bluuebunny/crossref_metadata_2025_split huggingface dataset:
Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases
Authors: He Ruxuan , Mo Ruo , Shen Ming , Kang Lulu , Song Jinqing , Liu Yi , Chen Zhehui , Zhang Hongwu , Yao Hongxin , Liu Yupeng , Zhang Yao , Dong Hui , Jin Ying , Li Mengqiu , Qin Jiong , Zheng Hong , Chen Yongxing , Li Dongxiao , Wei Haiyan , Li Xiyuan , Zhang Huifeng , Huang Min , Zhang Chunyan , Jiang Yuwu , Liang Desheng , Tian Yaping , Yang Yanling 
Published: August 2020

AbstractBackgroundCobalamin C deficiency (cblC) caused by theMMACHCmutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in ChinesecblCpatients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with theMMACHCc.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention.MethodsWe assessed 149cblCpatients caused byMMACHCc.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019.ResultsTwo patients (1.3%) were prenatally diagnosed, treated after birth and consequently showed normal development. In 15 patients (10.1%) detected by newborn screening, 10 were treated at the age of 2 weeks and showed normal development, while the other 5 were treated after onset and showed neurologic disorders. All 132 clinically diagnosed patients (88.6%) developed symptoms at age from few minutes after birth to 72 months. Among them, 101 (76.5%) had early-onset (before the age of 12 months) and 31 (23.5%) had late-onset (after the age of 12 months). Totally 5 patients died and 24 were lost to follow-up. Of the 132 clinical diagnosed patients, 92 (69.7%) presented with developmental delay, 65 (49.2%) had seizures, 37 (28.0%) had anemia, 24 (18.2%) had feeding difficulty, 23 (17.4%) had ocular problems, and 22 (16.7%) had hydrocephalus. Compared with the non-developmental delay group, the onset age, the age at treatment initiation and the time from onset to treatment initiation were later in the developmental delay group. Seizure group showed significantly higher urinary methylmalonic acid concentration. During long-term follow-up, plasma total homocysteine (tHcy) levels were significantly higher in patients in the uncontrolled group than those in the seizure-free group.ConclusionsMostcblCpatients caused byMMACHCc.609G > A homozygous mutation showed early-onset. The clinically diagnosed patients usually showed the presence of irreversible brain disorders. Patients treated from the pre-symptomatic stage showed favorable outcomes. Therefore, newborn screening, prenatal diagnosis and early treatment are crucial and the c.609G > A mutant allele should be listed in the pre-pregnancy carrier screening panel in China.
Predictors of surgical management of high grade blunt splenic injuries in adult trauma patients: a 5-year retrospective cohort study from an academic level I trauma center
Authors: Nijdam Thomas M. P. , Spijkerman Roy , Hesselink Lilian , Leenen Luke P. H. , Hietbrink Falco 
Published: August 2020

Abstract
Backgrounds
Splenic injury accounts for 40% of all injuries after blunt abdominal trauma. Blunt splenic injury in hemodynamically unstable patients is preferably treated by splenectomy. Nowadays hemodynamically stable patients with low grade splenic injuries are mostly treated by non-operative management (NOM). However no consensus exists about the management of high grade splenic injuries in hemodynamically stable patients. Therefore the aim of this study was to analyze patients with high grade splenic injuries in our institution.

Methods
We retrospectively included all patients with a splenic injury presented to our level I trauma center during the 5-year period from January 1, 2012, until December 31, 2017. Baseline characteristics, data regarding complications and mortality were collected from the electronic patient registry. Patients were grouped based on splenic injury and the treatment they received.

