bluuebunny/crossref_metadata_2025_split huggingface dataset:
Honest calibration assessment for binary outcome predictions
Authors: Dimitriadis Timo , Dümbgen Lutz , Henzi Alexander , Puke Marius , Ziegel Johanna 
Published: December 2022

Summary
Probability predictions from binary regressions or machine learning methods ought to be calibrated: if an event is predicted to occur with probability $x$, it should materialize with approximately that frequency, which means that the so-called calibration curve $p(\cdot)$ should equal the identity, i.e., $p(x) = x$ for all $x$ in the unit interval. We propose honest calibration assessment based on novel confidence bands for the calibration curve, which are valid subject to only the natural assumption of isotonicity. Besides testing the classical goodness-of-fit null hypothesis of perfect calibration, our bands facilitate inverted goodness-of-fit tests whose rejection allows for the sought-after conclusion of a sufficiently well-specified model. We show that our bands have a finite-sample coverage guarantee, are narrower than those of existing approaches, and adapt to the local smoothness of the calibration curve $p$ and the local variance of the binary observations. In an application to modelling predictions of an infant having low birth weight, the bounds give informative insights into model calibration.
Medical and surgical postoperative complications after breast conservation versus mastectomy in older women with breast cancer: Swedish population-based register study of 34 139 women
Authors: de Boniface Jana , Szulkin Robert , Johansson Anna L V 
Published: December 2022

Abstract

Background
Mastectomy rates in breast cancer are higher in older patients. The aim was to compare postoperative complication rates after breast-conserving surgery (BCS) to mastectomy in women aged 70–79 and older than 80 years versus those aged 50–69 years, and to evaluate survival effects.

Methods
This population-based cohort included women aged 50 years and older with invasive breast cancer T1–3 N0–3 M0 operated on in Sweden 2008–2017. Major surgical and medical 30-day postoperative complications were assessed in adjusted logistic regression models. Overall survival was assessed in Cox models adjusted for clinical confounders, socio-economics, and comorbidity.

Results
Of 34 139 women, 8372 (24.5 per cent) were aged 70–79 years, 3928 (11.5 per cent) were 80 years of age or older, and 21 839 (64.0 per cent) were aged 50–69 years. Major surgical postoperative complications did not differ between age groups receiving equivalent surgery (BCS: 2.1 per cent and 2.0 per cent versus 2.1 per cent (P = 0.90); mastectomy: 4.6 per cent and 5.1 per cent versus 4.6 per cent (P = 0.49)). Major medical postoperative complications were higher in women aged &gt;70 years than in women aged 50–69 years (BCS: 1.0 per cent and 2.3 per cent versus 0.4 per cent (P &lt; 0.001); mastectomy: 3.1 per cent and 6.2 per cent versus 1.1 per cent (P &lt; 0.001)), which persisted after adjustments. In women treated by mastectomy, major medical and surgical postoperative complications were associated with worse overall survival in all but the middle age group.

Conclusion
Mastectomy has higher medical and surgical postoperative complication rates than BCS. Major medical postoperative complications increase significantly with age. Major postoperative complications are associated with worse survival after mastectomy, which should be used with caution in older women.
Downregulation of PMP22 ameliorates myelin defects in iPSC-derived human organoid cultures of CMT1A
Authors: Van Lent Jonas , Vendredy Leen , Adriaenssens Elias , Da Silva Authier Tatiana , Asselbergh Bob , Kaji Marcus , Weckhuysen Sarah , Van Den Bosch Ludo , Baets Jonathan , Timmerman Vincent 
Published: December 2022

