bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan
Authors: Ikubo Yumiko , Sanada Takayuki Jujo , Hosomi Koji , Park Jonguk , Naito Akira , Shoji Hiroki , Misawa Tomoko , Suda Rika , Sekine Ayumi , Sugiura Toshihiko , Shigeta Ayako , Nanri Hinako , Sakao Seiichiro , Tanabe Nobuhiro , Mizuguchi Kenji , Kunisawa Jun , Suzuki Takuji , Tatsumi Koichiro 
Published: April 2022

Abstract
Background
The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be associated with chronic inflammation; however, the underlying mechanism remains unclear. Recently, altered gut microbiota were found in patients with pulmonary arterial hypertension (PAH) and in experimental PAH models. The aim of this study was to characterize the gut microbiota in patients with CTEPH and assess the relationship between gut dysbiosis and inflammation in CTEPH.

Methods
In this observational study, fecal samples were collected from 11 patients with CTEPH and 22 healthy participants. The abundance of gut microbiota in these fecal samples was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Inflammatory cytokine and endotoxin levels were also assessed in patients with CTEPH and control participants.

Results
The levels of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were elevated in patients with CTEPH. Plasma endotoxin levels were significantly increased in patients with CTEPH (P < 0.001), and were positively correlated with TNF-α, IL-6, IL-8, and MIP-1α levels. The 16S rRNA gene sequencing and the principal coordinate analysis revealed the distinction in the gut microbiota between patients with CTEPH (P < 0.01) and control participants as well as the decreased bacterial alpha-diversity in patients with CTEPH. A random forest analysis for predicting the distinction in gut microbiota revealed an accuracy of 80.3%.

Conclusion
The composition of the gut microbiota in patients with CTEPH was distinct from that of healthy participants, which may be associated with the elevated inflammatory cytokines and endotoxins in CTEPH.
Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: a cross-sectional study
Authors: Yan Yuerong , Xu Mingtong , Wu Muchao , Wang Xiaoyi , Li Feng , Zhang Jin , You Lili , Pan Xiaofang , Feng Weilian , Wu Jiayun , Chen Caixia , Li Xiaohui , Yan Li 
Published: April 2022

Abstract
Background
Both obesity and subclinical hypothyroidism (SCH) have adverse effects on human body, but the relationship between these two conditions remains inconsistent. The presence of thyroid autoantibodies influences thyroid hormone levels, and may further mediate the interaction between obesity and SCH. This study aimed to explore the association among obesity, SCH and thyroid autoantibodies.

Methods
This study was a cross-sectional survey of 2505 subjects. Obesity was defined as a body mass index ≥28 kg/m2. Serum concentrations of thyroid hormones, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were examined. Logistic analysis was used to explore the relation among obesity, SCH and thyroid autoantibodies.

Results
A proportion of 11.54% (289/2505) subjects were obese, and 165 subjects had SCH. The positive rates of thyroid autoantibodies, TPO-Ab and Tg-Ab were 17.64% (442/2505), 11.02% (276/2505) and 14.13% (354/2505), respectively. The proportion of SCH was significantly higher in obese than nonobese subjects among those with positive thyroid autoantibodies [22.41% (13/58) vs. 11.72% (45/384), p = 0.025, χ2 test]. Moreover, obesity was significantly associated with SCH in the presence of thyroid autoantibodies after adjusting for confounding factors (OR 2.212, 95% CI 1.103 to 4.433, p = 0.025). A higher proportion of subjects with obesity had Tg-Ab positivity [17.99% (52/289) vs. 13.63% (302/2216), p = 0.045, χ2 test], and obesity remained significantly associated with Tg-Ab positivity by multiple logistic analysis (OR 1.504, 95% CI 1.077 to 2.101, p = 0.017).

