tbuckley/cabot-search huggingface dataset:
Lack of K140 immunoreactivity in junctional epidermolysis bullosa skin and keratinocytes associates with misfolded laminin epidermal growth factor-like motif 2 of the β3 short arm
Authors: A.G. Condorelli, P. Fortugno, F. Cianfarani, V. Proto, G. Di Zenzo, B. Didona, G. Zambruno, D. Castiglia
Journal: British Journal of Dermatology (2017)

Recessive mutations in the LAMA3, LAMB3 and LAMC2 genes that encode laminin‐332 (LM332) (α3a, β3 and γ2 chains, respectively) cause different junctional epidermolysis bullosa (JEB) subtypes. Biallelic truncating mutations in any of these three genes usually lead to lack of protein expression resulting in the severe generalized JEB subtype, while missense or splice‐site mutations in at least one allele lead to reduced expression typical of JEB generalized intermediate (JEB‐gen intermed) or localized. Here, we molecularly characterized an adult patient with JEB showing negative skin staining for the anti‐β3 chain monoclonal antibody K140. This antibody recognizes an as yet unidentified epitope within the laminin β3 short arm. The patient harbours a homozygous splice‐site mutation resulting in highly aberrant transcripts with partial skipping of the LAMB3 exon that encodes the laminin epidermal growth factor‐like motif 2 of the β3 short arm (β3‐LE2). At the protein level, mutation consequences predict a misfolded β3‐LE2 motif and, indeed, we found that LM332 is correctly assembled but retained in the endoplasmic reticulum (ER) where it colocalizes with the lumenal ER chaperone protein BiP, leading to dramatically reduced secretion. Lack of K140 reactivity to mutant LM332 was confirmed by immunoprecipitation and Western blot analyses. Our findings not only identify the β3‐LE2 subdomain as the region recognized by K140, but also show that misfolding of LM332 structural motifs and subsequent protein retention in the ER is a common pathomechanism in JEB‐gen intermed. In addition to its usefulness in antigen mapping diagnosis of JEB subtypes, this knowledge is relevant to the design of therapeutic strategies aimed at releasing ER‐retained LM332 in JEB.
First report of successful treatment of splenic artery pseudoaneurysm with endoscopic ultrasound-guided coil and glue
Authors: Praveer Rai, Bhavin Bhera, Malay Sharma
Journal: Endoscopy (2017)

A 33-year-old man with chronic alcoholism presented with recurrent episodes of hematemesis and melena over an 18-month period. He had received about 20 units of packed red blood cells (PRBC). Upper gastrointestinal (GI) endoscopy performed elsewhere showed large esophageal varices and gastric varices (GOV2F2) for which three sessions of endoscopic sclerotherapy and glue injection had been performed. An abdominal ultrasound showed normal liver, with splenic vein thrombosis and collaterals around the splenic hilum.
Перший дільничний санітарний лікар Катеринослава
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2017)

Висвітлено життєвий шлях і професійну діяльність Василя Тимофійовича Скрильникова — відомого лікаря-гігієніста, вченого, громадського діяча. В.Т. Скрильников сприяв розвитку санітарно-профілактичного напрямку земської медицини Катеринославської губернії в другій половині ХIХ століття, був першим дільничним санітарним лікарем у Катеринославі. Вчений активно займався вивченням лікувальних властивостей природних факторів, зокрема тимофіївської глини. Успішно працював на Слов’янському курорті, був редактором місцевої газети. Автор наукових праць із бальнеолікування.
Enhanced Delivery and Effects of Acid Sphingomyelinase by ICAM-1-Targeted Nanocarriers in Type B Niemann-Pick Disease Mice
Authors: Carmen Garnacho, Rajwinder Dhami, Melani Solomon, Edward H. Schuchman, Silvia Muro
Journal: Molecular Therapy (2017)

