bluuebunny/crossref_metadata_2025 huggingface dataset:
Ribosome footprint profiling enables elucidating the systemic regulation of fatty acid accumulation in Acer truncatum
Authors: Ma Qiuyue , Wang Yuxiao , Li Shushun , Wen Jing , Zhu Lu , Yan Kunyuan , Du Yiming , Li Shuxian , Yan Liping , Xie Zhijun , Lyu Yunzhou , Shen Fei , Li Qianzhong
Published: April 2023

Background

The accumulation of fatty acids in plants covers a wide range of functions in plant physiology and thereby affects adaptations and characteristics of species. As the famous woody oilseed crop, Acer truncatum accumulates unsaturated fatty acids and could serve as the model to understand the regulation and trait formation in oil-accumulation crops. Here, we performed Ribosome footprint profiling combing with a multi-omics strategy towards vital time points during seed development, and finally constructed systematic profiling from transcription to proteomes. Additionally, we characterized the small open reading frames (ORFs) and revealed that the translational efficiencies of focused genes were highly influenced by their sequence features.

Results

The comprehensive multi-omics analysis of lipid metabolism was conducted in A. truncatum. We applied the Ribo-seq and RNA-seq techniques, and the analyses of transcriptional and translational profiles of seeds collected at 85 and 115 DAF were compared. Key members of biosynthesis-related structural genes (LACS, FAD2, FAD3, and KCS) were characterized fully. More meaningfully, the regulators (MYB, ABI, bZIP, and Dof) were identified and revealed to affect lipid biosynthesis via post-translational regulations. The translational features results showed that translation efficiency tended to be lower for the genes with a translated uORF than for the genes with a non-translated uORF. They provide new insights into the global mechanisms underlying the developmental regulation of lipid metabolism.

Conclusions

We performed Ribosome footprint profiling combing with a multi-omics strategy in A. truncatum seed development, which provides an example of the use of Ribosome footprint profiling in deciphering the complex regulation network and will be useful for elucidating the metabolism of A. truncatum seed oil and the regulatory mechanisms.
Downregulation of AC092894.1 promotes oxaliplatin resistance in colorectal cancer via the USP3/AR/RASGRP3 axis
Authors: Zheng Zhijian , Wu Ming , Li Hongyan , Xu Wenxia , Yang Mengxiang , Pan Kailing , Ni Yuqi , Jiang Ting , Zheng Hongjuan , Jin Xiayun , Zhang Yanfei , Ding Linchao , Fu Jianfei
Published: April 2023

Background

Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood.

Methods

The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments.

Results

AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells.

Conclusions

In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.
Rheumatoid arthritis and the risk of postpartum psychiatric disorders: a Nordic population-based cohort study
Authors: Luan Min , Yang Fen , Miao Maohua , Yuan Wei , Gissler Mika , Arkema Elizabeth V. , Lu Donghao , Li Jiong , László Krisztina D.
Published: April 2023

Background

Postpartum psychiatric disorders (PPD) are common complications of childbirth. A common explanation for their development is that the psychological, hormonal, and immune changes associated with pregnancy and parturition may trigger psychiatric symptoms postpartum. Rheumatoid arthritis (RA) is characterized by abnormalities in the activity of the hypothalamic–pituitary–adrenal axis and of the immune system, but its association with PPD is unknown. We analyzed whether women with RA before childbirth have an increased risk of PPD.

Methods

We conducted a large population-based cohort study including mothers of singleton births in the Danish (1995–2015), Finnish (1997–2013), and Swedish Medical Birth Registers (2001–2013) (N = 3,516,849). We linked data from the Medical Birth Registers with data from several national socioeconomic and health registers. Exposure was defined as having a diagnosis of RA before childbirth, while the main outcome was a clinical diagnosis of psychiatric disorders 90 days postpartum. We analyzed the association between RA and PPD using Cox proportional hazard models, stratified by a personal history of psychiatric disorders.

Results

Among women without a history of psychiatric disorders, the PPD incidence rate was 32.2 in the exposed and 19.5 per 1000 person-years in the unexposed group; women with RA had a higher risk of overall PPD than their unexposed counterparts [adjusted hazard ratio (HR) = 1.52, 95% confidence intervals (CI) 1.17 to 1.98]. Similar associations were also observed for postpartum depression (HR = 1.65, 95% CI 1.09 to 2.48) and other PPD (HR = 1.59, 95% CI 1.13 to 2.24). Among women with a history of psychiatric disorders, the incidence rate of overall PPD was 339.6 in the exposed and 346.6 per 1000 person-years in the unexposed group; RA was not associated with PPD. We observed similar associations between preclinical RA (RA diagnosed after childbirth) and PPD to those corresponding to clinical RA.

Conclusions

Rheumatoid arthritis was associated with an increased PPD risk in women without, but not in those with a psychiatric history. If our findings are confirmed in future studies, new mothers with RA may benefit from increased surveillance for new-onset psychiatric disorders postpartum.
Aberrant accumulation of NIK promotes tumor growth by dysregulating translation and post-translational modifications in breast cancer
Authors: Hayashi Yusuke , Nakayama Jun , Yamamoto Mizuki , Maekawa Masashi , Watanabe Shinya , Higashiyama Shigeki , Inoue Jun-ichiro , Yamamoto Yusuke , Semba Kentaro
Published: April 2023

Background

In vivo investigations with cancer cells have powerful tools to discover cancer progression mechanisms and preclinical candidate drugs. Among these in vivo experimental models, the establishment of highly malignancy cell lines with xenograft has been frequently used. However, few previous researches targeted malignancy-related genes whose protein levels translationally changed. Therefore, this study aimed to identify malignancy-related genes which contributed to cancer progression and changed at the protein level in the in vivo selected cancer cell lines.

