bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163
Authors: Anton-Pampols Paula , Martínez Valenzuela Laura , Fernández Lorente Loreto , Quero Ramos Maria , Gómez Preciado Francisco , Martín Capón Irene , Morandeira Francisco , Manrique Escola Joaquín , Fulladosa Xavier , Cruzado Josep Maria , Torras Joan , Draibe Juliana
Published: December 2022

Background

CD163 and calprotectin have been proposed as biomarkers of active renal vasculitis. This study aimed to determine whether the combination of serum/urine calprotectin (s/uCalprotectin) and urinary soluble CD163 (suCD163) increases their individual performance as activity biomarkers.

Methods

We included 138 patients diagnosed with ANCA vasculitis (n = 52 diagnostic phase, n = 86 remission). The study population was divided into the inception (n = 101) and the validation cohorts (n = 37). We determined the s/uCalprotectin and suCD163 concentration using enzyme-linked immunoassay at the diagnostic or at the remission phase. Receiver operating characteristic (ROC) curves were conducted to assess the biomarkers’ classificatory values. We elaborated a combinatorial biomarker model in the inception cohort. The ideal cutoffs were used in the validation cohort to confirm the model's accuracy in the distinction between active disease and remission. We added the classical ANCA vasculitis activity biomarkers to the model to increase the classificatory performance.

Results

The concentrations of sCalprotectin and suCD163 were higher in the diagnostic compared with the remission phase (P = .013 and P < .0001). According to the ROC curves, sCalprotectin and suCD163 were accurate biomarkers to discern activity [area under the curve 0.73 (0.59–0.86), P = .015 and 0.88 (0.79–0.97), P < .0001]. The combinatory model with the best performance in terms of sensitivity, specificity and likelihood ratio included sCalprotectin, suCD163 and haematuria. Regarding the inception and the validation cohort, we obtained a sensitivity, specificity and likelihood ratio of 97%, 90% and 9.7, and 78%, 94% and 13, respectively.

Conclusions

In patients with ANCA vasculitis, a predictive model combining sCalprotectin, suCD163 and haematuria could be useful in detecting active kidney disease.
Backtracking cryptic recurrence of esophageal cancer from membranous nephropathy: the detection of glomerular NELL-1 and IgG4
Authors: Zhou Shuai , Meng FuLei , Yue ShuLing , Li Hang , Zhang LiHong , Wang Tao
Published: December 2022

We reported the detection of neural epidermal growth factor-like 1 (NELL-1) and immunoglobulin G4 (IgG4) on glomerular capillary wall in membrane nephropathy (MN), which led to the discovery of early post-operative recurrence of esophageal squamous cell cancer (ESCC) in a 68-year-old man. Further, NELL-1 was also identified in the cancerous tissue sampled by esophagoscope. Moreover, serum IgG4 percentage seemed to be higher when comparing with both previous reports and another age-matched male with NELL-1-negative MN upon fully recovered ESCC. Therefore, the finding of NELL-1 in a renal biopsy should trigger a detailed workup in search of malignancy, especially with concomitant IgG4 dominance.
Drugs associated with incident fragility fractures in kidney transplant recipients
Authors: Batteux Benjamin , Nowak Alban , Séjourné Alice , Penet Clémence , Masmoudi Kamel , Brazier François , Laville Solène M , Bennis Youssef , Gras-Champel Valérie , Choukroun Gabriel , Liabeuf Sophie
Published: December 2022

Background

The risk of fragility fractures is high in kidney transplant recipients, and steroids are reportedly a major cause. Other drugs known to induce fragility fractures have been studied in the general population but not in kidney transplant recipients. Here, we investigated the association between exposure over time to drugs that can injure bone (namely vitamin K antagonists, insulin, loop diuretics, proton pump inhibitors, opioids, selective serotonin reuptake inhibitors, antiepileptics and benzodiazepines) and incident fractures and changes over time in T-scores in this population.

Methods

A total of 613 consecutive kidney transplant recipients were included between 2006 and 2019. Drug exposures and incident fractures during the study period were comprehensively documented, and dual-energy X-ray absorptiometry was performed regularly. The data were analyzed using Cox proportional hazards models with time-dependent covariates and linear mixed models.

Results

Incident fractures occurred in 63 patients, giving a fracture incidence of 16.9 per 1000 person-years. Exposures to loop diuretics [hazard ratio (95% confidence interval) 2.11 (1.17–3.79)] and opioids [5.94 (2.14–16.52)] were associated with incident fractures. Exposure to loop diuretics was associated with a decrease over time in the T-score for the lumbar spine (P = .022) and for the wrist (P = .028).

