bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy, Patient-Reported Outcomes, and Safety for Millennial Subjects Treated With OnabotulinumtoxinA for Moderate to Severe Horizontal Forehead Lines
Authors: Palm Melanie D. , Few Julius , Patel Tapan , Safa Marva , Drinkwater Adrienne , Mao Cheri , Garcia Julie K.
Published: October 2019

BACKGROUND

Millennials (aged 18–34 years) represent a growing segment of the facial aesthetic market.

OBJECTIVE

To evaluate investigator-assessed efficacy, patient-reported outcomes (PROs), and safety for millennials versus subjects aged at least 35 years after onabotulinumtoxinA treatment of forehead lines (FHL) across 2 phase 3 studies.

METHODS

Eligible subjects with moderate to severe FHL received onabotulinumtoxinA (FHL: 20 U; glabellar lines: 20 U, with/without 24 U in crow's feet line regions) or placebo. All findings were pooled by the age group.

RESULTS

Millennials composed 15% of subjects (176/1,178). Day 30 responder rates of at least 1-grade Facial Wrinkle Scale improvement in FHL severity for millennials versus subjects aged 35 years and older were 100% versus 97.8% at maximum eyebrow elevation and 78.4% versus 83.5% at rest, respectively. Responder rates were significantly greater with onabotulinumtoxinA than placebo (p ≤ .015) for both groups through Day 180. Similar trends were observed for achieving none/mild severity. Both age groups reported high satisfaction rates and improved psychological impacts with onabotulinumtoxinA treatment. No new safety signals were detected.

CONCLUSION

OnabotulinumtoxinA treatment was well tolerated, and both age groups experienced significant improvements in FHL severity, high satisfaction, and improved psychological impacts after treatment. Millennials reported numerically greater improvements.
Uncommon presentation of a huge intrathoracic ganglioneuroma in an 8-year-old child: a rare case report
Authors: Kan Chan Siang , Chang Tze Sen , Cheong Lu Jeat , Dzin Manisah Binti Mohd. , Karupiah Saravanan , Jong Yuan Hsun , Soon Sing Yang
Published: October 2019

Ganglioneuroma (GN) is a rare benign neurogenic tumor which arises from the neural crest cells that represent the final maturation stage of neuroblasts. GN is commonly encountered in adolescent or young adult. Until now, only a few cases of intrathoracic GN were reported in pediatric patients, especially in below 10 years of age. We report here an 8-year-old boy, who first presented to primary care with symptoms of upper respiratory tract infection. Radiologic investigations revealed a giant posterior mediastinal mass extending from T4 to T9 vertebrae without evidence of vascular invasion or infiltration into adjacent structures. The patient subsequently underwent left thoracotomy and resection of mass under general anesthesia. He was discharged 3 days after operation without complication. Histopathologic examination confirmed the diagnosis of thoracic GN. Grades of the neuroblastic differentiation increase with the median age at diagnosis. Although GNs are usually benign, they can grow aggressively and cause compression to an adjacent structure. Therefore, surgical resection is the only treatment. Debulking of tumor provides an alternative solution, especially when vital structures are involved. Complete resection remains the gold standard treatment for GN. However, in cases of incomplete resection, all residual tumors require regular clinical and radiodiagnostic follow-up.
Risk Factors for Recurrent Community-associated Clostridiodes Difficile Infection in Children
Authors: Parmar Deepika , Dang Rebecca , Miranda-Katz Margot , Alabaster Amy , Greenhow Tara L.
Published: October 2019

Background:

Recurrence of community-associated (CA) Clostridiodes difficile infection (CDI) approaches 30%. Studies on risk factors and treatment of choice for pediatric CA-CDI are scarce with variable recommendations.

Methods:

This was a retrospective cohort study of the electronic health records of children 1–17 years with stool specimens sent for C. difficile at Kaiser Permanente Northern California from January 01, 2012 to December 31, 2016. Children with (1) CA disease, (2) confirmatory C. difficile laboratory testing with no other identified causes of diarrhea and (3) clinical symptoms consistent with CDI were defined as cases. Recurrent CA-CDI was defined using the above-described case criteria and onset of diarrhea within 8 weeks of primary CA-CDI.

Results:

Of the 7350 children with stool samples sent for C. difficile testing, 408 had primary CA-CDI. Forty-five (11%) experienced a recurrence. Using multivariable logistic regression, inflammatory bowel disease [odds ratio (OR) 7.5; 95% confidence interval (CI): 2.6–21.1] and cancer (OR 6.3; 95% CI: 1.6–24.1) diagnoses were risk factors for recurrent disease. Compared with children of Caucasian race, those with multi/other/unknown race had an OR of 3.03 (95% CI: 1.04–8.82) of recurrence. There was no statistically significant difference in the type or duration of therapy as a predictor for recurrent CA CDI. Six percent of children who received metronidazole were switched to vancomycin due to subjective metronidazole allergy or intolerance or metronidazole treatment failure.

