bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between photoperiod and variation in circadian rhythms in tomato
Authors: Xiang Yanli , Sapir Thomas , Rouillard Pauline , Ferrand Marina , Jiménez-Gómez José M. 
Published: April 2022

Abstract
Background
Many biological processes follow circadian rhythmicity and are controlled by the circadian clock. Predictable environmental changes such as seasonal variation in photoperiod can modulate circadian rhythms, allowing organisms to adjust the timing of their biological processes to the time of the year. In some crops such as rice, barley or soybean, mutations in circadian clock genes have altered photoperiod sensitivity, enhancing their cultivability in specific seasons and latitudes. However, how changes in circadian rhythms interact with the perception of photoperiod in crops remain poorly studied. In tomato, the appearance during domestication of mutations in EMPFINDLICHER IM DUNKELROTEN LICHT 1 (EID1, Solyc09g075080) and NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED GENE 2 (LNK2, Solyc01g068560) delayed both the phase and period of its circadian rhythms. The fact that variation in period and phase are separated in tomato provides an optimal tool to study how these factors affect the perception of photoperiod.

Results
Here we develop tomato near isogenic lines carrying combinations of wild alleles of EID1 and LNK2 and show that they recreate the changes in phase and period that occurred during its domestication. We perform transcriptomic profiling of these near isogenic lines under two different photoperiods, and observe that EID1, but not LNK2, has a large effect on how the tomato transcriptome responds to photoperiod. This large effect of EID1 is likely a consequence of the global phase shift elicited by this gene in tomato's circadian rhythms.

Conclusions
Our study shows that changes in phase that occurred during tomato domestication determine photoperiod perception in this species, while changes in period have little effect.
Pulmonary valve perforation with multiple cardiac anomalies: a case report
Authors: Chen Yan , Gao Huanhuan , Mou Yun , Zheng Zhelan 
Published: April 2022

Abstract
Background
Large pulmonary valve perforation, which is rarely seen with infective endocarditis, general atrophy, or congenital fenestration, often leads to potentially fatal outcomes, including heart failure.

Case presentation
Transthoracic and transesophageal echocardiographic evaluation of a 69-year-old woman revealed a severely eccentric pulmonary regurgitation with concomitant pulmonary valve stenosis, patent ductus arteriosus, patent foramen ovale, and pulmonary artery aneurysm. In the operation, a large perforation was found in the pulmonary valve leaflet. She underwent complicated surgery that involved closure of the congenital heart defects and replacement of a pulmonary valve with successful results. But the cause of her pulmonary valve perforation remained undetermined.

Conclusion
This case highlights two important points: the need for timely management of congenital heart disease and being aware of the possibility of pulmonary valve perforation, which in this case was indicated by an eccentric pulmonary regurgitant jet seen on echocardiography.
Retrospective analysis of patterns of opioid overdose and interventions delivered at a tertiary hospital emergency department: impact of COVID-19
Authors: Potaka Katherine L. , Freeman Rebecca , Soo Danny , Nguyen Nam-Anh , Sim Tin Fei , Moullin Joanna C. 
Published: April 2022

Abstract
Background
Opioid-related overdoses cause substantial numbers of preventable deaths. Naloxone is an opioid antagonist available in take-home naloxone (THN) kits as a lifesaving measure for opioid overdose. As the emergency department (ED) is a primary point of contact for patients with high-risk opioid use, evidence-based recommendations from the Society of Hospital Pharmacists of Australia THN practice guidelines include the provision of THN, accompanied by psychosocial interventions. However, implementation of these guidelines in practice is unknown. This study investigated ED opioid-related overdose presentations, concordance of post-overdose interventions with the THN practice guidelines, and the impact, if any, of the SARS-CoV-2 (COVID-19) pandemic on case presentations.

Methods
A single-centre retrospective audit was conducted at a major tertiary hospital of patients presenting with overdoses involving opioids and non-opioids between March to August 2019 and March to August 2020. Patient presentations and interventions delivered by the paramedics, ED and upon discharge from the ED were collated from medical records and analysed using descriptive statistics, chi square and independent T-tests.