Conclusions

This study suggests that the exposure to loop diuretics and opioids increases the risk of fracture in kidney transplant recipients.
In sea trout, the physiological response to salmon louse is stronger in female than in males
Authors: Fjelldal Per Gunnar , Dalvin Sussie , Ugelvik Mathias Stølen , Pedersen Audun Østby , Hansen Tom J , Skjold Bjørnar , Dyrhovden Lise , Kroken Ann Kathrin , Karlsen Ørjan
Published: December 2022

The aims of this study were to compare male and female sea trout (Salmo trutta) with respect to their hypo-osmoregulatory ability over a simulated migration to seawater and their clinical and physiological response to salmon louse (Lepeophtheirus salmonis) infection in seawater and over a simulated pre-mature return to freshwater. For this purpose, 2-year-old hatchery-reared male and female brown trout (F1 offspring of wild caught anadromous fish) were infected with salmon lice and measured for changes in plasma ions, glucose, lactate and osmolality and relative heart, liver and gonad sizes during a simulated seawater migration and thereafter a premature return to freshwater after 4 weeks in seawater (pre-adult louse). Un-infected trout served as control. Male trout used longer time to develop full hypo-osmoregulatory ability in seawater and showed a stronger response in plasma glucose and lactate following simulated premature return to freshwater, compared to female trout. Response to salmon louse was stronger in female trout, shown by stronger osmotic stress by chalimus (plasma Cl−) and pre-adult louse (plasma osmolality) and elevated relative liver size (hepatosomatic index) by pre-adult louse in female compared to male trout. Moreover, high plasma cortisol in infected female and low plasma cortisol in infected male trout produced a significant treatment–sex interaction on plasma cortisol. Lice infection intensity was initially higher in male (0.18 lice g−1) compared to female trout (0.11 lice g−1) at the chalimus stage, but equal between sexes at the pre-adult stage (male 0.15 and female 0.17 lice g−1). This study showed that female trout were better adapted for changes in water salinity, while male trout were more robust against salmon louse infection. These results suggests that the elevated salmon louse infection pressure generated by salmon farming have strong and unexplored negative effects on wild sea trout populations. Further research on this topic is vital for the conservation of wild sea trout populations.
Adverse social behaviour at work and health-related employment exit: a prospective population-based four-wave survey
Authors: Sterud Tom , Marti Andrea R , Degerud Eirik M
Published: December 2022

Background

The level of evidence for various aspects of adverse social behaviour (ASB) at work as risk factors for exit from employment due to health problems or diseases is inconclusive.

Methods

We obtained data from four consecutive surveys (2006/09/13/16) of the general population of Norway. Respondents who were interviewed in two consecutive surveys and employed at the first survey time point constituted the sample (n = 17 110 observations). We investigated associations of self-reported exposure to ASB (i.e. experiencing sexual harassment, bullying or violence/threats in the first survey) and health-related employment exit (i.e. individuals reporting exit from employment due to health problems or disease between two consecutive surveys) by means of mixed-effect logistic regression.

Results

The prevalence of ASB and health-related employment exit was 10.8% (n = 1853) and 2.6% (n = 440), respectively. Adjusted for age, sex, level of education, occupation and weekly work hours, sexual harassment, bullying and violence/threats were associated with an increased risk of exit from employment. The odds ratios (ORs) for the association between exposure to any of the three aspects of ASB and employment exit was 1.78 [95% confidence interval (CI) 1.33–2.38]; the estimated corresponding population attributable risk was PAR% = 7.32 [95% CI 2.67–12.27]. Further adjustment of mental distress attenuated the observed association between exposure to any ASB and exit from employment (OR = 1.45 [95% CI 1.07–1.95], i.e. a reduction of 42% in the OR).

Conclusions

ASB at work increases the risk of health-related exit from employment in the Norwegian workforce.
Education Moderates the Association between Depressive Symptoms and Self-Rated Health among Older Adults with Cancer
Authors: Wang Kaipeng , Zhang Anao , De Fries Carson M , Hasche Leslie K
Published: December 2022

This study examined the association between depressive symptoms and self-rated health (SRH) and whether and how such association varies by education among older adults with cancer. Data came from the 2019 National Health Interview Survey. A total of 2,470 participants aged 65 or older who had been diagnosed with cancer by a doctor or other health professional were included in this study. Ordinal logistic regression was used to examine the association between depressive symptoms and SRH and whether and how such association varies by education among older adults with cancer. More depressive symptoms were associated with worse SRH. Such association became stronger with higher education among older adults with cancer. Findings confirm the associations between depressive symptoms and SRH among older adults with cancer. The differential impact of education on SRH and on the association between depressive symptoms and SRH highlights the importance of considering patients’ educational attainment in a more comprehensive way when working with older adults with cancer. When conducting distress screening among cancer survivors, oncology social workers should be aware of the complex relationship between education and depression in relation to cancer survivors’ SRH.
Identifying social practices to inform fisheries management—the case of bycatch practices of marine mammals and seabirds of German gillnet fishers
Authors: Barz Fanny
Published: December 2022

Gillnets are one of the most common fishing gears globally and provide a fundamental contribution towards the income of millions of people as well as to the supply of protein. At the same time, bycatch from gillnet fisheries is one of the biggest threats to seabirds and marine mammals worldwide, because their habitats coincide spatially and temporally with gillnet fisheries. There has been research on technical solutions to unwanted bycatch, yet the social-science perspective is rather understudied. Little is known about fishers’ bycatch behaviour, which can be researched as a social practice. Against the background of Anthony Giddens’ structuration theory, this study used social sciences methods to analyse the bycatch practices of gillnet fishers in the German Baltic Sea. The results show that fishers normalize bycatch of seabirds as part of their fishing routine, while bycatch of marine mammals is experienced as a crisis. Underlying mechanisms for different bycatch practices are identified, and their meaning for management as well as further research questions are discussed. The perspective of normalizing and non-normalizing bycatch practices as well as fishers’ own mitigation strategies should be considered by fisheries management when addressing bycatch mitigation measures as they could be designed more effectively.
The UK reform of data protection: key changes and their ethical, social and legal implications
Authors: Mazzi Francesca , Adonis Abid , Cowls Josh , Tsamados Andreas , Taddeo Mariarosaria , Floridi Luciano
Published: December 2022

