bluuebunny/crossref_metadata_2025_split huggingface dataset:
(3R,7S)‐12‐Hydroxy‐jasmonoyl‐l‐isoleucine is the genuine bioactive stereoisomer of a jasmonate metabolite in Arabidopsis thaliana
Authors: Saito Rina , Muto Toshiya , Urano Haruyuki , Kitajima Tsumugi , Kato Nobuki , Kwon Eunsang , Ueda Minoru 
Published: April 2023

SUMMARYThe oxylipin plant hormone (3R,7S)‐jasmonoyl‐l‐isoleucine [or (+)‐7‐iso‐jasmonoyl‐l‐isoleucine, JA‐Ile] is widely recognized as a plant defense hormone against pathogens and chewing insects. The metabolism of JA‐Ile into 12‐OH‐JA‐Ile and 12‐COOH‐JA‐Ile is the central mechanism for the inactivation of JA signaling. Recently, 12‐OH‐JA‐Ile was reported to function as a ligand for the JA‐Ile co‐receptor COI1‐JAZ. However, in previous studies, ‘12‐OH‐JA‐Ile’ used was a mixture of four stereoisomers, the naturally occurring cis‐isomer (3R,7S)‐12‐OH‐JA‐Ile and the trans‐isomer (3R,7R)‐12‐OH‐JA‐Ile, and the unnatural cis‐isomer (3S,7R)‐12‐OH‐JA‐Ile and the trans‐isomer (3S,7S)‐12‐OH‐JA‐Ile. Thus, the genuine bioactive form of 12‐OH‐JA‐Ile has not yet been identified. In the present study, we prepared pure stereoisomers of 12‐OH‐JA‐Ile and identified (3R,7S)‐12‐OH‐JA‐Ile as the naturally occurring bioactive form of 12‐OH‐JA‐Ile and found that it binds to COI1‐JAZ9 as effectively as (3R,7S)‐JA‐Ile. In addition, we revealed that the unnatural trans‐isomer (3S,7S)‐12‐OH‐JA‐l‐Ile functions as another bioactive isomer. The pure (3R,7S)‐12‐OH‐JA‐Ile causes partial JA‐responsive gene expression without affecting the expression of JAZ8/10, which is involved in the negative feedback regulation of JA‐signaling. Thus, (3R,7S)‐12‐OH‐JA‐Ile could cause weak and sustainable expression of certain JA‐responsive genes until the catabolism of (3R,7S)‐12‐OH‐JA‐Ile into (3R,7S)‐12‐COOH‐JA‐Ile occurs. The use of chemically pure (3R,7S)‐12‐OH‐JA‐Ile confirmed the genuine biological activities of ‘12‐OH‐JA‐Ile’ by excluding the possible effects of other stereoisomers. A chemical supply of pure (3R,7S)‐12‐OH‐JA‐Ile with an exact bioactivity profile will enable further detailed studies of the unique role of 12‐OH‐JA‐Ile in planta.
Durable remission of thrombotic thrombocytopenic purpura in the setting of pembrolizumab therapy
Authors: Kozak Michael , Rubenstein Wesley , Okwan‐Duodu Derick , Friedman Kenneth , Nassir Youram , Perez‐Alvarez Ingrid , Gibb David R. , Klapper Ellen , Pepkowitz Samuel 
Published: April 2023

AbstractBackgroundThere is a small but growing number of thrombotic thrombocytopenic purpura (TTP) cases attributed to immune checkpoint inhibitor therapy, with nivolumab and ipilimumab therapy being the most frequently described in the literature.Study Design and MethodsThis report evaluates the course of a patient with a history of metastatic adenocarcinoma of the lung who developed TTP following treatment with the PD‐1 inhibitor Pembrolizumab. The patient was treated with six sessions of therapeutic plasma exchange and appeared to be in remission. Exacerbation occurred 4 days later, and seven more sessions of plasma exchange were performed along with four total doses of Rituximab, and a steroid taper with monitoring of platelet counts and ADAMTS13 activity.ResultsHis platelet count recovered to a peak of 318,000 UL with an ADAMTS13 activity of 77% at the time of discharge. The patient has been following up regularly for outpatient testing with no TTP relapse as of the completion of this report.DiscussionThis is one of a few cases of Pembrolizumab‐associated TTP reported in the literature with successful complete remission following treatment. Plasma exchange in this setting may be an especially beneficial therapeutic intervention because of the removal of both the anti‐ADAMTS13 antibody as well as the immune system upregulating anti‐PDL1 monoclonal antibody with replacement of ADAMTS13 from donor plasma. Longer duration of plasma exchange and monitoring for normalization of ADAMTS13 levels in addition to platelet count before cessation of treatment may improve durable remission rates in this entity.
Study on Lubricating Performance of the Bubbly Oil Under High Shear Rate—Part 2: Application Study in High-Speed Bearing
Authors: Jiang Shuyun , Li Shaohua , Zhou Feida , Lin Xiaohui 
Published: April 2023