Results
The majority (66.2%) of patients presented to hospital with mixed drug overdoses involving opioids and non-opioids. Pharmaceutical opioids were implicated in a greater proportion (72.1%) of overdoses than illicit opioids. Fewer patients presented in March to August 2020 as compared with 2019 (26 vs. 42), and mixed drug overdoses were more frequent in 2020 than 2019 (80.8% vs. 57.1%). Referral to outpatient psychology (22.0%) and drug and alcohol services (20.3%) were amongst the most common post-discharge interventions. Naloxone was provided to 28 patients (41.2%) by the paramedics and/or ED. No patients received THN upon discharge.

Conclusions
This study highlights opportunities to improve ED provision of THN and other interventions post-opioid overdose. Large-scale multi-centre studies are required to ascertain the capacity of EDs to provide THN and the impact of COVID-19 on opioid overdose presentations.
Establishing the content validity of a new emergency department patient-reported experience measure (ED PREM): a Delphi study
Authors: Bull Claudia , Crilly Julia , Latimer Sharon , Gillespie Brigid M. 
Published: April 2022

AbstractBackgroundPatient-reported experience measures aim to capture the patient’s perspective of what happened during a care encounter and how it happened. However, due to a lack of guidance to support patient-reported experience measure development and reporting, the content validity of many instruments is unclear and ambiguous. Thus, the aim of this study was to establish the content validity of a newly developed Emergency Department Patient-Reported Experience Measure (ED PREM).MethodsED PREM items were developed based on the findings of a systematic mixed studies review, and qualitative interviews with Emergency Department patients that occurred during September and October, 2020. Individuals who participated in the qualitative interviews were approached again during August 2021 to participate in the ED PREM content validation study. The preliminary ED PREM comprised 37 items. A two-round modified, online Delphi study was undertaken where patient participants were asked to rate the clarity, relevance, and importance of ED PREM items on a 4-point content validity index scale. Each round lasted for two-weeks, with 1 week in between for analysis. Consensus was a priori defined as item-level content validity index scores of ≥0.80. A scale-level content validity index score was also calculated.ResultsFifteen patients participated in both rounds of the online Delphi study. At the completion of the study, two items were dropped and 13 were revised, resulting in a 35-item ED PREM. The scale-level content validity index score for the final 35-item instrument was 0.95.ConclusionsThe newly developed ED PREM demonstrates good content validity and aligns strongly with the concept of Emergency Department patient experience as described in the literature. The ED PREM will next be administered in a larger study to establish its’ construct validity and reliability. There is an imperative for clear guidance on PREM content validation methodologies. Thus, this study may inform the efforts of other researchers undertaking PREM content validation.
Emergency cricothyroidotomy in difficult airway simulation – a national observational study of Air Ambulance crew performance
Authors: Andresen Åke Erling L. , Kramer-Johansen Jo , Kristiansen Thomas 
Published: April 2022

Abstract
Background
Advanced prehospital airway management includes complex procedures carried out in challenging environments, necessitating a high level of technical and non-technical skills. We aimed to describe Norwegian Air Ambulance-crews’ performance in a difficult airway scenario simulation, ending with a “cannot intubate, cannot oxygenate”-situation.

Methods
The study describes Air Ambulance crews’ management of a simulated difficult airway scenario. We used video-observation to assess time expenditure according to pre-defined time intervals and technical and non-technical performance was evaluated according to a structured evaluation-form.

Results
Thirty-six crews successfully completed the emergency cricothyroidotomy with mean procedural time 118 (SD: ±70) seconds. There was variation among the crews in terms of completed procedural steps, including preparation of equipment, patient- monitoring and management. The participants demonstrated uniform and appropriate situational awareness, and effective communication and resource utilization within the crews was evident.