In September 2021, the UK government published a set of proposed reforms to its data protection regime for public consultation, later in June 2022 it released the response to the consultation, acknowledging the reforms it intends to adopt. The reforms are part of a broader national strategy, which aims to incentivize data-driven innovation and make the UK an international ‘data hub’. In this article, we review the reforms that represent the most controversial points of divergence from the GDPR and are worth watching to evaluate their effects on the overall data protection framework once implemented.
‘People still want a face and that’s where we can fill in’: a qualitative study of community pharmacists’ experiences of providing healthcare advice about preconception and pregnancy
Authors: Silverio Sergio A , Karki Pujan , Lakhani Shivali , Alter Marsha , Weinman John , Flynn Angela C
Published: December 2022

Objectives

This study aimed to explore community pharmacists’ practices and attitudes towards the provision of healthcare advice regarding preconception and pregnancy.

Methods

A qualitative focus group study was conducted virtually with community pharmacists around urban areas of London in October 2021. A topic guide was utilised to cover pharmacy practice, barriers and confidence in counselling women, education and training and thoughts on how to improve preconception and pregnancy health services. Focus groups were transcribed and analysed using thematic analysis.

Key findings

Eleven community pharmacists participated. Three themes were identified: ‘Community Driven Needs’; ‘Needs of Community Pharmacists’; ‘Shared Needs and Understanding’ which were related through a central organising concept of ‘Unmet Needs in Pharmacy-led Preconception and Pregnancy Care’. Community pharmacists are frequently consulted by women before and during pregnancy, however, a discord was uncovered between current pharmacy practice and the needs of the community. A clear need was identified for the incorporation of risk minimisation counselling focusing on smoking, alcohol intake and drug use. Education and organisational factors were reported as challenges to providing advice.

Conclusions

Community pharmacists can play a pivotal role in providing information and support to women before and during pregnancy. Our findings suggest integration of community pharmacy-led structured counselling may be a useful public health strategy to optimise pregnancy health. Our work highlights educational and organisational barriers which hinder the ability of pharmacists to promote preconception and pregnancy health. These must be addressed, and we provide recommendations for change to both policy and practice.
Usability of an animated diabetes information tool for patients with different health literacy levels: a qualitative study
Authors: Visscher Boudewijn B , Heerdink Eibert R , Rademakers Jany
Published: December 2022

Objectives

Most currently available medication self-management support tools do not meet the needs of patients with limited health literacy. Recently, tools that are better tailored to the needs of patients with limited health literacy have been developed. This study aimed to assess the usability of an animated diabetes information tool by patients with diabetes with limited and adequate health literacy levels.

Methods

Participants with limited and adequate health literacy levels were selected based on three health literacy questions in a screening interview, and asked to use the tool three times a week, after which individual semistructured interviews were conducted. The interview topics were based on the technology acceptance model (i.e. perceived ease of use, perceived usefulness, and intention to use). Twenty-five patients with diabetes were included in the study.

Key findings

All participants perceived the tool as easy to use due to a clear overview of topics and only personalized information being provided. Those with limited health literacy indicated that they had learned from the tool and had the intention to continue using it in the future. These participants also expressed the need for the tool to be more actively offered by healthcare professionals, while participants with adequate health literacy expressed the need for more in-depth information.

Conclusion

The tailored self-management support tool was perceived as usable by all participants. To better serve them, the tool could be further improved by addressing the additional needs of people with limited as well as adequate health literacy.
Triage nurse–initiated X-ray radiography in minor trauma
Authors: Gautier Julie , Verdan Matthieu , Rochette Emmanuelle , LAMBERT Céline , Caron Nicolas , Merlin Etienne
Published: December 2022

Background

Overcrowding of paediatric emergency departments (EDs) is a worldwide issue, where improving the quality of care is a priority. The main objective of this study was to determine the effect of triage nurse–initiated X-ray radiography on length of stay in paediatric emergency admissions.

Methods

This retrospective, monocentric, descriptive study was performed in two successive 3-month periods: a pre-protocol (‘before’) period from 3 February to 3 May 2020 and a protocol (‘after’) period from 4 May to 2 August 2020, when patients underwent nurse-initiated X-ray radiography. The study involved all patients who were aged ≥3 years, valid, non-hyperalgic, accompanied by their parents and consulting at the paediatric ED for a simple closed distal trauma, involving a single limb segment or joint.

Results

A total of 695 patients were included, 298 in the first period and 397 in the second period. The median length of stay in the paediatric ED was significantly shorter during the second period (119 min [80, 165] vs. 80 min [60, 105], P < 0.001), i.e. a median reduction time of 39 min or 33% (effect size = − 0.68, 95% confidence interval [−0.84 to −0.53]). Triage nurse requests were judged ‘adequate and sufficient’ in 95.2% of cases, with only 2.0% of instances deemed ‘unnecessary’ by the medical team. In 2.8% of cases, ‘another X-ray’ was required to support diagnosis.

