Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma.

PURPOSE To evaluate the efficacy, safety, and pharmacokinetics of multiple doses of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma (RCC). PATIENTS AND METHODS Patients (n = 111) were randomly assigned to receive 25, 75, or 250 mg CCI-779 weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, survival, and adverse events. Blood samples were collected to determine CCI-779 pharmacokinetics. RESULTS CCI-779 produced an objective response rate of 7% (one complete response and seven partial responses) and minor responses in 26% of these advanced RCC patients. Median time to tumor progression was 5.8 months and median survival was 15.0 months. The most frequently occurring CCI-779-related adverse events of all grades were maculopapular rash (76%), mucositis (70%), asthenia (50%), and nausea (43%). The most frequently occurring grade 3 or 4 adverse events were hyperglycemia (17%), hypophosphatemia (13%), anemia (9%), and hypertriglyceridemia (6%). Neither toxicity nor efficacy was significantly influenced by CCI-779 dose level. Patients were retrospectively classified into good-, intermediate-, or poor-risk groups on the basis of criteria used by Motzer et al for a first-line metastatic RCC population treated with interferon alfa. Within each risk group, the median survivals of patients at each dose level were similar. CONCLUSION In patients with advanced RCC, CCI-779 showed antitumor activity and encouraging survival and was generally well tolerated over the three dose levels tested.
Bacterial rRNA Genes Associated with Soil Suppressiveness against the Plant-Parasitic Nematode Heterodera schachtii

ABSTRACT The goal of this study was to identify bacteria involved in soil suppressiveness against the plant-parasitic nematode Heterodera schachtii. Since H. schachtii cysts isolated from the suppressive soil can transfer this beneficial property to nonsuppressive soils, analysis of the cyst-associated microorganisms should lead to the identification of the causal organisms. Our experimental approach was to identify bacterial rRNA genes (rDNA) associated with H. schachtii cysts obtained from soil mixtures with various levels of suppressiveness. We hypothesized that we would be able to identify bacteria involved in the suppressiveness by correlating population shifts with differing levels of suppressiveness. Soil treatments containing different amounts of suppressive and fumigation-induced nonsuppressive soils exhibited various levels of suppressiveness after two nematode generations. The 10%-suppressive-soil treatment contained numbers of eggs per gram of soil similar to those of the 100%-suppressive-soil treatment, indicating that the suppressive factor(s) had been transferred. Bacterial rDNA associated with H. schachtii cysts were identified using a culture-independent method termed oligonucleotide fingerprinting of rRNA genes. Bacteria from five major taxonomic groups (Actinobacteria, Cytophaga-Flexibacter-Bacteroides, α-Proteobacteria, β-Proteobacteria, and γ-Proteobacteria) were identified. Three bacterial rDNA groups contained clones that were more prevalent in the highly suppressive soil treatments than in the less suppressive treatments, indicating a potential involvement in the H. schachtii suppressiveness. When these three groups were examined with specific PCR analyses performed on H. schachtii cysts that developed in soils treated with three biocidal compounds, only one bacterial rDNA group with moderate to high sequence identity to rDNA from several Rhizobium species and uncultured α-proteobacterial clones was consistently associated with the highly suppressive treatments. A quantitative PCR analysis confirmed the association of this Rhizobium-like rDNA group with the H. schachtii suppressiveness.
The cost-effectiveness of treatment for alcoholism: a second approximation.

