bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular diagnosis of visceral leishmaniasis: a French study comparing a reference PCR method targeting kinetoplast DNA and a commercial kit targeting ribosomal DNA
Authors: Pasquier Grégoire , Andreotti Quentin , Ravel Christophe , Sterkers Yvon 
Published: October 2023

ABSTRACT

Visceral leishmaniasis is a life-threatening disease caused by the
Leishmania donovani
species complex. For direct diagnosis, molecular diagnosis on blood and bone marrow is an increasingly used technique. For
Leishmania
, most PCR assays are laboratory-developed, but marketed PCR assays are now available and should be evaluated independently of manufacturers. The “quanty Leishmaniae, Clonit” kit was compared to a laboratory-developed method widely used in France and considered here as a reference method. Performances were evaluated on serial dilution assays, on 5 external quality controls and on 35 clinical samples. The reference method performed better than the Clonit kit with higher “performance scores”: 20 of 28 (71%) and 4 of 12 (33%) vs 17 of 28 (61%) and 1 of 12 (8%) for the reference method and the Clonit kit, respectively. On clinical samples, six false negative results out of 27 positive samples (22%) were observed with the quanty Leishmaniae, Clonit method. These results are most likely due to the difference in the number of repeats of the PCR targets. The quanty Leishmaniae, Clonit, like most of marketed methods, targets the ribosomal DNA that has a lower number of copies than the kinetoplast DNA targeted by the reference PCR. This study confirms that the choice of target is crucial and should be taken into account in the development of new highly sensitive PCR methods.

IMPORTANCE

PCR revolutionized the direct diagnosis of infectious diseases, especially protozooses, where the infectious load is usually low. Commercial PCR methods are available and offer many advantages, including convenience and batch tracking as part of a quality system. For most parameters, the performance of commercial methods is at least as good as that of finely optimized methods developed in expert laboratories. This comparison work has not been done for the molecular diagnosis of visceral leishmaniasis.
Leishmania
sp. has a unique organelle, the kinetoplast, which corresponds to the mitochondrial DNA. It is organized into a large number of minicircles, which has made it a target for the development of diagnostic PCR. The quanty Leishmaniae, Clonit kit targeting ribosomal DNA was compared to a widely used laboratory-developed method based on kinetoplast DNA. This reference method gave significantly better results, probably due to the difference in the number of repeats of the PCR targets.
A novel double-ribonuclease toxin-antitoxin system linked to the stress response and survival of
Acidovorax citrulli
Authors: Wang Xudong , Kan Yumin , Bai Kaihong , Xu Xiaoli , Chen Xing , Yu Chengxuan , Shi Jia , Jiang Na , Li Jianqiang , Luo Laixin 
Published: October 2023

ABSTRACT

Toxin-antitoxin (TA) systems are widespread among prokaryotes and can play an important role in the maintenance of genetic elements and pathogen virulence. Their roles in bacterial stress response and antimicrobial persistence currently remain highly controversial. The current study investigated a novel TA system (Aave_1720-Aave_1719) from the phytopathogenic bacterium
Acidovorax citrulli
, which had characteristics of both type II and type V TA systems. Heterologous expression in
Escherichia coli
confirmed that
Aave_1720
functions as a toxin gene, while
Aave_1719
acts as antitoxin gene. The Aave_1720 toxin functions as a ribonuclease, and antitoxin Aave_1719 binds directly to Aave_1720 to inhibit its ribonuclease activity, which is typical of type II TA systems. Interestingly, Aave_1719 itself was found to exhibit ribonuclease activity with a preference for targeting
Aave_1720
mRNA, which indicates that it can also neutralize the Aave_1720 toxin in a manner characteristic of type V TA systems. Expression analysis revealed that the
Aave_1719
gene is upregulated in response to sodium hypochlorite stress and that deletion of the
Aave_1720
gene individually or in combination with
Aave_1719
affected biofilm formation, as well as the survival of
A. citrulli
in response to sodium hypochlorite stress. Taken together, these findings expand our understanding of TA systems revealing a novel mechanism of toxin neutralization that combines aspects of both type II and type V TA systems.

