bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron is a modifier of the phenotypes of JAK2-mutant myeloproliferative neoplasms
Authors: Stetka Jan , Usart Marc , Kubovcakova Lucia , Rai Shivam , Nageswara Rao Tata , Sutter Joshua , Hao-Shen Hui , Dirnhofer Stefan , Geier Florian , Bader Michael Stephan , Passweg Jakob R , Manolova Vania , Dürrenberger Franz , Ahmed Nouraiz , Schroeder Timm , Ganz Tomas , Nemeth Elizabeta , Silvestri Laura , Nai Antonella , Camaschella Clara , Skoda Radek C.
Published: February 2023

JAK2-V617F mutation causes myeloproliferative neoplasms (MPN) that can manifest as polycythemia vera (PV), essential thrombocythemia (ET) or primary myelofibrosis (PMF). PV patients at diagnosis already exhibited iron deficiency, whereas ET patients had normal iron stores. We examined the influence of iron availability on MPN phenotype in mice expressing JAK2-V617F and in mice expressing JAK2 with a N542-E543del mutation in exon 12 (E12). At baseline on control diet, all JAK2-mutant mouse models with PV-like phenotype displayed iron deficiency, although E12 mice maintained more iron for augmented erythropoiesis than JAK2-V617F mutant mice. In contrast, JAK2-V617F mutant mice with an ET-like phenotype had normal iron stores comparable to wildtype (WT) mice. On low-iron diet, JAK2-mutant mice and WT controls increased platelet production at the expense of erythrocytes. Mice with PV phenotype responded to parenteral iron injections by decreasing platelet counts and further increasing hemoglobin and hematocrit, whereas no changes were observed in WT controls. Alterations of iron availability primarily affected the pre-megakaryocyte erythrocyte progenitors (pre-MegE), which constitute the iron-responsive stage of hematopoiesis in JAK2-mutant mice. The orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 normalized hematocrit and hemoglobin levels in JAK2-V617F and E12 mutant mouse models of PV, suggesting that ferroportin inhibitors and minihepcidins could be used in the treatment of PV patients.
Minimal clinically important difference for impulse oscillometry in adults with asthma
Authors: Abdo Mustafa , Kirsten Anne-Marie , von Mutius Erika , Kopp Matthias , Hansen Gesine , Rabe Klaus F. , Watz Henrik , Trinkmann Frederik , Bahmer Thomas
Published: February 2023

Background

Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCIDs) for IOS measures are lacking. Here, we provide MCIDs for frequently used IOS measures, namely frequency dependence of resistance (FDR) and area of reactance (AX), in patients with asthma.

Methods

We performed IOS at baseline and 1 year later in adult patients with mild-to-severe asthma (n=235). In a two-step approach, we first applied a distribution-based method to statistically determine the MCID. Next, we validated the proposed MCID according to patient-reported outcome measures (PROMs): Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire-7 (ACQ-7) and Asthma Control Test (ACT). We used multivariable analyses to investigate the proposed MCIDs as predictors for improvements in PROMs compared with the established MCID of forced expiratory volume in 1 s (FEV1).

Results

The proposed MCID was a decline of ≥0.06 kPa·L−1·s−1and ≥0.65 kPa·L−1for FDR and AX, respectively. Patients who had changes beyond the MCIDs for both FDR and AX showed greater improvements in all PROMs than those who had not. The mean improvements in PROMs were beyond the established MCIDs for ACQ-7 and AQLQ, and approximated the MCID for ACT. Multivariable analyses demonstrated the MCIDs for both FDR and AX as independent predictors for the MCIDs of all PROMs. The MCID for FDR was a stronger predictor of all PROMs than the MCID for FEV1.

Conclusions

This study provides MCIDs for IOS-derived measures in adult patients with asthma and emphasises that small airway function is a distinguished end-point beyond the conventional measure of FEV1.
Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis
Authors: Wu Xiuju , Zhang Daoqin , Qiao Xiaojing , Zhang Li , Cai Xinjiang , Ji Jaden , Ma Jocelyn A. , Zhao Yan , Belperio John A. , Boström Kristina I. , Yao Yucheng
Published: February 2023

Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions.
Morphometric analysis of the size-adjusted linear dimensions of the skull landmarks revealed craniofacial dysmorphology in Mid1-cKO mice
Authors: Liang Yaohui , Song Chao , Li Jieli , Li Ting , Zhang Chunlei , Zou Yi
Published: February 2023

Background

The early craniofacial development is a highly coordinated process involving neural crest cell migration, proliferation, epithelial apoptosis, and epithelial-mesenchymal transition (EMT). Both genetic defects and environmental factors can affect these processes and result in orofacial clefts. Mutations in MID1 gene cause X-linked Opitz Syndrome (OS), which is a congenital malformation characterized by craniofacial defects including cleft lip/palate (CLP). Previous studies demonstrated impaired neurological structure and function in Mid1 knockout mice, while no CLP was observed. However, given the highly variable severities of the facial manifestations observed in OS patients within the same family carrying identical genetic defects, subtle craniofacial malformations in Mid1 knockout mice could be overlooked in these studies. Therefore, we propose that a detailed morphometric analysis should be necessary to reveal mild craniofacial dysmorphologies that reflect the similar developmental defects seen in OS patients.

