bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo
Authors: Watson-Jones Deborah , Kavunga-Membo Hugo , Grais Rebecca F , Ahuka Steve , Roberts Natalie , Edmunds W John , Choi Edward M , Roberts Chrissy H , Edwards Tansy , Camacho Anton , Lees Shelley , Leyssen Maarten , Spiessens Bart , Luhn Kerstin , Douoguih Macaya , Hatchett Richard , Bausch Daniel G , Muyembe Jean-Jacques 
Published: March 2022

IntroductionEbola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness.Methods and analysisThis open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants.Ethics and disseminationApproved by Comité National d’Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l’Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access.Trial registration numberNCT04152486.
Perspective of geriatric patients on advance care planning in Denmark: a qualitative study
Authors: Dahmke Kirstine , Nielsen-Hannerup Elisabeth , Madsen Ida Søndergaard , Rerup Sofie , Ramberg Emilie , Lembeck Maurice A , Pedersen Hanne , Holm Ellen Astrid 
Published: March 2022

ObjectiveMost previous studies on advance care planning (ACP) have focused on patients with specific diseases and only a few on frail ageing individuals. We therefore decided to examine the perspective of geriatric patients on ACP. Our research questions include if, when, with whom and with which content geriatric patients wish to have ACP conversations.DesignParticipants were interviewed either in the hospital or in their own home. The interviewer followed a semistructured interview guide. Interviews were transcribed and analysed using the systemic text condensation method.SettingGeriatric department in a regional hospital in a rural area in Region Zealand, Denmark.ParticipantsWe included 11 geriatric patients aged above 65 who had been referred for geriatric inpatient or outpatient assessment. Participants were clinically judged by experienced geriatricians to have sufficient physical and mental capacity to take part in an interview.ResultsThis study’s main finding is that geriatric patients have varying preferences and feelings towards ACP. Some expressed concerns about ACP, especially regarding personal fear to talk about end-of-life (EOL) decisions, and whether a busy healthcare system has the resources to conduct ACP. Proper timing of ACP seemed unrelated to specific age but related to perception of health situation. The health professional involved should be well trained and a person the participant could trust. Most participants wanted family members to participate. Concerning content, participants mentioned quality of life, fear of losing their spouse, earlier experience with death, and practical concerns regarding funeral and will.ConclusionAmong geriatric patients, feelings towards ACP are mixed. Even participants who were generally positive towards the concept uttered concerns about the circumstances when talking about EOL topics. Health professionals therefore should approach ACP discussions with caution. Further studies aiming to develop guidelines describing the proper way to introduce and perform ACP in this patient group are needed.
Poisonings with ADHD medication in children under the age of 5 years in Australia: a retrospective study, 2004–2019
Authors: Arbaeen Abrar , Wheate Nial J , Cairns Rose 
Published: March 2022

ObjectiveTo describe the temporal relationships in attention-deficit hyperactivity disorder (ADHD) medication poisoning exposures in children; describe patient demographics, medications involved, poisoning exposure reasons and disposition.DesignA population-based, retrospective cohort study of calls to Australia’s largest Poisons Information Centre. Poisoning exposure counts and dispensing-adjusted rates were modelled with Poisson, quasi-Poisson and negative binomial regression where appropriate.SettingCalls to the New South Wales Poisons Information Centre and dispensings on the Pharmaceutical Benefits Scheme.PatientsChildren under the age of 5 years.ResultsThere were 1175 poisoning exposures to ADHD psychostimulants, 2004–2019; averaging 73 per year. Accidental poisonings accounted for 94% of cases. Methylphenidate was most frequently implicated (63%). Thirty-four per cent of cases were referred to hospital and a further 21% of calls were made by hospital staff. Poisoning exposure counts for all ADHD psychostimulants increased by 2.7% (95% CI=0.42% to 4.9%) per year; however, this differed by agent. Methylphenidate poisoning exposures increased by 5.2% per year (95% CI=4.3% to 6.1%), lisdexamfetamine increased by 62% per year (95% CI=48% to 76%), while dexamphetamine poisoning exposures decreased by 5.5% per year (95% CI=−9.5% to −1.4%). These trends are reflected in the number of dispensings; however, dispensings increased at a faster rate than exposures. When poisoning exposures were expressed as dispensing-adjusted rates, there was a 16% decrease (95% CI=−20% to −13%) per year.ConclusionsADHD medication use has increased, associated with an increased number of paediatric poisoning exposures. However, poisoning exposures per dispensed prescription has decreased. The majority of cases required hospitalisation, indicating the need for further poisoning prevention strategies.
Combination cancer immunotherapy targeting TNFR2 and PD-1/PD-L1 signaling reduces immunosuppressive effects in the microenvironment of pancreatic tumors
Authors: Zhang Xiaozhen , Lao Mengyi , Xu Jian , Duan Yi , Yang Hanshen , Li Muchun , Ying Honggang , He Lihong , Sun Kang , Guo Chengxiang , Chen Wen , Jiang Haitao , Zhang Xiaoyu , Bai Xueli , Liang Tingbo 
Published: March 2022

