bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRIG2 regulates cell proliferation, migration and apoptosis of osteosarcoma
Authors: Li Zhi-Qiang , Liao Wei-Jie , Sun Bo-Lin , Luo Zhi-Wen , Zhong Nan-Shan , Wu Jia-Bao , Liu Zhi-Li , Liu Jia-Ming 
Published: October 2022

Abstract
Background
Osteosarcoma (OS) is one of the malignant bone tumors with strong aggressiveness and poor prognosis. Leucine-rich repeats and immunoglobulin-like domains2 (LRIG2) is closely associated with the poor prognosis of a variety of tumors, but the role of LRIG2 in osteosarcoma and the underlying molecular mechanism remains unclear.

Objective
The aim of this study was to determine the function of LRIG2 in OS and the related molecular mechanism on cell proliferation, apoptosis and migration of OS.

Methods
The mRNA and protein expression of LRIG2 in OS tissues and cells was detected by qRT-PCR, western blot (WB) assay and immunohistochemistry (IHC). The cell counting Kit-8 (CCK-8), clone formation, transwell, TdT-mediated dUTP Nick-End Labeling (TUNEL) and WB assay were applied to determine the proliferation, migration and apoptosis abilities of OS cells and its molecular mechanisms. Spontaneous metastasis xenografts were established to confirm the role of LRIG2 in vivo.

Results
LRIG2 exhibited high expression in OS tissues and OS cell lines and the expression of which was significantly correlated with Enneking stage of patients, knockdown LRIG2 expression significantly inhibited OS cell proliferation, migration and enhanced apoptosis. Silencing LRIG2 also suppressed the growth of subcutaneous transplanted tumor in nude mice. Further, the mechanism investigation revealed that the protein level of cell proapoptotic proteins (Bax, caspase9 and caspase3) all increased attributed to LRIG2 deficiency, whereas expression of anti-apoptotic protein BCL2 decreased. LRIG2 silencing led to the decrease phosphorylation of AKT signaling, a decrease expression of vimentin and N-cadherin. Additionally, silencing LRIG2 significantly decreased the rate of tumor growth and tumor size.

Conclusions
LRIG2 acts as an oncogene in osteosarcoma, and it might become a novel target in the treatment of human OS.
Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer
Authors: Lai Ming-Yu , Kang Shi-Yang , Sun Yu-Ting , Quan Ting-Ting , Lu Shi-Xun , He Cai-Yun , Zhou Zhi-Wei , Yang Li-Qiong , Luo Hui-Yan , Wang Feng-Hua , Li Yu-Hong , Xu Rui-Hua , Guan Wen-Long , Qiu Miao-Zhen 
Published: October 2022

Abstract
Background
Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values.

Methods
Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0–1 and 2–3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method.

Result
One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0–1 group and was 16.13 months in TRG 2–3 group. TRG 2–3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001).

Conclusion
TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.
A cross-sectional national investigation of COVID-19 outbreaks in nurseries during rapid spread of the Alpha (B.1.1.7) variant of SARS-CoV-2 in England
Authors: Aiano Felicity , McOwat Kelsey , Obi Chinelo , Powell Annabel A. , Flood Jessica , Bhardwaj Shivraj , Stoker Kelly , Haskins Donna , Wong Brian , Bertran Marta , Zavala Maria , Bosowski Johanna , Jones Samuel E. I. , Amin-Chowdhury Zahin , Coughlan Laura , Sinnathamby Mary , Zaidi Asad , Merrick Rachel , Zhao Hongxin , Ismail Sharif , Ramsay Mary E. , Ladhani Shamez N. , Saliba Vanessa 
Published: October 2022

Abstract
Background
In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries were investigated to assess the risk of SARS-CoV-2 infection and cumulative incidence in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England.

Methods
This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England. Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak.

