bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Registrar Clinical Encounters in Training (ReCEnT) cohort study: updated protocol
Authors: Davey Andrew , Tapley Amanda , van Driel Mieke , Holliday Elizabeth , Fielding Alison , Ball Jean , Mulquiney Katie , Fisher Katie , Spike Neil , Clarke Lisa , Moad Dominica , Ralston Anna , Patsan Irena , Mundy Benjamin , Turner Alexandria , Tait Jordan , Tuccitto Lucrezia , Roberts Sarah , Magin Parker 
Published: December 2022

Abstract
Background
During vocational general practice training, the content of each trainee’s (in Australia, registrars’) in-consultation clinical experience is expected to entail a breadth of conditions that exemplify general practice, enabling registrars to gain competency in managing common clinical conditions and common clinical scenarios. Prior to the Registrar Clinical Encounters in Training (ReCEnT) project there was little research into the content of registrars’ consultations despite its importance to quality of training. ReCEnT aims to document the consultation-based clinical and educational experiences of individual Australian registrars.

Methods
ReCEnT is an inception cohort study. It is comprised of closely interrelated research and educational components. Registrars are recruited by participating general practice regional training organisations. They provide demographic information about themselves, their skills, and their previous training. In each of three 6-month long general practice training terms they provide data about the practice where they work and collect data from 60 consecutive patient encounters using an online portal. Analysis of data uses standard techniques including linear and logistic regression modelling. The ReCEnT project has approval from the University of Newcastle Human Research Ethics Committee, Reference H-2009–0323.

Discussion
Strengths of the study are the granular detail of clinical practice relating to patient demographics, presenting problems/diagnoses, medication decisions, investigations requested, referrals made, procedures undertaken, follow-up arranged, learning goals generated, and in-consultation help sought; the linking of the above variables to the presenting problems/diagnoses to which they pertain; and a very high response rate. The study is limited by not having information regarding severity of illness, medical history of the patient, full medication regimens, or patient compliance to clinical decisions made at the consultation. Data is analysed using standard techniques to answer research questions that can be categorised as: mapping analyses of clinical exposure; exploratory analyses of associations of clinical exposure; mapping and exploratory analyses of educational actions; mapping and exploratory analyses of other outcomes; longitudinal ‘within-registrar’ analyses; longitudinal ‘within-program’ analyses; testing efficacy of educational interventions; and analyses of ReCEnT data together with data from other sources. The study enables identification of training needs and translation of subsequent evidence-based educational innovations into specialist training of general practitioners.
Serum soluble T cell immunoglobulin mucin domain-3 as an early predictive marker for severity of acute pancreatitis; a retrospective analysis
Authors: Wang Fushuang , Zhu Minghui , Meng Yao , Lin Min 
Published: December 2022

Abstract
Background
Early prediction of severe acute pancreatitis (SAP) plays an important role in timely treatment decisions. Soluble T cell immunoglobulin and mucin domain-3 (sTIM-3) has been applied as a potential biomarker for the prediction of many diseases, while its predictive ability for AP severity remains largely unexplored. In this study, we aimed to identify whether serum sTIM-3 could be used as an indicator of AP severity in the early stage of the disease.

Methods
A retrospective study was conducted. The enrolled AP patients should meet the 2012 Atlanta guideline and have an onset to admission ≤ 48 h.

Results
A total of 94 AP patients were enrolled in the current analysis, including 42 (45%), 35 (37%), and 17 (18%) patients were diagnosed as mild AP (MAP), moderately SAP (MSAP), and SAP, respectively. SAP patients had significantly higher the white blood cells (WBCs) count, red blood cells (RBCs) count, C-reactive protein (CRP) level, direct bilirubin level, creatinine and procalcitonin levels compared with MAP and MSAP patients. Among SAP and MSAP patients, significantly higher APACHE II, BISAP, and MCTSI scores were observed compared with MAP patients, and there was significant difference in APACHE II and BISAP scores between SAP and MSAP patients. Stepwise multivariate linear regression analysis showed that the concentrations of serum sTIM-3, as well as the BISAP and MCTSI scores, were significantly associated with the severity of AP. The areas under the ROC curve were 0.914 (95% CI, 0.865-0.963), 0.855 (95%CI, 0.742-0.968) 0.853 (95%CI, 0.768-0.938), and 0.746 (95%CI, 0.633-0.860) for BISAP score, APACHE II score, sTIM-3 level, and MCTSI score, respectively.

