bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thorahcic SMARCA4-deficient undifferentiated tumors with ganglioneuroma and enchondroma: implications for SLC7A11 and ARID1A expression: a case report
Authors: Kito Yusuke , Kawashima Keisuke , Saigo Chiemi , Hasegawa Masayoshi , Nomura Shusuke , Mikamo Takuya , Hanamatsu Yuki , Matsuo Yasuhiro , Takeuchi Tamostu 
Published: February 2022

Abstract
Background
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4-deficient thoracic sarcoma (SMARCA4-DTS) is a rare disease that has recently been described as an entity. It is characterized by an aggressive clinical course and specific genetic alterations. As an immunohistological feature, the tumors are deficient in SMARCA4 and SMARCA2 and express sex-determining region Y (SRY)-box 2 (SOX2). Occasionally, there are cases that are less frequent and difficult to distinguish from SMARCA4-deficient non-small cell lung carcinoma (SMARCA4-dNSCLC). Therefore, the 5th edition of the World Health Organization (WHO) classification describes thoracic SMARCA 4-deficient undifferentiated tumors (SMARCA4-UT). In contrast, Carney’s triad is a syndrome that combines three rare soft tissue tumors: gastric leiomyosarcoma, pulmonary chondroma, and extra-adrenal paraganglioma. Protein kinase cAMP-dependent type I regulatory subunit alpha (PRKAR1A) has been proposed as the causative gene. Both diseases are valuable cases; moreover, there have been no previous reports of their coexistence.

Case presentation
A 43-year-old man visited our hospital because of respiratory distress. Computed tomography revealed a large mass measuring 55 mm in the upper lobe of the right lung and front mediastinum, with metastases in the surrounding lymph nodes. Needle biopsy was performed for diagnosis, and histological examination of the samples revealed monotonous epithelioid-like cells with loose binding and sheet-form proliferation. The tumor cells had distinct nuclei with some rhabdoid-like cells. Immunohistochemical analysis revealed that the tumor cells were positive for AE1AE3, SOX2, CD34, and p53 and negative for SMARCA4 and SMARCA2. The patient died 6 months after admission, without any treatment. Autopsy revealed ganglioneuroma and enchondroma suggestive of an incomplete Carney complex.

Conclusion
SMARCA4-UT is a rare and recently established disease. While it is difficult to diagnose, it is necessary to distinguish undifferentiated carcinoma, large cell carcinoma, Ewing sarcoma, and epithelioid sarcoma when diagnosing tumors involving the mediastinum. Moreover, cases of SMARCA4-UT with ganglioneuroma and enchondroma are very rare. We discuss and report a case of SMARCA4-UT in which we also examined ARID1A and SLC7A11expression.
Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy
Authors: Zhang Jiaqiang , Sum Shao-Yin , Hsu Jeng-Guan , Chiang Ming-Feng , Lee Tian-Shyug , Wu Szu-Yuan 
Published: February 2022

Abstract
Background
To date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).

Patients and methods
We enrolled 646 women with left-breast IDC at clinical stages I–IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs).

Results
In the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37–0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79–0.96; P = 0.0356) and 0.89 (0.54–1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group.

Conclusion
Adjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.
Diagnostic characteristics, treatment patterns, and clinical outcomes for patients with advanced/metastatic medullary thyroid cancer
Authors: Parikh Rohan , Hess Lisa M. , Esterberg Elizabeth , Bhandari Naleen Raj , Kaye James A. 
Published: February 2022

Abstract
Background
Medullary thyroid cancer (MTC) accounts for approximately 1.6% of new cases of thyroid cancer. The objective of this study was to describe patient characteristics, biomarker testing, treatment patterns, and clinical outcomes among patients with advanced/metastatic MTC in a real-world setting in the United States and to identify potential gaps in the care of these patients.

Methods
Selected oncologists retrospectively reviewed medical records of patients aged ≥ 12 years diagnosed with advanced MTC. Patients must have initiated ≥ 1 line of systemic treatment for advanced/metastatic MTC between January 2013–December 2018 to be eligible. Patient characteristics, biomarker testing, and treatment patterns were summarized descriptively; progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method.

Results
The 203 patients included in this study had a mean (SD) age of 52.2 (10.4) years; mean (SD) duration of follow-up from start of first-line treatment was 24.5 (16.0) months. Most patients (82.8%) were initially diagnosed with stage IVA, IVB, or IVC disease. Among all patients, 121 (59.6%) had testing for RET mutations, of whom 37.2% had RET-mutant MTC. The RET-mutation type was reported for 28 patients; the most common mutations reported were M918T (64.3%) and C634R (32.1%). Of the 203 patients, 75.9% received only one line of systemic treatment for advanced disease, and 36% were still undergoing first-line therapy at the time of data extraction. Cabozantinib (30.0%), vandetanib (30.0%), sorafenib (17.2%), and lenvatinib (4.9%) were the most common first-line treatments. Among 49 patients who received second-line treatment, most received cabozantinib (22.4%), vandetanib (20.4%), lenvatinib (12.2%), or sunitinib (12.2%). Median PFS (95% confidence interval [CI]) from start of first- and second-line treatments was 26.6 months (20.8–60.8) and 15.3 months (6.6-not estimable [NE]), respectively. Median OS from initiation of first- and second-line treatment was 63.8 months (46.3-NE) and 22.4 months (12.4-NE), respectively.