Results
Three hundred and twenty-four nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21–3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01–4.19%) or staff (3.44%; 95%CI, 3.10–3.82%). Among staff, cumulative incidence was lower if the index case was a child (26.28%; 95%CI, 23.54–29.21%%) compared to a staff member (32.98%; 95%CI, 31.19–34.82%), with the highest cumulative incidence when the index case was also a staff member (37.52%; 95%CI, 35.39–39.70%). Compared to November 2020, outbreak sizes and cumulative incidence was higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in < 5 year-olds remained low and followed trends in older age-groups, increasing during December 2020 and declining thereafter.

Conclusions
In this cross-sectional study of COVID-19 outbreaks in nurseries, one in three staff were affected compared to one in thirty children. There was some evidence of increased transmissibility and higher cumulative incidence associated with the Alpha variant, highlighting the importance of maintaining a low level of community infections.
Impact of refractory and unexplained chronic cough on disease burden: a qualitative study
Authors: Ueda Naoya , Yakushiji Anzu , Schelfhout Jonathan , Tokita Shigeru , Kubo Takekazu 
Published: October 2022

Abstract
Background
Chronic cough lasting for > 8 weeks is a common medical condition that burdens patients. This study aimed to qualitatively describe knowledge, awareness, experiences, and subtypes of burdens (physical, social, psychological) among Japanese patients with refractory chronic cough (refractory to treatment of underlying relevant medical conditions) and unexplained chronic cough (symptoms of unexplained origin).

Methods
This non-interventional, cross-sectional study was conducted between February and March 2021 among patients (aged ≥ 20 years) with self-reported refractory or unexplained chronic cough. Subjects with a history of comorbid respiratory conditions were excluded. Eligible subjects participated in a 60-min online semi-structured interview. Verbatim terms from interviews were qualitatively transcribed and generated into word clouds, followed by a clustering analysis in which meaningful clusters were chosen, manually coded, and utterances and burdens categorized.

Results
A total of 21 participants (95.2% with refractory chronic cough, mean age 53.5 years, and 76.2% being males) with Leicester Cough Questionnaire mean ± standard deviation scores of physical 4.8 ± 1.1, psychological 4.4 ± 1.3, social 4.9 ± 1.4, and total 14.1 ± 3.5 were included. The word cloud identified the most frequently used word (‘cough’); etiology (‘asthma’); and words associated with change in states (‘influence,’ ‘changing,’ ‘change’) and expressions (‘tough,’ ‘pain,’ ‘hard,’ ‘terrible,’ ‘unpleasant’). The patients experienced ‘mental/social burden,’ ‘physical burden,’ ‘impact on sleep and meals,’ ‘impact on work and housework,’ ‘impact on communication,’ ‘impact on hobbies and leisure,’ and ‘economic burden.’ By closed coding analysis, the situations or types of burden patients experienced from the cough were ordered sequentially as emotion, working style, acquaintanceship, hobbies and leisure, and sleeping pattern.

Conclusions
The present study indicated that there were two types of participant clusters, in which one showed mainly the burdens in the social communications such as work-related communication and another one showed the burdens of relationships with others. Also, some participants highlighted ‘mental burden,’ on social life due to the current pandemic. To relieve these burdens, disease awareness and knowledge should be improved for patients with refractory and unexplained chronic cough.
Trial registration The trial was registered under UMIN-CTR as UMIN000042772, on 17/12/2020. The study was approved by the Medical Corporation Toukeikai Kitamachi Clinic (IRB registration number: 11001110).
Morphological changes of TMJ disc in surgically treated ADDwoR patients: a retrospective study
Authors: Wang Ruiyu , Bi Ruiye , Liu Yao , Cao Pinyin , Abotaleb Bassam , Zhu Songsong 
Published: October 2022

