bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes
Authors: Sun Xiaoying , Liu Lili , Wan Ting , Huang Qidan , Chen Jieping , Luo Rongzhen , Liu Jihong 
Published: November 2022

Abstract
Background
We investigate the correlation between programmed cell death-ligand 1 (PD-L1) and tumor-associated immune cell (TAIC) density in small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) and their correlation with clinicopathologic features.

Methods
PD-L1 and mismatch repair protein (MMR) expression in cancer cells and the density of TAIC were evaluated by immunohistochemistry in 89 SCNEC patients. The combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) of PD-L1 were measured, along with their correlation with clinicopathologic features in SCNEC patients using statistical analyses.

Results
CPS of PD-L1 ≥ 1 was seen in 68.5% of patients, positive TPS and ICS of PD-L1 were detected in 59.6% and 33.7% of patients, respectively. PD-L1CPS was higher in tumor-infiltrating immune cells (r = 0.387, p = 0.001) and positively correlated with programmed cell death-1 and forkhead box P3 + regulatory T cell (FOXP3 + Treg) infiltration (r = 0.443, p < 0.001; r = 0.532, p < 0.001). There was no statistical correlation between PD-L1 and MMR status. PD-L1CPS and PD-L1ICS positivity were independent prognostic factors, correlating with a favorable survival (HR (95%CI) = 0.363(0.139–0.950), p = 0.039 and HR (95% CI) = 0.199(0.050–0.802), p = 0.023, respectively). PD-L1ICS positivity was an independent indicator of recurrence in SCNEC patients and associated with better disease-free survival (HR (95% CI) = 0.124(0.036–0425), p = 0.001). TAIC and MMR levels had no statistical impact on survival results.

Conclusions
PD-L1 positivity was seen in over half of SCNEC tumors. It may work synergistically with FOXP3 + Treg and other infiltrating immune cells to support an adaptive immune response. PD-L1 positivity may be a favorable prognostic factor in SCNEC.
A malaria knowledge, attitudes and practice survey in a rural community in Guinea
Authors: Ravi Nirmal , Holsted Erin , Kadiebwe Barclay , Salthouse Abigail , Sattar Amer 
Published: November 2022

AbstractBackgroundMalaria is the top public health problem in the Republic of Guinea, with more than 4 million cases and 10,000 deaths in 2021 among a population of approximately 13 million. It is also the second highest cause of death there. The purpose of this quantitative survey in a rural area of Guinea was to understand knowledge, attitudes, and practices (KAP) about malaria and to assess water and sanitation practices among community members.MethodsIn 2016, the authors conducted a cross-sectional household survey in Timbi-Touni, Guinea using community workers. The survey included respondent demographic characteristics, malaria knowledge, child health, water and sanitation, and health services access. Malaria knowledge and sleeping under bed nets were the primary outcome variables and multiple logistic regression was used to determine odds ratios.ResultsMajority of the respondents were women (89.41%) and had never been to school (71.18%). Slightly more than half the children were reported to have ever had malaria and 45% reported to have ever had diarrhoea. There was no statistically significant association between gender or level of education and malaria knowledge. Eighty six percent of respondents had received a free bed net during national campaigns and 61% slept under a bed net the night before the survey. Knowing mosquitoes to be the cause of malaria and receiving free bed net were significantly associated with sleeping under a bed net. There was no statistically significant association between drinking water source and malaria or diarrhoea.ConclusionsBoth malaria and diarrhoea were considered to be serious illnesses for adults and children by nearly all respondents. Receiving free bed nets and having correct knowledge about malaria were the greatest predictors of sleeping under a bed net. Insights from this detailed KAP survey—such as focusing on radio to transmit malaria prevention information and reinforcing free malaria treatments—can guide policy makers and practitioners who design and implement malaria control and prevention measures in Guinea.
How long is the last mile? Evaluating successful malaria elimination trajectories
Authors: Cohen Justin M. , Kandula Deepika , Smith David L. , Le Menach Arnaud 
Published: November 2022

