bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eczema herpeticum subsequent to septic shock in early pregnancy: a first case report
Authors: Furuya Kiichiro , Takemoto Yuki , Kurahashi Hiroki , Hayashida Harue , Fujiwara Sho , Yamashita Saya , Chang Yangsil , Tsubouchi Hiroaki , Shikado Kayoko , Ogita Kazuhide 
Published: December 2021

Abstract
Background
Eczema herpeticum (EH) is a severe skin complication caused by human simplex virus (HSV) infection concomitant with immune dysfunction and dermatological conditions, mainly atopic dermatitis. We present the first case of EH subsequent to sepsis-related immunological suppression in pregnancy.

Case presentation
Septic shock developed in a 30-year-old primiparous woman at 14 weeks of pregnancy during admission for hyperemesis gravidarum. Although her life-threatening status due to sepsis improved by prompt treatment, on day 3 of treatment in the intensive care unit, blisters suddenly erupted on her face and neck and spread over her body. EH was diagnosed according to HSV type-1 antigen positivity and a past medical history of EH and atopic dermatitis. Antiviral agents were administered immediately, with positive results. Her general condition improved quickly, without central nervous system defects. This is the first report of EH following septic shock in early pregnancy. At present, we speculate that EH develops as a complication due to immunological changes in the late phase of sepsis because sepsis is mainly characterized by both an inflammatory state in the acute phase and an immunosuppressive state in the late phase. Pregnancy can also contribute to its pathogenesis, as it causes an immunosuppressive state. Mortality due to EH is relatively high; in this case, a history of EH and atopic dermatitis contributed to the initiation of prompt medical interventions for the former, with improvement in the patient’s severe condition. The combination of immunological changes in sepsis and pregnancy can cause HSV reactivation, resulting in EH recurrence.

Conclusions
In conclusion, if dermatological symptoms develop in a pregnant woman with a history of EH and/or atopic dermatitis treated for sepsis, EH should be suspected based not only on clinical features but also on immunological changes along with sepsis, and prompt medical interventions should be initiated.
Training programs to improve identification of sick newborns and care-seeking from a health facility in low- and middle-income countries: a scoping review
Authors: Fung Alastair , Hamilton Elisabeth , Du Plessis Elsabé , Askin Nicole , Avery Lisa , Crockett Maryanne 
Published: December 2021

Abstract
Background
Most neonatal deaths occur in low- and middle-income countries (LMICs). Limited recommendations are available on the optimal personnel and training required to improve identification of sick newborns and care-seeking from a health facility. We conducted a scoping review to map the key components required to design an effective newborn care training program for community-based health workers (CBHWs) to improve identification of sick newborns and care-seeking from a health facility in LMICs.

Methods
We searched multiple databases from 1990 to March 2020. Employing iterative scoping review methodology, we narrowed our inclusion criteria as we became more familiar with the evidence base. We initially included any manuscripts that captured the concepts of “postnatal care providers,” “neonates” and “LMICs.” We subsequently included articles that investigated the effectiveness of newborn care provision by CBHWs, defined as non-professional paid or volunteer health workers based in communities, and their training programs in improving identification of newborns with serious illness and care-seeking from a health facility in LMICs.

Results
Of 11,647 articles identified, 635 met initial inclusion criteria. Among these initial results, 35 studies met the revised inclusion criteria. Studies represented 11 different types of newborn care providers in 11 countries. The most commonly studied providers were community health workers. Key outcomes to be measured when designing a training program and intervention to increase appropriate assessment of sick newborns at a health facility include high newborn care provider and caregiver knowledge of newborn danger signs, accurate provider and caregiver identification of sick newborns and appropriate care-seeking from a health facility either through caregiver referral compliance or caregivers seeking care themselves. Key components to consider to achieve these outcomes include facilitators: sufficient duration of training, refresher training, supervision and community engagement; barriers: context-specific perceptions of newborn illness and gender roles that may deter care-seeking; and components with unclear benefit: qualifications prior to training and incentives and remuneration.

