bluuebunny/crossref_metadata_2025_split huggingface dataset:
Craniofacial Fellowship Applicant Perceptions of Virtual Interviews
Authors: Yoon Joshua , Pan Judy , Major Melanie , Chang Daniel R. , Ha Michael , Rasko Yvonne , Naran Sanjay , Grant Michael P. , Yang Robin , Liang Fan , Steinberg Jordan P. 
Published: July 2022

Introduction:
The 2021 interview cycle for craniofacial fellowship applicants was the first to be held virtually due to the coronavirus disease 2019 pandemic. Here, we detail the craniofacial fellowship applicant perceptions and experience on the virtual interview process.

Materials and Methods:
An institutional review board–approved 35-question survey study on the perception of the virtual interview process among craniofacial fellowship applicants was conducted. Surveys were distributed to individuals who had applied through the match, overseen by the American Society of Craniofacial Surgeons (ASCFS).

Results:
Ten surveys were fully completed with a corresponding response rate of 48%. The average number of interviews completed was 12.7±7.7 and 50% of applicants interviewed at >1 program in a single day. Overall, 90% of respondents preferred in-person interviews before the interview season, however, only 10% preferred the in-person format afterwards. Preference for a virtual-only format increased from 10% to 70%. Applicants cited cost (100%), ease of scheduling (90%), and ability to participate in more interviews (70%) as the primary strengths of the virtual platform; none reported difficulties with self-advocacy. After the interview cycle, 90% stated they would recommend virtual interviews.

Conclusions:
The greatest strengths of virtual interviews were the ability to participate in more interviews, the ease of scheduling, and the cost benefits. Most applicants reported the same or increased ability for self-advocacy with virtual interviews. Following the index interview cycle for 2021, the majority of fellowship applicants now appear to prefer a virtual-only or hybrid format and would recommend virtual interviews in the future.
Follow-up Schedule for Patients With Sentinel Node–negative Cutaneous Melanoma (The MELFO Study)
Authors: Moncrieff Marc D. , Bastiaannet Esther , Underwood Beverly , Francken Anne Brecht , Garioch Jennifer , Damude Samantha , Heaton Martin , Deckers Eric A. , Patel Nakul , Hoekstra-Weebers Josette E. , Hoekstra Harald J. 
Published: July 2022

Objectives and Design:
The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines.

Background:
Evidence-based guidelines for the follow-up of sentinel node–negative melanoma patients are lacking.

Methods:
Overall, 388 adult patients diagnosed with sentinel node–negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016. The conventional schedule group (control: n=196) was reviewed as per current national guidelines. The experimental schedule group (n=192) was reviewed in a reduced-frequency schedule. Quality of life was the primary outcome measurement. Detection rates and survival outcomes were recorded. Patient satisfaction rates and compliance with allocated schedules were compared.

Results:
At 5 years, both arms expressed high satisfaction with their regimens (>97%). This study found no significant group effect on any patient-reported outcome measure scores between the follow-up protocols. In total, 75/388 (19.4%) patients recurred, with no difference in incidence found between the 2 arms (hazard ratio=0.87, 95% confidence interval: 0.54–1.39, P=0.57). Self-examination was the method of detection for 25 experimental patients and 32 control patients (75.8% vs. 76.2%; P=0.41). This study found no difference in any survival outcomes between the 2 study arms (disease-free survival: hazard ratio=1.00, 95% confidence interval: 0.49–2.07, P=0.99).

Conclusions:
A reduced-intensity, American Joint Committee on Cancer (AJCC) stage-adjusted follow-up schedule for sentinel node–negative melanoma patients is a safe strategy, and patient self-examination is effective for recurrence detection with no evidence of diagnostic delay. Patients’ acceptance is very high.
Executive Dysfunction, Social Cognition Impairment, and Gray Matter Pathology in Myotonic Dystrophy Type 2: A Pilot Study
Authors: Theodosiou Thomas , Christidi Foteini , Xirou Sofia , Karavasilis Efstratios , Bede Peter , Papadopoulos Constantinos , Argyropoulos Georgios D. , Kourtesis Panagiotis , Pantolewn Varvara , Ferentinos Panagiotis , Kararizou Evangelia , Velonakis Georgios , Zalonis Ioannis , Papadimas Georgios 
Published: July 2022

Background:
In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized.

Objective:
To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2.

Method:
Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: P
FDR < 0.05 and Bayes factor (BF10) >10.

Results:
The DM2 group exhibited cognitive impairment (ECAS Total score; P
FDR = 0.001; BF10 = 108.887), which was dominated by executive impairment (P
FDR = 0.003; BF10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami.

