bluuebunny/crossref_metadata_2025 huggingface dataset:
Agnostic-Histology Approval of New Drugs in Oncology: Are We Already There?
Authors: Hierro Cinta , Matos Ignacio , Martin-Liberal Juan , Ochoa de Olza Maria , Garralda Elena
Published: January 2019

Over the last several years, several molecular aberrations have been unevenly described across cancers, although the distinct functional relevance in each biological context is not yet fully understood. Novel discoveries have led to the development of drugs tailored to the molecular profile of patients, thus increasing the likelihood of response among biomarker-selected patients. In this context, there has been a progressive redefinition of a precision medicine framework where evidence-based development and earlier approvals might now be driven by this molecular information. Innovative trial designs have greatly facilitated the evaluation and approval of new drugs in small cohorts of orphan cancers in which histology-dependent molecularly defined trials might be logistically difficult. However, accelerated approvals based on this agnostic-histology development model have brought new clinical, regulatory, and reimbursement challenges. In this article, we will highlight many of the biologic issues and clinical trial design challenges characterizing the development of tissue-agnostic compounds. Also, we will review some of the key factors involved in the development of pembrolizumab and larotrectinib, the first two drugs that have been approved by the U.S. Food and Drug Administration in an histology-agnostic manner. Because we anticipate that agnostic-histology approvals will continue to grow, we aim to provide insight into the current panorama of targeted drugs that are following this strategy and some premises to take into consideration. Clinicians and regulators should be prepared to overcome the associated potential hurdles, ensuring that uncertainties are dealt with properly and allowing new, promising agents to arrive faster to the market.
Methylation Biomarker Panel Performance in EsophaCap Cytology Samples for Diagnosing Barrett's Esophagus: A Prospective Validation Study
Authors: Wang Zhixiong , Kambhampati Thiruvengadam Swetha , Cheng Yulan , Ma Ke , Simsek Cem , Tieu Alan H. , Abraham John M. , Liu Xi , Prasath Vishnu , Duncan Mark , Stark Alejandro , Trick Alexander , Tsai Hua-Ling , Wang Hao , He Yulong , Khashab Mouen A. , Ngamruengphong Saowanee , Shin Eun J. , Wang Tza-Huei , Meltzer Stephen J.
Published: January 2019

Purpose:

Barrett's esophagus is the only known precursor of esophageal adenocarcinoma (EAC). Although endoscopy and biopsy are standard methods for Barrett's esophagus diagnosis, their high cost and risk limit their use as a screening modality. Here, we sought to develop a Barrett's esophagus detection method based on methylation status in cytology samples captured by EsophaCap using a streamlined sensitive technique, methylation on beads (MOB).

Experimental Design:

We conducted a prospective cohort study on 80 patients (52 in the training set; 28 in the test set). We used MOB to extract and bisulfite-convert DNA, followed by quantitative methylation-specific PCR to assess methylation levels of 8 previously selected candidate markers. Lasso regression was applied to establish a prediction model in the training set, which was then tested on the independent test set.

Results:

In the training set, five of eight candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in Barrett's esophagus patients than in controls. We built a four-biomarker-plus-age lasso regression model for Barrett's esophagus diagnosis. The AUC was 0.894, with sensitivity 94.4% [95% confidence interval (CI), 71%–99%] and specificity 62.2% (95% CI, 44.6%–77.3%) in the training set. This model also performed with high accuracy for Barrett's esophagus diagnosis in an independent test set: AUC = 0.929 (P < 0.001; 95% CI, 0.810%–1%), with sensitivity=78.6% (95% CI, 48.8%–94.3%) and specificity = 92.8% (95% CI, 64.1%–99.6%).

Conclusions:

EsophaCap, in combination with an epigenetic biomarker panel and the MOB method, is a promising, well-tolerated, low-cost esophageal sampling strategy for Barrett's esophagus diagnosis. This approach merits further prospective studies in larger populations.
Beta Human Papillomavirus and Associated Diseases
Authors: Sichero Laura , Rollison Dana E. , Amorrortu Rossybelle P. , Tommasino Massimo
Published: January 2019

The cutaneous human papillomavirus (HPV), mostly from β- and γ-HPV genus, is ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of β-HPVs and cutaneous squamous cell carcinoma (cSCC) development was initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis. Likewise, immunosuppressed organ transplant recipients have an increased susceptibility to β-HPV infections in the skin as well as to cSCC development. Although ultraviolet radiation (UVR) is the main risk factor of cSCC, experimental data points toward β-HPVs as co-carcinogens, which appear to be required solely at early stages of skin carcinogenesis by facilitating the accumulation of UVR-induced DNA mutations. Several epidemiological studies relying on different biomarkers of β-HPV infections have also been conducted in immunocompetent individuals to access their association with cSCC development. Additionally, in vivo and in vitro studies are presenting cumulative evidence that E6 and E7 proteins from specific β-HPVs exhibit transforming activities and may collaborate with different environmental factors in promoting carcinogenesis. Nevertheless, further research is crucial to better understand the pathological implications of the broad distribution of these HPVs.
Age- and Sex-Related Percentiles of Skinfold Thickness, Waist and Hip Circumference, Waist-to-Hip Ratio and Waist-to-Height Ratio: Results from a Population-Based Pediatric Cohort in Germany (LIFE Child)
Authors: Rönnecke Elisa , Vogel Mandy , Bussler Sarah , Grafe Nico , Jurkutat Anne , Schlingmann Maike , Koerner Antje , Kiess Wieland
Published: January 2019

