bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Varying Numbers of Quadrivalent Human Papillomavirus Vaccine Doses on Anogenital Warts in the United States: A Database Study
Authors: Zeybek Burak , Lin Yu-Li , Kuo Yong-Fang , Rodriguez Ana M.
Published: May 2018

Objective

The aim of the study was to investigate the effects of 3 or less quadrivalent human papillomavirus (HPV) vaccine doses on anogenital warts in both males and females in the United States.

Materials and Methods

We conducted a retrospective database study that included males and females aged 9 to 26 years who received varying numbers of vaccine doses between 2006 and 2015. The primary outcome was the incidence of anogenital warts starting 3 months after the last dose of the HPV vaccine. Proportional hazard regression models were used to examine the association between the number of HPV vaccine doses and the incidence of anogenital warts. The Kaplan-Meier method was used to estimate the proportion of subjects.

Results

A total of 440,532 females and 133,394 males were included in the study. We found a significant 2-way interaction (p < .0001) between the number of doses and age. For the group between 15 and 19 years of age, the hazard ratio of anogenital warts for the 3-dose vaccine was 0.58 (95% CI = 0.49–0.70), whereas it was 0.65 (95% CI = 0.49–0.85) and 0.67 (95% CI = 0.51–0.89) for the 1- and 2-dose groups, respectively.

Conclusions

Our findings showed that 1, 2, and 3 doses of the quadrivalent HPV vaccine were similarly effective against anogenital warts in 15- to 19-year-old adolescents, irrespective of sex.
Flow Cytometry
Authors: Pane Marco , Allesina Serena , Amoruso Angela , Nicola Stefania , Deidda Francesca , Mogna Luca
Published: May 2018

Goals:

The purpose of this trial was to verify that the analytical method ISO 19344:2015 (E)-IDF 232:2015 (E) is valid and reliable for quantifying the concentration of the probiotic Lactobacillus rhamnosus GG (ATCC 53103) in a finished product formulation.

Background:

Flow cytometry assay is emerging as an alternative rapid method for microbial detection, enumeration, and population profiling. The use of flow cytometry not only permits the determination of viable cell counts but also allows for enumeration of damaged and dead cell subpopulations. Results are expressed as TFU (Total Fluorescent Units) and AFU (Active Fluorescent Units). In December 2015, the International Standard ISO 19344-IDF 232 “Milk and milk products—Starter cultures, probiotics and fermented products—Quantification of lactic acid bacteria by flow cytometry” was published. This particular ISO can be applied universally and regardless of the species of interest.

Study:

Analytical method validation was conducted on 3 different industrial batches of L. rhamnosus GG according to USP39<1225>/ICH Q2R1 in term of: accuracy, precision (repeatability), intermediate precision (ruggedness), specificity, limit of quantification, linearity, range, robustness.

Results:

The data obtained on the 3 batches of finished product have significantly demonstrated the validity and robustness of the cytofluorimetric analysis.

Conclusions:

On the basis of the results obtained, the ISO 19344:2015 (E)-IDF 232:2015 (E) “Quantification of lactic acid bacteria by flow cytometry” can be used for the enumeration of L. rhamnosus GG in a finished product formulation.
Ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for chronic hepatitis C virus genotype 1b-infected cirrhotics (TURQUOISE-IV)
Authors: Isakov Vasily , Paduta Dzmitry , Viani Rolando M. , Enejosa Jeffrey V. , Pasechnikov Viktor , Znoyko Olga , Ogurtsov Pavel , Bogomolov Pavel O. , Maevskaya Marina V. , Chen Xiaotian , Shulman Nancy S.
Published: May 2018

Objective

An estimated 336 per 100 000 people in Russia are infected with hepatitis C virus, including up to 75% with genotype (GT) 1b. In the TURQUOISE-II/-III trials, a 12-week regimen of the direct-acting antiviral agents ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) in GT1b-infected patients with compensated cirrhosis resulted in 12-week sustained virologic response (SVR) rates of 100%.

Patients and methods

In TURQUOISE-IV, GT1b-infected patients (n=36) from Russia and Belarus with compensated cirrhosis, who were treatment naive or previously treated with pegylated interferon/ribavirin (RBV), received OBV/PTV/ritonavir+DSV+RBV for 12 weeks. The primary efficacy end point was SVR at 12 weeks. Safety assessments included adverse event (AE) monitoring and laboratory testing.

Results

At baseline, patients had Child–Pugh scores of 5 (92%) or 6 (8%). Overall, 69% were treatment experienced (44% prior null responders, 32% relapsers, and 16% partial responders). All patients achieved SVR at 12 weeks (36/36; 100%). No patient experienced a serious AE or discontinued treatment prematurely. Treatment-emergent AEs possibly related to study drugs occurring in greater than or equal to 10% of patients were asthenia (19%), anemia (14%), cough (14%), and headache (11%); most events were mild in severity. Clinically significant laboratory abnormalities were infrequent.

