bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of monoclonal gammopathy of undetermined significance in Eswatini: a population-based study in Africa
Authors: Cicero Kara I , Dlamini Xolisile , Mavengere Yvonne , Justman Jessica , Nuwagaba-Biribonwoha Harriet , Dlamini Sindisiwe , Dlamini Mxolisi , Ngwenyama Simphiwe , Ngcamphalala Cebisile , Low Andrea , Philip Neena M , El-Sadr Wafaa M , Sahabo Ruben , Abreha Tesfay , Temesgen Sintayehu , Mahlalela Nokuthula , Chiuzan Codruta , Chen Yuxuan , Pan Samuel S , Lentzsch Suzanne , Neugut Alfred I
Published: July 2024

Background

Although monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma disproportionately affect Black individuals, few epidemiological studies have been conducted on these plasma cell disorders in Africa. Here we describe the prevalence of MGUS in Eswatini and compare our results to the landmark Olmsted County, Minnesota study.

Methods

Between 2016 and 2017, 13 339 residents of Eswatini participated in the Swaziland HIV Incidence Measurement Survey, from which a nationally representative biorepository was created. Plasma samples were then randomly selected and analyzed for MGUS. MGUS prevalence in Eswatini was compared with that of Olmsted County. In addition, demographic and HIV-related associations with MGUS were assessed.

Results

Of the 515 samples randomly selected, the median age was 50 years (range = 35-80 years); 60% were female; and 38.6% were HIV positive, of whom 82.4% were on antiretroviral therapy. We found that 68 participants had evidence of MGUS, for a prevalence of 13.2%. HIV status was not significantly associated with MGUS (odds ratio = 1.05, 95% confidence interval = 0.62 to 1.77), but among HIV-positive individuals, MGUS was less frequent for patients on antiretroviral therapy (adjusted odds ratio = 0.31, 95% confidence interval = 0.11 to 0.82). The prevalence of conventional MGUS was similar between Eswatini and Olmsted County (3.4% vs 3.2%-3.4%), whereas the incidence of light-chain MGUS was significantly greater in Eswatini (12.3% vs 0.8%).

Conclusion

Our study suggests that the incidence of MGUS is similar between ethnicities and raises the question of whether the current definition of light-chain MGUS reliably reflects a true monoclonal protein precursor state. Perhaps the current definition of light-chain MGUS may be capturing alternate etiologies, such as untreated HIV infection.
Analysis of cancer drugs receiving FDA’s Accelerated Approval between 1992 and 2021
Authors: Lim Heeyeon , Kim Minji , Kang Geeyoon , Ko Minji , Kim Eunyoung
Published: July 2024

Objectives

This cross-sectional study examines the Food and Drug Administration (FDA)’s Accelerated Approval (AA) pathway for cancer drugs from 1992 to 2021, which expedites the development and approval of new drugs, including biologics, for severe or life-threatening conditions such as cancers.

Methods

Based on the ‘CDER Drug and Biologic AAs Based on a Surrogate Endpoint’ report, the number of indications where anticancer agents received AA and the conversion rates to Full Approval (FA) were analysed. Outcome measures used in phase II and phase III trials for these drugs were obtained from US National Library of Medicine for comparison.

Key findings

Of the 278 AA-granted indications, 67% were for anticancer agents. Lymphoma, leukemia, and lung cancer had the highest number of AA indications among all cancer types. The conversion rates to FA varied among periods: Early (1995–2003), Middle (2004–2012), and Late (2013–2021). The conversion rates for drugs were 82%, 79%, and 31%, while biologics exhibited rates of 100%, 78%, and 27%, respectively. The overall response rate was often the primary outcome measure in phase II trials, whereas overall survival and progression-free survival were the common outcome measures in phase III trials. Secondary outcome measures included disease control rate and duration of response.

Conclusions

This study provides valuable insights for stakeholders seeking to understand the approval criteria and processes for cancer drugs via the AA pathway. However, limitations in data availability, phase-specific variations in drug doses and combinations, and the inability to manage uncertain data should be acknowledged. Research on the AA program to non-cancer drugs is also required.
Understanding the Regulatory Pathways Used to Develop, Evaluate, Authorize, and Approve New Drugs and Vaccines in the United States
Authors: Domachowske Joseph B
Published: July 2024

The United States (U.S.) Food and Drug Administration (FDA) oversees the safety and quality of drugs and vaccines that are used in the U.S. Administration of the FDA falls under the jurisdiction of the U.S. Department of Health and Human Services (HHS). The regulatory oversight of the FDA is complex and comprehensive, requiring the various roles and responsibilities to be divided across six main centers. The activities of two of these centers, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are the primary focus of this review.
Heat-related deaths during the 2024 Hajj pilgrimage
Authors: Memish Ziad A , Zumla Alimuddin , Parker Salim
Published: July 2024

Heat-related illnesses have been well-documented in millions of travellers who attend mass gathering religious events such as the Kumbh Mehla and Hajj. The 2024 Hajj has recently attracted media attention due to significant HRIs among pilgrims attributed to excessive heat and significant number of unregistered pilgrims.
Roles of plastoglobules and lipid droplets in leaf neutral lipid accumulation during senescence and nitrogen deprivation
Authors: Coulon Denis , Nacir Houda , Bahammou Delphine , Jouhet Juliette , Bessoule Jean-Jacques , Fouillen Laëtitia , Bréhélin Claire
Published: July 2024

