Miracle-dz/UniFAR-FTUs huggingface dataset:
Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity

When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein–1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1’s normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.
Urodynamic Evaluation and Management prior to Renal Transplantation

Objectives: To evaluate the indications for urodynamics studies (UDS) previous to renal transplantation (RT) and the results of bladder cycling (BC), performed in selected cases.Methods: Among 475 RT, 33 patients (6.9%) required UDS according our protocol. Indications were: (1) low urinary tract symptoms (LUTS); (2) defunctionalized bladder (DB), and (3) complex urologic history (reflux, neurogenic bladder, urethral valves, etc.). DB was defined as a total urinary output of <300 ml/24 h. Patients with DB underwent BC through a suprapubic catheter, undergoing UDS after BC. The rate and type of urodynamic anomalies were compared among the 3 groups. Cystometric capacity (CysCap) and compliance were evaluated according to the etiology of renal failure, diuresis, and number of previous bladder surgeries.Results: Fifteen patients (45%) showed abnormal UDS, Increased pressure at cystometry was the most frequent finding (46%). The rate of abnormal UDS among the 3 groups was not statistically significant (66.6% in DB, 42.8% in LUTS, and 35% in those with complex urologic history). Compliance and CysCap were significantly lower in the patients with DB, showing a significant correlation with diuresis. These parameters did not correlate with the number of previous bladder surgeries. BC resulted in normal UDS in 3 patients (33%) and a change in diagnosis in 2 patients (22%). Conclusion: Our indications gave a good diagnostic yield. Patients with DB represent a group with different urodynamic findings. BC provides a more precise diagnosis or normalization of UDS in some cases.
Advanced multiple sclerosis and the psychosocial impact on families

This study explores family relationships and support needs when adapting to a relative's advanced-multiple sclerosis (MS) around transition into care. A multi-site qualitative study of relatives of people with advanced-MS was conducted. A purposive sample of 25 relatives was selected and interviewed either in the care home or participants’ homes. Interviews were recorded, transcribed and analysed using grounded theory methodology and Atlas.ti 5.2 software. Data quality enhancement involved: a self-report questionnaire; triangulation and member-checking. Themes derived from the data were: information, communication and understanding; family relationships, roles and responsibilities; emotions, coping and support; life outlook and reflection. Provision of information and support for families around the transition into care appears to be inconsistent despite there being a need for family members to ask questions and discuss the impact of the condition. Relatives reported that as a family and as individuals they faced significant challenges and were in great need of support at times, but reflected that they would have found it very difficult to accept. Relatives were also often unsure what type of support would have helped. For care providers, there needs to be a shift from the traditional health care professional ‘patient-centred’ mindset towards more proactive family-centred approaches and steps to encourage this are articulated.
Induction of Apoptosis by ASK1, a Mammalian MAPKKK That Activates SAPK/JNK and p38 Signaling Pathways

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-α (TNF-α). Moreover, TNF-α-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.
Podocytes that detach in experimental membranous nephropathy are viable.

BACKGROUND Podocyte loss contributes to the development of glomerulosclerosis. Although podocytes have been detected in the urine in certain glomerular diseases, the viability of detached cells is not known. METHODS Urine was collected from rats with experimental membranous nephropathy [passive Heymann nephritis (PHN) model], centrifuged, and following resuspension in tissue culture media, cells were seeded onto collagen-coated tissue culture plates. Cells were grown under typical cell culture conditions. Cell number was measured, the cell type was identified by immunostaining with specific antibodies, and cell morphology was assessed by light and electron microscopy. RESULTS Cells obtained in the urine from PHN rats were positive for synaptopodin, nephrin, podocin, WT-1, and GLEPP1 (podocyte-specific antigens). When grown ex vivo under cell culture conditions, cells obtained in the urine from PHN rats adhered to tissue culture plates, and expressed podocyte-specific proteins at the mRNA [reverse transcription-polymerase chain reaction (RT-PCR)] and protein (immunostaining) level. Cells did not stain with antibodies to mesangial (OX-7), tubular (Tamm-Horsfall protein) and endothelial (RECA) cells. Electron microscopy showed the presence of foot processes, and podocytes from PHN rats stained positive for C5b-9. Although podocyte number increased transiently during the first 5 days ex vivo, apoptosis increased significantly thereafter, reducing overall cell number. CONCLUSION Rats with experimental membranous nephropathy shed podocytes into the urine that attach to tissue culture plates ex-vivo, and proliferate. These results suggest that detached podocytes are viable. These results add new perspectives into our understanding of podocyte loss in the development of glomerulosclerosis.
Pancreaticoduodenectomy for nonampullary duodenal lesions: indications and results