Conclusion
Evidence regarding key components and outcomes of newborn care training programs to improve CBHW identification of sick newborns and care-seeking can inform future newborn care training design in LMICs. These training components must be adapted to country-specific contexts.
Clinicopathological characteristics and survival outcomes in patients with synchronous lung metastases upon initial metastatic breast cancer diagnosis in Han population
Authors: Lin Shaoyan , Mo Hongnan , Li Yiqun , Guan Xiuwen , Chen Yimeng , Wang Zijing , Xu Binghe 
Published: December 2021

AbstractBackgroundWe investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population.MethodsWe attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses.ResultsPatients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients.ConclusionsOur study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.
Population-level interventions targeting risk factors of diabetes and hypertension in South Africa: a document review
Authors: Uwimana - Nicol Jeannine , Hendricks Lynn , Young Taryn 
Published: December 2021

Abstract
Background
South Africa bears an increasing burden of non-communicable diseases (NCDs), particularly diabetes, cardiovascular diseases, and cancer. The objective of this study was to identify which population-level interventions, implemented at the level of governmental or political jurisdictions only, targeting risk factors of diabetes and hypertension were included in policies in South Africa. We also looked at whether these have been implemented or not.

Methods
A review of relevant reports, journal articles, and policy documents was conducted. Documentation from government reports that contains information regarding the planning, implementation and evaluation of population-level interventions targeting diabetes and hypertension were considered, and various databases were searched. The identified population-level interventions were categorized as supportive policies, supportive programs and enabling environments according to the major risk factors of NCDs i.e., tobacco use, harmful consumption of alcohol, unhealthy diet/nutrition and physical inactivity, in accordance with the WHO ‘Best buys’. A content document analysis was conducted.

Results
The source documents reviewed included Acts and laws, regulations, policy documents, strategic plans, case studies, government reports and editorials. South Africa has a plethora of policies and regulations targeting major risk factors for diabetes and hypertension implemented in line with WHO ‘Best buys’ since 1990. A total of 28 policies, legislations, strategic plans, and regulations were identified - 8 on tobacco use; 7 on harmful consumption of alcohol; 8 on unhealthy diet and 5 on physical inactivity - as well as 12 case studies, government reports and editorials. There is good progress in policy formulation in line with the ‘Best buys’. However, there are some gaps in the implementation of these policies and programs.

Conclusion
Curbing the rising burden of NCDs requires comprehensive strategies which include population-level interventions targeting risk factors for diabetes and hypertension and effective implementation with robust evaluation to identify successes and ways to overcome challenges.
Regulation of medicines advertisement in Zimbabwe: an assessment of the impact of pharmaceutical promotion on the prescribing behaviour of healthcare professionals
Authors: Semu Tafadzwa Collins , Ngara Bernard , Mudzviti Tinashe 
Published: December 2021

Abstract
Background
The pharmaceutical industry plays a key role in drug discovery and is considered useful regards to informing the health care workers health care workers about new medicines. Investigations concerning health care workers to industry interactions are less common. The objective of this study is to determine levels of knowledge, attitude and perception towards regulation of pharmaceutical promotion among healthcare practitioners in Zimbabwe.

Methods
A cross-sectional study was used and 330 healthcare practitioners were enrolled into the study. Data collection was done through combined face-to-face interviews and web-based online survey. The relative importance index score and used as a measure of knowledge, attitude and perception levels towards pharmaceutical promotion. Univariate and bivariate analysis was performed using STATA software package.

Results
Our study estimated that 95%, 67%, and 90% of the healthcare practitioners in Zimbabwe have a favourable (i.e. > 65%) relative importance index score of knowledge, attitudes, and perception, respectively, towards regulation of pharmaceutical promotion. Further exploration of the data indicated that the factors that had an association with the knowledge, attitude and perception levels towards regulation of pharmaceutical regulation at 5% level of significance include health care workers’ profession, gender, education level, the nature of the working institution and the number of prescriptions involved per week.

Conclusion
In conclusion, the findings of this study highlighted that in general the health care workers in Zimbabwe have higher levels of knowledge, attitude and perception towards regulation of pharmaceutical promotion, though the attitudes levels weres a bit lower compared to other domains.
Protective effects of wogonin on lipopolysaccharide-induced inflammation and apoptosis of lung epithelial cells and its possible mechanisms
Authors: Ge Jinlin , Yang Huanhuan , Zeng Yufeng , Liu Yunjie 
Published: December 2021

