bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of end-of-life care stress, calling, and resilience on end-of-life care performance: a descriptive correlational study
Authors: Kim Ji-Young , Choi Eun-Hi
Published: May 2022

Background

Prolonging the end-of-life process means that the duration of health care work increases and the management of death is delegated to health care providers by patients’ families. Thus, it is important to explore measures to enhance the quality of end-of-life care by identifying the predictors thereof. End-of-life care should be people-centred, relieving serious health-related suffering, be it physical, psychological, social, or spiritual. Nurses who provide end-of-life care usually spend the most time with dying patients, administering care to help patients who wish to die with dignity; therefore, end-of-life nursing care is highly significant.

Methods

This study was conducted on nurses of 500-bed or larger university hospitals in city D and province C in South Korea from 20 August to 10 September 2020 using a structured questionnaire. A total of 213 nurses with a minimum clinical career of one year and at least one EOLC experience participated. The final analysis sample consisted of 206 nurses. Descriptive analysis, Pearson’s correlation coefficients, ANOVA, t-test, and multiple-regression analysis were used to analyse the data.

Results

This study found that end-of-life care performance was significantly positively correlated with end-of-life care stress [r = .253, p < .001], sense of calling [r = .424, p < .001], and resilience [r = .397, p < .001]. End-of-life care stress [β = .185, p = .003], sense of calling [β = .259, p < .001], resilience [β = .252, p < .001], and working in a hospice ward [β = .140, p = .041] or intensive care unit [β = .218, p = .008], as opposed to the emergency department, were identified as predictors of end-of-life care performance. These factors explained 28.3% of the variance in the end-of-life care performance in this study.

Conclusions

Boosting the sense of calling and resilience among nurses providing palliative care can improve overall end-of-life care performances. Subsequent studies should develop and evaluate interventions and programs that could improve these factors to ensure a positive change in health care and enhance the quality of end-of-life care in hospitals.
Clinician based decision tool to guide recommended interval between colonoscopies: development and evaluation pilot study
Authors: Shafer Leigh Anne , Restall Gayle , Simms Alexandria , Lee Eugene , Park Jason , Singh Harminder
Published: May 2022

Background

Optimal intervals between repeat colonoscopies could improve patient outcomes and reduce costs. We evaluated: (a) concordance between clinician and guideline recommended colonoscopy screening intervals in Winnipeg, Manitoba, (b) clinician opinions about the utility of an electronic decision-making tool to aid in recommending screening intervals, and (c) the initial use of a decision-making smartphone/web-based application.

Methods

Clinician endoscopists and primary care providers participated in four focus groups (N = 22). We asked participating clinicians to evaluate up to 12 hypothetical scenarios and compared their recommended screening interval to those of North American guidelines. Fisher’s exact tests were used to assess differences in agreement with guidelines. We developed a decision-making tool and evaluated it via a pilot study with 6 endoscopists.

Result

53% of clinicians made recommendations that agreed with guidelines in ≤ 50% of the hypothetical scenarios. Themes from focus groups included barriers to using a decision-making tool: extra time to use it, less confidence in the results of the tool over their own judgement, and having access to the information required by the tool (e.g., family history). Most were willing to try a tool if it was quick and easy to use. Endoscopists participating in the tool pilot study recommended screening intervals discordant with guidelines 35% of the time. When their recommendation differed from that of the tool, they usually endorsed their own over the guideline.

Conclusions

Endoscopists are overconfident and inconsistent with applying guidelines in their polyp surveillance interval recommendations. Use of a decision tool may improve knowledge and application of guidelines. A change in practice may require that the tool be coupled with continuing education about evidence for improved outcomes if guidelines are followed.
An evaluation of an Extension for Community Healthcare Outcomes (ECHO) intervention in cancer prevention and survivorship care
Authors: Milgrom Zheng Z. , Severance Tyler S. , Scanlon Caitlin M. , Carson Anyé T. , Janota Andrea D. , Vik Terry A. , Duwve Joan M. , Dixon Brian E. , Mendonca Eneida A.
Published: May 2022

To improve cancer care in Indiana, a telementoring program using the Extension for Community Healthcare Outcomes (ECHO) model was introduced in September 2019 to promote best-practice cancer prevention, screening, and survivorship care by primary care providers (PCPs). The aim of this study was to evaluate the program’s educational outcomes in its pilot year, using Moore’s Evaluation Framework for Continuing Medical Education and focusing on the program’s impact on participants’ knowledge, confidence, and professional practice. We collected data in 22 semi-structured interviews (13 PCPs and 9 non-PCPs) and 30 anonymous one-time surveys (14 PCPs and 16 non-PCPs) from the program participants (hub and spoke site members), as well as from members of the target audience who did not participate. In the first year, average attendance at each session was 2.5 PCPs and 12 non-PCP professionals. In spite of a relatively low PCP participation, the program received very positive satisfaction scores, and participants reported improvements in knowledge, confidence, and practice. Both program participants and target audience respondents particularly valued three features of the program: its conversational format, the real-life experiences gained, and the support received from a professional interdisciplinary community. PCPs reported preferring case discussions over didactics. Our results suggest that the Cancer ECHO program has benefits over other PCP-targetted cancer control interventions and could be an effective educational means of improving cancer control capacity among PCPs and others. Further study is warranted to explain the discrepancies among study participants’ perceptions of the program’s strengths and the relatively low PCP participation before undertaking a full-scale effectiveness study.
Cdk5-mediated JIP1 phosphorylation regulates axonal outgrowth through Notch1 inhibition
Authors: Im Doo Soon , Joselin Alvin , Svoboda Devon , Takano Tesuya , Rousseaux Maxime W. C. , Callaghan Steve , Slack Ruth S. , Hisanaga Shin-ichi , Davis Roger J. , Park David S. , Qu Dianbo
Published: May 2022

