bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of age on intravesical instillation of Bacille Calmette–Guerin treatment in patients with high-grade T1 bladder cancer
Authors: Calò B. , Sanguedolce F. , Fortunato F. , Stallone G. , d’Altilia N. , Chirico M. , Falagario U. , Mancini Vito , Carrieri G. , Cormio L.
Published: August 2019

Intravesical instillation of Bacille Calmette–Guèrin (BCG) is the standard adjuvant treatment for high-risk non muscle invasive bladder cancer (NMIBC). Since its mechanism of action is supposed to be linked to the immune system efficiency and senescence could negatively affect this efficiency, BCG efficacy in the elderly has been questioned. This study aimed to assess the impact of age on BCG efficacy and safety in patients with high-grade T1 bladder cancer (BC).

Among 123 patients with high-grade T1 BCG scheduled for BCG treatment, 82 were <75 year-old (group A) and 41 were ≥75 year-old (group B). Follow-up: urine cytology and cystoscopy every 3 months for the first 2 years, every 6 months for the third year, and then yearly. Tumor recurrence was defined as pathological evidence of disease at the bladder biopsy; tumor progression was defined as pathological shift to muscle invasive disease at the bladder biopsy or the imaging techniques showing recurrent BC and distant metastasis likely related to it.

The median follow-up was 65 months (range 11-152). Recurrence occurred in 35 patients, 19 (23.2%) in the group A and 16 (39%) in the group B. Progression occurred in 18 patients, 12 (14.6%) in the group A and 6 (14.6%) in the group B. Recurrence free rate was similar in both groups up to 2 years. The 5 years progression rate was almost the same in both groups A and B (85.9% vs 84.7%), whereas the 5 years cancer-specific survival (CSS) was 92.6% in the group A and 85.4% in the group B. Of the 18 patients with progression, 11 underwent cystectomy; 12 patients died because of their BC. Kaplan–Meier plots pointed out no difference in recurrence-free, progression-free, and CSS between the 2 groups. Adverse events were similar in the 2 groups. Only 4 (3.3%) patients, 2 (2.4%) in the group A and 2 (4.8%) in the group B, experienced mild adverse reactions compatible with treatment.

Elderly patients with high-grade T1 BC are not poorer candidates to BCG treatment, as they had similar benefit and adverse reactions than those aging ≥75 years.
Serum thyroglobulin elevation after needle aspiration of the lymph nodes: the predictive value for detecting metastasis in papillary thyroid cancer patients – a pilot study
Authors: Hong Chae Moon , Jeong Ju Hye , Son Seung Hyun , Lee Chang-Hee , Jeong Shin Young , Lee Sang-Woo , Lee Jaetae , Ahn Byeong-Cheol
Published: August 2019

Ultrasonography (USG)-guided fine needle aspiration (FNA) is widely used for diagnosis of lymph node (LN) metastasis in papillary thyroid cancer (PTC). However, FNA cytology sometimes shows inconclusive results. Recently, the measurement of thyroglobulin (Tg) in FNA washout fluid (aspirate-Tg) has been widely adopted, but there are some difficulties in the preparation of the sample and standardization of the procedure. Here, we examined serum Tg after FNA as a new predictive marker for LN metastasis of PTC. We performed USG-guided FNA cytology and examined aspirate-Tg in PTC patients showing suspicious metastatic LNs during follow-up. We measured baseline serum thyroid stimulating hormone (TSH), Tg, and Tg antibody levels before FNA, and serum Tg level within an hour after FNA. We defined aspirate-Tg level above 0.9 ng/mL as positive, and a 30% increase in serum Tg level after FNA compared to the baseline as elevation of serum Tg. Twenty-two patients were included in our study. Nine patients (40.9%) showed elevation of Tg level after FNA, and the mean value of Tg elevation was 24.8 ± 48.0 ng/mL. Among these 9 patients, 8 were diagnosed with PTC and 1 patient showed cellular atypia on cytopathology. All these patients showed positive aspirate-Tg. Thirteen patients (59.1%) did not show elevation of Tg level after FNA. Among these patients, 2 had PTC, 2 had cellular atypia, and 9 yielded negative results for malignancy on cytopathology. Elevation of serum Tg level after FNA might have a diagnostic role for predicting LN metastasis of PTC.
Combined use of salivary biomarkers and carcinoembryonic antigen for lung cancer detection in a Chinese population
Authors: Shang Xi , Zi Huanpu , Li Yangyang , Gao Yu , Ge Changsheng , Sun Zhongmei , Zhang Youmin
Published: August 2019

Blood-based biomarkers, such as carcinoembryonic antigen (CEA), and saliva-based biomarkers, such as mRNA, have emerged as potential liquid biopsies for non-invasive detection of many cancers. However, current tests typically use single type of biomarkers, and their sensitivity and specificity is often unsatisfactory.

In this study, we developed a novel biomarker panel that measures both CEA level in blood and GREB1 and FRS2 levels in saliva to achieve high sensitivity and high specificity in detecting Non-Small Cell Lung Cancer (NSCLC).

In the discovery phase, we achieved sensitivity of 96.67% and specificity of 93.33% for 30 NSCLC patients and 30 healthy controls. To further evaluate the prediction performance of our biomarker panel, we applied it to an independent set of 15 NSCLC cancer patients and 25 healthy controls. The sensitivity and specificity of our test reached 93.33% and 80.00% respectively.

