bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple novel technique [PUIT] for closure of urethrocutaneous fistula after hypospadias repair: Preliminary results
Authors: Awad M S
Published: January 2020

Urethrocutaneous fistula is a common complication of urethroplasty for severe hypospadias, even when a microsurgical technique is applied, the closure of the fistula is a challenging problem. We present a simple surgical procedure, posterior urethral incision technique [PUIT] to close the fistula in our department.

Between February 2001 and December 2004 we prospectively evaluated 32 patients, 26 patients with initial hypospadias fistulas and 6 with recurrent fistulas who underwent closure of urethrocutaneous fistula after hypospadias repair. The mean age of patients was 5 years, the operation consisted of trimming the fistula edge after mobilization of the skin all-around then a midline posterior urethral incision was done 2 mm above and 2 mm below the fistula opening then re-approximation of the urethral edges using 6/0 vicryl sutures with loop magnification.

The timing of fistula repair was between 6 and 13 months after it was formed, all of these were effectively closed except three cases with stricture and fistula. Of these, two were completely relieved after repeated urethral dilatation, three times a week for 2 weeks. The third failed case will need another sitting after 6 months.

The posterior midline urethral incision gives a good opportunity for repair without tension with a good cosmetic outcome. This may be done under local anesthesia in adults. The procedure is considered simple rapid and easy to be done for variable fistulas types whatever of its site and the age.
Post-traumatic posterior heel soft tissue defect reconstruction
Authors: Suri M P , Patel A G , Vora H J , Raibagkar S C , Mehta D R , Vyas U H
Published: January 2020

We present a simple algorithm for management of post-traumatic posterior heel defect. We covered these with various flaps depending upon the defect size, its exact location, associated injuries, extent of zone of trauma, and complexity of the defect. The aim was to select the most suitable method for soft tissue coverage for posterior heel reconstruction.
Single stage reconstruction of alar rim defect using auricular composite graft: a case report
Authors: Soni A
Published: January 2020

A case report of reconstruction of a post infective alar rim defect, in a girl of 13 years of age, occurring as a result of septic piercing of the nose, using a composite graft taken from the ear in a single stage is described.
Fournier′s gangrene of the penis
Authors: Tauro Francis Leo , Roshan M , Sathish Rao B S , Ravikrishnan J , Menezes Leo T
Published: January 2020

Fournier′s gangrene is a rare, fulminant, though generally localized disease of the scrotum and penis with occasional extension up the abdominal wall. The usual organism is an anaerobic streptococcus synergistic with some second organism. Our case was unusual in that only the penis was involved without involving the scrotum or abdominal wall. Early therapy is the key, including hospitalization, debridement of entire shaft of the penis distal to the devasted area without excising the normal skin, parenteral broad-spectrum antibiotics & skin grafting. Only few cases of Fournier′s gangrene of the penis have been reported.
Pectus carinatum
Authors: Dogra BB B , Dogra BB B , Manmohan Singh , Vijay Langer
Published: January 2020

Pectus carinatum is an uncommon congenital anomaly. Surgical correction for the deformity is infrequently sought but is usually very rewarding. There are three types of the deformity, viz. chondro- gladiolar, chondro-manubrial and the lateral variety, of which the latter is the most rare. We present a fifteen year girl who had pectus carinatum of the lateral variety involving the left second to the eighth costo-chondral junctions. The indication for surgical intervention was purely aesthetic. Subperichondrial excision of the lateral halves of the affected costal cartilages and shaving of the adjacent ribs was done. The post-operative recovery was uneventful and the deformity was corrected satisfactorily.
Cornu cutaneum at an unusual site
Authors: Tauro Francis Leo , Martis John Joseph S , John K Sijo , Prem K kumar
Published: January 2020

Cutaneous horn (cornu cutaneum) is a clinical diagnosis referring to a conical projection above the surface of the skin that resembles a miniature horn. The base of the horn may be flat, nodular or crateriform. The horn is composed of compacted keratin. Various histologic lesions have been documented at the base of the keratin mound and histological confirmation is often necessary to rule out malignant changes. Tenderness at the base of the lesion and lesions of larger size favour malignancy. Malignancy is present in 16-20% of the cases with squamous cell carcinoma being the most common type. We report a young male patient with a keratin horn on the right index finger tip.
Anterolateral thigh flap for phalloplasty - Gandhi Hospital technique: An innovative method
Authors: Mohan Krishna , Ramani Parvati , Krishna Sri , Gnaneswar G
Published: January 2020

The objective of this paper is to report on the innovative technique of using Anterolateral Thigh Fasciocutaneous Thigh Island flap for the reconstruction of penis following Electrical Burns .This is an addition in the armamentariom of reconstructive surgeon doing phalloplasty. The advantages are that this is a single stage procedure, in the same operative field, can be undertaken under Epidural anesthesia and can be undertaken in a place without infrastructure to perform a microvascular surgery. In addition, we presume that the flap will have similar sensation as the penis to an extent.
Inflatable Indian travel pillow as a pneumatic patient jack
Authors: Gopalakrishna A , Agrawal Karoon
Published: January 2020