Upon abiotic stress or senescence, the size and/or abundance of plastid-localized plastoglobules and cytosolic lipid droplets, both compartments devoted to neutral lipid storage, increase in leaves. Meanwhile, plant lipid metabolism is also perturbed, notably with the degradation of thylakoidal monogalactosyldiacylglycerol (MGDG) and the accumulation of neutral lipids. Although these mechanisms are probably linked, they have never been jointly studied, and the respective roles of plastoglobules and lipid droplets in the plant response to stress are totally unknown. To address this question, we determined and compared the glycerolipid composition of both lipid droplets and plastoglobules, followed their formation in response to nitrogen starvation, and studied the kinetics of lipid metabolism in Arabidopsis leaves. Our results demonstrated that plastoglobules preferentially store phytyl-esters, while triacylglycerols (TAGs) and steryl-esters accumulated within lipid droplets. Thanks to a pulse–chase labeling approach and lipid analyses of the fatty acid desaturase 2 (fad2) mutant, we showed that MGDG-derived C18:3 fatty acids were exported to lipid droplets, while MGDG-derived C16:3 fatty acids were stored within plastoglobules. The export of lipids from plastids to lipid droplets was probably facilitated by the physical contact occurring between both organelles, as demonstrated by our electron tomography study. The accumulation of lipid droplets and neutral lipids was transient, suggesting that stress-induced TAGs were remobilized during the plant recovery phase by a mechanism that remains to be explored.
The baryon cycle in modern cosmological hydrodynamical simulations
Authors: Wright Ruby J , Somerville Rachel S , Lagos Claudia del P , Schaller Matthieu , Davé Romeel , Anglés-Alcázar Daniel , Genel Shy
Published: July 2024

In recent years, cosmological hydrodynamical simulations have proven their utility as key interpretative tools in the study of galaxy formation and evolution. In this work, we present a comparative analysis of the baryon cycle in three publicly available, leading cosmological simulation suites: EAGLE, IllustrisTNG, and SIMBA. While these simulations broadly agree in terms of their predictions for the stellar mass content and star formation rates of galaxies at $z\approx 0$, they achieve this result for markedly different reasons. In EAGLE and SIMBA, we demonstrate that at low halo masses ($M_{\rm 200c}\lesssim 10^{11.5}\, \mathrm{M}_{\odot }$), stellar feedback (SF)-driven outflows can reach far beyond the scale of the halo, extending up to $2\!-\!3\times R_{\rm 200c}$. In contrast, in TNG, SF-driven outflows, while stronger at the scale of the interstellar medium, recycle within the circumgalactic medium (within $R_{\rm 200c}$). We find that active galactic nucleus (AGN)-driven outflows in SIMBA are notably potent, reaching several times $R_{\rm 200c}$ even at halo masses up to $M_{\rm 200c}\approx 10^{13.5}\, \mathrm{M}_{\odot }$. In both TNG and EAGLE, AGN feedback can eject gas beyond $R_{\rm 200c}$ at this mass scale, but seldom beyond $2\!-\!3\times R_{\rm 200c}$. We find that the scale of feedback-driven outflows can be directly linked with the prevention of cosmological inflow, as well as the total baryon fraction of haloes within $R_{\rm 200c}$. This work lays the foundation to develop targeted observational tests that can discriminate between feedback scenarios, and inform subgrid feedback models in the next generation of simulations.
Comparison of models for the warm-hot circumgalactic medium around Milky Way-like galaxies
Authors: Singh Priyanka , Lau Erwin T , Faerman Yakov , Stern Jonathan , Nagai Daisuke
Published: July 2024

A systematic comparison of the models of the circumgalactic medium (CGM) and their observables is crucial to understanding the predictive power of the models and constraining physical processes that affect the thermodynamics of CGM. This paper compares four analytic CGM models: precipitation, isentropic, cooling flow, and baryon pasting models for the hot, volume-filling CGM phase, all assuming hydrostatic or quasi-hydrostatic equilibrium. We show that for fiducial parameters of the CGM of a Milky Way (MW)-like galaxy ($M_{\rm vir} \sim 10^{12}~{\rm M}_{\odot }$ at $z\sim 0$), the thermodynamic profiles – entropy, density, temperature, and pressure – show most significant differences between different models at small ($r\lesssim 30$ kpc) and large scales ($r\gtrsim 100$ kpc) while converging at intermediate scales. The slope of the entropy profile, which is one of the most important differentiators between models, is $\approx 0.8$ for the precipitation and cooling flow models, while it is $\approx 0.6$ and 0 for the baryon pasting and isentropic models, respectively. We make predictions for various observational quantities for an MW mass halo for the different models, including the projected Sunyaev–Zeldovich effect, soft X-ray emission (0.5–2 keV), dispersion measure, and column densities of oxygen ions (O vi, O vii, and O viii) observable in absorption. We provide Python packages to compute the thermodynamic and observable quantities for the different CGM models.
The timing of pronuclear transfer critically affects the developmental competence and quality of embryos
Authors: Znachorova Tereza , Dudko Nataliia , Ming Hao , Jiang Zongliang , Fulka Helena
Published: July 2024

