bluuebunny/crossref_metadata_2025 huggingface dataset:
Health effects of repeated exposures during wildland firefighting: a data-linkage cohort study from Alberta, Canada
Authors: Cherry Nicola , Fedun Mike , Galarneau Jean-Michel , Senkevics Doryen , Zadunayski Tanis
Published: November 2024

Introduction

Very little is known about the effects on the health of work as a wildland firefighter over repeated fire seasons. In Alberta, where the fire season runs from 1 March to 31 October, the great majority of firefighters are hired seasonally. We examined whether there was a dose–response relationship between hours of firefighting and ill-health.

Methods

A cohort was established linking employment records from Alberta Wildfire to administrative health data and cancer records. The employment records contained information on each deployment for all firefighters with employment from 1998 to 2022. Health records had details of diagnoses recorded at all physician consultations for the same period. Cancer records included diagnostic information for all confirmed cancers in the province. Exposure indices (hours worked) were related to health outcomes, with relative risk estimated by multilevel Poisson regression, using data lagged by 10 years for cancer outcomes.

Results

Of 16,816 firefighters with employment records, 12,731 were matched on name, age, and sex in health records and were living in Alberta at the end of at least one fiscal year. One in three had only been employed for one fire season with 10% employed in 10 or more years. The overall mean cumulative exposure was 795 h with 568 h of sustained attack (SA). In multivariable regression, adjusted for age, sex, and inferred First Nation origin, the risk of chronic obstructive pulmonary disease (COPD) and pneumonia increased with hours of firefighting on foot and decreased with fighting less complex fires or holding a permanent appointment. Hours of firefighting in the year of health report were protective for cardiovascular disease (CVD) and mental ill-health but the risk of injury from external causes increased with firefighting hours. The risk of COPD, pneumonia, and asthma increased with cumulative hours over multiple fire seasons of SA firefighting and decreased with cumulative hours fighting less complex fires. Risks of CVD and mental ill-health were also positively related to cumulative hours of SA. No increase in risk was found with cancer incidence (all cancers, bladder cancer, lung cancer, skin: melanoma or nonmelanoma), with exposures unlagged or lagged by 10 years.

Conclusion

Wildland firefighters were found to be at increased risk of lung conditions, both acutely in the year of firefighting and in subsequent years. No increased risk was found for cancer.
BWT construction and search at the terabase scale
Authors: Li Heng
Published: November 2024

Motivation

Burrows–Wheeler Transform (BWT) is a common component in full-text indices. Initially developed for data compression, it is particularly powerful for encoding redundant sequences such as pangenome data. However, BWT construction is resource intensive and hard to be parallelized, and many methods for querying large full-text indices only report exact matches or their simple extensions. These limitations have hampered the biological applications of full-text indices.

Results

We developed ropebwt3 for efficient BWT construction and query. Ropebwt3 indexed 320 assembled human genomes in 65 h and indexed 7.3 terabases of commonly studied bacterial assemblies in 26 days. This was achieved using up to 170 gigabytes of memory at the peak without working disk space. Ropebwt3 can find maximal exact matches and inexact alignments under affine-gap penalties, and can retrieve similar local haplotypes matching a query sequence. It demonstrates the feasibility of full-text indexing at the terabase scale.

Availability and implementation

https://github.com/lh3/ropebwt3.
Multiparametric MRI assessment of primary tumours for predicting axillary tumour burden in women with invasive breast cancer
Authors: Kim Jin Joo , Kim Jin You , Nam Kyung Jin , Lee Kye Young , Choo Ki Seok , Kang Taewoo , Park Heeseung , Bae Seong Hwan
Published: November 2024

Objective

To assess the association between multiparametric MRI features of primary tumours and axillary lymph node tumour burden in women with invasive breast cancer.

Methods

In this retrospective study, women diagnosed with invasive breast cancer who underwent 3T multiparametric MRI, including diffusion-weighted imaging (DWI) from 2019 to 2020, were evaluated. Two radiologists reviewed T2-weighted images (T2WI) for peritumoural oedema and intratumoural necrosis and measured apparent diffusion coefficient (ADC) values by manually placing regions of interest within breast tumours. We also analysed quantitative kinetic features of breast cancer using computer-aided diagnosis (CAD) and clinical-pathologic characteristics. Uni- and multivariable logistic regression analyses were conducted to identify predictors of a high axillary nodal burden (≥3 positive nodes).

Results

In total, 301 women (mean age, 54.13 years) were evaluated. Forty-three (14.3%) had a high axillary nodal burden by surgical pathology. Multivariate analysis revealed that factors significantly associated with high axillary nodal burden included peritumoural oedema (OR: 7.970; P < .001), lower tumour ADCmax (≤1.098 × 10−3 mm2/s) (OR: 6.978; P < .001), larger tumour size (>2 cm) (OR: 2.986; P = .046), lobular histology (OR: 12.620; P < .001), and the presence of lymphovascular invasion (OR: 3.622; P = .003). CAD-derived kinetic features did not show an association with axillary nodal burden. In subgroup analysis of 238 patients with early clinically node-negative breast cancer, both peritumoural oedema (OR: 7.831; P = .002) and lower tumour ADCmax (≤1.098 × 10−3 mm2/s) (OR: 8.002; P = .002) remained significant predictors.

Conclusion

Our results suggest that peritumoural oedema as viewed in T2WI and the ADCmax value of breast cancer in DWI are valuable for predicting axillary nodal burden in women with invasive breast cancer.

