Miracle-dz/UniFAR-FTUs huggingface dataset:
Within-host mathematical modelling of the incubation period of Salmonella Typhi

Mechanistic mathematical models are often employed to understand the dynamics of infectious diseases within a population or within a host. They provide estimates that may not be otherwise available. We have developed a within-host mathematical model in order to understand how the pathophysiology of Salmonella Typhi contributes to its incubation period. The model describes the process of infection from ingestion to the onset of clinical illness using a set of ordinary differential equations. The model was parametrized using estimated values from human and mouse experimental studies and the incubation period was estimated as 9.6 days. A sensitivity analysis was also conducted to identify the parameters that most affect the derived incubation period. The migration of bacteria to the caecal lymph node was observed as a major bottle neck for infection. The sensitivity analysis indicated the growth rate of bacteria in late phase systemic infection and the net population of bacteria in the colon as parameters that most influence the incubation period. We have shown in this study how mathematical models aid in the understanding of biological processes and can be used in estimating parameters of infectious diseases.
Factors Affecting Early Antibody Secreting Cell Maturation Into Long-Lived Plasma Cells

Antibody secreting cells (ASCs) are terminally differentiated cells of the humoral immune response and must adapt morphologically, transcriptionally, and metabolically to maintain high-rates of antibody (Ab) secretion. ASCs differentiate from activated B cells in lymph nodes and transiently circulate in the blood. Most of the circulating ASCs undergo apoptosis, but a small fraction of early ASCs migrate to the bone marrow (BM) and eventually mature into long-lived plasma cells (LLPCs). LLPC survival is controlled both intrinsically and extrinsically. Their differentiation and maintenance programs are governed by many intrinsic mechanisms involving anti-apoptosis, autophagy, and metabolism. The extrinsic factors involved in LLPC generation include BM stromal cells, cytokines, and chemokines, such as APRIL, IL-6, and CXCL12. In humans, the BM CD19−CD38hiCD138+ ASC subset is the main repository of LLPCs, and our recent development of an in vitro BM mimic provides essential tools to study environmental cues that support LLPC survival and the critical molecular mechanisms of maturation from early minted blood ASCs to LLPCs. In this review, we summarize the evidence of LLPC generation and maintenance and provide novel paradigms of LLPC maturation.
Cellular regulation of skeletal muscle atrophy by microRNAs during inflammatory conditions

Die Skelettmuskulatur ist von essentieller Bedeutung fur den menschlichen Korper und ein Defizit kann zu ernstzunehmenden gesundheitlichen Schaden bzw. einer reduzierten Lebensqualitat fuhren. Ihre Plastizitat und Sensitivitat der Umwelt gegenuber ist unter gunstigen Bedingungen eine wunschenswerte Eigenschaft, macht das Gewebe aber auch gleichzeitig angreifbar in kritischen Situationen. Im Falle einer Muskelatrophie ist die Balance zwischen Synthese und Abbau von Proteinen gestort. Das fuhrt zu verringerter Muskelfasergrose und, daraus resultierend, zu einer verringerten totalen Muskelmasse. Bei kritisch kranken Patienten und vielen chronischen Erkrankungen wie Krebs, AIDS usw. sowie Immobilitat und dem physiologischen Alterungsprozess kommt es zu einem gesteigertem Verlust der Muskelkraft und –masse (Strasser et al., 2007). Interessanterweise werden Zustande des Muskelverlustes oft begleitet vom Auftreten einer akuten oder chronischen Inflammation. Zellkultur und Tierversuchsmodelle haben gezeigt, dass proinflammatorische Zytokine direkt das Insulin-like growth factor (IGF)-1 system, einen der Hauptregulatoren des Skelettmuskelwachstums, beeinflussen (Frost et al., 2003; Frost et al., 2004). Kurzlich wurde gezeigt, das miRNAs ebenfalls involviert sind im ‘Fine-Tuning’ der Expression der Transkriptionsfaktoren und Signalmediatoren wichtig fur die Muskelbiologie, eingeschlossen der Regulation der Proliferation und der Differenzierung wahrend der Myogenese (Callis et al., 2008). Das Ziel dieser Studie ist es darum festzustellen, in welchem Umfang IGF-1 system, Muskelmarker und miRNAs direkt durch die Inflammation beeinflusst werden.
Community access to mental health services : lessons and recommendations : Primary Health Care : programme areas