Conclusions
Obesity was associated with SCH in the presence of thyroid autoantibodies. Examination of SCH is recommended in obese subjects with thyroid autoantibody positivity.
Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
Authors: Takeda Tomoki , Yamano Shotaro , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Daghlian George , Hong Young-Kwon , Yoshimatsu Yasuhiro , Hirashima Masanori , Kobashi Yoichiro , Okamoto Kenzo , Kishimoto Takumi , Umeda Yumi 
Published: April 2022

AbstractBackgroundIn Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace.MethodsMale and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days.ResultsCWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages.ConclusionsPulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.Graphical Abstract
Non-linear relationship of gamma-glutamyl transpeptidase to lymphocyte count ratio with the recurrence of hepatocellular carcinoma with staging I–II: a retrospective cohort study
Authors: Li Zeping , Liang Lili , Duan Wen , Zhou Chengmao , Yang Jian-Jun 
Published: April 2022

Abstract
Background
High recurrence rate was a major factor for the poor postoperative prognosis of hepatocellular carcinoma (HCC) patients. The present study was intended to evaluate the association of gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) and the recurrence of HCC with staging I–II in Chinese.

Methods
The retrospective cohort data was derived from the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2018 on 496 patients who underwent radical resection of HCC with staging I–II. Multivariable Cox regression models were used to determine hazard ratios (HR) and 95% confidence interval (CI) for the recurrence of HCC with staging I–II of each GLR tertile category. The restricted cubic spline model was used to find out the threshold effect.

Results
With the low tertile of GLR as the reference, multivariable-adjusted HR and 95% CI of the middle and high tertile categories were 1.748 (1.170–2.612) and 2.078 (1.339–3.227). In addition, there was a positive correlation (HR 1.002; 95% CI 1.001–1.004) and a non-liner relationship was found, whose point was 27.5. When the GLR was less than 27.5, the risk of recurrence increased, obviously with the increase in GLR levels (HR 1.041; 95% CI 1.014–1.068).

Conclusions
The GLR was independently associated with the recurrence of HCC patients with staging I–II. Furthermore, the relationship was positive and no-linear.
Addressing recall bias in (post-)conflict data collection and analysis: lessons from a large-scale health survey in Colombia
Authors: Moreno-Serra Rodrigo , Anaya-Montes Misael , León-Giraldo Sebastián , Bernal Oscar 
Published: April 2022

Abstract
Background
Much applied research on the consequences of conflicts for health suffers from data limitations, particularly the absence of longitudinal data spanning pre-, during- and post-conflict periods for affected individuals. Such limitations often hinder reliable measurement of the causal effects of conflict and their pathways, hampering also the design of effective post-conflict health policies. Researchers have sought to overcome these data limitations by conducting ex-post surveys, asking participants to recall their health and living standards before (or during) conflict. These questions may introduce important analytical biases due to recall error and misreporting.

Methods
We investigate how to implement ex-post health surveys that collect recall data, for conflict-affected populations, which is reliable for empirical analysis via standard quantitative methods. We propose two complementary strategies based on methods developed in the psychology and psychometric literatures—the Flashbulb and test-retest approaches—to identify and address recall bias in ex-post health survey data. We apply these strategies to the case study of a large-scale health survey which we implemented in Colombia in the post-peace agreement period, but that included recall questions referring to the conflict period.

Results
We demonstrate how adapted versions of the Flashbulb and test-retest strategies can be used to test for recall bias in (post-)conflict survey responses. We also show how these test strategies can be incorporated into post-conflict health surveys in their design phase, accompanied by further ex-ante mitigation strategies for recall bias, to increase the reliability of survey data analysis—including by identifying the survey modules, and sub-populations, for which empirical analysis is likely to yield more reliable causal inference about the health consequences of conflict.

Conclusions
Our study makes a novel contribution to the field of applied health research in humanitarian settings, by providing practical methodological guidance for the implementation of data collection efforts in humanitarian contexts where recall information, collected from primary surveys, is required to allow assessments of changes in health and wellbeing. Key lessons include the importance of embedding appropriate strategies to test and address recall bias into the design of any relevant data collection tools in post-conflict or humanitarian contexts.
Design of the PERSPECTIVE study: PERsonalized SPEeCh Therapy for actIVE conversation in Parkinson’s disease (randomized controlled trial)
Authors: Maas J. J. L. , De Vries N. M. , Bloem B. R. , Kalf J. G. 
Published: April 2022

Abstract
Objective
To evaluate the effectiveness of personalized and home-based speech therapy on quality of life, intelligibility, and social participation for people with Parkinson’s disease (PD) who have a reduced intelligibility of speech.

