bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct cell type-specific protein signatures in GRN and MAPT genetic subtypes of frontotemporal dementia
Authors: Miedema Suzanne S. M. , Mol Merel O. , Koopmans Frank T. W. , Hondius David C. , van Nierop Pim , Menden Kevin , de Veij Mestdagh Christina F. , van Rooij Jeroen , Ganz Andrea B. , Paliukhovich Iryna , Melhem Shamiram , Li Ka Wan , Holstege Henne , Rizzu Patrizia , van Kesteren Ronald E. , van Swieten John C. , Heutink Peter , Smit August B. 
Published: July 2022

AbstractFrontotemporal dementia is characterized by progressive atrophy of frontal and/or temporal cortices at an early age of onset. The disorder shows considerable clinical, pathological, and genetic heterogeneity. Here we investigated the proteomic signatures of frontal and temporal cortex from brains with frontotemporal dementia due to GRN and MAPT mutations to identify the key cell types and molecular pathways in their pathophysiology. We compared patients with mutations in the GRN gene (n = 9) or with mutations in the MAPT gene (n = 13) with non-demented controls (n = 11). Using quantitative proteomic analysis on laser-dissected tissues we identified brain region-specific protein signatures for both genetic subtypes. Using published single cell RNA expression data resources we deduced the involvement of major brain cell types in driving these different protein signatures. Subsequent gene ontology analysis identified distinct genetic subtype- and cell type-specific biological processes. For the GRN subtype, we observed a distinct role for immune processes related to endothelial cells and for mitochondrial dysregulation in neurons. For the MAPT subtype, we observed distinct involvement of dysregulated RNA processing, oligodendrocyte dysfunction, and axonal impairments. Comparison with an in-house protein signature of Alzheimer’s disease brains indicated that the observed alterations in RNA processing and oligodendrocyte function are distinct for the frontotemporal dementia MAPT subtype. Taken together, our results indicate the involvement of different brain cell types and biological mechanisms in genetic subtypes of frontotemporal dementia. Furthermore, we demonstrate that comparison of proteomic profiles of different disease entities can separate general neurodegenerative processes from disease-specific pathways, which may aid the development of disease subtype-specific treatment strategies.
Identification of mRNA vaccines and conserved ferroptosis related immune landscape for individual precision treatment in bladder cancer
Authors: Gui Cheng-Peng , Li Jia-Ying , Fu Liang-Min , Luo Cheng-Gong , Zhang Chi , Tang Yi-Ming , Zhang Li-zhen , Shu Guan-nan , Wu Rong-Pei , Luo Jun-Hang 
Published: July 2022

Abstract
Background
The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment.

Methods
Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment.

Results
Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits.

Conclusions
TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy.
High tibial osteotomy for medial meniscus posterior root tears in knees with moderate varus alignment can achieve favorable clinical outcomes
Authors: Itou Junya , Kuwashima Umito , Itoh Masafumi , Okazaki Ken 
Published: July 2022

Abstract
Purpose
Favorable clinical results have been reported following high tibial osteotomy (HTO) for medial meniscus posterior root tear (MMPRT) in knees with varus alignment. However, the effect on the preoperative neutral alignment of the knee is not known. This study sought to evaluate the clinical outcomes of medial open-wedge HTO for MMPRT with neutral alignment.

Methods
We retrospectively reviewed 119 medial open-wedge HTOs and analyzed 22 knees with MMPRT. The knees were divided according to the preoperative hip-knee-ankle angle into a moderate varus alignment group (≤4° of varus alignment) and a varus alignment group (> 4° of varus alignment). The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Forgotten Joint Score-12 (FJS-12) values were evaluated preoperatively and at the latest follow-up. The healing status of MMPRT at the time of second-look arthroscopy, performed at a mean of 15.4 ± 4.2 months, was compared with that after the primary HTO.

Results
There were 11 knees in the moderate varus alignment group and 11 in the varus alignment group. In terms of perioperative patient-reported outcome measures, there was no significant difference in the preoperative or postoperative KOOS subscale score or FJS-12 score between the moderate varus and varus alignment groups. The healing rate was significantly higher in the moderate varus alignment group.