Our study discovered that the combined analysis of CEA and mRNA can be a novel liquid-biopsy technology for non-invasive detection of NSCLC.
Evaluation of hepatic fibrosis by ultrasonic acoustic structure quantification
Authors: Cheng Lei , Chen Yongan , Xiao Rui , Pan Yan , Guo Jia
Published: August 2019

To evaluate the diagnostic accuracy of ultrasonic acoustic structure quantification (ASQ) for grading hepatic fibrosis/cirrhosis by comparing ultrasonographic features of regions of interest on ASQ images with the pathological characteristics of stage F0–F4 hepatic fibrosis cases.

We retrospectively analyzed the medical records of 97 patients with chronic hepatitis who underwent ASQ evaluation at the Ultrasound Room of Dongfang Hepatobiliary Surgery Hospital (Shanghai, China) between July 2012 and October 2013. Regions of interest on stored ASQ images were analyzed to obtain cm2 values on modes, averages, and standard deviations. Correlation analysis, principal component analysis (PCA), and multivariate analysis of variance (MANOVA) of the mean cm2 values with hepatic fibrosis staging were performed. A receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of ASQ.

The mean cm2 of ASQ correlated with the pathological stage of hepatic fibrosis, with the best correlation coefficient (r = 0.81) in the right lobe below rib 2. The best cm2 average 1 and 2 values, which differed significantly among different hepatic fibrosis/cirrhosis stages, were also found in this area. The maximal area under the ROC curve (0.969) was for cm2average 1 for the F0 versus F1 to F4 group, with a low criterion (110), while the maximal criterion (145) was for cm2 average 2 for the F0–F3 versus F4 group, with a relatively small AUC (0.882).

With objective and accurate results, ASQ analysis is a promising non-invasive method for grading hepatic fibrosis, although this should be verified in further studies.
Evaluation of ocular surface impairment in meibomian gland dysfunction of varying severity using a comprehensive grading scale
Authors: Fu Jiayu , Chou Yilin , Hao Ran , Jiang Xiaodan , Liu Yushi , Li Xuemin
Published: August 2019

This study aimed to propose a comprehensive grading scale to evaluate different clinical manifestations in patients with varying severity of meibomian gland dysfunction (MGD) and analyze the correlations between the parameters of ocular surface impairment in MGD.

A total of 63 patients with MGD were enrolled. Ten specific symptoms were evaluated each with a subjective score and total score was applied to grade the severity of MGD. Thirty-seven patients were diagnosed with mild, 19 with moderate, and 7 with severe MGD. Slit-lamp and keratography were used to assess the signs of ocular surface and meibomian gland (MG). In vivo confocal microscopy (IVCM) was performed to evaluate the corneal nerves and dendritic cells. The differences and correlations between symptoms, signs, and IVCM parameters were analyzed.

Dryness, foreign body sensation, asthenopia, and photophobia were the most common and severe symptoms in our patients. The severe MGD group showed worse MG expressibility, Meibum score, Meiboscore, MG score, and higher nerve reflectivity (P < .05). The mild MGD group showed higher nerve density (P < .05). Total symptom score was negatively correlated with nerve density (r = –0.374, P < .05), while positively correlated with nerve reflectivity and dendritic cell density (r = 0.332 and 0.288, respectively, P < .05). MG score was correlated with nerve reflectivity (r = 0.265, P < .05).

The comprehensive grading scale was suitable for evaluating clinical manifestations in MGD of varying severity. The relationship between the specific symptoms, signs, and IVCM results concerning whole ocular surface impairment could help elucidate MGD pathophysiology and benefit evaluation or treatment in the future.
IgG4-related sialadenitis complicated with type III mixed cryoglobulinemia
Authors: Zhang Rui-Yu , Zhao Zhi-Rui , Xu Xiao-Yi , Sun Li-Jun , Dong Hong-Rui , Rui Hong-Liang , Wang Guo-Qin , Cheng Hong , Chen Yi-Pu
Published: August 2019

Rationale:

IgG4-related disease (IgG4-RD) is a systemic autoimmune disease and mixed cryoglobulinemia may be caused by autoimmune diseases. However, so far only 1 case of IgG4-RD complicated with mixed cryoglobulinemia is reported. Our case further confirms the close relationship between these 2 diseases.

Patient concerns:

A 55-year-old female was admitted because of dry mouth and teeth falling off.

Diagnoses:

The patient was diagnosed as IgG4-related sialadenitis (IgG4-RS) complicated with type III mixed cryoglobulinemia. IgG4-RS was confirmed by elevated serum IgG4 levels and diffuse IgG4
+
plasmocyte infiltration and storiform fibrosis in the interstitium of labial gland. Type III mixed cryoglobulinemia was confirmed by positive serum cryoglobulins and no monoclonal immunoglobulin in serum and urine.

Interventions and Outcomes:

After treatment with prednisone and cyclophosphamide, serum cryoglobulins rapidly turned negative with the remission of IgG4-RS.

Lessons:

Type III mixed cryoglobulinemia can be caused by IgG4-RS, and the underlying mechanisms need to be further explored.
Optimal treatment for spermatogenesis in male patients with hypogonadotropic hypogonadism
Authors: Lin Jianli , Mao Jiangfeng , Wang Xi , Ma Wanlu , Hao Ming , Wu Xueyan
Published: August 2019

Background:

To compare the efficacies of gonadotropin-releasing hormone (GnRH) pulse subcutaneous infusion with combined human chorionic gonadotropin and human menopausal gonadotropin (HCG/HMG) intramuscular injection have been performed to treat male hypogonadotropic hypogonadism (HH) spermatogenesis.

