bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Definitive Fracture Fixation is Safely Performed in the Presence of an Open Abdomen in Multiply Injured Patients
Authors: Glass Nina E. , Burlew Clay Cothren , Hahnhaussen Jens , Weckbach Sebastian , Pieracci Fredric M. , Moore Ernest E. , Stahel Philip F.
Published: August 2017

Objective:

To investigate the safety and feasibility of performing definitive fracture fixation in multiply injured patients in the presence of an open abdomen after laparotomy.

Design:

Retrospective observational cohort study.

Setting:

Level-I academic trauma center.

Patients:

Adult polytrauma patients with the presence of an open abdomen after “damage control” laparotomy and associated major fractures of long bones, acetabulum, pelvis, or spine, requiring surgical repair (n = 81).

Intervention:

Timing of definitive fracture fixation in relation to the timing of abdominal wall closure.

Main Outcome Measure:

Incidence of orthopedic surgical site infections.

Results:

During a 15-year time window from January 1, 2000 until December 31, 2014, we identified a cohort of 294 consecutive polytrauma patients with an open abdomen after laparotomy. Surgical fixation of associated fractures was performed after the index laparotomy in 81 patients. In group 1 (n = 32), fracture fixation occurred significantly sooner despite a concurrent open abdomen, compared with group 2 (n = 49) with abdominal wall closure before fixation (mean 4.4 vs. 11.8 days; P = 0.01). The incidence of orthopaedic surgical site infections requiring a surgical revision was significantly lower in group 1 (3.1%) compared to group 2 (30.6%; P = 0.002).

Conclusions:

Definitive fracture fixation in the presence of an open abdomen is performed safely and associated with a significant decrease in clinically relevant surgical site infections, compared with delaying fracture fixation until abdominal wall closure. These data suggest that the strategy of imposing a time delay in orthopaedic procedures while awaiting abdominal wall closure is unjustified.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Risk Factors Associated With Cephalomedullary Nail Cutout in the Treatment of Trochanteric Hip Fractures
Authors: Ciufo David J. , Zaruta Douglas A. , Lipof Jason S. , Judd Kyle T. , Gorczyca John T. , Ketz John P.
Published: August 2017

Objectives:

To evaluate the association of cephalomedullary nail cutout in trochanteric femur fractures with the presence of the following radiographic variables: lateral wall fracture, posteromedial fragment, angular malreduction, residual basicervical fracture gapping, screw placement, and tip–apex distance.

Design:

Retrospective review.

Setting:

Academic medical center.

Patients:

A total of 362 patients were included in the study. The average age was 83 years and the majority was female. All sustained low-energy trochanteric femur fractures treated operatively with cephalomedullary nails. Minimum radiographic follow-up was 3 months, with an average of 11 (range 3–88) months.

Intervention:

Cephalomedullary nailing with either a lag screw or helical blade.

Main Outcome Measures:

Cutout of the lag screw or helical blade.

Results:

A total of 22 (6%) cutouts occurred. Univariate analysis showed significantly (P ≤ 0.01) more frequent cutout with fracture of the lateral wall, posteromedial fragment, residual gapping (>3 mm) at basicervical component, neck–shaft malreduction >5 degrees varus or 15 degrees valgus, and tip–apex distance >25 mm, and superior screw/blade positioning. There was no difference with unstable fracture pattern (P = 0.58) or fellowship training (P = 0.21). Multivariate regression analysis demonstrates that lateral wall fracture (Odds ratios [OR] = 8.0, 95% confidence interval [CI], 2.4–27.1), neck–shaft malreduction (OR = 4.3, CI, 1.3–14.7), and residual basicervical gapping (OR = 3.6, CI, 1.0–13.0) were associated with fixation cutout.

Conclusions:

Risk factors for cutout of trochanteric fractures in our study can be viewed as modifiable or nonmodifiable factors. Statistically significant factors included lateral wall fracture (nonmodifiable) as well as basicervical gapping and malreduction (modifiable).

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Incidence of Vacuum Phenomenon Related Intra-articular or Subfascial Gas Found on Computer-Assisted Tomography (CT) Scans of Closed Lower Extremity Fractures
Authors: Noble Tyler , Romeo Nicholas M. , LeBrun Christopher T. , DiPasquale Thomas
Published: August 2017

Objectives:

To determine the incidence of vacuum phenomenon related intra-articular or subfascial gas found on computer-assisted tomography (CT) scans of closed lower extremity fractures.

Design:

Retrospective Review.

Setting:

Level I Trauma Center.

Patients/Participants:

A total of 153 patients with closed lower extremity fractures.

Intervention:

CT scans of identified individuals were reviewed for the presence or absence of gaseous accumulations.

Main Outcome Measurements:

The presence or absence of gas on CT.

Results:

Twenty seven (17.6%) of the 153 fractures were found to have intra-articular or subfascial gas on CT despite clear documentation, indicating a closed injury with no significant skin compromise. Of the intra-articular fractures (OTA/AO 33B/C, 41B/C and 43B/C), 20% (23 of 113) were found to have gas on CT. All cases were associated with fracture of the tibia (P = 0.002).

