bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDA Orphan Designations, Approvals, and Regulatory Review Time since the Enactment of the Orphan Drug Act (1983)
Authors: Althobaiti Hana , Seoane-Vazquez Enrique , Brown Lawrence M , Fleming Marc L. , Rodriguez-Monguio Rosa 
Published: August 2022

Abstract
Background
Drug approvals for rare diseases and conditions have increased significantly since the Orphan Drug Act (ODA) enactment in 1983. Yet, the factors explaining the increase in orphan drug approvals are poorly understood. This study assessed the characteristics of orphan drug designations and approvals and evaluated factors associated with the approval of orphan designations and the time lag between orphan designation and approval in the US from 1983 to 2021.
Methods
Data were collected from the FDA Orphan Drug Product Designations and Approvals database of the FDA Office of Orphan Products Development. We conducted regression analyses to ascertain factors associated with the likelihood of approval of an orphan designation and the time lag between orphan designation and approval after controlling for the orphan drug designation date.
Results
As of December 31, 2021, the FDA had granted 6,137 orphan designations and 1,045 (17.0%) orphan drug approvals of which 285 drugs (27.3%) were first approved for non-rare diseases and conditions. FDA granted an annual average of 90.4 orphan designations since implementing the Orphan Drug Modernization Plan (ODMP) through December 31, 2021. After controlling for the orphan drug designation date, drugs with prior orphan designations, drugs sponsored by companies that had already obtained orphan approval, and drugs with orphan pediatric indications had a greater likelihood of approval. The time lag from orphan designation to approval was inversely associated with the number of prior orphan approvals of the sponsored company and the implementation of the ODMP.
Conclusions
The number of FDA approved orphan drugs increased significantly after enacting the Orphan Drug Act of 1983. The likelihood of approval of an orphan drug designation and the time lag from orphan designation to approval was significantly associated with enacted regulation, the experience of the sponsor companies obtaining orphan approval, the patient population indication, and previous designation for other orphan indications. There is a significant reduction in the time lag between orphan drug designation and approval after ODMP enactment.
Neuropilin-2 upregulation by stromal TGFβ1 induces lung disseminated tumour cells dormancy escape and promotes metastasis outgrowth
Authors: Recalde-Percaz Leire , Jauregui Patricia , López-Plana Anna , Fernandéz-Nogueira Patricia , Iniesta-González Minerva , Manzano Sara , Alonso Raul , Noguera-Castells Aleix , Moragas Nuria , Baquero Cristina , Rodrigo-Faus Maria , Palao Nerea , Dalla Erica , Aviles-Jurado Francesc Xavier , Vilaseca Isabel , Camacho Mercedes , Leon-Vintro Xavier , Fuster Gemma , Alcaraz Jordi , Aguirre-Ghiso Julio , Gascón Pere , Gutierrez-Uzquiza Álvaro , Porras Almudena , Carbo Neus , Bragado Paloma 
Published: August 2022

Abstract
Metastasis is the main cause of death from solid tumours and, therefore, identifying the mechanisms that govern metastatic growth poses a major biomedical challenge. We and others have contributed to demonstrate that tumour microenvironment (TME) signals regulate the fate and survival of disseminated tumour cells (DTCs) in secondary organs. However, very little is known about the role of the nervous system mediators in this process. We have previously described that neuropilin-2 (NRP2) expression in breast cancer correlates with bad prognosis. Here we describe that NRP2 positively regulates breast and head and neck cancer cells proliferation, invasion and survival in vitro. NRP2 deletion in tumour cells inhibits tumour growth in vivo and decreases the number and size of lung metastases by promoting p27-mediated lung DTCs quiescence. Moreover, we show that several abundant stromal cells of the lung, such as fibroblasts and macrophages, induce NRP2 upregulation in DTCs, through secretion of TGFβ1. Therefore, we conclude that the TGFβ1-NRP2 axis is a new key dormancy awakening inducer, promoting DTCs proliferation and lung metastases development, positioning NRP2 expression as a central biomarker to predict metastatic recurrences and as a potential candidate for advanced therapies.
Development of a Survey-based Women Empowerment Index for Afghanistan (SWEIA): An Explanatory Analyses of the Afghanistan Demographic Health Survey 2015
Authors: Dadras Omid 
Published: August 2022

