bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of vitamin D supplementation on risk of keratinocyte cancer: an exploratory analysis of the D-Health randomized controlled trial
Authors: Ali Sitwat , Pham Hai , Waterhouse Mary , Baxter Catherine , Romero Briony Duarte , McLeod Donald S.A. , Armstrong Bruce K. , Ebeling Peter R. , English Dallas R. , Hartel Gunter , van der Pols Jolieke C. , Venn Alison J. , Webb Penelope M. , Whiteman David C. , Neale Rachel E. 
Published: July 2022

Summary

Background
Vitamin D may play a role in prevention of keratinocyte cancer (KC), but observational studies examining the association between serum 25-hydroxy vitamin D concentration and KC are largely uninformative because sun exposure causes both KC and vitamin D production. There is scant evidence from clinical trials of supplementary vitamin D.

Objectives
To examine the effect of vitamin D supplementation on the risk of developing KC.

Methods
We used data from the D-Health Trial, a randomized placebo-controlled trial of vitamin D supplementation (60 000 international units monthly for 5 years) among Australians aged ≥60 years. KC outcomes were captured through linkage to a national administrative dataset for those who consented (N = 20 334; 95%). We used negative binomial regression to analyse the incidence of KC excisions and the incidence of actinic lesions treated using cryotherapy or serial curettage, and flexible parametric survival models for analysis of time to first KC excision.

Results
Randomization to vitamin D supplementation did not reduce the incidence of KC lesions treated by excision [incidence rate ratio (IRR) 1·04; 95% confidence interval (CI) 0·98–1·11], the incidence of actinic lesions treated using other methods (IRR 1·01; 95% CI 0·95–1·08) or time to first histologically confirmed KC excision (hazard ratio 1·02; 95% CI 0·97–1·08). However, in subgroup analysis vitamin D increased the incidence of KC excisions in adults aged ≥ 70 years (IRR 1·13, 95% CI 1·04–1·23; P-value for interaction = 0·01).

Conclusions
Vitamin D supplementation did not reduce the incidence of KC or other actinic lesions.
What is already known about this topic? Laboratory studies have suggested possible protective effects of vitamin D on skin cancer.Observational studies investigating the association between vitamin D and risk of keratinocyte cancer are largely uninformative as ultraviolet radiation both causes skin cancer and is the primary source of vitamin D.The evidence from randomized controlled trials of vitamin D is limited and inconclusive.
What does this study add? This population-based, randomized controlled trial suggests that supplementing older adults with a high monthly dose of vitamin D for 5 years does not affect the incidence of keratinocyte cancer.
A reaction norm framework for the evolution of learning: how cumulative experience shapes phenotypic plasticity
Authors: Wright Jonathan , Haaland Thomas R. , Dingemanse Niels J. , Westneat David F. 
Published: July 2022

ABSTRACTLearning is a familiar process to most people, but it currently lacks a fully developed theoretical position within evolutionary biology. Learning (memory and forgetting) involves adjustments in behaviour in response to cumulative sequences of prior experiences or exposures to environmental cues. We therefore suggest that all forms of learning (and some similar biological phenomena in development, aging, acquired immunity and acclimation) can usefully be viewed as special cases of phenotypic plasticity, and formally modelled by expanding the concept of reaction norms to include additional environmental dimensions quantifying sequences of cumulative experience (learning) and the time delays between events (forgetting). Memory therefore represents just one of a number of different internal neurological, physiological, hormonal and anatomical ‘states’ that mediate the carry‐over effects of cumulative environmental experiences on phenotypes across different time periods. The mathematical and graphical conceptualisation of learning as plasticity within a reaction norm framework can easily accommodate a range of different ecological scenarios, closely linking statistical estimates with biological processes. Learning and non‐learning plasticity interact whenever cumulative prior experience causes a modification in the reaction norm (a) elevation [mean phenotype], (b) slope [responsiveness], (c) environmental estimate error [informational memory] and/or (d) phenotypic precision [skill acquisition]. Innovation and learning new contingencies in novel (laboratory) environments can also be accommodated within this approach. A common reaction norm approach should thus encourage productive cross‐fertilisation of ideas between traditional studies of learning and phenotypic plasticity. As an example, we model the evolution of plasticity with and without learning under different levels of environmental estimation error to show how learning works as a specific adaptation promoting phenotypic plasticity in temporally autocorrelated environments. Our reaction norm framework for learning and analogous biological processes provides a conceptual and mathematical structure aimed at usefully stimulating future theoretical and empirical investigations into the evolution of plasticity across a wider range of ecological contexts, while providing new interdisciplinary connections regarding learning mechanisms.
ASCL1 regulates super‐enhancer‐associated miRNAs to define molecular subtypes of small cell lung cancer
Authors: Miyakawa Kazuko , Miyashita Naoya , Horie Masafumi , Terasaki Yasuhiro , Tanaka Hidenori , Urushiyama Hirokazu , Fukuda Kensuke , Okabe Yugo , Ishii Takashi , Kuwahara Naomi , Suzuki Hiroshi I. , Nagase Takahide , Saito Akira 
Published: July 2022