Conclusions
For the treatment of advanced/metastatic MTC, no specific preference of sequencing systemic agents was observed in the first- and second-line settings. Considering the recent approval of selective RET inhibitors for patients with RET-mutant MTC, future research should investigate how treatment patterns evolve for these patients.
Curcumin assists anti-EV71 activity of IFN-α by inhibiting IFNAR1 reduction in SH-SY5Y cells
Authors: Wang Yanfang , Dan Kena , Xue Xiaoling , Chen Bangtao , Chen Cheng 
Published: February 2022

Abstract
Background and aim
Enterovirus 71(EV71) can cause severe hand, foot, and mouth disease (HFMD) with brain tissue involvement. Few effective anti-EV71 drugs are presently available in clinical practice. Interferon-α (IFN-α) was ineffective while Curcumin was effective in restricting EV71 replication in non-neuronal cells. Ubiquitin–proteasome-mediated degradation of interferon-alpha receptor 1 (IFNAR1) protein contributes to IFN-α resistance. Current study aimed to determine synergistic inhibition of EV71 by Curcumin and IFN-α in human neuroblastoma SH-SY5Y cells.

Methods
SH-SY5Y cells were infected with mock-/Curcumin-pre-incubated EV71 or transfected with plasmid containing interferon-stimulated response element (ISRE) or mRNA containing viral internal ribosomal entry site (IRES) following by post-treatment with Curcumin with or without IFN-α. Supernatant IFN-α/β was detected by ELISA. ISRE, IRSE, proteasome and deubiquitinating activity were measured by luciferase assay. EV71 RNA and viral protein or IFNAR1 were determined by qPCR and western blot, respectively.

Results
EV71 flailed to completely block IFN-α/β production but inhibited IFN-α signal. Curcumin only slightly inhibited EV71 proliferation without modulating virus attachment and internalization. However, Curcumin addition restored IFN-α-mediated ISRE activity thus significantly inhibiting EV71 replication. Furthermore, EV71 also reduced IFNAR1 protein with proteasome-dependence in SH-SY5Y cells, which can be reversed by Curcumin addition with the evidence that it lowered proteasome activity.

Conclusion
These data demonstrate that Curcumin assists anti-EV71 activity of IFN-α by inhibiting IFNAR1 reduction via ubiquitin–proteasome disruption in SH-SY5Y cells.
Global research alliance in infectious disease: a collaborative effort to combat infectious diseases through dissemination of portable sequencing
Authors: Runtuwene Lucky R. , Sathirapongsasuti Nuankanya , Srisawat Raweewan , Komalamisra Narumon , Tuda Josef S. B. , Mongan Arthur E. , Aboge Gabriel O. , Shabardina Victoria , Makalowski Wojciech , Nesti Dela Ria , Artama Wayan T. , Nguyen-Thi Lan Anh , Wan Kiew-Lian , Na Byoung-Kuk , Hall William , Pain Arnab , Eshita Yuki , Maeda Ryuichiro , Yamagishi Junya , Suzuki Yutaka 
Published: February 2022

Abstract
Objective
To disseminate the portable sequencer MinION in developing countries for the main purpose of battling infectious diseases, we found a consortium called Global Research Alliance in Infectious Diseases (GRAID). By holding and inviting researchers both from developed and developing countries, we aim to train the participants with MinION’s operations and foster a collaboration in infectious diseases researches. As a real-life example in which resources are limited, we describe here a result from a training course, a metagenomics analysis from two blood samples collected from a routine cattle surveillance in Kulan Progo District, Yogyakarta Province, Indonesia in 2019.

Results
One of the samples was successfully sequenced with enough sequencing yield for further analysis. After depleting the reads mapped to host DNA, the remaining reads were shown to map to Theileria orientalis using BLAST and OneCodex. Although the reads were also mapped to Clostridium botulinum, those were found to be artifacts derived from the cow genome. An effort to construct a consensus sequence was successful using a reference-based approach with Pomoxis. Hence, we concluded that the asymptomatic cow might be infected with T. orientalis and showed the usefulness of sequencing technology, specifically the MinION platform, in a developing country.
Economic and caregiver impact of Alzheimer’s disease across the disease spectrum: a cohort study
Authors: Dauphinot Virginie , Potashman Michele , Levitchi-Benea Mihaela , Su Ray , Rubino Ivana , Krolak-Salmon Pierre 
Published: February 2022

Abstract
Background
Alzheimer’s disease (AD) substantially increases health-related costs. This study investigates direct medical costs and characterizes the caregiver burden across AD stages.