Conclusion

In Russian and Belarusian patients with hepatitis C GT1b infection and compensated cirrhosis, 100% achieved SVR at 12 weeks after 12 weeks’ treatment with OBV/PTV/ritonavir+DSV+RBV. The treatment was well tolerated.
Microbial Fermentation of Starch
Authors: Kalhan Satish C.
Published: May 2018

Starch, a major source of carbohydrates in human nutrition, is extensively hydrolyzed in the gastrointestinal tract of children and adults. A small fraction of the ingested starch reaches the cecum and colon where it is fermented by the gut microbiome into short‐chain fatty acids (SCFA) and other products. Recent data in humans and in animal models have demonstrated the extensive effects of short‐chain fatty acids on whole body energy metabolism, appetite, insulin resistance, fatty acid oxidation, fat accretion, obesity, and diabetes. Clear discernible effects of SCFA on the rates of production of glucose, its oxidation and uptake in the fasting state were, however, not observed. In the fed state, the effects on glucose metabolism are related to the effects of SCFA on insulin sensitivity, possibly the consequence of their influence on lipid metabolism. The suggested limits of carbohydrate intake were based upon the kinetics and metabolism of glucose in the basal state and on the responses to glucose administration. It is postulated that in healthy subjects, the present data do not suggest any significant impact of microbial fermentation of starch on the range of acceptable intake of carbohydrates.
Use of Starch and Modified Starches in Infant Feeding
Authors: Greer Frank R.
Published: May 2018

There is a long history of the use of starch in infant feeding. Proprietary infant foods (1867–1920) contained added starch from either cereal grains or malted carbohydrates. When evaporated milk became available in the 1920s, the use of proprietary foods fell out of favor. Evaporated milk formulas were a mixture of milk, water, and modified starch or milk sugar (lactose). By the late 1920s, however, corn syrup became the most common modified starch added to evaporated milk formulas as it was widely available, inexpensive, and readily accepted. The ongoing development of the modern calorie‐based infant formula, made from non‐fat cow's milk, lactose, oleo and vegetable oils, largely replaced the evaporated milk formulas in the 1960s. On the other hand, after 1940, added starch and modified starch became increasingly important in the production of pureed fruits and vegetables. Not surprisingly, this included their use in the modern “industrialized” food for use in infants, including their use in a proliferation of grain based fortified infant cereals. This coincided with the increasing production largely due to the earlier introduction of complementary foods, commonly before 3 months of age by 1958. After 1969, the increasing public awareness and media scrutiny of infant foods lead to a growing criticism of the use of modified starches. Even though the National Research Council and the American Academy of Pediatrics concluded that modified starches were safe for use, continued public pressure led to their removal from most infant foods in the 1990s. This paralleled the natural food and organic food movements in the United States. Though modified starches are still used in infant dinners of mixed foods today, their use has been minimized and this issue is not currently of significant concern to the public.
Starch Malabsorption in Infants
Authors: Shulman Robert J.
Published: May 2018

Based on the developmental physiology of pancreatic amylase production, starch digestion in young infants was anticipated to be compromised whenever compared with that in older infants and toddlers. This appears to be the case, but with great variability among infants to digest starch. Evidence points to the importance of maltase‐glucoamylase in young infants and its effect on starch digestion. These observations have critical importance for recommendations regarding the feeding of starch‐containing foods to young infants.
Structural Studies of the Intestinal α‐Glucosidases, Maltase‐glucoamylase and Sucrase‐isomaltase
Authors: Rose David R. , Chaudet Marcia M. , Jones Kyra
Published: May 2018

Objectives:

Maltase‐glucoamylase and sucrase‐isomaltase are enzymes in the brush‐border membrane of the small intestinal lumen responsible for the breakdown of postamylase starch polysaccharides to release monomeric glucose. As such, they are critical players in healthy nutrition and their malfunction can lead to severe disorders.

Methods:

This review covers investigations of the structures and functions of these enzymes.

Results:

Each consists of 2 enzyme domains of the glycoside hydrolase family GH31 classification, yet with somewhat differing enzymatic properties.

Conclusions:

Crystallographic structures of 3 of the domains have been published. Insights into substrate binding and specificity will be discussed, along with future lines of inquiry related to the enzymes’ roles in disease and potential avenues for therapeutics.
Starch Tolerance and the Short Bowel
Authors: de Laffolie Jan , Naim Hassan Y. , Rudloff Silvia , Zimmer Klaus‐Peter
Published: May 2018

Short bowel syndrome with intestinal failure is a rare disease with a massive impairment in quality of life, requiring a multidisciplinary team approach to medical, surgical, and nutritional therapy. Current pharmacological and surgical therapeutic options are limited; an important cornerstone is enteral and parenteral nutrition. The changed physiology of carbohydrate digestion plays a major role in the adaptation process and can be a target for specific enteral nutrition interventions. An important prognostic factor is the preservation of at least portions of the colon in continuity with small bowel. This strategy has to include an evaluation of the anatomical situation and small bowel absorptive capacity, adaptation processes, and luminal microbiota including its fermentative properties. Starch is probably the most important complex carbohydrate in short bowel syndrome nutrition, because it is absorbed or fermented almost completely. Benefits of supplementation with complex carbohydrates include improved adaptive processes, positive trophic effects on the mucosa and its hormonal response, longer transit time, and possibly a faster time to wean from parenteral nutrition, but supplementation advice needs to weigh carefully the risks and benefits, especially considering bacterial overgrowth, osmotic load, and D‐lactate acidosis.
Molecular Regulations of Mucosal Maltase Expressions
Authors: Goda Toshinao , Honma Kazue
Published: May 2018