AbstractBackgroundWogonin (5, 7-dihydroxy-8-methoxyflavone) is a natural di-hydroxyl flavonoid extracted from the root ofScutellaria baicalensisGeorgi. This paper was intended to investigate the mechanism of action of wogonin in alleviating the inflammation and apoptosis in acute lung injury (ALI).Materials and methodsLipopolysaccharide (LPS) was used to establish the in vitro model of ALI. After wogonin treatment, the cell viability and apoptosis of LPS-induced A549 cells were, respectively, measured by CCK-8, TUNEL assays and acridine orange/ethidium bromide dual staining, while the contents of inflammatory cytokines and oxidative stress markers were estimated by RT-qPCR, ELISA assay, western blot analysis and commercial kits. Western blot was also conducted to assess the expression of proteins involved. Subsequently, the effect of wogonin on the sirtuin 1 (SIRT1)-mediated high-mobility group box 1 protein (HMGB1) deacetylation was investigated. SIRT1 inhibitor EX527 was used to evaluate the regulatory effects of wogonin on SIRT1-mediated HMGB1 deacetylation in A549 cells under LPS stimulation.ResultsLPS induced inflammation, oxidative stress and apoptosis of A549 cells, which was abolished by wogonin. It was also found that wogonin promoted the HMGB1 deacetylation, accompanied by upregulated SIRT1 expression. However, SIRT1 inhibitor EX527 partially reversed the protective effects of wogonin on the inflammation and apoptosis of LPS-induced A549 cells.ConclusionWogonin alleviated the inflammation and apoptosis in LPS-induced A549 cells by SIRT1-mediated HMGB1 deacetylation, which might represent the identification of a novel mechanism by which wogonin exerts protective effects on ALI and provide ideas for the application of wogonin to ALI treatment.
Modeling ischemic stroke in a triculture neurovascular unit on-a-chip
Authors: Wevers Nienke R. , Nair Arya Lekshmi , Fowke Tania M. , Pontier Maria , Kasi Dhanesh G. , Spijkers Xandor M. , Hallard Charlie , Rabussier Gwenaëlle , van Vught Remko , Vulto Paul , de Vries Helga E. , Lanz Henriëtte L. 
Published: December 2021

Abstract
Background
In ischemic stroke, the function of the cerebral vasculature is impaired. This vascular structure is formed by the so-called neurovascular unit (NVU). A better understanding of the mechanisms involved in NVU dysfunction and recovery may lead to new insights for the development of highly sought therapeutic approaches. To date, there remains an unmet need for complex human in vitro models of the NVU to study ischemic events seen in the human brain.

Methods
We here describe the development of a human NVU on-a-chip model using a platform that allows culture of 40 chips in parallel. The model comprises a perfused vessel of primary human brain endothelial cells in co-culture with induced pluripotent stem cell derived astrocytes and neurons. Ischemic stroke was mimicked using a threefold approach that combines chemical hypoxia, hypoglycemia, and halted perfusion.

Results
Immunofluorescent staining confirmed expression of endothelial adherens and tight junction proteins, as well as astrocytic and neuronal markers. In addition, the model expresses relevant brain endothelial transporters and shows spontaneous neuronal firing. The NVU on-a-chip model demonstrates tight barrier function, evidenced by retention of small molecule sodium fluorescein in its lumen. Exposure to the toxic compound staurosporine disrupted the endothelial barrier, causing reduced transepithelial electrical resistance and increased permeability to sodium fluorescein. Under stroke mimicking conditions, brain endothelial cells showed strongly reduced barrier function (35-fold higher apparent permeability) and 7.3-fold decreased mitochondrial potential. Furthermore, levels of adenosine triphosphate were significantly reduced on both the blood- and the brain side of the model (4.8-fold and 11.7-fold reduction, respectively).

Conclusions
The NVU on-a-chip model presented here can be used for fundamental studies of NVU function in stroke and other neurological diseases and for investigation of potential restorative therapies to fight neurological disorders. Due to the platform’s relatively high throughput and compatibility with automation, the model holds potential for drug compound screening.
Feasibility study of volumetric modulated arc therapy with Halcyon™ linac for total body irradiation
Authors: Uehara Takuya , Monzen Hajime , Tamura Mikoto , Inada Masahiro , Otsuka Masakazu , Doi Hiroshi , Matsumoto Kenji , Nishimura Yasumasa 
Published: December 2021

Abstract
Background
The use of total body irradiation (TBI) with linac-based volumetric modulated arc therapy (VMAT) has been steadily increasing. Helical tomotherapy has been applied in TBI and total marrow irradiation to reduce the dose to critical organs, especially the lungs. However, the methodology of TBI with Halcyon™ linac remains unclear. This study aimed to evaluate whether VMAT with Halcyon™ linac can be clinically used for TBI.

