bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells
Authors: Yoshida Kazushige , Okamoto Masanori , Sasaki Jun , Kuroda Chika , Ishida Haruka , Ueda Katsuya , Ideta Hirokazu , Kamanaka Takayuki , Sobajima Atsushi , Takizawa Takashi , Tanaka Manabu , Aoki Kaoru , Uemura Takeshi , Kato Hiroyuki , Haniu Hisao , Saito Naoto 
Published: January 2020

Abstract
Background
There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear.

Methods
In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFNγ for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry.

Results
We discovered that IFNγ increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes.

Conclusions
Here we clarify for the first time an additional mechanism of anti-tumour effect—as exerted by anti-PD-1 antibody decreasing Treg— we anticipate that our findings will lead to the development of new methods for cancer treatment.
Macular vessel density versus ganglion cell complex thickness for detection of early primary open-angle glaucoma
Authors: Wang Yiwei , Xin Chen , Li Meng , Swain David L. , Cao Kai , Wang Huaizhou , Wang Ningli 
Published: January 2020

Abstract
Background
To evaluate the macular vessel density (VD) and ganglion cell complex (GCC) thickness in pre-perimetric (PPG) and early perimetric primary open-angle glaucoma (PG) eyes, and to compare the diagnostic ability of the two measurements to discriminate PPG and early PG eyes from healthy eyes.

Methods
Seventy-nine eyes in 72 subjects (31 normal, 26 PPG, and 22 early PG eyes) were included in the consecutive case series. Macular VD and GCC thickness were acquired simultaneously using the 6 × 6 mm2 high-density AngioRetina scanning mode. Diagnostic abilities were assessed using the area under the receiver operating characteristic curve (AUROC).

Results
Compared to healthy eyes, whole image VD (wiVD) and GCC thickness were significantly lower in PPG and early PG eyes (all P < 0.025). The percent reduction of wiVD was lower than that of GCC thickness in early PG eyes (P < 0.05), while they were similar in PPG eyes (P > 0.05). Regionally, greater VD attenuation and GCC thinning were identified in the perifovea than in the parafovea in both groups (all P < 0.05). Moreover, the percent reduction of VD was less than that of GCC thickness in the perifoveal region in PPG eyes (P < 0.05). The AUROCs for wiVD and GCC thickness were 0.824 and 0.881, respectively, in PPG eyes (P > 0.05), and 0.918 and 0.977, respectively, in early PG eyes (P > 0.05).

Conclusions
Macular VD and GCC thickness significantly decreased in PPG and early PG eyes. The perifoveal region appeared to be more vulnerable to macular VD attenuation and GCC thinning in early glaucoma. Our results showed that macular VD measurements may be helpful for detecting and understanding early glaucomatous damage.
An outbreak of norovirus-related acute gastroenteritis associated with delivery food in Guangzhou, southern China
Authors: Lu Ying , Ma Mengmeng , Wang Hui , Wang Dahu , Chen Chun , Jing Qinlong , Geng Jinmei , Li Tiegang , Zhang Zhoubin , Yang Zhicong 
Published: January 2020

AbstractBackgroundA large number of students at a school in Guangzhou city developed a sudden onset of symptoms of diarrhea and vomiting. To help control the outbreak, we conducted an epidemiological investigation to determine the causative agent, sources, role of transmission and risk factors of the infections.MethodsThe study population consisted of probable and confirmed cases. An active search was conducted for cases among all students, teachers and other school staff members. A case control study was carried out using standardized online questionnaires. Data were obtained regarding demographic characteristics, gastrointestinal symptoms, personal hygiene habits, history of contact with a person who had diarrhea and/or vomiting and dining locations during the past 3 days. Rectal swabs or stool samples of the cases and, food handlers, as well as environmental samples were collected to detect potential intestinal viruses and bacteria. We calculated odds ratios and 95% confidence intervals (CIs).ResultsA total of 157 individuals fit the definition of a probable case, including 46 with laboratory-confirmed norovirus infection between March 8 and March 22, 2018. The proportion of students who had eaten delivery food 3 days before the onset of illness in the case group was 2.69 times that in the control group (95%CI: 1.88–3.85). Intake of take-out food 3 days earlier, and exposure to similar cases 72 h before onset and case in the same dormitory were risk factors. A total of 20 rectal swab samples from students, 10 rectal swabs from food handlers and 2 environmental swab samples from the out-campus restauranttested positive for norovirus (GII, genogroup II strain).ConclusionsWe investigated an outbreak of norovirus infectious diarrhea. Food handling practices carry potential risk of acute gastroenteritis outbreaks owing to a lack of surveillance and supervision. Greater attention should be paid to the monitoring and supervision of food handlers in off campus restaurant to reduce the incidence of norovirus-related acute gastroenteritis associated with delivery food.
Cricopharyngeal myotomy for delayed Cricopharyngeal dysfunction after head and neck surgery – case report
Authors: Sung An , Lee Ka-Wo 
Published: January 2020

