bluuebunny/crossref_metadata_2025_split huggingface dataset:
The therapeutic promises of Lianhuaqingke in the mice model of coronavirus pneumonia (HCoV-229E and SARS-CoV-2)
Authors: Wang Mingye , Li Wenyan , Cui Wenwen , Hao Yuanyuan , Mi Yao , Wang Hongtao , Hou Yunlong , Jia Zhenhua 
Published: October 2021

Abstract
Background
Lianhuaqingke (LHQK) has been approved for the treatment of acute tracheobronchitis and exerts a broad-spectrum antiviral effect in our previous study.

Methods
Acute pneumonia caused by HCoV-229E was modeled in BALB/c mice. The anti-viral effect of LHQK was assessed by measuring the lung index and virus titer of lung tissues. The expression levels of pro-inflammatory cytokines in lung tissues and peripheral blood were measured by ELISA. The morphological changes of lung tissues were observed by H&E staining. The subsets of Th cells were assayed by the flow cytometry, including Th0, Th1, Th2, Treg, and Th17. The expression level of MUC5AC in 16HBE cells treated with TNFα was measured by ELISA. Immunofluorescence staining for β-IV tubulin was used to identify the airway epithelial ciliary in the condition-cultured RTE cells treated with TNFα. The direct antiviral effect of LHQK was assessed in vitro in Vero E6 infected by SARS-CoV-2, validated in vivo in the COVID-19 model of hACE2 transgenic mouse by detecting the lung index, the SARS-CoV-2 virus load, and the morphological changes of lung tissues.

Results
LHQK reduced the weight loss and the lung index by inhibiting the HCoV-229E replication and reducing the expression of pro-inflammatory cytokines in lung tissues. An assay for the Th cell subsets in peripheral blood revealed that LHQK could reduce the ratio of Th1/Th2 and increase the Treg/Th17 ratio in a dose-dependent way, which indicated that LHQK could coordinate the Th-mediated immune responses against the virus. In in vitro injury by TNFα, LHQK inhibited MUC5AC expression in 16HBE cells and increased the number of β-IV tubulin positive staining cells in the condition-cultured RTE cells. In the SARS-CoV-2-infected mice, LHQK could reduce weight loss, inhibit viral replication, and alleviate lung tissue damage.

Conclusions
Our results demonstrate that LHQK exerts therapeutic effects on pneumonia caused by HCoVs (HCoV-229E and SARS-CoV-2) in mice, and that the anti-HCoV effects might depend on its immunomodulatory capacities. All these results suggest that LHQK serves as a potential adjuvant for anti-HCoV therapies.
Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) in a phase 2 clinical study
Authors: Padilla Brad , Shields Alan L. , Taylor Fiona , Li Xiaoran , Mcdonald Jeffrey , Green Tanya , Boral Anthony L. , Lin Hui-Min , Akin Cem , Siebenhaar Frank , Mar Brenton 
Published: October 2021

Abstract
Background
Indolent systemic mastocytosis (ISM) is a rare, clonal mast cell neoplasm characterized by severe, unpredictable symptoms. The Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) items compose a Total Symptom Score (TSS), Gastrointestinal Symptom Score (GSS), and Skin Symptom Score (SSS) to assess symptom severity. This study evaluated the psychometric performance of ISM-SAF among ISM patients.

Methods
In PIONEER, a Phase 2 trial evaluating safety and efficacy of selective kinase inhibitor avapritinib in patients with ISM, the 12-item ISM-SAF was administered daily. Psychometric evaluation of score reliability, validity, and clinical interpretation was conducted using the trial data.

Results
Thirty-eight patients contributed to analyses (78.9% female; mean age = 49). Baseline internal consistency reliability (α) for bi-weekly TSS, GSS, and SSS was 0.86, 0.83, and 0.82, respectively. Test–retest reliability among patients exhibiting no change in Patient Global Impression of Symptom Severity (PGIS) between Baseline and Day 15 exceeded 0.74 universally. Construct validity and known-groups analysis showed moderate to strong ISM-SAF score correlation (r = 0.382–0.881) to supportive patient-reported questionnaires (e.g., PGIS and Mastocytosis Quality of Life Questionnaire) symptom and skin scores, and ability to distinguish among clinically unique groups. Correlations of ISM-SAF and other assessment change scores reflect evidence of score sensitivity. Clinically important difference and response estimates were 7–10 and 19, respectively.

