Miracle-dz/UniFAR-FTUs huggingface dataset:
Determinants of the Nasal Microbiome: Pilot Study of Effects of Intranasal Medication Use

Introduction A role for bacteria and other microbes has long been suspected in the chronic inflammatory sinonasal diseases. Recent studies utilizing culture-independent, sequence-based identification have demonstrated aberrant shifts in the sinus microbiota of chronic rhinosinusitis subjects, compared with ostensibly healthy controls. Examining how such microbiota shifts occur and the potential for physician-prescribed interventions to influence microbiota dynamics are the topics of the current article. Methods The nasal cavity microbiota of 5 subjects was serially examined over an 8-week period using pan-bacterial 16S rRNA gene sequencing. Four of the subjects were administered topical mometasone furoate spray, while 1 subject underwent a mupirocin decolonization procedure in anticipation of orthopedic surgery. Results Measures of microbial diversity were unaffected by intranasal treatment in 2 patients and were markedly increased in the remaining 3. The increase in microbial diversity was related to clearance of Moraxella spp. and a simultaneous increase in members of the phylum Actinobacteria. Both effects persisted at least 2 weeks beyond cessation of treatment. Transient changes in the relative abundance of several bacterial genera, including Staphylococcus and Priopionibacteria, were also observed during treatment. Conclusions The effects of intranasal steroids on the sinonasal microbiome are poorly understood, despite their widespread use in treating chronic sinonasal inflammatory disorders. In this longitudinal study, administration of intranasal mometasone furoate or mupirocin resulted in shifts in microbial diversity that persisted to some degree following treatment cessation. Further characterization of these effects as well as elucidation of the mechanism(s) underlying these changes is needed.
Switching inhaled iloprost formulations in patients with pulmonary arterial hypertension: the VENTASWITCH Trial

Inhaled iloprost is an effective therapy for patients with pulmonary arterial hypertension (PAH); however, some patients experience extended inhalation times when using the V10 formulation (10.0 µg/mL) to deliver a 5 -µg dose (at mouthpiece) and are at risk of incomplete inhalations and reduced inhalation frequency. VENTASWITCH was an observational, case-crossover study to evaluate inhalation behavior in patients with PAH switched from iloprost V10 to V20 (20.0 µg/mL) formulation for delivering a 5 -µg dose using the I-Neb® AAD® device. Adults with PAH participating in a German Ventavis® (iloprost) patient-support program, who were switched from the V10 to V20 formulation, were enrolled. The co-primary endpoints were mean daily proportion of complete inhalations and mean daily inhalation frequency. The secondary endpoint was mean daily inhalation duration. Data were collected for three months before and after switching. Overall, 63 patients were included. Switching from V10 to V20 resulted in a significant increase in the mean daily proportion of complete inhalations (92% vs. 97%, P < 0.0001) and inhalation frequency (4.6 vs. 4.9 inhalations/day, P = 0.0430), and reduction in mean inhalation duration (11.8 vs. 6.5 min; P < 0.0001). Greater increases in daily proportions of complete inhalations were observed in older patients (≥ 65 vs. < 65 years) and those receiving more (3 vs. < 3) concomitant PAH medications. Switching from V10 to V20 iloprost formulation significantly improved inhalation behavior in patients with PAH and may facilitate improved adherence to therapy.
Ipilimumab in combination with nivolumab for the treatment of renal cell carcinoma

