bluuebunny/crossref_metadata_2025 huggingface dataset:
O-arm Navigation Combined With Microscope-assisted MIS-TLIF in the Treatment of Lumbar Degenerative Disease
Authors: Chen Kangwu , Chen Hao , Zhang Kai , Yang Peng , Sun Jiajia , Mo Jianqiang , Zhou Feng , Yang Huilin , Mao Haiqing
Published: February 2019

Study design:

This is a retrospective study.

Objective:

The purpose of this study is to compare the clinical outcomes between O-arm navigation combined with microscope-assisted minimally invasive transforaminal lumbar interbody fusion (novel MIS-TLIF) and open-TLIF for the treatment of 1-level lumbar degenerative disease.

Summary of Background Data:

MIS-TLIF is becoming increasingly popular; however, the limited visualization may increase various surgical complications. O-arm navigation and microscope have the potential to display the specific anatomic structures and better magnification.

Materials and Methods:

This study involved 45 patients with 1-level lumbar degenerative disease who underwent novel MIS-TLIF or open-TLIF. Operating time, intraoperative blood loss, and hospitalization stay were analyzed. The accuracy of pedicle screw placement was assessed by computed tomography. Visual analog scale (VAS) scoring and Oswestry disability index (ODI) were assessed preoperatively and postoperatively.

Results:

Intraoperative blood loss was significantly less in the novel MIS-TLIF group compared with the open-TLIF group (P<0.05). The average time for hospitalization stay in the novel MIS-TLIF group was significantly shorter than open-TLIF group (P<0.05). However, the operative time of novel MIS-TLIF group was longer than open-TLIF group (P<0.05). The accuracy rate of pedicle screw position in the novel MIS-TLIF group which guided by O-arm navigation was higher than conventional open-TLIF group (96.4% vs. 86.5%; P<0.05). Meanwhile, the VAS score for the low back pain and ODI score in the novel MIS-TLIF group were lower than that in the open-TLIF group 1 month after surgery (P<0.05). No difference of the VAS score for leg pain was found between these 2 groups (P>0.05), neither as the fusion rate in between the 2 groups (P>0.05).

Conclusions:

O-arm navigation combined with microscope-assisted MIS-TLIF may has several advantages including less blood loss, shorter hospitalization stay, higher accuracy of pedicle screw placement, and faster recovery period in treating 1-level lumbar degenerative disease.
Hydrodissection and Hydrodelineation of Hamstring Tendons: Novel Technique for Graft Harvesting
Authors: Kamath Surendra Umesh , Kamath Krithika
Published: February 2019

Hamstring graft harvest is an important step in modern day arthroscopic anterior cruciate ligament reconstruction surgery. Various techniques of hamstring graft harvest has been reported. We have described a novel method of graft harvesting which eases the identification of the desired tendons and offers protection to saphenous nerve and superficial medial collateral ligament, which could be damaged. Our method is easy to perform after some training and does not require any additional equipment. It is also reproducible as the structures over the medial side of the tibia have a consistent anatomic pattern.
Concurrent Versus Sequential Chemoradiation for Low-grade Gliomas Meeting RTOG 9802 Criteria
Authors: Ryckman Jeffrey M. , Appiah Adams K. , Lyden Elizabeth , Verma Vivek , Zhang Chi
Published: February 2019

Purpose:

Radiation Therapy Oncology Group (RTOG) 9802 has established postoperative radiation therapy (RT) and chemotherapy sequentially as the new standard of care for patients with high-risk low-grade glioma (LGG) meeting trial criteria. Although this trial investigated sequential chemoradiation therapy (sCRT) with RT followed by chemotherapy, it is unknown whether concurrent chemoradiation therapy (cCRT) may offer advantages over sCRT.

Materials and Methods:

The National Cancer Database (NCDB) was queried for newly diagnosed World Health Organization (WHO) grade II glioma. Patients with unknown surgery, RT, or chemotherapy status were excluded, along with patients below 40 years old who underwent gross total resection to coincide with RTOG 9802 exclusion criteria. The χ2, the Fisher exact, or Wilcoxon rank-sum tests evaluated differences in characteristics between groups. Kaplan-Meier analysis was used to evaluate overall survival (OS) between groups (sCRT vs. cCRT). Cox proportional hazards modeling determined variables associated with OS.

Results:

In total, 496 patients were analyzed (n=416 [83.9%] cCRT, n=80 [16.1%] sCRT). Sequencing or concurrency of therapy did not independently influence survival on univariable/multivariable analysis. Factors associated with worse OS on multivariable analysis included advanced age (P<0.001), whereas mixed glioma (P=0.017) and oligodendroglioma (P=0.005) were associated with better OS than astrocytoma histologies.

Conclusions:

This is the only analysis of which we are aware of cCRT versus sCRT for LGG. There is no evidence that cCRT improves outcomes over sCRT.
IMPACT OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVIEW STRATEGY ON DETECTION OF CHOROIDAL NEOVASCULARIZATION
Authors: Babiuch, MD Amy S. , Uchida, MD, PhD Atsuro , Figueiredo, MD Natalia , Hu, PhD Ming , Khan, MD Mehnaz , Srivastava, MD Sunil K. , Singh, MD Rishi P. , Rachitskaya, MD Aleksandra , Kaiser, MD Peter K. , Reese, BSN Jamie L. , Ehlers, MD Justis P.
Published: February 2019

Purpose:

To compare optical coherence tomography angiography (OCTA) review strategies for optimizing choroidal neovascularization (CNV) detection.