According to the Alma Ata Declaration, health is a fundamental human right. Post-1994, South Africa passed legislation that moved the country in the direction of Primary Health Care at the district level. This chapter reviews the challenges to community-wide access to mental heath services in South Africa. The background to mental health care in South Africa is first presented. The introduction of Primary Health Care in South Africa is discussed in relation to the Alma Ata Declaration and other international developments, such as selective Primary Health Care. The challenges regarding the integration of mental health care into the Primary Health Care system, namely poverty, the biomedical orientation of health care, staff workload and inadequate support, poor infrastructure, and limited funding and resources, are discussed, followed by an overview of the de-institutionalisation process. It is argued that integration within the framework of a biomedical model is insufficient. A holistic approach to integration, incorporating the social, economic, psychological and cultural aspects of illness, is necessary. The chapter concludes with recommendations for policy implementation, training and research.
One hundred sixty pancreaticoduodenectomies for periampullary cancers in a growing-volume setting: a single-institution and a single-surgeon's experience

Purpose Many studies have concluded that cancer patients may have better outcomes when their surgery is performed in high-volume centers, especially when the procedure is pancreaticoduodenectomy (PD). However, some studies concluded that experienced surgeons or incorporation of expertise from high-volume centers may achieve satisfactory outcomes after PD in low-volume centers. Methods I retrospectively collected and analyzed the outcomes of PD for periampullary cancers treated with curative intent in my center. Results From August 2, 2005 to December 10, 2018, 160 pancreatic resections were done with curative intent in my center. The number of operations per year was 1 in 2005 and gradually increased to 21 in 2018. Thirty-day mortality was 0, and 90-day mortality was 1 (0.6%). Morbidity was found in 65 cases (40.6%). The median follow-up period was 23.2 months and 5-year survival rates were 28.5% for pancreas head cancer, 48.2% for distal CBD cancer, and 72.6% for AOV cancer. I divided patients into 2 groups by the number of annual operations, which is more than 21 per 2 years. The 2 groups showed no differences in terms of morbidity and mortality. Conclusion A well-trained low-volume surgeon may perform PD safely at a well-equipped low-volume center.
Protecting Audit Data using Segmentation-Based Anonymization for Multi-Tenant Cloud Auditing (SEGGUARD)

With the rise of security concerns regarding cloud computing, the importance of security auditing, conducted either in-house or by a third party, has become evident more than ever. However, the input data required for auditing a multi-tenant cloud environment typically contains sensitive information, such as the topology of the underlying cloud infrastructure. Additionally, audit results intended for one tenant may unexpectedly reveal private information, such as unpatched security flaws, about other tenants. How to anonymize audit data and results in order to prevent such information leakage is a novel challenge that has received little attention. Directly applying most existing anonymization techniques to such a context would either lead to insufficient protection or render the data unsuitable for auditing. In this thesis, we propose SegGuard, a novel anonymization approach that protects the sensitive information in both the audit data and auditing results, while assuring the data utility for effective auditing. Specifically, SegGuard prevents cross-tenant information leakage through per-tenant encryption, and it prevents information leakage to auditors through an innovative way of applying property-preserving anonymization. We apply SegGuard on audit data collected from an OpenStack cloud, and evaluate its effectiveness and efficiency using both synthetic and real data. Our experimental results demonstrate that SegGuard can reduce information leakage to a negligible level (e.g., less than 1% for an adversary with 50% pre-knowledge) with a practical response time (e.g., 62 seconds to anonymize a cloud virtual infrastructure with 25,000 virtual machines).
The Obese Liver Environment Mediates Conversion of NK Cells to a Less Cytotoxic ILC1-Like Phenotype

