Miracle-dz/UniFAR-FTUs huggingface dataset:
Germline PALB2 mutation analysis in breast–pancreas cancer families

Background Germline mutations in the PALB2 gene have been implicated in both breast cancer and pancreatic cancer susceptibility. The extent to which PALB2 mutations account for cancer susceptibility in breast–pancreas cancer families is unknown. Methods High Resolution Melting analysis and Multiplex Ligation-dependent Probe Amplification were performed to investigate the prevalence of PALB2 mutations in patients with either a personal history of both breast and pancreatic cancer or a personal history of breast cancer and a family history of a first degree relative with pancreatic cancer. Results No PALB2 mutations were identified in 77 breast–pancreas cancer families, which included 22 probands with a personal history of both breast and pancreatic cancer. Conclusion Mutations within the PALB2 gene are rare events that do not account for a substantial proportion of cancer susceptibility in breast–pancreas cancer families. Routine screening of breast–pancreas cancer families for the presence of PALB2 mutations appears to be low yield.
Accounting for genetic heterogeneity in homozygosity mapping: application to Mendelian susceptibility to mycobacterial disease

Introduction Genome-wide homozygosity mapping is a powerful method for locating rare recessive Mendelian mutations. However, statistical power decreases dramatically in the presence of genetic heterogeneity. Methods The authors applied an empirical approach to test for linkage accounting for genetic heterogeneity by calculating the sum of positive per-family multipoint LOD scores (S) across all positions, and obtaining corresponding empirical p values (EmpP) through permutations. Results The statistical power of the approach was found to be consistently higher than the classical heterogeneity LOD by simulations. Among 21 first-cousin matings with a single affected child, for five families linked to a locus of interest and 16 families to other loci, S/EmpP achieved a power of 40% versus 28% for heterogeneity LOD at an α level of 0.001. The mean size of peak linkage regions was markedly higher for true loci than false positive regions. The S/EmpP approach was applied to a sample of 17 consanguineous families with Mendelian susceptibility to mycobacterial disease, leading to the identification of two mutations in IL12RB1 and TYK2 from the largest of six linkage regions at p<10−3. Conclusions The S/EmpP approach is a flexible and powerful approach that can be applied to linkage analysis of families with suspected Mendelian disorders.
Malay syllable recognition based on multilayer perceptron and dynamic time warping

Attempts at creating and using the first database for Malay syllables are presented. The speech vocabulary consists of 16 Malay syllables which are initialized with plosives and followed by succeeding vowels. The paper investigates the use of multilayer perceptron (MLP) and dynamic time warping (DTW) in recognizing these Malay syllable sounds that are quite similar to each other. From the experimental results, DTW and MLP achieved 77.09% and 90.82% respectively in overall average recognition rate.
Lamina propria group 2 innate lymphoid cells impair the antibacterial defense of burned mice to enterococcal translocation

Gut microbiota that invades to the defective mucosal barrier is one of the major sources of infectious complications in severely burned hosts. In this study, a role of group 2 innate lymphoid cells (ILC2) and effects of N‐{4‐[2,2,2‐trifluoro‐1‐hydroxy‐1‐(trifluoromethyl)ethyl]phenyl}‐2‐thiophenesulfonamide (SR3335) on the host antibacterial resistance against infectious complications caused by Enterococcus faecalis oral infection were investigated in burned mice. Retinoic acid receptor‐related orphan receptor α (RORα) is a transcription factor required for the development of ILC2, and SR3335 is an RORα‐selective inverse agonist. All of burned mice died within 6 d of E. faecalis infection (5 × 106 CFU/mouse), whereas 100% of the same mice treated with SR3335 survived. The increased ILC2 and their cytokine products (IL‐5 and IL‐13) were detected in the lamina propria of mice, 1–7 d after burn injury. However, the number of ILC2 did not increase in the lamina propria of burned mice treated with SR3335. The antibacterial resistance of SCID‐beige (SCIDbg) mice to E. faecalis infection was impaired by the inoculation of ILC2. BALB/c, SCIDbg, and polymorphonuclear leukocyte (PMN)‐depleted SCIDbg mice were shown to be resistant against E. faecalis infection. However, all Mϕ depleted SCIDbg mice died after the infection. These results indicate that host antibacterial effector Mϕ against enterococcal translocation are influenced by ILC2, increased in the bacterial translocation site of burned mice, and sepsis stemming from E. faecalis oral infection was amazingly mitigated in these mice after treatment with SR3335, an inhibitor of cellular differentiation from an ILC precursor (ILCP) to ILC2.
Surgonomics of unruptured intracranial aneurysms

