bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computed tomography-guided biopsy of small lung nodules: diagnostic accuracy and analysis for true negatives
Authors: Liu Xing-Li , Li Wei , Yang Wei-Xin , Rui Mao-Ping , Li Zhi , Lv Liang , Yang Li-Peng 
Published: October 2019

Objective We evaluated the diagnostic accuracy of computed tomography (CT)-guided transthoracic core needle biopsy (TCNB) for small (≤20-mm) lung nodules and identified predictive factors for true negatives among benign biopsy results. Methods From March 2010 to June 2015, 222 patients with small lung nodules underwent CT-guided TCNB. We retrospectively analysed data regarding technical success, diagnostic accuracy, and predictors of true negatives. Results The technical success rate was 100%. The TCNB results of the 222 lung nodules included malignancy (n = 136), suspected malignancy (n = 8), specific benign lesion (n = 17), and nonspecific benign lesion (n = 61). The final diagnosis of 222 lung nodules included malignant (n = 160), benign (n = 60), and nondiagnostic lesions (n = 2). The sensitivity, specificity, and overall diagnostic accuracy of CT-guided TCNB for small lung nodules were 90.0%, 100%, and 92.7%, respectively. Pneumothorax and haemoptysis occurred in 23 and 41 patients, respectively. Based on the Cox regression analysis, the significant independent predictive factor for true negatives was a biopsy result of chronic inflammation with fibroplasia. Conclusions CT-guided TCNB offers high diagnostic accuracy for small lung nodules, and a biopsy result of chronic inflammation with fibroplasia can predict a true-negative result.
Collagenous Ultrastructure of the Torn Medial Meniscus Posterior Root: A Transmission Electron Microscopy Study
Authors: Seo Young-Jin , Kim Sung-Jae , Jung Dawoon , Kim Jeehyoung , Shin Young-Soo , Choi Seungbi , Shin Eun , Song Si Young 
Published: October 2019

Background: The collagen ultrastructure of torn medial meniscus posterior roots (MMPRs) has not been precisely defined. Purpose: To investigate the ultrastructure of torn MMPRs, focusing on their collagen fibers, and to compare the collagen net architecture between intact and torn MMPRs using the Collagen Meniscal Architecture (CMA) scoring system. Study Design: Descriptive laboratory study. Methods: Forty-three human meniscal specimens were obtained from 32 patients with osteoarthritis during total knee arthroplasty between January 2018 and November 2018. There were 23 specimens taken from patients with an MMPR tear and 20 taken from patients without an MMPR tear served as a control group. The presence of an MMPR tear was defined as a complete radial tear within 9 mm of the posterior root attachment. The collagen ultrastructure of the meniscal specimens was assessed with transmission electron microscopy using the CMA scoring system. Patient demographics included sex, age, and body mass index, and radiographic assessments included the Kellgren-Lawrence (K-L) grading system and the mechanical axis angle. Results: The median CMA score was significantly higher in torn MMPRs (5.5 [interquartile range, 3.5-6.0]) than in intact MMPRs (2.0 [interquartile range, 1.5-3.8]) ( P < .001). When the CMA scores were converted to CMA grading, 23 torn MMPRs had 1 grade I, 9 grade II, and 13 grade III menisci. In 20 intact MMPRs, there were 12 grade I, 7 grade II, and 1 grade III menisci. No significant differences in sex, age, body mass index, K-L grade, or mechanical axis angle were found between groups. Conclusion: This study showed that torn MMPRs had decreased numbers and disorganized courses of collagen fibers. The structural problem of torn MMPRs can negatively affect meniscal healing, function, and long-term survival after root repair. Clinical Relevance: These results might provide a histopathological reason for the low healing rate after MMPR repair.
Urinary tract infection and subclinical bacteriuria in cats: A clinical update
Authors: Dorsch Roswitha , Teichmann-Knorrn Svenja , Sjetne Lund Heidi 
Published: October 2019