Pronuclear transfer has been successfully used in human-assisted reproduction to suppress the adverse effects of a defective oocyte cytoplasm or to bypass an idiopathic developmental arrest. However, the effects of the initial parental genome remodelling in a defective cytoplasm on the subsequent development after pronucleus transfer have not been systematically studied. By performing pronuclear transfer in pre-replication and post-replication mouse embryos, we show that the timing of the procedure plays a critical role. Although apparently morphologically normal blastocysts were obtained in both pre- and post-replication pronuclear transfer groups, post-replication pronuclear transfer led to a decrease in developmental competence and profound changes in embryonic gene expression. By inhibiting the replication in the abnormal cytoplasm before pronuclear transfer into a healthy cytoplasm, the developmental potential of embryos could be largely restored. This shows that the conditions under which the first embryonic replication occurs strongly influence developmental potential. Although pronuclear transfer is the method of choice for mitigating the impact of a faulty oocyte cytoplasm on early development, our results show that the timing of this intervention should be restricted to the pre-replication phase.
SMCHD1 activates the expression of genes required for the expansion of human myoblasts
Authors: Wong Matthew Man-Kin , Hachmer Sarah , Gardner Ed , Runfola Valeria , Arezza Eric , Megeney Lynn A , Emerson Charles P , Gabellini Davide , Dilworth F Jeffrey
Published: July 2024

SMCHD1 is an epigenetic regulatory protein known to modulate the targeted repression of large chromatin domains. Diminished SMCHD1 function in muscle fibers causes Facioscapulohumeral Muscular Dystrophy (FSHD2) through derepression of the D4Z4 chromatin domain, an event which permits the aberrant expression of the disease-causing gene DUX4. Given that SMCHD1 plays a broader role in establishing the cellular epigenome, we examined whether loss of SMCHD1 function might affect muscle homeostasis through additional mechanisms. Here we show that acute depletion of SMCHD1 results in a DUX4-independent defect in myoblast proliferation. Genomic and transcriptomic experiments determined that SMCHD1 associates with enhancers of genes controlling cell cycle to activate their expression. Amongst these cell cycle regulatory genes, we identified LAP2 as a key target of SMCHD1 required for the expansion of myoblasts, where the ectopic expression of LAP2 rescues the proliferation defect of SMCHD1-depleted cells. Thus, the epigenetic regulator SMCHD1 can play the role of a transcriptional co-activator for maintaining the expression of genes required for muscle progenitor expansion. This DUX4-independent role for SMCHD1 in myoblasts suggests that the pathology of FSHD2 may be a consequence of defective muscle regeneration in addition to the muscle wasting caused by spurious DUX4 expression.
Implementing an Antimicrobial Stewardship Program in an Oncology Center in Lima, Peru: A Model for Low- and Middle-Income Countries
Authors: Seas Carlos , Legua Pedro , Delfin Brian , Villavicencio Karol , Palomino Angie , Montenegro Paola , Aguilar Ivan , La Rosa Yenka , Robles Maribel , Young Frank
Published: July 2024

Our center launched the first antimicrobial stewardship program in Peru. From 2016 to 2023, the proportion of antimicrobial prescriptions audited increased from 60% to 95%, and 65% to 95% of recommendations were accepted. Vancomycin and meropenem use dropped by 95% and 84%, respectively. The proportion of recommendations for surgical prophylaxis exceeded 90%.
Similar Viral and Immune Characteristics of Kaposi Sarcoma in ART-treated People Living With HIV and Older Patients With Classic Kaposi Sarcoma
Authors: Royston Léna , Jary Aude , Berini Carolina A , Mabanga Tsoarello , Lin John , Pagliuzza Amélie , Chomont Nicolas , Litvinov Ivan V , Calmy Alexandra , Leducq Valentin , Calvez Vincent , Marcelin Anne-Geneviève , Isnard Stéphane , Routy Jean-Pierre
Published: July 2024

Background

Reemergence of human herpesvirus 8 (HHV-8)–induced Kaposi sarcoma (KS) in people living with HIV (PLWH) despite antiretroviral therapy (ART) poses a clinical challenge because they already have favorable CD4 T-cell numbers and undetectable viral loads. We observed that clinical presentation in PLWH on ART resembled classic KS found in older HIV-uninfected patients and hypothesized that immunosenescence may thus play a role in occurrence of KS on ART. We compared viral and immune factors implicated in the development of KS in ART-treated PLWH (HIV KS) and HIV-uninfected classic KS patients (cKS), compared to controls without KS (HIV Control, cControls respectively).

Methods

Plasma, peripheral blood mononuclear cell, and skin tissues were obtained from 11 HIV KS and 11 cKS patients and 2 groups of age-matched controls.