Acid sphingomyelinase deficiency in type B Niemann-Pick disease leads to lysosomal sphingomyelin storage, principally affecting lungs, liver, and spleen. Infused recombinant enzyme is beneficial, yet its delivery to the lungs is limited and requires higher dosing than liver and spleen, leading to potentially adverse reactions. Previous studies showed increased enzyme pulmonary uptake by nanocarriers targeted to ICAM-1, a protein overexpressed during inflammation. Here, using polystyrene and poly(lactic-co-glycolic acid) nanocarriers, we optimized lung delivery by varying enzyme dose and nanocarrier concentration, verified endocytosis and lysosomal trafficking in vivo, and evaluated delivered activity and effects. Raising the enzyme load of nanocarriers progressively increased absolute enzyme delivery to all lung, liver, and spleen, over the naked enzyme. Varying nanocarrier concentration inversely impacted lung versus liver and spleen uptake. Mouse intravital and postmortem examination verified endocytosis, transcytosis, and lysosomal trafficking using nanocarriers. Compared to naked enzyme, nanocarriers increased enzyme activity in organs and reduced lung sphingomyelin storage and macrophage infiltration. Although old mice with advanced disease showed reactivity (pulmonary leukocyte infiltration) to injections, including buffer without carriers, antibody, or enzyme, younger mice with mild disease did not. We conclude that anti-ICAM nanocarriers may result in effective lung enzyme therapy using low enzyme doses.
Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity
Authors: Anna Ludovica Fracanzani, Salvatore Petta, Rosa Lombardi, Giuseppina Pisano, Maurizio Russello, Dario Consonni, Vito Di Marco, Calogero Cammà, Laura Mensi, Paola Dongiovanni, Luca Valenti, Antonio Craxì, Silvia Fargion
Journal: Clinical Gastroenterology and Hepatology (2017)
Efficiency of an active rehabilitation intervention in a slow-to-recover paediatric population following a sport-related concussion
Authors: Phil Fait, Sarah Imhoff, Frédérike Carrier-Toutant, Boulard Geneviève
Journal: British Journal of Sports Medicine (2017)

Objective The aim of this study was to identify whether the addition of an individualised Active Rehabilitation Intervention to standard care influences recovery of young patients who are slow to recover following a sport-related concussion and remain symptomatic at rest. Design Quasi-experimental, prospective study Setting: Interdisciplinary private concussion clinic Subjects Fifteen participants aged 15±2 years. Intervention Standard care and an individualised Active Rehabilitation Intervention which included: 1) low- to high-intensity aerobic training; 2) specific coordination exercises; and, 3) balance exercises. Outcome measures List of symptoms before and after the intervention, duration of symptoms, adherence to the individualised exercice program. Results The Active Rehabilitation Intervention lasted 49 (SD=17 days) days. The duration of the intervention was correlated to self-reported adherence (x=84.64 19.63%, r=−0.792, p&lt;0.001). The average postconcussion symptom inventory (PCSI) score went from a total of 36.85±23.21 points to 4.31±5.04 points after the intervention (Z=−3.18, p=0.001). Conclusions A progressive sub-maximal Active Rehabilitation Intervention may represent an important asset in the recovery of young patients who are slow to recover following a sport-related concussion. Competing interests Phil Fait: Co-owner of the Cortex Mdecine et Radaptation clinic Sarah Imhoff, Frdrike Carrier-Toutant, Genevive Boulard: None.
Post-translational control of T cell development by the ESCRT protein CHMP5
Authors: Stanley Adoro, Kwang Hwan Park, Sarah E Bettigole, Raphael Lis, Hee Rae Shin, Heewon Seo, Ju Han Kim, Klaus-Peter Knobeloch, Jae-Hyuck Shim, Laurie H Glimcher
Journal: Nature Immunology (2017)
Mmp-2 And Mmp-9 Promoter Polymorphisms And Pleural Gelatinase Activity In The Patients With Pleural Effusions
Authors: F. C. Liu, W. Y. Hsieh, Y. H. Hung, M. Y. Chen, C. L. Wu, F. Y. Yeh, C. S. Lin
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Offending in theatre: the case of Ian Paterson
Authors: Gwen Adshead
Journal: BMJ (2017)

What is the psychology and motivation for doctors who do wrong?

Ian Paterson is a surgeon who has recently been found guilty of grievous bodily harm with intent. He faces a life sentence for deliberately carrying out operations, mainly on women, that he said were necessary to save their lives, but which had no therapeutic effect and put their lives at risk. Many of the women had been referred to him for surgery as part of treatment for suspected breast cancer.

