bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of a refractory prolactin-secreting pituitary adenoma into a pituitary carcinoma: report of a challenging case and literature review
Authors: Dai Congxin , Sun Bowen , Guan Shusen , Wang Wei , Liu Honggang , Li Yong , Zhang Jialiang , Kang Jun 
Published: October 2021

Abstract
Background
Pituitary carcinomas (PCs), defined as distant metastases of pituitary neoplasms, are very rare malignancies. Because the clinical presentation of PCs is variable, early diagnosis and management remain challenging. PCs are always refractory to comprehensive treatments, and patients with PCs have extremely poor prognoses.

Case presentation
We describe one case of a prolactin-secreting pituitary adenoma (PA) refractory to conventional therapy that evolved into a PC with intraspinal metastasis. A 34-year-old female was diagnosed with an invasive prolactin-secreting PA in 2009 and was unresponsive to medical treatment with bromocriptine. The tumor was gross totally removed via transsphenoidal surgery (TSS). However, the patient experienced multiple tumor recurrences or regrowth despite comprehensive treatments, including medical therapy, two gamma knife radiosurgeries (GKSs), and four frontal craniotomies. In 2016, she was found to have an intradural extramedullary mass at the level of the fourth lumbar vertebra. The intraspinal lesion was completely resected and was confirmed as a metastatic PC based on histomorphology and immunohistochemical staining. The literature on the diagnosis, molecular pathogenesis, treatment, and prognosis of patients with prolactin-secreting PCs was reviewed.

Conclusion
PCs are very rare neoplasms with variable clinical features and poor prognosis. Most PCs usually arise from aggressive PAs refractory to conventional therapy. There is no reliable marker to identify aggressive PAs with a risk for progression to PCs; thus, it is difficult to diagnose these PCs early until the presence of metastatic lesions. It is still very challenging to manage patients with PCs due to a lack of standardized protocols for diagnosis and treatment. Establishing molecular biomarkers and the pathobiology of PCs could help in the early identification of aggressive PAs most likely to evolve into PCs.
A study of correlations between metabolic syndrome factors and osteosarcopenic adiposity
Authors: Su Yu-Hsiang , Chang Yu-Ming , Kung Chih-Ying , Sung Chiu-Kuei , Foo Wei-Shin , Wu Mei-Hua , Chiou Shang-Jyh 
Published: October 2021

Abstract
Background
Aging reduces the quality and strength of bones and muscles and increases body fat, which can lead to the simultaneous occurrence of sarcopenia, osteopenia, and adiposity, a condition referred to as OsteoSarcopenic Adiposity (OSA).
While previous studies have demonstrated that metabolic syndrome is associated with sarcopenia, osteopenia, and adiposity, the relationship between metabolic syndrome and OSA remains largely unknown.

Methods
We analyzed data for a sample of middle-aged individuals from a Health Management Center database, which was collected in 2016–2018. There are 2991 cases of people over 50 years from a physical examination center in a hospital in Taiwan during 2016–2018. In addition to descriptive statistics, chi-squared test, analysis of variance, and multinomial logistic regression analysis were conducted to examine OSA risk and associated factors.

Results
Based on multinomial logistic regression analysis, in different OSA severity level (1–3 more serious), those who are with metabolic syndrome has increased the 2.49–2.57 times risk of OSA (p < 0.001) in OSA = 2 and 3 groups while there is no significant difference in OSA =1 group.

Conclusion
The prevalence of OSA may impair the health and quality of life in the elderly group, especially those diagnosed with metabolic syndrome, increasing the risk of OSA. These results can help promote early diagnosis and treatment of OSA in clinical settings, particularly among aging individuals with abnormal physical function, the group with the highest OSA incidence.
Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models
Authors: Peng Ying , Peng Chongsheng , Wu Yang , Sun Chongzhi , Li Xiaobo 
Published: October 2021

Abstract
Background
The Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control.

Methods
In this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule’an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis.

Results
The BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively.

Conclusions
These results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.
Students with global experiences during medical school are more likely to work in settings that focus on the underserved: an observational study from a public U.S. institution
Authors: Slifko Shay E. , Vielot Nadja A. , Becker-Dreps Sylvia , Pathman Donald E. , Myers Justin G. , Carlough Martha 
Published: October 2021

Abstract
Background
Global health interest has grown among medical students over the past 20 years, and most medical schools offer global health opportunities. Studies suggest that completing global health electives during medical school may increase the likelihood of working with underserved populations in a clinical or research capacity. This study aimed to assess the association of global electives in medical school on subsequently working in global health and with underserved populations in the United States (U.S.), additionally considering students’ interests and experiences prior to medical school. We also examined whether respondents perceived benefits gained from global electives.

