Christian A. , Eladari Dominique , Alexander R. Todd , Cordat Emmanuelle
Published: August 2024

Distal renal tubular acidosis (dRTA) results in metabolic acidosis due to impaired urinary acidification and can also result in an unexplained urinary sodium-wasting phenotype. Here, we report the generation and characterization of a novel dRTA mutant mouse line, Ae1 L919X knockin (KI). Homozygous L919X KI mice exhibit typical dRTA features including a reduced ability to acidify urine in response to an acid load. This renal acidification defect was associated with a reduced number of Ae1-positive type A intercalated cells. To assess whether these mice exhibit urinary sodium-wasting as seen in some dRTA patients, homozygous KI L919X and the previously described R607H KI mice were fed a salt-depleted acid diet. In line with human patients, both mouse strains exhibited urinary sodium loss. Additionally, we identified increased expression of tight junction proteins claudin-4 and -10b, suggesting a compensatory paracellular pathway in the loop of Henle. Consistent with data from human patients, L919X KI mice displayed a milder phenotype than R607H KI mice. Our findings reveal that both mouse strains are appropriate models for dRTA with a urinary salt-wasting phenotype and a compensatory up-regulation of the paracellular pathway in the ascending limb of the loop of Henle.
CD4+but not CD8+T cells are required for protection against severe guinea pig cytomegalovirus infections
Authors: Rollman Tyler B. , Berkebile Zachary W. , Hicks Dustin M. , Hatfield Jason S. , Chauhan Priyanka , Pravetoni Marco , Schleiss Mark R. , Milligan Gregg N. , Morgan Terry K. , Bierle Craig J.
Published: August 2024

Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus and the leading cause of infectious disease related birth defects worldwide. How the immune response modulates the risk of intrauterine transmission of HCMV after maternal infection remains poorly understood. Maternal T cells likely play a critical role in preventing infection at the maternal-fetal interface and limiting spread across the placenta, but concerns exist that immune responses to infection may also cause placental dysfunction and adverse pregnancy outcomes. This study investigated the role of CD4+and CD8+T cells in a guinea pig model of primary cytomegalovirus infection. Monoclonal antibodies specific to guinea pig CD4 and CD8 were used to deplete T cells in non- pregnant and in pregnant guinea pigs after mid-gestation. CD4+T cell depletion increased the severity of illness, caused significantly elevated viral loads, and increased the rate of congenital guinea pig cytomegalovirus (GPCMV) infection relative to animals treated with control antibody. CD8+T cell depletion was comparably well tolerated and did not significantly affect the weight of infected guinea pigs or viral loads in their blood or tissue. However, significantly more viral genomes and transcripts were detected in the placenta and decidua of CD8+T cell depleted dams post-infection. This study corroborates earlier findings made in nonhuman primates that maternal CD4+T cells play a critical role in limiting the severity of primary CMV infection during pregnancy while also revealing that other innate and adaptive immune responses can compensate for an absent CD8+T cell response in α-CD8-treated guinea pigs.

Author Summary

Congenital cytomegalovirus infection is a leading cause of adverse pregnancy outcomes and preventable disability in children. Using guinea pigs, a well-established small animal model of congenital infection and intrauterine development, this study tested how depleting T cells affects the course of primary cytomegalovirus infections. Severe illness and high rates of congenital infection were observed when helper CD4+T cells were depleted. The depletion of killer CD8+T cells did not affect the severity of disease or the rate of congenital infection but did increase the amount of virus that was detected in the placenta. A greater understanding how an immune response can prevent the infection of the placenta and developing offspring is needed to inform vaccine and therapeutic development. This study not only describes a new reagent that can be used to study the guinea pig immune system but also sheds new light in how adaptive immunity regulates congenital viral infection.