Conclusion:
DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.
Integrating Mendelian randomization and literature-mined evidence for breast cancer risk factors
Authors: Vabistsevits Marina , Robinson Tim , Elsworth Ben , Liu Yi , Gaunt Tom R 
Published: July 2022

AbstractAbstract FigureGraphical AbstractObjectiveAn increasing challenge in population health research is efficiently utilising the wealth of data available from multiple sources to investigate disease mechanisms and identify potential intervention targets. The use of biomedical data integration platforms can facilitate evidence triangulation from these different sources, improving confidence in causal relationships of interest. In this work, we aimed to integrate Mendelian randomization (MR) and literature-mined evidence from the EpiGraphDB biomedical knowledge graph to build a comprehensive overview of risk factors for developing breast cancer.MethodsWe utilised MR-EvE (“Everything-vs-Everything”) data to identify candidate risk factors for breast cancer and generate hypotheses for potential mediators of their effect. We also integrated this data with literature-mined relationships, which were extracted by overlapping literature spaces of risk factors and breast cancer. The literature-based discovery (LBD) results were followed up by validation with two-step MR to triangulate the findings from two data sources.ResultsWe identified 129 novel and established lifestyle risk factors and molecular traits with evidence of an effect on breast cancer, and made the MR results available in an R/Shiny app (https://mvab.shinyapps.io/MR_heatmaps/). We developed an LBD approach for identifying potential mechanistic intermediates of identified risk factors. We present the results of MR and literature evidence integration for two case studies (childhood body size and HDL-cholesterol), demonstrating their complementary functionalities.ConclusionWe demonstrate that MR-EvE data offers an efficient hypothesis-generating approach for identifying disease risk factors. Moreover, we show that integrating MR evidence with literature-mined data may be used to identify causal intermediates and uncover the mechanisms behind the disease.
Incorporating Algorithmic Uncertainty into a Clinical Machine Deep Learning Algorithm for Urgent Head CTs
Authors: Yoon Byung C. , Pomerantz Stuart R. , Mercaldo Nathaniel D. , Goyal Swati , L’Italien Eric , Lev Michael H. , Buch Karen , Buchbinder Bradley R. , Chen John W. , Conklin John , Gupta Rajiv , Hunter George J. , Kamalian Shahmir M. , Kelly Hillary R. , Rapalino Otto , Rincon Sandra P. , Romero Javier M. , He Julian , Schaefer Pamela W. , Do Synho , González R. Gilberto 
Published: July 2022

AbstractMachine learning (ML) algorithms to detect critical findings on head CTs may expedite patient management. Most ML algorithms for diagnostic imaging analysis utilize dichotomous classifications to determine whether a specific abnormality is present. However, imaging findings may be indeterminate, and algorithmic inferences may have substantial uncertainty. We incorporated awareness of uncertainty into an ML algorithm that detects intracranial hemorrhage or other urgent intracranial abnormalities and evaluated prospectively identified, 1000 consecutive noncontrast head CTs assigned to Emergency Department Neuroradiology for interpretation. The algorithm classified the scans into high (IC+) and low (IC-) probabilities for intracranial hemorrhage or other urgent abnormalities. All other cases were designated as No Prediction (NP) by the algorithm. The positive predictive value for IC+ cases (N = 103) was 0.91 (CI: 0.84-0.96), and the negative predictive value for IC-cases (N = 729) was 0.94 (0.91-0.96). Admission, neurosurgical intervention, and 30-day mortality rates for IC+ was 75% (63-84), 35% (24-47), and 10% (4-20), compared to 43% (40-47), 4% (3-6), and 3% (2-5) for IC-. There were 168 NP cases, of which 32% had intracranial hemorrhage or other urgent abnormalities, 31% had artifacts and postoperative changes, and 29% had no abnormalities. An ML algorithm incorporating uncertainty classified most head CTs into clinically relevant groups with high predictive values and may help accelerate the management of patients with intracranial hemorrhage or other urgent intracranial abnormalities.
Computational Causal Discovery for Posttraumatic Stress and Negative Self Image in Young Maltreated Children
Authors: Saxe Glenn N. , Morales Leah J. , Ma Sisi , Urgurbil Mehmet , Aliferis Constantin 
Published: July 2022