Abstract
Background
Although there are several scales to measure women empowerment, the multidimensionality of women empowerment introduced enormous challenges in the quantification and comparability of the results across different contexts. Therefore, in this study, we aimed to develop a country-specific index to measure women's empowerment in Afghanistan.
Methods
The data from the 2015 Afghanistan demographic health survey (ADHS) was used for the analysis. The dataset was randomly divided into two samples‒one for exploratory factor analysis (EFA) and the other for confirmatory factor analysis (CFA)‒ of women aged 15–49 years. The data on 26 variables across different domains (labor force participation, attitude toward violence, decision-making, access to healthcare, literacy, age at critical life events, and property-owning) were used in EFA to probe the underlying domains in the data. CFA examines the structural validity of hypothesized factors in EFA.
Results
The final model included 22 indicators across seven domains including labor force participation, attitude toward violence, decision-making, access to healthcare, literacy, age at critical life events, and property-owning.
Discussion
The index developed in this study shares a common ground for future research concerning Afghan women empowerment and its associated outcomes such as intimate partner violence, reproductive and maternity outcomes, and child health; thus, enhancing the comparability of the results. In addition, having a standard index for women empowerment at the individual and country level could help assess the progress and efforts that have been made to achieve gender equality (SDG 5), and guide the direction of future policies and interventions.
The value of undenatured collagen for the normalization of the function of the cartilaginous tissue of the joints
Authors: Dydykina I. S. , Kovalenko P. S. , Kovalenko A. A. , Aboleshina A. V. 
Published: August 2022

Among the proteins of the human body, collagen accounts for at least 25–45% collagen; it is an essential structural component of skeletal tissues, connective tissue of internal organs (heart, intestines, lungs, liver, kidneys), as well as blood vessels. The variety of types of collagen is due to their role and function. The article presents information about the structure and synthesis of collagen, a high concentration of glycine, proline and hydroxyproline in the alpha chains of the collagen helix. Attention is drawn to the fact that cross-links and orientation of collagen fibers in the direction of the vector of external forces and loads provide protection to tissues and organs. The clinical significance of type II collagen is considered on the example of the cartilaginous tissue of the joints and tendons. It is emphasized that an imbalance in the structure of nutrition, genetic mutations, dysfunction of the endocrine and immune systems, especially in old age, are associated with the occurrence of one of the most common joint diseases – osteoarthritis (ОА). It has been established that the degradation or reduction of type II collagen in the cartilage matrix is accompanied by the progression of this disease. Due to the increasing prevalence of OA, signs of metabolic disorders and post-traumatic joint injuries, there is a growing interest in non-pharmacological and pharmacological interventions for the prevention and treatment of osteoarthritis. In recent years, convincing evidence has emerged of the successful use of drugs (biologically active food supplements) of collagen in osteoarthritis. The article presents the results of experimental and clinical studies, meta-analysis and systematic review, confirming the possibility of using these drugs (products) as part of the complex treatment of OA. The possibility of using compositions based on undenatured (native) collagen type II, with the inclusion of ascorbic acid, vitamin D, methylsulfonylmethane and boswellic acids promotes the synergy of these substances, slows down the rate of cartilage destruction, reduces the manifestation of pain and inflammation in the joints, improves functional joint and spinal conditions, promotes the synthesis of endogenous collagen.
What affects the neurovisualisational detection of ischemic stroke?
Authors: Akhatova Z. A. , Musin R. S. , Vlasov P. N. , Trukhanov S. A. , Makarova Yu. I. 
Published: August 2022

Introduction. The incidence of stroke is 2.5–3 cases per 1 000 population per year, mortality – 1 case per 1 000 population per year. According to various data, up to 20% of computed tomography (CT) scans performed on the first day do not reveal signs of an ischemic focus.Aim of the study. To assess the detectability of acute ischemia foci using CT, depending on the location of the foci, the timing of neuroimaging, the severity of stroke, and other indicators.Material and methods. We analyzed 100 cases of acute cerebrovascular accident (ACV) by ischemic type. The timing of the CT scan, glucose level, coagulogram parameters, NIHSS scores at admission, focus localization, the presence of atherosclerosis of the arteries of the head, and atrial fibrillation were taken into account. Patients were divided into two groups depending on the fact of detection of the focus during the primary tomographic examination. Repeated neuroimaging (magnetic resonance imaging) was performed in 54 patients.Results. In the “CT-negative” group, stem strokes predominated (p = 0.01), patients were younger (р = 0.038), and there were significantly more women than men (р = 0.00006). An increase in glucose over 8 mmol/l, on the contrary, was more often detected in the “CT-positive” group (14 cases in “CT-positive” against 5 cases in “CT-negative” group, p = 0.022). NIHSS scores ≥ 5 were found in 24 patients (47%) in the “CT-positive” group and in 13 patients (26.5%) in the “CT-negative” group (p = 0.034).Conclusions. Cases of stroke that are not detected on CT scan upon admission to the hospital are more common among women, with stem localization, are associated with low NIHSS scores. High glucose levels at admission is associated with the detection of ischemic foci during the initial CT examination.
Functional ingredient taurine: adequate and clinically effective doses
Authors: Kodentsova V. M. , Risnik D. V. , Ladodo O. B. 
Published: August 2022