Abstract
Background
Head and neck surgeries can perturb normal structures of neck muscles and nerve innervations, which are supposed to function in harmony to allow complicated process like swallowing. It is still likely that cricopharyngal dysfunction emerges years after the head and neck surgeries.

Case presentation
We report a case with history of left unilateral vocal cord immobility and development of dysphagia and aspiration 2 years after radical thyroidectomy with neck lymph nodes dissection and medialization thyroplasty. Cricopharyngeal dysfunction was impressed and was confirmed with visualization of cricopharyngeal narrowing segment in radiographic contrast swallow examination. The patient was treated successfully by cricopharyngeal myotomy, achieving long-term relief in our 4 years of follow up.

Conclusions
Our case of delayed cricopharyngal dysfunction after radical thyroidectomy and medialization thyroplasty shows that it is important to follow up swallowing functions after patients with UVCI undergo medialization thyroplasty. In the event of delayed manifestation of cricopharyngeal function, it can still be treated successfully by cricoharyngeal myotomy, achieving long term relief of dysphagia.
Assessment of the half-life of cationic periodontal pocket irrigation
Authors: Kirtiloglu Tugrul , Keskiner Ilker , Sahin Murathan , Kirtiloglu Banu , Aygul Safak , Sakallioglu Umur , Acikgoz Gokhan 
Published: January 2020

Abstract
Background
The concentration and persisting time of antimicrobial agents in the periodontal pockets are important factors for their antimicrobial efficacy. Increased clearance time in the periodontal pocket is a significant criterion for the selection of intrapocket irrigants. The aim of this study was to estimate the clearance time of a cationic agent from the periodontal pocket.

Methods
Thallium-201(Tl-201) was chosen as a tracer to simulate the clearance of cationic substance because of its electrical activity. Twenty patients with periodontitis and probing depths 6 to 9 mm were included in this study. In each patient, 3 Mega Becquerel (MBq) of Tl-201 were inserted into the periodontal pocket. Dynamic imaging was performed and clearance of radioactivity was measured.

Results
Clearance of radioactivity was 67.1 ± 16.9, 83.1 ± 13.9, 90.4 ± 10.4, 93.39 ± 8.0% at 30, 60, 90 and 120 min, respectively. Half-life of wash-out was determined as 20.3 ± 10.2 min.

Conclusion
The results of this study demonstrate that the half-life of the cationic solution applied subgingivally was approximately 20 min and labelling of oral irrigants with radiotracers may be used to determine their clearance in further research.
Bevacizumab treatment of meningeal melanoma metastases
Authors: Simonsen Trude G. , Gaustad Jon-Vidar , Rofstad Einar K. 
Published: January 2020

Abstract
Background
Melanoma patients with metastatic growth in the meninges have poor prognosis and few treatment options. Although treatment with BRAF inhibitors or immune checkpoint inhibitors has provided promising results, most patients with advanced melanoma are resistant to these treatments and develop severe side effects. Novel treatment strategies are needed for patients with meningeal melanoma metastases, and the potential of antiangiogenic therapy was investigated in this preclinical study.