Conclusions:

Recurrent CA-CDI in children in our population is less common than previously reported. This study supports first-line treatment with the standard, short course metronidazole in most cases of primary CA-CDI.
Utility of Surface and Blood Polymerase Chain Reaction Assays in Identifying Infants With Neonatal Herpes Simplex Virus Infection
Authors: Samies Nicole , Jariwala Ravi , Boppana Suresh , Pinninti Swetha
Published: October 2019

Of 27 neonates with herpes simplex virus, DNAemia was observed in 100% with disseminated disease, 57% with central nervous system disease and 28% with skin, eye, mouth disease, suggesting DNAemia occurs frequently in these infants. Herpes simplex virus culture and polymerase chain reaction were performed on surface specimens from 13/27 infants, and ~50% tested positive only by polymerase chain reaction, suggesting the superiority of this technique.
Norovirus Activity and Genotypes in Sporadic Acute Diarrhea in Children in Shanghai During 2014–2018
Authors: Wang Xiangshi , Wei Zhongqiu , Guo Jiayin , Cai Jiehao , Chang Hailing , Ge Yanling , Zeng Mei
Published: October 2019

Background:

Based on the impact public health of norovirus and the current progress in norovirus vaccine development, it is necessary to continuously monitor the epidemiology of norovirus infection, especially in children who are more susceptible to norovirus.

Objectives:

To monitor the activity and genotypes of norovirus infection in sporadic diarrhea in Shanghainese children during 2014–2018.

Study design:

Acute diarrheal cases were prospectively enrolled in the outpatient setting. Real-time reverse transcription-polymerase chain reaction was used for screening norovirus GI and GII genogroups. Dual norovirus genotypes were identified based on the partial capsid and polymerase gene sequences.

Results:

Of the 3422 children with diarrhea, 510 (14.9%) were positive for noroviruses with 13 (2.5%) strains being GI genogroup and 497 (97.5%) strains being GII genogroup. Five distinct capsid GII genotypes were identified, including GII.4-Sydney/2012 (71.8%), GII.3 (13.8%), GII.17 (7.8%), GII.2 (6.0%), GII.6 (0.3%) and GII.8 (0.3%). Seven polymerase GII genotypes were identified, including GII.Pe (77.0%), GII.P12 (11.0%), GII.P17 (9.0%), GII.P16 (2.1%), and GII.P7, GII.P8 and GII.P2 in each (0.3%). Eleven distinct polymerase/capsid genotypes were identified with GII.Pe/GII.4-Sydney/2012 (74.2%), GII.P12/GII.3 (11.7%) and GII.P17/GII.17 (7.7%) being common. GII.P17/GII.17 strains were detected since September 2014. Recombinant GII.P16/GII.2 strains were detected since December 2016.

Conclusions:

Norovirus is a major pathogen causing diarrhea in Shanghainese children. GII.Pe/GII.4-Sydney/2012 strains remained the predominant genotype. The emergence of GII.P17/GII.17 and GII.P16/GII.2 strains in sporadic diarrhea was consistent with norovirus-associated outbreaks attributable to these 2 novel variants in China. Continuous monitoring norovirus genotypes circulating in pediatric population is needed for current vaccine development.
Associations between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases
Authors: Zhao Dongdong , Li Yuerong , Yu Xiuyan , Zhu Yuezhi , Ma Baoxin
Published: October 2019

Background:

Many studies investigated the association between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases. However, the results were inconsistent.

Methods:

We searched the PubMed, EMBASE, Cochrane library, Web of Science, Chinese National Knowledge Infrastructure, VIP, and Wanfang databases for appropriate studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations. Heterogeneity, sensitivity, and publication bias were conducted to measure the robustness of our findings.

All analyses were based on previous published studies, thus, no ethical approval and patient consent are required.

Results:

We conducted a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphisms and risk of ischemic cardio-cerebrovascular diseases. A total of 26 related studies involving 11,602 cases and 14,016 controls were identified and included in our meta-analysis. After considering the heterogeneity of the global analysis, we inferred that rs2910164 polymorphisms were associated with a lower risk of coronary heart disease (CHD) significantly in all genetic models. In addition, it was also found that the miR-146a rs2910164 polymorphisms were associated with the low risk of ischemic cardio-cerebrovascular diseases in large sample size subgroup analysis.

Conclusion:

These results indicate that miR-146a rs2910164 polymorphisms were significantly associated with a lower risk of ischemic cardio-cerebrovascular. The miR-146a rs29101164 might be recommended as a predictor for susceptibility of ischemic cardio-cerebrovascular diseases.
Genetic association of ADAM33 polymorphisms with childhood asthma in Chinese Han population
Authors: Ning Xuecong , Zhang Yunxia , Wu Hongzhi , Bai Linlin , Gong Cuike , Wang Zhihua
Published: October 2019

To explore the association of a disintegrin and metalloprotease 33 (ADAM33) polymorphisms with childhood asthma susceptibility, we conducted this case-control study.

In this case-control study, we selected 96 asthma children and 86 healthy children to conduct the genotyping of ADAM33 polymorphisms through polymerase chain reaction-direct sequencing (PCR-DS). Hardy-Weinberg equilibrium (HWE) status in the control group was detected adopting chi-square test. Frequency differences of genotypes, alleles, and haplotypes were compared by chi-square test between the case and control groups. Linkage disequilibrium (LD) between polymorphisms was checked using Haploview software. Association intensity of the polymorphisms with the disease risk was assessed by odds ratio (OR) and 95% confidence interval (95%CI).

The frequency of rs678881 GA genotype was obviously higher in cases than in controls (P = .03) and the carriage of this genotype conferred higher risk of asthma among children than GG genotype (OR = 2.03, 95%CI = 1.05–3.91). However, neither rs2280089 nor rs2853209 polymorphism was significantly associated with the risk of childhood asthma. Strong LD was found among rs678881, rs2280089 and rs2853209, and haplotype GGT was distinctly associated with the risk of asthma in children (OR = 0.28, 95%CI = 0.13–0.57).