Background Pancreaticoduodenectomy (PD) is a complex procedure, associated with a definite risk of mortality and 30–50% risk of complications. For nonampullary duodenal lesions, PD can carry a higher morbidity as they are more commonly associated with a soft pancreas and narrow-calibre main pancreatic ducts. It is therefore paramount that the risks and benefits of surgery are considered carefully in this group of patients. A preoperative histological diagnosis for duodenal lesions is normally achieved by endoscopic biopsy. In this study, we aim to assess the outcome of PD in patients with nonampullary duodenal lesions and correlate the preoperative endoscopic histology work-up with the definitive postoperative pathology. Materials and methods We reviewed a prospectively collected PD database from January 2007 to December 2013. Demographic and clinical data were included. Preoperative endoscopic histology was compared with final specimen histology to assess concordance. Results Forty patients (55% women, mean age 69.4 years, range 45–83 years) underwent PD for duodenal lesions over a 7-year time period. The most common presenting symptom was epigastric pain (32.5%), followed by anaemia (20%). Overall, the complication rate was 55%, with the most frequent adverse event being pancreatic fistula in 13/40 (32.5%). The perioperative mortality was 2/40 (5%). Duodenal adenocarcinoma (65%) was the most common postoperative histological diagnosis. The mean tumour size was 36 mm (range 5–103 mm) and a median of 13 nodes were harvested. The median length of stay was 15 days (range 7–66 days). Overall, 12/40 patients (30%) had a preoperative diagnosis of high-grade dysplasia. The postoperative specimen in this subgroup of patients was reviewed carefully and only 3/12 (25%) patients had high-grade dysplasia in the resection specimen. In the remaining patients, 3/12 (25%) had adenocarcinoma in the resection specimen and 6/12 patients (50%) had low-grade dysplasia. Conclusion PD carries a high mortality and morbidity, especially for duodenal lesions. We recommend a careful endoscopic review after the index case with a high-definition optical evaluation of duodenal lesions. This, in addition to an experienced histological assessment of the index biopsy material, forms an essential prerequisite in aiding the multidisciplinary team in the decision-making process with respect to triage of these lesions to conservative management, surveillance, endoscopic resection or finally surgical resection.
InfiniViz: Interactive Visual Exploration using Progressive Bin Refinement

Interactive visualizations can accelerate the data analysis loop through near-instantaneous feedback. To achieve interactivity, techniques such as data cubes and sampling are typically employed. While data cubes can speedup querying for moderate-sized datasets, they are ineffective at doing so at a larger scales due to the size of the materialized data cubes. On the other hand, while sampling can help scale to large datasets, it adds sampling error and the associated issues into the process. While increasing accuracy by looking at more data may sometimes be valuable, providing result minutiae might not be necessary if they do not impart additional significant information. Indeed, such details not only incur a higher \emph{computational} cost, but also tax the \emph{cognitive} load of the analyst with worthless trivia. To reduce both the computational and cognitive expenses, we introduce \emph{InfiniViz}. Through a novel result refinement-based querying paradigm, \emph{InfiniViz} provides error-free results for large datasets by increasing bin resolutions progressively over time. Through real and simulated workloads over real and benchmark datasets, we evaluate and demonstrate \emph{InfiniViz}'s utility at reducing both cognitive and computational costs, while minimizing information loss.
Facing the Music: Pre- and Postconcert Assessment of Hearing in Teenagers

Objective Determine the effect of exposure to a single rock/pop concert on pure-tone hearing thresholds and outer hair cell function in teenagers. Study Design Repeated measures pre- and postconcert assessment of hearing. Setting Mobile hearing conservation test vehicle and large indoor concert venue. Subjects Twenty-nine normal-hearing teenagers and young adults ages 13 to 20 years. Intervention Attendance at a public rock/pop concert. Main Outcome Measures Pre- and postconcert pure-tone thresholds in both ears from 500 Hz to 8 kHz, pure-tone average (PTA) for 2, 3, and 4 kHz, distortion product otoacoustic emissions (DPOAEs), proportion of subjects experiencing a PTA change of 10 dB or greater. Results Concert sound levels at the subjects’ position averaged 98.5 dBA. Only 3 subjects used the hearing protection provided. Thresholds for 2 to 6 kHz increased significantly from pre- to postconcert (p ⩽ 0.001). The increase in PTA (2, 3, and 4 kHz) between test intervals averaged 6.3 and 6.5 dB for the right and left ears, respectively, and 33.3% of subjects had a threshold shift of 10 dB or greater in the PTA in at least 1 ear (p ⩽ 0.001). The number of subjects experiencing a reduction in DPOAE amplitude (17/25) and the change in mean amplitude were statistically significant (p ⩽ 0.001 and p ⩽ 0.004, respectively). Conclusion Exposure to a single live-music rock/pop concert can produce a threshold shift and decrease in otoacoustic emissions amplitude indicating impact on outer hair cell function. Results clearly indicate a need for research on this public health issue regarding “safe” listening levels, especially in younger people with more years for accrual of damage.
A Century of Gaps