Methods:

Eyes with CNV in the differential diagnosis were imaged with the Avanti RTVue XR HD (Optovue, Fremont, CA). Three modalities of review for CNV presence were used in each case: a single report generated using automated segmentation within Avanti software; a continuous slab descent video OCTA export; and a manual segmentation approach using cross-sectional OCT with decorrelation signal overlay. Scans were reviewed by two masked expert reviewers; a third reviewer was used for discrepancies.

Results:

The study included 421 eyes, and 350 eyes had reports deemed sufficient quality for interpretation. Choroidal neovascularization was in the differential diagnosis in 107 of 350 patients. Overall CNV was identified in 55% (59/107) eyes. In those eyes with CNV, the automated segmentation identified CNV in 56% (33/59) of cases, continuous slab descent method identified CNV in 53% (31/59) of cases, and the manual segmentation group identified CNV in 92% (54/59) of cases.

Conclusion:

Review strategies for detection of CNV on OCTA were highest using the manual segmentation method as compared to both the automated report and continuous slab descent methods. Although the manual segmentation method had a higher rate of detection, the practical aspects of the time required for segmentation make this method challenging in routine clinical practice.
Deep Anterior Lamellar Keratoplasty in Eyes With Intrastromal Corneal Ring Segments
Authors: Ravera Vittoria , Bovone Cristina , Scorcia Vincenzo , D'Angelo Sergio , Busin Massimo
Published: February 2019

Purpose:

To evaluate the possibility of using the intrastromal corneal ring segments (ICRSs) previously implanted as a depth reference for performing pneumatic dissection in deep anterior lamellar keratoplasty (DALK).

Methods:

The depth of placement of 2 symmetrical ICRSs placed in the superior and inferior midperipheral cornea of 4 eyes of 4 patients with keratoconus was measured by means of anterior segment optical coherence tomography. Because of irregular and/or high astigmatism, DALK using pneumatic dissection was performed in all eyes. The standardized procedure included the following: 1) Deep trephination of the recipient cornea outside the ICRSs (9 mm in diameter), aimed at facilitating the insertion and advancement of a dedicated cannula under the ICRS implant, just within its peripheral margin; 2) air injection for pneumatic dissection; 3) removal of about 80% of the anterior stroma; 4) perforation of the “big bubble” ceiling under viscoelastic protection and removal of its central 6 mm; and 5) suturing of a donor lamella of the anterior stroma obtained by microkeratome dissection using a 450-μm head and punched to a diameter of 9 mm.

Results:

In all cases, the site for air injection was selected where the thickness of the stroma underlying the superior ICRS did not exceed 150 μm. Pneumatic dissection succeeded uneventfully in all eyes; postoperative best spectacle-corrected visual acuity was 20/20 in 3 of 4 eyes, whereas refractive astigmatism was less than 3 diopters in all cases.

Conclusions:

The presence of ICRSs facilitates gauging the depth of cannula insertion at the time of DALK, to succeed with pneumatic dissection.
Etiopathogenesis of Primary Acquired Nasolacrimal Duct Obstruction: What We Know and What We Need to Know
Authors: Ali Mohammad Javed , Paulsen Friedrich
Published: February 2019

Purpose:

To provide a systematic review of the literature on the etiopathogenesis of primary acquired nasolacrimal duct obstruction (PANDO).

Methods:

The authors performed a PubMed search of all articles published in English with specific reference to etiopathogenesis of PANDO or associations of PANDO. Data captured include demographics, study techniques, hypothesis, presumed or confirmed interpretations with regards to pathogenesis, mechanisms, or pathways. Specific emphasis was laid on addressing the lacunae and potential directions for future research.

Results:

Numerous factors are believed to contribute to the etiopathogenesis of PANDO. The basic pathogenesis involves inflammation, vascular congestion, mucosal edema, fibrosis, obstruction, and stasis. Bony nasolacrimal duct diameter does not appear to play a significant role. There is no convincing data to substantiate nose as the site of disease origin and nasal factors appear to be comorbidities. Hormonal mechanisms are more evidence-based but can only partly explain the pathogenesis. Vascular theories are based on the behavior of perilacrimal cavernous bodies, their autonomic control, and additional structural changes in the helical patterns of connective tissue fiber arrangements. Repeated vascular malfunction leading to structural epithelial and subepithelial changes currently appears to be the most evidence-based and accepted theory. Tear proteomics holds a promise in decoding the etiopathogenesis of PANDO, at least in part.

Conclusions:

The etiopathogenesis of PANDO appears to be multifactorial. Hormonal microenvironments, vascular factors, and tear proteomics are promising candidates for further work. There is a need for focused work by Clinician-Scientists and the answers can have far reaching clinical implications.
Meningoencephalitis Following Endoscopic Dacryocystorhinostomy
Authors: Cheong Timothy Z. , Davies Rodger P.
Published: February 2019

