Miracle-dz/UniFAR-FTUs huggingface dataset:
Can improved diagnostics reduce mortality from Tuberculous meningitis? Findings from a 6.5-year cohort in Uganda

Background: Tuberculous meningitis (TBM) is the second most common cause of meningitis in sub-Saharan Africa and is notoriously difficult to diagnose. We describe the impact of improved TBM diagnostics over 6.5 years at two Ugandan referral hospitals. Methods: Cohort one received cerebrospinal fluid (CSF) smear microscopy only (2010-2013). Cohort two received smear microscopy and Xpert MTB/Rif (Xpert) on 1ml unprocessed CSF at physician discretion (2011-2013). Cohort three received smear microscopy, routine liquid-media culture and Xpert on large volume centrifuged CSF (2013-2017) for all meningitis suspects with a negative CSF cryptococcal antigen. We compared rates of microbiologically confirmed TBM and hospital outcomes over time. Results: 1672 HIV-infected adults presenting with suspected meningitis underwent lumbar puncture, of which 33% (558/1672) had negative CSF cryptococcal antigen and 12% (195/1672) were treated for TB meningitis. Over the study period, microbiological confirmation of TBM increased from 3% to 41% (P<0.01) and there was a decline in in-hospital mortality from 57% to 41% (P=0.27) amongst those with a known outcome. Adjusting for definite TBM diagnosis and antiretroviral therapy use, and using imputed data, assuming 50% of those with an unknown outcome died, the odds of dying were nearly twice as high in cohort one (adjusted odds ratio 1.7, 95% CI 0.7 to 4.4) compared to cohort three. Sensitivity of Xpert was 63% (38/60) and culture was 65% (39/60) against a composite reference standard. Conclusions: As TBM diagnostics have improved, microbiologically-confirmed TBM diagnoses have increased and in-hospital mortality has declined. Yet, mortality due to TB meningitis remains unacceptably high and further measures are needed to improve outcomes from TBM in Uganda.
IQ Domain-Containing GTPase-Activating Protein 1 Regulates Cytoskeletal Reorganization and Facilitates NKG2D-Mediated Mechanistic Target of Rapamycin Complex 1 Activation and Cytokine Gene Translation in Natural Killer Cells

Natural killer (NK) cells are innate lymphocytes that play essential roles in mediating antitumor immunity. NK cells respond to various inflammatory stimuli including cytokines and stress-induced cellular ligands which activate germline-encoded activation receptors (NKRs), such as NKG2D. The signaling molecules activated downstream of NKRs are well defined; however, the mechanisms that regulate these pathways are not fully understood. IQ domain-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein. It regulates diverse cellular signaling programs in various physiological contexts, including immune cell activation and function. Therefore, we sought to investigate the role of IQGAP1 in NK cells. Development and maturation of NK cells from mice lacking IQGAP1 (Iqgap1−/−) were mostly intact; however, the absolute number of splenic NK cells was significantly reduced. Phenotypic and functional characterization revealed a significant reduction in the egression of NK cells from the bone marrow of Iqagp1−/− mice altering their peripheral homeostasis. Lack of IQGAP1 resulted in reduced NK cell motility and their ability to mediate antitumor immunity in vivo. Activation of Iqgap1−/− NK cells via NKRs, including NKG2D, resulted in significantly reduced levels of inflammatory cytokines compared with wild-type (WT). This reduction in Iqgap1−/− NK cells is neither due to an impaired membrane proximal signaling nor a defect in gene transcription. The levels of Ifng transcripts were comparable between WT and Iqgap1−/−, suggesting that IQGAP1-dependent regulation of cytokine production is regulated by a post-transcriptional mechanism. To this end, Iqgap1−/− NK cells failed to fully induce S6 phosphorylation and showed significantly reduced protein translation following NKG2D-mediated activation, revealing a previously undefined regulatory function of IQGAP1 via the mechanistic target of rapamycin complex 1. Together, these results implicate IQGAP1 as an essential scaffold for NK cell homeostasis and function and provide novel mechanistic insights to the post-transcriptional regulation of inflammatory cytokine production.
Tight Regret Bounds for Bayesian Optimization in One Dimension