ABSTRACT Introduction: Renal cell carcinoma (RCC) is a highly immunogenic neoplasm, and cytokine-based immunotherapies have been used for decades with limited success. In recent years, antibody-based immunotherapies targeting immune checkpoint receptors PD-1 and CTLA-4 have demonstrated clinical efficacy in metastatic RCC (mRCC) patients, leading to FDA approval of the combination of nivolumab and ipilimumab in treatment-naïve patients with intermediate- or poor-risk disease in April 2018. Areas covered: The pharmacodynamics and pharmacokinetics of nivolumab and ipilimumab are reviewed. Clinical safety and efficacy results from pivotal phase I and III trials of the combination of nivolumab plus ipilimumab in mRCC are summarized, and the combination is reviewed in the context of other available systemic therapies for RCC. Ongoing clinical studies involving the combination of nivolumab plus ipilimumab in RCC are discussed. Expert opinion: The combination of nivolumab and ipilimumab has demonstrated superior efficacy for treatment-naïve patients with intermediate- and poor-risk mRCC with clear cell histology and is likely to replace anti-angiogenic therapies as the treatment-of-choice in this patient population in the United States. Development of additional combination strategies, novel trial designs, and predictive biomarkers of response will be important to further optimize therapeutic selection and clinical outcomes.
Impact of clinicopathological characteristics on survival in patients treated with immune checkpoint inhibitors for metastatic melanoma

Immune checkpoint inhibitors (ICIs) have unprecedented effects on the treatment of metastatic melanoma. However, little is known about the prognostic values of various clinicopathological characteristics. Here, PubMed, Embase and Cochrane database were searched from inception to April 2018 for random controlled trials (RCTs) that compared ICIs with controls. The hazard ratios (HRs) for overall survival (OS) according to gender, age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), lactate dehydrogenase (LDH) level and metastasis stage were extracted. Four phase III RCTs involving 1,598 patients with metastatic melanoma were included in this study. Compared with conventional agents, ICIs were associated with prolonged OS (HR, 0.67; 95% CI, 0.50–0.88; p = 0.005). The pooled OS HR was 0.60 (95% CI, 0.42–0.84; p = 0.003) in men; 0.84 (95% CI, 0.69–1.01; p = 0.07) in women. The difference in efficacy between men and women was significant (pinteraction = 0.03). The OS HR was 0.59 (95% CI, 0.41–0.83; p = 0.003) in patients >65 years old; 0.74 (95% CI, 0.55–1.01; p = 0.054) in patients <65 years old. The OS HR was 0.75 (95% CI, 0.60–0.94; p = 0.01) in patients with ECOG PS = 1; 0.64 (95% CI, 0.38–1.06; p = 0.08) in patients with ECOG PS = 0. Additionally, the long‐term benefits were independent of metastasis stage and LDH level. In summary, although immunotherapy significantly prolongs OS in metastatic melanoma, the long‐term benefits in women, younger patients (<65 years old) and patients with ECOG PS = 0 were marginal. These results may assist in treatment decision‐making, design and interpretation of clinical trials and economic analyses.
An Ecological Momentary Assessment of Cigarette and Cigar Dual Use Among African American Young Adults

Abstract Introduction The dual use of cigarettes and cigars among African American young adults is a significant public health issue. Patterns of and reasons for dual use are difficult to capture using traditional self-report methods. This study used ecological momentary assessment (EMA) to characterize patterns of dual smoking and examine the personal and environmental predictors of cigarette and cigar smoking among African American young adult dual users (ages 18–29) in real-time. Methods For 14 days, 64 participants smoked ad libitum and were prompted four times daily to record their smoking, craving, emotions, social smoking, and environment via text message on their mobile phones. The odds of single product and dual use were examined using adjusted generalized estimating equations. Results Participants smoked an average of 7.9 cigarettes and 4.2 cigars per day. Cigarettes and cigars were smoked as frequently during periods of dual use as they were during periods of single product use. Cigarette craving was positively associated with cigarette-only smoking (OR: 1.07), whereas cigar craving was positively associated with cigar-only smoking (OR: 1.43) and dual use (OR: 1.08). Cigars had the greatest odds of dual use when with others (OR: 4.69) and in others’ homes (OR: 4.33). Cigarettes had the greatest odds of being smoked while alone (OR: 1.57). Conclusions EMA was useful for capturing variable smoking patterns and predictors. In this study population, cigarettes and cigars appeared to be smoked additively, and cigars smoked socially. These findings can inform future interventions addressing dual use in this high priority population. Implications This is the first study to use EMA to examine naturalistic patterns and predictors of multiple tobacco use in real-time. African American young adults smoked cigarettes and cigars during periods of dual use as frequently as during periods of single product use. This suggests that most use was additive (one product smoked in addition to another) and less often as substitution (one product smoked instead of another). Social smoking and craving were strongly associated with cigar smoking in single and dual use periods. This study suggests the need for cessation messaging specifically targeted to reduce dual use in this population.
Penicillium tunisiense sp. nov., a novel species of Penicillium section Ramosa discovered from Tunisian orchard apples.