Methods:

In total, 220 idiopathic/isolated HH patients were divided into the GnRH pulse therapy and HCG/HMG combined treatment groups (n = 103 and n = 117, respectively). The luteinizing hormone and follicle-stimulating hormone levels were monitored in the groups for the 1st week and monthly, as were the serum total testosterone level, testicular volume and spermatogenesis rate in monthly follow-up sessions.

Results:

In the GnRH group and HCG/HMG group, the testosterone level and testicular volume at the 6-month follow-up session were significantly higher than were those before treatment. There were 62 patients (62/117, 52.99%) in the GnRH group and 26 patients in the HCG/HMG (26/103, 25.24%) group who produced sperm following treatment. The GnRH group (6.2 ± 3.8 months) had a shorter sperm initial time than did the HCG/HMG group (10.9 ± 3.5 months). The testosterone levels in the GnRH and HCG/HMG groups were 9.8 ± 3.3 nmol/L and 14.8 ± 8.8 nmol/L, respectively.

Conclusion:

The GnRH pulse subcutaneous infusion successfully treated male patients with HH, leading to earlier sperm production than that in the HCG/HMG-treated patients. GnRH pulse subcutaneous infusion is a preferred method.
Assessment of the quality and content of clinical practice guidelines for post-stroke rehabilitation of aphasia
Authors: Wang Yu , Li Huijuan , Wei Huiping , Xu Xiaoyan , Jin Pei , Wang Zheng , Zhang Shian , Yang Luping
Published: August 2019

Objectives:

The purpose of this study was to evaluate the quality of guidelines for rehabilitation of post-stroke aphasia using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) instrument and identify consistency of different guidelines.

Methods:

A systematic search was undertaken from inception to October 2018. Two reviewers independently screened all titles and abstracts, and assessed eligible guidelines using the AGREE-II. Agreement among reviewers was measured by using intra-class correlation coefficient (ICC).

Results:

From 5008 records screened, 8 guidelines met the inclusion criteria. The quality of guidelines was heterogeneous. Three guidelines were rated high (6.5) across; the highest rated domain was “scope and purpose" (median score 95.8%); the lowest rated domain was “rigor of development" (median score 67.2%). An overall high degree of agreement among reviewers to each domain was observed (ICC ranged from 0.60 to 0.99). The speech language therapy was recommended in 3 guidelines. Four guidelines described group treatment was beneficial for the continuum of care. However, other therapies for aphasia varied in the level of detail across guidelines.

Conclusions:

Our study indicated the quality of guidelines for post-stroke aphasia needed to be improved. Moreover, the treatment recommendations of aphasia existed discrepancy among the included guidelines. Therefore, it is suggested to pay more attention on the rigor of methodology and applicability during the process of the formulation of guideline. Future research should focus on the effectiveness, intensity, and duration of treatment measures.
Monitoring of home recovery using the 317-nursing mobile application following day-case surgery in children
Authors: Li Canping , Huang Shoujiang , Su Xiaohua , Zhang Tingting , Jiang Kewen
Published: August 2019

The number of elective day-case surgeries has considerably increased in recent years, especially in China. Few studies have investigated the ability of mobile applications to assist recovery for patients having undergone day-surgery; however, these studies have indicated that the use of mobile applications is cost-efficient and has a positive effect on recovery after surgery. This study aimed to evaluate the utility and efficacy of using the 317-nursing mobile application program (317NAPP) for monitoring home recovery following day-surgery involving high ligation of the hernial sac in pediatric patients.

Prospective clinical study involving 2 parallel groups.

Patients were randomly divided into the “intervention 317NAPP group” (n = 64) and the control group (n = 63). Patients were followed-up using the 317NAPP in the intervention group and via telephonic consultations in the control group. All patients were enrolled after being provided sufficient guidance with respect to discharge and health education. The health index, including the physiological function, ability to perform daily activities, and the injury response, was evaluated before and 24 hours after surgery. The time duration of each follow-up session was also evaluated in both groups.

The preoperative (T1) health index scores were significantly higher than the postoperative (T0) ones in both groups (P = .00). The quality of recovery (T1–T0) of the intervention group (10.75 ± 5.28) was better than that of the control group (11.78 ± 5.16), but the differences were not significant (P = .27). In the intervention group, the follow-up time duration was significantly lower in comparison to that in the control group (P = .00).

This study demonstrated that 317NAPP had a positive effect on recovery following day-surgery, and the time-duration for follow-up was shorter than that performed using telephonic consultation. Monitoring recovery using 317NAPP was safe, efficient, inexpensive, and relatively easy; therefore, it may help improve the recovery of patients having undergone day-surgery.
Traumatic posterior atlantooccipital dislocation with Jefferson and occipital condyle fractures
Authors: Chang Dong-Gune , Park Jong-Beom , Cho Kwang Hyun
Published: August 2019

Rationale:

To the best of our knowledge, this is the first report on a case of a traumatic posterior atlantooccipital dislocation (AOD) with 3-part Jefferson and occipital condyle fractures.

Patient concerns:

We report the case of a 60-year-old male with posterior AOD with 3-part Jefferson fracture and fracture of right occipital condyle. This injury occurred as a result of rolling down from a mountain. The patient complained of severe neck pain showing bony tenderness and ecchymosis in the high cervical area but did not show any neurologic abnormalities.

