bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAPT haplotype-associated transcriptomic changes in progressive supranuclear palsy
Authors: Ressler Hadley W. , Humphrey Jack , Vialle Ricardo A. , Babrowicz Bergan , Kandoi Shrishtee , Raj Towfique , Dickson Dennis W. , Ertekin-Taner Nilüfer , Crary John F. , Farrell Kurt 
Published: August 2024

AbstractProgressive supranuclear palsy (PSP) is a neurodegenerative movement and cognitive disorder characterized by abnormal accumulation of the microtubule-associated protein tau in the brain. Biochemically, inclusions in PSP are enriched for tau proteoforms with four microtubule-binding domain repeats (4R), an isoform that arises from alternative tau pre-mRNA splicing. While preferential aggregation and reduced degradation of 4R tau protein is thought to play a role in inclusion formation and toxicity, an alternative hypothesis is that altered expression of tau mRNA isoforms plays a causal role. This stems from the observation that PSP is associated with common variation in the tau gene (MAPT) at the 17q21.31 locus which contains low copy number repeats flanking a large recurrent genomic inversion. The complex genomic structural changes at the locus give rise to two dominant haplotypes, termed H1 and H2, that have the potential to markedly influence gene expression. Here, we explored haplotype-dependent differences in gene expression using a bulk RNA-seq dataset derived from human post-mortem brain tissue from PSP (n = 84) and controls (n = 77) using a rigorous computational pipeline, including alternative pre-mRNA splicing. We found 3579 differentially expressed genes in the temporal cortex and 10,011 in the cerebellum. We also found 7214 differential splicing events in the temporal cortex and 18,802 in the cerebellum. In the cerebellum, total tau mRNA levels and the proportion of transcripts encoding 4R tau were significantly increased in PSP compared to controls. In the temporal cortex, the proportion of reads that expressed 4R tau was increased in cases compared to controls. 4R tau mRNA levels were significantly associated with the H1 haplotype in the temporal cortex. Further, we observed a marked haplotype-dependent difference in KANSL1 expression that was strongly associated with H1 in both brain regions. These findings support the hypothesis that sporadic PSP is associated with haplotype-dependent increases in 4R tau mRNA that might play a causal role in this disorder.
Advancing SERS as a quantitative technique: challenges, considerations, and correlative approaches to aid validation
Authors: Sloan-Dennison Sian , Wallace Gregory Q. , Hassanain Waleed A. , Laing Stacey , Faulds Karen , Graham Duncan 
Published: August 2024

AbstractSurface-enhanced Raman scattering (SERS) remains a significant area of research since it’s discovery 50 years ago. The surface-based technique has been used in a wide variety of fields, most prominently in chemical detection, cellular imaging and medical diagnostics, offering high sensitivity and specificity when probing and quantifying a chosen analyte or monitoring nanoparticle uptake and accumulation. However, despite its promise, SERS is mostly confined to academic laboratories and is not recognised as a gold standard analytical technique. This is due to the variations that are observed in SERS measurements, mainly caused by poorly characterised SERS substrates, lack of universal calibration methods and uncorrelated results. To convince the wider scientific community that SERS should be a routinely used analytical technique, the field is now focusing on methods that will increase the reproducibility of the SERS signals and how to validate the results with more well-established techniques. This review explores the difficulties experienced by SERS users, the methods adopted to reduce variation and suggestions of best practices and strategies that should be adopted if one is to achieve absolute quantification.
Graphical Abstract
Placental growth factor mediates pathological uterine angiogenesis by activating the NFAT5-SGK1 signaling axis in the endometrium: implications for preeclampsia development
Authors: Raja Xavier Janet P. , Okumura Toshiyuki , Apweiler Melina , Chacko Nirzari A. , Singh Yogesh , Brucker Sara Y , Takeda Satoru , Lang Florian , Salker Madhuri S 
Published: August 2024

