tbuckley/cabot-search huggingface dataset:
Light Weight and Flexible High‐Performance Diagnostic Platform
Authors: Daniil Karnaushenko, Bergoi Ibarlucea, Sanghun Lee, Gungun Lin, Larysa Baraban, Sebastian Pregl, Michael Melzer, Denys Makarov, Walter M. Weber, Thomas Mikolajick, Oliver G. Schmidt, Gianaurelio Cuniberti
Journal: Advanced Healthcare Materials (2015)

A flexible diagnostic platform is realized and its performance is demonstrated for early detection of avian influenza virus (AIV) subtype H1N1 DNA sequences. The key component of the platform is high‐performance biosensors based on high output currents and low power dissipation Si nanowire field effect transistors (SiNW‐FETs) fabricated on flexible 100 μm thick polyimide foils. The devices on a polymeric support are about ten times lighter compared to their rigid counterparts on Si wafers and can be prepared on large areas. While the latter potentially allows reducing the fabrication costs per device, the former makes them cost efficient for high‐volume delivery to medical institutions in, e.g., developing countries. The flexible devices withstand bending down to a 7.5 mm radius and do not degrade in performance even after 1000 consecutive bending cycles. In addition to these remarkable mechanical properties, on the analytic side, the diagnostic platform allows fast detection of specific DNA sequences of AIV subtype H1N1 with a limit of detection of 40 × 10 −12 m within 30 min suggesting its suitability for early stage disease diagnosis.
Immunoelectron Microscopic Localization of the Electrogenic Na/HCO3 Cotransporter in Rat and Ambystoma Kidney
Authors: ARVID B. MAUNSBACH, HENRIK VORUM, TAE-HWAN KWON, SØREN NIELSEN, BRIAN SIMONSEN, INYEONG CHOI, BERNHARD M. SCHMITT, WALTER F. BORON, CHRISTIAN AALKJæR
Journal: Journal of the American Society of Nephrology (2000)

Immunofluorescence analysis has revealed that electrogenic Na(+)/HCO(3)(-) (NBC1) is expressed in the proximal tubule of rat kidney and in the proximal and distal tubules of the salamander AMBYSTOMA: tigrinum kidney. The present study was undertaken to define the detailed subcellular localization of the NBC1 in rat and AMBYSTOMA: kidney using high-resolution immunoelectron microscopy. For this purpose, two rabbit polyclonal antibodies raised against amino acids 928 to 1035 and amino acids 1021 to 1035 of the C-terminus of rat kidney (rkNBC1) were developed. The affinity-purified antibodies revealed a strong band of approximately 140 kD in immunoblots of membranes from rat kidney cortex but no signal in membranes isolated from outer and inner medulla. Deglycosylation reduced the apparent molecular weight to approximately 120 kD, corresponding to the predicted molecular weight. A similar but weaker band was also present in membranes isolated from the lateral part of Ambystoma: kidney. In rat kidney, immunohistochemistry confirmed the presence of rkNBC1 in convoluted segments of the proximal tubules. In ultrathin cryosections or Lowicryl HM20 sections from rat kidney cortex, distinct immunogold labeling was associated with the basolateral plasma membrane of segments S1 and S2 of proximal tubules, whereas in S3 no labeling was observed. The labeling density was similar at the basal and lateral plasma membrane and was specifically associated with the inner surface of the membrane consistent with the internal position of the C-terminus of the transporter. In contrast, rkNBC1 was absent from the apical plasma membrane and not observed in intracellular vesicles, including those closely associated with basolateral plasma membrane. In Ambystoma: kidney, a weak labeling was present in the basolateral membrane of the proximal tubule and stronger labeling was observed in the late distal segment. The results demonstrate that rkNBC1 is expressed only in segment S1 and segment S2 of rat proximal tubule as well as Ambystoma: proximal and late distal tubule and that rkNBC1 is present in both basal and lateral plasma membranes and absent in intracellular vesicles of the apical plasma membrane.
FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer.
Authors: D Kelsen, O T Atiq, L Saltz, D Niedzwiecki, D Ginn, D Chapman, R Heelan, C Lightdale, V Vinciguerra, M Brennan
Journal: Journal of Clinical Oncology (1992)