Advances in knowledge

Multiparametric MRI features of a primary tumour are useful for predicting axillary nodal burden in patients with invasive breast cancer.
The specialization/collaboration paradox: Investigating specialization within child welfare as a barrier to collaboration
Authors: Steive Karin , Tham Pia , Grell Pär , Wiklund Stefan , Kåreholt Ingemar
Published: November 2024

Existing research highlights the trend of organizing social services into specialized units, addressing specific areas such as child welfare. Further specialization within child welfare extends to target groups (youth vs child) and work task dimensions. The literature remains inconclusive about whether specialization enhances or hinders social work practice. Potential drawbacks of specialization, like gaps between services and a lack of a holistic view, are assumed to increase the need for collaboration. However, specialization might impede collaboration due to profession-specific tensions, such as differing cultures or turf issues. Empirical findings suggest challenges in collaboration both within and between specialized organizations. This study explores how various specializations in child welfare relate to social workers’ perceptions of collaboration within their workgroup, between different social service units, and with external organizations, considering factors like work demand, time spent with clients, and work experience. Analysing survey data from 2003 to 2018 with 895 social workers in Stockholm County, the present study uses generalized estimating equations to address clustering within organizations. The findings indicate a potential positive association between target group specialization and perceived collaboration functionality within the workgroup and with external organizations, challenging assumptions that specialization hinders collaboration and suggesting that target group specialization could facilitate collaboration.
Development and application of on-site multielement simultaneous rapid determination system using microdroplets and a handheld X-ray fluorescence spectrometer
Authors: Kato Takeshi , Ando Ryo , Takagai Yoshitaka
Published: November 2024

We developed an on-site system for the rapid simultaneous determination of multiple elements that integrates microdroplet technology with a handheld X-ray fluorescence spectrometer. This system combines the concentration of heavy metals in microdroplets through homogeneous liquid–liquid extraction with the widespread application of handheld X-ray fluorescence spectrometry. The focus of our research was the analysis of heavy metals, specifically lead. Under optimal conditions, we achieved a high extraction percentage of 93.3%, and a high volume ratio of 120 times was achieved (from 23.9 to 0.200 mL). Building on these optimal conditions, we explored a mixed solution of copper and lead to facilitate the simultaneous rapid determination of multiple elements. By exposing a 200-μL microdroplet to a focused X-ray beam (9.0 mm in diameter), we confirmed a good proportional relationship for copper and lead concentrations ranging from 0.0837 to 0.126 mg/L. The determination limit (10 σ) was 0.040 mg/L for copper and 0.030 mg/L for lead. This system enables the stable evaluation of heavy metals at low concentrations (ppb level) with a straightforward operation.
The Efficacy and Safety of RNA Interference for the Treatment of Primary Hyperoxaluria: A Systematic Review and Meta-analysis
Authors: Yu Huyan , Zhong Hongfei , Liu Youxia , Zhang Guilian
Published: November 2024

Background

Primary hyperoxaluria (PH) are rare inherited disorders of liver glyoxylate metabolism. The main symptoms are related to the precipitation of calcium oxalate crystals in the urinary tract with progressive renal damage. The severity of disease can result in kidney failure and systemic oxalosis. Until recently, RNA interference (RNAi) has been demonstrated as a therapeutic avenue for PH.

Methods

We conducted a systematic review and meta-analysis to assessed the efficacy and safety of RNAi in the treatment of PH patients.

Results

The present systemic review systematically and comprehensively summarizes the pathophysiological mechanisms by which hyperoxalemia leads to kidney failure. Furthermore, we provide a detailed summary of the mechanisms of RNAi drug action in the pharmacological treatment of PH. The enrolled studies indicated that early RNAi intervention is beneficial for patients, especially in maintaining stable kidney function and reversing the effects of hyperoxaluria. Furthermore, the high-dose and long time-duration RNAi therapy may have a better clinical effect. The efficacy of RNAi combined with hemodialysis seems to be promising, and it deserves more well-designed trials with large sample sizes in the future. RNAi therapy play an important role in the treatment of PH.

Conclusion

Early RNAi intervention is beneficial for patients, especially in maintaining stable kidney function and reversing the effects of hyperoxaluria. Furthermore, the high-dose and long time-duration RNAi therapy may have a better clinical effect and acceptable safety. The efficacy of RNAi combined with hemodialysis seems to be promising in PH treatment.
Bone strain index for fracture risk assessment in older men—the prospective STRAMBO study
Authors: Blanc Quentin , Chapurlat Roland , Duboeuf François , Szulc Pawel
Published: November 2024

Objective

Bone strain index (BSI) is a noninvasive index of bone strength assessed on lumbar spine and femur dual energy X-ray absorptiometry scans using the finite-element method. In this study, we assess the link of the lumbar spine and hip BSI with fracture risk in older men.

Design

Prospective cohort study.

Methods

A cohort of 825 men aged ≥60 was followed up for 12 years. Lumbar spine and hip bone mineral density, BSI, Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOPFx), and lumbar spine trabecular bone score (TBS) were assessed at baseline. Overall, 159 men had 198 incident fractures.

Results

After adjustment for FRAX and prior falls, a higher BSI was associated with a higher fracture risk, eg, trochanter BSI: (HR = 1.34 per standard deviation (SD) increase, 95% CI: 1.14-1.58, P < .001). Patterns were similar for MOPFx, vertebral, nonvertebral, and multiple fractures. The fracture risk was higher in the highest vs the lowest BSI quartiles. The associations were the strongest for the BSI of the lumbar spine and trochanter. When the TBS and BSI were analyzed jointly, their respective contributions to fracture prediction varied according to the fracture and the site of the BSI, eg, both the TBS and the trochanter BSI contributed to the MOPFx prediction (TBS: HR = 1.38/SD decrease, 95%CI: 1.04-1.84, P < .05; BSI: HR = 1.49/SD increase, 95% CI: 1.16-1.91, P < .005).