IMPORTANCE

Bacterial fruit blotch (BFB), which is caused by the seed-borne bacterium
Acidovorax citrulli
, is a devastating disease affecting cucurbit crops throughout the world. Although seed fermentation and treatment with disinfectants can provide effective management of BFB, they cannot completely guarantee pathogen-free seedstock, which suggests that
A. citrulli
is a highly stress-resistant pathogen. Toxin-antitoxin (TA) systems are common among a diverse range of bacteria and have been reported to play a role in bacterial stress response. However, there is currently much debate about the relationship between TA systems and stress response in bacteria. The current study characterized a novel TA system (Aave_1720-Aave_1719) from
A. citrulli
that affects both biofilm formation and survival in response to sodium hypochlorite stress. The mechanism of neutralization differed from typical TA systems as two separate mechanisms were associated with the antitoxin, which exhibited characteristics of both type II and type V TA systems. The Aave_1720-Aave_1719 system described here also constitutes the first known report of a double-ribonuclease TA system in bacteria, which expands our understanding of the range of regulatory mechanisms utilized by bacterial TA systems, providing new insight into the survival of
A. citrulli
in response to stress.
Supplemental Material: Reconciling complex stratigraphic frameworks reveals temporally and geographically variable depositional patterns of the Campanian Ignimbrite
Authors: Gallo Rose I. , et al.  
Published: October 2023

<p>File S1 includes an elaboration of our methods, a figure portraying our geochemical data in greater detail, and a figure showing some trends in quantitative shard shape parameters. File S2 is a catalog of all the samples used in our study with an image of the exposure. File S3 is a series of Excel documents containing all data sets. </p>
Tracking progress towards equitable maternal and child health in Yunnan: a systematic assessment for the Health Programme for Poverty Alleviation in China during 2015–2020
Authors: Huang Yuan , Xiao Xia , Wan Ying , Ye Qingyun , Yang Zhongting , Xu Lingling , Chen Shuqi , Li Huifang , Wang Fangfang , Chen Yurong , Zhao Dandan , Zhang Qian , Zheng Jiarui , Guo Guangping , Li Yan 
Published: October 2023

ObjectivesTo inform the impacts of health programmes which aimed at preventing women and children from being trapped in or returning to poverty because of illness in Yunnan, the main battlefield against poverty in China.DesignThe longitudinal comparative evaluation design.Data collection and analysisNational and Yunnan policy documents related to maternal and child health programmes for poverty alleviation during 2015–2020 were analysed. The changes in disparities in maternal and child health system inputs, service coverage, and health outcomes between poor and non-poor areas, as well as out-of-pocket payments between poor and non-poor populations were assessed before and after 2017.ResultsIn total 12 policies and 15 programmes related to poverty alleviation for poor women and children in Yunnan were summarised. As a result of health system strengthening in Yunnan, the densities of licensed doctors, nurses, obstetricians, midwives, township health workers and female village doctors had been increased substantially in poor areas, with the annual rates of 14.3%, 22.5%, 21.8%, 23.9%, 14.1% and 7.1% separately. Although disparities existed in some of service coverage between poor and non-poor areas, the health programmes had narrowed the gaps in utilisation of facility birth, caesarean section, prenatal screening and newborn screening across Yunnan (p<0.01). The out-of-pocket payments for inpatient care for serious illnesses among women and children with poverty registration had been considerably decreased to 10.0%. Paralleling the universal coverage, maternal deaths per 100 000 livebirths and child deaths per 1000 livebirths had further declined in both poor and non-poor areas, and the impacts of health programmes on closing the gaps in child survivals across Yunnan were significant (p<0.01).ConclusionsRemarkable progress in equitable maternal and child survival has been achieved in Yunnan. The practices in Yunnan have shown the Chinese model in ending poverty by strengthening health system and implementing universal coverage with firm commitment, determined leadership, detailed blueprint and social participation.
Effect of physical exercise on the functional capacity of patients with liver cirrhosis: systematic review with meta-analysis
Authors: Corrêa Fabiana C.C.R. , Corrêa Gabriela C.C.R. , Silva Elirez B. 
Published: October 2023

