bluuebunny/crossref_metadata_2025 huggingface dataset:
Virological and serological tools to optimize the management of patients with chronic hepatitis B
Authors: Martinot‐Peignoux Michelle , Marcellin Patrick
Published: January 2016

Molecular biology techniques are routinely used to diagnose and monitor treatment in patients with chronic hepatitis B (CHB). These tools can detect and quantify viral genomes and analyse their sequences to determine genotype. The increasing use of these tools to monitor patients has greatly improved the management of CHB infection by maximizing the potential for individualized treatment. HBV genotyping has become increasingly important and provides additional information to predict a response to therapy. More sensitive methods to determine HBV DNA levels are now available and the units of measurements have been standardized. HBsAg levels in serum have been shown to reflect active intrahepatic covalently closed circular DNA (cccDNA) and to have additional value in treatment decisions, especially as an on‐treatment marker.
Chronic HBV: which pregnant women should be treated?
Authors: He Tianyu , Jia Jidong
Published: January 2016

Universal HBV vaccination in infants has led to a dramatic decline of HBsAg prevalence in many parts of the world, but the positive rate of HBsAg in women of childbearing age is still high in endemic areas. Antiviral therapy during pregnancy may be indicated to control the liver disease of the mother or to prevent the MTCT. The decision on initiation, switching, continuation or stopage of the antiviral therapy should be made after careful consideration of the benefit and risk to both mothers and foetuses. For prepregnant women of childbearing age, a finite course of interferon is preferred if a pregnancy in the distant future is planned, whereas safer NAs could be started if a pregnancy in the near future is desired. For those who already started therapy with interferon or NAs before pregnancy, the switch to safer NAs is preferred. For women with newly diagnosed or with flare of CHB during pregnancy, category B NAs may be taken to treat their liver disease. For pregnant women with serum HBV DNA >106–7IU/ml, safer NAs could be started in the third trimester to further the reduce MTCT rate.
Universal screening for chronic hepatitis C virus
Authors: Shiffman Mitchell L.
Published: January 2016

Chronic hepatitis C virus (HCV) infection affects an estimated 123 million persons worldwide and is the leading cause of cirrhosis and hepatocellular carcinoma in most countries. Approximately 75% of persons with chronic HCV were born between the years 1945–1965 and screening of patients in this birth cohort is now advocated. Unfortunately, these recommendations are not readily applied and a sizable population of infected persons who could benefit from treatment fall outside the birth cohort. Universal screening for HCV would be optimal. However, the primary limitation once patients are identified is accessing treatment which remains restricted in most countries.
Management of uninfected and infected ascites in cirrhosis
Authors: Solà Elsa , Solé Cristina , Ginès Pere
Published: January 2016

Ascites is the most frequent complication of patients with cirrhosis. Ascites is related to increased renal sodium retention as a result of increased activity of the renin–angiotensin–aldosterone system in response to marked vasodilation of the splanchnic circulation. Management of uncomplicated ascites is based on a low‐sodium diet and diuretics. However, approximately 10% of patients develop refractory ascites during follow‐up, which is associated with a poor prognosis. The treatment of choice in patients with refractory ascites is large‐volume paracentesis associated with intravenous albumin. Moreover, patients who develop refractory ascites should be considered as candidates for liver transplantation. Patients with ascites are all at risk of developing spontaneous bacterial peritonitis (SBP). SBP is a common infection in patients with cirrhosis with a risk of mortality of 20%. Empirical antibiotics are the treatment of choice in patients with SBP but differ depending on the acquisition site of infection, because nosocomial infections have a higher risk of being caused by multiresistant bacteria. In addition to antibiotic treatment, all patients with SBP should also receive intravenous albumin. This review summarizes the management of uninfected ascites and SBP in cirrhosis.
Estimation of a Two-component Mixture Model with Applications to Multiple Testing
Authors: Patra Rohit Kumar , Sen Bodhisattva
Published: January 2016

We consider a two-component mixture model with one known component. We develop methods for estimating the mixing proportion and the unknown distribution non-parametrically, given independent and identically distributed data from the mixture model, using ideas from shape-restricted function estimation. We establish the consistency of our estimators. We find the rate of convergence and asymptotic limit of the estimator for the mixing proportion. Completely automated distribution-free honest finite sample lower confidence bounds are developed for the mixing proportion. Connection to the problem of multiple testing is discussed. The identifiability of the model and the estimation of the density of the unknown distribution are also addressed. We compare the estimators proposed, which are easily implementable, with some of the existing procedures through simulation studies and analyse two data sets: one arising from an application in astronomy and the other from a microarray experiment.
International Migration and Child labour in Developing Countries
Authors: De Paoli Anna , Mendola Mariapia
Published: January 2016

This paper investigates the labor market effect of international migration on child work in countries of origin. We use an original cross‐country survey dataset, which combines information on international migration with detailed  individual‐level data on child labour at age 5–14 in a wide range of developing countries. By exploiting both within and cross‐country variation and controlling for country fixed effects, we find strong and robust evidence on the role of international mobility of workers in reducing child labour in disadvantaged households through changes in the local labour market.
Precise stellar surface gravities from the time scales of convectively driven brightness variations
Authors: Kallinger Thomas , Hekker Saskia , García Rafael A. , Huber Daniel , Matthews Jaymie M.
Published: January 2016