Conclusion

The BSI at both the lumbar and the femoral sites was associated with a higher fracture risk independently of FRAX and prior falls in older men followed prospectively for 12 years.
Earnings development among new immigrants in Finland: does a native-born partner enhance economic integration?
Authors: Vaalavuo Maria , Rask Shadia
Published: November 2024

Many studies have analysed the role of individual characteristics on the labour market outcomes of immigrants. However, there is only limited evidence on how an immigrant’s partnership status and intermarriage with a native-born person are associated with earnings development. Partnerships in general can be considered a proxy for social capital, productivity, and characteristics valued in the labour market. A partnership with a native person is also indicative of sociocultural resources, accomplished integration, and an intention to remain in the country as well as a possible reason for migration. Our study contributes to understanding the link between intermarriage and earnings with evidence from a Nordic perspective and based on unique register data spanning from 2004 to 2018. We employ growth curve models and analyse earnings and employment development in the years following entry to Finland among seven different immigrant groups and separately for men and women. The results demonstrate that the role of having a native-born partner varies according to the country of origin and gender. In general, those with a native-born partner upon arrival in Finland have a more positive earnings development over time. Long observation period is necessary to reveal ineteresting differences between groups.
The Community Acute Respiratory Infection surveillance programme: an evaluation of a newly established surveillance programme in Scotland
Authors: Laird Tonje S , Hamilton Mark , Oliver Catriona , Sadiq Fatima , Moawad Yomna , Evans Josie
Published: November 2024

The Community Acute Respiratory Infection (CARI) surveillance programme, established by Public Health Scotland (PHS) in November 2021, aims to monitor respiratory infections in communities, replacing prior schemes to ensure early detection of outbreaks and inform public health interventions. Positioned as a cornerstone of PHS’s national infectious respiratory diseases plan, CARI is pivotal for safeguarding public health. This study presents key findings from the 2022/23 CARI season and evaluates the programme’s performance during this period. CARI uses a network of sentinel general practitioner (GP) practices across Scotland to monitor patients with acute respiratory infection symptoms, employing multiplex polymerase chain reaction testing for 10 common pathogens. Results are linked to enhanced surveillance data, providing insights into infection trends during the season. The evaluation comprised an online GP survey and a quantitative assessment of programme performance. In the 2022/23 season, 180 GP practices participated in CARI, testing 15,823 samples. Swab positivity peaked in December 2022, driven by a large spike in influenza A activity. The evaluation showed that CARI is highly useful, with positive feedback on simplicity, flexibility, and acceptability. Representativeness varied across health boards and age groups. Despite occasional laboratory processing delays, data quality remained good, with timely reporting and stable participation. CARI reflected patterns in infections observed in secondary care in Scotland and Europe, providing valuable insights into disease patterns and impact. It also provided timely intelligence to key decision-makers, enabling prompt public health response. Changes for the 2023/24 season aim to further optimize the programme.
Debunking taste
Authors: Nguyen C Thi
Published: November 2024

We are often confronted with attempts to debunk our aesthetic tastes, like: “You only like jazz because you’re a pretentious hipster,” or, “Your love of the Western canon is just colonialism speaking.” Such debunking arguments often try to give a socio-historical accounting, intended to de-legitimize our tastes by showing that they arise from processes uninterested in real aesthetic value. One common version is the Art Populist debunk: that claims of aesthetic expertise in esoteric arts are really just elitist gatekeeping. Then we have its mirror twin, the Art Expert debunk: that the populist love of simple arts serves the interests of profiteering entertainment corporations dispensing simplified slop. Suppose we accept one of these debunking arguments. How are we supposed to get on? Are we supposed to not like the things we like, or force ourselves to choke down food we don’t enjoy? And suppose we accept both of these debunking arguments — what then? Are we supposed to simply give up our grip on beauty altogether? This is hard to imagine. Aesthetic debunking arguments have a harder time getting a grip on us, because aesthetic life involves a distinctively tight relationship between our felt aesthetic phenomena and our aesthetic judgments. Aesthetic life gives us phenomenal resistance to debunking arguments, when our felt loves lag behind our endorsed beliefs. I suggest a way through that offers a livable accommodation. We may be able to treat such debunking arguments, not as targeting the positive content of our taste, but as targeting the boundaries and limitations on our taste. That is, a Populist may not be able to debunk my deep felt love of opera, but they may be able to debunk my dismissal of dance-pop. In this case, we can take onboard both the Art Expert’s and the Art Populist’s debunking arguments, as targeting different varieties of narrowness and dismissal. These debunkings, then, move us, not towards aesthetic nihilism, but aesthetic expansionism.
Forecasting the distribution range of Hylurgus ligniperda (Fabricius) (Coleoptera: Curculionidae) in the present and future under the influence of climate change
Authors: Wang Bu-Xin , Li Cheng-Jin , Zhou Zhong-Fu , Yao Yan-Xia , Wang Xiao-Yi , Zhong Kai , Yang Hui-Qiong , Wei Jian-Rong , Huai Wen-Xia
Published: November 2024

