bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of serum reproductive hormones and ovarian genes in pubertal female goats
Authors: Zhu Yanyun , Ye Jing , Qin Ping , Yan Xu , Gong Xinbao , Li Xiaoqian , Liu Ya , Li Yunsheng , Yu Tong , Zhang Yunhai , Ling Yinghui , Wang Juhua , Cao Hongguo , Fang Fugui 
Published: April 2023

Abstract
Background
Age at puberty is an important factor affecting goat fertility, with endocrine and genetic factors playing a crucial role in the onset of puberty. To better understand the relationship between endocrine and genetic factors and mechanisms underlying puberty onset in goats, reproductive hormone levels were analyzed by ELISA and ultraperformance liquid chromatography–multiple reaction monitoring–multistage/mass spectrometry and RNA sequencing was performed to analyze ovarian genes.

Results
Serum follicle stimulating hormone, luteinizing hormone, estradiol, 11-deoxycortisol, 11-deoxycorticosterone, corticosterone, cortisone, and cortisol levels were found to be higher but progesterone were lower in pubertal goats as compared to those in prepubertal goats (P < 0.05). A total of 18,139 genes were identified in cDNA libraries, and 75 differentially expressed genes (DEGs) were identified (|log2 fold change|≥ 1, P ≤ 0.05), of which 32 were significantly up- and 43 were down-regulated in pubertal goats. Gene ontology enrichment analyses indicated that DEGs were mainly involved in “metabolic process,” “signaling,” “reproduction,” and “growth.” Further, DEGs were significantly enriched in 91 Kyoto Encyclopedia of Genes and Genomes pathways, including estrogen signaling pathway, steroid hormone biosynthesis, and cAMP signaling pathway. Bioinformatics analysis showed that PRLR and THBS1 were highly expressed in pubertal ovaries, and ZP3, ZP4, and ASTL showed low expression, suggesting their involvement in follicular development and lutealization.

Conclusions
To summarize, serum hormone changes and ovarian DEGs expression were investigated in our study. Further studies are warranted to comprehensively explore the functions of DEGs in goat puberty.
Mechanisms of ovarian aging in women: a review
Authors: Wang Xiangfei , Wang Lingjuan , Xiang Wenpei 
Published: April 2023

AbstractOvarian aging is a natural and physiological aging process characterized by loss of quantity and quality of oocyte or follicular pool. As it is generally accepted that women are born with a finite follicle pool that will go through constant decline without renewing, which, together with decreased oocyte quality, makes a severe situation for women who is of advanced age but desperate for a healthy baby. The aim of our review was to investigate mechanisms leading to ovarian aging by discussing both extra- and intra- ovarian factors and to identify genetic characteristics of ovarian aging. The mechanisms were identified as both extra-ovarian alternation of hypothalamic–pituitary-ovarian axis and intra-ovarian alternation of ovary itself, including telomere, mitochondria, oxidative stress, DNA damage, protein homeostasis, aneuploidy, apoptosis and autophagy. Moreover, here we reviewed related Genome-wide association studies (GWAS studies) from 2009 to 2021 and next generation sequencing (NGS) studies of primary ovarian insufficiency (POI) in order to describe genetic characteristics of ovarian aging. It is reasonable to wish more reliable anti-aging interventions for ovarian aging as the exploration of mechanisms and genetics being progressing.
Diagnostic accuracy of clinical examination to identify life- and limb-threatening injuries in trauma patients
Authors: Wohlgemut Jared M. , Marsden Max E. R. , Stoner Rebecca S. , Pisirir Erhan , Kyrimi Evangelia , Grier Gareth , Christian Michael , Hurst Thomas , Marsh William , Tai Nigel R. M. , Perkins Zane B. 
Published: April 2023

Abstract
Background
Timely and accurate identification of life- and limb-threatening injuries (LLTIs) is a fundamental objective of trauma care that directly informs triage and treatment decisions. However, the diagnostic accuracy of clinical examination to detect LLTIs is largely unknown, due to the risk of contamination from in-hospital diagnostics in existing studies. Our aim was to assess the diagnostic accuracy of initial clinical examination for detecting life- and limb-threatening injuries (LLTIs). Secondary aims were to identify factors associated with missed injury and overdiagnosis, and determine the impact of clinician uncertainty on diagnostic accuracy.

