bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health Technology Assessment (HTA) and Access Policies
Authors: Stühlinger Verena 
Published: June 2020

Abstract
For patients, innovations in healthcare can be both a great blessing (when saving people’s life or improving quality of life), as well as a curse (when only few people have access, e.g., because of high prices). Thus, when healthcare innovations are proven safe and ready for application, decision makers have to apply access policies and sometimes face difficult assessments. In this context, health technology assessment (HTA) plays a crucial role at European Union level, forming an evidence-based, transparent basis for decision making through joint assessments. However, pricing and reimbursement aspects are exempt from collaborative assessments, since these are in the responsibility of the EU Member States: according to Art. 168(7) TFEU the ‘organisation and delivery of health services and medical care [… including] the allocation of the resources assigned to them’ remain an exclusive competence of Member States. However, future challenges may require further cooperation.
Synesthesia as (Multimodal) Mental Imagery
Authors: Nanay Bence 
Published: June 2020

Abstract
It has been repeatedly suggested that synesthesia is intricately connected with unusual ways of exercising one’s mental imagery, although it is not always entirely clear what the exact connection is. My aim is to show that all forms of synesthesia are forms of (often very different kinds of) mental imagery and, further, if we consider synesthesia to be a form of mental imagery, we get significant explanatory benefits, especially concerning less central cases of synesthesia where the inducer is not sensory stimulation.
Enalapril inhibits inflammatory osteolysis induced by wear debris in a mouse model
Authors: Ma Huanzhi , Zhang Qin , Shi Jun , Gao Yutong , Sun Chengliang , Zhang Wei 
Published: June 2020

Objective Aseptic loosening, the most frequent complication after total joint replacement, is probably caused by an inflammatory response to the shedding of wear debris from the implant. The only effective treatment is surgical revision. Using a mouse model, we investigated whether enalapril inhibits wear debris-induced inflammatory osteolysis. Methods Titanium (Ti) alloy particles were introduced, and calvarial bone from syngeneic mice was implanted into air pouches established in BALB/c mice. Histological and molecular analyses were performed with inflammatory tissue samples obtained from mice treated with and without enalapril. Results Enalapril inhibited tissue inflammation and inflammatory osteolysis induced by Ti particles, reducing pouch membrane thickness and decreasing inflammatory cell infiltration. In addition, enalapril inhibited the expression of the inflammatory cytokines vascular endothelial growth factor and tumor necrosis factor-α. Conclusions Our study provides evidence that enalapril inhibits Ti particle-induced inflammatory osteolysis, and it may be a potentially useful treatment for aseptic loosening.
The Invisible MGHL Test: Diagnostic Value and Benefits for the Repair of Retracted Subscapularis Tears
Authors: Chauvet Thomas , Haritinian Emil , Baudin Florian , Collotte Philippe , Nové-Josserand Laurent 
Published: June 2020

Background: Some full-thickness subscapularis tendon tears and partial tears of the deep layer are difficult to characterize, leading to misdiagnosis. Purpose: To evaluate the association between displacement of the middle glenohumeral ligament (MGHL) and retracted tears of the subscapularis tendon as a possible test to improve diagnosis. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Videos (N = 100) recorded during arthroscopic rotator cuff repair involving a torn subscapularis tendon were analyzed retrospectively to assess the association between the MGHL test (nonvisibility of the MGHL) and other objective anatomic criteria. The invisible MGHL test was defined as positive if the MGHL was initially nonvisible in the beach-chair position and appeared only when the subscapularis tendon was pulled back into position by using a 30° arthroscope from the standard posterior portal. The parameters considered during the initial exploration were (1) visibility of the horizontal part of the subscapularis tendon; (2) visibility of the MGHL in its usual position, crossing the superior border of the subscapularis tendon; (3) exposure of the lateral border of the subscapularis tendon (full-thickness retracted tear); and (4) complete or partial exposure of the lesser tuberosity of the humerus. Tendon retraction was evaluated in 3 stages according to the Patte classification. Results: The invisible MGHL test result was positive in 45% of cases. It was positive in 6% of cases (2 of 31) when there was no subscapularis tendon retraction and in 62% of cases (43 of 69) when there was partial or complete retraction ( P < .001). The invisible MGHL test was significantly associated with the width of the tear ( P < .001) and exposure of the lateral border of the subscapularis tendon (full-thickness retracted tear, P = .0002). After repair, the MGHL was visible in its anatomic position in 96% of cases. Conclusion: A positive invisible MGHL test is an alternative indication of subscapularis tendon retraction, and the relocation of the MGHL can also be used after repair to assess the proper anatomic repositioning of the subscapularis tendon.
Potential Cytochrome P450 Drug‐Drug Interaction Among Adult and Adolescent Patients Undergoing Tonsillectomy
Authors: Nimmagadda Sai , Wong Stephanie Jung‐ying , Faria Madlin , Allen Paul , Faria John 
Published: June 2020