Discussion
ISM-SAF produced reliable, construct-valid, sensitive scores when administered in PIONEER to patients in the target population. Results of this study support the use of the ISM-SAF as a reliable and valid measure to evaluate disease symptomology in ISM patients.
Trial registration ClinicalTrials.gov, NCT03731260. Registered 10 October 2018, https://clinicaltrials.gov/ct2/show/study/NCT03731260.
Being a caregiver of a Behçet’s syndrome patient: challenges and perspectives during a complex journey
Authors: Talarico Rosaria , Marinello Diana , Manzo Arianna , Cannizzo Sara , Palla Ilaria , Ticciati Simone , Gaglioti Andrea , Trieste Leopoldo , Pisa Lorenzo , Badalamenti Luciano , Randisi Girolamo , Del Bianco Alessandra , Lorenzoni Valentina , Turchetti Giuseppe , Mosca Marta 
Published: October 2021

AbstractBackgroundAs often seen in many chronic diseases, the disease impact on patients also induces a significant impact on the quality of life (QoL) of caregivers. Caregivers are the ones who are really willing to offer care in the general approach of many aspects of the disease, including the awareness of the diseases itself, the daily management of therapy, and all the potential challenges that living with a chronic disease can include. The main objectives of the study were to explore the perspectives and views of caregivers of Behçet’s syndrome (BS) patients, to study their level of awareness on the disease and the impact that BS may have on their lives by means of a survey co-designed with caregivers and patients with this purpose. A survey was entirely co-designed with a panel of caregivers of patients living with BS patients.ResultsResults show that BS caregivers organise their life according to the needs of the patient, that they (79%) considered themselves as helpful for the patient and 53% of them replied that they can freely express their emotions. Notably, 70% and 68% of the respondents reported they renounced with a variable frequency to sexual relationships due to concerns regarding the health of the partner or to the partner’s illness, respectively. The majority (79%) of respondents indicated that they are familiar with the treatment taken by the patients and that 68% deal with the administration of some medicines. In terms of awareness, a good percentage (64%) of respondents reported to understand the illness and, in terms of education, 68% of participants are willing to take part in training programmes dedicated to BS.ConclusionsThe results of this survey contribute to provide new information on BS caregivers and on their important role, and to identify areas in which new initiatives could provide BS caregivers (and therefore patients) with tools and knowledge that can empower them in reducing the burden of the disease on their lives, on families, and on the patient.
Types of stigma experienced by patients with mental illness and mental health nurses in Indonesia: a qualitative content analysis
Authors: Subu Muhammad Arsyad , Wati Del Fatma , Netrida Netrida , Priscilla Vetty , Dias Jacqueline Maria , Abraham Mini Sarah , Slewa-Younan Shameran , Al-Yateem Nabeel 
Published: October 2021

Abstract
Background
Stigma refers to the discrediting, devaluing, and shaming of a person because of characteristics or attributes that they possess. Generally, stigma leads to negative social experiences such as isolation, rejection, marginalization, and discrimination. If related to a health condition such as mental illness, stigma may affect a person’s illness and treatment course, including access to appropriate and professional medical treatment. Stigma has also been reported to affect patients’ families or relatives, along with professionals who work in mental healthcare settings. Stigma is strongly influenced by cultural and contextual value systems that differ over time and across contexts. However, limited information is available on how types of stigma are experienced by patients with mental illness and mental health nurses in Indonesia.

Method
We explored the stigma-related experiences of 15 nurses and 15 patients in Indonesia. The study design and analysis of interview data were guided by deductive (directed) content analysis.

Results
Five themes emerged. Four themes were patient-related: personal/patients’ stigma, public/social stigma, family stigma, and employment stigma. The fifth theme related to stigma toward healthcare professionals working with patients with mental illnesses, which we categorized as professional stigma.