Two major α‐glucosidase (maltase) genes, sucrase‐isomaltase (SI) and maltase‐glucoamylase (MGAM), respectively, are expressed in the small intestine. In this review, we have summarized whether jejunal expression of these maltase genes is regulated by dietary manipulations, which may affect carbohydrate availability from the luminal side, through changes in the binding of transcription factors and/or histone code on these genes. Studies using a model of mice fed either a low‐starch or a high‐starch diet for 7 days, found the mRNA levels of SI, MGAM, and Na+‐glucose cotransporter (SGLT1) genes in the jejunum to be increased in parallel by feeding a high‐starch diet. Chromatin immunoprecipitation assays, using jejunal tissue of mice and rats fed a high‐starch diet, revealed that the diet increased the acetylations of histones H3 and H4, bindings of coactivators, including general control of amino acid synthesis (GCN5) and the transcriptional factors, including caudal‐related homeobox 2 (CDX2), and hepatocyte nuclear factor 1 (HNF1), not only in the promoter/enhancer regions, but also in the transcribed regions of SI and MGAM genes. Feeding rats a diet rich in resistant starch led to a concomitant reduction of mRNA levels of the MGAM gene and histone H3 modifications (acetylations and di‐/tri‐methylations) in the jejunum. These data suggest that a signal elicited by available glucose in the jejunal mucosa is associated with SI and MGAM gene expressions through a histone code, such as acetylation and di‐/tri‐methylations of histone H3 in the promoter/enhancer and transcribed regions of SI and MGAM genes.
Recent Advances in the Diagnosis and Pathogenesis of Neurofibromatosis Type 1 (NF1)-associated Peripheral Nervous System Neoplasms
Authors: Longo Jody F. , Weber Shannon M. , Turner-Ivey Brittany P. , Carroll Steven L.
Published: May 2018

The diagnosis of a neurofibroma or a malignant peripheral nerve sheath tumor (MPNST) often raises the question of whether the patient has the genetic disorder neurofibromatosis type 1 (NF1) as well as how this will impact the patient’s outcome, what their risk is for developing additional neoplasms and whether treatment options differ for NF1-associated and sporadic peripheral nerve sheath tumors. Establishing a diagnosis of NF1 is challenging as this disorder has numerous neoplastic and non-neoplastic manifestations which are variably present in individual patients. Further, other genetic diseases affecting the Ras signaling cascade (RASopathies) mimic many of the clinical features of NF1. Here, we review the clinical manifestations of NF1 and compare and contrast them with those of the RASopathies. We also consider current approaches to genetic testing for germline NF1 mutations. We then focus on NF1-associated neurofibromas, considering first the complicated clinical behavior and pathology of these neoplasms and then discussing our current understanding of the genomic abnormalities that drive their pathogenesis, including the mutations encountered in atypical neurofibromas. As several neurofibroma subtypes are capable of undergoing malignant transformation to become MPNSTs, we compare and contrast patient outcomes in sporadic, NF1-associated and radiation-induced MPNSTs, and review the challenging pathology of these lesions. The mutations involved in neurofibroma-MPNST progression, including the recent identification of mutations affecting epigenetic regulators, are then considered. Finally, we explore how our current understanding of neurofibroma and MPNST pathogenesis is informing the design of new therapies for these neoplasms.
Quality and Safety in Health Care, Part XLI
Authors: Harolds Jay A.
Published: May 2018

The IMPACT Registry is a repository of information for heart catheterizations for congenital heart disease regardless of age and also the catheterizations for acquired heart disease in children. The registry collects information on outcomes, provides quality improvement opportunities for participants, provides reports to participants comparing their results with national results, compares the volume of catheter work done at an institution with the frequency of adverse events, and provides information that may be helpful in evaluating the use of medical devices and treatment options.
Quality and Safety in Health Care, Part XL
Authors: Harolds Jay A.
Published: May 2018

Percutaneous coronary interventions (PCI) are done for a variety of indications. Data from the CathPCI Registry is highly useful to evaluate the outcomes from performing a PCI procedure in unusual circumstances, such as in cases of chronic total coronary artery occlusion, cardiogenic shock after a myocardial infarction, syncopal patients, asymptomatic patients, and before surgery that is noncardiac. Registry information is also valuable in evaluating the efficacy of coronary stents. This article summarizes some of the information available on these subjects.
Acute Pancreatitis Following Peptide Receptor Radionuclide Therapy
Authors: Karfis Ioannis , Marin Gwennaëlle , Machiels Godelieve , Hendlisz Alain , Flamen Patrick
Published: May 2018

A 54-year-old man with grade 2 rectal neuroendocrine tumor and hepatic, pancreatic, and bone metastases was treated with 177Lu-DOTATATE as second-line therapy, after failure of somatostatin analogues. Two weeks after the first injection, he presented at the emergency department with acute pancreatitis. We hypothesized that this unusual adverse event, never been reported so far, was the result of acute tumor irradiation after PRRT, leading to peritumoral inflammation and edema with obstruction of an accessory pancreatic duct.
Growth Plate Suppression in an Adolescent Patient With Acute Lymphoblastic Leukemia After Treatment
Authors: Tiktinsky Ekaterina , Levin Daniel , Lantsberg Sophia , Kapelushnik Joseph
Published: May 2018