Diagnoses:

Reconstructed computed tomography scans clearly demonstrated a 3-part Jefferson fracture and fracture of right occipital condyle, and posteriorly displaced occiput with respect to the anterior arch of C1 and dens of C2.

Intervention:

We planned to perform occipitocervical fusion; however, the patient refused treatment. He was transferred to another hospital and lost to follow-up.

Outcomes:

Although extremely rare, patient who had posterior AOD with 3-part Jefferson and occipital condyle fractures can survive without neurological compromise, as was observed in our patient.

Lessons:

Clinical suspicion with thorough radiographic and physical examinations are very important for diagnosing of the upper cervical spine injuries such as AOD with Jefferson and occipital condyle fractures.
A laryngeal disorders prediction model based on cluster analysis and regression analysis
Authors: Byeon Haewon
Published: August 2019

This study provided the baseline for establishing policies for community health promotion programs to propose the clusters of multiple health risk factors and identify the risks of laryngeal disorders according to the clusters by using the national level survey representing the South Korean population. This study targeted 5941 people who completed the 5th Korean National Health and Nutrition Examination Survey. The independent variables were age, sex, smoking, high-risk drinking, education level, occupation, household income, and self-reported voice problems. The identify cluster relationship with laryngeal disorders by conducting 2-way cluster analysis and multinomial logit analysis. The prevalence of laryngeal disorder was 6.7%. The results of analysis, 3 clusters were automatically extracted. Multinomial logistic regression analysis showed that sociodemographic factors, health risk behaviors, and health status clusters were significantly related to the risk of laryngeal disorders. The males who were smoking, high-risk drinking, college graduate and above, high income, and non-manual workers had a higher risk of laryngeal disorders than females who were non-smokers, non-drinkers, 60 years old and older, economically inactive, and high school graduate. The results of this study suggested that it may be effective to classify population according to sociodemographic and health behaviors and develop health education materials and health promotion program accordingly in order to prevent laryngeal disorders.
Mature ovarian cystic teratoma with “sack of marbles” appearance on magnetic resonance imaging
Authors: Wang Anlong , Shu Yefei
Published: August 2019

Introduction:

Mature ovarian cystic teratoma is a cystic fatty tumor. Presence of floating fat balls in an ovarian cystic teratoma looking like a “sack of marbles” on magnetic resonance imaging (MRI) is a rare finding.

Patient concerns:

Herein, we report a 38-year old woman who was admitted to our hospital presenting with an abdominal mass and abdominal pain.

Diagnosis:

Ultrasonography revealed a giant cystic mass in the pelvis; T1-weighted MRI revealed multiple spherical signals in the lesion.

Interventions:

She underwent exploratory laparotomy and was histopathologically diagnosed with benign cystic teratoma.

Outcomes:

Finally, the patient recovered after operation. Until December 2018, she had been still healthy without recurrence of tumors.

Conclusion:

The aim of this case report was to present “sack of marbles” appearance on MRI, which will impress other doctors and improve the diagnosis of such diseases.
Ultrasound-guided peri-brachial plexus polydeoxyribonucleotide injection for a patient with postherpetic brachial plexopathy
Authors: Kim Jun Young , Hwang Jong-Moon , Park Jin-Sung , Park Sungwon , Lee Byung Joo , Park Donghwi
Published: August 2019

Rationale:

Although most complications of herpes zoster (HZ) are associated with the spread of varicella-zoster virus from the initially involved sensory ganglion, motor nerve impairment, such as limb weakness, is a rare but severe complication that is difficult to treat.

Patient concern:

A 73-year-old female presented with sudden left upper limb pain and weakness after HZ.

Diagnosis:

Brachial plexopathy following HZ (postherpetic brachial plexopathy).

Intervention:

Despite alleviation of the vesicles with antiviral treatments, the left upper limb weakness and neuropathic pain did not improve. After obtaining patient's consent, ultrasound-guided polydeoxyribonucleotide (PDRN) injection was performed around the left brachial plexus.

Outcomes:

The patient showed marked improvement in left arm pain from numerical rating scale (NRS) 9 to 4, 1 day after PDRN injection. Subsequently, the pain improved to NRS 3, and motor weakness improved to Medical Research Council grade 2 to 4.

Lessons:

PDRN can be considered a viable substitute for corticosteroid injection in treatment of motor weakness and neuropathic pain after HZ.
Efficacy and safety of 0.05% cyclosporine ophthalmic emulsion in treatment of Chinese patients with moderate to severe dry eye disease: A 12-week, multicenter, randomized, double-masked, placebo-controlled phase III clinical study
Authors: Chen Di , Zhang Shunhua , Bian Ailing , Hong Jing , Deng Yingping , Zhang Mingchang , Chen Wei , Shao Yan , Zhao Jialiang
Published: August 2019

Background:

Dry eye disease (DED) is a chronic ocular surface disease that affects hundreds of millions of people worldwide. Although 0.05% cyclosporine ophthalmic emulsion (CsA OE) has long been prescribed in the U.S. for the treatment of DED, it is not commercially available in China. Our study aims to compare the efficacy and safety profile of 0.05% CsA OE versus vehicle in Chinese patients with moderate to severe DED.

Methods:

This was a multicenter, randomized, double-masked, 2-parallel-arm, 3-month phase III study. Patients with moderate to severe DED were randomized to receive twice-daily 0.05% CsA OE or its vehicle, along with unpreserved hypromellose eye drops 3 times per day. Patients were followed up at day 7, 28, 56, and 84, as well as 2 weeks after the medications were discontinued for safety assessment.