AbstractBackgroundMany national malaria programmes have set goals of eliminating malaria, but realistic timelines for achieving this goal remain unclear. In this investigation, historical data are collated on countries that successfully eliminated malaria to assess how long elimination has taken in the past, and thus to inform feasible timelines for achieving it in the future.MethodsAnnual malaria case series were sought for 56 successful elimination programmes through a non-systematic review. Up to 40 years of annual case counts were compiled leading up to the first year in which zero locally acquired or indigenous cases were reported. To separate the period over which effective elimination efforts occurred from prior background trends, annual case totals were log transformed, and their slopes evaluated for a breakpoint in linear trend using thesegmentedpackage in R. The number of years from the breakpoint to the first year with zero cases and the decline rate over that period were then calculated. Wilcox-Mann-Whitney tests were used to evaluate whether a set of territory characteristics were associated with the timelines and decline rates.ResultsCase series declining to the first year with zero cases were compiled for 45/56 of the candidate elimination programmes, and statistically significant breakpoints were identified for 42. The median timeline from the breakpoint to the first year with zero local cases was 12 years, over which cases declined at a median rate of 54% per year. Prior to the breakpoint, the median trend was slightly decreasing with median annual decline of < 3%. Timelines to elimination were fastest among territories that lacked land boundaries, had centroids in the Tropics, received low numbers of imported cases, and had elimination certified by the World Health Organization.ConclusionThe historical case series assembled here may help countries with aspirations of malaria elimination to set feasible milestones towards this goal. Setting goals for malaria elimination on short timescales may be most appropriate in isolated, low importation settings, such as islands, while other regions aiming to eliminate malaria must consider how to sustainably fund and maintain vital case management and vector control services until zero cases are reached.
Comparative effect of artemether-lumefantrine and artesunate-amodiaquine on gametocyte clearance in children with uncomplicated Plasmodium falciparum malaria in Madagascar
Authors: Rakotoarisoa Malalanandrianina A. , Fenomanana Jocia , Dodoson Bronislaw Tchesterico , Andrianaranjaka Voahangy Hanitriniaina I. , Ratsimbasoa Arsène 
Published: November 2022

Abstract
Background
Gametocytes are the sexual stages ensuring continuity of the development cycle of the parasite, as well as its transmission to humans. The efficacy of artemisinin-based anti-malarials against asexual stages of Plasmodium has been reported in Madagascar, but their effects on gametocytes are not well documented. The present study aims to determine the emergence of gametocyte and gametocyte clearance after artesunate-amodiaquine (ASAQ) or artemether-lumefantrine (AL) treatment in children with uncomplicated Plasmodium falciparum malaria in 5 regions of Madagascar.

Methods
558 children with uncomplicated P. falciparum malaria, aged between 1 and 15 years, were assigned randomly to AL or ASAQ treatment. They come from 5 regions of Madagascar with different epidemiological facies related to malaria: Ankilivalo, Benenitra, Ampanihy, Ankazomborona and Matanga. Gametocytes were identified by microscopy, from t blood smears at day 1, day 2, day 3, day 7, day 14, day 21 and day 28 after treatment.

Results
At baseline, 9.7% (54/558) children [95% CI: 7.4–12.5%] had detectable gametocyte by microscopy. Among the 54 enrolled children, gametocytes emergence rate was high during the first days of treatment in both treatment arms (AL and ASAQ), especially on day 1. Gametocytes were undetectable from day 14 for AL arm while for ASAQ arm, gametocyte carriage was gradually decreased but persisted until day 21.