Background: Skinfold thickness (ST), waist circumference (WC) and hip circumference (HC) measurements are simple methods for assessing fat tissue at defined body parts. We examined these parameters in a cohort of healthy children and adolescents in Leipzig. Our study provides current percentile curves for biceps, triceps, subscapular and iliac crest ST, plus WC, HC, waist-to-hip ratio and waist-to-height ratio. Methods: 6,344 visits were recorded involving 2,363 individuals from 3 to 16 years in age. Continuous age- and gender-related percentiles (3rd, 10th, median, 90th, 97th percentiles) were estimated using Cole’s LMS method. Results: For biceps and triceps ST, boys show a peak at the beginning of adolescence with a subsequent decrease, while percentile values among girls rise across the age range. Subscapular and iliac crest percentiles also show increasing curves with disproportionately high values for P90 and P97. Boys show higher values of WC, girls have higher levels of HC. WC and HC median percentiles constantly increase in both sexes with a plateau at the age of 16 for girls. Conclusion: Trends for all parameters of body fat are in line with other national and international studies. Unlike the KiGGS study, our study provides circumference data across the whole of our age range, i.e. from 3 to 16 years.
Development of a Novel Approach to Studying Corneodesmosomes and Stratum Corneum Adhesion: Extending Knowledge on the Pathophysiology of Sensitive Skin
Authors: Richters Renée J.H. , Uzunbajakava Natallia E. , Timofeeva Nadya , van de Kerkhof Peter C.M. , van Erp Piet E.J.
Published: January 2019

Background/Aims: Aberrant skin barrier and intercorneocyte adhesion are potential contributors to the pathomechanism of sensitive skin (SS). Here we aimed to develop a novel and easy-to-apply method to analyze corneodesmosomes and to interrogate potential differences between corneocytes of subjects with SS and non-SS (NSS). Methods: Corneocytes of the volar forearm and upper outer quadrant of the left buttock of SS (n = 10) and NSS (n = 8) subjects were extracted as a function of depth using adhesive tape and stained with anti-desmoglein 1 (DSG1) antibody. The total area of corneocytes and the number and average size of cells per tape was estimated using image processing. Results: The total area of extracted corneocytes and the quantity of DSG1 decreased with depth. The level of decrease, total area of corneocytes, and average area of individual cells differed between anatomical locations. In SS, a larger total area of extracted corneocytes and a larger average cell size per tape was found at all inspected depths. Conclusion: The developed novel and easy-to-apply approach allows investigation of corneodesmosome components. We confirm a role of altered corneocytes in the pathomechanism of SS. The disclosed protocol can further be optimized in studies of skin conditions with strongly affected corneodesmosomes.
Combining Tumor-Selective Bacterial Therapy with Salmonella typhimurium A1-R and Cancer Metabolism Targeting with Oral Recombinant Methioninase Regressed an Ewing’s Sarcoma in a Patient-Derived Orthotopic Xenograft Model
Authors: Miyake Kentaro , Kiyuna Tasuku , Li Shukuan , Han Qinghong , Tan Yuying , Zhao Ming , Oshiro Hiromichi , Kawaguchi Kei , Higuchi Takashi , Zhang Zhiying , Razmjooei Sahar , Barangi Maryam , Wangsiricharoen Sintawat , Murakami Takashi , Singh Arun S. , Li Yunfeng , Nelson Scott D. , Eilber Fritz C. , Bouvet Michael , Hiroshima Yukihiko , Chishima Takashi , Matsuyama Ryusei , Singh Shree Ram , Endo Itaru , Hoffman Robert M.
Published: January 2019

Background: Ewing’s sarcoma (ES) is a recalcitrant disease in need of transformative therapeutics. Objectives: The aim of this study was to investigate the efficacy of tumor-selective Salmonella typhimurium A1-R combined with tumor metabolism targeting with oral administration of recombinant methioninase (o-rMETase), on an ES patient-derived orthotopic xenograft (PDOX) model. Methods: The ES PDOX models were previously established in the right chest wall. The ES PDOX models were randomized into 5 groups when the tumor volume reached 80 mm3: G1: untreated control; G2: doxorubicin; G3: S. typhimurium A1-R; G4: o-rMETase; G5: S. typhimurium A1-R combined with o-rMETase. All mice were sacrificed on day 15. Body weight and tumor volume were assessed twice a week. Results: S. typhimurium A1-R and o-rMETase respectively suppressed tumor growth as monotherapies (p = 0.050 and p = 0.032). S. typhimurium A1-R combined with o-rMETase regressed tumor growth significantly compared to untreated group on day 15 (p < 0.032). S. typhimurium A1-R combined with o-rMETase group was significantly more effective than S. typhimurium A1-R or o-rMETase monotherapy (p = 0.032, p = 0.032). Conclusions: The present results suggest that the combination of S. typhimurium A1-R and o-rMETase has promise to be a transformative therapy for ES.
Two Web Resources Linking Major Human Embryology Collections Worldwide
Authors: Hill Mark A.
Published: January 2019