ADAM33 rs678881 polymorphism is significantly correlated with increased susceptibility to asthma in Chinese Han children. Besides, haplotype GGT among the 3 polymorphisms was obviously associated with decreased risk of childhood asthma.
Increased expression of long non-coding RNA CCAT2 predicts poorer prognosis in patients with hepatocellular carcinoma
Authors: Fu Changbo , Xu Xuan , Lu Weijun , Nie Lei , Yin Tao , Wu Dongde
Published: October 2019

Background:

Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is a 1752-bp lncRNA transcribed from m8q24 genomic region. A lot of investigations have confirmed the involvement of CCAT2 in the tumorigenesis of many cancer types. Previous studies found that over-expression of CCAT2 significantly promoted cell migration and proliferation, and inhibited apoptosis of HCC cells. In the present investigation, the clinical value and prognostic significance of CCAT2 were investigated.

Methods:

The 122 pairs of HCC tissues and adjacent normal liver tissues were acquired between September 2013 and February 2018. The expression levels of CCAT2 in HCC tissues and their corresponding adjacent normal liver tissues were examined by RT-qPCR analysis. Survival was calculated using the Kaplan-Meier method and analyzed using the log-rank test. Independent prognostic indicators were determined in the multivariate analysis using Cox's proportional hazard model.

Results:

CCAT2 expression levels were significantly increased in HCC tissues compared to that in their normal counterparts (P < .001). CCAT2 expression was significantly correlated with vascular invasion (P = .001), histopathologic grading (P = .001), distant metastasis (P = .002) and TNM stage (P = .018). A Kaplan–Meier survival curve showed that the overall survival rate of HCC patients in high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = .016). In addition, COX multivariate analysis showed that high expression of CCAT2 was an independent risk factor for predicting shorter overall survival time in HCC (HR = 2.126, 95%CI:1.273–8.775, P = .021).

Conclusions:

Taken together, this research revealed that lncRNA CCAT2 may serve as a potential biomarker for predicting overall survival time in HCC.
VACTERL association complicated with multiple airway abnormalities
Authors: Yang Lin , Li Shu , Zhong Lin , Qiu Li , Xie Liang , Chen Lina
Published: October 2019

Introduction:

VACTERL association is an acronym that includes vertebral anomalies (V), anal atresia (A), cardiac defects (C), tracheoesophageal fistula (TEF) or esophageal atresia (EA), renal anomalies (R), and limb defects (L). Airway anomalies have rarely been reported with VACTERL association.

Patient concerns:

A 10-month-old boy who had been diagnosed with anal atresia and received surgical corrections soon after birth consulted our institution by complaining repeated cough and fever.

Diagnosis:

Diagnosis of VACTERL association was finally made. Bronchoscopy and chest CT with computed tomography angiography confirmed multiple airway abnormalities including bridging bronchus, airway malacia, and complete tracheal rings.

Interventions:

Supplemental oxygen was provided and antibiotics was initiated.

Outcomes:

The patient resolved gradually and was discharged 10 days later. The follow-up showed the patient has remained well just with mild psychomotor retardation.

Conclusion:

Multiple airway anomalies may be seen in VACTERL association. It is worthwhile to make special note for evaluating the tracheobronchial pulmonary system by chest CT and bronchoscopy, especially patients presenting with breathing anomalies.
Paget disease of bone in an elderly patient with chronic renal disease and weight loss
Authors: Chan Po-Kai , Lyu Sin-Yi , Lu Chun-Chi
Published: October 2019

Rationale:

Asymptomatic Paget disease of bone (PDB) is mostly diagnosed by accidental finding of osteolytic lesion on the plain film. However, in elderly patient with chronic renal insufficiency and weight loss, it is crucial to differentiate PDB from metabolic and metastatic bone diseases for further treatment and better outcome.

Patient concerns:

An 80-year-old man with chronic kidney disease presented to our emergency department due to fever with chillness for a day, while the abdominal fullness, anorexia, and weight loss had been noted for 3 months. Mixed osteoblastic and lytic changes in the pelvic bone were accidentally found on the abdominal plain film.

Diagnosis:

The patient was diagnosed as asymptomatic PDB and urinary tract infection of Pseudomonas aeruginosa.

Interventions and outcome:

The patient received 7 days intravenous and followed by 7 days oral antibiotic treatment, which lead to clinical improvement of his urinary tract infection. No pharmacological treatment was initiated for the asymptomatic and localized PDB. The patient was discharged under stable condition afterward.

Lessons:

In patients with mixed osteolytic and blastic lesions, the differential diagnoses include metabolic and metastatic bone disease. Thorough understanding of the morphology of the bone lesions in high risk patient, not only helps to make differential diagnosis, but it also leads to precise treatment and better outcome.
Prenatal echocardiographic classification and prognostic evaluation strategy in fetal pulmonary atresia with intact ventricular septum
Authors: Liu Lin , Wang Hongdan , Cui Cunying , Li Yanan , Liu Yuanyuan , Wang Ying , Fan Taibing , Peng Bangtian
Published: October 2019

Fetal pulmonary atresia with intact ventricular septum (PA/IVS) is a rare congenital heart disease. The present study aimed to classify PA/IVS and determine the relationship between prenatal echocardiographic characteristics and postnatal biventricular or univentricular repair strategies.