Results
A total of 123 patients were included, of which 93 (75.6%) were male with a median age of 31 (24–52) and a median injury severity score of 27 (17–34). High grade injuries (n = 28) consisted of 20 Grade IV injuries and 8 grade V injuries. Splenectomy was required in 15/28 (53.6%) patients, of whom all remained hemodynamically unstable after resuscitation, including all grade V injuries. A total of 13 patients with high grade injuries were treated with spleen preserving therapy. Seven of these patients received angio-embolization. One patient went for laparotomy and the spleen was treated with a hemostatic agent. Secondary hemorrhage was present in 3 of these patients (initial treatment: 1 embolization/ 2 observational), resulting in a success rate of 76.9%. There is no mortality seen in patient with high grade splenic injuries.

Conclusion
Non-operative treatment in high grade splenic injuries is a safe treatment modality in hemodynamically stable patients. Hemodynamic status and peroperative bleeding, not injury severity or splenic injury grade were the drivers for surgical management by splenectomy. This selected cohort of patients must be closely monitored to prevent adverse outcomes from secondary delayed bleeding in case of non-operative management.
Long-read-based human genomic structural variation detection with cuteSV
Authors: Jiang Tao , Liu Yongzhuang , Jiang Yue , Li Junyi , Gao Yan , Cui Zhe , Liu Yadong , Liu Bo , Wang Yadong 
Published: August 2020

AbstractLong-read sequencing is promising for the comprehensive discovery of structural variations (SVs). However, it is still non-trivial to achieve high yields and performance simultaneously due to the complex SV signatures implied by noisy long reads. We propose cuteSV, a sensitive, fast, and scalable long-read-based SV detection approach. cuteSV uses tailored methods to collect the signatures of various types of SVs and employs a clustering-and-refinement method to implement sensitive SV detection. Benchmarks on simulated and real long-read sequencing datasets demonstrate that cuteSV has higher yields and scaling performance than state-of-the-art tools. cuteSV is available athttps://github.com/tjiangHIT/cuteSV.
Genetic relatedness of Leptospira interrogans serogroup Autumnalis isolated from humans, dogs, and mice in Japan
Authors: Koizumi Nobuo , Izumiya Hidemasa , Ohnishi Makoto 
Published: August 2020

AbstractObjectiveLeptospirosis is a zoonotic disease caused by pathogenic spirochetes ofLeptospiraspp., and peridomiciliary rodents are the most important reservoir animals for human infection. Dogs are known to be the reservoir animal ofL. interrogansserovar Canicola, but the importance of dogs in zoonotic transmission of otherLeptospiraserotypes/genotypes remains unclear. This study reports the isolation ofL. interrogansserogroup Autumnalis from two human patients in Japan and describes the genetic comparison between canine and mouse isolates using multiple-locus variable-number tandem repeat analysis (MLVA).ResultsMLVA revealed that 8 out of the 11 loci compared were identical between the two human isolates. The human isolates clustered with the dog but not the mouse isolates. Moreover, the profile of one of the human isolates was identical to that of one of the dog isolates.
Expression of smooth muscle-like effectors and core cardiomyocyte regulators in the contractile papillae of Ciona
Authors: Johnson Christopher J. , Razy-Krajka Florian , Stolfi Alberto 
Published: August 2020

Abstract
Background
The evolution of vertebrate smooth muscles is obscured by lack of identifiable smooth muscle-like cells in tunicates, the invertebrates most closely related to vertebrates. A recent evolutionary model was proposed in which smooth muscles arose before the last bilaterian common ancestor, and were later diversified, secondarily lost or modified in the branches leading to extant animal taxa. However, there is currently no data from tunicates to support this scenario.

Methods and results
Here, we show that the axial columnar cells, a unique cell type in the adhesive larval papillae of the tunicate Ciona, are enriched for orthologs of vertebrate smooth/non-muscle-specific effectors of contractility, in addition to developing from progenitors that express conserved cardiomyocyte regulatory factors. We show that these cells contract during the retraction of the Ciona papillae during larval settlement and metamorphosis.

