bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tuberculosis infection prevention and control: why we need a whole systems approach
Authors: Kielmann Karina , Karat Aaron S. , Zwama Gimenne , Colvin Christopher , Swartz Alison , Voce Anna S. , Yates Tom A. , MacGregor Hayley , McCreesh Nicky , Kallon Idriss , Vassall Anna , Govender Indira , Seeley Janet , Grant Alison D. 
Published: May 2020

AbstractInfection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an on-going project entitled Umoya omuhle (“good air”), conducted in two provinces of South Africa, that adopts an interdisciplinary, ‘whole systems’ approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis (Mtb) through improved IPC. We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines, health facility space, infrastructure, organisation of care, and management culture. Methods drawn from epidemiology, anthropology, and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs, as well as opportunities to address the problem holistically. A ‘whole systems’ approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission.
Pharmacists reinventing their roles to effectively respond to COVID-19: a global report from the international pharmacists for anticoagulation care taskforce (iPACT)
Authors: Alves da Costa Filipa , Lee Vivian , Leite Silvana Nair , Murillo Maria Dolores , Menge Tom , Antoniou Sotiris 
Published: May 2020

AbstractSARS-CoV2 is dramatically impacting the global population. Worldwide, pharmacists are changing their roles and being increasingly recognized for their role as essential service providers. This commentary provides some examples collected from Asia, Europe, the Americas and Africa, ranging from essential services to meet human rights basic needs, extended generalist services developed to ensure continuity of care and supply of essential medicines to the development of differentiated extended responsibilities in emergency care. All examples were collected using a network of pharmacists from 27 countries, representing various areas of pharmacy practice, education and research and outreaching to include patient advocates. Selected services illustrate good practice, capability to adapt and contribution to universal health coverage. Above all, it demonstrates the commitment and innovation of the pharmaceutical workforce in the fight against COVID-19.
A method for high-throughput screening hydrolase of lignin β-aryl ether linkage from directed evolution by glutathione (GSH) assay
Authors: Wang Jiaxi , Yan Kun , Wang Wenya , Zhou Yan 
Published: May 2020

Abstract
Background
Lignin’s valorization plays a critical role in refining the bioresource. Considering that the β-aryl ether linkage (β-O-4 bond) accounts for 50–70% of lignin chemical linkage between aromatic rings, the hydrolase of lignin β-aryl ether linkage, especially the β-etherase, provided a promising way for the lignin depolymerization and valorization. As a result, it is essential to develop the effective high-throughput methods for screening the mutant library of β-etherase from directed evolution.

Results
Based on the enzymatic mechanism of β-O-4 bond’s cleavage by β-etherase, the LigF was selected as the model to study high-throughput method by GSH assay for screening the mutant library of β-etherase from directed evolution. After the primary study with purified LigF and cell lysate, the GSH assay was used to screen mutant library of β-etherase. The study on screening the mutant library with about 600 colonies indicated that the selected transformants all have one or two mutated sites in the gene sequence of LigF, and the activities from GSH assay of most selected transformants were the same as their activities from HPLC assay.

Conclusions
The results from the high-throughput screening of mutant library demonstrated that GSH assay could be applied to screen β-etherase mutant from directed evolution.
Assessment of the dynamics of the Volta river estuary shorelines in Ghana
Authors: Appeaning Addo K. , Brempong E. K. , Jayson-Quashigah P. N. 
Published: May 2020

AbstractEstuarine shorelines similar to marine coastlines are highly dynamic and may increase disaster risk in vulnerable communities. The situation is expected to worsen with climate change impacts and increasing anthropogenic activities such as upstream water management. This study assessed shoreline changing trends along the Volta river estuary in Ghana as well as the marine coastline using satellite imageries, orthophotos and topographic maps spanning a period of 120 years (1895, 1990, 2000, 2005 and 2015). Linear regression method in the Digital Shoreline Analysis System (DSAS) was used to determine the estuary shoreline migration trend by estimating the shorelines rate of change for the eastern and western sides of the estuary. The rates of change of the marine coastlines on the east and west of the estuary were also estimated. The results show that the eastern and western shoreline of the estuary are eroding at an average rate of about 1.94 m/yr and 0.58 m/yr respectively. The coastlines on the marine side (eastern and western) are eroding at an average rate of about 2.19 m/yr and 0.62 m/yr respectively. Relatively high rates of erosion observed on the eastern estuarine shoreline as well as the coastline could be explained by the reduced sediment supply by the Volta River due to the damming of the Volta River in Akosombo and the sea defence structures constructed to manage erosion problems. The trend is expected to increase under changing oceanographic conditions and increased subsidence in the Volta delta. Effective management approach, such as developing disaster risk reduction strategy, should be adopted to increase the resilience of the communities along the estuarine shoreline and increase their adaptive capacity to climate change hazards and disasters.
The role of labour market integration in migrants’ decisions about family reunification: a comparative study of Polish migrants in Norway, Sweden, and the UK
Authors: Ryndyk Oleksandr 
Published: May 2020