Conclusions
Serum sTIM-3 might be ultimately incorporated into a predictive system for assessing the severity of AP.
Application of a WeChat-based mini-app as a patient reminder in Helicobacter pylori eradication: a prospective multi-center randomized controlled study
Authors: Sun Kefang , Chen Yishu , Wang Zhenzhen , Liu Yi , Pan Yue , Mao Xinli , Xu Lei , Jin Chaohui , Chen Ming , Yu Chaohui , Li Lan 
Published: December 2022

Abstract
Background
To improve the eradication rate of H. pylori, researchers have investigated the role of WeChat-based mini-app as an electronic reminding system in H. pylori treatment.

Methods
Subjects from three medical centers were divided into two groups. Patients in the daily mini-app-based notification system group received daily notifications via the WeChat mini-app. Patients in the control group received one-time verbal education on the first clinical visit. Both groups received a 14-day quadruple therapy to eradicate H. pylori infection. Eradication rate, compliance, adverse events and satisfaction were evaluated.

Results
Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted. The eradication rate in the daily mini-app-based notification system group was slightly higher compared with the control group (ITT analysis: 76.70% vs. 70.73%, p = 0.312; PP analysis: 85.87% vs. 82.86%, p = 0.562). The compliance was significantly higher in the daily mini-app-based notification system group (ITT analysis: 85.52% vs. 70.48%, p = 0.028; PP analysis: 92.39% vs. 81.90%, p = 0.030). The adverse event rates were similar between the two groups (PP analysis: 36.96% vs. 40.95%, p = 0.566). No significant difference in eradication rate was seen in each subgroup analysis by age, place of residence, grade of education, or endoscopic findings.

Conclusion
The study showed that daily mini-app-based notification improved patient compliance but not H. pylori eradication rate.
Trial registration The research was registered in the Chinese Clinical Trial Registry (ChiCTR2000031011, 21/03/2020).
Clinical characteristics and risk factors for a prolonged length of stay of patients with asymptomatic and mild COVID-19 during the wave of Omicron from Shanghai, China
Authors: Hu Chen , Liu Yu-Kai , Sun Qi-Di , Du Zheng , Fang Yu-Qiang , Guo Fei , Wang Yu-Bo , He Yong , Cen Yuan , Zeng Fan 
Published: December 2022

Abstract
Background
This study aims to investigate the clinical characteristics and the length of hospital stay (LOS), as well as risk factors for prolonged LOS in a cohort of asymptomatic and mild COVID-19 patients infected with the Omicron variant.

Methods
A total of 1166 COVID-19 patients discharged from the inpatient ward of the largest makeshift hospital (May 8–10, 2022) in Shanghai, China, were included. The demographics, medical history, and the lowest and admission cycle threshold (Ct) values of the RT-PCR tests for SARS-CoV-2 genes of the open reading frame 1ab (Ct-ORF) and the nucleocapsid protein (Ct-N) during hospitalization were recorded. Patients with LOS > 7 days, or LOS ≤ 7 days were included in the Prolonged group or the Control group, separately. The clinical characteristics and LOS of the participants in the two groups were described and compared. Multivariate Logistic and linear regression analyses were applied to explore the risk factors for prolonged LOS. The diagnostic efficacy of the lowest and admission Ct values for the Prolonged group was tested via the receiver operating characteristic (ROC) curve analysis.

Results
The median LOS was 6 days in the total study population. The age was older (45.52 ± 14.78 vs. 42.54 ± 15.30, P = 0.001), while both the lowest and admission Ct-ORF (27.68 ± 3.88 vs. 37.00 ± 4.62, P < 0.001; 30.48 ± 5.03 vs. 37.79 ± 3.81, P < 0.001) and Ct-N (25.79 ± 3.60 vs. 36.06 ± 5.39, P < 0.001; 28.71 ± 4.95 vs. 36.95 ± 4.59, P < 0.001) values were significantly lower in the Prolonged group. There were more mild cases in the Prolonged group (23.8% vs. 11.5%, P < 0.001). The symptom spectrum differed between the two groups. In multivariate analyses, age, disease category, and the lowest Ct-N values were shown to be associated with prolonged LOS. Besides, both the lowest and admission Ct-ORF (AUC = 0.911 and 0.873) and Ct-N (AUC = 0.912 and 0.874) showed robust diagnostic efficacy for prolonged LOS.