Human embryology is a core subject for medicine and current research. While animal models of development now have significant online resources available, the vast majority of human embryonic material is locked up in historic collections. When accessed today, these collections are still contributing to our understanding of human development. This paper describes two online resources for studying human development that are unlocking these invaluable collections and providing related human developmental resources. The first of these is the online Embryology website (http://tiny.cc/Embryo) that links the human developmental timeline to historic and current research findings. Secondly is the Digital Embryology Consortium (https://human-embryology.org), an international research partnership to digitise, preserve, and make the major embryology histological collections available for researchers. By making this histological material more widely available to researchers with new methods of analysis, a better understanding of human development can be reached. This also opens the opportunity for new 3D reconstruction and virtual reality representation of these embryos.
Evaluating the Role of a Neurosurgery Consultation in Management of Pediatric Isolated Linear Skull Fractures
Authors: Kommaraju Kavya , Haynes Jeffrey H. , Ritter Ann M.
Published: January 2019

Background: The purpose of this study was to determine if a pediatric neurosurgical consultation for isolated linear skull fractures (ILSF) in pediatric patients with Glasgow Coma Scale (GCS) scores of ≥14 changed their management. Methods: A 10-year retrospective chart review at a Level 1 Pediatric Trauma Center was performed. Exclusion criteria were age > 18 years, open, depressed, or skull base fractures, pneumocephalus, poly-trauma, any hemorrhage (intraparenchymal, epidural, subdural, subarachnoid), cervical spine fractures, penetrating head trauma, and initial GCS scores ≤13. Primary outcomes were neurosurgery recommendations to change acuity of care, obtain additional imaging studies, and perform invasive procedures. Secondary outcomes were patient demographics, injury type, transfer status, admitting service, length of hospital stay, consult location, and clinical course. Results: There were 127 cases of ILSF meeting study criteria with an average age of 2.36 years. Unilateral parietal bone fracture was the most common injury (46.5%). Falls were the most common mechanism (81.1%). All patients received pediatric neurosurgical consultations within 24 h of hospital arrival. There were no neurosurgical recommendations to obtain additional imaging studies, change acuity of care, or perform invasive procedures. Conclusions: Routine neurosurgical consultation in children with ILSF and GCS 14–15 does not appear to alter clinical management.
Outcome of Primary Bone Fragment Replacement in Pediatric Patients with Depressed Skull Fracture
Authors: Oktay Kadir , Guzel Ebru , Unal Emre , Yilmaz Tevfik , Okten Ali Ihsan , Guzel Aslan
Published: January 2019

Objective: To evaluate pediatric patients who were operated with the diagnosis of depressed skull fracture. Methods: The records of pediatric patients who presented with traumatic head injury to multicenter neurosurgery clinics between 2002 and 2018 and who were operated with a diagnosis of depressed skull fracture were retrospectively reviewed. All of the patients underwent primary bone fragment replacement operation, and the patients’ own bone flaps were used to repair depressed skull fractures in all of them. Results: A total of 78 patients were included in the study. Of the study group, 20 patients presented with mild head injury, 37 had moderate head injury, and 21 had severe head injury. Dural injury was present in 67 patients (86%) and the dura was intact in 11 patients (14%). After surgery, 63 patients (81%) had good outcome, 8 patients (10%) had moderate disability, and 5 patients (6.5%) had severe disability. Two patients with multiple accompanying cranial pathologies died and the mortality rate was 2.5%. Infection was detected in only 2 of the 78 patients who were treated within the first 72 h after trauma. One of them had meningitis and the other skin infection. Both patients were treated with appropriate antibiotherapy. None of the patients in the study group had an infection involving the bone, such as osteomyelitis, or the tissues under the bone, such as subdural-epidu­ral empyema or abscess. None of the patients required reoperation and removal of the bone. Conclusion: In the present study, as the pathologies accompanying the depressed skull fractures of the patients increased, Glasgow Coma Scale scores at arrival and Glasgow Outcome Scale scores at discharge decreased. Regardless of whether the depressed fracture is simple or compound, primary bone fragment replacement with appropriate decontamination of the fractured bone and operation area via single-session intervention gives good results. It is important to perform the surgery as soon as possible to reduce the risk of contamination. Primary bone fragment replacement seems to be an appropriate treatment option for depressed skull fractures.
Normative and Clinical Self-Perceptions of Sexuality and Their Links to Psychopathology among Adolescents
Authors: Efrati Yaniv , Dannon Pinhas
Published: January 2019

Background: Compulsive sexual behavior (CSB) has been linked to psychopathology among adults. Only preliminary research has been conducted on adolescents. In our study, we examined whether CSB is linked to psychopathology among adolescents or whether it is a part of normal sexual development. We also, examined potential risk and resiliency factors that might influence this link. Methods: The study population included 311 high school students (184 males and 127 females) aged 16–18 years who completed self-report measures regarding CSB, psychopathology, temperament, and attachment orientations. Results: Adolescents with clinical CSB had more severe psychopathologies than nonclinical ones (with moderate and low levels of CSB) and were unable to utilize resilience factors (i.e., low negative affectivity, high effortful control, and/or attachment security). Conclusions: Low and moderate levels of CSB seem to be part of the normal development of sexuality among adolescents. Clinical CSB seems to be a deviation from this normal development.
The Moderating Role of Social Neighbourhood Factors in the Association between Features of the Physical Neighbourhood Environment and Weight Status
Authors: Hoenink Jody C. , Lakerveld Jeroen , Rutter Harry , Compernolle Sofie , De Bourdeaudhuij Ilse , Bárdos Helga , Charreire Helene , Oppert Jean Michel , Mackenbach Joreintje D.
Published: January 2019