AbstractBackgroundThis study aimed to quantify the morphological changes of temporomandibular joint (TMJ) discs after disc repositioning surgery using the three-dimensional (3D) modeling.MethodsThirty patients who diagnosed with unilateral ADDwoR were included to compare the morphological differences between ADDWoR discs and normal discs, and fifteen patients who experienced unilateral or bilateral disc repositioning surgery were included to analyze the morphological changes before and after disc repositioning surgery. Disc 3D reconstruction and analyses were performed using magnetic resonance imaging (MRI) data.ResultsIn the unilateral ADDwoR patients, volume, superficial area, length, and maximum longitudinal-sectional area of the ADDwoR disc were significantly smaller compared with the non-affected discs. However, there was no significant difference in width and cross-sectional areas between ADDwoR discs and non-affected discs. In patients who subjected to disc repositioning surgery, disc volume, superficial area, length, width and maximum longitudinal-sectional area of TMJ discs were markedly increased 6 months after surgery.ConclusionsThis study demonstrated that the TMJ discs tended to be morphologically smaller in volume and shorter in length under ADDwoR status. Importantly, the ADDwoR discs tended to morphologically recover toward non-affected discs after 6 months follow-up following TMJ disc repositioning surgery.
Dealing with pluralism: the managerial work of CEOs in Italian public healthcare organizations
Authors: Lega Federico , Rotolo Andrea , Sartirana Marco 
Published: October 2022

AbstractBackgroundHealthcare organizations are extremely complex. The work of their CEOs is particularly demanding, especially in the public sector, though little is known about how the managerial work of a healthcare organization CEO unfolds. Drawing from scholarship on managerial work and management in pluralistic organizations, we sought to answer the questions: What is the content of managerial work of CEOs in public healthcare in Italy? How do healthcare CEOs perform their managerial work in complex interactions with multiple stakeholders?MethodsFor this study we adopted a multi-method approach in which we conducted a survey to investigate CEO behaviors, tracked CEO working time for 4 weeks, and conducted semi-structured interviews with senior CEOs.ResultsCEOs in public healthcare devote most of their time to interaction, which half of which is perceived as being occupied with apparently mundane problems. Nonetheless, devoting time to such activities is functional to a CEO’s goals because change in pluralistic contexts can be achieved only if the CEO can handle the organization’s complexity. CEOs do this by engaging in routines and conversations with professionals, creating consensus, and establishing networks with external stakeholders.ConclusionsCEOs are called to reduce fragmentation and foster cooperation across disciplines and professional groups, with the overarching aim to achieve integrated care. Using an analytical approach we were able to take into account the context and the relational dimension of the managerial work of healthcare CEOs and the specificities of this role.Trial registrationThis article does not report the results of a healthcare intervention on human participants, and the material used in the research did not require ethical approval according to Italian law.
A healthcare workers’ mHealth adoption instrument for the developing world
Authors: Addotey-Delove Michael , Scott Richard E. , Mars Maurice 
Published: October 2022

Abstract
Introduction
Healthcare workers’ adoption of mHealth is critical to the success or failure of clinician based mHealth services in the developing world. mHealth adoption is affected or promoted by certain factors, some of which are peculiar to the developing world. Identifying these factors and evaluating them will help develop a valid and reliable measuring instrument for more successful prediction of mHealth adoption in the future. The aim of this study was to design and develop such an instrument.

Method
A Healthcare workers’ mHealth Adoption Questionnaire (HmAQ) was developed based on five constructs identified through a prior literature review: multi-sectorial engagement and ownership; staffing and technical support; reliable infrastructure; usefulness and stewardship; and intention to adopt. After testing face and content validity, the questionnaire was administered to 104 nurses and midwives in the Ewutu-Senya district of the Central Region of Ghana who used a maternal mHealth intervention. After data collection confirmatory factor analysis and structural equation modelling were applied and the Healthcare Worker mHealth Adoption Impact Model (HmAIM) developed.

Results
Exploratory factor analysis showed the eigenvalue of all five components to be significant (cumulative total greater than 1.0). Bartlett’s Test of Sphericity was significant, the Kaiser-Meyer-Olkin value was 0.777, and the mean Cronbach’s α value was 0.82 (range 0.81–0.83). Confirmatory factor analysis showed that constructs for the HmAQ were within acceptable limits and valid. Structural equation modelling showed the causal relationships between components. This resulted in development of the HmAIM. A modified model was then developed using the averages of individual construct items. This model showed strong correlation among the constructs. Further research will be required to understand new dimensions of mHealth adoption as a result of emerging technology needs, new complexities in the healthcare work environment, and how different cadres of healthcare workers respond to it.

