bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of hydroxyurea on SP1, LIN28B, IGF2BP3, COL4A5, BCL2, gamma globin genes expression: an in vitro study
Authors: Fashami Akram Agha-Amini , Alemzadeh Esmat , Safarpour Hossein , Miri-Moghaddam Ebrahim 
Published: November 2023

Abstract
Background
In some β-thalassemia intermedia patients, hydroxyurea (HU) increases hemoglobin and HbF levels. However, HUs’ effects molecular mechanism is still unclear.

Methods
In this study, a weighted gene co-expression network analysis was conducted on the GSE109186 dataset. The genes LIN28A, COL4A5, SP1, BCL2, and IGF2BP3 were identified as hub genes involved in the γ-gene switching process. The effect of HU treatment at doses of 50, 100, and 150 μM for 12, 24, and 48 h on the K562 cell line was examined by using qRT-PCR to measure the expression levels of these hub genes.

Results
SP1 gene expression decreased after treatment with 50, 100, and 150 μM HU for 12, 24, and 48 h. The expression of the LIN28A gene was tripled at three concentrations of 50, 100, and 150 μM for 12 h. The IGF2BP3 gene expression was doubled after 24 and 48 h at a concentration of 150 μM HU. Regarding COL4A5 gene expression, except at 12 h after treatment at a concentration of 50 μM, a significant increase was observed in other concentrations and times. The BCL2 gene expression pattern at all concentrations decreased significantly after 12 h. The γ gene showed a significant increase compared to the control group after 24 and 48 h at the different concentrations.

Conclusion
The results showed that in HU-treated cells, changes in the expression of LIN28A, COL4A5, SP1, and IGF2BP3 genes were accompanied by an increase in γ-gene expression. By elucidating precisely the mechanism of γ-to-β gene switching, we can hope for less complicated drugs.
A rare presentation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) as acute hemorrhagic longitudinally extensive transverse myelitis
Authors: Nerlekar Aniket , Malvadkar Sharad , Patil Dhairyasheel , Bhoir Bhagyashree , Shaikh Neha , Sambare Jagdish 
Published: November 2023

Abstract
Background
Myelin oligodendrocyte glycoprotein antibody-associated disease is usually associated with optic neuritis, acute disseminated encephalomyelitis or transverse myelitis. We are presenting a rare case report wherein myelin oligodendrocyte glycoprotein antibody seropositivity was associated with hemorrhagic longitudinally extensive transverse myelitis. To our knowledge, no such cases were found to be published.

Case presentation
A 15-year-old female came with complaints of sudden onset paraparesis. MRI was performed within 48 h from the episode of paraparesis, which revealed a long-segment, intramedullary, expansile and heterogeneously enhancing spinal cord lesion extending from T1 vertebral level up to conus medullaris. Few foci of blooming were also noted within the spinal cord on gradient sequences. Laboratory evaluation of cerebrospinal fluid analysis revealed no significant abnormality. Neuromyelitis optica antibodies were negative, and myelin oligodendrocyte glycoprotein antibodies (MOG) showed seropositivity. The patient was started on methylprednisolone and plasmapheresis for the same after which the patient gradually improved and regained her ability to walk. Follow-up MRI was performed after 4 weeks, which revealed significant reduction in the extent of the intramedullary lesion described earlier.

Conclusions
Hemorrhagic longitudinally extensive transverse myelitis without any involvement of optic nerves and brain may show MOG seropositivity, and it should be considered as one of the differential diagnosis in acute myelopathy.
Process development and quality attributes for the freeze-drying process in pharmaceuticals, biopharmaceuticals and nanomedicine delivery: a state-of-the-art review
Authors: Pardeshi Sagar R. , Deshmukh Nilesh S. , Telange Darshan R. , Nangare Sopan N. , Sonar Yogesh Y. , Lakade Sameer H. , Harde Minal T. , Pardeshi Chandrakantsing V. , Gholap Amol , Deshmukh Prashant K. , More Mahesh P. 
Published: November 2023