Methods

We established the high malignancy breast cancer cell line (LM05) by orthotopic xenograft as an in vivo selection method. To explore the altered genes by translational or post-translational regulation, we analyzed the protein production by western blotting in the highly malignant breast cancer cell line. Functional analyses of the altered genes were performed by in vitro and in vivo experiments. To reveal the molecular mechanisms of the regulation with protein level, we evaluated post-translational modification by immunoprecipitation. In addition, we evaluated translational production by click reaction-based purification of nascent protein.

Results

As a result, NF-κB inducing kinase (NIK) increased at the protein level and promoted the nuclear localization of NF-κB2 (p52) and RelB in the highly malignant breast cancer cell line. The functional analyses indicated the NIK upregulation contributed to tumor malignancy via cancer-associated fibroblasts (CAFs) attraction and partially anti-apoptotic activities. Additionally, the immunoprecipitation experiment revealed that the ubiquitination of NIK decreased in LM05 cells. The decline in NIK ubiquitination was attributed to the translational downregulation of cIAP1.

Conclusions

Our study identified a dysregulated mechanism of NIK production by the suppression of NIK post-modification and cIAP1 translation. The aberrant NIK accumulation promoted tumor growth in the highly malignant breast cancer cell line.
A comparison of transmissibility of SARS-CoV-2 variants of concern
Authors: Manathunga S. S. , Abeyagunawardena I. A. , Dharmaratne S. D.
Published: April 2023

Background

The World Health Organization (WHO) has currently detected five Variants of Concern of SARS-CoV-2 having the WHO labels of ‘Alpha’, ‘Beta’, ‘Gamma’, ‘Delta’ and ‘Omicron’. We aimed to assess and compare the transmissibility of the five VOCs in terms of basic reproduction number, time-varying reproduction number and growth rate.

Methods

Publicly available data on the number of analyzed sequences over two-week windows for each country were extracted from covariants.org and GISAID initiative database. The ten countries which reported the highest number of analyzed sequences for each of the five variants were included in the final dataset and was analyzed using R language. The epidemic curves for each variant were estimated utilizing the two-weekly discretized incidence data using local regression (LOESS) models. The basic reproduction number was estimated with the exponential growth rate method. The time-varying reproduction number was calculated for the estimated epidemic curves by the ratio of the number of new infections generated at time step t to the total infectiousness of infected individuals at time t, using the EpiEstim package.

Results

The highest R0 for the variants Alpha (1.22), Beta (1.19), Gamma (1.21), Delta (1.38) and Omicron (1.90) were reported from Japan, Belgium, the United States, France and South Africa, respectively. Nine out of ten epidemic curves with the highest estimated growth rates and reproduction numbers were due to the Omicron variant indicating the highest transmissibility.

Conclusions

The transmissibility was highest in the Omicron variant followed by Delta, Alpha, Gamma and Beta respectively.
The association of long-term calcium and dairy products intake in adolescence with carotid intima media thickness and metabolic syndrome in early adulthood: Tehran Lipid and Glucose Study
Authors: AkbarySedigh Assa , Asghari Golaleh , Mahdavi Maryam , Mirmiran Parvin , Valizadeh Majid , Azizi Fereidoun
Published: April 2023

Background

Calcium could impact on vascular functions and structures and cause atherosclerosis. Thus, we aimed to examine the association of long-term calcium and dairy products intake in adolescence with cIMT and MetS in early adulthood.

Methods

We considered 217 adolescents aged 12–18 years in the frame work of the Tehran Lipid and Glucose Study (2006–2009) and follow-up them to early adulthood (2015–2017). The valid food frequency questionnaire was used to assess dietary intake. Ultrasound examination was used to measure common carotid artery. The joint interim statement and cook et al. criteria were used for adults and adolescents to consider MetS, respectively.

Results

Adolescents’ average calcium intake from dairy and non-dairy sources were 395 mg/d and 1088 mg/d, respectively while adults had 212 mg/d and 1191 mg/d. In addition, the mean of cIMT in adults was 0.54 mm. There was no relationship of non-dairy (β: − 0.03; P = 0.804), and total calcium (β: − 0.001; P = 0.591) intake with cIMT and TG. None of the dairy products had link with cIMT, MetS and its components, except cream with cIMT after full adjustment of potential confounders (β: 0.245; P = 0.009). Also, we found that the intake of non-dairy products could increase DBP after controlling for potential confounders (β: 0.365; P = 0.012). Adolescence with higher quartiles of total calcium intake had no odds ratio of MetS in early adulthood (β: 2.05, P = 0.371).

Conclusions

Adolescence calcium and dairy products intake, with the exception of cream did not increase early adulthood cIMT and MetS and its components.
Analysis of plant cuticles and their interactions with agrochemical surfactants using a 3D printed diffusion chamber
Authors: Vittal Lakshmi Venkatesha Manyu , Rookes James , Boyd Ben , Cahill David
Published: April 2023

Background

Decades of research is available on their effects of single component surfactant on active ingredient diffusion across plant cuticular membranes, but ingredient diffusion is rarely analysed in the presence of commercial surfactants. Also, diffusion studies require expensive or specialized apparatus the  fabrication of which often requires skilled labour and specialized facilities. In this research we have addressed both problems where the effects of four commercially available surfactants on a known tracer molecule were investigated using a 3D printed customized diffusion chamber.