Researchers measure precise stellar surface gravity through the characteristic time scale of the combined granulation and oscillation signal.
A wearable multiplexed silicon nonvolatile memory array using nanocrystal charge confinement
Authors: Kim Jaemin , Son Donghee , Lee Mincheol , Song Changyeong , Song Jun-Kyul , Koo Ja Hoon , Lee Dong Jun , Shim Hyung Joon , Kim Ji Hoon , Lee Minbaek , Hyeon Taeghwan , Kim Dae-Hyeong
Published: January 2016

An ultrathin, stretchable memory skin patch that can reliably store bio-signals such as heart rate is newly developed.
Shear deformation of bridgmanite and magnesiowüstite aggregates at lower mantle conditions
Authors: Girard Jennifer , Amulele George , Farla Robert , Mohiuddin Anwar , Karato Shun-ichiro
Published: January 2016

Mantle minerals won't share the strain

The deformation of a mixed block of material depends on the strength of the components of which it is made. Weak materials will deform more than the strong ones in a mixture that is squished or stretched. Girard
et al.
find a large difference in strength between the two primary minerals making up Earth's lower mantle (see the Perspective by Chen). Deformation in the convecting mantle may occur only near boundary layers as a result, leaving large regions potentially unaffected. This could explain long-lived chemical reservoirs in Earth's interior and the lack of seismic anisotropy in the lower mantle.

Science
, this issue p.
144
; see also p.
122
Photonic chip–based optical frequency comb using soliton Cherenkov radiation
Authors: Brasch V. , Geiselmann M. , Herr T. , Lihachev G. , Pfeiffer M. H. P. , Gorodetsky M. L. , Kippenberg T. J.
Published: January 2016

Timing on a chip

Laser-induced optical frequency combs allow precision measurements and affect a broad range of technologies. Brasch
et al.
generated optical frequency combs on an optical chip (see the Perspective by Akhmediev and Devine). They induced an optical soliton, or optical bullet, and propagated it in an engineered microcavity waveguide. The emitted output light formed a coherent comb of frequencies spanning two-thirds of an octave. Such an on-chip demonstration bodes well for miniaturization of metrological technology and its adaption for widespread application.

Science
, this issue p.
357
; see also p.
340
In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy
Authors: Nelson Christopher E. , Hakim Chady H. , Ousterout David G. , Thakore Pratiksha I. , Moreb Eirik A. , Rivera Ruth M. Castellanos , Madhavan Sarina , Pan Xiufang , Ran F. Ann , Yan Winston X. , Asokan Aravind , Zhang Feng , Duan Dongsheng , Gersbach Charles A.
Published: January 2016

Editing can help build stronger muscles

Much of the controversy surrounding the gene-editing technology called CRISPR/Cas9 centers on the ethics of germline editing of human embryos to correct disease-causing mutations. For certain disorders such as muscular dystrophy, it may be possible to achieve therapeutic benefit by editing the faulty gene in somatic cells. In proof-of-concept studies, Long
et al.
, Nelson
et al.
, and Tabebordbar
et al.
used adeno-associated virus-9 to deliver the CRISPR/Cas9 gene-editing system to young mice with a mutation in the gene coding for dystrophin, a muscle protein deficient in patients with Duchenne muscular dystrophy. Gene editing partially restored dystrophin protein expression in skeletal and cardiac muscle and improved skeletal muscle function.

Science
, this issue p.
400
, p.
403
, p.
407
In vivo gene editing in dystrophic mouse muscle and muscle stem cells
Authors: Tabebordbar Mohammadsharif , Zhu Kexian , Cheng Jason K. W. , Chew Wei Leong , Widrick Jeffrey J. , Yan Winston X. , Maesner Claire , Wu Elizabeth Y. , Xiao Ru , Ran F. Ann , Cong Le , Zhang Feng , Vandenberghe Luk H. , Church George M. , Wagers Amy J.
Published: January 2016

Editing can help build stronger muscles

Much of the controversy surrounding the gene-editing technology called CRISPR/Cas9 centers on the ethics of germline editing of human embryos to correct disease-causing mutations. For certain disorders such as muscular dystrophy, it may be possible to achieve therapeutic benefit by editing the faulty gene in somatic cells. In proof-of-concept studies, Long
et al.
, Nelson
et al.
, and Tabebordbar
et al.
used adeno-associated virus-9 to deliver the CRISPR/Cas9 gene-editing system to young mice with a mutation in the gene coding for dystrophin, a muscle protein deficient in patients with Duchenne muscular dystrophy. Gene editing partially restored dystrophin protein expression in skeletal and cardiac muscle and improved skeletal muscle function.

Science
, this issue p.
400
, p.
403
, p.
407
Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy
Authors: Long Chengzu , Amoasii Leonela , Mireault Alex A. , McAnally John R. , Li Hui , Sanchez-Ortiz Efrain , Bhattacharyya Samadrita , Shelton John M. , Bassel-Duby Rhonda , Olson Eric N.
Published: January 2016

Editing can help build stronger muscles

Much of the controversy surrounding the gene-editing technology called CRISPR/Cas9 centers on the ethics of germline editing of human embryos to correct disease-causing mutations. For certain disorders such as muscular dystrophy, it may be possible to achieve therapeutic benefit by editing the faulty gene in somatic cells. In proof-of-concept studies, Long
et al.
, Nelson
et al.
, and Tabebordbar
et al.
used adeno-associated virus-9 to deliver the CRISPR/Cas9 gene-editing system to young mice with a mutation in the gene coding for dystrophin, a muscle protein deficient in patients with Duchenne muscular dystrophy. Gene editing partially restored dystrophin protein expression in skeletal and cardiac muscle and improved skeletal muscle function.

