Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Identification of a Phytoplasma Associated with Witches'-Broom Disease of Black Raspberry in Oregon and Its Classification in Group 16SrIII, New Subgroup Q.

Plants of Rubus occidentalis (black raspberry) 'Munger' exhibiting symptoms of black raspberry witches'-broom (BRWB) disease were observed in commercial fields in Oregon (1). Symptoms were often severe, leading to death of infected plants, and a phytoplasma (mycoplasmalike bodies) was observed in ultrathin sections of diseased plants (1). In the current work, the association of phytoplasma with BRWB was assessed using the polymerase chain reaction (PCR) for specific amplification of phytoplasmal rDNA. DNA template for use in the PCR was extracted from plants as described elsewhere (2). Phytoplasmal 16S rDNA was amplified from diseased black raspberry plants in PCR primed by primer pair P1/P7 and reamplified in nested PCR primed by primer pair R16F2n/R2 (F2n/R2) by a method described previously (2). These results indicated the presence of a phytoplasma, designated BRWB phytoplasma, in the diseased plants. Identification of BRWB phytoplasma was accomplished by restriction fragment length polymorphism (RFLP) analysis of DNA amplified in PCR primed by F2n/R2. Phytoplasma classification was done according to the system of Lee et al. (3). On the basis of collective RFLP patterns of the amplified 16S rDNA, the BRWB phytoplasma was classified as a member of group 16SrIII (group III, X-disease phytoplasma group). The HhaI RFLP pattern of BRWB 16S rDNA differed from that of its close relative, clover yellow edge (CYE) phytoplasma. The RsaI RFLP pattern of BRWB rDNA differed from that of rDNA from all phytoplasmas previously described in group III. Based on these results, BRWB phytoplasma was classified in a new subgroup, designated subgroup Q (III-Q) within group III. The 1.8 kbp DNA product of PCR primed by primer pair P1/P7 was cloned and its nucleotide sequence determined. The sequence was deposited in GenBank under Accession no. AF302841. Results from putative restriction site analysis of the cloned and sequenced rDNA were in excellent agreement with the results from enzymatic RFLP analysis of uncloned rDNA amplified from BRWB diseased black raspberry. Sequence similarity between the 1.8 kbp rDNA of BRWB phytoplasma and that of CYE phytoplasma was 99.4%. The nucleotide sequence data support the conclusion that the BRWB phytoplasma is related to, but is distinct from, other strains that are classified in group III. These findings contribute knowledge about the diversity of phytoplasmas affiliated with group III and provide information to aid the diagnosis of BRWB disease. References: (1) R. H. Converse et al. Plant Dis. 66:949, 1982. (2) R. Jomantiene et al. Int. J. Syst. Bacteriol. 48:269, 1998. (3) I. -M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998.
Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion.

In a previous limb-girdle muscular dystrophy type 2D (LGMD2D) clinical trial, robust alpha-sarcoglycan gene expression was confirmed following intramuscular gene (SGCA) transfer. This paved the way for first-in-human isolated limb infusion (ILI) gene transfer trial to the lower limbs. Delivery of scAAVrh74.tMCK . hSGCA via an intravascular route through the femoral artery predicted improved ambulation. This method was initially chosen to avoid safety concerns required for large systemic vascular delivery viral loads. ILI methods were adopted from the extensive chemotherapy experience for treatment of malignancies confined to the extremities. Six LGMD2D subjects were enrolled in a dose-ascending open-label clinical trial. Safety of the procedure was initially assessed in the single limb of a non-ambulant affected adult at a dose of 1 × 1012 vg/kg. Subsequently, ambulatory children (aged 8-13 years) were enrolled and dosed bilaterally with either 1 × 1012 vg/kg/limb or 3 × 1012 vg/kg/limb. The six-minute walk test (6MWT) served as the primary clinical outcome; secondary outcomes included muscle strength (maximum voluntary isometric force testing) and SGCA expression at 6 months. All ambulatory participants except one had pre- and post-treatment muscle biopsies. All four subjects biopsied had confirmed SGCA gene delivery by immunofluorescence, Western blot analysis (14-25% of normal), and vector genome copies (5.4 × 103-7.7 × 104 vg/μg). Muscle strength in the knee extensors (assessed by force generation in kilograms) showed improvement in two subjects that correlated with an increase in fiber diameter post gene delivery. Six-minute walk times decreased or remained the same. Vascular delivery of AAVrh74.tMCK. hSGCA was effective at producing SGCA protein at low doses that correlated with vector copies and local functional improvement restricted to targeted muscles. Future trials will focus on systemic administration to enable targeting of proximal muscles to maximize clinical benefit.
Community-based participatory research remodelling occupational therapy to foster older adults’ social participation

