Miracle-dz/UniFAR-FTUs huggingface dataset:
Laboratory Evaluation of Neonatal Sepsis

Bacterial infections can be a devastating complication in the newborn and continue to be a significant cause of mortality and long-term morbidity of hospitalized newborns and premature infants. The diagnosis of neonatal sepsis is difficult to establish and remains a challenge for neonatal health care providers. Early signs and symptoms of neonatal sepsis are often nonspecific and easily confused with conditions that are expected in this population. Neonatal care providers have evaluated numerous tests searching for one that would be helpful in the diagnosis of neonatal sepsis, one that quickly confirms the diagnosis, and one that conclusively rules it out. This article examines the tests in current use and some of the more recent diagnostic markers used alone or in combination to improve sensitivity and specificity for early detection of sepsis.
The B-type cyclin CYB-1 maintains the proper position and number of centrosomes during spermatogenesis in Caenorhabditis elegans

ABSTRACT Depletion of cyb-1, a major B-type cyclin expressed during Caenorhabditis elegans spermatogenesis, causes a meiotic division arrest in diakinesis-stage spermatocytes with multiple and mispositioned centrosomes. Association of the two nuclear membrane proteins SUN-1 and ZYG-12 is essential for centrosome–nuclear envelope attachment. We found that depletion of sun-1 causes centrosome defects similar to those caused by cyb-1 depletion in diakinesis-stage spermatocytes. In addition, Ser8 and Ser43 residues in SUN-1 are dephosphorylated in cyb-1-depleted diakinesis-stage spermatocytes. Nevertheless, dephosphorylation of these residues was not sufficient to reproduce the cyb-1-related centrosome defects. We then found that the ZYG-12::GFP signal in the nuclear envelope was significantly reduced in the cyb-1-depleted diakinesis-stage spermatocytes. However, only mispositioned but not multiplied centrosomes were observed in zyg-12 mutant diakinesis-stage spermatocytes, suggesting that zyg-12 is not involved in the centrosome duplication at this stage. Our results suggest that CYB-1 functions to maintain proper positioning of centrosomes during spermatogenesis by regulating phosphorylation of SUN-1, which is possibly crucial for the association between SUN-1 and ZYG-12. This phosphorylation of SUN-1 may also regulate centrosome duplication independently of ZYG-12. Highlighted Article: CYB-1 is the major B-type cyclin expressed in the proximal region of Caenorhabditis elegans male gonads. The CYB-1–CDK-1 complex maintains proper centrosome position and number during spermatogenesis, possibly by regulating phosphorylation of SUN-1.
Towards a social model of childbirth: part two

Modern childbirth has been appropriated by the biomedical model, such that clinical parameters, not social process, dominate its every phase. An exploration of a social model will assist in reconnecting and integrating childbirth phases with its traditionally strong sociocultural base. This requires a shift in values and an orientation to wellbeing, rather than pathology.
Protein localization screening in vivo reveals novel regulators of multiciliated cell development and function

ABSTRACT Multiciliated cells (MCCs) drive fluid flow in diverse tubular organs and are essential for the development and homeostasis of the vertebrate central nervous system, airway and reproductive tracts. These cells are characterized by dozens or hundreds of motile cilia that beat in a coordinated and polarized manner. In recent years, genomic studies have not only elucidated the transcriptional hierarchy for MCC specification but also identified myriad new proteins that govern MCC ciliogenesis, cilia beating and cilia polarization. Interestingly, this burst of genomic data has also highlighted that proteins with no obvious role in cilia do, in fact, have important ciliary functions. Understanding the function of proteins with little prior history of study presents a special challenge, especially when faced with large numbers of such proteins. Here, we define the subcellular localization in MCCs of ∼200 proteins not previously implicated in cilia biology. Functional analyses arising from the screen provide novel links between actin cytoskeleton and MCC ciliogenesis. Summary: An unbiased screen reveals the localization of ∼200 proteins in multiciliated cell. Functional analyses arising from the screen provide novel links between actin cytoskeleton and MCC ciliogenesis.
Weibel−Palade bodies at a glance

ABSTRACT The vascular environment can rapidly alter, and the speed with which responses to both physiological and pathological changes are required necessitates the existence of a highly responsive system. The endothelium can quickly deliver bioactive molecules by regulated exocytosis of its secretory granules, the Weibel−Palade bodies (WPBs). WPBs include proteins that initiate both haemostasis and inflammation, as well those that modulate blood pressure and angiogenesis. WPB formation is driven by von Willebrand factor, their most abundant protein, which controls both shape and size of WPBs. WPB are generated in a range of sizes, with the largest granules over ten times the size of the smallest. In this Cell Science at a Glance and the accompanying poster, we discuss the emerging mechanisms by which WPB size is controlled and how this affects the ability of this organelle to modulate haemostasis. We will also outline the different modes of exocytosis and their polarity that are currently being explored, and illustrate that these large secretory organelles provide a model for how elements of secretory granule biogenesis and exocytosis cooperate to support a complex and diverse set of functions. Summary: This Cell Science at a Glance discusses the emerging mechanisms of Weibel–Palade body size control and their effect on modulating haemostasis.
Complexes of plexin-A4 and plexin-D1 convey semaphorin-3C signals to induce cytoskeletal collapse in the absence of neuropilins