An 81-year-old man with unilateral nasolacrimal duct obstruction underwent routine endonasal dacryocystorhinostomy and 2 days postoperatively developed a severe headache and rigors. Subsequent CT and MRI imaging demonstrated a defect in the floor of the right anterior cranial fossa, which possibly was damaged during the operation, and meningoencephalitis of the adjacent frontal lobe gyrus. Following intravenous antibiotic treatment, the patient made a full recovery with no ongoing sequelae, and his epiphora completely resolved. To the authors' knowledge, this is the first report of meningoencephalitis following endonasal dacryocystorhinostomy. This complication should be considered in any patient with a febrile septic presentation or headache following endonasal dacryocystorhinostomy.
The Impact of HIV Infection on TB Disparities Among US-Born Black and White Tuberculosis Patients in the United States
Authors: Marks Suzanne M. , Katz Dolly J. , Davidow Amy L. , Pagaoa Melissa A. , Teeter Larry D. , Graviss Edward A.
Published: February 2019

Background/Objectives:

US-born non-Hispanic black persons (blacks) (12% of the US population) accounted for 41% of HIV diagnoses during 2008-2014. HIV infection significantly increases TB and TB-related mortality. TB rate ratios were 6 to 7 times as high in blacks versus US-born non-Hispanic whites (whites) during 2013-2016. We analyzed a sample of black and white TB patients to assess the impact of HIV infection on TB racial disparities.

Methods:

In total, 552 black and white TB patients with known HIV/AIDS status were recruited from 10 US sites in 2009-2010. We abstracted data from the National TB Surveillance System, medical records, and death certificates and interviewed 477 patients. We estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations of TB with HIV infection, late HIV diagnosis (≤3 months before or any time after TB diagnosis), and mortality during TB treatment.

Results:

Twenty-one percent of the sample had HIV/AIDS infection. Blacks (AOR = 3.4; 95% CI, 1.7-6.8) and persons with recent homelessness (AOR = 2.5; 95% CI, 1.5-4.3) had greater odds of HIV infection than others. The majority of HIV-infected/TB patients were diagnosed with HIV infection 3 months or less before (57%) or after (4%) TB diagnosis. Among HIV-infected/TB patients, blacks had similar percentages to whites (61% vs 57%) of late HIV diagnosis. Twenty-five percent of HIV-infected/TB patients died, 38% prior to TB diagnosis and 62% during TB treatment. Blacks did not have significantly greater odds of TB-related mortality than whites (AOR = 1.1; 95% CI, 0.6-2.1).

Conclusions:

Black TB patients had greater HIV prevalence than whites. While mortality was associated with HIV infection, it was not significantly associated with black or white race.
The Epidemiology of Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand Confirms the Highest Risk for Grade 4 Surface Breast Implants
Authors: Magnusson Mark , Beath Kenneth , Cooter Rodney , Locke Michelle , Prince H. Miles , Elder Elisabeth , Deva Anand K.
Published: February 2019

Background:

The epidemiology and implant-specific risk for breast implant–associated (BIA) anaplastic large cell lymphoma (ALCL) has been previously reported for Australia and New Zealand. The authors now present updated data and risk assessment since their last report.

Methods:

New cases in Australia and New Zealand were identified and analyzed. Updated sales data from three leading breast implant manufacturers (i.e., Mentor, Allergan, and Silimed) were secured to estimate implant-specific risk.

Results:

A total of 26 new cases of BIA-ALCL were diagnosed between January of 2017 and April of 2018, increasing the total number of confirmed cases in Australia and New Zealand to 81. This represents a 47 percent increase in the number of reported cases over this period. The mean age and time to development remain unchanged. The implant-specific risk has increased for Silimed polyurethane (23.4 times higher) compared with Biocell, which has remained relatively static (16.5 times higher) compared with Siltex implants.

Conclusions:

The number of confirmed cases of BIA-ALCL in Australia and New Zealand continues to rise. The implant-specific risk has now changed to reflect a strong link to implant surface area/roughness as a major association with this cancer.
Concurrent Pancreatic Metastasis From Lung Adenocarcinoma and Primary Cholangiocarcinoma on FDG PET/CT Imaging
Authors: Wang Wei , Kan Ying , Yang Xu , Liu Jie , Yang Jigang
Published: February 2019

A 67-year-old man with a history of left upper lobe resection of poorly differentiated adenocarcinoma 1 year ago underwent FDG PET/CT for restaging. The images demonstrated a round cystic lesion with peripheral FDG uptake and centrally photopenic region. Additional focus of increased activity was detected in the left lobe of the liver. The patient underwent the Whipple and partial hepatectomy. The surgical pathology demonstrated concurrently the metastasis to the pancreas from the lung adenocarcinoma and a primary moderately differentiated cholangiocarcinoma.
Appropriate Neck Ultrasonography Surveillance During the First 10 Years After Hemithyroidectomy in Papillary Thyroid Microcarcinoma Patients: A Single-Center Study
Authors: Choi Yun Seok , Kim Dong Wook , Lee Yoo Jin , Ha Tae Kwun , Jung Soo Jin , Baek Hye Jin
Published: February 2019