Taurine is a sulfur-containing amino acid. Taurine is necessary for the conjugation of bile acids, has antioxidant, anti-inflammatory properties, acts as an anti-apoptotic factor; cell membrane stabilizer; regulator of Ca2+ signaling, fluid homeostasis in cells, retinal photoreceptor activity; contributes to osmoregulation and conduction in the nervous and muscular systems; a neurodevelopmental stimulant; and an inhibitory neurotransmitter in the central nervous system. Taurine is not only synthesized from cysteine and methionine, but also comes from food. Taurine intake is 40–400 mg/day. The main food sources are animal products: shellfish, fish, meat. Taurine is part of breast milk and adapted milk formulas for the nutrition of young children. Under stress and some diseases, the endogenous synthesis of taurine is reduced. The risk groups for taurine deficiency include people who follow a vegetarian diet and observe religious fasts. There are a number of products in which taurine is added: specialized food products (SF) and food supplements (FS) contain 60–1200 mg of taurine per serving, energy drinks – 300–400 mg per 100 ml. The clinical effects of taurine in diabetes mellitus, heart failure are manifested when it is included in diet therapy in doses of 1.5–3 g for 2–16 weeks. Even the maximum doses allowed for use as part of SFP and dietary supplements are significantly less than the doses that ensure the achievement of a clinical effect, which does not guarantee the expected result when using SF.
Evaluation of the rate of anterior segment retraction in orthodontic patients with bimaxillary protrusion using friction vs frictionless mechanics: a single-center, single-blind randomized clinical trial
Authors: Tawfik Monica Guirguis Youssif , Izzat Bakhit Dorra M. H. D. , El Sharaby Fouad A. , Moustafa Yehya A. , Dehis Heba Mohamed 
Published: August 2022

ABSTRACT

Objectives
To evaluate the effect of friction vs frictionless mechanics on the rate of anterior segment retraction (ASR) in patients with bimaxillary protrusion.

Materials and Methods
Thirty females (18.3 ± 3.7 years) with bimaxillary protrusion were randomly allocated into the friction group, using elastomeric power chains, and the frictionless group, using T-loop springs for ASR. Eligibility criteria included absence of skeletal discrepancies and any systemic diseases or medications, among others. Randomization in a 1:1 ratio was generated by Microsoft Excel. Opaque sealed envelopes were sequentially numbered for allocation concealment. Only blinding of the outcome assessor was applicable. Activations were done every 4 weeks until completion of ASR. The primary outcome was the rate of ASR measured on digital models. Anchorage loss, molar rotation, and pain experienced were also assessed.

Results
Two patients were lost to follow-up. The rate of ASR was 0.68 ± 0.18 mm/mo in the friction group vs 0.88 ± 0.27 mm/mo in the frictionless group, with no significant difference. A significant difference in anchorage loss of 1.63 mm and molar rotation of 7.06° was observed, being higher in the frictionless group. A comparable pain experience associated with both mechanics was reported.

Conclusions
No difference in the rate of ASR or pain experience was observed between friction and frictionless mechanics. However, extra anchorage measures should be considered when using frictionless mechanics as greater anchorage loss and molar rotations are anticipated.
Pengembangan Model Permainan Futsal Kids
Authors: Dewi Rahma , T.Sihaloho Sahman 
Published: August 2022

