bluuebunny/crossref_metadata_2025_split huggingface dataset:
GraphDTI: A robust deep learning predictor of drug-target interactions from multiple heterogeneous data
Authors: Liu Guannan , Singha Manali , Pu Limeng , Neupane Prasanga , Feinstein Joseph , Wu Hsiao-Chun , Ramanujam J. , Brylinski Michal 
Published: August 2021

AbstractTraditional techniques to identify macromolecular targets for drugs utilize solely the information on a query drug and a putative target. Nonetheless, the mechanisms of action of many drugs depend not only on their binding affinity toward a single protein, but also on the signal transduction through cascades of molecular interactions leading to certain phenotypes. Although using protein-protein interaction networks and drug-perturbed gene expression profiles can facilitate system-level investigations of drug-target interactions, utilizing such large and heterogeneous data poses notable challenges. To improve the state-of-the-art in drug target identification, we developed GraphDTI, a robust machine learning framework integrating the molecular-level information on drugs, proteins, and binding sites with the system-level information on gene expression and protein-protein interactions. In order to properly evaluate the performance of GraphDTI, we compiled a high-quality benchmarking dataset and devised a new cluster-based cross-validation protocol. Encouragingly, GraphDTI not only yields an AUC of 0.996 against the validation dataset, but it also generalizes well to unseen data with an AUC of 0.939, significantly outperforming other predictors. Finally, selected examples of identified drugtarget interactions are validated against the biomedical literature. Numerous applications of GraphDTI include the investigation of drug polypharmacological effects, side effects through offtarget binding, and repositioning opportunities.
Biotechnological applications of S-adenosyl-methionine-dependent methyltransferases for natural products biosynthesis and diversification
Authors: Zhang Congqiang , Sultan Stella Amelia , T Rehka , Chen Xixian 
Published: August 2021

AbstractIn the biosynthesis of natural products, methylation is a common and essential transformation to alter molecules’ bioavailability and bioactivity. The main methylation reaction is performed by S-adenosylmethionine (SAM)-dependent methyltransferases (MTs). With advancements in genomic and chemical profiling technologies, novel MTs have been discovered to accept complex substrates and synthesize industrially valuable natural products. However, to achieve a high yield of small molecules in microbial hosts, many methyltransferase activities have been reported to be insufficient. Moreover, inadequate co-factor supplies and feedback inhibition of the by-product, S-adenosylhomocysteine (SAH), further limit MTs’ activities. Here, we review recent advances in SAM-dependent MTs to produce and diversify natural products. First, we surveyed recently identified novel methyltransferases in natural product biosynthesis. Second, we summarized enzyme engineering strategies to improve methyltransferase activity, with a particular focus on high-throughput assay design and application. Finally, we reviewed innovations in co-factor regeneration and diversification, both in vitro and in vivo. Noteworthily, many MTs are able to accept multiple structurally similar substrates. Such promiscuous methyltransferases are versatile and can be tailored to design de novo pathways to produce molecules whose biosynthetic pathway is unknown or non-existent in nature, thus broadening the scope of biosynthesized functional molecules.
Prognostic impact of CT severity score in childhood cancer with SARS-CoV-2
Authors: Romeih Marwa , Mahrous Mary Rabea , Shalby Lobna , Khedr Reham , Soliman Sonya , Hassan Reem , El-Ansary Mohamed Gamal , Ismail Amira , Al Halfway Ahmed , Mahmoud Abeer , Refeat Amal , Zaki Iman , Hammad Mahmoud 
Published: August 2021