Abstract
This paper aims to investigate the lubricating performance of the bubbly oil. Due to space limitation, the work is divided into two parts. Part 1 concluded that the bubbly oil under high shear rate has a lower viscosity than the non-aerated oil, and the air volume fraction can be adjusted conveniently to reach a high value. Based on this, in Part 2, we intend to explore the feasibility of using the bubbly oil in lubricating high-speed bearings. Here, we select a step thrust bearing as object and analyze its static characteristics under the bubbly oil lubrication. A test rig for the high-speed step thrust bearing was developed to measure the static characteristics of the bearing under the bubbly oil lubrication. The lubrication models for the hydrodynamic step thrust bearing were established to predict the bearing static characteristics. The results show that the static characteristics parameters of the bearing under the bubbly oil lubrication are less than those under the non-aerated oil lubrication, and the differences of static characteristics parameters of the bearing between the non-aerated oil lubrication and the bubbly oil one become larger with the increase of air volume fraction and the external load, especially at a higher speed.
Are children with prolonged fever at a higher risk for serious illness? A prospective observational study
Authors: Nijman Ruud G , Tan Chantal D , Hagedoorn Nienke N , Nieboer Daan , Herberg Jethro Adam , Balode Anda , von Both Ulrich , Carrol Enitan D , Eleftheriou Irini , Emonts Marieke , van der Flier Michiel , de Groot Ronald , Kohlmaier Benno , Lim Emma , Martinón-Torres Federico , Pokorn Marko , Strle Franc , Tsolia Maria , Yeung Shunmay , Zachariasse Joany M , Zavadska Dace , Zenz Werner , Levin Michael , Vermont Clementien L , Moll Henriette A , Maconochie Ian K 
Published: April 2023

ObjectivesTo describe the characteristics and clinical outcomes of children with fever ≥5 days presenting to emergency departments (EDs).DesignProspective observational study.Setting12 European EDs.PatientsConsecutive febrile children <18 years between January 2017 and April 2018.InterventionsChildren with fever ≥5 days and their risks for serious bacterial infection (SBI) were compared with children with fever <5 days, including diagnostic accuracy of non-specific symptoms, warning signs and C-reactive protein (CRP; mg/L).Main outcome measuresSBI and other non-infectious serious illness.Results3778/35 705 (10.6%) of febrile children had fever ≥5 days. Incidence of SBI in children with fever ≥5 days was higher than in those with fever <5 days (8.4% vs 5.7%). Triage urgency, life-saving interventions and intensive care admissions were similar for fever ≥5 days and <5 days. Several warning signs had good rule in value for SBI with specificities >0.90, but were observed infrequently (range: 0.4%–17%). Absence of warning signs was not sufficiently reliable to rule out SBI (sensitivity 0.92 (95% CI 0.87–0.95), negative likelihood ratio (LR) 0.34 (0.22–0.54)). CRP <20 mg/L was useful for ruling out SBI (negative LR 0.16 (0.11–0.24)). There were 66 cases (1.7%) of non-infectious serious illnesses, including 21 cases of Kawasaki disease (0.6%), 28 inflammatory conditions (0.7%) and 4 malignancies.ConclusionChildren with prolonged fever have a higher risk of SBI, warranting a careful clinical assessment and diagnostic workup. Warning signs of SBI occurred infrequently but, if present, increased the likelihood of SBI. Although rare, clinicians should consider important non-infectious causes of prolonged fever.
Molnupiravir and risk of post-acute sequelae of covid-19: cohort study
Authors: Xie Yan , Choi Taeyoung , Al-Aly Ziyad 
Published: April 2023

Abstract

Objective
To examine whether treatment with the antiviral agent molnupiravir during the first five days of SARS-CoV-2 infection is associated with reduced risk of post-acute adverse health outcomes.

Design
Cohort study.

Setting
US Department of Veterans Affairs.

Participants
229 286 participants who tested positive for SARS-CoV-2 between 5 January 2022 and 15 January 2023, had at least one risk factor for progression to severe covid-19, and survived the first 30 days after testing positive were enrolled. 11 472 participants received a prescription for molnupiravir within five days of the positive test result and 217 814 received no covid-19 antiviral or antibody treatment (no treatment group).