The Indian travel pillow readily available in the market has been utilized as a patient jack in the operation theatre. This has been used to raise the shoulders of an anaesthetized patient for surgery in the head and neck region and a set of two pillows have been used to prop-up a prone anaesthetized patient. This allows smooth positioning of the patient after intubation without disturbance to the airway with minimal manpower.
A technique for introducing looped sutures in flexor tendon repair
Authors: Jagannath Kamath B , Praveen Bhardwaj
Published: January 2020

Stronger flexor tendon repairs facilitate early active motion therapy protocols. Core sutures using looped suture material provide 1 ½ to twice the strength of Kessler′s technique (with four strand and six strand Tsuge technique respectively). The technique is well-described and uses preformed looped sutures (supramid). This is not available in many countries and we describe a technique whereby looped sutures can be introduced in flexor tendon repair by the use of 23 G hypodermic needle and conventional 4.0 or 5.0 sutures. This is an alternative when the custom made preformed sutures are not available. This can be practiced in zone 3 to zone 5 repairs. Technical difficulties limit its use in zone 2 repairs.
A simple novel technique for closure of simple and complex pilonidal sinus with either simple (tongueshaped) or bilobed rotation fl ap
Authors: Mohamed M.S. Awad , Mohamed Tolba , Osama H. Gharib
Published: January 2020

Background:Pilonidal sinus is a common disease in young adults that carries high postoperative morbidity and patients′ discomfort; controversy still exists regarding the best surgical technique for the treatment of the disease. We successfully treat it with a rotation flap technique (simple rotation and bilobed rotation flap).Materials and Methods: Sixty-two patients were randomized to receive surgical treatment in the form of either simple rotation or bilobed rotation flap by eccentric elliptical excision of the diseased tissues down to the sacral fascia and closure of the defect with the flap, then placing a closed suction drain at the base of the wound, with its tip being brought out in the gluteal region at least 5 cm laterally to the lower end of the suture. Results: All our patients healed completely without recurrence after a mean follow-up of about one year. Mean hospital stay 1.5 days (range 1-3) Mean time to complete healing 11.9 days (range 8-14). Mean time off work was 11.5 days (range 10-21), wound infection and breakdown, three (4.8%), recurrence (0%), and time to sitting on the toilet and walking without pain was 10-15 days.Conclusions: A tension-free suture and cleft left via the rotation flap, either the bilobed flap or monolobed, is the key to success without recurrence and low patient discomfort.
An arteriovenous fi stula following chalazion excision
Authors: Yuri A.R. Dias-Amborcar , Nitin J. Mokal , Suhas V. Abhyanka , Uday B. Bhat
Published: January 2020

An arteriovenous fistula secondary to a chalazion is a rare occurrence. It may follow spontaneous necrosis or surgical trauma. Digital subtraction angiography and identification of the arterial feeders combined with direct puncture of the nidus and embolization is recommended, as surgical excision becomes much easier and results in a complete excision of the lesion. Conchal cartilage graft is a useful lining material for reconstruction of the tarsal plate due to its natural curvature. It restores lid integrity and ensures a stable and functional eyelid.
Munchausen′s syndrome in plastic surgery practice: A bewildering situation!
Authors: Nardella D , Sohawon M S , Heymans O
Published: January 2020

The plastic surgeon rarely encounters patients expressing factitious disorders. Through their incredible imagination, these patients conjure numerous lesions for themselves and willingly accept to undergo invasive diagnostic procedures and risky therapies. We report four cases of Munchausen′s syndrome in the field of plastic surgery and follow with a discussion of as to when should the alarm bells start ringing for the unsuspecting plastic surgeon, to assist him in dealing with these too often-ignored disorders.
Lipofibromatous hamartoma of the median nerve: A case report and review of the literature
Authors: Patil V. S. , Nagle Sunila
Published: January 2020

A case of lipofibromatous hamartoma of the median nerve in an adult is described in this article. A 33-year-old male presented with tingling, numbness and swelling in the palm of the left non dominant hand that had been present for a few months. Examination revealed that there was fullness in the volar aspect of the wrist and in the inter-thenar area. Another mass was present at the base of the index finger, which appeared to be involving subcutaneous tissues. The clinical diagnosis was carpal tunnel syndrome due to a space occupying tumor mass in the carpal tunnel. On exploration of the carpal tunnel, a large median nerve was seen 4 cm proximal to the wrist crease line and extending distally until it divided into its branches. Another mass was present at the base of the index finger, which was adherent to the skin. The radial digital nerve of the index finger was normal in size. For the enlarged nerve, an epineurotomy was performed and a biopsy was taken. Another biopsy was taken from the distal mass. His postoperative period was uneventful. In July 2004, at the end of 5 years, the patient had no symptoms and the size of the tumor had not increased.
Aplasia cutis congenita: Two cases of non-scalp lesions
Authors: Abulezz Tarek A. , Shalkamy Mahmoud A.
Published: January 2020

