bluuebunny/crossref_metadata_2025 huggingface dataset:
Keratin 17 is a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma
Authors: Delgado-Coka Lyanne A , Roa-Peña Lucia , Babu Sruthi , Horowitz Michael , Petricoin Emanuel F , Matrisian Lynn M , Blais Edik M , Marchenko Natalia , Allard Felicia D , Akalin Ali , Jiang Wei , Larson Brent K , Hendifar Andrew E , Picozzi Vincent J , Choi Minsig , Shroyer Kenneth R , Escobar-Hoyos Luisa F
Published: April 2024

Objectives

To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

Methods

We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

Results

Patients with advanced-stage, low K17 PDACs treated using 5-fluorouracil (5-FU)–based chemotherapeutic regimens had 3-fold longer survival than corresponding cases treated with gemcitabine-based chemotherapy. By contrast, PDACs with high K17 did not respond to either regimen. The predictive value of K17 was independent of tumor mutation status and other clinicopathologic variables.

Conclusions

The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU–based treatment was more likely than gemcitabine-based therapies to extend survival.
Factor VIII and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Stoutenburg Eric , Sherman Sarah , Bravo Maria , Howard Virginia , Mukaz Debora Kamin , Cushman Mary , Zakai Neil A , Judd Suzanne , Plante Timothy B
Published: April 2024

BACKGROUND

Nearly half of all Americans have hypertension, and Black adults experience a disproportionate burden. Hypercoagulability may relate to hypertension risk, and higher levels of factor VIII increase thrombosis risk. Black adults have higher factor VIII and more hypertension than other groups. Whether higher factor VIII associates with incident hypertension is unknown.

METHODS

The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study measured certain biomarkers in a sex-race stratified sample of 4,400 REGARDS participants who attended both visits. We included BioMedioR participants, excluding those with prevalent hypertension, missing factor VIII level, or covariates of interest. Modified Poisson regression estimated risk ratios (RR) for incident hypertension by higher log-transformed factor VIII level per SD (SD of log-transformed factor VIII, 0.33). Weighting was applied to take advantage of REGARDS sampling design.

RESULTS

Among the 1,814 participants included (55% female, 24% Black race), the median follow-up was 9.5 years and 35% (2,146/6,138) developed hypertension. Black participants had a higher median (IQR) factor VIII level (105.6%; 87.1%–126.9%) than White participants (95.6%; 79.8%–115.9%; P < 0.001). The age- and sex-adjusted Black–White hypertension RR was 1.45 (95% CI 1.28, 1.63). Higher factor VIII was not associated with more hypertension (final model RR 1.01; 95% CI 0.94, 1.07).

CONCLUSIONS

In a prospective study of Black and White adults without prevalent hypertension, factor VIII was not associated with greater hypertension risk.
‘Substantial clinical benefit’ and ‘substantial clinical worsening’ cutoff of Vitiligo Impact Scale (VIS)-22 change scores
Authors: Gupta Vishal , Taneja Neha , Sati Hem Chandra , Sreenivas Vishnubhatla , Ramam M
Published: April 2024

Patient-centric outcome measures focus on clinically meaningful change in various aspects of disease, including severity, quality of life and psychological distress. The minimal important change (MIC) is a commonly used threshold of patient-reported outcome measures, representing the smallest difference that is considered significant by the patient and/or physician. However, it has been suggested that MIC is too low a bar for determining treatment success, and alternative thresholds such as substantial clinical benefit (SCB) and patient acceptable symptom state (PASS) may be preferred.
Increased frequency and mortality in persons with neurological disorders during COVID-19
Authors: Marsters Candace M , Bakal Jeffrey A , Lam Grace Y , McAlister Finlay A , Power Christopher
Published: April 2024

Determining the frequency and outcomes of neurological disorders associated with coronavirus disease 2019 (COVID-19) is imperative for understanding risks and for recognition of emerging neurological disorders. We investigated the susceptibility and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among persons with premorbid neurological disorders, in addition to the post-infection incidence of neurological sequelae, in a case–control population-based cohort.

Using health service data collected between 1 March 2020 and 30 June 2021, we constructed a cohort of SARS-CoV-2 RNA-positive (n = 177 892) and -negative (n = 177 800) adults who were age, sex and comorbidity matched and underwent RT-PCR testing at similar times. COVID-19-associated mortality rates were examined within the cohort. Neurological sequelae were analysed during the acute (<3 months) and the post-acute (3–9 months) phases post-infection.

The risk of death was significantly greater in the SARS-CoV-2 RNA-positive (2140 per 100 000 person years) compared with RNA-negative (922 per 100 000 person years) over a follow-up of 9 months, particularly amongst those with premorbid neurological disorders: adjusted odds ratios (95% confidence interval) in persons with a prior history of parkinsonism, 1.65 (1.15–2.37); dementia, 1.30 (1.11–1.52); seizures, 1.91 (1.26–2.87); encephalopathy, 1.82 (1.02–3.23); and stroke, 1.74 (1.05–2.86). There was also a significantly increased risk for diagnosis of new neurological sequelae during the acute time phase after COVID-19, including encephalopathy, 2.0 (1.10–3.64); dementia, 1.36 (1.07–1.73); seizure, 1.77 (1.22–2.56); and brain fog, 1.96 (1.20–3.20). These risks persisted into the post-acute phase after COVID-19, during which inflammatory myopathy (2.57, 1.07–6.15) and coma (1.87, 1.22–2.87) also became significantly increased.