Osteotoxic effect is a common adverse effect of chemotherapy for childhood acute lymphoblastic leukemia. The pathophysiology of impaired bone growth is multifactorial and can affect both osteoblast and osteoclast function. Significant contribution in affecting skeletal metabolism belongs to high-dose corticosteroid treatment. We present the case of a 12-year-old adolescent girl who was treated for high-risk pro-B acute lymphoblastic leukemia. The Tc-MDP bone scan, as a sensitive indicator of osteoblastic activity, shows that growth plate inhibition after intensive treatment may be temporary and reversible.
Diagnostic Performance of 18F-Fluciclovine in Detection of Prostate Cancer Bone Metastases
Authors: Chau Albert , Gardiner Peter , Colletti Patrick M. , Jadvar Hossein
Published: May 2018

Purpose

18F-fluciclovine is a synthetic amino acid radiotracer that has recently been approved in Europe and the United States for PET imaging in men with biochemical recurrence (BCR) of prostate cancer after prior definitive treatment. Accurate identification of the sites of disease in patients presenting with BCR of prostate cancer is important in determining the appropriate treatment. Bone is the most frequent site of metastatic disease in patients with prostate cancer.

Methods

We conducted a comprehensive review of the available preclinical and clinical data on the diagnostic performance of 18F-fluciclovine PET/CT in an attempt to draw practical and general conclusions on the utility and limitations of 18F-fluciclovine PET/CT in localization of osseous metastatic disease in prostate cancer.

Results

The cumulative preclinical data and results of some retrospective and 2 prospective clinical studies suggest that 18F-fluciclovine can detect early bone marrow involvement in patients with BCR of prostate cancer and negative prior bone-specific imaging findings.

Conclusions

18F-fluciclovine PET/CT seems to offer useful information for early detection of bone metastases in men with BCR of prostate cancer. Additional investigations will be needed to compare the diagnostic performance of 18F-fluciclovine PET/CT to other standard and novel imaging methods in initial staging, BCR, and castrate-resistant phases of disease.
Primary Congenital Lymphedema
Authors: Mrhac Lubomir , Bukovansky Kamil , Kafkova Jana , Kraft Otakar
Published: May 2018

We present the case of a 26-year-old man with congenital primary lymphedema. A lymphedema of the right upper limb appeared at the age of 2 years, followed by edemas of the right lower limb and of the right part of the head and neck. A lymphedema of the left lower limb began 5 years ago, and finally an edema of the external genitalia began 2 years ago. Lymphoscintigraphy of the lower limbs and pelvic/abdominal region (including SPECT/ldCT) revealed interesting abnormalities.
Preoperative Analysis of Venous Anatomy Before Deep Inferior Epigastric Perforator Free-Flap Breast Reconstruction Using Ferumoxytol-enhanced Magnetic Resonance Angiography
Authors: Dortch John , Forte Antonio J. , Bolan Candice , Kandel Pujan , Perdikis Galen
Published: May 2018

Background

Venous congestion after deep inferior epigastric artery perforator (DIEP) flap breast reconstruction is a complication that may be partially attributable to variations in venous abdominal wall anatomy. In previous work, we have shown that ferumoxytol may be used as a bloodpool contrast agent to perform high-resolution venous imaging. Our current aim was to use this technology to perform a detailed analysis of the venous anatomy among patients undergoing DIEP flap breast reconstruction.

Methods

All patients undergoing DIEP flap reconstruction with preoperative ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) were retrospectively reviewed. A detailed anatomic analysis of each abdominal wall on FE-MRAwas performed before review of operative findings. Statistical analysis was used to determine venous characteristics associated with superficial inferior epigastric vein (SIEV) augmentation.

Results

From 2012 to 2016, 59 patients underwent preoperative FE-MRA. This resulted in imaging for 118 hemiabdomen and 99 flaps. Superficial-deep communication was identified in 117 of 118 hemiabdomen. Fifty (93%) of 59 patients had greater than 1-mm venous communication of the superficial system across midline. Reconstructed breasts were based on dominant medial row perforators in 82 (83%) of 99 flaps. The mean diameters of the SIEVand dominant venous perforator were 3.8 and 2.8mm, respectively. Anatomic characteristics associated with SIEVaugmentation included SIEVdiameter (P = 0.01), dominant perforator diameter (P = 0.04), and the ratio between these 2 variables (P = 0.001).

Conclusions

Ferumoxytol-enhanced magnetic resonance angiography provides excellent imaging of the venous system. Anatomic characteristics such as the diameter of the SIEVand the diameter of the dominant perforator may be useful in determining which flaps require venous augmentation using the SIEV.
Primary Premaxillary Ostectomy and Setback
Authors: Farhadi Rana , Wallace Robert D.
Published: May 2018

Objective

This study aimed to analyze our outcomes of primary premaxillary ostectomy and setback combined with lip adhesion as the first stage in repair of the bilateral cleft lip with fly-away premaxilla.

Methods

This retrospective study included all patients who required primary premaxillary setback by a single surgeon to achieve successful lip repair between 2011 and 2017 at a tertiary children's hospital. All patients had bilateral cleft lip and complete cleft palate with significant premaxillary protrusion. All patients either had failed presurgical orthodontic manipulation or were thought to be poor candidates because of the rigidity of the premaxilla on clinical examination. Patient data were obtained from review of medical records and photographs. Surgical technique is described.