Background

Activated Cdk5 regulates a number of processes during nervous system formation, including neuronal differentiation, growth cone stabilization, and axonal growth. Cdk5 phosphorylates its downstream substrates located in axonal growth cones, where the highly expressed c-Jun N-terminal kinase (JNK)-interacting protein1 (JIP1) has been implicated as another important regulator of axonal growth. In addition, stringent control of the level of intracellular domain of Notch1 (Notch1-IC) plays a regulatory role in axonal outgrowth during neuronal differentiation. However, whether Cdk5-JIP1-Notch1 cooperate to regulate axonal outgrowth, and the mechanism of such joint contribution to this pathway, is presently unknown, and here we explore their potential interaction.

Results

Our interactome screen identified JIP1 as an interactor of p35, a Cdk5 activator, and we sought to explore the relationship between Cdk5 and JIP1 on the regulation of axonal outgrowth. We demonstrate that JIP1 phosphorylated by Cdk5 at Thr205 enhances axonal outgrowth and a phosphomimic JIP1 rescues the axonal outgrowth defects in JIP1−/− and p35−/− neurons. Axonal outgrowth defects caused by the specific increase of Notch1 in JIP1−/− neurons are rescued by Numb-mediated inhibition of Notch1. Finally, we demonstrate that Cdk5 phosphorylation of JIP1 further amplifies the phosphorylation status of yet another Cdk5 substrate E3-ubiquitin ligase Itch, resulting in increased Notch1 ubiquitination.

Conclusions

Our findings identify a potentially critical signaling axis involving Cdk5-JIP1-Itch-Notch1, which plays an important role in the regulation of CNS development. Future investigation into the way this pathway integrates with additional pathways regulating axonal growth will further our knowledge of normal central nervous system development and pathological conditions.
Effectiveness of a digital intervention versus alcohol information for online help-seekers in Sweden: a randomised controlled trial
Authors: Bendtsen Marcus , Åsberg Katarina , McCambridge Jim
Published: May 2022

Background

The ubiquity of Internet connectivity, and widespread unmet needs, requires investigations of digital interventions for people seeking help with their drinking. The objective of this study was to test the effectiveness of a digital alcohol intervention compared to existing online resources for help seekers.

Methods

This parallel randomised controlled trial included 2129 risky drinkers with access to a mobile phone and aged 18 years or older. Randomised sub-studies investigated consent procedures and control group design. Simple computerised randomisation was used. Participants were aware of allocation after randomisation; research personnel were not. The digital intervention was designed around weekly monitoring of alcohol consumption followed by feedback and tools for behaviour change. Primary outcomes were total weekly consumption (TWC) and frequency of heavy episodic drinking (HED), measured 2 and 4 months post-randomisation.

Results

Between 25/04/2019 and 26/11/2020, 2129 participants were randomised (intervention: 1063, control: 1066). Negative binomial regression was used to contrast groups, with both Bayesian and maximum likelihood inference. The posterior median incidence rate ratio (IRR) of TWC was 0.89 (95% CI = 0.81;0.99, 98.2% probability of effect, P-value = 0.033) at 2 months among 1557 participants and 0.77 (95% CI = 0.69;0.86, > 99.9% probability of effect, P-value < 0.001) at 4 months among 1429 participants. For HED, the IRR was 0.83 (95% CI = 0.75;0.93, > 99.9% probability of effect, P-value = 0.0009) at 2 months among 1548 participants and 0.71 (95% CI = 0.63;0.79, probability of effect > 99.9%, P-value < 0.0001) at 4 months among 1424 participants. Analyses with imputed data were not markedly different.

Conclusions

A digital alcohol intervention produced self-reported behaviour change among online help seekers in the general population. The internal and external validity of this trial is strong, subject to carefully considered study limitations arguably inherent to trials of this nature. Limitations include higher than anticipated attrition to follow-up and lack of blinding.

Trial registration

The trial was prospectively registered (ISRCTN48317451).
A kia ora, a wave and a smile: an urban marae-led response to COVID-19, a case study in manaakitanga
Authors: Davies Cheryl , Timu-Parata Carmen , Stairmand Jeannine , Robson Bridget , Kvalsvig Amanda , Lum Dominique , Signal Virginia
Published: May 2022

Background

When COVID-19 emerged, there were well-founded fears that Māori (indigenous peoples of Aotearoa (New Zealand)) would be disproportionately affected, both in terms of morbidity and mortality from COVID-19 itself and through the impact of lock-down measures. A key way in which Kōkiri (a Māori health provider) responded was through the establishment of a pātaka kai (foodbank) that also provided a gateway to assess need and deliver other support services to whānau (in this case, client). Māori values were integral to this approach, with manaakitanga (kindness or providing care for others) at the heart of Kōkiri’s actions. We sought to identify how Kōkiri operated under the mantle of manaakitanga, during Aotearoa’s 2020 nationwide COVID-19 lockdown and to assess the impact of their contributions on Māori whānau.