Conclusion
This study demonstrates that AL has a more rapid effect on gametocyte clearance compared to ASAQ in children with uncomplicated Plasmodium falciparum malaria.
Neuroinflammation regulates the balance between hippocampal neuron death and neurogenesis in an ex vivo model of thiamine deficiency
Authors: Cassiano Larissa M. G. , Oliveira Marina S. , Pioline Jeanne , Salim Anna C. M. , Coimbra Roney S. 
Published: November 2022

Abstract
Background
Thiamine (vitamin B1) is a cofactor for enzymes of central energy metabolism and its deficiency (TD) impairs oxidative phosphorylation, increases oxidative stress, and activates inflammatory processes that can lead to neurodegeneration. Wernicke–Korsakoff syndrome (WKS) is a consequence of chronic TD, which leads to extensive neuronal death, and is associated with neuropathological disorders, including cognitive deficits and amnesia. The hippocampus is one of the brain areas most affected by WKS. B1 replacement may not be enough to prevent the irreversible cognitive deficit associated with WKS.

Materials and methods
An organotypic hippocampal slice culture (OHC) model was developed to investigate, using immunofluorescence and confocal microscopy and transcriptome analysis, the molecular mechanisms underlying the neurodegeneration associated with TD. The effect of anti-inflammatory pharmacological intervention with resveratrol (RSV) was also assessed in B1-deprived OHCs.

Results
In OHCs cultured without B1, neuronal density decayed after 5 days and, on the 7th day, the epigenetic markings H3K4me3 and H3K9me3 were altered in mature neurons likely favoring gene transcription. Between the 7th and the 14th day, a pulse of neurogenesis was observed followed by a further massive neuron loss. Transcriptome analysis at day nine disclosed 89 differentially expressed genes in response to B1 deprivation. Genes involved in tryptophan metabolism and lysine degradation KEGG pathways, and those with Gene Ontology (GO) annotations related to the organization of the extracellular matrix, cell adhesion, and positive regulation of synaptic transmission were upregulated. Several genes of the TNF and FoxO signaling pathways and with GO terms related to inflammation were inhibited in response to B1 deprivation. Nsd1, whose product methylates histone H3 lysine 36, was upregulated and the epigenetic marking H3K36me3, associated with negative regulation of neurogenesis, was increased in neurons. Treating B1-deprived OHCs with RSV promoted an earlier neurogenesis pulse.

Conclusion
Neuroregeneration occurs in B1-deficient hippocampal tissue during a time window. This phenomenon depends on reducing neuroinflammation and, likely, on metabolic changes, allowing acetyl-CoA synthesis from amino acids to ensure energy supply via oxidative phosphorylation. Thus, neuroinflammation is implicated as a major regulator of hippocampal neurogenesis in TD opening a new search space for treating WKS.
Androgen receptor function and targeted therapeutics across breast cancer subtypes
Authors: Kolyvas Emily A. , Caldas Carlos , Kelly Kathleen , Ahmad Saif S. 
Published: November 2022

AbstractDespite significant progress in breast cancer (BC) therapy, it is globally the most commonly diagnosed cancer and leads to the death of over 650,000 women annually. Androgen receptor (AR) is emerging as a potential new therapeutic target in BC. While the role of AR is well established in prostate cancer (PCa), its function in BC remains incompletely understood. Emerging data show that AR’s role in BC is dependent on several factors including, but not limited to, disease subtype, tumour microenvironment, and levels of circulating oestrogens and androgens. While targeting AR in PCa is becoming increasingly effective, these advances have yet to make any significant impact on the care of BC patients. However, this approach is increasingly being evaluated in BC and it is clear that improvements in our understanding of AR’s role in BC will increase the likelihood of success for AR-targeted therapies. This review summarizes our current understanding of the function of AR across BC subtypes. We highlight limitations in our current knowledge and demonstrate the importance of categorizing BC subtypes effectively, in relation to determining AR activity. Further, we describe the current state of the art regarding AR-targeted approaches for BC as monotherapy or in combination with radiotherapy.
Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker
Authors: Johansson Patricia , Laguna Teresa , Ossowski Julio , Pancaldi Vera , Brauser Martina , Dührsen Ulrich , Keuneke Lara , Queiros Ana , Richter Julia , Martín-Subero José I. , Siebert Reiner , Schlegelberger Brigitte , Küppers Ralf , Dürig Jan , Murga Penas Eva M. , Carillo-de Santa Pau Enrique , Bergmann Anke K. 
Published: November 2022

Abstract
Background
The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor αβ-positive CD8+ memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples.