This highly trained and experienced doctor seems to have deliberately conned people into having surgery that they did not need, and in doing so convinced them that they were seriously ill and he was saving their lives. The question has been raised as to what his motivation could be. There have been references to Lancelot Spratt, surgeons with a God complex, and other familiar tropes. Making money seems an obvious motivator, and malevolence is implied, although many patients said that he was kind and charming. Inevitably the term …
Death and liver transplantation within 2 years of onset of drug‐induced liver injury
Authors: Paul H. Hayashi, Don C. Rockey, Robert J. Fontana, Hans L. Tillmann, Neil Kaplowitz, Huiman X. Barnhart, Jiezhan Gu, Naga P. Chalasani, K. Rajender Reddy, Averell H. Sherker, Jay H. Hoofnagle
Journal: Hepatology (2017)

Drug‐induced liver injury (DILI) is an important cause of death and indication for liver transplantation (fatality). The role of DILI in these fatalities is poorly characterized, particularly when fatalities occur &gt;26 weeks after DILI onset. We analyzed patients in the US Drug‐Induced Liver Injury Network prospective study having a fatal outcome within 2 years of onset. Each case was reviewed by eight network investigators and categorized as DILI having a primary, a contributory, or no role in the fatality. We subcategorized primary role cases as acute, chronic, acute‐on‐chronic, or acute cholestatic liver failure. For contributory and no role cases, we assigned a primary cause of death. Among 1,089 patients, 107 (9.8%) fatalities occurred within 2 years. DILI had a primary role in 68 (64%), a contributory role in 15 (14%), and no role in 22 (21%); 2 had insufficient data. Among primary role cases, 74% had acute, 13% chronic, 7% acute on chronic, and 6% acute cholestatic failure. For the 15 contributory role cases, common causes of death included sepsis, malignancy, and severe cutaneous reactions with multiorgan failure. For the 22 no role cases, malignancies accounted for most fatalities. Higher bilirubin, coagulopathy, leukocytosis, and thrombocytopenia were independently associated with DILI fatalities. New R ratio Hy's law had a higher positive predictive value for overall fatality (14% versus 10%) and a stronger independent association with DILI fatalities within 26 weeks compared to the original version of Hy's law (hazard ratio, 6.2, 95% confidence interval 3.4‐11.1, versus 2.2, 95% confidence interval 1.3‐3.7). Conclusions: DILI leads directly or indirectly to fatality in 7.6% of cases; 40% of these had nonacute liver failure courses. New R ratio Hy's law better identifies risk for death compared to the original Hy's law. (H epatology 2017;66:1275‐1285).
Abstract 110: Noncoding RNAs: A Possible "Linc" to Atrial Fibrillation
Authors: Shamone R Gore, Jeffery Hsu, Peter Hanna, David R Van Wagoner, John Barnard, Mina K Chung, Jonathan D Smith
Journal: Circulation Research (2012)

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with a 2-fold increased risk of mortality and a ~5- fold increased risk of stroke. Genome wide association studies have identified a locus on chromosome 4q25 that has the strongest association with AF. The SNPs in this locus most strongly associated with AF are located in an intergenic region that is 78 to 157 kb distal to the closest gene PITX2. PITX2 is a candidate gene for AF, due to its role in left/right patterning during heart development and expression found only in the left vs. right atrium. Our lab performed RNA-seq on human atria and identified a long intergenic non-coding RNA (linc-RNA) adjacent to PITX2 that is expressed with the same left/right atrial asymmetry as PITX2. We hypothesized that there may be functional genetic variants in the 4q25 region that directly affect expression of PITX2 or the linc-RNA adjacent to PITX2. Further, we hypothesized that the linc-RNA may control in trans the expression of genes that can alter cellular electrophysiology and lead to AF susceptibility. First we used qPCR to determine whether the expression of PITX2 and this linc-RNA were correlated in 199 human left atria samples. We found the expression of these genes to be highly and positively correlated with an r2 value of 0.47 (p &lt; .0001). We obtained genome-wide SNP information for each of these subjects using an Illumina SNP microarray. We determined the association of SNPs on chromosome 4 with the expression levels of PITX2 and the linc-RNA by performing expression QTL (eQTL) analysis. In the 4q25 region, common genetic variation was more strongly associated with expression of the linc-RNA than PITX2. Two of the strongest linc-RNA eQTL SNPs (p-value ~10-4) were associated with AF with a p-value of ~10 15. We are now starting functional studies to determine if this linc-RNA can modulate gene expression in trans by transfection of a linc-RNA expression plasmid into HEK-293 cells. We plan to determine the effects of over expression this linc-RNA on global gene expression profiles using expression arrays and RNA-seq
Psychosocial impact of prostate cancer surgery on sexual intimacy
Authors: T. L. Krupski, V. Mouraviev, J. Mayes, T. Polascik
Journal: Journal of Clinical Oncology (2009)