Two similar Penicillium isolates could not be identified as previously described species in a survey of orchard apples from Tunisia for patulin-producing fungi. These isolates are described as novel species using multilocus DNA sequence analysis of partial β-tubulin, calmodulin and nuclear ribosomal internal transcribed spacer regions; and morphological, physiological and biochemical characteristics. The isolates were considered negative for patulin production since the IDH gene fragment was not detected and the compound detected at the same retention time of patulin (14.9 min) showed a different UV spectrum using U-HPLC/UV-DAD. In terms of phylogeny, the two isolates clustered with Penicillium section Ramosa and are closely related to Penicillium chroogomphum, Penicillium lenticrescens and Penicillium soppii. Furthermore, their macro- and micromorphological traits differed from these species. Hence, the isolates represent a novel species in Penicillium section Ramosa and the name Penicillium tunisiense sp. nov. is proposed, with the type strain MUM 17.62T (=ITEM 17445T).
The need for enhanced psychological support in esophageal cancer-an exploratory study of the perception of HCPs, patients, and carers.

Esophageal cancer patients and carers report significant levels of psychological distress. Despite this, only a small number of patients and carers engage with existing psychological services. This study aims to explore the perception of esophageal cancer patients, carers, and healthcare professionals (HCPs) of psychological distress and current provision of support, the need for and format of tailored support and barriers to patient/carer engagement. Semistructured interviews were undertaken with n = 14 esophageal cancer patients, carers, and HCPs. Directed content analysis was utilized to code the transcripts according to the preconceived categories as defined by study aim. Participants reported key periods for heightened distress around diagnosis and postsurgery on discharge from hospital. Provision of existing support was not felt to be adequate. A number of patient/carer barriers to engaging with support were identified in addition to HCP barriers. Participants perceived enhanced psychological support as a priority supportive care need with a number of recommendations for tailoring existing support services more adequately to the clinical population. With reports of heightened psychological morbidity yet with few esophageal cancer patients engaging with psychological services, there is an impetus to develop detailed care pathways to facilitate meeting this prioritized support need.
Homozygous and Heterozygous Nuclear Lamin A p.R582C Mutation: Different Lipodystrophic Phenotypes in the Same Kindred

Background: Dunnigan-type familial partial lipodystrophy (FPLD2) is a rare autosomal dominant disease caused by heterozygous mutations in the LMNA gene that results in regional loss of subcutaneous adipose tissue with onset in puberty. However, a generalized lipodystrophy phenotype has also been associated with heterozygous mutations in this gene, demonstrating the noticeable phenotypic heterogeneity of this disease. Methods: We report and describe clinical and metabolic features of four patients from the same family with the p.R582C LMNA mutation, three homozygous and one in the heterozygous state that present with three distinct lipodystrophic phenotypes. Results: Case description: The proband was a 12-year-old girl who developed severe subcutaneous fat atrophy in limbs and abdomen followed by a remarkable dorsocervical fat accumulation in adulthood along with diabetes at age 23. The proband's sister was a phenotypically normal girl who developed hypertriglyceridemia at age 8, progressive features of partial lipodystrophy at age 11, and diabetes at age 22. The proband's mother was first examined at age 32, presenting diabetes and a severe generalized lipodystrophic phenotype; she developed kidney failure at age 41 and died due to diabetic complications. The proband's father was a 50-year-old man with abdominal fat concentration that was initially considered phenotypically normal. Massively parallel sequencing using a platform of genes related to genetic lipodystrophies, followed by Sanger sequencing, revealed the transversion c.1744C>T at exon 11 of the LMNA gene (p.R582C) in the homozygous (mother and daughters) and heterozygous (father) states. Conclusion: We documented three distinct phenotypes of the homozygous and heterozygous p. R582C LMNA mutation in the same kindred, illustrating that FPLD2 linked to mutations in this gene is a disease of great clinical heterogeneity, possibly due to associated environmental or genetic factors.
Life-changing or trivial: Electricians’ views about electrical accidents