Results

HIV KS participants were younger than cKS (aged 53 vs 75 years). HHV-8 genotypes did not differ between groups. Despite the younger age and a lower CD4/CD8 ratio, activated, exhausted, and senescent T-cell frequencies were similar between HIV KS and cKS. Anti–HHV-8 immunoglobulin G levels were higher and circulating HHV-8 DNA lower in HIV KS compared with cKS. Circulating platelet-derived growth factors AA-BB and granulocyte colony-stimulating factors were higher in HIV KS We observed similar levels of HHV-8 DNA and PD-1 expression in skin lesions from HIV KS and cKS patients.

Conclusions

Altogether, early immune senescence could be involved in the development of KS in ART-treated PLWH. Higher anti–HHV-8 immunoglobulin G levels could be linked with lower circulating viral load. Such insights should help developing therapeutical strategies to prevent development and treat KS in PLWH on ART.
Not so different: Comparing British MPs’ and voters’ attitudes to climate change
Authors: Pearson Mitya , Wager Alan
Published: July 2024

There is a growing literature investigating the attitudes of political elites and citizens in a range of areas, and this article uses matched survey data of British MPs and voters to contribute a new comparison of their views on climate change. It finds limited evidence of systematic differences between MPs’ and voters’ attitudes to climate change: neither group is clearly more concerned about the issue than the other nor more polarized along partisan lines. However, there does appear to be incongruence between MPs’ and voters’ views on some specific climate policies. The research builds on previous analyses of British MPs’ approaches to climate change, including finding that party identity is more useful in predicting their perspectives on climate change than their perception of public attitudes.
DWARF AND LESS TILLERS ON CHROMOSOME 3 promotes tillering in rice by sustaining FLORAL ORGAN NUMBER 1 expression
Authors: Fan Yongyi , Chen Hongmei , Wang Beifang , Li Dian , Zhou Ran , Lian Wangmin , Shao Gaoneng , Wei Xiangjin , Wu Weixun , Liu Qunen , Sun Lianping , Zhan Xiaodeng , Cheng Shihua , Zhang Yingxin , Cao Liyong
Published: July 2024

Three key factors determine yield in rice (Oryza sativa): panicle number, grain number, and grain weight. Panicle number is strongly associated with tiller number. Although many genes regulating tillering have been identified, whether Dof proteins are involved in controlling plant architecture remains unknown. The dwarf and less tillers on chromosome 3 (dlt3) rice mutant produces fewer tillers than the wild type. We cloned DLT3, which encodes a Dof protein that interacts with MONOCULM 3 (MOC3) in vivo and in vitro and recruits MOC1, forming a DLT3-MOC3-MOC1 complex. DLT3 binds to the promoter of FLORAL ORGAN NUMBER 1 (FON1) to activate its transcription and positively regulate tiller number. The overexpression of MOC1, MOC3, or FON1 in the dlt3 mutant increased tiller number. Collectively, these results suggest a model in which DLT3 regulates tiller number by maintaining the expression of MOC1, MOC3, and FON1. We discovered that DLT3 underwent directional selection in the Xian/indica and Geng/japonica populations during rice domestication. To provide genetic resources for breeding varieties with optimal panicle numbers, we performed large-scale diversity sequencing of the 1,080-bp DLT3 coding region of 531 accessions from different countries and regions. Haplotype analysis showed that the superior haplotype, DLT3H1, produced the most tillers, while haplotype DLT3H6 produced the fewest tillers. Our study provides important germplasm resources for breeding super high-yielding rice varieties with combinations of superior haplotypes in different target genes, which will help overcome the challenge of food and nutritional security in the future.
Myo-inositol oxygenase CgMIOX3 alleviates S-RNase-induced inhibition of incompatible pollen tubes in pummelo
Authors: Xu Qiang , Liu Chenchen , Zhang Zhezhong , Cao Zonghong , Liang Mei , Ye Changning , Lin Zongcheng , Deng Xiuxin , Ye Junli , Bosch Maurice , Chai Lijun
Published: July 2024

Pummelo (Citrus grandis L. Osbeck) exhibits S-RNase-based self-incompatibility (SI), during which S-RNase cytotoxicity inhibits pollen tubes in an S-haplotype-specific manner. The entry of S-RNase into self-pollen tubes triggers a series of reactions. However, these reactions are still poorly understood in pummelo. In the present study, we used S-RNases as baits to screen a pummelo pollen cDNA library and characterized a myo-inositol oxygenase (CgMIOX3) that physically interacts with S-RNases. CgMIOX3 is highly expressed in pummelo pollen tubes, and its downregulation leads to a reduction in pollen tube growth. Upon entering pollen tubes, S-RNases increase the expression of CgMIOX3 and enhance its activity by directly binding to it in an S-haplotype-independent manner. CgMIOX3 improves pollen tube growth under oxidative stress through ascorbic acid (AsA) accumulation and increases the length of self-pollen tubes. Furthermore, over-expression of CgMIOX3 increases the relative length of self-pollen tubes growing in the style of petunia (Petunia hybrida). This study provides intriguing insights into the pumelo SI system, revealing a regulatory mechanism mediated by CgMIOX3 that plays an important role in the resistance of pollen tubes to S-RNase cytotoxicity.
The Dynamics of Electoral Manipulation and Institutional Trust in Democracies: Election Timing, Blatant Fraud, and the Legitimacy of Governance
Authors: Higashijima Masaaki , Kadoya Hisashi , Yanai Yuki
Published: July 2024