Practical relevance: Urinary tract infection (UTI) is an important cause of feline lower urinary tract disease (FLUTD), particularly in female cats older than 10 years of age. In addition to cats with typical clinical signs of FLUTD or upper UTI, many cats have subclinical bacteriuria, but the clinical relevance of this is currently uncertain. UTIs are one of the most important indications for antimicrobial use in veterinary medicine and contribute to the development of antimicrobial resistance. Adherence to treatment guidelines and confinement to a few first-line antimicrobial agents is imperative to avoid further deterioration of the antimicrobial resistance situation. The decision to treat with antimicrobials should be based on the presence of clinical signs, and/or concurrent diseases, and the results of urine culture and susceptibility testing. Clinical challenges: Distinguishing between cats with bacterial cystitis, and those with idiopathic cystitis and concurrent clinical or subclinical bacteriuria, is challenging, as clinical signs and urinalysis results may be identical. Optimal treatment of subclinical bacteriuria requires clarification as there is currently no evidence that demonstrates a beneficial effect of routine treatment. Management of recurrent UTIs remains a challenge as evidence for most alternatives used for prevention in cats is mainly anecdotal, and no preventive treatment modality is currently recommended. Evidence base: This review draws on an extensive literature base in veterinary and human medicine, including the recently updated guidelines of the International Society for Companion Animal Infectious Diseases for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Where published evidence is lacking, the authors describe their own approach; notably, for the bacteriuric cat with chronic kidney disease.
Cognitive trajectories in relapsing–remitting multiple sclerosis: A longitudinal 6-year study
Authors: Damasceno Alfredo , Pimentel-Silva Luciana Ramalho , Damasceno Benito Pereira , Cendes Fernando 
Published: October 2019

Background: Information concerning longitudinal cognitive trajectories in multiple sclerosis (MS) is relatively scarce. Moreover, it is unclear which factors are associated with cognitive decline and what is the clinical impact of cognitive impairment (CI) in the long run. Objective: To investigate cognitive trajectories in relapsing–remitting multiple sclerosis (RRMS) patients, analyzing clinical and magnetic resonance imaging (MRI) predictors of cognitive decline. Methods: We enrolled 42 patients and 30 controls. They underwent brain MRI and clinical/neuropsychological evaluation at baseline and after 1, 2, and 6 years. We evaluated cognitive domains with principal component analysis and performed multivariable regression analyzing predictors of clinical/cognitive deterioration. We also performed repeated measures analysis to assess whether clinical progression was different according to CI at baseline. Results: A total of 23 (62.2%) patients deteriorated in combined cognitive domains after 6 years, most in processing speed and memory. The number of baseline impaired cognitive domains was strongly associated with 6-year cognitive ( R2 = 0.452; p < 0.001) and Expanded Disability Status Scale (EDSS) deterioration ( R2 = 0.263; p < 0.001). Patients with baseline CI in combined domains had worse clinical progression. Conclusion: Isolated CI tends to become more widespread, affecting memory and processing speed alongside. The extent of baseline CI was the best predictor of both clinical and cognitive deterioration after 6 years.
WS PRO 160 I 120 mg (a combination of sabal and urtica extract) in patients with LUTS related to BPH
Authors: Kirschner-Hermanns Ruth , Funk Petra , Leistner Nadine 
Published: October 2019

Introduction: Lower urinary tract symptoms (LUTS) caused by prostatic enlargement are a common impairing condition in men aged 50 years and older. In the management of LUTS related to benign prostatic hyperplasia (BPH), medication, particularly by α-adrenoceptor antagonists, 5α-reductase inhibitors, and phytopharmaceuticals, is considered the first-line therapy. Despite their popularity, a number of adverse effects on the cardiovascular or cognitive systems have been reported for some of the synthetic drugs. One of the promising herbal preparations for the treatment of patients suffering from LUTS related to BPH is WS PRO 160 I 120 mg, a combination of sabal fruit extract and urtica root extract. Methods: This review of the literature summarizes clinical evidence for WS PRO 160 I 120 mg derived from four randomized placebo- or reference-controlled double-blind clinical trials including men aged 50 years and older. In all trials, symptomatic improvement was evaluated by the International Prostate Symptom Score (I-PSS) total score. Results: Treatment effects of WS PRO 160 I 120 mg were shown to be superior over placebo and comparable with the 5α-reductase inhibitor finasteride or the α1-adrenoceptor antagonist tamsulosin with more favorable tolerability and safety profiles as compared with the reference drugs. Conclusions: The results suggest WS PRO 160 I 120 mg to be considered as a valid alternative in the treatment of patients with early BPH, especially with view to sexual function and a good quality of life, especially in long-term use.
Transplant Donor KIR Genotype Influences the Rate of CMV Reactivation Following T-Replete Stem Cell Transplantation.
Authors: Cook Mark , Briggs David C. , Craddock Charles F. , Mahendra Premini , Milligan Donald , Fegan Christopher , Darbyshire Philip , Lawson Sarah , Boxall Elizabeth , Moss Paul 
Published: October 2019