Abstract
Background
Process intensification is a major hurdle in pharmaceutical process scale-up. Solvent removal strategies have limited the effectiveness of the overall stability of pharmaceutical formulations. The main aim of present review article is to focus on the use of the freeze-drying process in pharmaceuticals, biopharmaceuticals and nanoderived therapeutics and their translation into commercial viable products. Unwavering efforts of scientists in the process intensification of lyophilization promote unique features of products for commercialization. Regulatory agencies are promoting the utilization of a quality-by-design approach to improve product characteristics. Among 300 FDA-approved pharmaceutical industries, 50% of products are freeze-dried. The freeze-drying process is costlier and requires more time than other drying methodologies. Unstable pharmaceutical dispersions and solutions can be preferably stabilized by using the freeze-drying method.

Main text
This review highlights the utilization of critical quality attributes and process parameters for the freeze-drying process, which helps to improve the integrity and stability of the formulation. The quality-by-design approach possibly cuts the cost of the process and saves money, time, and laborious work. The present review focuses preliminarily on the applications of freeze-drying in the development of biopharmaceuticals, including vaccines, proteins and peptides, and injectable products. In addition, a separate section demonstrating the potential of freeze-drying in nanoderived therapeutics has been illustrated briefly. The present clinical scenario of freeze-dried pharmaceuticals and biopharmaceuticals has also been described in later sections of the review.

Conclusions
This review underscores the value of integrating Quality by Design into the development of lyophilization processes for pharmaceutical and biopharmaceutical products. By identifying critical process parameters, delineating a design space, and leveraging advanced monitoring techniques, manufacturers can effectively address the intricacies of lyophilization. This approach empowers them to produce stable, superior quality products with confidence and consistency.

Graphical abstract
Vestibular evoked myogenic potentials and videonystagmography findings in type 2 diabetes mellitus patients with and without polyneuropathy
Authors: Koura Rabab Ahmed , El-Badry Mohamed Mohamed , Othman Asmaa Mohamed , Anwar Rehab Hassan El , Elsharkawy Sara Ahmed Mahmoud , Basiouny Iman Mostafa 
Published: November 2023

Abstract
Background
Vestibular impairment is a common pathology in patients with type 2 diabetes mellitus (DM) due to ischemia of the vestibular end organs and lysis of the myelin of the vestibular nerve. We aimed to evaluate function of the vestibular end organs and vestibular nerve in patients with type 2 DM with polyneuropathy and compare results to those of the patients without polyneuropathy.

Method
The participants consisted of three groups: thirty patients with type 2 diabetes mellitus without polyneuropathy (DM), thirty patients with type 2 diabetes mellitus with polyneuropathy (DPN), and thirty healthy non-diabetic individuals as the control group. Clinical examination, videonystagmography, cervical vestibular evoked myogenic potential(cVEMP), ocular vestibular evoked myogenic potential (oVEMP), Gans Sensory Organization Performance (SOP) test, and nerve conduction study were all performed on all groups.

Results
P1 and N1 cVEMP latencies and n1 and p1 oVEMP latencies were statistically significantly delayed in both the DM and DPN groups than the control. Also, amplitudes of P1-N1 and n1-p1 were statistically significantly lower in the DM and DPN groups than the control group. DPN patients had longer latencies and lower amplitude of the cVEMP and oVEMP response compared to diabetes patients without neuropathy. There was a statistically significant prevalence of BPPV in the DPN group compared to the control and DM groups. DPN included the following: 4 (13.3%) had vestibular pattern, 12 had polyneuropathic pattern, and 5 (16.7%) had vestibular and polyneuropathic pattern as regards the Gans Sensory Organization Performance (SOP) test.

Conclusion
VEMP is considered a promising objective tool in the assessment of the vestibular end organ disorders in patients with type 2 DM with and without polyneuropathy. Diabetics with prominent diabetic polyneuropathy showed higher vestibular impairment than diabetics without DPN, which may increase the risk of falling.
Impact of comorbid pulmonary disease on COVID-19 disease severity and outcome: a retrospective cohort study
Authors: Magdy Sally , Elkorashy Reem , Elsebaie Eman Hany , Assal Hebatallah Hany , Abdel-Hamid Hoda M. 
Published: November 2023

Abstract
Background
Identifying patients with comorbid pulmonary disease may guide prognosis and aid in developing strategies regarding who would benefit the most from vaccines. This study was designed to clarify the influence of comorbid lung disease on COVID-19 severity and outcome.