Results

As a proof-of-concept a customized 3D printed diffusion chamber was devised using two different thermoplastics and was successfully used in a range of diffusion tests . The effect of various solvents and surfactants on S. lycopersicum cuticular membrane indicated an increased rate of flux of tracer molecules across the membranes. This research has validated the application of 3D printing in diffusion sciences and demonstrated the flexibility and potential of this technique.

Conclusions

Using a 3D printed diffusion apparatus, the effect of commercial surfactants on molecular diffusion through isolated plant membranes was studied. Further, we have included  here the steps involved in material selection, design, fabrication, and post processing procedures for successful recreation of the chamber. The customizability and rapid production process of the 3D printing demonstrates the power of additive manufacturing in the design and use of customizable labware.
The effect of flipped approach in teaching critical respiratory care among nurses during the COVID-19 era
Authors: Bazrafkan Leila , Panahian Razieh , Zarifsanaiey Nahid
Published: April 2023

Objectives

This study investigated the efficacy of flipped approach on the nurses’ knowledge and motivation regarding critical respiratory care during the COVID-19 pandemic.

Results

This pretest-posttest quasi-experimental study was performed in a hospital affiliated with Shiraz University of Medical Sciences during March-December 2021. One hundred and twenty eligible nurses selected by convenience sampling underwent a seven-day flipped approach respiratory intensive care training. The nurses’ motivation and knowledge were evaluated using the Students’ Motivation Towards Science Learning (SMTSL) and a 20-researcher-made four-option questionnaire before and two weeks after the intervention, for knowledge assessment respectively. The nurses’ knowledge and learning motivation were significantly higher after the intervention (P < 0.001). The flipped approach can improve learning motivation and nurses’ knowledge of critical respiratory care.
LinChemIn: SynGraph—a data model and a toolkit to analyze and compare synthetic routes
Authors: Pasquini Marta , Stenta Marco
Published: April 2023

Background

The increasing amount of chemical reaction data makes traditional ways to navigate itscorpusless effective, while the demand for novel approaches and instruments is rising. Recent data science and machine learning techniques support the development of new ways to extract value from the available reaction data. On the one side, Computer-Aided Synthesis Planning tools can predict synthetic routes in a model-driven approach; on the other side, experimental routes can be extracted from the Network of Organic Chemistry, in which reaction data are linked in a network. In this context, the need to combine, compare and analyze synthetic routes generated by different sources arises naturally.

Results

Here we present LinChemIn, a python toolkit that allows chemoinformatics operations on synthetic routes and reaction networks. Wrapping some third-party packages for handling graph arithmetic and chemoinformatics and implementing new data models and functionalities, LinChemIn allows the interconversion between data formats and data models and enables route-level analysis and operations, including route comparison and descriptors calculation. Object-Oriented Design principles inspire the software architecture, and the modules are structured to maximize code reusability and support code testing and refactoring. The code structure should facilitate external contributions, thus encouraging open and collaborative software development.

Conclusions

The current version of LinChemIn allows users to combine synthetic routes generated from various tools and analyze them, and constitutes an open and extensible framework capable of incorporating contributions from the community and fostering scientific discussion. Our roadmap envisages the development of sophisticated metrics for routes evaluation, a multi-parameter scoring system, and the implementation of an entire “ecosystem” of functionalities operating on synthetic routes. LinChemIn is freely available at https://github.com/syngenta/linchemin.

Graphical Abstract
Differences in clinical characteristics and quantitative lung CT features between vaccinated and not vaccinated hospitalized COVID-19 patients in Italy
Authors: Chiumello Davide , Tavelli Alessandro , Serio Lorenzo , De Benedittis Sara , Pozzi Tommaso , Maj Roberta , Velati Mara , Brusatori Serena , D’Albo Rosanna , Zinnato Carmelo , Marchetti Giulia , Camporota Luigi , Coppola Silvia , D’Arminio Monforte Antonella
Published: April 2023

Background

To evaluate the differences in the clinical characteristics and severity of lung impairment, assessed by quantitative lung CT scan, between vaccinated and non-vaccinated hospitalized patients with COVID-19; and to identify the variables with best prognostic prediction according to SARS-CoV-2 vaccination status. We recorded clinical, laboratory and quantitative lung CT scan data in 684 consecutive patients [580 (84.8%) vaccinated, and 104 (15.2%) non-vaccinated], admitted between January and December 2021.

Results

Vaccinated patients were significantly older 78 [69–84] vs 67 [53–79] years and with more comorbidities. Vaccinated and non-vaccinated patients had similar PaO2/FiO2 (300 [252–342] vs 307 [247–357] mmHg; respiratory rate 22 [8–26] vs 19 [18–26] bpm); total lung weight (918 [780–1069] vs 954 [802–1149] g), lung gas volume (2579 [1801–3628] vs 2370 [1675–3289] mL) and non-aerated tissue fraction (10 [7.3–16.0] vs 8.5 [6.0–14.1] %). The overall crude hospital mortality was similar between the vaccinated and non-vaccinated group (23.1% vs 21.2%). However, Cox regression analysis, adjusted for age, ethnicity, age unadjusted Charlson Comorbidity Index and calendar month of admission, showed a 40% reduction in hospital mortality in the vaccinated patients (HRadj = 0.60, 95%CI 0.38–0.95).