Conclusion
Favorable clinical results were obtained by medial open-wedge HTO in knees with MMPRT and moderate varus alignment in the short term. Surgeons should consider the indications for medial open-wedge HTO, even with moderate varus alignment, when planning treatment for MMPRT with persistent knee pain.

Level of evidence
IV
Plugging efficiency of pouring aggregates through multiple boreholes into an inundated tunnel to prevent groundwater inrush disasters
Authors: Hui Shuang , Sui Wanghua , Zhang Gailing , Chen Jiaxing , Yu Shibo 
Published: July 2022

AbstractThis paper presents an experimental investigation of the plugging efficiency of aggregate pouring through multiple boreholes under flowing water conditions into an inundated mine tunnel. Aggregate pouring into an inundated mine tunnel has been widely used and constitutes the premise for the salvage of flooded underground mines through further grouting. However, corresponding in-depth research is relatively limited due to the concealment of underground engineering. A visual experimental setup for aggregate pouring into a tunnel replica was built based on the theory of similarity between sediment movement and slurry pipeline transportation. Four factors, each with four levels, including the aggregate particle size (0.25–0.5, 0.5–1, 1–2 and 2–5 mm), distance between boreholes (0.5, 0.75, 1 and 1.5 m), initial water flow rate (0, 1.5 × 10−2 m/s, 2.4 × 10−2 m/s and 3 × 10−2 m/s) and tunnel inclination (0°, 3°, 5° and 8°) were selected in orthogonal experiments to investigate the plugging efficiency. Range and variance analysis of the four-level orthogonal array experimental results indicated that the factors influencing the plugging efficiency, varying between 83.96 and 98.15%, could be ranked in descending order as the initial water flow rate, aggregate particle size, distance between boreholes and tunnel inclination. The former two factors yielded a more significant influence than that of the latter two factors. The measured water pressure difference ranging from 16 to 32% between the front and back ends of the formed aggregate mass in the pouring process indicated that there remained a high resistance to water flow, even if the aggregate mass was not capped but reached a certain length. Plugging criteria for aggregate pouring into horizontal and inclined tunnels were then proposed. Moreover, the optimal distance between boreholes to form an effective bulkhead was determined, which could be defined as the distance between boreholes when the aggregate mass exhibits the fastest build-up and the plugging capacity is reached.
Over-prescription of short-acting β2-agonists and asthma management in the Gulf region: a multicountry observational study
Authors: Alzaabi Ashraf , Al Busaidi Nasser , Pradhan Rohit , Shandy Fathelrahman , Ibrahim Naseem , Ashtar Moulham , Khudadah Khaled , Hegazy Khaled , Samir Mohamed , Negm Mohamed , Farouk Hisham , Al Khalidi Arwa , Beekman Maarten 
Published: July 2022

Abstract
Background
The overuse of short-acting β2-agonists (SABA) is associated with poor asthma control. However, data on SABA use in the Gulf region are limited. Herein, we describe SABA prescription practices and clinical outcomes in patients with asthma from the Gulf cohort of the SABA use IN Asthma (SABINA) III study.

Methods
In this cross-sectional study conducted at 16 sites across Kuwait, Oman, and the United Arab Emirates, eligible patients (aged ≥ 12 years) with asthma were classified based on investigator-defined disease severity guided by the 2017 Global Initiative for Asthma report and by practice type, i.e., respiratory specialist or primary care physician. Data on demographics, disease characteristics, and prescribed asthma treatments, including SABA, in the 12 months prior to a single, prospective, study visit were transcribed onto electronic case report forms (eCRFs). All analyses were descriptive in nature. Continuous variables were summarized by the number of non-missing values, given as mean (standard deviation [SD]) and median (range). Categorical variables were summarized by frequency counts and percentages.