We consider the problem of Bayesian optimization (BO) in one dimension, under a Gaussian process prior and Gaussian sampling noise. We provide a theoretical analysis showing that, under fairly mild technical assumptions on the kernel, the best possible cumulative regret up to time $T$ behaves as $\Omega(\sqrt{T})$ and $O(\sqrt{T\log T})$. This gives a tight characterization up to a $\sqrt{\log T}$ factor, and includes the first non-trivial lower bound for noisy BO. Our assumptions are satisfied, for example, by the squared exponential and Mat\'ern-$\nu$ kernels, with the latter requiring $\nu > 2$. Our results certify the near-optimality of existing bounds (Srinivas {\em et al.}, 2009) for the SE kernel, while proving them to be strictly suboptimal for the Mat\'ern kernel with $\nu > 2$.
Study of Extrinsic Apoptotic Pathway in Oral Pemphigus Vulgaris Using TNFR 1 and FasL Immunohistochemical Markers and TUNEL Technique

Statement of the Problem: Pemphigus vulgaris is characterized by intraepithelial vesicles, but pathogenesis of vesicle formation in this disease has not been substantiated yet. Purpose: The present study investigate extrinsic apoptotic pathway in oral pemphigus vulgaris using TUNEL and important immunohistochemical markers of extrinsic pathway, TNFR1 and FasL. Materials and Method: In the present cross sectional study, 25 oral pemphigus vulgaris samples and 6 normal oral mucosa were analyzed for the presence of apoptosis by TUNEL and the staining of TNFR1 and FasL in basal and parabasal layers around vesicle, vesicle floor, vesicle roof and acantholytic cells. The staining expression and intensity were measured and the obtained data were analyzed by Wilcoxon and Mann-Whitney tests. Results: There was no or faint staining of TUNEL, FasL and TNFR1 in normal oral mucosa. In addition, there was no significant difference between the staining of TUNEL technique in different layers. The staining of TNFR1 marker was very high in all regions. FasL marker was not positive in the basal and parabasal layers around vesicle in 92% of samples but showed a varied and different staining in vesicle region. There was a significant difference between the each two markers in all layers (p <0.001). Conclusion: Apoptosis is probably is a preceding phenomenon to acantholysis in pemphigus vulgaris. It appears that the apoptosis occurs mostly by extrinsic pathway using proapototic mediators TNFR1 and FasL.
Force Control Characteristics for Generation and Relaxation in the Lower Limb

Summary We investigated the characteristics for force generation and relaxation using graded isometric contractions of the knee extensors. Participants performed the following tasks as quickly and accurately as possible. For the force generation task, force was increased from 0% to 20%, 40% and 60% of the maximal voluntary force (MVF). For the force relaxation task, force was decreased from 60% to 40%, 20% and 0%. The following parameters of the recorded force were calculated: error, time, and rate of force development. The error was consistently greater for force relaxation than generation. Reaction and adjustment times were independent of the tasks. The control strategy was markedly different for force relaxation and generation, this tendency was particularly evident for the lower limb compared to the upper limb.
From Scrum to Agile: a journey to tackle the challenges of distributed development in an Agile team

Background: Agile and distributed software development are two trends that continue to increase rapidly in today's software industry. Even though the benefits achievable by combining them are potentially many, the intrinsic challenges of such marriage often lead to severe complications that can jeopardize the successful completion of software projects. Method: To investigate empirically how these two trends can coexist without compromising on the agile core values and principles, we conducted an exploratory holistic case study. Focusing on the development team of a Danish SME having both distributed offices as well as teleworking arrangements, we showcase (the evolution of) their practices. Results: The case is an example of the effective application of the agile reflective culture that allowed the company to evolve to a level in which the collocation restrictions of agile software development are overcome by a continuously evolving software process geared towards reducing waste to achieve speed and simplicity. Conclusions: Even though results need to be considered carefully due to the single nature of the reported case, we highlight five elements that have been fundamental in such journey: agile servant-leader, agile team, trust, virtual work environment, inspect & adapt, and reduce waste. Extensive information is provided to frame the context and to allow meaningful future comparisons.
Bovine esophageal and glossal ulceration associated with Pseudomonas aeruginosa and Fusobacterium spp. in a 10-month-old Holstein heifer