Hylurgus ligniperda (Fabricius) is an important pest that attacks Pinus species in China. It impacts the vitality of local pine vegetation, reduces the ability to prevent windbreak and sand fixation, and causes ecological loss. MaxEnt and ArcGIS are used to predict and analyze the changes in suitable distribution areas of H. ligniperda under current and future climate scenarios, based on 12 climate factor datasets and 1,001 field distribution data points for this pest. The environmental variables used significantly influence the potential distribution of H. ligniperda. Highly suitable areas of this beetle are located in western Europe, central Asia, and the southeastern regions of Oceania, with sporadic occurrences across North America, South America, and Africa. Highly suitable areas in China occur across the east, central south, and southwest regions. There is a significant increase in the high and medium suitability areas, while the area of low suitability decreases under the 4 future climate scenarios (SSP126, SSP245, SSP370, and SSP585). The suitable distribution area for H. ligniperda shows an overall trend of moving northwestward. The purpose of this current study is to provide important theoretical support for the prevention and management of this pest by predicting and analyzing suitable distribution areas under current and future climate scenarios.
How To Discipline Financial Markets: Reputation Is Not Enough
Authors: Bigoni Maria , Camera Gabriele , Casari Marco
Published: November 2024

Historically, shocks originating in the financial sector often spilled over into the real sector with dramatic consequences. We study in the lab how interventions targeting disclosure and capital requirements of financial intermediaries can reduce insolvencies or prevent their negative effects from propagating to the broader economy. In our two-sector economy, consumers and producers can fund financial intermediaries, who, in turn, provide them with liquidity to settle trades. However, intermediaries may undertake risky investments and become insolvent, which depresses real economic activity. In the experiment, insolvencies were frequent. As a consequence, consumers and producers often refused to fund intermediaries, which lowered the trade volume. Imposing the disclosure of risky investments did not reduce risk-taking and insolvencies. Instead, imposing capital requirements prevented insolvencies from disrupting real economic activity, thus boosting financial intermediation and trade.
A chromosome-level reference genome for the common bed bug, Cimex lectularius, with identification of sex chromosomes
Authors: Miles Lindsay S , Adams Richard , Francioli Yannick Z , Card Daren C , Castoe Todd A , Booth Warren
Published: November 2024

The common bed bug, Cimex lectularius, is a globally distributed pest insect of medical, veterinary, and economic importance. Previous reference genome assemblies for this species were generated from short read sequencing data, resulting in a ~650 Mb composed of thousands of contigs. Here, we present a haplotype-resolved, chromosome-level reference genome, generated from an adult Harlen strain female specimen. Using PacBio long read and Omni-C proximity sequencing, we generated a 540 Mb genome with 15 chromosomes (13 autosomes and 2 sex chromosomes - X1X2) with an N50 > 30 Mb and BUSCO > 90%. Previous karyotyping efforts indicate an XY sex chromosome system, with 2n=26 and X1X1X2X2 females and X1X2Y males; however significant fragmentation of the X chromosome has also been reported. We further use whole genome resequencing data from males and females to identify the X1 and X2 chromosomes based on sex biases in coverage. This highly contiguous reference genome assembly provides a much-improved resource for identifying chromosomal genome architecture, and for interpreting patterns of urban outbreaks and signatures of selection linked to insecticide resistance.
Ground-cover vegetation composition shapes the abundance of Sphaerophoria scripta (Diptera: Syrphidae) in Mediterranean olive groves
Authors: Madureira Marta , Rodrigues Isabel , Pereira José Alberto
Published: November 2024

The ground-cover vegetation, commonly found in olive groves, provides shelter and vital floral resources for syrphids. Such resources can contribute to syrphids’ growth, development, reproduction, and survival, allowing them to maximize their function as natural pest enemies, pollinators, and decomposers of organic matter. Therefore, identifying the flowering plant families driving the abundance of Sphaerophoria scripta Linnaeus, 1758, is essential to promote its presence and abundance. Here, we described the flowering plants present in the vegetation cover of olive groves and studied how these flowering plant families shape the abundance of S. scripta. A total of 90 plant species belonging to 20 families were identified. Asteraceae was the dominant flowering family, followed by Poaceae. The generalized linear model showed that the presence of flowering plants of the families Campanulaceae, Asteraceae, Orobanchaceae, and Plantaginaceae in the ground-cover vegetation promotes the abundance of S. scripta in olive groves. Conversely, flowering plants of the families Poaceae and Polygonaceae were associated with the decreased abundance of this syrphid species. Our results suggest that increasing particular plant families and decreasing others in the ground-cover vegetation may favor S. scripta abundance in the Mediterranean olive groves.
The Violent Mind and Brain
Authors: Wijdicks Eelco F.M.
Published: November 2024

There is no shortage of gratuitous violence in cinema, and all the diverse types of violence have been disturbingly visualized. Violence in film, including mass killings, is used to show madness and mental illness. The way directors use “psychiatry” in film on violence is criticized in detail. The highly contentious relationship of epilepsy and violence is discussed. In many filmmakers’ predetermined view, neurologic disease is strongly linked with violence and murder. Some scriptwriters and film directors develop plots where individuals in altered neurologic states commit murders. Violence intersects with medicine (and forensic psychiatry) and is discussed herein. Healthcare professionals witness suffering, which means they must understand and help. Excluding gratuitous violence, one does not expect that the film industry improved medical understanding of violence, but simply corrupted it.
“Should I Go to the Emergency Room?”: Their First Episode of Low Back Pain
Authors: Standaert Christopher J.
Published: November 2024