Background. Occupational therapists who provide community-based services are well positioned to foster older adults’ social participation. However, community occupational therapists rarely address social participation and require support to change their practice. Purpose. This study initiated a remodelling of community occupational therapy services by (a) selecting practices fostering older adults’ social participation and (b) identifying factors that could affect their integration. Method. A community-based participatory research study was conducted in a large Canadian city. Four focus group meetings and seven individual interviews were held with 28 key informants. Findings. A continuum of emerging practices was identified, including personalized, group-based, and community-based interventions. Potential enablers of these practices included clinical support, better communication, and user involvement. Organizational and systemic barriers were related to the institutional culture and performance indicators. Implications. These results point to innovative ways to foster older adults’ social participation and identify potential enablers and barriers affecting their integration.
Long-Term Safety and Real-World Effectiveness of Trastuzumab in Breast Cancer

Trastuzumab is a milestone in the treatment of human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), in both the early and metastatic settings. Over the last two decades, clinical trials have established the good safety profile of trastuzumab. Cardiotoxicity remains the most frequent adverse event, more commonly exemplified by an asymptomatic decline in the left ventricular ejection fraction rather than congestive heart failure. Results from several long-term (>5 years) safety analyses have been recently published, with the inherent evidence substantially confirming the findings from previous trials. The clinical experience gained over the years in the use of trastuzumab has also fueled a number of observational studies focused on the effectiveness of this drug in the real-world settings. We herein reviewed the evidence available from tree major databases, namely, PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), to explore and critically discuss key issues related to the long-term safety and effectiveness of trastuzumab in clinical practice.
Patient-Specific Computational Fluid Dynamics in Ruptured Posterior Communicating Aneurysms Using Measured Non-Newtonian Viscosity : A Preliminary Study

Objective The objective of this study was to analyze patient-specific blood flow in ruptured aneurysms using obtained non-Newtonian viscosity and to observe associated hemodynamic features and morphological effects. Methods Five patients with acute subarachnoid hemorrhage caused by ruptured posterior communicating artery aneurysms were included in the study. Patients’ blood samples were measured immediately after enrollment. Computational fluid dynamics (CFD) was conducted to evaluate viscosity distributions and wall shear stress (WSS) distributions using a patient-specific geometric model and shear-thinning viscosity properties. Results Substantial viscosity change was found at the dome of the aneurysms studied when applying non-Newtonian blood viscosity measured at peak-systole and end-diastole. The maximal WSS of the non-Newtonian model on an aneurysm at peaksystole was approximately 16% lower compared to Newtonian fluid, and most of the hemodynamic features of Newtonian flow at the aneurysms were higher, except for minimal WSS value. However, the differences between the Newtonian and non-Newtonian flow were not statistically significant. Rupture point of an aneurysm showed low WSS regardless of Newtonian or non-Newtonian CFD analyses. Conclusion By using measured non-Newtonian viscosity and geometry on patient-specific CFD analysis, morphologic differences in hemodynamic features, such as changes in whole blood viscosity and WSS, were observed. Therefore, measured non-Newtonian viscosity might be possibly useful to obtain patient-specific hemodynamic and morphologic result.
Effect of intrathecal morphine and epidural analgesia on postoperative recovery after abdominal surgery for gynecologic malignancy: an open-label randomised trial