PURPOSE The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer. PATIENTS AND METHODS Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis. RESULTS Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04). CONCLUSIONS FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.
Genome‐Wide Copy Number Variation Analysis Identifies Deletion Variants Associated With Ankylosing Spondylitis
Authors: Seung‐Hyun Jung, Seon‐Hee Yim, Hae‐Jin Hu, Kyu Hoon Lee, Joo‐Hyun Lee, Dong‐Hyuk Sheen, Mi‐Kyoung Lim, Soon‐Young Kim, Sung‐Won Park, So‐Hee Kim, Kyudong Han, Tae‐Hwan Kim, Seung‐Cheol Shim, Yeun‐Jun Chung
Journal: Arthritis & Rheumatology (2014)

To identify ankylosing spondylitis (AS)-associated copy number variations (CNVs) in Korean subjects and their synergistic roles in the development of AS.A genome-wide association study (GWAS) was performed in 309 patients with AS and 309 control subjects, using a copy number variant (CNV) microarray. AS-associated CNV regions were replicated in 2 independent sets (625 patients and 891 control subjects) by quantitative polymerase chain reaction (PCR) and deletion-typing PCR.In the CNV GWAS, 227 CNV regions were shown to be significantly associated with the risk of AS. Of the candidate CNV regions, 9 were successfully replicated in the first replication analysis: 1q32.2 (HHAT), 1p34.2 (BMP8A), 2q31.2 (PRKRA), 6p21.32 (HLA-DPB1), 11q22.1 (CNTN5), 13q13.1 (EEF1DP3), 14q24.2 (RGS6), 16p13.3, and 22q11.1 (IL17RA). The 5 deletion-type CNV regions, in 1q32.2, 2q31.2, 6p21.32, 13q13.1, and 16p13.3, were associated with an increased risk of AS, and the other 4 CNV regions were protective. In the second replication analysis, 4 CNV regions in 1q32.2, 2q31.2, 6p21.32, and 16p13.3 were replicated. Among patients with CNV regions in ≥4 risk-increasing loci, the risk was 18.0 times higher than that in patients without any deletions (odds ratio [OR] 17.98, P = 2.3 × 10(-7) ). Among patients with CNV regions in ≥2 protective loci, the risk was 5.2 times lower than that in those without any deletions (OR 0.19, P = 4.0 × 10(-10) ). The additive effects of simultaneous events were shown to be dependent on the frequency of CNV regions. Through deletion-typing PCR and sequencing, the exact sizes and breakpoint sequences were defined in 4 CNV regions. The mechanism of all 3 deletions was shown to be microhomology-based nonhomologous end joining.The results of this study can help to identify pathogenic mechanisms of AS and can easily be applied in the development of algorithms estimating the risk of AS.
Pollen asthma treatment: Comparative efficacy study
Authors: Iryna Sygaieva
Journal: European Respiratory Journal (2011)

Background: Airborne pollen has always been one of the most common triggers of asthma, so there is vital need in efficient specific hyposensibilisation.  Aims and objectives: Principal aim was to check efficacy of different combinations of inhaled corticosteroid/long-acting β2-agonist upheld by specific immunotherapy and/or montelukast.  Methods: In open-label, randomized, parallel group, one-year panel study were involved 468 patients with pollen asthma (moderate-to-severe airflow limitations, bronchitis symptoms, and a history of exacerbations). All participants had completed allergy examination (prick skin test), immunologic, and functional assessment corroborating their asthma status. Participants were randomized in three equal groups, 156 patients each. First group got specific immunotherapy, second - montelukast (Singulair), and third – both treatments. Entire population received budesonide/formoterol (Symbicort Turbuhaler) as well.  Results: After 52-week treatment first group exhibited strong remission in 68% patients assigned, second group – in 61% patients, and third group – in 79% patients. These changes were statistically independent of patient9s age, sex, and smoking status (P  Conclusions: Budesonide/formoterol in conjunction with allergen-specific immunotherapy and montelukast proved to be the most successful combination for curing pollen asthma.
Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy.
Authors: J D Hainsworth, E P Wright, G F Gray, F A Greco
Journal: Journal of Clinical Oncology (1987)