Aplasia cutis congenita (ACC) is a rare condition characterized by a localized absence of skin and in some cases, the subcutaneous tissues. The majority of cases occur in the scalp; however, the lesion may occur anywhere in the trunk and extremities. ACC is most often an isolated defect, but it can be associated with other anomalies. Most reported cases are sporadic with a few reports of familial occurrence. Neither the pathogenesis nor the aetiology is clarified. Healing is spontaneous in most cases, and apart from keeping the lesion clean, no specific treatment is required. In this report, two cases of non-scalp ACC occurring in the lower limbs are presented and a brief review of the literature is conducted.
Peroperative evaluation of vascularity of various flaps by fluorescein technique
Authors: Bhattacharya V , Sunish Goyal , Nepram Sanjib Singh , Manihar H Singh , Sheikh Adil Bashir
Published: January 2020

Background: The viability of any pedicled flap depends upon its vascularity. When a flap is dissected it becomes relatively ischaemic. Ultimately, the viability of the flap depends on the vessels incorporated in the pedicle and their perfusion capacity. There are different techniques to evaluate the blood supply of a flap.

Aims: This study deals with experimental and clinical efficiency of fluorescein dye technique to evaluate the vascularity of flaps of various compositions.

Materials and Methods: The experimental study was conducted on rats to standardize the technique. Thereafter clinical evaluation was conducted for different flaps namely fasciocutaneous, skeletonized perforator based fasciocutaneous, adipofascial, fasciocutaneous flap with adipofascial extension, fasciocutaneous flap with fascial extension and fasciocutaneous flap with split fascial extension.

Conclusions: The paper deals in detail with the technique and method of documentation of a fluorescein study on flaps both experimentally and clinically. The appearance of fluorescein on both the surfaces and distal margin of the flap confirmed the adequacy of vascularity soon after dissection of the flaps. It was found to be an easy, safe and reliable objective method.
The effect of tissue expanders on the growing craniofacial skeleton
Authors: Mohamed MS Awad
Published: January 2020

Background: Tissue expansion can safely be considered one of the major advances in reconstructive plastic surgery. Reported complication rates for tissue expansion have been as low as zero and as high as 48% when expanding the head and neck region in pediatric patients.[1] Our study is to discuss the osseous effects during and after tissue expansion in children.

Materials and Methods: Thirty four expanders were implanted, 30 in scalp and 4 in face. In 4 patients, 2 expanders were used. The mean age of the patients was 3.8 years. All CT examinations (pre-expansion, post-expansion and after reconstruction) were done correspondingly with each other to be able to compare the following parameters: bone thickness and bone density under the expander; certain intracranial dimensions under the center and the edge of the expander and observing the contour of the skull in the 3D reconstruction.

Results: Variable bony changes were observed in the 30 patients, apposition at the edge of expander (Periosteal reaction) being the most frequent change, which was observed in, all except 3 patients. Bone resorption and thinning occurred in 9 patients. Inward bone displacement varied from 1 to 3 mm in two patients.

Conclusions: In spite of the reported complications like thinning and deformation of underlying bone, expansion in infants and children is safe if done with a proper preoperative planning and we prefer to delay the expansion after two years as possible.
Management of acute open tendo-achilles injuries in Indian lavatory pans
Authors: Sasanka S Chatterjee , Arindam Sarkar , Ashutosh Misra
Published: January 2020

Injuries to the Tendo-achilles are common but rarely do they present directly to plastic surgeons. Eighteen patients with acute tendo-achilles injury due to fall in the lndian type of lavatory pan came directly to the emergency department of Institute of Post Graduate Medical Education and Research, Kolkata and subsequently were treated in the Department of Plastic Surgery. Direct repair with prolene or stainless steel (SS) wires with or without flap cover were performed for management. Exercises were started 1 month later with gradual increase in activity. Complications were minor and temporary in nature. Long term results in the form of performing previous activities were excellent.
Nutrition in burns: A practical solution to a difficult problem
Authors: Suri M P , Patel C K , Dhingra VJ S , Raibagkar S C , Mehta D R
Published: January 2020

The nutritional aspects of burns is an important but yet not properly looked after problem in the management of burns. We present our experience with dealing with such a problem giving a practical and easy to deliver solution to nutrition. Early enteral nutrition should be started with frequent assessment to the need of the patient and it requires a team approach.
The Role of Combined Therapy in the Treatment of Retinopathy and Optic Neuropathy Due to Radiotherapy in the Uveal Melanoma
Authors: Cihan Yasemin Benderli
Published: January 2020

Introduction Uveal melanoma has a relatively low incidence. Transpupillary thermotherapy (TTT), hypofractioned stereotactic radiotherapy (RT), stereotactic radiosurgery, plaque brachytherapy, charged particle radiation therapy, local tumor resection, enucleation, and exantation are applied in the treatment.

Methods The importance given to radiotherapy has increased to get more satisfactory results while treating the patient. However, it is the treatment of radiation retinopathy and optic neuropathy from complications.

Results Radiation retinopathy and optic neuropathy are the most important complications related to radiotherapy in the treatment of uveal melanoma. In recent years, many studies have been performed on the treatment of radiation retinopathy and optic neuropathy.