Conclusions:

Computed tomography demonstrated the presence of intra-articular or subfascial gas in 17.6% (27/153) of closed lower extremity fractures and in 20% (23/113) of closed intra-articular fractures. The possibility of vacuum phenomenon must be considered when using this imaging modality as the confirmatory test for open intra-articular fracture or traumatic arthrotomy.

Level Of Evidence:

Level IV.
Triple Furrowed Atrophic Tongue of Myasthenia Gravis
Authors: Young Nathan P. , Sorenson Eric J. , Milone Margherita , Harper C. Michel
Published: August 2017

The authors present a case and image of a patient with refractory tongue weakness and characteristic triple furrowed pattern of atrophy due to autoimmune myasthenia gravis.
Type 1 Diabetes, Celiac Disease, and Neuropathy—A Nationwide Cohort Study
Authors: Thawani Sujata , Brannagan Thomas H. , Lebwohl Benjamin , Mollazadegan Kaziwe , Green Peter H. R. , Ludvigsson Jonas F.
Published: August 2017

Objective:

Both type 1 diabetes (T1D) and celiac disease (CD) have been linked to an increased risk of neuropathy. This study examined the risk of neuropathy in patients with T1D compared with patients with both T1D and CD.

Methods:

In a nationwide population-based cohort, T1D was defined as having a diagnosis of diabetes between 1964 and 2009 recorded in the Swedish National Patient Register in individuals ≤30 years of age. CD was defined as having villous atrophy (Marsh histopathology stage III) on small intestinal biopsy. CD cases were identified through biopsies examined between 1969 and 2008 at any of Sweden's 28 pathology departments. Nine hundred fifty-eight patients had both T1D and CD and were matched for sex, age, and calendar period with 4590 controls who only had T1D. Through Cox regression analysis, with CD as the time-dependent covariate, we estimated the risk of neuropathy in T1D patients with CD.

Results:

Fifty-four individuals with T1D and CD had later neuropathy (expected: n = 42). This corresponded to an adjusted hazard ratio of 1.27 (95% confidence interval = 0.95–1.71) compared with those who had T1D alone. The hazard ratio was statistically significant in the first 5 years with CD (1.67; 95% confidence interval = 1.13–2.47) but decreased to neutrality thereafter. Risk estimates were similar in men and women, and did not differ by age at CD onset.

Conclusions:

CD does not seem to influence the risk of neuropathy in individuals with T1D, although a small excess risk cannot be ruled out.
Deltopectoral and Pectoralis Musculocutaneous Flap Technique for Cervical Esophageal Reconstruction after Free-Jejunal-Flap Necrosis
Authors: Matsumine Hajime , Kubo Kazuyuki , Hamahata Atsumori , Sakurai Hiroyuki
Published: August 2017

Background:

Free jejunal transfer has a high success rate, but if vascular thrombosis occurs, the salvage of failing flap with reanastomosis is difficult. This study described a combined deltopectoral (DP) and pectoralis major musculocutaneous (PMMC) flap 2-step technique for cervical esophageal reconstruction after free-jejunal-flap necrosis.

Methods:

In step 1, the detection of free jejunal flap with the subsequent debridement of necrotic and infected tissue was followed by the construction of external fistula on the pharyngeal side with the hole in cervical skin and the construction of another external fistula on the esophageal side and tracheal stoma with a single or double DP flap. In step 2, after the primary healing of all wounds was confirmed, a wide hinge flap was elevated for reconstructing the posterior wall or full circumferential defect of cervical esophagus. PMMC flap harvested from either the left or right anterior chest wall was used for reconstructing the cervical surface defect or anterior pharyngeal wall.

Results:

This technique was used for cervical esophageal reconstruction after free-jejunal-flap necrosis in 5 patients. Step 1 surgery was performed at an average of 10 days after primary-free-jejunal flap transfer. Oral intake was resumed in all cases at an average of 117 days after step 2 surgery. No complications including esophageal stricture were found during a 6-month follow-up period.

Conclusions:

Combined DP and PMMC flap technique was useful for cervical esophageal reconstruction after free-jejunal-flap necrosis and applicable to patients with the late detection of jejunal necrosis and surgical-site infection.
The North Wind and the Sun: Pediatric Antimicrobial Stewardship Program Combining Restrictive and Persuasive Approaches in Hematology-Oncology Ward and Hematopoietic Stem Cell Transplant Unit
Authors: Horikoshi Yuho , Kaneko Tetsuji , Morikawa Yoshihiko , Isogai Mihoko , Suwa Junichi , Higuchi Hiroshi , Yuza Yuki , Shoji Takayo , Ito Kenta
Published: August 2017

Background:

The Japanese government’s goal for the reduction of antimicrobial consumption is two-thirds of the 2013 rate by 2020. While the antimicrobial stewardship programs (ASPs) are essential in health care facilities, ASP data on pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are limited. Our aim was to evaluate the impact of restrictive and persuasive ASP on immunocompromised children.