AbstractWith about 2.7 million nationals residing elsewhere in the European Economic Area, Poland was the second largest country of origin of all intra-European migrants in 2018. After the country’s accession to the European Union in 2004, some Polish migrants have brought abroad their families, while others continue living alone and commuting to visit their families in Poland. Based on a sample of 1153 survey respondents in three European contexts—Norway, Sweden, and the United Kingdom—this article investigates from a comparative perspective how Polish migrants’ family reunification status is related to their integration on the labour market. Results show that only in the Scandinavian labour markets, and not in the British, is migrants’ economic integration decisive for family reunification. This article argues that in contexts which offer broader employment opportunities for family migrants, who tend to be women, such as in the UK between 2004 and 2016, the lead migrant’s labour market integration may not be crucial for family reunification. The findings may be of special interest for migration policymakers in the Scandinavian countries working towards greater gender equality outcomes among its immigrant populations.
A computational outlook on neurostimulation
Authors: Capogrosso Marco , Lempka Scott F. 
Published: May 2020

AbstractEfficient identification of effective neurostimulation strategies is critical due to the growing number of clinical applications and the increasing complexity of the corresponding technology. In consequence, investigators are encouraged to accelerate translational research of neurostimulation technologies and move quickly to clinical applications. However, this process is hampered by rigorous, but necessary, regulations and lack of a mechanistic understanding of the interactions between electric fields and neural circuits. Here we discuss how computational models have influenced the field of neurostimulation for pain and movement recovery, deep brain stimulation, and even device regulations. Finally, we propose our vision on how computational models will be key to accelerate clinical developments through mechanistic understanding.
Retrospective analysis of burn windows for fire and fuels management: an example from the Lake Tahoe Basin, California, USA
Authors: Striplin Randy , McAfee Stephanie A. , Safford Hugh D. , Papa Michael J. 
Published: May 2020

Abstract
Background
In fire-adapted ecosystems of the western USA, prescribed fire is an essential restoration and fuel reduction tool. There is general concern that, as the fire season lengthens, the window for conducting prescribed burns will contract unless management changes are made. This could occur because a number of conditions must be met before prescribed fire can be used in the field, and those are most common during the spring and autumn when the need for fire suppression response has been historically less. To assess patterns of potential prescribed burning feasibility, this study evaluated three conditions: (1) permission to burn as granted by air quality regulators; (2) weather within burn plan prescription; and (3) availability of operational and contingency resources. Our 21-year analysis (1999 to 2019) combines three independent datasets for a daily comparison of when prescribed fires could have been implemented (henceforth, burn windows) in the Lake Tahoe Basin (LTB) and analyzes seasonality, interannual variability, and trends.

Results
Burn windows were most frequent during spring, followed by autumn, with the fewest burn windows during the summer and winter. Burn windows lasting multiple days occurred infrequently. Two- to three-day burn windows did not often occur more than twice per month over the study period, and longer burn windows were very rare. Interannual variation was considerable. Finally, an abrupt increase in burn windows was detected in 2008. This was determined to be related to a methodological change by air quality regulators and not to any changes in climate or resource availability.

Conclusions
While this case study focuses on the LTB, the analysis was performed with readily available data and could be applied easily to other land management units, demonstrating a valuable method for planning and prioritizing fire and fuels management activities. This type of tool can also identify areas for research. For example, if there were unused burn windows during the winter and early spring—or they were projected to increase—research into the ecological impacts of winter and spring burning may allow managers to more confidently adapt to changing climate. Moreover, this analysis demonstrated that modest and reasonable regulatory changes can increase opportunities for prescribed burning.
Formulation and evaluation of buccal films of piroxicam co-crystals
Authors: Ammanage Anand , Rodriques Paul , Kempwade Amolkumar , Hiremath Ravindra 
Published: May 2020