Acute low back pain (LBP) is a common clinical symptom affecting almost every person at some point in their life. Although most acute episodes of LBP are self-limiting, recurrent pain occurs in about 50–75% of individuals within 1 year. For the majority of patients, LBP is a chronic-recurrent problem and thus initial treatment recommendations should focus on long-term active approaches to health and well-being. Psychosocial and affective factors are the best predictors of an episode of acute LBP transitioning to a chronic pain state. These include depression, anxiety, trauma, social marginalization, passive coping, and fear. Exercise is generally the best supported treatment for LBP, although there are no real data to suggest that any one particular approach is uniquely beneficial. Excessive rest, unnecessary imaging, negative language, inaccurate and unhelpful diagnoses, excessive activity restrictions, and reliance on generally unhelpful or overtly harmful medications lead to iatrogenic disability and worse outcomes.
“I Can’t Stand Up!”: Severe Acute Pain in a 63-Year-Old Male
Authors: Kazi Eman , Standaert Christopher J.
Published: November 2024

A subset of lumbar disc herniations, usually seen in patients from 50 to 80 years old, are termed “far lateral disc herniations,” referring to the location of the disc relative to the spinal canal. These typically occur higher in the spine, mostly affecting the L3 and L4 roots, and with more severe leg pain and higher rates of sensory dysesthesia and motor weakness than in posterolateral disc herniations. The pain tends to refer into the hip, anterior thigh, and/or anterior calf; is often mistaken for a hip joint or renal process; and, importantly, is usually worse standing than sitting. An upper lumbar radiculopathy is frequently misdiagnosed and needs to be considered in patients with acute flank and hip or thigh pain. An MRI of the lumbar spine provides optimal identification for a far lateral disc herniation. Patients can be treated successfully with time and nonoperative care, and very few require surgery.
A “Clunk” in the Night: A 51-Year-Old Female with Back Pain
Authors: Shivers Joseph P. , Standaert Christopher J.
Published: November 2024

Degenerative spondylolisthesis becomes more common with age and may be associated with low back pain (LBP) and leg pain. “Spondylolisthesis” describes the anterior/forward displacement of one vertebral body over another. In degenerative spondylolisthesis, the underlying problem is laxity in the facet joints and degenerative change in the disc allowing the vertebra to “slip.” More common in women than men, in Black than White people, and after age 50, degenerative spondyoloisthesis occurs most often at the L4/L5 level, LBP, leg pain, leg weakness, and occasionally a sensation of “clunking” or motion in the spine can occur. As it progresses, the spondylolisthesis can contribute to lumbar spinal stenosis. Radiographs need to include standing flexion/extension views. Nonoperative management focuses on improving the strength, endurance, and coordination of the stabilizing muscles of the trunk and lumbopelvic junction. Operative indications include progressive lower extremity neurologic changes and severe LBP accompanied by radiographic dynamic instability.
“My Back Is OK as Long as I Don’t Do Anything, but I Love Soccer and Tennis.”: Back Pain in a Recreational Athlete
Authors: Vanushkina Maria A. , Standaert Christopher J.
Published: November 2024

Although low back pain (LBP) is less common in those who are physically active than those who are not, LBP is a common complaint in recreational athletes. When individuals present with activity-limiting LBP, clinicians need to understand the effects and challenges of specific forms of exercise, the influence of aging and prior injury on future performance and injury, and the complicating effects of lifestyle and medical comorbidities. Although physiologic changes occur with aging, including alterations in metabolism, loss of lean muscle mass, and reductions in cardiovascular function, guidelines generally recommend a combination of aerobic exercise and resistance training to optimize long-term health. In patients where spinal pain interferes with performance in particular activities, it is helpful to explore factors that may offer opportunities to improve pain and function. These include stretching, balancing the stresses of/ overuse from specific activities, improving activity-specific spine function, cross training, and adding in recovery time.
Utilizing insights of DNA repair machinery to discover MMEJ deletions and novel mechanisms
Authors: Kadam Aditee , Shilo Shay , Naor Hadas , Wainstein Alexander , Brilon Yardena , Feldman Tzah , Minden Mark , Kaushansky Nathali , Chapal-Ilani Noa , Shlush Liran
Published: November 2024

We developed Del-read, an algorithm targeting medium-sized deletions (6–100 bp) in short-reads, which are challenging for current variant callers relying on alignment. Our focus was on Micro-Homolog mediated End Joining deletions (MMEJ-dels), prevalent in myeloid malignancies. MMEJ-dels follow a distinct pattern, occurring between two homologies, allowing us to generate a comprehensive list of MMEJ-dels in the exome. Using Del-read, we identified numerous novel germline and somatic MMEJ-dels in BEAT-AML and TCGA-breast datasets. Validation in 672 healthy individuals confirmed their presence. These novel MMEJ-dels were linked to genomic features associated with replication stress, like G-quadruplexes and minisatellite. Additionally, we observed a new category of MMEJ-dels with an imperfect-match at the flanking sequences of the homologies, suggesting a mechanism involving mispairing in homology alignment. We demonstrated robustness of the repair system despite CRISPR/Cas9-induced mismatches in the homologies. Further analysis of the canonical ASXL1 deletion revealed a diverse array of these imperfect-matches. This suggests a potentially more flexible and error-prone MMEJ repair system than previously understood. Our findings highlight Del-read's potential in uncovering previously undetected deletions and deepen our understanding of repair mechanisms.
DNA sequence and lesion-dependent mitochondrial transcription factor A (TFAM)-DNA-binding modulates DNA repair activities and products
Authors: Urrutia Kathleen , Chen Yu Hsuan , Tang Jin , Hung Ta I , Zhang Guodong , Xu Wenyan , Zhao Wenxin , Tonthat Dylan , Chang Chia-En A , Zhao Linlin
Published: November 2024

