bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary superscaffolding and chromosome anchoring to improve Anopheles genome assemblies
Authors: Waterhouse Robert M. , Aganezov Sergey , Anselmetti Yoann , Lee Jiyoung , Ruzzante Livio , Reijnders Maarten J. M. F. , Feron Romain , Bérard Sèverine , George Phillip , Hahn Matthew W. , Howell Paul I. , Kamali Maryam , Koren Sergey , Lawson Daniel , Maslen Gareth , Peery Ashley , Phillippy Adam M. , Sharakhova Maria V. , Tannier Eric , Unger Maria F. , Zhang Simo V. , Alekseyev Max A. , Besansky Nora J. , Chauve Cedric , Emrich Scott J. , Sharakhov Igor V. 
Published: January 2020

Abstract
Background
New sequencing technologies have lowered financial barriers to whole genome sequencing, but resulting assemblies are often fragmented and far from ‘finished’. Updating multi-scaffold drafts to chromosome-level status can be achieved through experimental mapping or re-sequencing efforts. Avoiding the costs associated with such approaches, comparative genomic analysis of gene order conservation (synteny) to predict scaffold neighbours (adjacencies) offers a potentially useful complementary method for improving draft assemblies.

Results
We evaluated and employed 3 gene synteny-based methods applied to 21 Anopheles mosquito assemblies to produce consensus sets of scaffold adjacencies. For subsets of the assemblies, we integrated these with additional supporting data to confirm and complement the synteny-based adjacencies: 6 with physical mapping data that anchor scaffolds to chromosome locations, 13 with paired-end RNA sequencing (RNAseq) data, and 3 with new assemblies based on re-scaffolding or long-read data. Our combined analyses produced 20 new superscaffolded assemblies with improved contiguities: 7 for which assignments of non-anchored scaffolds to chromosome arms span more than 75% of the assemblies, and a further 7 with chromosome anchoring including an 88% anchored Anopheles arabiensis assembly and, respectively, 73% and 84% anchored assemblies with comprehensively updated cytogenetic photomaps for Anopheles funestus and Anopheles stephensi.

Conclusions
Experimental data from probe mapping, RNAseq, or long-read technologies, where available, all contribute to successful upgrading of draft assemblies. Our evaluations show that gene synteny-based computational methods represent a valuable alternative or complementary approach. Our improved Anopheles reference assemblies highlight the utility of applying comparative genomics approaches to improve community genomic resources.
Therapeutic effect of subcutaneous injection of low dose recombinant human granulocyte-macrophage colony-stimulating factor on pulmonary alveolar proteinosis
Authors: Zhang Fen , Weng Dong , Su Yiliang , Yin Chengsheng , Shen Li , Zhang Yuan , Zhou Ying , Li Qiuhong , Hu Yang , Li Huiping 
Published: January 2020

Abstract
Objective
To observe the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for pulmonary alveolar proteinosis (PAP).

Materials and methods
A total of 55 patients with PAP were screened at Shanghai Pulmonary Hospital between May 2014 and May 2018. Among these, 42 were diagnosed with idiopathic PAP, 24 were included in this study, 20 were treated for 6 months, and 17 were followed up for additional 6 months. All patients received a subcutaneous injection of 75μg/d GM-CSF qd for 1 month. The therapeutic dose was adjusted according to the changes in the lesions of chest CT. If the lesions were absorbed, subcutaneous injections of 75μg/d GM- CSF qd and 75μg/d GM-CSF qod were given for 2 and 3 months, otherwise, the dose was increased to 150μg/d GM-CSF qd and 150μg/d qod for 2 and 3 months, respectively. All cases were treated once a day in the first 3 months and once every other day in the last 3 months. The total course of treatment was 6 months. After withdrawal, the patients were followed up for another 6 months. The deadline of follow up was September 30, 2019.