Methods

We used qualitative methods underpinned by Māori research methodology. Twenty-six whānau interviews and two focus groups were held, one with eight kaimahi (workers) and the other with seven rangatahi (youth) kaimahi. Data was gathered between June and October 2020 (soon after the 2020 lockdown restrictions were lifted), thematically analysed and interpreted using a Māori worldview.

Results

Three key themes were identified that aligned to the values framework that forms the practice model that Kōkiri kaimahi work within. Kaitiakitanga, whānau and manaakitanga are also long-standing Māori world values. We identified that kaitiakitanga (protecting) and manaakitanga (with kindness) - with whānau at the centre of all decisions and service delivery - worked as a protective mechanism to provide much needed support within the community Kōkiri serves.

Conclusions

Māori health providers are well placed to respond effectively in a public-health crisis when resourced appropriately and trusted to deliver. We propose a number of recommendations based on the insights generated from the researchers, kaimahi, and whānau. These are that: Māori be included in pandemic planning and decision-making, Māori-led initiatives and organisations be valued and adequately resourced, and strong communities with strong networks be built during non-crisis times.
Estimating cardiovascular health gains from eradicating indoor cold in Australia
Authors: Singh Ankur , Mizdrak Anja , Daniel Lyrian , Blakely Tony , Baker Emma , Fleitas Alfonzo Ludmila , Bentley Rebecca
Published: May 2022

Background

Exposure to cold indoor temperature (< 18 degrees Celsius) increases cardiovascular disease (CVD) risk and has been identified by the WHO as a source of unhealthy housing. While warming homes has the potential to reduce CVD risk, the reduction in disease burden is not known. We simulated the population health gains from reduced CVD burden if the temperature in all Australian cold homes was permanently raised from their assumed average temperature of 16 degrees Celsius to 20 degrees Celsius.

Methods

The health effect of eradicating cold housing through reductions in CVD was simulated using proportional multistate lifetable model. The model sourced CVD burden and epidemiological data from Australian and Global Burden of Disease studies. The prevalence of cold housing in Australia was estimated from the Australian Housing Conditions Survey. The effect of cold indoor temperature on blood pressure (and in turn stroke and coronary heart disease) was estimated from published research.

Results

Eradication of exposure to indoor cold could achieve a gain of undiscounted one and a half weeks of additional health life per person alive in 2016 (base-year) in cold housing through CVD alone. This equates to 0.447 (uncertainty interval: 0.064, 1.34; 3% discount rate) HALYs per 1,000 persons over remainder of their lives through CVD reduction. Eight percent of the total health gains are achievable between 2016 and 2035. Although seemingly modest, the gains outperform currently recommended CVD interventions including persistent dietary advice for adults 5–9% 5 yr CVD risk (0.017 per 1000 people, UI: 0.01, 0.027) and persistent lifestyle program for adults 5–9% 5 yr CVD risk (0.024, UI: 0.01, 0.027).

Conclusion

Cardiovascular health gains alone achievable through eradication of cold housing are comparable with real-life lifestyle and dietary interventions. The potential health gains are even greater given cold housing eradication will also improve respiratory and mental health in addition to cardiovascular disease.
Chronic effects of two rutile TiO2 nanomaterials in human intestinal and hepatic cell lines
Authors: Jalili Pégah , Krause Benjamin-Christoph , Lanceleur Rachelle , Burel Agnès , Jungnickel Harald , Lampen Alfonso , Laux Peter , Luch Andreas , Fessard Valérie , Hogeveen Kevin
Published: May 2022

Background

TiO2 nanomaterials (NMs) are present in a variety of food and personal hygiene products, and consumers are exposed daily to these NMs through oral exposition. While the bulk of ingested TiO2 NMs are eliminated rapidly in stool, a fraction is able to cross the intestinal epithelial barrier and enter systemic circulation from where NMs can be distributed to tissues, primarily liver and spleen. Daily exposure to TiO2 NMs, in combination with a slow rate of elimination from tissues, results in their accumulation within different tissues. Considerable evidence suggests that following oral exposure to TiO2 NMs, the presence of NMs in tissues is associated with a number of adverse effects, both in intestine and liver. Although numerous studies have been performed in vitro investigating the acute effects of TiO2 NMs in intestinal and hepatic cell models, considerably less is known about the effect of repeated exposure on these models. In this study, we investigated the cytotoxic effects of repeated exposure of relevant models of intestine and liver to two TiO2 NMs differing in hydrophobicity for 24 h, 1 week and 2 weeks at concentrations ranging from 0.3 to 80 µg/cm2. To study the persistence of these two NMs in cells, we included a 1-week recovery period following 24 h and 1-week treatments. Cellular uptake by TEM and ToF–SIMS analyses, as well as the viability and pro-inflammatory response were evaluated. Changes in the membrane composition in Caco-2 and HepaRG cells treated with TiO2 NMs for up to 2 weeks were also studied.