Background: This paper investigated the independent and joint associations between aspects of the physical neighbourhood environment and social neighbourhood factors with BMI and overweight status in European adults. Methods: Data from 5,199 participants in the SPOTLIGHT survey were analysed. Participants reported on their height, weight and perceptions of the neighbourhood. Objectively measured aspects of the physical neighbourhood environment included: presence of recreational facilities, features of the active transportation environment, neighbourhood aesthetics and presence of different types of food outlets. Social factors included the self-reported variables social network, social cohesion, social trust and perceived crime and the census variable neighbourhood socioeconomic status. Outcome measures were BMI and overweight status. Main associations between physical and social factors and BMI/overweight status were analysed using multilevel regression analyses adjusted for confounders. Moderation analysis was conducted by adding the interaction terms between physical and social neighbourhood factors one by one to the multivariable models. Significant interaction terms were then stratified. Results: Significant associations with BMI/overweight status were found for features of the active transportation environment and all social factors, except perceived crime. Several significant interaction terms were detected, but no significant associations between the physical neighbourhood environment and BMI/overweight status were found after stratification. Conclusion: We did not find consistent interactions between physical and social neighbourhood factors to explain BMI and overweight status.
Association between Dyslipidemia and Nephrolithiasis Risk in a Chinese Population
Authors: Ding Qi , Ouyang Jun , Fan Bo , Cao Cheng , Fan Zhijiang , Ding Li , Li Feng , Tu Wenjian , Jin Xiaohua , Wang Jing , Shi Ying
Published: January 2019

Purpose: To evaluate the association between dyslipidemia and nephrolithiasis risk in a Chinese population. Materials and Methods: Fasting plasma lipid profiles were measured in a case-control study of 540 nephrolithiasis cases and 656 kidney stone-free controls. Results: Triglycerides (TG) levels were significantly higher, but total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower in nephrolithiasis patients than those in the control group (each p < 0.05). Similar associations were found in both primary and recurrent nephrolithiasis patients except for TC levels. Significantly lower TC and LDL-C levels were found in all patients except those with uric acid stones. Patients with calcium oxalate (CaOx) and uric acid stones had significantly higher TG levels. Individuals with hypertriglyceridemia and low HDL-cholesterolemia were associated with increased risk of nephrolithiasis (OR 1.31, 95% CI 1.01–1.71 and OR 7.57, 95% CI 5.64–10.17, respectively). Conversely, those with hypercholesterolemia and high LDL-cholesterolemia were associated with decreased nephrolithiasis risk (OR 0.60, 95% CI 0.46–0.79 and OR 0.61, 95% CI 0.42–0.90, respectively). The risk remained in patients with CaOx stones. Conclusions: Our results suggest that dyslipidemia was associated with nephrolithiasis risk in a Chinese population, especially in patients with CaOx stones.
Lipedematous Alopecia: Clinical, Histopathological, and Trichoscopic Findings of a Single Case and Review of the Literature
Authors: Accaputo Ornella , White Jonathan Michael , Kolivras Athanassios , Sadeghi Niloufar , Berlingin Evelyne , del Marmol Véronique
Published: January 2019

A 66-year-old African woman suffered from a boggy thickening of the scalp in the frontoparietal area and the vertex accompanied by headache since infancy. In her thirties, she developed diffuse hair loss in the same area. Clinical and trichoscopic examination were unhelpful, but the histopathological and radiologic findings led to a diagnosis by demonstrating thick subcutaneous adipose tissue. First described in 1935 by Cornbleet [Arch Dermatol Syphilol. 1935; 32: 688], lipedematous scalp is a rare scalp disease marked by a soft thickening of the scalp. A similar clinicopathologic entity associated with nonscarring but permanent acquired alopecia was described in 1961 by Coskey et al. [Arch Dermatol. 1961 Oct; 84(4): 619–22] and termed lipedematous alopecia. In this article, we report a rare case of lipedematous alopecia with emphasis on a trichoscopic and histopathological description with review of the literature. Our case highlights the importance of palpation during the clinical examination. It remains to be determined whether this is actually a specific disease entity or a combination of 2 separate conditions. Symptomatic treatment is advisable given the lack of robust published data on treatment. Only 40 cases of lipedematous alopecia and 52 cases of lipedematous scalp have been published in the literature. Our case is the 93rd.
Low Body Mass Index and Myeloablative Conditioning Regimen Prolong the Duration of Parenteral Nutrition During Hematopoietic Stem Cell Transplantation
Authors: Kamiya Takaki , Hira Daiki , Hoshino Nobuo , Kurihara Mika , Nakagawa Mayumi , Sasaki Masaya , Terada Tomohiro
Published: January 2019

Background/Aims: Patients undergoing hematopoietic stem cell transplantation (HSCT) often receive total parenteral nutrition (TPN) due to poor oral intake. In clinical practice, it is difficult to predict adequate nutritional management, especially the duration of parenteral nutrition (PN), because of inter-individual variability in the conditions and types of treatment regimens. This study investigated the relationship between patient factors and the duration of TPN and the duration of PN. Methods: Data on clinical features, patient characteristics, and the duration of TPN and PN were collected from medical records of 61 of 73 patients who underwent HSCT between April 2010 and December 2014 and were analyzed by multiple linear regression analysis. Results: Forty-nine patients (80.3%) received TPN and 53 (86.9%) received PN. Sixty patients were affected by poor oral intake soon after pretreatment. Body mass index (BMI) was significantly correlated with the duration of TPN (β = –2.733; 95% CI –4.679 to –0.787). BMI (β = –2.260; 95% CI –4.304 to –0.213) and conditioning regimen (β = 12.726; 95% CI 0.692–24.76) were significantly correlated with the duration of PN. Conclusions: BMI at admission and the type of conditioning regimen should be considered in choosing the nutritional management plan in patients with HSCT with poor oral intake.
Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children
Authors: Chen Ting , Wang Fengyun , Chu Zhenyu , Sun Ling , Lv Haitao , Zhou Wanping , Shen Jie , Chen Linqi , Hou Miao
Published: January 2019