Methods
This study analyzed data from the French Primary Health Insurance Fund claims database and reflected this public payer perspective. Outpatients (N = 1998) visiting a memory clinic at Lyon University Hospital in France between 2014 and 2019 were included. Real healthcare costs (ie, ambulatory medicine, paramedical care, pharmaceutical treatment, public and private hospital stays, and medical transportation) were collected for patients 1 year prior to the date of the first memory visit and 2 years following the first visit (reference year: 2019). Patients were grouped based on a clinical diagnosis of cognitively normal with a subjective cognitive complaint (SCC), all-cause mild cognitive impairment (MCI), or AD dementia. The severity of AD dementia was defined by the Mini-Mental State Examination score. Caregiver burden was measured using the mini Zarit Burden Interview. A generalized linear model was used for statistical analyses. Other patient nonmedical and indirect costs and caregiver costs were not included.

Results
The study sample included patients with SCC (n = 640), MCI (n = 630), mild (n = 212), moderate (n = 256), or moderately severe/severe AD dementia (n = 260). One year after the first consultation, mean total costs were higher with progressive cognitive deficit, with little difference between dementia groups (SCC = €8028; MCI = €9758; mild AD dementia = €10,558; moderate AD dementia = €10,544; moderately severe/severe AD dementia = €10,345; P < .001). Public hospital stays comprised the majority of direct medical costs during the first semester following the visit (49.4% of the total costs), regardless of the severity of cognitive deficit. Caregiver burden increased with the severity of cognitive deficit (P < .0001).

Conclusions
Direct medical costs and caregiver burden rose from SCC to AD dementia; in patients with AD dementia, the direct medical costs increased over the 2 years after the first consultation. These results, in conjunction with data from other care components, will be critical to elucidate the potential economic value of a therapeutic intervention that slows AD progression.
Reversible anomia and cerebral venous thrombosis: a case report and review of the literature
Authors: Ayele Biniyam A. , Abdella Riyad Ibrahim , Wachamo Leilt Zewdie 
Published: February 2022

Abstract
Background
Cerebral venous thrombosis is a rare form of venous stroke with diverse clinical manifestations. Word-finding difficulty (anomia) is rarely reported in patients with cerebral venous thrombosis.

Case presentation
We report a 30-year-old right-handed Ethiopian female patient, who presented with global headache associated with a new onset word-finding difficulty of 2 weeks duration. The headache was not responsive to over-the-counter medications. She reported blurring of vision and nausea. Two months previously, she gave birth to a dead fetus. On neurological assessment, the patient was fully conscious and oriented, with a Glasgow coma score of 15/15, and cranial nerves, motor, and sensory examinations were unremarkable. Examination of fundus showed grade 2 papilledema bilaterally. Language assessment showed normal fluency, compression, naming, reading, and repetition. Naming was assessed using a 60 second word generating test, which indicated anomia. Brain magnetic resonance imaging showed left temporoparietal ischemia, magnetic resonance venography showed thrombosis of the left transverse, sigmoid sinus, and corresponding cortical veins. She was started on warfarin 5 mg daily for 6 months and showed significant resolution of symptoms, including the anomia.

Conclusion
The present case describes a young female patient with reversible anomia as a complication of cerebral venous thrombosis. The case also highlights the importance of timely diagnosis and treatment of cerebral venous thrombosis for a benign prognosis.
Muscle stem cell adaptations to cellular and environmental stress
Authors: Gugliuzza Maria Vittoria , Crist Colin 
Published: February 2022