Methods
Two GFP-transfected melanoma models (A-07 and D-12) differing substantially in VEGF-A expression were included in the study, and the anti-VEGF-A antibody bevacizumab was used as therapeutic agent. Meningeal metastases were initiated in BALB/c nu/nu mice by intracranial inoculation of melanoma cells, and bevacizumab treatment was given twice a week in i.p. doses of 10 mg/kg until the mice became moribund. Therapeutic effects were evaluated by determining tumor host survival time, assessing tumor growth and angiogenic activity by quantitative analyses of histological preparations, and measuring the expression of angiogenesis-related genes by quantitative PCR.

Results
Meningeal A-07 melanomas showed higher expression of VEGF-A than meningeal D-12 melanomas, whereas the expression of ANGPT2 and IL8, two important angiogenesis drivers in melanoma, was much higher in D-12 than in A-07 tumors. Bevacizumab treatment inhibited tumor angiogenesis and prolonged host survival in mice with A-07 tumors but not in mice with D-12 tumors. Meningeal A-07 tumors in bevacizumab-treated mice compensated for the reduced VEGF-A activity by up-regulating a large number of angiogenesis-related genes, including ANGPT2 and its receptors TIE1 and TIE2. Melanoma cells migrated from meningeal tumors into the cerebrum, where they initiated metastatic growth by vessel co-option. In the A-07 model, the density of cerebral micrometastases was higher in bevacizumab-treated than in untreated mice, either because bevacizumab treatment increased mouse survival or induced increased tumor gene expression.

Conclusions
The development of antiangiogenic strategies for the treatment of meningeal melanoma metastases is a challenging task because the outcome of treatment will depend on the angiogenic signature of the tumor tissue, treatment-induced alterations of the angiogenic signature, and the treatment sensitivity of metastatic lesions in other intracranial sites.
Atraumatic bleeding of the subclavian artery 20 years after surgical treatment of pneumothorax
Authors: Miura Kentaro , Kobayashi Nobutaka 
Published: January 2020

Abstract
Background
Bleeding of the subclavian artery is a fatal condition. Adhesion between the pleura and staple line may develop after surgical treatment of pneumothorax, and collateral arteries often develop from the subclavian artery toward the adhesion at the lung apex; however, atraumatic tearing and bleeding of these collateral arteries into the extrapleural and intrathoracic cavities is rare.

Case presentation
A 70-year-old man visited the hospital for evaluation of left chest pain. Contrast-enhanced chest computed tomography showed a huge tumor in the left apex of the lung. It was suspected to be an extrapleural huge hematoma, and it ruptured into the thoracic cavity. Bleeding from the left subclavian artery was suspected; therefore, emergency angiography was performed. Angiography showed some collateral circulation from the left subclavian artery to the apex of the left lung. Distal and proximal bleeding points were identified. The distal bleeding point was embolized using coils. The proximal bleeding point was blown out, and stents were placed in the left subclavian artery. He had undergone pneumothorax surgery 20 years previously, and the present bleeding episode was strongly suspected to be associated with that surgery. The collateral circulation from the subclavian artery could have developed because of post-pneumothorax inflammation, eventually rupturing and bleeding into the extrapleural space.

Conclusions
This report described an important case of atraumatic subclavian artery bleeding considered to have been caused by surgical treatment of pneumothorax 20 years previously. Emergency angiography and percutaneous stent placement or coil embolization should be considered first in such cases.
Neuropeptide Y regulates proliferation and apoptosis in granulosa cells in a follicular stage-dependent manner
Authors: Urata Yoko , Salehi Reza , Lima Patricia D. A. , Osuga Yutaka , Tsang Benjamin K. 
Published: January 2020

Abstract
Background
The complex regulatory mechanism involved in ovarian follicular development is not completely understood. Neuronal neuropeptide Y (NPY) is involved in the regulation of feeding behavior, energy homeostasis, and reproduction behavior, while its function in ovarian follicular development is not clear. The objective of this study was to investigate if and how NPY regulates follicle development in the ovary.