The liver contains both NK cells and their less cytotoxic relatives, ILC1. Here, we investigate the role of NK cells and ILC1 in the obesity-associated condition, non-alcoholic fatty liver disease (NAFLD). In the livers of mice suffering from NAFLD, NK cells are less able to degranulate, express lower levels of perforin and are less able to kill cancerous target cells than those from healthy animals. This is associated with a decreased ability to kill cancer cells in vivo. On the other hand, we find that perforin-deficient mice suffer from less severe NAFLD, suggesting that this reduction in NK cell cytotoxicity may be protective in the obese liver, albeit at the cost of increased susceptibility to cancer. The decrease in cytotoxicity is associated with a shift towards a transcriptional profile characteristic of ILC1, increased expression of the ILC1-associated proteins CD200R1 and CD49a, and an altered metabolic profile mimicking that of ILC1. We show that the conversion of NK cells to this less cytotoxic phenotype is at least partially mediated by TGFβ, which is expressed at high levels in the obese liver. Finally, we show that reduced cytotoxicity is also a feature of NK cells in the livers of human NAFLD patients.
Long Non-coding RNAs as Functional and Structural Chromatin Modulators in Acute Myeloid Leukemia

Acute myeloid leukemia is a hematopoietic neoplasm of dismal prognosis that results from the accumulation of immature myeloid blasts in the bone marrow and the peripheral blood. It is strongly dependent on epigenetic regulation for disease onset, maintenance and in response to treatment. Epigenetic regulation refers to the multiple chemical modifications of DNA or DNA-associated proteins that alter chromatin structure and DNA accessibility in a heritable manner, without changing DNA sequence. Unlike sequence-specific transcription factors, epigenetic regulators do not necessarily bind DNA at consensus sequences, but still achieve reproducible target binding in a manner that is cell and maturation-type specific. A growing body of evidence indicates that epigenetic regulators rely, amongst other factors, on their interaction with untranslated RNA molecules for guidance to particular targets on DNA. Non (protein)-coding RNAs are the most abundant transcriptional products of the coding genome, and comprise several different classes of molecules with unique lengths, conformations and targets. Amongst these, long non-coding RNAs (lncRNAs) are species of 200 bp to >100 K bp in length, that recognize, and bind unique and largely uncharacterized DNA conformations. Some have been shown to bind epigenetic regulators, and thus constitute attractive candidates to mediate epigenetic target specificity. Herein, we postulate that lncRNAs are central players in the unique epigenetic programming of AML and review recent evidence in support of this view. We discuss the value of lncRNAs as putative diagnostic, prognostic and therapeutic targets in myeloid leukemias and indicate novel directions in this exciting research field.
Pleiotropic Effects of mTOR and Autophagy During Development and Aging

Autophagy as a ubiquitous catabolic process causes degradation of cytoplasmic components and is generally considered to have beneficial effects on health and lifespan. In contrast, inefficient autophagy has been linked with detrimental effects on the organism and various diseases, such as Parkinson’s disease. Previous research, however, showed that this paradigm is far from being black and white. For instance, it has been reported that increased levels of autophagy during development can be harmful, but become advantageous in the aging cell or organism, causing enhanced healthspan and even longevity. The antagonistic pleiotropy hypothesis postulates that genes, which control various traits in an organism, can be fitness-promoting in early life, but subsequently trigger aging processes later. Autophagy is controlled by the mechanistic target of rapamycin (mTOR), a key player of nutrient sensing and signaling and classic example of a pleiotropic gene. mTOR acts upstream of transcription factors such as FOXO, NRF, and TFEB, controlling protein synthesis, degradation, and cellular growth, thereby regulating fertility as well as aging. Here, we review recent findings about the pleiotropic role of autophagy during development and aging, examine the upstream factors, and contemplate specific mechanisms leading to disease, especially neurodegeneration.
The Rise of Coccidioides: Forces Against the Dust Devil Unleashed

Coccidioidomycosis (Valley fever) is a fungal disease caused by the inhalation of Coccidioides posadasii or C. immitis. This neglected disease occurs in the desert areas of the western United States, most notably in California and Arizona, where infections continue to rise. Clinically, coccidioidomycosis ranges from asymptomatic to severe pulmonary disease and can disseminate to the brain, skin, bones, and elsewhere. New estimates suggest as many as 350,000 new cases of coccidioidomycosis occur in the United States each year. Thus, there is an urgent need for the development of a vaccine and new therapeutic drugs against Coccidioides infection. In this review, we discuss the battle against Coccidioides including the development of potential vaccines, the quest for new therapeutic drugs, and our current understanding of the protective host immune response to Coccidioides infection.
Multi-Decadal Change in Reef-Scale Production and Calcification Associated With Recent Disturbances on a Lizard Island Reef Flat