Results

In this research, morphometric study of the P0 male Mid1-cKO mice were performed using Procrustes superimposition as well as EMDA analysis of the size-adjusted three-dimensional coordinates of 105 skull landmarks, which were collected on the bone surface reconstructed using microcomputed tomographic images. Our results revealed the craniofacial deformation such as the increased dimension of the frontal and nasal bone in Mid1-cKO mice, in line with the most prominent facial features such as hypertelorism, prominent forehead, broad and/or high nasal bridge seen in OS patients.

Conclusion

 While been extensively used in evolutionary biology and anthropology in the last decades, geometric morphometric analysis was much less used in developmental biology. Given the high interspecies variances in facial anatomy, the work presented in this research suggested the advantages of morphometric analysis in characterizing animal models of craniofacial developmental defects to reveal phenotypic variations and the underlining pathogenesis.
Subclinical atherosclerosis burden in non-diabetic hypertensives treated in primary care center: the IMTABI study
Authors: Ramírez-Torres José M. , López-Téllez Antonio , Ariza María J. , Rioja José , García-Casares Natalia , Rodríguez Elena E. González , García José A. Ramírez , Chaparro Miguel A. Sánchez , Barbancho Miguel A. , Valdivielso Pedro
Published: February 2023

Background

Identifying patients at high risk of cardiovascular disease in primary prevention is a challenging task. This study aimed at detecting subclinical atherosclerosis burden in non-diabetic hypertensive patients in a primary care centre.

Methods

Clinical, anthropometric and analytical data were collected from patients with hypertension who were free from clinical vascular disease and diabetes. The cardiovascular risk was assessed using the SCORE system. Subclinical atherosclerosis burden was assessed by carotid ultrasonography (intima-medial thickness [IMT] and plaque) and measurement of the ankle-brachial index (ABI).

Results

Out of 140 patients, 59 (42%) have carotid plaque, 32 (23%) have IMT higher than 75% and 12 (9%) have an ABI < 0.9. Total atherosclerosis burden was present in 91 (65%) of the subjects. Consequently, 59 (42%) patients were re-classified into the very high-risk category. In multivariate analyses, smoking, creatinine levels and duration of hypertension were associated with atherosclerosis burden. In contrast, only smoking and age were associated with the presence of carotid plaque. Almost 90% of patients were treated with hypotensive drugs, half of them combined several drugs and 60% were well-controlled. Only 30% received statins in monotherapy and only less than 20% had an LDL cholesterol < 100 mg/dL.

Conclusions

In non-diabetic hypertensive patients managed at a primary care centre, 4 out of 10 had subclinical atherosclerosis burden and were re-classified into the very high- risk category. There was clear undertreatment with lipid-lowering drugs of most LDL cholesterol inappropriate levels, according to current clinical guidelines.
Multicompartment body composition analysis in older adults: a cross-sectional study
Authors: Rossini-Venturini Ana Claudia , Veras Lucas , Abdalla Pedro Pugliesi , Santos André Pereira dos , Tasinafo-Junior Márcio Fernando , Silva Leonardo Santos Lopes da , Alves Thiago Cândido , Ferriolli Eduardo , Romo-Perez Vicente , Garcia-Soidan Jose Luis , Mota Jorge , Machado Dalmo Roberto Lopes
Published: February 2023

Background

During aging, changes occur in the proportions of muscle, fat, and bone. Body composition (BC) alterations have a great impact on health, quality of life, and functional capacity. Several equations to predict BC using anthropometric measurements have been developed from a bi-compartmental (2-C) approach that determines only fat mass (FM) and fat-free mass (FFM). However, these models have several limitations, when considering constant density, progressive bone demineralization, and changes in the hydration of the FFM, as typical changes during senescence. Thus, the main purpose of this study was to propose and validate a new multi-compartmental anthropometric model to predict fat, bone, and musculature components in older adults of both sexes.

Methods

This cross-sectional study included 100 older adults of both sexes. To determine the dependent variables (fat mass [FM], bone mineral content [BMC], and appendicular lean soft tissue [ALST]) whole total and regional dual-energy X-ray
absorptiometry (DXA) body scans were performed. Twenty-nine anthropometric measures and sex were appointed as independent variables. Models were developed through multivariate linear regression. Finally, the predicted residual error sum of squares (PRESS) statistic was used to measure the effectiveness of the predicted value for each dependent variable.

Results

An equation was developed to simultaneously predict FM, BMC, and ALST from only four variables: weight, half-arm span (HAS), triceps skinfold (TriSK), and sex. This model showed high coefficients of determination and low estimation errors (FM: R2adj: 0.83 and SEE: 3.16; BMC: R2adj: 0.61 and SEE: 0.30; ALST: R2adj: 0.85 and SEE: 1.65).