Results

Despite the uptake of NM-103 and NM-104 in cells, no significant cytotoxic effects were observed in either Caco-2 or HepaRG cells treated for up to 2 weeks at NM concentrations up to 80 µg/cm2. In addition, no significant effects on IL-8 secretion were observed. However, significant changes in membrane composition were observed in both cell lines. Interestingly, while most of these phospholipid modifications were reversed following a 1-week recovery, others were not affected by the recovery period.

Conclusion

These findings indicate that although no clear effects on cytotoxicity were observed following repeated exposure of differentiated Caco-2 and HepaRG cells to TiO2 NMs, subtle effects on membrane composition could induce potential adverse effects in the long-term.
Sleep patterns and potential risk factors for disturbed sleep quality in patients after surgery for infective endocarditis
Authors: Hu Xiang-Ming , Wei Wen-Ting , Huang De-Yi , Lin Cai-Di , Lu Fen , Li Xiao-Ming , Liao Huo-Sheng , Yu Zhi-Hong , Weng Xiao-Ping , Wang Shi-Bin , Hou Cai-Lan , Jia Fu-Jun
Published: May 2022

Background

The current study aimed to investigate the sleep quality of patients after valve replacement surgery due to infective endocarditis and identify risk factors for disturbed sleep post hospitalisation.

Methods

Eighty patients were assessed postoperatively using subjective scale measures, the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale, and an objective measure, actigraphy. Scale measures were assessed approximately 2 weeks and 6 months after surgery. Actigraphy monitoring was performed for 2 consecutive weeks during hospitalisation. Logistic regression was used to identify risk factors for disturbed sleep.

Results

The study population (n = 80) had an average age of 42.8 ± 14.2 years, and 67.5% were male. The median sleep efficiency was 85.3% in week 1 and 86.8% in week 2. The frequency of awakenings was significantly higher in week 1 (20.0 times vs. 19.3 times, p = 0.017). The scale measures showed significant improvement in sleep by 6 months after surgery compared to that during hospitalisation. Multivariable logistic regression analysis suggested that the possible risk factors for disturbed sleep 6 months after surgery included age (OR = 1.479, 95%CI 1.140–1.920) and a few parameters of early postoperative disturbed sleep quality (PSQI: OR = 2.921, 95%CI 1.431–5.963; sleep efficiency: OR = 0.402, 95%CI 0.206–0.783; and average duration of awakenings: OR = 0.006, 95%CI 0.000–0.827).

Conclusions

Disturbed sleep quality was witnessed in postoperative patients during hospitalisation and up to 6 months after surgery. Over time, the patients’ sleep quality improved significantly. Age and a few early postoperative sleep quality variables were risk factors for disturbed sleep 6 months after surgery.
Substitution impacts of Nordic wood-based multi-story building types: influence of the decarbonization of the energy sector and increased recycling of construction materials
Authors: Myllyviita Tanja , Hurmekoski Elias , Kunttu Janni
Published: May 2022

Background

The building and construction sectors represent a major source of greenhouse gas (GHG) emissions. Replacing concrete and steel with wood is one potential strategy to decrease emissions. On product level, the difference in fossil emissions per functional unit can be quantified with displacement factors (DFs), i.e., the amount of fossil emission reduction achieved per unit of wood use when replacing a functionally equivalent product. We developed DFs for substitution cases representative of typical wood-frame and non-wood frame multi-story buildings in the Nordic countries, considering the expected decarbonization of the energy sector and increased recycling of construction products.

Results

Most of the DFs were positive, implying lower fossil emissions, if wood construction is favored. However, variation in the DFs was substantial and negative DFs implying higher emissions were also detected. All DFs showed a decreasing trend, i.e., the GHG mitigation potential of wood construction significantly decreases under future decarbonization and increased recycling assumptions. If only the decarbonization of the energy sector was considered, the decrease was less dramatic compared to the isolated impact of the recycling of construction materials. The mitigation potential of wood construction appears to be the most sensitive to the GHG emissions of concrete, whereas the emissions of steel seem less influential, and the emissions of wood have only minor influence.

Conclusions

The emission reduction due to the decarbonization of the energy sector and the recycling of construction materials is a favorable outcome but one that reduces the relative environmental benefit of wood construction, which ought to be considered in forest-based mitigation strategies. Broadening the system boundary is required to assess the overall substitution impacts of increased use of wood in construction, including biogenic carbon stock changes in forest ecosystems and in wood products over time, as well as price-mediated market responses.
Infertility and risk of breast cancer in men: a national case–control study in England and Wales
Authors: Swerdlow Anthony J. , Bruce Cydney , Cooke Rosie , Coulson Penny , Jones Michael E.
Published: May 2022

Purpose

Breast cancer is uncommon in men and its aetiology is largely unknown, reflecting the limited size of studies thus far conducted. In general, number of children fathered has been found a risk factor inconsistently, and infertility not. We therefore investigated in a case–control study, the relation of risk of breast cancer in men to infertility and number of children.

Patients and methods

We conducted a national case–control study in England and Wales, interviewing 1998 cases incident 2005–17 and 1597 male controls, which included questions on infertility and offspring.

Results

Risk of breast cancer was statistically significantly associated with male-origin infertility (OR = 2.03 (95% confidence interval (CI) 1.18–3.49)) but not if a couple’s infertility had been diagnosed as of origin from the female partner (OR = 0.86 (0.51–1.45)). Risk was statistically significantly raised for men who had not fathered any children (OR = 1.50 (95% CI 1.21–1.86)) compared with men who were fathers. These associations were statistically significantly present for invasive tumours but not statistically significant for in situ tumours.