Methods
We surveyed medical school graduates (classes of 2011-2015) from a large public medical school in the U.S. to describe current practice settings and previous global health experience. We evaluated work, volunteer, and educational experiences preceding medical school, socioeconomic status, race and ethnicity using American Medical College Application Service (AMCAS) data. We assessed the association between students’ backgrounds, completing global health electives in medical school and current work in global health or with underserved populations in the U.S.

Results
In the 5 to 8 years post-graduation, 78% of 161 respondents reported work, research, or teaching with a focus on global or underserved U.S. populations. Completing a global health elective during medical school (p = 0.0002) or during residency (p = 0.06) were positively associated with currently working with underserved populations in the U.S. and pre-medical school experiences were marginally associated (p = 0.1). Adjusting for pre-medical school experiences, completing a global health elective during medical school was associated with a 22% greater prevalence of working with an underserved population. Perceived benefits from global electives included improved cultural awareness, language skills, public health and research skills, and ability to practice in technology-limited settings.

Conclusion
Medical school graduates who participated in global electives as students were more likely than their peers to pursue careers with underserved populations, independent of experiences prior to medical school. We hypothesize that by offering global health experiences, medical schools can enhance the interests and skills of graduates that will make them more likely and better prepared to work with underserved populations in the U.S. and abroad.
Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation
Authors: Shen Jian , Hao Junnian , Chen Yini , Liu Hairong , Wu Jianrong , Hu Bing , Wang Yan , Zheng Yuanyi , Cai Xiaojun 
Published: October 2021

AbstractBackgroundThe risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake.ResultsHerein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy.ConclusionsThis effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies.Graphical Abstract
How could nanobiotechnology improve treatment outcomes of anti-TNF-α therapy in inflammatory bowel disease? Current knowledge, future directions
Authors: Eder Piotr , Zielińska Aleksandra , Karczewski Jacek , Dobrowolska Agnieszka , Słomski Ryszard , Souto Eliana B. 
Published: October 2021

AbstractDespite significant advances in therapeutic possibilities for the treatment of inflammatory bowel disease (IBD) in recent years, there is still a big room for improvement. In particular, biological treatment can induce not only clinical remission but also mucosal healing of the gastrointestinal tract. Among these therapeutic molecules, anti-tumor necrosis factor-alpha (anti-TNF-α) antibodies were the first to revolutionize treatment algorithms in IBD. However, due to the parenteral route of administration and systemic mode of action, TNF-α blockers are characterised by high rates of immunogenicity-related loss of response and serious adverse events. Moreover, intravenous or subcutaneous therapy is not considered patient-friendly and requires occasional, direct contact with healthcare centres. To overcome these limitations, several attempts have been made to design oral pharmaceutical formulations of these molecules. It is hypothesized that oral anti-TNF-α antibodies therapy can directly provide a targeted and potent anti-inflammatory effect in the inflamed gastrointestinal tissues without significant systemic exposure, improving long-term treatment outcomes and safety. In this review, we discuss the current knowledge and future perspectives regarding different approaches made towards entering a new era of oral anti-TNF-α therapy, namely, the tailoring of biocompatible nanoparticles with anti-TNF-α antibodies for site-specific targeting to IBD. In particular, we discuss the latest concepts applying the achievements of nanotechnology-based drug design in this area.Graphical Abstract
Platelet-derived sCD40L: specific inflammatory marker for early-stage severe acute respiratory syndrome coronavirus 2 infection
Authors: Hamzeh-Cognasse Hind , Mansour Alexandre , Reizine Florian , Mismetti Patrick , Gouin-Thibault Isabelle , Cognasse Fabrice 
Published: October 2021