An underweight 10-month-old Holstein heifer presented with anorexia and ananastasia and was euthanized. Postmortem examination revealed extensive ulceration in the esophagus, tongue, and omasum. Histopathological examination revealed severe necrotic esophagitis, glossitis, and omasitis. Many Gram-negative bacilli were detected throughout the necrotic area in the digestive tract; these were identified as Pseudomonas aeruginosa on the basis of isolation tests, molecular examinations, and immunohistochemistry. Gram-negative long filamentous organisms in the superficial layers of the necrotic lesions reacted positively with antibodies against Fusobacterium necrophorum subsp. necrophorum. Thus, the necrotic lesions were confirmed to be associated with P. aeruginosa and Fusobacterium spp. This is the first detection of P. aeruginosa in bovine esophageal and glossal ulcers associated with Fusobacterium spp.
EFFECTS OF STRENGTH-TRAINING TRIALS FOR CHILDREN AND ADOLESCENTS WITH SPASTIC CEREBRAL PALSY : A SYSTEMATIC

Objective To evaluate the effects of strength-training on lower limb muscles and motor activity among children and adolescents with spastic Cerebral Palsy. Methods A comprehensive search of full text published studies in English was performed. Electronic databases were searched with no limit for year of publication. Terms used included: exercise, children, youth, disability, treatment, strength training, spastic cerebral palsy, muscle strength, training program, therapeutic exercise, gait training, and physical function. Reference lists of retrieved articles were also examined to identify additional studies. To be included, studies had to be: randomised controlled trials evaluating strength training outcomes on children and adolescents with spastic CP. Those with intellectual disability were excluded. Evaluation for quality: Trials were rated for methodological quality using the PEDro scale independently by the 2 researchers. Results Of 4 selected trials, 1 an abstract was excluded, 3 full articles were included. Trials methodological quality ranged from 6 to 8 on PEDro scale. Two studies reported significant muscle strength changes following strength training, with effect sizes ranging from d equal to 1.17 to 1.78 and another reported improved gait and perceived body image. Conclusion Trials demonstrate that strength-training improves strength of targeted muscle and motor functioning. More rigorous trials on larger samples should evaluate the impact of specificity in strength-training and cost-effectiveness of programs.
The energetic cost of parasitism in a wild population

Parasites have profound fitness effects on their hosts, yet these are often sub-lethal, making them difficult to understand and quantify. A principal sub-lethal mechanism that reduces fitness is parasite-induced increase in energetic costs of specific behaviours, potentially resulting in changes to time and energy budgets. However, quantifying the influence of parasites on these costs has not been undertaken in free-living animals. We used accelerometers to estimate energy expenditure on flying, diving and resting, in relation to a natural gradient of endo-parasite loads in a wild population of European shags Phalacrocorax aristotelis. We found that flight costs were 10% higher in adult females with higher parasite loads and these individuals spent 44% less time flying than females with lower parasite loads. There was no evidence for an effect of parasite load on daily energy expenditure, suggesting the existence of an energy ceiling, with the increase in cost of flight compensated for by a reduction in flight duration. These behaviour specific costs of parasitism will have knock-on effects on reproductive success, if constraints on foraging behaviour detrimentally affect provisioning of young. The findings emphasize the importance of natural parasite loads in shaping the ecology and life-history of their hosts, which can have significant population level consequences.
A reusable e-learning tool for paediatric physio- therapy education: a preliminary report