Results
This study analyzed data from 301 patients with asthma, 54.5% of whom were treated by respiratory specialists. Most patients were female (61.8%), with a mean age of 43.9 years, and 84.4% were classified with moderate-to-severe disease, with a mean (SD) asthma duration of 14.8 (10.8) years. Asthma was partly controlled or uncontrolled in 51.2% of patients, with 41.9% experiencing ≥ 1 severe exacerbation in the 12 months preceding their study visit. Overall, 58.5% of patients were prescribed ≥ 3 SABA canisters, 19.3% were prescribed ≥ 10 canisters, and 13.3% purchased SABA over-the-counter (OTC) in the 12 months before the study visit. Most patients who purchased OTC SABA (92.5%) also received SABA prescriptions. Inhaled corticosteroid/long-acting β2-agonist combinations and oral corticosteroid bursts were prescribed to 87.7% and 22.6% of patients, respectively.

Conclusions
SABA over-prescription was highly prevalent in the Gulf region, compounded by purchases of nonprescription SABA and suboptimal asthma-related outcomes. Increased awareness among policymakers and healthcare practitioners is needed to ensure implementation of current, evidence-based, treatment recommendations to optimize asthma management in this region.

Trial registration
NCT03857178 (ClinicalTrials.gov).
Muscle activation patterns around knee following neuromuscular training in patients with knee osteoarthritis: secondary analysis of a randomized clinical trial
Authors: Rashid Shahzada Aadil , Hussain Mohammad Ejaz , Bhati Pooja , Veqar Zubia , Parveen Adila , Amin Insha , Rashid Shahzada Mudasir 
Published: July 2022

Abstract
Objective
To compare the effects of neuromuscular training (NMT) to a quadriceps strength training (QT) program on co-contraction index (CCI) of knee muscles in patients with knee osteoarthritis (OA).

Methods
Sixty-six knee OA patients with varus malalignment were recruited from the physiotherapy outpatient department of the university. After baseline measurements, they were randomly assigned into two groups: NMT (n = 33) and QT (n = 33). Patients in NMT group received neuromuscular exercises whereas QT group received conventional strengthening exercises for a period of 12 weeks, three times per week. Electromyographic (EMG) activity of quadriceps, hamstring and gastrocnemius muscle was evaluated during treadmill walking before and after 12 weeks of intervention period and CCI of medial quadriceps-medial hamstring (med QH), lateral quadriceps-lateral hamstring (lat QH), medial quadriceps-medial gastrocnemius (med QG) and, lateral quadriceps and lateral gastrocnemius (lat QG) was calculated.

Results
There was a significantly greater reduction in CCI of med QH (p = 0.02) and lat QH (p = 0.01) in the NMT group than the QT group. Whereas both NMT and QT led to statistically similar reductions in CCI of med QG (p = 0.08) and lat QG (p = 0.66).

Conclusion
Findings of this study suggest that NMT led to a greater reduction in CCI of knee muscles than QT which indicates that enhanced sensori-motor control attained by NMT could reduce knee loading in knee OA patients with varus malalignment.
Pediatric vs. adult stroke: comparative study in a tertiary referral hospital, Cairo, Egypt
Authors: Alloush Ramy , Eldin Nahed Salah , El-Khawas Hala , Shatla Rania , Nada Maha , Mohammed Maha Z. , Alloush Adel 
Published: July 2022

Abstract
Background
Even though stroke is rare in children, it is associated with serious or life-threatening consequences. Despite its rarity, the occurrence of stroke in children has age-related differences in risk factors, etiopathogenesis, and clinical presentations. Unlike adults, who have arteriosclerosis as the major cause of stroke, risk factors for pediatric strokes are multiple, including cardiac disorders, infection, prothrombotic disorders, moyamoya disease, moyamoya syndrome, and others. The goal of the current study was to compare the characteristics, clinical features, etiology, subtypes, and workup of pediatric and adult strokes.

Methods
This was a hospital-based observational study conducted on 222 participants. All patients underwent a full clinical and neurological examination, full laboratory study, cardiac evaluation, and neuroimaging; CT scan, MRI, MRA, MRV, carotid duplex, and transcranial Doppler (TCD). Ischemic stroke (IS) etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, the "proposed classification for subtypes of arterial ischemic stroke in children," and the Oxfordshire Community Stroke Project (OCSP). Stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) and PedNIHSS on admission.