Conclusion

Our data give strong evidence that risk of breast cancer is increased for men who are infertile. The reason is not clear and needs investigation.
The mucin-like, secretory type-I transmembrane glycoprotein GP900 in the apicomplexan Cryptosporidium parvum is cleaved in the secretory pathway and likely plays a lubrication role
Authors: Li Xiaohui , Yin Jigang , Wang Dongqiang , Gao Xin , Zhang Ying , Wu Mingbo , Zhu Guan
Published: May 2022

Background

Cryptosporidium parvum is a zoonotic parasite and member of the phylum Apicomplexa with unique secretory organelles, including a rhoptry, micronemes and dense granules that discharge their contents during parasite invasion. The mucin-like glycoprotein GP900 with a single transmembrane domain is an immunodominant antigen and micronemal protein. It is relocated to the surface of excysted sporozoites and shed to form trails by sporozoites exhibiting gliding motility (gliding sporozoites). However, the biological process underlying its relocation and shedding remains unclear. The primary aim of this study was to determine whether GP900 is present as a transmembrane protein anchored to the plasma membrane on the surface of sporozoites and whether it is cleaved before being shed from the sporozoites.

Methods

Two anti-GP900 antibodies, a mouse monoclonal antibody (mAb) to the long N-terminal domain (GP900-N) and a rabbit polyclonal antibody (pAb) to the short C-terminal domain (GP900-C), were produced for the detection of intact and cleaved GP900 proteins in sporozoites and other parasite developmental stages by microscopic immunofluorescence assay and in discharged molecules by enzyme-linked immunosorbent assay.

Results

Both anti-GP900 antibodies recognized the apical region of unexcysted and excysted sporozoites. However, anti-GP900-N (but not anti-GP900-C) also stained both the pellicles/surface of excysted sporozoites and the trails of gliding sporozoites. Both antibodies stained the intracellular meronts, both developing and developed, but not the macro- and microgamonts. Additionally, the epitope was recognized by anti-GP900-N (but not anti-GP900-C) and detected in the secretions of excysted sporozoites and intracellular parasites.

Conclusions

GP900 is present in sporozoites and intracellular meronts, but absent in sexual stages. It is stored in the micronemes of sporozoites, but enters the secretory pathway during excystation and invasion. The short cytoplasmic domain of GP900 is cleaved in the secretory pathway before it reaches the extracellular space. The molecular features and behavior of GP900 imply that it plays mainly a lubrication role.

Graphical Abstract
Aberrant hypomethylation at imprinted differentially methylated regions is involved in biparental placental mesenchymal dysplasia
Authors: Aoki Saori , Higashimoto Ken , Hidaka Hidenori , Ohtsuka Yasufumi , Aoki Shigehisa , Mishima Hiroyuki , Yoshiura Koh-ichiro , Nakabayashi Kazuhiko , Hata Kenichiro , Yatsuki Hitomi , Hara Satoshi , Ohba Takashi , Katabuchi Hidetaka , Soejima Hidenobu
Published: May 2022

Background

Placental mesenchymal dysplasia (PMD) is a morphological abnormality resembling partial hydatidiform moles. It is often associated with androgenetic/biparental mosaicism (ABM) and complicated by Beckwith–Wiedemann syndrome (BWS), an imprinting disorder. These phenomena suggest an association between PMD and aberrant genomic imprinting, particularly of CDKN1C and IGF2. The existence of another type of PMD containing the biparental genome has been reported. However, the frequency and etiology of biparental PMD are not yet fully understood.

Results

We examined 44 placental specimens from 26 patients with PMD: 19 of these were macroscopically normal and 25 exhibited macroscopic PMD. Genotyping by DNA microarray or short tandem repeat analysis revealed that approximately 35% of the macroscopic PMD specimens could be classified as biparental, while the remainder were ABM. We performed a DNA methylation analysis using bisulfite pyrosequencing of 15 placenta-specific imprinted differentially methylated regions (DMRs) and 36 ubiquitous imprinted DMRs. As expected, most DMRs in the macroscopic PMD specimens with ABM exhibited the paternal epigenotype. Importantly, the biparental macroscopic PMD specimens exhibited frequent aberrant hypomethylation at seven of the placenta-specific DMRs. Allelic expression analysis using single-nucleotide polymorphisms revealed that five imprinted genes associated with these aberrantly hypomethylated DMRs were biallelically expressed. Frequent aberrant hypomethylation was observed at five ubiquitous DMRs, including GRB10 but not ICR2 or ICR1, which regulate the expression of CDKN1C and IGF2, respectively. Whole-exome sequencing performed on four biparental macroscopic PMD specimens did not reveal any pathological genetic abnormalities. Clinical and molecular analyses of babies born from pregnancies with PMD revealed four cases with BWS, each exhibiting different molecular characteristics, and those between BWS and PMD specimens were not always the same.