Background/Aims A comparison of reimbursement for endovascular coil embolization and surgical clipping of unruptured aneurysms has not been previously reported. The aim of this study is to assess the reimbursement to physicians and hospitals for each of these two unruptured aneurysm treatments with long-term follow-up. Methods Hospital and physician payents were determined for 14 patients treated with coil embolization or surgical clipping of a single unruptured aneurysm per patient from 2004 to 2005, retrospectively. For this analysis, each considered hospital and physician payment encompassed one clipping or coiling procedure plus all pre- and post-operative diagnostic angiograms performed through 2007 to evaluate the treated aneurysm. Reimbursements were analyzed in three categories: physician payments, hospital payments and total payments. Results Average physician payments were significantly lower for coil embolization ($3422) than surgical clipping ($5645). Average length of stay after coil embolization was 2.6 days (range: 1–7) and after surgical clipping was 4.7 days (range: 2–11). The length of hospital stay directly affected hospital and total payments only, but was not significantly altered by which procedure was performed. Conclusion This study suggests that physician payment for an unruptured aneurysm coil embolization treatment was statistically lower than for a surgical clip treatment. Although physicians were compensated at a lower rate for performing a coil embolization, there was no significant difference in the hospital or total payments between coil or clip treatment modalities.
The Role of Nutrition Intervention in Wound Healing

This article reviews the role of nutrition in the healing of skin breakdown. The components of a nutritional assessment, which include social history, dietary intake, anthropometrics, and serum laboratory values, are discussed with abnormal values highlighted. The three phases of wound healing and a general overview of key nutrients needed at each stage for proper wound healing are stressed.
Minimizing risk in applying metrics on multiple projects

Using the author's own metrics validation methodology, he shows how this methodology can be used across dissimilar multiple projects. He shows how to reduce the risk of using metrics on multiple projects. He also shows that the choice of metrics and their values can have a significant effect on the quality of software that is achieved and on the cost and amount of inspection that is incurred on multiple projects. A multi-project example, emphasizing the discriminative power validity criterion in support of the quality control function, is presented. A metrics validation process is defined that integrates quality factors, metrics and quality functions. <<ETX>>
Impeding DNA Break Repair Enables Oocyte Quality Control

Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death is triggered by defects in chromosome synapsis and recombination, which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocytes elimination in meiotic mutants require RNF212. RNF212 sensitizes cells to DSB-induced apoptosis within a narrow window when chromosomes desynapse during the transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a “memory” of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.
Heterogeneity of cerebral perfusion 1 week after haemorrhage is an independent predictor of clinical outcome in patients with aneurysmal subarachnoid haemorrhage

Background and purpose: Aneurysmal subarachnoid haemorrhage (aSAH) can be associated with acute global and regional decrease in cerebral perfusion. Furthermore, cerebral vasospasm may lead to development of delayed ischaemic deficits. The aim of the study was to find out whether cerebral perfusion heterogeneity, an indicator of cerebral microvascular function and autoregulation, measured by single-photon emission tomography (SPET), is able to predict the long-term clinical outcome of aSAH. Methods: The perfusion SPET data of 55 patients with aSAH were analysed by dividing the brain into 384 regions of interest. Spatial perfusion heterogeneity was assessed by calculating the relative dispersions (RD, coefficient of variation) from the SPETs performed before treatment (RD1) and 1 week after early surgical or endovascular treatment of the ruptured aneurysm (RD2). Both RDs were compared to the clinical outcome (Glasgow Outcome Scale, GOS), neuropsychological test scores and late ischaemic findings in MRI 1 year after SAH. Results: High RD2 (OR 1.96; 95% CI 1.18–3.26; p = 0.009) and poor clinical condition (Hunt and Hess grade) on admission (OR 6.60; 95% CI 1.78–24.52; p = 0.005) proved to be independent predictors of poor or moderate clinical outcome (GOS 1–4). RD2 was higher in patients with ischaemic findings in 12-month MRI than in those without ischaemic findings (p = 0.008). RD2 also correlated with neuropsychological outcome 1 year after aSAH. Conclusions: Perfusion heterogeneity is an independent predictor of the clinical outcome of aSAH and may thus be a valuable measure in the assessment of the disease.
On certifying mobile code for secure applications

Summary form only given. The security issues in mobile code arise from the fact that someone else's program is running on your machine often without your knowledge and approval, often without controls on its privileges, and often without knowledge for how trustworthy that program is. Several different approaches have emerged for providing some assurance against malicious behavior. Javasoft implemented a "sandbox" for constraining the privileges of applets executing within a browser. Microsoft has implemented a trust-based approach called Authenticode which comes in the form of a certificate attached to any mobile piece of software. The approach espoused by this author is to combine the best of both solutions. The proposed solution involves distributing certificates with mobile code that verify not only the authenticity of the organization or individual that produced the code, but also the secure behavior of that code. Certification would be based on a process that involves testing the program for security-related defects (such as buffer overflow flaws) and verifying that the program is free from malicious code. The former activity can benefit from software reliability engineering (SRE), while the latter cannot. While SRE can be useful for producing reliable, if not correct, code, it does not address malicious intentions of either developers or hackers. To this end, software produced from an SRE process or otherwise must be certified as being free from security-related defects and malicious behavior.
Late-onset Tay–Sachs disease presenting as a childhood stutter