OBJECTIVE This review builds on the innovative research synthesis of Holder and his colleagues, addresses some of the limitations of the box-score approach to assessing treatment effectiveness that they used and provides a second approximation of the cost-effectiveness of treatment for alcoholism. METHOD For each of 141 comparative treatment studies, we determined whether or not it found at least one statistically significant positive effect on a drinking-related outcome variable for each of the modalities examined in a paired contrast with one other condition. We next calculated the predicted probability of each study yielding at least one statistically significant treatment effect, based on the number of tests for treatment effects conducted. Following that, for each study of a particular treatment modality, the strength of the "weakest competitor" against which the modality had been compared was determined. For each modality, we used the average predicted probability of the relevant studies finding a significant effect and the average effectiveness of the weakest competitor to predict the modality's effectiveness. RESULTS We calculated an Adjusted Effectiveness Index (AEIn) for each modality, which was the difference between its predicted and actual effectiveness score. Our AEIn results were consistent with those of Holder et al. in suggesting that some of the same modalities appear to be effective or ineffective. Our results differed from their findings with respect to other modalities, however. Using data presented by Holder and his colleagues on the minimum estimated cost of providing different modalities, we offer a second approximation of the modalities' cost-effectiveness. CONCLUSIONS Overall, we found a smaller range of effectiveness across modalities than did Holder and his colleagues and a nonsignificant relationship between cost and effectiveness. Like Holder et al., we do not believe major treatment provision or funding decisions should be based solely on this type of review.
Vagal afferent fibres determine the oxytocin‐induced modulation of gastric tone

• Oxytocin (OXT) inputs to the brainstem modulate cardiorespiratory, feeding and gastric functions. • Vagal afferent (sensory) inputs are known to modulate brainstem synapses involved in visceral reflexes; however, the neurocircuits through which OXT exerts its actions are still unknown. • In this study we elucidate these mechanisms of actions and report that vagal sensory fibres control these neurocircuits in a conditionally controlled manner such that brainstem synapses can prepare the neurocircuits to allow appropriate modulation of digestive processes. • The results presented here improve our understanding of the central regulation of gastrointestinal functions and have the potential of being extended to the understanding of cardiorespiratory and feeding functions controlled by adjacent brainstem centres.
Effects of Dietary Salt Load and Salt Depletion on the Course of Hypertension and Angiotensin II Levels in Male and Female Heterozygous Ren-2 Transgenic Rats

Background: In the present study we evaluated plasma and kidney angiotensin II (ANG II) levels in female and male Ren-2 transgenic rats (TGR) in comparison to age-matched female and male normotensive Hannover Sprague-Dawley rats. Methods: The rats were maintained on a normal sodium (NS) diet (0.6% NaCl) or fed a high sodium (HS) diet (2% NaCl) for 4 days or were sodium depleted by administration of 40 mg furosemide per liter drinking water overnight followed by 3 days of low sodium diet (0.01% NaCl) (LS + F). ANG II levels were determined by radioimmunoassay. Results: Female TGR at the age of 38 days were already hypertensive and had developed cardiac hypertrophy, whereas male TGR at this age still exhibited a normotensive phenotype. HS diet increased the blood pressure (BP) but did not alter the ANG II levels in TGR at any age. LS + F decreased the BP without significant change in ANG II concentrations in TGR. Female TGR responded to salt loading and salt depletion by more pronounced changes in BP than male TGR. Conclusions: Female TGR develop hypertension more rapidly and the salt-sensitive component of hypertension is more pronounced in female than in male TGR.
Temporal properties of surround suppression in cat primary visual cortex

The responses of neurons in primary visual cortex (V1) are suppressed by stimuli presented in the region surrounding the receptive field. There is debate as to whether this surround suppression is due to intracortical inhibition, is inherited from lateral geniculate nucleus (LGN), or is due to a combination of these factors. The mechanisms involved in surround suppression may differ from those involved in suppression within the receptive field, which is called cross-orientation suppression. To compare surround suppression to cross-orientation suppression, and to help elucidate its underlying mechanisms, we studied its temporal properties in anesthetized and paralyzed cats. We first measured the temporal resolution of suppression. While cat LGN neurons respond vigorously to drift rates up to 30 Hz, most cat V1 neurons stop responding above 10–15 Hz. If suppression originated in cortical responses, therefore, it should disappear above such drift rates. In a majority of cells, surround suppression decreased substantially when surround drift rate was above ∼15 Hz, but some neurons demonstrated suppression with surround drift rates as high as 21 Hz. We then measured the susceptibility of suppression to contrast adaptation. Contrast adaptation reduces responses of cortical neurons much more than those of LGN neurons. If suppression originated in cortical responses, therefore, it should be reduced by adaptation. Consistent with this hypothesis, we found that prolonged exposure to the surround stimulus decreased the strength of surround suppression. The results of both experiments differ markedly from those previously obtained in a study of cross-orientation suppression, whose temporal properties were found to resemble those of LGN neurons. Our results provide further evidence that these two forms of suppression are due to different mechanisms. Surround suppression can be explained by a mixture of thalamic and cortical influences. It could also arise entirely from intracortical inhibition, but only if inhibitory neurons respond to somewhat higher drift rates than most cortical cells.
Multidisciplinary perceptions of the role of nurses and healthcare assistants in rehabilitation of older adults in acute health care.