Thus, persons with SARS-CoV-2 infection and premorbid neurological disorders are at greater risk of death, and SARS-CoV-2 infection was complicated by increased risk of new-onset neurological disorders in both the acute and post-acute phases of COVID-19.
Spatial enrichment and genomic analyses reveal the link of NOMO1 with amyotrophic lateral sclerosis
Authors: Guo Jingyan , You Linya , Zhou Yu , Hu Jiali , Li Jiahao , Yang Wanli , Tang Xuelin , Sun Yimin , Gu Yuqi , Dong Yi , Chen Xi , Sato Christine , Zinman Lorne , Rogaeva Ekaterina , Wang Jian , Chen Yan , Zhang Ming
Published: April 2024

Amyotrophic lateral sclerosis (ALS) is a severe motor neuron disease with uncertain genetic predisposition in most sporadic cases. The spatial architecture of cell types and gene expression are the basis of cell–cell interactions, biological function and disease pathology, but are not well investigated in the human motor cortex, a key ALS-relevant brain region. Recent studies indicated single nucleus transcriptomic features of motor neuron vulnerability in ALS motor cortex. However, the brain regional vulnerability of ALS-associated genes and the genetic link between region-specific genes and ALS risk remain largely unclear.

Here, we developed an entropy-weighted differential gene expression matrix-based tool (SpatialE) to identify the spatial enrichment of gene sets in spatial transcriptomics. We benchmarked SpatialE against another enrichment tool (multimodal intersection analysis) using spatial transcriptomics data from both human and mouse brain tissues. To investigate regional vulnerability, we analysed three human motor cortex and two dorsolateral prefrontal cortex tissues for spatial enrichment of ALS-associated genes. We also used Cell2location to estimate the abundance of cell types in ALS-related cortex layers. To dissect the link of regionally expressed genes and ALS risk, we performed burden analyses of rare loss-of-function variants detected by whole-genome sequencing in ALS patients and controls, then analysed differential gene expression in the TargetALS RNA-sequencing dataset.

SpatialE showed more accurate and specific spatial enrichment of regional cell type markers than multimodal intersection analysis in both mouse brain and human dorsolateral prefrontal cortex. Spatial transcriptomic analyses of human motor cortex showed heterogeneous cell types and spatial gene expression profiles. We found that 260 manually curated ALS-associated genes are significantly enriched in layer 5 of the motor cortex, with abundant expression of upper motor neurons and layer 5 excitatory neurons. Burden analyses of rare loss-of-function variants in Layer 5-associated genes nominated NOMO1 as a novel ALS-associated gene in a combined sample set of 6814 ALS patients and 3324 controls (P = 0.029). Gene expression analyses in CNS tissues revealed downregulation of NOMO1 in ALS, which is consistent with a loss-of-function disease mechanism. In conclusion, our integrated spatial transcriptomics and genomic analyses identified regional brain vulnerability in ALS and the association of a layer 5 gene (NOMO1) with ALS risk.
Sulfur-containing soft Lewis base polymers for improved lithium-ion conductivity under polymer-in-salt conditions
Authors: Chiba Akinari , Hatakeyama-Sato Kan , Oyaizu Kenichi
Published: April 2024

Solid polymer electrolytes have been intensively studied to improve the safety and energy density of lithium-ion batteries (LiBs). Although high-rate performance of LiBs has been reported in electrolytes under polymer-in-salt conditions with an excess of lithium salts and polymers, effective conditions for achieving high ionic conductivity remain unresolved. In this study, we elucidate the mechanism and high Li-ion transportability of poly(sulfone-thioether) under polymer-in-salt conditions. In particular, the composition of the polymer with an asymmetric Li salt, lithium(fluorosulfonyl)(trifluoromethane sulfonyl)imide (LiFTFSI), induced a high ionic conductivity above 10−5 S/cm, which is higher than that of the poly(ethylene oxide) (PEO)-Li salt system. Under polymer-in-salt conditions, the enhanced conductivity of poly(sulfone-thioether) contrasts with the conductivity drop observed in the conventional PEO system. These results show the superiority of polymers with soft Lewis bases, such as sulfur donor atoms, for Li-ion transport under polymer-in-salt conditions.
Uncombable hair syndrome: burdensome or captivating?
Authors: Heyers Ariane , Basmanav F Buket , Betz Regina C
Published: April 2024

Uncombable hair syndrome (UHS) is a rare abnormality of the hair shaft where the affected person has dry, wiry and frizzy hair that cannot be combed straight. We have had contact with well over 100 individuals affected (or their parents) and found that UHS is not only a hair anomaly, but also a major stressor for many of these individuals, especially in terms of bullying and unwanted touching of their hair. However, some of those affected (or their parents) are also very proud of their special hair; thus, it was important for us to hear the voice of someone affected by UHS.
Hallux patch during anti-transcription intermediary factor-1γ dermatomyositis
Authors: Kluger Nicolas
Published: April 2024