This study aimed to assess the prevalence of tumor recurrence/persistence and determine the appropriate frequency and interval of follow-up neck ultrasonography (US) in papillary thyroid microcarcinoma (PTMC) patients who underwent hemithyroidectomy and long-term follow-up US. From January 2005 to December 2006, 179 patients underwent a hemithyroidectomy for the treatment of PTMC and at least 1 postoperative US surveillances. The postoperative follow-up US was performed by 2 radiologists for all patients. Based on the US and histopathologic results, tumor recurrence/persistence was determined. Of the 179 patients, the following results were determined after hemithyroidectomy: all patients exhibited T1 stage, while nodal metastasis to the ipsilateral level VI node (n = 27) and ipsilateral multifocality (n = 16) were found. Tumor recurrence was found in 5 (2.8%) of 179 and tumor persistence in 2 (1.1%) of 179. In the tumor recurrence cases, all patients underwent US-guided fine-needle aspiration for the newly detected thyroid nodule because of suspicious features on postoperative follow-up US (8-, 24-, 36-, 87-, and 96-month intervals). Differences were observed in the number of follow-up US sessions (mean, 5.2; range, 1–13) and in the interval period to the last follow-up (mean, 80.7 months; range, 8–138 months). Among the patients, 82 (45.8%) had a more than 120-month interval to the last follow-up US after hemithyroidectomy. In conclusion, the PTMC tumor recurrence rate was low, indicating that only 1 or 2 sessions of postoperative US follow-up may be sufficient to detect tumor recurrence within the first 10 years after hemithyroidectomy in PTMC patients.
Reverse Distraction for Treatment of Hydrocephalic Macrocephaly in Late Childhood
Authors: Miller Hannah , Grabb Paul , Lypka Michael
Published: February 2019

Macrocephaly diminishes quality of life for children whose head size inhibits independent mobility and appropriate interaction with caregivers. Cranial reduction is a method of addressing these issues, historically with a high morbidity due most commonly to bleeding and shunt complications. The authors present a 9-year-old girl with holoprosencephaly and severe macrocephaly from progressive hydrocephalus who underwent cranial reduction via reverse distraction osteogenesis, a method to slowly reduce the skull volume. The patient underwent circumferential occipital temporoparietal frontal craniotomy with placement of 4 cranial distractors, followed approximately 1 month later by removal of the distractors and cranioplasty with resorbable fixation devices. The patient demonstrated significant postoperative improvement in head control and interaction in school activities. This is the oldest patient with macrocephaly treated with reverse distraction in the literature to date. The slow contraction of the cranial vault with limited bony surgery at the time of initial reduction provides an additional safety margin, and should be considered in older children presenting with profound macrocephaly.
Reconstruction of Deep Circumflex Iliac Artery Free Flap for Multiple Recurrent Ameloblastoma in Mandible
Authors: Hu YongJie , Cao Rui , Wang ZhongHua , Hong WeiSheng , Zheng ChongYang
Published: February 2019

Ameloblastoma is the most common odontogenic tumor of epithelial origin. These tumors are benign in nature but have a high rate of recurrence and possible malignant development when treated inadequately. However, recurrent ameloblastomas in bone grafts are rare. This article presents a rare case of a multiple recurrent ameloblastoma, with the last recurrence in a nonvascularized free iliac bone graft of the mandible, reconstructed with vascularized deep circumflex iliac artery free flap for the surgical defect. Furthermore, an updated review of the literature on recurrent ameloblastomas affecting the bone graft is provided.
Heat hardening capacity in
Drosophila melanogaster
is life stage-specific and juveniles show the highest plasticity
Authors: Moghadam Neda N. , Ketola Tarmo , Pertoldi Cino , Bahrndorff Simon , Kristensen Torsten N.
Published: February 2019

Variations in stress resistance and adaptive plastic responses during ontogeny have rarely been addressed, despite the possibility that differences between life stages can affect species' range margins and thermal tolerance. Here, we assessed the thermal sensitivity and hardening capacity of
Drosophila melanogaster
across developmental stages from
larval
to the adult stage. We observed strong differences between life stages in heat resistance, with adults being most heat resistant followed by
puparia
,
pupae
and
larvae
. The impact of heat hardening (1 h at 35°C) on heat resistance changed during ontogeny, with the highest positive effect of hardening observed in
puparia
and
pupae
and the lowest in adults. These results suggest that immobile life stages (
puparia
and
pupae
) have evolved high plasticity in upper thermal limits whereas adults and
larvae
rely more on behavioural responses to heat stress allowing them to escape from extreme high temperatures. While most studies on the plasticity of heat resistance in ectotherms have focused on the adult life stage, our findings emphasize the crucial importance of juvenile life stages of arthropods in understanding the thermal biology and life stage-specific physiological responses to variable and stressful high temperatures. Failure to acknowledge this complication might lead to biased estimates of species' ability to cope with environmental changes, such as climate change.
Sovereign states in the Caribbean have lower social-ecological vulnerability to coral bleaching than overseas territories
Authors: Siegel Katherine J. , Cabral Reniel B. , McHenry Jennifer , Ojea Elena , Owashi Brandon , Lester Sarah E.
Published: February 2019

Coral reef social-ecological systems worldwide face major impacts from climate change, and spatial variation in vulnerability is driven by differential exposure to climatic threats, ecological and socio-economic sensitivity to those threats, ecological recovery potential, and socio-economic adaptive capacity. We assess variation in social-ecological vulnerability to climate change-induced coral bleaching, specifically for reef-based fisheries and tourism, of islands throughout the insular Caribbean, thus providing the first region-wide quantitative analysis of island-scale social-ecological vulnerability to coral bleaching. We show that different components of vulnerability have distinct spatial patterns and that variability in overall vulnerability is driven more by socio-economic than ecological components. Importantly, we find that sovereign islands are less vulnerable on average than overseas territories and that the presence of fisheries management regulations is a significant predictor of adaptive capacity and socio-economic sensitivity, with important implications for island-level governance and policies to reduce climate vulnerability.
A full annual perspective on sex-biased migration timing in long-distance migratory birds
Authors: Briedis Martins , Bauer Silke , Adamík Peter , Alves José A. , Costa Joana S. , Emmenegger Tamara , Gustafsson Lars , Koleček Jaroslav , Liechti Felix , Meier Christoph M. , Procházka Petr , Hahn Steffen
Published: February 2019