AbstractSmall cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with dismal prognosis. Recently, molecular subtypes of SCLC have been defined by the expression status of ASCL1, NEUROD1, YAP1, and POU2F3 transcription regulators. ASCL1 is essential for neuroendocrine differentiation and is expressed in the majority of SCLC. Although previous studies investigated ASCL1 target genes in SCLC cells, ASCL1‐mediated regulation of miRNAs and its relationship to molecular subtypes remain poorly explored. Here, we performed genome‐wide profiling of chromatin modifications (H3K27me3, H3K4me3, and H3K27ac) by CUT&Tag assay and ASCL1 knockdown followed by RNA sequencing and miRNA array analyses in SCLC cells. ASCL1 could preferentially regulate genes associated with super‐enhancers (SEs) defined by enrichment of H3K27ac marking. Moreover, ASCL1 positively regulated several SE‐associated miRNAs, such as miR‐7, miR‐375, miR‐200b‐3p, and miR‐429, leading to repression of their targets, whereas ASCL1 suppressed miR‐455‐3p, an abundant miRNA in other molecular subtypes. We further elucidated unique patterns of SE‐associated miRNAs in different SCLC molecular subtypes, highlighting subtype‐specific miRNA networks with functional relevance. Notably, we found apparent de‐repression of common target genes of different miRNAs following ASCL1 knockdown, suggesting combinatorial action of multiple miRNAs underlying molecular heterogeneity of SCLC (e.g., co‐targeting of YAP1 by miR‐9 and miR‐375). Our comprehensive analyses provide novel insights into SCLC pathogenesis and a clue to understanding subtype‐dependent phenotypic differences.
Effects of intraperitoneal injection of lipopolysaccharide‐induced peripheral inflammation on dopamine neuron damage in rat midbrain
Authors: Yang Qiu‐Yu , Li Xian‐Wei , Yang Rong , Qin Ting‐Yang , Long Hong , Zhang Shi‐Bin , Zhang Feng 
Published: July 2022

AbstractIntroductionCurrent studies have documented neuroinflammation is implicated in Parkinson's disease. Recently, growing evidence indicated peripheral inflammation plays an important role in regulation of neuroinflammation and thus conferring protection against dopamine (DA) neuronal damage. However, the underlying mechanisms are not clearly illuminated.MethodsThe effects of intraperitoneal injection of LPS (LPS[i.p.])‐induced peripheral inflammation on substantia nigra (SN) injection of LPS (LPS[SN])‐elicited DA neuronal damage in rat midbrain were investigated. Rats were intraperitoneally injected with LPS (0.5 mg/kg) daily for 4 consecutive days and then given single injection of LPS (8 μg) into SN with an interval of 0 (LPS(i.p.) 0 day ± LPS(SN)), 30 (LPS(i.p.) 30 days ± LPS(SN)), and 90 (LPS(i.p.) 90 days ± LPS(SN)) days after LPS(i.p.) administration.ResultsLPS(i.p.) increased the levels of inflammatory factors in peripheral blood in (LPS(i.p.) 0 day ± LPS(SN)). Importantly, in (LPS(i.p.) 0 day ± LPS(SN)) and (LPS(i.p.) 30 days ± LPS(SN)), LPS(i.p.) attenuated LPS(SN)‐induced DA neuronal loss in SN. Besides, LPS(i.p.) reduced LPS(SN)‐induced microglia and astrocytes activation in SN. Furtherly, LPS(i.p.) reduced pro‐inflammatory M1 microglia markers mRNA levels and increased anti‐inflammatory M2 microglia markers mRNA levels. In addition, the increased T‐cell marker expression and the decreased M1 microglia marker expression and more DA neuronal survival were discerned at the same area of rat midbrain in LPS(SN)‐induced DA neuronal damage 30 days after LPS(i.p.) application.ConclusionThis study suggested LPS(i.p.)‐induced peripheral inflammation might cause T cells to infiltrate the brain to regulate microglia‐mediated neuroinflammation, thereby protecting DA neurons.
Fungal dominance of gross nitrogen mineralisation in an acidic upland soil amended with organic fertiliser
Authors: Wang Jing , Fu Ruibiao , Li Yong , Tu Xiaoshun , Chen Zhaoxiong , Elrys Ahmed S. , Cheng Yi , Zhang Jinbo , Cai Zucong , Müller Christoph , Ma Lifeng 
Published: July 2022