This case illustrates that the hallux patch sign, among others, is not restricted to anti-MDA5 dermatomyositis.
Disrupting B and T-cell collaboration in autoimmune disease: T-cell engagers versus CAR T-cell therapy?
Authors: Shah Kavina , Leandro Maria , Cragg Mark , Kollert Florian , Schuler Franz , Klein Christian , Reddy Venkat
Published: April 2024

B and T cells collaborate to drive autoimmune disease (AID). Historically, B- and T-cell (B–T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B-cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab, or ofatumumab. Refractory AID is a significant problem for patients with incomplete BCD with a greater frequency of IgD−CD27+ switched memory B cells, CD19+CD20− B cells, and plasma cells that are not directly targeted by anti-CD20 antibodies, whereas most lymphoid tissue plasma cells express CD19. Furthermore, B–T-cell collaboration is predominant in lymphoid tissues and at sites of inflammation such as the joint and kidney, where BCD may be inefficient, due to limited access to key effector cells. In the treatment of cancer, chimeric antigen receptor (CAR) T-cell therapy and T-cell engagers (TCE) that recruit T cells to induce B-cell cytotoxicity have delivered promising results for anti-CD19 CAR T-cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab, or epcoritamab. Limited evidence suggests that anti-CD19 CAR T-cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. Therefore, here, we discuss the potential mechanistic advantages of novel therapies that rely on T cells as effector cells to disrupt B–T-cell collaboration toward overcoming rituximab-resistant AID.
Effects of captive-breeding conditions on metabolic and performance traits in an endangered, endemic cyprinidontiform fish
Authors: Masó Guillem , García-Berthou Emili , Merciai Roberto , Latorre Dani , Vila-Gispert Anna
Published: April 2024

Captive breeding and stocking are commonly employed strategies for enhancing fisheries and conserving endangered fish species. However, hatchery-raised fish often exhibit reduced performance in the wild, displaying alterations in physiological, morphological, and behavioral traits. We tested for differences in swimming capacity and metabolic traits between wild and hatchery-reared individuals of the Spanish toothcarp (Aphanius iberus) from 2 different populations. Furthermore, we experimentally tested if these changes translated into fitness differences after their stocking into the wild. There were significant differences in swimming capacity and metabolic traits between wild and hatchery-reared individuals and also between the 2 populations. Captive-bred individuals displayed consistently lower metabolic rates than wild individuals from the same population (30–76% lower). Critical swimming speed rather differed between the 2 populations. Sex-specific differences were observed in maximum and standard metabolic rates, with wild individuals and females generally exhibiting higher values but with some exceptions. During a 3-month experiment, survival rates did not significantly differ between wild and captive-bred fish. Captive-bred individuals started smaller but exhibited rapid growth during the experiment. Initially, larger captive-bred fish had lower body conditions than their wild counterparts, but these differences progressively diminished. In summary, captive-bred individuals of this fish species showed lower metabolic rates, although the differences with wild individuals slightly depended on sex and size.
TOpCLASS Expert Consensus Classification of Perianal Fistulising Crohn’s Disease: A Real-world Application in a Serial Fistula MRI Cohort
Authors: Schroeder Matthew K , Abushamma Suha , George Alvin T , Ravella Balakrishna , Hickman John , Elumalai Anusha , Wise Paul , Zulfiqar Maria , Ludwig Daniel R , Shetty Anup , Viswanath Satish E , Luo Chongliang , Sebastian Shaji , Ballard David H , Deepak Parakkal
Published: April 2024

Background and Aims

Perianal fistuliing Crohn’s disease [PFCD] is an aggressive phenotype of Crohn’s disease defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by the TOpCLASS consortium, which seeks to unify disease severity with patient-centred goals but has not yet been validated. We aimed to apply this to a real-world cohort and to identify factors that predict transition between classes over time.

Methods

We identified all patients with PFCD and at least one baseline and one follow-up pelvic MRI [pMRI]. TOpCLASS classification, disease characteristics, and imaging indices were collected retrospectively at time periods corresponding with respective MRIs.

Results

We identified 100 patients with PFCD, of whom 96 were assigned TOpCLASS Classes 1–2c at baseline. Most patients [78.1%] started in Class 2b, but changes in classification were observed in 52.1% of all patients. Male sex [72.0%, 46.6%, 40.0%, p = 0.03] and prior perianal surgery [52.0% vs 44.6% vs 40.0%, p = 0.02] were more frequently observed in those with improved class compared to unchanged and worsened class. Baseline pMRI indices were not associated with changes in classification; however, greater improvements in mVAI, MODIFI-CD, and PEMPAC were seen among those who improved. Linear mixed effect modelling identified only male sex [-0.31, 95% CI -0.60 to -0.02] with improvement in class.