Methods:

The ASP for hematology-oncology and HSCT patients at Tokyo Metropolitan Children’s Medical Center was assessed. Phase 1 was a postprescriptive review of carbapenem conducted between April 2010 and September 2011. Phase 2 consisted of the preauthorization of carbapenem, prospective audit with feedback, a weekly luncheon meeting among physicians, consensus on febrile neutropenia management, and implementation of viral molecular diagnostics between October 2011 and September 2015. Both phases were compared for day-of-therapy per 1,000 patient-days, cost of intravenous antimicrobial agents, average hospitalization duration, all-cause mortality, infection-related mortality at 30 days, and appropriateness of empirical treatment of bacteremia.

Results:

The ASP did not differ from phase 1 to phase 2 in terms of average hospitalization length, mortality rate, or appropriateness of empirical treatment for bacteremia. Day-of-therapies of cefepime, piperacillin/tazobactam, meropenem, vancomycin, liposomal amphotericin B, and fosfluconazole decreased by 20%, 45%, 57%, 38%, 85% and 44%, respectively (P < 0.05). The total cost of antibiotic and antifungal agents decreased by 27%, for a savings of $59,905 USD annually.

Conclusion:

Restrictive and persuasive ASP in the hematology-oncology ward and the HSCT unit safely decreased the use of antibacterial and antifungal agents.
Urinary Tract Infection in Children With Nephrotic Syndrome
Authors: Narain Upma , Gupta Arvind
Published: August 2017

Background:

The occurrence of urinary tract infection (UTI) in nephrotic syndrome has been reported. However, the only causes for the infection reported to date are bacteria and prior reported series did not identify yeast or fungi as causative organisms.

Methods:

A retrospective study of 2880 children with nephrotic syndrome was made to determine the incidence of UTI, predisposing factor and bacterial and fungal etiologies.

Results:

Between January 2000 and November 2016, we identified that 15% of the children developed UTI. Within this group, bacterial UTI and fungal UTI were 84.0% and 16.0%, respectively. The genus Klebsiella (25.33%) predominates among bacteria, while Candida cruzi (26.08%) predominates among fungal etiologies. Statistical analysis was performed for biochemical indices and UTI and was found significant for low serum albumin and high serum cholesterol (P ≤ 0.05).

Conclusion:

This study emphasizes the importance of UTI in children and can be underdiagnosed in children with nephrotic syndrome because steroid therapy is anti-inflammatory and can mask the symptoms of UTI.
The Individual Experience of Aging Patients and the Current Service Provision in the Context of Italian Forensic Psychiatry: A Case Study
Authors: Di Lorito Claudio , Castelletti Luca , Tripi Giuseppa , Gandellini Maria Gloria , Dening Tom , Völlm Birgit
Published: August 2017

Introduction

After the recent development of residential units for the execution of security measures managed by the National Health Service and the closing down of forensic psychiatric hospitals, no study has been conducted to investigate the individual experience of aging patients and to assess whether the new service is adequately meeting their needs. We aimed to explore the experience of the service of a sample of patients aged 50 years and above living in one of the Italian residential units for the execution of security measures.

Methods

We adopted a case study design and included a sample of five patients. We collected their basic demographic data, administered the Camberwell Assessment Needs Forensic Short Version and carried out in-depth qualitative semi-structured interviews.

Results

Results from the Camberwell Assessment Needs Forensic Short Version evidenced that met needs were more prevalent than unmet needs. The qualitative interviews demonstrated high levels of satisfaction around accommodation, healthcare provision, activities, availability of benefits and company, and lower levels of satisfaction around psychological and practical support.

Discussion

This study gave voice to aging forensic psychiatric patients and provided through personal accounts, based on their lived experience, preliminary evidence around the benefits and limitations of the Italian residential forensic psychiatric system for this age group. Implications for clinical nursing forensic practitioners operating within different service frameworks are discussed.
Rehabilitation of an Individual with Transfemoral Amputation Combining Aquatic Ambulation With Prosthetic Socket Incorporating High-Fidelity Skeletal Capture
Authors: Cutler Thomas J.
Published: August 2017

Introduction

The High-Fidelity skeletal capture socket has shown promise in improving outcomes for persons with transfemoral amputation. This case report looks at a synergistic benefit when incorporating aquatic therapy with successful skeletal capture subischial transfemoral socket fitting. Although previous studies have shown some transfemoral prosthetic sockets to be ineffective as preserving femoral adduction angle, knee disarticulation level and high-fidelity transfemoral level sockets were not assessed, both of which use skeletal capture.

Case Presentation

A 64-year-old, 290-lb male individual with amputation had been unsuccessfully fit with six ischial containment suction sockets without skeletal capture over a 3-year period. Multiple complications, including a 45° hip flexion contracture and 100-ft maximum ambulation range, limited his rehabilitation.

