bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomedical relation extraction via knowledge-enhanced reading comprehension
Authors: Chen Jing , Hu Baotian , Peng Weihua , Chen Qingcai , Tang Buzhou 
Published: January 2022

AbstractBackgroundIn biomedical research, chemical and disease relation extraction from unstructured biomedical literature is an essential task. Effective context understanding and knowledge integration are two main research problems in this task. Most work of relation extraction focuses on classification for entity mention pairs. Inspired by the effectiveness of machine reading comprehension (RC) in the respect of context understanding, solving biomedical relation extraction with the RC framework at both intra-sentential and inter-sentential levels is a new topic worthy to be explored. Except for the unstructured biomedical text, many structured knowledge bases (KBs) provide valuable guidance for biomedical relation extraction. Utilizing knowledge in the RC framework is also worthy to be investigated. We propose a knowledge-enhanced reading comprehension (KRC) framework to leverage reading comprehension and prior knowledge for biomedical relation extraction. First, we generate questions for each relation, which reformulates the relation extraction task to a question answering task. Second, based on the RC framework, we integrate knowledge representation through an efficient knowledge-enhanced attention interaction mechanism to guide the biomedical relation extraction.ResultsThe proposed model was evaluated on the BioCreative V CDR dataset and CHR dataset. Experiments show that our model achieved a competitive document-level F1 of 71.18% and 93.3%, respectively, compared with other methods.ConclusionResult analysis reveals that open-domain reading comprehension data and knowledge representation can help improve biomedical relation extraction in our proposed KRC framework. Our work can encourage more research on bridging reading comprehension and biomedical relation extraction and promote the biomedical relation extraction.
vCOMBAT: a novel tool to create and visualize a computational model of bacterial antibiotic target-binding
Authors: Tran Vi Ngoc-Nha , Shams Alireza , Ascioglu Sinan , Martinecz Antal , Liang Jingyi , Clarelli Fabrizio , Mostowy Rafal , Cohen Ted , Abel zur Wiesch Pia 
Published: January 2022

Abstract
Background
As antibiotic resistance creates a significant global health threat, we need not only to accelerate the development of novel antibiotics but also to develop better treatment strategies using existing drugs to improve their efficacy and prevent the selection of further resistance. We require new tools to rationally design dosing regimens from data collected in early phases of antibiotic and dosing development. Mathematical models such as mechanistic pharmacodynamic drug-target binding explain mechanistic details of how the given drug concentration affects its targeted bacteria. However, there are no available tools in the literature that allow non-quantitative scientists to develop computational models to simulate antibiotic-target binding and its effects on bacteria.

Results
In this work, we have devised an extension of a mechanistic binding-kinetic model to incorporate clinical drug concentration data. Based on the extended model, we develop a novel and interactive web-based tool that allows non-quantitative scientists to create and visualize their own computational models of bacterial antibiotic target-binding based on their considered drugs and bacteria. We also demonstrate how Rifampicin affects bacterial populations of Tuberculosis bacteria using our vCOMBAT tool.

Conclusions
The vCOMBAT online tool is publicly available at https://combat-bacteria.org/.
Divergence of X-linked trans regulatory proteins and the misexpression of gene targets in sterile Drosophila pseudoobscura hybrids
Authors: Go Alwyn C. , Civetta Alberto 
Published: January 2022

Abstract
Background
The genetic basis of hybrid incompatibilities is characterized by pervasive cases of gene interactions. Sex chromosomes play a major role in speciation and X-linked hybrid male sterility (HMS) genes have been identified. Interestingly, some of these genes code for proteins with DNA binding domains, suggesting a capability to act as trans-regulatory elements and disturb the expression of a large number of gene targets. To understand how interactions between trans- and cis-regulatory elements contribute to speciation, we aimed to map putative X-linked trans-regulatory elements and to identify gene targets with disrupted gene expression in sterile hybrids between the subspecies Drosophila pseudoobscura pseudoobscura and D. p. bogotana.