A total of 51 fetuses with PA/IVS were examined from 2012 to 2019. Data on prenatal echocardiography, associated anomaly, karyotype, and outcome were collected. Two-dimensional measurements included tricuspid valve (TV) z-score, mitral valve (MV) z-score, TV/MV ratio, and ratio of right to left ventricle (RV/LV) length, whereas color Doppler measurements included degree of tricuspid regurgitation (TR), ventriculo-coronary artery communication (VCAC), tricuspid inflow duration (TID), cardiac cycle duration (CCD), middle cerebral artery pulsatility index (MCA PI), and umbilical artery pulsatility index (UA PI). Diagnostic classification was based on the development of RV and the presence or absence of VCAC. Postnatal evaluation was divided according biventricular or univentricular repair.

Of the 51 fetuses with PA/IVS, 20 were type I, 17 were type II, and 14 were type III. Only one fetus exhibited right aortic arch. The karyotype of all the fetuses was normal. Of the 28 patients who underwent postnatal surgery, 13 (46%) underwent biventricular repair and 15 (54%) underwent univentricular repair. TV z-score was significantly higher for the biventricular repair group compared with univentricular repair group (−1.20 ± 0.98 vs −4.33 ± 0.80, P = .000). TV/MV, RV/LV length, and TID/CCD were significantly higher for the biventricular repair group than the univentricular repair group (0.81 ± 0.14 vs 0.54 ± 0.09, 0.71 ± 0.11 vs 0.49 ± 0.09, 39.20 ± 3.84 vs 29.16 ± 4.58, P = .000). Moderate or severe TR and VCAC were significantly different between the 2 groups (P = .000). Gestational age, MCA PI, and UA PI did not differ between the 2 groups (P = .72, P = .36, P = .06). The cutoff values for the biventricular repair characteristic curves were TV z-score >−3.28, TV/MV ratio >0.71, RV/LV length >0.62, and TID/CCD >33.95%. The sensitivities of the TV z-score, TV/MV, RV/LV length, and TID/CCD were 100%, 77%, 85%, and 92%, respectively. The specificities of the TV z-score, TV/MV, RV/LV length, and TID/CCD were 94%, 100%, 100%, and 94%, respectively.

Fetal echocardiography was able to classify PA/IVS according to variable degree of RV and VCAC. In fetal PA/IVS, TV z-score >−3.28, TV/MV >0.71, RV/LV length >0.62, TID/CCD >33.95%, moderate and severe TR, and the absence of VCAC were associated with postnatal biventricular repair strategy. These findings may have implications for prenatal counseling and prediction of fetal outcome.
The relationship between levels of self-esteem and the development of depression in young adults with mild depressive symptoms
Authors: Choi Yoobin , Choi Soo-Hee , Yun Je-Yeon , Lim Jae-A , Kwon Yoonhee , Lee Hwa Young , Jang Joon Hwan
Published: October 2019

Little is known about the relationship between levels of self-esteem and the development of depression in young adults. The present study investigated the relationship between self-esteem and depression to determine whether self-esteem levels are a risk factor for the development of depression in young adults. This study was conducted with 113 college students aged 19 to 35 (major depressive disorder (MDD) n = 44, Mild Depressive Symptoms (MDS) n = 37, Healthy Control n = 32). The levels of clinical symptoms, self-esteem, resilience, social support, and quality of life, as well as personality traits, were assessed (by Patient Health Questionnaire-9, generalized anxiety disease-7, State-Trait Anxiety Inventory-S, Resilience Appraisal Scale, Rosenberg Self-Esteem Scale, Quality of Life, and NEO-personality inventory (NEO-PI)). The MDS group with high self-esteem reported having the lowest levels of social support, resilience, agreeableness, and extraversion compared to those of the MDD group and control group with high self-esteem. In contrast, the MDS group with low self-esteem showed no differences in social support, resilience, agreeableness and openness according to the NEO-PI scale. Sex and age had no significant impact on the results. Levels of self-esteem are strongly associated with the development of depression. Results suggest that early intervention for depression in young adults needs to focus on improving their levels of social support, resilience, and positive domains of personality. Further studies on the effects of high self-esteem in the development of depression are warranted.
Effect of daily consumption of extra virgin olive oil on the lipid profile and microbiota of HIV-infected patients over 50 years of age
Authors: Olalla Julián , García de Lomas José M. , Chueca Natalia , Pérez-Stachowski Xavier , De Salazar Adolfo , Del Arco Alfonso , Plaza-Díaz Julio , De la Torre Javier , Prada José Luis , García-Alegría Javier , Fernández-Sánchez Fernando , García Federico
Published: October 2019

Background:

Extra virgin olive oil (EVOO) has shown beneficial effects on the lipid profile and inflammatory parameters in general population. Our goal is to analyze these changes together with those of intestinal microbiota in human immunodeficiency virus (HIV)-infected patients over 50 years of age.

Methods:

Experimental single arm open study. HIV patients over the age of 50 with undetectable viral load were selected. EVOO was distributed among the patients so that each one consumed 50 g daily for 12 weeks. Lipid profile, C-reactive protein (CRP), and intestinal microbiota composition were analyzed at the beginning and at the end of the intervention.

Results:

Total cholesterol decreased significantly (5 mg/dL), and a nonsignificant decrease in low-density lipoprotein cholesterol (12 mg/dL), triglycerides (21 mg/dL), and CRP (1.25 mg/dL) was observed. There was a significant increase in alpha diversity after the intervention in men and a decrease in proinflammatory genera such as Dethiosulfovibrionaceae was observed. Differences were also observed in the microbiota of men and women and according to the type of antiretroviral treatment.