AbstractBackgroundCT chest severity score (CTSS) is a semi-quantitative measure done to correlate the severity of the pulmonary involvement on the CT with the severity of the disease.The objectives of this study are to describe chest CT criteria and CTSS of the COVID-19 infection in pediatric oncology patients, to find a cut-off value of CTSS that can differentiate mild COVID-19 cases that can be managed at home and moderate to severe cases that need hospital care.A retrospective cohort study was conducted on 64 pediatric oncology patients with confirmed COVID-19 infection between 1 April and 30 November 2020. They were classified clinically into mild, moderate, and severe groups. CT findings were evaluated for lung involvement and CTSS was calculated and range from 0 (clear lung) to 20 (all lung lobes were affected).ResultsOverall, 89% of patients had hematological malignancies and 92% were under active oncology treatment. The main CT findings were ground-glass opacity (70%) and consolidation patches (62.5%). In total, 85% of patients had bilateral lung involvement, ROC curve showed that the area under the curve of CTSS for diagnosing severe type was 0.842 (95% CI 0.737–0.948). The CTSS cut-off of 6.5 had 90.9% sensitivity and 69% specificity, with 41.7% positive predictive value (PPV) and 96.9% negative predictive value (NPV). According to the Kaplan–Meier analysis, mortality risk was higher in patients with CT score>7 than in those with CTSS < 7.ConclusionPediatric oncology patients, especially those with hematological malignancies, are more vulnerable to COVID-19 infection. Chest CT severity score > 6.5 (about 35% lung involvement) can be used as a predictor of the need for hospitalization.
Understanding the value of adhering to or adapting evidence-based interventions: a study protocol of a discrete choice experiment
Authors: von Thiele Schwarz Ulrica , Lyon Aaron R. , Pettersson Kristoffer , Giannotta Fabrizia , Liedgren Pernilla , Hasson Henna 
Published: August 2021

AbstractBackgroundWhereas the value of an evidence-based intervention (EBI) is often determined by its effect on clinical outcomes, the value of implementing and using EBIs in practice is broader, reflecting qualities such as appropriateness, equity, costs, and impact. Reconciling these value conflicts involves a complicated decision process that has received very limited scholarly attention. Inspired by studies on decision-making, the objective of this project is to explore how practitioners appraise the values of different outcomes and to test how this appraisal influences their decisions surrounding the so-called fidelity–adaptation dilemma. This dilemma is related to the balance between using an EBI as it was designed (to ensure its effectiveness) and making appropriate adaptations (to ensure alignment with constraints and possibilities in the local context).MethodsThis project consists of three sub-studies. The participants will be professionals leading evidence-based parental programs in Sweden and, in Sub-study 1, parents and decision-makers. Sub-study 1 will use sequential focus groups and individual interviews to explore parameters that influence fidelity and adaptation decisions—the dilemmas encountered, available options, how outcomes are valued by practitioners as well as other stakeholders, and value trade-offs. Sub-study 2 is a discrete choice experiment that will test how value appraisals influence decision-making using data from Sub-study 1 as input. Sub-study 3 uses a mixed-method design, with findings from the two preceding sub-studies as input in focus group interviews to investigate how practitioners make sense of findings from optimal decision situations (experiment) and constrained, real-world decision situations.DiscussionThe project will offer unique insights into decision-making processes that influence how EBIs are used in practice. Such knowledge is needed for a more granular understanding of how practitioners manage the fidelity–adaptation dilemma and thus, ultimately, how the value of EBI implementation can be optimized. This study contributes to our knowledge of what happens once EBIs are adopted—that is, the gap between the way in which EBIs areintendedto be used and the way in which theyareused in practice.
Implementing at-birth, point-of-care HIV testing in Kenya: a qualitative study using the Consolidated Framework for Implementation Research
Authors: Wexler Catherine , Kamau Yvonne , Muchoki Elizabeth , Babu Shadrack , Maosa Nicodemus , Maloba May , Brown Melinda , Goggin Kathy , Mabachi Natabhona , Gautney Brad , Finocchario-Kessler Sarah 
Published: August 2021