In many taxa, the most common form of sex-biased migration timing is protandry—the earlier arrival of males at breeding areas. Here we test this concept across the annual cycle of long-distance migratory birds. Using more than 350 migration tracks of small-bodied trans-Saharan migrants, we quantify differences in male and female migration schedules and test for proximate determinants of sex-specific timing. In autumn, males started migration about 2 days earlier, but this difference did not carry over to arrival at the non-breeding sites. In spring, males on average departed from the African non-breeding sites about 3 days earlier and reached breeding sitesca4 days ahead of females. A cross-species comparison revealed large variation in the level of protandry and protogyny across the annual cycle. While we found tight links between individual timing of departure and arrival within each migration season, only for males the timing of spring migration was linked to the timing of previous autumn migration. In conclusion, our results demonstrate that protandry is not exclusively a reproductive strategy but rather occurs year-round and the two main proximate determinants for the magnitude of sex-biased arrival times in autumn and spring are sex-specific differences in departure timing and migration duration.
Drivers of recovery and reassembly of coral reef communities
Authors: Gouezo Marine , Golbuu Yimnang , Fabricius Katharina , Olsudong Dawnette , Mereb Geory , Nestor Victor , Wolanski Eric , Harrison Peter , Doropoulos Christopher
Published: February 2019

Understanding processes that drive community recovery are needed to predict ecosystem trajectories and manage for impacts under increasing global threats. Yet, the quantification of community recovery in coral reefs has been challenging owing to a paucity of long-term ecological data and high frequency of disturbances. Here we investigate community re-assembly and the bio-physical drivers that determine the capacity of coral reefs to recover following the 1998 bleaching event, using long-term monitoring data across four habitats in Palau. Our study documents that the time needed for coral reefs to recover from bleaching disturbance to coral-dominated state in disturbance-free regimes is at least 9–12 years. Importantly, we show that reefs in two habitats achieve relative stability to a climax community state within that time frame. We then investigated the direct and indirect effects of drivers on the rate of recovery of four dominant coral groups using a structural equation modelling approach. While the rates of recovery differed among coral groups, we found that larval connectivity and juvenile coral density were prominent drivers of recovery for fast growingAcroporabut not for the other three groups. Competitive algae and parrotfish had negative and positive effects on coral recovery in general, whereas wave exposure had variable effects related to coral morphology. Overall, the time needed for community re-assembly is habitat specific and drivers of recovery are taxa specific, considerations that require incorporation into planning for ecosystem management under climate change.
Sinorhodobacter populi sp. nov., isolated from the symptomatic bark tissue of Populus × euramericana canker
Authors: Xu Guan-tang , Piao Chungen , Chang Ju-pu , Guo Li-min , Yang Xu-qi , Li Yong
Published: February 2019

We isolated five novel bacterial strains from symptomatic bark tissue of Populus × euramericana canker that were Gram-stain-negative, non-motile, aerobic oxidase-negative and catalase-positive. Growth occurred at 10–41 °C and at pH 5.0–7.0, with optimum growth at 30 °C and pH 7.0. Additionally, growth occurred in conditions of 0–5 % (w/v) salinity, but not above 7 % NaCl. The 16S rRNA gene sequences of the novel strains shared the highest similarity with

Sinorhodobacter ferrireducens

SgZ-3T (97.1 %). The average nucleotide identity values between the novel strains and two type strains (S.inorhodobacter ferrireducens CCTCC AB2012026T and ‘

S

inorhodobacter
hungdaonensis’ CGMCC 1.12963T) were 78.4–78.9 %, which were lower than the proposed species boundary cut-off (95–96 %). The main polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified lipid and phosphatidylcholine. The main respiratory quinone was Q-10, and major fatty acids were C18 : 1ω7c and/or C18 : 1
ω6c. Based on data from a polyphasic taxonomy study, the novel strains represent a novel species of the genus

Sinorhodobacter

, for which the name

Sinorhodobacter
populi sp. nov. is proposed. The type strain is sk2b1T (=CFCC 14580T=KCTC 52802T).
Empowering the annotation and discovery of structured RNAs with scalable and accessible integrative clustering
Authors: Miladi Milad , Sokhoyan Eteri , Houwaart Torsten , Heyne Steffen , Costa Fabrizio , Grüning Björn , Backofen Rolf
Published: February 2019

RNA plays essential regulatory roles in all known forms of life. Clustering RNA sequences with common sequence and structure is an essential step towards studying RNA function. With the advent of high-throughput sequencing techniques, experimental and genomic data are expanding to complement the predictive methods. However, the existing methods do not effectively utilize and cope with the immense amount of data becoming available.

