Miracle-dz/UniFAR-FTUs huggingface dataset:
Distal posterior inferior cerebellar artery aneurysms: clinical features and management.

OBJECT Aneurysms located on the distal portion of the posterior inferior cerebellar artery (PICA) are uncommon, and their underlying pathology, natural history, and clinical management are poorly understood. To clarify these lesions more fully, the authors undertook a retrospective analysis of the clinical features and management results of 22 distal PICA aneurysms in 20 consecutive patients treated at one institution by the same surgeon during the past decade. METHODS The series included 10 men and 10 women (mean age at presentation 51 years). Nine patients presented with only subarachnoid and/or intraventricular hemorrhage (median Hunt and Hess Grade II). In seven patients intracerebellar hemorrhage was also found; two patients presented with pressure effects and two hemorrhages were incidentally discovered. Prominent comorbidities included cigarette smoking (50%) and hypertension (50%). The 13 saccular and nine fusiform distal PICA aneurysms were distributed on the following segments of the PICA: lateral medullary (seven lesions), tonsillomedullary (five lesions), telovelotonsillar (five lesions), and cortical (five lesions). Six oases were associated with cerebellar arteriovenous malformations. Skull-base and far-lateral transcondylar surgical approaches were used to secure the aneurysms in 86% of cases, either by direct clipping (13 lesions), vessel sacrifice (four lesions), or vessel sacrifice plus bypass (two lesions). Two aneurysms were treated using endovascular PICA ablation. Overall outcome at hospital discharge was excellent or good in 70% of cases. At long-term follow up (100% of patients, mean 123 days), an excellent or good outcome had been achieved in 85% of cases. CONCLUSIONS Depending on the PICA segment that was affected, variations in clipping strategies and surgical exposures aimed at the PICA branch and main trunk preservation were major contributors to good long-term results.
Interscalene brachial plexus catheter versus single-shot interscalene block with periarticular local infiltration analgesia for shoulder arthroplasty.

BACKGROUND Interscalene brachial plexus block is a commonly employed regional anesthetic technique for total shoulder arthroplasty, and a continuous catheter is often placed to extend the analgesic benefit of the block. As periarticular local infiltration analgesia (LIA) for total joint arthroplasty is a re-emerging trend, we evaluated the analgesic efficacy of continuous interscalene block (CISB) compared to single-shot interscalene block (SSISB) with LIA. METHODS We conducted a retrospective review of 130 consecutive patients treated by one surgeon in a single institution, with 12 patients excluded for history of chronic opioid tolerance and two for incomplete data. The SSISB with LIA treatment group (n=53) was compared to a control group who received CISB (n=63). Primary end points were a difference in pain score (0- 10 numeric rating scale) and opioid requirements as oral morphine equivalents (OMEs) on postoperative days (PODs) 0 and 1. Secondary end points included nausea and vomiting, length of hospital stay, block failure rate, adverse events due to block, and 30-day readmission. RESULTS When compared to SSISB with LIA, patients who received CISB exhibited decreased opioid requirements in OMEs on POD 0 (11.9 mg vs 28.7 mg, P<.01) and POD 1 (24.0 mg vs 50.3 mg, P<.01). There was no significant difference in pain on POD 0, but a statistically significant decrease in average pain scores with CISB on POD 1 (2.3 vs 4.3, P<.01). CONCLUSIONS SSISB with LIA may provide clinically similar postoperative analgesia compared to CISB, but with escalating doses of opioid requirements.
Thailand diabetes registry project: prevalence and risk factors of stroke in thai diabetic patients.

