bluuebunny/crossref_metadata_2025_split huggingface dataset:
InContext: curation of medical context for drug indications
Authors: Moodley Kody , Rieswijk Linda , Oprea Tudor I. , Dumontier Michel 
Published: February 2021

AbstractAccurate and precise information about the therapeutic uses (indications) of a drug is essential for applications in drug repurposing and precision medicine. Leading online drug resources such as DrugCentral and DrugBank provide rich information about various properties of drugs, including their indications. However, because indications in such databases are often partly automatically mined, some may prove to be inaccurate or imprecise. Particularly challenging for text mining methods is the task of distinguishing between general disease mentions in drug product labels and actual indications for the drug. For this, the qualifying medical context of the disease mentions in the text should be studied. Some examples include contraindications, co-prescribed drugs and target patient qualifications. No existing indication curation efforts attempt to capture such information in a precise way. Here we fill this gap by presenting a novel curation protocol for extracting indications and machine processable annotations of contextual information about the therapeutic use of a drug. We implemented the protocol on a reference set of FDA-approved drug product labels on the DailyMed website to curate indications for 150 anti-cancer and cardiovascular drugs. The resulting corpus - InContext - focuses on anti-cancer and cardiovascular drugs because of the heightened societal interest in cancer and heart disease. In order to understand how InContext relates with existing reputable drug indication databases, we analysed it’s overlap with a state-of-the-art indications database - LabeledIn - as well as a reputable online drug compendium - DrugCentral. We found that 40% of indications sampled from DrugCentral (and 23% from LabeledIn) respectively, could not be accounted for in InContext. This raises questions about the veracity of indications not appearing in InContext. The additional contextual information curated by InContext about disease mentions in drug SPLs provides a foundation for more precise, structured and formal representations of knowledge related to drug therapeutic use, in order to increase accuracy and agreement of drug indication extraction methods for in silico drug repurposing.
Quantitation of cancer treatment response by 2-[18F]FDG PET/CT: multi-center assessment of measurement variability using AUTO-PERCIST™
Authors:   QIN PET Readers, O Joo Hyun , Lim Su Jin , Wang Hao , Leal Jeffrey P. , Shu Hui-Kuo G. , Wahl Richard L. 
Published: February 2021

Abstract
Background
The aim of this study was to assess the reader variability in quantitatively assessing pre- and post-treatment 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans in a defined set of images of cancer patients using the same semi-automated analytical software (Auto-PERCIST™), which identifies tumor peak standard uptake value corrected for lean body mass (SULpeak) to determine [18F]FDG PET quantitative parameters.

Methods
Paired pre- and post-treatment [18F]FDG PET/CT images from 30 oncologic patients and Auto-PERCIST™ semi-automated software were distributed to 13 readers across US and international sites. One reader was aware of the relevant medical history of the patients (readreference), whereas the 12 other readers were blinded to history but had access to the correlative images. Auto-PERCIST™ was set up to first automatically identify the liver and compute the threshold for tumor measurability (1.5 × liver mean) + (2 × liver standard deviation [SD]) and then detect all sites with SULpeak greater than the threshold. Next, the readers selected sites they believed to represent tumor lesions. The main performance metric assessed was the percent change in the SULpeak (%ΔSULpeak) of the hottest tumor identified on the baseline and follow-up images.

Results
The intra-class correlation coefficient (ICC) for the %ΔSULpeak of the hottest tumor was 0.87 (95%CI: [0.78, 0.92]) when all reads were included (n = 297). Including only the measurements that selected the same target tumor as the readreference (n = 224), the ICC for %ΔSULpeak was 1.00 (95%CI: [1.00, 1.00]). The Krippendorff alpha coefficient for response (complete or partial metabolic response, versus stable or progressive metabolic disease on PET Response Criteria in Solid Tumors 1.0) was 0.91 for all reads (n = 380) and 1.00 including for reads with the same target tumor selection (n = 270).