Results:

A total of 240 patients were randomized. The overall effective rate (OER) and efficacy index were significantly better in the CsA OE than vehicle group at all follow up times (all P < .05), and the OER of CsA OE and vehicle group at month 3 was 70.6% and 27.8%, respectively (P < .001) (primary endpoint). The patients in CsA OE group displayed a significant improvement in dry eye symptoms from day 28 and ocular surface test results from day 7 (all P < .05). The ocular surface disease index scores of 0.05% CsA OE treated patients were significantly better than those treated with vehicle control at day 56 and 84 (P = .0061 and <.001, respectively). Drug related adverse events (AEs) were recorded in 6(5%) and 3(2.5%) patients in the CsA OE and vehicle groups respectively (P = .4061) with ocular pain as the most frequently reported AEs, and it was mostly mild to moderate. There were no detrimental effects on visual acuity, intraocular pressure, or vital signs.

Conclusions:

Twice-daily instillation of 0.05% CsA OE was effective and well tolerated for the treatment of moderate to severe DED in Chinese population during the 3 months of the study.
Expression and prognostic impact of alpha thalassemia/mental retardation X-linked and death domain-associated protein in human lung cancer
Authors: Buentzel Judith , Yao Sha , Elakad Omar , Lois Anna-Maria , Brünies Jana , König Julia , Hinterthaner Marc , Danner Bernhard C. , Ströbel Philipp , Emmert Alexander , Bohnenberger Hanibal
Published: August 2019

Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators alpha thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) have recently been described in different cancer entities as a useful prognostic biomarker. This study was initiated to explore their protein expression patterns and prognostic value in patients with operable lung cancer disease.

The protein abundance (in the following text also named protein expression) of ATRX and DAXX were analyzed by immunohistochemistry in 194 samples of squamous cell lung carcinoma (SQCLC), 111 samples of pulmonary adenocarcinoma (AC) and 40 samples of small cell lung cancer (SCLC). The protein levels of ATRX and DAXX were correlated with clinicopathological characteristics and patient outcome.

ATRX showed strong protein expression in 16.2% of AC, 11.9% of SQCLC, and 42.5% of SCLC. DAXX was highly expressed in 54.9% of AC, 76.2% of SQCLC, and 82.5% of SCLC. Immunostaining of both ATRX and DAXX were seen in 14.4% of AC, 11.3% of SQCLC, and 42.5% of SCLC. High protein expression of ATRX was a favorable prognostic marker for patients with AC (hazard ratio 0.38, P = .02). Sub-group analyses showed a significant correlation between ATRX and the clinical stage of SQCLC and SCLC. Histological grading and ATRX were also significantly associated in cases of SQCLC.

The presence of ATRX and DAXX are correlated with lung cancer histology. Strong ATRX protein expression is associated with a significantly longer overall survival in patients with AC.
Association of GTF2I gene polymorphisms with renal involvement of systemic lupus erythematosus in a Chinese population
Authors: Meng Yanming , He Yao , Zhang Junlong , Xie Qibing , Yang Min , Chen Yuning , Wu Yongkang
Published: August 2019

The purposes of the study was to validate the relationship between General transcription factor II-I (GTF2I) genetic variants and kidney involvements of systemic lupus erythematosus (SLE) patients in a Chinese Han population.

Samples from 400 SLE patients and 400 age- and sex-matched healthy controls were collected and genotyped by improved multiplex ligation detection reaction technique. The relationship between gene polymorphism of rs117026326, rs73366469, and susceptibility, progression of SLE were analyzed.

The present study provided evidence that rs117026326 and rs73366469 were both associated with SLE susceptibility (both C vs T: P < .001). The analysis of dominant, recessive disease model provided us with further validation (P < .001). Both gene polymorphisms are associated with a triad of disease manifestations among SLE patients. Patients carrying genotype TT of rs117026326 had lower 24-hour urinary total protein (24 hours UTP, g/24 hours), 24-hour urinary protein level (g/L·24 hours), lower frequency of the proteinuria and lupus nephritis (LN). Patients carrying genotype TT at rs73366469 had higher 24-hour urinary protein level, higher frequency of the proteinuria, LN and positive anti-dsDNA than those with other genotypes.

This study identified the involvement of GTF2I gene polymorphisms in development of SLE, particularly in renal involvement.
Protocol for Pilot Study on Self-Management of Depressive Symptoms in Pregnancy
Authors: Kinser Patricia A. , Moyer Sara , Mazzeo Suzanne , York Timothy P. , Amstadter Ananda , Thacker Leroy , Starkweather Angela
Published: August 2019

Background

Pregnant women with depressive symptoms face significant treatment challenges and are in great need of safe, effective, accessible, inexpensive, and nonpharmacological self-management therapies to enhance well-being, reduce the burden of symptoms both during their pregnancy and postpartum, and prevent chronic sequelae.

Objectives

In this article, we describe the protocol for our pilot study testing a self-management intervention entitled, “Mindful Moms,” designed to foster women’s ability to address current depressive symptoms and enhance resilience to prevent recurrence.

Methods

We will conduct a longitudinal pilot trial of the 12-week intervention with pregnant women with depressive symptoms (n = 40); the primary aim is to determine the feasibility and acceptability of the intervention. The secondary aim is to examine preliminary effects of the intervention on maternal psychobehavioral outcomes in pregnancy and 6 weeks postpartum. The third aim will quantify genome-wide and gene-specific DNA methylation patterns associated with depressive symptoms during pregnancy and investigate whether intervention participation influences these patterns.