ObjectiveTo assess the frequency of potential drug‐drug interactions affecting cytochrome P450 (CYP)–mediated metabolism of opioids among adult and adolescent patients who underwent adenotonsillectomy.Study DesignRetrospective chart review.SettingTertiary care university hospital.Patients and MethodsA retrospective review was conducted of 279 patients who underwent adenotonsillectomy at the University of Rochester. The discharge medication list was reviewed for all patients, and their postoperative medications were compared with a reference list published by the Food and Drug Administration and the University of Indiana’s Department of Clinical Pharmacology (Flockhart Table) to determine whether CYP‐inducing or CYP‐inhibiting medication was present.ResultsOut of 279 patients, 197 different medications were taken postoperatively. Approximately 70% of patients were taking 2 medications in addition to the standard postoperative analgesics (acetaminophen, hydrocodone, oxycodone, morphine, and/or ibuprofen). The 5 most commonly prescribed medications excluding the posttonsillectomy medications were oral contraceptives, ondansetron, amoxicillin, albuterol, and methylprednisolone. Four percent of patients were taking a medication that inhibits CYP3A4; <1% were taking a medication that induces CYP3A4; and 15% were taking a medication that inhibits CYP2D6.ConclusionsNearly 20% of the patients in this cohort were taking a medication that may alter opioid metabolism through induction or inhibition of CYP3A4 or CYP2D6. Some of these interactions have the potential to be more clinically relevant than others, particularly interactions that can lead to enhanced toxicity of opioids due to accumulation of active metabolites.
Peripheral perfusion index predicting prolonged ICU stay earlier and better than lactate in surgical patients: an observational study
Authors: Shi Xinge , Xu Ming , Yu Xu , Lu Yibin 
Published: June 2020

Abstract
Background
Peripheral perfusion index (PPI) is an indicator reflecting perfusion. Patients undergoing long time surgeries are more prone to hypoperfusion and increased lactate. Few studies focusing on investigating the association between PPI and surgical patients’ prognoses. We performed this study to find it out.

Methods
From January 2019 to September 2019, we retrospected all surgical patients who were transferred to ICU, Xinyang Central hospital, Henan province, China. Inclusive criteria: age ≥ 18 years old; surgical length ≥ 120 min. Exclusive criteria: died in ICU; discharging against medical advice; existing diseases affecting blood flow of upper limbs, for example, vascular thrombus in arms; severe liver dysfunction.
We defined “prolonged ICU stay” as patients with their length of ICU stay longer than 48 h. According to the definition, patients were divided into two groups: “prolonged group” (PG) and “non-prolong group” (nPG). Baseline characteristics, surgical and therapeutic information, ICU LOS, SOFA and APACHE II were collected. Besides we gathered data of following parameters at 3 time points (T0: ICU admission; T1: 6 h after admission; T2: 12 h after admission): mean artery pressure (MAP), lactate, heart rate (HR), PPI and body temperature. Data were compared between the 2 groups. Multivariable binary logistic regression and ROC (receiver operating characteristic) curves were performed to find the association between perfusion indictors and ICU LOS.

Results
Eventually, 168 patients were included, 65 in PG and 103 in nPG. Compared to nPG, patients in PG had higher blood lactate and lower PPI. PPI showed significant difference between two groups earlier than lactate (T0 vs T1). The value of PPI at two time points was lower in PG than nPG(T0: 1.09 ± 0.33 vs 1.41 ± 0.45, p = 0.001; T1: 1.08 ± 0.37 vs 1.49 ± 0.41, p < 0.001).
Increased lactateT1(OR 3.216; 95% CI 1.253–8.254, P = 0.015) and decreased PPIT1 (OR 0.070; 95% CI 0.016–0.307, P < 0.001) were independently associated with prolonged ICU stay. The area under ROC of the PPIT1 for predicting ICU stay> 48 h was 0.772, and the cutoff value for PPIT1 was 1.35, with 83.3% sensitivity and 73.8% specificity.