Objectives We aimed to determine whether regional analgesia with intrathecal morphine (ITM) in an enhanced recovery programme (enhanced recovery after surgery [ERAS]) gives a shorter hospital stay with good pain relief and equal health-related quality of life (QoL) to epidural analgesia (EDA) in women after midline laparotomy for proven or assumed gynaecological malignancies. Design An open-label, randomised, single-centre study. Setting A tertiary referral Swedish university hospital. Participants Eighty women, 18–70 years of age, American Society of Anesthesiologists I and II, admitted consecutively to the department of Obstetrics and Gynaecology. Interventions The women were allocated (1:1) to either the standard analgesic method at the clinic (EDA) or the experimental treatment (ITM). An ERAS protocol with standardised perioperative routines and standardised general anaesthesia were applied. The EDA or ITM started immediately preoperatively. The ITM group received morphine, clonidine and bupivacaine intrathecally; the EDA group had an epidural infusion of bupivacaine, adrenalin and fentanyl. Primary and secondary outcome measures Primary endpoint was length of hospital stay (LOS). Secondary endpoints were QoL and pain assessments. Results LOS was statistically significantly shorter for the ITM group compared with the EDA group (median [IQR]3.3 [1.5–56.3] vs 4.3 [2.2–43.2] days; p=0.01). No differences were observed in pain assessment or QoL. The ITM group used postoperatively the first week significantly less opioids than the EDA group (median (IQR) 20 mg (14–35 mg) vs 81 mg (67–101 mg); p<0.0001). No serious adverse events were attributed to ITM or EDA. Conclusions Compared with EDA, ITM is simpler to administer and manage, is associated with shorter hospital stay and reduces opioid consumption postoperatively with an equally good QoL. ITM is effective as postoperative analgesia in gynaecological cancer surgery. Trial registration number NCT02026687; Results.
Cardiovascular disease in Williams syndrome.

Williams syndrome (WS), also referred to as Williams-Beuren syndrome (Online Mendelian Inheritance in Man 194050), is a congenital, multisystem disorder involving the cardiovascular, connective tissue, and central nervous systems.1 WS occurs in ≈1 in 10 000 live births2 as a result of the de novo deletion of ≈1.55 to 1.83 Mb on chromosome 7q11.23. 3 Familial cases can occur but are far less common than de novo cases.4 The deletion involves 26 to 28 genes, including the ELN gene, which codes for the protein elastin.5 Hemizygosity of the ELN gene coding for elastin has been demonstrated to be responsible for the vascular pathology in WS.6 The remaining 25 to 27 deleted genes contribute to the phenotypic findings in patients with WS and have recently been reviewed in detail elsewhere.5 In 1961, Williams et al7 reported their experience with 4 patients with supravalvar aortic stenosis (SVAS), mental retardation, and abnormal facial features. The following year, Beuren and colleagues8 reported similar findings in 5 patients, and they subsequently reported detailed cardiac and angiographic data from 10 such patients.9 Their findings, combined with other characteristic features, led both groups to theorize that a previously unrecognized syndrome was the likely origin, a theory that led to the eponym Williams-Beuren syndrome. After the reports of Williams et al7 and Beuren et al8 were published, the basis for the diagnosis of WS was the presence of a constellation of distinctive phenotypic characteristics. Genetic analysis at that time was limited essentially to karyotyping and microscopic inspection of individual chromosomes, which Beuren et al9 reported in 3 of their patients. With improved molecular genetics diagnostic techniques, Ewart et al10 used fluorescent in situ hybridization to demonstrate hemizygosity of the ELN locus in patients with WS. …
Interventions following hearing screening in adults: A systematic descriptive review

