Miracle-dz/UniFAR-FTUs huggingface dataset:
An autopsy case of familial amyotrophic lateral sclerosis with a TARDBP Q343R mutation

We describe a Japanese autopsy case of familial amyotrophic lateral sclerosis (FALS) with a TARDBP Q343R mutation. This male patient developed dysarthria at the age of 52 years, and bulbar symptoms progressed, with weakness and atrophy in the extremities. His mental status was normal, but he became bedridden, received artificial respiratory support at 54 years of age, and gradually acquired a locked‐in state and died at 58 years of age. Microscopically, marked diffuse myelin pallor was observed in the anterolateral columns of the spinal cord. The remaining anterior horn cells contained Bunina bodies and phosphorylation‐dependent transactivation response DNA‐binding protein of 43 kDa (pTDP‐43)‐positive neuronal cytoplasmic inclusions (NCIs). Glial cytoplasmic inclusions (GCIs) were also observed. The number of ubiquitin‐ and p62‐positive inclusions was markedly lower than that of pTDP‐43‐positive inclusions. NCIs and many fine dot‐like pTDP‐43‐positive granules in the neuropil were mainly seen in the temporal and motor cortices, and striatum. NCIs were rare in hippocampal granular cells. Immunoblotting of samples from the cerebral cortex using an anti‐pTDP‐43 antibody was slightly different from previous TDP‐43 pathological subtypes.
Birth choice following primary Caesarean section: mothers' perceptions of the influence of health professionals on decision‐making

This study explored mothers' perceptions of the influences of health professionals (GPs, midwives and consultants) on decisions as to mode of delivery of second children, following a previous Caesarean section (CS). Qualitative semi‐structured interviews were conducted with 10 pregnant women (31–40 years), expecting a second child following a first delivery by Caesarean section (20–40 weeks gestation). Interpretative phenomenological analysis revealed four themes accounting for participants' understandings of relevant influences. Participants regarded themselves as: (1) lacking relevant knowledge to make an informed choice, (2) obtaining probabilistic information, and (3) receiving latent communication from health professionals regarding choice of mode of delivery. Their perceived response was (4) to relinquish control over the mode of second delivery to the health professionals involved.
TMEM119 marks a subset of microglia in the human brain