AbstractAfter menstruation the uterine spiral arteries are repaired through angiogenesis. This process is tightly regulated by the paracrine communication between endometrial stromal cells (EnSCs) and endothelial cells. Any molecular aberration in these processes can lead to complications in pregnancy including miscarriage or preeclampsia (PE). Placental growth factor (PlGF) is a known contributing factor for pathological angiogenesis but the mechanisms remain poorly understood. In this study, we investigated whether PlGF contributes to pathological uterine angiogenesis by disrupting EnSCs and endothelial paracrine communication. We observed that PlGF mediates a tonicity-independent activation of nuclear factor of activated T cells 5 (NFAT5) in EnSCs. NFAT5 activated downstream targets including SGK1, HIF-1α and VEGF-A. In depth characterization of PlGF - conditioned medium (CM) from EnSCs using mass spectrometry and ELISA methods revealed low VEGF-A and an abundance of extracellular matrix organization associated proteins. Secreted factors in PlGF-CM impeded normal angiogenic cues in endothelial cells (HUVECs) by downregulating Notch-VEGF signaling. Interestingly, PlGF-CM failed to support human placental (BeWo) cell invasion through HUVEC monolayer. Inhibition of SGK1 in EnSCs improved angiogenic effects in HUVECs and promoted BeWo invasion, revealing SGK1 as a key intermediate player modulating PlGF mediated anti-angiogenic signaling. Taken together, perturbed PlGF-NFAT5-SGK1 signaling in the endometrium can contribute to pathological uterine angiogenesis by negatively regulating EnSCs-endothelial crosstalk resulting in poor quality vessels in the uterine microenvironment. Taken together the signaling may impact on normal trophoblast invasion and thus placentation and, may be associated with an increased risk of complications such as PE.
Multiple fractures due to hungry bone syndrome following parathyroidectomy: a clinical case report and review of literature
Authors: Tavakoli Farnaz , Yaghoubi Fatemeh , Dalil Davood , Rezaei Mahdi 
Published: August 2024

Abstract
Background
Hungry bone syndrome (HBS) is defined as prolonged hypocalcemia caused by a sudden decrease in parathyroid hormone (PTH) levels after parathyroidectomy (PTX). Multiple fractures after PTX due to HBS in an end-stage renal disease (ESRD) patient on chronic hemodialysis (HD) are challenging and rare medical conditions presented in this study.

Case Presentation
A 42-year-old ESRD patient on HD 3 times a week presented to Shariati Hospital, Tehran, Iran, complaining of worsening bone pain and loss of appetite. Laboratory data revealed an intact parathyroid hormone (iPTH) concentration of 2500 pg/mL, an alkaline phosphatase (Alp) level of 4340 IU/L, a phosphorus (P) level of 9 mg/dL, and a calcium (Ca) concentration of 7.2 mg/dL. Sestamibi scintigraphy revealed parathyroid adenoma. The findings suggested tertiary hyperparathyroidism (HPT-III), and the patient was scheduled for total PTX. Approximately one month after surgery, the patient was referred due to convulsions, leg mobility problems, and worsening bone pain. There was bilateral femoral ecchymosis. The Ca concentration was 5.8 mg/dL, and radiological evaluations revealed multiple skeletal fractures. HBS after PTX was suggested for this patient. After several days of hospitalization, he suffered subcutaneous emphysema followed by rib fractures and passed away.

Conclusions
Multiple fractures after PTX due to HBS following HPT-III in ESRD patients are rare and demanding, highlighting the necessity of timely diagnosis and management of patients with HPT-III. Severe hypocalcemia following PTX can cause skeletal disorders. However, the surgical treatment of parathyroid adenomas may be more important than the risk of complications associated with bone health.
Growth performance, biochemical outcomes, and testicular histological features in male Japanese quails supplemented with milk thistle seeds
Authors: Hosny Mohamed , Khalil Nasser S. Abou , Alghriany Alshaimaa A. I. , Younis Mohammed , Abdelfattah Mostafa Galal 
Published: August 2024

Abstract
Background
Due to its rich content of active phytochemicals, milk thistle is regarded as a promising nutritional supplement for quails, particularly in regions with limited financial resources. Thus, our study aimed to evaluate the possible beneficial impact of aqueous extract of milk thistle seeds (MTS) at two graded concentrations (10 and 20 ml/L of drinking water) on male Japanese quails during their reproductive period.