Conclusion
Quantitative tumor [18F]FDG SULpeak changes measured across multiple global sites and readers utilizing Auto-PERCIST™ show very high correlation. Harmonization of methods to single software, Auto-PERCIST™, resulted in virtually identical extraction of quantitative tumor response data from [18F]FDG PET images when the readers select the same target tumor.
Low-dose Diosbulbin-B (DB) activates tumor-intrinsic PD-L1/NLRP3 signaling pathway mediated pyroptotic cell death to increase cisplatin-sensitivity in gastric cancer (GC)
Authors: Li Chunfeng , Qiu Junqiang , Xue Yingwei 
Published: February 2021

Abstract
Background
Emerging evidences suggests that Diosbulbin-B (DB) is effective to improve cisplatin (DDP)-sensitivity in gastric cancer (GC), but its molecular mechanisms were not fully delineated, and this study managed to investigate this issue.

Methods
Genes expressions were determined by Real-Time qPCR and Western Blot at transcriptional and translational levels. Cell proliferation and viability were evaluated by cell counting kit-8 (CCK-8) and trypan blue staining assay. Annexin V-FITC/PI double staining assay was used to examine cell apoptosis. The Spheroid formation assay was used to evaluated cell stemness. The xenograft tumor-bearing mice models were established, and the tumors were monitored and the immunohistochemistry (IHC) was employed to examine the expressions and localization of Ki67 protein in mice tumor tissues.

Results
Low-dose DB (12.5 μM) downregulated PD-L1 to activate NLRP3-mediated pyroptosis, and inhibited cancer stem cells (CSCs) properties, to sensitize cisplatin-resistant GC (CR-GC) cells to cisplatin. Mechanistically, the CR-GC cells were obtained, and either low-dose DB or cisplatin alone had little effects on cell viability in CR-GC cells, while low-dose DB significantly induced apoptotic cell death in cisplatin treated CR-GC cells. In addition, low-dose DB triggered cell pyroptosis in CR-GC cells co-treated with cisplatin, which were abrogated by silencing NLRP3. Next, CSCs tended to be enriched in CR-GC cells, instead of their parental cisplatin-sensitive GC (CS-GC) cells, and low-dose DB inhibited spheroid formation and stemness biomarkers (SOX2, OCT4 and Nanog) expressions to eliminate CSCs in CR-GC cells, which were reversed by upregulating programmed death ligand-1 (PD-L1). Furthermore, we proved that PD-L1 negatively regulated NLRP3 in CR-GC cells, and low-dose DB activated NLRP3-mediated pyroptotic cell death in cisplatin treated CR-GC cells by downregulating PD-L1. Also, low-dose DB aggravated the inhibiting effects of cisplatin on tumorigenesis of CR-GC cells in vivo.

Conclusions
Collectively, low-dose DB regulated intrinsic PD-L1/NLRP3 pathway to improve cisplatin-sensitivity in CR-GC cells, and this study provided alternative therapy treatments for GC.
A road-map for addressing antimicrobial resistance in low- and middle-income countries: lessons learnt from the public private participation and co-designed antimicrobial stewardship programme in the State of Kerala, India
Authors: Singh Sanjeev , Charani Esmita , Devi Sarada , Sharma Anuj , Edathadathil Fabia , Kumar Anil , Warrier Anup , Shareek P. S. , Jaykrishnan A. V. , Ellangovan K. 
Published: February 2021