Conclusions

The application of a triage nurse X-ray protocol significantly reduced the length of stay in a paediatric ED. The quality of patient management remained unchanged, and nurse requests were relevant.
Assessment of antimicrobial mismatches in empirical treatment in early PJI after aseptic revision arthroplasty
Authors: Veerman C M , Goosen J H M , Telgt D S C , Rijnen W H M , Nabuurs M H , Wertheim H F L
Published: December 2022

Background

In early periprosthetic joint infection (PJI), ‘debridement, antibiotics and implant retention’ (DAIR) is a widely accepted form of treatment. Empirical antimicrobial treatment is started while culture results of tissue samples taken during debridement are pending.

Objectives

In this retrospective study we assessed the antimicrobial mismatch rate between empirical treatment and the susceptibility of the causative microorganisms of PJI after aseptic revision arthroplasty. We analysed risk factors for antimicrobial mismatches and the impact of mismatches on the outcome of PJI treatment.

Results

A total of 119 patients were included in the analysis. In 72% (86/119) of the cases there was an antimicrobial mismatch in empirical treatment. Most of the antimicrobial mismatches were caused by multidrug-resistant (MDR) Staphylococcus spp. (77%, 66/86). In multivariable analysis, polymicrobial PJI was significantly associated with antimicrobial mismatch (OR: 6.89; 95% CI: 2.38–19.53; P < 0.001), and antimicrobial mismatch was significantly associated with reduced success rate of PJI treatment (OR: 0.20; 95% CI: 0.05 ± 0.82; P = 0.026). There was no difference in successful outcome between PJI caused by Gram-negative bacilli (61%) and Gram-positive bacteria (69%, P = 0.516).

Conclusions

Mismatching empirical antimicrobial treatment after DAIR following aseptic revision arthroplasty was significantly associated with failure of PJI treatment. Polymicrobial PJI is a risk factor for antimicrobial mismatch of the empirical treatment of PJI. Antimicrobial mismatch and delay in targeted treatment should be integrated in the approach to optimize antibiotic treatment to improve clinical outcomes, while minimizing unintended side effects of antimicrobial use (antimicrobial stewardship).
Learning from undercoded clinical records for automated International Classification of Diseases (ICD) coding
Authors: Jin Yucheng , Xiong Yun , Shi Dan , Lin Yifei , He Lifang , Zhang Yao , Plasek Joseph M , Zhou Li , Bates David W , Tang Chunlei
Published: December 2022

Objectives

To develop an unbiased objective for learning automatic coding algorithms from clinical records annotated with only partial relevant International Classification of Diseases codes, as annotation noise in undercoded clinical records used as training data can mislead the learning process of deep neural networks.

Materials and Methods

We use Medical Information Mart for Intensive Care III as our dataset. We employ positive-unlabeled learning to achieve unbiased loss estimation, which is free of misleading training signal. We then utilize reweighting mechanism to compensate for the imbalance between positive and negative samples. To further close the performance gap caused by poor quality annotation, we integrate the supervision provided by the automatic annotation tool Medical Concept Annotation Toolkit which can ease the heavy burden of manual validation.

Results

Our benchmarking results show that positive-unlabeled learning with reweighting outperforms competitive baseline methods over a range of missing label ratios. Integrating supervision provided by annotation tool further boosted the performance.

Discussion

Considering the annotation noise and severe imbalance, unbiased loss estimation and reweighting mechanism are both important for learning from undercoded clinical records. Unbiased loss requires the estimation of false negative ratios and estimation through trained models is practical and competitive.

Conclusions

The combination of positive-unlabeled learning with reweighting and supervision provided by the annotation tool is a promising solution to learn from undercoded clinical records.
VACtrac: enhancing access immunization registry data for population outreach using the Bulk Fast Healthcare Interoperable Resource (FHIR) protocol
Authors: Lenert Leslie , Jacobs Jeff , Agnew James , Ding Wei , Kirchoff Katie , Weatherston Duncan , Deans Kenneth
Published: December 2022

COVID-19 vaccination uptake has been suboptimal, even in high-risk populations. New approaches are needed to bring vaccination data to the groups leading outreach efforts. This article describes work to make state-level vaccination data more accessible by extending the Bulk Fast Healthcare Interoperability Resource (FHIR) standard to better support the repeated retrieval of vaccination data for coordinated outreach efforts. We also describe a corresponding low-foot-print software for population outreach that automates repeated checks of state-level immunization data and prioritizes outreach by social determinants of health. Together this software offers an integrated approach to addressing vaccination gaps. Several extensions to the Bulk FHIR protocol were needed to support bulk query of immunization records. These are described in detail. The results of a pilot study, using the outreach tool to target a population of 1500 patients are also described. The results confirmed the limitations of current patient-by-patient approach for querying state immunizations systems for population data and the feasibility of a Bulk FHIR approach.
The social movement was live streamed: a relational analysis of mobile live streaming during the 2019 Hong Kong protests
Authors: Fang Kecheng
Published: December 2022