Conclusion

These data clarify the prevalence of biparental PMD and ABM-PMD and strongly implicate hypomethylation of DMRs in the pathogenesis of biparental PMD, particularly placenta-specific DMRs and the ubiquitous GRB10, but not ICR2 or ICR1. Aberrant hypomethylation of DMRs was partial, indicating that it occurs after fertilization. PMD is an imprinting disorder, and it may be a missing link between imprinting disorders and placental disorders incompatible with life, such as complete hydatidiform moles and partial hydatidiform moles.
Concomitant myocarditis and painless thyroiditis after AstraZeneca coronavirus disease 2019 vaccination: a case report
Authors: Marsukjai Apichai , Theerasuwipakorn Nonthikorn , Tumkosit Monravee , Chattranukulchai Pairoj , Srichomkwun Panudda , Prechawat Somchai
Published: May 2022

Background

Incidence of myocarditis following messenger RNA coronavirus disease 2019 vaccination has been widely described, but this clinical scenario after adenoviral vector coronavirus disease 2019 vaccination has only been rarely reported. In addition, a few case reports of thyroiditis after adenoviral vector coronavirus disease 2019 vaccination have been published.

Case presentation

A 55-year-old Thai woman presented with palpitation without neck pain 14 days after receiving AstraZeneca coronavirus disease 2019 vaccination. Electrocardiography revealed sinus tachycardia. Her blood tests showed elevation of cardiac troponin and free triiodothyronine with suppressed serum thyroid stimulating hormone, reflecting a hyperthyroid status. Evidence of myocardial inflammation and necrosis from cardiac magnetic resonance imaging supported the diagnosis of recent myocarditis. Laboratory results and imaging findings were consistent with thyroiditis. After 3 weeks of symptomatic treatment, her symptom and blood tests had returned to normal.

Conclusions

This case demonstrates that the adenoviral vector coronavirus disease 2019 vaccine could possibly cause myocarditis and painless thyroiditis. Clinicians should have a high index of suspicion and promptly evaluate these conditions, despite minimal symptoms.
Using machine learning to improve the accuracy of genomic prediction of reproduction traits in pigs
Authors: Wang Xue , Shi Shaolei , Wang Guijiang , Luo Wenxue , Wei Xia , Qiu Ao , Luo Fei , Ding Xiangdong
Published: May 2022

Background

Recently, machine learning (ML) has become attractive in genomic prediction, but its superiority in genomic prediction over conventional (ss) GBLUP methods and the choice of optimal ML methods need to be investigated.

Results

In this study, 2566 Chinese Yorkshire pigs with reproduction trait records were genotyped with the GenoBaits Porcine SNP 50 K and PorcineSNP50 panels. Four ML methods, including support vector regression (SVR), kernel ridge regression (KRR), random forest (RF) and Adaboost.R2 were implemented. Through 20 replicates of fivefold cross-validation (CV) and one prediction for younger individuals, the utility of ML methods in genomic prediction was explored. In CV, compared with genomic BLUP (GBLUP), single-step GBLUP (ssGBLUP) and the Bayesian method BayesHE, ML methods significantly outperformed these conventional methods. ML methods improved the genomic prediction accuracy of GBLUP, ssGBLUP, and BayesHE by 19.3%, 15.0% and 20.8%, respectively. In addition, ML methods yielded smaller mean squared error (MSE) and mean absolute error (MAE) in all scenarios. ssGBLUP yielded an improvement of 3.8% on average in accuracy compared to that of GBLUP, and the accuracy of BayesHE was close to that of GBLUP. In genomic prediction of younger individuals, RF and Adaboost.R2_KRR performed better than GBLUP and BayesHE, while ssGBLUP performed comparably with RF, and ssGBLUP yielded slightly higher accuracy and lower MSE than Adaboost.R2_KRR in the prediction of total number of piglets born, while for number of piglets born alive, Adaboost.R2_KRR performed significantly better than ssGBLUP. Among ML methods, Adaboost.R2_KRR consistently performed well in our study. Our findings also demonstrated that optimal hyperparameters are useful for ML methods. After tuning hyperparameters in CV and in predicting genomic outcomes of younger individuals, the average improvement was 14.3% and 21.8% over those using default hyperparameters, respectively.

Conclusion

Our findings demonstrated that ML methods had better overall prediction performance than conventional genomic selection methods, and could be new options for genomic prediction. Among ML methods, Adaboost.R2_KRR consistently performed well in our study, and tuning hyperparameters is necessary for ML methods. The optimal hyperparameters depend on the character of traits, datasets etc.
Release of lead from Renaissance lead-glazed ceramics from southern Denmark and northern Germany: implications from acetic acid etching experiments
Authors: Rasmussen Kaare Lund , Milner George R. , Delbey Thomas , Jensen Lisa Kathrine Ivalu , Witte Frauke , Rehren Thilo , Kjaer Ulla , Grinder-Hansen Poul
Published: May 2022