Science
, this issue p.
400
, p.
403
, p.
407
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals
Authors: Sharma Upasna , Conine Colin C. , Shea Jeremy M. , Boskovic Ana , Derr Alan G. , Bing Xin Y. , Belleannee Clemence , Kucukural Alper , Serra Ryan W. , Sun Fengyun , Song Lina , Carone Benjamin R. , Ricci Emiliano P. , Li Xin Z. , Fauquier Lucas , Moore Melissa J. , Sullivan Robert , Mello Craig C. , Garber Manuel , Rando Oliver J.
Published: January 2016

Offspring affected by sperm small RNAs

Paternal dietary conditions in mammals influence the metabolic phenotypes of offspring. Although prior work suggests the involvement of epigenetic pathways, the mechanisms remains unclear. Two studies now show that altered paternal diet affects the level of small RNAs in mouse sperm. Chen
et al.
injected sperm transfer RNA (tRNA) fragments from males that had been kept on a high-fat diet into normal oocytes. The progeny displayed metabolic disorders and concomitant alteration of genes in metabolic pathways. Sharma
et al.
observed the biogenesis and function of small tRNA-derived fragments during sperm maturation. Further understanding of the mechanisms by which progeny are affected by parental exposure may affect human diseases such as diet-induced metabolic disorders.

Science
, this issue p.
397
, p.
391
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Authors: Chen Qi , Yan Menghong , Cao Zhonghong , Li Xin , Zhang Yunfang , Shi Junchao , Feng Gui-hai , Peng Hongying , Zhang Xudong , Zhang Ying , Qian Jingjing , Duan Enkui , Zhai Qiwei , Zhou Qi
Published: January 2016

Offspring affected by sperm small RNAs

Paternal dietary conditions in mammals influence the metabolic phenotypes of offspring. Although prior work suggests the involvement of epigenetic pathways, the mechanisms remains unclear. Two studies now show that altered paternal diet affects the level of small RNAs in mouse sperm. Chenet al.injected sperm transfer RNA (tRNA) fragments from males that had been kept on a high-fat diet into normal oocytes. The progeny displayed metabolic disorders and concomitant alteration of genes in metabolic pathways. Sharmaet al.observed the biogenesis and function of small tRNA-derived fragments during sperm maturation. Further understanding of the mechanisms by which progeny are affected by parental exposure may affect human diseases such as diet-induced metabolic disorders.

Science, this issue p.397, p.391
Draft Genome Sequences of 14 Escherichia coli Phages Isolated from Cattle Slurry
Authors: Smith R. , O’Hara M. , Hobman J. L. , Millard A. D.
Published: January 2016

The diversity of bacteriophages in slurry from dairy cows remains largely unknown. Here, we report the draft genome sequences of 14 bacteriophages isolated from dairy cow slurry using
Escherichia coli
K-12 MG1655 as a host.
Complete Genome Sequence of
Curtobacterium
sp. Strain MR_MD2014, Isolated from Topsoil in Woods Hole, Massachusetts
Authors: Mariita Richard M. , Bhatnagar Srijak , Hanselmann Kurt , Hossain Mohammad J. , Korlach Jonas , Boitano Matthew , Roberts Richard J. , Liles Mark R. , Moss Anthony G. , Leadbetter Jared R. , Newman Dianne K. , Dawson Scott C.
Published: January 2016

Here, we present the 3,443,800-bp complete genome sequence of
Curtobacterium
sp. strain MR_MD2014 (phylum
Actinobacteria
). This strain was isolated from soil in Woods Hole, MA, as part of the 2014 Microbial Diversity Summer Program at the Marine Biological Laboratory in Woods Hole, MA.
Complete Genome Sequence of
Streptomyces
sp. Strain CCM_MD2014, Isolated from Topsoil in Woods Hole, Massachusetts
Authors: Mariita Richard M. , Bhatnagar Srijak , Hanselmann Kurt , Hossain Mohammad J. , Korlach Jonas , Boitano Matthew , Roberts Richard J. , Liles Mark R. , Moss Anthony G. , Leadbetter Jared R. , Newman Dianne K. , Dawson Scott C.
Published: January 2016

Here, we present the complete genome sequence of
Streptomyces
sp. strain CCM_MD2014 (phylum
Actinobacteria
), isolated from surface soil in Woods Hole, MA. Its single linear chromosome of 8,274,043 bp in length has a 72.13% G+C content and contains 6,948 coding sequences.
Permanent Draft Genome Sequence of
Frankia
sp. Strain AvcI1, a Nitrogen-Fixing Actinobacterium Isolated from the Root Nodules of
Alnus viridis
subsp.
crispa
Grown in Canada
Authors: Swanson Erik , Oshone Rediet , Simpson Stephen , Morris Krystalynne , Abebe-Akele Feseha , Thomas W. Kelley , Tisa Louis S.
Published: January 2016