We have previously reported complete responses and long-term survival in patients with metastatic poorly differentiated carcinoma (PDC) of unknown primary site who received intensive cisplatin-containing chemotherapy regimens. We reviewed the light microscopic specimens from 113 patients with PDC in an attempt to identify common histopathologic features in the chemotherapy-responsive subgroup, and to rule out the presence of previously unrecognized germ cell tumors. Relatively few diagnoses more specific than PDC could be made. We could identify no histopathologic features by light microscopy that distinguished responsive from unresponsive neoplasms. Only one patient was found to have a previously unrecognized yolk sac carcinoma, and in five other patients the possibility of a germ cell neoplasm was considered in the differential diagnosis by at least one reviewer. The remaining tumors had no histologic features suggestive of germ cell neoplasms. Ninety-six patients had received combination chemotherapy (89 with cisplatin-containing regimens); 27 patients (28%) achieved complete remission, and 16 remain free of disease at a median of 65 months after completion of therapy. Patients with PDC of unknown primary site who are responsive to cisplatin-containing chemotherapy regimens cannot be reliably identified by light microscopy. At present, all such patients should be considered for an empiric trial of chemotherapy with cisplatin-based regimens, since cure is achievable in a minority.
Topographical and Conformational Epitopes of Bovine Papillomavirus Type 1 Defined by Monoclonal Antibodies&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L M Cowsert, P Lake, A B Jenson
Journal: JNCI Journal of the National Cancer Institute (1987)

Monoclonal antibodies (MAbs) were generated against sodium dodecyl sulfate-disrupted bovine papillomavirus type 1 (BPV-1). When screened by enzyme-linked immunosorbent assay (ELISA) on intact and disrupted BPV-1, -2, and deer papillomavirus, three patterns of reactivity were defined: reactivity only with intact virus, with both intact and disrupted virus, and only with disrupted virus. On the basis of ELISA results, the topographical location and requirement for conformation for immunoreactivity of epitopes was defined as external conformational, external linear, and internal linear. Cross-reactivity of MAbs with other papillomavirus types was analyzed by immunofluorescence on warts from different species. Type-specific, BPV-1 and/or -2 cross-reactive, broadly cross-reactive, and genus-specific MAbs were identified. MAb reactivity with structural polypeptides of BPV-1 was analyzed by Western blot. MAbs reactive with epitopes defined as conformational by ELISA did not react in Western blot. All MAbs reactive in Western blot reacted with the major capsid protein (MCP) [55 kilodalton (kDa)], demonstrating that the MCP carries both type-specific and cross-reactive epitopes. Most MAbs reactive with the MCP were cross-reactive with structural polypeptides of 48 and 96 kDa, demonstrating the immunologic relatedness of these three polypeptides.
Immune monitoring technology primer: Single Cell Network Profiling (SCNP)
Authors: Rachael E. Hawtin, Alessandra Cesano
Journal: Journal for ImmunoTherapy of Cancer (2015)

Understanding a patients' immune status not only from immune cell phenotyping, but also through analysis of functional signaling capacity, enables the generation of a more comprehensive understanding of the complex mechanisms responsible for immunological tolerance in cancer, and generates data
Daytime sleepiness in patients on intrathecal chronic opioid (IT) therapy is not related to sleep disordered breathing (SDB)
Authors: Francesco Fanfulla, Laura Demartini, Paola Fulgoni, Michelangelo Buonocore, Massimo Barbieri, Cesare Bonezzi
Journal: European Respiratory Journal (2011)

Persistent pain is a pervasive problem in modern medicine. Intrathecal therapy offers an alternative tool for the long-term management of patients with chronic pain who did not respond to less invasive therapies or systemic opioids, mainly in terms of reduced side effects. SDB as well as excessive daytime sleepiness (EDS) are common in chronic pain patients on oral opioid therapy, but no data are available for patients receiving IT. Aim of our study was to study two groups of consecutive patients receiving IT opioid therapy, according to absence (A, n=6) or presence (P, n=5) of EDS. All the patients (8 F, age 56.9±8.3 yrs, BMI 25.6±6 kg/m 2 ) underwent polysomnography (PSG) and maintenance wakefulness test (MWT). Table 1 shows sleep indices for both group of patients:  Both EDS and sleep latency at MWT were statistically significantly correlated with the amount of NREM2 percentage (r=0.68, p=0.003; r= -0.61, p=0.04; respectively). 6 patients were affected by sleep apnea (AHI 32.8±26): central in 1, mixed in 1 and obstructive in 4 patients. Age was statistically significantly correlated with AHI (r=0.76, p
Role of genetic factors on smoking habits and secondhand smoke sensitivity: A twin study
Authors: Adam Domonkos Tarnoki, David Laszlo Tarnoki, Zsofia Lazar, Kinga Karlinger, Andrea Agnes Molnar, Zsolt Garami, Viktor Berczi, Ildiko Horvath
Journal: European Respiratory Journal (2012)