Results

Eleven patients with bilateral cleft lip, all of whom also had complete cleft palate, underwent primary premaxillary setback and lip adhesion at an average age of 8.2 months. The mean follow-up was 1.9 years (range, 139 days to 4.5 years). All patients subsequently completed formal lip repair, of which 10 have undergone palatoplasty. Serial photography documented stable premaxillary position and successful lip repair within the follow-up time frame. No patient had postoperative premaxillary instability or vascular compromise. One patient had dehiscence of the lip adhesion requiring reoperation.

Conclusions

Primary premaxillary ostectomy and setback allows for successful staged formal lip repair in patients with bilateral cleft lip and palate who have failed presurgical infant orthopedics. Further research is required regarding longterm follow-up with respect to midfacial growth.
Endoscopically Assisted Modified Caldwell-Luc Approach to Enucleation of Dentigerous Cyst With Ectopic Tooth From the Maxillary Sinus
Authors: Liau Isaac , Lynch Nicholas , Hearn Brenton , Cheng Andrew
Published: May 2018

Dentigerous cysts in the craniomaxillofacial complex are a benign pathology commonly associated with ectopically placed teeth. Owing to slow and asymptomatic growth, they often attain considerable size before diagnosis that may compromise adjacent anatomical structures. Various techniques for removal of dentigerous cysts from the maxillary sinus have been described. This case report demonstrates a hybrid endoscopically assisted modification of the Caldwell-Luc approach to provide the technical advantages of both techniques
Maternal Folic Acid Supplementation and the Risk of Oral Clefts in Offspring
Authors: Jahanbin Arezoo , Shadkam Elaheh , Miri Hamid Heidarian , Shirazi Alireza Sarraf , Abtahi Mostafa
Published: May 2018

Introduction:

There is controversial evidence from the literature regarding the protective effect of folic acid supplementation during pregnancy against orofacial clefts. The authors undertook this meta-analysis to assess whether folate supplementation during pregnancy can reduce the risk of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO) in infants.

Methods:

Eligible articles were identified by searching databases, including PubMed, Medline, Scopus, ISI (Web of Knowledge) to September 2017. A meta-analysis was performed to evaluate the effects of maternal supplementation on oral clefts. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using Stata software. Publication bias was assessed by the Begg and Egger test. (Registration ID: CRD42018083922)

Results:

Out of the 1630 articles found in the authors’ initial literature searches, 6 cohort studies, and 31 case-control studies were included in the authors’ final meta-analysis. The results of the main analysis revealed that maternal folate supplementation was associated with a modest but statically significant decreased risk of all cleft subtypes (OR = 0.69, 95% CI: 0.60, 0.78). Folic acid intake alone was inversely associated with CL/P (OR = 0.73, 95% CI: 0.62–0.85,) but to a lesser extent than CPO (OR = 0.75, 95% CI = 053–1.04). Multivitamin intake had a significant protective effect for CL/P (OR = 0.65 95% CI = 0.55–0.80) as well as CPO (OR = 0.69, 95% CI = 0.53–0.90).

Conclusions:

Our results indicate that maternal supplementation in early pregnancy reduces the risk of nonsyndromic CL/P and CPO in infants. These data can serve to reassure women planning a pregnancy to consume multivitamins during the periconception period to protect against oral clefts.
Nodular Tenosynovitis of the Temporomandibular Joint: An Entity Not Yet Described
Authors: Cariati Paolo , Garcia-Martin Miguel , Perez de Perceval Tara Miguel , Roman Ramos Maria , Garcia Medina Blas
Published: May 2018

Nodular tenosynovitis usually affects the hands and it represents a benign pathology with locally aggressive behavior. Its etiology could be related to chronic inflammatory processes such as trauma, metabolic disturbance, and joint diseases. Histopathological analysis is required for a diagnosis of certainty and surgery represents the treatment of choice. There are no cases in the literature that describe a nodular tenosynovitis affecting the temporomandibular joint (TMJ) The main aim of the present report therefore, is to describe this unusual case and to show the utility of arthroscopic procedures in managing intra-articular tumors of the TMJ.
Rare Location for Pilonidal Sinus: the Nasal Dorsum
Authors: Kars Ayhan , Atalay Fatma , Kilic Korhan , Bingöl Fatih , Can Yusuf
Published: May 2018

Pilonidal sinuses are recurrent chronic inflammatory lesions which may occur due to penetration of hair particles into skin. Herein, the authors report a pilonidal sinus case that is unusually seen on nasal dorsum and totally excised with the open technique rhinoplasty method. A 20-year-old male patient was admitted to the authors’ outpatient clinic with complaints of dysmorphism and discharge from nasal dorsum. Physical examination revealed a swelling in nasal dorsum and hair-containing fistula. Excision was performed with an open rhinoplasty approach. Histo-pathology examination revealed pilonidal sinus. While pilonidal sinus is usually located in sacro-coccygeal region, it may also be seen in atypical localizations like nasal dorsum. Although the prediagnosis of a hair-containing lesion usually includes dermoid cyst, pilonidal sinus should also be considered and histo-pathological examination should certainly be performed. It is a problematic condition when it is symptomatic; however, management and treatment of the disease is easy when correct diagnosis is made.
Treatment of Craniosynostosis: The Impact of Hospital Surgical Volume on Cost, Resource Utilization, and Outcomes
Authors: Chattha Anmol , Bucknor Alexandra , Curiel Daniel A. , Ultee Klaas H.J. , Afshar Salim , Lin Samuel J.
Published: May 2018