AbstractBackgroundThe aim of the present study was to enhance the solubility of piroxicam (BCS class II drug) using co-crystallization technique and formulate the buccal films of selected co-crystals for improved therapeutic utilization of drug. Co-crystals of drug with various co-formers (molar ratio 1:1) were prepared by solvent evaporation method and were screened for their aqueous solubility and percent drug content. The formation of co-crystals was confirmed by FTIR, DSC and XRD. Piroxicam co-crystals loaded buccal films were prepared and evaluated for in vitro drug release, ex vivo drug permeation while safety of formulation was determined by histopathological study.ResultsThe co-crystals prepared with different co-formers have proved their potential to improve the solubility of the drug. Co-crystals of piroxicam-sucralose have shown six-folds more solubility than parent drug. FTIR analysis indicated shifting in characteristics peaks of piroxicam. DSC analysis showed an extra exothermic peak and alteration in characteristic endothermic peak. The powder x-ray diffraction pattern exhibited changes in 2θvalues of intense peaks. Thus, formation of co-crystal was confirmed. Physical characters of buccal films were found to be within limits. Formulation F6 showed highest mucoadhesive strength (5617 ± 636 dynes /cm2) while formulation F2 showed highest in vitro drug release after 8 h, i.e., 94.557%. The ex vivo drug permeation of F2 was found to be 84.74%. The hisopathological study revealed that there was no damage to buccal mucosal tissue and was found to be intact.ConclusionThe piroxicam-suralose co-crystals based mucoadhesive films of piroxicam could be a better formulation approach with improved solubility, safety, and therapeutic efficacy as compared to conventional tablets.Graphical abstract
Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial.
Authors: Olson Daniel , Luke Jason J. , Poklepovic Andrew Stewart , Bajaj Madhuri , Higgs Emily , Carll Timothy C. , Labadie Brian , Krausz Thomas , Zha Yuanyuan , Karrison Theodore , Lutzky Jose , Hallmeyer Sigrun , Brockstein Bruce , Sondak Vernon K. , Eroglu Zeynep , Gajewski Thomas , Khushalani Nikhil I. 
Published: May 2020

10004 Background: Combination PD1 + CTLA4 antibodies (Abs) shows greater response rate (RR) versus PD1 Ab alone in MEL, but RR after initial PD1 Ab progression awaits robust investigation. CTLA4 Ab alone after PD1 Ab progression has a historical RR of 13%. We report final results of the first prospective clinical trial evaluating IPI 1mg/kg + PEMBRO immediately following progression on PD1 Ab (NCT02743819). Methods: Patients (pts) with advanced MEL, no prior CTLA4 Ab for metastatic disease, and who had progressed on PD1 Ab as immediately prior therapy (or non-CTLA4 Ab combination) were eligible. Pts received PEMBRO 200 mg + IPI 1 mg/kg Q3W for 4 doses, then PEMBRO alone for up to two years. The primary endpoint was RR by irRECIST. After 35 pts, the study met its primary endpoint with 10/22 evaluable pts achieving a response. The trial was expanded to enroll a total of 70 pts in open-label accrual to further describe the RR for this regimen in an exploratory fashion. The data analysis cutoff was January 30, 2020. Results: 67/70 accrued patients were evaluable for treatment response. Prior treatments included 60 on PD1 Ab alone and 10 on PD1 Ab-based combinations. Of these, 10 pts had progressed in the adjuvant setting. Median length of treatment on prior PD1 Ab was 4.8 months. Response assessments included 4 CR, 17 PR and 16 SD for a RR of 31% (21/67) in evaluable pts, and 30% (21/70) in all enrolled pts. 4 pts with a PR and 6 with SD had unconfirmed responses making the irRECIST response rate 25% (17/67) and 24% (17/70) among evaluable and enrolled pts, respectively. Median progression free survival (PFS) was 4.7 mo (95% CI: 2.8-8.3) and PFS at six months was 45% (95% CI: 33%-57%). 15/70 (21%) pts experienced ≥ grade 3-4 drug-related AEs, the most common being diarrhea, rash and transaminase elevation. PD-L1 positive vs negative status from historical tumor specimens did not associate with RR. Conclusions: This is the largest prospective study of IPI 1mg/kg + PEMBRO, demonstrating significant antitumor activity and tolerability in MEL post-PD1 Ab. Clinical trial information: NCT02743819.
Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma.
Authors: Sheng Xinan , Yan Xieqiao , Chi Zhihong , Si Lu , Cui Chuanliang , Tang Bixia , Li Siming , Mao Lili , LIAN BIN , Wang Xuan , Bai Xue , Zhou Li , Kong Yan , Dai Jie , Flaherty Keith , Guo Jun ,   Shanghai Junshi Biosciences
Published: May 2020