Background
Speech problems in PD have a profound negative impact on social interaction and quality of life. Evidence for speech therapy in PD is growing, but more work remains needed to explore its full potential. Efficacy exists for highly intensive standardized speech treatment programs, but not all patients can comply with this rather intense intervention, especially the more severely affected ones. Here, we aim to study the effectiveness of personalized and home-based (remote) speech therapy in PD on quality of life and speech. The intervention will be supported by a dedicated speech training app. We expect that this approach will improve speech intelligibility and quality of life in patients irrespective of disease stage.

Methods
We will perform a single blind, randomized controlled trial, comparing 8 weeks of speech therapy to no intervention using a waiting list design. A total of 215 PD patients with problems in intelligibility will be recruited by 12 highly experienced speech therapists. All patients will be measured at baseline and after 8 weeks (primary endpoint). Additionally, the experimental group will be re-assessed one more time, after a wash-out period of 24 weeks. The control group will receive deferred treatment after 8 weeks, but without additional follow-up assessments. Our primary outcome is quality of life (as measured with PDQ-39). Secondary outcomes include speech and voice quality, intelligibility, severity of voice and speech complaints, and caregiver burden.

Results
The inclusion of participants has started on March 1, 2019, and is expected to be finalized on April 1, 2021. We expect to have the first results in January 2022.

Conclusions
We will investigate the effectiveness of speech therapy in PD. Particular strengths of our study include a randomized and single-blinded design, the personalized treatment approach, the inclusion of PD patients irrespective of disease stage or severity of the speech complaint, the long-term follow-up, the adequate power, and the use of a patient-relevant primary endpoint. This will allow us to draw firm conclusions about the effectiveness of personalized and remote speech therapy for PD patients in all disease stages.

Trial registration
ClinicalTrials.govNCT03963388. Registered on May 24, 2019
Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial
Authors: Mayer Katharina A. , Budde Klemens , Halloran Philip F. , Doberer Konstantin , Rostaing Lionel , Eskandary Farsad , Christamentl Anna , Wahrmann Markus , Regele Heinz , Schranz Sabine , Ely Sarah , Firbas Christa , Schörgenhofer Christian , Kainz Alexander , Loupy Alexandre , Härtle Stefan , Boxhammer Rainer , Jilma Bernd , Böhmig Georg A. 
Published: April 2022

Abstract
Background
Antibody-mediated rejection (ABMR) is a cardinal cause of renal allograft loss. This rejection type, which may occur at any time after transplantation, commonly presents as a continuum of microvascular inflammation (MVI) culminating in chronic tissue injury. While the clinical relevance of ABMR is well recognized, its treatment, particularly a long time after transplantation, has remained a big challenge. A promising strategy to counteract ABMR may be the use of CD38-directed treatment to deplete alloantibody-producing plasma cells (PC) and natural killer (NK) cells.

Methods
This investigator-initiated trial is planned as a randomized, placebo-controlled, double-blind, parallel-group, multi-center phase 2 trial designed to assess the safety and tolerability (primary endpoint), pharmacokinetics, immunogenicity, and efficacy of the fully human CD38 monoclonal antibody felzartamab (MOR202) in late ABMR. The trial will include 20 anti-HLA donor-specific antibody (DSA)-positive renal allograft recipients diagnosed with active or chronic active ABMR ≥ 180 days post-transplantation. Subjects will be randomized 1:1 to receive felzartamab (16 mg/kg per infusion) or placebo for a period of 6 months (intravenous administration on day 0, and after 1, 2, 3, 4, 8, 12, 16, and 20 weeks). Two follow-up allograft biopsies will be performed at weeks 24 and 52. Secondary endpoints (preliminary assessment) will include morphologic and molecular rejection activity in renal biopsies, immunologic biomarkers in the blood and urine, and surrogate parameters predicting the progression to allograft failure (slope of renal function; iBOX prediction score).

Discussion
Based on the hypothesis that felzartamab is able to halt the progression of ABMR via targeting antibody-producing PC and NK cells, we believe that our trial could potentially provide the first proof of concept of a new treatment in ABMR based on a prospective randomized clinical trial.