Late-onset Tay–Sachs disease (LOTS) is a rare lysosomal storage disorder caused by deficient beta-hexosaminidase A (HEXA) activity. Toxicity results from the accumulation of gangliosides in the central nervous system. In juvenile-onset forms, patients present in childhood with progressive incoordination and/or developmental regression; in the “chronic” or “adult-onset” forms, patients present from childhood through early adulthood with weakness, ataxia, dysarthria, spasticity, dystonia, tremor or psychosis. While stutter is reported accompanying other symptoms of LOTS,1 it is not reported as the sole initial manifestation. We report three patients who presented in childhood with developmental stutter, years before developing other neurological manifestations. Patient 1: This 6-year-old girl, born to non-consanguineous parents of Ashkenazi Jewish and non-Jewish European background, was the product of an uncomplicated pregnancy and delivery. She spoke her first words at 10 months, sat independently and crawled at 7 months, and walked independently at 12.5 months. She developed a marked stutter at 3 years, fine motor delays at 4 years, and subsequent deterioration of gross and fine motor skills, social regression, cognitive decline and reduced speech output. Neurological exam at age 6 showed poor attention, difficulty following one-step commands, sparse and dysarthric speech, tongue weakness, limb rigidity …
Clinical referral patterns and cognitive profile in mild cognitive impairment

Background There is current interest in exploring the different subtypes of mild cognitive impairment (MCI), in terms of both their epidemiology and their cognitive profile. Aims To examine the frequency of MCI subtypes presenting to a memory clinic and to document detailed neuropsychological profiles of patients with the amnestic subtype. Method Consecutive tertiary referrals (n = 187) were psychiatrically evaluated; 45 patients met criteria for amnestic mild cognitive impairment (aMCI). A subgroup of 33 patients with aMCI as well as 21 healthy controls took part in a thorough neuropsychological examination. Results Of the patients who were examined in greater neuropsychological detail, ten had pure aMCI (none with visual memory impairment only). Fifteen met criteria for non-amnestic MCI. Fifteen had normal neuropsychological profiles. Using more than one test increased sensitivity to detect episodic memory impairment. Conclusions Amnestic MCI is an important diagnosis in secondary and tertiary memory clinics. There is scope to improve the efficacy and sensitivity of the clinical assessment of this impairment.
Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis

A wide spectrum of pathological conditions may result from the interaction of Aspergillus fumigatus and the immune system of its human host. Allergic bronchopulmonary aspergillosis is one of the most severe A. fumigatus‐related diseases due to possible evolution toward pleuropulmonary fibrosis and respiratory failure. Allergic bronchopulmonary aspergillosis occurs almost exclusively in cystic fibrosis or asthmatic patients. An estimated 8%‐10% of patients with cystic fibrosis experience this condition. The diagnosis of allergic bronchopulmonary aspergillosis relies on criteria first established in 1977. Progress in the understanding of host‐pathogen interactions in A. fumigatus and patients with cystic fibrosis and the ongoing validation of novel laboratory tools concur to update and improve the diagnosis of allergic bronchopulmonary aspergillosis.
Utilisation behaviour in frontotemporal dementia

Objective To study the occurrence of utilisation behaviour (UB) in patients with frontotemporal dementia (FTD). Materials and methods Twenty patients who fulfilled all core Consensus statement criteria for FTD were examined by a neurologist experienced in dementia and by a clinical neuropsychologist. All patients had imaging evidence of predominantly frontal or frontotemporal involvement. Behavioural data were obtained from care givers using a semistructured questionnaire. Questions related to UB were asked in detail. Further assessment for UB was done during the interview with the patient using common objects. Only frank and coherent UB was considered for the study. For comparison, 34 patients with probable Alzheimer's disease diagnosed by the NINCDS-ADRDA criteria were also similarly studied. Results 80 per cent of our patients with FTD but none with probable Alzheimer's disease exhibited UB. Fourteen out of the 16 patients with FTD who exhibited UB were less than 70 years old. Among patients with UB, 88% exhibited a wide range of ‘incidental’ UB. Objects of daily use tended to trigger UB most commonly. Utilisation behaviour tended to correspond to premorbid habits in at least 75% of our patients. Conclusion Utilisation behaviour may be more common in FTD patients than is currently recognised. The presence of UB should be queried in every patient suspected to be suffering from FTD. A comprehensive questionnaire for UB such as that used here could be useful.
Association of breast milk fatty acids with allergic disease outcomes—A systematic review