Methods
Retrospective diagnostic accuracy study of consecutive adult (≥ 16 years) patients examined at the scene of injury by experienced trauma clinicians, and admitted to a Major Trauma Center between 01/01/2019 and 31/12/2020. Diagnoses of LLTIs made on contemporaneous clinical records were compared to hospital coded diagnoses. Diagnostic performance measures were calculated overall, and based on clinician uncertainty. Multivariate logistic regression analyses identified factors affecting missed injury and overdiagnosis.

Results
Among 947 trauma patients, 821 were male (86.7%), median age was 31 years (range 16–89), 569 suffered blunt mechanisms (60.1%), and 522 (55.1%) sustained LLTIs. Overall, clinical examination had a moderate ability to detect LLTIs, which varied by body region: head (sensitivity 69.7%, positive predictive value (PPV) 59.1%), chest (sensitivity 58.7%, PPV 53.3%), abdomen (sensitivity 51.9%, PPV 30.7%), pelvis (sensitivity 23.5%, PPV 50.0%), and long bone fracture (sensitivity 69.9%, PPV 74.3%). Clinical examination poorly detected life-threatening thoracic (sensitivity 48.1%, PPV 13.0%) and abdominal (sensitivity 43.6%, PPV 20.0%) bleeding. Missed injury was more common in patients with polytrauma (OR 1.83, 95% CI 1.62–2.07) or shock (systolic blood pressure OR 0.993, 95% CI 0.988–0.998). Overdiagnosis was more common in shock (OR 0.991, 95% CI 0.986–0.995) or when clinicians were uncertain (OR 6.42, 95% CI 4.63–8.99). Uncertainty improved sensitivity but reduced PPV, impeding diagnostic precision.

Conclusions
Clinical examination performed by experienced trauma clinicians has only a moderate ability to detect LLTIs. Clinicians must appreciate the limitations of clinical examination, and the impact of uncertainty, when making clinical decisions in trauma. This study provides impetus for diagnostic adjuncts and decision support systems in trauma.
Clinical evaluation of molecular surrogate subtypes in patients with ipsilateral multifocal primary breast cancer
Authors: Janeva Slavica , Krabbe Ellen , Parris Toshima Z. , Nasic Salmir , Sundquist Marie , Karlsson Per , Audisio Riccardo A. , Olofsson Bagge Roger , Kovács Anikó 
Published: April 2023

AbstractBackgroundWhen ipsilateral multifocal primary breast cancer (IMBC) is detected, standard routine is to evaluate the largest tumor with immunohistochemistry (IHC). As all foci are not routinely characterized, many patients may not receive optimal adjuvant treatment. Here, we assess the clinical relevance of examining at least two foci present in patients with IMBC.MethodsPatients diagnosed and treated for IMBC at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2012 and 2017 were screened. In total, 180 patients with ≥ 2 invasive foci (183 specimens) were assessed with IHC and included in this study. Expression of the estrogen (ER) and progesterone (PR) receptors, Ki67, HER2, and tumor grade were used to determine the molecular surrogate subtypes and discordance among the foci was recorded. An additional multidisciplinary team board was then held to re-assess whether treatment recommendations changed due to discordances in molecular surrogate subtype between the different foci.ResultsDiscordance in ER, PR, HER2, and Ki67 was found in 2.7%, 19.1%, 7.7%, and 16.9% of invasive foci, respectively. Discordance in the molecular surrogate subtypes was found in 48 of 180 (26.7%) patients, which resulted in therapy changes for 11 patients (6.1%). These patients received additional endocrine therapy (n = 2), chemotherapy (n = 3), and combined chemotherapy and trastuzumab (n = 6).ConclusionTaken together, when assessing at least two tumor foci with IHC, regardless of shared morphology or tumor grade between the different foci, 6.1% of patients with IMBC were recommended additional adjuvant treatment. A pathologic assessment using IHC of all foci is therefore recommended to assist in individualized treatment decision making.
Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects
Authors: Li Qun , Zhao Lin , Zeng Yang , Kuang Yanping , Guan Yichun , Chen Biaobang , Xu Shiru , Tang Bin , Wu Ling , Mao Xiaoyan , Sun Xiaoxi , Shi Juanzi , Xu Peng , Diao Feiyang , Xue Songguo , Bao Shihua , Meng Qingxia , Yuan Ping , Wang Wenjun , Ma Ning , Song Di , Xu Bei , Dong Jie , Mu Jian , Zhang Zhihua , Fan Huizhen , Gu Hao , Li Qiaoli , He Lin , Jin Li , Wang Lei , Sang Qing 
Published: April 2023