Conclusions
We propose that the axial columnar cells of Ciona are a myoepithelial cell type required for transducing external stimuli into mechanical forces that aid in the attachment of the motile larva to its final substrate. Furthermore, they share developmental and functional features with vertebrate myoepithelial cells, vascular smooth muscle cells, and cardiomyocytes. We discuss these findings in the context of the proposed models of vertebrate smooth muscle and cardiomyocyte evolution.
The co-culture of ASCs and EPCs promotes vascularized bone regeneration in critical-sized bone defects of cranial bone in rats
Authors: He Yuanjia , Lin Shuang , Ao Qiang , He Xiaoning 
Published: August 2020

Abstract
Background
The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.

Method
The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.

Results
The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASC/EPC group could promote bone regeneration and vascularization in the meantime and then significantly accelerate the repair of critical-sized bone defects.

Conclusion
It is feasible to replace traditional single seed cells with ASC/EPC co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.
Comprehensive transcriptomic and proteomic analyses of antroquinonol biosynthetic genes and enzymes in Antrodia camphorata
Authors: Liu Xiaofeng , Xia Yongjun , Zhang Yao , Yang Caiyun , Xiong Zhiqiang , Song Xin , Ai Lianzhong 
Published: August 2020

AbstractAntroquinonol (AQ) has several remarkable bioactivities in acute myeloid leukaemia and pancreatic cancer, but difficulties in the mass production of AQ hamper its applications. Currently, molecular biotechnology methods, such as gene overexpression, have been widely used to increase the production of metabolites. However, AQ biosynthetic genes and enzymes are poorly understood. In this study, an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ) were used to identify AQ synthesis-related genes and enzymes in Antrodia camphorata during coenzyme Q0-induced fermentation (FM). The upregulated genes related to acetyl-CoA synthesis indicated that acetyl-CoA enters the mevalonate pathway to form the farnesyl tail precursor of AQ. The metE gene for an enzyme with methyl transfer activity provided sufficient methyl groups for AQ structure formation. The CoQ2 and ubiA genes encode p-hydroxybenzoate polyprenyl transferase, linking coenzyme Q0 and the polyisoprene side chain to form coenzyme Q3. NADH is transformed into NAD+ and releases two electrons, which may be beneficial for the conversion of coenzyme Q3 to AQ. Understanding the biosynthetic genes and enzymes of AQ is important for improving its production by genetic means in the future.
Cognitive and psychosocial outcomes of mechanically ventilated intensive care patients with and without delirium
Authors: Bulic Daniella , Bennett Michael , Georgousopoulou Ekavi N. , Shehabi Yahya , Pham Tai , Looi Jeffrey C. L. , van Haren Frank M. P. 
Published: August 2020

Abstract
Objective
Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium.

Methods
This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver).

Results
103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient’s caregiver, the patient’s cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months.

Conclusions
Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term PTSD symptoms.
Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616001116415, 15/8/2016 retrospectively registered, https://www.anzctr.org.au
Lactobacillus salivarius alleviates inflammation via NF-κB signaling in ETEC K88-induced IPEC-J2 cells
Authors: Qiao Jiayun , Sun Zeyang , Liang Dongmei , Li Haihua 
Published: August 2020

Abstract
Background
Enterotoxigenic Escherichia coli (ETEC) K88 commonly colonize in the small intestine and keep releasing enterotoxins to impair the intestinal barrier function and trigger inflammatory reaction. Although Lactobacillus salivarius (L. salivarius) has been reported to enhance intestinal health, it remains to be seen whether there is a functional role of L. salivarius in intestinal inflammatory response in intestinal porcine epithelial cell line (IPEC-J2) when stimulated with ETEC K88. In the present study, IPEC-J2 cells were first treated with L. salivarius followed by the stimulation of ETEC K88 for distinct time period. ETEC K88 adherent status, pattern recognition receptors (PRRs) mRNA, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation, the release of pro-inflammation cytokines and cell integrity were examined.