Conclusions
Our study firstly reports the clinical characteristics and risk factors for prolonged LOS during the wave of the Omicron epidemic in Shanghai, China. These findings provide evidence for the early identification of asymptomatic and mild COVID-19 patients at a high risk of prolonged hospitalization who may require early intervention, and long-term monitoring and management.
Tender cervical lymphadenitis as a herald of multi-system inflammatory syndrome in COVID-19 infection of children and adolescents: a report of two cases
Authors: Wanninayake Leonard , de Abrew Gayathree , Logeshwaran Dinusha , Weerasinghe Chathurika , Gowinna Piyumi , Mettananda Sachith , Premaratna Ranjan 
Published: December 2022

Abstract
Background
Post-COVID-19 multisystem inflammatory syndrome (MIS) has been increasingly recognized but fever with isolated tender cervical lymphadenitis as the initial presentation has been rarely reported. We present 2 female patients one a child and the other an adolescent.

Case presentation
Case 1 was a 13-year-old girl who presented with tender cervical lymphadenopathy and fever 3-weeks post-COVID-19, and then developed features of MIS 5 days later. Case 2, also female, was 18 years old. She had no history of COVID-19 infection or immunization but had a serologic diagnosis of COVID-19. She similarly presented with fever and tender cervical lymphadenopathy, and then progressed rapidly to develop features of MIS. Both patients responded well to treatment with immunosuppressants and intravenous immunoglobulin.

Conclusion
Tender cervical lymphadenopathy could be the herald of multi-system inflammatory syndrome following COVID-19 infection among children and adolescents, which the clinicians must have a good suspicion about.
Oncogenic KRAS alters splicing factor phosphorylation and alternative splicing in lung cancer
Authors: Lo April , McSharry Maria , Berger Alice H. 
Published: December 2022

Abstract
Background
Alternative RNA splicing is widely dysregulated in cancers including lung adenocarcinoma, where aberrant splicing events are frequently caused by somatic splice site mutations or somatic mutations of splicing factor genes. However, the majority of mis-splicing in cancers is unexplained by these known mechanisms. We hypothesize that the aberrant Ras signaling characteristic of lung cancers plays a role in promoting the alternative splicing observed in tumors.

Methods
We recently performed transcriptome and proteome profiling of human lung epithelial cells ectopically expressing oncogenic KRAS and another cancer-associated Ras GTPase, RIT1. Unbiased analysis of phosphoproteome data identified altered splicing factor phosphorylation in KRAS-mutant cells, so we performed differential alternative splicing analysis using rMATS to identify significantly altered isoforms in lung epithelial cells. To determine whether these isoforms were uniquely regulated by KRAS, we performed a large-scale splicing screen in which we generated over 300 unique RNA sequencing profiles of isogenic A549 lung adenocarcinoma cells ectopically expressing 75 different wild-type or variant alleles across 28 genes implicated in lung cancer.

Results
Mass spectrometry data showed widespread downregulation of splicing factor phosphorylation in lung epithelial cells expressing mutant KRAS compared to cells expressing wild-type KRAS. We observed alternative splicing in the same cells, with 2196 and 2416 skipped exon events in KRASG12V and KRASQ61H cells, respectively, 997 of which were shared (p < 0.001 by hypergeometric test). In the high-throughput splicing screen, mutant KRAS induced the greatest number of differential alternative splicing events, second only to the RNA binding protein RBM45 and its variant RBM45M126I. We identified ten high confidence cassette exon events across multiple KRAS variants and cell lines. These included differential splicing of the Myc Associated Zinc Finger (MAZ). As MAZ regulates expression of KRAS, this splice variant may be a mechanism for the cell to modulate wild-type KRAS levels in the presence of oncogenic KRAS.