AbstractBackgroundAt-birth and point-of-care (POC) testing can expedite early infant diagnosis of HIV and improve infant outcomes. Guided by the Consolidated Framework for Implementation Research (CFIR), this study describes the implementation of an at-birth POC testing pilot from the perspective of implementing providers and identifies the factors that might support and hinder the scale up of these promising interventions.MethodsWe conducted 28 focus group discussions (FGDs) with 48 providers across 4 study sites throughout the course of a pilot study assessing the feasibility and impact of at-birth POC testing. FGDs were audio-recorded, transcribed, and analyzed for a priori themes related to CFIR constructs. This qualitative study was nested within a larger study to pilot and evaluate at-birth and POC HIV testing.ResultsOut of the 39 CFIR constructs, 30 were addressed in the FGDs. While all five domains were represented, major themes revolved around constructs related to intervention characteristics, inner setting, and outer setting. Regarding intervention characteristics, the advantages of at-birth POC (rapid turnaround time resulting in improved patient management and enhanced patient motivation) were significant enough to encourage provider uptake and enthusiasm. Challenges at the intervention level (machine breakdown, processing errors), inner settings (workload, limited leadership engagement, challenges with access to information), and outer setting (patient-level challenges, limited engagement with outer setting stakeholders) hindered implementation, frustrated providers, and resulted in missed opportunities for testing. Providers discussed how throughout the course of the study adaptations to implementation (improved channels of communication, modified implementation logistics) were made to overcome some of these challenges. To improve implementation, providers cited the need for enhanced training and for greater involvement among stakeholders outside of the implementing team (i.e., other clinicians, hospital administrators and implementing partners, county and national health officials). Despite provider enthusiasm for the intervention, providers felt that the lack of engagement from leadership within the hospital and in the outer setting would preclude sustained implementation outside of a research setting.ConclusionDespite demonstrated feasibility and enthusiasm among implementing providers, the lack of outer setting support makes sustained implementation of at-birth POC testing unlikely at this time. The findings highlight the multi-dimensional aspect of implementation and the need to consider facilitators and barriers within each of the five CFIR domains.Trial registrationClinicalTrials.gov,NCT03435887. Retrospectively registered on 19 February 2020
Laser fabrication of modular superhydrophobic chips for reconfigurable assembly and self-propelled droplet manipulation
Authors: Wang Huan , Zhang Yong-Lai , Han Dong-Dong , Wang Wei , Sun Hong-Bo 
Published: August 2021

AbstractNatural creatures that enables controllable liquid transport provides the inspiration for developing novel microfluidic devices by engineering functional surfaces with superwettability. However, towards microfluidic applications, the strict requirements of sophisticated droplet manipulation make it challenging to reach this end. In this work, we report a conceptually new self-propelled droplet manipulation strategy based on reconfigurable superhydrophobic chips. The modular droplet chip (MDC) is developed by laser embossing a series of superhydrophobic structures on elastomer jigsaws that act as functional units. MDC is potable since only gravity is used as the driving force for dynamic manipulation of liquid droplets, including droplets transporting, splitting, merging and bouncing without mass loss. The MDC demonstrated reasonable anti-cross-contamination property due to the water repellence of the superhydrophobicity. Modular assembly of MDC enables different chip functions including solution dilution, SERS detection, cell labeling and chemical synthesis. As a miniature and portable experimental platform, the MDC is promising for next-generation lab-on-a-chip systems.
Feasibility of home and hospital colorectal irrigation with continuous tube placement for Hirschsprung’s disease in neonates and infants: a comparative retrospective study
Authors: Sakurai Tsuyoshi , Nakamura Megumi , Endo Naobumi 
Published: August 2021

Abstract
Background
Since the length of the affected colon widely varies, the preoperative management of Hirschsprung’s disease varies from one hospital to another. For our cases in which the length of the aganglionic colon cannot be managed by enema, anal bougienage, or rectal irrigation, colorectal irrigation is used along with the placement of a transanal catheter for these patients as home or hospital management, until one-stage definitive surgery can be performed. No comparative studies have been conducted on the continuous tube placement method, and no study has utilized this method as home management. Thus, this study aimed to analyze the efficacy and feasibility of our proposed continuous tube placement management for patients with Hirschsprung’s disease in the hospital or even at home.

Results
We included 22 infants with Hirschsprung’s disease between 2008 and 2018. The patients were divided into two groups: those who were managed with enema, bougienage, and rectal irrigation (n = 6), and those who were managed with the placement of a continuous transanal tube and colorectal irrigation (n = 16). The group with continuous transanal tube placement was further divided into two groups: those who were preoperatively managed with a continuous anorectal tube at home (n = 7), and those at a hospital (n = 9). Preoperative demographic information and clinical details were retrospectively examined and compared between the two groups. Univariate analysis showed no significant differences in the backgrounds and clinical status between the enema, bougienage, and rectal irrigation group and the colorectal irrigation group. The patients in the home group were older and weighed more at the time of radical surgery than those in the hospital group (p = 0.0267, p = 0.0377, respectively). The total duration of hospitalization until radical surgery was significantly decreased in the home group (p = 0.0315).