Conclusions

Hospitalized vaccinated patients with COVID-19, although older and with more comorbidities, presented a similar impairment in gas exchange and lung CT scan compared to non-vaccinated patients, but were at a lower risk of mortality.
Human liver organoid: modeling liver steatosis and beyond
Authors: Wei Jinsong , Zhang Wen , Zhao Bing
Published: April 2023

Steatosis, as the early stage of nonalcoholic fatty acid disease (NAFLD), would progress into nonalcoholic steatohepatitis (NASH) and liver failure without intervention. Despite the development of animal models, there is still a lack of the human-relevant platform for steatosis modeling and drug & target discovery. Hendriks et al., reporting in Nature Biotechnology, leveraged human fetal liver organoids to recapitulate steatosis by introducing nutritional and genetic triggers. Using these engineered liver organoid-derived steatosis models, they screened drugs that alleviate steatosis, and mined common mechanism of effective compounds. Further, inspired by the results of drug screening, the arrayed CRISPR-LOF screening targeting 35 lipid metabolism genes was performed, and FADS2 was identified as a critical regulator of steatosis.
Education on medically unexplained symptoms: a systematic review with a focus on cultural diversity and migrants
Authors: Mariman An , Vermeir Peter , Csabai Marta , Weiland Anne , Stegers-Jager Karen , Vermeir Ruben , Vogelaers Dirk
Published: April 2023

Background

Health care providers often struggle with the management of patients with medically unexplained symptoms (MUS), especially in case of a different ethnicity and/or cultural background. These challenges are insufficiently addressed in their training.

Objectives

A systematic review on education in the field of MUS in a diverse context to improve MUS healthcare provider–patient interaction focused on intercultural communication.

Methods

Screening of PubMed, Web of Science, Cinahl and Cochrane Library on the keywords ‘Medical unexplained (physical) symptoms (MUS)’, ‘Somatoform disorder’, ‘Functional syndrome’, ‘Diversity’, ‘Migrants’, ‘Ethnicity’, ‘Care models’, ‘Medical education’, ‘Communication skills’, ‘Health literacy’.

Results

MUS patients, especially with a different ethnic background, often feel not understood or neglected. Health care providers experience feelings of helplessness, which may provoke medical shopping and resource consumption. Attitudes and perceptions from undergraduate trainees to senior physicians tend to be negative, impacting on the quality of the patient/health care provider relationship and subsequently on health outcomes, patient satisfaction and therapeutic adherence. Current undergraduate, graduate and postgraduate education and training does not prepare health care providers for diagnosing and managing MUS patients in a diverse context. A continuum of training is necessary to achieve a long term and lasting change in attitudes towards these patients and trainers play a key role in this process. Hence, education should pay attention to MUS, requiring a specific competency profile and training, taken into account the variety in patients’ cultural backgrounds.

Conclusions

This systematic review identified significant gaps and shortcomings in education on MUS in a diverse context. These need to be addressed to improve outcomes.
Starburst amacrine cells, involved in visual motion perception, lose their synaptic input from dopaminergic amacrine cells and degenerate in Parkinson’s disease patients
Authors: Sánchez-Sáez Xavier , Ortuño-Lizarán Isabel , Sánchez-Castillo Carla , Lax Pedro , Cuenca Nicolás
Published: April 2023

Background

The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the starburst amacrine cells, which are the main cellular type involved in motion direction selectivity, are degenerated in PD and if the dopaminergic system is related to this degeneration.

Methods

Human eyes from control (n = 10) and PD (n = 9) donors were available for this study. Using immunohistochemistry and confocal microscopy, we quantified starburst amacrine cell density (choline acetyltransferase [ChAT]-positive cells) and the relationship between these cells and dopaminergic amacrine cells (tyrosine hydroxylase-positive cells and vesicular monoamine transporter-2-positive presynapses) in cross-sections and wholemount retinas.

Results

First, we found two different ChAT amacrine populations in the human retina that presented different ChAT immunoreactivity intensity and different expression of calcium-binding proteins. Both populations are affected in PD and their density is reduced compared to controls. Also, we report, for the first time, synaptic contacts between dopaminergic amacrine cells and ChAT-positive cells in the human retina. We found that, in PD retinas, there is a reduction of the dopaminergic synaptic contacts into ChAT cells.

Conclusions

Taken together, this work indicates degeneration of starburst amacrine cells in PD related to dopaminergic degeneration and that dopaminergic amacrine cells could modulate the function of starburst amacrine cells. Since motion perception circuitries are affected in PD, their assessment using visual tests could provide new insights into the diagnosis of PD.
Sex differences in pre-incarceration mental illness, substance use, injury and sexually transmitted infections and health service utilization: a longitudinal linkage study of people serving federal sentences in Ontario
Authors: Butsang Tenzin , McLuhan Arthur , Keown Leslie A. , Fung Kinwah , Matheson Flora I.
Published: April 2023

Background

People who experience incarceration have poorer health than the general population. Yet, we know little about the health and health service utilization of people during the critical period prior to their incarceration, relative to during incarceration and post-release. In this study, we conducted a longitudinal cohort study of 39,498 adults in Ontario, Canada between January 1, 2002, and December 31, 2011 using linked administrative health and correctional data to describe mental illness, substance use, injury, sexually transmitted infections and health service utilization of men and women in federal prisons in the 3 years prior to their incarceration, compared to a matched group.