Mitochondrial DNA (mtDNA) is indispensable for mitochondrial function and is maintained by DNA repair, turnover, mitochondrial dynamics and mitophagy, along with the inherent redundancy of mtDNA. Base excision repair (BER) is a major DNA repair mechanism in mammalian mitochondria. Mitochondrial BER enzymes are implicated in mtDNA-mediated immune response and inflammation. mtDNA is organized into mitochondrial nucleoids by mitochondrial transcription factor A (TFAM). The regulation of DNA repair activities by TFAM-DNA interactions remains understudied. Here, we demonstrate the modulation of DNA repair enzymes by TFAM concentrations, DNA sequences and DNA modifications. Unlike previously reported inhibitory effects, we observed that human uracil-DNA glycosylase 1 (UNG1) and AP endonuclease I (APE1) have optimal activities at specific TFAM/DNA molar ratios. High TFAM/DNA ratios inhibited other enzymes, OGG1 and AAG. In addition, TFAM reduces the accumulation of certain repair intermediates. Molecular dynamics simulations and DNA-binding experiments demonstrate that the presence of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) in certain sequence motifs enhances TFAM-DNA binding, partially explaining the inhibition of OGG1 activity. Bioinformatic analysis of published 8-oxodG, dU, and TFAM-footprint maps reveals a correlation between 8-oxodG and TFAM locations in mtDNA. Collectively, these results highlight the complex regulation of mtDNA repair by DNA sequence, TFAM concentrations, lesions and repair enzymes.
Optogenetic control of Corynebacterium glutamicum gene expression
Authors: Deng Chen , Xin Ruijie , Li Xingjian , Zhang Jie , Fan Liqiang , Qiu Yongjun , Zhao Liming
Published: November 2024

Corynebacterium glutamicum is a key industrial workhorse for producing amino acids and high-value chemicals. Balancing metabolic flow between cell growth and product synthesis is crucial for enhancing production efficiency. Developing dynamic, broadly applicable, and minimally toxic gene regulation tools for C. glutamicum remains challenging, as optogenetic tools ideal for dynamic regulatory strategies have not yet been developed. This study introduces an advanced light-controlled gene expression system using light-controlled RNA-binding proteins (RBP), a first for Corynebacterium glutamicum. We established a gene expression regulation system, ‘LightOnC.glu’, utilizing the light-controlled RBP to construct light-controlled transcription factors in C. glutamicum. Simultaneously, we developed a high-performance light-controlled gene interference system using CRISPR/Cpf1 tools. The metabolic flow in the synthesis network was designed to enable the production of chitin oligosaccharides (CHOSs) and chondroitin sulphate oligosaccharides A (CSA) for the first time in C. glutamicum. Additionally, a light-controlled bioreactor was constructed, achieving a CHOSs production concentration of 6.2 g/L, the highest titer recorded for CHOSs biosynthesis to date. Herein, we have established a programmable light-responsive genetic circuit in C. glutamicum, advancing the theory of dynamic regulation based on light signaling. This breakthrough has potential applications in optimizing metabolic modules in other chassis cells and synthesizing other compounds.
Estimated potassium intake and the progression of chronic kidney disease
Authors: Suenaga Tatsuya , Tanaka Shigeru , Kitamura Hiromasa , Tsuruya Kazuhiko , Nakano Toshiaki , Kitazono Takanari
Published: November 2024

Background

Lower potassium intake is associated with a higher risk of chronic kidney disease (CKD) in the general population. However, there are no stated recommendations on potassium intake in the CKD population owing to limited evidence of benefits from potassium intake and concerns about the risk of hyperkalaemia. This study aimed to investigate the relationship between potassium intake and CKD progression.

Methods

A total of 4314 patients aged 18 years or older in Japan were prospectively followed for 5 years using data from the Fukuoka Kidney Disease Registry study. The patients were divided into quartiles according to estimated potassium intake levels assessed by the Tanaka formula from spot urine samples. The primary outcome was CKD progression, which was defined as a composite of a 1.5-fold increase in creatinine concentrations from baseline and development of end-stage kidney disease. We evaluated the relationship between estimated potassium intake and CKD progression using Cox proportional hazards models.

Results

A total of 1490 patients showed CKD progression during the follow-up with an incidence rate of 90.1/1000 person-years. Patients in the lowest estimated potassium intake quartile had higher hazard ratios for CKD progression than those in the highest quartiles in the multivariable-adjusted Cox models [hazard ratio (95% confidence interval) 1.24 (1.03–1.48)]. Similarly, each 1-standard deviation decrease in estimated potassium intake as a continuous variable was associated with a higher risk of CKD progression [hazard ratio (95% confidence interval) 1.10 (1.03–1.19)].

Conclusions

Lower estimated potassium intake is associated with CKD progression in patients with CKD. Therefore, we recommend adequate potassium intake, taking care not to cause serious adverse events.
Association Between Monounsaturated Fatty Acid Intake and Risk of Total Stroke and Its Subtypes: A Systematic Review and Dose–Response Meta-analysis of Prospective Cohort Studies
Authors: Mehrabani Amirmasoud , Jalalzadeh Moharam , Jannati Nooshin , Lotfi Keyhan , Arzhang Pishva , Azadbakht Leila
Published: November 2024

Context

There are contradictory results regarding the relationship between dietary intakes of monounsaturated fatty acids (MUFAs) and risk of stroke.