Abstract
Charcot–Marie–Tooth disease is the most common inherited disorder of the PNS. CMT1A accounts for 40–50% of all cases and is caused by a duplication of the PMP22 gene on chromosome 17, leading to dysmyelination in the PNS. Patient-derived models to study such myelination defects are lacking as the in vitro generation of human myelinating Schwann cells has proved to be particularly challenging. Here, we present an induced pluripotent stem cell-derived organoid culture, containing various cell types of the PNS, including myelinating human Schwann cells, which mimics the human PNS. Single-cell analysis confirmed the PNS-like cellular composition and provides insight into the developmental trajectory. We used this organoid model to study disease signatures of CMT1A, revealing early ultrastructural myelin alterations, including increased myelin periodic line distance and hypermyelination of small axons. Furthermore, we observed the presence of onion-bulb-like formations in a later developmental stage. These hallmarks were not present in the CMT1A-corrected isogenic line or in a CMT2A iPSC line, supporting the notion that these alterations are specific to CMT1A. Downregulation of PMP22 expression using short-hairpin RNAs or a combinatorial drug consisting of baclofen, naltrexone hydrochloride and D-sorbitol was able to ameliorate the myelin defects in CMT1A-organoids. In summary, this self-organizing organoid model can capture biologically meaningful features of the disease and capture the physiological complexity, forms an excellent model for studying demyelinating diseases and supports the therapeutic approach of reducing PMP22 expression.
Transcriptome Analysis of the Differentially Expressed Heat-resistant Genes betweenCalliptamus italicusandGomphocerus sibiricus
Authors: Luo Di , Liu Qian , Wang Jinfeng , Jashenko Roman , Ji Rong 
Published: December 2022

AbstractCalliptamus italicus and Gomphocerus sibiricus are indicator species in Xinjiang’s low-altitude (700–1,900 m) and high-altitude (2,000–3,400 m) grasslands, respectively. C. italicus is tolerant to high-temperature stress, with its semilethal temperature (LT50) being 10.5°C higher than that of G. sibiricus. The two locust species were subjected to high-temperature stress to explore the molecular mechanisms and differences in high temperature tolerance between the two locust species. Next, the next generation sequencing (NGS) data were mapped to reference transcripts obtained using single molecule real Time (SMRT) sequencing to construct a nonparameter transcriptome. The transcriptomic response of these two locust species displayed different patterns. C. italicus had 126 differentially expressed genes (DEGs), with 59 and 67 being significantly up-regulated and down-regulated, respectively. The heat shock protein (Hsp) genes were highly expressed upon two locust species exposure to high-temperature stress, with Hsp70 being expressed the most. G. sibiricus had 86 DEGs, of which 45 were significantly up-regulated and 41 significantly down-regulated. In addition, the expression of the key enzyme encoding gene Myo-inositol oxygenase (MIOX) in inositol degradation was the highest in G. sibiricus. In the KEGG pathway, the biological processes and metabolic pathways were the most enriched pathways in C. italicus and G. sibiricus, respectively. Moreover, the quantitative fluorescence results were consistent with the transcriptome results, implying that the transcriptome results were accurate. The findings in this study provide valuable information for future research exploring the evolution mechanisms of heat resistance in C. italicus and G. sibiricus.
Duration of exposure to epidural anesthesia at delivery, DNA methylation in umbilical cord blood and their association with offspring asthma in Non-Hispanic Black women
Authors: Wang Yaxu , Tzeng Jung-Ying , Huang Yueyang , Maguire Rachel , Hoyo Cathrine , Allen Terrence K 
Published: December 2022

Abstract
Epidural anesthesia is an effective pain relief modality, widely used for labor analgesia. Childhood asthma is one of the commonest chronic medical illnesses in the USA which places a significant burden on the health-care system. We recently demonstrated a negative association between the duration of epidural anesthesia and the development of childhood asthma; however, the underlying molecular mechanisms still remain unclear. In this study of 127 mother–child pairs comprised of 75 Non-Hispanic Black (NHB) and 52 Non-Hispanic White (NHW) from the Newborn Epigenetic Study, we tested the hypothesis that umbilical cord blood DNA methylation mediates the association between the duration of exposure to epidural anesthesia at delivery and the development of childhood asthma and whether this differed by race/ethnicity. In the mother–child pairs of NHB ancestry, the duration of exposure to epidural anesthesia was associated with a marginally lower risk of asthma (odds ratio = 0.88, 95% confidence interval = 0.76–1.01) for each 1-h increase in exposure to epidural anesthesia. Of the 20 CpGs in the NHB population showing the strongest mediation effect, 50% demonstrated an average mediation proportion of 52%, with directional consistency of direct and indirect effects. These top 20 CpGs mapped to 21 genes enriched for pathways engaged in antigen processing, antigen presentation, protein ubiquitination and regulatory networks related to the Major Histocompatibility Complex (MHC) class I complex and Nuclear Factor Kappa-B (NFkB) complex. Our findings suggest that DNA methylation in immune-related pathways contributes to the effects of the duration of exposure to epidural anesthesia on childhood asthma risk in NHB offspring.
Need for home care or nursing home admission after myocardial infarction complicated by cardiogenic shock and/or out-of-hospital cardiac arrest
Authors: Lauridsen Marie D , Rørth Rasmus , Butt Jawad H , Strange Jarl E , Schmidt Morten , Kristensen Søren L , Kragholm Kristian , Johnsen Søren P , Møller Jacob E , Hassager Christian , Køber Lars , Fosbøl Emil L 
Published: December 2022