Conclusion:

Sustained consumption of 50 g of EVOO in elderly HIV-infected patients might be associated with an improvement in lipid profile and alfa diversity of intestinal microbiota.
Merkel cell carcinoma in Taiwan
Authors: Chang John Wen-Cheng , Chang Yao-Yu , Huang Yen-Lin , Lo Yun-Feng , Ho Tsung-Ying , Huang Yi-Ting , Chen Huan-Wu , Yeh Chun-Nan , Wu Chiao-En
Published: October 2019

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma of the skin. The available reports of MCC in Asia are limited; in this study, we report the largest series of MCC in Taiwan to date.

The series is composed by 24 pathologically proven MCC cases, which were retrospectively reviewed in Chang Gung Memorial Hospital in Taiwan between 2000 and 2018.

The tumor occurred predominantly in men (80%) and in the elderly (median 74.8 years). Twenty-one patients had locoregional MCC and 3 had metastatic MCC at the time of diagnosis. Patients with pathologically proven negative nodes by sentinel lymph node biopsy (SLNB) showed better survival time than those without SLNB in 16 clinically node-negative MCC cases undergoing primary surgery. Salvage surgery for loco-regional recurrence lengthened the survival time and possibly cured recurrent MCC. Palliative chemotherapy with cisplatin and etoposide showed a response rate of 25%, progression-free survival of 3.6 months, and overall survival of 14.8 months in 4 metastatic/recurrent MCC. Avelumab treatment was effective in 1 patient, who achieved a durable disease control.

This observational cohort of MCC patients in Taiwan suggests aggressive surgical intervention including wide excision and lymph node management, salvage operation is critical for early MCC patients, and palliative chemotherapy and immunotherapy showed their efficacy for advanced MCC patients.
Idiopathic pulmonary arterial hypertension associated with a novel frameshift mutation in the bone morphogenetic protein receptor II gene and enhanced bone morphogenetic protein signaling
Authors: Choi Sun Ha , Jung Youn-Kwan , Jang Ji-Ae , Han Seungwoo
Published: October 2019

Rationale:

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by intense remodeling of small pulmonary arteries. Loss-of-function mutation of bone morphogenetic protein receptor II (BMPR2) gene and exaggerated activation of transforming growth factor (TGF)-β signaling play a critical role in this process.

Patient concerns and diagnosis:

We report a novel frameshift mutation (c.117InsT, p.Y40fsX48) of the BMPR2 gene identified in a 19-year-old IPAH patient with syncope. Despite BMPR2 mutation, the phosphorylation of Smad2/3 and Samd1/5/8 was increased in the patient's peripheral blood mononuclear cells, and this event was accompanied by the upregulation of bone morphogenetic protein (BMP) signaling target genes, but not TGF-β signaling target genes. Moreover, we observed an increased expression of other BMPRs, that is, anti-Mullerian hormone type-2 receptor and the activin receptor-like kinases (ALK) 1, ALK3, and ALK6.

Interventions and outcomes:

The patient was prescribed a combination of macitentan, sildenafil, and nifedipine, which successfully controlled her symptom of syncope and normalized N-terminal pro-brain natriuretic peptide level after 3 months of medication.

Lessons:

In light of these results, we propose a new pathogenetic mechanism for IPAH, based on enhanced BMP signaling via the functional replacement of mutated BMPR2 by other BMP receptors.
Risk factors for the development of hyperuricemia
Authors: Ni Qun , Lu Xiaomin , Chen Congcong , Du Huaqing , Zhang Renbing
Published: October 2019

Hyperuricemia has received increasing attention as a major public health problem. This study aims to investigate the risk factors for hyperuricemia and to explore the relationship between changes in biochemical variables and incident hyperuricemia.

A cross-sectional and subsequently prospective study was performed among adults who took their health checkups at Zhejiang University Hospital. The participants who were free of hyperuricemia at baseline received annual follow-up examinations during a 6-year period. Cox proportional hazards regression analyses were conducted to calculate the risks for incident hyperuricemia.

Of the 9238 participants enrolled, 1704 (18.4%) were diagnosed as hyperuricemia. During 21,757 person-years of follow-up, 1492 incident hyperuricemia cases were identified. The incidence of hyperuricemia was 68.58 cases per 1000 person-year of follow-up in the overall participants. The prevalence and the incidence of hyperuricemia increased greatly in female older than 50 years. High levels of BMI, SBP, FPG, TG, LDL-C, ALT, BUN, and creatinine increased the risk of hyperuricemia. Suffering fatty liver also increased the risk of hyperuricemia. Subjects with increasing DBP, TG, BUN, creatinine, or decreasing HDL-C were more likely to incident hyperuricemia.

This study revealed that the change of diastolic blood pressure (DBP), serum triglycerides (TG), blood urea nitrogen (BUN), creatinine, and high-density lipoprotein cholesterol (HDL-C) level were independently associated with incident hyperuricemia.
Can sural nerve injury be avoided in the sinus tarsi approach for calcaneal fracture?
Authors: Park Jeong-Hyun , Chun Dong-Il , Park Kwang-Rak , Park Gun-Hyun , Park Suyeon , Yang Jinseo , Cho Jaeho
Published: October 2019

There is no consensus regarding the references to determine the exact location of the skin incision to minimize iatrogenic sural nerve injury in the sinus tarsi approach for calcaneal fracture.

The purpose of this cadaveric study was to describe the anatomical course of the sural nerve in relation to easily identifiable landmarks during the sinus tarsi approach and to provide a more practical reference for surgeons to avoid sural nerve injury.