Management and Outcome

Aquatic ambulation increased in-therapy walking time from 5 to 45 minutes. Thirty-day results included prosthetic side hip flexion contracture reduction from 45° to 20° ambulation range increased from 100 to 400 ft. The 120–day results showed contracture reduced to 12° and ambulation range to greater than 500 ft. Additional 120-day outcomes included disability rating reduction from 78% to 48% and Tinetti fall score increase from 10 of 28 to 17 of 28.

Discussion

Initial success with socket fit revealed limitations in certain approaches to rehabilitation of persons with amputation that were overcome in a reduced gravity environment. By combining both the additional reported stability benefit of the High-Fidelity Interface and the increased duration and confidence provided by the aquatic-based ambulation, the outcomes exceeded those anticipated with land-based ambulation alone.

Conclusion

By considering skeletal capture, the case report challenges the assumption that socket design cannot secure the femur and provide better outcomes. By having success in a reduced-gravity environment, one concludes that a scrutiny of the goals of transfemoral amputation is warranted.
A systematic review of retracted publications in emergency medicine
Authors: Chauvin Anthony , De Villelongue Cedric , Pateron Dominique , Yordanov Youri
Published: August 2017

The objective of this study was to characterize retracted publications in emergency medicine. We searched MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials to identify all retracted publications in the field of emergency medicine. We also searched an independent website that reports and archives retracted scientific publications. Two researchers independently screened titles, abstracts and full text of search results. Data from all included studies were then independently extracted. We identified 28 retraction notes. Eleven (39%) articles were published by authors from Europe. The oldest retracted article was published in 2001. The 28 retracted papers were published by 22 different journals. Two authors were named on multiples retractions. The median impact factor of journals was 1.03 (0.6–1.9). Almost all studies were available online [26/28 (93%)], but only 40% had watermarking on the article. The retraction notification was available for all articles. Three (11%) retraction notices did not clearly report the retraction reasons, and most retraction notices were issued by the editors [14 (56%)]. The most frequent retraction reasons were plagiarism [eight (29%)], duplicate publication [three (11%)] and overlap [two (2%)]. Retracted articles were cited on average 14 times. In most cases, the retraction cause did not invalidate the study’s results [17 (60%)]. The most common reason for retraction was related to a misconduct by the authors. These results can question the necessity to normalize retraction procedures among the large number of biomedical editors and to educate future researchers on research integrity.
Brief Report: Weight Gain in Persons With HIV Switched From Efavirenz-Based to Integrase Strand Transfer Inhibitor–Based Regimens
Authors: Norwood Jamison , Turner Megan , Bofill Carmen , Rebeiro Peter , Shepherd Bryan , Bebawy Sally , Hulgan Todd , Raffanti Stephen , Haas David W. , Sterling Timothy R. , Koethe John R.
Published: August 2017

Background:

With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy, persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients who switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression who switched from EFV/TDF/FTC to an INSTI-containing regimen.

Methods:

We performed a retrospective observational cohort study among adults on EFV/TDF/FTC for at least 2 years who had virologic suppression. We assessed weight change over 18 months in patients who switched from EFV/TDF/FTC to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen versus those on EFV/TDF/FTC over the same period. In a subgroup analysis, we compared patients switched to DTG/ABC/3TC versus raltegravir- or elvitegravir-containing regimens.

Results:

A total of 495 patients were included: 136 who switched from EFV/TDF/FTC to an INSTI-containing regimen and 34 switched to a PI-containing regimen. Patients switched to an INSTI-containing regimen gained an average of 2.9 kg at 18 months compared with 0.9 kg among those continued on EFV/TDF/FTC (P = 0.003), whereas those switched to a PI regimen gained 0.7 kg (P = 0.81). Among INSTI regimens, those switched to DTG/ABC/3TC gained the most weight at 18 months (5.3 kg, P = 0.001 compared with EFV/TDF/FTC).

Conclusion:

Adults living with HIV with viral suppression gained significantly more weight after switching from daily, fixed-dose EFV/TDF/FTC to an INSTI-based regimen compared with those remaining on EFV/TDF/FTC. This weight gain was greatest among patients switching to DTG/ABC/3TC.
Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy
Authors: Pintye Jillian , Bacchetti Peter , Teeraananchai Sirinya , Kerr Stephen , Prasitsuebsai Wasana , Singtoroj Thida , Kuncze Karen , Louie Alexander , Koss Catherine A. , Jin Chengshi , Phung Nhi , Horng Howard , Sohn Annette H. , Gandhi Monica
Published: August 2017

Background:

Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir (LPV) levels on viremia among youth on second-line ART.

Methods:

We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/mL) at least 24 weeks after switch to LPV-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of LPV were measured through liquid chromatography/tandem mass spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models.

Results:

Overall, 244 children met the inclusion criteria for the present analysis. Approximately half (55%) were boys and the median age 10 years [interquartile range (IQR) 7–13]; 40% were older than 11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146–547) cells/mm3 and median HIV-RNA level was 5.0 (IQR 4.3–5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1–5) hair samples were collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher LPV hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/mL adjusted odds ratio = 0.41 per doubling in hair concentration, 95% confidence interval: 0.29 to 0.58, P < 0.001; HIV-RNA >1000 copies/mL, adjusted odds ratio = 0.54, 95% confidence interval: 0.45 to 0.65, P < 0.001).