Results

We found that, in the 3-year period prior to their incarceration, men (n = 6,134) and women (n = 449) experiencing their first federal sentence had poorer health across all indicators examined (e.g., psychosis, drug/alcohol use, and self-harm) and higher outpatient psychiatric and emergency department visits, compared with the matched group. Women in the pre-incarceration group exhibited a higher prevalence of self-harm and substance use, relative to women in the matched comparison group and higher relative prevalence to that of men in the pre-incarceration group, compared to their matched counterparts.

Conclusions

Disparities in health and health service utilization are gendered and exist prior to incarceration. The gendered nature of these findings, specifically the significantly higher prevalence of poor health among women across several indicators, necessitates a focus on the social and systemic factors that contribute to these disparities. Gender-responsive and trauma-informed primary, secondary, and tertiary prevention strategies, alongside transformative approaches to justice should be considered in addressing the health needs of men and women who experience incarceration.
Tailored exercise management (TEMPO) versus usual care for people aged 80 years or older with hip/knee osteoarthritis: study protocol for a feasibility randomised controlled trial
Authors: Nicolson Philippa J. A. , Holden Melanie A. , Marian Ioana R. , Williamson Esther , Dutton Susan J. , Garrett Angela , Hopewell Sally , Lamb Sarah E.
Published: April 2023

Background

Exercise is recommended for all people with osteoarthritis. However, these recommendations are based on randomised clinical trials including people with an average age between 60 and 70 years, and these findings cannot reliably be generalised to people aged 80 years or older. Rapid loss of muscle occurs after 70 years of age, and older people are more likely to also have other health conditions that contribute to difficulties with daily activities and impact on their response to exercise. To improve care for people aged 80 or older with osteoarthritis, it is thought that a tailored exercise intervention targeting both osteoarthritis and any other health conditions they have, may be needed. The aim of this study will be to test if it is possible to conduct a randomised controlled trial (RCT) for people over 80 years of age with hip/knee osteoarthritis of a tailored exercise intervention.

Methods

A multicentre, parallel, 2-group, feasibility RCT with embedded qualitative study, conducted in ≥ 3 UK NHS physiotherapy outpatient services. Participants (n ≥ 50) with clinical knee and/or hip osteoarthritis and ≥ 1 comorbidity will be recruited by screening referrals to participating NHS physiotherapy outpatient services, via screening of general practice records and via identification of eligible individuals from a cohort study run by our research group. Participants will be randomised (computer-generated: 1:1) to receive either: a 12-week education and tailored exercise intervention (TEMPO); or usual care and written information. The primary feasibility objectives are to estimate: (1) ability to screen and recruit eligible participants; (2) retention of participants, measured by the proportion of participants who provide outcome data at 14-week follow-up. Secondary quantitative objectives are to estimate: (1) participant engagement assessed by physiotherapy session attendance and home exercise adherence; (2) sample size calculation for a definitive RCT. One-to-one semi-structured interviews will explore the experiences of trial participants and physiotherapists delivering the TEMPO programme.

Discussion

Progression criteria will be used to determine whether a definitive trial to evaluate the clinical and cost-effectiveness of the TEMPO programme is considered feasible with or without modifications to the intervention or trial design.

Trial registration

ISRCTN75983430. Registered 3/12/2021. https://www.isrctn.com/ISRCTN75983430.
Valuing options to renew at future market value: the case of commercial property leases
Authors: Wang Jenny Jing , Shen Jianfu , Pretorius Frederik
Published: April 2023

In this study, we develop and empirically test a valuation model for a commonly encountered option in office leases: a tenant’s option to renew at future market rent (a fair market value) with lease termination as the maturity date. The model integrates decision analysis with real options analysis and market risk with private risks. “Option value” is defined as the private value of the option to either party pre-contract, while “option price” assumes a fair agreement between transacting parties and can be positive (rental premium paid) or negative (rental discount offered). Without manifest expectations, an analysis of a sample of office leases supports the model’s logic with price estimates in a practical range. The tenants’ option price/value is shown to have a negative relationship with the original/renewal lease term; conversely, the landlords’ option value is positively related to the original/renewal term. Comparative analyses show that transaction costs have a positive effect on tenants’ option value and on prices, while vacancy costs and the vacancy period are both positively related to the landlords’ option value and negatively related to price. Market rent is found to have a negative relationship with option price. Overall, this study provides a theoretical analysis and empirical tests of the value of a real option that allows option holders to renew/extend their contracts at a fair market value.
Quail on fire: changing fire regimes may benefit mountain quail in fire-adapted forests
Authors: Brunk Kristin M. , Gutiérrez R. J. , Peery M. Zachariah , Cansler C. Alina , Kahl Stefan , Wood Connor M.
Published: April 2023

Background

Fire-adapted forests in western North America are experiencing rapid changes to fire regimes that are outside the range of historic norms. Some habitat-specialist species have been negatively impacted by increases in large, high-severity fire, yet, the responses of many species to fire, especially at longer time scales, remain ambiguous. We studied the response of a widely distributed species, the mountain quail (Oreortyx pictus), to wildfire across the Sierra Nevada of California, because its habitat selection patterns provided an opportunity to evaluate potentially contrasting responses among habitat specialists.