AbstractObjectivesThis article features the application of computational causal discovery (CCD) methods to determine the mechanism for Posttraumatic Stress (PTS) in young, maltreated children, in order to advance knowledge for prevention. Advances in prevention require research that identifies causal factors, but the scientific literature that would inform the identification of causes are almost exclusively based on the application of correlational methods to observational data. Causal inferences from such research will frequently be in error. We conducted the present study to explore the application of CCD methods as an alternative – or a supplement – to experimental methods, which can rarely be applied in human research on causal factors for PTS.MethodsA data processing pipeline that integrates state-of-the-art CCD algorithms was applied to an existing observational, longitudinal data set collected by the Consortium for Longitudinal Studies in Child Abuse and Neglect (LONGSCAN). This data set contains a sample of 1,354 children who were identified in infancy to early childhood as being maltreated or at risk.ResultsA causal network model of 251 variables (nodes) and 818 bivariate relations (edges) was discovered, revealing four direct causes and two direct effects for PTS at age 8, within a network containing a broad diversity of causal pathways. Specific causal factors included stress, social, family and development problems: and several of these factors point to promising approaches for prevention.ConclusionsThese results indicate that CCD methods show promise for research on the complex etiology of PTS in young, maltreated children.
Investigating causality in the association between DNA methylation and prevalent T2D using a bidirectional two-sample Mendelian Randomization
Authors: Juvinao-Quintero Diana L. , Sharp Gemma C. , Sanderson Eleanor , Relton Caroline L. , Elliott Hannah R. 
Published: July 2022

ABSTRACTAimSeveral studies have identified associations between type 2 diabetes (T2D) and DNA methylation (DNAm). However, the causal role of these associations remains unclear. This study aims to provide evidence for a causal relationship between DNA methylation and T2D.MethodsWe implemented a bidirectional two-sample Mendelian randomization (2SMR) to evaluate causality at 58 CpG sites previously detected in a meta-analysis of epigenome-wide association studies (meta-EWAS) of prevalent T2D in Europeans. We retrieved genetic proxies for T2D and DNAm from the largest GWAS available. We also used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, UK) when associations of interest were not available in the larger datasets. We identified 62 independent SNPs as proxies for T2D, and 39 methylation quantitative trait loci or mQTL as proxies for 30 of the 58 T2D-related CpGs. We applied correction for multiple testing using Bonferroni and inferred causality based on a P < 1.0×10−3 or P < 2.0×10−3 for the T2D⟶ DNAm direction, and the opposing DNAm ⟶ T2D direction of the 2SMR, respectively.ResultsWe found strong evidence of causality of DNAm at cg25536676 (DHCR24) on T2D, where an increase in transformed residuals of DNAm at this site were associated with 43% (OR=1.43, 95%CI=1.15-1.78, P=0.001) higher risk of T2D. We infer a likely causal direction for the remaining CpG sites assessed. In silico analyses showed that CpGs analyzed were enriched for eQTMs, and for specific traits dependent on the direction of causality predicted by 2SMR.ConclusionsWe identified one CpG mapping to a gene related with the metabolism of lipids (DHCR24), as a novel causal biomarker for the risk of T2D. CpGs within the same gene-region have previously been associated with T2D-related traits in observational studies (BMI, waist circumference, HDL-cholesterol, insulin) and in MR analyses (LDL-cholesterol). Thus, we hypothesize that our candidate CpG in DHCR24 may be a causal mediator of the association between known modifiable risk factors and T2D. Formal causal mediation analysis should be implemented to further validate this assumption.
Mixed Methods Sequential Epidemiological Protocol (MMSEP) for Evaluation of Time Utilization by the Community Health Workers and Factors Affecting its Optimization
Authors: Kalne Poonam Sanjay , Joshi Shiv Hiren , Kalne Pooja Sanjay , Mehendale Ashok Madhukar 
Published: July 2022

AbstractBackgroundMany countries have a significant shortage of healthcare staff, resulting in a reduction in the range and quality of services. Low and middle-income countries rely heavily on Community Health Workers. Existing data suggests a lack of clarity regarding the scope of work as well as about the utilization of the working hours. The purpose of this work is to propose a protocol to evaluate the time utilization of the Community Health Workers and to identify the promoters and challenges that they come across while delivering their duties so that the workflow optimization processes can be hypothesized.MethodsThe Mixed Methods Sequential Epidemiological Protocol incorporates three phases. Phase I includes free listing to identify Community Health Workers’ workflow using a generic form with a single open-ended question for each cadre. After pile-sorting the free lists, the pile names should be used as categories for the time-motion study to be done in phase II. For each of these categories, time spent should be recorded and analyzed. Phase III includes in-depth interviews with Community Health Workers who use considerably varied times for the same category of work.DiscussionThe intended study will help in comparing the workflow of different cadres of health workers and finding out different factors promoting and inhibiting better utilization of their working hours. This approach will inform reasonable and feasible improvements to health-related planning of services and utilization of the health workforce and will help in increasing the efficiency of health workers to deliver services.Author contributions
Temperature dependence of competitive ability differs from that of growth rate
Authors: Sunday Jennifer M. , Bernhardt Joey , Harley Christopher , O’Connor Mary I. 
Published: July 2022