This paper considers the role of financial information in the estimation and dynamics of the US output gap over more than a century. To this end, we extend the parsimonious approach of Borio, Disyatat, and Juselius (2016, 2014) to allow for time-varying effects of financial factors. This novel feature significantly improves real-time estimates of the output gap. It signals the peak and trough in economic activity related to both the Great Recession and the Great Depression. Two major insights follow. Credit dynamics are the primary drivers of the observed financial crisis, albeit with different conduits over the century: the stock market in 1929 and the housing market in 2008. Accounting for credit growth, the US potential growth has been stable at 2% since the beginning of 1980.
Sudden death from aneurysmal subarachnoid hemorrhage

Article abstract—Some patients with aneurysmal subarachnoid hemorrhage (SAH) never reach the hospital alive (“sudden death”) and, although their numbers are significant, they are not included in most studies of SAH. To clarify the clinical profile of sudden death from aneurysmal SAH, we reviewed the epidemiology and clinicopathologic features of patients with aneurysmal SAH who never reached medical attention. Using the medical record linkage system employed for epidemiologic studies for the population of Rochester, Minnesota, we identified all patients who were diagnosed with aneurysmal SAH between 1960 and 1989. There were 80 women and 33 men with a mean age of 55 years. Of these 113 patients, 13 (12%) died without reaching medical attention. The proportion of those with sudden death remained stable during the study period. In comparing patients with sudden death with those who reached medical attention, the only significant variable was the frequency of posterior circulation aneurysms that was found in 38%, compared with 14% in those who received medical attention (p = 0.042). At autopsy, intraventricular hemorrhage was present in 12 patients (92%) with sudden death, and intracerebral hemorrhage was present in two (15%). Twelve patients (92%) had acute pulmonary edema. In our community, the frequency of sudden death from aneurysmal SAH has not changed during the last three decades in spite of the advances in medical care. The typical clinical profile of sudden death in SAH includes intraventricular hemorrhage, pulmonary edema, and a ruptured posterior circulation aneurysm. Intracerebral hemorrhage is uncommonly associated with sudden death from aneurysmal SAH.
Aggregation with non-convex labor supply, unobservable effort, and efficiency wages of the no-shirking type

The purpose of this note is to explore the problem of non-convex labor supply decision in an economy with imperfect observability of work effort, and the need to use effciency wages to prevent shirking as in Shapiro and Stiglitz 1984. In addition, the paper and explicitly performs the aggregation presented in Vasilev 2017 without a formal proof, and thus provide - starting from micto-foundations - the derivation of the expected utility functions used for the aggregate household. We show how lotteries as in Rogerson 1988 can be used to convexify consumption sets, and aggregate over individual preferences. With a discrete labor supply decisions, the elasticity of aggregate labor supply increases from unity to infinity.
Considerations for the Selection of Time-Limited Walk Tests Poststroke: A Systematic Review of Test Protocols and Measurement Properties

Background and Purpose: Systematic reviews of research evidence describing the quality and methods for administering standardized outcome measures are essential to developing recommendations for their clinical application. The purpose of this systematic review was to synthesize the research literature describing test protocols and measurement properties of time-limited walk tests in people poststroke. Methods: Following an electronic search of 7 bibliographic data-bases, 2 authors independently screened titles and abstracts. One author identified eligible articles, and performed quality appraisal and data extraction. Results: Of 12 180 records identified, 43 articles were included. Among 5 walk tests described, the 6-minute walk test (6MWT) was most frequently evaluated (n = 36). Only 5 articles included participants in the acute phase (<1 month) poststroke. Within tests, protocols varied. Walkway length and walking aid, but not turning direction, influenced 6MWT performance. Intraclass correlation coefficients for reliability were 0.68 to 0.71 (12MWT) and 0.80 to 1.00 (2-, 3-, 5- and 6MWT). Minimal detectable change values at the 90% confidence level were 11.4 m (2MWT), 24.4 m (5MWT), and 27.7 to 52.1 m (6MWT; n = 6). Moderate-to-strong correlations (≥0.5) between 6MWT distance and balance, motor function, walking speed, mobility, and stair capacity were consistently observed (n = 33). Moderate-to-strong correlations between 5MWT performance and walking speed/independence (n = 1), and between 12MWT performance and balance, motor function, and walking speed (n = 1) were reported. Discussion and Conclusions: Strong evidence of the reliability and construct validity of using the 6MWT poststroke exists; studies in the acute phase are lacking. Because protocol variations influence performance, a standardized 6MWT protocol poststroke for use across the care continuum is needed. Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A150).
Patients with refractory reflux symptoms often do not have GERD

In patients with typical reflux symptoms that persist despite proton pump inhibitors (PPIs) it is sometimes overlooked that treatment fails due to the presence of other disorders than gastroesophageal reflux disease (GERD). The aim of this study was to determine the underlying cause of reflux symptoms not responding to PPI therapy in tertiary referral patients.
Missed opportunities: racial disparities in adjuvant breast cancer treatment.