Conclusion

The TOpCLASS classification highlights the dynamic nature of PFCD over time. However, our ability to predict transitions between classes remains limited and requires prospective assessment. Improvement in MRI index scores over time was associated with a transition to lower TOpCLASS classification.
Genetic and Functional Diversity Help Explain Pathogenic, Weakly Pathogenic, and Commensal Lifestyles in the Genus Xanthomonas
Authors: Pena Michelle M , Bhandari Rishi , Bowers Robert M , Weis Kylie , Newberry Eric , Wagner Naama , Pupko Tal , Jones Jeffrey B , Woyke Tanja , Vinatzer Boris A , Jacques Marie-Agnès , Potnis Neha
Published: April 2024

The genus Xanthomonas has been primarily studied for pathogenic interactions with plants. However, besides host and tissue-specific pathogenic strains, this genus also comprises nonpathogenic strains isolated from a broad range of hosts, sometimes in association with pathogenic strains, and other environments, including rainwater. Based on their incapacity or limited capacity to cause symptoms on the host of isolation, nonpathogenic xanthomonads can be further characterized as commensal and weakly pathogenic. This study aimed to understand the diversity and evolution of nonpathogenic xanthomonads compared to their pathogenic counterparts based on their cooccurrence and phylogenetic relationship and to identify genomic traits that form the basis of a life history framework that groups xanthomonads by ecological strategies. We sequenced genomes of 83 strains spanning the genus phylogeny and identified eight novel species, indicating unexplored diversity. While some nonpathogenic species have experienced a recent loss of a type III secretion system, specifically the hrp2 cluster, we observed an apparent lack of association of the hrp2 cluster with lifestyles of diverse species. We performed association analysis on a large data set of 337 Xanthomonas strains to explain how xanthomonads may have established association with the plants across the continuum of lifestyles from commensals to weak pathogens to pathogens. Presence of distinct transcriptional regulators, distinct nutrient utilization and assimilation genes, transcriptional regulators, and chemotaxis genes may explain lifestyle-specific adaptations of xanthomonads.
Dementia Prevalence, Incidence, and Mortality Trends Among U.S. Adults Ages 72 and Older, 2011–2021
Authors: Freedman Vicki A , Cornman Jennifer C
Published: April 2024

Background

U.S.-focused studies have reported decreasing dementia prevalence in recent decades, but have not yet focused on the implications of the coronavirus disease 2019 (COVID-19) pandemic for trends.

Methods

We use the 2011–2021 National Health and Aging Trends Study (N = 48 065) to examine dementia prevalence, incidence, and mortality trends among adults ages 72 and older, and the contribution to prevalence trends of changes in the distribution of characteristics of the older population (“compositional shifts”) during the full and prepandemic periods. To minimize classification error, individuals must meet dementia criteria for 2 consecutive rounds.

Results

The prevalence of probable dementia declined from 11.9% in 2011 to 9.2% in 2019 and 8.2% in 2021 (3.1% average annual decline). Pre-pandemic declines continued for women and non-Hispanic White individuals and emerged over the 2011–2021 period for men and those ages 80–89. Declines in dementia incidence were stronger for the 2011–2021 period than for the prepandemic period, while mortality among those with dementia rose sharply with the onset of the COVID-19 pandemic. Shifts in the composition of the older population accounted for a smaller fraction of the decline over the full period (27%) than over the prepandemic period (45%).

Conclusions

Declines in dementia prevalence continued into years marked by onset of the COVID-19 pandemic, along with declines in incidence and sharp increases in mortality among those with dementia. However, declines are no longer largely attributable to compositional changes in the older population. Continued tracking of dementia prevalence, incidence, and mortality among those with and without dementia is needed to understand long-run consequences of the pandemic.
Kinship and Care: Racial Disparities in Potential Dementia Caregiving in the United States From 2000 to 2060
Authors: Feng Kai , Song Xi , Caswell Hal
Published: April 2024

Background

Although the family plays a pivotal role in older adults’ care, there is limited research on how evolving demographic trends affect older adults’ support networks and how the trends vary by race. To fill this gap, we examine the influence of shifting family demographics on future care needs for older adults with dementia, emphasizing the unequal health and potential caregiving burdens by race in the United States.

Methods

Using demographic models of kinship, we estimate the availability of potential caregivers, and dementia prevalence among one’s kin by race, kin type, and the age of a focal person from 2000 to 2060. We introduce an index called the Dementia Dependency Ratio to assess dementia caregiving demands at the population level, taking into account the age and kinship structure of the population.

Results

Our findings suggest that Black individuals tend to have more children, grandchildren, and nieces/nephews as they age. However, Black individuals also tend to have more kin with dementia compared to their White counterparts. This elevated prevalence of dementia among Black kinship networks counterbalances the advantage of having more kin as potential caregivers. A further projection analysis suggests that the racial gap in caregiving demand within the kinship network will widen in the next 4 decades if the racial gap in dementia prevalence remains unchanged.