10007 Background: Metastatic mucosal melanoma responds poorly to PD-1 blockade therapy in comparison with cutaneous melanoma. Vascular endothelial growth factor (VEGF) is indicated to play an important immunosuppressive role in mucosal melanoma. Combination of VEGF inhibition with PD-1 blockade might provide therapeutic opportunities. Toripalimab was approved as a second-line treatment for metastasis melanoma in Dec 2018. This study is to evaluate the safety and clinical efficacy of toripalimab combined with axitinib for the treatment of metastatic mucosal melanoma. (Clinical trial ID: NCT03086174). Methods: Patients with metastatic melanoma receive 1 or 3 mg/kg toripalimab Q2W in combination with 5 mg axitinib BID until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and gene expression profile (GEP) will be evaluated for correlation with clinical response. Results: From April 2017 to April 2018, 33 patients were enrolled in the study. No DLT or treatment related death was observed. 97% patients experienced treatment related AE (TRAE) and 39.4% patients experienced Grade 3-4 TRAEs. Most common TRAEs include diarrhea, proteinuria, hand and foot syndrome and hypothyroidism. Only one patient discontinued treatment due to TRAE. Among 29 treatment naïve mucosal melanoma patients, 14 PR and 11 SD were observed for an ORR of 48.3% and a DCR of 86.2%. The median DOR was 13.7 months. The median PFS was 7.5 months and the median OS was 20.7 months. PD-L1 expression or TMB had no significant differences in responders versus non-responders. In contrast, GEP scores of eight selected immune-related and four angiogenesis-related genes showed strong correlation with clinical response, whereas previous published immune related signature or angiogenesis signature alone had no correlation. Conclusions: Toripalimab combined with axitinib is a promising treatment option for metastatic mucosal melanoma. GEP scores of selected immune-related and angiogenesis-related genes might predict the response to the combination. A randomized 3-arm Phase 2 trial has been initiated to compare toripalimab plus axitinib with toripalimab or axitinib alone. Clinical trial information: NCT03086174.
Results of a phase II randomized trial of cisplatin +/- veliparib in metastatic triple-negative breast cancer (TNBC) and/or germline BRCA-associated breast cancer (SWOG S1416).
Authors: Sharma Priyanka , Rodler Eve , Barlow William E. , Gralow Julie , Huggins-Puhalla Shannon Leigh , Anders Carey K. , Goldstein Lori J. , Brown-Glaberman Ursa Abigail , Huynh Thu-Tam , Szyarto Christopher Scott , Godwin Andrew K. , Pathak Harsh B , Swisher Elizabeth M. , Radke Marc R , Timms Kirsten M , Lew Danika L. , Miao Jieling , Pusztai Lajos , Hayes Daniel F. , Hortobagyi Gabriel N. 
Published: May 2020

1001 Background: PARP inhibitors(i) are effective in BRCA-mutation -associated metastatic breast cancer(MBC). However, there are no studies evaluating PARPi + platin chemotherapy in BRCA wild-type(wt) TNBC. Approximately 1/2 of BRCAwt TNBC demonstrate homologous recombination deficiency (HRD) resulting in a BRCA-like phenotype which might render them sensitive to PARPi. S1416 compared the efficacy of cisplatin plus PARPi veliparib (Vel) or placebo (P) in 3 groups of MBC: gBRCA+; BRCA-like; and non-BRCA-like. Methods: Patients (pts) with metastatic TNBC or g BRCA1/2-associated MBC, who had received < 1 line of prior therapy were treated with cisplatin (75mg/m2) plus Vel or P (300 mg po BID days 1-14), every 3 weeks. All pts underwent central gBRCA testing. A priori established multipronged biomarker panel was used to classify BRCAwt pts into BRCA-like and non-BRCA-like groups, and included myChoice HRD score, somatic BRCA1/2 mutations, BRCA1 methylation and non- BRCA1/2 HR germline mutations. Primary end-point was progression-free survival (PFS) in the three pre-defined groups; secondary end-points included objective response rate (ORR), overall survival (OS), toxicity. Results: 323/335 randomized pts were eligible for efficacy evaluation; 31% had received 1 prior chemotherapy for MBC. 248 pts were classified into the three groups: (1) 37 gBRCA+ (2) 101 BRCA-like; (3) 110 non- BRCA-like. Remaining 75 could not be classified due to missing biomarker information. In the gBRCA+ group (which reached 62% of its projected accrual), numerically better PFS was noted with Vel compared to P (HR=0.64; p=0.26) though this difference was not statistically significant. In BRCA-like group improved PFS was noted with Vel vs P (median PFS 5.7 vs 4.3 months HR=0.58; p=0.023, 1 years PFS 20% vs 7%). Numerically better OS (median OS 13.7 vs 12.1 months, HR=0.66; p=0.14) and ORR (45% vs 35%, p=0.38) were noted with Vel vs P in BRCA-like group. Non-BRCA-like group did not show benefit of veliparib for PFS (HR=0.85; p=0.43) neither did the unclassified group (HR=0.97). Grade 3/4 neutropenia (46% vs 19%) and anemia (23% vs 7%) occurred at higher frequency in Vel arm compared to P. Conclusions: Addition of Vel to cisplatin significantly improved PFS and showed a trend towards improved OS for BRCA-like advanced TNBC. Integral biomarkers used in this study identified a subgroup of BRCAwt TNBC who benefited from addition of PARPi to cisplatin; platinum plus PARPi combination should be explored further in BRCA-like TNBC. Clinical trial information: NCT02595905 .