Conclusion

The equations provide a reliable, practical, and low-cost instrument to monitor changes in body components during the aging process. The internal cross-validation method PRESS presented sufficient reliability in the model as an inexpensive alternative for clinical field use.
Well-being of professional older adults’ caregivers in Alberta’s assisted living and long-term care facilities: a cross-sectional study
Authors: Awosoga Oluwagbohunmi A. , Odole Adesola Christiana , Onyeso Ogochukwu Kelechi , Doan Jon , Nord Christina , Nwosu Ifeoma Blessing , Steinke Claudia , Ojo Joshua O. , Ekediegwu Ezinne Chika , Murphy Sheli
Published: February 2023

Background

For the care need of older adults, long-term care (LTC) and assisted living (AL) facilities are expanding in Alberta, but little is known about the caregivers’ well-being. The purpose of the study was to investigate the physical health conditions, mental and emotional health (MEH), health behaviour, stress levels, quality of life (QOL), and turnover and absenteeism (TAA) among professional caregivers in Alberta’s LTC and AL facilities.

Methods

This cross-sectional survey involved 933 conveniently selected caregivers working in Alberta’s LTC and AL facilities. Standardised questions were selected from the Canadian Community Health Survey, Patient Health Questionnaire-9, and Short Form-36 QOL survey revalidated and administered to the participants. The new questionnaire was used to assess the caregivers’ general health condition (GHC), physical health, health behaviour, stress level, QOL, and TAA. Data were analysed using descriptive statistics, Cronbach alpha, Pearson’s correlation, one-way analysis of variance, and multiple linear regression.

Results

Of 1385 surveys sent to 39 facilities, 933 valid responses were received (response rate = 67.4%). The majority of the caregivers were females (90.8%) who were ≥ 35 years (73.6%), worked between 20 to 40 h weekly (67.3%), and were satisfied with their GHC (68.1%). The Registered Nurses had better GHC (mean difference [MD] = 0.18, p = 0.004) and higher TAA than the Health Care Aides (MD = 0.24, p = 0.005). There were correlations between caregivers’ TAA and each of MEH (r = 0.398), QOL (r = 0.308), and stress (r = 0.251); p < 0.001. The most significant predictors of TAA were the propensity to quit a workplace or the profession, illness, job stress, and work-related injury, F (5, 551) = 76.62, p < 0.001, adjusted R2 = 0.998.

Conclusion

Reducing the caregivers’ job stressors such as work overload, inflexible schedule, and poor remuneration, and improving their quality of life, health behaviour, and mental, emotional, and physical health conditions may increase their job satisfaction and reduce turnover and absenteeism.
Life-threatening pulmonary coinfection with Mycobacterium tuberculosis and Aspergillus lentulus in a diabetic patient diagnosed by metagenome next-generation sequencing
Authors: Zhang Hua , Liu Guangming , He Lin , Zhu Yun , Tu Haobo , Zhuang Shifang
Published: February 2023

Background

China has a double burden of diabetes mellitus and tuberculosis. Diabetes mellitus and tuberculosis are both important risk factors for Aspergillus infection. Aspergillus lentulus is an emerging fungal pathogen in China and invasive aspergillosis due to A. lentulus is associated with high mortality.

Case presentation

A 79-year-old man was admitted to our hospital, complaining of a 7-day history of fever. Five days before admission, he was diagnosed with pulmonary infection at a local hospital, but his symptoms did not relieve after antibiotic therapy. The patient was diagnosed with diabetes mellitus two months ago. About 20 days ago, he began to present chest tightness and shortness of breath after physical activity. After admission, he developed continuous fever and rapid respiratory deterioration, and finally died after his family abandoned treatment. Pulmonary coinfection with M. tuberculosis and A. lentulus was identified by metagenome next-generation sequencing (mNGS) from bronchoalveolar lavage fluid.

Conclusions

Clinicians and laboratories should be alert to the emerging A. lentulus infection in China due to its drug-resistance and high mortality. In comparison with conventional methods, mNGS has a great advantage for the diagnosis of mixed pulmonary infection.
Performance of spleen stiffness measurement by 2D-shear wave elastography in evaluating the presence of high-risk varices: comparative analysis of idiopathic portal hypertension versus hepatitis B virus
Authors: Zhou Huihui , Zhang Zhilin , Zhang Jun , Sang Lin , Liu Lina , Gong Xue , Sun Yuanyuan , Zheng Yu , Yu Ming
Published: February 2023

Background

Noninvasive assessment of high-risk varices (HRV) in idiopathic portal hypertension (IPH) is rare. The purpose of this study was to investigate the performance of spleen stiffness (SS) for evaluating the presence of HRV in IPH patients as compared the measurements in patients with hepatitis B virus (HBV).

Methods

A retrospective single-center study was performed to evaluate the performance of SS for assessing HRV in IPH and HBV-infected patients, in comparison with liver stiffness (LS), spleen stiffness-to-liver stiffness ratio (SS/LS), LS spleen-diameter-to-platelet-ratio score (LSPS), portal hypertension risk score (PH risk score) and varices risk score, by using upper gastrointestinal endoscopy (UGE) as the gold standard. Finally, 86 IPH and 102 HBV-infected patients were enrolled. UGE, two-dimensional shear wave elastography (2D-SWE) and laboratory data were collected, and noninvasive parameters were calculated. Analysis of receiver operating characteristic (ROC) curves was conducted to acquire the optimal area under the ROC curve (AUC) and cutoff value for predicting the presence of HRV.