AIM This paper describes the perceptions of nurses, healthcare assistants, doctors and therapists of rehabilitation and the role of nurses and healthcare assistants on an acute older adults ward in a London teaching hospital. BACKGROUND The role perception, education and training and attitudes towards the older adults have been identified as barriers that have an impact upon the nurses' role within rehabilitation. However, little is known about the role of nurses and healthcare assistants in rehabilitation of older adults in acute health care. DESIGN Action research study. METHOD Twenty-four semi-structured interviews were conducted and audio recorded about healthcare professionals' understanding of rehabilitation, the type of skills needed and their perceptions of the role of nurses and healthcare assistants in rehabilitation. The interview transcripts were analysed using the thematic content analysis. RESULTS The findings suggest that the therapists relied on nurses and healthcare assistants for therapy carry-over. Healthcare assistants were perceived as the professional group who could deliver therapy carry-over. There was an evidence of role hierarchy as healthcare assistants perceived that they were not actively involved in decision-making or discharge planning. CONCLUSION This paper suggests that healthcare assistants and nurses are viewed as the professional group best placed to deliver therapy carry-over. However, whilst there is an acknowledgement of their role, there remains a reluctance to acknowledge healthcare assistants as a professional group and to involve them within decision-making and discharge planning. RELEVANCE TO CLINICAL PRACTICE Employers must be seen to advocate, support and implement education and training programs for healthcare assistants. However, whilst nurses and healthcare assistants have an integral role in rehabilitation, there needs to be more research into the how they are supported by therapy professionals.
Systemic and Central Immunity in Alzheimer's Disease: Therapeutic Implications

Clinical pharmaceutical trials aimed at modulating the immune system in Alzheimer's Disease have largely focused on either dampening down central proinflammatory innate immunity or have manipulated adaptive immunity to facilitate the removal of centrally deposited beta amyloid. To date, these trials have had mixed clinical therapeutic effects. However, a number of clinical studies have demonstrated disturbances of both systemic and central innate immunity in Alzheimer's Disease and attention has been drawn to the close communication pathways between central and systemic immunity. This paper highlights the need to take into account the potential systemic effects of drugs aimed at modulating central immunity and the possibility of developing novel therapeutic approaches based on the manipulation of systemic immunity and its communication with the central nervous system.
Evaluation of meatal stenosis following neonatal circumcision.

INTRODUCTION Meatal stenosis almost always develops following neonatal circumcision, and it usually does not become apparent until the child is toilet trained. The present study was conducted to determine the value of diagnostic ultrasonography in patients with meatal stenosis. MATERIALS AND METHODS A descriptive study was performed on 120 patients with meatal stenosis, referred to Naghavi Hospital, Kashan, Iran, from July 2000 to March 2002. Symptoms and findings on physical examination were recorded for every patient, ultrasonography of the urinary tract, and urinalysis and urine culture were also performed. RESULTS Mean age of the patients was 2.5 years (range, 3 months to 6 years). The common symptoms were dysuria (35%), decreased urine caliber (33.3%), and bloody spotting (15%), while 26.6% of the patients were asymptomatic. Paraclinical findings were microscopic hematuria (17.5%), bacteriuria (1.6%), and ureteral duplication (0.8%). No case of obstructive uropathy was detected by ultrasonography. CONCLUSION Meatal stenosis rarely causes obstructive uropathy. Hence, urinary tract ultrasonography is rarely necessary, unless symptoms persist after meatotomy.
Hepatitis C in Cameroon: What is the progress from 2001 to 2016?