Abstract
Background
Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated.

Results
To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A.

Conclusions
Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.
Identification of cell barcodes from long-read single-cell RNA-seq with BLAZE
Authors: You Yupei , Prawer Yair D. J. , De Paoli-Iseppi Ricardo , Hunt Cameron P. J. , Parish Clare L. , Shim Heejung , Clark Michael B. 
Published: April 2023

AbstractLong-read single-cell RNA sequencing (scRNA-seq) enables the quantification of RNA isoforms in individual cells. However, long-read scRNA-seq using the Oxford Nanopore platform has largely relied upon matched short-read data to identify cell barcodes. We introduce BLAZE, which accurately and efficiently identifies 10x cell barcodes using only nanopore long-read scRNA-seq data. BLAZE outperforms the existing tools and provides an accurate representation of the cells present in long-read scRNA-seq when compared to matched short reads. BLAZE simplifies long-read scRNA-seq while improving the results, is compatible with downstream tools accepting a cell barcode file, and is available at https://github.com/shimlab/BLAZE.
The HAVEN study—hydroxychloroquine in ANCA vasculitis evaluation—a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan
Authors: Learoyd Annastazia E. , Arnold Lauren , Reid Fiona , Beckley-Hoelscher Nicholas , Casian Alina , Sangle Shirish , Morton Neil , Nel Louise , Cape Angela , John Susan , Kim Sangmi , Shivapatham Dharshene , Luqmani Raashid , Jayne David , Galloway James , Douiri Abdel , D’Cruz David ,   on behalf of the HAVEN study group
Published: April 2023

Abstract
Background
Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus.

Methods
Double-blind, placebo-controlled multicentre trial recruiting 76 patients across 20 sites. Participants will be randomised 1:1 to hydroxychloroquine or placebo in addition to standard of care immunosuppressive therapies over the course of 52 weeks. A phase II selection design will be used to determine hdroxychloroquine’s efficacy, using prednisolone dosage and Birmingham Vasculitis Activity Score as a measure of disease activity. Secondary outcomes will explore other elements of AAV progression, including disease flares and time to remission.

Discussion
This trial aims to explore Hydroxychloroquine as a treatment for patients with AAV. If effective, the need for immunosuppressive treatments such as prednisolone could be reduced. Hydroxychloroquine is safer, cheaper and has fewer adverse effects than conventional immunosuppressive treatments. This could improve patient outcomes while saving money for the NHS.

Trial registration
ISRCTN: ISRCTN79334891. Registered 07 June 2021.
EudraCT: 2018-001268-40. Registered 13 September 2019.
Clinicaltrials.gov: NCT04316494. Registered 20 March 2020.
Mitochondrial metabolism of the facultative parasite Chilodonella uncinata (Alveolata, Ciliophora)
Authors: Bu Xia-lian , Zhao Wei-shan , Li Wen-xiang , Zou Hong , Wu Shan-gong , Li Ming , Wang Gui-tang 
Published: April 2023

Abstract
Background
Chilodonella uncinata is an aerobic ciliate capable of switching between being free-living and parasitic on fish fins and gills, causing tissue damage and host mortality. It is widely used as a model organism for genetic studies, but its mitochondrial metabolism has never been studied. Therefore, we aimed to describe the morphological features and metabolic characteristics of its mitochondria.

