bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of MRTF activation as a clinically achievable anti-fibrotic mechanism for pirfenidone
Authors: Ma Hsiao-Yen , Vander Heiden Jason A. , Uttarwar Salil , Xi Ying , N'Diaye Elsa-Noah , LaCanna Ryan , Caplazi Patrick , Gierke Sarah , Moffat John , Wolters Paul J. , Ding Ning 
Published: December 2022

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease characterised by aberrant fibroblast/myofibroblast accumulation and excessive collagen matrix deposition in the alveolar areas of lungs. As the first approved IPF medication, pirfenidone (PFD) significantly decelerates lung function decline while its underlying anti-fibrotic mechanism remains elusive.MethodsWe performed transcriptomic and immunofluorescence analyses of primary human IPF tissues.ResultsWe showed that myocardin-related transcription factor (MRTF) signalling is activated in myofibroblasts accumulated in IPF lungs. Furthermore, we showed that PFD inhibits MRTF activation in primary human lung fibroblasts at clinically achievable concentrations (half-maximal inhibitory concentration 50–150 µM, maximal inhibition >90%, maximal concentration of PFD in patients <100 µM). Mechanistically, PFD appears to exert its inhibitory effects by promoting the interaction between MRTF and actin indirectly. Finally, PFD-treated IPF lungs exhibit significantly less MRTF activation in fibroblast foci areas than naïve IPF lungs.ConclusionsOur results suggest MRTF signalling as a direct target for PFD and implicate that some of the anti-fibrotic effects of PFD may be due to MRTF inhibition in lung fibroblasts.
Bowel obstruction secondary to internal hernia in a hereditary angioedema patient: a case report
Authors: Tanaka Atsuhito , Huh Ji Young , Yamamoto Takamasa , Washio Ken , Ariyoshi Koichi 
Published: December 2022

Abstract
Background
Gastrointestinal attacks are frequent symptoms in patients diagnosed with hereditary angioedema (HAE). Cases of self-limited bowel intussusception and unneeded exploratory laparotomy due to lack of knowledge about HAE have been reported. Furthermore, after the introduction of C1-esterase inhibitor (C1-INH) concentrate, the recommended medication for HAE attacks, treatment has become typically medical in nature. We share a rare case where operative exploration was indicated to resolve a mechanical small bowel obstruction secondary to an HAE attack.

Case report
An 80-year-old woman with HAE presented with lower left abdominal pain, vomiting, and nausea. Computed tomography (CT) showed edema of the small bowel and stomach as well as possible signs of mechanical small bowel obstruction. The patient was treated with C1-INH concentrate but showed only mild signs of relief, warranting diagnostic laparoscopy. Intraoperative findings showed internal herniation and strangulation of the small bowel caused by adhesions forming a band. After surgical intervention, no bowel resection was needed.

Conclusion
Although C1-INH concentrate remains the principal treatment for HAE, gastrointestinal attacks may potentially cause surgical emergencies.
Left atrial myxoma: an unusual cause of pre-syncope and symptomatic bradycardia
Authors: Vongbunyong Kenny , Sinfield Steven , Premyodhin Ned , Chen Kevin , Zargarian Emin , Ng Angie , Kern Morton 
Published: December 2022

Abstract
Background
Atrial myxomas account for approximately 50% of all primary cardiac tumors. The size, location, risk of embolic event, and involvement of other cardiac structures, are all factors that contribute to the wide range of presentation for cardiac myxomas. Patients with myxomas may remain asymptomatic, while others may report symptoms such as fatigue and fever, dyspnea, and syncope. It is important to recognize arrhythmias as an uncommon symptom of myxomas.

Case presentation
We report a rare case of a 67-year-old man who presented with pre-syncopal episodes, symptomatic bradycardia, and night sweats found to have a 5.5 × 5.1 × 3 cm myxoma in the left atrium. During diastole the mass caused dynamic flow obstruction across the mitral valve. The patient underwent surgical resection of the mass given his symptomatology and risk of embolic events. Removal of the myxoma resulted in resolution of both pre-syncopal episodes and the patient’s sinus bradycardia.