Conclusion
The study presents a valid and reliable instrument, the HmAIM, to serve as a tool for assessment of healthcare workers’ mHealth adoption in the developing world. Use of the instrument will enhance the likelihood of successful adoption of mHealth implementations.
Inhaled mosliciguat (BAY 1237592): targeting pulmonary vasculature via activating apo-sGC
Authors: Becker-Pelster Eva M. , Hahn Michael G. , Delbeck Martina , Dietz Lisa , Hüser Jörg , Kopf Johannes , Kraemer Thomas , Marquardt Tobias , Mondritzki Thomas , Nagelschmitz Johannes , Nikkho Sylvia M. , Pires Philippe V. , Tinel Hanna , Weimann Gerrit , Wunder Frank , Sandner Peter , Schuhmacher Joachim , Stasch Johannes-Peter , Truebel Hubert K. F. 
Published: October 2022

Abstract
Background
Oxidative stress associated with severe cardiopulmonary diseases leads to impairment in the nitric oxide/soluble guanylate cyclase signaling pathway, shifting native soluble guanylate cyclase toward heme-free apo-soluble guanylate cyclase. Here we describe a new inhaled soluble guanylate cyclase activator to target apo-soluble guanylate cyclase and outline its therapeutic potential.

Methods
We aimed to generate a novel soluble guanylate cyclase activator, specifically designed for local inhaled application in the lung. We report the discovery and in vitro and in vivo characterization of the soluble guanylate cyclase activator mosliciguat (BAY 1237592).

Results
Mosliciguat specifically activates apo-soluble guanylate cyclase leading to improved cardiopulmonary circulation. Lung-selective effects, e.g., reduced pulmonary artery pressure without reduced systemic artery pressure, were seen after inhaled but not after intravenous administration in a thromboxane-induced pulmonary hypertension minipig model. These effects were observed over a broad dose range with a long duration of action and were further enhanced under experimental oxidative stress conditions. In a unilateral broncho-occlusion minipig model, inhaled mosliciguat decreased pulmonary arterial pressure without ventilation/perfusion mismatch. With respect to airway resistance, mosliciguat showed additional beneficial bronchodilatory effects in an acetylcholine-induced rat model.

Conclusion
Inhaled mosliciguat may overcome treatment limitations in patients with pulmonary hypertension by improving pulmonary circulation and airway resistance without systemic exposure or ventilation/perfusion mismatch. Mosliciguat has the potential to become a new therapeutic paradigm, exhibiting a unique mode of action and route of application, and is currently under clinical development in phase Ib for pulmonary hypertension.
Human umbilical cord mesenchymal stem cells combined with pirfenidone upregulates the expression of RGS2 in the pulmonary fibrosis in mice
Authors: Wu Xian , Gou Hao , Zhou Ou , Qiu Huijun , Liu Hanmin , Fu Zhou , Chen Lina 
Published: October 2022

Abstract
Objective
The therapeutic effect of umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in combination with pirfenidone (PFD) on pulmonary fibrosis in mice and its possible mechanism were investigated.

Methods
C57BL/6 mice were randomly divided into six groups: control group, model group, P10 group, P30 group, P100 group, and P300 group. Modeled by tracheal intubation with 3 mg/kg bleomycin drip, each dose of PFD was administered daily by gavage from day 7 onwards. The mice were observed continuously for 21 days and survival was recorded. Lung tissues were collected on day 21, and hematoxylin–eosin (HE) and Masson staining were performed to assess morphological changes and collagen deposition in the lungs. Collagen content was measured by the Sircol method, and fibrosis marker levels were detected by PCR and Western blot. Another batch of C57BL/6 mice was then randomly divided into five groups: hUC-MSC control group, model group, P100 group, hUC-MSC treatment group, and hUC-MSCs + P30 group. On day 7, 5 × 105 hUC-MSCs were injected into the tail vein, the mice were administered PFD gavage daily from day 7 onwards, and their survival was recorded. Lung tissues were collected on day 21 to detect pathological changes, the collagen content, and the expression of regulator of G protein signaling 2 (RGS2). Pulmonary myofibroblasts (MFBs) were divided into an MFB group and an MFB + hUC-MSCs group; different doses of PFD were administered to each group, and the levels of RGS2, intracellular Ca2+, and fibrosis markers were recorded for each group.