Results

In patients with HRV, the significantly different parameters between IPH (34.9%) and HBV-infected patients (46.1%) were as follows: spleen size (diameter 18.5 ± 3.9 cm vs. 20.8 ± 2.7 cm), SS (50.2 kPa vs. 42.9 kPa), LS (11.1 kPa vs. 18.3 kPa) and PT (prothrombin time 15.1 s vs. 16.7 s). No statistically significant differences were found in liver function, platelet counts, spleen thickness and flow volumes in the portal venous system (p > 0.05). The AUCs of SS were 0.98 and 0.96 for predicting the presence of HRV in IPH (44.0 kPa cutoff value; 0.93 sensitivity; 0.96 specificity) and HBV-infected patients (35.2 kPa cutoff value; 1.00 sensitivity; 0.82 specificity), respectively, which were significantly better than other parameters.

Conclusion

SS shows the optimal overall performance for predicting the presence of HRV in IPH and HBV-infected patients, in comparison with other noninvasive parameters.
MRI-based radiomics nomogram for differentiation of solitary metastasis and solitary primary tumor in the spine
Authors: Li Sha , Yu Xinxin , Shi Rongchao , Zhu Baosen , Zhang Ran , Kang Bing , Liu Fangyuan , Zhang Shuai , Wang Ximing
Published: February 2023

Background

Differentiating between solitary spinal metastasis (SSM) and solitary primary spinal tumor (SPST) is essential for treatment decisions and prognosis. The aim of this study was to develop and validate an MRI-based radiomics nomogram for discriminating SSM from SPST.

Methods

One hundred and thirty-five patients with solitary spinal tumors were retrospectively studied and the data set was divided into two groups: a training set (n = 98) and a validation set (n = 37). Demographics and MRI characteristic features were evaluated to build a clinical factors model. Radiomics features were extracted from sagittal T1-weighted and fat-saturated T2-weighted images, and a radiomics signature model was constructed. A radiomics nomogram was established by combining radiomics features and significant clinical factors. The diagnostic performance of the three models was evaluated using receiver operator characteristic (ROC) curves on the training and validation sets. The Hosmer–Lemeshow test was performed to assess the calibration capability of radiomics nomogram, and we used decision curve analysis (DCA) to estimate the clinical usefulness.

Results

The age, signal, and boundaries were used to construct the clinical factors model. Twenty-six features from MR images were used to build the radiomics signature. The radiomics nomogram achieved good performance for differentiating SSM from SPST with an area under the curve (AUC) of 0.980 in the training set and an AUC of 0.924 in the validation set. The Hosmer–Lemeshow test and decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model.

Conclusions

A radiomics nomogram as a noninvasive diagnostic method, which combines radiomics features and clinical factors, is helpful in distinguishing between SSM and SPST.
Tobacco exposure in adults and children with proteinuric glomerulopathies: a NEPTUNE cohort study
Authors: Wang Linda , Smith-Salzberg Bayle , Meyers Kevin EC , Glenn Dorey A. , Tuttle Katherine R. , Derebail Vimal K. , Brady Tammy M. , Gibson Keisha , Smith Abigail R. , O’Shaughnessy Michelle M. , Srivastava Tarak , Hall Gentzon , Zee Jarcy , Bitzer Markus , Sethna Christine B.
Published: February 2023

Background

Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored.

Methods

Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified as non-smoker, active smoker, former smoker, or exclusive passive smoker. Baseline serum cotinine levels were measured in a sub-cohort of 178 participants.

Results

The prevalence of active smokers, former smokers and exclusive passive smoking among adults at baseline was 14.6%, 29.1% and 4.9%, respectively. Passive smoke exposure was 16.7% among children. Active smoking (reference non-smoking) was significantly associated with greater total cholesterol among adults (β 17.91 95% CI 0.06, 35.76, p = 0.049) while passive smoking (reference non-smoking) was significantly associated with greater proteinuria over time among children (β 1.23 95% CI 0.13, 2.33, p = 0.03). Higher cotinine levels were associated with higher baseline eGFR (r = 0.17, p = 0.03).

Conclusion

Tobacco exposure is associated with greater risk for CVD and worse kidney disease outcomes in adults and children with proteinuric glomerulopathies. Preventive strategies to reduce tobacco exposure may help protect against future cardiovascular and kidney morbidity and mortality in patients with proteinuric glomerulopathies.
Evaluating patient reported outcomes and experiences in a novel proton beam clinic – challenges, activities, and outcomes of the ProtonCare project
Authors: Sjövall K , Langegård U , Fransson P , Nevo-Ohlsson E , Kristensen I , Ahlberg K , Johansson B
Published: February 2023

Background

The ProtonCare Study Group (PCSG) was formed with the purpose to develop and implement a framework for evaluation of proton beam therapy (PBT) and the related care at a novel clinic (Skandionkliniken), based on patient reported data.

Method

A logic model framework was used to describe the process of development and implementation of a structured plan for evaluation of PBT for all diagnoses based on patient reported data. After the mission for the project was determined, meetings with networks and stakeholders were facilitated by PCSG to identify assumptions, resources, challenges, activities, outputs, outcomes, and outcome indicators.