Conclusions
We found that Norwegian Air Ambulance crews managed a prehospital “cannot intubate, cannot oxygenate”-situation with an emergency cricothyroidotomy under stressful conditions with effective communication and resource utilization, and within a reasonable timeframe. Some discrepancies between standard operating procedures and performance are observed. Further studies to assess the impact of check lists on procedural aspects of airway management in the prehospital environment are warranted.
Computed tomography features and clinicopathological characteristics of gastric glomus tumor
Authors: Xing Jing-jing , Huang Wen-peng , Wang Fang , Chai Ya-ru , Gao Jian-bo 
Published: April 2022

Abstract
Background
Gastric glomus tumor (GGT) is a rare neoplasm that is difficult to distinguish from other gastric submucosal tumors due to a lack of diagnostic experience. The goal of this study was to better understand GGT by looking at its clinicopathological features, computed tomography (CT) features, and differential diagnosis.

Methods
The clinical data and CT findings of 21 pathologically confirmed GGT patients were examined. The clinical characteristics and CT findings of benign GGT were compared to gastric stromal tumors (GST) (n = 30) and heterotopic pancreas (n = 30).

Results
The 21 cases included six males and fifteen females ranging in age from 42 to 64 years. The lesions were found in the gastric body in four cases and the antrum in seventeen. GGT was diagnosed as benign in 20 cases and malignant in one. In benign cases, the glomus cells were small, uniform, showed perivascular hemangiopericytoma‑like or solid nest‑like structures. Obvious mitotic figures were observed in the malignant case. SMA staining was positive in the tumor cells. A quasi-round or round solid mass protruded into the gastric cavity in 20 benign cases, with a clear and smooth edge. The long to short diameter ratio was 1.01 ± 0.15. All of the benign cases had obvious enhancement, with homogeneous enhancement in ten cases and heterogeneous enhancement in ten cases, as well as central filling enhancement in 12 cases. The ratio of CT value of lesion to abdominal aorta in arterial phase and venous phase were (0.41 ± 0.11) and (0.81 ± 0.20), which were significantly higher than GST and heterotopic pancreas. The irregular mass broke through the gastric wall and invaded liver with poorly defined boundary and internal necrosis, heterogeneous persistent moderate enhancement with thickening blood supply arteries was seen in one malignant case with a long diameter of 150 mm and a thick diameter of 30 mm.

Conclusions
CT enhancement usually shows persistent obvious enhancement, especially in arterial phase, which provides important value for the diagnosis. CT findings can help in the differential diagnosis of GGT and other submucosal tumors.
Determine the impact of a structured pharmacist-led medication review - a controlled intervention study to optimise medication safety for residents in long-term care facilities
Authors: Lexow M. , Wernecke K. , Sultzer R. , Bertsche T. , Schiek S. 
Published: April 2022

Abstract
Background
Medication reviews contribute to protecting long-term care (LTC) residents from drug related problems (DRPs). However, few controlled studies have examined the impact on patient-relevant outcomes so far.

Objective
We examined the impact of a one-time, pharmacist-led medication review on medication changes (primary endpoint) including discontinued medication, the number of chronic medications, hospital admissions, falls, and deaths (secondary endpoints).

Methods
A prospective, controlled intervention study was performed in three LTC facilities. In the intervention group (IG), after performing a medication review, a pharmacist gave recommendations for resolving DRPs to physicians, nurses and community pharmacists. The control group (CG) received usual care without a medication review. (i) We assessed the number of medication changes and the secondary endpoints in both groups before (t0) and after (t1, t2) the intervention. (ii) Additionally, the medication review was evaluated in the IG with regard to identified DRPs, the healthcare professional’s feedback on the forwarded pharmacist recommendations and whether DRPs were finally resolved.