Conclusions

These findings emphasize the urgency of reducing racial inequality in dementia prevalence rates and increasing public support for families with extended members affected by dementia. With the shrinkage of nuclear families and population aging in the next few decades, extended family members may undertake more caregiving responsibilities for dementia. We call for a kinship perspective in understanding dementia care in future research.
Detectability of gravity changes on the sea surface due to magma accumulation beneath submarine volcanoes
Authors: Nishiyama Ryuichi
Published: April 2024

This study estimated the gravity change expected on the sea surface due to magma accumulation beneath submarine volcanoes. For calculation, a semi-analytical model describing the deformation of an infinite elastic cone was considered, in which a point spherical source was embedded on the axis. The expected gravity change exceeds 0.2 mGal in certain scenarios when $\delta V = 10^8\, \mathrm{m^3}$ of source volume change occurs 2 km below the summit, and the summit is shallower than 300 m below the sea surface. The steeper the slope of a submarine volcano, the greater the expected gravity change. 0.2 mGal of gravity variation can be detected with recent marine gravimeters such as cold atom interferometers. The computation method for the gravity change based on the integral transform (Mellin type) is elaborated in this paper.
SARS-CoV-2 infection in IVF-conceived early pregnancy and the risk of miscarriage: a matched retrospective cohort study
Authors: Xu Jian , Mao Di , Liu Chunlin , Sun Ling
Published: April 2024

STUDY QUESTION

Is SARS-CoV-2 infection in IVF-conceived early pregnancy associated with a higher risk of miscarriage?

SUMMARY ANSWER

Infection with SARS-CoV-2 during early pregnancy in women conceiving by IVF may not be associated with an increased rate of miscarriage.

WHAT IS KNOWN ALREADY

In naturally conceived pregnancies, most findings have shown that SARS-CoV-2 infection does not increase the risk of miscarriage, while some studies have shown that SARS-CoV-2 infection is associated with a higher risk of miscarriage.

STUDY DESIGN, SIZE, DURATION

A matched retrospective cohort study was conducted in a tertiary hospital-based reproductive medicine center. The infection group included women who contracted coronavirus disease 2019 (COVID-19) before 20 weeks gestation from 6 December 2022 to 10 January 2023. Each infected woman was matched with three historical control subjects from 1 January 2018 to 31 May 2022.

PARTICIPANTS/MATERIALS, SETTING, METHODS

The infection group was matched with historical control subjects based on female age (±1 year), number of gestational sacs, number of previous miscarriages, BMI (±2 kg/cm2), main causes of infertility, gestational week, and fresh versus frozen embryo transfer.

MAIN RESULTS AND THE ROLE OF CHANCE

A total of 150 pregnant women infected with COVID-19 before 20 weeks of gestation were included in the infection group, which was matched at a 3:1 ratio with 450 historically pregnant controls. There were no significant differences in age, BMI, and endometrial thickness between the two groups. The overall incidence of miscarriage was not significantly different between the infection group and the control group (4.7% versus 5.8%, P = 0.68). When the infection group was stratified into three subgroups based on the gestational age at the onset of infection (0–7 + 6, 8–11 + 6, and 12-19 + 6 weeks), no significant differences were observed in the incidence of miscarriage between the infection group and the matched control group in any of the subgroups (9.8% versus 13.8%, P = 0.60; 5.4% versus 4.5%, P = 1.00; and 1.4% versus 1.9%, P = 1.00, respectively).

LIMITATIONS, REASONS FOR CAUTION

The major limitation of this study is the relatively small sample size; therefore, caution is suggested when drawing any definitive conclusions. Nonetheless, our study is the largest sample study of the influence of COVID-19 infection on the miscarriage rate in early pregnancy after IVF.

WIDER IMPLICATIONS OF THE FINDINGS

Our findings may provide important insights for reproductive physicians and obstetricians during preconception and early pregnancy counseling.

STUDY FUNDING/COMPETING INTEREST(S)

This study was supported by the Natural Science Foundation of Guangdong Province (No. 2023A1515010250). The authors report no conflicts of interest.

TRIAL REGISTRATION NUMBER

N/A.
Factor modification in the association between high-density lipoprotein cholesterol and liver cancer risk in a nationwide cohort
Authors: Nam Su Youn , Jo Junwoo , Lee Won Kee , Cho Chang Min
Published: April 2024

Background/aims

The effect modification by smoking and menopausal status in the association between high-density lipoprotein cholesterol (HDL-C) and liver cancer risk has not been reported.

Methods

This population-based cohort study included 4.486 million cancer-free individuals among those who underwent national cancer screening in 2010 and were followed up until December 2017. We conducted analyses in populations that excluded people with chronic hepatitis B, chronic hepatitis C and liver cirrhosis (Model I) and that included those diseases (Model III). HDL-C level was classified into eight groups at 10-mg/dL intervals. Liver cancer risk by HDL-C was measured using adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results

During follow-up, 18 795 liver cancers in Model I and 20 610 liver cancers in Model III developed. In Model I, low HDL-C levels (aHR 1.83; 95% CI 1.65–2.04) and extremely high HDL-C levels (aHR 1.24; 95% CI 1.10–1.40) were associated with an increased liver cancer risk compared with a moderate HDL-C level of 50–59mg/dL. This association was similar in both men and women with larger effect size in men (aHR, 1.91; 95% CI, 1.70–2.15). The hazardous association between low HDL-C and liver cancer risk was remarkable in current smokers (aHR, 2.19; 95% CI, 1.84–2.60) and in pre-menopausal women (aHR, 2.91; 95% CI, 1.29–6.58) compared with post-menopausal women (aHR, 1.45; 95% CI, 1.10–1.93). This association was similarly observed in Model III.