Methods
This is a retrospective cohort analysis of 587 COVID-19 patients. The clinical, laboratory, and imaging data and comorbidities as reported by the patients were obtained from the Kasr Alainy Hospital medical records. Also, data regarding whether the patient is hospitalized or not, the length of hospital stay, complications, and mortality are gathered from the records.

Results
The patients’ mean ages are 51 ± 15 years (63.9% are males with the remaining 36.1% which are females). Patients with chronic comorbid pulmonary diseases represented 113 patients among the whole study population. with the COPD being 11.4%. Patients with comorbid lung diseases associated or not with other comorbidities were at higher risk of acquiring severe COVID-19 and had higher complication and mortality rates compared to patients without comorbidities (p-value < 0.001). Patients with preexisting diabetes, hypertension, COPD, and chronic kidney disease have a significantly higher risk of severe infection (p-value < 0.001, 0.001, 0.001, < 0.001), complications (p-value 0.038, 0.005, < 0.001, < 0.001), and mortality (p-value 0.021, 0.001, < 0.001, < 0.001), respectively.

Conclusion
This study provides a better understanding of COVID-19 patients with comorbid lung disease and highlights the importance of the data deduced from our study and similar studies in aiding the designation of vaccination programs for those patients if needed.
Changes in sleep and the prevalence of probable insomnia in undergraduate university students over the course of the COVID-19 pandemic: findings from the U-Flourish cohort study
Authors: King Nathan , Pickett William , Keown-Stoneman Charles D. G. , Miller Christopher B. , Li Melanie , Duffy Anne 
Published: November 2023

Background
Sleep problems associated with poor mental health and academic outcomes may have been exacerbated by the COVID-19 pandemic.

Aims
To describe sleep in undergraduate students during the COVID-19 pandemic.

Method
This longitudinal analysis included data from 9523 students over 4 years (2018–2022), associated with different pandemic phases. Students completed a biannual survey assessing risk factors, mental health symptoms and lifestyle, using validated measures. Sleep was assessed with the Sleep Condition Indicator (SCI-8). Propensity weights and multivariable log-binomial regressions were used to compare sleep in four successive first-year cohorts. Linear mixed-effects models were used to examine changes in sleep over academic semesters and years.

Results
There was an overall decrease in average SCI-8 scores, indicating worsening sleep across academic years (average change −0.42 per year; P-trend < 0.001), and an increase in probable insomnia at university entry (range 18.1–29.7%; P-trend < 0.001) before and up to the peak of the pandemic. Sleep improved somewhat in autumn 2021, when restrictions loosened. Students commonly reported daytime sleep problems, including mood, energy, relationships (36–48%) and concentration, productivity, and daytime sleepiness (54–66%). There was a consistent pattern of worsening sleep over the academic year. Probable insomnia was associated with increased cannabis use and passive screen time, and reduced recreation and exercise.

Conclusions
Sleep difficulties are common and persistent in students, were amplified by the pandemic and worsen over the academic year. Given the importance of sleep for well-being and academic success, a preventive focus on sleep hygiene, healthy lifestyle and low-intensity sleep interventions seems justified.
EDGE-Gastric Arm A1: Phase 2 study of domvanalimab, zimberelimab, and FOLFOX in first-line (1L) advanced gastroesophageal cancer.
Authors: Janjigian Yelena Y. , Oh Do-Youn , Pelster Meredith , Wainberg Zev A. , Sison Edward Allan R. , Scott Jennifer R. , Ronayne Jack , Wishengrad Dana , Rhee Joon , Nuyten Dimitry S. A. , Rha Sun Young 
Published: November 2023