Conclusions:

Hair concentrations predict viremia among children with HIV on second-line ART and could guide clinical decisions for this population.
Infiltrative Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis Treated With a Single High-Dose Y90 Radioembolization and Subsequent Liver Transplantation Without a Recurrence
Authors: Dendy Meaghan S. , Camacho Juan C. , Ludwig Johannes M. , Krasinskas Alyssa M. , Knechtle Stuart J. , Kim Hyun S.
Published: August 2017

Background

Infiltrative hepatocellular carcinoma with macrovascular invasion is a relatively rare presentation and usually fatal disease.

Methods

Both patients exceeded Milan and University of California-San Francisco (UCSF) criteria, and per Barcelona Clinic Liver Cancer group guidelines, they were enrolled in a prospective open-label radioembolization phase II trial that gave them optimized lobar doses of Yttrium-90 as solely the first-line therapy without concomitant or additional pharmacological or locoregional therapies.

Results

Three months after radioembolization, the patients demonstrated no residual viable disease on surveillance imaging. The patients were then followed up with serial imaging for 2 years in 3-month intervals, without documenting recurrence or extrahepatic disease. Finally, both patients underwent transplantation and after more than 20 months of imaging surveillance, no locoregional or systemic recurrence have been observed.

Conclusions

We present, to our knowledge, the first 2 reports of transplantation after successfully downstaging infiltrative disease with portal vein tumoral thrombosis, which traditionally poses as a relative contraindication for resection or transplantation.
Influence of HLA Matching on the Efficacy of Allogeneic Mesenchymal Stromal Cell Therapies for Osteoarthritis and Degenerative Disc Disease
Authors: García-Sancho Javier , Sánchez Ana , Vega Aurelio , Noriega David C. , Nocito Mercedes
Published: August 2017

Background

The necessity for more effective therapies for chronic osteoarticular diseases has led to the development of treatments based on mesenchymal stem cells (MSCs), the natural precursors of musculoskeletal tissue. Treatments with autologous MSCs yielded excellent results, with nearly 70% improvement of pain and disability in osteoarthritis and degenerative disc disease. Using allogeneic MSCs is logistically more convenient and would widen the pool of eligible patients, but potential immune rejection should be considered. In this context, MSCs are purportedly immune evasive and better tolerated than other cell types.

Methods

We used samples collected during the performance of 2 randomized clinical trials using allogeneic bone marrow MSCs for treatment of osteoarthritis (NCT01586312) and degenerative disc disease (NCT01860417). Serum samples were used to determine anti-HLA antibodies, whereas either blood or MSC samples were used for HLA typing of recipients and donors, respectively. Algofunctional indexes were used as indicators of clinical evolution, and the correlation between the number of donor-host HLA mismatches and the efficacy of treatment was determined.

Results

Immune response was weak and transient, with reactivity decaying during the first year. Consistently, better donor-recipient HLA matching did not enhance efficacy.

Conclusions

This lack of reactivity is presumably due to the cooperation of 2 factors, (1) downregulation of the host immune responses by the transplanted MSCs and (2) effective insulation of these cells inside the articular cavity or the intervertebral disc, respectively. Interestingly, better HLA matching did not enhance efficacy. These observations have medical relevance as they support the clinical use of allogeneic cells, at least as a single-dose administration. Multiple-dose applications will require further research to exclude possible sensitization.
The metaphysics of evolution
Authors: Dupré John
Published: August 2017

This paper briefly describes process metaphysics, and argues that it is better suited for describing life than the more standard thing, or substance, metaphysics. It then explores the implications of process metaphysics for conceptualizing evolution. After explaining what it is for an organism to be a process, the paper takes up the Hull/Ghiselin thesis of species as individuals and explores the conditions under which a species or lineage could constitute an individual process. It is argued that only sexual species satisfy these conditions, and that within sexual species the degree of organization varies. This, in turn, has important implications for species' evolvability. One important moral is that evolution will work differently in different biological domains.
Extended genomes: symbiosis and evolution
Authors: Hurst Gregory D. D.
Published: August 2017