Conclusions

Low and extremely high HDL-C levels were associated with an increased liver cancer risk. The unfavourable association between low HDL-C and liver cancer was remarkable in smokers and pre-menopausal women.
Clonal Hematopoiesis in Patients With Human Immunodeficiency Virus and Cancer
Authors: Gillis Nancy , Dickey Brittney L , Colin-Leitzinger Christelle , Tang Yi-Han , Putney Ryan M , Mesa Tania E , Yoder Sean J , Suneja Gita , Spivak Adam M , Patel Ami B , Extermann Martine , Giuliano Anna R , Teng Mingxiang , Kresovich Jacob , Berglund Anders , Coghill Anna E
Published: April 2024

Background

Cancer-related deaths for people with human immunodeficiency virus (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH.

Methods

We conducted a retrospective study to compare the prevalence and clinical outcomes of CH in PWH and people without HIV (PWoH) and cancer. Included in the study were PWH and similar PWoH based on tumor site, age, tumor sequence, and cancer treatment status. Biological aging was also measured using epigenetic methylation clocks.

Results

In 136 patients with cancer, PWH had twice the prevalence of CH compared to similar PWoH (23% vs 11%, P = .07). After adjusting for patient characteristics, PWH were 4 times more likely than PWoH to have CH (odds ratio, 4.1 [95% confidence interval, 1.3–13.9]; P = .02). The effect of CH on survival was most pronounced in PWH, who had a 5-year survival rate of 38% if they had CH (vs 59% if no CH), compared to PWoH who had a 5-year survival rate of 75% if they had CH (vs 83% if no CH).

Conclusions

This study provides the first evidence that PWH may have a higher prevalence of CH than PWoH with the same cancers. CH may be an independent biological aging risk factor contributing to inferior survival for PWH and cancer.
Using forensic intelligence as a model for determining future toxicology methods: TBI forensic toxicology and forensic drug chemistry nitazene identification
Authors: Gray Adam , Douglas Sarah , Tiller Michael , Bleakley Michael
Published: April 2024

The Tennessee Bureau of Investigation (TBI) serves all 95 counties of Tennessee, but the data included in this article are primarily focused in Upper East and East Tennessee (the parts of the state included in the eastern time zone). The forensic chemistry (seized drug) unit of the TBI began reporting nitazene analogues in late 2019. The primary analogues found in forensic chemistry cases were isotonitazene and metonitazene. After discussion and review of reporting statistics, the forensic toxicology unit began to monitor for these compounds in toxicology samples by using ion characteristics with the nitazene analogues. Between March 2021 and December 2023, TBI toxicology received 49,639 cases statewide. Of those, 20,105 (40.5%) received toxicology testing. Approximately 95% of TBI toxicology cases are related to Driving Under the Influence (DUI)/motor vehicle–related incidents. Fatal overdoses and cases from the medical examiner office comprise <5% of TBI toxicology caseload. The toxicology section utilizes the SCIEX 3200 Qtrap with a SCIEX Exion LC AC autosampler system to monitor multiple reaction monitoring transition of nitazene analogues. The ion monitoring for two nitazene analogues, isotonitazene and metonitazene, started in March 2021. Ion monitoring should not be construed as a confirmed result but rather as an indication that a drug may be present. A comparison of this data from the forensic toxicology and forensic chemistry units revealed the rise of new drugs that required a more in-depth review to understand the magnitude and scope. This article is also intended to encourage collaboration between forensic toxicology and forensic chemistry (seized drug) units.
Complete remission after a single bisphosphonate infusion in isolated bone Langerhans cell histiocytosis lesion: a case report and a narrative review of the literature
Authors: Kachaner Alexandra , Seror Raphaèle , Aubart Fleur Cohen , Henry Julien , Lazure Thierry , Emile Jean François , Mariette Xavier , Bitoun Samuel
Published: April 2024

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH.
Safety and effectiveness of clofarabine in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia: a post-marketing surveillance study
Authors: Kazama Hirotaka , Nishina Satoshi , Seto Takeshi
Published: April 2024

Objective

Clofarabine is used to treat acute lymphoblastic leukaemia, but evidence of its safety and effectiveness in Japanese patients is limited. We evaluated the safety and effectiveness of clofarabine in patients with relapsed/refractory acute lymphoblastic leukaemia in real-world clinical practice in Japan.

Methods

An observational, multicenter, post-marketing, all-case surveillance was conducted for safety. Effectiveness analyses were conducted in patients aged ≤21 years and those treated with clofarabine monotherapy and combination therapy (clofarabine plus etoposide and cyclophosphamide).

Results

In the all-case survey, 260 of 264 registered patients were eligible for safety analysis. Among the 225 patients eligible for effectiveness analysis, 139 were aged ≤21 years. For monotherapy and combination therapy, 20/31 and 34/88 patients were eligible, respectively. In the all-case survey, the median age was 16.0 years, and 47.7% of patients were <15 years old. Adverse drug reaction incidence was 83.5% and the most common were hematologic toxicities. The best overall response rates in the population aged ≤21 years were complete remission, 29.7%; complete remission without platelet recovery, 7.3% and partial remission, 10.9%. The rest (52.2%) were classified as ineffective. The sum of complete remission, complete remission without platelet recovery and partial remission rates (effectiveness rate) was 47.8% (66/138 patients). The effectiveness rates in the monotherapy and combination therapy surveys were 10.0% (2/20 patients) and 58.8% (20/34 patients), respectively.