Conclusions
PPI and blood lactate at T1(6 h after ICU admission) are associated with ICU LOS in surgical patient. Compared to lactate, PPI indicates hypoperfusion earlier and more accurate in predicting prolonged ICU stay.
Tandem gene duplications drive divergent evolution of caffeine and crocin biosynthetic pathways in plants
Authors: Xu Zhichao , Pu Xiangdong , Gao Ranran , Demurtas Olivia Costantina , Fleck Steven J. , Richter Michaela , He Chunnian , Ji Aijia , Sun Wei , Kong Jianqiang , Hu Kaizhi , Ren Fengming , Song Jiejie , Wang Zhe , Gao Ting , Xiong Chao , Yu Haoying , Xin Tianyi , Albert Victor A. , Giuliano Giovanni , Chen Shilin , Song Jingyuan 
Published: June 2020

Abstract
Background
Plants have evolved a panoply of specialized metabolites that increase their environmental fitness. Two examples are caffeine, a purine psychotropic alkaloid, and crocins, a group of glycosylated apocarotenoid pigments. Both classes of compounds are found in a handful of distantly related plant genera (Coffea, Camellia, Paullinia, and Ilex for caffeine; Crocus, Buddleja, and Gardenia for crocins) wherein they presumably evolved through convergent evolution. The closely related Coffea and Gardenia genera belong to the Rubiaceae family and synthesize, respectively, caffeine and crocins in their fruits.

Results
Here, we report a chromosomal-level genome assembly of Gardenia jasminoides, a crocin-producing species, obtained using Oxford Nanopore sequencing and Hi-C technology. Through genomic and functional assays, we completely deciphered for the first time in any plant the dedicated pathway of crocin biosynthesis. Through comparative analyses with Coffea canephora and other eudicot genomes, we show that Coffea caffeine synthases and the first dedicated gene in the Gardenia crocin pathway, GjCCD4a, evolved through recent tandem gene duplications in the two different genera, respectively. In contrast, genes encoding later steps of the Gardenia crocin pathway, ALDH and UGT, evolved through more ancient gene duplications and were presumably recruited into the crocin biosynthetic pathway only after the evolution of the GjCCD4a gene.

Conclusions
This study shows duplication-based divergent evolution within the coffee family (Rubiaceae) of two characteristic secondary metabolic pathways, caffeine and crocin biosynthesis, from a common ancestor that possessed neither complete pathway. These findings provide significant insights on the role of tandem duplications in the evolution of plant specialized metabolism.
Proceedings of the 4th BEAT-PCD Conference and 5th PCD Training School
Authors: Gardner Laura E. , Horton Katie L. , Shoemark Amelia , Lucas Jane S. , Nielsen Kim G. , Kobbernagel Helene , Rubbo Bruna , Hirst Robert A. , Kouis Panayiotis , Ullmann Nicola , Reula Ana , Rumman Nisreen , Mitchison Hannah M. , Pinto Andreia , Richardson Charlotte , Schmidt Anne , Thompson James , Gaupmann René , Dabrowski Maciej , Mill Pleasantine , Carr Siobhan B. , Norris Dominic P. , Kuehni Claudia E. , Goutaki Myrofora , Hogg Claire 
Published: June 2020

AbstractPrimary ciliary dyskinesia (PCD) is an inherited ciliopathy leading to chronic suppurative lung disease, chronic rhinosinusitis, middle ear disease, sub-fertility andsitusabnormalities. As PCD is rare, it is important that scientists and clinicians foster international collaborations to share expertise in order to provide the best possible diagnostic and management strategies. ‘Better Experimental Approaches to Treat Primary Ciliary Dyskinesia’ (BEAT-PCD) is a multidisciplinary network funded by EU COST Action (BM1407) to coordinate innovative basic science and clinical research from across the world to drive advances in the field. The fourth and final BEAT-PCD Conference and fifth PCD Training School were held jointly in March 2019 in Poznan, Poland. The varied program of plenaries, workshops, break-out sessions, oral and poster presentations were aimed to enhance the knowledge and skills of delegates, whilst also providing a collaborative platform to exchange ideas. In this final BEAT-PCD conference we were able to build upon programmes developed throughout the lifetime of the COST Action. These proceedings report on the conference, highlighting some of the successes of the BEAT-PCD programme.
Evaluation of the protective effects of icariin on nicotine-induced reproductive toxicity in male mouse –a pilot study
Authors: Ni Guochao , Zhang Xuhui , Afedo Seth Yaw , Rui Rong 
Published: June 2020

Abstract
Background
Nicotine, a pharmacologically active component of tobacco adversely affects the male reproductive system and fertility whereas icariin (ICA), the main active ingredient in Epimedium herba has been used in the treatment of several male reproductive problems. This study aimed at evaluating the protective or ameliorative effect of ICA against reproductive toxicity induced by intraperitoneal injection of nicotine in mice.