Results
Compared with other PFD group doses, the P100 group had significantly improved mouse survival and lung pathology and significantly reduced collagen and fibrosis marker levels (p < 0.05). The hUC-MSCs + P30 group had significantly improved mouse survival and lung pathology, significantly reduced collagen content and fibrosis marker levels (p < 0.05), and the efficacy was better than that of the P100 and hUC-MSCs groups (p < 0.05). RGS2 expression was significantly higher in the MSCs + P30 group compared with the P100 and hUC-MSCs groups (p < 0.05). PFD increased RGS2 expression in MFBs (p < 0.05) in a dose-dependent manner. Compared with PFD and hUC-MSCs treatment alone, combination of hUC-MSCs and PFD increased RGS2 protein levels, significantly decreased intracellular Ca2+ concentration, and significantly reduced fibrosis markers.

Conclusion
The findings suggest that hUC-MSCs combined with low-dose PFD have a therapeutic effect better than that of the two treatments used separately. Its effect on attenuating bleomycin-induced pulmonary fibrosis in mice is related to the increase of RGS2.
Implication of asymptomatic and clinical Plasmodium falciparum infections on biomarkers of iron status among school-aged children in Malawi
Authors: Ntenda Peter A. M. , Chirambo Angeziwa C. , Nkoka Owen , El-Meidany Walaa M. , Goupeyou-Youmsi Jessy 
Published: October 2022

AbstractBackgroundIron status is considered as a continuum from an iron deficiency with anaemia, without anaemia, varying amounts of stored iron to iron overload. The burden ofPlasmodium falciparuminfections is typically high among school-aged children (SAC). Nonetheless, SAC are often less likely to be covered by malaria interventions, making them a group with an untreated reservoir of parasite transmission. This study aimed to assess the effects of asymptomatic and clinical malaria infections on biochemical markers of iron status among SAC in Malawi.MethodsData from the 2015–2016 Malawi Micronutrient Survey (MNS) was used and multivariable logistic regression models using a generalized estimating equation to account for the complex cluster survey design were constructed. Blood samples of 684 children aged 5 to 14 years old were evaluated for clinical and asymptomatic malaria infections. Furthermore, blood samples were used to estimate haemoglobin (Hb), serum ferritin (SF) and, soluble transferrin receptors (sTfR) concentrations.ResultsOf the 684 SAC analysed, approximately 42% had asymptomatic malaria, while 41.0% had clinical malaria. Anaemia (low Hb levels), iron deficiency (low SF concentration), and functional iron deficiency (high sTfR levels) were found in 20%, 5%, and 30% of the children, respectively. School-aged children with asymptomatic malaria had increased odds of being anaemic (adjusted odds ratio [aOR]: 3.71, 95% confidence interval [CI]: 2.29–5.99) and increased levels of sTfR (aOR: 3.00, 95% CI 2.01–4.47). Similarly, SAC with clinical malaria had increased odds of being anaemic (aOR: 3.54, 95% CI 2.19–5.72) and increased levels of sTfR (aOR: 3.02, 95% CI 2.02–4.52).ConclusionsBoth asymptomatic and clinical malaria were independent risk factors for anaemia and functional iron deficiency (FID). The notion that asymptomatic and clinical malaria were associated with both anaemia and FID underscores the need for public health programmers to consider adding mass screening and treatment for malaria to existing school-based health programmes.