Conclusions

These post-marketing surveys provide real-world evidence of the safety and effectiveness of clofarabine regimens, including monotherapy and combination therapy in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia. The safety and effectiveness profiles were comparable with those of previous prospective studies.
Warming and increased precipitation alter soil carbon cycling in a temperate desert steppe of Inner Mongolia
Authors: Lan Mu , Qiu Xiao , La Wei , Wang Huimin , Liu Yahong , Zhao Liqing , Sun Hailian
Published: April 2024

Warming and precipitation are key global change factors driving soil carbon (C) dynamics in terrestrial ecosystems. However, the effects of warming and altered precipitation on soil microbial diversity and functional genes involved in soil C cycling remain largely unknown. We investigated the effects of warming and increased precipitation on soil C cycling in a temperate desert steppe of Inner Mongolia using metagenomic sequencing. We found that warming reduced plant richness, Shannon–Wiener and Simpson index. In contrast, increased precipitation significantly influenced Shannon–Wiener and Simpson index. Warming reduced soil microbial species by 5.4% while increased precipitation and warming combined with increased precipitation led to increases in soil microbial species by 23.3% and 2.7%, respectively. The relative abundance of Proteobacteria, which involve C cycling genes, was significantly increased by warming and increased precipitation. Warming significantly reduced the abundance of GAPDH (Calvin cycle) and celF (cellulose degradation) while it enhanced the abundance of glxR (lignin degradation). Increased precipitation significantly enhanced the abundance of pgk (Calvin cycle), coxL (carbon monoxide oxidation), malZ (starch degradation), and mttB (methane production). Moreover, a wide range of correlations among soil properties and C cycling functional genes was detected, suggesting the synergistic and/or antagonistic relationships under scenario of global change. These results may suggest that warming is beneficial to soil C storage while increased precipitation negatively affects soil C sequestration. These findings provide a new perspective for understanding the response of microbial communities to warming and increased precipitation in the temperate desert steppe.
Primary thyroid fibrosarcoma in a 32-year-old female: case report and literature review
Authors: Jaber Fouad , Rahal Mark , Alkassabin Amira Shikh , Hamza Hanin , Haddad Salim , Shbat Mohamad , Chaban Hussain , Basha Zein , Haddad Sultaneh
Published: April 2024

Thyroid fibrosarcomas represent a rare subset of tumors with exceedingly limited documented cases in the medical literature. This study delineates an unusual occurrence involving a 32-year-old female presenting with symptoms including neck pain, dysphagia, and dyspnea. Notably, the patient experienced symptom recurrence 3 months postthyroidectomy, accompanied by aggressive tumor growth. Despite the considerable size of the tumor and its infiltration into critical anatomical structures, a complex surgical intervention was executed with successful outcomes. The study underscores the imperative for further exploration into the efficacy of proposed therapeutic modalities tailored for managing this neoplasm. Moreover, it emphasizes the necessity for considering the histological classification of fibrosarcoma within the differential diagnoses spectrum for thyroid tumors.
DanceCam: atmospheric turbulence mitigation in wide-field astronomical images with short-exposure video streams
Authors: Bialek Spencer , Bertin Emmanuel , Fabbro Sébastien , Bouy Hervé , Rivet Jean-Pierre , Lai Olivier , Cuillandre Jean-Charles
Published: April 2024

We introduce a novel technique to mitigate the adverse effects of atmospheric turbulence on astronomical imaging. Utilizing a video-to-image neural network trained on simulated data, our method processes a sliding sequence of short-exposure (∼0.2 s) stellar field images to reconstruct an image devoid of both turbulence and noise. We demonstrate the method with simulated and observed stellar fields, and show that the brief exposure sequence allows the network to accurately associate speckles to their originating stars and effectively disentangle light from adjacent sources across a range of seeing conditions, all while preserving flux to a lower signal-to-noise ratio than an average stack. This approach results in a marked improvement in angular resolution without compromising the astrometric stability of the final image.
Stellar populations and merger rates of brightest cluster galaxies a billion years ago: SDSS MaNGA IFU spectroscopy
Authors: Edwards Louise O V , Hamel Kevin A S J , Shy Joseph C , Hernandez Jonathan , Holguin Luna Priscilla , Higgins Denvir J , Chawla Theo , Gavidia Adriana , Cole Samuel
Published: April 2024