Abstract
Background
CMV reactivation is the commonest viral complication following allogeneic stem cell transplantation (SCT) and is a direct consequence of immunodeficiency. Natural killer (NK) and T-cells are the primary effector populations that suppress CMV replication. Killer immunoglobulin-like receptors (KIRs) are expressed on the surface of NK cells and T-cell subsets. Inhibitory KIRs have specificity for defined alleles of class I HLA and deliver an inhibitory signal to the cell. Activating KIRs bind weakly to HLA molecules and their true ligands remain unknown. KIR genes are polymorphic. Two broad haplotypes exist which differ in the number of activatory KIR genes that they contain. Haplotype A has 1 activatory KIR gene whereas haplotype B contains additional activatory genes.
Methods
We studied 107 patients undergoing allogeneic SCT at 3 UK Institutions to evaluate the effect of activating KIRs on CMV reactivation. Two thirds received standard myeloablative conditioning with TBI/Cy or Bu/Cy. One third received non-myeloablative conditioning. Recipient/donor CMV sero-status was determined by ELISA. Reactivation was defined as two successive PCR assays detecting >400 copies/ml. KIR genotyping was performed by PCR-SSP.
Results
In CMV seropositive recipients, the CMV reactivation rate was 50% in transplants from sibling donors and 64% in transplants from unrelated or HLA non-identical donors. In sibling transplants where both donor and recipient were CMV seropositive and the donor was homozygous for KIR Haplotype A (group A) the CMV reactivation rate was 65% .In contrast if the donor possessed at least one KIR haplotype B (group B) the reactivation rate was reduced to 27.5% (p=0.014). The protective effect of group B donors was seen only in patients who received a myeloablative non-T-depleted transplant. Here, the reactivation rate was 70.6% (12 from 17) when transplanted from a group A donor compared with 23.8% (5 from 21) when transplanted from a group B donor (p=0.0039). If a group B donor was used no reactivation was seen after 41 days, whereas in transplants from group A donors the risk of reactivation continued until day 100 (figure 1,p=0.018). The donor KIR genotype did not influence CMV reactivation rates in patients who received T-depleted grafts from sibling, unrelated or haploidentical donors.
Conclusion
In T-cell replete sibling donor transplants the use of a donor with multiple activating KIRs significantly reduces the risk of CMV reactivation when both donor and recipient are CMV seropositive. This is the first direct evidence of activating KIRs exerting a controlling effect on CMV in humans.
Stable RNAi-Mediated Knock-Down of P-Glycoprotein by a Transposon-Based Vector System Restores Imatinib Sensitivity.
Authors: Rumpold Holger F. , Wolf Anna M. , Gastl Guenther A. , Gunsilius Eberhard , Wolf Dominik G.F. 
Published: October 2019

Abstract
Overexpression of P-glycoprotein (PgP) is critical for resistance of malignant cells against cytotoxic agents. However, the role of PgP overexpression for the sensitivity of chronic myeloid leukemia (CML) to imatinib remains controversial. We therefore constructed a transposon-based (Sleeping beauty) RNAi system for the stable down-regulation of PgP in imatinib/doxorubicin resistant K562/Dox cell lines. RT-PCR demonstrated the stable integration of the transposon into the genome. Real-time PCR revealed a rapid and almost complete degradation of MDR1 mRNA 72 h after nucleofection. PgP knockdown on protein level was much more efficient in the stable setting as compared to the transient approach. This observation points out to the requirement of stable knockdown approaches for siRNA-mediated downregulation of proteins with long half-life time. The functional impact of stable PgP knock-down was demonstrated by a reduced efflux of rhodamine and doxorubicin. In parallel, MDR1 knockdown cells were re-sensitized to doxorubicin as well as to imatinib-induced cell death. This observation supports the notion that up-regulation of MDR1 in CML might contribute to imatinib resistance in vivo.
In summary we describe a very efficient tool for the stable knock-down of PgP by transposon-mediated siRNA delivery in CML cells and propose that the down-regulation of PgP in CML can restore sensitivity to imatinib.
Donor Activating Kir Genes and Survival after Haplo-Identical Hematopoietic Transplantation.
Authors: Mancusi Antonella , Ruggeri Loredana , McQueen Karina , Perruccio Katia , Aversa Franco , Martelli Massimo F. , Parham Peter , Velardi Andrea 
Published: October 2019