Twenty-four foot and ankle specimens were dissected. The bony landmarks used in the following reference points were the tip of the lateral malleolus (point A), lateral border of the Achilles tendon on the collinear line with point A (point B), posteroinferior apex of the calcaneus (point C), inferior margin of the calcaneus on the plumb line through point A (point D), and tip of the fifth metatarsal base (point E). After careful dissection, the distances of the sural nerve to points A and B in the horizontal direction (lines D1 and D2), points A and C in the diagonal direction (lines D3 and D4), points A and D in the vertical direction (lines D5 and D6), and points A and E in the diagonal direction (lines D7 and D8) were measured.

The median ratio of D1 to D1+D2, D3 to D3+D4, D5 to D5+D6, and D7 to D7+D8 were 0.37 (range, 0.26–0.50), 0.23 (range, 016–0.33), 0.35 (range, 0.25–0.45), and 0.32 (range, 0.20–0.45), respectively.

The distance ratios from this study can be helpful to avoid sural nerve injury during the sinus tarsi approach for calcaneal fractures. Established standard incision may have to be modified to minimize sural nerve injury.
Systematic Review and Meta-Analysis of Comparing Phacoemulsification Combined with goniosynechialysis to other mainstream procedures in treating patients with angle-closure glaucoma
Authors: Liu Yang , Li Wenjie , Jiu Xudong , Lei Xunwen , Liu Lin , Yan Chengying , Li Xiaojun
Published: October 2019

Background:

The aim of this meta-analysis is to compare the efficacy and safety of combined phacoemulsification (Phaco) with goniosynechialysis (GSL) to either Phaco or to Phaco combined with trabeculectomy or trabeculectomy alone in patients with angle closure glaucoma (ACG).

Methods:

Five main electronic databases were searched for the eligible studies. Intraocular pressure (IOP) decrease was set as the primary outcome, while anti-glaucomatous medication decrease, changes of anterior chamber depth (ACD), range of peripheral anterior synechia (PAS), and complication occurrence were the secondary outcomes. Standard mean difference (SMD) and relative risk (RR) were the size effects for continuous and binomial data, respectively. Either fixed-effects model or random-effects model was chosen to pool the data based on the heterogeneities.

Results:

A total of 7 eligible studies were included. The combined data showed the IOP decreased more significantly after Phaco-GSL than that after Phaco alone (SMD = –0.42,95%CI: –0.70 – 0.14, I2 = 17.6%, Z = 2.90, P = .004). However, there were no distinct differences regarding medication decrease (SMD =  –0.25,95%CI: –0.70 – 0.21, I2 = 0%, Z = 1.06, P = 0.29), ACD, the range of PAS and complication occurrence rate when compared Phaco-GSL to Phaco. Moreover, Phaco-GSL was comparable to Phaco-trabeculectomy/trabeculectomy in decreasing IOP (SMD =  –0.08, 95%CI = –0.32 – 0.15, I2 = 0%, Z = 0.70, P = .49).

Conclusions:

Phaco-GSL might be an optimal procedure to treat ACG with concomitant cataract due to its bleb-less nature, and its capacity for lowering IOP seems superior to Phaco alone and comparable to Phaco-trabeculectomy/trabeculectomy.
Homeostatic model assessment of insulin resistance closely related to lobular inflammation in nonalcoholic fatty liver disease
Authors: Ye Fang-Zhou , Liu Wen-Yue , Zheng Kenneth I. , Pan Xiao-Yan , Ma Hong-Lei , Wang Xiao-Dong , Chen Yong-Ping , Zheng Ming-Hua
Published: October 2019

Objective

Insulin resistance (IR) has been established as a major risk factor for nonalcoholic fatty liver disease (NAFLD) where it exerts effects on plasma glucose homeostasis, cellular anabolism, and organ glucose uptake. Owing to paucity of studies focused on peripheral IR in relation to pathological outcome, we aim to investigate homeostatic model assessment of insulin resistance (HOMA-IR) by histological characteristics of NAFLD.

Methods

Liver biopsy of 588 patients was screened. After excluding etiologies other than NAFLD and factors contributing to IR, serum HOMA-IR was compared with patients’ histologic features. Univariate and multivariate analyses were conducted to assess their relationship. Area under the receiver operating characteristic (AUROC) was calculated to assess the discriminatory ability of homeostatic model assessment of IR for advanced lobular inflammation (LI).

Results

We observed higher serum level of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and low-density lipoprotein as HOMA-IR increased. HOMA-IR is significantly associated with severity of LI (odds ratio = 1.222, 95% confidence interval = 1.135–1.315, P < 0.001), similar association remained after adjusting for age, BMI, hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, high-density lipoprotein, and triglycerides (odds ratio = 1.205, 95% confidence interval = 1.102–1.317, P < 0.001). HOMA-IR is discriminant of LI with AUROC = 0.832 and cutoff = 2.995 (sensitivity = 0.938, specificity = 0.569).

Conclusion

This study demonstrated a strong and independent association of HOMA-IR with the severity of liver inflammation by histological evaluation in NAFLD patients without diabetes or metabolic syndrome, and its possible role in diagnosis of LI could be translated into clinical assessment of NAFLD patients with uncertainty of nonalcoholic steatohepatitis progression.
Hemophagocytic Lymphohistiocytosis in Critically Ill Patients
Authors: Knaak Cornelia , Schuster Friederike S. , Spies Claudia , Vorderwülbecke Gerald , Nyvlt Peter , Schenk Thomas , Balzer Felix , La Rosée Paul , Janka Gritta , Brunkhorst Frank M. , Keh Didier , Lachmann Gunnar
Published: October 2019

Background:

Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the intensive care unit (ICU) is challenged by the clinical overlap with sepsis. Here, we analyze HLH patients to better understand its clinical presentation, diagnosis, and treatment.