Conclusion The consecutive use of triamcinolone in combination with anti-VEGF supports that it may be a future therapeutic agent in the treatment of complications.
Compact circular polarizer based on cross-shaped slot for high-power microwave applications
Authors: Zhao Xuhao , Yuan Chengwei , Zhang Jiande , Zhang Qiang
Published: January 2020

A compact high-power waveguide circular polarizer working at the C-band is presented in this paper. By introducing a split-ring slot and an orthogonally crossed rectangular slot into a circular waveguide, high transmission efficiency and 90° phase difference of two linearly polarized orthogonal TE11 modes are achieved by using the polarizer within a half wavelength. In the meantime, the power handling capacity of the designed polarizer is expected to be over 120 MW, which can be applied in the high-power microwave region. The designed circular polarizer is fabricated and measured by the cold test; the results of experiments and simulations agree well with each other. It is shown in the experiments that the axial ratio is less than 0.9 dB, the voltage standing-wave ratio is less than 1.2, and the conversion efficiency is over −0.15 dB at 4.2–4.4 GHz.
Echolocation and foraging ecology of the bristle-faced free-tailed bat, Setirostris eleryi, in central Australia
Authors: McKenzie N. L. , Bullen R. D. , Pennay M.
Published: January 2020

We document the spectral characteristics of echolocation sequences of Setirostris eleryi recorded from riparian zones in the Central Ranges in Western Australia, near Warakurna. These are the first records of this species in Western Australia. The sequences are comparable to reference S. eleryi sequences from near Alice Springs, as well as to sequences from a nearby vouchered specimen locality (Hull River in the Northern Territory), yet distinct from Scotorepens greyii sequences from Western Australia, including locations in the Central Ranges. The central Australian S. eleryi sequences average 3kHz higher in frequency than reference S. eleryi recordings from eastern Australia. We deduce the species’ foraging strategy, microhabitat, wing beat frequency and flight speed from the echolocation sequences, then show that these deductions are consistent with calculations based on an airframe analysis of museum specimens, and with available field observations. The echolocation recordings provided a quick, passive, cost-effective characterisation of foraging niche, useful for conservation planning.
汉语自然会话转换型回应及其互动功能
Authors: Xie Xinyang
Published: January 2020

本文对汉语自然口语会话中的转换型回应进行探讨，将转换型回应划分为措辞转换型回应和规程转换型回应两类。就汉语自然口语而言，措辞转换型回应在互动中的主要功能在于答者希望提供更为准确和足量的信息，形式上大部分是单小句或短语形式。规程转换型回应则基本上是多小句的形式，而且一般都会带来序列上的扩展。
Modes of Delivery in Concurrent Nicotine and Cannabis use (“Co-Use”) among Youth: Findings from the International Tobacco Control (ITC) Survey
Authors: Smith Danielle M. , Miller Connor , O'Connor Richard J. , Kozlowski Lynn T. , Wadsworth Elle , Fix Brian V. , Collins R. Lorraine , Wei Binnian , Goniewicz Maciej L. , Hyland Andrew J. , Hammond David
Published: January 2020

Background

Cannabis use is more common among nicotine users than non-users. This study characterized concurrent use of nicotine and cannabis (“co-use”) among 12,064 youth aged 16–19 years residing in Canada, the United States, and England in 2017.

Methods

Data were from the ITC Youth Tobacco & Vaping Survey (Wave 1). Seven modes of cannabis delivery (MOD) were characterized by country of residence and past 30-day use of combusted tobacco and electronic cigarettes. Weighted multivariable regression models were fitted to assess the correlates of co-use and each cannabis MOD.

Results

Seventy percent of cannabis users reported nicotine use. Co-users exhibited behavioral and demographic differences compared to exclusive users of either substance. “Smoking cannabis without tobacco” was the most popular form of use (78%). Use of nicotine-containing e-cigarettes was associated with “using an e-cigarette to vape cannabis oil/liquid” (aOR: 4.96, 95%CI: 2.23–11.06). Combustible tobacco use was associated with “smoking cannabis with tobacco in a joint/blunt” (aOR: 2.93, 95%CI: 1.89–4.56). Country-level differences were detected.

Conclusions

Nicotine use is substantial among cannabis users, and associations exist between modes of delivery for both drugs. Results underscore the importance of studying cannabis and nicotine use concurrently, and the need to address the use of both substances in developing interventions for youth users.
Ghost network analyzer
Authors: Zhang Xiao , Yin He , Li Rui , Hong Jiaying , Li Qin , Xue Ping
Published: January 2020

Ghost imaging obtains an image of an amplitude/phase object by spatial correlation between two separated light beams. In ghost imaging, two detectors are used in a counter-intuitive way. One is a multi-pixel detector that does not view the object in reference arm, and the other one is a single-pixel detector that does view the object but only record the total light power in object arm. Neither detector could recovery the object independently, but spatial correlation from two detectors allows the reconstruction of a ghost image of the object. Here for the first time we present ghost network analyzer for obtaining frequency properties of a target. Interestingly, this novel technique proves insensitive to the distortion introduced by nonlinear devices, while conventional frequency-domain measurement modalities such as network analyzer can hardly work properly with distortion. The proposed technique provides a breakthrough method for distortion-free dynamic frequency response analysis.
The Association Between Unemployment and Mortality: A Cohort Study of Workplace Downsizing and Closure
Authors: Junna Liina , Moustgaard Heta , Huttunen Kristiina , Martikainen Pekka
Published: January 2020