Objective

The purpose of this study was to review the existing body of research on the relationship between MUFA consumption and stroke risk through a systematic review and meta-analysis.

Data Source

PubMed, Scopus, and ISI Web of Science were all systematically searched up to January 2023.

Data Extraction

A total of 11 prospective cohort studies that investigated MUFA consumption in relation to stroke risk were included.

Data Analysis

Relative risk (RR) and 95% CIs for the highest vs lowest category of dietary MUFA intake were combined using a random-effects model. Linear and nonlinear dose–response relations were assessed through 1-stage weighted mixed-effects meta-analysis. These studies included 475 207 participants and 8438 cases. In highest vs lowest consumption analysis, MUFA intake was inversely associated with total stroke (RR: 0.80; 95% CI: 0.67, 0.96; I2 =65.2%, Q-test P = .001; n = 11) and hemorrhagic stroke (RR: 0.80; 95% CI: 0.68, 0.95; I2 = 0.0%, Q-test P = .77; n = 5) risk. Conversely, this association was not significant for ischemic stroke (RR: 0.86; 95% CI: 0.69, 1.07; I2 =62.3%, Q-test P = .01; n = 8). An inverse association was observed between each 10-g/d MUFA intake and hemorrhagic stroke (RR: 0.79; 95% CI: 0.65, 0.96) but not total and ischemic stroke. We did not find any evidence for a nonlinear association between MUFA intake and total stroke and its subtypes.

Conclusion

This meta-analysis shows that higher MUFA intake could lower the risk of total and hemorrhagic, but not ischemic, stroke. This could be important for public health.

Systematic Review Registration

PROSPERO registration no. CRD42023458555.
Levofloxacin Prophylaxis in Pediatric and Young Adult Allogeneic Hematopoietic Stem Cell Transplantation Recipients Does not Prevent Infective Complications and Infections-related Deaths
Authors: Leardini Davide , Gambuti Giacomo , Muratore Edoardo , Baccelli Francesco , Gottardi Francesca , Venturelli Francesco , Belotti Tamara , Prete Arcangelo , Fabbrini Marco , Brigidi Patrizia , Turroni Silvia , Masetti Riccardo
Published: November 2024

Background

The prophylactic use of quinolones in the setting of allogeneic hematopoietic stem cell transplantation (allo-HCT) is controversial and solid evidence is missing, particularly in children.

Methods

In this single-center retrospective study, we compared outcomes in patients receiving (n = 74) or not receiving (n = 70) levofloxacin (LVX) prophylaxis, assessing overall survival, event-free survival, acute graft-versus-host disease (aGvHD) and bloodstream infection incidence, and infection-related mortality. Gut microbiota composition was analyzed in a subgroup using 16S rRNA sequencing of stool samples collected pre-HCT and at engraftment.

Results

We analyzed 144 allo-HCT in 143 patients performed for any indication. No differences were found in the 2 groups regarding main HCT outcomes, namely, cumulative incidence of aGvHD (37.9% vs 43.5%; P = .733), grade III-IV aGvHD (12.2% vs 8.7%; P = .469), gut aGVHD (12.2% vs 17.5%; P = .451), bloodstream infections (25.6% vs 34.1%; P = .236) and death from bacterial infection (9.5% vs 4.3%; P = 0.179). In patients experiencing bacterial infections, those receiving prophylaxis showed higher incidence of quinolone-resistant strains (P = .001). On a subgroup of 50 patients, we analyzed the gut microbiota composition, showing a lower abundance of Blautia (P = .015), Enterococcus (P = .011), and Actinomyces (P = .07) at neutrophil engraftment in patients receiving LVX prophylaxis.

Conclusions

LVX prophylaxis in the setting of allo-HCT does not prevent infective complications and increases the prevalence of antibiotic-resistant strains.
Triage performance of DNA methylation for women with high-risk human papillomavirus infection
Authors: Kong Linghua , Xiao Xiaoping , Wu Huanwen , You Yan , Jin Xitong , Liou Yuligh , Liu Pei , Lang Jinghe , Li Lei
Published: November 2024

Objective

DNA methylation is a promising biomarker for cervical cancer screening. This study aimed to validate the triage performance of cytological DNA methylation for detecting cervical intraepithelial neoplasia of grade 3 or worse (CIN3+) in women with high-risk human papillomavirus (hrHPV) infection from a large prospective cohort undergoing opportunistic screening in China (METHY3).

Methods

The triage performance for detecting CIN3+ lesions was compared between HPV16/18 genotyping, a liquid-based cytology (LBC) test, and the PAX1 and JAM3 methylation (PAX1m/JAM3m) test according to cervical pathologic outcomes. Among the 4394 women infected with hrHPV, 1105 had definitive cervical histological findings that were analyzed.

Results

For detecting CIN3+, the specificity of HPV16/18(+), the LBC result of ≥atypical squamous cells of undetermined significance (ASCUS), and PAX1m/JAM3m(+) was 66.4%, 23.9%, and 89.6%, respectively, with odds ratios of 4.24 (95% confidence interval [CI], 2.85-6.40), 4.44 (2.27-10.1), and 18.5 (12.1-28.7) (P < .001), respectively. PAX1m/JAM3m(+) had the highest area under the receiver operating characteristic curve (0.790, 95% CI, 0.747-0.832) in the whole cohort and in women of various ages. PAX1m/JAM3m (+) was detected in all patients with cancer (n = 28). Compared with HPV16/18 genotyping and the LBC test, PAX1m/JAM3m testing reduced referrals to colposcopy by 20.64 percentage points and 61.18 percentage points, respectively.