OBJECTIVE To determine the prevalence of stroke and its risk factors in Thai diabetic patients who attended the diabetes clinics of university and tertiary-care hospitals. MATERIAL AND METHOD A cross-sectional, multi-center hospital-based diabetes registry was carried out at diabetes clinics of 11 university and tertiary-care hospitals. Demographic data, clinical characteristics, common drugs used and laboratory parameters were analyzed for prevalence and risk factors associated with stroke. RESULTS The prevalence of stroke in the patients studied was 3.5%. Most of the patients were type 2 diabetes and had ischemic stroke. One of the risk factors associated with stroke was age greater than 60 years, and the risk appeared to be highest if the patients' age was greater than 70 years (adjust OR = 3.29, p = 0.012). Other risk factors included male sex, systolic blood pressure of > or =140 mmHg, use of oral hypoglycemic agents, lipid lowering agents and aspirin. There was no association between stroke and duration of diabetes, occupation, educational level, BMI, smoking, alcohol drinking, diastolic blood pressure, use of antihypertensive drugs or insulin, glycemic control, lipid profiles and kidney function. CONCLUSION Ischemic stroke was common among Thai patients with diabetes especially in the elderly. The present result emphasizes the relationship between level of systolic blood pressure and the occurrence of stroke. Optimal blood pressure control should be underscored in caring for diabetic patients.
A comprehensive search of functional sequence space using large mammalian display libraries created by gene editing

ABSTRACT The construction of large libraries in mammalian cells allows the direct screening of millions of molecular variants for binding properties in a cell type relevant for screening or production. We have created mammalian cell libraries of up to 10 million clones displaying a repertoire of IgG-formatted antibodies on the cell surface. TALE nucleases or CRISPR/Cas9 were used to direct the integration of the antibody genes into a single genomic locus, thereby rapidly achieving stable expression and transcriptional normalization. The utility of the system is illustrated by the affinity maturation of a PD-1-blocking antibody through the systematic mutation and functional survey of 4-mer variants within a 16 amino acid paratope region. Mutating VH CDR3 only, we identified a dominant “solution” involving substitution of a central tyrosine to histidine. This appears to be a local affinity maximum, and this variant was surpassed by a lysine substitution when light chain variants were introduced. We achieve this comprehensive and quantitative interrogation of sequence space by combining high-throughput oligonucleotide synthesis with mammalian display and flow cytometry operating at the multi-million scale.
Antibiotic resistance as a tragedy of the commons: An ethical argument for a tax on antibiotic use in humans

Abstract To the extent that antibiotic resistance (ABR) is accelerated by antibiotic consumption and that it represents a serious public health emergency, it is imperative to drastically reduce antibiotic consumption, particularly in high‐income countries. I present the problem of ABR as an instance of the collective action problem known as ‘tragedy of the commons’. I propose that there is a strong ethical justification for taxing certain uses of antibiotics, namely when antibiotics are required to treat minor and self‐limiting infections, such as respiratory tract infections, in otherwise healthy individuals. Taxation would allow a reduction in consumption (given certain behavioural economics assumptions) and/or ensure that individuals internalize or compensate for their contribution to the erosion of the common good of antibiotic effectiveness. I suggest that revenue from the tax could be used to fund conservation and innovation strategies. Taxation might be a coercive policy, especially for certain individuals, but the ethical case for coercive policies is very strong when the good to be preserved is important enough and when they force individuals to do something they have a moral obligation to do anyway. I argue that, in the case of mild and self‐limiting infections, individuals have a moral duty of easy rescue and a moral duty of fairness to make their contribution to the preservation of the common good of antibiotic effectiveness by foregoing antibiotics. I also suggest that taxing antibiotics in such cases is an all things considered ethically justified policy even if it would introduce inequalities in access to healthcare.
Testing a positive affect induction to reduce verbally induced nocebo hyperalgesia in an experimental pain paradigm.