Penelitian ini bertujuan untuk mengembangkan model permainan futsal kids. Populasi dalam penelitian ini adalah anak sekolah dasar yang berasal dari 6 sekolah dasar yang ada di Sumatera utara, yaitu SD Genesis Medan, SD 1 HKBP Sidorame Medan, SD 2 HKBP Sidorame Medan, SD Negeri 127696 Pematangsiantar, SD Negeri 122384 Pematangsiantar, dan SD Negeri 124391 Pematangsiantar, Sumatera utara. Model yang telah dibuat terlebih dahulu divalidasi 3 orang ahli, 1 orang ahli akademisi olahraga, 1 orang ahli pelatih dan 1 orang ahli wasit. Uji kelompok kecil melibatkan 36 orang anak sekolah dasar dan uji kelompok besar melibatkan 72 orang anak sekolah dasar. Model permainan futsal kids telah divalidasi dan hasil dari validasi ahli bahwa setiap model valid dan dapat digunakan sebagai model permainan futsal untuk anak-anak, dengan persentase validitasnya 72%-89%. Hasil uji kelompok kecil terhadap 36 orang anak sekolah dasar menunjukkan bahwa model permainan futsal kids sudah memenuhi kriteria layak atau valid. Persentase validitas dari angket yang telah dibagikan kepada sampel menunjukkan bahwa 93%-100% mereka mengakui bahwa futsal kids tersebut sudah memenuhi kriteria. Hasil uji kelompok besar terhadap 72 orang anak sekolah dasar menunjukkan bahwa model permainan futsal kids sudah memenuhi kriteria layak atau valid. Persentase validitas dari angket yang telah dibagikan kepada sampel menunjukkan bahwa 92%-100% mereka mengakui bahwa futsal kids tersebut sudah memenuhi kriteria
Efektivitas Penggunaan Difa SS Pada Soil-Bottom Ash Dan Soil Cement Dalam Meminimalkan Kerusakan Sub-Grade Jalan
Authors: Sumiati Sumiati , Mahmuda Mahmuda , Indra Siswa 
Published: August 2022

<p align="center"><strong>Abstrak</strong></p><p> </p><p class="11daftarpustaka">Salah satu penyebab kerusakan jalan adalah seringnya struktur perkerasan jalan terendam air saat musim hujan. Tanah lempung berplastisitas tinggi mempunyai sifat fisik dan teknik yang kurang baik jika digunakan sebagai lapisan tanah dasar (<em>sub grade</em>), karena mempunyai sifat kembang susut yang tinggi dan nilai CBR yang rendah jika terendam air. Stabilisasi menggunakan <em>chemical additive</em> dan limbah pabrik merupakan salah satu cara untuk memperbaiki sifat fisik dan teknik tanah, di mana akan memberikan hasil yang memadai jika komposisi campuran yang digunakan sesuai dan tepat. Oleh sebab itu akan diteliti efektifitas penggunaan aditif Difa SS pada <em>Soil-Bottom ash</em> dan <em>Soil-Cement</em> dengan melakukan pengujian CBR laboratorium <em>unsoaked </em>dan <em>soaked</em>. Hasil penelitian didapatkan bahwa penambahan Difa SS tidak memberikan peningkatan nilai CBR <em>soaked</em> pada <em>Soil-bottom ash</em>. Nilai CBR <em>soaked</em> <em>Soil-Cement</em> menunjukkan peningkatan dan lebih besar dibandingkan nilai CBR <em>unsoaked</em> sehingga Difa SS lebih efektif digunakan sebagai <em>chemical additive</em> pada <em>Soil-Cement</em> dalam usaha meminimalkan kerusakan jalan.</p><p class="11daftarpustaka"> </p><p class="11daftarpustaka">Kata kunci: <em>tanah-bottom ash, tanah-semen, Difa soil stabilizer.</em><em></em></p><p align="center"><strong> </strong></p><p align="center"><strong> </strong></p><p align="center"><strong>Abstract</strong></p><p> </p><p class="11daftarpustaka">One of the causes of road damage is that the pavement structure is often submerged in water during the rainy season. High plasticity clays soils have poor physical and technical properties when used as a subgrade layer, because they have high sweeling and shrinkage properties and low CBR values when submerged in water. Stabilization using chemical additives and factory waste is one way to improve the physical and engineering properties of the soil, which will give adequate results if the composition of the mixture used is appropriate and appropriate. Therefore, the effectiveness of the use of Difa SS additive in Soil-Bottom ash and Soil-Cement will be investigated by conducting unsoaked and soaked laboratory CBR testing. The results showed that the addition of Difa SS did not increase the soaked CBR value in soil-bottom ash. Soil-Cement soaked CBR value shows an increase and is greater than the unsoaked CBR value so that Difa SS is more effectively used as a chemical additive in Soil-Cement in an effort to minimize road damage.</p><p class="11daftarpustaka"> </p><p class="11daftarpustaka">Keywords: <em>soil-bottom ash, </em><em>soil-</em><em>cemen</em><em>t, Difa soil stabilizer </em><em></em></p><p class="11daftarpustaka"> </p>
Clinical Severity of Patients with COVID-19 Presenting to Nepal Armed Police Force Hospital: A Descriptive Cross-sectional Study
Authors: Nepal Prabin , Thapa Ashish , Rawal Prabhat , Dhungana Sundar , Parajuli Roshan 
Published: August 2022