In this paper, we verify the effect of physical exercise on the functional capacity of people diagnosed with liver cirrhosis (LC). Inclusion criteria were people with LC, at any stage of the disease, over 18 years of age, of either sex, who performed any type of physical exercise in comparison with any other intervention or no intervention, obtaining functional capacity as the outcome, of the controlled and randomized experimental studies. The search for articles was carried out in 11 databases. The descriptors considered for the search were physical exercise, functional capacity, LC, and their synonyms. Methodological quality and study bias were assessed using the Jadad scale and the risk of bias 2 scale, respectively. Review Manager 5.4 was used for the meta-analysis of the data. Functional capacity was considered a continuous variable. The difference in standardized means was considered as the effect measure. The random effect analysis model was used. The confidence level adopted was 0.05. The level of evidence of the meta-analysis result was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. The 113 participants with LC, who belonged to the physical exercise group, had a standardized mean difference in functional capacity of 0.57 (0.01–1.13); p = 0.05, more than the 107 participants who were in the control situation. The level of evidence from the meta-analysis assessed through the GRADE was considered moderate. Physical exercise caused a significant increase of moderate clinical relevance in the functional capacity of patients diagnosed with LC.
Zeolites identification for wastewater radionuclides removal in the decommissioning of a former Italian nuclear power plant
Authors: Ambrosino Fabrizio , Esposito Alfonso Maria , Mancini Francesco , La Verde Giuseppe , Sabbarese Carlo , Caputo Domenico , Pugliese Mariagabriella 
Published: October 2023

AbstractRadionuclides are widely known to produce serious problem when released and dispersed in the environment because they can contaminate humans through food chains, affecting metabolic process and causing health diseases to the population. A large amount of radionuclides is produced as waste during the process of nuclear facility operation, maintenance, and decommissioning. Wastewater contains many radioactivemetal ions. During the last three decades, after Chernobyl accident and then that of Fukushima, several techniques have been developed for the removal of radionuclides from the environment and from wastewater aiming of inertization. One of the most recent techniques, and in continuous progress, is the radionuclides removal by adsorption using natural and/or synthesized materials having high retention capacity and being resistant to radiation. The most used type of material, cheap and easy-to-find, is zeolite due to its high ion exchange capacity, adsorption efficiency and abundance. This work concerns a preliminary study on zeolites identification for the removal of radionuclides in wastewater samples from the fuel storage of the former nuclear power plant of Latina, Italy. The activity concentration of the radionuclides in the samples was investigated by γ- and α-spectrometry. The wastewater samples contain the radionuclides 137Cs, 60Co and 241Am, and the best solution for their removal was discovered to be the zeolite A. The obtained results can be enlarged to all former Italian nuclear facilities.
MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion
Authors: Ichihara Genki , Katsumata Yoshinori , Sugiura Yuki , Matsuoka Yuta , Maeda Rae , Endo Jin , Anzai Atsushi , Shirakawa Kohsuke , Moriyama Hidenori , Kitakata Hiroki , Hiraide Takahiro , Goto Shinichi , Ko Seien , Iwasawa Yuji , Sugai Kazuhisa , Daigo Kyohei , Goto Shinya , Sato Kazuki , Yamada Ken-ichi , Suematsu Makoto , Ieda Masaki , Sano Motoaki 
Published: October 2023

BACKGROUND:
The membrane components of cardiomyocytes are rich in polyunsaturated fatty acids, which are easily oxidized. Thus, an efficient glutathione-based lipid redox system is essential for maintaining cellular functions. However, the relationship between disruption of the redox system during ischemia-reperfusion (IR), oxidized lipid production, and consequent cell death (ferroptosis) remains unclear. We investigated the mechanisms underlying the disruption of the glutathione-mediated reduction system related to ferroptosis during IR and developed intervention strategies to suppress ferroptosis.

METHODS:
In vivo fluctuations of both intra- and extracellular metabolite levels during IR were explored via microdialysis and tissue metabolome analysis. Oxidized phosphatidylcholines were assessed using liquid chromatography high-resolution mass spectrometry. The areas at risk following IR were assessed using triphenyl-tetrazolium chloride/Evans blue stain.

