bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid genetic adaptation to recently colonized environments is driven by genes underlying life history traits
Authors: Yin Xiaoshen , Martinez Alexander S. , Sepúlveda Maria S. , Christie Mark R. 
Published: April 2021

AbstractBackgroundUncovering the mechanisms underlying rapid genetic adaptation can provide insight into adaptive evolution and shed light on conservation, invasive species control, and natural resource management. However, it can be difficult to experimentally explore rapid adaptation due to the challenges associated with propagating and maintaining species in captive environments for long periods of time. By contrast, many introduced species have experienced strong selection when colonizing environments that differ substantially from their native range and thus provide a “natural experiment” for studying rapid genetic adaptation. One such example occurred when sea lamprey (Petromyzon marinus), native to the northern Atlantic, naturally migrated into Lake Champlain and expanded their range into the Great Lakes via man-made shipping canals.ResultsUtilizing 368,886 genome-wide single nucleotide polymorphisms (SNPs), we calculated genome-wide levels of genetic diversity (i.e.,heterozygosity andπ) for sea lamprey collected from native (Connecticut River), native but recently colonized (Lake Champlain), and invasive (Lake Michigan) populations, assessed genetic differentiation between all populations, and identified candidate genes that responded to selection imposed by the novel environments. We observed a 14 and 24% reduction in genetic diversity in Lake Michigan and Lake Champlain populations, respectively, compared to individuals from the Connecticut River, suggesting that sea lamprey populations underwent a genetic bottleneck during colonization. Additionally, we identified 121 and 43 outlier genes in comparisons between Lake Michigan and Connecticut River and between Lake Champlain and Connecticut River, respectively. Six outlier genes that contained synonymous SNPs in their coding regions and two genes that contained nonsynonymous SNPs may underlie the rapid evolution of growth (i.e., GHR), reproduction (i.e., PGR,TTC25,STARD10), and bioenergetics (i.e., OXCT1,PYGL,DIN4,SLC25A15).ConclusionsBy identifying the genomic basis of rapid adaptation to novel environments, we demonstrate that populations of invasive species can be a useful study system for understanding adaptive evolution. Furthermore, the reduction in genome-wide levels of genetic diversity associated with colonization coupled with the identification of outlier genes underlying key life history traits known to have changed in invasive sea lamprey populations (e.g.,growth, reproduction) illustrate the utility in applying genomic approaches for the successful management of introduced species.
Phase I dose-escalation oncology trials with sequential multiple schedules
Authors: Günhan Burak Kürsad , Weber Sebastian , Seroutou Abdelkader , Friede Tim 
Published: April 2021

AbstractBackgroundConventional methods for phase I dose-escalation trials in oncology are based on a single treatment schedule only. More recently, however, multiple schedules are more frequently investigated in the same trial.MethodsHere, we consider sequential phase I trials, where the trial proceeds with a new schedule (e.g. daily or weekly dosing) once the dose escalation with another schedule has been completed. The aim is to utilize the information from both the completed and the ongoing schedules to inform decisions on the dose level for the next dose cohort. For this purpose, we adapted the time-to-event pharmacokinetics (TITE-PK) model, which were originally developed for simultaneous investigation of multiple schedules. TITE-PK integrates information from multiple schedules using a pharmacokinetics (PK) model.ResultsIn a simulation study, the developed approach is compared to the bridging continual reassessment method and the Bayesian logistic regression model using a meta-analytic-predictive prior. TITE-PK results in better performance than comparators in terms of recommending acceptable dose and avoiding overly toxic doses for sequential phase I trials in most of the scenarios considered. Furthermore, better performance of TITE-PK is achieved while requiring similar number of patients in the simulated trials. For the scenarios involving one schedule, TITE-PK displays similar performance with alternatives in terms of acceptable dose recommendations. The and code for the implementation of an illustrative sequential phase I trial example in oncology is publicly available (https://github.com/gunhanb/TITEPK_sequential).ConclusionIn phase I oncology trials with sequential multiple schedules, the use of all relevant information is of great importance. For these trials, the adapted TITE-PK which combines information using PK principles is recommended.
The impact of grey zones on the accuracy of agreement measures for ordinal tables
Authors: Tran Quoc Duyet , Dolgun Anil , Demirhan Haydar 
Published: April 2021

Abstract
Background
In an inter-rater agreement study, if two raters tend to rate considering different aspects of the subject of interest or have different experience levels, a grey zone occurs among the levels of a square contingency table showing the inter-rater agreement. These grey zones distort the degree of agreement between raters and negatively impact the decisions based on the inter-rater agreement tables. In this sense, it is important to know how the existence of a grey zone impacts the inter-rater agreement coefficients to choose the most reliable agreement coefficient against the grey zones to reach out with more reliable decisions.