AbstractBackgroundThe SARS-CoV-2 virus is the causing agent of the Coronavirus disease 2019 (COVID-19) characterized by a huge pro-inflammatory response and coagulation disorders that may lead to for its severe forms, in organ failure or even death. As major players of thrombo-inflammation, platelets release large amounts of immunomodulatory molecules and regulate leukocyte and endothelial activity, which are both altered in COVID-19. Altogether, this makes platelets a very likely actor of the thrombo-inflammatory complications of COVID-19. Thus, we propose to identify a platelet inflammatory signature of severe COVID-19 specifically modulated throughout the course of the disease.MethodsLuminex technology and enzyme-linked immunosorbent assay were used to assess plasma levels of platelet inflammatory markers in patients with severe acute respiratory syndrome coronavirus 2 infection on admission and for 14 days afterwards.ResultsIn accordance with the observations of other teams, we evidence that the plasma levels of the platelet soluble (s)CD40L is significantly elevated in the early stages of the disease. Interestingly we observe that the plasma level of sCD40L decreases overtime while that of sCD62P increases significantly.ConclusionsOur data suggest that there is a platelet signature of inflammatory response to SARS-COv-2 infection which varies overtime and could serve as monitoring biomarkers of patient inflammatory state.Clinical trial registration number: 2020-A01100-39; title: Human Ab Response & immunoMONItoring of COVID-19 Patients, registration date: 05/25/2020; URL of the registry:https://clinicaltrials.gov/ct2/history/NCT04373200?V_5=View.
Epidemiologic and clinical characteristics of human bocavirus infection in infants and young children suffering with community acquired pneumonia in Ningxia, China
Authors: Ji Kai , Sun Jinhan , Yan Yan , Han Lei , Guo Jianhui , Ma Anwen , Hao Xueqi , Li Fang , Sun Yuning 
Published: October 2021

Abstract
Background
Pneumonia has a high incidence rate and is a major cause of mortality in children, mostly community-acquired pneumonia (CAP). Human bocavirus (HBoV), since it first identified in 2005, has been repeatedly associated with respiratory tract infections. Nevertheless, the role and related information of HBoV as a pathogen of CAP has not been fulfilled. Here our study is to assess the epidemiological and clinical features in HBoV-positive children with CAP.

Methods
A total of 878 secretions of lower respiratory samples were obtained, multiplex PCR was used to detect HBoV and other respiratory viruses.

Results
Of all cases, HBoV was detected in 10.0%, with a peak incidence of infection among children < 2 year old, and predominantly noted in autumn and winter. Only 8 patients were HBoV single infection. Co-infection with other respiratory viruses was observed in 86.4%. Moreover, co-infection with bacteria occurred in 27.3% and with Mycoplasma pneumoniae (MP) in 33.0% of HBoV-positive patients. Among all HBoV-positive samples co-infected with bacteria, 87.5% are gram negative bacteria. Compared with HBoV-negative group, age (P = 0.048), wheezing (P = 0.015), tachypnea (P = 0.016), lactate dehydrogenase (P = 0.026) and severe pneumonia (P = 0.023) were statistically significant in HBoV-positive patients. Furthermore, HBoV-positive patients less than 1 year old were more likely to have co-infection with bacteria (P = 0.007).

Conclusions
HBoV can be detected alone in respiratory samples of children with CAP, maybe it is one of the causes of CAP in infants. The high incidence of severe pneumonia was found in HBoV-positive patients compared with HBoV-negative cases may indicate a relationship between severe pneumonia and HBoV.
Predictors for timely initiation of breastfeeding after birth in the hospitals of Nepal- a prospective observational study
Authors: Gurung Rejina , Sunny Avinash K. , Paudel Prajwal , Bhattarai Pratiksha , Basnet Omkar , Sharma Srijana , Shrestha Durgalaxmi , Sharma Seema , Malla Honey , Singh Dela , Mishra Sangeeta , KC Ashish 
Published: October 2021

Abstract
Background
Timely initiation of breastfeeding can reduce neonatal morbidities and mortality. We aimed to study predictors for timely initiation of breastfeeding (within 1 h of birth) among neonates born in hospitals of Nepal.

Method
A prospective observational study was conducted in four public hospitals between July and October 2018. All women admitted in the hospital for childbirth and who consented were included in the study. An independent researchers observed whether the neonates were placed in skin-to-skin contact, delay cord clamping and timely initiation of breastfeeding. Sociodemographic variables, obstetric and neonate information were extracted from the maternity register. We analysed predictors for timely initiation of breastfeeding with Pearson chi-square test and multivariate logistic regression.

Results
Among the 6488 woman-infant pair observed, breastfeeding was timely initiated in 49.5% neonates. The timely initiation of breastfeeding was found to be higher among neonates who were placed skin-to-skin contact (34.9% vs 19.9%, p - value < 0.001). The timely initiation of breastfeeding was higher if the cord clamping was delayed than early cord clamped neonates (44.5% vs 35.3%, p - value < 0.001). In multivariate analysis, a mother with no obstetric complication during admission had 57% higher odds of timely initiation of breastfeeding (aOR 1.57; 95% CI 1.33, 1.86). Multiparity was associated with less timely initiation of breastfeeding (aOR 1.56; 95% CI 1.35, 1.82). Similarly, there was more common practice of timely initiation of breastfeeding among low birthweight neonates (aOR 1.46; 95% CI 1.21, 1.76). Neonates who were placed skin-to-skin contact with mother had more than two-fold higher odds of timely breastfeeding (aOR 2.52; 95% CI 2.19, 2.89). Likewise, neonates who had their cord intact for 3 min had 37% higher odds of timely breastfeeding (aOR 1.37; 95% CI 1.21, 1.55).