This study proposes a sociotechnical framework to study digital media and social movements and uses it to analyze the 2019 protests in Hong Kong. Informed by actor-network theory, this framework examines media technology as infrastructure, practice, and text, and discusses its relation to other actors/actants in the network of social movements. Based on qualitative analysis of live streaming sessions and in-depth interviews with journalists and audiences, I identify and explicate the major actors/actants related to mobile live streaming and argue that mobile live streaming became an obligatory passage point through which actors/actants reached other parts of the network and realized their goals. The assemblage of heterogeneous actors/actants not only contributed to the solidarity and longevity of the movement but also brought risks. This study extends the line of research on media technology and social movements by proposing a framework that examines one specific media technology while maintaining an ecological lens.
When International Legal Standards Meet Transitional Justice Processes
Authors: Arévalo-Ramírez Walter , Martini Pauline
Published: December 2022

The present contribution explores the interactions between international legal standards, as determined by the Rome Statute of the International Criminal Court (ICC), and national law before the Colombian Special Jurisdiction for Peace (SJP), and studies their respective rationales. It contrasts two situations: divergences between the two regimes, on the one hand, and their convergences on the other. First, it analyses three instances where the SJP Statute diverges from international criminal law, which resulted from decisions of the executive and legislative authorities in Colombia when drafting the Statute, namely: the SJP’s restorative penalties; the differentiated treatment of members of armed forces; and the notion of command responsibility. The authors offer three possible explanations for these departures of the Columbian legislation from international legal standards: Colombia’s willingness to carry out judicial proceedings at the national level instead of having recourse to the international community; the context of the negotiated peace in the country; and the national nature of the SJP. Second, the article addresses the convergences by examining recent practice of the judiciary in light of Macro Case 01 before the SJP, which shows a tendency towards the implementation of international legal standards in the SJP’s jurisprudence. The authors discuss the possible justification for this convergence, arguing that the adoption of international standards serves both to demonstrate the genuine character of the Colombian transitional justice process and subsequent judicial proceedings, and to allow for the closing of the preliminary examination before the ICC.
A Preliminary Study of Body Decomposition and Arthropod Succession in an Arid Area in Northwest China During Summer
Authors: Hu Gengwang , Kang Chengtao , Zhu Rui , Guo Yi , Li Liangliang , Wang Yinghui , Zhang Yanan , Wang Yu , Wang Jiangfeng
Published: December 2022

The study of insect fauna and their development and succession patterns on decaying cadavers is crucial to promoting insect evidence as a useful tool in forensic science, particularly for estimating the postmortem interval (PMI). Body decomposition and arthropod succession are affected by many factors and exhibit substantial regional variations; therefore, detailed succession studies in different biogeographic regions are required for understanding the successional patterns of insects in various environments. This study was conducted in the summer of 2021 using three domestic pig carcasses (Sus scrofa domestica L., 1758) in the field of Shizuishan City, Ningxia, Northwest China. A total of 40 species of necrophagous insects belonging to three orders and 16 families were collected. Among Diptera, Lucilia sericata (Meigen,1826), Chrysomya megacephala (Fabricius,1794), and Phormia regina (Meigen,1826) (Diptera: Calliphoridae) were the dominant species. As for Coleoptera, the dominant species changed throughout the process of carcass decomposition from Saprinus semipunctatus (Fabricius,1792) (Coleoptera: Histeridae) to Dermestes maculatus DeGeer,1774 and Dermestes frischii Kugelann,1792 (Coleoptera: Dermestidae). The carcasses desiccated rapidly and reached the remains stage under extreme conditions of high temperatures and low humidity, after which a large amount of dried tissue of the carcasses attracted populations of Coleoptera, particularly Dermstidae, which were abundant and remained until the end of the experiment on day 50. The current study is the first forensic entomological investigation of succession in Northwest China and provides basic data for the estimation of PMI during summer in this region.
Physical activity and breast cancer survival: results from the Nurses’ Health Studies
Authors: Fortner Renée Turzanski , Brantley Kristen D , Tworoger Shelley S , Tamimi Rulla M , Rosner Bernard , Farvid Maryam S , Holmes Michelle D , Willett Walter C , Eliassen A Heather
Published: December 2022

Background

Physical activity is generally associated with better outcomes following diagnosis; however, few studies have evaluated change in pre- to postdiagnosis activity and repeated measures of activity by intensity and type.

Methods

We evaluated physical activity and survival following a breast cancer diagnosis in the Nurses’ Health Study and Nurses’ Health Study II (n = 9308 women, n = 1973 deaths). Physical activity was evaluated as updated cumulative average of metabolic equivalent of task (MET)-h/wk (assigned per activity based on duration and intensity) and change in pre- to postdiagnosis activity. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Higher postdiagnosis activity was inversely associated with breast cancer–specific mortality in categories from ≥9 MET-h/wk (vs <3 MET h/wk, HR≥9 to <18 = 0.74 [95% CI = 0.55 to 0.99]; HR≥27 = 0.69 [95% CI = 0.50 to 0.95]; Ptrend = .04) and all-cause mortality from ≥3 MET-h/wk (HR≥3 to <9 = 0.73 [95% CI = 0.61 to 0.88]; HR≥27 = 0.51 [95% CI = 0.41 to 0.63]; Ptrend < .001). Associations were predominantly observed for estrogen receptor–positive tumors and in postmenopausal women. Walking was associated with lower risk of all-cause mortality (≥9 vs <3 MET-h/wk, HR= 0.69 [95% CI = 0.57 to 0.84]) as was strength training. Relative to stable activity pre- to postdiagnosis (±3 MET-h/wk), increases from ≥3 to 9 MET-h/wk were associated with lower all-cause mortality risk (Ptrend < .001). Results were robust to adjustment for prediagnosis physical activity.