Methods:

For the purpose of this retrospective observational study, we searched for suspected and diagnosed adult HLH of all patients admitted to at least one adult surgical, anesthesiological or medical ICU between January 2006 and August 2018 at the university hospital Charité — Universitätsmedizin Berlin. All cases were reviewed by two HLH experts, who confirmed or declined the diagnosis.

Results:

Of 6,340 ICU patients with ferritin measurement, 40 suffered from HLH (0.63%). Of these, in-hospital mortality was 60.0% over all cases, which was highest in malignancy-associated HLH (71.4%). Infections were identified as most common triggers (42.5%). A variety of 19 different treatment strategies were applied. Non-survivors showed higher ferritin at diagnosis compared with survivors (
P
= 0.021), which was also seen in multivariable analyses. A minimum ferritin of 4083 μg/L after diagnosis was most predictive for 30-day mortality (AUC 0.888, 95% CI 0.771–1.000; sensitivity 93.8%, specificity 78.9%).

Conclusions:

Mortality in adult HLH patients in the ICU is high, particularly in malignancy-associated HLH. Infections are the most frequent HLH triggers in critically ill patients. At present, there is no standardized treatment for HLH in adult patients available. Assessment of ferritin is valuable for diagnosis, prognosis, and treatment monitoring.

Trial registration: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.
Overexpression of BCL-2 in the Intestinal Epithelium Prevents Sepsis-Induced Gut Barrier Dysfunction via Altering Tight Junction Protein Expression
Authors: Otani Shunsuke , Oami Takehiko , Yoseph Benyam P. , Klingensmith Nathan J. , Chen Ching-wen , Liang Zhe , Coopersmith Craig M.
Published: October 2019

Sepsis induces both intestinal hyperpermeability and epithelial apoptosis. While each has been implicated in mediating sepsis mortality, the relationship between these two processes is unclear. We hypothesized that preventing intestinal apoptosis would prevent gut barrier dysfunction. To test this hypothesis, transgenic mice that overexpress the anti-apoptotic protein Bcl-2 in the gut epithelium (Fabpl-Bcl-2 mice) and wild-type (WT) mice were subjected to sham laparotomy or cecal ligation and puncture and orally gavaged with fluorescein isothiocyanate conjugated-dextran (FD-4) 5 h before sacrifice. Serum FD-4 concentration was assayed to measure intestinal permeability, and jejunal tight junctions were assayed for mRNA and protein expression. Baseline FD-4 concentration was similar between WT and Fabpl-Bcl-2 mice. Intestinal permeability increased 6, 12, 24, and 48 h following sepsis in WT mice; however, FD-4 concentration was significantly lower at each timepoint in Fabpl-Bcl-2 mice. In addition, there were no statistically significant changes in permeability between septic and sham transgenic mice. Intestinal mRNA expression of claudin 3, claudin 5, and occludin was lower in septic Fabpl-Bcl-2 mice, while claudin 4 mRNA levels were higher in Fabpl-Bcl-2 mice. In contrast, no differences were detected in claudins 2, 7, 15, JAM-A, or ZO-1. Protein levels followed the same trend for all tight junction mediators different between WT and Fabpl-Bcl-2 mice except occludin was significantly higher in transgenic mice. Together these results demonstrate that decreasing intestinal epithelial apoptosis prevents hyperpermeability following sepsis via tight junction alterations which may be at least partially responsible for improved survival conferred by Bcl-2 overexpression.
Genistein Protects Against Burn-Induced Myocardial Injury via Notch1-Mediated Suppression of Oxidative/Nitrative Stress
Authors: Fang Zhuoqun , Wu Gaofeng , Zhang Dongliang , Wang Kejia , Deng Xudong , Liu Mengdong , Han Juntao , Hu Dahai , Yang Xuekang
Published: October 2019

Genistein (Gen) exhibits strong anti-oxidative/antinitrative activity and cardioprotective effects in several models; however, its role in burn-induced myocardial injury is unknown. This study investigated the protective effect of Gen on burn-induced myocardial injury and aimed to elucidate the mechanism of protection. Mice were injected with Gen, intraperitoneally, at different dose immediately after burn injury. The expression levels of Notch-1 intracellular domain (NICD1) and hairy and enhancer of split (Hes-1) were determined by immunoblotting. Conditional Notch-RBP-J knockout mice were used to investigate the mechanisms of Gen-induced cardioprotection. Gen alleviated burn-induced myocardial injury, as shown by improved left ventricle ejection fraction, decreased serum lactate dehydrogenase and creatine kinase levels, and apoptosis. Moreover, Gen decreased expressions of inducible nitric oxide (NO) synthase and gp91phox, reduced NO and superoxide anions production, and ameliorated their cytotoxic reaction product, peroxynitrite. More importantly, Gen significantly up-regulated the expression of NICD1 and Hes1 after burn injury. In addition, genetic knockout of Notch1 not only blocked the cardioprotection of Gen but also markedly attenuated Gen-induced anti-oxidative/antinitrative effect. These results demonstrate, for the first time, that Gen treatment attenuates burn-induced myocardial injury via the Notch1 mediated suppression of oxidative/nitrative stress.
Mad dephosphorylation at the nuclear envelope is essential for asymmetric stem cell division
Authors: Sardi Justin , Bener Muhammed Burak , Simao Taylor , Descoteaux Abigail E. , Slepchenko Boris M. , Inaba Mayu
Published: October 2019