Conclusion
Atrial myxomas are a rare cause of pre-syncope and symptomatic bradycardia. It is important to have a clinical suspicion for atrial myxomas given early diagnosis and surgical intervention are key in improving the prognosis of these patients. This case also highlights the importance of taking into account the source of the myxoma’s blood supply in relationship to other cardiac structures, and further correlating these findings with clinical symptoms.
Opsoclonus-myoclonus syndrome associated with pancreatic neuroendocrine tumor: a case report
Authors: Reinecke Raphael , Reiländer Annemarie , Seiler Alexander , Koch Christine , Voss Martin 
Published: December 2022

Abstract
Background
Opsoclonus-myoclonus syndrome (OMS) is a rare, immune-mediated neurological disorder. In adults, the pathogenesis can be idiopathic, post-infectious or paraneoplastic, the latter etiology belonging to the ever-expanding group of defined paraneoplastic neurological syndromes (PNS). In contrast to other phenotypes of PNS, OMS cannot be ascribed to a single pathogenic autoantibody. Here, we report the first detailed case of paraneoplastic, antibody-negative OMS occurring in association with a pancreatic neuroendocrine tumor (pNET).

Case presentation
A 33-year-old female presented with a two-week history of severe ataxia of stance and gait, dysarthria, head tremor, myoclonus of the extremities and opsoclonus. Her past medical history was notable for a metastatic pancreatic neuroendocrine tumor, and she was subsequently diagnosed with paraneoplastic opsoclonus-myoclonus syndrome. Further workup did not reveal a paraneoplastic autoantibody. She responded well to plasmapheresis, as she was refractory to the first-line therapy with corticosteroids.

Conclusions
This case expands current knowledge on tumors associated with paraneoplastic opsoclonus-myoclonus syndrome and the age group in which it can occur. It further adds evidence to the effectiveness of plasmapheresis in severe cases of opsoclonus-myoclonus syndrome with a lack of response to first-line therapy.
Mendelian randomization study of causal link from gut microbiota to colorectal cancer
Authors: Ni Jing-Jing , Li Xiao-Song , Zhang Hong , Xu Qian , Wei Xin-Tong , Feng Gui-Juan , Zhao Min , Zhang Zi-Jia , Zhang Lei , Shen Gen-Hai , Li Bin 
Published: December 2022

AbstractRecent studies have shown the relevance of gut microbiota in the occurrence and development of colorectal cancer (CRC), but the causal relationship remains unclear in the human population. The present study aims to assess the causal relationship from the gut microbiota to CRC and to identify specific causal microbe taxa via genome-wide association study (GWAS) summary statistics based two-sample Mendelian randomization (MR) analyses. Microbiome GWAS (MGWAS) in the TwinsUK 1,126 twin pairs was used as discovery exposure sample, and MGWAS in 1,812 northern German participants was used as replication exposure sample. GWAS of CRC in 387,156 participants from the UK Biobank (UKB) was used as the outcome sample. Bacteria were grouped into taxa features at both family and genus levels. In the discovery sample, a total of 30 bacteria features including 15 families and 15 genera were analyzed. Five features, including 2 families (Verrucomicrobiaceae and Enterobacteriaceae) and 3 genera (Akkermansia, Blautia, and Ruminococcus), were nominally significant. In the replication sample, the genus Blautia (discovery beta=-0.01, P = 0.04) was successfully replicated (replication beta=-0.18, P = 0.01) with consistent effect direction. Our findings identified genus Blautia that was causally associated with CRC, thus offering novel insights into the microbiota-mediated CRC development mechanism.
The protective effect of URP20 on ocular Staphylococcus aureus and Escherichia coli infection in rats
Authors: Li Meng , Xin Danli , Gao Jian , Yi Quanyong , Yuan Jianshu , Bao Yongbo , Gong Yan 
Published: December 2022

Abstract
Background
Infectious keratitis, a medical emergency with acute and rapid disease progression may lead to severe visual impairment and even blindness. Herein, an antimicrobial polypeptide from Crassostrea hongkongensis, named URP20, was evaluated for its therapeutic efficacy against keratitis caused by Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infection in rats, respectively.