Microglia are resident myeloid cells of the central nervous system (CNS), activated in the brains of various neurological diseases. Microglia are ontogenetically and functionally distinct from monocyte‐derived macrophages that infiltrate the CNS under pathological conditions. However, a lack of specific markers that distinguish resident microglia from circulating blood‐derived macrophages in human brain tissues hampers accurate evaluation of microglial contributions to the human brain pathology. By comparative analysis of five comprehensive microglial transcriptome datasets, we identified an evolutionarily conserved protein TMEM119 as the most promising candidate for human microglial markers. TMEM119 was expressed on immortalized human microglia, in which the expression levels were not elevated by exposure to lipopolysaccharide, IFNγ, IL‐4, IL‐13 or TGFβ1. Notably, TMEM119 immunoreactivity was expressed exclusively on a subset of Iba1+ CD68+ microglia with ramified and amoeboid morphologies in the brains of neurodegenerative diseases, such as Alzheimer's disease (AD), whereas Iba1+ CD68+ infiltrating macrophages do not express TMEM119 in demyelinating lesions of multiple sclerosis and necrotic lesions of cerebral infarction. TMEM119 mRNA levels were elevated in AD brains, although the protein levels were not significantly different between AD and non‐AD cases by western blot and morphometric analyses. TMEM119‐positive microglia did not consistently express polarized markers for M1 (CD80) or M2 (CD163, CD209) in AD brains. These results suggest that TMEM119 serves as a reliable microglial marker that discriminates resident microglia from blood‐derived macrophages in the human brain.
Lung Function and Incident Kidney Disease: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND Reduced lung function is associated with clinical outcomes such as cardiovascular disease. However, little is known about its association with incident end-stage renal disease (ESRD) and chronic kidney disease (CKD). STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 14,946 participants aged 45 to 64 years at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) Study (45.0% men and 25.2% black), with follow-up through 2012. PREDICTORS Race- and sex-specific quartiles of percent-predicted forced vital capacity (FVC) and the proportion of forced expiratory volume in 1 second of expiration to FVC (FEV1/FVC) at baseline determined with spirometry. OUTCOMES Incident ESRD (defined here as renal replacement therapy or death due to CKD) as the primary outcome and incident CKD (defined here as ESRD, ≥25% decline in estimated glomerular filtration rate to a level <60mL/min/1.73m2, or CKD-related hospitalizations/deaths) as the secondary outcome. RESULTS During a median follow-up of 23.6 years, 526 (3.5%) participants developed ESRD. After adjusting for potential confounders, the cause-specific HR of incident ESRD for the lowest (vs highest) quartile was 1.72 (95% CI, 1.31-2.26) for percent-predicted FVC and 1.33 (95% CI, 1.03-1.73) for FEV1/FVC. Compared to a high-normal lung function pattern, a mixed pattern (ie, percent-predicted FVC<80% and FEV1/FVC<70%; 3.4% of participants) demonstrated the highest adjusted cause-specific HR of ESRD at 2.28 (95% CI, 1.50-3.45), followed by the restrictive pattern (ie, percent-predicted FVC<80% and FEV1/FVC≥70%; 4.8% of participants) at 2.03 (95% CI, 1.47-2.81), obstructive pattern (ie, percent-predicted FVC≥80% and FEV1/FVC<70%; 18.9% of participants) at 1.47 (95% CI, 1.09-1.99), and low-normal pattern (ie, percent-predicted FVC 80%-<100% and FEV1/FVC≥70%, or percent-predicted FVC≥80% and FEV1/FVC 70%-<75%; 44.3% of participants) at 1.21 (95% CI, 0.94-1.55). Similar associations were seen with incident CKD. LIMITATIONS Limited number of participants with moderate/severe lung dysfunction and spirometry only at baseline. CONCLUSIONS Reduced lung function, particularly lower percent-predicted FVC, is independently associated with CKD progression. Our findings suggest a potential pathophysiologic contribution of reduced lung function to the development of CKD and a need for monitoring kidney function in persons with reduced lung function.
Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD.

BACKGROUND Clinical practice guidelines recommend referral to nephrology when estimated glomerular filtration rate (eGFR) decreases to <30mL/min/1.73m2; however, evidence for benefits of nephrology care are mixed. STUDY DESIGN Observational cohort using landmark analysis. SETTINGS & PARTICIPANTS A national cohort of veterans with advanced chronic kidney disease, defined as an outpatient eGFR≤30mL/min/1.73m2 for January 1, 2010, through December 31, 2010, and a prior eGFR<60mL/min/1.73m2, using administrative and laboratory data from the Department of Veterans Affairs and the US Renal Data System. PREDICTOR Receipt and frequency of outpatient nephrology care over 12 months. OUTCOMES Survival and progression to end-stage renal disease (ESRD; receipt of dialysis or kidney transplantation) were the primary outcomes. In addition, control of associated clinical parameters over 12 months were intermediate outcomes. RESULTS Of 39,669 patients included in the cohort, 14,983 (37.8%) received nephrology care. Older age, heart failure, dementia, depression, and rapidly declining kidney function were independently associated with the absence of nephrology care. During a mean follow-up of 2.9 years, 14,719 (37.1%) patients died and 4,310 (10.9%) progressed to ESRD. In models adjusting for demographics, comorbid conditions, and trajectory of kidney function, nephrology care was associated with lower risk for death (HR, 0.88; 95% CI, 0.85-0.91), but higher risk for ESRD (HR, 1.48; 95% CI, 1.38-1.58). Among patients with clinical parameters outside guideline recommendations at cohort entry, a significantly higher adjusted proportion of patients who received nephrology care had improvement in control of hemoglobin, potassium, albumin, calcium, and phosphorus concentrations compared with those who did not receive nephrology care. LIMITATIONS May not be generalizable to nonveterans. CONCLUSIONS Among patients with advanced chronic kidney disease, nephrology care was associated with lower mortality, but was not associated with lower risk for progression to ESRD.
Public Perceptions and Knowledge of the Ebola Virus, Willingness to Vaccinate, and Likely Behavioral Responses to an Outbreak