This paper explores the dynamic relationship between electoral manipulation and popular trust in political institutions. Governments often manipulate election results by resorting to electoral fraud. They also tilt the electoral field by opportunistically deciding when to hold elections, in other words, election timing maneuvering. How do these two different types of electoral manipulation affect citizens’ trust in the government, legislature, and election management bodies (EMBs)? We suggest that although the short-term effects of election timing manipulation are unclear due to its ambiguous nature as an electioneering strategy, substantial electoral margins created by timing maneuvering facilitate smooth decision-making, leading to boosting trust in the government and legislature over the long run. In contrast, as electoral fraud is an unambiguous form of manipulation, it may undermine trust in the government and parliament, although such effects may not last. By combining an original dataset of election timing with existing survey data comprising 335,000 citizens from fifty-eight democratic countries, we find evidence in support of our theoretical expectations.
Does Exposure to Election Fraud Research Undermine Confidence in Elections?
Authors: Kuk John S , Lee Don S , Rhee Inbok
Published: July 2024

Can academic research on election fraud undermine public confidence in elections? As election results become instantaneously accessible all over the world, academic research can increasingly influence perceptions of election integrity. To examine how electoral fraud information from academic research can affect voters’ beliefs about the legitimacy of election results, we conducted a survey experiment following the 2020 general election in South Korea. Using a nationally representative sample of Korean voters and exploiting a unique real-world situation featuring foreign academics considered relatively impartial, we found that exposure to hypothetical election fraud claims undermined confidence in electoral outcomes, measured via both self-reports and behavioral measures. Moreover, the claims’ impact was conditional on voters’ partisan attachments—strongest among supporters of the losing party—which is in line with the logic of motivated reasoning. Our work contributes to the literature on election integrity, using a relatively new yet stable democracy as its test case.
Trust in the Count: Improving Voter Confidence with Post-election Audits
Authors: Jaffe Jacob , Loffredo Joseph R , Baltz Samuel , Flores Alejandro , Stewart Charles
Published: July 2024

Post-election audits are thought to bolster voter confidence in elections, but it is unclear which aspects of audits drive public trust. Using preregistered vignette and conjoint survey experiments administered by YouGov on a sample of 2,000 American respondents, we find that how an audit is conducted is more important than what an audit finds. Structural features of audits, like who conducts it and how its results are announced, turn out to be more consequential to voter evaluations of election results than the actual discrepancy found. Moreover, while Democrats and Republicans have increasingly divided views of the state of democracy in the United States, they are similarly receptive to information presented about audits and largely agree that audits are effective tools for detecting errors in vote counting. Our findings thus reinforce the expectation that audits do increase voter trust and highlight that election administrators can strengthen voter confidence by making audits as transparent as possible.
Unpacking stakeholder perceptions on challenges for increasing adoption of solar-powered irrigation systems in India: A Q methodology study
Authors: Korekallu Srinivasa Aditya , Mithöfer Dagmar
Published: July 2024

Solar-powered irrigation systems (SPISs) are instruments for sustainable energy transition in agriculture. Despite the government of India's efforts, the adoption of SPIS has remained low. This paper uses the Q method to examine shared stakeholder views on the challenges of increasing SPIS adoption. The aim is to understand barriers to and drivers for SPIS adoption, and the necessary institutional setting to scale up adoption. To capture the discourse on challenges to SPIS adoption, a Q sample of 20 statements was extracted after stakeholder interviews and expert ratings. The statements were Q sorted by 22 respondents across SPIS stakeholder groups. Factor analysis identifies two distinct perspectives on constraints to expanding SPIS: (1) economic and financial barriers; and (2) institutional and governance challenges. This calls for re-framing SPIS from the incentive side of things and convergence across concerned implementing agencies.
Analysis of the relationship between ambient dose, ambient dose equivalent and effective dose in operational neutron spectra
Authors: Endo Akira
Published: July 2024

This study examines the relationship between ambient dose H*, ambient dose equivalent H*(10), and effective dose E for external neutron irradiation over 163 operational spectra from different workplaces. The results show that H* provides a reasonable estimate with a controlled margin, even if overestimated, to assess E compared with H*(10), which can lead to a significant overestimation or underestimation of E depending on the neutron spectra. The results highlight the limitations of H*(10) and the superiority of H* in estimating E according to the requirements of the operational quantities, especially in environments with high-energy neutrons.
Modification of algorithm for accurate estimation of Hp(3) based on response of head TLD badge calibrated using ISO cylindrical phantom
Authors: Bhattacharya Madhumita , Samuel Kasthuri , Srivastava Kshama , Bakshi Ashok Kumar
Published: July 2024