Methods
A needle was used to scratch the surface of the eyeballs of rats and infect them with S. aureus and E.coli to construct a keratitis model. The two models were treated by giving 100 μL 100 μM URP20 drops. Positive drugs for S. aureus and E. coli infection were cefazolin eye drops and tobramycin eye drops, respectively. For the curative effect, the formation of blood vessels in the fundus was observed by a slit lamp (the third day). At the end of the experiment, the condition of the injured eye was photographed by cobalt blue light using 5 μL of 1% sodium fluorescein. The pathological damage to corneal tissues was assessed using hematoxylin–eosin staining, and the expression level of vascular endothelial growth factor (VEGF) was detected by immunohistochemistry.

Results
URP20 alleviated the symptoms of corneal neovascularization as observed by slit lamp and cobalt blue lamp. The activity of S. aureus and E.coli is inhibited by URP20 to protect corneal epithelial cells and reduce corneal stromal bacterial invasion. It also prevented corneal thickening and inhibited neovascularization by reducing VEGF expression at the cornea.

Conclusion
URP20 can effectively inhibit keratitis caused by E.coli as well as S. aureus in rats, as reflected by the inhibition of corneal neovascularization and the reduction in bacterial damage to the cornea.
Massive foreign body reaction and osteolysis following primary anterior cruciate ligament reconstruction with the ligament augmentation and reconstruction system (LARS): a case report with histopathological and physicochemical analysis
Authors: Ambrosio Luca , Vadalà Gianluca , Castaldo Rachele , Gentile Gennaro , Nibid Lorenzo , Rabitti Carla , Ambrosio Luigi , Franceschetti Edoardo , Samuelsson Kristian , Senorski Eric Hamrin , Papalia Rocco , Denaro Vincenzo 
Published: December 2022

AbstractBackgroundAutologous hamstrings and patellar tendon have historically been considered the gold standard grafts for anterior cruciate ligament reconstruction (ACLR). In the last decades, the utilization of synthetic grafts has re-emerged due to advantageous lack of donor site morbidity and more rapid return to sport. The Ligament Augmentation and Reconstruction System (LARS) has demonstrated to be a valid and safe option for ACLR in the short term. However, recent studies have pointed out the notable frequency of associated complications, including synovitis, mechanical failure, and even chondrolysis requiring joint replacement.Case presentationWe report the case of a 23-year-old male who developed a serious foreign body reaction with wide osteolysis of both femoral and tibial tunnels following ACLR with LARS. During first-stage arthroscopy, we performed a debridement of the pseudocystic mass incorporating the anterior cruciate ligament (ACL) and extending towards the tunnels, which were filled with autologous anterior iliac crest bone graft chips. Histological analysis revealed the presence of chronic inflammation, fibrosis, and foreign body giant cells with synthetic fiber inclusions. Furthermore, physicochemical analysis showed signs of fiber depolymerization, increased crystallinity and formation of lipid peroxidation-derived aldehydes, which indicate mechanical aging and instability of the graft. After 8 months, revision surgery was performed and ACL revision surgery with autologous hamstrings was successfully carried out.ConclusionsThe use of the LARS grafts for ACLR should be cautiously contemplated considering the high risk of complications and early failure.
Effect of self-etch primer application on the bond failure rate of a mandibular bonded lingual retainer
Authors: Cakmak Ozlu Fethiye , Yazıcıoğlu Sabahat 
Published: December 2022

Abstract
Background
The aim of this study was to examine the effect of self-etch primer (SEP) application on the bond failure rate of a mandibular bonded lingual retainer over 24 months.

Methods
The average age of the 86 individuals included in this study was 17 years 4 months. After the removal of the orthodontic appliances, the lingual retainers, which were made of six-stranded stainless steel wire, were bent and bonded onto the lingual surface of all mandibular anterior teeth. The study was performed using a split-mouth design. In the study group, the SEP was administered to the teeth’s lingual surfaces. In the control group, they were etched using 37% phosphoric etchant liquid gel. After etching, the primer was applied. The adhesive resin was applied and the retainer was fitted. The patients were re-evaluated over 24 months. The first bond failures and the amount of adhesive remaining on the tooth were recorded as the adhesive remnant index (ARI) scores. The chi-square test was used to compare the bond failure rates (P = 0.231) and ARI scores between the groups (P = 0.162). The survival rates of the retainers were estimated using the Kaplan–Meier test (P = 0.237). The significance level was P < 0.05.

Results
The bond failure rates, ARI scores, and survival rates did not differ significantly between the groups.