Conclusions

Physical activity was associated with lower risk of death following diagnosis. Increased pre- to postdiagnosis activity corresponding to at least 1-3 h/wk of walking was associated with lower risk of death. These results provide further impetus for women to increase their activity after a breast cancer diagnosis, though reverse causation cannot be fully excluded.
Refugee Status, Permanent Residency, and Citizenship: The re-making of categories among Palestinian youth in East Jerusalem
Authors: Procter Caitlin
Published: December 2022

This article ethnographically explores ways that young Palestinian refugees seek to strengthen their claims to residency in Jerusalem. It describes the complex layers of colonial subjugation faced by these young people and the ways they attune their everyday life choices in this context of long-term insecurity. I argue that through situations forced upon them in efforts by the Israeli government to reduce the Palestinian demographic of the city, young people are re-making the categories they live under, away from their bureaucratic and assumed political meaning. This article explores different examples of engagement with Israeli state institutions as tactics undertaken to mitigate the increasing uncertainty surrounding residency revocation and subsequent forcible transfer of Palestinians from Jerusalem. I argue that the reason young people are re-attributing meaning of these categories is to safeguard their futures, in light of the failure of international frameworks to do the same.
Functional hepatobiliary organoids recapitulate liver development and reveal essential drivers of hepatobiliary cell fate determination
Authors: He Juan , Cui Haoyue , Shi Xiaohan , Jin Qiqi , Han Ximeng , Han Tiantian , Peng Jiayin , Guo Shiwei , Zhang Lei , Zhao Yun , Zhou Bin , Chen Luonan , Chen Lei , Arial Zeng Yi , Wang Hongyang , Jin Gang , Gao Dong
Published: December 2022

During liver development, hepatocytes, and cholangiocytes are concurrently differentiated from common liver progenitor cells and are assembled into hepatobiliary architecture to perform proper hepatic function. However, the generation of functional hepatobiliary architecture from hepatocytes in vitro is still challenging, and the exact molecular drivers of hepatobiliary cell lineage determination is largely unknown. In this study, functional hepatobiliary organoids (HBOs) are generated from hepatocytes. These HBOs contain a bile duct network surrounded by mature hepatocytes and stably maintain hepatic characteristics and function in vitro and upon transplantation in vivo. Morphological transition and expression profile of hepatocyte-derived organoids recapitulate the process of liver development. Gene regulation landscape of hepatocyte-derived organoids reveal that Tead4 and Ddit3 promote the cell fate commitment of liver progenitors to functional cholangiocytes and hepatocytes, respectively. Liver cell fate determination is reversed by inhibiting Tead4 or increasing Ddit3 expression both in vitro and upon transplantation in vivo. Collectively, hepatocyte-derived HBOs reveal the essential transcription drivers of liver hepatobiliary cell lineage determination and represent powerful models for liver development and regeneration.
Modelling the evolution of silicate/volatile accretion discs around white dwarfs
Authors: Okuya Ayaka , Ida Shigeru , Hyodo Ryuki , Okuzumi Satoshi
Published: December 2022

A growing number of debris discs have been detected around metal-polluted white dwarfs. They are thought to be originated from tidally disrupted exoplanetary bodies and responsible for metal accretion on to host WDs. To explain (1) the observationally inferred accretion rate higher than that induced by Poynting–Robertson drag, $\dot{M}_{\rm PR}$, and (2) refractory-rich photosphere composition indicating the accretion of terrestrial rocky materials, previous studies proposed runaway accretion of silicate particles due to gas drag by the increasing silicate vapour produced by the sublimation of the particles. Because re-condensation of the vapour diffused beyond the sublimation line was neglected, we revisit this problem by one-dimensional advection/diffusion simulation that consistently incorporates silicate sublimation/condensation and back-reaction to particle drift due to gas drag in the solid-rich disc. We find that the silicate vapour density in the region overlapping the solid particles follows the saturating vapour pressure and that no runaway accretion occurs if the re-condensation is included. This always limits the accretion rate from mono-compositional silicate discs to $\dot{M}_{\rm PR}$ in the equilibrium state. Alternatively, by performing additional simulations that couple the volatile gas (e.g. water vapour), we demonstrate that the volatile gas enhances the silicate accretion to $\gt \dot{M}_{\rm PR}$ through gas drag. The refractory-rich accretion is simultaneously reproduced when the initial volatile fraction of disc is $\lesssim 10$ wt per cent because of the suppression of volatile accretion due to the efficient back-reaction of solid to gas. The discs originating from C-type asteroid analogues might be a possible clue to the high-$\dot{M}$ puzzle.
SPARCS-North Wide-field VLBI Survey: exploring the resolved μJy extragalactic radio source population with EVN + e-MERLIN
Authors: Njeri Ann , Beswick Robert J , Radcliffe Jack F , Thomson A P , Wrigley N , Muxlow T W B , Garrett M A , Deane Roger P , Moldon Javier , Norris Ray P , Kothes Roland
Published: December 2022