Here we present GraphClust2, a comprehensive approach for scalable clustering of RNAs based on sequence and structural similarities. GraphClust2 provides an integrative solution by incorporating diverse types of experimental and genomic data in an accessible fashion via the Galaxy framework. We demonstrate that the tasks of clustering and annotation of structured RNAs can be considerably improved, through a scalable methodology that also supports structure probing data. Based on this, we further introduce an off-the-shelf procedure to identify locally conserved structure candidates in long RNAs. In this way, we suggest the presence and the sparsity of phylogenetically conserved local structures in some long non-coding RNAs. Furthermore, we demonstrate the advantage of a scalable clustering for discovering structured motifs under inherent and experimental biases and uncover prominent targets of the double-stranded RNA binding protein Roquin-1 that are evolutionary conserved.
Effects of the secondhand smoking exposure in the early stages of the bone development
Authors: Alves Cristiano Fittipaldi , Carvalho Cesar Alexandre Fabrega , Iemma Antônio Francisco , Neto Francisco Haiter , Caria Paulo Henrique Ferreira
Published: February 2019

Objective

The objective of this study was to evaluate the effects of the secondhand smoking in the trabecular bone micro-architecture of the mandible of rats, offsprings of passive smoking matrices.

Materials and Methods

Fifty-five rats,Rattus norvegicus albinus, offsprings of passive smoking and non-passive smoking matrices, were divided into three groups: continuous smoking offsprings (CSO), interrupted smoking offsprings (ISO) and non-smoking offsprings (NSO/control). After the 21st, 42nd, 63rdand 128thdays, the mandibles were analyzed by micro-computer tomography(micro-CT). Images of inter-radicular alveolar bone of the mandibular first molars underwent three-dimensional reconstruction and were analyzed. The bone volume fraction (BV/TV, bone volume/total volume), the trabecular thickness (Tb.Th), the trabecular spacing (Tb.Sp), the trabecular number (Tb.N) and the structure model index (SMI) were analyzed.

Results

The BV/TV analysis revealed increase of the average values in the CSO group, at 21stand 42nddays (p=0,0124), tending to decrease related to the mean from the 42ndday. The animals of ISO group did not show significant difference in BV/TV, about the control group (p=0,9751). The results of Tb.Th were different and significant during all the experimental period among the three groups: CSO and control (p<0,0001), ISO and control (p=0,0030) and CSO / ISO (p=0,0020). About Tb.Sp, the differences were not significant among the three groups. About Tb.N, the difference was significant into each group, with increasing values (p<0.0001). The SMI showed significant difference between the CSOs and control, CSO and ISO, both with (p<0,0001). The difference between control and ISO group was not significant (p=0,1253).

Conclusion

The passive inhalation of cigarette smoke by the offsprings of smoking matrices had a harmful effect in the micro-archicteture of the trabecular bone of the rats’ mandible in developing. About the ISO groups, the recovery of the micro-archicteture occurred partially.
The autophagic membrane tether ATG2A transfers lipids between membranes
Authors: Maeda Shintaro , Otomo Chinatsu , Otomo Takanori
Published: February 2019

An enigmatic step in de novo formation of the autophagosome membrane compartment is the expansion of the precursor membrane phagophore, which requires the acquisition of lipids to serve as building blocks. Autophagy-related 2 (ATG2), the rod-shaped protein that tethers phosphatidylinositol 3-phosphate (PI3P)-enriched phagophores to the endoplasmic reticulum (ER), is suggested to be essential for phagophore expansion, but the underlying mechanism remains unclear. Here, we demonstrate that human ATG2A is a lipid-transferring protein. ATG2A can extract lipids from membrane vesicles and unload them to other vesicles. Lipid transfer by ATG2A is more efficient between its tethered vesicles than between untethered vesicles. The PI3P effectors WIPI4 and WIPI1 associate ATG2A stably to PI3P-containing vesicles, thereby facilitating ATG2A-mediated tethering and lipid transfer between PI3P-containing vesicles and PI3P-free vesicles. Based on these results, we propose that ATG2-mediated transfer of lipids from the ER to the phagophore enables phagophore expansion.
Synaptic and Gene Regulatory Mechanisms in Schizophrenia, Autism, and 22q11.2 CNV Mediated Risk for Neuropsychiatric Disorders
Authors: Forsyth Jennifer K. , Nachun Daniel , Gandal Michael J. , Geschwind Daniel H. , Anderson Ariana E. , Coppola Giovanni , Bearden Carrie E.
Published: February 2019

Background

22q11.2 copy number variants (CNVs) are among the most highly penetrant genetic risk variants for developmental neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD). However, the specific mechanisms through which they confer risk remain unclear.

Methods

Using a functional genomics approach, we integrated transcriptomic data from the developing human brain, genome-wide association findings for SCZ and ASD, protein interaction data, and pathophysiological signatures of SCZ and ASD to: 1) organize genes into the developmental cellular and molecular systems within which they operate; 2) identify neurodevelopmental processes associated with polygenic risk for SCZ and ASD across the allelic frequency spectrum; and 3) elucidate pathways and individual genes through which 22q11.2 CNVs may confer risk for each disorder.

Results

Polygenic risk for SCZ and ASD converged on partially overlapping gene networks involved in synaptic function and transcriptional regulation, with ASD risk variants additionally enriched for networks involved in neuronal differentiation during fetal development. The 22q11.2 locus formed a large protein network that disproportionately affected SCZ- and ASD-associated neurodevelopmental networks, including loading highly onto synaptic and gene regulatory pathways.SEPT5, PI4KA, andSNAP29genes are candidate drivers of 22q11.2 synaptic pathology relevant to SCZ and ASD, andDGCR8andHIRAare candidate drivers of disease-relevant alterations in gene regulation.