Results

This study is currently ongoing.

Discussion

Findings from this study will inform future research addressing the need for nonpharmacological self-management interventions for pregnant women with depressive symptoms.
Subbrow Blepharoplasty Combined with Periorbital Muscle Manipulation for Periorbital Rejuvenation in Asian Women
Authors: Wang Jianzhang , Su Yingjun , Zhang Juan , Guo Peng , Song Baoqiang
Published: August 2019

Background:

With advancing age, Asian women are often plagued by lateral hooding of the upper eyelid skin, eyebrow ptosis, and obvious periorbital wrinkles. The authors propose a novel technique to revive the natural eyelid shape with a stable eyebrow position and alleviate periorbital wrinkles in Asian women.

Methods:

Sixty-six patients underwent subbrow blepharoplasty combined with periorbital muscle manipulation. An ellipse shape of the skin and subcutaneous tissue below the eyebrow was measured, demarcated, and removed. Then, the orbicularis oculi muscle beneath the subcutaneous tissue was exposed and dissected at the upper third. The lower muscle flap was fixed to the supraorbital rim periosteum and the upper musculocutaneous flaps, forming a cross flap for interlocking fixation. The lateral border of the orbicularis oculi muscle was detached from the subcutaneous tissue, splayed out, and sutured upward and inward to the periosteum. The corrugator supercilii muscle temporal to the origin of the supraorbital nerve notch was separated by 1 to 2 mm. The operation results were evaluated by patient satisfaction and comparisons between preoperative and postoperative photographs.

Results:

Subbrow blepharoplasty combined with periorbital muscle manipulation significantly corrected lateral hooding with a stable eyebrow position and reduced the crow’s feet and glabellar frown lines in all patients. The persistence of the improved outcome was stable during the follow-up period. Postoperative scarring was inconspicuous; however, eight cases had transient postoperative forehead numbness.

Conclusions:

This novel procedure provides a simple, effective, and comprehensive technique for improving periorbital aging in Asian women. The surgical outcomes are predictable, and the postoperative scarring is inconspicuous.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Genetic tool development in marine protists: Emerging model organisms for experimental cell biology
Authors: Faktorová Drahomíra , Nisbet R. Ellen R. , Robledo José A. Fernández , Casacuberta Elena , Sudek Lisa , Allen Andrew E. , Ares Manuel , Aresté Cristina , Balestreri Cecilia , Barbrook Adrian C. , Beardslee Patrick , Bender Sara , Booth David S. , Bouget François-Yves , Bowler Chris , Breglia Susana A. , Brownlee Colin , Burger Gertraud , Cerutti Heriberto , Cesaroni Rachele , Chiurillo Miguel A. , Clemente Thomas , Coles Duncan B. , Collier Jackie L. , Cooney Elizabeth C. , Coyne Kathryn , Docampo Roberto , Dupont Christopher L. , Edgcomb Virginia , Einarsson Elin , Elustondo Pía A. , Federici Fernan , Freire-Beneitez Veronica , Freyria Nastasia J. , Fukuda Kodai , García Paulo A. , Girguis Peter R. , Gomaa Fatma , Gornik Sebastian G. , Guo Jian , Hampl Vladimír , Hanawa Yutaka , Haro-Contreras Esteban R. , Hehenberger Elisabeth , Highfield Andrea , Hirakawa Yoshihisa , Hopes Amanda , Howe Christopher J. , Hu Ian , Ibañez Jorge , Irwin Nicholas A.T. , Ishii Yuu , Janowicz Natalia Ewa , Jones Adam C. , Kachale Ambar , Fujimura-Kamada Konomi , Kaur Binnypreet , Kaye Jonathan Z. , Kazana Eleanna , Keeling Patrick J. , King Nicole , Klobutcher Lawrence A. , Lander Noelia , Lassadi Imen , Li Zhuhong , Lin Senjie , Lozano Jean-Claude , Luan Fulei , Maruyama Shinichiro , Matute Tamara , Miceli Cristina , Minagawa Jun , Moosburner Mark , Najle Sebastián R. , Nanjappa Deepak , Nimmo Isabel C. , Noble Luke , Vanclová Anna M.G. Novák , Nowacki Mariusz , Nuñez Isaac , Pain Arnab , Piersanti Angela , Pucciarelli Sandra , Pyrih Jan , Rest Joshua S. , Rius Mariana , Robertson Deborah , Ruaud Albane , Ruiz-Trillo Iñaki , Sigg Monika A. , Silver Pamela A. , Slamovits Claudio H. , Smith G. Jason , Sprecher Brittany N. , Stern Rowena , Swart Estienne C. , Tsaousis Anastasios D. , Tsypin Lev , Turkewitz Aaron , Turnšek Jernej , Valach Matus , Vergé Valérie , von Dassow Peter , von der Haar Tobias , Waller Ross F. , Wang Lu , Wen Xiaoxue , Wheeler Glen , Woods April , Zhang Huan , Mock Thomas , Worden Alexandra Z. , Lukeš Julius
Published: August 2019

Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and advancement of tools for 8 other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.
Long-term, functional culture andin vitromanipulation of adult mouse cardiomyocytes
Authors: Callaghan Neal I. , Lee Shin-Haw , Hadipour-Lakmehsari Sina , Lee Xavier A. , Siraj M. Ahsan , Driouchi Amine , Yip Christopher M. , Husain Mansoor , Simmons Craig A. , Gramolini Anthony O.
Published: August 2019