Methods
In this article, we propose two approaches to create grey zones in simulations setting and conduct an extensive Monte Carlo simulation study to figure out the impact of having grey zones on the weighted inter-rater agreement measures for ordinal tables over a comprehensive simulation space.

Results
The weighted inter-rater agreement coefficients are not reliable against the existence of grey zones. Increasing sample size and the number of categories in the agreement table decreases the accuracy of weighted inter-rater agreement measures when there is a grey zone. When the degree of agreement between the raters is high, the agreement measures are not significantly impacted by the existence of grey zones. However, if there is a medium to low degree of inter-rater agreement, all the weighted coefficients are more or less impacted.

Conclusions
It is observed in this study that the existence of grey zones has a significant negative impact on the accuracy of agreement measures especially for a low degree of true agreement and high sample and tables sizes. In general, Gwet’s AC2 and Brennan-Prediger’s κ with quadratic or ordinal weights are reliable against the grey zones.
Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore
Authors: Tyagi Shilpa , Koh Gerald Choon-Huat , Luo Nan , Tan Kelvin Bryan , Hoenig Helen , Matchar David B. , Yoong Joanne , Chan Angelique , Lee Kim En , Venketasubramanian N. , Menon Edward , Chan Kin Ming , De Silva Deidre Anne , Yap Philip , Tan Boon Yeow , Chew Effie , Young Sherry H. , Ng Yee Sien , Tu Tian Ming , Ang Yan Hoon , Kong Keng He , Singh Rajinder , Merchant Reshma A. , Chang Hui Meng , Yeo Tseng Tsai , Ning Chou , Cheong Angela , Ng Yu Li , Tan Chuen Seng 
Published: April 2021

AbstractBackgroundOutpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke.MethodStroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0–3 months (early) and 4–12 months (late) post-stroke.ResultsFor the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits.ConclusionWe demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.
Network meta-analysis of triazole, polyene, and echinocandin antifungal agents in invasive fungal infection prophylaxis in patients with hematological malignancies
Authors: Zeng Huilan , Wu Zhuman , Yu Bing , Wang Bo , Wu Chengnian , Wu Jie , Lai Jing , Gao Xiaoyan , Chen Jie 
Published: April 2021

Abstract
Background and aim
Triazole, polyene, and echinocandin antifungal agents are extensively used to treat invasive fungal infections (IFIs); however, the optimal prophylaxis option is not clear. This study aimed to determine the optimal agent against IFIs for patients with hematological malignancies.

Methods
Randomized controlled trials (RCTs) comparing the effectiveness of triazole, polyene, and echinocandin antifungal agents with each other or placebo for IFIs in patients with hematological malignancies were searched. This Bayesian network meta-analysis was performed for all agents.

Results
The network meta-analyses showed that all triazoles, amphotericin B, and caspofungin, but not micafungin, reduced IFIs. Posaconazole was superior to fluconazole [odds ratio (OR), 0.30; 95% credible interval (CrI), 0.12–0.60], itraconazole (OR, 0.40; 95% CrI, 0.15–0.85), and amphotericin B (OR, 4.97; 95% CrI, 1.73–11.35). It also reduced all-cause mortality compared with fluconazole (OR, 0.35; 95% CrI, 0.08–0.96) and itraconazole (OR, 0.33; 95% CrI, 0.07–0.94), and reduced the risk of adverse events compared with fluconazole (OR, 0.02; 95% CrI, 0.00–0.03), itraconazole (OR, 0.01; 95% CrI, 0.00–0.02), posaconazole (OR, 0.02; 95% CrI, 0.00–0.03), voriconazole (OR, 0.005; 95% CrI, 0.00 to 0.01), amphotericin B (OR, 0.004; 95% CrI, 0.00–0.01), and caspofungin (OR, 0.05; 95% CrI, 0.00–0.42) despite no significant difference in the need for empirical treatment and the proportion of successful treatment.

Conclusions
Posaconazole might be an optimal prophylaxis agent because it reduced IFIs, all-cause mortality, and adverse events, despite no difference in the need for empirical treatment and the proportion of successful treatment.
Understanding the patient journey to diagnosis of lung cancer
Authors: Zhang Yichen , Simoff Michael J. , Ost David , Wagner Oliver J. , Lavin James , Nauman Beth , Hsieh Mei-Chin , Wu Xiao-Cheng , Pettiford Brian , Shi Lizheng 
Published: April 2021

Abstract
Objective
This research describes the clinical pathway and characteristics of two cohorts of patients. The first cohort consists of patients with a confirmed diagnosis of lung cancer while the second consists of patients with a solitary pulmonary nodule (SPN) and no evidence of lung cancer. Linked data from an electronic medical record and the Louisiana Tumor Registry were used in this investigation.