Abstract Objective: Adult hearing screening may be a solution to the under-diagnosis and under-treatment of hearing loss in adults. Limited use and satisfaction with hearing aids indicate that consideration of alternative interventions following hearing screening may be needed. The primary aim of this study is to provide an overview of all intervention types that have been offered to adult (≥ 18 years) screen-failures. Design: Systematic literature review. Articles were identified through systematic searches in PubMed, EMBASE, Cinahl, the Cochrane Library, private libraries, and through reference checking. Results: Of the initial 3027 papers obtained from the searches, a total of 37 were found to be eligible. The great majority of the screening programmes (i.e. 26) referred screen-failures to a hearing specialist without further rehabilitation being specified. Most of the others (i.e. seven) led to the provision of hearing aids. Four studies offered alternative interventions comprising communication programme elements (e.g. speechreading, hearing tactics) or advice on environmental aids. Conclusions: Interventions following hearing screening generally comprised referral to a hearing specialist or hearing aid rehabilitation. Some programmes offered alternative rehabilitation options. These may be valuable as an addition to or replacement of hearing aid rehabilitation. It is recommended that this be addressed in future research. Sumario Objetivo: El tamiz auditivo en adultos puede ser una solución al diagnóstico y tratamiento insuficiente de las alteraciones auditivas en adultos. El uso y satisfacción limitados con los auxiliares auditivos indica que pueden necesitarse intervenciones alternativas luego del tamiz auditivo. El propósito primario de este estudios es echar un vistazo a todos los tipos de intervención que han sido ofrecidas a adultos (≥ 18 años) que fallan dicho tamiz. Diseño: Revisión sistemática de la literatura. Se identificaron artículos a través de una búsqueda sistemática en PubMed, EMBASE, Cinahl, la Biblioteca Cochran, bibliotecas privadas y a través de revisión de referencias. Resultados: De los 3027 trabajos iniciales obtenidos de las búsquedas, se encontró un total de 37 que eran elegibles. La gran mayoría de los programas de tamiz auditivo (p.e., 26) refirieron los fallos del tamiz a un especialista en audición, sin especificar nada adicional sobre rehabilitación. La mayoría de los otros (p.e., 7) llevaron a la adaptación de auxiliares auditivos. Cuatro estudios ofrecieron intervenciones alternativas que involucraban programas de comunicación (p.e., lectura labio-facial, tácticas para escuchar) o consejo sobre ayudas ambientales. Conclusiones: Las intervenciones que siguez al tamiz auditivo involucraron referencia a especialistas en audición o rehabilitación con auxiliares auditivos. Algunos programas ofrecieron opciones alternativas de rehabilitación. Estos pueden ser valiosos como una adición o en reemplazo de la rehabilitación con auxiliares auditivos. Se recomienda que esto sea analizado en investigaciones futuras.
A 2-year retrospective study of viral and host-associated risk factors in Pakistani hepatocellular carcinoma patients.

OBJECTIVE Persistent chronic hepatitis C (CHC) infection is associated strongly with serious complications such as hepatitis C virus-associated liver cirrhosis (HCV-LC) and hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC). The aim of this study was to assess the distribution of hepatitis C virus (HCV) genotypes among HCV-positive patients and examine the potential associations between viral and host-associated factors with the risk of developing HCV-HCC. PATIENTS AND METHODS HCV-positive patients (n=300) were enrolled and divided into three groups: CHC (n=171), HCV-LC (n=51), and HCV-HCC (n=78). RESULTS HCV genotype 3a showed the highest prevalence among HCV-positive individuals (66% of patients), followed by genotype 1a (15% of patients). The proportion of individuals infected with mixed HCV genotypes was higher among HCV-HCC patients. Interestingly, there were a significantly higher proportion of women (54/78; 69.2%) among HCV-HCC patients compared with CHC patients (89/171 or 52%; χ=6.47; P=1×10). Women with HCV had two-fold higher odds of developing HCV-HCC (odds ratio=2.07, 95% confidence interval: 1.18-3.71). In comparison with CHC patients, significantly more HCV-HCC patients were 50 years of age or older (59/78 or 75.6% of HCV-HCC patients and 61/171 or 35.7% of CHC patients; χ=34.27; P<0.0001), suggesting that HCV-positive patients aged 50 years or older had an ~five-fold higher risk of developing HCV-HCC (odds ratio=5.6, 95% confidence interval: 3.02-10.01). CONCLUSION In summary, HCV genotype 3a had the highest prevalence in the studied HCV-positive population, and women and older patients were at a higher risk of developing HCV-LC and HCV-HCC following CHC infections.
The haematological, proinflammatory cytokines and IgG changes during an ovine experimental theileriosis