BackgroundsIn advanced pancreatic ductal adenocarcinoma (PDAC), immune therapy, including immune checkpoint inhibitors, has limited efficacy, encouraging the study of combination therapy.MethodsTumor necrosis factor receptor 2 (TNFR2) was analyzed via immunohistochemistry, immunofluorescence, western blotting, and ELISAs. The in vitro mechanism that TNFR2 regulates programmed cell death 1 ligand 1 (PD-L1) was investigated using immunofluorescence, immunohistochemistry, flow cytometry, western blotting, and chromatin immunoprecipitation (ChIP). In vivo efficacy and mechanistic studies, using C57BL/6 mice and nude mice with KPC cell-derived subcutaneous and orthotopic tumors, employed antibodies against TNFR2 and PD-L1. Survival curves were constructed for the orthotopic model and a genetically engineered PDAC model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre). Mass cytometry, immunohistochemistry, and flow cytometry analyzed local and systemic alterations in the immunophenotype.ResultsTNFR2 showed high expression and is a prognostic factor in CD8+ T cell-enriched pancreatic cancer. TNFR2 promotes tumorigenesis and progression of pancreatic cancer via dual effect: suppressing cancer immunogenicity and partially accelerating tumor growth. TNFR2 positivity correlated with PD-L1, and in vitro and in vivo, it could regulate the expression ofPDL1at the transcription level via the p65 NF-κB pathway. Combining anti-TNFR2 and PD-L1 antibodies eradicated tumors, prolonged overall survival in pancreatic cancer, and induced strong antitumor immune memory and secondary prevention by reducing the infiltration of Tregs and tumor-associated macrophages and inducing CD8+ T cell activation in the PDAC microenvironment. Finally, the antitumor immune response derived from combination therapy is mainly dependent on CD8+ T cells, partially dependent on CD4+ T cells, and independent of natural killer cells.ConclusionsAnti-TNFR2 and anti-PD-L1 combination therapy eradicated tumors by inhibiting their growth, relieving tumor immunosuppression, and generating robust memory recall.
Opportunistic screening for asymptomatic left ventricular dysfunction in type 2 diabetes mellitus
Authors: Zhou Mi , Huang Duo , Cheng Yangyang , Lau Yee Man , Lai Wing Hon , Lau Yuk-Ming , Hai JoJo , Lau Chu Pak , Chan Esther W , Yue Wen Sheng , Zuo Ming-Liang , Yin Li Xue , Feng Yingqing , Tan Ning , Chen Jiyan , Li Xin Li , Tse Hung Fat , Lee Chi Ho , Chow Wing-Sun , Siu Chung Wah , Wong Chun Ka 
Published: March 2022

Abstract

Background
International guidelines recommend natriuretic peptide biomarker-based screening for patients at high heart failure (HF) risk to allow early detection. There have been few reports about the incorporation of screening procedure to existing clinical practice.

Objective
To implement screening of left ventricular dysfunction in patients with type 2 diabetes mellitus (DM).

Method
A prospective screening study at the DM complication screening centre was performed.