The authors aim to quantify the impact of hospital volume of craniosynostosis surgery on inpatient complications and resource utilization using national data. Children <12 months with nonsyndromic craniosynostosis who underwent surgery in 2012 at academic hospitals in the United States were identified from the Kids’ Inpatient Database (KID) developed by the Healthcare Cost and Utilization Project (HCUP). Hospital craniosynostosis surgery volume was stratified into tertiles based on total annual hospital cases: low volume (LV, 1–13), intermediate volume (IV, 14–34), and high volume (HV, ≥35). Outcomes of interest include major complications, blood transfusion, charges, and length of stay (LOS). In 2012, 154 hospitals performed 1617 total craniosynostosis surgeries. Of these 580 cases (35.8%) were LV, 549 cases (33.9%) were IV, and 488 cases (30.2%) were HV. There was no difference in major complications between hospital volume tertiles (4.3% LV; 3.8% IV; 3.1% HV; P = 0.487). The highest blood transfusion rates were seen at LV hospitals (47.8% LV; 33.9% IV; 26.2%; P < 0.001). Hospital charges were lowest at HV hospitals ($55,839) compared with IV hospitals ($65,624; P < 0.001) and LV hospitals ($62,325; P = 0.005). Mean LOS was shortest at HV hospitals (2.96 days) compared with LV hospitals (3.31 days; P = 0.001); however, there was no difference when compared with IV hospitals (3.07 days; P = 0.282). Hospital case volume may be an important associative factor of blood transfusion rates, LOS, and hospital charges; however, there is no difference in complication rates. These results may be used to guide quality improvement within the surgical management of craniosynostosis.
Alzheimer's disease neuroimaging
Authors: Whitwell Jennifer L.
Published: May 2018

Purpose of review

The aim of this study was to discuss the contribution of neuroimaging studies to our understanding of Alzheimer's disease. We now have the capability of measuring both tau and beta-amyloid (Aβ) proteins in the brain, which together with more traditional neuroimaging modalities, has led the field to focus on using neuroimaging to better characterize disease mechanisms underlying Alzheimer's disease.

Recent findings

Studies have utilized tau and Aβ PET, as well as [18F]fluorodeoxyglucose PET, and structural and functional MRI, to investigate the following topics: phenotypic variability in Alzheimer's disease , including how neuroimaging findings are related to clinical phenotype and age; multimodality analyses to investigate the relationships between different neuroimaging modalities and what that teaches us about disease mechanisms; disease staging by assessing neuroimaging changes in the very earliest phases of the disease in cognitively normal individuals and individuals carrying an autosomal dominant Alzheimer's disease mutation; and influence of other comorbidities and proteins to the disease process.

The findings shed light on the role of tau and Aβ, as well as age and other comorbidities, in the neurodegenerative process in Alzheimer's disease. This knowledge will be crucial in the development of better disease biomarkers and targeted therapeutic approaches.
A web bench for analysis and prediction of oncological status from proteomics data of urine samples
Authors: Bhalla Sherry , Chaudhary Kumardeep , Gautam Ankur , Sharma Suresh , Raghava Gajendra P. S.
Published: May 2018

Urine-based cancer biomarkers offer numerous advantages over the other biomarkers and play a crucial role in cancer management. In this study, an attempt has been made to develop proteomics-based prediction models to discriminate patients of oncological disorders related to urinary tract and healthy controls from their urine samples. The dataset used in this study was obtained from human urinary peptide database that contains urine proteomics data of 1525 oncological and 1503 healthy controls with the spectral intensity of 5605 peptides. First, we identified peptide spectra using various feature selection techniques, which display different intensity and occurrence in oncological samples and healthy controls. Based on selected 173 peptide-based biomarkers, we developed models for predicting oncological samples and achieved maximum accuracy of 91.94% with 0.84 MCC. Prediction models were also developed based on spectral intensities with known peptide sequences. We also quantitated the amount of protein in a sample based on intensities of its fragments/peptides and developed prediction models based on protein expression. It was observed that certain proteins and their peptides such as fragments of collagen protein are more abundant in oncological samples. Based on this study, we also developed a web bench, CancerUBM, for mining proteomics data, which is freely available athttp://webs.iiitd.edu.in/raghava/cancerubm/.
Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer
Authors: Shinde Aparna , Wilmanski Tomasz , Chen Hao , Teegarden Dorothy , Wendt Michael K.
Published: May 2018

Background: Overcoming systemic dormancy and initiating secondary tumor grow under unique microenvironmental conditions is a major rate-limiting step in metastatic progression. Disseminated tumor cells encounter major changes in nutrient supplies and oxidative stresses compared to the primary tumor and must demonstrate significant metabolic plasticity to adapt to specific metastatic sites. Recent studies suggest that differential utilization of pyruvate sits as a critical node in determining the organotropism of metastatic breast cancer. Pyruvate carboxylase (PC) is key enzyme that converts pyruvate into oxaloacetate for utilization in gluconeogenesis and replenishment of the TCA cycle.