Introduction: The role of genetic factors on nicotine dependence, withdrawal and quitting is well understood, however no information is available on secondhand smoke (SHS) exposure sensibility. Our aim was to assess SHS exposure, smoking habits and characteristics, smoking regulations at home, during driving and at workplace of monozygotic (MZ) and dizygotic (DZ) twins, and the contribution of genetic factors to SHS sensibility.

Methods: 161 Hungarian and 50 American adult twin pairs (151 MZ and 62 DZ; mean age 44±17 years±standard deviation/SD/) were recruited in this classical twin study.

Results: The overall rate of current, ex and never smokers was 14.6%, 16.4% and 69.2%. MZ twins reported higher rate of everyday and regular smoking for at least one year (p<0.05). 88% of MZ twins were both ex or current smokers, while the number was 70% in DZ twins (p<0.01). Significantly higher concordance was found in the disturbing effect of secondhand smoke in MZ versus DZ pairs (58 to 94% versus 39 to 79%, p<0.05 to p<0.005) on a self-reported smoke pollution scale between 1-7. Significantly smaller difference was observed in self-reported smoke pollution rate in MZ twins compared to DZ pairs concerning the restaurants and cafes (1.2±1.3 vs 1.8±1.5, p<0.05) which was not present regarding restaurants and cafes and transportation facilities.

Conclusions: In conclusion, this study estimated a genetic influence on smoking habits and secondhand smoke sensibility especially in smoke pollution rate of restaurants and cafes.
Active cytomegalovirus infection in non-immunosuppressed children with chronic respiratory disease
Authors: Maria Teresa Romero Rubio, David Navarro Ortega, Raquel Lucas Sendra, Marifina Chilet Saez, Silvia Castillo Corullon, Amparo Escribano Montaner
Journal: European Respiratory Journal (2012)

Cytomegalovirus (CMV) is reactivated in lower respiratory tract in the context of local or systemic inflammatory processes, increasing its morbimortality.  Objective: To set the incidence of active CMV infection in children with chronic respiratory diseases and no acute exacerbation.  Material and methods:Mixed retrospective-prospective study (May 2009-September 2011) of non-immunosuppressed children who underwent a diagnostic bronchoscopy.The serological test for the CMV was performed using CLIA (DiaSorin, Italy).Detection and quantification of DNA in respiratory samples and plasma by PCR QRT-PCR in the m2000RT system (AbbottDiagnostics, USA).  Results: 36 patients (45%male),mean age 5.5 years.Underlying diseases were cystic fibrosis(10),middle lobe syndrome(6), laryngotracheomalacia(4),poorly controlled asthma(3),obliterans bronchiolitis(2),interstitial lung disease(2),tracheostomy complications(2), bronchiectasis(2),persistent atelectasis(2),bronchial sequelae after bronchial tuberculosis (1),pulmonary hypoplasia(1) and pulmonary hemosiderosis(1). 11 patients were IgG positive.CMV DNA detected in 6 respiratory samples (16.6%;54.5% of the IgG positive population),4 in bronchoalveolar lavage and 2 in brochoaspirated.Viral DNA detected in plasma in two of them. The mean viral load at respiratory samples was 180 copies/mL (range 27-815 copies/mL) and in plasma 18 and 123 copies/mL.All the positive CMV children were under inhaled corticosteroid treatment.  Conclusion: Active CMV infection is common in non-immunosuppressed children with chronic respiratory disease.Prospective studies should elucidate the effects of CMV replication in their lower respiratory tract and clinical evolution.
Who should take responsibility for antisocial personality disorder?
Authors: N. Eastman
Journal: BMJ (1999)

