bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spexin role in human granulosa cells physiology and PCOS: expression and negative impact on steroidogenesis and proliferation
Authors: Kurowska Patrycja , Dawid Monika , Oprocha Julia , Respekta Natalia , Serra Loïse , Estienne Anthony , Pawlicki Piotr , Kotula-Balak Małgorzata , Guérif Fabrice , Dupont Joelle , Rak Agnieszka 
Published: September 2023

Abstract
Spexin (SPX) is a novel neuropeptide and adipokine negatively correlated with obesity and insulin resistance. A recent study investigated expression and regulatory function of SPX in the hypothalamus and pituitary; however, the effect on ovarian function is still unknown. The aim of this study was to characterize the expression of SPX and its receptors, galanin receptors 2 and 3 (GALR2/3), in the human ovary and to study its in vitro effect on granulosa cells (GC) function. Follicular fluid (FF) and GC were obtained from normal weight and obese healthy and diagnosed with polycystic ovarian syndrome (PCOS) women. Expression of SPX and GALR2/3 in the ovary was studied by qPCR, western blot, and immunohistochemistry. The level of SPX in FF was assessed by enzyme-linked immunosorbent assay. The in vitro effect of recombinant human SPX on GC proliferation, steroidogenesis, and signaling pathways (MAP3/1, STAT3, AKT, PKA) was analyzed. Moreover, GC proliferation and estradiol (E2) secretion were measured with and without an siRNA against GALR2/3 and pharmacological inhibition of the above kinases. The results showed that both the SPX concentration in FF and its gene expression were decreased in GC of obese and PCOS women, while the protein expression of GALR2/3 was increased. We noted that SPX reduced GC proliferation and steroidogenesis; these effects were mediated by GALR2/3 and kinases MAP3/1, AKT, and STAT3 for proliferation or kinases MAP3/1 and PKA for E2 secretion. The obtained data clearly documented that SPX is a novel regulator of human ovarian physiology and possibly plays a role in PCOS pathogenesis.
The role of enhancers in psoriasis and atopic dermatitis
Authors: Sui Jennifer Y , Eichenfield Dawn Z , Sun Bryan K 
Published: September 2023

Abstract
Regulatory elements, particularly enhancers, play a crucial role in disease susceptibility and progression. Enhancers are DNA sequences that activate gene expression and can be affected by epigenetic modifications, interactions with transcription factors (TFs) or changes to the enhancer DNA sequence itself. Altered enhancer activity impacts gene expression and contributes to disease. In this review, we define enhancers and the experimental techniques used to identify and characterize them. We also discuss recent studies that examine how enhancers contribute to atopic dermatitis (AD) and psoriasis. Articles in the PubMed database were identified (from 1 January 2010 to 28 February 2023) that were relevant to enhancer variants, enhancer-associated TFs and enhancer histone modifications in psoriasis or AD. Most enhancers associated with these conditions regulate genes affecting epidermal homeostasis or immune function. These discoveries present potential therapeutic targets to complement existing treatment options for AD and psoriasis.
Variation in the practice of wide local excision for melanoma in Ireland and the UK: a questionnaire survey
Authors: O’Connor Eileen , O’Connor Cathal , O’Connell Garret , Peach Howard , O’Shea Sally 
Published: September 2023

Abstract

Background
Wide local excision (WLE) is standard practice in the management of melanoma, but no national or international guidelines exist regarding its technique.

Objectives
To assess variation in the practice of WLE and to explore the effect of clinicians’ specialty and grade on such variation.

Methods
This was an international, anonymized, cross-sectional study. An online questionnaire was distributed to the Irish Association of Dermatologists, British Association of Dermatologists, British Association of Plastic and Reconstructive and Aesthetic Surgeons, Melanoma Focus and BioGenoMEL members.

Results
Of 128 respondents, 57% were dermatologists and 38% plastic surgeons. Most (80%) were consultants. Almost all clinicians learned their technique from colleagues (99%) ‘on the job’, although 21% also used textbooks or other media as part of WLE training. There was significant variation in planning and performing WLE: 59% considered margins already achieved, 71% marked margins with the skin relaxed. For 1 cm WLE, 84% delineated 1 cm from the edge of the scar; with a greater proportion of plastic surgeons than dermatologists marking from the centre of the scar (P &lt; 0.05). Most followed a longitudinal/oblique axis on the limbs for WLE (81%). Only 40% sent ‘dog ears’ for histology. Most (70%) incised through the marked line, 27% incised outside it. Most (79%) excised to deep fascia, 18% to the next biological margin.