Results
We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation.

Conclusions
DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed.
An educational video on long-acting reversible contraception as a counseling tool for postpartum adolescents
Authors: Santibenchakul Somsook , Thanativakul Kittithorn , Jaisamrarn Unnop 
Published: November 2022

Abstract
Objective
To assess the effects of using an animated local language educational video to counsel postpartum adolescents on the benefits and use of long-acting reversible contraception (LARC).

Materials and methods
A two-stage, single group, experimental study was conducted. A total of 124 female adolescents aged < 20 years who had given birth within the last six weeks participated in the study. An educational video and a questionnaire were developed and validated. Participants were asked to fill out a questionnaire on basic demographic data, contraception preferences, and 10 true/false statements to test general contraceptive knowledge, after which they were shown an educational video in a private room. Following this, participants completed the second part of the questionnaire that assessed their knowledge using the same true/false statements and contraception preferences administered earlier.

Results
The mean age (standard deviation) of participants was 18.1 (1.5) years. Participants’ mean age (SD) at the time of their first sexual intercourse was 16.2 (1.6) years. Among the 124 participants, 31 (25%) indicated that they would use LARC before viewing the educational video. After viewing the educational video, this number increased to 48 (38.7%). The participants’ knowledge score was independently associated with their preference to select LARC (adjusted odds ratio 1.46, 95% confidence interval 1.09- 1.97).

Conclusion
This study demonstrated that counseling tools such as animated local language educational video might effectively improve contraceptive knowledge and the preference for LARC in postpartum adolescents. An educational video regarding LARC could be used as a counseling tool for postpartum adolescents.
Rediscovering the Monk-Sculptor Ch’ŏnsin: The Missing Link between the Ŭngwŏn-In'gyun and Saengnan Schools of the Honam Area in the Late Chosŏn Period
Authors: Song Unsok 
Published: November 2022

Abstract
Of the monk-sculptor groups active in the Honam area in the southwest part of the Korean Peninsula during the late Chosŏn period, the Saengnan School was the largest, both in terms of the number of artists in the group and of the works they left behind. Studies of the group have largely focused on the sculpting activities of the Buddhist monk Saengnan (fl. late seventeenth to the early eighteenth century; 1663–1709) and his followers, while little is known about the origins of the school due to a lack of records about his formative years as an assistant. The recent discovery of four Buddhist parwŏn prayer texts has revealed that Saengnan spent the early years of his career as a sculptor assisting the monk-sculptors In'gyun and Ch’ŏnsin, who were key members of the Ŭngwŏn-In'gyun School that played a central role in the production of Buddhist sculptures in the early to late seventeenth century in the region. This study shows that the Saengnan School, the most productive group of monk-sculptors from the late seventeenth to the early eighteenth century in the Honam region, was a successor to the Ŭngwŏn-In'gyun School, through a comparative examination of these highly informative prayers and relevant Buddhist sculptures. My examination also reveals that the two schools were linked by Ch’ŏnsin, who studied sculpture under In'gyun, and in turn, taught Saengnan.
“All That He Seen Burnt a Hole in His Brain”
Authors: Waller Ryan 
Published: November 2022

Abstract
The title of this playlist comes from the chorus of Armand Hammer's “Rehearse with Ornette,” wherein billy woods repeats, “All that he seen burnt a hole in his brain/only came back to tell ’em bout them fucking flames.” This idea of a mind swallowed in shock, bellowing out its truth, is a deeply disturbing image and a generative point of entry into the psychic terror of black being in the afterlife of slavery. Thus the tracks in this playlist explore the impressionistic and visceral qualities of the Afro-Gothic mindset through songs that lyrically and sonically express themes of faith and grief as part of the soundtrack to everyday black life.
Position of meristems and the angles of the cell division plane regulate the uniqueness of lateral organ shape
Authors: Kinoshita Ayaka , Naito Makiko , Wang Zining , Inoue Yasuhiro , Mochizuki Atsushi , Tsukaya Hirokazu 
Published: November 2022