Methods
Fluorescence staining and transmission electron microscopy (TEM) were used to observe the morphology of mitochondria. Single-cell transcriptome data of C. uncinata were annotated by the Clusters of Orthologous Genes (COG) database. Meanwhile, the metabolic pathways were constructed based on the transcriptomes. The phylogenetic analysis was also made based on the sequenced cytochrome c oxidase subunit 1 (COX1) gene.

Results
Mitochondria were stained red using Mito-tracker Red staining and were stained slightly blue by DAPI dye. The cristae and double membrane structures of the mitochondria were observed by TEM. Besides, many lipid droplets were evenly distributed around the macronucleus. A total of 2594 unigenes were assigned to 23 functional classifications of COG. Mitochondrial metabolic pathways were depicted. The mitochondria contained enzymes for the complete tricarboxylic acid (TCA) cycle, fatty acid metabolism, amino acid metabolism, and cytochrome-based electron transport chain (ETC), but only partial enzymes involved in the iron-sulfur clusters (ISCs).

Conclusions
Our results showed that C. uncinata possess typical mitochondria. Stored lipid droplets inside mitochondria may be the energy storage of C. uncinata that helps its transmission from a free-living to a parasitic lifestyle. These findings also have improved our knowledge of the mitochondrial metabolism of C. uncinata and increased the volume of molecular data for future studies of this facultative parasite.

Graphical Abstract
Particle bombardment-assisted peptide-mediated gene transfer for highly efficient transient assay
Authors: Kimura Mitsuhiro , Endo Akira , Nagira Yozo , Yoshizumi Takeshi 
Published: April 2023

Abstract
Objective
A centrifugation-assisted peptide-mediated gene transfer (CAPT) method was recently developed as an efficient system for gene delivery into plant cells. However, the gene transfer efficiency of CAPT into plant cells was not entirely satisfactory for detecting transient expression of a transgene driven into mitochondria. Here, we report a new gene delivery system using a method called particle bombardment-assisted peptide-mediated gene transfer (PBPT).

Results
We investigated various parameters of the PBPT method to increase transient gene expression efficiency in Brassica campestris. The optimal conditions for PBPT were a single bombardment with gold particles coated with a DNA‒peptide complex (6 µg of DNA and 2 µg of peptide) at an acceleration pressure of 5 kg/cm2 and a target distance of 12.5 cm. Moreover, bombardment under the optimal conditions successfully transferred the transgene into the cells of other plant species, namely B. juncea and tomato. Thus, we developed a PBPT method for highly efficient delivery of a DNA‒peptide complex into plant mitochondria.
Fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome: a case report
Authors: Hemachudha Pasin , Rattanawong Wanakorn , Pongpitakmetha Thanakit , Phuenpathom Warongporn 
Published: April 2023

Abstract
Background
Fluorouracil-induced leukoencephalopathy is a rare complication and has been reported to present as confusion, oculomotor abnormality, ataxia, and parkinsonism; however, there is no previous report of a presentation mimicking neuroleptic malignant syndrome. Acute cerebellar syndrome may occur, which can be explained by the extremely high accumulation of the drug in the cerebellum. However, presentation mimicking neuroleptic malignant syndrome similar to our case has never been reported.

Case presentation
Here, we describe a 68-year-old Thai male presenting with advanced-stage cecal adenocarcinoma, as well as symptoms and signs indicative of neuroleptic malignant syndrome. He received two doses of intravenous metoclopramide 10 mg 6 hours before his symptoms occurred. Magnetic resonance imaging scan revealed signal hyperintensity within the bilateral white matter. Further evaluation showed that his thiamine level was extremely low. Thus, he was diagnosed with fluorouracil-induced leukoencephalopathy mimicking neuroleptic malignant syndrome. The concomitant fluorouracil-induced thiamine deficiency eventually leads to rapid depletion of thiamine and was considered a risk factor for fluorouracil-induced leukoencephalopathy.