Methods
All experiments were performed using Sprague Dawley rats. To understand NPY expression pattern at different stages of follicular development, NPY content was assessed using immunohistochemistry in individual follicles. NPY and its receptors expression pattern were evaluated in granulosa cells isolated from preantral (PA), early antral (EA) and late antral follicles (LAF). The influence of NPY on granulosa cell proliferation and apoptosis were further assessed in vitro, using Ki67- and TUNEL-positivity assays. To investigate whether NPY induced-proliferation in EA granulosa cells is mediated through the activation of NPY receptor Y5 (NPY5R) and Mitogen-activated protein kinase (MEK) signal pathway, EA granulosa cells were treated with NPY5R antagonist (CGP71683) and MEK inhibitors (PD98059 and U0126), and Ki67-positive cells were assessed.

Results
NPY protein expression was follicular stage-dependent and cell type-specific. NPY signal intensity in EA was higher than those in PA and LAF. Antral granulosa cells showed the highest signal intensity compared to mural granulosa cells, cumulus cells and theca cells. Granulosa cells NPY protein content and mRNA abundance were higher in EA than in LAF. NPY receptor contents in granulosa cells were follicular stage-dependent. While NPY reduced apoptosis of EA granulosa cells, it increased the proliferation through NPY5R and MEK pathway. In contrast, in LAF granulosa cells, NPY reduced proliferation and increased the number of apoptotic cells, with no significant effects on PA granulosa cells.

Conclusion
This study is the first to evaluate the intraovarian role of NPY in granulosa cells at various stage of follicular development. These results indicate that NPY regulates granulosa cells proliferation and apoptosis in a follicular stage-dependent and autocrine manner. NPY may play a role in pathogenesis of ovarian follicular disorders.
Is there an interest in repeating the vaginal administration of dinoprostone (Propess®), to promote induction of labor of pregnant women at term? (RE-DINO): study protocol for a randomized controlled trial
Authors: Coste Mazeau P. , Hessas M. , Martin R. , Eyraud J.-L. , Margueritte F. , Aubard Y. , Sallee C. , Sire F. , Gauthier T. 
Published: January 2020

Abstract
Background
Labor is induced in over 20% of women in France. Prostaglandins, especially intravaginal dinoprostone (Propess®), are widely used to initiate cervical ripening. If labor does not start within 24 h, there is uncertainty about whether to administer a second dinoprostone pessary or to use oxytocin to induce labor in order to achieve a vaginal delivery.

Methods
RE-DINO is a prospective, open-label, multicenter, randomized superiority trial with two parallel arms running in six French hospitals. A total of 360 patients ≥ 18 years of age at > 37 weeks of gestation who exhibit unfavorable cervical conditions (Bishop score < 6) 24 h after placement of the first Propess®, with fetuses in cephalic presentation, will be included. Patients with premature membrane rupture, uterine scars, or multiple pregnancies will be excluded. Our principal objective is to determine whether placement of a second Propess® (followed by oxytocin [Syntocinon®], if necessary) in women for whom the first Propess® failed to induce cervical ripening increases the vaginal delivery rate compared to direct oxytocin injection. The vaginal delivery rate is therefore the primary outcome. The secondary outcomes are the induction failure rates and maternofetal morbidity and mortality.

Discussion
This study may help in determining the optimal way to induce labor after failure of a first Propess®, an unresolved problem to date. This trial explores the effectiveness and safety of placing a second Propess® and may contribute to development of an obstetric consensus.

Trial registration
Registered on 2 September 2016 at clinicaltrials.gov (identification number NCT02888041).
SINE Retrotransposon variation drives Ecotypic disparity in natural populations of Coilia nasus
Authors: Liu Dong , Yang Jinquan , Tang Wenqiao , Zhang Xing , Royster Clay Matthew , Zhang Ming 
Published: January 2020