Results
We find six putative trans-regulatory proteins within previously mapped X chromosome HMS loci with sequence changes that differentiate the two subspecies. Among them, the previously characterized HMS gene Overdrive (Ovd) had the largest number of amino acid changes between subspecies, with some substitutions localized within the protein’s DNA binding domain. Using an introgression approach, we detected transcriptional responses associated with a sterility/fertility Ovd allele swap. We found a network of 52 targets of Ovd and identified cis-regulatory effects among target genes with disrupted expression in sterile hybrids. However, a combined analysis of polymorphism and divergence in non-coding sequences immediately upstream of target genes found no evidence of changes in candidate regulatory proximal cis-elements. Finally, peptidases were over-represented among target genes.

Conclusions
We provide evidence of divergence between subspecies within the DNA binding domain of the HMS protein Ovd and identify trans effects on the expression of 52 gene targets. Our results identify a network of trans-cis interactions with possible effects on HMS. This network provides molecular evidence of gene × gene incompatibilities as contributors to hybrid dysfunction.
Reduction of leakage from insertion site during continuous femoral nerve block with catheter-through-needle versus catheter-over-needle technique for postoperative analgesia after total knee arthroplasty: a randomized controlled trial
Authors: Hattammaru Yoshiyasu , Mio Yasushi , Hascilowicz Tomasz , Utsumi Isao , Murakami Yuichi , Omi Sachiko 
Published: January 2022

Abstract
Background
Continuous femoral nerve block (CFNB) is a common procedure used for postoperative analgesia in total knee arthroplasty. Continuous nerve block using a conventional needle (catheter-through-needle/CTN) is complicated by leakage of the anesthetic from the catheter insertion site. A different type of needle (catheter-over-needle/ CON) is now available, which is believed to reduce leakage as the diameter of the catheter is larger than that of the needle. The purpose of this study was to compare the incidence of leakage from the catheter insertion site during CFNB while using CTN and CON for postoperative analgesia after total knee arthroplasty (TKA).

Methods
This prospective, randomized, single-blinded controlled study included 60 patients who were scheduled for TKA at our facility between May 2016 and November 2017. Patients were randomly allocated to the CTN or CON groups. All patients in both groups received CFNB and sciatic nerve block for postoperative analgesia. The administration of 0.16% levobupivacaine mixed with 6 mg of indigo carmine (a dye added to easily identify leakage) was started at 6 ml/h at the end of surgery. The primary outcome was the incidence of leakage from the catheter insertion site. We further investigated the degree of leakage, the incidence of catheter migration, pain scores using the numerical rating scale at 48 h postoperatively, and the number of days until the operated knee could be flexed 120 degrees postoperatively in both groups.

Results
The CON group had a significantly lower incidence and degree of leakage from the catheter insertion site. There were no significant differences in other measurement outcomes.

Conclusions
Use of CON reduces the incidence of leakage from the catheter insertion site during CFNB in the use of postoperative analgesia for total knee arthroplasty. Future research is needed to determine additional benefits of using CON related to decreased leakage.

Trial registration
The study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000021537), prospectively registered on 18 March 2016.
Predictors of preoperative cognitive dysfunction in adults with Moyamoya disease: a preliminary research
Authors: Sun Jian , Shi Zhiyong , Yu Lebao , Wen Yujie , Zhang Dong 
Published: January 2022

Abstract
Objective
To explore potential risk factors of preoperative cognitive dysfunction in adult patients with moyamoya disease (MMD) and discuss significance of moyamoya vessels.

Methods
The author reviewed adult MMD patients harboring no parenchymal infarction or hemorrhage underwent a standardized neuropsychological assessment test battery from December 2018 to May 2019. The authors defined patients with cognitive dysfunction as cognitive impairment shown on 3 or more neuropsychological tests. According to the presence of cerebral angiography, arterial stenosis, moyamoya vessels, and compensatory arteries were conducted. Univariate and multivariate analyses were performed to identify predictors for cognitive dysfunction before surgery. Subgroup analyses by onset type and Suzuki stage were carried out to identify specific predictors for preoperative cognitive dysfunction.

