bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost of goods sold analysis and recommendations to reduce costs of co-packaged mifepristone–misoprostol for medical abortion
Authors: Chinery Lester , Allaouidine Chadia , Tomazzini Alessandra , Larson Melanie , Gülmezoglu A. Metin 
Published: November 2020

Abstract

Objective
Understanding the price components of the mifepristone/misoprostol (combi-pack) for medical abortion to improve access is critical for identifying strategies to reduce product costs for quality-assured formulations and expanding its availability and use.

Methods
We constructed a cost of goods sold analysis using data collected from manufacturing companies in Bangladesh, China and India supported by publicly available information related to the product formulation, active pharmaceutical ingredients (API), manufacturing location, manufacturer profiles and other individual model components. Key model components were the active pharmaceutical ingredients (quality-assured or not), excipients, labour cost, operating cost and packaging.

Results
Combi-pack direct production cost ranges from US$1.08 for finished products which are not quality assured to US$3.05 for products containing quality assured active pharmaceutical ingredients, which means that with a 30% administrative fee applied to those prices, it could be made available between US$1.40 and US$3.97 depending on location, manufacturer’s profile, optimal market situation and the quality of the active pharmaceutical ingredients. The main model component impacting on the cost range is the purchase price of mifepristone active pharmaceutical ingredient and the current differential between quality-assured material supported by adequate documentation and API for which quality assurance cannot be demonstrated. Compared to India cost of goods sold is lower in Bangladesh primarily due to lower operating costs, including the cost of labour.

Conclusions
It is feasible to lower the cost of quality-assured combi-packs, through reducing mifepristone API cost and selection of the manufacturing location. However, manufacturers need to be incentivised to achieve WHO pre-qualification with a carefully built business case and require support in identifying and sourcing competitively priced material and manufacturing products to the necessary standard.
Evaluation of maize lodging resistance based on the critical wind speed of stalk breaking during the late growth stage
Authors: Xue Jun , Ming Bo , Xie Ruizhi , Wang Keru , Hou Peng , Li Shaokun 
Published: November 2020

Abstract

Background
The accurate evaluation of the stalk-lodging resistance during the late stage of maize growth can provide a basis for the selection of cultivars, the evaluation of cultivation techniques, and timely mechanical grain harvesting. In this study, the critical wind speed of stalk breaking, plant morphology, stalk mechanical strength, and lodging rate were investigated in 10 maize cultivars to identify the parameters evaluate lodging resistance during the later growth stage of maize. Clarify the relationship with the stalk mechanical strength, critical wind speed of stalk breaking, and natural lodging rate in the field.

Results
The results showed that, in the late growth stage, with increasing number of days after physiological maturity, (1) the stalk lodging rate gradually increased, (2) the stalk breaking force and rind penetration strength (RPS) of the third internode above the soil gradually decreased, and (3) the critical wind speed of stalk breaking increased first and then decreased, and was highest at about 16–24 days after physiological maturity. The position of stalk lodging mostly occurred between second and fifth internodes. The torque at the base of maize plant increased as wind speed increased, and the different of torque was excited among different maize cultivars under same wind speed. Furthermore, the stalk lodging rate was significantly negatively correlated with the critical wind speed of stalk breaking. Additionally, the critical wind speed of stalk breaking was significantly positively correlated with the stalk breaking force and the RPS.

Conclusion
This indicates that the critical wind speed of stalk breaking is a superior way to determine the stalk lodging resistance. These results suggest that, in the late growth stage, the decrease in the stalk mechanical strength is an important reason for the decrease in the critical wind speed of stalk breaking and the increase in the lodging rate.
Hypofractionated proton beam radiotherapy in patients with unresectable liver tumors: multi-institutional prospective results from the Proton Collaborative Group
Authors: Parzen Jacob S. , Hartsell William , Chang John , Apisarnthanarax Smith , Molitoris Jason , Durci Michael , Tsai Henry , Urbanic James , Ashman Jonathan , Vargas Carlos , Stevens Craig , Kabolizadeh Peyman 
Published: November 2020

Abstract

Background
Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).