Trial registration
EU Clinical Trials Register (EudraCT) 2021-000545-40. Registered on 23 June 2021. ClinicalTrials.gov NCT05021484. Registered on 25 August 2021
Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19: a summary of the protocol and analysis plan for a decentralized randomized controlled trial
Authors: Kaizer Alexander M. , Wild Jessica , Lindsell Christopher J. , Rice Todd W. , Self Wesley H. , Brown Samuel , Thompson B. Taylor , Hart Kimberly W. , Smith Clay , Pulia Michael S. , Shapiro Nathan I. , Ginde Adit A. 
Published: April 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs suitable for decentralized study in outpatients will have efficacy among infected outpatients

Methods
The TREAT NOW platform is designed to accommodate testing multiple agents with the ability to incorporate new agents in the future. TREAT NOW is an adaptive, blinded, multi-center, placebo-controlled superiority randomized clinical trial which started with two active therapies (hydroxychloroquine and lopinavir/ritonavir) and placebo, with the hydroxychloroquine arm dropped shortly after enrollment began due to external evidence. Each arm has a target enrollment of 300 participants who will be randomly assigned in an equal allocation to receive either an active therapy or placebo twice daily for 14 days with daily electronic surveys collected over days 1 through 16 and on day 29 to evaluate symptoms and a modified COVID-19 ordinal outcome scale. Participants are enrolled remotely by telephone and consented with a digital interface, study drug is overnight mailed to study participants, and data collection occurs electronically without in-person interactions.

Discussion
If effective treatments for COVID-19 can be identified for individuals in the outpatient setting before they advance to severe disease, it will prevent progression to more severe disease, reduce the need for hospitalization, and shorten the duration of symptoms. The novel decentralized, “no touch” approach used by the TREAT NOW platform has distinction advantages over traditional in-person trials to reach broader populations and perform study procedures in a pragmatic yet rigorous manner.

Trial registration
ClinicalTrials.gov NCT04372628. Registered on April 30, 2020. First posted on May 4, 2020.
The development of theory-informed participant-centred interventions to maximise participant retention in randomised controlled trials
Authors: Newlands Rumana , Duncan Eilidh , Treweek Shaun , Elliott Jim , Presseau Justin , Bower Peter , MacLennan Graeme , Ogden Margaret , Wells Mary , Witham Miles D. , Young Bridget , Gillies Katie 
Published: April 2022

Abstract
Background
A failure of clinical trials to retain participants can influence the trial findings and significantly impact the potential of the trial to influence clinical practice. Retention of participants involves people, often the trial participants themselves, performing a behaviour (e.g. returning a questionnaire or attending a follow-up clinic as part of the research). Most existing interventions that aim to improve the retention of trial participants fail to describe any theoretical basis for the potential effect (on behaviour) and also whether there was any patient and/or participant input during development. The aim of this study was to address these two problems by developing theory- informed, participant-centred, interventions to improve trial retention.

Methods
This study was informed by the Theoretical Domains Framework and Behaviour Change Techniques Taxonomy to match participant reported determinants of trial retention to theoretically informed behaviour change strategies. The prototype interventions were described and developed in a co-design workshop with trial participants. Acceptability and feasibility (guided by (by the Theoretical Framework of Acceptability) of two prioritised retention interventions was explored during a focus group involving a range of trial stakeholders (e.g. trial participants, trial managers, research nurses, trialists, research ethics committee members). Following focus group discussions stakeholders completed an intervention acceptability questionnaire.

Results
Eight trial participants contributed to the co-design of the retention interventions. Four behaviour change interventions were designed: (1) incentives and rewards for follow-up clinic attendance, (2) goal setting for improving questionnaire return, (3) participant self-monitoring to improve questionnaire return and/or clinic attendance, and (4) motivational information to improve questionnaire return and clinic attendance. Eighteen trial stakeholders discussed the two prioritised interventions. The motivational information intervention was deemed acceptable and considered straightforward to implement whilst the goal setting intervention was viewed as less clear and less acceptable.

Conclusions
This is the first study to develop interventions to improve trial retention that are based on the accounts of trial participants and also conceptualised and developed as behaviour change interventions (to encourage attendance at trial research visit or return a trial questionnaire). Further testing of these interventions is required to assess effectiveness.