Introduction: Coronavirus Disease 2019 (COVID-19), since its emergence, has spread rapidly as a pandemic causing massive loss of human life. This study aims to describe clinical severity of the disease in relation to age, mode of oxygen delivery and clinical outcome of patients admitted to a tertiary care center in Nepal.
Methods: This was a descriptive cross-sectional study of data records of 130 COVID-19 patients 18 years and above admitted in Nepal Armed Police Force Hospital from April 2021 to June 2021 with Severe Acute Respiratory syndrome SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction positive status. Ethical approval was obtained from Nepal Health research Council. Data were collected using structured proforma and analyzed using SPSS version 23.
Results: Patients with severe illness (52/130) constituted 40% of the bulk of COVID-19 patients, 48 of them requiring intensive care. Among them, 38.5% required non-invasive ventilation and 32.7% were intubated during treatment. Severity of illness was variable among different age groups but mortality was high among severely ill patients, 19/52 (36.5%) and with increasing age. The overall mortality was 19/130 (14%) over the study period, all of which were among severely ill patients.
Conclusions: Most of the clinically severe cases required Intensive Care Unit admission, the majority receiving oxygen therapy via non-invasive or invasive mechanical ventilation, with a high mortality rate. The number of severely ill COVID-19 patients was variable in different age groups. Mortality, however, was observed in severely ill patients only and proportionately increased in COVID-19 patients with advancing age.
Prevalence of Risk Factors of Cardiovascular Diseases among Government Employees of Hetauda Sub-Metropolitan City
Authors: Sapkota Suprima , Devkota Nishchal , Nepal Sujita 
Published: August 2022

Introduction: The epidemiological transition in Nepal has increased the burden of non-communicable diseases which have resulted in lower production and longer disability. Thus, the aim of the study was to estimate the prevalence of risk factors of Cardiovascular Diseases (CVDs) among government employees of Hetauda Sub-Metropolitan City.
Methods: A cross-sectional descriptive study was conducted among 393 government employees of Hetauda sub metropolitan city. The ethical approval was taken from Nepal Health Research Council and informed consent was taken from each respondent before conducting the study. Cluster sampling was done where a modified WHO STEPS survey questionnaire was self-administered among the respondents. The collected data was entered and analyzed using SPSS Version 20.
Results: Out of 393 respondents, the prevalence of current smokers was 16.3%, more than two-third (72.9%) consumed alcohol in the past 30 days, and a vast majority did not consume both fruit and vegetables in adequate amounts. Similarly, more than two-third respondents (67.2%) never practiced any physical activity. The self-reported diabetes was found among 11.7% of participants whereas 19.4% had hypertension. Majority (70%) had normal BMI however; both male and female were found to be at risk for waist/hip ratio.
Conclusions: Almost every government employee was found to have one or more established risk factors of CVDs. This emphasizes the importance of taking quick action to avert the epidemic of cardiovascular disease.
Associations between parenthood, relationship, and sexual satisfaction in sex therapy patients
Authors: Gurreri Stella , Lachapelle Maude , Godbout Natacha 
Published: August 2022

Parenthood has often been associated with lower levels of relationship and sexual satisfaction. However, this effect has rarely been studied beyond transition to parenthood and/or in clinical samples and few studies have examined parenthood as a moderator between relationship satisfaction and sexual satisfaction. Therefore, the objective of this study was to examine whether parenthood (being a parent or not) acts as a moderator of the relationship between relationship satisfaction and sexual satisfaction among women and men consulting in sex therapy ( n = 219). Results indicated that mothers report lower levels of relationship satisfaction compared to non-parent women, whereas no difference was found for sexual satisfaction. Results also showed that parenthood acts as a moderator between relationship and sexual satisfaction, with differing effects for men and women. More precisely, relationship satisfaction was associated with increased sexual satisfaction in men and in non-parent women only. For mothers, relationship satisfaction was not linked to sexual satisfaction. Findings suggest that relationship satisfaction is lower in mothers compared to non-parent women and is also unrelated to sexual satisfaction in mothers, indicating specificities regarding sexual satisfaction and its correlates in others. These results have implications, particularly for interventions with mothers attending sex therapy.