Methods
We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.

Results
To date, 63 patients have been treated at 9 institutions between 2013 and 2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range 32.5–75) and 80.5 GyE (range 53.6–100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ≥ 3 toxicity. With median follow-up of 5.1 months (range 0.1–40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC.

Conclusions
Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.
Conformation-selective tau monoclonal antibodies inhibit tau pathology in primary neurons and a mouse model of Alzheimer’s disease
Authors: Gibbons Garrett S. , Kim Soo-Jung , Wu Qihui , Riddle Dawn M. , Leight Susan N. , Changolkar Lakshmi , Xu Hong , Meymand Emily S. , O’Reilly Mia , Zhang Bin , Brunden Kurt R. , Trojanowski John Q. , Lee Virginia M. Y. 
Published: November 2020

AbstractBackgroundThe spread of tau pathology in Alzheimer’s disease (AD) is mediated by cell-to-cell transmission of pathological tau seeds released from neurons that, upon internalization by recipient neurons, template the misfolding of naïve cellular tau, thereby propagating fibrillization. We hypothesize that anti-tau monoclonal antibodies (mAbs) that selectively bind to pathological tau seeds will inhibit propagation of tau aggregates and reduce the spread of tau pathology in vivo.MethodsWe inoculated mice with human AD brain-derived extracts containing tau paired helical filaments (AD-tau) and identified two novel mAbs, DMR7 and SKT82, that selectively bind to a misfolded pathological conformation of tau relative to recombinant tau monomer. To evaluate the effects of these mAbs on the spread of pathological tau in vivo,5xFAD mice harboring significant brain Aβ plaque burden were unilaterally injected with AD-tau in the hippocampus, to initiate the formation of neuritic plaque (NP) tau pathology, and were treated weekly with intraperitoneal (i.p.) injections of DMR7, SKT82, or IgG isotype control mAbs.ResultsDMR7 and SKT82 bind epitopes comprised of the proline-rich domain and c-terminal region of tau and binding is reduced upon disruption of the pathological conformation of AD-tau by chemical and thermal denaturation. We found that both DMR7 and SKT82 immunoprecipitate pathological tau and significantly reduce the seeding of cellular tau aggregates induced by AD-tau in primary neurons by 60.5 + 13.8% and 82.2 + 8.3%, respectively, compared to IgG control. To investigate the mechanism of mAb inhibition, we generated pH-sensitive fluorophore-labeled recombinant tau fibrils seeded by AD-tau to track internalization of tau seeds and demonstrate that the conformation-selective tau mAbs inhibit the internalization of tau seeds. DMR7 and SKT82 treatment reduced hyperphosphorylated NP tau as measured with AT8 immunohistochemistry (IHC) staining, but did not achieve statistical significance in the contralateral cortex and SKT82 significantly reduced tau pathology in the ipsilateral hippocampus by 24.2%;p = 0.044.ConclusionsThese findings demonstrate that conformation-selective tau mAbs, DMR7 and SKT82, inhibit tau pathology in primary neurons by preventing the uptake of tau seeds and reduce tau pathology in vivo,providing potential novel therapeutic candidates for the treatment of AD.
Detection and prevalence of depression among adult type 2 diabetes mellitus patients attending non-communicable diseases clinics in Lilongwe, Malawi
Authors: Udedi Michael , Pence Brian W. , Stewart Robert C. , Muula Adamson S. 
Published: November 2020

Abstract

Background
Depression is associated with chronic physical illnesses and negatively affects health outcomes. However, it often goes undiagnosed and untreated. We investigated the prevalence of depression among adult type 2 diabetes mellitus (T2DM) patients attending non-communicable diseases (NCD) clinics in Lilongwe, Malawi, and estimated the level of routine detection by NCD clinicians. This study set out to determine the prevalence of major depression and its detection among adult type 2 diabetes mellitus (T2DM) patients attending NCD clinics in Lilongwe, Malawi.