AbstractThe effect of climate warming on future community composition is expected to be contingent on competitive outcomes, yet we currently lack mechanistic ecological understanding of how temperature affects competitive ability. Here, we combine resource competition theory with metabolic scaling theory and test hypotheses about how the temperature dependence of competitive ability changes with temperature. We find that the minimum resource requirement for growth, R* – an inverse indicator of competitive ability in phytoplankton – changes with temperature following a U-shaped pattern in all four species tested. The shape of temperature-dependence of competitive ability is systematically different from the temperature-dependence of population growth rates, both in our experiments and in collated data from previous studies. Our results suggest that exploitative competitive success is highest at temperatures that are sub-optimal for growth, and declines rapidly at both cold and warm ends of the thermal performance curve.
Two major extinction events in the evolutionary history of turtles: one caused by a meteorite, the other by hominins
Authors: Pereira Anieli G. , Antonelli Alexandre , Silvestro Daniele , Faurby Søren 
Published: July 2022

ABSTRACTWe live in a time of highly accelerated extinction, which has the potential to mirror past mass extinction events. However, the rarity of these events and the restructuring of diversity that they cause complicate direct comparisons between the current extinction crisis and earlier mass extinctions. Among animals, turtles (Testudinata) are one of few groups which both have a sufficient fossil record and a sufficiently stable ecological importance to enable meaningful comparisons between the end Cretaceous mass extinction and the ongoing extinction event. In this paper we analyze the fossil record of turtles and recover three significant peaks in extinction rate. Two of these are in the Cretaceous, the second of these took place at the Cretaceous–Paleogene transition (K-Pg), reflecting the overall patterns previously reported for many other taxa. The third major extinction event started in the Pliocene and continues until now. This peak only affected terrestrial turtles and started much earlier in Eurasia and Africa lineages than elsewhere. This suggests that it may be linked to co-occurring hominins rather than having been caused by global climate change.
Genetic affinities and sub-structuring in Coorg population of Southern India
Authors: Mukhopadhyay Anirban , Kumar Lomous , Sran Kiran , Thangaraj Kumarasamy , Thelma B K 
Published: July 2022

AbstractThe Coorgs, also known as Kodavas, are one of the smallest religious and socio-culturally homogenous communities in the world, currently residing in the state of Karnataka, India. Due to a stark contrast with the surrounding subpopulations, their genetic architecture and population & demographic history have been a matter of debate for long. To better understand the population structure and demographic history of this caste group, we analysed the population, using high-resolution autosomal (n=70) as well uniparentally inherited markers (Y-chromosomal and mitochondrial DNA) (n=144). Our first ever findings elucidate that origin of Coorgs traces back to early or middle Bronze Age. We further found population substructure among Coorgs, which manifested as three distinct clusters in a Principal component analysis. One of these subgroups has undergone a rare and immense amount of population-specific drift but all three eventually admixed, both genetically and socio-culturally. The mtDNA analysis showed 40% South Asian-specific mitochondrial lineages among Coorgs; while the Y-chromosomal analysis revealed predominant presence of Eurasian, Middle-Eastern and Indian-specific haplogroups suggesting male-centric migration and eventual assimilation with local females. Our results for the first time identify these ancient and distinct genealogies that make up the contemporary Coorgs and may explain the socio-cultural differences with their immediate and distant neighbours in the country and the prevalent narrative history. In a wider context, the study also reveals an ancient, yet unknown, Middle Eastern source population that might have contributed to an early west to east migration into India.
Coupling of oxytocin and cholecystokinin pathways in the hypothalamus is required for gut-to-brain homeostatic feeding control
Authors: Gruber T , Lechner F , Murat C , Contreras RE , Sanchez-Quant E , Miok V , Le Thuc O , González-García I , Williams RH , Pfluger PT , Müller TD , Woods SC , Martinez-Jimenez CP , Tschöp MH , Grinevich V , García-Cáceres C 
Published: July 2022

SummaryOxytocin-expressing paraventricular hypothalamic neurons (PVNOT neurons) integrate afferent signals from the gut including cholecystokinin (CCK) to adjust whole-body energy homeostasis. However, the molecular underpinnings by which PVNOT neurons orchestrate gut-to-brain feeding control remain unclear. Here, we show that mice undergoing selective ablation of PVNOT neurons fail to reduce food intake in response to CCK and develop hyperphagic obesity on chow diet. Notably, exposing wildtype mice to a high-fat/high-sugar (HFHS) diet recapitulates this insensitivity towards CCK, which is linked to diet-induced transcriptional and electrophysiological aberrations specifically in PVNOT neurons. Restoring OT pathways in DIO mice via chemogenetics or polypharmacology sufficiently re-establishes CCK’s anorexigenic effects. Lastly, by single-cell profiling, we identify a specialized PVNOT neuronal subpopulation with increased κ-opioid signaling under HFHS diet, which restrains their CCK-evoked activation. In sum, we here document a novel (patho)mechanism by which PVNOT signaling uncouples a gut-brain satiation pathway under obesogenic conditions.