Materials and methods
REACHnet is one of 9 clinical research networks (CRNs) in PCORnet®, the National Patient-Centered Clinical Research Network and includes electronic health records for over 8 million patients from multiple partner health systems. Data from Ochsner Health System and Tulane Medical Center were linked to Louisiana Tumor Registry (LTR), a statewide population-based cancer registry, for analysis of patient’s clinical pathways between July 2013 and 2017. Patient characteristics and health services utilization rates by cancer stage were reported as frequency distributions. The Kaplan-Meier product limit method was used to estimate the time from index date to diagnosis by stage in lung cancer cohort.

Results
A total of 30,559 potentially eligible patients were identified and 2929 (9.58%) had primary lung cancer. Of these, 1496 (51.1%) were documented in LTR and their clinical pathway to diagnosis was further studied. Time to diagnosis varied significantly by cancer stage. A total of 24,140 patients with an SPN were identified in REACHnet and 15,978 (66.6%) had documented follow up care for 1 year. 1612 (10%) had no evidence of any work up for their SPN. The remaining 14,366 had some evidence of follow up, primarily office visits and additional chest imaging.

Conclusion
In both cohorts multiple biopsies were evident in the clinical pathway. Despite clinical workup, 70% of patients in the lung cancer cohort had stage III or IV disease. In the SPN cohort, only 66% were identified as receiving a diagnostic work-up.
Consensus on pre-operative total knee replacement education and prehabilitation recommendations: a UK-based modified Delphi study
Authors: Anderson Anna M. , Comer Christine , Smith Toby O. , Drew Benjamin T. , Pandit Hemant , Antcliff Deborah , Redmond Anthony C. , McHugh Gretl A. 
Published: April 2021

Abstract
Background
Over 90,000 total knee replacement (TKR) procedures are performed annually in the United Kingdom (UK). Patients awaiting TKR face long delays whilst enduring severe pain and functional limitations. Almost 20% of patients who undergo TKR are not satisfied post-operatively. Optimising pre-operative TKR education and prehabilitation could help improve patient outcomes pre- and post-operatively; however, current pre-operative TKR care varies widely. Definitive evidence on the optimal content and delivery of pre-operative TKR care is lacking. This study aimed to develop evidence- and consensus-based recommendations on pre-operative TKR education and prehabilitation.

Methods
A UK-based, three-round, online modified Delphi study was conducted with a 60-member expert panel. All panellists had experience of TKR services as patients (n = 30) or professionals (n = 30). Round 1 included initial recommendations developed from a mixed methods rapid review. Panellists rated the importance of each item on a five-point Likert scale. Panellists could also suggest additional items in Round 1. Rounds 2 and 3 included all items from Round 1, new items suggested in Round 1 and charts summarising panellists’ importance ratings from the preceding round. Free-text responses were analysed using content analysis. Quantitative data were analysed descriptively. All items rated as ‘Important’ or ‘Very important’ by at least 70% of all respondents in Round 3 were included in the final set of recommendations.

Results
Fifty-five panellists (92%) (patients n = 26; professionals n = 29) completed Round 3. Eighty-six recommendation items were included in Round 1. Fifteen new items were added in Round 2. Rounds 2 and 3 therefore included 101 items. Seventy-seven of these reached consensus in Round 3. Six items reached consensus amongst patient or professional panellists only in Round 3. The final set of recommendations comprises 34 education topics, 18 education delivery approaches, 10 exercise types, 13 exercise delivery approaches and two other treatments.

Conclusions
This modified Delphi study developed a comprehensive set of recommendations that represent a useful resource for guiding decision-making on the content and delivery of pre-operative TKR education and prehabilitation. The recommendations will need to be interpreted and reviewed periodically in light of emerging evidence.
Evaluation of changes in shoulder balance and prediction of final shoulder imbalance during growing-rod treatment for early-onset scoliosis
Authors: Liu Ziyang , Liu Tie , Hai Yong , Wu Lingyun , Hai Junrui Jonathan , Gao Kang , Guo Xuanrong , Yang Honghao , Kang Nan , Zhao Fan 
Published: April 2021

Abstract
Background
Obtaining and maintaining final shoulder balance after the entire treatment course is essential for early-onset scoliosis (EOS) patients. The relatively small number of growing-rod (GR) graduates who complete final fusion has resulted in an overall paucity of research on the GR treatment of EOS and a lack of research on the shoulder balance of EOS patients during GR treatment.