Methods
VMAT planning with Halcyon™ linac was conducted using a whole-body computed tomography data set. The planning target volume (PTV) included the body cropped 3 mm from the source. A dose of 12 Gy in six fractions was prescribed for 50% of the PTV. The organs at risk (OARs) included the lens, lungs, kidneys, and testes.

Results
The PTV D98%, D95%, D50%, and D2% were 8.9 (74.2%), 10.1 (84.2%), 12.6 (105%), and 14.2 Gy (118%), respectively. The homogeneity index was 0.42. For OARs, the Dmean of the lungs, kidneys, lens, and testes were 9.6, 8.5, 8.9, and 4.4 Gy, respectively. The V12Gy of the lungs and kidneys were 4.5% and 0%, respectively. The Dmax of the testes was 5.8 Gy. Contouring took 1–2 h. Dose calculation and optimization was performed for 3–4 h. Quality assurance (QA) took 2–3 h. The treatment duration was 23 min.

Conclusions
A planning study of TBI with Halcyon™ to set up VMAT-TBI, dosimetric evaluation, and pretreatment QA, was established.
Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules
Authors: Zhou Jian , Cheng Tong , Li Xing , Hu Jie , Li Encheng , Ding Ming , Shen Rulong , Pineda John P. , Li Chun , Lu Shaohua , Yu Hongyu , Sun Jiayuan , Huang Wenbin , Wang Xiaonan , Si Han , Shi Panying , Liu Jing , Chang Meijia , Dou Maosen , Shi Meng , Chen Xiaofeng , Yung Rex C. , Wang Qi , Zhou Ning , Bai Chunxue 
Published: December 2021

Abstract
Background
Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions.

Results
Using the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5–100.0%) and 92.1% specificity (95% CI 83.5–100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6–100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0–100.0%) noted for pulmonary nodules with diameters ≤ 2 cm.

Conclusions
Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.
Impact of comorbidities on risk of angioedema without urticaria in elderly patients
Authors: Bożek Andrzej , Zając Magdalena 
Published: December 2021

Abstract
Background
Angioedema without urticaria (AWU) is a disease found in the elderly population but is still poorly studied. The aim of this study was to investigate potential factors, especially comorbidities, that may affect the induction of angioedema without urticaria in patients over 60 years of age.

Methods
This was an observational, retrospective study of 242 patients with a diagnosis of AWU and 263 controls. The inclusion criteria were as follows: at least one episode of confirmed AWU based on the ICD-10 code (T78.3) that required treatment in the last 15 years (2004–2019); age above 60 years; detailed medical history of comorbidities; and details regarding the use of drugs at that time. Serum functional and quantitative C1 inhibitor assays were performed, and serum C4 was measured.
Comorbidities were grouped into the following panels: autoimmune, cancer, cardiac, metabolic, respiratory and allergic, liver failure and renal failure. Individual diseases were checked according to ICD code and treatment.

Results
In 1 (0.4%) patient, hereditary angioedema was confirmed. Decreased levels of C1INH were observed in 4 (1.65%) patients, dysfunction of C1INH was observed in 5 (1.76%) patients, and low levels of C4 were observed in 9 (3.71%) patients in the study group. The multiple logistic regression model revealed that patients with hyperuricemia or Hashimoto’s disease had a significantly higher chance of angioedema (OR = 3.21, 95% CI 2.92–3.66, p = 0.002; OR = 1.78 95% CI 1.37–2.21, p = 0.034, respectively).

Conclusion
The obtained results may indicate a significant influence of hyperuricemia or Hashimoto’s disease on angioedema manifestations.
First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer
Authors: Klein Nulent Thomas J. W. , van Es Robert J. J. , Willems Stefan M. , Braat Arthur. J. A. T. , Devriese Lot A. , de Bree Remco , de Keizer Bart 
Published: December 2021

Abstract
Background
Advanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA.

Methods
This study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT.

Results
Six patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects.

Conclusions
Palliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.