Frankia
strain AvcI1, isolated from root nodules of
Alnus viridis
subsp.
crispa
, is a member of
Frankia
lineage Ia, which is able to reinfect plants of the
Betulaceae
and
Myricaceae
families. Here, we report a 7.7-Mbp draft genome sequence with a G+C content of 72.41% and 6,470 candidate protein-encoding genes.
Complete Genome Sequence of
Southern tomato virus
Naturally Infecting Tomatoes in Bangladesh
Authors: Padmanabhan Chellappan , Zheng Yi , Li Rugang , Fei Zhangjun , Ling Kai-Shu
Published: January 2016

The complete genome sequence of a
Southern tomato virus
(STV) isolate on tomato plants in a seed production field in Bangladesh was obtained for the first time using next-generation sequencing. The identified isolate, STV_BD-13, shares a high degree of sequence identity (99%) with several known STV isolates worldwide.
Cannabinoid hyperemesis syndrome: a guide for the practising clinician
Authors: Bajgoric Sanjin , Samra Kiran , Chandrapalan Subashini , Gautam Nishant
Published: January 2016

Cannabis is the most widely used illicit drug in the world. The medicinal value of cannabis as an antiemetic is well known by the medical fraternity. A less well-recognised entity is the potential for certain chronic users to develop hyperemesis. We describe the case of a young man who presented to us with features of cannabinoid hyperemesis syndrome. We review the current literature on this condition, its pathogenesis and management.
Possible ACTH-independent, cortisol-secreting and DHEA-secreting metastatic hepatocellular carcinoma causing Cushing’s syndrome
Authors: Sacerdote Alan , Inoue Taiga , Thomas Nithin , Bahtiyar Gul
Published: January 2016

Cortisol production by hepatocellular carcinoma (HCC) has not been previously reported and dehydroepiandrosterone (DHEA) secretion by HCC is rare. We report a case of a 53-year-old woman admitted with dyspnoea and headache. Serum cortisol by immunoassay (IA) was 42.3 μg/dL, urine free cortisol (UFC) by liquid chromatography mass spectrometry (LC/MS/MS) was 106.1 μg/24 h, serum DHEA by LC/MS/MS was 4886 ng/mL, serum DHEA-S by LC/MS/MS was 4477 ng/mL and plasma adrenocorticotrophic hormone (ACTH) by IA was 10 pg/mL. CT showed likely HCC metastatic to the left adrenal gland, brain and lungs. Liver and adrenal gland biopsies confirmed HCC. ACTH tumour staining was negative. High serum and UFC levels and high serum DHEA and DHEA-S with low-normal plasma ACTH and negative tumour ACTH staining suggested ACTH-independent ectopic Cushing's syndrome (CS); cortisol and DHEA being likely secreted by the HCC. To the best of our knowledge, this is the first reported case of HCC associated with CS.
Increased internal higher-order aberrations as a useful parameter for indication of vitrectomy in three asteroid hyalosis cases
Authors: Yokoyama Sho , Kojima Takashi , Kaga Tatsushi , Ichikawa Kazuo
Published: January 2016

We report three asteroid hyalosis cases in which internal higher-order aberrations (HOAs) were improved concomitant with improved visual symptoms after vitrectomy. Cases 1 and 2 reported severe floaters and glare disability, although their visual acuities were fairly good. Case 3 showed poor visual acuity since this patient also suffered from mild macular degeneration. For these three asteroid hyalosis cases, we were unsure if treatment with vitrectomy could improve visual symptoms. Therefore, we measured internal HOAs with an aberrometer, and found that the internal HOA values in these cases were high. We suspected that internal high HOAs values were associated with visual disturbance, and performed vitrectomy. After the vitrectomy, the internal HOA values in these three asteroid hyalosis cases markedly decreased, and visual symptoms improved. These observations suggested that measurement of internal HOAs may be useful to determine the indication for vitrectomy.
Mixed odontogenic tumour with dentinoid and ghost cells
Authors: Kumar Pavan , Jayam Cheranjeevi , Patil Shruthi , Zingade Jyoti
Published: January 2016

Ameloblastomas do not generally show evidence of induction, however, rare cases associated with odontome have been reported and are referred to as odontoameloblastomas. We report an unusual case of an ameloblastoma with features of an adenomatoid odontogenic tumour, showing evidence of induction of dentinoid by tumour cells—but without concomitant formation of enamel—and with features of ghost cells. The lesion occurred on the left side of the maxilla in a 31-year-old woman.
Posterior reversible encephalopathy syndrome (PRES) after bariatric surgery—a potential consequence associated with rapid withdrawal of antihypertensive medications
Authors: Stanford Fatima Cody , Pratt Janey S , Meireles Ozanan R , Bredella Miriam A
Published: January 2016

A 61-year-old woman with a medical history of intracerebral haemorrhage, hypertension, hyperlipidaemia and carotid stenosis presented to the emergency department with altered mental status 3 weeks after undergoing a vertical sleeve gastrectomy for severe obesity. She presented with a hypertensive emergency and a National Institutes of Health Stroke Scale of 4. CT of the head was unrevealing. MRI showed an abnormal signal within the bilateral posterior border-zone areas, with several foci in the parietal and occipital lobes, and thalami, suggestive of posterior reversible encephalopathy syndrome (PRES). The patient was initially placed on a labetalol drip and her preoperative antihypertensive medications—amlodipine, captopril, triamterene and hydrochlorothiazide—were gradually reintroduced. She returned to her baseline and was stable on discharge. Rapid withdrawal of antihypertensive medications in the early postoperative period of bariatric surgery was the aetiology of PRES in this patient. This case report discusses postoperative care of bariatric surgery patients having hypertension.
ANCA negative eosinophilic granulomatosis with polyangiitis: sometimes it really IS vasculitis
Authors: Tyagi Niharika , Maheswaran Tim , Wimalaratna Sunil
Published: January 2016