Results

We used passive acoustic monitoring across > 22,000 km2 of the Sierra Nevada and Bayesian hierarchical occupancy modeling to conduct the first study of the effects of habitat, fire severity, and time since fire (1–35 years) on the occupancy of a little-understood management indicator species, the mountain quail. Mountain quail responded positively to high-severity fire and neutrally to low-moderate-severity fire. Occupancy of quail peaked 6–10 years after high-severity fire and remained high even 11–35 years after an area burned at high severity.

Conclusions

Our work demonstrates that high-severity fire is strongly and positively related to mountain quail occupancy, which is a markedly different response than previously studied species that are also of management concern in the Sierra Nevada. Taken together, our results suggest that mountain quail may actually be “winners” in the face of altered fire regimes in the Sierra Nevada. Given the forecasted intensification of large, severe wildfires in many fire-adapted forests, understanding the ecology and nuanced fire responses of species beyond those that have been historically considered is an important and time-sensitive effort. The relationship between mountain quail and high-severity fire is a reminder that there will be both winners and losers as the dynamics of wildfire change in the era of climate change.
Mining for net zero: The impossible task
Authors: Jones Alan G.
Published: April 2023

If current predictions of anthropogenically induced climate change are accurate, and they are becoming more robust and prescient with time, the world must transition away from fossil fuels and embrace transportation, energy generation, and energy storage from renewables so that future generations are not in peril. More than 190 countries have each signed the Paris Agreement, which has as its goal a reduction of global greenhouse gas emissions to limit the global temperature increase in this century to 2°C while pursuing efforts to limit the increase even further to 1.5°C. Additionally, more than 70 countries, including the biggest polluters, have set a net-zero greenhouse gas emissions target, which covers about 76% of global emissions — a commendable and laudable goal. However, a number of fundamental challenges make achieving this goal difficult, perhaps impossible. One such challenge is the lack of a broad appreciation that there needs to be much more mining of metals and minerals, in excess of already mining more than at any other time in prior human history. For example, one estimate is that there needs to be as much copper mined over the next 20–25 years as has been mined to date. Many countries have become aware of the need for access to “critical minerals” for futureproofing, but they appear to be unaware of the fundamental issues that will hamper that access. This is a fast-moving issue. Some of the specific details raised here will become less relevant, and new ones will appear. However, the core issues raised, of the need for a more positive public perception of mining, of the need for more mining, and of the need for far more skilled talent, will not change.
Microdeletion at ESR1 Intron 6 (DEL_6_75504) Is a Susceptibility Factor for Cryptorchidism and Hypospadias
Authors: Masunaga Yohei , Fujisawa Yasuko , Massart Francesco , Spinelli Claudio , Kojima Yoshiyuki , Mizuno Kentaro , Hayashi Yutaro , Sasagawa Isoji , Yoshida Rie , Kato Fumiko , Fukami Maki , Kamatani Naoyuki , Saitsu Hirotomo , Ogata Tsutomu
Published: April 2023

Context

We have previously reported that a specific “AGATC” haplotype in a >34 kb tight linkage disequilibrium (LD) block within ESR1 is strongly associated with cryptorchidism and hypospadias in Japanese boys.

Objective

We aimed to determine the true susceptibility factor for cryptorchidism and hypospadias linked to the “AGATC” haplotype.

Methods

We performed various molecular studies in hitherto unreported 230 Italian boys (80 with cryptorchidism and 150 with normal genitalia) and previously reported and newly recruited 415 Japanese boys (149 with cryptorchidism, 141 with hypospadias, and 125 with normal genitalia). We also performed ESR1 expression analyses using breast cancer–derived MCF-7 cells.

Results

Haplotype analysis revealed the LD block and positive association of the “AGATC” haplotype with cryptorchidism in Italian boys. Whole genome sequencing identified an identical 2249-bp microdeletion (ΔESR1) generated by a microhomology-mediated replication error in both Japanese and Italian boys with the specific haplotype. ΔESR1 was found to be strongly associated with cryptorchidism and hypospadias by Cochran-Armitage trend test and was revealed to show nearly absolute LD with the “AGATC” haplotype. ESR1 expression was upregulated in MCF-7 cells with a homozygous deletion encompassing ΔESR1 and those with a homozygous deletion involving a CTCF-binding site within ΔESR1.

Conclusion

The results reveal that ΔESR1, which has been registered as “DEL_6_75504” in gnomAD SVs v2.1, is the true susceptibility factor for cryptorchidism and hypospadias. It appears that ΔESR1 was produced in a single ancestral founder of modern humans and has been maintained within the genome of multiple ethnic groups by selection.
Clinical Impact and Predictors of Aneurysmal Rebleeding in Poor-Grade Subarachnoid Hemorrhage: Results From the National POGASH Registry
Authors: Panni Pietro , Riccio Lucia , Cao Roberta , Pedicelli Alessandro , Marchese Enrico , Caricato Anselmo , Feletti Alberto , Testa Mattia , Zanatta Paolo , Gitti Nicola , Piva Simone , Mardighian Dikran , Semeraro Vittorio , Nardin Giordano , Lozupone Emilio , Paiano Giafranco , Picetti Edoardo , Montanaro Vito , Petranca Massimo , Bortolotti Carlo , Scibilia Antonino , Cirillo Luigi , Lanterna Andrea Luigi , Ambrosi Alessandro , Mortini Pietro , Beretta Luigi , Falini Andrea
Published: April 2023

BACKGROUND:

Scarce data are available regarding rebleeding predictors in poor-grade aneurysmal subarachnoid hemorrhage (aSAH).