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.
Correlation between Intrinsic Brain Activity and Thyroid-Stimulating Hormone Level in Unmedicated Bipolar II Depression
Authors: Zhong Shuming , Chen Guanmao , Zhao Lianping , Jia Yanbin , Chen Feng , Qi Zhangzhang , Huang Li , Wang Ying
Published: January 2019

Background/Aims: Although abnormalities of amplitude of low-frequency fluctuations (ALFF) and hormone levels of hypothalamus-pituitary-thyroid axis have been reported in patients with bipolar disorder (BD), the association between abnormal ALFF and serum thyroid hormone levels remains unknown. Method: A total of 90 patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging, and then routine band (0.01–0.1 Hz), slow-5 band (0.01–0.027 Hz), and slow-4 band (0.027–0.073 Hz) ALFF analysis were performed. Additionally, serum thyroid hormone levels including free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4), and thyroid-stimulating hormone (TSH) were detected. The correlation between abnormal serum thyroid hormone levels and ALFF values in patients with BD II depression was calculated. Results: Compared with the HCs, patients with BD II depression showed decreased ALFF in bilateral precuneus (PCu)/posterior cingulate cortex (PCC) in routine and slow-4 frequency bands, decreased ALFF in the right PCu, and increased ALFF in the right middle occipital gyrus (MOG) in the slow-5 frequency band. Additionally, patients with BD II depression showed lower TSH level than HCs, and TSH level was positively correlated with ALFF values in the bilateral PCu/PCC in the routine frequency band. Conclusions: These findings suggest that patients with BD II depression display intrinsic activity abnormalities, mainly in the PCu/PCC and MOG, which are associated with specific frequency bands. Moreover, altered intrinsic activity in the PCu/PCC may be related to TSH levels in bipolar II depression.
OPTIMIZATION BACTERIAL DENSITY AND FERTILIZER DOSAGE FOR BIOREMEDIATION OF OIL CONTAMINATED SANDY BEACH: A CASE OF CILACAP, INDONESIA
Authors: Darmayati Yeti , Sanusi Harpasis S. , Prartono Tri , Santosa Dwi Andreas , Nuchsin Ruyitno
Published: January 2019

Bioremediation, involving biostimulation and/or bioaugmentation, is a promising method to overcome oil spills in Cilacap coastal waters. Cilacap coastal area has high risk on oil pollution. This study investigated the stimulatory effect of nitrogen concentration, bacterial density and the composition of bacterial culture in enhancing oil degradation in this area. The applications of 4 different concentrations of Slow Release Fertilizer (SRF) and 2 different densities of bacterial cells in the form of single (RCO/B/08_008) and mixed culture were employed in microcosm experiments for 28 days. The efficacy of combining bacterial culture and fertilizer application in various concentrations was also tested. Oil degradation, bacterial growth and environmental parameters were monitored periodically during the experiments. The results showed that oil degradation rate was more influenced by nutrient concentration (biostimulation) than bacterial number or culture composition (bioaugmentation) added. The efficacy of biostimulation in degrading oil was better than that of bioaugmentation. Biostimulation increased oil degradation up to 6.4 times higher than the control. The optimum of fertilizer concentration added was 7.5 mg N/g (C:N ratio of 1,000:75), which increased depletion rate both in biostimulation-only and the combination of biostimulation with bioaugmentation up to 6.4 and 7.5 times higher than the control, respectively. It is suggested that bioremediation of oil-contaminated sandy beach in Cilacap would be optimal by employing a combination of Slow Release Fertilizer at concentration having C/N ratio = 1,000 : 75 and RCO/B/08_008 culture at density of 0.5 x 108 cells/mL (100% homology with Alcanivorax sp. TE-9).
BIOCHEMICAL CHARACTERISTICS OF THIONIC FLUVISOL LINKED TO LAND USE TYPES IN SOUTHERN VIETNAM
Authors: Chung Nguyen Tan , Chung Sy Danh , Thoi Hoang Van
Published: January 2019

Thionic Fluvisols soil in Southern Vietnam is like typical acid sulfate soil in the tropics and is severely polluted due to human activities. Salinity intrusion and industrial wastewater contamination are the main cause of environmental degradation in soil ecosystem. This research was aimed to determine a link between biochemical soil properties and land use types to provide suitable solutions for afforestation and soil restoration. Soil sampling was conducted in five different land use types at four soil layers (O, AB, Bj and Cp). The five land use types were sugarcane crop; Melaleuca plantation; 2-year Acacia plantation; 5-year Acacia plantation; and control (grass-covered land). The results showed that soil in those five land use types were very acidic (pH â‰¤ 4) having poor-nutrient condition with Â range of Â orthophosphate Â contentÂ  of 378 - 640 mg/kg, N-NH4 Â of 586 - 999 mg/kg and N-NO3 of 830 - 1,112 mg/kg. Concentration of toxic ions was very high with large variation among land use types and soil depths i.e. 1,799 â€“ 12,403 mg SO42-/kg; 22 - 1,645 mg exchangeable Fe/kg and 34 - 88 mg Al3+/kg soil. The lowest concentration of exchangeable Fe3+ and SO42- ions were found in sugarcane and Melaleuca plantations, respectively. Twenty-three sulfur-oxidizing bacteria and two iron-oxidizing bacteria were identified. All these bacteria were initially identified as Thiobacillus sp. Sugarcane and Melaleuca plantations exhibited the most diverse Thiobacillus species which linked to reduction of exchangeable Fe and SO42- concentrations in these two land use types. This study indicated that Thiobacillus sp. could grow well in the Thionic Fluvisols. It is proposed that Melaleuca and sugarcane species could reduce iron and sulfur contents in Thionic Fluvisols in the tropics.
GENOTYPIC AND PHENOTYPIC CHARACTERIZATION OF Alcaligenes javaensis JG3 POTENTIAL AS AN EFFECTIVE BIODEGRADER
Authors: Ethica Stalis Norma , Oedjijono Oedjijono , Semiarti Endang , Widada Jaka , Raharjo Tri Joko
Published: January 2019