BACKGROUND: It is well known that electrical accidents can cause physical injury. Less well known is that long-term consequences may include emotional and cognitive problems. OBJECTIVE: To explore electricians’ experiences and perceptions of work-related electrical accidents, with focus on psychological short- and long-term consequences, including how contacts with health care services and the workplace were perceived. METHODS: Semi-structured interviews with 23 Swedish male electricians, aged 25– 68, who had experienced at least one electrical accident and reported residual sensory, musculoskeletal, cognitive or emotional symptoms. Data was analyzed by means of qualitative content analysis. RESULTS: Immediate emotional reactions included surprise, confusion, fear, anxiety, and anger; also long-term consequences were seen. Experiencing a no-let-go situation was particularly stressful. The cause of the accident, and questions about guilt and blame were central in the aftermath. Lack of knowledge and routine among health care professionals concerning electrical injury was reported, as well as lack of medical and psychological follow-up. CONCLUSIONS: For some informants, the accident had been a life-changing event, while for others it was an event of little importance. Adequate handling at the workplace, and from health care personnel, including follow-up, could facilitate rehabilitation and return to work.
Cost-effectiveness of somatostatin analogues in the treatment of acromegaly

ABSTRACT Introduction: Somatostatin analogues (SSAs) are the largest contributor to the direct medical cost of acromegaly management worldwide. The aim of this review was to identify and report available evidence on the cost-effectiveness of SSAs in the treatment of acromegaly. Areas covered: A literature search on relevant papers published up to April 2018 was performed. A total of 22 eligible studies (10 full-text articles and 12 conference abstracts) conducted in 14 countries were included in the analysis. In majority of studies, modelling technique was the principal research method. Expert commentary: The results of cost-effectiveness analyses: 1) support published recommendations where SSAs are indicated as first-line medical treatment for patients with persistent disease after surgery or who are not eligible for surgery; 2) suggest that preoperative medical therapy with SSAs may be highly cost-effective in acromegalic patients with macroadenoma, in centres without optimal surgical results 3) indicate that in some countries pasireotide and pegvisomant appeared to be cost-effective or even dominant strategies in comparison to first-generation SSAs. The main limitation of economic evaluations was the lack of high-quality studies designed to directly compare various treatment strategies in acromegaly.
Self- and Informant-Reported Memory Complaints: Frequency and Severity in Cognitively Intact Individuals and those with Mild Cognitive Impairment and Neurodegenerative Dementias.

BACKGROUND Subjective memory complaints (SMCs) are incorporated into the diagnosis of mild cognitive impairment (MCI) and neurodegenerative dementias; however, the relative frequency of SMCs in cognitively intact older adults and those with different types of dementia is poorly understood. Similarly, the concordance between self- versus informant-reported SMCs has not been compared across different diagnostic groups. OBJECTIVE This study aimed to evaluate the frequency of self-reported (Objective 1) and informant-reported (Objective 2) SMCs in cognitively intact adults or those diagnosed with MCI or a neurodegenerative dementia. Agreement between participant and informant complaints was also evaluated (Objective 3). METHODS Baseline evaluation data were drawn from 488 participants (Mage = 70.49 years; Medu = 15.62 years) diagnosed as cognitively intact, non-amnestic MCI, amnestic single domain MCI, amnestic multi-domain MCI, possible/probable Alzheimer's disease, dementia with Lewy bodies, or frontotemporal dementia. Participants and their informants completed the Memory Assessment Clinic Questionnaire. RESULTS One-way ANCOVAs controlling for age, education, and depression revealed no group differences in severity of self-reported SMCs. In contrast, informant memory ratings followed the expected clinical pattern, with comparable and most impaired ratings given to participants with any dementia diagnosis, followed by those with any MCI diagnosis, followed by cognitively intact participants. There was inconsistent agreement between self- and informant-reported SMC ratings in any of the impaired groups. CONCLUSIONS Given greater diagnostic specificity and internal consistency of informant report, clinicians should weigh this information more heavily than self-report in the diagnostic process.
Regional Review Workshop on Completed Research Activities