Conclusions
This study demonstrates significant variation among clinicians performing WLE, an essential component of melanoma management. We postulate that this could have an impact on patient outcomes. A consensus statement should be developed, to achieve more consistency in the practice of WLE.
Cardiac sarcoidosis preceded by sick sinus syndrome presenting as biventricular involvement and intracardiac giant thrombus: a case report
Authors: Hirai Akeo , Shiraishi Yasuyuki , Fukuda Keiichi , Fujita Jun 
Published: September 2023

Abstract

Background
Sarcoidosis is a granulomatous disorder characterized by the formation of non-necrotizing granulomas in various organs. Cardiac sarcoidosis presents with various clinical, anatomical, and electrophysiological manifestations. As cardiac involvement is related to adverse outcomes, the early diagnosis of cardiac sarcoidosis is crucial and sometimes challenging.

Case summary
A 65-year-old woman was initially treated for sick sinus syndrome (SSS) with normal cardiac function. Cardiac conduction defects and biventricular dysfunction continued to progress over a short clinical course, and the patient was eventually referred to our hospital for further investigation and treatment of cardiogenic shock due to pacemaker pacing failure. An echocardiography revealed a large thrombus formation in the right ventricle and atrium. An urgent thrombectomy was performed, and myocardial biopsy confirmed the diagnosis of cardiac sarcoidosis. Steroid pulse therapy was initiated and was effective in treating the cardiogenic shock. One year after discharge, the patient manifested with sustained ventricular tachycardia and ultimately died of severe cardiac pump failure. On autopsy, diffuse fibrotic tissues were noted in both ventricles and atria.

Discussion
While conduction abnormalities, such as right bundle brunch block and atrioventricular block, are common clinical manifestations, SSS is rarely reported as a primary manifestation of cardiac sarcoidosis. Thus, clinicians should ensure that sufficient investigations are carried out when diagnosing idiopathic SSS.
Prominent myocardial bridging as a first clue to recognize haemorrhagic shock during percutaneous coronary intervention: a case report
Authors: Aono Mio , Miyoshi Toru , Higaki Akinori , Yamaguchi Osamu 
Published: September 2023

Abstract

Background
Haemorrhage at the puncture site is a serious complication of percutaneous coronary intervention (PCI).

Case summary
A 73-year-old man underwent transfemoral intervention because of stable angina pectoris. After a rotational atherectomy, an everolimus-eluting stent was implanted from the left main trunk to the proximal site of the left anterior descending (LAD) artery. We also recognized that myocardial bridging was significantly induced at the middle portion of the LAD, which was not evident before the PCI. We suspected puncture-related haemorrhage and immediately performed lower limb arteriography. As a result, contrast media extravasation was observed at the branch of the right inferior epigastric artery. Finally, we performed coil embolization into the left common femoral artery, and the extravasation successfully disappeared. Four months later, he underwent coronary angiography. There were no findings of myocardial bridging.

Discussion
Myocardial bridging during a PCI procedure may indicate hypercontraction because of haemorrhage.
Late-onset MELAS syndrome in a 46-year-old man with initial symptom of chest tightness: a case report
Authors: Wang Ai , Zhao Ji , Zhao Yun , Yan Yan 
Published: September 2023

Abstract

Background
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder caused by mutations in mitochondrial DNA, resulting in impaired energy production and affecting multiple organs. We present a suspected MELAS syndrome case with the initial symptom of chest tightness.

Case summary
A 46-year-old man sought medical attention due to progressively worsening chest tightness during physical activity. He had been receiving treatment for type 2 diabetes for 15 years. One year ago, he presented with symptoms of hearing impairment. Transthoracic echocardiography revealed increased thickness of the left ventricular wall. Serum protein electrophoresis showed no evidence of light-chain amyloidosis, and the 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scan showed no definite uptake in the heart muscle. The patient’s head magnetic resonance imaging (MRI) indicated lacunar infarcts. The lactate threshold test was positive. The biopsy of the skeletal muscle showed broken red fibre infiltration on modified Gomori trichrome staining, and electron microscopy revealed signs of mitochondrial cardiomyopathy, including mild mitochondrial swelling, lipid accumulation, and myofibril damage. A whole-exome genetic test was used to detect the m.3243A&gt;G mutation in the MT-TL1 gene. Based on these findings, MELAS syndrome was the most probable diagnosis.