433248 Background: The addition of programmed cell death protein 1 (PD-1) inhibitors to chemotherapy (chemo) confers a survival advantage in 1L gastroesophageal cancers. However, long term outcomes remain poor. Dual PD-1 and anti-T-cell immunoglobulin and ITM domain (TIGIT) blockade increases tumor antigen-specific CD8+ T cell expansion, resulting in potent antitumor activity. The ongoing, multi-arm, global EDGE-Gastric trial (NCT05329766) is evaluating the safety and efficacy of various combinations of the anti-TIGIT Fc-silent monoclonal antibody (mAb) domvanalimab (D) and the anti-PD-1 mAb zimberelimab (Z) in patients (pts) with locally advanced unresectable or metastatic gastric (G)/gastroesophageal junction (GEJ)/esophageal (E) adenocarcinoma. Arm A1 is fully enrolled and results from this 1L arm are presented here. Methods: Patients with previously untreated G/GEJ/E adenocarcinoma received D 1600 mg intravenously (IV) every 4 weeks (Q4W) + Z 480 mg IV Q4W + FOLFOX (oxaliplatin 85 mg/m2 IV, leucovorin 400 mg/m2 IV, fluorouracil 400 mg/m2 IV bolus + 2400 mg/m2 continuous 46-48-hour IV infusion) Q2W. Primary endpoints are safety and objective response rate (ORR) per RECIST 1.1. Secondary endpoints include ORR by PD-L1 expression and PFS. Results: As of the data cutoff (5 June 2023), 41 pts were enrolled and had the opportunity to have ≥2 imaging assessments. There was an even distribution of pts accrued in Asia vs. rest of world and 63% of pts had gastric cancer. Median time on treatment was 23 weeks (1 to 40), 31 pts (76%) continue on protocol therapy, and there were no deaths on study. Intent-to-treat ORR was 59% (95% CI 42 to 74). Clinical outcomes by PD-L1 status are in the Table. The most common treatment-emergent adverse events (TEAE) were neutropenia (56% of pts), nausea (54%), and anemia (27%). Infusion related reactions were observed in 10% and none were deemed related to D/Z. Grade ≥3 TEAEs occurred in 66% pts, with 54% and 12% having grade ≥3 TEAEs related to FOLFOX and D/Z, respectively. Serious TEAEs occurred in 24% pts: 7% had serious TEAEs related to FOLFOX and no pts had serious TEAEs related to D/Z. TEAE related FOLFOX discontinuation occurred in 13 pts (32%), and in 1 pt due to D/Z. Conclusions: Addition of DZ to FOLFOX showed encouraging ORR and early PFS, particularly in pts with PD-L1-high tumors. The regimen is well tolerated, with a similar AE profile to anti-PD-1+FOLFOX. Updated safety and efficacy will be presented. The randomized phase 3 1L STAR-221 trial of DZ+chemo vs. SOC is underway. Clinical trial information: NCT05329766 . [Table: see text]
Nanohybrid Based on (Mn, Zn) Ferrite Nanoparticles Functionalized With Chitosan and Sodium Alginate for Loading of Curcumin Against Human Breast Cancer Cells
Authors: Ahmadi Fatemeh , Saeedi Majid , Akbari Jafar , Seyedabadi Mohammad , Ebrahimnejad Pedram , Morteza-Semnani Katayoun , Ghasemi Shahram , Moalem-Banhangi Monire , Babaei Amirhossein , Hashemi Seyyed Mohammad Hassan , Asare-Addo Kofi , Nokhodchi Ali 
Published: November 2023

AbstractThis study reports on the synthesis of Mn1 − xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.
Graphical Abstract
Diabetes Mellitus, Energy Metabolism, and COVID-19
Authors: Conte Caterina , Cipponeri Elisa , Roden Michael 
Published: November 2023