AbstractFungi typically prevail in acidic soils and have a stronger preference for complex organic compounds than bacteria. Thus, we hypothesized that fungi would play a more important role in gross nitrogen (N) transformation in acidic soil than bacteria, and the dominance of fungi on gross N transformations in acidic soil would increase following complex organic inputs. Herein, we determined bacterial and fungal contributions to gross N transformation processes using a 15N tracing approach combined with selective inhibition in an acidic upland soil under aerobic conditions. Streptomycin was used as the bacterial inhibitor and cycloheximide as the fungal inhibitor. Our results showed that bacteria appeared to dominate autotrophic nitrification but fungi were also involved, and both bacteria and fungi contributed to the gross rate of dissimilatory nitrate reduction to ammonium (NH4+). When rape seed cake was added to the soil, fungi dominated gross N mineralisation and played an important role in gross NH4+ immobilisation. Our results suggest that the addition of organic fertiliser into acidic upland soil can enhance the contribution of fungi to the mineralisation‐immobilisation turnover of N.Highlights
Bacterial and fungal contributions to gross N transformation rates were quantified.
Bacteria dominated autotrophic nitrification in acidic upland soil.
Fungi dominated gross N mineralisation following organic fertiliser addition.
Adding complex carbon to acidic soil boosts fungal‐mediated N transformations.
A 10‐year follow‐up survey of US academic libraries highlights the COVID‐19 experience and greater interest in health information outreach
Authors: Jameson Jodi , Duhon Lucy 
Published: July 2022

AbstractBackgroundAs follow‐up to their previous survey on health information outreach (HIO) in 2010, the authors became interested in the evolving nature of HIO activities at academic libraries within the past decade.ObjectivesThe aim of this study was to understand how HIO activities at academic libraries have evolved since 2010, especially considering the current COVID‐19 pandemic.MethodsAn online survey, designed to collect quantitative data on general HIO activities and qualitative data specifically on COVID‐19 information outreach, was distributed to over 1700 librarians at US general academic and academic health science libraries.ResultsTwo hundred and fifty‐five respondents completed the survey. Quantitative findings generally paralleled the 2010 results, except in a few areas. Most notably, a greater percentage of librarians in 2020 were participating in HIO (44%) than in 2010 (37%). Qualitative findings revealed that librarians are leveraging traditional information services and implementing innovative partnerships to promote reputable health information resources on COVID‐19.DiscussionEvidence suggests that further engagement and campus partnerships can enhance libraries' supportive roles as trustworthy purveyors of quality health information.ConclusionUS academic librarians are increasingly engaging in HIO to support the health information needs of campus communities and should consider aligning outreach activities with national health goals.
Paternal knockdown of tRNA(cytosine‐5‐)‐methyltransferase (Dnmt2) increases offspring susceptibility to infection in red flour beetles
Authors: Schulz Nora K. E. , Mohamed Fakry F. , Lo Lai Ka , Peuß Robert , de Buhr Maike F. , Kurtz Joachim 
Published: July 2022