Results
Between 2018 and 2019, 1043 patients (age: 63.7±12.4 years; male: 56.3%) with mean glycated haemoglobin of 7.25%±1.34% were recruited. 81.8% patients had concomitant hypertension, 31.1% had coronary artery disease, 8.0% had previous stroke, 5.5% had peripheral artery disease and 30.7% had chronic kidney disease (CKD) stages 3–5. 43 patients (4.1%) had an elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration above the age-specific diagnostic thresholds for HF, and 43 patients (4.1%) had newly detected atrial fibrillation (AF). The prevalence of elevated NT-proBNP increased with age from 0.85% in patients aged &lt;50 years to 7.14% in those aged 70–79 years and worsening kidney function from 0.43% in patients with CKD stage 1 to 42.86% in CKD stage 5. In multivariate logistic regression, male gender (OR: 3.67 (1.47–9.16), p = 0.005*), prior stroke (OR: 3.26 (1.38–7.69), p = 0.007*), CKD (p&lt;0.001*) and newly detected AF (OR: 7.02 (2.65–18.57), p&lt;0.001*) were significantly associated with elevated NT-proBNP. Among patients with elevated NT-proBNP, their mean left ventricular ejection fraction (LVEF) was 51.4%±14.7%, and 45% patients had an LVEF &lt;50%.

Conclusion
NT-proBNP and ECG screening could be implemented with relative ease to facilitate early detection of cardiovascular complication and improve long-term outcomes.
Eosinophilic granulomatosis with polyangiitis exhibits T cell activation and IgG4 immune response in the tissue; comparison with IgG4-related disease
Authors: Kubo Satoshi , Kanda Ryuichiro , Nawata Aya , Miyazaki Yusuke , Kawabe Akio , Hanami Kentaro , Nakatsuka Keisuke , Saito Kazuyoshi , Nakayamada Shingo , Tanaka Yoshiya 
Published: March 2022

ObjectiveTo study the pathophysiological differences of EGPA and IgG4-related disease (RD) by clarifying their clinical, pathological and immunological features.MethodsClinical and pathological findings were compared in patients with EGPA and IgG4-RD. Peripheral blood mononuclear cells were used for comprehensive flow cytometric analysis.ResultsAn elevation of the IgG4 level was found in all EGPA cases, with the accompanying pathological findings of lymphocytic infiltration and fibrosis observed in 30.8% patients, and the elevation of IgG4/IgG ratio in 61.5% patients. However, actual IgG4 levels, as well as the degree of the infiltration of IgG4-positive plasma cells, were still higher in patients with IgG4-RD than patients with EGPA. Examination by ACR/EULAR classification criteria showed only 13.6% of the EGPA patients met entry criteria, while all of them met the exclusion criteria. In regard to the immunophenotyping, EGPA patients had increases in activated CD4 and CD8 T cells compared with the healthy controls. However, no such similar changes occurred in IgG4-RD patients. On the other hand, both the EGPA and IgG4-RD patient groups had correlated increased plasmablasts and Tfh. These results indicate the presence of two axes: namely, the activation of T cells and that of B cells. Both axes are present in EGPA, but the T cell activation axis was not observed in IgG4-RD.ConclusionsThe elevation of serum IgG4 as well as pathological IgG4 infiltration are not specific. Meanwhile, EGPA and IgG4-RD differ in immunological phenotypes, indicating the possible importance of the predominant activation of T cells in the development of vasculitis.
Difference between delayed anastomosis and early anastomosis in damage control laparotomy affecting the infusion volume and NPWT output volume: is infusion restriction necessary in delayed anastomosis? A single-center retrospective analysis
Authors: Tanahashi Yohta , Sato Hisaho , Kawakami Akiko , Sasaki Shusaku , Nishinari Yutaka , Ishida Kaoru , Kojika Masahiro , Endo Shigeatsu , Inoue Yoshihiro , Sasaki Akira 
Published: March 2022