Results
Aside from an inhibited adhesion of ETEC K88 to IPEC-J2 cells, L. salivarius was capable of remarkably attenuating the expression levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-8, Toll-like receptor (TLR) 4, nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein (NLRP) 3 and NLRP6. This alternation was accompanied by a significantly decreased phosphorylation of p38 MAPK and p65 NF-κB during ETEC K88 infection with L. salivarius pretreatment. Western blot analysis revealed that L. salivarius increased the expression levels of zona occludens 1 (ZO-1) and occludin (P < 0.05) in ETEC K88-infected IPEC-J2 cells. Compared with ETEC K88-infected groups, the addition of L. salivarius as well as extra inhibitors for MAPKs and NF-κB to ETEC K88-infected IPEC-J2 cells had the capability to reduce pro-inflammatory cytokines.

Conclusions
Collectively, our results suggest that L. salivarius might reduce inflammation-related cytokines through attenuating phosphorylation of p38 MAPK and blocking the NF-κB signaling pathways. Besides, L. salivarius displayed a potency in the enhancement of IPEC-J2 cell integrity.
A population pharmacokinetic model is beneficial in quantifying hair concentrations of ritonavir-boosted atazanavir: a study of HIV-infected Zimbabwean adolescents
Authors: Ngara Bernard , Zvada Simbarashe , Chawana Tariro Dianah , Stray-Pedersen Babill , Nhachi Charles Fungai Brian , Rusakaniko Simbarashe 
Published: August 2020

AbstractBackgroundAdolescents experience higher levels of non-adherence to HIV treatment. Drug concentration in hair promises to be reliable for assessing exposure to antiretroviral (ARV) drugs. Pharmacokinetic modelling can explore utility of drug in hair. We aimed at developing and validating a pharmacokinetic model based on atazanavir/ritonavir (ATV/r) in hair and identify factors associated with variabilities in hair accumulation.MethodsWe based the study on secondary data analysis whereby data from a previous study on Zimbabwean adolescents which collected hair samples at enrolment and 3 months follow-up was used in model development. We performed model development in NONMEM (version 7.3) ADVAN 13.ResultsThere is 16% / 18% of the respective ATV/r in hair as a ratio of steady-state trough plasma concentrations. At follow-up, we estimated an increase of 30% /42% of respective ATV/r in hair. We associated a unit increase in adherence score with 2% increase in hair concentration both ATV/r. Thinner participants had 54% higher while overweight had 21% lower atazanavir in hair compared to normal weight participants. Adolescents receiving care from fellow siblings had atazanavir in hair at least 54% less compared to other forms of care.ConclusionThe determinants of increased ATV/r concentrations in hair found in our analysis are monitoring at follow up event, body mass index, and caregiver status. Measuring drug concentration in hair is feasibly accomplished and could be more accurate for monitoring ARV drugs exposure.
Low-temperature smoothing method of scalloped DRIE trench by post-dry etching process based on SF6 plasma
Authors: Park Jin Soo , Kang Dong-Hyun , Kwak Seung Min , Kim Tae Song , Park Jung Ho , Kim Tae Geun , Baek Seung-Hyub , Lee Byung Chul 
Published: August 2020

AbstractDeep reactive-ion etching (DRIE) is commonly used for high aspect ratio silicon micromachining. However, scalloping, which is the result of the alternating Bosch process of DRIE, can cause many problems in the subsequent process and degrade device performance. In this work, we propose a simple and effective method to smoothen the scalloping of DRIE trenches. The proposed method utilizes sidewall dry etching by reactive-ion etching (RIE) based sulfur hexafluoride (SF6) plasmas, following the DRIE process. To investigate the effect of the etch parameter on the scallop smoothing effect, the radio frequency (RF) power and gas flow are controlled. After the RIE treatment, the scallop smoothing effects were evaluated by measuring the average scallop depth under each condition. The scallop depth was reduced by 91% after implementing the scallop smoothing technique using RIE. Thus, our smoothening method based on SF6 plasmas would provide broad availabilities and applicability in silicon micromachining with the simple low-temperature process.
Anaplastic transformation of thyroid cancer in mesentery metastases presenting as intestinal perforation: a case report
Authors: Hosoda Kiyotaka , Kusama Kei , Yanagisawa Naoe , Machida Taiichi , Nishio Akihito , Nakata Shinji , Ito Ichiro , Watanabe Masahide , Sodeyama Harutsugu 
Published: August 2020