AbstractBackgroundThe global concern over antimicrobial resistance (AMR) is gathering pace. Low- and middle-income countries (LMICs) are at the epicentre of this growing public health threat and governmental and healthcare organizations are at different stages of implementing action plans to tackle AMR. The South Indian state of Kerala was one of the first in India to implement strategies and prioritize activities to address this public health threat.StrategiesThrough a committed and collaborative effort from all healthcare related disciplines and its professional societies from both public and private sector, the Kerala Public Private Partnership (PPP) has been able to deliver a state-wide strategy to tackle AMR A multilevel strategic leadership model and a multilevel implementation approach that included developing state-wide antibiotic clinical guidelines, a revision of post-graduate and undergraduate medical curriculum, and a training program covering all general practitioners within the state the PPP proved to be a successful model for ensuring state-wide implementation of an AMR action plan. Collaborative work of multi-professional groups ensured co-design and development of disease based clinical treatment guidelines and state-wide infection prevention policy. Knowledge exchange though international and national platforms in the form of workshops for sharing of best practices is critical to success. Capacity building at both public and private institutions included addressing practical and local solutions to the barriers e.g. good antibiotic prescription practices from primary to tertiary care facility and infection prevention at all levels.ConclusionThrough 7 years of stakeholder engagement, lobbying with government, and driving change through co-development and implementation, the PPP successfully delivered an antimicrobial stewardship plan across the state. The roadmap for the implementation of the Kerala PPP strategic AMR plan can provide learning for other states and countries aiming to implement action plans for AMR.
Ultraviolet disinfection robots to improve hospital cleaning: Real promise or just a gimmick?
Authors:   for the ESCMID Study Group on Nosocomial Infections “The decontamination research working group”, Diab-El Schahawi Magda , Zingg Walter , Vos Margreet , Humphreys Hilary , Lopez-Cerero Lorena , Fueszl Astrid , Zahar Jean Ralph , Presterl Elisabeth 
Published: February 2021

AbstractThe global COVID-19 pandemic due to the novel coronavirus SARS-CoV-2 has challenged the availability of traditional surface disinfectants. It has also stimulated the production of ultraviolet-disinfection robots by companies and institutions. These robots are increasingly advocated as a simple solution for the immediate disinfection of rooms and spaces of all surfaces in one process and as such they seem attractive to hospital management, also because of automation and apparent cost savings by reducing cleaning staff. Yet, there true potential in the hospital setting needs to be carefully evaluated. Presently, disinfection robots do not replace routine (manual) cleaning but may complement it. Further design adjustments of hospitals and devices are needed to overcome the issue of shadowing and free the movement of robots in the hospital environment. They might in the future provide validated, reproducible and documented disinfection processes. Further technical developments and clinical trials in a variety of hospitals are warranted to overcome the current limitations and to find ways to integrate this novel technology in to the hospitals of to-day and the future.
NeoCLEAN: a multimodal strategy to enhance environmental cleaning in a resource-limited neonatal unit
Authors: Dramowski A. , Aucamp M. , Bekker A. , Pillay S. , Moloto K. , Whitelaw A. C. , Cotton M. F. , Coffin S. 
Published: February 2021

Abstract
Background
Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings.

Methods
A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention for surfaces and equipment in a 30-bed neonatal ward. The intervention included cleaning audits with feedback, cleaning checklists, in-room cleaning wipes and training of staff and mothers in cleaning methods. Cleaning adequacy was evaluated for 100 items (58 surfaces, 42 equipment) using quantitative bacterial surface cultures, adenosine triphosphate bioluminescence assays and fluorescent ultraviolet markers, performed at baseline (P1, October 2019), early intervention (P2, November 2019) and late intervention (P3, February 2020).

Results
Environmental swabs (55/300; 18.3%) yielded growth of 78 potential neonatal pathogens with Enterococci, S. marcescens, K. pneumoniae, S. aureus and A. baumannii predominating. Highest aerobic colony counts were noted from moist surfaces such as sinks, milk kitchen surfaces, humidifiers and suction tubing. The proportion of surfaces and equipment exhibiting no bacterial growth increased between phases (P1 = 49%, P2 = 66%, P3 = 69%; p = 0.007). The proportion of surfaces and equipment meeting the ATP “cleanliness” threshold (< 200 relative light units) increased over time (P1 = 40%, P2 = 54%, P3 = 65%; p = 0.002), as did the UV marker removal rate (P1 = 23%, P2 = 71%, P3 = 74%; p < 0.001).