Results
The phytochemical analysis revealed the presence of 29 active compounds, including nine flavonoids and ten phenolic compounds. The supplemented groups showed significant improvements in body weight gain. MTS1 group exhibited a notable decrease in daily feed consumption, while MTS2 group showed a significant increase in daily water consumption. There was a dose-dependent increase in cecum length. The total count of intestinal bacteria decreased in a dose-dependent manner. Incorporating aqueous extract of MTS at concentration of 10 ml /L resulted in a significant increase in total protein and packed cell volume. Similar increases in globulin and decreases in the albumin/globulin ratio and aspartate aminotransferase (AST) were observed with both doses of supplementation. A significant decrease in total cholesterol and AST was observed in the high-dose group. Significantly higher plasma testosterone and triiodothyronine levels were observed only in the high-dose group, while plasma thyroxine levels were similarly increased in both supplemented groups. Intervention with MTS resulted in dose-dependent increases in cloacal gland index and cloacal foam production. Both supplemented groups showed significant increases in the diameter of seminiferous tubules and the number of Sertoli cells.

Conclusion
Marked growth-promoting, antibacterial, and reproductive-enhancing effects were observed when incorporating aqueous extract of MTS into the quails’ drinking water, particularly at a dosage of 20 ml/L.
The effect of tocilizumab administration on inflammatory markers in COVID-19 patients
Authors: Soliman Engy Mohamed Riyad , Wageh Khaled Mohamed , Mohamed Mahmoud Mokhtar , Mohamed Hoda Attiatullah 
Published: August 2024

Abstract
Background
The COVID-19 outbreak was declared a worldwide emergency as a result of its rapid spread. The number of people infected with COVID-19 is increasing rapidly around the world, and pneumonia can develop in COVID-19 cases. The monoclonal antibody tocilizumab blocks the interleukin-6 receptor, which in turn reduces inflammation.

Aim
of the work
The study aims to determine how tocilizumab affects inflammatory markers, laboratory indices, and oxygen therapy.
Subjects and methods
This retrospective observational study aimed to assess the effect of tocilizumab on inflammatory markers, laboratory parameters, and short-term outcomes in COVID-19 cases. Data was collected from 55 patients with COVID-19 who tested positive for SARS-CoV-2 using PCR. These patients were admitted to Ain Shams University Specialized Hospital—Obour between June 1, 2021, and May 31, 2022.

Results
After tocilizumab administration, C-reactive protein levels decreased significantly, but there was no statistically significant change in hemoglobin, serum ferritin, or D-dimer levels. Following tocilizumab administration, the leukocyte counts, and platelet count increased significantly. There was a significant correlation between the presence of comorbidities in the studied patients (e.g., heart failure, post-renal transplantation, and hepatitis C virus) and the risk of mortality. The study's final result showed a significant decrease in platelet count in dead patients compared to discharged patients after receiving tocilizumab. Regarding oxygen therapy following tocilizumab administration, the use of face masks and non-rebreather facemasks was high in dead patients, while nasal prong usage was high in discharged patients. After receiving tocilizumab, there was an increase in the mean liters of oxygen required in dead patients compared to discharged patients.

Conclusion
After administration of tocilizumab in COVID-19 hospitalized patients who have progressing disease, there was highly and significantly decrease in CRP level with no statistically significant alteration in the levels of hemoglobin, serum ferritin, and D-dimer and an increase in TLC and platelets was observed. Following tocilizumab administration, there was a decrease in oxygen demands, an improvement in oxygen therapy and oxygen saturation. Tocilizumab is a recommended therapy option.
Ultrasound assessment of diaphragmatic excursion in chronic obstructive pulmonary disease patients with different severities
Authors: Fekri Kholod Tarek , El-Sorougi Waleed Kamal Eldin , Abdalrazik Fatmaalzahraa Saad 
Published: August 2024

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is associated with dysfunctional diaphragmatic breathing we assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound.

Objective
The present study aimed to assess the diaphragmatic excursion at different stages of COPD patients by transthoracic ultrasound.

Patients and methods
In this observational case–control study, 80 COPD patients were included according to GOLD guidelines 2020 attending the Chest Clinic in Badr Hospital, Helwan University. All patients were divided equally into 5 groups according to FEV1 measured by spirometer: group (1) normal person; group (2) mild stage FEV1_80% predicted; group (3) moderate stage 50%_FEV1 < 80% predicted; group (4) severe stage 30%_FEV1 < 50% predicted; and group (5) very severe stage FEV1 < 30% predicted. We measured diaphragmatic movement in all these patients using ultrasound.