The study was conducted in Gutogida, Diga and Sibu sire districts of East Wollega, Bakotibe and Ilu galan of West Shaw zones and in Bako agricultural research center with the objectives to assess constraints associated with hormonal assisting artificial insemination and to evaluate the response of Horro (Bosindicus) cows after estrous synchronization. In this study, structured questioner was used and a total of 210 respondents (180 small holder dairy farmers, 10 animal health workers, 10 animal production professionals and 10 AI technicians were interviewed. Retrospective data from specified districts were also included to identify constraints associated with hormonal assisting artificial insemination in the study areas. The study indicated that most of the respondents (93.33%) were took training on the issue of mass estrous synchronization, AI services before the commencement of the program. However, most of the respondents (57.78%) had moderate knowledge on heat detection and only few (27.22%) of them can keep the record of their synchronized cows/heifers. The main restraints for the low success rate of on farm hormone assisted artificial insemination (estrus synchronization)were identified as failure of conception (42.22%), using of poor management of cows/heifers (15%), difficulty in heat detection by the farmers (13.89%), skill gap and unavailability of artificial insemination technicians (AITs)(12.78%) and poor hormonal responses (11.11%). Therefore, to enhance the genetic potential of low dairy cows through cross breeding scheme, revising of the existing hormone assisted estrus synchronization, artificial insemination delivery system, improving the ability of farmers and experts on the handling and management of dairy cows/heifers should be due in place. Moreover, awareness creation should be done to change the attitude of farmers on hormone assisted estrus synchronization.
Patient survival on haemodiafiltration and haemodialysis: a cohort study using the Australia and New Zealand Dialysis and Transplant Registry

Background It is unclear if haemodiafiltration improves patient survival compared with standard haemodialysis. Observational studies have tended to show benefit with haemodiafiltration, while meta-analyses have not provided definitive proof of superiority. Methods Using data from the Australia and New Zealand Dialysis and Transplant Registry, this binational inception cohort study compared all adult patients who commenced haemodialysis in Australia and New Zealand between 2000 and 2014. The primary outcome was all-cause mortality. Cardiovascular mortality was the secondary outcome. Outcomes were measured from the first haemodialysis treatment and were examined using multivariable Cox regression analyses. Patients were censored at permanent discontinuation of haemodialysis or at 31 December 2014. Analyses were stratified by country. Results The study included 26 961 patients (4110 haemodiafiltration, 22 851 standard haemodialysis; 22 774 Australia, 4187 New Zealand) with a median follow-up of 5.31 (interquartile range 2.87-8.36) years. Median age was 62 years, 61% were male, 71% were Caucasian. Compared with standard haemodialysis, haemodiafiltration was associated with a significantly lower risk of all-cause mortality [adjusted hazard ratio (HR) for Australia 0.79, 95% confidence interval (95% CI) 0.72-0.87; adjusted HR for New Zealand 0.88, 95% CI 0.78-1.00]. In Australian patients, there was also an association between haemodiafiltration and reduced cardiovascular mortality (adjusted HR 0.78, 95% CI 0.64-0.95). Conclusion Haemodiafiltration was associated with superior survival across patient subgroups of age, sex and comorbidity.