Main outcome measures
Risks of post-acute sequelae of SARS-CoV-2 (PASC, defined based on a prespecified set of 13 post-acute sequelae), post-acute death, post-acute hospital admission, and each individual post-acute sequela between the molnupiravir group and no treatment group were examined after application of inverse probability weighting to balance the treatment and no treatment groups. Post-acute outcomes were ascertained from 30 days after the first SARS-CoV-2 positive test result until end of follow-up. Risks on the relative scale (relative risk or hazard ratio) and absolute scale (absolute risk reduction at 180 days) were estimated.

Results
Compared with no treatment, molnupiravir use within five days of a positive SARS-CoV-2 test result was associated with reduced risk of PASC (relative risk 0.86 (95% confidence interval 0.83 to 0.89); absolute risk reduction at 180 days 2.97% (95% confidence interval 2.31% to 3.60%)), post-acute death (hazard ratio 0.62 (0.52 to 0.74); 0.87% (0.62% to 1.13%)), and post-acute hospital admission (0.86 (0.80 to 0.93); 1.32% (0.72% to 1.92%)). Molnupiravir was associated with reduced risk of eight of the 13 post-acute sequelae: dysrhythmia, pulmonary embolism, deep vein thrombosis, fatigue and malaise, liver disease, acute kidney injury, muscle pain, and neurocognitive impairment. Molnupiravir was also associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received at one or two vaccine doses, and had received a booster dose, and in people with primary SARS-CoV-2 infection and reinfection.

Conclusions
In people with SARS-CoV-2 infection and at least one risk factor for progression to severe covid-19, compared with no treatment, molnupiravir use within five days of infection was associated with reduced risk of PASC in people who had not received a covid-19 vaccine, had received one or two vaccine doses, and had received a booster dose, and in those with primary SARS-CoV-2 infection and reinfection. Among people at high risk of progression to severe covid-19, molnupiravir use within five days of SARS-CoV-2 infection may be a viable approach to reduce the risk of PASC.
Food handlers’ knowledge, attitudes and self-reported practices regarding safe food handling in charitable food assistance programmes in the eThekwini District, South Africa: cross-sectional study
Authors: Makhunga Sizwe Earl , Macherera Margaret , Hlongwana Khumbulani 
Published: April 2023

ObjectiveThis study aimed to assess food handlers’ knowledge, attitudes and self-reported practices towards safer donated foods.DesignThis cross-sectional study was conducted from January to May 2021.SettingThis study was conducted in the eThekwini District, South Africa.ParticipantsA convenience sampling-based cross-sectional survey of food handlers (n=252) served as the study’s main source of data. A total of eight study sites across five municipal planning regions of eThekwini District were visited. The principal investigator administered the validated structured standardised questionnaire, using participants’ language of choice, which was either English or isiZulu. All the questions in the questionnaire were asked in exactly the same manner, following the same flow, in order to avoid bias and ensure consistency. Furthermore, the close-ended nature of questions in the questionnaire mitigated the risks of question manipulation. The questionnaire was adapted from the WHO’s five keys to a safer food manual.Primary and secondary outcome measuresThe primary outcome was the knowledge, attitudes and self-reported practices towards safer donated foods. The secondary outcomes were the sanitary conditions of infrastructure and facilities, food handlers’ observed food handling behaviour and nutritional information/labelling.ResultsThe results show that the food handlers had good knowledge, positive attitude and acceptable behaviours towards safe food handling and general hygiene, with mean scores (SD) of 62.8 (14.6), 92.5 (14.1) and 80.4 (13.3), respectively. Significant correlations were found between knowledge and attitudes (p=0001), knowledge and practices (p<0001), and attitudes and practices (p=0.02). However, the correlations between knowledge versus attitude and attitude versus practice were poor (Spearman’s r<0.3), and the association between knowledge versus practice was moderate (0.3–0.7). The majority of food handlers (92.5%) did not understand the value of thorough cooking and temperature control. About 53% of respondents acknowledged to never adequately reheating cooked meals, 5% did not see the significance of preventing cross-contamination and 5% were unsure.ConclusionsDespite the relatively positive knowledge, attitude and practice levels of the food handlers, safe food handling and hygiene practices, such as thorough cooking and temperature control, properly reheating cooked meals and taking precautions to prevent cross-contamination, require some emphasis.
Associations between autistic traits and early ear and upper respiratory signs: a prospective observational study of the Avon Longitudinal Study of Parents and Children (ALSPAC) geographically defined childhood population
Authors: Hall Amanda , Maw Richard , Iles-Caven Yasmin , Gregory Steven , Rai Dheeraj , Golding Jean 
Published: April 2023