Many aspects of an individual's biology derive from its interaction with symbiotic microbes, which further define many aspects of the ecology and evolution of the host species. The centrality of microbes in the function of individual organisms has given rise to the concept of the holobiont—that an individual's biology is best understood as a composite of the ‘host organism’ and symbionts within. This concept has been further elaborated to posit the holobiont as a unit of selection. In this review, I critically examine whether it is useful to consider holobionts as a unit of selection. I argue that microbial heredity—the direct passage of microbes from parent to offspring—is a key factor determining the degree to which the holobiont can usefully be considered a level of selection. Where direct vertical transmission (VT) is common, microbes form part of extended genomes whose dynamics can be modelled with simple population genetics, but that nevertheless have subtle quantitative distinctions from the classic mutation/selection model for nuclear genes. Without direct VT, the correlation between microbial fitness and host individual fitness erodes, and microbe fitness becomes associated with host survival only (rather than reproduction). Furthermore, turnover of microbes within a host may lessen associations between microbial fitness with host survival, and in polymicrobial communities, microbial fitness may derive largely from the ability to outcompete other microbes, to avoid host immune clearance and to minimize mortality through phage infection. These competing selection pressures make holobiont fitness a very minor consideration in determining symbiont evolution. Nevertheless, the importance of non-heritable microbes in organismal function is undoubted—and as such the evolutionary and ecological processes giving rise to variation and evolution of the microbes within and between host individuals represent a key research area in biology.
ICTV Virus Taxonomy Profile: Ophioviridae
Authors: García María Laura , Bó Elena Dal , da Graça John V. , Gago-Zachert Selma , Hammond John , Moreno Pedro , Natsuaki Tomohide , Pallás Vicente , Navarro Jose A. , Reyes Carina A. , Luna Gabriel Robles , Sasaya Takahide , Tzanetakis Ioannis E. , Vaira Anna María , Verbeek Martin ,   ICTV Report Consortium
Published: August 2017

The Ophioviridae is a family of filamentous plant viruses, with single-stranded negative, and possibly ambisense, RNA genomes of 11.3–12.5 kb divided into 3–4 segments, each encapsidated separately. Virions are naked filamentous nucleocapsids, forming kinked circles of at least two different contour lengths. The sole genus, Ophiovirus, includes seven species. Four ophioviruses are soil-transmitted and their natural hosts include trees, shrubs, vegetables and bulbous or corm-forming ornamentals, both monocots and dicots. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Ophioviridae, which is available at http://www.ictv.global/report/ophioviridae.
Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions
Authors: Silvas Tania V. , Hou Shurong , Myint Wazo , Somasundaran Mohan , Kelch Brian A. , Matsuo Hiroshi , Yilmaz Nese Kurt , Schiffer Celia A.
Published: August 2017

The APOBEC3 (A3) family of human cytidine deaminases is renowned for providing a first line of defense against many exogenous and endogenous retroviruses. However, the ability of these proteins to deaminate deoxycytidines in ssDNA makes A3s a double-edged sword. When overexpressed, A3s can mutate endogenous genomic DNA resulting in a variety of cancers. Although the sequence context for mutating DNA varies among A3s, the mechanism for substrate sequence specificity is not well understood. To characterize substrate specificity of A3A, a systematic approach was used to quantify the affinity for substrate as a function of sequence context, length, substrate secondary structure, and pH. We identified the A3A ssDNA binding motif as (T/C)TC(A/G), and found that A3A binds RNA in a sequence specific manner. Furthermore, A3A bound tighter to its substrate binding motif when in a loop compared to linear oligonucleotide. Our results suggest that the A3A affinity and preference for substrate is modulated by the structure of DNA, and not just its chemical identity. Analysis of previously published co-crystal structures of A3A bound to ssDNA in light of the above findings directed the proposal of a new model for the molecular mechanism underlying A3A sequence preference. On a broader scale, the results of this work not only provide key insights into the mechanism of A3’s beneficial roles in the cell, especially in viral restriction, but also into A3’s deleterious activity such as in the development of cancer.
A Method for Quantifying Molecular Interactions Using Stochastic Modelling and Super-Resolution Microscopy
Authors: Bermudez-Hernandez Keria , Keegan Sarah , Whelan Donna R. , Reid Dylan A. , Zagelbaum Jennifer , Yin Yandong , Ma Sisi , Rothenberg Eli , Fenyö David
Published: August 2017

We introduce the Interaction Factor (IF), a measure for quantifying the interaction of molecular clusters in super-resolution microscopy images. The IF is robust in the sense that it is independent of cluster density, and it only depends on the extent of the pair-wise interaction between different types of molecular clusters in the image. The IF for a single or a collection of images is estimated by first using stochastic modelling where the locations of clusters in the images are repeatedly randomized to estimate the distribution of the overlaps between the clusters in the absence of interaction (IF=0). Second, an analytical form of the relationship between IF and the overlap (which has the random overlap as its only parameter) is used to estimate the IF for the experimentally observed overlap. The advantage of IF compared to conventional methods to quantify interaction in microscopy images is that it is insensitive to changing cluster density and is an absolute measure of interaction, making the interpretation of experiments easier. We validate the IF method by using both simulated and experimental data and provide an ImageJ plugin for determining the IF of an image.
A High Performance, Inexpensive Setup for Simultaneous Multisite Recording of Electrophysiological Signals and Wide-Field Optical Imaging in the Mouse Cortex
Authors: Contreras Edgar Bermudez , Chekhov Sergey , Tarnowsky Jennifer , Sun Jianjun , McNaughton Bruce L. , Mohajerani Majid H.
Published: August 2017