e20685 Background: Prostate cancer survivors live with the day-to-day consequences of the disease and its treatment. Prostate cancer, has been labeled a “relationship disease” because it impacts both partners. Traditional research does not include psychosocial aspects of sexual well-being. We designed a retrospective survey asking patients’ and their partners’ about the physiologic and psychosocial changes experienced after prostate cancer treatment. Methods: The study design is a cross sectional retrospective mailing sent to men treated surgically for prostate cancer. Questions related to physiologic changes centered around foreplay, libido, erection, orgasm and ejaculation while emotional status, relationship/partnership quality, self image, and social support comprised the psychological questions. Of the total 47 items, 18 items assessed the above concepts in binary fashion while the remaining 29 used a Likert scale. Results: After obtaining IRB approval, we mailed consents to 368 men. Only 65 men acknowledged receiving the information and 51 consented to participate. The participants were a median age of 59.6, predominantly Caucasian (80%), and treated by prostatectomy or cryotherapy. In terms of emotional status, 20% were diagnosed with depression and 10% with anxiety since their prostate cancer diagnosis and of those 32% felt it affected their sexual status. One third of the men rated their overall sexual relationship with their partner as “poor.” Of those men, 44% also perceived their partner was supportive. Over 80% felt their partnership quality was “stable,” “strong,” and “happy.” Almost half (43%) of the men experienced a decrease in self-esteem while 16% were unhappy with their physical appearance. While few men (4%) availed themselves of support groups, 18% found the advice of other patients helpful in coping with their sexuality. The side effects were unexpected in nearly half (43%) of the men. Conclusions: These preliminary findings suggest that prostate cancer treatment may be associated with psychosocial problems related to depression, anxiety, and self- esteem that impact sexual relationships. Although prospective validated questionnaires are needed to confirm these findings, better counseling through the disease trajectory may help combat these emotional issues. No significant financial relationships to disclose.
Perspectives on gesture from autism spectrum disorder: Alterations in timing and function
Authors: Inge-Marie Eigsti, Ashley de Marchena
Journal: Behavioral and Brain Sciences (2017)

Abstract The target article highlights the utility of new technology to study sign language and gesture. Research in special populations – specifically, individuals with autism spectrum disorder, ASD – may further illuminate sign/gesture similarities and differences and lead to a deeper understanding of the mechanisms of growth and change. Even verbally fluent speakers with ASD display distinctive qualities in sign and gesture.
Defining Treatment-Resistant Depression—Reply
Authors: Charles R. Conway, Mark S. George, Harold A. Sackeim
Journal: JAMA Psychiatry (2017)

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Reply to Jae Heon Kim and Benjamin I. Chung's Letter to the Editor re: Julien Dagenais, Matthew J. Maurice, Pascal Mouracade, Onder Kara, Ercan Malkoc, Jihad J. Kaouk. Excisional Precision Matters: Understanding the Influence of Excisional Volume Loss on Renal Function After Partial Nephrectomy. Eur Urol 2017;72:168–70
Authors: Julien Dagenais, Jihad H. Kaouk
Journal: European Urology (2017)
A gene expression profile to predict recurrence of advanced tongue squamous cell carcinoma (TSCC): Discovery and external validation.
Authors: Tomohiro Enokida, Tetsuro Wakasugi, Tomoko Yamazaki, Mari Takahashi, Yoichi Higuchi, Ryuichi Hayashi, Satoshi Fujii, Makoto Tahara
Journal: Journal of Clinical Oncology (2015)