ObjectivesDuring temporary abdominal closure (TAC) with damage control laparotomy (DCL), infusion volume and negative-pressure wound therapy (NPWT) output volume are associated with the success and prognosis of primary fascial closure. The same may also hold true for anastomosis. The aim of this research is to evaluate whether the difference between early anastomosis and delayed anastomosis in DCL is related to infusion volume and NPWT output volume.MethodsThis single-center retrospective analysis targeted patients managed with TAC during emergency surgery for trauma or intra-abdominal sepsis between January 2011 and December 2019. It included patients who underwent repair/anastomosis/colostomy in the first surgery and patients who underwent intestinal resection in the first surgery followed by delayed anastomosis with no intestinal continuity.ResultsSeventy-three patients were managed with TAC using NPWT, including 19 cases of repair, 17 of colostomy, and 37 of anastomosis. In 16 patients (trauma 5, sepsis 11) with early anastomosis and 21 patients (trauma 16, sepsis 5) with delayed anastomosis, there was no difference in the infusion volume (p=0.2318) or NPWT output volume (p=0.7128) 48 hours after surgery. Additionally, there was no difference in the occurrence of suture failure (p=0.8428). During the second-look surgery after 48 hours, the anastomosis was further postponed for 48% of the patients who underwent delayed anastomosis. There was no difference in the infusion volume (p=0.0783) up to the second-look surgery between the patients whose delayed anastomosis was postponed and those who underwent delayed anastomosis, but there was a tendency toward a large NPWT output volume (p=0.024) in the postponed delayed anastomosis group.ConclusionDelayed anastomosis may be managed with the same infusion volume as that used for early anastomosis. There is also the option of postponing anastomosis if the planned delayed anastomosis is complicated.Level of evidenceTherapeutic/Care Management, Level IV.
Diluting quark flavor hierarchies using dihedral symmetry
Authors: Srivastava Ayushi , Levy Miguel , Das Dipankar 
Published: March 2022

AbstractWe present a $$D_4$$

D
4

flavored extension of the SM which provides an intuitive reasoning for the masses and mixing patterns in the quark sector. In our model, the Cabibbo mixing angle becomes related to the ratio of two vacuum expectation values. In fact, the orders of magnitude of the CKM matrix elements are readily obtained from the hierarchical nature of the vacuum expectation values. Moreover, we also show that the smallness of the off-Cabibbo elements in the CKM matrix is strongly connected to the heaviness of the third generation of quarks.
The Influence of Mixed Teaching Mode on the Learning Effects of Psychology Students’ Experiment Course in Higher Vocational Colleges
Authors: Quan Haiying , Guo Zimeng , Ni Rongjing , Li Chen , Deng Xin 
Published: March 2022

In this paper, we are going to analyze the influence of mixed teaching mode on the teaching effect of psychology students’ experiment courses in higher vocational colleges. To realize and verify these claims, 80 psychology students of grade 2020 in our school were selected for observation. Class 1 of the psychology major in our school was randomly selected as the observation group (n = 40) and Class 2 as the control group (n = 40). The mixed teaching mode and the traditional teaching mode were adopted, respectively. After intervention, the experimental examination results, experimental report score, general evaluation results of the experiment, and experimental pass rate of the observation group were higher than those before intervention

P
<
0.05

. The control group had no significant change before and after intervention

P
>
0.05

. The experimental examination results, experimental report score, general evaluation results of the experiment, and experimental pass rate of the observation group were all higher than those of the control group, with statistical significance

P
<
0.05

. The results show that in the observation group, 92.50% of the students believed that the mixed teaching mode could arouse the enthusiasm for learning and improve the activity of the experimental class. 97.50% of the students thought that the mixed teaching mode could stimulate students’ interest in learning and improve the ability of experimental operation. 100.00% of the students thought the mixed teaching mode could be helpful in understanding the experimental. The evaluation result of the teaching mode was significantly higher than that of the control group, and the comparison result was statistically significant

P
<
0.05

. After receiving the mixed teaching mode, the observation group had a higher satisfaction with the teaching effect, with a satisfaction rate of 95.00%. The control group had low satisfaction with the teaching effect, with a satisfaction rate of 52.50%, and the difference was statistically significant

P
<
0.05

. Through the application of the mixed teaching mode combining online and offline, psychology students in higher vocational colleges can achieve better learning results and improve students’ evaluation and satisfaction of teaching effect of the mixed teaching mode of psychology experiment teaching mode in higher vocational colleges.
Efficacy of Super-Mini-PCNL and Ureteroscopy in Kidney Stone Sufferers and Risk Factors of Postoperative Infection
Authors: Yuan Wenbing , Li Yingyi , Dai Yu , Luo Cheng , Zhang Hui , Xiong Haijun 
Published: March 2022