Climate change is threatening the persistence of coral reef ecosystems resulting in both chronic and acute impacts which include higher frequency and severity of cyclones, warming sea surface temperatures, and ocean acidification. This study measured net ecosystem primary production (NEP) and net ecosystem calcification (NEC) on a reef flat after the most severe El Nino-driven mass bleaching event on Australia’s Great Barrier Reef (GBR) in 2016 and again in 2018 after another consecutive bleaching event in 2017. Our results indicate that reef metabolism is altered as result of both the continuing press disturbance of ocean acidification and severe pulse disturbances (cyclones and bleaching events). In 2016, NEP was within the range of values reported in past studies, however it declined in 2018. NEC over a 12-h period was lower in 2016 than 2018; but when compared with past studies there was a severe decline in daytime net calcification from 2008-2009, to 2016 followed by an increase in 2018 (but still NEC remained lower than values reported in 2008-2009). Conversely, nighttime net calcification was similar to that reported in 2009 indicating nighttime dissolution did not increase over the past decade. Overall coral cover remained stable following recent disturbances, however algal turf was the dominant benthic component on the reef flat, while calcifiers (corals and calcified algae) were minor components (< 20% of total benthic cover). This study documented changes in community function following major pulse disturbances (bleaching events and cyclones) within the context of ongoing OA at the same location over the last decade. Repeated pulse disturbances could jeopardize the persistence of the reef flat as a net calcifying entity, with the potential for cascading effects on other ecosystem services.
Influence of Pre-Treatment Bacillary Load on Treatment Outcome of Pulmonary Tuberculosis Patients Receiving DOTS Under RNTCP

Objective. To study the influence of initial bacillary load on sputum conversion rates and treatment outcome of new smear positive pulmonary tuberculosis patients. Methods. A retrospective study was done among 2938 new smear positive pulmonary tuberculosis patients, registered at the peripheral centres, covering a population of 1.6 million in Delhi, India. The patients pre-treatment sputum smears were graded as 1+, 2+ or 3+ based on three samples. Patients were given intermittent short-course chemotherapy under supervision and the treatment outcome was analysed. Results. Sputum conversion rates among patients graded as sputum 3+ and rest of the patients (combined graded sputum 1+ and 2+) at the end of two months were 62.2% and 76.8% respectively (p<0.001), and at the end of three months were 81.3% and 89.5% respectively (p<0.001). Cure rates among same group of patients were 76.6% and 85.1% respectively (p<0.001), and failure rates were 7.7% and 4.5% respectively (p<0.001). Conclusions. Under field conditions even with directly observed treatment (DOT) new smear positive patients with heavy bacillary load showed statistically significant poor sputum conversion rates at two and three months and higher failure rates as compared to patients with lesser bacillary load. To investigate possible reasons for this poor response and possible solutions further studies are needed.
The Influence of Footwear on Functional Balance in a Population of Institutionalized Elderly Women

The purpose of this study was to evaluate the influence of footwear on functional balance in a sample of 19 institutionalized elderly women. The Tinetti Balance and Mobility Assessment, a fall risk indicator, was used to evaluate functional balance in three footwear conditions: shoes, slippers, and barefoot. An ANOVA test (alpha < 0.05) was used to determine if there was a significant difference between the three footwear conditions. A significant difference was found between each footwear condition for the balance (p=.008) and summary scores (p=.004), but not for the gait score (p=. 155). Posthoc analysis revealed that the shoe condition provided significantly superior scores than the slipper (p=.005) and barefoot conditions (p=.043). Recommendations from this study include support for the standardization of the Tinetti Balance and Mobility Assessment for footwear, and recommendations that institutionalized elderly should wear shoes and avoid the use of slippers or barefoot to reduce fall risk.
INFLUENCE OF REPETITIVE MICRO-TRAUMA ON PATHOGENESIS AND PROGRESSION OF HAND AND NECK OSTEOARTHROSIS