Abstract
Although NK cell alloreactivity impacts beneficially on the outcome of haploidentical transplantation in AML patients, largely through its GvL effect (Ruggeri et al, Science 2002), TRM (~40%, largely due to infections) remains a major problem. In a search for additional donor selection criteria, here we determined the donor KIR genotypes and correlated them with transplantation outcomes in 74 AML recipients. Transplants from donors carrying group A KIR haplotype genes, which mainly encode for inhibitory receptors (and for the activating KIR2DS4 gene) (n=22), were compared with those from donors carrying group B KIR haplotype genes, which encode for additional activating KIRs (KIR2DS1, 2, 3, 5 and KIR3DS1) (n=52). Event-free survival appeared better in AML patients transplanted from donors bearing B haplotype genes (48% vs 23%, p=0.066). As expected, other well established factors of good prognosis, such as NK cell alloreactivity and disease status at transplant, played significant independent roles (H.R.=0.42 donor NK cell alloreactivity present vs absent, 95% C.I.=0.22–0.79, p=0.007; H.R.=0.39 remission vs relapse at transplant, 95% C.I.=0.21–0.72, p=0.003). However, after adjusting for donor-vs-recipient NK cell alloreactivity and transplantation in remission, transplantation from donors carrying group B haplotype KIR genes still tended to emerged as an independent predictor of survival (H.R.=0.56 B haplotype genes present vs absent, 95% C.I.=0.3–1.0, p=0.07). This might have been the consequence of reduced incidence of leukaemia relapse. In an analysis of factors involved in relapse, donor-vs-recipient NK alloreactivity and disease status at transplant were confirmed as strong independent protective factors (H.R.=0.18 donor NK cell alloreactivity present vs absent, 95% C.I.=0.05–0.68, p=0.01; H.R.=0.15 remission vs relapse at transplant, 95% C.I.=0.04–0.58, p=0.006). Transplantation from donors carrying activating group B haplotype KIR genes had no effect on relapse (H.R.=0.59 B haplotype genes present vs absent, 95% C.I.= 0.17–2.05, p>0.1). Strikingly, in analyzing TRM, transplantation from these donors was associated with a markedly reduced TRM (59% vs 30%, p=0.03), and emerged as the only statistically significant protective factor (H.R.=0.46 B haplotype genes present vs absent, 95% C.I.= 0.22–0.97, p=0.04), even when compared with NK cell alloreactivity (H.R.=0.56 donor NK cell alloreactivity present vs absent, 95% C.I.=.026–1.20, p>0.1) and disease status at transplant (H.R.=0.53 remission vs relapse at transplant, 95% C.I.=0.25–1.11, p=0.09). Thus, transplantation from donors carrying activating (group B haplotype) genes could be a new donor selection criterion which might help reduce infectious mortality after haploidentical hematopoietic transplantation.
The mechanisms underlying this apparently improved immune competence remain to be investigated.
Home Telemetric System for Pulmonary Function Surveillance: A Useful Procedure for Detection of Late-Onset Noninfectious Pulmonary Complications (LONIPC) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Guihot Amélie , Becquemin Marie-Hélène , Couderc Louis-Jean , Randrianarivelo Odile , Rivaud Elisabeth , Philippe Bruno , Neveu Hélène , Vernant Jean-Paul , Dhedin Nathalie 
Published: October 2019