Conclusions
This study has achieved a deep understanding of the concept of stigma in the Indonesian context. This understanding is a prerequisite for developing appropriate interventions that address this phenomenon and thereby for the development of mental health services in Indonesia. This study may also be transferable to other countries that share similar cultural backgrounds and adhere to traditional and religious value systems.
Integrated traditional Chinese and conventional medicine in the treatment of anemia due to lower-risk myelodysplastic syndrome: study protocol for a randomized placebo-controlled trial
Authors: Zheng Qin , Xu Haitao , Song Luxi , Yan Zeying , Sun Manqin , Peng Xia , Jiang Yiling , Shi Ling , Zhang Aiping , Wu Zhihao , Lu Jiahui , Luo Meihong 
Published: October 2021

AbstractBackgroundErythropoiesis and iron homeostasis are closely related; anemia due to lower-risk myelodysplastic syndromes (MDS) remains difficult to treat. In the last decade, we have been committed to improving the regulation of iron metabolism using traditional Chinese medicine (TCM). Previous studies have found that the TCM Yi Gong San (YGS) can reduce the expression of transferrin by inhibiting hepcidin overexpression caused by inflammation, promote the outward transfer of intracellular iron, and improve the symptoms of anemia. Here, our study aimed to compare the efficacy of a conventional drug with YGS with that of conventional medicine with placebo to provide a scientific basis for making clinical decisions.MethodsA prospective, multicenter, double-blinded, randomized controlled clinical trial will be conducted to evaluate the therapeutic efficacy of conventional medicine combined with YGS with that of conventional medicine alone in the treatment of MDS. A total of 60 patients would be enrolled in this study, with each treatment group (conventional medicine + YGS and conventional medicine + placebo) comprising 30 patients. Oral medication would be administered twice daily for 3 months. All patients would be followed up throughout the 3-month period. The primary outcome was measured by assessing blood hemoglobin level. The secondary outcome was measured by assessing TCM symptom score, iron metabolism, hepcidin levels, and inflammatory factors.DiscussionThis trial would aim to demonstrate the effectiveness and feasibility of YGS in the treatment of lower-risk MDS anemia, as well as its impact on inflammatory factors and iron metabolism in patients with lower-risk MDS.Trial registrationChinese Clinical Trials Registry (http://www.chictr.org.cn/)ChiCTR1900026774. Registered on October 21, 2019.
Scapular stabilization exercise based on the type of scapular dyskinesis versus traditional rehabilitation training in the treatment of periarthritis of the shoulder: study protocol for a randomized controlled trial
Authors: Tang Lan , Chen Kang , Ma Yuhui , Huang Lihua , Liang Juan , Ma Yanhong 
Published: October 2021

Abstract
Background
Periarthritis of the shoulder is a common disease leading to dysfunction of the shoulder joint and have a significant impact on patients’ daily life. Evidence shows that there is a close relationship between scapular dyskinesis (SD) and shoulder diseases. Scapular stabilization exercise has been proved to be efficacious in relieving pain and improving function. However, there is no targeted exercise based on the type of scapular dyskinesis. This study will investigate the potential of scapular stabilization exercise based on the type of scapular dyskinesis in treating periarthritis of the shoulder.

Methods
This study is a prospective, randomized controlled, parallel-group trial, intending to recruit 90 patients diagnosed with periarthritis of the shoulder. Patients will receive scapular stabilization exercise training based on the type of scapular dyskinesis or receive traditional rehabilitation training conducted for 30 min, once a day, for 6 weeks. The primary outcome is Constant-Murley score (CMS), and other outcomes include pain degree, range of motion (ROM), type of scapular dyskinesis, scapula position, and patients’ satisfaction with shoulder function. Assessments will be performed at baseline, 2-, 4- and 6-week treatment, and at the 6-week follow-up after the end of treatment.

Discussion
This study will be the first study to investigate the clinical efficacy of scapular stabilization exercise based on the type of scapular dyskinesis in patients with periarthritis of the shoulder. The results may provide evidence of the effect of targeted scapular stabilization exercise in improving shoulder function and correcting scapular dyskinesis, and provide valuable information for future research.