Abstract Objective We examined public perceptions of the risk of an Ebola outbreak, knowledge about transmission, and the factors associated with planned protective behavior, including willingness to vaccinate. Methods We conducted a cross-sectional telephone survey using random digit dialing of 750 members of the New Zealand public between February 12 and 19, 2015. Results Most of the sample (72%) reported that they had been following news of the outbreak closely and 28% were concerned that there would be a large outbreak in New Zealand. High rates of planned protective behavior, in terms of avoiding contact with other people, were reported, with 23% reporting they would avoid going to work, 49% reporting they would avoid using public transport, 42% reporting they would avoid sending children to school, and 52% reporting they would avoid public events. A younger age, a higher concern, and lower confidence in the ability of hospitals to contain the outbreak were significantly associated with both a greater willingness to vaccinate and a larger number of protective behaviors. Conclusions An Ebola outbreak would have large social and economic consequences owing to the large proportion of the population who intended to avoid social contact in order to protect their health. (Disaster Med Public Health Preparedness. 2016;10:674–680)
The effect of reactive atypia/inflammation on the laser‐induced fluorescence diagnosis of non‐dysplastic Barrett's esophagus

Differential Normalized Fluorescence (DNF) technique has been used to distinguish high‐grade dysplasia from non‐dysplastic Barrett's esophagus. This technology may assist gastroenterologists in targeting biopsies, reducing the number of biopsies using the standard protocol. In the presence of reactive atypia/inflammation, it becomes difficult for the pathologist to differentiate non‐dysplastic Barrett's esophagus from Barrett's esophagus with low‐grade dysplasia. Before DNF technique may be used to guide target biopsies, it is critical to know whether reactive atypia/inflammation in non‐dysplastic Barrett's may result in false positives.
In Reply to 'How Valid Are GFR Estimation Results From the CKD-EPI Databases?'

We do not agree with the assertions by Bj€ ork et al. First, the coefficients for the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation were not modified using results from the external validation. Second, results from the CKD-EPI database have been confirmed in numerous studies despite variation in serum creatinine assays following standardization. Third, the reanalysis of the CKD-EPI data set by Bj€ ork et al does not show that the Lund-Malm€ o-revised (LMR) equation is more accurate than the CKD-EPI equation. Fourth, comparative performance in external validation data sets is essential for selection of equations for clinical use. The goal in reporting glomerular filtration rate estimates is for all clinical laboratories to use a single equation for each filtration marker or each combination of filtration markers, if possible. Because even the most accurate equations using serum creatinine concentration are imprecise, the use of multiple equations with similar accuracy could lead to different estimates for the same patient. For this reason, the KDIGO (Kidney Disease: Improving Global Outcomes) 2012 CKD guideline recommended the use of the CKD-EPI equation, unless other equations are more accurate. Unlike the CKD-EPI equation, the LMR equation does not include a coefficient for African American race-ethnicity, and our results show that it is not appropriate for use in African Americans, an important subgroup of patients with CKD. Although some evaluations have shown that the LMR equation is as accurate as or more accurate than the CKD-EPI equation in some other subgroups, we are not aware of
A qualitative exploration of the experiences of people living alone and receiving community-based palliative care.

BACKGROUND It is projected that in Australia there will be between 28% and 48% of palliative care patients living alone by the year 2031. As such, it will become increasingly important to provide appropriate home-based care in order to support these patients to be cared for and die at home. AIM This study explored the experiences of community-based palliative care cancer patients who live alone without a caregiver and what psychosocial issues they face. METHODS Face-to-face semistructured interviews were conducted with eight participants, and constant comparison was used for the analysis. FINDINGS Four main themes emerged: (1) loss of social networks; (2) maintaining independence; (3) balancing independence and the need for assistance; and (4) planning for the end of life. DISCUSSION Participants balanced independence with the need to accept help in order to maintain independence. Participants became more flexible about their preferred place of death. CONCLUSION The practice implications for working with people close to death who are living alone are that supports and assistance may be needed to maintain social networks and also a sense of independence.
Distribution of porcine parvovirus in porcine circovirus 2-infected pigs with postweaning multisystemic wasting syndrome as shown by in-situ hybridization.