Conclusions

The current approach provides a powerful framework to identify neurodevelopmental processes affected by diverse risk variants for SCZ and ASD, and elucidate the mechanisms through which highly penetrant multi-gene CNVs contribute to disease risk.
Machine Learning of Synthetic Biological Sequences for Designer Attribution
Authors: Howser Craig , Filone Claire Marie , Dymond Jessica S , Chee Brant , Downs Joseph , Wilt Miller , Rivera Corban , Wolfe Joshua T
Published: February 2019

Advances in genome editing and gene synthesis technologies have increased the ease with which biological agents can be engineered. Existing methods to identify the engineering source are insufficient for attribution. We hypothesized that strategies used for DNA design and optimization could act as identifiable fingerprints of design software or particular vendors, making engineered agents more attributable to their source. To test this hypothesis, sequences optimized using various gene synthesis vendors were characterized using a machine learning model. By capturing optimization signatures unique to each vendor, the trained model showed an ability to identify a sequences origin with an accuracy up to 92%, indicating it is possible to distinguish the algorithm utilized to optimize a genetic sequence based on the DNA sequence output alone.
MicroRNA-mediated control of developmental lymphangiogenesis
Authors: Jung Hyun Min , Hu Ciara , Fister Alexandra M. , Davis Andrew E. , Castranova Daniel , Pham Van N. , Price Lisa M. , Weinstein Brant M.
Published: February 2019

The post-transcriptional mechanisms contributing to molecular regulation of developmental lymphangiogenesis and lymphatic network assembly are not well understood. Here, we use high throughput small RNA sequencing to identify miR-204, a highly conserved miRNA dramatically enriched in lymphatic vs. blood endothelial cells, and we demonstrate that this miRNA plays a critical role during lymphatic development. Suppressing miR-204 leads to loss of lymphatic vessel formation, while overproducing miR-204 in lymphatic vessels accelerates lymphatic vessel formation, suggesting a positive role during developmental lymphangiogenesis. We also identify the NFATC1 transcription factor as a key conserved target for post-transcriptional regulation by miR-204 during lymphangiogenesis. While miR-204 suppression leads to loss of lymphatics, knocking down its target NFATC1 leads to lymphatic hyperplasia, and the loss of lymphatics in miR-204-deficient animals can be rescued by NFATC1 knockdown. Together, our results highlight a miR-204/NFATC1 molecular regulatory axis required for proper lymphatic development.
An open-source platform to distribute and interpret data from multiplexed assays of variant effect
Authors: Esposito Daniel , Weile Jochen , Shendure Jay , Starita Lea M , Papenfuss Anthony T , Roth Frederick P , Fowler Douglas M , Rubin Alan F
Published: February 2019

Multiplex Assays of Variant Effect (MAVEs), such as deep mutational scans and massively parallel reporter assays, test thousands of sequence variants in a single experiment. Despite the importance of MAVE data for basic and clinical research, there is no standard resource for their discovery and distribution. Here we present MaveDB, a public repository for large-scale measurements of sequence variant impact, designed for interoperability with applications to interpret these datasets. We also describe the first of these applications, MaveVis, which retrieves, visualizes, and contextualizes variant effect maps. Together, the database and applications will empower the community to mine these powerful datasets.
A Bayesian Approach for Estimating Branch-Specific Speciation and Extinction Rates
Authors: Höhna Sebastian , Freyman William A. , Nolen Zachary , Huelsenbeck John P. , May Michael R. , Moore Brian R.
Published: February 2019

Species richness varies considerably among the tree of life which can only be explained by heterogeneous rates of diversification (speciation and extinction). Previous approaches use phylogenetic trees to estimate branch-specific diversification rates. However, all previous approaches disregard diversification-rate shifts on extinct lineages although 99% of species that ever existed are now extinct. Here we describe a lineage-specific birth-death-shift process where lineages, both extant and extinct, may have heterogeneous rates of diversification. To facilitate probability computation we discretize the base distribution on speciation and extinction rates intokrate categories. The fixed number of rate categories allows us to extend the theory of state-dependent speciation and extinction models (e.g.,BiSSE and MuSSE) to compute the probability of an observed phylogeny given the set of speciation and extinction rates. To estimate branch-specific diversification rates, we develop two independent and theoretically equivalent approaches: numerical integration with stochastic character mapping and data-augmentation with reversible-jump Markov chain Monte Carlo sampling. We validate the implementation of the two approaches in RevBayes using simulated data and an empirical example study of primates. In the empirical example, we show that estimates of the number of diversification-rate shifts are, unsurprisingly, very sensitive to the choice of prior distribution. Instead, branch-specific diversification rate estimates are less sensitive to the assumed prior distribution on the number of diversification-rate shifts and consistently infer an increased rate of diversification for Old World Monkeys. Additionally, we observe that as few as 10 diversification-rate categories are sufficient to approximate a continuous base distribution on diversification rates. In conclusion, our implementation of the lineage-specific birth-death-shift model in RevBayes provides biologists with a method to estimate branch-specific diversification rates under a mathematically consistent model.
Conjugated linolenic fatty acids trigger ferroptosis in triple-negative breast cancer
Authors: Beatty Alexander , Singh Tanu , Tyurina Yulia Y. , Nicolas Emmanuelle , Maslar Kristen , Zhou Yan , Cai Kathy Q. , Tan Yinfei , Doll Sebastian , Conrad Marcus , Bayır Hülya , Kagan Valerian E. , Rennefahrt Ulrike , Peterson Jeffrey R.
Published: February 2019