A 21-year-old woman, with a background of asthma, presented to medical admissions ward, with diarrhoea and vomiting; the clinical picture during her admission evolved to include acute shortness of breath, seizures, unsteadiness, low mood and apathy. Investigations revealed pericardial, pleural effusions, myocardial infiltration and vasculitic lesions in the brain. Although serological tests for autoantibodies were negative, an eventual diagnosis of eosinophilic granulomatosis with polyangiitis, formerly known as Churg-Strauss syndrome, was performed based on the clinical picture. The multiorgan involvement meant that the initial diagnosis and effective management required multidisciplinary input from cardiology, neurology, rheumatology, psychiatry, immunology and occupational and physiotherapy.
Outcome of cataract surgery following simple limbal epithelial transplantation for lime injury-induced limbal stem cell deficiency
Authors: Nair Dhanyasree , Mohamed Ashik , Sangwan Virender S
Published: January 2016

A 19-year-old woman presented to us after being diagnosed elsewhere with right eye total limbal stem cell deficiency resulting from a lime burn. She was advised to undergo limbal stem cell transplantation, but failed to immediately do so. Two years later, she underwent cultivated limbal epithelial transplantation (CLET). As she had severe loss of vision with persisting conjunctival nodule and symblepharon 2 years following surgery, an impression of failed CLET was formed. Subsequently, simple limbal epithelial transplantation (SLET) was performed. Nine months later, she developed a cataract in her right eye; the cataract was extracted and posterior chamber intraocular lens implanted. The unaided visual acuity improved from light perception at presentation to 20/60 at 1-week postoperatively. At 5 months follow-up, the patient continued to maintain 20/60 visual acuity in her right eye. This case describes the outcome of cataract surgery following SLET, emphasising the need to perform cataract surgery in complicated cataracts for a better visual prognosis.
Abdominal pain and faeculent vomiting in a 64-year-old woman
Authors: Winters Leigha , Krell Robert W , Machado-Aranda David
Published: January 2016

A 64-year-old woman with a previous right colectomy presented with severe epigastric abdominal pain and nausea of several weeks’ duration, which then escalated to projectile faeculent emesis. During her clinical course, she remained afebrile with normal vital signs. Physical examination revealed abdominal distension, moderate tenderness in the bilateral upper quadrants and provoked voluntary abdominal wall guarding. Haematology and laboratory chemistries were only notable for a mild (14.6 K/μL) leucocytosis. Acute abdominal plain radiological series revealed dilated small bowel loops and possible pneumoperitoneum. Abdominal CT demonstrated a mechanical small bowel obstruction and no extraluminal air. An exploratory laparotomy was performed, revealing an obstructing enterolith related to actively inflamed jejunal diverticulitis (complicated JD). This case report aims to describe the non-specific presentation of a poorly understood disease entity that presents a diagnostic and therapeutic challenge for the medical community.
A spontaneously resolving breast lesion: imaging and cytological findings of nodular fasciitis of the breast with FISH showing USP6 gene rearrangement
Authors: Kang Alexandra , Kumar Jayant Brij , Thomas Anitha , Bourke Anita Geraldine
Published: January 2016

We report a case of nodular fasciitis of the breast in a 48-year-old woman who presented with a tender rapidly growing right breast lump. Ultrasound guided fine needle aspiration (FNA) of the solid mass was performed. Cytology was reported as atypical spindle cell neoplasm and the patient was referred to a breast surgeon at a tertiary institution for a definitive diagnosis and further management. Follow-up ultrasound showed partial regression and MRI, mammogram after 2–3 weeks confirmed spontaneous and total resolution of the lesion. Nodular fasciitis of the breast is rarely diagnosed on cytology alone and a histological diagnosis is usually required for a definitive diagnosis. However, in this case, the lesion spontaneously resolved prior to core biopsy or diagnostic open biopsy. The cytological features in conjunction with immunohistochemistry and the clinical history strongly suggest nodular fasciitis, which is further supported by a USP6 FISH positive result.
Delayed diagnosis of a high-grade B-cell non-Hodgkin's lymphoma presenting as an obstructing rectal mass
Authors: Sudworth Oliver , Hameed Aisha
Published: January 2016

This case describes a 54-year-old man who presented to the surgical triage unit and was found to have a rare underlying rectal lymphoma. The patient had previously sought medical advice on multiple occasions, reporting a chronic inability to open his bowels. This case report aims to highlight the importance of thorough history taking and examination, in order to reduce delaying the diagnosis of significant pathology.
Synchronous phalangeal metastases in upper and lower limbs from primary breast malignancy: a rare case scenario with a review of the literature
Authors: Ravind Rahul , Prameela Chelakkot G , Gurram Bharath Chandra , Dinesh Makuny
Published: January 2016

Osseous metastasis from a primary breast cancer is common, and the skeletal related morbidity is high. However, solitary acral bony metastasis is rare and the diagnosis of these lesions poses a challenge to the physician. We describe a case of a patient treated with primary breast cancer who later presented with metastatic osteolytic bone lesions confined to a forefinger and toe.
Duodenal perforation as result of blunt abdominal trauma in childhood
Authors: Hartholt Klaas Albert , Dekker Jan Willem T
Published: January 2016