Results
In total, 29 of 92 (31.52%) patients had cognitive dysfunction. Multivariate analysis showed that moyamoya vessels generating from left hemisphere was recognized as independent predictor for cognitive dysfunction (P = 0.025, OR [95%CI], 0.085 [0.012–0.874]). For patients in left ICA-moyamoya subgroup, 19 of 45 (42.22%) cases with sparse moyamoya vessels had cognitive dysfunction (P = 0.031), while 22 (91.67%) of patients with dense moyamoya vessels had normal cognition (P = 0.004). Moyamoya vessels arising from ophthalmic artery had no significant association with cognitive dysfunction (P = 0.111). Multivariate analysis found that moyamoya vessels originating from left ICA was recognized as independent predictors for preoperative cognitive dysfunction (P = 0.048, OR [95%CI], 0.394 [0.132–0.926]).

Conclusions
Moyamoya vessels arising from left hemisphere was a risk factor for the preoperative cognitive dysfunction in adult patients with MMD, with the denser moyamoya vessels, the less cognitive dysfunction. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.
Comparison of pregnancy outcomes and placental characteristics between selective fetal growth restriction with and without thick arterio-arterial anastomosis in monochorionic diamniotic twins
Authors: Wang Xueju , Li Luyao , Yuan Pengbo , Zhao Yangyu , Wei Yuan 
Published: January 2022

Abstract
Background
Unequal placental territory in monochorionic diamniotic twins is a primary cause of selective fetal growth restriction (sFGR), and vascular anastomoses play important role in determining sFGR prognosis. This study investigated differences in placental characteristics and pregnancy outcomes in cases of sFGR with and without thick arterio-arterial anastomosis (AAA).

Methods
A total of 253 patients diagnosed with sFGR between April 2013 and April 2020 were retrospectively analyzed. An AAA greater than 2 mm in diameter was defined as a thick AAA. We compared placental characteristics and pregnancy outcomes between cases of sFGR with and without thick AAA.

Results
Prevalence of AAA, thick arterio-venous anastomosis (AVA), veno-venous anastomosis (VVA), and thick VVA were significantly higher in the thick AAA group relative to the non-thick AAA group (100.0 vs. 78.5%, P < 0.001; 44.3 vs. 15.4%, P < 0.001; 27.1 vs. 10.8%, P = 0.017, and 24.3 vs. 6.2%, P = 0.004, respectively). The total numbers of AVA and total anastomoses were significantly higher in thick AAA group relative to the non-thick AAA group (5 [1, 14] vs. 3 [1, 15, P = 0.016; and 6 [1, 15] vs. 5 [1, 16], P = 0.022, respectively). The total diameter of AAA, AVA, VVA, and all anastomoses in the thick AAA group was larger than in the non-thick AAA group (3.4 [2.0,7.1] vs. 1.4 [0.0, 3.3], P < 0.001; 6.3 [0.3, 12.0] vs. 2.5 [0.3, 17.8], P < 0.001; 4.2±1.8 vs. 1.9±1.2, P =0.004; and 10.7 [3.2,22.4] vs. 4.4 [0.5, 19.3], P < 0.001, respectively). Growth-restricted fetuses in the thick AAA group exhibited significantly increased birthweight relative to those in thenon-thick AAA group (1570 (530, 2460)g vs. 1230 (610, 2480)g, p = 0.002).

Conclusions
In the placentas associated with sFGR, thick AAA can co-occur with thick AVA and VVA, and placental angiogenesis may differ significantly based upon whether or not thick AAA is present. The birth weights of growth-restricted fetuses in cases of sFGR with thick AAA are larger than in cases without thick AAA.
Stabilization of refractive error and associated factors following small incision phacoemulsification cataract surgery
Authors: Khan Ammar M , Waldner Derek M. , Luong Micah , Sanders Emi , Crichton Andrew C. S. , Ford Bryce A. 
Published: January 2022

Abstract
Background
Accumulating evidence suggests that refractive stabilization occurs rapidly following small incision cataract surgery. Nonetheless, many guidelines still suggest waiting four to 6 weeks before prescribing corrective lenses. This study was undertaken to supplement the existing literature regarding refractive stabilization, and evaluate multiple contributing factors that could dissuade clinicians from confidently correcting refractive error in the early post-operative course following routine cataract surgeries.

Methods
Adult patients undergoing phacoemulsification cataract surgery with uncomplicated surgeries and post-surgical courses at the Calgary Ophthalmology Centre (Calgary, Alberta, Canada) were included in this prospective observational case series. Exclusion criteria included known corneal dystrophies, infectious keratitis, complicated surgery or toric/multifocal IOLs. Data was collected at weekly intervals for a total of 6 weeks. Collected data included autorefraction, visual acuity, corneal pachymetry, and effective lens position.