News p 211 and Personal view p 271 

The diagnostic boundaries and treatability of personality disorders have always been medically controversial. Whether offenders with antisocial1 or dissocial2 personality disorder—“a most elusive category [with] wavering confines”3—should be treated in hospital or punished in prison is profoundly controversial. Now, because of highly publicised cases of paedophilic violent offenders released from prison and the case of Michael Stone, a convicted psychopathic murderer, the medical response to personality disorder has become a subject of national political debate. The dispute between the home secretary4 and the president of the Royal College of Psychiatrists5 about whether psychiatrists should be preventively detaining untreatable psychopaths under the Mental Health Act illustrates well the field of political conflict.

Into this debate comes the Fallon inquiry into the personality disorder unit at Ashworth high security hospital.6 This will soon be followed by the announcement of government policy on future services and legal provisions for personality disordered offenders, arising out of a Home Office-Department of Health working party that has been running in parallel with the inquiry. Fallon investigated and largely confirmed complaints of patients trading in …
Analyzing risk factors for intrahepatic cholangiocarcinoma
Authors: Tetsuji Fujita
Journal: Hepatology (2013)

Using a case-control analysis, Chaiteerakij et al.1 revealed that diabetes mellitus (DM) was associated with a 3.6-fold risk of developing intrahepatic cholangiocarcinoma (ICC) and that metformin use for DM reduced the risk of ICC by 60%. Furthermore, hyperlipidemia was found to be a protective factor against ICC. These findings are impressive, but may not be translated into the general population. Chaiteerakij et al. recruited 594 participants as controls from the Mayo Clinic Biobank to compare to 612 patients with ICC. The case-control study, which is, in a way, analogous to the prospective cohort study, has been used for over 60 years to examine the association between disease and potential risk factors, but this method has some limitations, one of which is susceptibility to selection bias. Case-control sampling is carried out in the context of an actual cohort study, but sampling fractions for controls are much smaller than those for cases as noted in the study by Chaiteerakij et al. In such situations, selection bias does occur if exposed controls are more or less likely to be sampled than nonexposed controls. For instance, if the frequency of sampled exposed persons as controls was twice the frequency as nonexposed persons, the estimated odds ratio would be twice the correct value.2 In Table 1 of the article,1 the incidence of hyperlipidemia in controls is 43.1%, which appears to be higher than that in the U.S. general population,3 suggesting that the protective effect of hyperlipidemia was overestimated. There are some concerns with regard to the analysis of the relationship between metformin use and risk of ICC. To eliminate such concerns, further analysis would be warranted. Tetsuji Fujita, M.D. Department of Surgery, Jikei University School of Medicine, Tokyo, Japan
Comparative study of community-acquired pneumonia between diabetic and nondiabetic patients with hyperglycemia
Authors: Amaia Urrutia, Rafael Zalacain, Ainhoa Gomez, Lorea Martinez-Indart, Carmen Jaca, Maria Alfonso, Ruth Diez, Marta Inchausti, Luis Alberto Ruiz
Journal: European Respiratory Journal (2012)

AIM: To study the differences in clinical presentation and evolution of community acquired pneumonia (CAP) between patients with known-diabetes and non-diabetic but with hyperglycemia status (HG) at hospital admission.  METHODS: We performed a prospective, observational study of patients admitted to Pneumology department consecutively with a diagnosis of CAP. The plasma glucose levels were measured on admission and patients were divided into two groups: diabetic patients and non-diabetic with HG. We consider HG when plasma glucose level =>200mg/dl. We studied different variables, included severe clinical course (mortality and/or septic shock and/or invasive mechanical ventilation (IMV) during hospital stay.  RESULTS: we studied 1389 patients, 274 were known diabetic and 53 (3,8%) were non-diabetic with HG.  CONCLUSIONS: 1.- Non-diabetic patients with HG had a more severe clinical course comparing to known-diabetic, althoug mortality was similar. 2.- Non-diabetic patients with HG had more respiratory comorbidities, reached clinical stability later, had a higher admission to ICU and needed more IMV, with a longer hospital stay. 3.- 4% of patients admitted with a CAP had a not-known HG.