OBJECTIVES:

To investigate predictors and clinical impact of rebleeding in a national multicentric poor-grade aSAH.

METHODS:

Retrospective analysis of prospectively collected data from the multicentric Poor Grade Aneurysmal Subarachnoid Hemorrhage Study Group (POGASH) registry of consecutive patients treated from January 1, 2015, to June 30th, 2021. Grading was defined as pretreatment World Federation of Neurological Surgeons grading scale IV-V. Ultra-early vasospasm (UEV) was defined as luminal narrowing of intracranial arteries not due to intrinsic disease. Rebleeding was defined as clinical deterioration with evidence of increased hemorrhage on subsequent computed tomography scans, fresh blood from the external ventricular drain, or deterioration before neuroradiological evaluation. Outcome was assessed by the modified Rankin Scale.

RESULTS:

Among 443 consecutive World Federation of Neurological Surgeons grades IV-V patients with aSAH treated within a median of 5 (IQR 4-9) hours since onset, rebleeding occurred in 78 (17.6%). UEV (adjusted odds ratio [OR] 6.8, 95% CI 3.2-14.4; P < .001) and presence of dissecting aneurysm (adjusted OR 3.5, 95% CI 1.3-9.3; P = .011) independently predicted rebleeding while history of hypertension (adjusted OR 0.4, 95% CI 0.2-0.8; P = .011) independently reduced its chances. 143 (32.3) patients died during hospitalization. Rebleeding emerged, among others, as an independent predictor of intrahospital mortality (adjusted OR 2.2, 95% CI 1.2-4.1; P = .009).

CONCLUSION:

UEV and presence of dissecting aneurysms are the strongest predictors of aneurysmal rebleeding. Their presence should be carefully evaluated in the acute management of poor-grade aSAH.
Association of Sit-to-Stand Capacity and Free-Living Performance Using Thigh-Worn Accelerometers among 60- to 90-Yr-Old Adults
Authors: LÖPPÖNEN ANTTI , DELECLUSE CHRISTOPHE , SUORSA KRISTIN , KARAVIRTA LAURA , LESKINEN TUIJA , MEULEMANS LIEN , PORTEGIJS ERJA , FINNI TAIJA , RANTANEN TAINA , STENHOLM SARI , RANTALAINEN TIMO , VAN ROIE EVELIEN
Published: April 2023

Purpose

Five times sit-to-stand (STS) test is commonly used as a clinical assessment of lower-extremity functional ability, but its association with free-living performance has not been studied. Therefore, we investigated the association between laboratory-based STS capacity and free-living STS performance using accelerometry. The results were stratified according to age and functional ability groups.

Methods

This cross-sectional study included 497 participants (63% women) 60–90 yr old from three independent studies. A thigh-worn triaxial accelerometer was used to estimate angular velocity in maximal laboratory-based STS capacity and in free-living STS transitions over 3–7 d of continuous monitoring. Functional ability was assessed with short physical performance battery.

Results

Laboratory-based STS capacity was moderately associated with the free-living mean and maximal STS performance (r = 0.52–0.65, P < 0.01). Angular velocity was lower in older compared with younger and in low- versus high-functioning groups, in both capacity and free-living STS variables (all P < 0.05). Overall, angular velocity was higher in capacity compared with free-living STS performance. The STS reserve (test capacity − free-living maximal performance) was larger in younger and in high-functioning groups compared with older and low-functioning groups (all P < 0.05).

Conclusions

Laboratory-based STS capacity and free-living performance were found to be associated. However, capacity and performance are not interchangeable but rather provide complementary information. Older and low-functioning individuals seemed to perform free-living STS movements at a higher percentage of their maximal capacity compared with younger and high-functioning individuals. Therefore, we postulate that low capacity may limit free-living performance.
Resistance Training for Older Women: Do Adaptive Responses Support the ACSM and NSCA Position Stands?
Authors: CAVALCANTE EDILAINE F. , KASSIANO WITALO , RIBEIRO ALEX S. , COSTA BRUNA , CYRINO LETÍCIA T. , CUNHA PAOLO M. , ANTUNES MELISSA , SANTOS LEANDRO DOS , TOMELERI CRISIELI M. , NABUCO HELLEN C. G. , SUGIHARA-JÚNIOR PAULO , FERNANDES RODRIGO R. , RODRIGUES RICARDO J. , CARNEIRO MARCELO A. S. , PINA FÁBIO L. C. , DIB MÁRCIA M. , TEIXEIRA DENILSON C. , ORSATTI FÁBIO L. , VENTURINI DANIELLE , BARBOSA DÉCIO S. , CYRINO EDILSON S.
Published: April 2023

Purpose

The optimal intensity of resistance training (RT) to improve muscular, physical performance, and metabolic adaptations still needs to be well established for older adults. Based on current position statements, we compared the effects of two different RT loads on muscular strength, functional performance, skeletal muscle mass, hydration status, and metabolic biomarkers in older women.

Methods

One hundred one older women were randomly allocated to perform a 12-wk whole-body RT program (eight exercises, three sets, three nonconsecutive days a week) into two groups: 8–12 repetitions maximum (RM) and 10–15RM. Muscular strength (1RM tests), physical performance (motor tests), skeletal muscle mass (dual-energy X-ray absorptiometry), hydration status (bioelectrical impedance), and metabolic biomarkers (glucose, total cholesterol, HDL-c, HDL-c, triglycerides, and C-reactive protein) were measured at baseline and posttraining.