Trial registration
This study had been registered in the Chinese Clinical Trials Registry. Registration number: ChiCTR2100044332 at March 14, 2021.
Optimization of sepsis therapy based on patient-specific digital precision diagnostics using next generation sequencing (DigiSep-Trial)—study protocol for a randomized, controlled, interventional, open-label, multicenter trial
Authors: Brenner Thorsten , Skarabis Annabell , Stevens Philip , Axnick Jennifer , Haug Peter , Grumaz Silke , Bruckner Thomas , Luntz Steffen , Witzke Oliver , Pletz Mathias W. , Ruprecht Thomas M. , Marschall Ursula , Altin Sibel , Greiner Wolfgang , Berger Marc Moritz ,   for the TIFOnet Critical Care Trials Group
Published: October 2021

Abstract
Background
Sepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures represent a promising alternative. In particular, the plasmatic detection of circulating, cell-free DNA by next-generation sequencing (NGS) has shown to be suitable for identifying disease-causing pathogens in patients with bloodstream infections.

Methods
The DigiSep-Trial is a randomized, controlled, interventional, open-label, multicenter trial characterizing the effect of the combination of NGS-based digital precision diagnostics with standard-of-care microbiological analyses compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis/septic shock. Additional anti-infective expert consultations are provided for both study groups. In 410 patients (n = 205 per arm) with sepsis/septic shock, the study examines whether the so-called DOOR-RADAR (Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) intensive/intermediate care unit length of stay, (2) consumption of antibiotics, (3) mortality, and (4) acute kidney injury (AKI)) can be improved by an additional NGS-based diagnostic concept. We also aim to investigate the cost-effectiveness of this new diagnostic procedure. It is postulated that intensive/intermediate care unit length of stay, mortality rate, incidence of AKI, the duration of antimicrobial therapy as well as the costs caused by complications and outpatient aftercare can be reduced. Moreover, a significant improvement in patient’s quality of life is expected.

Discussion
The authors´ previous work suggests that NGS-based diagnostics have a higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. In combination with the here presented DigiSep-Trial, this work provides the optimal basis to establish a new NGS-driven concept as part of the national standard based on the best possible evidence.

Trial registrations
DRKS-ID DRKS00022782. Registered on August 25, 2020
ClinicalTrials.govNCT04571801. Registered October 1, 2020
The effect of a multidisciplinary lifestyle program for patients with rheumatoid arthritis, an increased risk for rheumatoid arthritis or with metabolic syndrome-associated osteoarthritis: the “Plants for Joints” randomized controlled trial protocol
Authors: Walrabenstein Wendy , van der Leeden Marike , Weijs Peter , van Middendorp Henriët , Wagenaar Carlijn , van Dongen Johanna Maria , Nieuwdorp Max , de Jonge Catharina Sophia , van Boheemen Laurette , van Schaardenburg Dirkjan 
Published: October 2021

AbstractLow-grade inflammation and metabolic syndrome are seen in many chronic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Lifestyle interventions which combine different non-pharmacological therapies have shown synergizing effects in improving outcomes in patients with other chronic diseases or increased risk thereof, especially cardiovascular disease. For RA and metabolic syndrome-associated OA (MSOA), whole food plant-based diets (WFPDs) have shown promising results. A WFPD, however, had not yet been combined with other lifestyle interventions for RA and OA patients. In this protocol paper, we therefore present Plants for Joints, a multidisciplinary lifestyle program, based on a WFPD, exercise, and stress management. The objective is to study the effect of this program on disease activity in patients with RA (randomized controlled trial [RCT] 1), on a risk score for developing RA in patients with anti-citrullinated protein antibody (ACPA) positive arthralgia (RCT 2) and on pain, stiffness, and function in patients with MSOA (RCT 3), all in comparison with usual care.We designed three 16-week observer-blind RCTs with a waiting-list control group for patients with RA with low to moderate disease activity (2.6 ≤ Disease Activity Score [DAS28] ≤ 5.1, RCT 1, n = 80), for patients at risk for RA, defined by ACPA-positive arthralgia (RCT 2, n = 16) and for patients with metabolic syndrome and OA in the knee and/or hip (RCT 3, n = 80). After personal counseling on diet and exercise, participants join 10 group meetings with 6–12 other patients to receive theoretical and practical training on a WFPD, exercise, and stress management, while medication remains unchanged. The waiting-list control group receives usual care, while entering the program after the RCT. Primary outcomes are: difference in mean change between intervention and control groups within 16 weeks for the DAS28 in RA patients (RCT 1), the RA-risk score for ACPA positive arthralgia patients (RCT 2), and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score for MSOA patients (RCT 3). Continued adherence to the lifestyle program is measured in a two-year observational extension study.
Effect of remimazolam besylate compared with propofol on the incidence of delirium after cardiac surgery: study protocol for a randomized trial
Authors: Yang Maopeng , Liu Xinyan , Yang Daqiang , Bai Yahu , Qin Bingxin , Tian Shoucheng , Dong Ranran , Song Xuan 
Published: October 2021