Results
Twenty patients completed the treatment and efficacy evaluation. One patient was completely cured, 16 cases improved, three cases were noneffective. After 1-month evaluation, 12 patients received an increased dose (150μg) from the second month of treatment. Seventeen patients completed the 12-month follow-up, among which fourteen improved. CT showed the lesions were slightly increased in three cases. Economic burden was the following: RMB 7324–15,190 Yuan were required for the 6-month treatment course, which is significantly lower compared to other treatment methods.

Conclusion
Subcutaneous injection of rhGM-CSF at low dose (75μg-150μg /d) is effective treatment for patients with idiopathic PAP.

Trial registration
NCT01983657. Registered 16 April 2013.
Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting
Authors: Liang Barry J. , Pigula Michael , Baglo Yan , Najafali Daniel , Hasan Tayyaba , Huang Huang-Chiao 
Published: January 2020

AbstractBackgroundPhotoimmunotherapy involves targeted delivery of photosensitizers via an antibody conjugate (i.e., photoimmunoconjugate, PIC) followed by light activation for selective tumor killing. The trade-off between PIC selectivity and PIC uptake is a major drawback limiting the efficacy of photoimmunotherapy. Despite ample evidence showing that photoimmunotherapy is most effective when combined with chemotherapy, the design of nanocarriers to co-deliver PICs and chemotherapy drugs remains an unmet need. To overcome these challenges, we developed a novel photoimmunoconjugate-nanoliposome (PIC-Nal) comprising of three clinically used agents: anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab (Cet), benzoporphyrin derivative (BPD) photosensitizer, and irinotecan (IRI) chemotherapy.ResultsThe BPD photosensitizers were first tethered to Cet at a molar ratio of 6:1 using carbodiimide chemistry to form PICs. Conjugation of PICs onto nanoliposome irinotecan (Nal–IRI) was facilitated by copper-free click chemistry, which resulted in monodispersed PIC–Nal–IRI with an average size of 158.8 ± 15.6 nm. PIC–Nal–IRI is highly selective against EGFR-overexpressing epithelial ovarian cancer cells with 2- to 6-fold less accumulation in low EGFR expressing cells. Successful coupling of PIC onto Nal–IRI enhanced PIC uptake and photoimmunotherapy efficacy by up to 30% in OVCAR-5 cells. Furthermore, PIC–Nal–IRI synergistically reduced cancer viability via a unique three-way mechanism (i.e., EGFR downregulation, mitochondrial depolarization, and DNA damage).ConclusionIt is increasingly evident that the most effective therapies for cancer will involve combination treatments that target multiple non-overlapping pathways while minimizing side effects. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. PIC–Nal–IRI offers a promising strategy to overcome the selectivity-uptake trade-off, improve photoimmunotherapy efficacy, and enable multi-tier cancer targeting. Controllable drug compartmentalization, easy surface modification, and high clinical relevance collectively make PIC–Nal–IRI extremely valuable and merits further investigations in living animals.
Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: current status and potential future applications
Authors: Wnorowska Urszula , Fiedoruk Krzysztof , Piktel Ewelina , Prasad Suhanya V. , Sulik Magdalena , Janion Marianna , Daniluk Tamara , Savage Paul B. , Bucki Robert 
Published: January 2020

AbstractNanotechnology-based therapeutic approaches have attracted attention of scientists, in particular due to the special features of nanomaterials, such as adequate biocompatibility, ability to improve therapeutic efficiency of incorporated drugs and to limit their adverse effects. Among a variety of reported nanomaterials for biomedical applications, metal and metal oxide-based nanoparticles offer unique physicochemical properties allowing their use in combination with conventional antimicrobials and as magnetic field-controlled drug delivery nanocarriers. An ever-growing number of studies demonstrate that by combining magnetic nanoparticles with membrane-active, natural human cathelicidin-derived LL-37 peptide, and its synthetic mimics such as ceragenins, innovative nanoagents might be developed. Between others, they demonstrate high clinical potential as antimicrobial, anti-cancer, immunomodulatory and regenerative agents. Due to continuous research, knowledge on pleiotropic character of natural antibacterial peptides and their mimics is growing, and it is justifying to stay that the therapeutic potential of nanosystems containing membrane active compounds has not been exhausted yet.
Developing item banks to measure three important domains of health-related quality of life (HRQOL) in Singapore
Authors: Uy Elenore Judy B. , Xiao Lynn Yun Shan , Xin Xiaohui , Yeo Joanna Peck Tiang , Pua Yong Hao , Lee Geok Ling , Kwan Yu Heng , Teo Edmund Pek Siang , Vaingankar Janhavi Ajit , Subramaniam Mythily , Chan Mei Fen , Kumar Nisha , Ang Alcey Li Chang , Bautista Dianne Carrol , Cheung Yin Bun , Thumboo Julian 
Published: January 2020