Discussion
The patient presented with chest tightness in adulthood, without any accompanying psychoneurological symptoms. However, the patient presented with other symptoms, including diabetes mellitus, hearing loss, abnormal lactate levels, ischaemic lesions on head MRI, and left ventricular hypertrophy. By identifying a mutation in the MT-TL1 gene and conducting a muscle biopsy, the diagnosis of MELAS syndrome was definitively confirmed.
Trade Shocks, Labour Markets and Migration in the First Globalisation
Authors: Bräuer Richard , Kersting Felix 
Published: September 2023

Abstract
This paper studies the economic and political effects of a large trade shock in agriculture—the grain invasion from the Americas—in Prussia during the first globalisation (1870–913). We show that this shock led to a decline in the employment rate and overall income. However, we do not observe declining per capita income and political polarisation, which we explain by a strong migration response. Our results suggest that the negative and persistent effects of trade shocks we see today are not a universal feature of globalisation, but depend on labour mobility. For our analysis, we digitise data from Prussian industrial and agricultural censuses on the county level and combine them with national trade data at the product level. We exploit the cross-regional variation in cultivated crops within Prussia and instrument with Italian and United States trade data to isolate exogenous variation.
Divergence in the internal genital morphology of females and correlated divergence in male intromittent structures among populations of a millipede
Authors: Sloan Nadia S , Kennington W Jason , Simmons Leigh W 
Published: September 2023

Abstract
Our understanding of genital evolution comes largely from studies of male genitalia. Females have received far less attention because of the difficulties inherent in quantifying the shapes of their internal genital structures. Here we combine advances in micro-computed tomography with a new landmark free method of quantifying three-dimensional trait shape, to document patterns of divergence in female genital shape, and the correlated divergence of male genitalia among populations of the millipede Antichiropus variabilis. We used single-nucleotide polymorphisms to estimate levels of neutral genetic divergence among seven populations of millipede. Genetic divergence was high and correlated with geographic distance. Comparing phenotypic divergence in genital shape to neutral genetic divergence, we found that genital shape for both females and males has diverged more than would be expected from random drift, consistent with a pattern of directional selection. While there was significant covariation between female and male genital shape across populations, the magnitude of divergence in genital shape between the sexes was not correlated. Our results demonstrate the utility of using three-dimensional scanning technologies to examine female genital traits and add to a small but growing number of studies showing that like male genitalia, female genitalia can be under strong directional selection.
Melatonin retards leaf senescence by modulating phytohormone metabolism in stored Chinese flowering cabbage
Authors: Li Chenxiang , Shen Xuemeng , Fan Zhongqi , Chen Jianye , Tao Nengguo , Tan Xiaoli 
Published: September 2023

Abstract
This paper was conducted to explore the effects of melatonin (MT) on the senescence of stored Chinese flowering cabbage and the potential modulatory mechanisms involved. The physiological findings demonstrated that MT successfully reduced chlorophyll loss and improved the photochemical effectiveness of cabbage leaves. In addition, MT decreased the transcription of senescence-associated genes (BrSAG12) and genes responsible for chlorophyll breakdown. Transcriptome analysis showed that MT-regulated genes were enriched in oxidative phosphorylation, hormone metabolism and signal transduction, and MT treatment reduced the high expression of genes linked to generation of reactive oxygen species (ROS), energy metabolism, phytohormone (abscisic acid (ABA), ethylene (ET), and jasmonic acid (JA)) biological synthesis and signal transduction while promoting the activation of genes related to scavenging ROS, energy biosynthesis and plant–pathogen interactions. We emphasized the examination of the potential interaction between phytohormone metabolism and MT. The results showed that the application of MT decreased ABA, ET, and JA levels as well as the expression of their biosynthesis genes, concurrently maintaining higher expression of cytokinin, auxin and gibberellin biosynthetic genes and lower expression of degradation genes. Regulatory networks of transcription factors (TFs) and genes related to ABA, ET and JA metabolism showed that TFs such as DNA-binding One Zinc Finger 5.7 (DOF5.7), WRKY40, and homeobox-leucine zipper protein-16 (ATHB-16) might play important transcriptional regulatory roles in mediating MT postponed leaf senescence. Taken together, these findings suggested that the postponed senescence of cabbage treated with MT might be ascribed to the regulated oxidative phosphorylation, energy, phytohormone metabolism, and transcription factors.
Mid-Life Vascular Risk and Rate of Physical Function Decline Among Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Skow Laura F , Sharrett A Richey , Gottesman Rebecca F , Coresh Josef , Deal Jennifer A , Palta Priya , Sullivan Kevin J , Griswold Michael E , Schrack Jennifer A , Windham B Gwen 
Published: September 2023