Results
107 (IG) and 104 (CG) residents were enrolled. (i) More medication changes were identified in the IG than in the CG at t1 (p = 0.001). However, no significant difference was identified at t2 (p = 0.680). Mainly, medication was discontinued in those medication changes. Chronic medications increased in the CG (p = 0.005) at t2 while hospital admissions, falls, and deaths showed no differences. (ii) Overall, 1252 DRPs (median: 10; minimum-maximum: 2–39) were identified. Recommendations for 82% of relevant DRPs were forwarded to healthcare professionals, of which 61% were accepted or clarified. 22% were not accepted, 12% required further review and 6% remained without feedback. 51% of forwarded DRPs were finally resolved.

Conclusions
We found more medication changes in the IG compared to controls. Mostly, medication was discontinued. This suggests that our intervention was successful in discontinuing unnecessary medication. Other clinical outcomes such as falls, hospitalisations, and deaths were not improved due to the one-time intervention. The medication review further identified a high prevalence of DRPs in the IG, half of which were finally resolved.

Trial registration
German Clinical Trials Register, DRKS00026120 (www.drks.de, retrospectively registered 07/09/2021).
Association between age at initial diagnosis and post-metastasis mortality among women with recurrent metastatic breast cancer in China
Authors: Xie Yuxin , Gou Qiheng , Zhang Yingjie , Xie Keqi , Zheng Dan , Luo Chuanxu , Suo Jiaojiao , Zhong Xiaorong , Luo Ting 
Published: April 2022

Abstract
Background
Little is known about whether age at initial diagnosis influences the prognosis of recurrent metastatic breast cancer (rMBC). Here, we analyzed the association between age at initial diagnosis and rMBC mortality in China.

Methods
A total of 1636 women diagnosed with rMBC between 1989 and 2020 at West China Hospital, Sichuan University were included in this study. The age at initial diagnosis was categorized as young (≤ 40 years), middle-aged (41–64 years) and elderly (≥ 65 years). Post-metastasis mortality was the primary outcome and its associated factors were analyzed by Cox proportional hazards models.

Results
During a median follow-up of 5.2 years after initial diagnosis of breast cancer, 620 deaths were identified. Compared with middle-aged patients, elderly patients had a 70% increased risk of post-metastasis mortality (95%CI, 1.24–2.33) after adjusting for demographics, tumor characteristics and treatment modes. Similarly, elderly patients were associated with a 75% increased risk of post-metastasis mortality (95%CI, 1.19–2.59) compared with young patients. Subgroup analyses also showed similar trends.

Conclusion
Our findings suggest that in breast cancer, elderly patients at initial diagnosis face a higher risk of post-metastasis mortality.
Tivozanib in renal cell carcinoma: a systematic review of the evidence and its dissemination in the scientific literature
Authors: Caquelin Laura , Gewily Mohamed , Mottais Wendy , Tebaldi Chloé , Laviolle Bruno , Naudet Florian , Locher Clara 
Published: April 2022

Abstract
Background
Tivozanib (Fotivda) is an anti-angiogenic tyrosine kinase inhibitor that was denied access to the US market by the Food and Drug Administration (FDA). In contrast, it was granted approval by the European Medicines Agency (EMA) for the treatment of Renal Cell Carcinoma in adults. Given the conflicting decisions from these regulatory agencies, the objectives of the following study are (i) to critically review the evidence supporting the approval of tivozanib; (ii) to analyse the dissemination of this evidence in the literature by way of a citation analysis.

Methods
Pivotal trials were searched by two independent reviewers using Medline, Cochrane Library, ClinicalTrials.gov and the European Public Assessment Report. The risk of bias for each trial was then inductively assessed. Articles citing any of these trials were identified using Web of Sciences. Finally, the quality of the citations was evaluated by two independent reviewers according to standard data extraction methods.