Results

Regarding muscular strength, 8–12RM promoted higher 1RM increases in chest press (+23.2% vs +10.7%, P < 0.01) and preacher curl (+15.7% vs +7.4%, P < 0.01), but not in leg extension (+14.9% vs +12.3%, P > 0.05). Both groups improved functional performance (P < 0.05) in gait speed (4.6%–5.6%), 30 s chair stand (4.6%–5.9%), and 6 min walking (6.7%–7.0%) tests, with no between-group differences (P > 0.05). The 10–15RM group elicited superior improves in the hydration status (total body water, intracellular and extracellular water; P < 0.01), and higher gains of skeletal muscle mass (2.5% vs 6.3%, P < 0.01), upper (3.9% vs 9.0%, P < 0.01) and lower limbs lean soft tissue (2.1% vs 5.4%, P < 0.01). Both groups improved their metabolic profile. However, 10–15RM elicited greater glucose reductions (−0.2% vs −4.9%, P < 0.05) and greater HDL-c increases (−0.2% vs +4.7%, P < 0.01), with no between-group differences for the other metabolic biomarkers (P > 0.05).

Conclusions

Our results suggest that 8–2RM seems more effective than 10–15RM for increasing upper limbs’ muscular strength, whereas the adaptative responses for lower limbs and functional performance appear similar in older women. In contrast, 10–15RM seems more effective for skeletal muscle mass gains, and increased intracellular hydration and improvements in metabolic profile may accompany this adaptation.
Η ανάλυση του Λουκ.17,20-21 στην πατερική και σύγχρονη ερμηνευτική
Authors: Ζαχίου Αντριάν-Σορίν
Published: April 2023

Το Λουκ. 17,20-21 αποδίδεται ως "Και όταν ερωτήθηκε από τους Φαρισαίους, πότε έρχεται η Βασιλεία του Θεού, [ο Ιησούς] τους απάντησε και τους είπε: Η Βασιλεία δεν έρχεται με σαφήνεια [με ευδιάκριτο τρόπο], και [οι άνθρωποι] δεν θα λένε [στο μέλλον] Νά [η Βασιλεία έχει φανερωθεί] εδώ! ή Νά [η Βασιλεία έχει φανερωθεί] εκεί!, διότι, νά την! η Βασιλεία βρίσκεται [ήδη] ενώπιόν σας." Παρουσιάζονται επιχειρήματα υπέρ της θέσης αυτής και επιχειρήματα κατά των άλλων θέσεων της Ιστορίας της Ερμηνείας του εδαφίου. Τα κύρια επιχειρήματα υπέρ της θέσης αυτής είναι αφηγηματικά και φιλολογικά που αφορούν στην χρήση των λέξεων "παρατήρησις" (=σαφήνεια) και "ἐντός' (=ενώπιον) στην εποχή που γράφτηκε το Κατά Λουκάν Ευαγγέλιο.
Mutation patterns of resistance genes for macrolides, aminoglycosides, and rifampicin in non-tuberculous mycobacteria isolates from Kenya
Authors: Mwangi Zakayo , Naeku Grace , Mureithi Marianne , Onyambu Frank , Bulimo Wallace
Published: April 2023

Background: Non-tuberculous mycobacteria (NTM) treatment constitutes a macrolide-based antibiotic regimen in combination with aminoglycosides for Rapid-Growing Mycobacteria (RGM), and rifampicin for Slow-Growing Mycobacteria (SGM). Mutations in the anti-NTM drug target regions promote NTM evolution to mutant strains that are insusceptible to NTM drugs leading to treatment failure. We, therefore, described the mutation patterns of anti-NTM drug target genes including rrl, rrs, and rpoB in NTM isolates from Kenya. 

Methods: We carried out a cross-sectional study that included 122 NTM obtained from the sputum of symptomatic tuberculosis-negative patients in Kenya. All 122 NTM underwent targeted sequencing of the rrl gene. The 54 RGM were also sequenced for rrs, and the 68 SGM were sequenced for rpoB genes using ABI 3730XL analyzer. The obtained sequences were aligned to their wild-type reference sequences for each gene using Geneious then mutations were identified. Pearson chi-square at a 95% confidence interval tested the association of NTM to mutation patterns for each gene.

Results: NTM harboring mutations associated with resistance to at least one of the antibiotics used in the macrolide-based therapy were 23% (28/122). Of these NTM, 10.4% (12/122) had mutations in the rrl gene with 58.3% (7/12) comprising RGM and 41.7% (5/12) being SGM. Mutation at position 2058 (A2058G, A2058C, A2058T) of the rrl gene was seen for 83.3% (10/12) of NTM, while 16.6% (2/12) harbored a A2059G mutation. Of the 54 RGM included for rrs characterization, 11.1% (6/54) exhibited mutations  at position 1408(A1408G), while 14.7% (10/68) of the SGM had mutations in the rpoB gene at positions S531W, S531L, S531Y, F506L, E509H with M.gastri having multiple mutations at positions D516V, H526D and, S531F.

Conclusion: We demonstrated a significant level of mutations associated with drug resistance for macrolides, aminoglycosides, and rifampicin in NTM isolated from symptomatic TB negative patients in Kenya.