Conclusion
Routine environmental cleaning of this neonatal ward was sub-optimal at baseline but improved significantly following a multimodal cleaning intervention. Involving mothers and nursing staff was key to achieving improved environmental and equipment cleaning in this resource-limited neonatal unit.
Contribution of rare homozygous and compound heterozygous VPS13C missense mutations to dementia with Lewy bodies and Parkinson’s disease
Authors:   BELNEU consortium, Smolders Stefanie , Philtjens Stéphanie , Crosiers David , Sieben Anne , Hens Elisabeth , Heeman Bavo , Van Mossevelde Sara , Pals Philippe , Asselbergh Bob , Dos Santos Dias Roberto , Vermeiren Yannick , Vandenberghe Rik , Engelborghs Sebastiaan , De Deyn Peter Paul , Martin Jean-Jacques , Cras Patrick , Annaert Wim , Van Broeckhoven Christine 
Published: February 2021

AbstractDementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are clinically, pathologically and etiologically disorders embedded in the Lewy body disease (LBD) continuum, characterized by neuronal α-synuclein pathology. Rare homozygous and compound heterozygous premature termination codon (PTC) mutations in the Vacuolar Protein Sorting 13 homolog C gene (VPS13C) are associated with early-onset recessive PD. We observed in two siblings with early-onset age (< 45) and autopsy confirmed DLB, compound heterozygous missense mutations in VPS13C, p.Trp395Cys and p.Ala444Pro, inherited from their healthy parents in a recessive manner. In lymphoblast cells of the index patient, the missense mutations reduced VPS13C expression by 90% (p = 0.0002). Subsequent, we performed targeted resequencing of VPS13C in 844 LBD patients and 664 control persons. Using the optimized sequence kernel association test, we obtained a significant association (p = 0.0233) of rare VPS13C genetic variants (minor allele frequency ≤ 1%) with LBD. Among the LBD patients, we identified one patient with homozygous missense mutations and three with compound heterozygous missense mutations in trans position, indicative for recessive inheritance. In four patients with compound heterozygous mutations, we were unable to determine trans position. The frequency of LBD patient carriers of proven recessive compound heterozygous missense mutations is 0.59% (5/844). In autopsy brain tissue of two unrelated LBD patients, the recessive compound heterozygous missense mutations reduced VPS13C expression. Overexpressing of wild type or mutant VPS13C in HeLa or SH-SY5Y cells, demonstrated that the mutations p.Trp395Cys or p.Ala444Pro, abolish the endosomal/lysosomal localization of VPS13C. Overall, our data indicate that rare missense mutations in VPS13C are associated with LBD and recessive compound heterozygous missense mutations might have variable effects on the expression and functioning of VPS13C. We conclude that comparable to the recessive inherited PTC mutations in VPS13C, combinations of rare recessive compound heterozygous missense mutations reduce VPS13C expression and contribute to increased risk of LBD.
Functional identification of an opsin kinase underlying inactivation of the pineal bistable opsin parapinopsin in zebrafish
Authors: Shen Baoguo , Wada Seiji , Nishioka Haruka , Nagata Takashi , Kawano-Yamashita Emi , Koyanagi Mitsumasa , Terakita Akihisa 
Published: February 2021

AbstractIn the pineal organ of zebrafish larvae, the bistable opsin parapinopsin alone generates color opponency between UV and visible light. Our previous study suggested that dark inactivation of the parapinopsin photoproduct, which activates G-proteins, is important for the regulation of the amount of the photoproduct. In turn, the photoproduct is responsible for visible light sensitivity in color opponency. Here, we found that an opsin kinase or a G-protein-coupled receptor kinase (GRK) is involved in inactivation of the active photoproduct of parapinopsin in the pineal photoreceptor cells of zebrafish larvae. We investigated inactivation of the photoproduct in the parapinopsin cells of various knockdown larvae by measuring the light responses of the cells using calcium imaging. We found that GRK7a knockdown slowed recovery of the response of parapinopsin photoreceptor cells, whereas GRK1b knockdown or GRK7b knockdown did not have a remarkable effect, suggesting that GRK7a, a cone-type GRK, is mainly responsible for inactivation of the parapinopsin photoproduct in zebrafish larvae. We also observed a similar knockdown effect on the response of the parapinopsin photoreceptor cells of mutant larvae expressing the opsin SWS1, a UV-sensitive cone opsin, instead of parapinopsin, suggesting that the parapinopsin photoproduct was inactivated in a way similar to that described for cone opsins. We confirmed the immunohistochemical distribution of GRK7a in parapinopsin photoreceptor cells by comparing the immunoreactivity to GRK7 in GRK7a-knockdown and control larvae. These findings suggest that in pineal photoreceptor cells, the cone opsin kinase GRK7a contributes greatly to the inactivation of parapinopsin, which underlies pineal color opponency.
Modified valsalva versus standard valsalva for cardioversion of supraventricular tachycardia: systematic review and meta-analysis
Authors: Abdulhamid Ahmed S. , Almehmadi Fahad , Ghaddaf Abdullah A. , Alomari Mohammed S. , Zagzoog Amin , Al-Qubbany Atif 
Published: February 2021