Utilization of glycerol by lipase producing bacteria offers great benefits for fat and oil waste degradation and waterwaste treatment. Nevertheless, there have been lack of reports about the availability of non-pathogenic, lipase producing bacteria, which could naturally degrade glycerol produced from the lipolysis process by lipase. This study reported a newly identified species of rhizobacteria, Alcaligenes javaensis JG3, which is not only able to produce high level of lipase, but also able to degrade glycerol molecules. Identification of strain JG3 was carried out using SEM (Scanning Electron Microscope), BD Phoenix 100 Automated Microbiology System and 16S rRNA gene analysis to determine its taxonomy status. The ability of the strain to metabolize glycerol was investigated both genotypically and phenotypically using degenerate PCR and a glycerol minimal medium. Identification test results showed that strain JG3 belongs to genus Alcaligenes, with the closest relationship with A. faecalis and A. aquatilis (96% nucleotide similarity maximum). Degenerate PCR resulted in a 248-bp sequence showing 93% similarity with glpK of Candidatus Sodalis pierantonius SOPE, a key gene involved in glycerol metabolism. In vitro glycerol utilization test result showed that Alcaligenes sp. JG3 was able to grow on glycerol aerobically, but not anaerobically. It is concluded that Alcaligenes sp. JG3 possesses genes coding for glycerol metabolism and this trait is phenotypically expressed, thus making the strain potential to be used as an effective fat and oil biodegrader.
ISOLATING MICROSATELLITE FROM Amorphophallus variabilis AND ITS APPLICATION FOR POPULATION STUDY IN DRAMAGA CONSERVATION FOREST, INDONESIA
Authors: Santosa Edi , Lian Chun Lan , Mine Yoko , Takahata Ken , Sugiyama Nobuo
Published: January 2019

Amorphophallus variabilis Blume, a member of Araceae, is a fleshy perennial tuber crop endemic in Java Island, Indonesia. The plant produces white edible corm; and it was used as food during famine time before 1960s. Rapid ecological changes and land fragmentations in Java in recent times threaten populations of A. variabilis. Here, compound microsatellite markers were developed in order to develop conservation strategies in the populations. Twelve primers pairs produced high polymorphism ranging from 5 to 22 alleles per locus. The observed and expected heterozygosities ranged from 0.191 to 0.851 and 0.380 to 0.943, respectively. This high allelic diversity indicates that these markers are suitable for the study on population genetic structure. Cross-amplification on related and non-related species was performed. Application of the markers on populations from Dramaga Conservation Forest revealed high allelic richness, high diversity within and among populations. Genetic distance among populations increased with an increase of geographic distance. Present study suggested that, it is important to study population of A. variabilis in Java in order to understand the population genetic structure and develop effective in situ conservation programs.
LIGHT-COLOR-INDUCED CHANGES IN FATTY ACID BIOSYNTHESIS IN Chlorella sp. STRAIN KS-MA2 IN EARLY STATIONARY GROWTH PHASE
Authors: Osman Siti-Mariam , Chuah Tse Seng , Loh Saw Hong , Cha Thye San , Ahmad Aziz
Published: January 2019

Optimization of light supply remains a critical issue in microalgae biotechnology. The impacts of light color on fatty acid production and biosynthesis in microalgae are poorly understood. The aim of this study was to determine the effect of light color on growth and fatty acid content in Chlorella strain KS-MA2. Cells were cultured on F/2 medium and incubated under blue, green, red or white light. The cellsâ€™ growth, fatty acid composition and the expression levels of the ketoacyl synthase 1 (KAS-1), omega-6 desaturase (Ï‰-6 FAD) and omega-3 desaturase (Ï‰-3 FAD) genes were measured at the early stationary growth phase. Results of this study indicated that light color affected cell density and fatty acid profile produced by Chlorella sp. strain KS-MA2. Cells cultured under blue, red and white light had higher cell density than those cultured under green light. Palmitic acid (38.62 Â± 3.29% of biomass dry weight) and linolenic acid (7.96 Â± 0.88% of biomass dry weight) were highly accumulated under white light. Stearic acid was dominant under blue light (11.11 Â± 0.14% of biomass dry weight), whereas oleic acid was dominant under red light (30.50 Â± 0.14% of biomass dry weight). Linoleic acid was highly produced under green and blue light (28.63 Â± 1.36% and 26.00 Â± 0.81 % of biomass dry weight, respectively). KAS-1 and Ï‰-6 FAD were highly expressed under blue light, whereas Ï‰-3 FAD was highly expressed under green light. The production of particular fatty acids of interest from Chlorella could be achieved by shifting color of light used during the incubation of the cell cultures. Blue-light is the most suitable light color for producing biomass and stearic acid by Chlorellastrain KS-MA2.Â
JABON (Anthocephalus cadamba Roxb) POTENCY FOR REMEDIATING LEAD (Pb) TOXICITY UNDER NUTRIENT CULTURE CONDITION
Authors: Setyaningsih Luluk , Setiadi Yadi , Budi Sri Wilarso , Hamim Hamim , Sopandie Didy
Published: January 2019