Results
One hundred six eyes of 104 patients were included in this study. Post-operative sphere, cylinder and spherical equivalent were not significantly different at any post-operative week compared with week six, and 80–86% of patients were within 0.5D of last follow-up spherical equivalent at any week. The secondary outcomes of central corneal thickness, effective lens position and visual acuity did, however, exhibit significant differences between early post-operative weeks and last follow-up values.

Conclusions
These data suggest that refractive error can be effectively measured and corrected as early as one-week post-operatively in the majority of patients, though other measures of post-operative stability including central corneal thickness, effective lens position and visual acuity can require up to 4 weeks to stabilize. Thus a conservative and pragmatic approach may be to wait until 4 weeks post-operatively prior to obtaining refractive correction following uncomplicated phacoemulsification cataract surgery.
The Gutenberg health study: a five-year prospective analysis of psychosocial working conditions using COPSOQ (Copenhagen psychosocial questionnaire) and ERI (effort-reward imbalance)
Authors: Nuebling Matthias , Hegewald Janice , Starke Karla Romero , Lincke Hans-Joachim , Jankowiak Sylvia , Liebers Falk , Latza Ute , Letzel Stephan , Riechmann-Wolf Merle , Gianicolo Emilio , Beutel Manfred , Pfeiffer Norbert , Lackner Klaus , Münzel Thomas , Wild Philipp S. , Seidler Andreas 
Published: January 2022

Abstract
Background
Psychosocial working conditions were previously analyzed using the first recruitment wave of the Gutenberg Health Study (GHS) cohort (n = 5000). We aimed to confirm the initial analysis using the entire GHS population at baseline (N = 15,010) and at the five-year follow-up. We also aimed to determine the effects of psychosocial working conditions at baseline on self-rated outcomes measured at follow-up.

Methods
At baseline, working GHS participants were assessed with either the Effort-Reward-Imbalance questionnaire (ERI) (n = 4358) or with the Copenhagen Psychosocial Questionnaire (COPSOQ) (n = 4322); participants still working after five years received the same questionnaire again (ERI n = 3142; COPSOQ n = 3091). We analyzed the association between working conditions and the outcomes job satisfaction, general health, burnout, and satisfaction with life at baseline, at follow-up and also prospectively from baseline to follow-up using linear regression models. We examined the outcome variance explained by the models (R2) to estimate the predictive performance of the questionnaires.

Results
The models’ R2 was comparable to the original baseline analyses at both t0 and t1 (R2 range: ERI 0.10–0.43; COPSOQ 0.10–0.56). However, selected scales of the regression models sometimes changed between assessment times. The prospective analysis showed weaker associations between baseline working conditions and outcomes after five years (R2 range: ERI 0.07–0.19; COPSOQ 0.07–0.24). This was particularly true for job satisfaction. After adjusting for the baseline levels of the outcomes, fewer scales still explained some of the variance in the distribution of the outcome variables at follow-up. The models using only data from t0 or t1 confirmed the previous baseline analysis. We observed a loss of explained variance in the prospective analysis models. This loss was greatest for job satisfaction, suggesting that this outcome is most influenced by short-term working conditions.

Conclusions
Both the COPSOQ and ERI instruments show good criterion validity and adequately predict contemporaneously measured self-reported measurements of health and (occupational) well-being. However, the COPSOQ provides a more detailed picture of working conditions and might be preferable for improvment strategies in workplaces. Additional prospective research with shorter follow-up times would be beneficial for estimating dose-response relationships.
The cost of community outreach HIV interventions: a case study in Thailand
Authors: Soe Kyaw Min , Hauck Katharina , Jiamton Sukhum , Kongsin Sukhontha 
Published: January 2022

Abstract
Background
There was an estimated 440,000 people living with HIV in Thailand in 2018. New cases are declining rapidly thanks to successful prevention programs and scaling up of anti-retroviral therapy (ART). Thailand aims to achieve its commitment to end the HIV epidemic by 2030 and implemented a cascade of HIV interventions through the Reach-Recruit-Test-Treat-Retain (RRTTR) program.