In India, the prevailing approach to eye lens dosimetry is the placement of an existing dosemeter on the forehead region after slight modification serves as a dedicated Eye Lens Dosemeter. A methodology for estimating the eye lens dose in terms of the Hp(3) has been previously explored employing an algorithm based on the response characteristics of this dosemeter using ISO slab phantom. It was observed that the performance of the dosemeter in terms of Hp(3) using previous algorithm showed under response at higher angles of incidence and photon beams of energy < 200 keV. Further, study was conducted to modify the algorithm following the latest ISO recommendations. This involved generation of data from the response of existing dosemeter on a cylindrical phantom. The results of this study revealed better performance of the newly established algorithm in estimating eye lens dose in terms of Hp(3) when compared to the earlier algorithm.
Associations of accelerometer-measured sleep duration with incident cardiovascular disease and cardiovascular mortality
Authors: Zhou Mingqing , Liang Yannis Yan , Ai Sizhi , Feng Hongliang , Zhou Yujing , Liu Yaping , Zhang Jihui , Jia Fujun , Lei Binbin
Published: July 2024

Study Objectives

This study aimed to determine the associations between accelerometer-measured sleep durations and the risks of incident cardiovascular disease (CVD) and CVD-related mortality.

Methods

A total of 92 261 participants (mean age: 62.4 ± 7.8 years, 56.4% female) were included in UK Biobank between 2013 and 2015. Average daily sleep durations were measured using wrist-worn accelerometers over a 7-day period. Sleep durations were categorized as <7 hours/day, 7–9 hours/day (reference), and >9 hours/day. The incidence of CVD and CVD-related mortality were ascertained by hospital records and death registries.

Results

During a median follow-up period of 7.0 years, a total of 13 167 participants developed CVD, and 1079 participants died of CVD. Compared with a sleep duration 7–9 hours/day, an accelerometer-measured sleep duration <7 hours/day but not >9 hours/day was associated with higher risks of incident CVD (HR 1.06, 95% CI: 1.02 to 1.10), CVD-related mortality (HR 1.29, 95% CI: 1.14 to 1.47), coronary heart disease (HR 1.11, 95% CI: 1.03 to 1.19), myocardial infarction (HR 1.14, 95% CI: 1.03 to 1.27), heart failure (HR 1.20, 95% CI: 1.08 to 1.34), and atrial fibrillation (HR 1.15, 95% CI: 1.07 to 1.24). A curvilinear dose‒response pattern was observed between accelerometer-measured sleep durations and incident CVD (poverall < .001), with L-shaped associations found for incident CVD and CVD-related mortality.

Conclusions

An accelerometer-measured sleep duration of <7 hours/day but not >9 hours/day was associated with elevated risks of incident CVD and CVD-related mortality. Maintaining adequate sleep may help promote cardiovascular health.
Determination of relative bioavailability of copper from copper glycinate in growing beef steers
Authors: Henderson Jacob A , Niedermayer-Conway Emma K , Hansen Stephanie L
Published: July 2024

Chelated copper (Cu) sources, such as Cu glycinate (CuGly), may be more bioavailable relative to Cu sulfate (CuSO4) when fed to ruminants under antagonistic pressure. The objective of this study was to determine the bioavailability of CuGly (GemStone Cu; Phibro Animal Health) relative to CuSO4 in steers fed a diet supplemented with 0.3% sulfur and 2 mg molybdenum/kg of dry matter (DM). Sixty Angus crossbred steers (n = 12 per treatment) averaging 288 ± 4.85 kg were enrolled in a 90-d study and fed a corn silage-based diet with one of five Cu supplementation strategies, including no supplemental Cu (CON), 5 or 10 mg supplemental Cu from CuSO4/kg DM, and 5 or 10 mg supplemental Cu from CuGly/kg DM. Steers were housed in pens equipped with GrowSafe feed bunks (GrowSafe Systems Ltd., Airdire, AB, Canada), with six steers per pen. Growth performance, liver Cu, and plasma Cu were analyzed in the MIXED procedure of SAS 9.4 (SAS Inst. Inc, Cary, NC) with orthogonal contrasts to compare CON vs. 5 mg Cu/kg DM, CON vs. 10 mg Cu/kg DM, 5 vs. 10 mg Cu/kg DM, and CuSO4 vs. CuGly. Copper indices were regressed against Cu intake and slopes were calculated using the GLM procedure SAS. Dietary Cu supplementation did not affect steer body weights on days 0, 28, 56, or 90 (P ≥ 0.52), average daily gain, dry matter intake, or gain:feed (P ≥ 0.36). Final plasma Cu concentration did not differ between CON vs. 5 mg Cu/kg DM (P = 0.79), CON vs. 10 mg Cu/kg DM (P = 0.65), or 5 vs. 10 mg Cu/kg DM (P = 0.39). Steers receiving CuSO4 tended to have greater final plasma Cu concentrations than those receiving CuGly (P = 0.08). Initial liver Cu concentration averaged 374 mg Cu/kg DM, which is considered highly adequate. No steers reached deficient Cu status by the end of the 90-d period. Control steers had lesser final liver Cu concentrations than supplemented steers (P ≤ 0.04). Steers receiving 10 mg supplemental Cu/kg DM had greater liver Cu concentrations than those receiving 5 mg supplemental Cu/kg DM (P = 0.01). Copper source had no effect on final liver Cu concentrations (P = 0.57) and based on liver Cu and Cu intake the bioavailability of CuGly was similar to CuSO4 (115%; P = 0.27). The initially high Cu status and the fact that cattle did not become Cu deficient may have impacted the relative bioavailability results, and more research is needed to investigate the role initial Cu status and antagonistic pressure play in the bioavailability of chelated Cu sources.
On-Site Dermatology Care for Older Adults
Authors: Mulholland Kalli , Gardner Kenzie
Published: July 2024