There is an ethical obligation to notify individuals about potential pain associated with diagnoses, treatments, and procedures; however, supplying this information risks inducing nocebo hyperalgesia. Currently there are few empirically-derived strategies for reducing nocebo hyperalgesia. Since nocebo effects are linked to negative affectivity, we tested the hypothesis that a positive affect induction can disrupt nocebo hyperalgesia from verbal suggestion. Healthy volunteers (N =147) were randomly assigned to conditions in a 2 (Affect Induction: Positive vs. Neutral) by 2 (Verbal Suggestion: No Suggestion vs. Suggestion of Pain Increase) between-subjects design. Participants were induced to experience positive or neutral affect by watching movie clips for 15 mins. Next, participants had an inert cream applied to their non-dominant hand and suggestion was manipulated by telling only half the participants the cream could increase the pain of the upcoming cold pressor test. Subsequently, all participants underwent the cold pressor test (8C ±.04C), wherein they submerged the non-dominant hand and rated pain intensity on numerical rating scales every 20 sec up to two mins. In the neutral affect conditions, there was evidence for the nocebo hyperalgesia effect: participants given the suggestion of pain displayed greater pain than participants not receiving this suggestion, ps<. 05. Demonstrating a blockage effect, nocebo hyperalgesia did not occur in the positive affect conditions, ps>. 5. This is the first study to show that positive affect may disrupt nocebo hyperalgesia thereby pointing to a novel strategy for decreasing nocebo effects without compromising the communication of medical information to patients in clinical settings.
The Use of Simulated Altitude Techniques for Beneficial Cardiovascular Health Outcomes in Nonathletic, Sedentary, and Clinical Populations: A Literature Review.

Lizamore, Catherine A. , and Michael J. Hamlin. The use of simulated altitude techniques for beneficial cardiovascular health outcomes in nonathletic, sedentary, and clinical populations: A literature review. High Alt Med Biol 18:305-321, 2017. BACKGROUND The reportedly beneficial improvements in an athlete's physical performance following altitude training may have merit for individuals struggling to meet physical activity guidelines. AIM To review the effectiveness of simulated altitude training methodologies at improving cardiovascular health in sedentary and clinical cohorts. METHODS Articles were selected from Science Direct, PubMed, and Google Scholar databases using a combination of the following search terms anywhere in the article: "intermittent hypoxia," "intermittent hypoxic," "normobaric hypoxia," or "altitude," and a participant descriptor including the following: "sedentary," "untrained," or "inactive. " RESULTS 1015 articles were returned, of which 26 studies were accepted (4 clinical cohorts, 22 studies used sedentary participants). Simulated altitude methodologies included prolonged hypoxic exposure (PHE: continuous hypoxic interval), intermittent hypoxic exposure (IHE: 5-10 minutes hypoxic:normoxic intervals), and intermittent hypoxic training (IHT: exercising in hypoxia). CONCLUSIONS In a clinical cohort, PHE for 3-4 hours at 2700-4200 m for 2-3 weeks may improve blood lipid profile, myocardial perfusion, and exercise capacity, while 3 weeks of IHE treatment may improve baroreflex sensitivity and heart rate variability. In the sedentary population, IHE was most likely to improve submaximal exercise tolerance, time to exhaustion, and heart rate variability. Hematological adaptations were unclear. Typically, a 4-week intervention of 1-hour-long PHE intervals 5 days a week, at a fraction of inspired oxygen (FIO2) of 0.15, was beneficial for pulmonary ventilation, submaximal exercise, and maximum oxygen consumption ([Formula: see text]O2max), but an FIO2 of 0.12 reduced hyperemic response and antioxidative capacity. While IHT may be beneficial for increased lipid metabolism in the short term, it is unlikely to confer any additional advantage over normoxic exercise over the long term. IHT may improve vascular health and autonomic balance.
Comparison of the Antibacterial Properties of Phage Endolysins SAL-1 and LysK

ABSTRACT In spite of the high degree of amino acid sequence similarity between the newly discovered phage endolysin SAL-1 and the phage endolysin LysK, SAL-1 has an approximately 2-fold-lower MIC against several Staphylococcus aureus strains and higher bacterial cell-wall-hydrolyzing activity than LysK. The amino acid residue change contributing the most to this enhanced enzymatic activity is a change from glutamic acid to glutamine at the 114th residue.
Extending Evidence for Inter-Individual Differences in Social Comparison Orientation to Pay Fairness Evaluations