AbstractObjectivesTo develop separate item banks for three health domains of health-related quality of life (HRQOL) ranked as important by Singaporeans – physical functioning, social relationships, and positive mindset.MethodsWe adapted the Patient Reported Outcomes Measurement Information System Qualitative Item Review protocol, with input and endorsement from laymen and experts from various relevant fields. Items were generated from 3 sources: 1) thematic analysis of focus groups and in-depth interviews for framework (n = 134 participants) and item(n = 52 participants) development, 2) instruments identified from a literature search (PubMed) of studies that developed or validated a HRQOL instrument among adults in Singapore, 3) a priori identified instruments of particular relevance. Items from these three sources were “binned” and “winnowed” by two independent reviewers, blinded to the source of the items, who harmonized their selections to generate a list of candidate items (each item representing a subdomain). Panels with lay and expert representation, convened separately for each domain, reviewed the face and content validity of these candidate items and provided inputs for item revision. The revised items were further refined in cognitive interviews.ResultsItems from our qualitative studies (51 physical functioning, 44 social relationships, and 38 positive mindset), the literature review (36 instruments from 161 citations), and three a priori identified instruments, underwent binning, winnowing, expert panel review, and cognitive interview. This resulted in 160 candidate items (61 physical functioning, 51 social relationships, and 48 positive mindset).ConclusionsWe developed item banks for three important health domains in Singapore using inputs from potential end-users and the published literature. The next steps are to calibrate the item banks, develop computerized adaptive tests (CATs) using the calibrated items, and evaluate the validity of test scores when these item banks are administered adaptively.
Implementation analysis of patient reported outcomes (PROs) in oncological routine care: an observational study protocol
Authors: Görlach Mirja Gianna , Schrage Theresa , Bokemeyer Carsten , Kröger Nicolaus , Müller Volkmar , Petersen Cordula , Betz Christian Stephan , Krüll Andreas , Schulz Holger , Bleich Christiane 
Published: January 2020

AbstractBackgroundThe successful implementation of patient-reported outcomes (PROs) in clinical routine faces many challenges, first and foremost the lack of consideration thereof in the patient care process. The aim of this study will be to first identify relevant barriers and facilitators and then design suitable implementation strategies which will be evaluated to improve the effectiveness of a PRO measure assessment in inpatient and outpatient cancer routine care.MethodsDuring the preparation phase, interviews with oncological patients (N = 28) and medical staff (N = 4) as well as focus groups with medical staff (N = 18) across five different departments caring for cancer patients were conducted. On the basis of these, qualitative content analysis revealed relevant barriers and facilitators for implementation of PROs in cancer care. Subsequently, implementation strategies and a model of implementation were developed. In the study phase, implementation strategies will be evaluated based on nine different implementation outcomes in five different oncological clinics. Evaluation of the implementation process will take place during three months in each clinic and data will be conducted pre, while and post implementation of the PRO measure. Therefore a sample size of 60 participants of whom 30 staff members and 30 participants will be questioned using existing and newly developed implementation outcome evaluation instruments.DiscussionKey to improving the effectiveness of PRO assessment in the time-critical clinical environment is the utilization of easy-to-use, electronic PRO questionnaires directly linked to patients’ records thereby improving consideration of PROs in patient care. In order to validate the effectiveness of this implementation process further, an evaluation parallel to implementation following an observational study design with a mixed-methods approach will be conducted. This study could contribute to the development of adequate evaluation processes of implementation of PROs to foster sustainable integration of PRO measures into routine cancer care.Trial registrationThis study was registered at Open Science Framework (https://osf.io/y7xce/).
Development and validation of a nomogram for preoperative prediction of lymph node metastasis in early gastric cancer
Authors: Yin Xiao-Yi , Pang Tao , Liu Yu , Cui Hang-Tian , Luo Tian-Hang , Lu Zheng-Mao , Xue Xu-Chao , Fang Guo-En 
Published: January 2020