Abstract
Late-onset noninfectious pulmonary complications (LONIPC) of allogeneic hematopoïetic stem cell transplantation (HSCT) occur in 2 to 25% of recipients. LONIPC include bronchiolitis obliterans (BrOb), which is associated with an obstructive syndrome, bronchiolitis obliterans with organizing pneumonia (BOOP) and interstitial pneumonia (IP), which are associated with a restrictive syndrome on pulmonary function tests. LONIPC have poor prognosis with death from respiratory failure in more than 30% of cases. We evaluated a telemetric system for home pulmonary function surveillance, for early diagnosis and treatment of LONIPC in allogeneic HSCT recipients.
We conducted a prospective study of 35 patients living in Paris area, who survived over 3 months after HSCT (median age 46 years, myeloablative conditioning regimen in 54.2% of patients, HLA-identical sibling donor in 65.7%) between June 2001 and January 2004. Three months after HSCT, patients were delivered a portable spirometer (Spirotel®, M-Elect France), measuring vital capacity, forced expiratory volume per second, and mid expiratory flow 25 to 75 values. Data were transmitted by phone to hospital twice a week. If significant deterioration (>20%) was confirmed by plethysmography, then patients were admitted in Pneumology Department.
Thirteen episodes of spirometric deterioration were detected in 11 patients during a median follow-up period of 18 months (1 to 42). LONIPC was diagnosed on spirometric, CT scan and broncho-alveolar lavage criteria during 8 episodes in 7/35 patients (20%), occurring after a median time of 11 months (6 to 18) after HSCT. One of these 7 patients had previously developed acute graft versus host disease (GVHD) and 5 had current chronic GVHD. LONIPC were BrOb, (n=3), interstitial pneumonia (n=4), or both BrOb and interstitial pneumonia (n=1). Patients were treated with increasing immunosuppressive regimens (prednisone and/or, mycophenolate mofetil, and/or cyclosporine A). Five patients improved and 2 were stabilised. There was no case of long-term oxygen therapy or death from respiratory failure (median follow-up 24 months (12 to 34) from LONIPC diagnosis). Telemetric home monitoring of pulmonary function is a reliable procedure easy-to-use for early diagnosis of LONIPC, which might improve the usual severe prognosis of LONIPC occurring after allogeneic HSCT.
Oral Administration of the Opium Alkaloid Noscapine (NOS) Exhibits Potent Anti-Tumor Activity Against Non-Hodgkin’s Lymphomas and Myeloma Cell Lines In Vitro and In Vivo in SCID-beige Murine Xenograft Models.
Authors: O’Connor Owen , Mastrella J. , Smith E. , Toner L. , Auerbach A. , Leonard J. P. 
Published: October 2019

Abstract
Noscapine is an oral opiate alkaloid with structural similarity to colchicine that induces cell cycle arrest and apoptosis. Its mechanism of action appears similar to vincristine (VCN). In a trypan blue exclusion assay, noscapine exhibits increasing potency with increasing duration of exposure in B- and T-cell lymphomas, and myelomas (MM). For example, following 24 hours of exposure to noscapine, the OPM2 (MM), H9 (TCL) and RL (BCL) lines exhibited an IC50 of approximately 10 to 15 mM. Exposure for up to 96 hours effected IC50 of 30 nM, 700 nM, and 500 nM for the OPM2, H9 and RL lines respectively. Across all cell lines studied, increasing the duration of exposure by only a couple of days resulted in multiple log decreases in IC50. Combining noscapine with doxorubicin and 4-hydroxycyclophosphamide in vitro resulted in at least additive or better cytotoxicity. In vivo, both intraperitoneal and oral doses of noscapine were evaluated on a daily schedule for 14 days (200, 300, 400 and 600 mg/kg). These data demonstrated that the toxicity was much greater when administered by the i.p. route, where 60% of animals died as a result of toxicity in the 600 mg/kg i.p. cohort, while none died from toxicity when given by oral gavage. Preliminary efficacy experiments demonstrated that by day 15, animals treated with 600 and 400 mg/kg noscapine by oral gavage exhibited tumor growth delays that were 30 to 50% of the control tumor volume. Activation of caspase 3 by noscapine demonstrated a linear dose response relationship which was strongly related to duration of drug exposure. Noscapine may represent a new well tolerated oral therapy for the control of lymphoma and myeloma. Antimitotic agents with effects like VCN may be improved with higher area under of the curve of exposure, and thus are well suited for oral administration. Ongoing phase I studies are determining the MTD and DLT associated with noscapine. Phase 2 studies are warranted.