Abstract

Aims
Myocardial infarction (MI) with cardiogenic shock (CS) and/or out-of-hospital cardiac arrest (OHCA) are conditions with potential loss of autonomy. In patients with MI, the association between CS and OHCA and need for home care or nursing home admission was examined.

Methods and results
Danish nationwide registries identified patients with MI (2008–19), who prior to the event lived at home without home care and discharged alive. One-year cumulative incidences and hazard ratios (HRs) were reported for home care need or nursing home admission, a composite proxy for disability in activities of daily living (ADL), along with all-cause mortality. The study population consisted of 67 109 patients with MI (by groups: −OHCA/−CS: 63 644; −OHCA/+CS: 1776; +OHCA/−CS: 968; and +OHCA/+CS: 721). The 1-year cumulative incidences of home care/nursing home were 7.1% for patients who survived to discharge with −OHCA/−CS, 20.9% for −OHCA/+CS, 5.4% for +OHCA/−CS, and 8.2% for those with +OHCA/+CS. The composite outcome was driven by home care. With the −OHCA/−CS as reference, the adjusted HRs for home care/nursing home were 2.86 (95% CI: 2.57–3.19) for patients with −OHCA/+CS; 1.31 (95% CI: 1.00–1.73) for + OHCA/−CS; and 2.18 (95% CI: 1.68–2.82) for those with +OHCA/+CS. The 1-year cumulative mortality were 5.1% for patients with −OHCA/−CS, 9.8% for −OHCA/+CS, 3.0% for +OHCA/−CS, and 3.4% for those with +OHCA/+CS.

Conclusion
In patients discharged alive after a MI, CS, and to a lesser degree OHCA were associated with impaired ADL with a two-fold higher 1-year incidence of home care or nursing home admission compared with MI patients without CS or OHCA.
Reducing gap in pre-hospital delay between women and men presenting with ST-elevation myocardial infarction
Authors: Foster-Witassek Fabienne , Rickli Hans , Roffi Marco , Pedrazzini Giovanni , Eberli Franz , Fassa Amir , Jeger Raban , Fournier Stéphane , Erne Paul , Radovanovic Dragana 
Published: December 2022

Abstract

Aims
This study aimed to analyse changes in pre-hospital delay over time in women and men presenting with ST-elevation myocardial infarction (STEMI) in Switzerland.

Methods and results
AMIS Plus registry data of patients admitted for STEMI between 2002 and 2019 were analysed using multivariable quantile regression including the following covariates: interaction between sex and admission year, age, diabetes, pain at presentation, myocardial infarction (MI) history, heart failure history, hypertension, and renal disease. Among the 15,350 patients included (74.5% men), the median (interquartile range) delay between 2002 and 2019 was 150 (84; 345) min for men and 180 (100; 414) min for women. The unadjusted median pre-hospital delay significantly decreased over time for both sexes but the decreasing trend was stronger for women. Specifically, the unadjusted sex differences in delay decreased from 60 min in 2002 (P = 0.0042) to 40.5 min in 2019 (P = 0.165). The multivariable model revealed a significant interaction between sex and admission year (P = 0.038) indicating that the decrease in delay was stronger for women (−3.3 min per year) than for men (−1.6 min per year) even after adjustment. The adjusted difference between men and women decreased from 26.93 min in 2002 to −1.97 min for women in 2019.