Workplace downsizing and closure have been considered natural experiments that strengthen causal inference when assessing the association between unemployment and health. Selection into unemployment plays a lesser role among those exposed to severe workplace downsizing. This study compared mortality for individuals unemployed from stable, downsized, and closed workplaces with a reference group unexposed to unemployment. We examined nationally representative register data of residents of Finland aged 25–63 years in 1990–2009 (n = 275,738). Compared with the control group, the hazard ratio for substance use–related mortality among men unemployed from stable workplaces was 2.43 (95% confidence interval (CI): 2.22, 2.67), from downsized workplaces 1.85 (CI: 1.65, 2.08), and from closed workplaces 2.16 (CI: 1.84, 2.53). Among women, the corresponding estimates were 3.01 (CI: 2.42, 3.74), 2.39 (CI: 1.75, 3.27), and 1.47 (CI: 1.09, 1.99). Unemployment from stable workplaces was associated with mortality from psychiatric and self-harm–related conditions. However, mortality due to ischemic heart disease and other somatic diseases decreased for those unemployed following closure. The results indicate that selection mechanisms partially explain the excess mortality among the unemployed. However, substance-use outcomes among men and women, and fatal accidents and violence among men, might be causally associated with unemployment.
Program development of a preceptor bootcamp for operational pharmacy preceptors
Authors: Smith Devlin V , Gautreaux Stefani , Gulbis Alison M , Bruno Jeffrey J , Garey Kevin , Roux Ryan K , Varkey Divya
Published: January 2020

Purpose

To describe the development, design, and implementation of a pilot preceptor development bootcamp and feedback related to its feasibility and impact on operational pharmacy preceptors.

The University of Texas MD Anderson Cancer Center designed and implemented a pilot preceptor development bootcamp for operational staff pharmacists serving as residency preceptors for longitudinal weekend staffing experiences. A systematic, multipronged approach was taken to identify preceptor development gaps and design a full-day bootcamp curriculum. The resultant curriculum was comprised of content in major functional areas including using the 4 preceptor roles, documenting performance, giving and receiving feedback, and dealing with difficult situations or learners. The impact of the pilot preceptor development bootcamp was assessed using survey methodology and qualitative feedback from debrief discussions.

Conclusion

Implementation of a pilot preceptor bootcamp program addressing major areas of precepting skill was well received, resulted in positive feedback from operational pharmacy preceptors, and was feasible to implement at a large academic medical center.
Sex, synchrony, and skin contact: integrating multiple behaviors to assess pathogen transmission risk
Authors: Leu Stephan T , Sah Pratha , Krzyszczyk Ewa , Jacoby Ann-Marie , Mann Janet , Bansal Shweta
Published: January 2020

Direct pathogen and parasite transmission is fundamentally driven by a population’s contact network structure and its demographic composition and is further modulated by pathogen life-history traits. Importantly, populations are most often concurrently exposed to a suite of pathogens, which is rarely investigated, because contact networks are typically inferred from spatial proximity only. Here, we use 5 years of detailed observations of Indo-Pacific bottlenose dolphins (Tursiops aduncus) that distinguish between four different types of social contact. We investigate how demography (sex and age) affects these different social behaviors. Three of the four social behaviors can be used as a proxy for understanding key routes of direct pathogen transmission (sexual contact, skin contact, and aerosol contact of respiratory vapor above the water surface). We quantify the demography-dependent network connectedness, representing the risk of exposure associated with the three pathogen transmission routes, and quantify coexposure risks and relate them to individual sociability. Our results suggest demography-driven disease risk in bottlenose dolphins, with males at greater risk than females, and transmission route-dependent implications for different age classes. We hypothesize that male alliance formation and the divergent reproductive strategies in males and females drive the demography-dependent connectedness and, hence, exposure risk to pathogens. Our study provides evidence for the risk of coexposure to pathogens transmitted along different transmission routes and that they relate to individual sociability. Hence, our results highlight the importance of a multibehavioral approach for a more complete understanding of the overall pathogen transmission risk in animal populations, as well as the cumulative costs of sociality.
Curation and annotation of planarian gene expression patterns with segmented reference morphologies
Authors: Roy Joy , Cheung Eric , Bhatti Junaid , Muneem Abraar , Lobo Daniel
Published: January 2020

Motivation

Morphological and genetic spatial data from functional experiments based on genetic, surgical and pharmacological perturbations are being produced at an extraordinary pace in developmental and regenerative biology. However, our ability to extract knowledge from these large datasets are hindered due to the lack of formalization methods and tools able to unambiguously describe, centralize and interpret them. Formalizing spatial phenotypes and gene expression patterns is especially challenging in organisms with highly variable morphologies such as planarian worms, which due to their extraordinary regenerative capability can experimentally result in phenotypes with almost any combination of body regions or parts.