Conclusions
The results of this study demonstrated that an SEP can be used successfully in mandibular lingual retainer bonding. In situations where saliva isolation is difficult, bonding a fixed lingual retainer with SEP is recommended.
m6A regulator-mediated methylation modification patterns and immune microenvironment infiltration characterization in osteoarthritis
Authors: Hu Shidong , Shen Chen , Yao Xudong , Zou Yulong , Wang Ting , Sun Xianding , Nie Mao 
Published: December 2022

AbstractOsteoarthritis (OA) is a common disease in orthopedics. RNA N6-methyladenosine (m6A) exerts an essential effect in a variety of biological processes in the eukaryotes. In this study, we determined the effect of m6A regulators in the OA along with performing the subtype classification. Differential analysis of OA and normal samples in the database of Gene Expression Omnibus identified 9 significantly differentially expressed m6A regulators. These regulators were monitored by a random forest algorithm so as to evaluate the risk of developing OA disease. On the basis of these 9 moderators, a nomogram was established. The results of decision curve analysis suggested that the patients could benefit from a nomogram model. The OA sample was classified as 2 m6A models through a consensus clustering algorithm in accordance with these 9 regulators. These 2 m6A patterns were then assessed with principal component analysis. We also determined the m6A scores for the 2 m6A patterns and their correlation with immune infiltration. The results indicated that type A had a higher m6A score than type B. Thus, we suggest that the m6A pattern may provide a new approach for diagnose and provide novel ideas for molecular targeted therapy of OA.
Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study
Authors: Jiang Li , Zhu Jie , Chen Xue , Wang Yi , Wu Lei , Wan Gang , Han Yongtao , Leng Xuefeng , Peng Lin , Wang Qifeng 
Published: December 2022

Abstract
Background and purpose
We evaluated and compared the efficacy and safety of chemotherapy with paclitaxel plus cisplatin (TP) or carboplatin (TC) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) who underwent neoadjuvant chemoradiotherapy (NCRT).

Materials and methods
This single-center retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4aNanyM0) receiving NCRT plus curative-intent esophagectomy with TP or TC regimen. The primary endpoints were grade ≥ 3 adverse events (AEs) and overall survival (OS). AEs were compared using a t-test according to CTCAE 4.0. The Kaplan–Meier survival curves were compared using the log-rank test; the treatment effect was measured using hazard ratios and 95% confidence intervals.

Results
We included 151 and 50 patients in the TC and TP groups, respectively. Baseline demographic and clinical characteristics were well balanced between groups. The TP group exhibited significantly higher hematologic and non-hematologic AEs than the TC group, and the noticeable difference was the incidence of febrile neutropenia of grade 3 or higher (P = 0.011). No significant intergroup differences were noted considering postoperative complications, resection margins, or pathological complete remission rate (all P > 0.05). OS and progression-free survival (PFS) did not significantly differ between groups. The estimated 3-year OS and PFS rates were 65.1% versus 69.4% and 58.4% versus 53.5% for TP and TC groups, respectively.

Conclusion
In patients with LA-ESCC, we recommend TC, not TP, as an optimal chemotherapy regimen for NCRT, given its superiorsafety profile and comparable efficacy.
Aonchotheca (Nematoda: Capillariidae) is validated as a separated genus from Capillaria by both mitochondrial and nuclear ribosomal DNA
Authors: Deng Yuan-Ping , Suleman  , Zhang Xue-Ling , Li Rong , Li Le-Yan , Fu Yi-Tian , Liu Guo-Hua , Yao Chaoqun 
Published: December 2022

Abstract
Background
The family Capillariidae is a group of thread-like nematodes of 27 genera and over 300 species that infect a great variety of hosts including humans. Among these, some taxa such as the genus Aonchotheca have remained controversial regarding their systematic status for decades. The aim of the current study was to verify Aonchotheca’s systemic status and to further determine whether it is a distinct genus from Capillaria using molecular and phylogenetic analyses.

Results
We sequenced the mitochondrial (mt) genome and nuclear small subunit (18S) rRNA gene of Aonchotheca putorii, a representative species of the genus, and investigated its systematic status in Trichinellida using maximum likelihood and Bayesian inference. The differences in amino acid sequences of 13 protein-coding genes were 12.69–67.35% among Aonchotheca, Capillaria, Eucoleus, and Pseudocapillaria with cox1 (12.69%) and atp8 (67.35%) as the most and the least conserved gene, respectively, and the difference of two mt rRNAs was 18.61–34.15%. Phylogenetic analyses of the complete mt genome and 18S rRNAs unequivocally showed that Aonchotheca was a distinct genus from Capillaria.