Primary adult cardiomyocyte (aCM) culture is challenged by poor survival and loss of phenotype, rendering extendedin vitroexperiments unfeasible. Here, we establish murine aCM culture methods that enhance survival and maintain sarcomeric structure and Ca2+cycling to enable physiologically-relevant contractile force measurements. We also demonstrate genetic and small-molecule manipulations that probe mechanisms underlying myocyte functional performance.
Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5’-tRNA halves
Authors: Cooke William R , Cribbs Adam , Zhang Wei , Kandzija Neva , Motta-Mejia Carolina , Dombi Eszter , Ri Rannya , Cerdeira Ana Sofia , Redman Christopher , Vatish Manu
Published: August 2019

The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EV) into the maternal circulation throughout gestation. STB-EV dependent signalling is believed to contribute to the widespread maternal adaptive physiological changes seen in pregnancy. Transfer RNA (tRNA) halves have been identified in vesicles released from other human and murine organ systems, which alter gene expression in target cells. Here, we characterise tRNA-half expression in STB-EV and demonstrate biological activity of a highly abundant tRNA-half. Short RNA from ex-vivo, dual-lobe placental perfusion STB-EV was sequenced, showing that most (>95%) comprised tRNA species. Whole placental tissue contained <50% tRNA species, suggesting selective packaging and export of tRNA into STB-EV. Most tRNA within STB-EV were 5’-tRNA halves cleaved at 30-32 nucleotides. The pattern of tRNA expression differed depending on the size/origin of the STB-EV; this was confirmed by qPCR. Protein synthesis was suppressed in human fibroblasts when they were cultured with a 5’-tRNA half identified from STB-EV sequencing. This study is the first to evaluate tRNA species in STB-EV. The presence of biologically active 5’-tRNA halves, specific to a vesicular origin, suggests a novel mechanism for maternal-fetal signalling in normal pregnancy.
Odorant receptors fromCulex quinquefasciatusandAedes aegyptisensitive to floral compounds
Authors: Zeng Fangfang , Xu Pingxi , Leal Walter S.
Published: August 2019

Mosquitoes rely heavily on the olfactory system to find a host for a bloodmeal, plants for a source of energy and suitable sites for oviposition. Here, we examined a cluster of 8 odorant receptors (ORs), which includes one OR, CquiOR1, previously identified to be sensitive to plant-derived compounds. We cloned 5 ORs fromCulex quinquefasciatusand 2 ORs fromAedes aegypti, ie, CquiOR2, CquiOR4, CquiOR5, CquiOR84, CquiOR85, AaegOR14, and AaegOR15 and then deorphanized these receptors using theXenopusoocyte recording system and a large panel of odorants. 2-Phenylethanol, phenethyl formate, and phenethyl propionate were the best ligands for CquiOR4 somewhat resembling the profile of AaegOR15, which gave the strongest responses to phenethyl propionate, phenethyl formate, and acetophenone. In contrast, the best ligands for CquiOR5 were linalool, PMD, and linalool oxide. CquiOR4 was predominantly expressed in antennae of nonblood fed female mosquitoes, with transcript levels significantly reduced after a blood meal. 2-Phenylethanol showed repellency activity comparable to that of DEET at 1%. RNAi experiments suggest that at least in part 2-phenylethanol-elicited repellency is mediated by CquiOR4 activation.
Priority effects, consumer pressure, and soil resources independently alter plant diversity and resource strategies during a multi-year successional field experiment
Authors: Wilfahrt Peter A. , Halliday Fletcher W. , Heckman Robert W.
Published: August 2019

Plant community succession is structured by priority effects, plant consumer pressure, and soil resource supply. Importantly, these drivers may interact, their effects may vary temporally, and they may influence different facets of plant community diversity by promoting different plant tradeoff strategies.

In an herbaceous successional system, we manipulated priority effects by altering initial plant richness, consumer pressure via pesticide spraying, and soil resource supply via fertilization. We examined how these processes jointly influenced succession, including taxonomic diversity and functional traits, over four years.

Diversity decreased in different years in response to more diverse priority effects, lower consumer pressure, and increased soil resource supply. Functionally, higher soil resource supply increased community height, SLA, and seed mass; higher consumer pressure decreased intraspecific community height, and increased interspecific SLA; priority effects led to decreased seed mass only when plots were unplanted.

Our results suggest species’ resource strategies underlie plant diversity responses. Resource addition promoted resource-acquisitive species, consumer pressure disadvantaged resource-conservative species, and diversity of priority effects altered subsequent community composition through persistence of early residents, not via traits. We show that community responses to drivers of succession depend on underlying trait tradeoffs of resident species, and these tradeoffs influence community diversity across succession.
Functional properties of habenular neurons are determined by developmental stage and sequential neurogenesis
Authors: Fore Stephanie , Cosacak Mehmet Ilyas , Diaz Verdugo Carmen , Kizil Caghan , Yaksi Emre
Published: August 2019