Results

Here, we present a computational methodology and mathematical formalism to encode and curate the morphological outcomes and gene expression patterns in planaria. Worm morphologies are encoded with mathematical graphs based on anatomical ontology terms to automatically generate reference morphologies. Gene expression patterns are registered to these standard reference morphologies, which can then be annotated automatically with anatomical ontology terms by analyzing the spatial expression patterns and their textual descriptions. This methodology enables the curation and annotation of complex experimental morphologies together with their gene expression patterns in a centralized standardized dataset, paving the way for the extraction of knowledge and reverse-engineering of the much sought-after mechanistic models in planaria and other regenerative organisms.

Availability and implementation

We implemented this methodology in a user-friendly graphical software tool, PlanGexQ, freely available together with the data in the manuscript at https://lobolab.umbc.edu/plangexq.

Supplementary information

Supplementary data are available at Bioinformatics online.
Inference of gene regulatory networks based on nonlinear ordinary differential equations
Authors: Ma Baoshan , Fang Mingkun , Jiao Xiangtian
Published: January 2020

Motivation

Gene regulatory networks (GRNs) capture the regulatory interactions between genes, resulting from the fundamental biological process of transcription and translation. In some cases, the topology of GRNs is not known, and has to be inferred from gene expression data. Most of the existing GRNs reconstruction algorithms are either applied to time-series data or steady-state data. Although time-series data include more information about the system dynamics, steady-state data imply stability of the underlying regulatory networks.

Results

In this article, we propose a method for inferring GRNs from time-series and steady-state data jointly. We make use of a non-linear ordinary differential equations framework to model dynamic gene regulation and an importance measurement strategy to infer all putative regulatory links efficiently. The proposed method is evaluated extensively on the artificial DREAM4 dataset and two real gene expression datasets of yeast and Escherichia coli. Based on public benchmark datasets, the proposed method outperforms other popular inference algorithms in terms of overall score. By comparing the performance on the datasets with different scales, the results show that our method still keeps good robustness and accuracy at a low computational complexity.

Availability and implementation

The proposed method is written in the Python language, and is available at: https://github.com/lab319/GRNs_nonlinear_ODEs

Supplementary information

Supplementary data are available at Bioinformatics online.
Much more than a clasp: evolutionary patterns of amplexus diversity in anurans
Authors: Carvajal-Castro Juan D , López-Aguirre Yelenny , Ospina-L Ana María , Santos Juan C , Rojas Bibiana , Vargas-Salinas Fernando
Published: January 2020

The evolution and diversification of animal reproductive modes have been pivotal questions in behavioural ecology. Amphibians present the highest diversity of reproductive modes among vertebrates, involving various behavioural, physiological and morphological traits. One such feature is the amplexus, which is the clasp or embrace of males on females during reproduction and is found almost universally in anurans. Hypotheses about the origin of amplexus are limited and have not been tested thoroughly, nor have they taken into account evolutionary relationships in most comparative studies. However, these considerations are crucial to an understanding of the evolution of reproductive modes. Here, using an evolutionary framework, we reconstruct the ancestral state of amplexus in 685 anuran species. We investigate whether the type of amplexus has a strong phylogenetic signal and test whether sexual size dimorphism could have influenced amplexus type or male performance while clasping females. Overall, we found evidence of ≥34 evolutionary transitions in amplexus type across anurans. We found that amplexus type exhibits a high phylogenetic signal and that amplexus type does not evolve in association with sexual size dimorphism. We discuss the implications of our findings for the diversity of amplexus types across anurans.
Can the impacts of cold-water pollution on fish be mitigated by thermal plasticity?
Authors: Parisi M A , Cramp R L , Gordos M A , Franklin C E
Published: January 2020

Increasingly, cold-water pollution (CWP) is being recognised as a significant threat to aquatic communities downstream of large, bottom-release dams. Cold water releases typically occur during summer when storage dams release unseasonably cold and anoxic hypolimnetic waters, which can decrease the temperature of downstream waters by up to 16°C. Depending on the release duration, these hypothermic conditions can persist for many months. The capacity of ectothermic species to tolerate or rapidly adjust to acute temperature changes may determine the nature and magnitude of the impact of CWP on affected species. This study assessed the impacts of an acute reduction in water temperature on the physiological function and locomotor performance of juvenile silver perch (Bidyanus bidyanus) and examined their capacity to thermally compensate for the depressive effects of low temperatures via phenotypic plasticity. Locomotor performance (Ucrit and Usprint) and energetic costs (routine and maximum metabolic rate) were measured at multiple points over a 10-week period following an abrupt 10°C drop in water temperature. We also measured the thermal sensitivity of metabolic enzymes from muscle samples taken from fish following the exposure period. Cold exposure had significant depressive effects on physiological traits, resulting in decreases in performance between 10% and 55%. Although there was partial acclimation of Ucrit (~35% increase in performance) and complete compensation of metabolic rate, this occurred late in the exposure period, meaning silver perch were unable to rapidly compensate for the depressive effects of thermal pollution. The results of this study have substantial implications for the management of cold water releases from large-scale dams and the conservation of native freshwater fish species, as this form of thermal pollution can act as a barrier to fish movement, cause reduced recruitment, ecological community shifts and disruptions to timing and success of reproduction.
OP01 Higher vs. standard adalimumab maintenance regimens in patients with moderately to severely active ulcerative colitis: Results from the SERENE-UC maintenance study
Authors: Colombel J F , Panés J , D’Haens G , Schreiber S , Panaccione R , Peyrin-Biroulet L , Loftus E V , Danese S , Louis E , Armuzzi A , Ferrante M , Vogelsang H , Lefebvre J , Doan T , Xie W , Huang B , Petersson J , Kalabic J , Robinson A , Sandborn W J
Published: January 2020