Summary. Repetitive micro-trauma is one of the causes of osteoarthrosis. The aim of our study was to determine if repetitive micro-trauma caused by prolonged use of a keyboard or a mechanical typewriter is associated with the increase in degenerative changes in the hand and cervical joints. We studied a sample of people of over 40 years of age, who have been working on a keyboard or a mechanical typewriter for at least 10 years. A clinical and radiological evaluation of the degree of osteoarthrosis of the hands and the neck spine was done according to the Kellgren-Lawrence grade; CRP and ESR were used as laboratory markers of secondary inflammation in osteoarthrosis. We also used some demographic and epidemiological data. We did a prospective study with 30 examinees, average age 47 years (SD 4.77), average effective working hours 8.88 (SD 6.59). The average usage of the keyboard was 18.71 years (SD 6.59). We found that the clinical degree of osteoarthrosis on distal interfalangeal joints (DIP) is in correlation with age (r = 0.516, p = 0.05) and years of working (r = 0.459, p = 0.05). The radiological grade of osteoarthrosis on DIP and proximal interfalangeal joints (PIP) are associated (r = 0.835, p = 0.01). We found no significant association with effective day working hours and the clinical and radiological grade of osteoarthrosis of DIP and PIP hand joints. The radiologically determined cervical osteoarthrosis grade is significantly higher than that of DIP (p = 0.004) and PIP (p = 0.035) joints of the hands.
Abstract 14864: Posttraumatic Stress Disorder and Mortality Among U.S. Army Veterans

Background: Posttraumatic stress disorder PTSD) has been associated with increased risk of multiple medical problems. This study investigates the mortality incidence of subjects with and without PTSD. Methods: The study population consisted of 286,194 Veterans (age 63±18 years, 85.1% male). Electronic medical records were used to assess diagnoses and outcomes. Psychological health status (PTSD vs. Non-PTSD) was assessed. 637 subjects underwent coronary artery calcium (CAC) scanning. All-cause mortality was defined as hard end point. Multivariable Cox proportional hazards models were developed to predict all-cause mortality Results: The prevalence of PTSD was 10.6% (30,460). During a mean follow-up of 116±24 months, the death rate was 13.2% in the overall population. The prevalence of PTSD in patients with and without hard end point was 28.9% and 8.1%, respectively. Risk-adjusted hazard ratio (HR) of all-cause mortality was 2.41 (95%CI 2.11-2.73, p=0.0001) for PTSD as compared to Non-PTSD cohort, and event.
Sex, Age, and Handedness Modulate the Neural Correlates of Active Learning

Background Self-generation of material compared to passive learning results in mproved memory performance; this may be related to recruitment of a fronto-temporal encoding network. Using a verbal paired-associate learning fMRI task, we examined the effects of sex, age, and handedness on the neural correlates of self-generation. Methods Data from 174 healthy English-speaking participants (78M, 56 atypically handed; ages 19–76) were preprocessed using AFNI and FSL. Independent component analysis was conducted using GIFT (Group ICA fMRI Toolbox). Forty-one independent components were temporally sorted by task time series. Retaining correlations (r > 0.25) resulted in three task-positive (“generate”) and three task-negative (“read”) components. Using participants’ back-projected components, we evaluated the effects of sex, handedness, and aging on activation lateralization and localization in task-relevant networks with two-sample t-tests. Further, we examined the linear relationship between sex and neuroimaging data with multiple regression, covarying for scanner, age, and handedness. Results Task-positive components identified using ICA revealed a fronto-parietal network involved with self-generation, while task-negative components reflecting passive reading showed temporo-occipital involvement. Compared to older adults, younger adults exhibited greater task-positive involvement of the left inferior frontal gyrus and insula, whereas older adults exhibited reduced prefrontal lateralization. Greater involvement of the left angular gyrus in task-positive encoding networks among right-handed individuals suggests the reliance on left dominant semantic processing areas may be modulated by handedness. Sex effects on task-related encoding networks while controlling for age and handedness suggest increased right hemisphere recruitment among males compared to females, specifically in the paracentral lobe during self-generation and the suparmarginal gyrus during passive reading. Implications Identified neuroimaging differences suggest that sex, age, and handedness are factors in the differential recruitment of encoding network regions for both passive and active learning.