Methods
In a cross-sectional study design, 323 T2DM patients aged ≥ 18 years were screened for depression with the Patient Health Questionnare-9 (PHQ-9) followed by diagnostic assessment with the Structured Clinical Interview for DSM-IV (SCID). We analysed the association between presence of major depression and sociodemographic factors using logistic regression.

Results
Three quarters of the participants (76%) were females. The participants’ ages ranged from 21–79 years. Of the 323 participants, 58 (18%) met criteria for DSM-IV major depression. None of the cases of major depression had been identified by the NCD clinicians. Major depression was found not to be significantly associated with any of the sociodemographic factors.

Conclusions
We found that depression is common among NCD clinic attendees with T2DM in Malawi, and poorly detected by NCD clinicians. Given the high prevalence and challenges in clinical identification, integration of depression screening with a standardized validated tool should be a high priority so as to link patients to appropriate services.
High-throughput screening reveals novel mutations in spinal muscular atrophy patients
Authors: Zhang Ruiping , Gu Chunyu , Pu Linjie , Meng Yingtao , Shu Jianbo , Cai Chunquan 
Published: November 2020

AbstractBackgroundSpinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA.MethodsEighty-three whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence ofSMN1gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing.ResultsTwenty-two probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3SMN1exon7 copies. SixSMN1single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C > T], c.[271C > T], c.[−39A > G] and g.[70240639G > C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients.SPTA1mutation c.[−41_-40insCTCT],FUT5SNV c.[1001A > G], andMCCC2SNV c.[−117A > G] were the 3 most frequent mutations in SMA group (95, 85 and 75%, respectively).ConclusionsWe identified some mutations in bothSMN1and other genes, and c.[271C > T], c.[−41_-40insCTCT], c.[1001A > G] and c.[−117A > G] might be associated with the onset of SMA.
Carriage of ESBL-producing Gram-negative bacteria by flies captured in a hospital and its suburban surroundings in Ethiopia
Authors: Tufa Tafese Beyene , Fuchs Andre , Wienemann Tobias , Eggers Yannik , Abdissa Sileshi , Schneider Marlen , Jensen Björn-Erik Ole , Bode Johannes G. , Pfeffer Klaus , Häussinger Dieter , Mackenzie Colin R. , Orth Hans Martin , Feldt Torsten 
Published: November 2020

Abstract

Background
Local data from the Asella Teaching and Referral Hospital in the town of Asella, Ethiopia reveal a high prevalence of extended-spectrum β-lactamase- (ESBL) producing Gram-negative bacteria (GNB) in clinical isolates. To investigate a possible route of transmission, we determined the proportions ESBL-producing GNB in isolates from flies caught in the hospital and in the town of Asella.

Methods
Flies were collected in August 2019 from the neonatal intensive care unit (NICU), the orthopedic ward, the hospital’s waste disposal area, and from a butchery situated 1.5 km from the hospital. After trapping, the flies were macerated and suspended in sterile normal saline. The suspensions were inoculated on MacConkey agar and incubated overnight. Species identification and antimicrobial susceptibility testing were performed using Vitek®-MS and VITEK® 2.

Results
In total, 103 bacterial isolates were obtained from 85 flies (NICU: 11 isolates from 20 flies, orthopedic ward: 10 isolates from 12 flies, waste disposal area: 37 isolates from 26 flies, butchery: 45 isolates from 27 flies). The proportions of ESBL-producing bacteria among isolates obtained from flies collected in the hospital compound were significantly higher (82%, 90%, and 57% in NICU, orthopedic ward and waste disposal area, respectively) compared to flies collected outside of the hospital compound (2% (@1/45) in the butchery) (p ≤ 0.001). The proportion of ESBL was 67% (6/9) among Raoultella spp. 67% (4/6) among Kluyvera spp., 56% (5/9) among Enterobacter spp., 50% (5/10) among E. coli, and 44% (8/18) among Klebsiella spp.. Of the 40 ESBL-genes detected, 85% were CTX-M-like, 83% TEM-like, 23% SHV-like, and 2% CTX-M-2-like. ESBL-producing bacteria showed higher rates of resistance against ciprofloxacin (66% vs. 5%), gentamicin (68% vs. 3%), piperacillin-tazobactam (78% vs. 5%), and trimethoprim-sulfamethoxazole (88% vs. 16%), compared to non-ESBL-producing bacteria.