AbstractBackgroundAnaplastic thyroid carcinoma is a highly aggressive form of thyroid cancer associated with a very poor prognosis. Anaplastic transformation most commonly occurs in the thyroid itself or within regional lymph nodes. Here we report the case of a patient with papillary thyroid cancer, presenting with colon perforation as a result of anaplastic transformation of metastases in the mesentery tissue. There have been no previous reports of this form of anaplastic transformation.Case presentationA 74-year-old man was admitted to our hospital, presenting with abdominal pain that he had been experiencing for 1 week prior to admission. The patient had a history of papillary thyroid carcinoma, for which he underwent a total thyroidectomy and mediastinal lymph node dissection 6 years earlier, and subsequently received radioactive iodine therapy for postoperative recurrence in the lung 2 years later. During the present reported admission, a computed tomography scan revealed a large intra-abdominal mass infiltrating into the colon and retroperitoneum and also highlighted the pneumoperitoneum. The patient was diagnosed with generalized peritonitis as a result of colon perforation, as such, we conducted an emergency laparotomy. Intraoperative findings showed a mass affecting the ascending colon and kidney, following which, an ileostomy and biopsy were completed. Poorly differentiated spindle cells were identified in the biopsy specimens, and histopathological and immunohistochemical findings revealed the absence of thyroid carcinoma cells. The tumor was therefore believed to be a primary sarcoma. Following surgery, the patient recovered from sepsis that had arisen as a result of colon perforation, however, rapidly developed systemic metastases and died 1 month post-operation. An autopsy was performed, and the patient was diagnosed with anaplastic papillary thyroid cancer at the mesentery site of metastasis. This conclusion was reached owing to the presence of the squamous differentiation of lymph node cells, and because tumor cells were positive results for paired-box gene 8 expressions.ConclusionsAnaplastic transformation of papillary thyroid carcinoma should be considered in the diagnosis of a large mesentery mass in patients with a history of papillary carcinoma. An appropriate biopsy and paired-box gene 8 immunostaining can be useful in confirming such a diagnosis.
Debulking of giant liver hemangiomas with severe symptoms: a case report
Authors: Ariizumi Shun-ichi , Kotera Yoshihito , Yamashita Shingo , Omori Akiko , Kato Takaaki , Shibuya Go , Egawa Hiroto , Yamamoto Masakazu 
Published: August 2020

Abstract
Background
There are no previous reports of debulking of giant liver hemangioma. This report describes our experience with debulking surgery for a patient with bilateral giant liver hemangiomas with severe symptoms.

Case presentation
We present a case of symptomatic giant liver hemangioma in a 41-year-old woman. She presented with abdominal pain and fullness at a local hospital and underwent trans-arterial embolization (TAE). TAE was not effective, and she was not able to walk a long distance. Giant liver hemangiomas, 30 cm and 15 cm in diameter, were located in the right liver and in the left lateral section, respectively, and normal liver parenchyma with tiny liver hemangiomas was present in segment 4. The liver function was normal. However, right hemi-hepatectomy with left lateral sectionectomy was considered to be risky according to the 3DCT volumetry. Therefore, we performed right hemi-hepatectomy in order to reduce her symptoms. The postoperative course was uneventful, and she was discharged on the 14th day after surgery. The abdominal fullness and abdominal pain disappeared immediately after surgery. The hemangiomas in the remnant liver, 15 cm in diameter, showed no change, and she is well without symptoms 7 years after surgery.

Conclusions
Debulking surgery is one of the options for bilateral giant liver hemangiomas with severe symptoms.