Conclusion
Over two decades, delay between symptom onset and hospital admission in STEMI decreased significantly for men and women. The decline was more pronounced in women, leading to the sex gap disappearing in the adjusted analysis for 2019.
Sustaining Carbon Storage: Lessons from Hemiboreal Old-Growth Coniferous and Deciduous Forest Stands
Authors: Ķēniņa Laura , Elferts Didzis , Jaunslaviete Ieva , Bāders Endijs , Jansons Āris 
Published: December 2022

AbstractFor the last three decades, the area of old-growth forest stands in Europe has continued to increase as has their importance in achieving forest-related policy goals. This has triggered an increase in research interest in old-growth forests, both from climate change mitigation and biodiversity protection perspectives. However, carbon stock in old-growth stands in European hemiboreal forests had not been systematically studied. Therefore, in this article, we characterize differences in carbon stock between mature and old-growth stands on fertile mineral soils in hemiboreal Latvia to contribute to the understanding of carbon storage changes under different management strategies for forest lands. Carbon stock varied significantly both between old-growth stands of different dominant tree species and between mature (1.9–2.3 times younger) and old-growth stages of the same dominant species in forest stands. The carbon stock of tree biomass and deadwood was larger in old-growth stands, but their mean annual carbon stock change was significantly lower than in mature stands (27% to 47% depending on dominant tree species). Old-growth stands can serve as carbon reservoirs in areas with limited natural disturbances; however, for maintenance of climate neutrality, it is essential to expand the area of managed stands with larger annual carbon stock increase.Study Implications: Forest ecosystems play a major role in regulation of global climate: They can store high quantities of carbon and also can gain or lose it rather quickly. For the last three decades, the area of old-growth forest stands in Europe has continued to increase as has their importance in achieving forest-related policy goals. Old-growth forests can represent the baseline carbon-carrying capacity in particular conditions. Therefore, we characterized differences in carbon stock between mature and old-growth stands on fertile mineral soils in hemiboreal Latvia to contribute to the understanding of carbon storage and for planning forest management activities.
Dual Domestication, Diversity, and Differential Introgression in Old World Cotton Diploids
Authors: Grover Corrinne E , Arick Mark A , Thrash Adam , Sharbrough Joel , Hu Guanjing , Yuan Daojun , Snodgrass Samantha , Miller Emma R , Ramaraj Thiruvarangan , Peterson Daniel G , Udall Joshua A , Wendel Jonathan F 
Published: December 2022

AbstractDomestication in the cotton genus is remarkable in that it has occurred independently four different times at two different ploidy levels. Relatively little is known about genome evolution and domestication in the cultivated diploid species Gossypium herbaceum and Gossypium arboreum, due to the absence of wild representatives for the latter species, their ancient domestication, and their joint history of human-mediated dispersal and interspecific gene flow. Using in-depth resequencing of a broad sampling from both species, we provide support for their independent domestication, as opposed to a progenitor–derivative relationship, showing that diversity (mean π = 6 × 10−3) within species is similar, and that divergence between species is modest (FST = 0.413). Individual accessions were homozygous for ancestral single-nucleotide polymorphisms at over half of variable sites, while fixed, derived sites were at modest frequencies. Notably, two chromosomes with a paucity of fixed, derived sites (i.e., chromosomes 7 and 10) were also strongly implicated as having experienced high levels of introgression. Collectively, these data demonstrate variable permeability to introgression among chromosomes, which we propose is due to divergent selection under domestication and/or the phenomenon of F2 breakdown in interspecific crosses. Our analyses provide insight into the evolutionary forces that shape diversity and divergence in the diploid cultivated species and establish a foundation for understanding the contribution of introgression and/or strong parallel selection to the extensive morphological similarities shared between species.
Prediction Abilities of SCORE2 Risk Algorithms for Incident Dementia and All-Cause Mortality: Results From the UK Biobank Cohort Study
Authors: Zheng Fanfan , Xie Wuxiang , Li Chenglong , Gao Darui , Liang Jie 
Published: December 2022