Malignant ovine theileriosis is caused by Theileria lestoquardi, which is highly pathogenic in sheep. Theileriosis involves different organs in ruminants. Little is known about the role of proinflammatory cytokines in the pathogenesis of T. lestoquardi infection. The aim of this study was to measure concentration changes of proinflammatory cytokines and immunoglobulin G (IgG) during an ovine experimental theileriosis and correlate it with clinical and haematological parameters. During an experimental study, seven healthy Baluchi sheep (four females and three males) about 6–8 months old were infected with T. lestoquardi by feeding of infected unfed ticks on the sheep’s ears. The infected sheep were clinically examined during the study and blood samples were collected on days 0, 2, 5, 7, 10, 12, 14, 17 and 21. The haematological parameters were analysed by an automatic veterinary haematology cell counter and the inflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IgG were measured by enzyme-linked immunosorbent assay. All infected sheep had temperatures above 40 °C on days 3–4 post infection (PI). The maximum temperature was noted on day 7, and it remained high until day 21. The parasitaemia of T. lestoquardi infection increased from 0.01% (day 7 PI) to 3.3% (day 21 PI). The mean white blood cell (WBC), red blood cell (RBC), lymphocyte, neutrophil and platelet values slightly increased on day 2 PI and decreased by day 17 and day 21 PI. The percentage parasitaemia and fever had a negative correlation with the numbers of WBCs, RBCs, lymphocytes, neutrophils and platelets. The serum concentration of IL-6, TNF-α and IFN-γ cytokines increased and peaked on day 12 and thereafter decreased to levels lower than 0. Out of all tested cytokines, the concentration of IL-6 was significantly higher, as early as day 2 PI. No significant changes were observed for the IgG levels during the course of disease. A significant and strong correlation was observed between IL-6, TNF-α and IFN-γ values and a moderate correlation between IL-6 and the numbers of lymphocytes in the present study. A strong correlation was determined between the percentage parasitaemia and haematological parameters in T. lestoquardi-infected sheep. In addition, preliminary results indicate that the measurement of the serum concentrations of IL-6 in combination with haematological parameters could be considered a good marker to estimate the pathogenicity of T. lestoquardi strain.
TRAIL‐expressing recombinant Lactococcus lactis induces apoptosis in human colon adenocarcinoma SW480 and HCT116 cells

We investigated the ability of Lactococcus lactis, a species generally regarded as safe, to express tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) protein. The expressed protein was either cell wall anchored or secreted, and it was assessed whether this could induce apoptosis in human colon adenocarcinoma cell lines SW480 and HCT116.
Pseudomonoballismus in a Deafferented Arm Following Combined Medullary and Cerebellar Lesions of the Proprioceptive Pathways

A 58 year-old, right-handed man was referred to neurology following the onset of left arm flinging movements during the first postoperative day after biopsy of a cervicomedullary lesion. The patient had a six-month history of altered sensation of the left arm and reported that the affected arm felt somewhat different than the right arm. On examination alteration in soft touch sensation of the left arm was noted but, abnormal movements were not present. Magnetic resonance imaging (MRI) studies of the brain and cervical spine demonstrated a left dorsal-caudal-medullary lesion (Fig. 1). A posterior-fossa craniectomy with biopsy of the left medullary lesion was performed. On waking from the procedure, the patient asked his wife, “Did they take my arm off? ” Within hours, abnormal movements of the left arm emerged. Neurological examination revealed involuntary, large-amplitude, ballistic movements of the left arm. At times, these hyperkinetic movements were self-injurious, and a weighted pillow was used to avoid injury to the patient. The abnormal movements persisted during sleep. In the immediate postoperative period, a degree of anosognosia for these movements existed. A grasp reflex was not elicited on the affected side, and there was no evidence of intermanual conflict. Leftarm proprioceptive and vibratory input was absent from the hand to the level of the shoulder. Spinothalamic input was intact (Video 1). Investigations
Silent progression in disease activity–free relapsing multiple sclerosis

Rates of worsening and evolution to secondary progressive multiple sclerosis (MS) may be substantially lower in actively treated patients compared to natural history studies from the pretreatment era. Nonetheless, in our recently reported prospective cohort, more than half of patients with relapsing MS accumulated significant new disability by the 10th year of follow‐up. Notably, “no evidence of disease activity” at 2 years did not predict long‐term stability. Here, we determined to what extent clinical relapses and radiographic evidence of disease activity contribute to long‐term disability accumulation.
Neuronal apolipoprotein E4 increases cell death and phosphorylated tau release in alzheimer disease

The apolipoprotein E (APOE) E4 isoform is the strongest genetic risk factor for sporadic Alzheimer disease (AD). Although APOE is predominantly expressed by astrocytes in the central nervous system, neuronal expression of APOE is of increasing interest in age‐related cognitive impairment, neurological injury, and neurodegeneration. Here, we show that endogenous expression of E4 in stem‐cell–derived neurons predisposes them to injury and promotes the release of phosphorylated tau.