Objectives: The aim of this study was to devise, implement and evaluate a paediatric contextualised reusable computeraided learning resource. Methods: This study is an evaluation of a curriculum development in which all 21 third year undergraduate physiotherapists at the University of Nottingham participated. Data collection was via an online survey tool comprising open and closed questions using Likert scaling (1-5). Closed questions were aimed at ease of use, task setting and development of clinical reasoning skills. Two free text opportunities were provided. Results: The five point Likert ranking most frequently selected was agree or strongly agree. The first prompt for “specific issues with practical use” provided a main theme of poor experience using podcast elements; whilst the second prompt “anything else . you would like to add” provided a main theme of appreciation for the realism and problem solving skills stimulation. Conclusions: The computer-aided learning resource was found to be an appropriate teaching and learning approach. Students perceived that it facilitated their practice of clinical
Subcritical Water-Carbon Dioxide Pretreatment of Oil Palm Mesocarp Fiber for Xylooligosaccharide and Glucose Production

The present work aimed to investigate the pretreatment of oil palm mesocarp fiber (OPMF) in subcritical H2O-CO2 at a temperature range from 150–200 °C and 20–180 min with CO2 pressure from 3–5 MPa. The pretreated solids and liquids from this process were separated by filtration and characterized. Xylooligosaccharides (XOs), sugar monomers, acids, furans and phenols in the pretreated liquids were analyzed by using HPLC. XOs with a degree of polymerization X2–X4 comprising xylobiose, xylotriose, xylotetraose were analyzed by using HPAEC-PAD. Enzymatic hydrolysis was performed on cellulose-rich pretreated solids to observe xylose and glucose production. An optimal condition for XOs production was achieved at 180 °C, 60 min, 3 MPa and the highest XOs obtained was 81.60 mg/g which corresponded to 36.59% of XOs yield from total xylan of OPMF. The highest xylose and glucose yields obtained from pretreated solids were 29.96% and 84.65%, respectively at cellulase loading of 10 FPU/g-substrate.
Current activity guidelines for CABG patients are too restrictive: comparison of the forces exerted on the median sternotomy during a cough vs. lifting activities combined with valsalva maneuver.

BACKGROUND The current activity guidelines for coronary artery bypass graft surgery (CABG) patients are overly restrictive, hindering recovery. As the sternotomy repair must withstand repeated coughs during convalescence, this provides a benchmark for the force tending to separate the incision that can be tolerated. METHODS Nine volunteers performed 5 weightlifting activities (lifting 5 lbs [2.3 kg], lifting a 25-lb simulated grandchild [11.4 kg], lifting a 30-lb suitcase [13.6 kg], lifting two 20-lb weights [18.2 kg], and lifting a gallon of milk to a counter [3.7 kg]), plus coughing. Valsalva forces were detected using a mouthpiece configured with an Ashcroft Inc. expiratory pressure gauge (model N10-120CMW). Three measurements were taken for each activity to calculate the mean internal forces while external forces on the sternotomy were calculated using vector algebra. Total force exerted on the sternotomy by the cough was compared to the total force exerted by each of the 5 activities using paired T-tests. RESULTS The cough exerted a significantly greater force across the median sternotomy (mean 27.5 kg-mass) than any of the five weightlifting activities ( P < 0.05). The greatest difference was observed was for lifting a 5-lb weight (22.5 kg-mass), and the smallest for lifting two 20-lb weights (4.4 kg-mass). CONCLUSION Lifting even 40 lbs puts less force on the median sternotomy incision than a cough. The strength of the repair is significantly greater than is implied by the recommendation to "not lift more than 5 lbs".
Apolipoprotein E region molecular signatures of Alzheimer's disease

Although the APOE region is the strongest genetic risk factor for Alzheimer's diseases (ADs), its pathogenic role remains poorly understood. Elucidating genetic predisposition to ADs, a subset of age‐related diseases characteristic for postreproductive period, is hampered by the undefined role of evolution in establishing molecular mechanisms of such diseases. This uncertainty is inevitable source of natural‐selection–free genetic heterogeneity in predisposition to ADs. We performed first large‐scale analysis of linkage disequilibrium (LD) structures characterized by 30 polymorphisms from five genes in the APOE 19q13.3 region (BCAM, NECTIN2, TOMM40, APOE, and APOC1) in 2,673 AD‐affected and 16,246 unaffected individuals from five cohorts. Consistent with the undefined role of evolution in age‐related diseases, we found that these structures, being highly heterogeneous, are significantly different in subjects with and without ADs. The pattern of the difference represents molecular signature of AD comprised of single nucleotide polymorphisms (SNPs) from all five genes in the APOE region. Significant differences in LD in subjects with and without ADs indicate SNPs from different genes likely involved in AD pathogenesis. Significant and highly heterogeneous molecular signatures of ADs provide unprecedented insight into complex polygenetic predisposition to ADs in the APOE region. These findings are more consistent with a complex haplotype than with a single genetic variant origin of ADs in this region.
Corruption in organizations: Ethical climate and individual motives