Lead-glazed potsherds from archaeological excavations at six Renaissance (1536–1660 CE) sites in southern Denmark and northern Germany have been subjected to etching experiments using 4 wt% acetic acid. The extracts of 45 sherds were analysed by Inductively Coupled Plasma Mass Spectrometry. At one site, the ducal hunting castle of Grøngaard, Pb levels in acid extracts from glazed dishes were so high (up to 29,000 µg Pb cm−2 day−1) that acute toxic effects likely occurred if the dishes were used for serving food containing vinegar. More moderate acid-etching Pb levels were found in dishes from other sites, but they still exceed the WHO critical level if used daily. Acetic acid etching experiments performed on pipkins (three-legged cooking pots with a handle) yielded somewhat lower Pb extract values, averaging ca. 25 µg Pb cm−2 day−1. Taking into account the widespread use of pipkins for cooking, they might easily have led to a higher weekly Pb intake than the use of the moderate-level dishes. The question remains whether such high levels of Pb exposure during meals led to injurious Pb intake. Prior skeletal analyses have shown that medieval to early modern individuals from the area, especially in towns, were exposed to Pb. While exposure could have come from various sources other than lead-glazed ceramics, such as cosmetics, paint, antibacterial ointments, and lead water pipes, widely distributed lead-glazed ceramics had the potential of being a main source of Pb. How the pottery was actually used is uncertain, and it certainly was not evenly distributed across all segments of society, but the etching experiment results suggest that severe poisonous effects could have resulted from the use of lead-glazed Renaissance ceramics.
Artificial Intelligence in Kidney Cancer
Authors: Rasmussen Robert , Sanford Thomas , Parwani Anil V. , Pedrosa Ivan
Published: May 2022

Artificial intelligence is rapidly expanding into nearly all facets of life, particularly within the field of medicine. The diagnosis, characterization, management, and treatment of kidney cancer is ripe with areas for improvement that may be met with the promises of artificial intelligence. Here, we explore the impact of current research work in artificial intelligence for clinicians caring for patients with renal cancer, with a focus on the perspectives of radiologists, pathologists, and urologists. Promising preliminary results indicate that artificial intelligence may assist in the diagnosis and risk stratification of newly discovered renal masses and help guide the clinical treatment of patients with kidney cancer. However, much of the work in this field is still in its early stages, limited in its broader applicability, and hampered by small datasets, the varied appearance and presentation of kidney cancers, and the intrinsic limitations of the rigidly structured tasks artificial intelligence algorithms are trained to complete. Nonetheless, the continued exploration of artificial intelligence holds promise toward improving the clinical care of patients with kidney cancer.
AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations
Authors: Lu Shun , Dong Xiaorong , Jian Hong , Chen Jianhua , Chen Gongyan , Sun Yuping , Ji Yinghua , Wang Ziping , Shi Jianhua , Lu Junguo , Chen Shaoshui , Lv Dongqing , Zhang Guojun , Liu Chunling , Li Juan , Yu Xinmin , Lin Zhong , Yu Zhuang , Wang Zhehai , Cui Jiuwei , Xu Xingxiang , Fang Jian , Feng Jifeng , Xu Zhi , Ma Rui , Hu Jie , Yang Nong , Zhou Xiangdong , Wu Xiaohong , Hu Chengping , Zhang Zhihong , Lu You , Hu Yanping , Jiang Liyan , Wang Qiming , Guo Renhua , Zhou Jianying , Li Baolan , Hu Chunhong , Tong Wancheng , Zhang Helong , Ma Lin , Chen Yuan , Jie Zhijun , Yao Yu , Zhang Longzhen , Jie Weng , Li Weidong , Xiong Jianping , Ye Xianwei , Duan Jianchun , Yang Haihua , Sun Meili , Sun Changan , Wei Hongying , Li Chuan , Ali Siraj M. , Miller Vincent A. , Wu Qiong
Published: May 2022

PURPOSE

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768 ).

METHODS

Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.

RESULTS

A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P < .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively.

CONCLUSION

Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.
Isocaloric-restricted Mediterranean Diet and Chinese Diets High or Low in Plants in Adults With Prediabetes
Authors: Luo Yaogan , Wang Jiqiu , Sun Liang , Gu Weiqiong , Zong Geng , Song Boyu , Shen Chongrong , Zhou Puchen , Chen Yufei , Wu Yanpu , Lin Huibin , Zheng He , Ni Mengshan , Yang Xiaowei , Chen Yanru , Xu Xinming , Zhang Juan , Shi Juan , Zhang Ru , Hu Jinfen , Hou Hong , Lu Ling , Xu Xiaoqiang , Liang Liming , Liu Ruixin , Liu Xiaoran , Li Huaixing , Hong Jie , Wang Weiqing , Lin Xu , Ning Guang
Published: May 2022

Context

Calorie restriction plus dietary advice is suggested as a preventive strategy for individuals with obesity and prediabetes; however, optimal diet is still debatable. We aimed to compare the effects of Mediterranean diet (MD) and Chinese diets high or low in plants on body weight and glucose homeostasis among high-risk Chinese.

Subjects and Methods

In this parallel-arm randomized controlled trial, 253 Chinese adults aged 25 to 60 years with a body mass index ≥ 24.0 kg/m2 and fasting blood glucose ≥ 5.6 mmol/L were randomly assigned to 3 isocaloric-restricted diets: MD (n = 84), a traditional Jiangnan diet high in plants (TJD, n = 85), or a control diet low in plants (CD, n = 84). During the 6-month trial, a 5-weekday full-feeding regimen was followed, along with mobile app–based monitoring. Abdominal fat measurement (magnetic resonance imaging), oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM) were conducted at baseline and 3 and 6 months.