Dietary polyunsaturated fatty acids (PUFAs) have immunoregulatory properties. Breast milk is rich in PUFA, and it has been hypothesized that these PUFAs may be important in the aetiology of allergic diseases. Despite a growing body of evidence, the associations between breast milk PUFA and allergic disease have not previously been systematically reviewed.
Specific immunotherapy in local allergic rhinitis: A randomized, double‐blind placebo‐controlled trial with Phleum pratense subcutaneous allergen immunotherapy

Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl‐SCIT) in LAR.
Physical activity and common mental disorders

Background Previous studies have suggested that physical activity may have antidepressant and/or anti-anxiety effects. Aims To examine the bidirectional relationship between physical activity and common mental disorders and establish the importance of context, type and intensity of activity undertaken. Method A clinical examination of 40 401 residents of Norway was undertaken. Participants answered questions relating to the frequency and intensity of both leisure-time and workplace activity. Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS). Biological and social data were also collected. Results There was an inverse relationship between the amount of leisure-time physical activity and case-level symptoms of depression. This cross-sectional association was only present with leisure-time (as opposed to workplace) activity and was not dependent on the intensity of activities undertaken. Higher levels of social support and social engagement were important in explaining the relationship between leisure activity and depression. Biological changes such as alterations to parasympathetic vagal tone (resting pulse) and changes to metabolic markers had a less important role. Conclusions Individuals who engage in regular leisure-time activity of any intensity are less likely to have symptoms of depression. The context and social benefits of exercise are important in explaining this relationship.
Long-term outcome of thalamic deep brain stimulation in two patients with Tourette syndrome

Objective Thalamic deep brain stimulation for intractable Tourette Syndrome was introduced in 1999 by Vandewalle et al. In this follow-up study, the authors report on the long-term (6 and 10 years) outcome in terms of tic reduction, cognition, mood and side effects of medial thalamic deep brain stimulation in two previously described Tourette patients. Methods The authors compared the outcome of two patients at 6 and 10 years after surgery with their preoperative status and after 8 months and 5 years of treatment, respectively. Standardised video recordings were scored by three independent investigators. Both patients underwent (neuro)psychological assessment at all time points of follow-up. Results Tic improvement observed at 5 years in patient 1 (90.1%) was maintained at 10 years (92.6%). In patient 2, the tic improvement at 8 months (82%) was slightly decreased at 6 years (78%). During follow-up, case 1 revealed no changes in cognition, but case 2 showed a decrease in verbal fluency and learning which was in line with his subjective reports. Case 2 showed a slight decrease in depression, but overall psychopathology was still high at 6 years after surgery with an increase in anger and aggression together with difficulties in social adaptation. Besides temporary hardware-related complications, no distressing adverse effects were observed. Conclusion Bilateral thalamic stimulation may provide sustained tic benefit after at least 6 years, but to maximise overall outcome, attention is needed for postoperative psychosocial adaptation, already prior to surgery.
Common mental disorders, subthreshold symptoms and disability: longitudinal study

Summary In a representative sample of the UK population we found that common mental disorders (as a group and in ICD–10 diagnostic categories) and subthreshold psychiatric symptoms at baseline were both independently associated with new-onset functional disability and significant days lost from work at 18-month follow-up. Subthreshold symptoms contributed to almost half the aggregate burden of functional disability and over 32 million days lost from work in the year preceding the study. Leaving these symptoms unaccounted for in surveys may lead to gross underestimation of disability related to psychiatric morbidity.
Clinical assessment of human gustatory function using event related potentials

Gustatory event related potentials (ERP) were developed more than a decade ago. Although the first studies were highly promising, no clinical routine application has yet been reported. The aim of the study was to use gustatory ERP in a clinical setting and to investigate gender related differences, concentration dependency and their test–retest reliability. The question of whether investigations in patients with documented taste disorders provide meaningful results was addressed. 17 healthy volunteers participated in two sessions. Acetic acid was presented to the left or right portion of the tongue; stimuli were embedded in a constantly flowing air stream. Subjects rated the stimulus intensity using visual analogue scales. Lateralised sour thresholds were established by means of a psychophysical taste test. ERP amplitude P1 was largest at frontocentral recording sites while amplitude P2 had a parietal maximum. Women had shorter response latencies than men. Concentration related differences were found for amplitudes P2 and for latencies P1 and N1. Shorter ERP response latencies were seen for stimulation of the right compared with the left side. Test–retest reliability was highest for the higher stimulus concentration, and highest coefficients of correlation were found for latencies of ERP peaks P1 and N1. Preliminary investigations in a patient with hemiageusia indicated the usefulness of gustatory ERP in the diagnostic process, especially with regard to medicolegal cases. In conclusion, the present work shows that gustatory ERP provide a relatively unbiased, reliable and easy approach to objective assessment of human taste function.