In-situ hybridization with a nonradioactive digoxigenin-labelled probe was used to study the distribution of porcine parvovirus (PPV) in formalin-fixed paraffin wax-embedded tissues from 10 porcine circovirus 2 (PCV2)-infected weaned pigs with naturally occurring postweaning multisystemic wasting syndrome (PMWS). A 226 base pair DNA fragment from a VP2 structural gene was generated by polymerase chain reaction (PCR) and used as a probe. Lymph node, spleen, thymus and tonsil were positive by PCR, demonstrating the presence of PPV DNA in the tissue samples from four of 10 pigs tested. PPV nucleic acid was also detected consistently in lymph node, spleen, thymus and tonsil by in-situ hybridization. Detection of PPV DNA from PCV2-infected pigs with PMWS suggests that PPV also plays a role in the pathogenesis of PMWS.
Protoporphyrin IX Fluorescence and Photobleaching During Interstitial Photodynamic Therapy of Malignant Gliomas for Early Treatment Prognosis

Interstitial photodynamic therapy (iPDT) of non‐resectable recurrent glioblastoma using 5‐aminolevulinic acid (ALA)‐induced protoporphyrin IX (PpIX) has shown a promising outcome. It remained unclear, however, to what extent inter‐ and intra‐tumoural differences of PpIX concentrations influence the efficacy of iPDT. In the current pilot study, we analysed PpIX concentrations quantitatively and assessed PpIX induced fluorescence and photobleaching intraoperatively.
Evidence for Abnormalities in Parasympathetic Nerve-Mediated Reflexes in Borderline Hypertension

This study was designed to elucidate the abnormalities in both the parasympathetic and sympathetic nervous systems in borderline hypertension. Utilizing the cold pressor test (CPT) for evaluation of the sympathetic nervous system and R-R interval variation for the assessment of the parasympathetic nervous system, fifteen male patients (37±4 y.o.) with borderline hypertension (mean arterial pressure=111±2mmHg) and age-matched normotensive controls participated in this study. The cold face test (CFT), which is able to evaluate the trigeminal-vagal-cardiac and trigeminal-sympathetic-peripheral vasculature pathways, was also employed to evaluate the balance between these two divisions of the autonomic nervous system. The coefficient of variation (CV) of R-R interval variation in the borderline hypertensives was significantly smaller than that in the controls (3.9±0.3vs. 6.3±0.4%, P<0.01). The CPT produced a significant elevation of blood pressure in both groups, but there were no significant differences between the two groups. The CFT induced bradycardia (P<0.01) in the controls, while hypertensive subjects were characterized by an increase in systolic blood pressure (P<0.01) without significant changes in heart rate. Epinephrine was significantly decreased by the CFT only in the controls. There was a positive correlation between CV of R-R interval and decrease in heart rate by the CFT (r=0.60, P<0.0005). These results suggest that even with a specifically vagal reflex, patients with borderline hypertension have decreased parasympathetic tone and that the CFT may be useful in the assessment of the balance between the sympathetic and parasympathetic nervous systems over the regulation of the effector organs. (Hypertens Res 1993; 16: 185- 190)
Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer.