Conclusion
A high proportion of ESBL was identified in isolates from flies caught in the hospital compound compared with isolates of flies collected at a distance of 1.5 km from the hospital. Flies can be potential vectors for transmission of multidrug-resistant (MDR) bacteria within hospitals. Further studies are needed to determine the source of MDR colonization in flies and possible impact of MDR for nosocomial infections.
Sorption and leaching characteristics of pesticides in volcanic ash soils of Jeju Island, Korea
Authors: Park Won-Pyo , Chang Kong-Man , Hyun Hae-Nam , Boo Kyung-Hwan , Koo Bon-Jun 
Published: November 2020

AbstractIt is important to evaluate leaching behavior in agricultural soils to prevent the pollution of groundwater by pesticides. We identified the distribution coefficients (Kd) of ten pesticides with different physicochemical properties and compared their leaching characteristics using wick lysimeters from three distinct soil types on Jeju Island. The Kdvalues varied by pesticide and soil, but were within the range of 1.2 to 4231 L kg−1. Based on the European standard (Kd < 10 L kg−1), six pesticides (alachlor, ethoprophos, carbofuran, napropamide, tebuconazole, and etridiazole) were mobile in at least one tested soil, and their soil organic carbon affinity was ≤ 5.811. This value differed greatly from the other pesticides (16.533 and higher). The solubility of the six mobile pesticides was ≥ 32 mg L−1, which substantially differed from the other pesticides (≤ 0.71 mg L−1). Thus, we conclude that our mobility assessment, which is based on Kdvalues, can be used to predict the leaching of pesticides in the volcanic ash soils of Jeju Island. The use of pesticides should be strictly controlled to reduce the possibility of groundwater contamination.
Particle size of ginseng (Panax ginseng Meyer) insoluble dietary fiber and its effect on physicochemical properties and antioxidant activities
Authors: Jiang Guihun , Wu Zhaogen , Ameer Kashif , Li Shanji , Ramachandraiah Karna 
Published: November 2020

Abstract
Dietary fibers (DFs) and associated phytochemicals in ginseng species are known to provide various functional and health benefits. The incorporation of ginseng insoluble dietary fiber (IDF) in food products often result in undesirable physicochemical properties. Thus, to overcome such demerits, micronization of IDF has been considered. This study investigated the effect of particle size on the physicochemical properties, antioxidant activities, structure and thermal analysis of ginseng IDF. Micronized IDF powder with median particle diameter of 15.83 μm was produced through fine grinding. Reduction of ginseng IDF resulted in increased brightness, water holding capacity and solubility. Decreasing particle sizes also lowered bulk, tapped density, Carr index and Hausner ratio. Reduction of particle size caused greater extractability of mineral and phenolic content and thereby increasing the DPPH radical scavenging activity and ferric reducing antioxidant power. Increased polyphenol extraction with smaller particle size also lowered the mice erythrocytes hemolysis percentage while the hemolysis inhibition rate was increased. Particle size also influenced the thermal stability of ginseng IDF powders. FTIR spectra revealed lack of impact on the major phenolic structures due to superfine grinding. Hence,micronized ginseng IDF powders with improved physicochemical properties and antioxidant activities possess the potential to be used in food and pharmaceutical industries.
The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)
Authors: Nkonge Ken Munene , Nkonge Dennis Karani , Nkonge Teresa Njeri 
Published: November 2020