Results
The outcomes result of normal, mild, moderate, severe, and very severe groups in terms of post-bronchodilator FEV1/FVC are 0.66 ± 0.05, 0.65 ± 0.05, 0.63 ± 0.04, 0.51 ± 0.068 respectively showed was a significant difference. There was a significant difference of FEV1 are 86.70 ± 5.62, 63.00 ± 13.81, 43.00 ± 6.78, 24.00 ± 4.17, respectively (P < 0.001). There was a significant difference in diaphragmatic thickness at the end of normal expiration are 0.49 ± 0.12, 0.51 ± 0.09, 0.47 ± 0.16, 0.37 ± 0.07, respectively (P < 0.001). There was a significant difference in the diaphragmatic thickness during maximum inspiration are 0.70 ± 0.16, 0.8 ± 0.17, 0.64 ± 0.19, and 0.47 ± 0.08, respectively (P < 0.001). There was a significant difference in the diaphragmatic excursion during normal breathing are 2.45 ± 0.39, 1.78 ± 0.67, 1.86 ± 0.67, 1.09 ± 0.16, respectively (P < 0.001). There was a significant difference in diaphragmatic Excursion during maximum inspiration are 4.41 ± 0.91, 3.83 ± 0.78, 3.36 ± 0.74, 2.36 ± 0.66 respectively (P < 0.001).

Conclusion
The use of ultrasonography for assessing the diaphragmatic excursion. Sonographically determined diaphragmatic excursion strongly correlates with FEV1/FVC.
Building integrated plant health surveillance: a proactive research agenda for anticipating and mitigating disease and pest emergence
Authors: Soubeyrand S. , Estoup A. , Cruaud A. , Malembic-Maher S. , Meynard C. , Ravigné V. , Barbier M. , Barrès B. , Berthier K. , Boitard S. , Dallot S. , Gaba S. , Grosdidier M. , Hannachi M. , Jacques M.-A. , Leclerc M. , Lucas P. , Martinetti D. , Mougel C. , Robert C. , Roques A. , Rossi J.-P. , Suffert F. , Abad P. , Auger-Rozenberg M.-A. , Ay J.-S. , Bardin M. , Bernard H. , Bohan D. A. , Candresse T. , Castagnone-Sereno P. , Danchin E. G. J. , Delmas C. E. L. , Ezanno P. , Fabre F. , Facon B. , Gabriel E. , Gaudin J. , Gauffre B. , Gautier M. , Guinat C. , Lavigne C. , Lemaire O. , Martinez C. , Michel L. , Moury B. , Nam K. , Nédellec C. , Ogliastro M. , Papaïx J. , Parisey N. , Poggi S. , Radici A. , Rasplus J.-Y. , Reboud X. , Robin C. , Roche M. , Rusch A. , Sauvion N. , Streito J.-C. , Verdin E. , Walker A.-S. , Xuéreb A. , Thébaud G. , Morris C. E. 
Published: August 2024

Abstract
In an era marked by rapid global changes, the reinforcement and modernization of plant health surveillance systems have become imperative. Sixty-five scientists present here a research agenda for an enhanced and modernized plant health surveillance to anticipate and mitigate disease and pest emergence. Our approach integrates a wide range of scientific fields (from life, social, physical and engineering sciences) and identifies the key knowledge gaps, focusing on anticipation, risk assessment, early detection, and multi-actor collaboration. The research directions we propose are organized around four complementary thematic axes. The first axis is the anticipation of pest emergence, encompassing innovative forecasting, adaptive potential, and the effects of climatic and cropping system changes. The second axis addresses the use of versatile broad-spectrum surveillance tools, including molecular or imaging diagnostics supported by artificial intelligence, and monitoring generic matrices such as air and water. The third axis focuses on surveillance of known pests from new perspectives, i.e., using novel approaches to detect known species but also anticipating and detecting, within a species, the populations or genotypes that pose a higher risk. The fourth axis advocates the management of plant health as a commons through the establishment of multi-actor and cooperative surveillance systems for long-term data-driven alert systems and information dissemination. We stress the importance of integrating data and information from multiple sources through open science databases and metadata, alongside developing methods for interpolating and extrapolating incomplete data. Finally, we advocate an Integrated Health Surveillance approach in the One Health context, favoring tailored and versatile solutions to plant health problems and recognizing the interconnected risks to the health of plants, humans, animals and the environment, including food insecurity, pesticide residues, environmental pollution and alterations of ecosystem services.
The Effect of Adrenalectomy on Overall Survival in Metastatic Adrenocortical Carcinoma
Authors: Assad Anis , Incesu Reha-Baris , Morra Simone , Scheipner Lukas , Baudo Andrea , Siech Carolin , De Angelis Mario , Tian Zhe , Ahyai Sascha , Longo Nicola , Chun Felix K H , Shariat Shahrokh F , Tilki Derya , Briganti Alberto , Saad Fred , Karakiewicz Pierre I 
Published: August 2024