AbstractIntergenerational effects from fathers to offspring are increasingly reported from diverse organisms, but the underlying mechanisms remain speculative. Paternal trans‐generational immune priming (TGIP) was demonstrated in the red flour beetle Tribolium castaneum: non‐infectious bacterial exposure of fathers protects their offspring against an infectious challenge for at least two generations. Epigenetic processes, such as cytosine methylation of nucleic acids, have been proposed to enable transfer of information from fathers to offspring. Here we studied a potential role in TGIP of the Dnmt2 gene (renamed as Trdmt1 in humans), which encodes a highly conserved enzyme that methylates different RNAs, including specific cytosines of a set of tRNAs. Dnmt2 has previously been reported to be involved in intergenerational epigenetic inheritance in mice and protection against viruses in fruit flies. We first studied gene expression and found that Dnmt2 is expressed in various life history stages and tissues of T. castaneum, with high expression in the reproductive organs. RNAi‐mediated knockdown of Dnmt2 in fathers was systemic, slowed down offspring larval development and increased mortality of the adult offspring upon bacterial infection. However, these effects were independent of bacterial exposure of the fathers. In conclusion, our results point towards a role of Dnmt2 for paternal effects, while elucidation of the mechanisms behind paternal TGIP needs further studies.
A new species of deep‐sea torquaratorid enteropneust (Hemichordata): A sequential hermaphrodite with exceptionally wide lips
Authors: Holland Nicholas D. , Hiley Avery S. , Rouse Greg W. 
Published: July 2022

AbstractSpecimens of a new species of torquaratorid acorn worm (Hemichordata, Enteropneusta) were video recorded and subsequently collected at abyssal depths in the eastern North Pacific at sites ranging from Oregon to northern Mexico. These worms are described here as Yoda demiankoopi n. sp. by molecular and morphological methods. The new species differs from its only described congener, Yoda purpurata, in three ways. First, the lips are extremely wide and indented by a deep ciliary groove for ingesting substrate and conveying it to the mouth. Second, a connective tissue bulge of unknown significance runs mid‐dorsally along the hepatic and posthepatic regions of the intestine. Third, the posthepatic intestine is strikingly sinuous and packed with gut contents presumably undergoing digestion for extended periods between infrequent defecations. Yoda demiankoopi n. sp. is hermaphroditic, a character so far known only for the genus Yoda in the entire class Enteropneusta. The gonads of each adult worm comprise hundreds of ovaries (each containing a single oocyte) and hundreds of testes located just beneath the dorsal epidermis of the anterior trunk and associated genital wings. In any given animal, at any given time, gametes of only one sex or the other become fully mature. Thus, the worm is a sequential hermaphrodite, alternately spawning purely as a female or purely as a male.
Being tied down—The experience of being physically restrained while mechanically ventilated in ICU
Authors: Perez Dawn , Murphy Gillian , Wilkes Lesley , Peters Kath 
Published: July 2022

AbstractAimsTo explore the experience of physical restraints during mechanical ventilation in intensive care from the perspectives of patients and family members.DesignThis research was a qualitative study with a naturalistic inquiry framework adhering to the Consolidated Criteria for Reporting Qualitative Research guidelines.MethodIn‐depth, semi‐structured conversations were conducted with five patients and six family members who had either personally experienced or witnessed their loved ones being physically restrained during mechanical ventilation in intensive care. Data collection occurred between March 2018 and June 2019. These conversations were audio‐recorded and transcribed. Reflexive thematic analysis was used to analyse the data.ResultsThree major themes emerged from the data. These themes were: Being tied down; Feeling helpless; and Finding light in the darkness.ConclusionThe experience of physical restraints during mechanical ventilation in intensive care leads to traumatic experiences which can impact patients and families long after their ICU stay. Holistic care, which considers the physical, emotional and psychological needs of patients and families, should be more thoroughly explored when managing treatment interference to minimize harm.ImpactThis study gained insight into the physical, emotional and psychological consequences of applying physical restraints to patients who are mechanically ventilated as an intervention for preventing treatment interference. The findings of this study have the potential to improve ICU patient and family outcomes by influencing current physical restraint practices. Recommendations from this research can contribute to practice change by informing policy, shifting workplace culture and norms about restraints, and encouraging education and training.
COVID‐19 pandemic and care of transfusion‐dependent patients of thalassaemia: Experience from a paediatric centre in North India
Authors: Parakh Nupur , Pahuja Sangeeta , Singh Varinder , Kumar Narender , Chandra Jagdish 
Published: July 2022