Methods
This study focused on community outreach HIV interventions implemented by Non-Governmental Organizations (NGOs) under the RRTTR program in 27 provinces. We calculated unit cost per person reached for HIV interventions targeted at key-affected populations (KAPs) including men who have sex with men/ transgender (MSM/TG), male sex workers (MSW), female sex workers (FSW), people who inject drugs (PWID) and migrants (MW). We studied program key outputs, costs, and unit costs in variations across different HIV interventions and geographic locations in Thailand. We used these estimates to determine costs of HIV interventions and evaluate economies of scale.

Results
The interventions for migrants in Samut Sakhon was the least costly with a unit cost of 21.6 USD per person to receive services, followed by interventions for migrants in Samut Prakan 23.2 USD per person reached, MSM/TG in Pratum Thani 26.5USD per person reached, MSM/TG in Nonthaburi 26.6 USD per person reached and, MSM/TG in Chon Buri with 26.7 USD per person. The interventions yielded higher efficiency in large metropolitan and surrounding provinces. Harm reduction programs were the costliest compare with other interventions. There was association between unit cost and scale of among interventions indicating the presence of economies scale. Implementing HIV and TB interventions jointly increased efficiency for both cases.

Conclusion
This study suggested that unit cost of community outreach HIV and TB interventions led by CSOs will decrease as they are scaled up. Further studies are suggested to follow up with these ongoing interventions for identifying potential contextual factors to improve efficiency of HIV prevention services in Thailand.
Primary care clinicians’ opinions before and after implementation of cancer screening and prevention clinical decision support in a clinic cluster-randomized control trial: a survey research study
Authors: Harry Melissa L. , Chrenka Ella A. , Freitag Laura A. , Saman Daniel M. , Allen Clayton I. , Asche Stephen E. , Truitt Anjali R. , Ekstrom Heidi L. , O’Connor Patrick J. , Sperl-Hillen Jo Ann M. , Ziegenfuss Jeanette Y. , Elliott Thomas E. 
Published: January 2022

Abstract
Background
Electronic health record (EHR)-linked clinical decision support (CDS) may impact primary care clinicians’ (PCCs’) clinical care opinions. As part of a clinic cluster-randomized control trial (RCT) testing a cancer prevention and screening CDS system with patient and PCC printouts (with or without shared decision-making tools [SDMT]) for patients due for breast, cervical, colorectal, and lung cancer screening and/or human papillomavirus (HPV) vaccination compared to usual care (UC), we surveyed PCCs at study clinics pre- and post-CDS implementation. Our primary aim was to learn if PCCs' opinions changed over time within study arms. Secondary aims including examining whether PCCs' opinions in study arms differed both pre- and post-implementation, and gauging PCCs’ opinions on the CDS in the two intervention arms.

Methods
This study was conducted within a healthcare system serving an upper Midwestern population. We administered pre-implementation (11/2/2017–1/24/2018) and post-implementation (2/2/2020–4/9/2020) cross-sectional electronic surveys to PCCs practicing within a RCT arm: UC; CDS; or CDS + SDMT. Bivariate analyses compared responses between study arms at both time periods and longitudinally within study arms.

Results
Pre-implementation (53%, n = 166) and post-implementation (57%, n = 172) response rates were similar. No significant differences in PCC responses were seen between study arms on cancer prevention and screening questions pre-implementation, with few significant differences found between study arms post-implementation. However, significantly fewer intervention arm clinic PCCs reported being very comfortable with discussing breast cancer screening options with patients compared to UC post-implementation, as well as compared to the same intervention arms pre-implementation. Other significant differences were noted within arms longitudinally. For intervention arms, these differences related to CDS areas like EHR alerts, risk calculators, and ordering screening. Most intervention arm PCCs noted the CDS provided overdue screening alerts to which they were unaware. Few PCCs reported using the CDS, but most would recommend it to colleagues, expressed high CDS satisfaction rates, and thought patients liked the CDS’s information and utility.

Conclusions
While appreciated by PCCs with high satisfaction rates, the CDS may lower PCCs’ confidence regarding discussing patients’ breast cancer screening options and may be used irregularly. Future research will evaluate the impact of the CDS on cancer prevention and screening rates.

Trial registration
clinicaltrials.gov, NCT02986230, December 6, 2016.