To investigate the efficacy of super-mini-PCNL (SMP) and ureteroscopy in kidney stone (KS) sufferers and learn the risk factors of postoperative infection. A retrospective analysis was performed on 180 KS sufferers who were diagnosed and treated in our hospital from May 2019 to May 2021. They were enrolled into an observation group (OG, n = 104) and a control group (CG, n = 76) based on different treatment methods. Therein, the former was treated with SMP, while the latter was treated with ureteroscopy. The operation time, blood loss, hospital stay, recent stone-free rate (one week after operation), changes of serum creatinine (SCr), blood urea nitrogen (BUN), and cystatin C (CysC) levels before and after operation and complications were compared. Those sufferers were assigned to infected and uninfected groups based on their postoperative infection. The risk factors were assessed through logistic regression, and the model formula was established. The predictive value of this model for infection was tested through RO. Compared with CG, the operation time of the OG was longer, the blood loss and hospital stay were lower

P
<
0.05

, and the stone-free rate was higher

P
<
0.05

. Renal function indexes before and after treatment

P
>
0.05

and postoperative complications revealed no significant difference

P
>
0.05

. Logistic regression analysis manifested that preoperative urinary tract infection (OR: 4.690, 95% CI: 1.170–18.802), preoperative blood glucose level (OR: 11.188, 95% CI: 2.106–59.442), positive urine culture (OR: 10.931, 95% CI: 2.453–48.705), and infectious stones (OR: 3.951, 95% CI: 1.020–15.300) were independently related to infection. The risk prediction equation is

logit

p

=
−
8.913
+
1.545
×
X
1
+
2.415
×
X
2
+
2.392
×
X
3
+
1.374
×
X
4

, with a goodness-of-fit value of 0.545. The AUC is 0.930, so SMP is superior to ureteroscopy in KS sufferers. Preoperative urinary tract infection, preoperative blood glucose level, positive urine culture, and infectious stones are independently related to infection.
FDA Approval Summary: Ivosidenib for the Treatment of Patients with Advanced Unresectable or Metastatic, Chemotherapy Refractory Cholangiocarcinoma with an IDH1 Mutation
Authors: Casak Sandra J. , Pradhan Shan , Fashoyin-Aje Lola A. , Ren Yi , Shen Yuan-Li , Xu Yuan , Chow Edwin Chiu Yuen , Xiong Ye , Zirklelbach Jeanne Fourie , Liu Jiang , Charlab Rosane , Pierce William F. , Fesenko Nataliya , Beaver Julia A. , Pazdur Richard , Kluetz Paul G. , Lemery Steven J. 
Published: March 2022

Abstract
On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease. The approval was based on data from Study AG120-C-005 (ClarIDHy), a double-blind placebo-controlled trial that randomly allocated (2:1) patients to receive either ivosidenib or placebo. Independently assessed progression-free survival (PFS) was the primary endpoint. With a median follow-up of 6.9 months, the HR for PFS was 0.37 [95% confidence interval (CI), 0.25–0.54; P &lt; 0.0001). Overall survival (OS) was the key secondary endpoint. At the final analysis of OS, with 70.5% of patients in the placebo arm receiving ivosidenib post disease progression, a non–statistically significant improvement in the ivosidenib arm with an HR = 0.79 (95% CI, 0.56–1.12) and median OS of 10.3 months (95% CI, 7.8–12.4) and 7.5 months (95% CI, 4.8–11.1) in the ivosidenib and placebo arms, respectively, were reported. Adverse reactions occurring in &gt;20% of patients receiving ivosidenib were fatigue/asthenia, nausea, diarrhea, abdominal pain, ascites, vomiting, cough, and decreased appetite. Adverse reactions occurring in &gt;20% of patients receiving placebo were fatigue/asthenia, nausea, abdominal pain, and vomiting. This is the first approval for the subset of patients with CCA harboring an IDH1 mutation.