Conclusions
The rate of timely initiation of breastfeeding practice is low in the health facilities of Nepal. Multiparity, no obstetric complication at admission, neonates placed in skin-to-skin contact and delay cord clamping were strong predictors for timely initiation of breastfeeding. Quality improvement intervention can improve skin-to-skin contact, delayed cord clamping and timely initiation of breastfeeding.
The role of estrogen deprivation therapy in premenopausal women with primary unresectable intracardiac leiomyomatosis: a systematic review and meta-analysis
Authors: Liang Jinxiao , Lei Ruilin , Xie Mingwei , Lin Shaodan , Xu Jing , Ling Xiaoting , Xie Qingsheng 
Published: October 2021

Abstract
Background
Intracardiac leiomyomatosis (ICLM) is a rare life-threatening form of intravenous leiomyomatosis (IVLM). The incomplete resection and recurrence are associated with high morbidity and mortality. The objective of this study is to identify that whether estrogen deprivation therapies, including bilateral salpingo-oophorectomy (BSO)-based surgery and gonadotrophin releasing hormone agonists (GnRHa) administration, could bring benefits to patients with primary unresectable ICLM.

Methods
PubMed/MEDLINE (Ovid) was searched (up to May 2021) for studies reporting individual patient data on demographics, clinicopathological features, treatment, and follow-up information. Exclusion criteria were patients who may have been included in two or more publications. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results
A total of 114 patients from 70 papers were included. Several reports showed that the tumor in the right atrium and inferior vena cava shrank dramatically after BSO-based surgery, or GnRHa administrated preoperatively in premenopausal women. The rate of complete resection was 64.04% in patients with ICLM, which was 85.25% in no/slight adhesion and no pulmonary nodules group, while 22.22% in firm/extensive adhesion and/or pulmonary nodules group (p < 0.0001). Meanwhile, the recurrence rates in patients with complete resection and incomplete resection were 4.29% and 37.84% respectively (p < 0.0001). Furthermore, complete resection with BSO had the lowest recurrence rate of 3.13%, incomplete resection with BSO had a progression rate of 45.45%, while incomplete resection with ovarian preservation had the highest progression rate of 75.00%.

Conclusions
The recurrence rate of ICLM was closely related to firm/extensive adhesion in IVC or above, and/or pulmonary nodules. BSO-based surgery might reduce the recurrence rate no matter ICLM could be completely resected or not. In addition, estrogen deprivation therapies could decrease tumor burden as a primary treatment, and further make a secondary complete resection feasible in premenopausal women with initially unresectable ICLM.
Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma
Authors: Xun Yang , Yang Hua , Kaminska Bozena , You Hua 
Published: October 2021

AbstractGlioma represents a fast proliferating and highly invasive brain tumor which is resistant to current therapies and invariably recurs. Despite some advancements in anti-glioma therapies, patients’ prognosis remains poor. Toll-like receptors (TLRs) act as the first line of defense in the immune system being the detectors of those associated with bacteria, viruses, and danger signals. In the glioma microenvironment, TLRs are expressed on both immune and tumor cells, playing dual roles eliciting antitumoral (innate and adaptive immunity) and protumoral (cell proliferation, migration, invasion, and glioma stem cell maintenance) responses. Up to date, several TLR-targeting therapies have been developed aiming at glioma bulk and stem cells, infiltrating immune cells, the immune checkpoint axis, among others. While some TLR agonists exhibited survival benefit in clinical trials, it attracts more attention when they are involved in combinatorial treatment with radiation, chemotherapy, immune vaccination, and immune checkpoint inhibition in glioma treatment. TLR agonists can be used as immune modulators to enhance the efficacy of other treatment, to avoid dose accumulation, and what brings more interests is that they can potentiate immune checkpoint delayed resistance to PD-1/PD-L1 blockade by upregulating PD-1/PD-L1 overexpression, thus unleash powerful antitumor responses when combined with immune checkpoint inhibitors. Herein, we focus on recent developments and clinical trials exploring TLR-based treatment to provide a picture of the relationship between TLR and glioma and their implications for immunotherapy.