Conclusion
Proteomic and transcriptomic profiling of lung epithelial cells uncovered splicing factor phosphorylation and mRNA splicing events regulated by oncogenic KRAS. These data suggest that in addition to widespread transcriptional changes, the Ras signaling pathway can promote post-transcriptional splicing changes that may contribute to oncogenic processes.
Galectin-9 expression clinically associated with mature dendritic cells infiltration and T cell immune response in colorectal cancer
Authors: Wang Yang , Zheng Ruizhi , Zhang Yanhui , Guo Yuhong , Hui Zhenzhen , Wang Peijing , Sun Yan 
Published: December 2022

Abstract
Background
Galectin-9 is a member of the galectin family and has been reported to have a tumor-promoting or antitumor effect in response to the immune microenvironment. However, the immunomodulatory effect of galectin-9 in colorectal cancer (CRC) remains unclear. The antigen presentation and antitumor immune effects of galectin-9 in CRC were examined in this study.

Methods
The expression of galectin-9, dendritic cell markers (CD208 and CD1a), T-cell markers (CD3 and CD8) and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) was assessed using immunohistochemistry in CRC samples. The correlation between galectin-9 and immune cells or immunomodulatory factors was also evaluated via multiple gene expression databases.

Results
The level of galectin-9 was decreased in mismatch repair-proficient patients compared with mismatch repair-deficient patients (p = 0.0335). GSEA showed that the regulatory mechanism of galectin-9 in CRC was related to a variety of immune pathways. Galectin-9 expression was strongly correlated with immune cell infiltration and immunomodulators (all p < 0.0001). In the relationship between galectin-9 expression and the infiltration of DCs, there was a negative correlation in CD1a + immature DCs (R = -0.263, p = 0.042). A strong positive correlation was observed in CD208 + mature DCs (R = 0.391, p < 0.01). Patients with high galectin-9 expression also exhibited abundant CD8 + T-cell and CD3 + T-cell infiltration.

Conclusion
Collectively, our findings provide evidence that galectin-9 may increase the antitumor immune response of patients with CRC. DCs play an important role in galectin-9-mediated antitumor immune responses, which provides further insight into the development of immunotherapy.
Evaluating impact of Nd: YAG laser associated defects on optical quality of hydrophilic and hydrophobic intraocular lenses using visualization of light propagation and USAF test targets
Authors: Borkenstein A. F. , Borkenstein E. M. , Omidi P. , Langenbucher A. 
Published: December 2022

Abstract
Background
Neodymium:yttrium aluminum garnet (Nd:YAG) laser capsulotomy is a well-accepted, safe, and effective measure in the treatment of posterior capsule opacification. However, iatrogenic intraocular lens damage is a relatively common side effect that happens due to inappropriate focusing during the procedure. This experimental study analyzes the impact of YAG-pits to obtain qualitative information.

Methods
Acrylic, monofocal hydrophilic and hydrophobic intraocular lenses (IOLs) with 6.0 mm optic and the with the same power (21D) were studied. First, all measurements were done with unmodified IOLs. Damage was intentionally created, performing YAG-pits (n = 5) in the central area of the lens optic (3.0 mm) using a photodisruption laser with the same energy level of 1.8 mJ. To simulate the cruciate pattern, the 5 defects were created in a cross shape within the 3.0 mm optical zone. Afterwards, all laboratory measurements were repeated: These included the United States Air Force (USAF) resolution test chart to study the imaging performance of the IOL, light field measurements to show the course of the rays behind the IOL and the modulation transfer function (MTF) measurements were analyzed.

Results
Evaluating USAF showed that unmodified lenses produced a sharper image. Damaged lenses led to a more blurred image and to the impression of a lower contrast with a kind of halo/glare effect. The light field measurement showed that YAG-pits led to a kind of dispersion and scattering effect, which was higher in hydrophobic IOLs. MTF showed a deterioration in damaged hydrophilic and hydrophobic IOLs, respectively.