We investigate the spectroscopic properties of 85 brightest cluster galaxies (BCGs) and their companions observed with the SDSS MaNGA integral field unit. Galaxy redshifts are between 0.08 < z < 0.15, allowing for a field-of-view up to 80 × 80 kpc. For the main galaxies: the average age of the BCG cores is 7.66$\, \pm \,$1.36 Gyr with no significant gradient out to $2\, R_ {e}$; the average metallicity of the BCG cores is $[Z/H]=0.23\, \pm \, 0.03$ with a negative gradient of Δ[Z/H]/Δ(R/Re)  = –0.14$\, \pm \, 0.09$ which flattens beyond $1.2\, R_ {e}$. Velocity dispersion gradients are mostly flat, but a few positive slopes are seen in the most massive galaxies. Emission lines are present in 12 of the BCGs, most often confined to the central $\sim 2\,$ kpc with emission line ratios well-described by a LINER or AGN excitation source. There are 78 companion galaxies identified and 9 have nebular emission lines that indicate recent star formation. The companions with flux ratios of 4:1 and 20:1 within 30 kpc of their BCG’s core are studied. The companion galaxies have a median age of 7.65$\, \pm \,$1.55 Gyr and are high-metallicity systems, with a median [Z/H] = 0.17  ±  0.07. Close spectroscopic companions with higher merging probabilities have an average merging time of 0.5 ± 0.2 Gyr. The average merger rate is 0.08$\, \pm \, 0.12 \,$ Gyr−1 for 4:1 companions and 0.26$\, \pm \, 0.22 \,$ Gyr−1 for 20:1 companions, allowing for an increase in mass of 2.3$\, \pm \,$3.4 per cent Gyr−1 and 3.5$\, \pm \,$3.2 per cent Gyr−1, respectively.
Missing metals in DQ stars: a compelling clue to their origin
Authors: Farihi J , Dufour P , Wilson T G
Published: April 2024

White dwarf stars frequently experience external pollution by heavy elements, and yet the intrinsically carbon-enriched DQ spectral class members fail to exhibit this phenomenon, representing a decades-old conundrum. This study reports a high-resolution spectroscopic search for Ca ii in classical DQ white dwarfs, finding that these stars are stunted both in pollution frequency and heavy element mass fractions, relative to the wider population. Compared to other white dwarf spectral classes, the average external accretion rate is found to be at least three orders of magnitude lower in the DQ stars. Several hypotheses are considered which need to simultaneously account for (i) an apparent lack of accreted metals, (ii) a dearth of circumstellar planetary material, (iii) an observed deficit of unevolved companions in post-common envelope binaries, (iv) relatively low helium mass fractions, and remnant masses that appear smaller than for other spectral classes, (v) a high incidence of strong magnetism, and (vi) modestly older disc kinematics. Only one hypothesis is consistent with all these constraints, suggesting DQ white dwarfs are the progeny of binary evolution that altered both their stellar structures and their circumstellar environments. A binary origin is already suspected for the warmer and more massive DQ stars, and is proposed here as an inclusive mechanism to expose core carbon material, in a potential evolutionary unification for the entire DQ spectral class. In this picture, DQ stars are not descended from DA or DB white dwarfs that commonly host dynamically active planetary systems.
Tobacco Packaging and Labeling Policies in the WHO African Region: Progress 15 Years After Adoption of the WHO Framework Convention on Tobacco Control Article 11 Implementation Guidelines
Authors: Sebrié Ernesto M , Donley Kaitlin , Fuss Caroline , Wasson Kai , Camara Bityeki Bintou , Muggli Monique E , Crosbie Eric
Published: April 2024

Introduction

Article 11 of the World Health Organization’s Framework Convention on Tobacco Control (WHO FCTC) requires Parties to adopt and implement effective tobacco packaging and labeling policies to communicate health risks and reduce tobacco consumption.

Aims and Methods

The goal of this study was to assess adoption of these policies in the WHO African Region (AFRO). We reviewed tobacco packaging and labeling policies adopted in AFRO from the Campaign for Tobacco-Free Kids’ Tobacco Control Laws database (www.tobaccocontrollaws.org). We assessed these policies based on WHO FCTC Article 11 and its Implementation Guidelines examining three subpolicy areas (health warning labels [HWLs], descriptive constituents and emissions information, and misleading packaging and labeling). We developed a scoring system to rank AFRO countries individually and by the World Bank’s income-level groups, and documented the progress during 1985–2023.

Results

Forty (of 47) AFRO countries adopted national laws, of which a majority adopted large rotating pictorial HWLs and banned misleading descriptors; only Cote d’Ivoire and Mauritius adopted standardized packaging. The higher a country is in the World Bank’s income-level group, the stronger their packaging and labeling policies. This observation was not present in the HWLs subpolicy area. Prior to approving the WHO FCTC Article 11 Implementation Guidelines, only 23 countries adopted text-only HWLs, whereas 26 countries adopted pictorial HWLs after the approval.

Conclusions

Several AFRO countries have adopted tobacco packaging and labeling policies that align with the WHO FCTC Article 11 Implementation Guidelines. More efforts could be directed toward the low-income group and disseminating standardized packaging throughout AFRO.

Implications

In the AFRO, the number of tobacco users is increasing, highlighting the need for tobacco packaging and labeling policies aligned with WHO FCTC Article 11 and its Implementation Guidelines as these are proven tobacco control strategies. This study provides a country- and income-level group ranking of tobacco packaging and labeling policies, and documents the evolution of HWLs adopted in AFRO. It also identifies regional and income-level group successes and gaps in tobacco product packaging and labeling policies and provides recommendations to further align with WHO FCTC Article 11 and its Implementation Guidelines.