The SKA PAthfinder Radio Continuum Surveys (SPARCS) are providing deep-field imaging of the faint (sub-mJy) extragalactic radio source populations through a series of reference surveys. One of the key science goals for SPARCS is to characterize the relative contribution of radio emission associated with active galactic nucleus (AGN) from star formation (SF) in these faint radio source populations, using a combination of high sensitivity and high angular resolution imaging over a range of spatial scales (arcsec to mas). To isolate AGN contribution from SF, we hypothesize that there exists a brightness temperature cut-off point separating pure AGN from SF. We present a multiresolution (10–100 mas) view of the transition between compact AGN and diffuse SF through a deep wide-field EVN + e-MERLIN, multiple phase centre survey of the centre of the Northern SPARCS (SLOAN) reference field at 1.6 GHz. This is the first (and only) VLBI (+ e-MERLIN) milliarcsecond angular resolution observation of this field, and of the wider SPARCS reference field programme. Using these high spatial resolution (9 pc–0.3 kpc at z ∼ 1.25) data, 11 milliarcsec-scale sources are detected from a targeted sample of 52 known radio sources from previous observations with the e-MERLIN, giving a VLBI detection fraction of $\sim 21{{\ \rm per\ cent}}$. At spatial scales of $\sim 9\,$pc, these sources show little to no jet structure whilst at $\sim 0.3\,$kpc one-sided and two-sided radio jets begin to emerge on the same sources, indicating a possible transition from pure AGN emissions to AGN and SF systems.
Ultraviolet imaging observations of three jellyfish galaxies: star formation suppression in the centre and ongoing star formation in stripped tails
Authors: George K , Poggianti B M , Tomičić N , Postma J , Côté P , Fritz J , Ghosh S K , Gullieuszik M , Hutchings J B , Moretti A , Omizzolo A , Radovich M , Sreekumar P , Subramaniam A , Tandon S N , Vulcani B
Published: December 2022

Spiral galaxies undergo strong ram-pressure effects when they fall into the galaxy cluster potential. As a consequence, their gas is stripped to form extended tails within which star formation can happen, giving them the typical jellyfish appearance. The ultraviolet imaging observations of jellyfish galaxies provide an opportunity to understand ongoing star formation in the stripped tails. We report the ultraviolet observations of the jellyfish galaxies JW39, JO60, JO194 and compare with observations in optical continuum and Hα. We detect knots of star formation in the disc and tails of the galaxies and find that their UV and Hα flux are well correlated. The optical emission line ratio maps of these galaxies are used to identify for every region the emission mechanism, due to either star formation, LINER or a mix of the two phenomena. The star-forming regions in the emission line maps match very well with the regions having significant UV flux. The central regions of two galaxies (JW39, JO194) show a reduction in UV flux which coincides with composite or LINER regions in the emission line maps. The galaxies studied here demonstrate significant star formation in the stripped tails, suppressed star formation in the central regions and present a possible case of accelerated quenching happening in jellyfish galaxies.
Antibiotic Cycling Affects Resistance Evolution Independently of Collateral Sensitivity
Authors: Brepoels Pauline , Appermans Kenny , Pérez-Romero Camilo Andres , Lories Bram , Marchal Kathleen , Steenackers Hans P
Published: December 2022

Antibiotic cycling has been proposed as a promising approach to slow down resistance evolution against currently employed antibiotics. It remains unclear, however, to which extent the decreased resistance evolution is the result of collateral sensitivity, an evolutionary trade-off where resistance to one antibiotic enhances the sensitivity to the second, or due to additional effects of the evolved genetic background, in which mutations accumulated during treatment with a first antibiotic alter the emergence and spread of resistance against a second antibiotic via other mechanisms. Also, the influence of antibiotic exposure patterns on the outcome of drug cycling is unknown. Here, we systematically assessed the effects of the evolved genetic background by focusing on the first switch between two antibiotics against Salmonella Typhimurium, with cefotaxime fixed as the first and a broad variety of other drugs as the second antibiotic. By normalizing the antibiotic concentrations to eliminate the effects of collateral sensitivity, we demonstrated a clear contribution of the evolved genetic background beyond collateral sensitivity, which either enhanced or reduced the adaptive potential depending on the specific drug combination. We further demonstrated that the gradient strength with which cefotaxime was applied affected both cefotaxime resistance evolution and adaptation to second antibiotics, an effect that was associated with higher levels of clonal interference and reduced cost of resistance in populations evolved under weaker cefotaxime gradients. Overall, our work highlights that drug cycling can affect resistance evolution independently of collateral sensitivity, in a manner that is contingent on the antibiotic exposure pattern.
Ecology, Not Host Phylogeny, Shapes the Oral Microbiome in Closely Related Species
Authors: Moraitou Markella , Forsythe Adrian , Fellows Yates James A , Brealey Jaelle C , Warinner Christina , Guschanski Katerina
Published: December 2022