Access to timely, satisfactory dermatology care is an ongoing challenge that specifically impacts aging adults. Among the numerous barriers that older generations face, transportation emerges as a central obstacle that affects their ability to receive proper treatment and follow-up care. Overcoming this potential hurdle requires innovation in healthcare delivery from the current traditional brick-and-mortar option. One solution to closing this gap and improving treatment opportunities includes the collaboration with senior living facilities to provide on-site dermatologic care to this vulnerable population. This forward-thinking healthcare delivery model not only addresses access and transportation barrier issues but also offers additional advantages including personalized timely care, flexible patient scheduling, a culture of safety, space for patient dignity, and privacy as well as strengthens partnerships with ecosystem stakeholders. Dermatology nurses are uniquely positioned to advocate for older adults in need of appropriate dermatology services. It is our hope that the information in this article will support the successful delivery of on-site dermatology care for older adults.
Examining the relationship between alterations in plasma cholesterol, vascular endothelin-1 levels, and the severity of sepsis in children: An observational study
Authors: Xu Jing , Shen Wenli , Zhang Xiaotao , Zhu Hongli , Wu Yunduo , Wang Qizheng , Cui Changqiang , Zha Li , Lu Yan Jiao , Liu Rui , Lin Xiaofei
Published: July 2024

Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.
Correlation analysis between the early diagnosis and severity of neuropathic pain and the activation level of NLRP3 inflammasome: A retrospective study
Authors: Wang Yu , Zhou Xiangling , Zhou Xiangling
Published: July 2024

To investigate the correlation between neuropathic pain’s early diagnosis, severity, and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome activation, we retrospectively evaluated 50 patients with neuropathic pain and 50 healthy individuals. Activation of the NLRP3 inflammasome was measured in blood samples, as well as pain levels and clinical markers. Neuropathic pain patients exhibited elevated NLRP3 inflammasome activation. Pain intensity positively correlated with activation. Correlation was also observed with inflammatory markers and pain-related biomarkers. NLRP3 inflammasome demonstrated high diagnostic sensitivity. In conclusion, NLRP3 inflammasome activation influences neuropathic pain initiation and progression. Measuring activation levels may serve as an early diagnostic indicator and severity gauge for neuropathic pain.
Research on cognitive impairment and potential risk factors in peritoneal dialysis patients: An observational study
Authors: Shi Chunxia , Jia Shujing , Wang Xiaoqi , Liu Conghui , Shao Feng , Shi Yanan , Li Zhongxin
Published: July 2024

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.
Relationship between serum levels of folic acid and homocysteine with cognitive impairment in patients diagnosed with multiple sclerosis
Authors: Imeni Kashan Azadeh , Mirzaasgari Zahra , Nouri Shirazi Shabnam
Published: July 2024

Multiple Sclerosis (MS), one of the most common neurological diseases, plays a major role in the ailments of adults. Studies on the role of homocysteine (Hcy) and folic acid in causing cognitive disorders in patients diagnosed with MS are still ongoing. This study aimed to evaluate the serum levels of folic acid and Hcy related to cognitive impairment in patients with multiple sclerosis. This prospective clinical study was conducted on 57 patients diagnosed with MS who were referred to Firoozgar Hospital, Tehran, Iran (Between November 2019 and September 2021). Demographic information and clinical characteristics of enrolled patients were recorded in a predesigned checklist. These characteristics were comprised of outcomes related to the Brief International Cognitive Assessment for MS, and the patient’s Hcy and acid folic levels. Data were analyzed using SPSS version 25. Out of 57 enrolled patients, 39 subjects (68.4%) were female and 18 subjects (31.6%) were male, with a mean age of 36.87 ± 9.40 years old. In terms of disease time span, there was a mean duration of 3.80 ± 4.94 years (range: 1–23 years). There were no significant differences between the mean score of Brief International Cognitive Assessment for MS scale with patient’s sex (P value: .88), and disease duration of patients (P value: .86). There was no significant relationship between the serum levels of acid folic and Hcy with cognitive impairment (P value > .05). The study results revealed that there were no significant relationships between the folic acid, Hcy levels, disease duration, and the type of MS disease with the severity of cognitive impairment. More randomized controlled clinical trials are needed to confirm the relationships between the folic acid and Hcy levels with cognitive impairment in patients with MS.
Exosomal miRNAs in prenatal diagnosis: Recent advances
Authors: Jin Keqin , Shen Shuangshuang , Shi Ruyong , Xu Xiayuan , Hu Min
Published: July 2024