Neural development is not just a linear expansion of the brain. Instead, the structure and function of developing brain circuits undergo drastic alterations that have a direct impact on the animals’ expanding behavioural repertoire. Here we investigated the developmental changes in the habenula, a brain region that mediates behavioural flexibility during learning, social interactions and aversive experiences. We showed that developing habenular circuits exhibit multiple alterations, which increase the structural and functional diversity of cell types, inputs and functional modules within habenula. As the neural architecture of habenula develops, it sequentially transforms into a multi-sensory brain region that can process visual and olfactory information. Moreover, we also observed that already at early developmental stages, the habenula exhibits spatio-temporally structured spontaneous neural activity that shows prominent alterations and refinement with age. Interestingly, these alterations in spontaneous activity are accompanied by sequential neurogenesis and integration of distinct neural clusters across development. Finally, by combining an in vivo neuronal birthdating method with functional imaging, we revealed that clusters of habenular neurons with distinct functional properties are born sequentially at distinct developmental time windows. Our results highlight a strong link between the function of habenular neurons and their precise birthdate during development, which supports the idea that sequential neurogenesis leads to an expansion of neural clusters that correspond to distinct functional modules in the brain.
Oxidative stress in retinal pigment epithelial cells increased endogenous complement-dependent inflammatory and angiogenic responses - independent from exogenous complement sources
Authors: Trakkides Timon-Orest , Schäfer Nicole , Reichenthaler Maria , Kühn Konstanze , Enzmann Volker , Pauly Diana
Published: August 2019

Oxidative stress-induced damage of the retinal pigment epithelium (RPE) together with chronic inflammation has been suggested as major contributors to retinal diseases. Here, we examine the effects of oxidative stress and endogenous complement components on the RPE and its pro-inflammatory and –angiogenic responses.

The RPE cell line, ARPE-19, treated with H2O2 reduced cell-cell contacts, increased marker for epithelial–mesenchymal transition but showed less cell death. Stressed ARPE-19 cells increased the expression of complement receptors CR3 and C5aR1. CR3 was co-localized with cell-derived complement protein C3, which was observed in its activated form in ARPE-19 cells. C3 as well as its regulators CFH and properdin accumulated in ARPE-19 cells after oxidative stress independent from external complement sources. This cell-associated complement accumulation promoted nlrp3 and foxp3 expression and subsequent increased secretion of pro-inflammatory and pro-angiogenic factors. The complement-associated ARPE-19 reaction to oxidative stress, independent from external complement source, was increased by the PARP-inhibitor olaparib.

Our results indicated that RPE cell-derived complement proteins and receptors are involved in RPE cell homeostasis following oxidative stress and should be considered as targets for treatment developments for retinal degeneration.

GRAPHICAL ABSTRACT

We show a functional link between oxidative stress, complement receptors, endogenous complement proteins, pro-angiogenic and -inflammatory responses in ARPE-19 cells. These effects are independent from extracellularly added complement proteins or receptor ligands. We suggest an oxidative stress-associated autocrine mechanism of complement receptor regulation in ARPE-19 cells in connection with upregulated intracellular proteases.

HIGHLIGHTS

Oxidative stress accumulates complement proteins and receptors in RPE cells

Oxidative stress activates the RPE inflammasome without external complement proteins

Oxidative stress increases foxp3 expression and IL-8/VEGF secretion in RPE cells

Olaparib enhances pro-inflammatory response of RPE
In-silicodefinition of theDrosophila melanogastermatrisome
Authors: Davis Martin N. , Horne-Badovinac Sally , Naba Alexandra
Published: August 2019

The extracellular matrix (ECM) is an assembly of hundreds of proteins that structurally supports the cells it surrounds and biochemically regulates their functions.Drosophilahas emerged as a powerful model organism to study fundamental mechanisms underlying ECM protein secretion, ECM assembly, and ECM roles in pathophysiological processes. However, as of today, we do not possess a well-defined list of the components forming the ECM of this organism. We previously reported the development of computational pipelines to define the matrisome - the ensemble of genes encoding ECM and ECM-associated proteins - of humans, mice, zebrafish andC. elegans. Using a similar approach, we report here that theDrosophilamatrisome is composed of 641 genes. We further classify these genes into different structural and functional categories, including an expanded way to classify genes encoding proteins forming apical ECMs. We illustrate how having a comprehensive list ofDrosophilamatrisome proteins can be used to annotate large proteomic datasets and identify unsuspected roles for the ECM in pathophysiological processes. Last, to aid the dissemination and usage of the proposed definition and categorization of theDrosophilamatrisome by the scientific community, our list has been made available through three public portals: The Matrisome Project, FlyBase, and GLAD.
ABA-dependent and ABA-independent functions of RCAR5/PYL11 in response to cold stress
Authors: Lim Chae Woo , Lee Sung Chul
Published: August 2019

Arabidopsis thaliana has 14 abscisic acid (ABA) receptors—PYR1/PYLs/RCARs—which have diverse and redundant functions in ABA signaling; however, the precise role of these ABA receptors remains to be elucidated. Here, we report the functional characterization of RCAR5/PYL11 in response to cold stress. Expression of RCAR5 gene in dry seeds and leaves was ABA-dependent and ABA-independent, respectively. Under cold stress conditions, seed germination was markedly delayed in RCAR5-overexpressing (Pro35S:RCAR5) plants, but not in Pro35S:RCAR5 in ABA-deficient (aba1-6) mutant background. Leaves of Pro35S:RCAR5 plants showed enhanced stomatal closure—independent of ABA—and high expression levels of cold, dehydration, and/or ABA-responsive genes; these traits conferred enhanced freezing tolerance. Our data suggest that RCAR5 functions in response to cold stress by delaying seed germination and inducing rapid stomatal closure via ABA-dependent and ABA-independent pathways, respectively.