Result

This paper presents the challenges and accomplishments PCSG made so far. We describe required resources, activities, and accomplished results. The long-term outcomes that were outlined as a result of the process are two; 1) Improved knowledge about health outcomes of patients that are considered for PBT and 2) The findings will serve as a base for clinical decisions when patients are referred for PBT.

Conclusion

Using the logical model framework proved useful in planning and managing the ProtonCare project. As a result, the work of PCSG has so far resulted in long-lasting outcomes that creates a base for future evaluation of patients’ perspective in radiotherapy treatment in general and in PBT especially. Our experiences can be useful for other research groups facing similar challenges. Continuing research on patients´ perspective is a central part in ongoing and future research. Collaboration, cooperation, and coordination between research groups/networks from different disciplines are a significant part of the work aiming to determine the more precise role of PBT in future treatment options.
Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
Authors: Zheng Axiu , Bai Jianrong , Ha Yanping , Yu Yaping , Fan Yonghao , Liang Meihua , Lu Yanda , Shen Zhihua , Luo Botao , Jie Wei
Published: February 2023

Background

Stonin1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the immune role of STON1 in kidney renal clear cell carcinoma (KIRC).

Methods

We undertook bioinformatics analyses of the expression and clinical significance of STON1 in KIRC through a series of public databases, and the role of STON1 in the tumor microenvironment and the predictive value for immunotherapy and targeted treatment in KIRC were identified with R packages. STON1 expression was validated in clinical KIRC tissues as well as in KIRC and normal renal tubular epithelial cells.

Results

Through public databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis and status of KIRC patients. Compared with normal controls, STON1 was found to be downregulated in KIRC tissues and cell lines. Furthermore, OncoLnc, Kaplan–Meier, and GEPIA2 analyses also suggested that KIRC patients with high STON1 expression had better overall survival. The high STON1 group with enriched immune cells had a more favorable prognosis than the low STON1 group with decreased immune cells. Single sample Gene Set Enrichment Analysis and Gene Set Variation Analysis indicated that STON1 creates an immune non-inflamed phenotype in KIRC. Moreover, STON1 was positively associated with mismatch repair proteins and negatively correlated with tumor mutational burden. Furthermore, Single sample Gene Set Enrichment Analysis algorithm and Pearson analysis found that the low STON1 group was more sensitive to immune checkpoint blockage whereas the high STON1 group was relatively suitable for targeted treatment.

Conclusions

Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, low STON1 expression is associated with an aberrant tumor immune microenvironment. Low STON1 is likely to be a favorable indicator for immunotherapy response but adverse indicator for targeted therapeutics in KIRC.
Development a prediction model for identifying bacterial meningitis in young infants aged 29–90 days: a retrospective analysis
Authors: Wu Jiahui , Shi Ting , Yue Yongfei , Kong Xiaoxing , Cheng Fangfang , Jiang Yanqun , Bian Yuanxi , Tian Jianmei
Published: February 2023

Background

The early diagnosis and treatment of bacterial meningitis (BM) in young infants was very critical. But, it was difficult to make a definite diagnosis in the early stage due to nonspecific clinical symptoms. Our objectives were to find the risk factors associated with BM and develop a prediction model of BM especially for young infants.

Methods

We retrospectively reviewed the clinical data of young infants with meningitis between January 2011 and December 2020 in Children’s Hospital of Soochow University. The independent risk factors of young infants with BM were screened using univariate and multivariate logistic regression analyses. The independent risk factors were used to construct a new scoring model and compared with Bacterial Meningitis Score (BMS) and Meningitis Score for Emergencies (MSE) models.

Results

Among the 102 young infants included, there were 44 cases of BM and 58 of aseptic meningitis. Group B Streptococcus (22, 50.0%) and Escherichia coli (14, 31.8%) were the main pathogens of BM in the young infants. Multivariate logistic regression analysis identified procalcitonin (PCT), cerebrospinal fluid (CSF) glucose, CSF protein as independent risk factors for young infants with BM. We assigned one point for CSF glucose ≤ 1.86 mmol/L, two points were assigned for PCT ≥ 3.80 ng/ml and CSF protein ≥ 1269 mg/L. Using the not low risk criterion (score ≥ 1) with our new prediction model, we identified the young infantile BM with 100% (95% CI 91.9%-100%) sensitivity and 60.3% (95% CI 46.4%-72.9%) specificity. Compared with BMS and MSE model, our prediction model had larger area under receiver operating characteristic curve and higher specificity, the differences were statistically significant.

Conclusion

Our new scoring model for young infants can facilitate early identification of BM and has a better performance than BMS and MSE models.
A neonate with multiple hand flexor tendon ruptures due to methicillin-susceptible Staphylococcus aureus sepsis: a case report
Authors: Nakamuara Tomomi , Iwai Masanori , Inoue Takeshi , Irie Hiroki , Karasugi Tatsuki , Seki Atsuhito , Hamaguchi Masayoshi , Kuraoka Shohei , Mizukami Tomoyuki , Nakamura Kimitoshi
Published: February 2023

Background

Neonatal pyogenic tenosynovitis is a highly emergent soft tissue infection. We report a case of a neonate with pyogenic tendinopathy and tendon rupture diagnosed by ultrasonography (US). He subsequently developed pyogenic arthritis and osteomyelitis during antimicrobial therapy.