RESULTS:
Metabolomic analysis combined with microdialysis revealed a significant release of glutathione from the ischemic region into extracellular spaces during ischemia and after reperfusion. The release of glutathione into extracellular spaces and a concomitant decrease in intracellular glutathione concentrations were also observed during anoxia-reperfusion in an in vitro cardiomyocyte model. This extracellular glutathione release was prevented by chemical inhibition or genetic suppression of glutathione transporters, mainly MRP1 (multidrug resistance protein 1). Treatment with MRP1 inhibitor reduced the intracellular reactive oxygen species levels and lipid peroxidation, thereby inhibiting cell death.
Subsequent in vivo evaluation of endogenously oxidized phospholipids following IR demonstrated the involvement of ferroptosis, as levels of multiple oxidized phosphatidylcholines were significantly elevated in the ischemic region 12 hours after reperfusion. Inhibition of the MRP1 transporter also alleviated intracellular glutathione depletion in vivo and significantly reduced the generation of oxidized phosphatidylcholines. Administration of MRP1 inhibitors significantly attenuated infarct size after IR injury.

CONCLUSIONS:
Glutathione was released continuously during IR, primarily in an MRP1-dependent manner, and induced ferroptosis. Suppression of glutathione release attenuated ferroptosis and reduced myocardial infarct size following IR.
Abstract P136: Association Of Undernutrition Severity With Development Of Incident Hypertension In Youth.
Authors: McMillan Kayla , South Andrew 
Published: October 2023

Cardiovascular disease (CVD) is a leading cause of death despite improved treatment, largely due to limitations in primordial prevention. Youth with chronic health conditions have higher risk of CVD and undernutrition, however it is unknown if undernutrition causes hypertension (HTN). Our goal was to investigate if undernutrition in youth is associated with incident HTN.
Interim analysis of electronic health record data from a bioinformatics-driven retrospective cohort study. Inclusion criteria were ages 6 months - 18 years with a first occurrence of undernutrition by ICD-10 code, weight-for-height z-score <-2, or BMI z-score <-2 in outpatient clinic or inpatient hospital encounters between 2015-2022. Exclusion criteria were premature birth, low birth weight, or diagnosis of heart disease, liver disease, or chronic kidney disease at index date. We created a Kaplan Meier curve and log-rank test.
Of 8,878 participants, 2,569 (58%) were males. We found that more severe undernutrition was associated with decreased risk of HTN.
More severe undernutrition was associated with decreased risk of HTN. However, only first instances of blood pressure in HTN range were included. Ongoing steps include refining the undernutrition population, building a Cox regression model, and developing a matched control population to compare the risk of HTN to. Concurrently, we have an animal study to further assess the impact of undernutrition on HTN development. Determining if undernutrition is a causal risk factor for HTN, which often leads to additional serious and life-threatening illnesses, will allow for earlier screening and intervention to prevent clinical diagnoses later in life.
Abstract P153: Protein Kinase A Inhibition Epigenetically Silences
Ren1
Authors: Smith Jason P , Paxton Robert , Sequeira Lopez Maria Luisa S , Gomez Roberto A 
Published: October 2023

Renin-expressing cells are myoendocrine cells crucial for survival which detect changes in blood pressure and release renin to maintain homeostasis. One of the pathways responsible for renin expression includes cAMP as a central factor. cAMP binds to subunits of protein kinase A (PKA), ultimately recruiting both CBP and p300. Binding to the cAMP-responsive element in the renin enhancer region thus amplifies renin transcription. To evaluate transcriptomic and epigenomic changes occurring at the renin locus via the cAMP pathway, we treated As4.1 cells (a tumoral cell line that constitutively expresses renin) with the PKA inhibitor H89 (treated) or DMSO (control).

Using scRNA-seq, we confirm that PKA inhibition leads to significant decreases in
Ren1
abundance (p=3.18e-25), and
Ccl8
,
Cilp
,
Cdkn1a
,
Lox
,
Ly6c1
,
Ccl7
,
Cryab
are all significantly increased. Analysis of bulk ATAC-seq of treated and control As4.1 cells revealed 527 significantly increased regions of accessible chromatin and 1523 significantly decreased. Within the increased accessibility regions, motifs for the transcription factors
Bach1
,
Fos
,
Fosb
,
Trp73
, and
Gli1
are overrepresented. Within the regions with decreased accessibility are enriched motifs for
Zfp161
,
Esr2
,
Zfa
,
Maz
,
Phf21a
,
Hlf
, and
Tcf7
.