Conclusions
The total duration of hospitalization was significantly reduced in patients undergoing home colorectal irrigation which was as effective as the conventional method, with no impact on the preoperative condition or postoperative outcomes. Hence, our home-based preoperative management for patients with Hirschsprung’s disease may be effective and potentially feasible for the management of patients with Hirschsprung’s disease.
Remembered jewels: The Role of Diagnosis in Psychiatry by Robert Kendell
Authors: Tyrer Peter 
Published: August 2021

SUMMARYThis is the first of a series of articles on key works in psychiatry that should not be forgotten. Many were published before our current generation of psychiatrists had easy access to them, but they need recall. It is my strong belief that originality of thought only occurs in youth. Robert Kendell's book The Role of Diagnosis in Psychiatry (1975) illustrates this perfectly.
RETRACTED: Utility of Homologous Recombination Deficiency Biomarkers Across Cancer Types
Authors: Takamatsu Shiro , Brown J.B. , Yamaguchi Ken , Hamanishi Junzo , Yamanoi Koji , Takaya Hisamitsu , Kaneyasu Tomoko , Mori Seiichi , Mandai Masaki , Matsumura Noriomi 
Published: August 2021

PURPOSE

Homologous recombination DNA repair deficiency (HRD) is associated with sensitivity to platinum and poly (ADP-ribose) polymerase inhibitors in certain cancer types, including breast, ovarian, pancreatic, and prostate. In these cancers,
BRCA1/2
alterations and genomic scar signatures are useful indicators for assessing HRD. However, alterations in other homologous recombination repair (HRR)-related genes and their clinical significance in other cancer types have not been adequately and systematically investigated.

METHODS

We obtained data sets of all solid tumors in The Cancer Genome Atlas and Cancer Cell Line Encyclopedia, and comprehensively analyzed HRR pathway gene alterations, their loss-of-heterozygosity status, and per-sample genomic scar scores, that is, the HRD score and mutational signature 3 ratio, DNA methylation profiles, gene expression profiles, somatic
TP53
mutations, sex, and clinical or in vitro response to chemical exposure.

RESULTS

Biallelic alterations in HRR genes other than
BRCA1/2
were also associated with elevated genomic scar scores. The association between HRR-related gene alterations and genomic scar scores differed significantly by sex and the presence of somatic
TP53
mutations. HRD tumors determined by a combination of indices also showed HRD features in gene expression analysis and exhibited significantly higher sensitivity to DNA-damaging agents than non-HRD cases in both clinical samples and cell lines.

CONCLUSION
This study provides evidence for the usefulness of HRD analysis in all cancer types, improves chemotherapy decision making and its efficacy in clinical settings, and represents a substantial advancement in precision oncology.
Progesterone Receptors in AVPV Kisspeptin Neurons Are Sufficient for Positive Feedback Induction of the LH Surge
Authors: Mohr Margaret A , Esparza Lourdes A , Steffen Paige , Micevych Paul E , Kauffman Alexander S 
Published: August 2021