Abstract
Background
The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients.

Methods
This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram.

Results
Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively.

Conclusions
Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.
Reweighting national survey data for small area behaviour estimates: modelling alcohol consumption in Local Authorities in England
Authors: Pryce Robert , Angus Colin , Holmes John , Gillespie Duncan , Buykx Penny , Meier Petra , Hickman Matt , de Vocht Frank , Brennan Alan 
Published: January 2020

Abstract
Background
There are likely to be differences in alcohol consumption levels and patterns across local areas within a country, yet survey data is often collected at the national or sub-national/regional level and is not representative for small geographic areas.

Methods
This paper presents a method for reweighting national survey data—the Health Survey for England—by combining survey and routine data to produce simulated locally representative survey data and provide statistics of alcohol consumption for each Local Authority in England.

Results
We find a 2-fold difference in estimated mean alcohol consumption between the lightest and heaviest drinking Local Authorities, a 4.5-fold difference in abstention rates, and a 3.5-fold difference in harmful drinking. The method compares well to direct estimates from the data at regional level.

Conclusions
The results have important policy implications in itself, but the reweighted data can also be used to model local policy effects. This method can also be used for other public health small area estimation where locally representative data are not available.
Globalization of national surgical, obstetric and anesthesia plans: the critical link between health policy and action in global surgery
Authors: Truché Paul , Shoman Haitham , Reddy Ché L. , Jumbam Desmond T. , Ashby Joanna , Mazhiqi Adelina , Wurdeman Taylor , Ameh Emmanuel A. , Smith Martin , Lugazia Edwin , Makasa Emmanuel , Park Kee B. , Meara John G. 
Published: January 2020

AbstractEfforts from the developed world to improve surgical, anesthesia and obstetric care in low- and middle-income countries have evolved from a primarily volunteer mission trip model to a sustainable health system strengthening approach as private and public stakeholders recognize the enormous health toll and financial burden of surgical disease. The National Surgical, Obstetric and Anesthesia Plan (NSOAP) has been developed as a policy strategy for countries to address, in part, the health burden of diseases amenable to surgical care, but these plans have not developed in isolation. The NSOAP has become a phenomenon of globalization as a broad range of partners – individuals and institutions – help in both NSOAP formulation, implementation and financing. As the nexus between policy and action in the field of global surgery, the NSOAP reflects a special commitment by state actors to make progress on global goals such as Universal Health Coverage and the United Nations Sustainable Development Goals. This requires a continued global commitment involving genuine partnerships that embrace the collective strengths of both national and global actors to deliver sustained, safe and affordable high-quality surgical care for all poor, rural and marginalized people.
Microarray expression studies on bone marrow of patients with Shwachman-Diamond syndrome in relation to deletion of the long arm of chromosome 20, other chromosome anomalies or normal karyotype
Authors: Khan Abdul Waheed , Minelli Antonella , Frattini Annalisa , Montalbano Giuseppe , Bogni Alessia , Fabbri Marco , Porta Giovanni , Acquati Francesco , Pinto Rita Maria , Bergami Elena , Mura Rossella , Pegoraro Anna , Cesaro Simone , Cipolli Marco , Zecca Marco , Danesino Cesare , Locatelli Franco , Maserati Emanuela , Pasquali Francesco , Valli Roberto 
Published: January 2020

Abstract
Background
Clonal chromosome changes are often found in the bone marrow (BM) of patients with Shwachman-Diamond syndrome (SDS). The most frequent ones include an isochromosome of the long arm of chromosome 7, i (7)(q10), and an interstitial deletion of the long arm of chromosome 20, del (20)(q). These two imbalances are mechanisms of somatic genetic rescue. The literature offers few expression studies on SDS.