6032 Background: Extracapsular spread and positive microscopic surgical margins are known high risk factors of recurrence in head and neck cancer patients. However, molecular biological markers to predict recurrence have not been identified. Here, we aimed to identify markers of recurrence using DNA microarray profiling in patients with squamous cell carcinoma of the tongue (TSCC). Methods: We conducted exploratory Affymetrix gene expression profiling using 26 primary tumor tissue samples from patients meeting the following criteria: 1) histologically confirmed TSCC, 2) surgical resection of the primary tumor and lymph node dissection, and 3) follow-up for longer than one year after surgery. Median age and pathological stage were 60 years (37-85) and pStageIII/IV = 8%/92% (pT: 2/3/4a = 3/1/22, pN: 0/1/2a/2b/2c = 5/5/0/8/8), respectively. The relationship between gene expression pattern and relapse-free survival (RFS) was examined. Predictive candidate genes were independently validated using published survival and gene expression data similarly derived from 23 patients with oral SCC (http://www.ncbi.nlm.nih.gov/geo, GSE31056). Results: Cases were classified into clusters A (n = 10) and B (n = 16) by unsupervised hierarchical clustering analysis. RFS of cluster B was longer than that of cluster A (median RFS: not reached vs. 111days, p= 0.025) with a median follow-up period of 253 days (58-1341). The number of genes highly expressed by more than two-fold their expression in the opposite cluster was 175 in cluster A and 400 in cluster B. We then identified 27 genes with the most predictive value for recurrence, 5 genes highly expressed in the low-risk group (e.g. ALDH3A1) and 22 highly expressed in the high-risk group (e.g. MMP-10). Clustering into high- and low-risk groups based on this 27-gene expression in a validation study also showed a significant association with recurrence (median RFS: low-risk not reached vs. high-risk 25.1 months, p = 0.046) with a median follow-up of 13.27 months (1.43-59.67). Conclusions: We identified27 genes which could predict recurrence, indicating a promising candidate factor for high-risk relapse. A larger prospective study is warranted.
GMC wins right to appeal ruling that registrar’s fitness to practise was not impaired
Authors: Clare Dyer
Journal: BMJ (2017)

The General Medical Council (GMC) has used a new right of appeal to overturn a finding in favour of a doctor by a medical practitioners tribunal.

In the first such case to be heard since the GMC was given a right of appeal in December 2015,1 the High Court ruled that the tribunal’s failure to find that a doctor’s actions were sexually motivated was “wrong and unsustainable.”

The …
DIPG-37. INFLUENCE OF AN INTRA-TUMORAL CYST ON DRUG DISTRIBUTION BY CONVECTION ENHANCED DELIVERY
Authors: Iryna Ivasyk, Peter Morgenstern, Eva Wembacher-Schroeder, Mark Souweidane
Journal: Neuro-Oncology (2017)

INTRODUCTION: Convection-enhanced delivery (CED) employs positive pressure to induce convective flow of molecules and maximize drug distribution. Concerns have been raised about the effect of cystic structures on uniform drug distribution with CED. We describe a patient with diffuse intrinsic pontine glioma (DIPG) with a large cyst and examine the effect on drug distribution after CED with a radiolabeled antibody. METHODS: The patient was treated according to protocol with CED of 124I-8H9 to the pons for non-progressive DIPG after radiation therapy as part of a Phase I trial (NCT01502917). Care was taken to avoid the cystic cavity in the planned catheter tract and target point. Co-infusion with Gd-DTPA was performed to assess drug distribution. Infusate distribution was examined by MRI immediately following infusion and analyzed using iPlan Flow software (Brainlab, Inc). RESULTS: Analysis of post-infusion MR images demonstrates convective distribution around the catheter tip and an elongated configuration of the drug distribution that is consistent with the superior-inferior corticospinal fiber orientation in the brainstem. This indicates that the catheter was functioning and a pressure gradient was established. No infusate entry into the cystic region could be identified on T2 FLAIR or T1-weighted images. CONCLUSION: The effects of ependymal and pial surfaces on drug delivery using CED in brainstem tumors remain controversial. Drug distribution is a critical component of effective application of CED to neurosurgical lesions. This case suggests that cyst cavities may not always behave as fluid “sinks” for drug distribution. We observed that infusate was not lost into the cyst cavity, suggesting that lesions with cystic components can be treated by CED without significant alterations to target and infusion planning.