Abstract
Kisspeptin, encoded by Kiss1, stimulates gonadotropin-releasing hormone neurons to govern reproduction. In female rodents, estrogen-sensitive kisspeptin neurons in the rostral anteroventral periventricular (AVPV) hypothalamus are thought to mediate estradiol (E2)-induced positive feedback induction of the preovulatory luteinizing hormone (LH) surge. AVPV kisspeptin neurons coexpress estrogen and progesterone receptors (PGRs) and are activated during the LH surge. While E2 effects on kisspeptin neurons have been well studied, progesterone’s regulation of kisspeptin neurons is less understood. Using transgenic mice lacking PGR exclusively in kisspeptin cells (termed KissPRKOs), we previously demonstrated that progesterone action specifically in kisspeptin cells is essential for ovulation and normal fertility. Unlike control females, KissPRKO females did not generate proper LH surges, indicating that PGR signaling in kisspeptin cells is required for positive feedback. However, because PGR was knocked out from all kisspeptin neurons in the brain, that study was unable to determine the specific kisspeptin population mediating PGR action on the LH surge. Here, we used targeted Cre-mediated adeno-associated virus (AAV) technology to reintroduce PGR selectively into AVPV kisspeptin neurons of adult KissPRKO females, and tested whether this rescues occurrence of the LH surge. We found that targeted upregulation of PGR in kisspeptin neurons exclusively in the AVPV is sufficient to restore proper E2-induced LH surges in KissPRKO females, suggesting that this specific kisspeptin population is a key target of the necessary progesterone action for the surge. These findings further highlight the critical importance of progesterone signaling, along with E2 signaling, in the positive feedback induction of LH surges and ovulation.
Barriers to recruitment to an orthopaedic randomized controlled trial comparing two surgical procedures for ankle arthritis
Authors: Realpe Alba X. , Blackstone James , Griffin Damian R. , Bing Andrew J. F. , Karski Michael , Milner Stephen A. , Siddique Malik , Goldberg Andrew ,   *On behalf of the UK TARVA Study Group
Published: August 2021

Aims A multicentre, randomized, clinician-led, pragmatic, parallel-group orthopaedic trial of two surgical procedures was set up to obtain high-quality evidence of effectiveness. However, the trial faced recruitment challenges and struggled to maintain recruitment rates over 30%, although this is not unusual for surgical trials. We conducted a qualitative study with the aim of gathering information about recruitment practices to identify barriers to patient consent and participation to an orthopaedic trial. Methods We collected 11 audio recordings of recruitment appointments and interviews of research team members (principal investigators and research nurses) from five hospitals involved in recruitment to an orthopaedic trial. We analyzed the qualitative data sets thematically with the aim of identifying aspects of informed consent and information provision that was either unclear, disrupted, or hindered trial recruitment. Results Recruiters faced four common obstacles when recruiting to a surgical orthopaedic trial: patient preferences for an intervention; a complex recruitment pathway; various logistical issues; and conflicting views on equipoise. Clinicians expressed concerns that the trial may not show significant differences in the treatments, validating their equipoise. However, they experienced role conflicts due to their own preference and perceived patient preference for an intervention arm. Conclusion This study provided initial information about barriers to recruitment to an orthopaedic randomized controlled trial. We shared these findings in an all-site investigators’ meeting and encouraged researchers to find solutions to identified barriers; this led to the successful completion of recruitment. Complex trials may benefit for using of a mixed-methods approach to mitigate against recruitment failure, and to improve patient participation and informed consent. Cite this article: Bone Jt Open 2021;2(8):631–637.
Head injuries in professional football (soccer): Results of video analysis verified by an accident insurance registry
Authors: Krutsch Volker , Krutsch Werner , Härtl Jonas , Bloch Hendrik , Alt Volker , Klein Christian , Reinsberger Claus , Seiffert Robin , Huber Lorenz , Weber Johannes 
Published: August 2021

BackgroundVideo analysis is one of the most commonly applied methods for analysing football injuries.PurposeThe objective of this study was to assess the accuracy of video analysis for recording head injuries in professional football from official matches in the four highest men’s professional football leagues in Germany.MethodsIn this cohort study, head injuries detected by means of video analysis of all official matches over one season (2017–18) were compared to head injuries registered with the German statutory accident insurance.ResultsOur video analysis yielded 359 head injuries of 287 players. The comparison of head injuries found in our video analysis to those registered with the accident insurance only yielded a match in 23.1% (n = 83), which presents a rather low verification rate. The verification rates varied between the leagues (7.0–30.8%). All injuries documented in the accident insurance registry were found in the video analysis (100%). The types of head injury most often verified by the accident insurance registry (n = 83) were contusion (43.4%), bone fractures (19.3%) and skin lacerations (18.1%). Only 66 of the 359 head injuries (18.4%) resulted in absence from at least one training session and involved a mean time loss of 18.5 days (1–87 days).ConclusionThe mismatch between the number of head injuries found in the video analysis and head injuries registered with the accident insurance is an important methodological issue in scientific research. The low verification rate seems to be due to the unclear correlation between injury severity and clinical consequences of head injuries detected by means of video analysis and the failure of football clubs to register minor head injuries with the accident insurance.