Stem cell niche signals act over a short range so that only stem cells but not the differentiating daughter cells receive the self-renewal signals.Drosophilafemale germline stem cells (GSCs) are maintained by short range BMP signaling; BMP ligands Dpp/Gbb activate receptor Tkv to phosphorylate Mad (phosphor-Mad or pMad) which accumulates in the GSC nucleus and activates the stem cell transcription program. pMad is highly concentrated in the nucleus of the GSC, but is immediately downregulated in the nucleus of the pre-cystoblast (preCB), a differentiating daughter cell, that is displaced away from the niche. Here we show that this asymmetry in the intensity of pMad is formed even before the completion of cytokinesis. A delay in establishing the pMad asymmetry leads to germline tumors through conversion of differentiating cells into a stem cell-like state. We show that a Mad phosphatase Dullard (Dd) interacts with Mad at the nuclear pore, where it may dephosphorylate Mad. A mathematical model explains how an asymmetry can be established in a common cytoplasm. It also demonstrates that the ratio of pMad concentrations in GSC/preCB is highly sensitive to Mad dephosphorylation rate. Our study reveals a previously unappreciated mechanism for breaking symmetry between daughter cells during asymmetric stem cell division.
The microevolutionary response to male-limited X-chromosome evolution inDrosophila melanogasterreflects macroevolutionary patterns
Authors: Abbott Jessica K. , Chippindale Adam K. , Morrow Edward H.
Published: October 2019

Due to its hemizygous inheritance and role in sex determination, the X chromosome is expected to play an important role in the evolution of sexual dimorphism, and to be enriched for sexually antagonistic genetic variation. By forcing the X chromosome to only be expressed in males over >40 generations, we changed the selection pressures on the X to become similar to those experienced by the Y. This releases the X from any constraints arising from selection in females, and should lead to specialization for male fitness, which could occur either via direct effects of X-linked loci or trans-regulation of autosomal loci by the X. We found evidence of masculinization via upregulation of male-benefit sexually antagonistic genes, and downregulation of X-linked female benefit genes. Interestingly, we could detect evidence of microevolutionary changes consistent with previously documented macroevolutionary patterns, such as changes in expression consistent with previously established patterns of sexual dimorphism, an increase in the expression of metabolic genes related to mitonuclear conflict, and evidence that dosage compensation effects can be rapidly altered. These results confirm the importance of the X in the evolution of sexual dimorphism and as a source for sexually antagonistic genetic variation, and demonstrate that experimental evolution can be a fruitful method for testing theories of sex chromosome evolution.
Combining Crowdsourcing and Deep Learning to Assess Public Opinion on CRISPR-Cas9
Authors: Müller Martin , Schneider Manuel , Salathé Marcel , Vayena Effy
Published: October 2019

The discovery of the CRISPR-Cas9-based gene editing method has opened un-precedented new potential for biological and medical engineering, sparking a growing public debate on both the potential and dangers of CRISPR applications. Given the speed of technology development, and the almost instantaneous global spread of news, it’s important to follow evolving debates without much delay and in sufficient detail, as certain events may have a major long-term impact on public opinion and later influence policy decisions. Social media networks such as Twitter have shown to be major drivers of news dissemination and public discourse. They provide a vast amount of semi-structured data in almost real-time and give direct access to the content of the conversations. Such data can now be mined and analyzed quickly because of recent developments in machine learning and natural language processing. Here, we used BERT, an attention-based transformer model, in combination with statistical methods to analyse the entirety of all tweets ever published on CRISPR since the publication of the first gene editing application in 2013. We show that the mean sentiment of tweets was initially very positive, but began to decrease over time, and that this decline was driven by rare peaks of strong negative sentiments. Due to the high temporal resolution of the data, we were able to associate these peaks with specific events, and to observe how trending topics changed over time. Overall, this type of analysis can provide valuable and complementary insights into ongoing public debates, extending the traditional empirical bioethics toolset.
Traditional functional groups capture limited variation in the trait space of macroalgae
Authors: Mauffrey Alizée R. L. , Cappelatti Laura , Griffin John N.
Published: October 2019

Macroalgal (seaweed) beds and forests fuel coastal ecosystems and are rapidly reorganising under global change, but quantifying their functional structure still relies on binning species into coarse groups on the assumption that they adequately capture relevant underlying traits.

To interrogate this “group gambit”, we first measured 12 traits relating to competitive dominance and resource economics across 95 macroalgal species collected from UK rocky shores. We then assessed trait variation explained by traditional grouping approaches consisting of (i) two highly-cited schemes based on gross morphology and anatomy and (ii) two commonly-used categorisations of vertical space use. To identify the limitations of traditional grouping approaches and to reveal potential alternatives, we also assessed the ability of (iii) emergent groups created from post hoc clustering of our dataset to account for macroalgal trait variation.

(i) Traditional groups explained about a third of multivariate trait expression with considerable group overlap. (ii) Classifications of vertical space use accounted for even less multivariate trait expression. Notwithstanding considerable overlap, the canopy vs. turf scheme explained significant differences in most individual traits, with turf species tending to display attributes of opportunistic forms. (iii) Emergent groups were substantially more parsimonious than all existing grouping approaches.

Synthesis: Our analysis using a comprehensive dataset of directly measured functional traits failed to strongly support the group gambit in macroalgae. While existing grouping approaches may allow first order approximations, they risk considerable loss of information at the trait and, potentially, ecosystem levels. We call for further development of a trait-based approach to macroalgal functional ecology to capture unfolding community and ecosystem changes with greater accuracy and generality.