Host-associated microbiomes are essential for a multitude of biological processes. Placed at the contact zone between external and internal environments, the little-studied oral microbiome has important roles in host physiology and health. Here, we investigate the roles of host evolutionary relationships and ecology in shaping the oral microbiome in three closely related gorilla subspecies (mountain, Grauer's, and western lowland gorillas) using shotgun metagenomics of 46 museum-preserved dental calculus samples. We find that the oral microbiomes of mountain gorillas are functionally and taxonomically distinct from the other two subspecies, despite close evolutionary relationships and geographic proximity with Grauer's gorillas. Grauer's gorillas show intermediate bacterial taxonomic and functional, and dietary profiles. Altitudinal differences in gorilla subspecies ranges appear to explain these patterns, suggesting a close connection between dental calculus microbiomes and the environment, likely mediated through diet. This is further supported by the presence of gorilla subspecies-specific phyllosphere/rhizosphere taxa in the oral microbiome. Mountain gorillas show a high abundance of nitrate-reducing oral taxa, which may promote adaptation to a high-altitude lifestyle by modulating blood pressure. Our results suggest that ecology, rather than evolutionary relationships and geographic distribution, shape the oral microbiome in these closely related species.
In vivo promotion of primordial follicle activation by stem cell factor treatment in mice with premature ovarian insufficiency and advanced age
Authors: Wang Yibo , Zhang Jiawei , Liang Jing , Jia Longzhong , Niu Shudong , Cheng Kaixin , Yang Chen , Lu Zining , Mu Lu , Yang Xuebing , Zhang Yan , Zhang Hua
Published: December 2022

Dormant primordial follicles (PFs) are the most abundant reproductive resource in mammalian ovaries. With advances in the mechanism of study of the regulation of PF activation, PFs have been used to improve fertility in clinical practice. As a central controlling element of follicle activation signaling, the pre-granulosa cell-secreted stem cell factor (SCF; also known as KIT ligand, KITL), which initiates the growth of dormant oocytes, is an ideal natural activator that stimulates follicle activation. However, no systematic study has been conducted to identify the activating effect of SCF in vivo and in vitro. In this study, by combining an in vitro whole ovary culture system and several mouse models, we provide a series of experimental evidence that SCF is an efficient activator for improving PF activation in mouse ovaries. Our in vitro study showed that SCF increased phosphatidylinositol 3-kinase (PI3K) signaling and PF activation ratio in neonatal ovaries. In vivo ovarian non-invasive topical administrations of SCF to the ovaries efficiently improved follicle activation and development, oocyte retrieval ratio and fertility in inducible premature ovarian insufficiency mouse models and aged mice. Our study suggests that SCF is an efficient growth factor that can be applied to improve PF activation.
NrnA is a 5′-3′ exonuclease that processes short RNA substrates in vivo and in vitro
Authors: Weiss Cordelia A , Myers Tanner M , Wu Chih Hao , Jenkins Conor , Sondermann Holger , Lee Vincent T , Winkler Wade C
Published: December 2022

Bacterial RNases process RNAs until only short oligomers (2–5 nucleotides) remain, which are then processed by one or more specialized enzymes until only nucleoside monophosphates remain. Oligoribonuclease (Orn) is an essential enzyme that acts in this capacity. However, many bacteria do not encode for Orn and instead encode for NanoRNase A (NrnA). Yet, the catalytic mechanism, cellular roles and physiologically relevant substrates have not been fully resolved for NrnA proteins. We herein utilized a common set of reaction assays to directly compare substrate preferences exhibited by NrnA-like proteins from Bacillus subtilis, Enterococcus faecalis, Streptococcus pyogenes and Mycobacterium tuberculosis. While the M. tuberculosis protein specifically cleaved cyclic di-adenosine monophosphate, the B. subtilis, E. faecalis and S. pyogenes NrnA-like proteins uniformly exhibited striking preference for short RNAs between 2–4 nucleotides in length, all of which were processed from their 5′ terminus. Correspondingly, deletion of B. subtilis nrnA led to accumulation of RNAs between 2 and 4 nucleotides in length in cellular extracts. Together, these data suggest that many Firmicutes NrnA-like proteins are likely to resemble B. subtilis NrnA to act as a housekeeping enzyme for processing of RNAs between 2 and 4 nucleotides in length.
KLF4 inhibits early neural differentiation of ESCs by coordinating specific 3D chromatin structure
Authors: Bi Jinfang , Wang Wenbin , Zhang Meng , Zhang Baoying , Liu Man , Su Guangsong , Chen Fuquan , Chen Bohan , Shi Tengfei , Zheng Yaoqiang , Zhao Xueyuan , Zhao Zhongfang , Shi Jiandang , Li Peng , Zhang Lei , Lu Wange
Published: December 2022

Neural differentiation of embryonic stem cells (ESCs) requires precisely orchestrated gene regulation, a process governed in part by changes in 3D chromatin structure. How these changes regulate gene expression in this context remains unclear. In this study, we observed enrichment of the transcription factor KLF4 at some poised or closed enhancers at TSS-linked regions of genes associated with neural differentiation. Combination analysis of ChIP, HiChIP and RNA-seq data indicated that KLF4 loss in ESCs induced changes in 3D chromatin structure, including increased chromatin interaction loops between neural differentiation-associated genes and active enhancers, leading to upregulated expression of neural differentiation-associated genes and therefore early neural differentiation. This study suggests KLF4 inhibits early neural differentiation by regulation of 3D chromatin structure, which is a new mechanism of early neural differentiation.