ABSTRACT
Leaf meristem is a cell proliferative zone present in the lateral organ primordia. In this study, we examined how cell proliferative zones in primordia of planar floral organs and polar auxin transport inhibitor (PATI)-treated leaf organs differ from those of non-treated foliage leaves of Arabidopsis thaliana, with a focus on the accumulation pattern of ANGUSTIFOLIA3 (AN3) protein, a key element for leaf meristem positioning. We found that PATI-induced leaf shape changes were correlated with cell division angle but not with meristem positioning/size or AN3 localisation. In contrast, different shapes between sepals and petals compared with foliage leaves were associated with both altered meristem position, due to altered AN3 expression patterns, and different distributions of cell division angles. A numerical simulation showed that meristem position majorly affected the final shape but biased cell division angles had a minor effect. Taken together, these results suggest that the unique shapes of different lateral organs depend on the position of the meristem in the case of floral organs and cell division angles in the case of leaf organs with different auxin flow.
Maternal heterozygosity of Slc6a19 causes metabolic perturbation and congenital NAD deficiency disorder in mice
Authors: Cuny Hartmut , Bozon Kayleigh , Kirk Rosemary B. , Sheng Delicia Z. , Bröer Stefan , Dunwoodie Sally L. 
Published: November 2022

ABSTRACT
Nicotinamide adenine dinucleotide (NAD) is a key metabolite synthesised from vitamin B3 or tryptophan. Disruption of genes encoding NAD synthesis enzymes reduces NAD levels and causes congenital NAD deficiency disorder (CNDD), characterised by multiple congenital malformations. SLC6A19 (encoding B0AT1, a neutral amino acid transporter), represents the main transporter for free tryptophan in the intestine and kidney. Here, we tested whether Slc6a19 heterozygosity in mice limits the tryptophan available for NAD synthesis during pregnancy and causes adverse pregnancy outcomes. Pregnant Slc6a19+/− mice were fed diets depleted of vitamin B3, so that tryptophan was the source of NAD during gestation. This perturbed the NAD metabolome in pregnant Slc6a19+/− females, resulting in reduced NAD levels and increased rates of embryo loss. Surviving embryos were small and exhibited specific combinations of CNDD-associated malformations. Our results show that genes not directly involved in NAD synthesis can affect NAD metabolism and cause CNDD. They also suggest that human female carriers of a SLC6A19 loss-of-function allele might be susceptible to adverse pregnancy outcomes unless sufficient NAD precursor amounts are available during gestation.
This article has an associated First Person interview with the first author of the paper.
An RNA granule for translation quality control in Saccharomyces cerevisiae
Authors: Dhaliwal James S. , Panozzo Cristina , Benard Lionel , Zerges William 
Published: November 2022

ABSTRACT
Cytoplasmic RNA granules compartmentalize phases of the translation cycle in eukaryotes. We previously reported the localization of oxidized RNA to cytoplasmic foci called oxidized RNA bodies (ORBs) in human cells. We show here that ORBs are RNA granules in Saccharomyces cerevisiae. Several lines of evidence support a role for ORBs in the compartmentalization of no-go decay and ribosome quality control, the translation quality control pathways that recognize and clear aberrant mRNAs, including those with oxidized bases. Translation is required by these pathways and ORBs. Translation quality control factors localize to ORBs. A substrate of translation quality control, a stalled mRNA–ribosome–nascent-chain complex, localizes to ORBs. Translation quality control mutants have altered ORB numbers, sizes or both. In addition, we identify 68 ORB proteins by immunofluorescence staining directed by proteomics, which further support their role in translation quality control and reveal candidate new factors for these pathways.