Results
The proportion of pediatric ischemic strokes in the current study was 63.4 percent, while hemorrhagic strokes were 36.5%. The majority of the adult patients had ischemic strokes (84.1%), while hemorrhagic strokes were noted in 15.8% of the patients. According to the original TOAST classification, in the current study, the etiology of pediatric IS was other determined causes in 63.6%, undetermined etiology in 27.2%, and cardioembolic in 9.0%. For the adult group, the major stroke subtypes were large artery disease, small vessel disease, cardioembolic, other determined causes, and undetermined etiology at 49.6%, 28.6%, 6.9%, 0.6%, and 12.5%, respectively.

Conclusions
There is a greater etiological role for non-atherosclerotic arteriopathies, coagulopathies, and hematological disorders in pediatric stroke, while adults have more atherothrombotic causes. The co-existence of multiple risk factors in pediatric ischemic stroke is noticed. Thrombophilia evaluation is helpful in every case of childhood stroke. Children who have had a stroke should undergo vascular imaging as soon as possible. Imaging modalities include TCD and Doppler ultrasound, CT, MRI, MRA, and MRV, and cerebral angiography.
The relationship between myasthenia gravis and COVID-19: a systematic review
Authors: Tugasworo Dodik , Kurnianto Aditya , Retnaningsih  , Andhitara Yovita , Ardhini Rahmi , Budiman Jethro 
Published: July 2022

AbstractIntroductionViral infection such as coronavirus disease 2019 (COVID-19) can exacerbate and aggravate neurological disorders due to autoimmune etiology like myasthenia gravis (MG). Experimental therapies used in COVID-19 are also factors that can cause the worsening of MG symptoms. This review aimed to assess and conclude the research-based study systematically to analyze the relationship of MG and COVID-19.MethodThis study was conducted in accordance to Cochrane handbook for systematic reviews and the guideline of preferred reporting items for systematic review and meta-analysis (PRISMA) and synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. Inclusion criteria in this review were primary studies of every design, articles published in English around January 2000–October 2021, and the study used human as subject. A systematic literature finding was applied in 15 electronic scientific resources. The authors evaluated the study quality and risk of bias of each retrieved article.ResultsThe authors found the study through electronic scientific resources that met inclusion and exclusion criteria. The authors evaluated 362 articles identified in literature searching, 22 articles met the criteria for this review and then underwent the evaluation of study quality and risk of bias.ConclusionCOVID-19 infection can increase the risk of new-onset MG, myasthenic crisis, respiratory failure, and mortality rate due to cytokine storm in MG patients. The management of COVID-19 patients with MG is tailored to each person and based on national guidelines and local expert recommendations.
Childhood depression and oxidative stress
Authors: Yıldız Miniksar Dilşad , Göçmen Ayşe Yeşim 
Published: July 2022

Abstract
Background
Oxidative stress is a contributing factor in the etiopathogenesis of major depressive disorder (MDD). Pediatric studies regarding MDD-oxidative stress relationship are insufficient. In this study, we aimed to compare oxidative stress parameters of pediatric MDD patients with those of the control group and to examine factors affecting these parameters.

Results
Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), malondialdehyde (MDA) and superoxide dismutase (SOD) activities of 42 patients with MDD and 38 healthy controls were evaluated. Children depression inventory (CDI) was applied to all participants. In the MDD group, serum levels of TOS, OSI and MDA were higher, while TAS and SOD levels were lower (p < 0.001). When all participants were examined, oxidative stress increased as the CDI score increased, but in the MDD group, SOD increased as the CDI score increased. Increase in body mass index (BMI) percentile increased the oxidative stress in the MDD group. When factors affecting the presence of MDD were analyzed by binary logistic regression analysis, a one-unit increase in SOD decreased depression by 0.190 times.