Methods
Using simple random allocation, forty male mice were randomly divided into 4 groups: control (received 0.35 mL physiological saline via gastric gavage), nicotine (0.75 mg/kg BW/day intraperitoneally), ICA (75 mg/kg BW/day gastric gavage), and nicotine plus ICA (nicotine, 0.75 mg/kg BW/day intraperitoneally + ICA, 75 mg/kg BW/day gastric gavage) group. After 35 days of treatment, the mice were weighed, sacrificed, and their reproductive organs (testis and epididymis) were collected and examined for further studies.

Results
The nicotine-treated group showed significantly decreased epididymal sperm density and serum testosterone concentration relative to the control group. Nicotine also caused oxidative damage shown by significant reduction in the activities of antioxidant enzymes and elevation in Malondialdehyde (MDA) levels. ICA on the other hand, improved the reduction in sperm density, hormone levels, and activities of antioxidant enzymes altered in the nicotine treated mice.

Conclusions
These findings indicate that nicotine-induced reproductive toxicity and oxidative damage on male reproductive tissues could be attenuated by ICA.
URG4 mediates cell proliferation and cell cycle in osteosarcoma via GSK3β/β-catenin/cyclin D1 signaling pathway
Authors: Liu Yayun , Xi Yizhe , Chen Gang , Wu Xidong , He Maolin 
Published: June 2020

Abstract
Background
Osteosarcoma is one of the most common malignant bone tumors with the annual global incidence of approximately four per million. Upregulated gene 4 (URG4) expression in the osteosarcoma tissue is closely associated with recurrence, metastasis, and poor prognosis of osteosarcoma. However, the biological function and underlying mechanisms of URG4 in osteosarcoma have not been elucidated. This study aimed to explore the expression and underlying mechanism of URG4 in osteosarcoma.

Methods
The expression level of URG4 in osteosarcoma and normal tissues was compared using immunohistochemistry (IHC). PCR and western blotting (WB) techniques are used to detect URG4 mRNA and protein levels. Wound healing and Transwell analysis to assess the effect of URG4 on osteosarcoma cell migration and invasion. Cell Counting Kit-8 assay and colony proliferation assay were performed to evaluate the effects of silencing URG4 on the inhibition of cell proliferation. The cell cycle distribution was detected by flow cytometry, and a xenograft mouse model was used to verify the function of URG4 in vivo.

Results
URG4 was found to be highly expressed in osteosarcoma tissues and cells, and its high expression was correlated with advanced Enneking stage, large tumor size, and tumor metastasis in osteosarcoma patients. The proliferation in osteosarcoma cell lines and cell cycle in the S phase was suppressed when siRNA was used to downregulate URG4. URG4 promoted cell proliferation and tumorigenesis in vitro and in vivo. WB verified that URG4 promotes cell proliferation in osteosarcoma via pGSK3β/β-catenin/cyclinD1 signaling.

Conclusion
URG4, which is high-expressed in osteosarcoma, promotes cell cycle progression via GSK3β/β-catenin/cyclin D1 signaling pathway and may be a novel biomarker and potential target for the treatment of osteosarcoma.
Simplified, minimally invasive, beating-heart technique for redo isolated tricuspid valve surgery
Authors: Lu Shuyang , Song Kai , Yao Wangchao , Xia Limin , Dong Lili , Sun Yongxin , Hong Tao , Yang Shouguo , Wang Chunsheng 
Published: June 2020

Abstract
Background
Redo isolated tricuspid valve surgery is associated with a high morbidity and mortality, and its optimal timing remains controversial. Hence, here we reviewed the early and midterm results of simplified, minimally invasive, beating-heart technique for redo isolated tricuspid valve surgery in patients at high risk.

Methods
A total of 32 consecutive patients underwent a redo isolated tricuspid valve surgery using minimally invasive, beating-heart technique through a right lateral thoracotomy in our center between June 2016 and April 2020. The mean age of patients was 57.4 ± 8.3 years, and 18 patients (56.3%) were women. The mean preoperative EuroSCORE was 7.8 ± 1.4 (range: 6–11). Follow-up was 87.1% complete, with a mean duration of 26.3 ± 12.3 months.