Case presentation

A 7-day-old boy was admitted to our hospital with redness and swelling of the right index finger. US on admission showed rupture of the flexor tendon of the right index finger with inactivity. The day after admission, he developed pyogenic arthritis of the right elbow and, subsequently, pyogenic osteomyelitis. Staphylococcus aureus was identified through bacterial culture, and the patient was treated with intravenous antibiotics for 6 weeks. However, after discharge from our hospital, rupture of the flexor tendon of the left thumb was confirmed. A two-stage flexor tendinoplasty was completed at the age of 2 years and 1 month for the flexor tendon rupture on his right index finger.

Conclusions

In addition to blood culture, ultrasonographic evaluation should be performed in neonates with erythematous and swollen joints to identify the focus of infection as soon as possible. Moreover, repeated regular US examination is important in the follow-up of bone and soft tissue infections.
The descriptive analysis of depressive symptoms and White Blood Cell (WBC) count between the sexual minorities and heterosexual identifying individuals in a nationally representative sample: 2005–2014
Authors: Lu Junjie , Yang Jiarui , Liang Jingyang , Mischoulon David , Nyer Maren
Published: February 2023

Background

Sexual minorities are at a higher risk of suffering from depressive symptoms compared with heterosexual individuals. Only a few studies have examined the conditions of having depressive symptoms within different sexual minority groups, especially people with sexual orientation uncertainty in a nationally representative sample. Furthermore, few studies have explored whether the mean white blood count (WBC) is different between people with and without depressive symptoms among different sexual minority groups in a nationally representative sample.

Methods

We analyzed the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2014 with a sample of 14,090 subjects. We compared the prevalence of depressive symptoms in subpopulations stratified by sex, sexual minority status, and race. We also examined the difference in mean WBC count between depressed and non-depressed people among heterosexual individuals and different sexual minority groups. Additionally, two multivariable logistic regression models were used to explore the association between sexual minority status and depressive symptoms, treating sexual minority status as both a binary and categorical variable.

Results

Female sex (OR: 1.96, 95% CI: 1.72—2.22) and sexual minority status (OR: 1.79, 95% CI: 1.47—2.17) were both independently associated with depressive symptoms. Within the sexual minority population, subjects who were unsure about their sexual identities had the highest odds of having depressive symptoms (OR: 2.56, 95% CI: 1.40—4.68). In the subgroup analysis considering intersectionality, black sexual minority females had the highest rate of depressive symptoms (19.4%, 95% CI: 7.72—40.98). Finally, the mean WBC count differed significantly between people with and without depressive symptoms among male heterosexual individuals, female heterosexual individuals, and female sexual minorities, but not among male sexual minorities.

Conclusions

Based on sex, race, and sexual minority status, black females of sexual minority status had the highest rate of depressive symptoms. Within sexual minority groups, participants who were unsure about their sexual identities had the highest odds of having depressive symptoms. Finally, the mean WBC count was significantly higher among people with depressive symptoms than those without depressive symptoms only among male heterosexuals, female heterosexuals, and female sexual minorities, but not among male sexual minorities. Future research should investigate the social and biological mechanisms of the differences.
What matters in development and sustainment of community dementia friendly initiatives and why? A realist multiple case study
Authors: Thijssen Marjolein , Kuijer-Siebelink Wietske , Lexis Monique A.S. , Nijhuis-van der Sanden Maria W. G. , Daniels Ramon , Graff Maud
Published: February 2023

Background

Dementia friendly communities (DFCs) are seen as key to participation of people with dementia and carers. Dementia-friendly initiatives (DFI) are important building blocks for the growth of DFCs. Therefore, it is essential to understand how DFIs are developed and sustained to secure the growth of DFCs. This study identifies contextual factors and mechanisms that influence the development and sustainment of Dutch DFIs. It also explains how these contextual factors and mechanisms are interrelated and the outcomes to which they lead.

Methods

Mixed methods, namely interviews, observations, documentation and focus groups, were used for this realist multiple case study. Participants were professionals (n = 46), volunteers (n = 20), people with dementia (n = 1) and carers (n = 2) who were involved in development and sustainment of DFIs in four Dutch DFCs.

Results

This study revealed three middle-range program theories as final outcomes: development of a support base, collaboration, and participation in DFIs by people with dementia and carers. These theories address institutional, organisational, interpersonal and individual levels in the community that are essential in development and sustainment of DFIs.

Conclusions

The development and sustainment of DFIs requires the development of a support base, collaboration, and participation in DFIs by people with dementia and their carers.
Migrant and native women’s perceptions of prenatal care communication quality: the role of host-country language proficiency
Authors: Hamwi Sousan , Lorthe Elsa , Severo Milton , Barros Henrique
Published: February 2023

Background

Despite the potentially significant impact of women-prenatal care provider communication quality (WPCQ) on women’s perinatal health, evidence on the determinants of those perceptions is still lacking, particularly among migrant women.

Methods

We aimed to examine the effect of women’s host-country language proficiency on their perceived WPCQ. We analyzed the data of 1210 migrant and 1400 native women who gave birth at Portuguese public hospitals between 2017 and 2019 and participated in the baMBINO cohort study. Migrants’ language proficiency was self-rated. Perceived WPCQ was measured as a composite score of 9 different aspects of self-reported communication quality and ranged from 0 (optimal) to 27.