Background

Adalimumab (ADA) is efficacious and well tolerated in adult patients with ulcerative colitis (UC).1,2 SERENE-UC (NCT02065622) is a study evaluating higher ADA dosing regimens from which induction study results have previously been reported3; here, we report data from the maintenance study.

Methods

This Phase 3, double-blind, randomised, multicentre study evaluated higher vs. standard ADA dosing regimens for induction and maintenance therapy in adult patients with moderately to severely active UC. Following completion of the induction study at Week 8, all patients were re-randomised 2:2:1 to ADA 40 mg every week (40 EW), ADA 40 mg every other week (40 EOW), or exploratory ADA 40 mg with therapeutic drug monitoring (TDM) regimens, stratified by induction treatment regimen, clinical response status at Week 8, and clinical remission (CRem) status at Week 8 among Week 8 responders. Efficacy endpoints were evaluated in Week 8 responders (ITT-RP) unless indicated differently. The primary efficacy endpoint was proportion of patients achieving CRem (full Mayo Score ≤2 with no subscore >1) at Week 52. The endoscopic component of the Mayo Score was scored via central reading. Non-responder imputation was used for missing values. Comparisons between 40 EW and 40 EOW dosing regimens used the Cochran–Mantel–Haenszel test adjusted for stratification. Safety assessment included a collection of adverse events (AEs), vital signs, and laboratory data.

Results

Of 852 patients in the Global (ex-Japan) induction study, 757 were re-randomised at Week 8 and 371 were included in the ITT-RP. In the ITT-RP, induction baseline demographics and disease characteristics were generally balanced across the 3 treatment arms; range across arms for mean UC disease duration was 6.2–7.8 years, 6.8–11.7% had prior infliximab use, and 62.5–63.5% were receiving corticosteroids. The overall mean ADA exposure was 252.2 days. The table displays results for efficacy endpoints. The observed safety profile was similar between maintenance treatment arms, including AEs of special interest (generally <1% across arms).

Conclusion

In the Global (ex-Japan) study of SERENE-UC, CRem at Week 52 was numerically higher among Week 8 responders in patients receiving ADA 40 EW compared with 40 EOW maintenance regimens (∆ = 10.5%), but not statistically significant. Higher maintenance treatment with 40 EW was generally safe and well tolerated with a similar safety profile to 40 EOW. No new long-term safety concerns were observed.

References
OP08 Inflammatory bowel disease and risk of small bowel cancer: A binational population-based cohort study from Denmark and Sweden
Authors: Axelrad J , Olen O , Sachs M , Erichsen R , Pedersen L , Halfvarson J , Askling J , Ekbom A , Sørensen H T , Ludvigsson J
Published: January 2020

Background

Crohn’s disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies were limited by a small number of cases, short follow-up, lack of individually matched comparators, and over-representation of tertiary referral centres, leading to exaggerated relative risks and incidence data. Data on ulcerative colitis (UC) and SBC are scarce.

Methods

In a binational, population-based cohort study from Sweden and Denmark of patients diagnosed with inflammatory bowel disease (IBD) during 1969–2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC, including SBC subtypes (small bowel adenocarcinoma, neuroendocrine tumours, and sarcoma). Cox regression was used to compute adjusted hazard ratios (aHRs) as a measure of relative risks for incident SBC and SBC subtypes.

Results

We identified 161,896 individuals with IBD (CD: 47,370; UC: 97,515; unclassified IBD:17,011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100,000 person-years; UC: 5.88/100,000 person-years), compared with 640 cases in reference individuals (2.81/100,000 person-years and 3.32/100,000 person-years, respectively, Table). This corresponded to one extra case of for small bowel cancer in 385 CD patients, and one extra case in 500 UC patients, followed-up for 10 years. The aHR for incident SBC of 9.09 (95% CI = 7.34–11.3) in CD patients and 1.85 (95% CI = 1.43–2.39) in UC patients (Figure). When the first year after IBD diagnosis was excluded, the aHRs for incident SBC decreased to 4.96 in CD patients and 1.69 in UC patients. Among CD patients, relative risks were highest for recently diagnosed, childhood-onset, ileal, and stricturing CD; among UC patients, relative risks were highest for those with extensive colitis and primary sclerosing cholangitis (PSC). In CD patients, the risk of all SBC subtypes was increased (aHR 15.8 for adenocarcinoma, 5.51 for neuroendocrine tumours, and 4.04 for sarcoma) whereas in UC patients only the risk of adenocarcinoma (aHR 1.99) and neuroendocrine tumours (aHR 2.01) were increased.