Methods: Patient survival was analyzed with respect to gene copy number alterations and differential mRNA expression levels of PC. Expression of PC was analyzed in the MCF-10A, D2-HAN and the 4T1 breast cancer progression series under in vitro and in vivo growth conditions. PC expression was depleted via shRNAs and the impact on in vitro cell growth, mammary fat pad tumor growth, and pulmonary and non-pulmonary metastasis was assessed by bioluminescent imaging. Changes in glycolytic capacity, oxygen consumption and response to oxidative stress were quantified upon PC depletion.

Results: Genomic copy number increases in PC were observed in 16-30% of metastatic breast cancer patients. High expression of PC mRNA was associated with decreased patient survival in the MCTI and METABRIC patient datasets. Enhanced expression of PC was not recapitulated in breast cancer progression models when analyzed under glucose-rich in vitro culture conditions. In contrast, PC expression was dramatically enhanced upon glucose deprivation and in vivo in pulmonary metastases. Depletion of PC led to a dramatic decrease in 4T1 pulmonary metastasis but did not affect orthotopic primary tumor growth. Tail vein inoculations confirmed the role of PC in facilitating pulmonary, but not extra-pulmonary tumor initiation. PC-depleted cells demonstrated a decrease in glycolytic capacity and oxygen consumption rates and an enhanced sensitivity to oxidative stress.

Conclusions: Our studies indicate that PC is specifically required for the growth of breast cancer that has disseminated to the lungs. Overall, these findings point to the potential of targeting PC for the treatment of pulmonary metastatic breast cancer.
MTL functional connectivity predicts stimulation-induced theta power
Authors: Solomon E. A. , Gross R. , Lega B. , Sperling M. R. , Worrell G. , Sheth S. A. , Zaghloul K. A. , Jobst B. C. , Stein J. M. , Das S. , Gorniak R. , Inman C. , Seger S. , Kragel J. E. , Rizzuto D. S. , Kahana M. J.
Published: May 2018

Abstract/Summary

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked changes in theta (5-8 Hz) power, but only when stimulation was applied in or adjacent to white matter. Furthermore, these power changes aligned with control-theoretic predictions of how exogenous stimulation flows through complex networks, such as a dispersal of induced activity when functional hubs are targeted. Our results demonstrate that functional connectivity is predictive of causal changes in the brain, but that access to structural connections is necessary to observe such effects.
The Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease
Authors: Noronha Alberto , Modamio Jennifer , Jarosz Yohan , Sompairac Nicolas , Gonzàlez German Preciat , Daníelsdóttir Anna Dröfn , Krecke Max , Merten Diane , Haraldsdóttir Hulda S. , Heinken Almut , Heirendt Laurent , Magnúsdóttir Stefanía , Ravcheev Dmitry A. , Sahoo Swagatika , Gawron Piotr , Guerard Elisabeth , Fiscioni Lucia , Garcia Beatriz , Prendergast Mabel , Puente Alberto , Rodrigues Mariana , Roy Akansha , Rouquaya Mouss , Wiltgen Luca , Alise Žagare Alise , John Elisabeth , Krueger Maren , Kuperstein Inna , Zinovyev Andrei , Schneider Reinhard , Fleming Ronan M.T. , Thiele Ines
Published: May 2018

A multitude of factors contribute to complex diseases and can be measured with “omics” methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH,http://vmh.life)database encapsulating current knowledge of human metabolism within five interlinked resources “Human metabolism”, “Gut microbiome”, “Disease”, “Nutrition”, and “ReconMaps”. The VMH captures 5,180 unique metabolites, 17,730 unique reactions, 3,288 human genes, 255 Mendelian diseases, 818 microbes, 632,685 microbial genes, and 8,790 food items. The VMH’s unique features are i) the hosting the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; ii) seven human metabolic maps for data visualization; iii) a nutrition designer; iv) a user-friendly webpage and application-programming interface to access its content; and v) user feedback option for community engagement. We demonstrate with four examples the VMH’s utility. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community.
Estimating Optimal Lysogenic Propensity for Viruses in Stressed Environments
Authors: Thakkar Devang , Saini Supreet
Published: May 2018

Having infected a bacterial cell, a temperate phage has to make a choice between (a) integrating itself into the bacterial genome, i.e.lysogeny, and (b) using the bacterial machinery to create multiple copies of itself and lysing the cell in the process, i.e.lysis. In order to maximize its long-term growth rate, phages need to ensure that they do not wipe off their bacterial hosts. Temperate phages have been observed to exhibit lysogenic propensities dependent on theMoI(Multiplicity of Infection), among other factors. We propose a model to estimate the propensity of lysogeny opted for by the phages in order to maximize coexistence. One possible approach to do so is to adopt a strategy that would help to attain and maintain an approximately equal proportion of phages with respect to their host. We find that the optimal fraction of phages opting for lysogeny follows a sigmoidal relationship with theMoIand is comparable to results obtained experimentally. We further assess the impact of phage and bacterial environmental stresses on the lysogenic propensity. Our results indicate that the optimal value of lysogenic propensity is greatly dependent on the intensity of these stresses.
Systems Biology Inferring edge function in protein-protein interaction networks
Authors: Esposito Daniel , Cursons Joseph , Davis Melissa
Published: May 2018

Motivation: Post-translational modifications (PTMs) regulate many key cellular processes. Numerous studies have linked the topology of protein-protein interaction (PPI) networks to many biological phenomena such as key regulatory processes and disease. However, these methods fail to give insight in the functional nature of these interactions. On the other hand, pathways are commonly used to gain biological insight into the function of PPIs in the context of cascading interactions, sacrificing the coverage of networks for rich functional annotations on each PPI. We present a machine learning approach that uses Gene Ontology, InterPro and Pfam annotations to infer the edge functions in PPI networks, allowing us to combine the high coverage of networks with the information richness of pathways.