Ferroptosis is a non-apoptotic form of cell death linked to the accumulation of reactive hydroperoxides generated by oxidation of polyunsaturated fatty acids (PUFAs) in membrane phospholipids. The therapeutic potential of promoting ferroptosis by enriching PUFAs in cancer cells is unknown. We found an association between elevated PUFA levels and vulnerability to ferroptosis in triple-negative breast cancer (TNBC) cells. A screen of PUFAs identified conjugated linolenic acids, including α-eleostearate, as ferroptosis inducers. Three conjugated double bonds were required for ferroptotic activity although their positioning and stereochemistry were less significant. Mechanistically, α-eleostearate differed from canonical ferroptosis inducers by a distinct dependence on acyl-CoA synthetase long-chain isoforms and by not altering glutathione or glutathione peroxidase 4 activity. Orally administered tung oil, naturally rich in α-eleostearate, limited tumor growth and metastasis in an aggressive TNBC xenograft model. These results expand our understanding of ferroptotic cell death and highlight the anti-cancer potential of conjugated PUFAs.
locBLAST v2.0 - an improved PHP library for embedding standalone NCBI BLAST+ program to an interactive graphical user interface
Authors: Kumar T. Ashok
Published: February 2019

Background

NCBI BLAST is a most popularly used sequence analysis platform in a broad range of applications. The final release of standalone WWW BLAST server (wwwBLAST v2.2.26) of NCBI was officially released on May 10, 2004, and discontinued its support. Due to the popularity and high demand, the BLAST algorithms were refined with rich features and released as online BLAST, standalone BLAST+, BLAST RESTful service, and cloud BLAST server. locBLAST v2.0 is a lightweight PHP library, designed in preference to WWW BLAST server. It masks command-line BLAST+ programs to a rich graphical user interface (GUI).

Methods

The locBLAST v2.0 library was designed using PHP, CSS, pure JavaScript, and standalone NCBI BLAST+ executables.

Results

locBLAST v2.0 provides an interactive web interface to input query sequences through the web form and provides a graphical report of the sequence alignment result. The graphical overview, tabular summary, and formatted sequence alignment of locBLAST v2.0 result mimic to the native format of online NCBI BLAST result. It allows users to perform both local and online database search.

Availability

Freely available at https://github.com/AshokHub/locBLAST
Programmable patterns in a DNA-based reaction-diffusion system
Authors: Chen Sifang , Seelig Georg
Published: February 2019

Biology offers compelling proof that macroscopic “living materials” can emerge from reactions between diffusing biomolecules. Here, we show that molecular self-organization could be a similarly powerful approach for engineering functional synthetic materials. We introduce a programmable DNA-hydrogel that produces tunable patterns at the centimeter length scale. We generate these patterns by implementing chemical reaction networks through synthetic DNA complexes, embedding the complexes in hydrogel, and triggering with locally applied input DNA strands. We first demonstrate ring pattern formation around a circular input cavity and show that the ring width and intensity can be predictably tuned. Then, we create patterns of increasing complexity, including concentric rings and non-isotropic patterns. Finally, we show “destructive” and “constructive” interference patterns, by combining several ring-forming modules in the gel and triggering them from multiple sources. We further show that computer simulations based on the reaction-diffusion model can predict and inform the programming of target patterns.
CDK1 dependent phosphorylation of hTERT contributes to cancer progression
Authors: Yasukawa Mami , Ando Yoshinari , Yamashita Taro , Matsuda Yoko , Shoji Shisako , Morioka Masaki S. , Kawaji Hideya , Shiozawa Kumiko , Abe Takaya , Yamada Shinji , Kaneko Mika K. , Kato Yukinari , Furuta Yasuhide , Kondo Tadashi , Shirouzu Mikako , Hayashizaki Yoshihide , Kaneko Shuichi , Masutomi Kenkichi
Published: February 2019

The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses revealed that phosphorylation of hTERT at threonine 249 occurs more frequently in advanced cancers. Using CRISPR/Cas9 genome editing, we introduced substitution mutations at threonine 249 in the endogenous hTERT locus and found that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase activity. Cap Analysis of Gene Expression (CAGE) demonstrated that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomerase independent manner.
Treatment-shortening effect of a novel regimen combining high-dose rifapentine and clofazimine in pathologically distinct mouse models of tuberculosis
Authors: Saini Vikram , Ammerman Nicole C. , Chang Yong Seok , Tasneen Rokeya , Chaisson Richard E. , Jain Sanjay , Nuermberger Eric , Grosset Jacques H.
Published: February 2019

High-dose rifapentine and clofazimine have each separately been associated with treatment-shortening activity when incorporated into tuberculosis (TB) treatment regimens. We hypothesized that both modifications, i.e., the addition of clofazimine and the replacement of rifampin with high-dose rifapentine, in the first-line regimen for drug-susceptible TB would significantly shorten the duration of treatment necessary for cure. We tested this hypothesis in a well-established BALB/c mouse model of TB chemotherapy and also in a C3HeB/FeJ mouse model in which mice can develop caseous necrotic lesions, an environment where rifapentine and clofazimine may individually be less effective. In both mouse models, replacing rifampin with high-dose rifapentine and adding clofazimine in the first-line regimen resulted in greater bactericidal and sterilizing activity than either modification alone, suggesting that a rifapentine- and clofazimine-containing regimen may have the potential to significantly shorten the treatment duration for drug-susceptible TB. These data provide preclinical evidence supporting the evaluation of regimens combining high-dose rifapentine and clofazimine in clinical trials.