Simultaneous recording of optical and electrophysiological signals from multiple cortical areas may provide crucial information to expand our understanding of cortical function. However, the insertion of multiple electrodes into the brain may compromise optical imaging by both restricting the field of view, and interfering with the approaches used to stabilize the specimen. Existing methods that combine electrophysiological recording and optical imagingin vivoimplement either multiple surface electrodes or a single electrode for deeper recordings. To address such limitation, we built a microelectrode array (hyperdrive) compatible with wide-field imaging that allows insertion of up to 12 probes into a large brain area (8 mm diameter). The developed hyperdrive is comprised of a circle of individual microdrives where probes are positioned at an angle leaving a large brain area unobstructed for wide-field imaging. Multiple tetrodes and voltage-sensitive dye imaging (VSDI) were used for simultaneous registration of spontaneous and evoked cortical activity. The electrophysiological signals were used to extract local field potential (LFP) traces, multiunit and single-unit spiking activity. To demonstrate our approach, we compared LFP and VSD signals over multiple regions of the cortex and analyzed the relationship between single-unit and global cortical population activities. The study of the interactions between cortical activity at local and global scales, such as the one presented in this work, can help to expand our knowledge of brain function.
Deep Recurrent Neural Network Reveals a Hierarchy of Process Memory during Dynamic Natural Vision
Authors: Shi Junxing , Wen Haiguang , Zhang Yizhen , Han Kuan , Liu Zhongming
Published: August 2017

The human visual cortex extracts both spatial and temporal visual features to support perception and guide behavior. Deep convolutional neural networks (CNNs) provide a computational framework to model cortical representation and organization for spatial visual processing, but unable to explain how the brain processes temporal information. To overcome this limitation, we extended a CNN by adding recurrent connections to different layers of the CNN to allow spatial representations to be remembered and accumulated over time. The extended model, or the recurrent neural network (RNN), embodied a hierarchical and distributed model of process memory as an integral part of visual processing. Unlike the CNN, the RNN learned spatiotemporal features from videos to enable action recognition. The RNN better predicted cortical responses to natural movie stimuli than the CNN, at all visual areas especially those along the dorsal stream. As a fully-observable model of visual processing, the RNN also revealed a cortical hierarchy of temporal receptive window, dynamics of process memory, and spatiotemporal representations. These results support the hypothesis of process memory, and demonstrate the potential of using the RNN for in-depth computational understanding of dynamic natural vision.
Weighted likelihood inference of genomic autozygosity patterns in dense genotype data
Authors: Blant Alexandra , Kwong Michelle , Szpiech Zachary A. , Pemberton Trevor J.
Published: August 2017

Background

Genomic regions of autozygosity (ROA) arise when an individual is homozygous for haplotypes inherited identical-by-descent from ancestors shared by both parents. Over the past decade, they have gained importance for understanding evolutionary history and the genetic basis of complex diseases and traits. However, methods to detect ROA in dense genotype data have not evolved in step with advances in genome technology that now enable us to rapidly create large high-resolution genotype datasets, limiting our ability to investigate their constituent ROA patterns.

Results

We report a weighted likelihood approach for identifying ROA in dense genotype data that accounts for autocorrelation among genotyped positions and the possibilities of unobserved mutation and recombination events, and variability in the confidence of individual genotype calls in whole genome sequence (WGS) data. Forward-time genetic simulations under two demographic scenarios that reflect situations where inbreeding and its effect on fitness are of interest suggest this approach is better powered than existing state-of-the-art methods to detect ROA at marker densities consistent with WGS and popular microarray genotyping platforms used in human and non-human studies. Moreover, we present evidence that suggests this approach is able to distinguish ROA arising via consanguinity from ROA arising via endogamy. Using subsets of The 1000 Genomes Project Phase 3 data we show that, relative to WGS, intermediate and long ROA are captured robustly with popular microarray platforms, while detection of short ROA is more variable and improves with marker density. Worldwide ROA patterns inferred from WGS data are found to accord well with those previously reported on the basis of microarray genotype data. Finally, we highlight the potential of this approach to detect genomic regions enriched for autozygosity signals in one group relative to another based upon comparisons of per-individual autozygosity likelihoods instead of inferred ROA frequencies.

Conclusions

This weighted likelihood ROA detection approach can assist population- and disease-geneticists working with a wide variety of data types and species to explore ROA patterns and to identify genomic regions with differential ROA signals among groups, thereby advancing our understanding of evolutionary history and the role of recessive variation in phenotypic variation and disease.
Structure and diversity of urinary cell-free DNA informative of host-pathogen interactions in human urinary tract infection
Authors: Burnham Philip , Dadhania Darshana , Heyang Michael , Chen Fanny , Westblade Lars F. , Suthanthiran Manikkam , Lee John Richard , De Vlaminck Iwijn
Published: August 2017