AbstractBackgroundSupraventricular tachycardia (SVT) is a major cause of emergency room visits where vagal maneuver is used as first-line therapy. The valsalva maneuver (VM) is proven to be safe and, to some extent, effective in terminating SVT episodes. We aimed to compare the standard VM (SVM) to the modified valsalva maneuver (MVM). We hypothesized that MVM is more effective in terminating SVT episodes and reducing the time spent in the emergency department.MethodsIn this systematic review and meta-analysis, we searched Medline/PubMed, Ovid, Web of Science, and Cochrane Central Register of Controlled trials. We included only randomized controlled trials (RCTs) that compared the modified valsalva to the standard valsalva maneuver in treating SVT. Our main outcome was the termination of SVT within 1 min.ResultsFour articles met the eligibility criteria of our review. Sinus rhythm was achieved 2.5 times more in the MVM group compared to the SVM group (risk ratio (RR) = 2.54, CI 1.98–3.24,P < 0.001) and thus lowered the need of intravenous SVT termination medication without any significant increase in adverse events or time spent in the emergency department.ConclusionOur review found MVM to be more effective than the SVM in terminating SVT. This should encourage broader adoption of the MVM as a first-line vagal maneuver in subjects presenting with SVT in the emergency room.
Robotic-assisted vs conventional surgery in medial unicompartmental knee arthroplasty: a clinical and radiological study
Authors: Negrín Roberto , Duboy Jaime , Iñiguez Magaly , Reyes Nicolás O. , Barahona Maximiliano , Ferrer Gonzalo , Infante Carlos , Jabes Nicolás 
Published: February 2021

Abstract
Background
The use of unicompartmental knee arthroplasty (UKA) has increased and new technologies have been developed to improve patient survival and satisfaction, soft tissue balance, alignment, and component size. Robot-assisted systems offer an increase in surgical precision and accuracy. The purpose of this study is to evaluate the precision of component position using five radiological parameters in conventional and robotic-assisted medial UKA using the NAVIO system.

Methods
A cohort study was designed for patients who underwent medial UKA between April 2017 and March 2019 in a single center. Patients were allocated in the conventional (UKA-C) or robotic-assisted (UKA-R) group. The variables analyzed were age, gender, affected knee side, length of hospital stay, surgical time, and radiological measurements such as anatomical medial distal femoral angle (aMDFA), anatomical medial proximal tibial angle (aMPTA), tibial slope, the sagittal femoral angle, and the component size. A target was defined for each measurement, and a successful UKA was defined if at least four radiological measures were on target after surgery. Also, patients’ reported outcomes were evaluated using the Oxford Knee Score (OKS) and a numeric rating scale (NRS) for pain.

Results
Thirty-four patients were included, 18 of them underwent UKA-R. The success rate for UKA in the UKA-R group was 87%; meanwhile, in the UKA-C group this was 28%, this difference was significant and powered (Fisher’s exact test, p = 0.001; 1 − β = 0.95). Also, a 5-point difference in favor of the UKA-R group in the median OKS (p = 0.01), and a significantly lower median NRS for pain (p < 0.000) were found after surgery.

Conclusions
UKA-R achieved more precision in the radiological parameters’ measure in this study. Also, UKA-R has a trend towards a better OKS and a lower NRS for pain at short-term follow-up.