AbstractBackgroundSINEs are a type of nonautonomous retrotransposon that can transpose from one site to be integrated elsewhere in an organism genome. SINE insertion can give rise to genetic variants and regulate gene expression, allowing organisms to acquire new adaptive capacity. Studies on this subject have focused on the impacts of SINEs on genes. However, ecological disparities in fish have not yet been explained by SINEs.ResultsNew SINEs were isolated fromCoilia nasus,which has two ecotypes—migratory and resident—that differ in their spawning and migration behaviors. The SINEs possess two structures that resemble a tRNA gene and a LINE retrotransposon tail. Comparison of olfactory tissue transcriptomes, intact SINE transcript copies were detected in only the migratory fish at the initial retrotransposition stage. The SINE DNA copy numbers were higher in the resident type than in the migratory type, while the frequency of SINE insertion was higher in the migratory type than in the resident type. Furthermore, SINE insertions can lead to new repeats of short DNA fragments in the genome, along with target site duplications. SINEs in the resident type have undergone excision via a mechanism in which predicted cleavage sites are formed by mutations, resulting in gaps that are then filled by microsatellites via microhomology-induced replication.ConclusionsNotably, SINEs in the resident type have undergone strong natural selection, causing genomic heteroplasmy and driving ecological diversity ofC. nasus. Our results reveal possible evolutionary mechanisms underlying the ecological diversity at the interface between SINE mobilization and organism defense.
Correction to: Nested plant LTR retrotransposons target specific regions of other elements, while all LTR retrotransposons often target palindromes and nucleosome-occupied regions: in silico study
Authors: Jedlicka Pavel , Lexa Matej , Vanat Ivan , Hobza Roman , Kejnovsky Eduard 
Published: January 2020

Following publication of the original article [1], the authors spotted an error in Table 2.
Biophysical classification of a CACNA1D de novo mutation as a high-risk mutation for a severe neurodevelopmental disorder
Authors: Hofer Nadja T. , Tuluc Petronel , Ortner Nadine J. , Nikonishyna Yuliia V. , Fernándes-Quintero Monica L. , Liedl Klaus R. , Flucher Bernhard E. , Cox Helen , Striessnig Jörg 
Published: January 2020

Abstract
Background
There is increasing evidence that de novo CACNA1D missense mutations inducing increased Cav1.3 L-type Ca2+-channel-function confer a high risk for neurodevelopmental disorders (autism spectrum disorder with and without neurological and endocrine symptoms). Electrophysiological studies demonstrating the presence or absence of typical gain-of-function gating changes could therefore serve as a tool to distinguish likely disease-causing from non-pathogenic de novo CACNA1D variants in affected individuals. We tested this hypothesis for mutation S652L, which has previously been reported in twins with a severe neurodevelopmental disorder in the Deciphering Developmental Disorder Study, but has not been classified as a novel disease mutation.

Methods
For functional characterization, wild-type and mutant Cav1.3 channel complexes were expressed in tsA-201 cells and tested for typical gain-of-function gating changes using the whole-cell patch-clamp technique.

Results
Mutation S652L significantly shifted the voltage-dependence of activation and steady-state inactivation to more negative potentials (~ 13–17 mV) and increased window currents at subthreshold voltages. Moreover, it slowed tail currents and increased Ca2+-levels during action potential-like stimulations, characteristic for gain-of-function changes. To provide evidence that only gain-of-function variants confer high disease risk, we also studied missense variant S652W reported in apparently healthy individuals. S652W shifted activation and inactivation to more positive voltages, compatible with a loss-of-function phenotype. Mutation S652L increased the sensitivity of Cav1.3 for inhibition by the dihydropyridine L-type Ca2+-channel blocker isradipine by 3–4-fold.
Conclusions and limitations
Our data provide evidence that gain-of-function CACNA1D mutations, such as S652L, but not loss-of-function mutations, such as S652W, cause high risk for neurodevelopmental disorders including autism. This adds CACNA1D to the list of novel disease genes identified in the Deciphering Developmental Disorder Study. Although our study does not provide insight into the cellular mechanisms of pathological Cav1.3 signaling in neurons, we provide a unifying mechanism of gain-of-function CACNA1D mutations as a predictor for disease risk, which may allow the establishment of a more reliable diagnosis of affected individuals. Moreover, the increased sensitivity of S652L to isradipine encourages a therapeutic trial in the two affected individuals. This can address the important question to which extent symptoms are responsive to therapy with Ca2+-channel blockers.