Results

With a 25% calorie restriction for 6 months, weight deduction was 5.72 kg (95% confidence interval, 5.03-6.40) for MD, 5.05 kg (4.38-5.73) for TJD, and 5.38 kg (4.70-6.06) for CD (Ptime < 0.0001). No between-group differences were found for fasting glucose, insulin, and the Matsuda index from OGTT. Notably, CD had significantly longer time below range (glucose < 3.9 mmol/L) than MD (0.81% [0.21-1.40], P = 0.024) and marginally longer time than TJD (0.56% [-0.03 to 1.15], P = 0.065), as measured by CGM.

Conclusions

With the 6-month isocaloric-restricted feeding, TJD and MD achieved comparable weight deduction and improved glucose homeostasis, whereas CD showed a higher risk for hypoglycemia.
Mass Education and Women's Autonomy: Evidence From Latin America
Authors: Urbina Daniela R.
Published: May 2022

Most low- and middle-income countries have implemented mass education reforms in the last few decades. Demographers and policymakers have posited that mass schooling would enhance women's autonomy and, therefore, accelerate population transformations in the Global South. However, gains in women's schooling may have unexpected implications for female autonomy in contexts where hypergamy norms—the ideal that men should marry down and women should marry up in education and other markers of status—are still dominant. This study addresses difficulties in evaluating the causal impact of additional education on women's autonomy by leveraging the timing of compulsory schooling reforms in three Latin American countries: Bolivia, Colombia, and Peru. Using Demographic and Health Surveys, I implement an instrumental variable design using random exposure to compulsory schooling laws as an instrument for years of education. Results show that for women who entered the school system as a result of compulsory reforms, further schooling decreased their level of autonomy in all countries—especially among women from rural Bolivia and Peru. Additional analyses suggest these results are explained by changes in the selection into schooling and the formation of unions defying hypergamy norms. Together, these findings highlight the importance of examining the returns to mass schooling considering population heterogeneity and the contextual meaning of women's education.
Sampling for resource evaluation and grade control in an underground gold operation: a case of compromise
Authors: Dominy Simon , Glass Hylke , Purevgerel Saranchimeg
Published: May 2022

The foundation of any resource evaluation and/or grade control programme is the collection of high-quality samples within a geological context. The requirement for quality samples has long been recognised, where they must be representative and fit-for-purpose. Correct application of the Theory of Sampling reduces sampling errors across the collection to assay process. This contribution presents a case study where small-sample based assays understate grade in geometrically simple, coarse gold-dominated veins. Drilling with whole core sampling and assaying is applied to estimate Inferred Mineral Resources that are accepted to understate grade. Dominant gold particle clustering drives the application of bulk sampling. Development drives are sampled as bulk composites and processed via an on-site plant. Upper and lower development drive grades are assigned to stope blocks and reported in the Indicated Mineral Resource category. The case study illustrates the challenges and potential solutions to achieve representative sampling. Solutions ranging from individual bulk samples processed through a plant, to bulk composites and whole-core sampling and screen fire assaying are discussed. These approaches account for the nature of the mineralisation, where extreme gold particle-clustering effects render the analysis of small samples problematic.
Πήλινες γυναικείες προτομές από τα νεκροταφεία της τράπεζας της Πολίχνης
Authors: Καριπίδου Ελένη
Published: May 2022

Οι προτομές αποτελούν μία κατηγορία της αρχαίας ελληνικής παραστατικής τέχνης, με παρουσία από την Αρχαϊκή μέχρι την όψιμη Ελληνιστική περίοδο. Αποτελούν κοινό εύρημα ιερών, κατοικιών και νεκροταφείων. Στα τελευταία, τις συναντούμε ως κτέρισμα σε τάφους όλων των τύπων, ενώ στα ιερά χρησιμοποιούνται ως αναθήματα. Ακόμη, έχουν βρεθεί σε οικίες, σε χώρους όπου υπήρχε γυναικεία δραστηριότητα, αλλά και σε μέρη όπου τελούνταν η οικιακή λατρεία.Οι πήλινες γυναικείες προτομές της τράπεζας της Πολίχνης, ενός σημαντικού πολίσματος στο μυχό του Θερμαϊκού κόλπου, προέρχονται από τις δύο νεκροπόλεις του οικισμού και χρονολογούνται στον 4ο αι. π.Χ. Η εικονογραφική τους απόδοση ακολουθεί τους διαδεδομένους τύπους προτομών στη Μακεδονία την εποχή αυτή. Εντοπίζονται αποκλειστικά σε γυναικείες και παιδικές ταφές, ενώ ο αριθμός και η θέση εύρεσής τους μέσα στους τάφους ποικίλει κατά περίπτωση.Η πλειονότητα των μελετητών θεωρεί ότι οι προτομές αποτελούν την απεικόνιση θεοτήτων που σχετίζονται με την γονιμότητα και την αναγέννηση, μία άποψη που ενισχύουν και τα εικονογραφικά χαρακτηριστικά τους. Ωστόσο, η αναγνώριση συγκεκριμένων θεοτήτων είναι αρκετά δύσκολη, καθώς οι προτομές, τις περισσότερες φορές, δε διαφοροποιούνται όσον αφορά τα εικονογραφικά τους στοιχεία. Στις προτομές των νεκροταφείων της Πολίχνης η αναγνώριση μίας χθόνιας θεότητας, προστάτιδας των νεκρών, φαίνεται ως η πιθανότερη εκδοχή.