ObjectiveTo determine whether early ear and upper respiratory signs are associated with the development of high levels of autistic traits or diagnosed autism.DesignLongitudinal birth cohort: Avon Longitudinal Study of Parents and Children (ALSPAC).SettingArea centred on the city of Bristol in Southwest England. Eligible pregnant women resident in the area with expected date of delivery between April 1991 and December 1992 inclusive.Participants10 000+ young children followed throughout their first 4 years. Their mothers completed three questionnaires between 18–42 months recording the frequency of nine different signs and symptoms relating to the upper respiratory system, as well as ear and hearing problems.Outcome measuresPrimary—high levels of autism traits (social communication, coherent speech, sociability, and repetitive behaviour); secondary—diagnosed autism.ResultsEarly evidence of mouth breathing, snoring, pulling/poking ears, ears going red, hearing worse during a cold, and rarely listening were associated with high scores on each autism trait and with a diagnosis of autism. There was also evidence of associations of pus or sticky mucus discharge from ears, especially with autism and with poor coherent speech. Adjustment for 10 environmental characteristics made little difference to the results, and substantially more adjusted associations were at p<0.001 than expected by chance (41 observed; 0.01 expected). For example, for discharge of pus or sticky mucus from ears the adjusted odds ratio (aOR) for autism at 30 months was 3.29 (95% CI 1.85 to 5.86, p<0.001), and for impaired hearing during a cold the aOR was 2.18 (95% CI 1.43 to 3.31, p<0.001).ConclusionsVery young children exhibiting common ear and upper respiratory signs appear to have an increased risk of a subsequent diagnosis of autism or demonstrated high levels of autism traits. Results suggest the need for identification and management of ear, nose and throat conditions in autistic children and may provide possible indicators of causal mechanisms.
Building an understanding of Ethnic minority people’s Service Use Relating to Emergency care for injuries: the BE SURE study protocol
Authors: Baghdadi Fadi , Evans Bridie Angela , Goodacre Steve , John Paul Anthony , Hettiarachchi Thanuja , John Ann , Lyons Ronan A , Porter Alison , Safari Solmaz , Siriwardena Aloysius Niroshan , Snooks Helen , Watkins Alan , Williams Julia , Khanom Ashrafunnesa 
Published: April 2023

IntroductionInjuries are a major public health problem which can lead to disability or death. However, little is known about the incidence, presentation, management and outcomes of emergency care for patients with injuries among people from ethnic minorities in the UK. The aim of this study is to investigate what may differ for people from ethnic minorities compared with white British people when presenting with injury to ambulance and Emergency Departments (EDs).Methods and analysisThis mixed methods study covers eight services, four ambulance services (three in England and one in Scotland) and four hospital EDs, located within each ambulance service. The study has five Work Packages (WP): (WP1) scoping review comparing mortality by ethnicity of people presenting with injury to emergency services; (WP2) retrospective analysis of linked NHS routine data from patients who present to ambulances or EDs with injury over 5 years (2016–2021); (WP3) postal questionnaire survey of 2000 patients (1000 patients from ethnic minorities and 1000 white British patients) who present with injury to ambulances or EDs including self-reported outcomes (measured by Quality of Care Monitor and Health Related Quality of Life measured by SF-12); (WP4) qualitative interviews with patients from ethnic minorities (n=40) and focus groups—four with asylum seekers and refugees and four with care providers and (WP5) a synthesis of quantitative and qualitative findings.Ethics and disseminationThis study received a favourable opinion by the Wales Research Ethics Committee (305391). The Health Research Authority has approved the study and, on advice from the Confidentiality Advisory Group, has supported the use of confidential patient information without consent for anonymised data. Results will be shared with ambulance and ED services, government bodies and third-sector organisations through direct communications summarising scientific conference proceedings and publications.
Association of trajectories of non-high-density lipoprotein cholesterol concentration with risk of cardiovascular disease: the Kailuan Study
Authors: Ding Xiong , Zhou Hui , Yue Qing , Shu Zhe , Ma Xiaoxu , Li Yun , Wu Shouling 
Published: April 2023