Blunt abdominal trauma may cause severe intra-abdominal injuries, while clinical findings could be mild or absent directly after the trauma. The absence of clinical findings could mislead physicians into underestimating the severity of the injury at the primary survey, and inevitably leads to a delay in the diagnosis. The Blunt Abdominal Trauma in Children (BATiC) score may help to identify children who are at a high risk for intra-abdominal injuries in an early stage and requires additional tests directly. A case of a 10-year-old girl with a duodenal perforation after a blunt abdominal trauma is presented. A delay in diagnosis may lead to an increased morbidity and mortality rate. A low admission threshold for children with abdominal pain after a blunt trauma is recommended.
A neonate born withMycobacterium cosmeticumbacteraemia
Authors: Koay Wei Li Adeline , Aigbivbalu Lemuel , Patel Janak
Published: January 2016

Mycobacterium cosmeticumis a rapidly growing mycobacterium that was recently identified. However, its role in human infection has not been well described. We present a case of an extremely premature neonate born with bacteraemia due toM. cosmeticumthat resolved without sequelae. The infection likely occurred during a prolonged intrauterine transfusion procedure.
A rare and life-threatening cause of epistaxis
Authors: McDonald Rory , Patel Anant Piyush , Horrocks Claudine
Published: January 2016

Epistaxis is a potentially life-threatening condition that can compromise a patient's airway, breathing and circulation. Early recognition of underlying bleeding diatheses that are amenable to medical therapy is imperative in order for timely treatment and to reduce morbidity. We present a case in which acquired haemophilia was diagnosed in an 83-year-old man presenting with seemingly uncomplicated epistaxis. The patient suffered multisite haemorrhages and haemodynamic compromise before definitive management with monoclonal antibody therapy. The case highlights the difficulties in managing this rare condition. It also emphasises the importance of clotting assay analysis in patients who present with epistaxis in the absence of an underlying anticoagulant.
The increase in non-cross-bridge forces after stretch of activated striated muscle is related to titin isoforms
Authors: Cornachione Anabelle S. , Leite Felipe , Bagni Maria Angela , Rassier Dilson E.
Published: January 2016

Skeletal muscles present a non-cross-bridge increase in sarcomere stiffness and tension on Ca2+ activation, referred to as static stiffness and static tension, respectively. It has been hypothesized that this increase in tension is caused by Ca2+-dependent changes in the properties of titin molecules. To verify this hypothesis, we investigated the static tension in muscles containing different titin isoforms. Permeabilized myofibrils were isolated from the psoas, soleus, and heart ventricle from the rabbit, and tested in pCa 9.0 and pCa 4.5, before and after extraction of troponin C, thin filaments, and treatment with the actomyosin inhibitor blebbistatin. The myofibrils were tested with stretches of different amplitudes in sarcomere lengths varying between 1.93 and 3.37 μm for the psoas, 2.68 and 4.21 μm for the soleus, and 1.51 and 2.86 μm for the ventricle. Using gel electrophoresis, we confirmed that the three muscles tested have different titin isoforms. The static tension was present in psoas and soleus myofibrils, but not in ventricle myofibrils, and higher in psoas myofibrils than in soleus myofibrils. These results suggest that the increase in the static tension is directly associated with Ca2+-dependent change in titin properties and not associated with changes in titin-actin interactions.
Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats
Authors: Liang Nan , Mitchell Jere H. , Smith Scott A. , Mizuno Masaki
Published: January 2016

The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20–50 μA in 10-μA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tibial nerve discharge during MLR stimulation significantly increased in an intensity-dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared with WKY across all stimulation intensities (e.g., at 50 μA, ΔRSNA: WKY 153±31%, SHR 287±42%; ΔMAP: WKY 87±9 mmHg, SHR 139±7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension.
Impact of 5-aminolevulinic acid with iron supplementation on exercise efficiency and home-based walking training achievement in older women
Authors: Masuki Shizue , Morita Atsumi , Kamijo Yoshi-ichiro , Ikegawa Shigeki , Kataoka Yufuko , Ogawa Yu , Sumiyoshi Eri , Takahashi Kiwamu , Tanaka Tohru , Nakajima Motowo , Nose Hiroshi
Published: January 2016