AbstractBackgroundLifelong regeneration of the skeletal muscle is dependent on a rare population of resident skeletal muscle stem cells, also named ‘satellite cells’ for their anatomical position on the outside of the myofibre and underneath the basal lamina. Muscle stem cells maintain prolonged quiescence, but activate the myogenic programme and the cell cycle in response to injury to expand a population of myogenic progenitors required to regenerate muscle. The skeletal muscle does not regenerate in the absence of muscle stem cells.Main bodyThe notion that lifelong regeneration of the muscle is dependent on a rare, non-redundant population of stem cells seems contradictory to accumulating evidence that muscle stem cells have activated multiple stress response pathways. For example, muscle stem cell quiescence is mediated in part by the eIF2α arm of the integrated stress response and by negative regulators of mTORC1, two translational control pathways that downregulate protein synthesis in response to stress. Muscle stem cells also activate pathways to protect against DNA damage, heat shock, and environmental stress. Here, we review accumulating evidence that muscle stem cells encounter stress during their prolonged quiescence and their activation. While stress response pathways are classically described to be bimodal whereby a threshold dictates cell survival versus cell death responses to stress, we review evidence that muscle stem cells additionally respond to stress by spontaneous activation and fusion to myofibres.ConclusionWe propose a cellular stress test model whereby the prolonged state of quiescence and the microenvironment serve as selective pressures to maintain muscle stem cell fitness, to safeguard the lifelong regeneration of the muscle. Fit muscle stem cells that maintain robust stress responses are permitted to maintain the muscle stem cell pool. Unfit muscle stem cells are depleted from the pool first by spontaneous activation, or in the case of severe stress, by activating cell death or senescence pathways.
Comparative study of the effect of National Health Insurance Scheme on use of delivery and antenatal care services between rural and urban women in Ghana
Authors: Kofinti Raymond Elikplim , Asmah Emmanuel Ekow , Ameyaw Edward Kwabena 
Published: February 2022

Abstract
Background
Despite the focus of the National Health Insurance Scheme (NHIS) to bridge healthcare utilisation gap among women in Ghana, recent evidence indicates that most maternal deaths still occur from rural Ghana. The objective of this study was to examine the rural-urban differences in the effects of NHIS enrolment on delivery care utilisation (place of delivery and assistance at delivery) and antenatal care services among Ghanaian women.

Methods
A nationally representative sample of 4169 women from the 2014 Ghana Demographic and Health Survey was used. Out of this sample, 2880 women are enrolled in the NHIS with 1229 and 1651 being urban and rural dwellers, respectively. Multivariate logistic and negative binomial models were fitted as the main estimation techniques. In addition, the Propensity Score Matching technique was used to verify rural-urban differences.

Results
At the national level, enrolment in NHIS was observed to increase delivery care utilisation and the number of ANC visits in Ghana. However, rural-urban differences in effects were pronounced: whereas rural women who are enrolled in the NHIS were more likely to utilise delivery care [delivery in a health facility (OR = 1.870; CI = 1.533–2.281) and assisted delivery by a medical professional (OR = 1.994; CI = 1.631–2.438)], and have a higher number of ANC visits (IRR = 1.158; CI = 1.110–1.208) than their counterparts who are not enrolled, urban women who are enrolled in the NHIS on the other hand, recorded statistically insignificant results compared to their counterparts not enrolled. The PSM results corroborated the rural-urban differences in effects.

Conclusion
The rural-urban differences in delivery and antenatal care utilisation are in favour of rural women enrolled in the NHIS. Given that poverty is endemic in rural Ghana, this positions the NHIS as a potential social equaliser in maternal health care utilisation especially in the context of developing countries by increasing access to delivery care services and the number of ANC visits.
COVID-19 and the efficiency of health systems in Europe
Authors: Lupu Dan , Tiganasu Ramona 
Published: February 2022

Abstract
Background
This study aims at analyzing the efficiency of the health systems of 31 European countries in treating COVID-19, for the period January 1, 2020 – January 1, 2021, by incorporating some factors from a multidimensional perspective.

Methods
The methodology used in the research was Data Envelopment Analysis (DEA), through which efficiency scores for health systems have been calculated. The research was performed considering three stages: the first wave (January 1–June 15), the relaxation period (June 15–October 1) and the second wave (October 1–December 31). In evaluating the determinants of the efficiency of health systems, six major fields of influence were taken into account: health care, health status, population, economic, cultural/societal and governmental issues, all covering 15 indicators. After measuring the efficiency, we used the Tobit type regression to establish the influencing elements on it.

Results
The results for the public health systems of European states were determined for each country and period. We evaluated the efficiency of health systems in Europe against COVID-19, starting from health inputs (COVID-19 cases, physicians, nurses, hospital beds, health expenditure) and output (COVID-19 deaths). The obtained outputs show that, especially in the first phase of the pandemic, the inefficiency of the health systems was quite high, mainly in Western countries (Italy, Belgium, Spain, UK). In the relaxation phase and in the second wave, the Western states, severely affected at the beginning of the pandemic, began to take adequate measures and improve the efficiency of their sanitary systems. Instead, Eastern European countries were hit hard by the inefficiency of health systems (Bulgaria, Greece, Hungary, Romania). After Tobit regression, results of the study show that the influencing elements are different for the three stages: concerning the first wave, comobirdities, population age, and population density are important; for relaxation period a great influence have government effectiveness and power distance; with respect to second wave, the relevant factors are education and population density.

Conclusions
The results obtained could serve as starting points for health policymakers to perform comparative analyzes in terms of good practices in the health system and to develop national plans to better deal with health crises. At the same time, they can be used internationally to achieve a coherent and effective community response to the pandemic.