ObjectivesThis study aimed to assess the association between longitudinal change in non-high-density lipoprotein cholesterol (non-HDL-C) and subsequent cardiovascular disease (CVD) risk.DesignA retrospective study.SettingData were obtained from the Kailuan Study, a dynamic cohort study initiated in 2006 in Tangshan, China.ParticipantsThe current study included 41 085 participants (mean age 53.9±11.6 years) free of CVD events in or before 2012. The non-HDL-C trajectory was developed according to the repeated measurement during 2006–2012 surveys to predict the CVD risk from 2012 to 2020.Primary outcome measuresCVD events included myocardial infarction and stroke.Results3 discrete non-HDL-C trajectories were identified: low-increasing (n=20 038), moderate-increasing (n=17 987) and high-increasing (n=3060). During 8 years of follow-up, 1797 CVD events were documented. Relative to the low-increasing pattern, adjusted HRs were 1.25 (95% CI: 1.13 to 1.38) for the moderate-increasing pattern and 1.46 (95% CI: 1.24 to 1.71) for the high-increasing pattern after adjustment for potential confounders such as age, sex, education background, smoking status, drinking status, physical activity, body mass index, low-density lipoprotein cholesterol, hypertension, diabetes and lipid-lowering medications.ConclusionsChanges in non-HDL-C were significantly associated with subsequent risk of CVD events, and participants with a high-increasing pattern had a higher CVD risk. Long-term monitoring of non-HDL-C could be useful to improve the prediction of CVD risk.Trial registration numberChiCTR-TNC-1100148.
A national longitudinal cohort study of factors contributing to UK medical students’ mental ill-health symptoms
Authors: Medisauskaite Asta , Silkens Milou E W M , Rich Antonia 
Published: April 2023

BackgroundThe mental health of current medical students is predictive of their mental health as future doctors. The prevalence of anxiety, depression and burnout is high among medical students, but less is known about the occurrence of other mental ill-health symptoms, such as eating or personality disorders, and factors contributing to mental ill-health.Aims(1) To explore the prevalence of various mental ill-health symptoms in medical students and (2) to investigate what medical school factors and students’ attitudes contribute to these mental ill-health symptoms.MethodsBetween November 2020 and May 2021, medical students from nine geographically spread medical schools in the UK participated by completing online questionnaires at two points in time, approximately 3 months apart.ResultsOf the 792 participants who filled in the questionnaire at baseline, over half experienced medium to high somatic symptoms (50.8%; 402) and drank alcohol at hazardous levels (62.4%; 494). Adjusted longitudinal data analysis of 407 students who completed the follow-up questionnaire demonstrated that less supportive educational climates that were more competitive and less centralised around the students, lower feelings of belongingness, greater stigma towards mental ill-health and lower intentions to seek help for mental ill-health, all contributed to students’ mental ill-health symptoms.ConclusionsMedical students experience a high prevalence of various mental ill-health symptoms. This study suggests that medical school factors and students’ attitudes towards mental ill-health are significantly associated with students’ mental health.
Causal links between socioeconomic status, leisure sedentary behaviours and gastro-oesophageal reflux disease: a multivariable two-sample Mendelian randomisation study
Authors: Lian Xingji , Lin Yifen , Peng Xiaohui , Wang Yanhui , He Ting , He Ziyong , Gu Wenlong , Wang Hongwu , He Feng , Huang Yuyu 
Published: April 2023

IntroductionWe implemented a two-sample multivariable Mendelian randomisation (MR) analyses to estimate the causal effect of socioeconomic status and leisure sedentary behaviours on gastro-oesophageal reflux disease (GERD).MethodsIndependent single-nucleotide polymorphisms associated with socioeconomic status and leisure sedentary behaviours at the genome-wide significance level from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) UK Biobank were selected as instrumental variables. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. Univariable and multivariable two-sample MR analyses, using inverse variance weighted method for primary analyses, were performed to jointly evaluate the effect of socioeconomic status and leisure sedentary behaviours on GERD risk.ResultsThree socioeconomic status, including educational attainment (OR 0.46; 95% CI 0.30 to 0.69; p<0.001), average total household income before tax (OR 0.65; 95% CI 0.47 to 0.90; p=0.009) and Townsend Deprivation Index at recruitment (OR 1.60; 95% CI 1.06 to 2.41; p=0.026), were independently and predominately responsible for the genetic causal effect on GERD. In addition, one leisure sedentary behaviour, such as time spent watching television, was independently and predominately responsible for genetic causal effect on GERD (OR 3.74; 95% CI 2.89 to 4.84; p<0.001). No causal effects of social activities and driving on GERD were observed.ConclusionsGenetically predicted Townsend Deprivation Index at recruitment and leisure watching television were causally associated with increased risk of GERD, and age at completion of full-time education and average total household income before tax were causally associated with decreased risk of GERD.