Conclusion
Our experimental study confirms that YAG-pits can reduce imaging quality of intraocular lenses. These defects behave as a new Huygens source, distribute a spherical wave that additionally illuminate the background of the USAF target. It can be assumed that material properties of the IOL (water content, refractive index) play an important role and affect results. The impact level is strongly dependent on the number, size and position of YAG-pits within the optic. Limitation: Only monofocal IOLs have been investigated so far, further tests with various IOL optics have to follow. In addition, simulating the circular pattern of YAG capsulotomy is necessary.
Protocol for a multi-site randomized controlled trial of a stepped-care intervention for emergency department patients with panic-related anxiety
Authors: Sung Sharon C. , Lim Leslie , Lim Swee Han , Finkelstein Eric A. , Chin Steven Lim Hoon , Annathurai Annitha , Chakraborty Bibhas , Strauman Timothy J. , Pollack Mark H. , Ong Marcus Eng Hock 
Published: December 2022

Abstract
Background
Approximately 40% of Emergency Department (ED) patients with chest pain meet diagnostic criteria for panic-related anxiety, but only 1–2% are correctly diagnosed and appropriately managed in the ED. A stepped-care model, which focuses on providing evidence-based interventions in a resource-efficient manner, is the state-of-the art for treating panic disorder patients in medical settings such as primary care. Stepped-care has yet to be tested in the ED setting, which is the first point of contact with the healthcare system for most patients with panic symptoms.

Methods
This multi-site randomized controlled trial (RCT) aims to evaluate the clinical, patient-centred, and economic effectiveness of a stepped-care intervention in a sample of 212 patients with panic-related anxiety presenting to the ED of Singapore’s largest public healthcare group. Participants will be randomly assigned to either: 1) an enhanced care arm consisting of a stepped-care intervention for panic-related anxiety; or 2) a control arm consisting of screening for panic attacks and panic disorder. Screening will be followed by baseline assessments and blocked randomization in a 1:1 ratio. Masked follow-up assessments will be conducted at 1, 3, 6, and 12 months. Clinical outcomes will be panic symptom severity and rates of panic disorder. Patient-centred outcomes will be health-related quality of life, daily functioning, psychiatric comorbidity, and health services utilization. Economic effectiveness outcomes will be the incremental cost-effectiveness ratio of the stepped-care intervention relative to screening alone.

Discussion
This trial will examine the impact of early intervention for patients with panic-related anxiety in the ED setting. The results will be used to propose a clinically-meaningful and cost-effective model of care for ED patients with panic-related anxiety.

Trial registration
ClinicalTrials.gov NCT03632356. Retrospectively registered 15 August 2018.
Evaluation of a pilot, community-led mental illness de-stigmatization theater intervention in rural Uganda
Authors: Lee Yang Jae , Rauben Kazungu , Liu Curtis , Kim Rebecca , van der Velde Nina , Taylor Chelsea , Walsh Alyssa , Asasira Mildred , Katongole Ivan , Hatfield-King Jolee , Blackwell Scott , Iheanacho Theddeus , Christ Ryan , Ssekalo Ibrahim 
Published: December 2022

Abstract
Background
In rural areas of low- and middle- income countries, mental health care is often unavailable and inaccessible, and stigma is a major barrier to treatment. Destigmatization can increase treatment-seeking attitudes, community support, and acceptance of individuals suffering from mental illness. This study’s primary objective was to evaluate the impact of a community-led, theater-based destigmatization campaign for mental illness conducted in the Busoga region of Eastern Uganda.

Methods
One hundred residents of the Busoga region were randomly selected via cluster sampling to complete a structured questionnaire assessing mental health stigma. Four focus groups were conducted for qualitative data on mental health stigma. Common misconceptions and specific points of stigma were identified from these responses, and local village health team personnel developed and performed a culturally-adapted theatrical performance addressing these points. Changes in perceptions of mental illness were measured among 57 attendees using two measures, the Broad Acceptance Scale (designed to reflect factors that contribute to structural stigma) and Personal Acceptance Scale (designed to reflect factors that contribute to interpersonal, or public stigma), before and after the performance.

Results
There was a significant increase in acceptance according to the Broad Acceptance Scale (p < .001) and Personal Acceptance Scale (p < .001). Qualitative responses from play attendees also indicated a decrease in stigma and an increased sense of the importance of seeking treatment for mentally ill patients.

Conclusion
This study shows community-led, theater intervention may be an effective tool for the destigmatization of mental illness in rural areas of Uganda. Larger studies are needed to further test the efficacy of this approach and potential for longer-term scalabilityand sustainability.