Results

A high percentage of women (29%) rated communication quality as “optimal”. Zero-inflated regression models were fitted to estimate the association between language proficiency and perceived WPCQ. Women with full (aIRR 1.35; 95% CI 1.22,1.50), intermediate (aIRR 1.41; 95% CI 1.23,1.61), and limited (aIRR 1.72; 95% CI 1.45,2.05) language proficiencies were increasingly more likely to have lower WPCQ when compared to natives.

Conclusions

Facilitating communication with migrant women experiencing language barriers in prenatal care could provide an important contribution to improving prenatal care quality and addressing potential subsequent disparities in perinatal health outcomes.
What is the role of attitudinal barriers on cervical cancer screening non-attendance? Findings from a cross-sectional study with migrant women in Portugal
Authors: Marques Patrícia , Geraldes Mariana , Gama Ana , Heleno Bruno , Dias Sónia
Published: February 2023

Background

Cervical cancer is a common disease which can be effectively and timely detected by cervical cancer screening. However, access to cervical cancer screening is unequal, and it is known that migrant women have a lower attendance to cervical cancer screening. These inequalities are associated with several factors, including attitudes and beliefs of the women regarding screening practices, which prevents them from participating. This study aims to explore the attitudinal barriers to cervical cancer screening among migrant women in Portugal.

Methods

A web-based cross-sectional survey was conducted with 1100 migrant women residing in Portugal. Women were recruited through social media platforms. The survey included items on socioeconomic characteristics, cervical cancer screening history and an 11-item attitudinal questionnaire to assess attitudinal barriers. Logistic regression models were used for statistical analysis.

Results

The attitudinal barriers to CCS most often reported by participants were fear of the test result (25.3%), worry about seeing a male health professional (23.8%), perceiving the test as painful (23.1%), embarrassment (18.5%), difficulties scheduling the test (14.3%), and having a negative experience in screening (12.4%). Low perceived need in absence of symptoms and lack of motivation to be screened were reported by less than 5% of the women. However, the results suggest that most of the attitudinal barriers with higher agreement percentage have no association with cervical cancer screening attendance. Among all the attitudinal barriers, low perceived need of screening and lack of motivation were associated with CCS non-attendance.

Conclusions

Based on the findings, out of all the factors analyzed, low perceived need of screening and lack of motivation are the most relevant factors associated with non-attendance among migrants in Portugal. Promoting health literacy and empowering women with knowledge about benefits of screening may help overcoming these barriers. Therefore, this study provides a foundation for stakeholders on which areas should be prioritized when developing strategies aiming to reduced cervical cancer screening non-attendance among migrant women.
Time and productivity loss associated with immunotherapy infusions for the treatment of melanoma in the United States: a survey of health care professionals and patients
Authors: Aguiar-Ibáñez Raquel , Scherrer Emilie , Grebennik Dmitri , Cook John , Bagga Shalini , Sawhney Baanie , Khandelwal Anvi , Soefje Scott A.
Published: February 2023

Introduction

A new dosing schedule for the oncology immunotherapy pembrolizumab, every 6 weeks (Q6W), has been approved by the U.S. FDA, reducing the frequency of visits to infusion centers. We quantified the time spent by oncologists, nurses, patients, and caregivers per melanoma-related immunotherapy infusion visit to evaluate its potential impact.

Methods

Surveys were self-completed by 100 oncologists, 101 oncology nurses, and 100 patients with melanoma across the U.S. to quantify the time spent per infusion visit with pembrolizumab (Q3W or Q6W), nivolumab (Q2W or Q4W), or nivolumab+ipilimumab (nivolumab in combination: Q3W; nivolumab maintenance: Q2W or Q4W). Time measures included traveling, waiting, consultation, infusion, post-treatment observation, and caregiving. Respondents were also surveyed regarding the impact of the COVID-19 pandemic on infusion treatments.

Results

Responses deemed valid were provided by 89 oncologists, 93 nurses, and 100 patients. For each new [returning] patient treated with pembrolizumab, nivolumab or nivolumab+ipilimumab, oncologists reported to spend an average of 90 [64], 87 [60] and 101 [69] minutes per infusion visit (p-value for between-group difference = 0.300 [0.627]). For first [subsequent] treatment cycles, nurses reported spending 160 [145] average minutes per visit for nivolumab+ipilimumab, versus roughly 120 [110] for the single agents (p-value for between-group difference = 0.018 [0.022]). Patients reported to spend an average of 263, 382, and 224 minutes per visit at the center for pembrolizumab (N = 47), nivolumab (n = 34), and nivolumab+ipilimumab (n = 15) respectively (p-value for between-group difference = 0.0002). Patients also reported that their unpaid (N = 20) and paid caregivers (N = 41) spent with them an average of 966 and 333 minutes, respectively, from the day before to the day after the infusion visit.