Conclusions
Large difference exists among Aonchotheca, Capillaria, Eucoleus, and Pseudocapillarias. Aonchotheca putorii is the first species in the genus Aonchotheca for which a complete mitogenome has been sequenced. These data are useful for phylogenetics, systematics and the evolution of Capillariidae.

Graphical Abstract
A sex difference in mouse dopaminergic projections from the midbrain to basolateral amygdala
Authors: Manion Matthew T. C. , Glasper Erica R. , Wang Kuan Hong 
Published: December 2022

AbstractBackgroundDopaminergic circuits play important roles in the motivational control of behavior and dysfunction in dopaminergic circuits have been implicated in several psychiatric disorders, such as schizophrenia and depression. While these disorders exhibit different incidence rates in men and women, the potential sex differences in the underlying neural circuits are not well-understood. Previous anatomical tracing studies in mammalian species have revealed a prominent circuit projection connecting the dopaminergic midbrain ventral tegmental area (VTA) to the basolateral amygdala (BLA), which is involved in emotional processing and associative learning. However, whether there is any sex difference in this anatomical circuit remains unknown.MethodsTo study the potential sex differences in the VTA-to-BLA dopaminergic circuit, we injected two viral vectors encoding fluorescent reporters of axons and synaptic boutons (AAV–FLEX–tdTomato and AAV–FLEX–SynaptophysinGFP, respectively) into the VTA of a mouse transgenic driver line (tyrosine hydroxylase promoter-driven Cre, or TH-Cre), which restricts the reporter expression to dopaminergic neurons. We then used confocal fluorescent microscopy to image the distribution and density of dopaminergic axons and synaptic boutons in serial sections of both male and female mouse brain.ResultsWe found that the overall labeling intensity of VTA-to-BLA dopaminergic projections is intermediate among forebrain dopaminergic pathways, significantly higher than the projections to the prefrontal cortex, but lower than the projections to the nucleus accumbens. Within the amygdala areas, dopaminergic axons are concentrated in BLA. Although the size of BLA and the density of dopaminergic axons within BLA are similar between male and female mice, the density of dopaminergic synaptic boutons in BLA is significantly higher in male brain than female brain.ConclusionsOur results demonstrate an anatomical sex difference in mouse dopaminergic innervations from the VTA to BLA. This finding may provide a structural foundation to study neural circuit mechanisms underlying sex differences in motivational and emotional behaviors and related psychiatric dysfunctions.
Background-foreground segmentation for interior sensing in automotive industry
Authors: Drygala Claudia , Rottmann Matthias , Gottschalk Hanno , Friedrichs Klaus , Kurbiel Thomas 
Published: December 2022

AbstractTo ensure safety in automated driving, the correct perception of the situation inside the car is as important as its environment. Thus, seat occupancy detection and classification of detected instances play an important role in interior sensing. By the knowledge of the seat occupancy status, it is possible to, e.g., automate the airbag deployment control. Furthermore, the presence of a driver, which is necessary for partially automated driving cars at the automation levels two to four can be verified. In this work, we compare different statistical methods from the field of image segmentation to approach the problem of background-foreground segmentation in camera based interior sensing. In the recent years, several methods based on different techniques have been developed and applied to images or videos from different applications. The peculiarity of the given scenarios of interior sensing is, that the foreground instances and the background both contain static as well as dynamic elements. In data considered in this work, even the camera position is not completely fixed. We review and benchmark three different methods ranging, i.e., Gaussian Mixture Models (GMM), Morphological Snakes and a deep neural network, namely a Mask R-CNN. In particular, the limitations of the classical methods, GMM and Morphological Snakes, for interior sensing are shown. Furthermore, it turns, that it is possible to overcome these limitations by deep learning, e.g. using a Mask R-CNN. Although only a small amount of ground truth data was available for training, we enabled the Mask R-CNN to produce high quality background-foreground masks via transfer learning. Moreover, we demonstrate that certain augmentation as well as pre- and post-processing methods further enhance the performance of the investigated methods.