A reduction in exercise efficiency with aging limits daily living activities. We examined whether 5-aminolevulinic acid (ALA) with sodium ferrous citrate (SFC) increased exercise efficiency and voluntary achievement of interval walking training (IWT) in older women. Ten women [65 ± 3(SD) yr] who had performed IWT for >12 mo and were currently performing IWT participated in this study. The study was conducted in a placebo-controlled, double-blind crossover design. All subjects underwent two trials for 7 days each in which they performed IWT with ALA+SFC (100 and 115 mg/day, respectively) or placebo supplement intake (CNT), intermittently with a 2-wk washout period. Before and after each trial, subjects underwent a graded cycling test at 27.0°C atmospheric temperature and 50% relative humidity, and oxygen consumption rate, carbon dioxide production rate, and lactate concentration in plasma were measured. Furthermore, for the first 6 days of each trial, exercise intensity for IWT was measured by accelerometry. We found that, in the ALA+SFC trial, oxygen consumption rate and carbon dioxide production rate during graded cycling decreased by 12% ( P < 0.001) and 11% ( P = 0.001) at every workload, respectively, accompanied by a 16% reduction in lactate concentration in plasma ( P < 0.001), although all remained unchanged in the CNT trial ( P > 0.2). All of the reductions were significantly greater in the ALA+SFC than the CNT trial ( P < 0.05). Furthermore, the training days, impulse, and time at fast walking were 42% ( P = 0.028), 102% ( P = 0.027), and 69% ( P = 0.039) higher during the ALA+SFC than the CNT intake period, respectively. Thus ALA+SFC supplementation augmented exercise efficiency and thereby improved IWT achievement in older women.
Gene transcripts associated with muscle strength: a CHARGE meta-analysis of 7,781 persons
Authors: Pilling L. C. , Joehanes R. , Kacprowski T. , Peters M. , Jansen R. , Karasik D. , Kiel D. P. , Harries L. W. , Teumer A. , Powell J. , Levy D. , Lin H. , Lunetta K. , Munson P. , Bandinelli S. , Henley W. , Hernandez D. , Singleton A. , Tanaka T. , van Grootheest G. , Hofman A. , Uitterlinden A. G. , Biffar R. , Gläser S. , Homuth G. , Malsch C. , Völker U. , Penninx B. , van Meurs J. B. J. , Ferrucci L. , Kocher T. , Murabito J. , Melzer D.
Published: January 2016

Lower muscle strength in midlife predicts disability and mortality in later life. Blood-borne factors, including growth differentiation factor 11 (GDF11), have been linked to muscle regeneration in animal models. We aimed to identify gene transcripts associated with muscle strength in adults. Meta-analysis of whole blood gene expression (overall 17,534 unique genes measured by microarray) and hand-grip strength in four independent cohorts ( n = 7,781, ages: 20–104 yr, weighted mean = 56), adjusted for age, sex, height, weight, and leukocyte subtypes. Separate analyses were performed in subsets (older/younger than 60, men/women). Expression levels of 221 genes were associated with strength after adjustment for cofactors and for multiple statistical testing, including ALAS2 (rate-limiting enzyme in heme synthesis), PRF1 (perforin, a cytotoxic protein associated with inflammation), IGF1R, and IGF2BP2 (both insulin like growth factor related). We identified statistical enrichment for hemoglobin biosynthesis, innate immune activation, and the stress response. Ten genes were associated only in younger individuals, four in men only and one in women only. For example, PIK3R2 (a negative regulator of PI3K/AKT growth pathway) was negatively associated with muscle strength in younger (<60 yr) individuals but not older (≥60 yr). We also show that 115 genes (52%) have not previously been linked to muscle in NCBI PubMed abstracts. This first large-scale transcriptome study of muscle strength in human adults confirmed associations with known pathways and provides new evidence for over half of the genes identified. There may be age- and sex-specific gene expression signatures in blood for muscle strength.
Computed Tomography Analysis of Postsurgery Femoral Component Rotation Based on a Force Sensing Device Method versus Hypothetical Rotational Alignment Based on Anatomical Landmark Methods: A Pilot Study
Authors: Kreuzer Stefan W. , Pourmoghaddam Amir , Leffers Kevin J. , Johnson Clint W. , Dettmer Marius
Published: January 2016

Rotation of the femoral component is an important aspect of knee arthroplasty, due to its effects on postsurgery knee kinematics and associated functional outcomes. It is still debated which method for establishing rotational alignment is preferable in orthopedic surgery. We compared force sensing based femoral component rotation with traditional anatomic landmark methods to investigate which method is more accurate in terms of alignment to the true transepicondylar axis. Thirty-one patients underwent computer-navigated total knee arthroplasty for osteoarthritis with femoral rotation established via a force sensor. During surgery, three alternative hypothetical femoral rotational alignments were assessed, based on transepicondylar axis, anterior-posterior axis, or the utilization of a posterior condyles referencing jig. Postoperative computed tomography scans were obtained to investigate rotation characteristics. Significant differences in rotation characteristics were found between rotation according to DKB and other methods (P<0.05). Soft tissue balancing resulted in smaller deviation from anatomical epicondylar axis than any other method. 77% of operated knees were within a range of ±3° of rotation. Only between 48% and 52% of knees would have been rotated appropriately using the other methods. The current results indicate that force sensors may be valuable for establishing correct femoral rotation.
MicroRNAs: Novel Crossroads between Myeloma Cells and the Bone Marrow Microenvironment
Authors: Raimondi Lavinia , De Luca Angela , Morelli Eugenio , Giavaresi Gianluca , Tagliaferri Pierosandro , Tassone Pierfrancesco , Amodio Nicola
Published: January 2016

Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulate in the bone marrow, where a complex microenvironment made by different cell types supports proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at posttranscriptional level. Emerging evidence indicates that miRNAs are aberrantly expressed or functionally deregulated in MM cells as the result of multiple genetic or epigenetic mechanisms and that also the tumor microenvironment regulates MM cell functions by miRNAs. Consistently, modulation of miRNA levels in MM cells has been demonstrated to impair their functional interaction with the bone marrow microenvironment and to produce significant antitumor activity even able to overcome the protective bone marrowmilieu. This review will describe the most recent findings on miRNA function in the context of MM bone marrow microenvironment, focusing on the therapeutic potential of miRNA-based approaches.
Altered Saturated and Monounsaturated Plasma Phospholipid Fatty Acid Profiles in Adult Males with Colon Adenomas
Authors: Pickens C. Austin , Lane-Elliot Ami , Comstock Sarah S. , Fenton Jenifer I.
Published: January 2016

Background: Altered lipid metabolism and plasma fatty acid (FA) levels are associated with colorectal cancer. Obesity and elevated waist circumference (WC) increase the likelihood of developing precancerous colon adenomas.