We further identified a cluster of differentially accessible regions composed of 172 chromatin regions that shift concurrently in accessibility following PKA inhibition. Within these regions, the KLF (p= 7.5e-11) and AP-1 (p= 1.4e-5) families of transcription factors are overrepresented. Interestingly, open chromatin around the
Ren1
locus is not differentially accessible following H89 treatment.

To better understand the effect of PKA inhibition, we evaluated H3K27Ac and P300 binding via ChIP-seq. H3K27Ac is significantly reduced at the renin locus (p=1.99e-08), and P300 binding is also significantly reduced (p=1.79e-13).
Taken together, the data suggests that cAMP pathway inhibition controls renin expression through a reduction not in accessibility, but via a switch from an active to poised state of epigenetic control and the rise in immediate early genes regulating cellular gene expression.
Inequality, Relative Deprivation and Financial Distress: Evidence from Swedish Register Data
Authors: Roth Paula 
Published: October 2023

Abstract
Several studies have linked rising insolvency rates to increasing inequality and argued that this might be explained by individuals' desire to “Keep up with the Joneses”. Using unique administrative register data on individual insolvencies in Sweden, I test whether the probability to become insolvent is related to one's income distance relative to peers. Identification relies on area fixed effects, an extensive set of background characteristics and varying the definition of the relevant reference group. I find that higher inequality increases the individual's probability to become insolvent and that this effect is mostly driven by men.
Crime and Mismeasured Punishment: Marginal Treatment Effect with Misclassification
Authors: Possebom Vitor 
Published: October 2023

Abstract
I partially identify the marginal treatment effect (MTE) when the treatment is misclassified. I explore two restrictions, allowing for dependence between the instrument and the misclassification decision. If the signs of the propensity scores' derivatives are equal, I identify the MTE sign. If those derivatives are similar, I bound the MTE. To illustrate, I analyze the impact of alternative sentences (fines and community service v. no punishment) on recidivism in Brazil, where Appeals processes generate misclassification. The estimated misclassification bias may be as large as 10% of the largest possible MTE, and the bounds contain the correctly estimated MTE.
Interpreting and Responding to Pandemics in Philosophical Traditions and Films of India
Authors: Jain Pankaj , Sharma Shikha 
Published: October 2023

Abstract
India and the rest of the world continue to witness waves of COVID-19. In this article, I present myriad examples of ethical issues in the context of pandemics that hit India in the last few centuries. I also analyze the relevance of Indian texts and films in the context of various pandemics. The article quotes several primary and secondary texts to explore interpreting and responding to different pandemics and broader health issues. As the world reels under the COVID mayhem, it is time to take inspiration from various other medical professionals at the forefront of fighting this pandemic. We urgently need their compassion and not any recurrence of colonialism or racism that rears its head even today. Our collective responses to COVID-19 can prompt us to collectively mitigate and adapt to various climate changes across the planet by combining the ideas and imaginations from the “East” and “West.”
Moral Dilemmas of Surrogate Motherhood
Authors: Kavarić Milena , Djoković Rajka 
Published: October 2023

Abstract
In the sphere of new modalities of creating offspring, one of the most controversial issues is related to surrogacy because it opens the space to unforeseeable ethical, legal, sociological and psychological world of dilemmas. Surrogacy is the process whereby a woman carries and gives birth to a baby for a couple who cannot conceive naturally and it has become increasingly popular worldwide. This reproductive method relativized the biological fact of birth and denied the central moment in identifying motherhood, expressed in the ancient Roman proverb that the mother of a child is the woman who gave birth to it. Surrogate motherhood changes the notion of motherhood as it separates the natural functions of a woman as a mother, or it separates the genetic from the gestational motherhood. In such a situation, the biological riddle is: Who is the real mother of the child: the one who gives the genetic material or the one who gives birth to it? The answer to this question opens many moral and ethical dilemmas in complex relationships: the surrogate mother, the couple-clients and the child. As the successful medical practice of giving birth to another undeniably exists in different countries of the world, the further fate of this method of reproduction will significantly depend on ethical justifications.