AbstractBackgroundWhether the updated Systematic COronary Risk Evaluation (SCORE2) risk algorithm is suitable for the prediction of incident dementia and all-cause mortality and whether its discrimination abilities for these outcomes are higher than those of the SCORE and Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) risk algorithms are unclear.MethodsThe present study included 429 033 participants (mean age: 57.1 ± 8.1 years; male: 46.2%; White: 94.1%) free of dementia from the UK Biobank at baseline, with a median follow-up of 12.8 years. Cox regression models were adopted to investigate the longitudinal relationships of SCORE2 risk categories with outcomes, and receiver operating characteristic curve analyses were used to compare the discrimination abilities of the 3 algorithms.ResultsDuring 5 376 778 person-years of follow-up, 6 477 all-cause dementia, 2 726 Alzheimer’s disease (AD), 1 439 vascular disease (VD), and 31 981 all-cause deaths were identified. We found that higher SCORE2 risk was associated with higher risks of all-cause dementia, AD, VD, and all-cause mortality. The C-indices of SCORE2 risk for discriminating incident all-cause dementia, AD, VD, and all-cause death were 0.750 (95% confidence interval [CI]: 0.745 to 0.755), 0.750 (95% CI: 0.743 to 0.757), 0.800 (95% CI: 0.791 to 0.809), and 0.721 (95% CI: 0.718 to 0.724), respectively, which were significantly improved in comparison to those of the SCORE and CAIDE risk algorithms.ConclusionThe SCORE2 risk algorithm is applicable in predicting incident all-cause dementia, AD, VD, and all-cause mortality in European populations, and its discrimination abilities for dementia and death are significantly higher than those of the SCORE and CAIDE risk algorithms. Further validations in other populations are warranted.
Can Digital Communication Protect Against Depression for Older Adults With Hearing and Vision Impairment During COVID-19?
Authors: Zhang Amanda , Wroblewski Kristen E , Imbery Terence E , McClintock Martha K , Hawkley Louise C , Pinto Jayant M 
Published: December 2022

AbstractObjectivesDuring social isolation imposed by the coronavirus disease 2019 (COVID-19) pandemic, older adults with impaired hearing and vision potentially experienced more communication challenges, increasing their risk for poor mental health. Digital communication (e.g., video calls, e-mail/text/social media) may alleviate in-person isolation and protect against depression. We addressed this question using data from the National Social Life, Health, and Aging Project, a nationally representative panel study of community-dwelling older adults.MethodTwo thousand five hundred fifty-eight adults aged 55 and older comprised the analytic sample. Interviewer rating at baseline (2015–2016) classified those with vision impairment (VI) or hearing impairment (HI). Olfactory impairment (OI) was measured by objective testing. During COVID-19 (2020–2021), respondents reported how often they contacted nonhousehold family or friends and whether this was by phone, e-mail/text/social media, video, or in-person. They also quantified the frequency of depressive feelings.ResultsOlder adults with VI or HI but not OI at baseline were significantly less likely to report regular use of video calling and e-mail/text/social media during the pandemic compared to those without impairment. Sensory impairments did not affect the frequency of phone or in-person communication. Adults with VI or HI were more likely to experience frequent depressive feelings during COVID-19. Video calls mitigated this negative effect of VI- and HI-associated depressive feelings in a dose-dependent manner.DiscussionAmong communication modalities, video calling had a protective effect against depressive feelings for people with sensory impairment during social isolation. Improving access to and usability of video communication for older adults with sensory impairment could be a strategy to improve their mental health.
High-throughput proteomics and in vitro functional characterization of the 26 medically most important elapids and vipers from sub-Saharan Africa
Authors: Nguyen Giang Thi Tuyet , O'Brien Carol , Wouters Yessica , Seneci Lorenzo , Gallissà-Calzado Alex , Campos-Pinto Isabel , Ahmadi Shirin , Laustsen Andreas H , Ljungars Anne 
Published: December 2022

Abstract
Venomous snakes are important parts of the ecosystem, and their behavior and evolution have been shaped by their surrounding environments over the eons. This is reflected in their venoms, which are typically highly adapted for their biological niche, including their diet and defense mechanisms for deterring predators. Sub-Saharan Africa is rich in venomous snake species, of which many are dangerous to humans due to the high toxicity of their venoms and their ability to effectively deliver large amounts of venom into their victims via their bite. In this study, the venoms of 26 of sub-Saharan Africa's medically most relevant elapid and viper species were subjected to parallelized toxicovenomics analysis. The analysis included venom proteomics and in vitro functional characterization of whole venom toxicities, enabling a robust comparison of venom profiles between species. The data presented here corroborate previous studies and provide biochemical details for the clinical manifestations observed in envenomings by the 26 snake species. Moreover, two new venom proteomes (Naja anchietae and Echis leucogaster) are presented here for the first time. Combined, the presented data can help shine light on snake venom evolutionary trends and possibly be used to further improve or develop novel antivenoms.