BACKGROUND & AIMS 5-Fluorouracil improves mortality in stage III colorectal cancer patients. In vitro studies suggest that microsatellite instability influences cell survival after 5-fluorouracil treatment. We investigated the survival influence of 5-fluorouracil in patients with microsatellite instability-high tumors. METHODS We collected data and tumors on 204 consecutive stage II and III colorectal cancer patients from registries at the University of California and Veterans Administration hospitals in San Diego, California, from 1982 to 1999. Archival DNA was extracted, and microsatellite instability was assessed by National Cancer Institute-recommended markers. Cox proportional hazard modeling was used to determine survival associations for microsatellite instability and 5-fluorouracil treatment status. RESULTS We identified 36 microsatellite instability-high (17.6%) and 168 non-microsatellite instability-high tumors (82.4%). Microsatellite instability-high tumors were significantly associated with proximal colon location, presence of mucin, and surrounding lymphoid reaction. Univariate and multivariate analyses showed no survival difference between microsatellite instability-high and non-microsatellite instability-high groups (hazard ratio, 1.04; P = 0.88). Dichotomized by use of 5-fluorouracil, there was increased risk of death in patients who received no adjuvant chemotherapy (hazard ratio, 2.02; P = 0.02). However, the benefit of 5-fluorouracil was different between microsatellite instability-high and non-microsatellite instability-high groups. Patients with non-microsatellite instability-high tumors who received 5-fluorouracil had better survival compared with patients who were not treated (P < 0.05). Conversely, patients with microsatellite instability-high tumors who were treated with 5-fluorouracil had no survival difference compared with patients without treatment (P = 0.52). CONCLUSIONS There is improved survival in patients with non-microsatellite instability-high tumors after 5-fluorouracil-based chemotherapy that does not extend to patients with microsatellite instability-high tumors. The microsatellite instability status of a patient's colorectal cancer may indicate differences in 5-fluorouracil-based chemosensitivity; this is consistent with in vitro studies.
A Na+-coupled C4-dicarboxylate transporter (Asuc_0304) and aerobic growth of Actinobacillus succinogenes on C4-dicarboxylates.

Actinobacillus succinogenes, which is known to produce large amounts of succinate during fermentation of hexoses, was able to grow on C4-dicarboxylates such as fumarate under aerobic and anaerobic conditions. Anaerobic growth on fumarate was stimulated by glycerol and the major product was succinate, indicating the involvement of fumarate respiration similar to succinate production from glucose. The aerobic growth on C4-dicarboxylates and the transport proteins involved were studied. Fumarate was oxidized to acetate. The genome of A. succinogenes encodes six proteins with similarity to secondary C4-dicarboxylate transporters, including transporters of the Dcu (C4-dicarboxylate uptake), DcuC (C4-dicarboxylate uptake C), DASS (divalent anion : sodium symporter) and TDT (tellurite resistance dicarboxylate transporter) family. From the cloned genes, Asuc_0304 of the DASS family protein was able to restore aerobic growth on C4-dicarboxylates in a C4-dicarboxylate-transport-negative Escherichia coli strain. The strain regained succinate or fumarate uptake, which was dependent on the electrochemical proton potential and the presence of Na(+). The transport had an optimum pH ~7, indicating transport of the dianionic C4-dicarboxylates. Transport competition experiments suggested substrate specificity for fumarate and succinate. The transport characteristics for C4-dicarboxylate uptake by cells of aerobically grown A. succinogenes were similar to those of Asuc_0304 expressed in E. coli, suggesting that Asuc_0304 has an important role in aerobic fumarate uptake in A. succinogenes. Asuc_0304 has sequence similarity to bacterial Na(+)-dicarboxylate cotransporters and contains the carboxylate-binding signature. Asuc_0304 was named SdcA (sodium-coupled C4-dicarboxylate transporter from A. succinogenes).
Autofluorescence of liver tissue and bile: Organ functionality monitoring during ischemia and reoxygenation

Autofluorescence (AF) based optical biopsy of liver tissue is a powerful approach for the real‐time diagnosis of its functionality. Since increasing attention is given to the bile production and composition to monitor the liver metabolic engagement in surgery and transplantation, we have investigated the bile AF properties as a potential, additional diagnostic parameter.
Cannabis use by people with severe mental illness – is it important?

Cannabis use is more common among people with severe mental illness than in the general population. It has detrimental effects on the course of the illness, physical health and social life of users, as well as being a financial burden on health services. It is important to understand why some people with severe mental illness continue to use cannabis, despite experiencing its effects on their condition. This article reviews research on the scale of cannabis use by such patients, the effects on the course of their illness, possible reasons to explain why they use it, and how they can be assessed in clinical settings, as well as providing some assessment tools to measure various characteristics related to cannabis use.