Abstract

Background
Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline.

Methods
This prospective cohort included 5 481 older adults aged 67–91 in the Atherosclerosis Risk in Communities Study (mean [standard deviation {SD}] age = 75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was the rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4.8 years. Primary mid-life (aged 45–64) exposures were Visit 1 hypertension (&gt;140/90 mm Hg or treatment), diabetes (&gt;126 mg/dL or treatment), high cholesterol (&gt;240 mg/dL or treatment), and smoking, and number of decades of vascular risk exposure across Visits 1–4.

Results
The average adjusted rate of SPPB decline (points per 5 years) for older adults was −0.79 (confidence interval [CI]: −0.87, 0.71) and was accelerated by mid-life hypertension (+57% decline vs normotension: additional decline of −0.47, 95% CI: −0.64, −0.30), diabetes (+73% decline vs no diabetes: additional decline of −0.67, 95% CI: −1.09, −0.24), elevated systolic blood pressure (+17% decline per SD: −0.16, 95% CI: −0.23, −0.10), and elevated fasting blood glucose (+16% decline per SD: −0.015, 95% CI: −0.24, −0.06). Each decade greater mid-life exposure to hypertension (+32% decline: −0.93, 95% CI: −1.25, −0.61) and diabetes (+35% decline: −1.03, 95% CI: −1.68, −0.38) was associated with faster SPPB decline.

Conclusions
Mid-life control of blood pressure and diabetes may offset aging-related functional decline.
Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo
Authors: Xie Jianhao , Wu Shengjie , Liao Wenfeng , Ning Jingru , Ding Kan 
Published: September 2023

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose’s action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski’s rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.
The Effectiveness and Safety of First-Line Thioguanine in Thiopurine-Naïve Inflammatory Bowel Disease Patients
Authors: Crouwel Femke , Bayoumy Ahmed B , Mulder Chris J J , Peters Job H C , Boekema Paul J , Derijks Luc J J , de Boer Sybrand Y , van de Meeberg Paul C , Ahmad Ishfaq , Buiter Hans J C , de Boer Nanne K 
Published: September 2023

Abstract

Background
Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease.

Methods
A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events.

Results
A total of 114 patients (male 39%, Crohn’s disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed.

Conclusions
At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile.
Learning river water quality models by l1-weighted regularization
Authors: Nho Hào Dinh , Xuan Hiep Duong , Quy Muoi Pham 
Published: September 2023

Abstract
We investigate the problem of learning a water quality model (BOD-DO model) from given data. Assuming that all parameters in the model are constants, we reformulate the problem as a system of linear equations for the unknown terms. Since in practice the system is often under-determined or over-determined and the observed data are noisy, we use an $l^{1}$-weighted regularization method to find a stable approximate solution. Then, Nesterov’s algorithm is used to solve the regularized problem. Learning models with variable coefficients are also discussed. Numerical examples show that our approach works well with noisy data and has the ability to learn the BOD-DO model.
Interpretable model learning in variational imaging: a bilevel optimization approach
Authors: De los Reyes Juan Carlos , Villacís David 
Published: September 2023

Abstract
In this paper, we investigate the use of bilevel optimization for model learning in variational imaging problems. Bilevel learning is an alternative approach to deep learning methods, which leads to fully interpretable models. However, it requires a detailed analytical insight into the underlying mathematical model. We focus on the bilevel learning problem for total variation models with spatially- and patch-dependent parameters. Our study encompasses the directional differentiability of the solution mapping, the derivation of optimality conditions, and the characterization of the Bouligand subdifferential of the solution operator. We also propose a two-phase trust-region algorithm for solving the problem and present numerical tests using the CelebA dataset.