Conclusions
This study showed that oxidative stress increases in children and adolescents with MDD, and the increase in the severity of depression further increases oxidative stress, but when the depression becomes very severe, level of SOD increases compensatorily. It has been observed that high BMI in MDD patients creates an additional burden on oxidative stress. The role of oxidative stress in the etiopathogenesis of MDD in children and adolescents should be evaluated more comprehensively.
Coronavirus disease 2019 in proportion to population: a historical analysis of Saudi Arabia
Authors: Salam Asharaf Abdul , Al-Khraif Rshood M. , Dilip Thandassery R. , Elsegaey Ibrahim 
Published: July 2022

Abstract
Background
Saudi Arabia is one of the countries seriously affected by coronavirus disease 2019 (COVID-19) worldwide. With a few cases in early March, the daily spread of this disease increased to nearly 5000 at one point in time during the first wave to mid-June 2020. With committed efforts and public health interventions, it has been controlled to nearly 1000 by the end of August 2020 and less than 217 by November 28, 2020; thereafter, reporting declines and small increases. However, by December 2021, a third wave started, lasting for 2 months, during which the infection rate increased rapidly. By April 1, 2022, the number of infected persons in the country was 750,998, with 9047 deaths, 7131 active, and approximately 400 critical cases. This analysis of COVID-19 statistics of the Ministry of Health of Saudi Arabia (March 2020–April 2022) is carried out along with population data to extract patient proportions per 100,000 persons to illustrate the hypothesized social and community impact, which influences families and households.

Results
The results showed a high rate of infection and mortality, but with recovery. These rates varied across localities and cities. A few cities with higher population densities are less affected by the spread of the epidemic. However, few localities and upcoming cities/townships were severely affected. These effects are explained as the percentage of the population affected, which exposes the impact on societies, families, and individual members. With concerted efforts, they are brought under control through recovery and adopting mitigation methods.

Conclusions
Localities could be classified into four categories based on the proportion of the infected population: rapidly increasing, moderately increasing, declining, and stabilizing. Moreover, differential proportions of the affected population have implications at social and familial levels. Analysis and understanding of these trends, considering the base population, are important for policy building and intervention strategies accounting for grassroots-level demographics, which might serve as a tool to enhance interventions at population and family levels. Strategies for awareness creation and compassionate care are essential to address the psychosocial impact of health emergencies, as proved by the Ministry of Health, Saudi Arabia.
Nanoformulated rosemary extract impact on oral cancer: in vitro study
Authors: Ellithy Marwa Mohamed , Aly Riham Mohamed , Tarek Heba El-Sayed 
Published: July 2022

Abstract
Background
Treating cancer is challenging for both the patient and the physician. This may be explained by the fact that treatment regimens rely on either chemotherapy alone or a combination with radiotherapy. Both modalities have damaging side effects that add to the patient suffer. This inconvenience from the patient part has led scientists to search for discovering new era in cancer management. Plant extracts have proved to be beneficial in many medical fields. Not surprisingly, tumor prevention and therapy is one of these bright fields. Rosmarinus Officinalis has attracted many researchers due to its diverse pharmaceutical capabilities. New drug delivery systems must be set to overcome biomedical as well as biophysical barriers. Nanoformulation of therapeutic agents may help bypassing these burdens. The aim of the present study was to investigate the role of rosemary extract (RE) loaded on chitosan nanoparticles as a cancer treatment modality. Synthesis of nanoparticles encapsulating rosemary extract was performed with subsequent characterization by electron microscopy. Assessment of their effect on OSCC cell line (Hep-2) regarding cell cytotoxicity and impact on cell cycle and apoptotic pathway as well as intracellular ROS quantification was performed.

Results
RE nanoparticles were found to be cytotoxic to Hep-2 cells in a dose-dependent manner. They induced apoptotic changes as well as cell cycle arrest at G2/M phase. They enhanced ROS expression in cancer cells. Autophagosomes appeared in treated cells.

Conclusion
Finally, it could be concluded that RE nanoparticles may be a new candidate in the field of cancer management, mainly oral cancer.