Results
Both in-hospital and 30-day mortalities were 3.1%. Tricuspid valve replacement with bioprosthesis was performed in 30 patients (93.8%), and the remaining two patients (6.2%) underwent tricuspid repair (annuloplasty and leaflet reconstruction). The mean cardiopulmonary bypass time was 81.5 ± 29.0 min. The overall in-hospital duration and intensive care unit (ICU) times were 13.6 ± 7.6 days and 4.1 ± 2.8 days, respectively. Postoperative complications included prolonged ventilation in six patients (18.8%), acute kidney injury in three patients (9.4%), and neurologic event, wound infection, or permanent third-degree atrioventricular block, in one patient (3.1%) each. A total of 96.9% patients were discharged uneventfully. Four patients were lost to follow-up; there were no midterm deaths in patients who were followed up.

Conclusions
Simplified, minimally invasive, beating-heart technique for redo tricuspid valve surgery is both feasible and safe, and the early and midterm results are excellent.
Combination therapy of BCR-ABL-positive B cell acute lymphoblastic leukemia by tyrosine kinase inhibitor dasatinib and c-JUN N-terminal kinase inhibition
Authors: Xiao Xinhua , Liu Ping , Li Donghe , Xia Zhizhou , Wang Peihong , Zhang Xiuli , Liu Mingzhu , Liao Lujian , Jiao Bo , Ren Ruibao 
Published: June 2020

Abstract
Background
The Philadelphia chromosome (Ph), which leads to the creation and expression of the fusion gene product BCR-ABL, underlines the pathogenesis of chronic myelogenous leukemia (CML) and a fraction of adult and pediatric acute B-lymphoblastic leukemia (B-ALL). The BCR-ABL tyrosine kinase inhibitors (TKIs) have shown a remarkable clinical activity in patients with CML, but their efficacy in treating Ph+ B-ALL is limited. Identifying additional therapeutic targets is important for the effective treatment of Ph+ B-ALL.

Methods
Activation of the JNK signaling pathway in human and mouse BCR-ABL+ B-ALL cells with or without dasatinib treatment was analyzed by Western blotting. JNK was inhibited either by RNA interference or chemical inhibitors, such as JNK-IN-8. The effect of JNK inhibition with or without BCR-ABL TKI dasatinib on BCR-ABL+ B-ALL cells was analyzed by the CellTiter-Glo® Luminescent Cell Viability Assay. The in vivo effects of JNK-IN-8 and dasatinib alone or in combination were tested using a BCR-ABL induced B-ALL mouse model.

Results
We found that the c-JUN N-terminal kinase (JNK) signaling pathway is abnormally activated in both human and mouse BCR-ABL+ B-ALL cells, but the BCR-ABL TKI does not inhibit JNK activation in these cells. Inhibition of JNK, either by RNAi-mediated downregulation or by JNK inhibitors, could significantly reduce viability of Ph+ B-ALL cells. JNK inhibition by RNAi-mediated downregulation or JNK inhibitors also showed a synergistic effect with the BCR-ABL TKI, dasatinib, in killing Ph+ B-ALL cells in vitro. Furthermore, a potent JNK inhibitor, JNK-IN-8, in combination with dasatinib markedly improved the survival of mice with BCR-ABL induced B-ALL, as compared to the treatment with dasatinib alone.

Conclusions
Our findings indicate that simultaneously targeting both BCR-ABL and JNK kinase might serve as a promising therapeutic strategy for Ph+ B-ALL.
Prevalence and impact of acute renal impairment on COVID-19: a systematic review and meta-analysis
Authors: Yang Xianghong , Jin Yiyang , Li Ranran , Zhang Zhongheng , Sun Renhua , Chen Dechang 
Published: June 2020

Abstract
Background
The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients.

Methods
The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors.

Results
A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7–13.5%) and 13.7% (95% CI 5.5–21.9%), respectively. Of all patients, 57.2% (95% CI 40.6–73.8%) had proteinuria, 38.8% (95% CI 26.3–51.3%) had proteinuria +, and 10.6% (95% CI 7.9–13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0–6.0%), while the incidence of AKI was 1.3% (95% CI 0.2–2.4%), 2.8% (95% CI 1.4–4.2%), and 36.4% (95% CI 14.6–58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5–71.4%), 0.7% (95% CI − 0.3–1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6–8.6%) severe patients, 0.1% (95% CI − 0.1–0.2%) non-severe patients and 15.6% (95% CI 10.8–20.5%) non-survivors and 0.4% (95% CI − 0.2–1.0%) survivors, respectively.

Conclusion
The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.