Conclusion

Less frequent immunotherapy infusion visits may result in substantial time savings for oncologists, nurses, patients, and caregivers.
Evaluation of an infection control link nurse program: an analysis using the RE-AIM framework
Authors: Dekker Mireille , Jongerden Irene P. , Caris Martine G. , de Bruijne Martine C. , Vandenbroucke-Grauls Christina M. J. E. , van Mansfeld Rosa
Published: February 2023

Background

Important elements of programs that train and support infection control link nurses (ICLN) are the engagement of stakeholders, support from hospital and ward management and a structure for iterative improvement. The effects of programs, that combine all these elements, are unknown. We evaluated such a comprehensive program to explore its impact on link nurses and infection prevention practices and routines.

Methods

We used the RE-AIM framework, a robust, evidence-based framework within the field of Implementation Science, to evaluate the impact of our ICLN training and support program. We used a mixed methods approach and organized the outcomes along its five dimensions: Reach, Effectiveness, Adoption, Implementation and Maintenance.

Results

Between 2014 and 2018, on average 91% of the inpatient wards and 58% of the outpatient clinics participated in the program (Reach) and impacted guideline adherence in inpatient wards. Link nurses felt engaged and empowered, and perceived their contribution to these results as pivotal. Ward managers confirmed the value of ICLN to help with implementing IPC practices (Effectiveness). The program was adopted both at the hospital and at the ward level (Adoption). Based on ongoing evaluations, the program was adapted by refining education, training and support strategies with emphasis on ward specific aspects (Implementation). The ICLN program was described as a key component of the infection prevention policy to sustain its effects (Maintenance).

Conclusions

Our infection control link nurse program helped ICLN to improve infection prevention practices, especially in inpatient wards. The key to these improvements lay within the adaptability of our link nurse program. The adjustments to the program led to a shift of focus from hospital goals to goals tailored to the ward level. It allowed us to tailor activities to align them with the needs specific to each ward.
Prenatal exposure to fine particulate matter and newborn anogenital distance: a prospective cohort study
Authors: Shen Xiaoli , Meng Xia , Wang Cuiping , Chen Xiangfeng , Chen Qian , Cai Jing , Zhang Jun , Zhang Qianlong , Fan Lichun
Published: February 2023

Background

Considerable attention has been paid to reproductive toxicity of fine particulate matter (PM2.5). However, the relationship between prenatal PM2.5 exposure and anogenital distance (AGD) has not been well studied. We aim to investigate the potential effects of prenatal exposure to PM2.5 on newborn AGD.

Methods

Prenatal PM2.5 exposure of 2332 participates in Shanghai (2013–2016) was estimated using high-performance machine learning models. Anoscrotal distance (AGDas) in male infants and anofourchette distance (AGDaf) in female infants were measured by well-trained examiners within 3 days after birth. We applied multiple linear regression models and multiple informant models to estimate the association between prenatal PM2.5 exposure and AGD.

Results

Multiple linear regression models showed that a 10 μg/m3 increase in PM2.5 exposure during full pregnancy, the second and third trimesters was inversely associated with AGDas (adjusted beta = − 1.76, 95% CI: − 2.21, − 1.31; − 0.73, 95% CI: − 1.06, − 0.40; and − 0.52; 95% CI: − 0.87, − 0.18, respectively) in males. A 10 μg/m3 increase in PM2.5 exposure during the full pregnancy, the first, second, and third trimesters was inversely associated with AGDaf (adjusted beta = − 4.55; 95% CI: − 5.18, − 3.92; − 0.78; 95% CI: − 1.10, − 0.46; − 1.11; 95% CI: − 1.46, − 0.77; − 1.45; 95% CI: − 1.78, − 1.12, respectively) in females after adjusting for potential confounders. Multiple informant models showed consistent but slightly attenuated associations.

Conclusion

Our study observed a significant association between gestational PM2.5 exposure during pregnancy and shortened AGD in newborns, and provided new evidence on potential reproductive toxicity of prenatal PM2.5 exposure.
Near-infrared light triggered in situ release of CO for enhanced therapy of glioblastoma
Authors: Ge Juan , Zuo Miaomiao , Wang Qirong , Li Zhen
Published: February 2023

Background

Photodynamic therapy (PDT) features high biocompatibility and high spatiotemporal selectivity, showing a great potential in glioblastoma (GBM) treatment. However, its application was restricted by the poor therapeutic efficacy and side effect.

Results

In this study, a therapeutic nanoplatform (UCNPs@Ce6/3HBQ@CM) with combination of PDT and CO therapy was constructed, in which a photoCORM and a photosensitizer were loaded onto the surface of upconversion nanoparticles (UCNPs) functioning as photon transducer. Benefitting from NIR excitation and multicolor emission of UCNPs, the penetration depth of excitation light is enhanced and meanwhile simultaneous generation of CO and ROS in tumor site can be achieved. The as-prepared nanocomposite possessed an elevated therapeutic efficiency with the assistance of CO through influencing mitochondrial respiration and depleting ATP, accompanying with the reduced inflammatory responses. By wrapping a homologous cell membrane, the nanocomposite can target GBM and accumulate in the tumor site, affording a powerful tool for precise and efficient treatment of GBM.

Conclusion

This therapeutic nanoplatform UCNPs@Ce6/3HBQ@CM, which combines PDT and CO therapy enables precise and efficient treatment of refractory glioblastoma.