The aim of this research was to examine how organizational and individual factors, in concert, shape corruption. We examined whether the ethical climate of organizations is related to corruption, and if so, whether it affects corruption through individual motives for corruption. A large-scale questionnaire study was conducted among public officials ( n = 234) and business employees ( n = 289) who were in a position to make corrupt decisions. The findings suggest that public and private sector employees who perceive their organizational climate as more egoistic and less ethical are more prone to corruption. This relationship was fully mediated by individual motives, specifically by personal and social norms on corruption. These results indicate that employees who perceive their organization’s ethical climate as more egoistic and less ethical experience weaker personal and social norms to refrain from corruption, making them more corruption-prone. Hence, strategies addressing the interplay between organizational factors and individual motives seem promising in curbing corruption. To effectively withhold employees from engaging in corruption, organizations could deploy measures that strengthen an organizations’ ethical climate and encourage ethical decision-making based on concern for the wellbeing of others, as well as measures increasing the strength of personal and social norms to refrain from corruption.
Cyclic Alternating Pattern in Obstructive Sleep Apnea Patients with versus without Excessive Sleepiness

Background One of the main hypotheses on the development of daytime sleepiness (ES) is increased arousal in obstructive sleep apnea (OSA). Cyclic alternating pattern (CAP) is considered to be the main expression of sleep microstructure rather than arousal. Therefore, we aimed to investigate whether there is any difference between OSA patients with versus without ES in terms of the parameters of sleep macro- and microstructure and which variables are associated with Epworth Sleepiness Scale (ESS) score. Methods Thirty-eight male patients with moderate to severe OSA were divided into two subgroups by having been used to ESS as ES or non-ES. Results There was no difference between two groups in clinical characteristics and macrostructure parameters of sleep. However, ES group had significantly higher CAP rate, CAP duration, number of CAP cycles, and duration and rate of the subtypes A2 (p = 0.033, 0.019, 0.013, and 0.019, respectively) and lower mean phase B duration (p = 0.028) compared with non-ES group. In correlation analysis, ESS score was not correlated with any CAP measure. Conclusions OSA patients with ES have increased CAP measures rather than those without ES.
HotSpot Wizard 3.0: web server for automated design of mutations and smart libraries based on sequence input information

Abstract HotSpot Wizard is a web server used for the automated identification of hotspots in semi-rational protein design to give improved protein stability, catalytic activity, substrate specificity and enantioselectivity. Since there are three orders of magnitude fewer protein structures than sequences in bioinformatic databases, the major limitation to the usability of previous versions was the requirement for the protein structure to be a compulsory input for the calculation. HotSpot Wizard 3.0 now accepts the protein sequence as input data. The protein structure for the query sequence is obtained either from eight repositories of homology models or is modeled using Modeller and I-Tasser. The quality of the models is then evaluated using three quality assessment tools—WHAT_CHECK, PROCHECK and MolProbity. During follow-up analyses, the system automatically warns the users whenever they attempt to redesign poorly predicted parts of their homology models. The second main limitation of HotSpot Wizard’s predictions is that it identifies suitable positions for mutagenesis, but does not provide any reliable advice on particular substitutions. A new module for the estimation of thermodynamic stabilities using the Rosetta and FoldX suites has been introduced which prevents destabilizing mutations among pre-selected variants entering experimental testing. HotSpot Wizard is freely available at http://loschmidt.chemi. muni.cz/hotspotwizard.