PURPOSE Underuse of adjuvant therapy is a potentially important and remediable explanation for the inferior survival of minority women with breast cancer. We sought to measure a racial disparity in the underuse of adjuvant treatments for early-stage breast cancer and to identify associated factors. METHODS Cross-sectional study with review of all inpatient and outpatient medical records of 677 women treated surgically for a primary American Joint Committee on Cancer stage I or II breast cancer in 1999 to 2000. Underuse was defined as omissions of radiation therapy after breast-conserving surgery, adjuvant chemotherapy after resection of hormone-receptor-negative tumors > or = 1 cm, or hormonal therapy for receptor-positive tumors > or = 1 cm. RESULTS One hundred forty-five (21%) of 677 women experienced underuse of appropriate adjuvant therapy: 16% in whites, 34% in blacks, and 23% in Hispanics (P < .001). Women referred to medical oncologists were less likely to experience underuse of necessary adjuvant treatments (relative risk [RR] for underuse = 0.2; 95% CI, 0.1 to 0.3). Women who were minorities (RR = 2.0; 95% CI, 1.3 to 3.1), had higher levels of comorbidity (RR = 1.4; 95% CI, 1.1 to 1.8) and lacked insurance (RR = 1.9; 95% CI, 0.9 to 4.0) were at greater risk for underuse. CONCLUSION Minority women with early-stage breast cancer have double the risk of white women for failing to receive necessary adjuvant treatments despite rates of oncologic consultation similar to those for white women. Oncology referrals are necessary to reduce treatment disparities but are not sufficient to ensure patients' receipt of efficacious adjuvant treatment.
Intravenous Immunoglobulin Therapy for Neuromuscular Disorders

Treatment of specific immune-mediated neuromuscular disorders involves consideration of many factors including severity of illness, concurrent medical problems, supportive therapies, and immune-modulating therapies. Many immune-modulating therapies are available, including steroids, an increasing number of immunosuppressive drugs, plasmapheresis, and intravenous immunoglobulin (IVIG). Deciding on which immune-modulating therapy involves selecting from those with proven efficacy for a specific disorder and global considerations of which therapies are most appropriate for an individual patient's circumstances. IVIG has become a commonly used therapy as it is well tolerated, easily administered, and is often efficacious with a relatively rapid action. IVIG has become a first-line therapy for several immune-mediated demyelinating polyneuropathies and may play a role in treating exacerbations of myasthenia gravis and selected chronic treatment-refractory cases of Lambert-Eaton myasthenic syndrome, dermatomyositis, and polymyositis.
Selection of Dictyostelium mutants defective in cytoskeletal proteins: use of an antibody that binds to the ends of alpha‐actinin rods.

A monoclonal antibody, mAb 47‐19‐2, was used to study the subunit topology of the rod‐shaped alpha‐actinin molecules of Dictyostelium discoideum and to screen for mutants defective in the production of alpha‐actinin. Electron microscopy of rotary‐shadowed alpha‐actinin‐antibody complexes showed binding of mAb 47‐19‐2 to both ends of the alpha‐actinin rods and cleavage of the rods into its subunits, indicating that the two subunits of alpha‐actinin extend in an anti‐parallel mode through the whole length of the rod. The antibody binding sites were located in close proximity to the sites responsible for actin cross‐linking, which is consistent with the blocking activity of the antibody. In a mutant, HG1130, no antibody label was detected in colony blots, and by immunoblotting of mutant proteins separated by SDS‐PAGE, only trace amounts of alpha‐actinin were found. The mutant showed normal binding of antibodies directed against the actin‐binding proteins severin and capping protein. The mutation responsible for the alpha‐actinin defect was recessive and located on linkage group I of the genetic map of D. discoideum. HG1130 cells grew on bacteria at a normal rate and also axenically like cells of the parent strain AX2. After starvation the mutant cells expressed the contact site A glycoprotein, a marker of the aggregation‐competent stage, and reacted chemotactically to cyclic AMP. The aggregation patterns and fruiting bodies of the mutant appeared to be normal. Patching and capping on the surface of HG1130 cells was induced by antibodies against the contact site A glycoprotein. (ABSTRACT TRUNCATED AT 250 WORDS)