Results: An ensemble method with a combination Logistic Regression and Random Forest classifiers trained on a high-quality set of annotated interactions, with a total of 18 unique labels, achieves high a average F1 score 0.88 despite not taking advantage of multi-label dependencies. When applied to the human interactome, our method confidently classifies 62% of interactions at a probability of 0.7 or higher.

Availability: Software and data are available at https://github.com/DavisLaboratory/pyPPI

Contact:davis.m@wehi.edu.au

Supplementary information: Supplementary data are available at Bioinformatics online.
Genome-wide analysis of genetic predisposition to Alzheimer’s disease and related sex-disparities
Authors: Nazarian Alireza , Yashin Anatoliy I. , Kulminski Alexander M.
Published: May 2018

Background

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly and the sixth leading cause of death in the United States. AD is mainly considered a complex disorder with polygenic inheritance. Despite discovering many susceptibility loci, a major proportion of AD genetic variance remains to be explained.

Methods

We investigated the genetic architecture of AD in four publicly available independent datasets through genome-wide association, transcriptome-wide association, and gene-based analyses. To explore differences in the genetic basis of AD between males and females, analyses were performed on three samples in each dataset: males and females combined, only males, or only females.

Results

Our genome-wide association analyses corroborated the associations of several previously detected AD loci and revealed novel significant associations of 54 single-nucleotide polymorphisms (SNPs) at a p-value of < 5E-06. In addition, 23 genes located outside the chromosome 19q13 region showed suggestive associations with AD at a false discovery rate of 0.05 in transcriptome-wide association and gene-based analyses. Most of the newly detected AD-associated SNPs and genes were sex specific, indicating sex disparities in the genetic basis of AD.

Conclusions

Our findings, particularly the newly discovered sex-specific genetic contributors, provide novel insight into the genetic architecture of AD and can advance our understanding of its pathogenesis.
Understanding psychophysiological interaction and its relations to beta series correlation
Authors: Di Xin , Zhang Zhiguo , Biswal Bharat B
Published: May 2018

Psychophysiological interaction (PPI) was proposed 20 years ago for study of task modulated connectivity on functional MRI (fMRI) data. A few modifications have since been made, but there remain misunderstandings on the method, as well as on its relations to a similar method named beta series correlation (BSC). Here, we explain what PPI measures and its relations to BSC. We first clarify that the interpretation of a regressor in a general linear model depends on not only itself but also on how other effects are modeled. In terms of PPI, it always reflects differences in connectivity between conditions, when the physiological variable is included as a covariate. Secondly, when there are multiple conditions, we explain how PPI models calculated from direct contrast between conditions could generate identical results as contrasting separate PPIs of each condition (a.k.a. “generalized” PPI). Thirdly, we explicit the deconvolution process that is used for PPI calculation, and how is it related to the trial-by-trial modeling for BSC, and illustrate the relations between PPI and those based upon BSC. In particular, when context sensitive changes in effective connectivity are present, they manifest as changes in correlations of observed trial-by-trial activations or functional connectivity. Therefore, BSC and PPI can detect similar connectivity differences. Lastly, we report empirical analyses using PPI and BSC on fMRI data of an event-related stop signal task to illustrate our points.
Differential integration of transcriptome and proteome identifies pan-cancer prognostic biomarkers
Authors: Schwartz Gregory W. , Petrovic Jelena , Zhou Yeqiao , Faryabi Robert B.
Published: May 2018

High-throughput analysis of the transcriptome and proteome individually are used to interrogate complex oncogenic processes in cancer. However, an outstanding challenge is how to combine these complementary, yet partially disparate data sources to accurately identify tumor-specific gene-programs and clinical biomarkers. Here, we introduceinteGREATfor robust and scalable differential integration of high-throughput measurements. WithinteGREAT, each data source is represented as a co-expression network, which is analyzed to characterize the local and global structure of each node across networks.inteGREATscores the degree by which the topology of each gene in both transcriptome and proteome networks are conserved within a tumor type, yet different from other normal or malignant cells. We demonstrated the high performance ofinteGREATbased on several analyses: deconvolving synthetic networks, rediscovering known diagnostic biomarkers, establishing relationships between tumor lineages, and elucidating putative prognostic biomarkers which we experimentally validated. Furthermore, we introduce the application of a clumpiness measure to quantitatively describe tumor lineage similarity. Together,inteGREATnot only infers functional and clinical insights from the integration of transcriptomic and proteomic data sources in cancer, but also can be readily applied to other heterogeneous high-throughput data sources.inteGREATis open source and available to download fromhttps://github.com/faryabib/inteGREAT.