Conclusion

SBC was more common in IBD patients, particularly among patients with CD, although absolute risks were low. Further studies should evaluate the utility of SBC surveillance in selected populations such as those with ileal CD, extensive colitis, or UC-PSC.
OP22 Crohn’s disease exclusion diet reduces bacterial dysbiosis towards healthy controls in paediatric Crohn’s disease
Authors: Van Limbergen J , Dunn K , Wine E , Sigall Boneh R , Bielawski J , Levine A
Published: January 2020

Background

Dietary therapy with the Crohn’s disease Exclusion Diet (CDED) or Exclusive Enteral Nutrition (EEN) induces remission, reduces inflammation and is associated with compositional changes in the microbiome. We performed metagenome analysis to elucidate whether diet induces remission via correction of dysbiosis and/or community structure.

Methods

Whole metagenome and 16S rDNA sequences were obtained in 178 samples from 70 participants at 3 time points (baseline, week 6, week 12) from the two study groups (CDED+PEN/EEN). For metagenome analysis, we divided the groups further into samples of patients achieving ITT-remission at week 6 (CDED+PEN: 31/38 and EEN: 23/32) and those who did not.

Results

Dietary therapy decreased the relative abundance of genera from Proteobacteria towards healthy controls. CDED+PEN remission is associated with a significant increase (p < .05) in Clostridiales, and a significant decrease (p < .05) in Proteobacteria (particularly Γproteobacteria). Microbiome comparison of all baseline CD samples with healthy controls showed significant (p < .05) increases in Proteobacteria in an active CD at baseline. Healthy controls had increased Firmicutes species notably Roseburia, Oscillibacter and Anaerostipes, as well as increased Bacteroides and Ascomycota (driven by Saccharomyces). Proteobacteria decreased when diet-induced remission was achieved (with either CDED+PEN or EEN) at week 6: relative abundance of Proteobacteria (including Α- and Γproteobacteria (e.g. Escherichia, Klebsiella and Citrobacter) were significantly lower compared with baseline but were still more abundant in CD patients, whereas Bacilli and Firmicutes remained more predominant in healthy samples. Continued dietary treatment with CDED+PEN between week 6 and week 12 was associated with a further decrease in Proteobacteria: although improving with dietary treatment, only Escherichia remained more abundant in CD. Faecalibacterium became more abundant in CD by week 12, as did Blautia and Sutterella. Anaerostipes, Ruminococcus, Bacilli, Porphyromonadaceae, Bifidobacteriales, Ascomycota and Caudovirales were more abundant in healthy samples compared with week 12 of CDED+PEN. Bayesian analysis of the 16S rDNA data training on patients in remission at week 6 compared with baseline (week 0) samples identified seven assemblages. Predominate taxa identified in these assemblages (Posterior Probability >.01) are shown as a connected network, with taxa (nodes) found in the same assemblage connected to each other by edges (Figures).

Conclusion

Dietary therapy corrected dysbiosis towards healthy controls. Sustained dietary therapy beyond 6 weeks with CDED+PEN avoids the ‘rebound’ in disease-associated species, notably Proteobacteria, when the oral diet is reintroduced.
OP33 Multi-omics analysis reveals specific bio-geographical and functional characteristics in inflammatory bowel disease intestinal mucosa
Authors: Maimon N , Gerassy-Vainberg S , Bar-Yosef H , Alpert A , Starosvetsky E , Abu-Arisha M , Shvedov T , Shen-Orr S , Chowers Y
Published: January 2020

Background

Anatomical location and extent of disease are main factors that affect inflammatory bowel disease (IBD) course and prognosis. No explanation is available for segmental intestinal involvement in either Crohn’s disease (CD) or ulcerative colitis (UC), or for selective segmental response to therapy or disease complications. Therefore, studying the cellular composition of different intestinal segments may provide pathophysiological insights into these phenomena.

Methods

We compared location-specific cell composition and function by Cytometry Time-of-Flight (CyTOF), gene expression and single-cell (sc) RNAseq data obtained from 3 independent cohorts of healthy donors and IBD patients during remission and flare-ups. Using CyTOF data (n = 38 biopsies), we built a high-resolution screening of immune cell behaviour along the intestine. We validated the findings with gene expression data of 370 samples, and expanded screening resolution by computational methodologies. We then tested a specific pathway in scRNAseq data (n = 10 paired biopsies from 5 patients) and validated its significance by cell-specific Significance Analysis of Microarrays (csSAM).

Results

We found a location along the intestine to be a dominant feature determining immune and non-immune cell composition. We observed that inflammation reduced anatomic segregation beyond cell infiltration, and decreased the ability to cope with oxidative stress. An upregulated IL-6 pathway in T regulatory cells in UC patients was recognised as sigmoid-specific compared with known inflammatory IL-6 roles in macrophages, as seen in the right colon. This observation may be linked to colonic perforations associated with anti-IL-6R treatment. Suppressor of cytokine signalling 3 (SOCS3) may control IL-6 location-specific action.

Conclusion

Our study displays a unique and comprehensive cell map of IBD in a location-specific context, providing potential explanations to unexplained clinical phenomena. These observations may allow to tailor therapies to affected areas with improved therapeutic index and efficacy.