Abstract
Background
Delirium is an acute cognitive disorder that presents with fluctuation in cognition, apathy, and non-organized thinking, resulting in increased morbidity, mortality, intensive care unit (ICU) stay, and total healthcare costs. In patients undergoing cardiac surgery, delirium also increases the risk of postoperative complications, such as respiratory insufficiency, sternum instability, and need for re-operation of the sternum. This study aims to understand the incidence of delirium in patients after cardiac surgery in patients sedated with remimazolam besylate versus propofol.

Methods
In this prospective, double-blind, randomized controlled clinical trial, we aim to recruit 200 patients undergoing cardiac surgery between January 1, 2021, and December 31, 2021, who will be randomized to receive either remimazolam besylate or propofol infusions postoperatively, until they are extubated. The primary outcome is the incidence of delirium within 5 days after surgery. Secondary outcomes include the time of delirium onset, duration of delirium, ICU length of stay, hospital length of stay, and mechanical ventilation time.

Discussion
The key objective of this study is to assess whether remimazolam besylate reduces the incidence of delirium in patients after cardiac surgery compared to propofol sedation. In this preliminary randomized controlled clinical trial, we will test the hypothesis that the use of remimazolam besylate lowers the incidence of delirium when compared to propofol in patients undergoing cardiac surgery.

Trial registration
chictr.org.cn ChiCTR2000038976. Registered on October 11, 2020
A desmoplastic fibroblastoma that developed in the anterior mediastinum: a case report
Authors: Hato Tai , Kashimada Hiroaki , Yamaguchi Masatoshi , Sugiyama Ato , Inoue Yoshiaki , Aoki Kohei , Fukuda Hiroki , Gika Masatoshi , Kikuchi Jun , Fujino Takashi , Yamaguchi Takehiko , Tamaru Jun-ichi , Kohno Mitsutomo , Nakayama Mitsuo 
Published: October 2021

Abstract
Background
Desmoplastic fibroblastoma (also known as collagenous fibroma) is a benign, slowly growing soft-tissue tumor. Most desmoplastic fibroblastomas develop in the limbs, neck, or trunk. A mediastinal origin is quite rare.

Case presentation
A 32-year-old Asian female was referred to us for the diagnosis and treatment of an anterior mediastinal tumor. The tumor was 80 mm in the largest diameter and was located on the pericardium. No invasion was evident. She underwent resection of the tumor via video-assisted thoracoscopic resection. The tumor was totally encapsulated, and its pedicle was on the pericardium. The resected specimen was very rigid, making it difficult to remove from the intercostal space. Histologically, the tumor was composed of a paucicellular dense collagenous tissue. Mitosis was rarely observed, and cellular atypia was not evident, suggesting that the tumor was benign. We diagnosed the tumor as a desmoplastic fibroblastoma by morphology and immunohistochemistry.

Conclusions
Desmoplastic fibroblastoma of the mediastinum is an extremely rare disease. Preoperative diagnosis is difficult. Early surgical resection is suitable for diagnosis and treatment planning.