AbstractBackgroundThe most common type of monogenic diabetes is maturity-onset diabetes of the young (MODY), a clinically and genetically heterogeneous group of endocrine disorders that affect 1–5% of all patients with diabetes mellitus. MODY is characterized by autosomal dominant inheritance but de novo mutations have been reported. Clinical features of MODY include young-onset hyperglycemia, evidence of residual pancreatic function, and lack of beta cell autoimmunity or insulin resistance. Glucose-lowering medications are the main treatment options for MODY. The growing recognition of the clinical and public health significance of MODY by clinicians, researchers, and governments may lead to improved screening and diagnostic practices. Consequently, this review article aims to discuss the epidemiology, pathogenesis, diagnosis, and treatment of MODY based on relevant literature published from 1975 to 2020.Main bodyThe estimated prevalence of MODY from European cohorts is 1 per 10,000 in adults and 1 per 23,000 in children. Since little is known about the prevalence of MODY in African, Asian, South American, and Middle Eastern populations, further research in non-European cohorts is needed to help elucidate MODY’s exact prevalence. Currently, 14 distinct subtypes of MODY can be diagnosed through clinical assessment and genetic analysis. Various genetic mutations and disease mechanisms contribute to the pathogenesis of MODY. Management of MODY is subtype-specific and includes diet, oral antidiabetic drugs, or insulin.ConclusionsIncidence and prevalence estimates for MODY are derived from epidemiologic studies of young people with diabetes who live in Europe, Australia, and North America. Mechanisms involved in the pathogenesis of MODY include defective transcriptional regulation, abnormal metabolic enzymes, protein misfolding, dysfunctional ion channels, or impaired signal transduction. Clinicians should understand the epidemiology and pathogenesis of MODY because such knowledge is crucial for accurate diagnosis, individualized patient management, and screening of family members.
Optical coherence tomography angiography measured area of retinal neovascularization is predictive of treatment response and progression of disease in patients with proliferative diabetic retinopathy
Authors: Vergmann Anna Stage , Sørensen Kristian Tølbøl , Torp Thomas Lee , Kawasaki Ryo , Wong Tien , Peto Tunde , Grauslund Jakob 
Published: November 2020

Abstract

Background
The purpose of this study was to evaluate the area of retinal neovascularization in patients with treatment-naïve proliferative diabetic retinopathy (PDR) as measured by optical coherence tomography angiography (OCT-A) as a marker of subsequent treatment response after panretinal photocoagulation (PRP), and to examine if this area correlated with area of retinal neovascularization as measured by fluorescein angiography (FA).

Methods
En face OCT-A scans (4.5 × 4.5 mm) of neovascularizations were obtained at baseline (BL) before PRP and at month (M) 3 and M6 after treatment. Progression of PDR were defined as lesion growth (assessed by ophthalmoscopy and wide-field fundus photo) or increasing leakage by Optos ultra-widefield FA, and patients were divided into two groups; progression or non-progression. Mann–Whitney U test and Wilcoxon signed-rank test were used to analyse differences between groups and between time points. Areas of retinal neovascularizations (OCT-A and FA) were calculated by algorithms developed in Python (version 3.6.8, The Python Software Foundation, USA).

Results
Of 21 eyes included, 14 had progression of disease. Median OCT-A area did not differ between the two groups (progression vs. non-progression) at BL (76.40 ± 162.03 vs. 72.62 ± 94.15, p = 0.43) but were statistically significantly larger in the progression group at M6 (276.69 ± 168.78 vs. 61.30 ± 70.90, p = 0.025). Median FA area did not differ in the progression vs. the non-progression group at BL (111.42 ± 143.08 vs. 60.80 ± 54.83, p = 0.05) or at M6 (200.12 ± 91.81 vs. 123.86 ± 162.16, p = 0.62). Intraclass correlation between area by OCT-A and FA was −5.99 (95% CI: −35.28–0.993), p = 0.71.

Conclusions
In this study of patients with treatment-naïve PDR, we showed that increasing area of retinal neovascularizations measured by OCT-A at M6 indicated progression of disease after PRP treatment. Our results suggest that area by OCT-A reflects disease activity and that it can be used as an indicator to monitor the progression of PDR over time, and to evaluate treatment response six months after PRP.
Trial registrationhttps://clinicaltrials.gov (identifier: NCT03113006). Registered April 13, 2017.