This research extends the limited support for social comparison tendencies as an individual difference variable and a key moderator of pay fairness perceptions. Through three studies comprised of five data collections, the following adapts a measure of social comparison orientation to pay contexts and examines its association with heightened perceptions of distributive fairness in hypothetical and actual scenarios of pay equity, over-reward, and under-reward. In keeping with Gibbons and Buunk’s construal, our targeted operationalization of social comparison orientation demonstrated inter-individual variation and intra-individual stability, providing corroboration of distinct individual predispositions towards social comparison. Our experimental findings further support this point in that socially relative pay information had a stronger impact on pay fairness evaluations among individuals predisposed to socially compare and a relatively weak impact on those that were not. This investigation is complementary but distinct from the prevalent focus on situational factors as drivers of social comparison. Further, examining this point in the context of pay is timely based on the recent level of public and managerial attention given to the fairness of relative pay differences.
The P274S Mutation of Lecithin-Cholesterol Acyltransferase (LCAT) and Its Clinical Manifestations in a Large Kindred.

RATIONALE & OBJECTIVE Lecithin-cholesterol acyltransferase (LCAT) catalyzes the maturation of high-density lipoprotein. Homozygosity for loss-of-function mutations causes familial LCAT deficiency (FLD), characterized by corneal opacities, anemia, and renal involvement. This study sought to characterize kidney biopsy findings and clinical outcomes in a family with FLD. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS 2 (related) index patients with clinically apparent FLD were initially identified. 110 of 122 family members who consented to genetic analysis were also studied. PREDICTORS Demographic and laboratory parameters (including lipid profiles and LCAT activity) and full sequence analysis of the LCAT gene. Kidney histologic examination was performed with samples from 6 participants. OUTCOMES Cardiovascular and renal events during a median follow-up of 12 years. Estimation of annual rate of decline in glomerular filtration rate. ANALYTICAL APPROACH Analysis of variance, linear regression analysis, and Fine-Gray competing-risk survival analysis. RESULTS 9 homozygous, 57 heterozygous, and 44 unaffected family members were identified. In all affected individuals, full sequence analysis of the LCAT gene revealed a mutation (c.820C>T) predicted to cause a proline to serine substitution at amino acid 274 (P274S). Homozygosity caused a complete loss of LCAT activity. Kidney biopsy findings demonstrated lipid deposition causing glomerular basement membrane thickening, mesangial expansion, and "foam-cell" infiltration of kidney tissue. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with worse kidney outcomes. Estimated glomerular filtration rate deteriorated among homozygous family members at an average annual rate of 3.56 mL/min/1.73 m2. The incidence of cardiovascular and renal complications was higher among homozygous family members compared with heterozygous and unaffected members. Mild thrombocytopenia was a common finding among homozygous participants. LIMITATIONS The presence of cardiovascular disease was mainly based on medical history. CONCLUSIONS The P274S LCAT mutation was found to cause FLD with renal involvement. Tubular atrophy, glomerular sclerosis, and complement fixation were associated with a worse renal prognosis.
Measuring biomaterials mechanics with atomic force microscopy. 1. Influence of the loading rate and applied force (pyramidal tips)

Atomic force microscopy (AFM) is today an established tool in imaging and determination of mechanical properties of biomaterials. Due to their complex organization, those materials show intricate properties such as viscoelasticity. Therefore, one has to consider that the loading rate at which the sample is probed will lead to different mechanical response (properties). In this work, we studied the dependence of the mechanical properties of endothelial cells on the loading rate using AFM in force spectroscopy mode. We employed a sharp, four‐sided pyramidal indenter and loading rates ranging from 0.5 to 20 μm/s. In addition, by variation of the load (applied forces from 100 to 10,000 pN), the dependence of the cell properties on indentation depth could be determined. We then showed that the mechanical response of endothelial cells depends nonlinearly on the loading rate and follows a weak power‐law. In addition, regions of different viscous response at varying indentation depth could be determined. Based on the results we obtained, a general route map for AFM users for design of cell mechanics experiments was described.
Estrogen + progestin therapy and cognition: A randomized placebo‐controlled double‐blind study