Methods: Venous blood was collected from 126 males, ages 48 to 65 years, who received routine colonoscopies. Plasma phospholipid (PPL) FAs were isolated, derivatized, and then analyzed using gas chromatography. ORs and 95% confidence intervals were determined using polytomous logistic regression after adjusting for confounding factors [i.e., age, smoking, WC, and body mass index (BMI)].

Results: PPL palmitic acid (PA) was inversely correlated with the presence of colon adenomas (P = 0.01). For each unit increase in palmitoleic acid (OR, 3.75; P = 0.04) or elaidic acid (OR, 2.92; P = 0.04), an individual was more likely to have adenomas relative to no colon polyps. Higher enzyme activity estimates (EAE) of stearoyl-CoA desaturase-1 (SCD-1; P = 0.02) and elongation of very long chain fatty acids protein-6 (ELOVL-6; P = 0.03) were associated with an individual being approximately 1.5 times more likely to have an adenoma compared with no polyps.

Conclusions: PPL FAs and EAEs, which have previously been associated with colorectal cancer, are significantly different in those with adenomas when compared with those without polyps. PPL PA, elaidic acid, and SCD-1 and ELOVL-6 EAEs are associated with adenomas independent of BMI and WC.

Impact: PPL PA, elaidic acid, and SCD-1 and ELOVL-6 EAEs are associated with adenomas even after adjusting for obesity-related risk factors and may function as novel biomarkers of early colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 25(3); 498–506. ©2015 AACR.
Statistical Methods for Estimating the Cumulative Risk of Screening Mammography Outcomes
Authors: Hubbard Rebecca A. , Ripping Theodora M. , Chubak Jessica , Broeders Mireille J.M. , Miglioretti Diana L.
Published: January 2016

Background: This study illustrates alternative statistical methods for estimating cumulative risk of screening mammography outcomes in longitudinal studies.

Methods: Data from the US Breast Cancer Surveillance Consortium (BCSC) and the Nijmegen Breast Cancer Screening Program in the Netherlands were used to compare four statistical approaches to estimating cumulative risk. We estimated cumulative risk of false-positive recall and screen-detected cancer after 10 screening rounds using data from 242,835 women ages 40 to 74 years screened at the BCSC facilities in 1993–2012 and from 17,297 women ages 50 to 74 years screened in Nijmegen in 1990–2012.

Results: In the BCSC cohort, a censoring bias model estimated bounds of 53.8% to 59.3% for false-positive recall and 2.4% to 7.6% for screen-detected cancer, assuming 10% increased or decreased risk among women screened for one additional round. In the Nijmegen cohort, false-positive recall appeared to be associated with subsequent discontinuation of screening leading to overestimation of risk of a false-positive recall based on adjusted discrete-time survival models. Bounds estimated by the censoring bias model were 11.0% to 19.9% for false-positive recall and 4.2% to 9.7% for screen-detected cancer.

Conclusion: Choice of statistical methodology can substantially affect cumulative risk estimates. The censoring bias model is appropriate under a variety of censoring mechanisms and provides bounds for cumulative risk estimates under varying degrees of dependent censoring.

Impact: This article illustrates statistical methods for estimating cumulative risks of cancer screening outcomes, which will be increasingly important as screening test recommendations proliferate. Cancer Epidemiol Biomarkers Prev; 25(3); 513–20. ©2015 AACR.
Association between Metformin Use and Mortality after Cervical Cancer in Older Women with Diabetes
Authors: Han Kathy , Pintilie Melania , Lipscombe Lorraine L. , Lega Iliana C. , Milosevic Michael F. , Fyles Anthony W.
Published: January 2016

Background: To examine the association between metformin use and mortality in patients with diabetes and cervical cancer.

Methods: Using Ontario health databases, a retrospective, population-based cohort study was conducted in women with diabetes ≥ age 66 years diagnosed with cervical cancer between 1997 and 2010. The association between metformin exposure and cervical cancer–specific mortality was examined using Fine–Gray regression models, with noncancer death as a competing risk and cumulative metformin use as a time-varying exposure. The association with overall mortality was examined using Cox regression models.

Results: Among the 181 women with diabetes and cervical cancer, there were 129 deaths, including 61 cervical cancer–specific deaths. The median follow-up was 5.8 years (interquartile range 4.2–9.6 years) for surviving patients. Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer–specific mortality and overall mortality in a dose-dependent fashion [HR 0.79; 95% confidence interval (CI), 0.63–0.98; and HR 0.95; 95% CI, 0.90–0.996 per each additional 365 g of metformin use, respectively]. There was no significant association between cumulative use of other antidiabetic drugs and cervical cancer–specific mortality.

Conclusion: This study suggests an association between cumulative metformin use after cervical cancer diagnosis and lower cervical cancer–specific and overall mortality among older women with diabetes.

Impact: Cumulative dose of metformin use after cervical cancer diagnosis among older women with diabetes may be associated with a significant decrease in mortality. This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer. Cancer Epidemiol Biomarkers Prev; 25(3); 507–12. ©2015 AACR.