Abstract Chronic hepatitis C is a major public health problem in sub-Saharan countries and particularly in Cameroon where the prevalence rate is around 7.6% in the age group of 55–59 years. Recent investigations into this infection allowed defining a national seroprevalence, characterizing virological and biological profiles of infected patients and identifying medicinal plants of potential interest in hepatitis C therapy. However, in Cameroon, no existing report currently presents a good overview of hepatitis C research in relation to these parameters. This review seeks to discuss major findings published since 2001 that have significantly advanced our understanding of the epidemiology and treatment of hepatitis C in Cameroonian patients and highlight the major challenges that remain to overcome. We performed a systematic search in Pubmed and Google Scholar. Studies evaluating prevalence, treatment, coinfection, and genetic diversity of HCV infection in Cameroon were included. Studies suggest that HCV prevalence in Cameroon would be low (around 1.1%) with a lot of disparities according to regions and age of participants. Elders, pregnant women, blood donors, health care workers, patients on hemodialysis, and homozygous sickle cell patients have been identified as risk groups. Moreover, HCV/HBV coinfection was found more prevalent than HCV/HIV coinfection. Phylogenic studies reported circulation of three main genotypes such genotypes 1, 2, and 4 but little is known about antiviral candidates from the Cameroonian pharmacopeia. In conclusion, some epidemiological data prove that hepatitis C in Cameroon is well known but efforts are still necessary to prevent or control this infection.
10-year survival and success rates of 511 titanium implants with a sandblasted and acid-etched surface: a retrospective study in 303 partially edentulous patients.

PURPOSE This retrospective study assessed the 10-year outcomes of titanium implants with a sandblasted and acid-etched (SLA) surface in a large cohort of partially edentulous patients. MATERIALS AND METHODS Records of patients treated with SLA implants between May 1997 and January 2001 were screened. Eligible patients were contacted and invited to undergo a clinical and radiologic examination. Each implant was classified according to strict success criteria. RESULTS Three hundred three patients with 511 SLA implants were available for the examination. The mean age of the patients at implant surgery was 48 years. Over the 10-year period, no implant fracture was noted, whereas six implants (1.2%) were lost. Two implants (0.4%) showed signs of suppuration at the 10-year examination, whereas seven implants had a history of peri-implantitis (1.4%) during the 10-year period, but presented with healthy peri-implant soft tissues at examination. The remaining 496 implants fulfilled the success criteria. The mean Plaque Index was 0.65 (±0.64), the mean Sulcus Bleeding Index 1.32 (±0.57), the mean Probing Depth 3.27 mm (±1.06), and the mean distance from the implant shoulder to the mucosal margin value -0.42 mm (±1.27). The radiologic mean distance from the implant shoulder to the first bone-to-implant contact was 3.32 mm (±0.73). CONCLUSION The present retrospective analysis resulted in a 10-year implant survival rate of 98.8% and a success rate of 97.0%. In addition, the prevalence of peri-implantitis in this large cohort of orally healthy patients was low with 1.8% during the 10-year period.
West Nile Virus lineage‐2 in Culex specimens from Iran

Screening of mosquitoes for viruses is an important forecasting tool for emerging and re‐emerging arboviruses. Iran has been known to harbour medically important arboviruses such as West Nile virus (WNV) and dengue virus (DENV) based on seroepidemiological data. However, there are no data about the potential mosquito vectors for arboviruses in Iran. This study was performed to provide mosquito and arbovirus data from Iran.
Changes in Outcome and Management of Perforated Diverticulitis over a 10 Year Period