Infections of the urinary tract are the most common form of infection in the human population. Here, we tested the utility of urinary cell-free DNA (cfDNA) to comprehensively monitor host and pathogen dynamics in the scope of bacterial and viral urinary tract infections. We assayed cfDNA isolated from 141 urine samples obtained from a cohort of 82 kidney transplant recipients by next-generation sequencing. We find that urinary cfDNA simultaneously informs about the composition of the bacterial and viral components of the microbiome, antimicrobial susceptibility, bacterial growth dynamics, kidney allograft injury, and the host response to infection. These different layers of information are accessible from a single assay and individually agree with corresponding clinical tests based on quantitative PCR, conventional bacterial culture, and urinalysis. In addition, cfDNA reveals the frequent occurrence of pathologies that remain undiagnosed in conventional diagnostic workups. Our work identifies urinary cfDNA as a highly versatile tool to monitor infections of the urinary tract.
Typical retinotopic locations impact the time course of object coding
Authors: Kaiser Daniel , Moeskops Merle M. , Cichy Radoslaw M.
Published: August 2017

In everyday visual environments, objects are non-uniformly distributed across visual space. Many objects preferentially occupy particular retinotopic locations: for example, lamps more often fall into the upper visual field, whereas carpets more often fall into the lower visual field. The long-term experience with natural environments prompts the hypothesis that the visual system is tuned to such retinotopic object locations. A key prediction is that typically positioned objects should be coded more efficiently. To test this prediction, we recorded electroencephalography (EEG) while participants viewed briefly presented objects appearing in their typical locations (e.g., an airplane in the upper visual field) or in atypical locations (e.g., an airplane in the lower visual field). Multivariate pattern analysis applied to the EEG data revealed that object classification depended on positional regularities: Objects were classified more accurately when positioned typically, rather than atypically, already at 140 ms, suggesting that relatively early stages of object processing are tuned to typical retinotopic locations. Our results confirm the prediction that long-term experience with objects occurring at specific locations leads to enhanced perceptual processing when these objects appear in their typical locations. This may indicate a neural mechanism for efficient natural scene processing, where a large number of typically positioned objects needs to be processed.
Transient Reduction of DNA Methylation at the Onset of Meiosis in Male Mice
Authors: Gaysinskaya Valeriya , Miller Brendan F. , van der Heijden Godfried W. , Hansen Kasper D. , Bortvin Alex
Published: August 2017

The quality of germ cells depends on successful chromatin organization in meiotic prophase I (MPI). To better understand the epigenetic context of MPI we studied the dynamics of DNA methylation in wild-type male mice. We discovered an extended period of genome-wide transient reduction of DNA methylation (TRDM) during early MPI. Our data show that TRDM arises by passive demethylation in the premeiotic S phase highlighting the abundance of hemimethylated DNA in MPI. Importantly, TRDM unmasks a deficit in retrotransposon LINE-1 DNA methylation contributing to its expression in early MPI. We propose that TRDM facilitates meiosis and gamete quality control.
A Zebrafish Model for Ocular Tuberculosis
Authors: Takaki Kevin , Ramakrishnan Lalita , Basu Soumyava
Published: August 2017

Ocular tuberculosis (TB) commonly causes severe inflammation and vision loss in TB-endemic countries. The mechanism by which tuberculous infection becomes established in the eye is poorly understood. We usedMycobacterium marinum-infected zebrafish larvae to study the early pathogenesis of ocular TB and found hematogenous bacterial seeding of the eye despite a functional blood retinal barrier. Prototypical early granulomas formed that involved the retinal vasculature and retinal pigment epithelium-choroid complex; characteristic locations for human ocular TB. Peripheral blood monocytes were recruited to the growing granuloma suggesting that the immune privileged nature of the eye is breached by this inflammatory focus.

Conflict of interest

none disclosed

Funding

This work was supported in part by a ‘Short-term fellowship’ to SB by Department of Health Research, Government of India.
Sleeping Beauty transposon integrates into non-TA dinucleotides via an alternative mechanism
Authors: Guo Yabin , Zhang Yin , Hu Kaishun
Published: August 2017

Sleeping Beauty transposon (SB) is an important genetic tool for generating mutations in vertebrates. It is well known that SB exclusively integrates into TA dinucleotides. However, this “TA law” has never been strictly tested in large number of insertion sites after next generation sequencing was widely utilized. In this study, we analyzed 600 million pairs of Illumina sequence reads and identified 28 thousand SB insertions in non-TA sites. We recovered some non-TA sites using PCR and confirmed that at least parts of the insertions at non-TA sites are real integrations. The consensus sequence of these non-TA sites showed an asymmetric pattern distinct from the symmetric pattern of the canonical TA sites. The right side of the consensus sequence is exactly the same as the sequence of SB transposon ends, indicating interaction between the transposon DNA and the target DNA. Based on these results we suggested that SB has an alternative integration mechanism besides the canonical one to integrate its DNA into non-TA sites.

Highlights

∼ For the first time, we proved that Sleeping Beauty transposon can integrate into non-TA dinucleotides.

∼ For the first time, we provided evidence that transposon DNA can directly interact with target DNA.

∼ And for the first time, we found that a transposon can have two independent integration mechanisms.