Results
The search for primary evidence identified two pivotal studies: TIVO-1 upon which the FDA and the EMA decisions were based, and TIVO-3 which was conducted after the agencies’ decisions had been issued. The TIVO-1 trial presented several limitations that compromised causal inference, in relation to (i) design (absence of blinding, inappropriate comparator, and one-way crossover), (ii) poor internal consistency in the results for the primary endpoint, (iii) a discrepancy between a benefit observed for progression-free survival (HR: 0.80, 95% CI [0.64–0.99]) and the absence of difference for overall survival (HR: 1.25, 95% CI [0.95 – 1.62]). Our citation search protocol identified 229 articles that cited TIVO-1 in the 7 years following its publication, among which 151 (65.9%) citing articles discussing efficacy. Presence of spin was identified in 64 (42.4%) of these 151 citing articles, and 39 (25.8%) additional articles citing results without providing enough elements to interpret the TIVO-1 results.

Conclusion
EMA’s approval was based on a single pivotal trial presenting critical limitations, rendering the results from the trial potentially inconclusive. The broad dissemination of TIVO-1 results in the scientific literature may have been affected by spin or results were presented in an inadequate critical manner.
A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial
Authors: Wu Xin , Feng Hao , Gao Shujun , Feng Hua , Diao Wenjing , Zhang Hongwei , Du Ming , Lou Weihua , Wang Xipeng , Zhu Tao , Zhang Yuyang , Hu Weiguo , Xue Xiaohong , Zhu Zhiling , Xiang Libing , Li Jiarui , Fang Xuhong , Bai Yongrui , Hou Yanli , Yan Weili , Qiu Ling , Yu Hailin , Zhu Shurong , Du Yan , Jiang Hua 
Published: April 2022

Abstract
Background
A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial.

Methods
This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life.

Discussion
The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients.

Trial registration
ClinicalTrials.gov (NCT04934982, Registered on 22 June 2021).
Retrospective analysis of secondary enucleation for uveal melanoma after plaque radiotherapy
Authors: Wang Heng , Zhang Ruiheng , Wang Yining , Chen Rongtian , Liu Yueming , Li Yang , Wei Wenbin 
Published: April 2022

Abstract
Background
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Plaque brachytherapy (PRT) is widely accepted as an effective globe-conserving treatment modality for UM. However, local treatment failure and complications lead to the enucleation of irradiated eyes. We conducted this study to explore the causes and long-term prognosis for UM patients who accepted secondary enucleation after plaque radiotherapy.

Methods
This was a retrospective cohort study. Data of patients who underwent secondary enucleation for UM after plaque radiotherapy, from July 2007 to July 2019, at Beijing Tongren Hospital were analyzed. Kaplan–Meier analysis was performed to assess the probability of indications, metastasis, and metastasis-related death. Cox regression analysis was used to analyze associations of the prognostic factors.

Results
Eight hundred and eighty patients were clinically diagnosed with uveal melanoma and initially treated by iodine-125 plaque radiotherapy, 132 of whom underwent secondary enucleation and pathological examination in the same hospital. Fifty-two (39.4%) eyes were enucleated simply because of uncontrollable neovascular glaucoma (NVG). Forty-four (33.3%) patients suffered from tumor recurrence. Tumor non-response occurred in 18 (13.6%) cases. Ten (7.6%) eyes received enucleation entirely due to other types of glaucoma. Failure to preserve the eyes for other reasons occurred in eight (6.1%) patients. At a median follow-up of 58.1 [IQR: 40.9–90.5] months, the systemic spread was detected in 45 (34.1%) patients, and 38 of them died. On multivariate analysis, tumor largest basal diameter (HR 1.15 [95% CI: 1.01, 1.31]), tumor non-response (HR 7.22 [95% CI: 2.63, 19.82]), and recurrence (HR 3.29 [95% CI: 1.54, 7.07]) were risk factors for metastasis. Increased age (HR 1.54 [95% CI: 1.07, 2.23]), tumor non-response (HR 7.91 [95% CI: 2.79, 22.48]), and recurrence (HR 3.08 [95% CI: 1.13, 7.23]) were risk factors for metastasis-related death.

Conclusions
NVG was the major reason for secondary enucleation for Chinese UM patients after PRT. Tumor non-response and recurrence were associated with a significantly higher risk of long-term metastasis and metastasis-related death.