Conclusion
Fluorouracil-induced leukoencephalopathy is believed to be caused by insult causing mitochondrial dysfunction. However, the exact mechanism remains unknown, but our finding suggests that thiamine deficiency plays a crucial role in fluorouracil-induced leukoencephalopathy. Diagnosis is usually delayed due to a lack of clinical suspicion and results in significant morbidity requiring unnecessary investigations.
Bilateral Grynfeltt lumbar hernia: a case report
Authors: Aza Matthieu Sumai , Yawi Joël Bosomi , Musumba Jackson Kambale , Muliwavyo Faida Kavugho , Kavuyiro Alpha Muhindo , Mitamo Alexendre Amini , Masumboko Claude Kasereka , Akinja Severain Uwanda 
Published: April 2023

Abstract
Introduction
Lumbar hernias are rare, with only 200–300 published cases listed in the literature. Two areas are described to have weakness points: the inferior lumbar triangle (Jean-Louis Petit triangle) and the superior lumbar triangle (Grynfeltt–Lesshaft triangle). Clinical diagnosis is confirmed by computed tomography and possibly by ultrasound or radiography. The surgeon must refine the clinical detection of this condition, as most patients do not have sufficient means to have a computed tomography scan performed, which remains the gold standard for diagnosis. Despite the different techniques recommended, the open route remains the most affordable in our environment.

Case presentation
This case presents an 84-year-old black congolese patient consulted for bilateral swellings of the lumbar regions. The patient was married and in the farming profession for several years. The patient had no notion of trauma or fever and no notion of vomiting or stopping of materials and gases. The lumbar region presented with swellings that were ovoid, soft, painless, impulsive and expansive on coughing or hyperpressure, and non-pulsatile, measuring 9 × 7 cm in diameter (right) and 6 × 5 cm in diameter (left). Ultrasound performed of the upper costolumbal region revealed two lipomatous masses facing Grynfeltt’s quadrilateral with a 1.5 cm hole on either side. The diagnosis of bilateral Grynfeltt hernia was made, and herniorrhaphy was indicated.

Conclusion
Grynfeltt–Lesshaft hernia is a rare surgical condition caused by congenital or acquired etiology. A lower back pain or a pain point localized on the hernia in addition to a lumbar mass that reduces when lying down suggests the diagnosis of lumbar hernia.
Safety, biodistribution and radiation dosimetry of [123I]ioflupane in healthy Chinese volunteers
Authors: Zhang Min , Wang Yue , Wang Jin , Li Xiang , Li Biao 
Published: April 2023

Abstract
Background
[123I]ioflupane is a radiopharmaceutical used to visualise the dopaminergic neuron terminals in the striata, to aid in the differential diagnosis among Parkinsonian syndromes (e.g., Parkinson’s disease). However, nearly all of the subjects in the initial development studies of [123I]ioflupane were Caucasian.

Methods
8 Chinese healthy volunteers (HVs) received a single 111 MBq ± 10% dose of [123I]ioflupane and had simultaneous whole-body (head to mid-thigh) anterior and posterior planar scintigraphy scans at 10 min and 1, 2, 4, 5, 24, and 48 h. To estimate biodistribution, dosimetry was evaluated for the Cristy–Eckerman female and hermaphrodite male phantoms. Single-photon emission computed tomography (SPECT) images of the brain were acquired at 3 and 6 h after injection. Blood samples and all voided urine were collected for 48 h for pharmacokinetic analysis. The results were then compared with those of a similar European study.

Results
There were strong similarities in uptake and biodistribution between the Chinese and European studies. Excretion was primarily renal, and the values were similar for the first 5 h but diverged after that, possibly because of differences in subjects’ height and weight. Tracer uptake in regions of interest in the brain was stable over the imaging window of 3 to 6 h. The difference in mean effective dose for Chinese HVs vs European HVs (0.028 ± 0.00448 vs 0.023 ± 0.00152 mSv/MBq) was not clinically significant. The [123I]ioflupane was well tolerated.

Conclusion
This study demonstrated that a single 111 MBq ± 10% dose of [123I]ioflupane injection was safe and well tolerated, and the SPECT imaging window of 3 to 6 h after injection of [123I]ioflupane was appropriate in Chinese subjects.
Trial registration number ClinicalTrials.gov: NCT04564092.