Abstract

Context
Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown.

Objective
This work aimed to assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting.

Methods
Patients with mACC aged 18 years or older with metastatic ACC at initial presentation who were treated between 2004 and 2020 were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020), and we tested for differences according to adrenalectomy status. Intervention included primary tumor resection status (adrenalectomy vs no adrenalectomy). Kaplan-Meier plots, multivariable Cox regression models, and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs historical (2004-2011), single vs multiple metastatic sites, and assessable specific solitary metastatic sites (lung only and liver only).

Results
Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; P &lt; .001), as well as with 3 months' landmark analyses (HR: 0.57; P = .002). The same association effect with 3 months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49; P &lt; .001), contemporary patients (HR: 0.57; P = .004), historical patients (HR: 0.42; P &lt; .001), and in those with lung-only solitary metastasis (HR: 0.50; P = .02). In contrast, no statistically significant association was recorded in patients naive to systemic therapy (HR: 0.68; P = .3), those with multiple metastatic sites (HR: 0.55; P = .07), and those with liver-only solitary metastasis (HR: 0.98; P = .9).

Conclusion
The present results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.
Neurodegenerative diseases - Characteristics and The role of physical activity
Authors: Madoń Magda , Sieniawska Julia , Sieniawska Daria , Kamizela Angelika 
Published: August 2024

Introduction
Neurodegenerative diseases, increasingly prevalent due to an aging population, involve the degeneration of nerve cells through processes like necrosis and apoptosis. These conditions, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and Huntington's, affect the brain, spinal cord, and peripheral nerves, leading to motor, psychological, and memory disorders, and can result in premature death. Research indicates that physical activity from a young age can reduce the risk of developing neurodegenerative diseases, with studies showing that exercise induces beneficial neuroplastic changes in both healthy individuals and patients.
Aim of the study
The aim of the study is to provide a comprehensive analysis of neurodegenerative diseases. Through a detailed discussion of these issues, our goal is to increase public awareness of neurodegenerative diseases and provide readers with comprehensive knowledge about this diseases.
Material and method
This article presents the current state of knowledge about neurodegenerative diseases. A literature review was conducted using the PubMed, Google Scholar and Web of Science databases, utilizing keywords such as " Parkinson's disease", " amyotrophic lateral sclerosis", "Alzhaimer's disease".
Current state of knowledge about spironolactone-induded gynecomastia. Review 2024
Authors: Iszczuk Oliwia Kamila , Silldorff Julia , Fura Tomasz , Dudek Marcin , Zaucha Radosław , Gajkiewicz Magdalena , Felińska Zuzanna , Zając Małgorzata , Anczyk Stanisław 
Published: August 2024

Spironolactone, a potassium-sparing diuretic, acts as an aldosterone antagonist but also has anti-androgen properties, leading to increased estrogen levels in the body. It can cause gynecomastia in men by blocking the production of androgens, preventing androgens from binding to specific receptors, and rising levels of both total and free estrogen. Numerous scientific articles and clinical cases have been analyzed and confirmed this statement. Evidence for gynecomastia with mineralocorticoid receptor antagonist usage was of high quality.Clinicians are advised to monitor patients taking these medications for developing gynecomastia and to consider this risk in the therapeutic decision-making process.