Exosomes, small membranous microvesicles released by cells, contain a range of bioactive molecules, including proteins and miRNAs, which play critical roles in intercellular communication and physiological and pathological processes. Current research suggests that exosomal miRNAs could serve as valuable biomarkers for prenatal diseases, offering a noninvasive method for early detection and monitoring. Studies linking exosomal miRNAs to various birth defects, including fetal growth restriction, urinary tract malformations, cardiovascular system malformations, and hereditary diseases like Down syndrome, were discussed. However, there are some conflicting study findings due to different exosome separation methods. Here, we also discussed exosome separation methods, emphasizing the importance of method selection based on specific purposes and sample types. Further studies are needed to standardize isolation techniques, understand the specific mechanisms underlying exosomal miRNA function, and develop reliable noninvasive prenatal diagnostic indicators. Overall, exosomal miRNAs show promise as potential biomarkers for prenatal diagnosis, but further research is necessary to validate their clinical utility.
Role of indocyanine green-guided near-infrared fluorescence imaging in identification of the cause of neonatal cholestasis
Authors: Zhang Hong , He Xiaobing , Ye Zhihua , Wu Qiang , Luo Yuanyuan
Published: July 2024

To evaluate the efficacy and safety of indocyanine green (ICG)-guided near-infrared fluorescence (NIRF) imaging during surgery to diagnose the cause of neonatal cholestasis (NC). Data on NC patients who underwent both NIRF with ICG and conventional laparoscopic bile duct exploration (the gold standard) at our institute from January 2022 to December 2022 were retrospectively analyzed. The patients’ baseline characteristics and liver function outcomes were collected and analyzed, and the diagnostic consistency was compared between the 2 methods. In total, 16 NC patients were included in the study, comprising 8 (50%) male and 8 (50%) female patients, ranging in age from 42 to 93 days, with a median age of 54.4 ± 21 days. During surgery, all the patients underwent NIRF with ICG, followed by conventional laparoscopic bile duct exploration. Finally, 15 of the patients were diagnosed with biliary atresia (BA) (1 with type-I BA, and 14 with type-II BA). The other patient was diagnosed with cholestasis. The diagnostic results from fluorescence imaging with ICG were consistent with those from conventional laparoscopic bile duct exploration. ICG-guided NIRF is associated with an easy operation, less trauma, and good safety. Also, its diagnostic accuracy is similar to conventional laparoscopic bile duct exploration.
Subclavian arterial rupture due to blunt trauma injury: A case report
Authors: Hwang Suyeong , Kim Gun Woo , Cho Sung Hoon , Hwang Deokbi , Lim Kyoung Hoon
Published: July 2024

Rationale:

Subclavian arterial injury due to blunt trauma is rare but can have devastating outcomes. Massive hemorrhage or limb ischemia might develop depending on the extent of damage, and open repair might be necessary to salvage the limb. However, life-saving treatments should be prioritized in critically unstable patients.

Patient concerns:

A 21-year-old male patient who was transferred to our trauma center following a motorcycle accident. Abdominal and chest computed tomography (CT) revealed right renal injury and massive hemothorax with several rib fractures in the right chest.

Diagnosis and interventions:

Right renal injury with multiple extravasations and right 8th intercostal arterial injury were detected during angiography. Emergent exploration with lateral thoracotomy was performed to manage right hemothorax. Pulsating bleeding from the thoracic roof observed in the operative field suggested a subclavian arterial injury. The unstable vital signs did not recover despite massive transfusion, and his right arm had already stiffened. Therefore, endovascular approach was adopted and the second portion of the right subclavian artery was embolized using microcoils and thrombin.

Outcomes:

Postoperative intensive care unit management performed to resuscitate patient from multiorgan failure included continuous renal replacement therapy (CRRT). After confirming the demarcation lines, transhumeral amputation of the right arm was performed on admission day 12. The patient recovered from multiorgan failure for more than 3 weeks after the accident; however, the patient survived.

Lessons:

Limb salvage, albeit critical for quality of life, is not possible in some cases where life-saving measures require its sacrifice. In these cases, quick decision-making by the surgeon is paramount for patient survival. As illustrated in this case, endovascular approaches should be considered less invasive measures to save the patient’s life.
A closed-loop negative feedback model for the pancreas: A new paradigm and pathway to a cure
Authors: Dressel Thomas D. , Custer Christine M.
Published: July 2024

Background and aims:

To develop a model that describes how the pancreas functions, how the rate of synthesis of digestive enzymes is regulated, and finally what puts the pancreas to rest between meals.

Methods:

We applied the principals of control theory to previously published canine data to develop a model for how the canine pancreas functions. Using this model, we then describe the steps needed to apply this model to the human pancreas.

Results:

This new closed-loop negative feedback model describes what regulates digestive enzyme synthesis. This model is based on basolateral exocytosis of butyrylcholinesterase (BCHE) into the interstitial space. It is this level of BCHE * BCHE activity that controls the rate of canine pancreas digestive enzyme synthesis, and in the absence of stimulation from the vagus nerve, puts the pancreas to rest between meals.

Conclusions:

Finding secretagogue-specific inhibitory enzymes in the human pancreas that are analogous to BCHE in the canine, and blocking its associated receptors, may lead to a cure for human pancreatitis.