Abstract Introduction : Aggressive non-operative intervention and evolving surgical strategies have altered the treatment of perforated diverticulitis in the acute setting. These strategies have predominantly been implemented over the last decade. The aim of this study was to assess the impact of this on patient outcome during their index admission and subsequently. Methods : Consecutive patients admitted with acute diverticulitis between 1999 and 2010 were identified. Patient demographics, treatment strategies and outcomes were collected and analysed. Patients who had an episode of perforated diverticulitis during their index admission were followed. Results : 739 patients were admitted with acute diverticulitis. Of these, 115 (15.7%) had perforated diverticulitis. 53 (47.8%) underwent an intervention. There was a reduction in the mean age of patients admitted with acute diverticulitis of 8.9% over the study period (p = 0.002). There was a significant increase in the use of CT scanning pre-operatively (p < 0.001). ‘Non-resectional’ interventions have emerged in the form of laparoscopic lavage (n = 5) and percutaneous abscess drainage (n = 14). There was associated improved length of stay (p < 0.001). Conclusion : Outcomes for patients with perforated diverticulitis have improved, contributed to in part by an increased use of non-resectional management strategies.
Transient Poly(ADP-ribosyl)ation of Nuclear Proteins and Role of Poly(ADP-ribose) Polymerase in the Early Stages of Apoptosis*

A transient burst of poly(ADP-ribosyl)ation of nuclear proteins occurs early, prior to commitment to death, in human osteosarcoma cells undergoing apoptosis, followed by caspase-3-mediated cleavage of poly(ADP-ribose) polymerase (PARP). The generality of this early burst of poly(ADP-ribosyl)ation has now been investigated with human HL-60 cells, mouse 3T3-L1, and immortalized fibroblasts derived from wild-type mice. The effects of eliminating this early transient modification of nuclear proteins by depletion of PARP protein either by antisense RNA expression or by gene disruption on various morphological and biochemical markers of apoptosis were then examined. Marked caspase-3-like PARP cleavage activity, proteolytic processing of CPP32 to its active form, internucleosomal DNA fragmentation, and nuclear morphological changes associated with apoptosis were induced in control 3T3-L1 cells treated for 24 h with anti-Fas and cycloheximide but not in PARP-depleted 3T3-L1 antisense cells exposed to these inducers. Similar results were obtained with control and PARP-depleted human Jurkat T cells. Whereas immortalized PARP +/+ fibroblasts showed the early burst of poly(ADP-ribosyl)ation and a rapid apoptotic response when exposed to anti-Fas and cycloheximide, PARP −/− fibroblasts exhibited neither the early poly (ADP-ribosyl)ation nor any of the biochemical or morphological changes characteristic of apoptosis when similarly treated. Stable transfection of PARP −/− fibroblasts with wild-type PARP rendered the cells sensitive to Fas-mediated apoptosis. These results suggest that PARP and poly(ADP-ribosyl)ation may trigger key steps in the apoptotic program. Subsequent degradation of PARP by caspase-3-like proteases may prevent depletion of NAD and ATP or release certain nuclear proteins from poly(ADP-ribosyl)ation-induced inhibition, both of which might be required for late stages of apoptosis.
Drosophila dany is essential for transcriptional control and nuclear architecture in spermatocytes

The terminal differentiation of adult stem cell progeny depends on transcriptional control. A dramatic change in gene expression programs accompanies the transition from proliferating spermatogonia to postmitotic spermatocytes, which prepare for meiosis and subsequent spermiogenesis. More than a thousand spermatocyte-specific genes are transcriptionally activated in early Drosophila spermatocytes. Here we describe the identification and initial characterization of dany, a gene required in spermatocytes for the large-scale change in gene expression. Similar to tMAC and tTAFs, the known major activators of spermatocyte-specific genes, dany has a recent evolutionary origin, but it functions independently. Like dan and danr, its primordial relatives with functions in somatic tissues, dany encodes a nuclear Psq domain protein. Dany associates preferentially with euchromatic genome regions. In dany mutant spermatocytes, activation of spermatocyte-specific genes and silencing of non-spermatocyte-specific genes are severely compromised and the chromatin no longer associates intimately with the nuclear envelope. Therefore, as suggested recently for Dan/Danr, we propose that Dany is essential for the coordination of change in cell type-specific expression programs and large-scale spatial chromatin reorganization. Summary: The nuclear protein Dany associates with euchromatic regions in Drosophila spermatocytes, controls the spermatocyte gene expression program, and regulates chromatin-nuclear envelope interactions.