Aims: The use of hormone therapy (HT) is a relevant and topical issue in the treatment of menopausal symptoms in women. Information regarding the effects of combination treatment with estrogen and progesterone as well as treatment timing on cognitive function is lacking and was evaluated in healthy pre‐ and postmenopausal women.
Changing Patterns of Gastric Carcinoma Over the Past Two Decades in a Single Institution: Clinicopathological Findings in 1557 Patients

Background: Reported differences in clinicopathological patterns of gastric carcinoma (GC) suggest the presence of time-related changes of cancer biology. The aim of this study was to analyse any fluctuations of GC biology in a large series of patients from Poland, where morbidity and mortality rates for GC are relatively high. Methods: Based on the prospectively collected data of 1557 GC patients treated surgically between 1977 and 1999, we analysed the differences in clinicopathological patterns for two consecutive periods: 1977-88 (group I) and 1989-99 (group II). Moreover, time-related trends of GC biology were assessed. Results: The mean age of the patients was 59.1 years (range 20-93) and increased from 58.1 years in group I to 59.9 years in group II ( P < 0.05). Early GC occurred in 6.2% of cases in group I and in 13.7% in group II ( P < 0.001). The incidence of stage IV carcinomas according to the UICC classification significantly decreased from 70.9% to 53.6% ( P < 0.001). The proportion of tumours located in the distal part of the stomach declined from 44.1% in group I to 37.6% in group II ( P < 0.05). Analysis did not reveal differences in histological type (according to the Lauren classification) between groups; nevertheless, a significant trend toward lowering incidence of intestinal type GC was observed ( P < 0.05). Overall, 5-year survival was 27.2% and increased over the period of study from 18.6% to 30.4% ( P < 0.001). Conclusions: The patterns of GC stage, location and histology have changed during the analysed period of time. Observed differences are probably related to fluctuations in carcinogenic factors and have diagnostic as well as therapeutic implications.
Insights into cognitive work hardening for return-to-work following depression: Qualitative findings from an intervention study.

BACKGROUND Workplace mental health disability claims are rising with concomitant challenges to return-to-work (RTW) success. Cognitive work hardening (CWH) addresses work re-entry issues including fatigue, coping skills, and reduced cognitive abilities which are relevant for people returning to work following an episode of depression. OBJECTIVE To gain insight into underlying factors contributing to CWH's effectiveness in RTW preparation following depression. METHODS Twenty-one individuals on paid disability leave due to depression completed a four week CWH treatment intervention prior to returning to work. At program completion and at three months follow up, participants provided qualitative information regarding their experience of the intervention in the form of written questionnaires and interviews. Data were analyzed using a directed approach to content analysis. RESULTS Intervention elements perceived by participants as helpful included structure, work simulations, and simulated work environment. Main treatment gains reported by participants related to routine, self-confidence, stamina, and cognitive abilities. Personal agency, empowerment, and skill development emerged as important consequences of interventions for RTW following depression. CONCLUSIONS Study findings enhance understanding of CWH with relevance to clinical practice. Key intervention elements deemed important for RTW are discussed and may provide guidance for other work-re-entry programs.
Monolingual and Bilingual Word Recognition and Word Learning in Background Noise

The question of whether bilingualism leads to advantages or disadvantages in linguistic abilities has been debated for many years. It is unclear whether growing up with one versus two languages is related to variations in the ability to process speech in the presence of background noise. We present findings from a word recognition and a word learning task with monolingual and bilingual adults. Bilinguals appear to be less accurate than monolinguals at identifying familiar words in the presence of white noise. However, the bilingual “disadvantage” identified during word recognition is not present when listeners were asked to acquire novel word-object relations that were trained either in noise or in quiet. This work suggests that linguistic experience and the demands associated with the type of task both play a role in the ability for listeners to process speech in noise.