Methods
Twenty-four consecutive patients who underwent GR treatment until final fusion were included. Radiographic shoulder balance parameters, including the radiographic shoulder height (RSH), clavicle angle (CA), and T1 tilt angle (T1T), before and after each step of the entire treatment were measured. Shoulder balance changes from GR implantation to the last follow-up after final fusion were depicted and analysed. Demographic data, surgical-related factors, and radiographic parameters were analysed to identify risk factors for final shoulder imbalance. The shoulder balance of patients at different time points was further analysed to explore the potential effect of the series of GR treatment steps on shoulder balance.

Results
The RSH showed substantial improvement after GR implantation (P = 0.036), during the follow-up period after final fusion (P = 0.021) and throughout the entire treatment (P = 0.011). The trend of change in the CA was similar to that of the RSH, and the T1T improved immediately after GR implantation (P = 0.037). Further analysis indicated that patients with shoulder imbalance before final fusion showed significantly improved shoulder balance after fusion (P = 0.045), and their RSH values at early postfusion and the final follow-up did not show statistically significant differences from those in the prefusion shoulder balance group (P > 0.05). Early postfusion shoulder imbalance (odds ratio (OR): 19.500; 95% confidence interval (CI) = 1.777–213.949; P = 0.015) was identified as an independent risk factor for final shoulder imbalance.

Conclusions
Shoulder balance could be improved by GR implantation but often changes during the multistep lengthening process, and the final result is relatively unpredictable. Final fusion could further adjust the prefusion shoulder imbalance. Focusing on the prefusion shoulder balance of GR graduates and providing patients with early shoulder balance after fusion might be necessary.
Acromegaly presenting with myelopathy due to ossification of posterior longitudinal ligament: a case report
Authors: Kamakura Daisuke , Fukutake Katsunori , Nakamura Kazumasa , Tsuge Shintaro , Hasegawa Keiji , Tochigi Naobumi , Wada Akihito , Mikami Tetsuo , Takahashi Hiroshi 
Published: April 2021

Abstract
Background
Acromegaly is a rare disease caused by high serum levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), often originating from a pituitary adenoma. Spinal and peripheral joint abnormalities are caused by these hormonal hypersecretions. In particular, the response to GH is involved in the onset of ossification of the spinal ligament in vitro, especially ossification of the posterior longitudinal ligament (OPLL). However, because acromegaly and OPLL are rare diseases, we seldom encounter them in combination. To the best of our knowledge in the English-language literature, this is the first reported case of acromegaly presenting with thoracic myelopathy due to OPLL.

Case presentation
A 47-year-old woman presented with lower extremity weakness and paresthesia, gait disorder, and bladder disorder without any trauma. The patient’s most remarkable symptom was paraplegia, and we diagnosed myelopathy due to cervical and thoracic OPLL. Furthermore, we suspected acromegaly because of the characteristic facial features, and we found a pituitary adenoma by contrast-enhanced MRI. Cervical and thoracic decompression, posterior fixation, and pituitary adenoma resection were performed.

Conclusion
We report a case of acromegaly that was detected after the diagnosis of OPLL. The main challenge in acromegaly is delayed in diagnosis. Even in this case, the facial features characteristic of acromegaly had appeared at least 9 years ago. Early diagnosis and treatment of acromegaly improve prognosis and reduce exposure to GH and IGF-1 through early intervention and seem to suppress the progression of ligament ossification. Orthopedic surgeons and neurosurgeons need to keep in mind that acromegaly is associated with bone/joint lesions and ossification of the spinal ligament and should aim to diagnose acromegaly early.
Fears and barriers: problems in breast cancer diagnosis and treatment in Pakistan
Authors: Saeed Sidra , Asim Muhammad , Sohail Malik Muhammad 
Published: April 2021

Abstract
Background
Women in Pakistan lack appropriate awareness about diagnosis and treatment for breast cancer due to a range of multifaceted barriers. There is a dearth of literature examining the socio-cultural factors that inhibit women from breast cancer screening, diagnosis and treatment in Punjab, Pakistan. Addressing this gap, this qualitative study sought to identify and explore the barriers that hinder women from seeking timely screening and treatment.

Methods
In this process 45 women (age = 18–50 years) with breast cancer were purposively sampled and interviewed from the Punjab Institute of Nuclear Medicine (PINUM) hospital, Faisalabad, Pakistan.

Results
An inductive approach was used to analyze the data which resulted in the emergence of eight subthemes under the umbrella of three major themes that delineate individual, socio-cultural and structural barriers to seek screening and treatment of breast cancer in Punjab. Individual barriers included lack of awareness, hesitance in accepting social support, and spiritual healing. The identified socio-cultural factors included feminine sensitivity, stigmatization, and aversion to male doctors. Lack of financial resources and apathetic medical services were structural barriers that hinder screening and treatment.

Conclusions
These barriers can be addressed through raising awareness and community mobilization about breast-self exam and treatment. The healthcare system should also pay attention to socio-psychological and cultural factors impeding women's access to available health facilities.