Results
We report the expression analysis of bone marrow (BM) cells of patients with SDS in relation to normal karyotype or to the presence of clonal chromosome anomalies: del (20)(q) (five cases), i (7)(q10) (one case), and other anomalies (two cases). The study was performed using the microarray technique considering the whole transcriptome (WT) and three gene subsets selected as relevant in BM functions. The expression patterns of nine healthy controls and SDS patients with or without chromosome anomalies in the bone marrow showed clear differences.

Conclusions
There is a significant difference between gene expression in the BM of SDS patients and healthy subjects, both at the WT level and in the selected gene sets. The deletion del (20)(q), with the EIF6 gene consistently lost, even in patients with the smallest losses of material, changes the transcription pattern: a low proportion of abnormal cells led to a pattern similar to SDS patients without acquired anomalies, whereas a high proportion yields a pattern similar to healthy subjects. Hence, the benign prognostic value of del (20)(q). The case of i (7)(q10) showed a transcription pattern similar to healthy subjects, paralleling the positive prognostic role of this anomaly as well.
0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial
Authors: Williams Vijai , Jayashree Muralidharan , Nallasamy Karthi , Dayal Devi , Rawat Amit 
Published: January 2020

Abstract
Background
Acute kidney injury (AKI) is an important complication encountered during the course of diabetic ketoacidosis (DKA). Plasma-Lyte with lower chloride concentration than saline has been shown to be associated with reduced incidence of AKI in adults with septic shock. No study has compared this in DKA.

Methods
This double-blind, parallel-arm, investigator-initiated, randomized controlled trial compared 0.9% saline with Plasma-Lyte-A as initial fluid in pediatric DKA. The study was done in a tertiary care, teaching, and referral hospital in India in children (> 1 month–12 years) with DKA as defined by ISPAD. Children with cerebral edema or known chronic kidney/liver disease or who had received pre-referral fluids and/or insulin were excluded. Sixty-six children were randomized to receive either Plasma-Lyte (n = 34) or 0.9% saline (n = 32).

Main outcomes
Primary outcome was incidence of new or progressive AKI, defined as a composite outcome of change in creatinine (defined by KDIGO), estimated creatinine clearance (defined by p-RIFLE), and NGAL levels. The secondary outcomes were resolution of AKI, time to resolution of DKA (pH > 7.3, bicarbonate> 15 mEq/L & normal sensorium), change in chloride, pH and bicarbonate levels, proportion of in-hospital all-cause mortality, need for renal replacement therapy (RRT), and length of ICU and hospital stay.

Results
Baseline characteristics were similar in both groups. The incidence of new or progressive AKI was similar in both [Plasma-Lyte 13 (38.2%) versus 0.9% saline 15 (46.9%); adjusted OR 1.22; 95% CI 0.43–3.43, p = 0.70]. The median (IQR) time to resolution of DKA in Plasma-Lyte-A and 0.9% saline were 14.5 (12 to 20) and 16 (8 to 20) h respectively. Time to resolution of AKI was similar in both [Plasma-Lyte 22.1 versus 0.9% saline 18.8 h (adjusted HR 1.72; 95% CI 0.83–3.57; p = 0.14)]. Length of hospital stay was also similar in both [Plasma-Lyte 9 (8 to 12) versus 0.9% saline 10 (8.25 to 11) days; p = 0.39].

Conclusions
The incidence of new or progressive AKI and resolution of AKI were similar in both groups. Plasma-Lyte-A was similar to 0.9% Saline in time to resolution of DKA, need for RRT, mortality, and lengths of PICU and hospital stay.

Trial registration
Clinical trial registry of India, CTRI/2018/05/014042 (ctri.nic.in) (Retrospectively registered).