AimCOVID‐19 has presented an unprecedented challenge to health services and has significantly affected the management of non‐Covid illnesses, like thalassemia. The present study documents the impact of Covid‐associated restrictions and disruptions on working of the pediatric thalassemia day care centre (TDCC), and measures taken by TDCC and blood transfusion services to adapt to and mitigate the negative impact of Covid pandemic and associated lockdown on patient care.MethodsPre‐transfusion haemoglobin and packed cell transfusion requirement were compared across three time periods, namely pre‐lockdown, lockdown and post‐lockdown in paediatric transfusion‐dependent thalassaemia (TDT) patients. Caregivers were interviewed to document any problems faced by them.ResultsThe study involved 181 TDT patients. There was a significant reduction in mean pre‐transfusion haemoglobin and red cells transfused during lockdown phase as compared to pre‐lockdown phase. Regular care was interrupted in 45% of patients and 76% of patients getting blood from outside could not get leukoreduced red cells. Investigations, monitoring and continuity of iron chelation were also affected. Blood centre faced 30.5% reduction in blood supply during lockdown. TDCC and blood centre took several steps, including prolongation of service hours and staggering of transfusions to ensure maximum transfusions while ensuring social distancing.ConclusionThe COVID‐19 pandemic imposed many unprecedented challenges to the routine care of thalassaemic patients; however, some of them could be dealt with by a proactive approach and micro‐planning at the institution level. Other similar resource‐limited settings could learn from experiences for continued quality care for chronic medical conditions during pandemic like situations.
Factors linked to hepatocellular carcinoma development beyond 10 years after viral eradication in patients with hepatitis C virus
Authors: Kumada Takashi , Toyoda Hidenori , Yasuda Satoshi , Ito Takanori , Tsuji Kunihiko , Fujioka Shinichi , Hiraoka Atsushi , Kariyama Kazuya , Nouso Kazuhiro , Ishikawa Toru , Tamai Tsutomu , Tada Toshifumi , Tanaka Junko 
Published: July 2022

AbstractThe risk factors for hepatocellular carcinoma (HCC) development in patients whose duration of sustained virological response (SVR) is over 10 years are not fully understood. We compared the incidence of HCC development within and beyond 10 years after SVR. A total of 1384 patients who achieved SVR (714, interferon‐based therapy; 670, direct‐acting antiviral therapy) were enrolled. Factors associated with HCC development were analysed within and beyond 10 years after SVR by Cox proportional hazards models. The annual incidence rates of HCC development were 0.568% within 10 years after SVR and 0.190% beyond 10 years, and there was a significant difference in the incidence of HCC development between the 2 periods (p = 0.0242, log‐rank test). Male gender (adjusted hazard ratio [aHR] 2.930; 95% confidence interval [CI] 1.508–5.693, p = 0.0015), fibrosis‐4 (FIB‐4) score > 3.25 (aHR 4.364; 95%CI 2.206–8.633, p < 0.0001) and alpha‐fetoprotein ≥5.0 ng/ml (aHR 2.381; 95%CI 1.325–4.280, p = 0.0037) were independently associated with HCC development within 10 years after SVR. Male gender (aHR 4.702; 95%CI 1.366–16.190, p = 0.0141), presence of diabetes mellitus (aHR 2.933; 95%CI 1.240–6.935, p = 0.0143) and gamma‐glutamyl transpeptidase (GGT) ≥ 56 U/l (aHR 4.157; 95%CI 1.400–12.350, p = 0.0103) were independently associated with HCC development beyond 10 years after SVR. The incidence of HCC development beyond 10 years after SVR was very low, and the associated factors were mainly extrahepatic, including DM and elevated GGT. Annual routine check‐ups with abdominal ultrasound may be sufficient for such patients. (242 words).