Information on metal adaptation of plants is necessary to understand the mechanism of heavy metal, including lead (Pb), remediation mediated by forest plants in contaminated land. This study aimed to find out the adaptation mechanism of jabon (Anthocephalus cadamba Roxb) seedlings to excessive lead level based on the tolerance index of growth performance and lead transport to plant tissue.Â  The seedlings were exposed to lead (Pb(NO3)2) with the concentrations of 0, 0.5, 1, 1.5, 5 and 10 mM in nutrient culture for 15 days. The result showed that the tolerance index (TI) of the seedlings was significantly decreased by Pb exposure up to 1.5 mM, but the TI values were more than 75%.Â  All seedlings died at Pb concentration of 5 mM and up.Â  Pb accumulated in all parts of the seedlings, with the highest concentration found in the leaves (735.9 ppm) under Pb concentration of 0.5 mM.Â Â  The Pb was found to be transported to the top portion of the seedlings indicated by Transport Factor (TF) that was more than 1. The results suggest that jabon can adapt to excessive Pb exposure up to 1.5 mM and has the potential as a remediator plant.
GROWTH PERFORMANCE AND ENZYME ACTIVITIES IN CATFISH [Pangasianodon hypophthalmus] FED WITH WATER HYACINTH-BASED DIET
Authors: Yuniati Dewi , Utomo Nur Bambang Priyo , Setiawati Mia , Alimuddin Alimuddin
Published: January 2019

An alternative subtitution of pollard as an imported feed ingredient is a neccesity and one of the potential ingredients is water hyacinth (Eichhornia crassipes). This study was conducted to evaluate growth performance and enzyme activity in catfish (Pangasianodon hypophthalmus). Diet with five different levels of water hyacinth subtitute of pollard (0%, 25%, 50%, 75%, and 100%) were fed to catfish for 60 days. Seventy (70) catfish fry with average initial body weight of 2.45Â±0.15 g were maintained in 100cm x 80cm x 60cm aquaria. Fish fed at satiation level three times daily at 8 am, 12 pm, and 4 pm. With dietary of 25% water hyacinth, growth performance and protease activity similar to 0% treatment. Feed intake, protein digestibility, feed efficiency, protein efficiency ratio, and protease and amylase enzyme activities decreased (p<0.05) in those fed with more than 25% water hyacinth. Catfish fed 25% water hyacinth showed significantly (p<0.05) higher daily growth rate, feed efficiency and protein digestibility than those with other treatments. Based on the growth performance and enzyme activity, we can conclude that the optimum dietary level of water hyacinth subtitute pollard for fry catfish is 25%.
THE EFFECTS OF RAINFALL ON Penaeus monodon Fabricius POPULATIONS IN THE SEGARA ANAKAN LAGOON, CENTRAL JAVA, INDONESIA
Authors: Pratiwi Rianta , Sukardjo Sukristiono
Published: January 2019

Segara Anakan Lagoon (SAL) is widely known as a traditional fishing ground for many aquatic organisms and is located in Central Java, in an area with high rainfall rates. The objectives of this study were to determine the effects of rainfall on the distribution of Penaeus monodon Fabricius in SAL and/or mangrove waters and to explain the cause of yearly fluctuations in this areaâ€™s fish catch during a 13-year period from 1998 to 2011. The effects of rainfall on the local distribution and abundance of shrimp in SAL, Cilacap, Central Java, Indonesia, were examined using the Anco method for three periods, namely: first period (i.e., commercial catch production, 1998â€“2011), second period (December 2010â€“November 2011) and third period (December 2011â€“April 2012) as part of a shrimp fishery and eco-biology study in this region. The marked increase in rainfall from 557 mm during the East Monsoon (Juneâ€“August) to 1,225 mm in the second transition season (Septemberâ€“November) and West Monsoon (Decemberâ€“February) in the Segara Anakan region enhanced the seasonal movement of shrimp into the Zone IV fishing ground and produced an initial increase in the abundance of adults (CL>25 mm) in the region from 312 to 2,630 individuals. This initial increase in adult abundance enhanced the shrimpâ€™s reproductive potential, while heavy rainfall indirectly assisted the recruitment of young shrimp into the estuary, their growth, and survival, to increase shrimp abundance in the following year. Lower rainfalls from July to September) adversely affected shrimp population and usually resulted in smaller populations (312 individuals). Statistical analysis of the relationship between shrimp catch and annual rainfall showed a high level of significance at 1%.
SOIL MICROBIAL POPULATION AND SOIL ENZYME ACTIVITY ON PT BUKIT ASAM VARIOUS RECLAIMED LAND SITES IN SOUTH SUMATRA
Authors: Tornando Hengki , Hudi Firdaus Alam , Prasetyo Lilik Budi , Santosa Dwi Andreas
Published: January 2019