Conclusions

PAX1 m /JAM3 m testing is highly specific for detecting CIN3+. As a triage biomarker, it is superior to HPV 16/18 genotyping and LBC testing for women with hrHPV infection.
Amide conjugates of the jasmonate precursor cis-(+)-12-oxo-phytodienoic acid regulate its homeostasis during plant stress responses
Authors: Široká Jitka , Ament Anita , Mik Václav , Pospíšil Tomáš , Kralová Michaela , Zhang Chao , Pernisová Markéta , Karady Michal , Nožková Vladimira , Nishizato Yuho , Kaji Takuya , Saito Rina , Htitich Mohamed , Floková Kristýna , Wasternack Claus , Strnad Miroslav , Ueda Minoru , Novák Ondřej , Brunoni Federica
Published: November 2024

Jasmonates are a family of oxylipin phytohormones regulating plant development and growth and mediating “defense versus growth” responses. The upstream JA biosynthetic precursor cis-(+)-12-oxo-phytodienoic acid (cis-OPDA) acts independently of CORONATIVE INSENSITIVE 1-mediated JA signaling in several stress-induced and developmental processes. However, its perception and metabolism are only partially understood. An isoleucine analog of the biologically active JA-Ile, OPDA-Ile, was detected years ago in wounded leaves of flowering plants, opening up the possibility that conjugation of cis-OPDA to amino acids might be a relevant mechanism for cis-OPDA regulation. Here, we extended the analysis of amino acid conjugates of cis-OPDA and identified naturally occurring OPDA-Val, OPDA-Phe, OPDA-Ala, OPDA-Glu, and OPDA-Asp accumulating in response to biotic and abiotic stress in Arabidopsis (Arabidopsis thaliana). The OPDA amino acid conjugates displayed cis-OPDA-related plant responses in a JA-Ile-dependent manner. We also showed that the synthesis and hydrolysis of cis-OPDA amino acid conjugates are mediated by members of the amidosynthetase GRETCHEN HAGEN 3 and the amidohydrolase INDOLE-3-ACETYL-LEUCINE RESISTANT 1/ILR1-like families. Thus, OPDA amino acid conjugates function in the catabolism or temporary storage of cis-OPDA in stress responses instead of acting as chemical signals per se.
Co-exposure impact of nickel oxide nanomaterials and Bacillus subtilis on soybean growth and nitrogen assimilation dynamics
Authors: Khan Kashif , Li Zhen Wei , Khan Rayyan , Ali Shahid , Ahmad Haseeb , Shah Muhammad Ali , Zhou Xun Bo
Published: November 2024

Nickel oxide nanoparticles (NiO-NPs) pose potential threats to agricultural production. Bacillus subtilis has emerged as a stress-mitigating microbe that alleviates the phytotoxicity caused by NiO-NPs. However, the mechanisms underlying its effectiveness, particularly in root-nodule symbiosis and biological N2-fixation (BNF), remain unclear. Here, we tested the combined exposure of NiO-NPs (50 mg kg−1) and B. subtilis on soybean (Glycine max L.) growth and BNF. Combined exposure increased root length, shoot length, root biomass, and shoot biomass by 19% to 26%, while Ni (200 mg kg−1) reduced them by 38% to 53% compared to the control. NiO-NPs at 100 and 200 mg kg−1 significantly (P < 0.05) reduced nodule formation by 16% and 58% and Nitrogen assimilation enzyme activities levels (urease, nitrate reductase, glutamine synthetase, and glutamate synthetase) by 13% to 57%. However, co-exposure with B. subtilis improved nodule formation by 22% to 44%. Co-exposure of NiO-NPs (200 mg kg−1) with B. subtilis increased peroxidase, catalase, and glutathione peroxidase activity levels by 20%, 16%, and 14% while reducing malondialdehyde (14%) and hydrogen peroxide (12%) levels compared to NiO-NPs alone. Additionally, co-exposure of NiO-NPs (100 and 200 mg kg−1) with B. subtilis enhanced the relative abundance of Stenotrophomonas, Gemmatimonas, and B. subtilis, is associated with N2-cycling and N2-fixation potential. This study confirms that B. subtilis effectively mitigates NiO-NP toxicity in soybean, offering a sustainable method to enhance BNF and crop growth and contribute to addressing global food insecurity.
Do Financial Concerns Make Workers Less Productive?
Authors: Kaur Supreet , Mullainathan Sendhil , Oh Suanna , Schilbach Frank
Published: November 2024

Workers who are worried about their personal finances may find it hard to focus at work. If so, reducing financial concerns could increase productivity. We test this hypothesis in a sample of low-income Indian piece-rate manufacturing workers. We stagger when wages are paid out: some workers are paid earlier and receive a cash infusion while others remain liquidity constrained. The cash infusion leads workers to reduce their financial concerns by immediately paying off debts and buying household essentials. Subsequently, they become more productive at work: their output increases by 7% (0.11 std. dev.), and they make fewer costly, unintentional mistakes. Workers with more cash on hand thus not only work faster but also more attentively, suggesting improved cognition. These effects are concentrated among more financially constrained workers. We argue that mechanisms such as gift exchange or nutrition cannot account for our results. Instead, our findings suggest that financial strain, at least partly through psychological channels, has the potential to reduce earnings exactly when money is most needed.