Abstract
Obesity, diabetes mellitus (mostly type 2), and COVID-19 show mutual interactions because they are not only risk factors for both acute and chronic COVID-19 manifestations, but also because COVID-19 alters energy metabolism. Such metabolic alterations can lead to dysglycemia and long-lasting effects. Thus, the COVID-19 pandemic has the potential for a further rise of the diabetes pandemic. This review outlines how preexisting metabolic alterations spanning from excess visceral adipose tissue to hyperglycemia and overt diabetes may exacerbate COVID-19 severity. We also summarize the different effects of SARS-CoV-2 infection on the key organs and tissues orchestrating energy metabolism, including adipose tissue, liver, skeletal muscle, and pancreas. Last, we provide an integrative view of the metabolic derangements that occur during COVID-19. Altogether, this review allows for better understanding of the metabolic derangements occurring when a fire starts from a small flame, and thereby help reducing the impact of the COVID-19 pandemic.
Machine Learning Accelerated Discovery of Subnanoparticles for Electrocatalytic Hydrogen Evolution
Authors: Zou Quan , Kuzume Akiyoshi , Yoshida Masataka , Imaoka Takane , Yamamoto Kimihisa 
Published: November 2023

Abstract
Metal and alloy subnanoparticles (SNPs) have been anticipated to be a class of promising catalysts because of their fundamental difference from nanoparticles (NPs). In general, the interaction among the surface and bulk atoms of SNPs is significant due to the higher degree of alloying in SNPs than that in NPs counterparts. This study compared the SNPs and NPs concerning their electrocatalytic activities of hydrogen evolution reaction (HER) to understand the essential difference between alloy SNPs and NPs by using machine learning.
Measuring data access and re-use in the European Legal Framework for Data, from the General Data Protection Regulation (GDPR) law to the Proposed Data Act: the case of vehicle data
Authors: Crepax Tommaso , Gaur Mitisha , da Rosa Lazarotto Barbara 
Published: November 2023

This article delves into the difficulties and opportunities associated with the acquisition, sharing, and re-purposing of vehicle data, particularly information derived from black boxes used by insurance companies and event data recorders installed by manufacturers. While this data is usually utilized by insurers and car makers, it may benefit consumers, rival firms, and public institutions profiting from access to data for objectives such as data portability between insurance companies, traffic and transportation management, and the development of intelligent mobility solutions. Among other regulations, the authors examine the proposed Data Act as the European chosen champion to address the legal and technical hurdles surrounding the reuse of privately held corporate data, including privacy and intellectual property, competition, and data interoperability issues. The text also offers an overview of the sorts of data obtained through vehicle recording systems and their potential benefits for various stakeholders. This paper presents a methodology for comparing and evaluating, in an ordinal fashion, the degree of access conferred by various regulations and put it to practical use to assess how much data is currently left out from access by the existing legislation, how much of such data is covered by the Data Act, and ultimately, how much still remains inaccessible for reuse.
Amplitude training in occupational therapy for the treatment of Parkinson's disease: a feasibility study
Authors: Venturino Nicole , Stepansky Kasey , Rodak Casey , Cramer Samuel 
Published: November 2023

Background/Aims Parkinson Wellness Recovery Moves is a functional, large-amplitude exercise programme aimed at reducing the symptoms of Parkinson's disease. To date, evidence supports the use of amplitude training to reduce the symptoms of Parkinson's disease; however, evidence is lacking in the feasibility of using Parkinson Wellness Recovery Moves as an adjunct to occupational therapy within inpatient rehabilitation. The aim of this study was to evaluate the feasibility of implementing the Parkinson Wellness Recovery Moves intervention into the treatment of patients with Parkinson's disease, within an inpatient rehabilitation hospital. Methods A total of five adults with Parkinson's disease participated in this 11-week quasi-experimental feasibility trial. The use of Parkinson Wellness Recovery Moves was standardised, requiring each participant to engage in at least two occupational therapy sessions that included Parkinson Wellness Recovery Moves. Outcomes collected included fidelity of intervention implementation, and participant-centred outcomes of quality of life satisfaction and function via the Parkinson's Disease Questionnaire-39 and Section GG respectively. Results Each participant had a positive change in Section GG scores and completed between eight and 13 occupational therapy sessions that included Parkinson Wellness Recovery Moves. Four out of five participants reported higher quality of life at the time of discharge. Conclusions The use of Parkinson Wellness Recovery Moves was found to be feasible to implement within an inpatient rehabilitation hospital, with increased functional performance and improved quality of life.