Open mining activities result in decreased microbial biomass and negatively impacts soil fertility. Soil microbes play a role in the decomposition of soil organic matter and in nutrient cycles through the process of mineralization by the enzymes they produce. The purpose of this study was to analyse soil fertility levels in PT Bukit Asamâ€™s various reclaimed land sites at Muara Enim Regency, South Sumatra, Indonesia, as determined by these areasâ€™ microbial populations and soil enzyme activity. The research was conducted by using the explorative method in PT Bukit Asamâ€™s various reclaimed land. Soil sample from 7 different reclamation age area were analysed. Our results showed that soil conditions and soil enzyme activity vary by reclamation age. At KTU, a 12-year-old reclaimed land site, urease enzyme activity had a value of 68.83 mg NH4+.g-1dm.h-1 with a microbial population of 82.64 x 104 CFU.g-1soil. The highest phosphatase enzyme activity value of 95.66 mg pNP.g-1 dm.h-1 was found on the 9-year-old SP702 reclaimed land site, with a soil pH of 5.23. Cellulase enzyme activity on the 21-year-old Udongan reclaimed site had a value of 21.51 mg GE.g-1dm.h-1 with a cellulolytic microbial population of 1.9 x 104 CFU.g-1soil, higher than on other reclamation sites. Invertase enzyme activity on the 15-year-old Tupak reclaimed land site had a value of 24.37 mg GE.g-1dm.h-1. Soil enzyme activity can be an indicator of soil quality and soil microbial activity as it relates to all forms of biochemical transformations occurring in the soil and is highly sensitive to environmental changes.
MOLECULAR CLONING OF THE VITELLOGENIN GENE IN THE HARD-LIPPED BARB (Osteochillus hasseltii C.V) AND PHOTOPERIOD'S EFFECTS ON GENE EXPRESSION
Authors: Prayogo Norman Arie , Siregar Asrul Sahri , Sukardi Purnama , Bessho Yasumasa
Published: January 2019

Photoperiod affects fish reproduction as it regulates activities of the endocrine glands, which produce the hormones needed for geonadal growth and development, gametogenesis, and reproductive cycles. This study aimed to determine the effects of photoperiod on the hard-lipped barb's reproductive performance by exposing the fish to three photoperiod treatments (light hour: L, darks hour: D), namely 14L:10D (control), 8L:16D (short photoperiod) and 18L:6D (long photoperiod), with four aquaria, each containing 9 fish, serving as replicates. The fish were kept under these photoperiods for 8 weeks. Liver activity, the observable variable in the study, was evaluated by measuring vitellogenin gene expression. Normalized data were then subjected to ANOVA, followed by Tukey's range test. The hard-lipped barb's vitellogenin cDNA was found have a 1136 bp sequence and the vitellogenin precursors encoded cDNA comprising 378 amino acids. The vitellogenin gene in each experimental group saw a significant increase on average when exposed to longer photoperiods (P<0.05), and the highest levels of vitellogenin gene expression occurred under long photoperiods (LP, 18 h light:6 h dark). These results indicate that longer photoperiods stimulate and improve the hard-lipped barb's reproductive performance.
Calamus vitiensis (ARECACEAE), A NEW RECORD OF RATTAN IN SUMBAWA ISLAND, INDONESIA
Authors: Rustiami Himmah , Sulistyaningsih Lulut Dwi
Published: January 2019

Calamus vitiensis, previously known to occur only in Papua New Guinea, Australia (Queensland), the Solomon Islands, Vanuatu, and Fiji is now also found in the mountainous area of Batudulang, West Sumbawa, Lesser Sunda Islands, Indonesia. This paper presents a complete report of the description, notes, and illustrations of the species.
GROWTH AND MEAT QUALITY ENHANCEMENT OF STRIPED CATFISH (Pangasianodon hypophthalmus) USING RECOMBINANT GROWTH HORMONE
Authors: Lubis Reni Agustina , Alimuddin Alimuddin , Utomo Nur Bambang Priyo
Published: January 2019

The application of fish recombinant growth hormone (rGH) has been known as one of the methods to improve the growth performance of cultured fishes, one of which is the striped catfish Pangasianodon hypophthalmus, a species that is becoming commercially attractive in Indonesia. Hence, this study was aimed to evaluate the effects of rGH supplementation in commercial diet on the growth, feed utilization and flesh quality in P. hypophthalmus grow out. The rGH was mixed with chicken egg yolk and sprayed on the commercial feeds with different protein levels (32, 28 and 23%). In the control, the feeds were also sprayed with chicken egg yolk but without rGH.Â  Striped catfish with body weights of 110.66 Â± 1.32 g ind-1 were fed on rGH-supplemented diets two times a week during the first and third months, and during the rest of the months they were fed on diet without rGH supplementation. The fishes were reared for 120 days in 18 hapa (2Ã—1Ã—1.5 m3) with initial density of 20 fishes per hapa. The result showed that the highest weight gain, specific growth rate (SGR), and lowest feed conversion ratio (FCR) were obtained by fishes fed on 32% protein content with rGH-supplemented diet. No significant difference was observed in the weight gain, SGR and FCR in rGH treated group with 28% protein content with rGH supplemented diet and non-rGH control group receiving 32% protein diet. Similar moisture content of meat, protein content of meat, belly fat and edible portion were observed in rGH-supplemented diet and their control. Except in the treatment 23% protein content rGH supplemented diet that has lower lipid content in fish body and meat. The highest SGR was obtained when the fishes were fed on the 32% protein feed combined with rGH. Enrichment with rGH depleted the fat content in the meat of fish fed on all levels of protein in which the lowest fat was found in the 23% protein feed.