ABSTRACT Class-3 semaphorin guidance factors bind to receptor complexes containing neuropilin and plexin receptors. A semaphorin may bind to several receptor complexes containing somewhat different constituents, resulting in diverse effects on cell migration. U87MG glioblastoma cells express both neuropilins and the four class-A plexins. Here, we show that these cells respond to Sema3A or Sema3B by cytoskeletal collapse and cell contraction but fail to contract in response to Sema3C, Sema3D, Sema3G or Sema3E, even when class-A plexins are overexpressed in the cells. In contrast, expression of recombinant plexin-D1 enabled contraction in response to these semaphorins. Surprisingly, unlike Sema3D and Sema3G, Sema3C also induced the contraction and repulsion of plexin-D1-expressing U87MG cells in which both neuropilins were knocked out using CRISPR/Cas9. In the absence of neuropilins, the EC50 of Sema3C was 5.5 times higher, indicating that the neuropilins function as enhancers of plexin-D1-mediated Sema3C signaling but are not absolutely required for Sema3C signal transduction. Interestingly, in the absence of neuropilins, plexin-A4 formed complexes with plexin-D1, and was required in addition to plexin-D1 to enable Sema3C-induced signal transduction. Summary: Sema3C, previously believed to require receptors of the neuropilin family to repel migrating cells, can also repel cells following binding to a complex of plexin-A4 and plexin-D1.
Virtual trip lines for distributed privacy-preserving traffic monitoring

Automotive traffic monitoring using probe vehicles with Global Positioning System receivers promises significant improvements in cost, coverage, and accuracy. Current approaches, however, raise privacy concerns because they require participants to reveal their positions to an external traffic monitoring server. To address this challenge, we propose a system based on virtual trip lines and an associated cloaking technique. Virtual trip lines are geographic markers that indicate where vehicles should provide location updates. These markers can be placed to avoid particularly privacy sensitive locations. They also allow aggregating and cloaking several location updates based on trip line identifiers, without knowing the actual geographic locations of these trip lines. Thus they facilitate the design of a distributed architecture, where no single entity has a complete knowledge of probe identities and fine-grained location information. We have implemented the system with GPS smartphone clients and conducted a controlled experiment with 20 phone-equipped drivers circling a highway segment. Results show that even with this low number of probe vehicles, travel time estimates can be provided with less than 15% error, and applying the cloaking techniques reduces travel time estimation accuracy by less than 5% compared to a standard periodic sampling approach.
The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane

ABSTRACT Cilia-mediated signal transduction involves precise targeting and localization of selected molecules along the ciliary membrane. However, the molecular mechanism underlying these events is unclear. The Joubert syndrome protein ARL13B is a membrane-associated G-protein that localizes along the cilium and functions in protein transport and signaling. We identify tubulin as a direct interactor of ARL13B and demonstrate that the association occurs via the G-domain and independently from the GTPase activity of ARL13B. The G-domain is necessary for the interaction of ARL13B with the axoneme both in vitro and in vivo. We further show that exogenously expressed mutants lacking the tubulin-binding G-domain (ARL13B-ΔGD) or whose GTPase domain is inactivated (ARL13B-T35N) retain ciliary localization, but fail to rescue ciliogenesis defects of null Arl13bhnn mouse embryonic fibroblasts (MEFs). However, while ARL13B-ΔGD and the membrane proteins Smoothened (SMO) and Somatostatin receptor-3 (SSTR3) distribute unevenly along the cilium of Arl13bhnn MEFs, ARL13B-T35N distributes evenly along the cilium and enables the uniform distribution of SMO and SSTR3. Thus, we propose a so far unknown function of ARL13B in anchoring ciliary membrane proteins to the axoneme through the direct interaction of its G-domain with tubulin. Summary: The Joubert syndrome protein ARL13B binds tubulin to maintain uniform distribution of proteins along the ciliary membrane.
Malvolio is a copper transporter in Drosophila melanogaster

SUMMARY Divalent metal ion transporter 1 (DMT1; also known as SLC11A2) can transport several metals including Fe and Cu in mammalian systems. We set out to determine whether Malvolio (Mvl), the Drosophila melanogaster orthologue of DMT1, can also transport Cu. Overexpression of Mvl caused Cu accumulation in Drosophila S2 cultured cells and conversely dsRNAi knockdown of endogenous Mvl reduced cellular Cu levels. Cell viability under Cu limiting conditions was reduced following dsRNAi knockdown. A homozygous viable Mvl loss-of-function mutant (Mvl97f) was sensitive to excess Cu and female Mvl97f flies were also sensitive to Cu limitation. An MtnA-EYFP reporter was used as a proxy measure of Cu distribution within Mvl97f/+ larvae. Under basal conditions Cu levels were reduced in the anterior midgut and proventriculus relative to control larvae. These results demonstrate Mvl is a functional Cu transporter and that despite partial functional redundancy with the Ctr1 proteins, Cu uptake through this pathway is necessary for optimal viability at the cellular and organismal levels.
A classification and treatment protocol for low back disorders. Part 3 - Functional restoration for intervertebral disc related disorders.

AbstractBackground: It has been widely recommended that clinical trials on people with low back disorders (LBDs) should have a greater focus on subgroup specific treatment in order to increase the likelihood of clinically meaningful effects being demonstrated. Functional restoration is a treatment approach that has demonstrated some evidence of effectiveness in subacute and chronic LBDs. However, studies to date have not used a clearly defined and appropriately detailed clinical protocol or applied the treatment to homogenous pathoanatomical based subgroups.Objectives: This paper presents a detailed classification and treatment protocol for people with LBDs and clinical features thought to be indicative of non-reducible discogenic pain or disc herniation with associated radiculopathy.Discussion: A pathoanatomical interpretation of traditional functional restoration, classification principles and particular treatment components in the clinical protocol are discussed.Conclusion: The described clinical proto.
Undirected connectivity in log-space

We present a deterministic, log-space algorithm that solves st-connectivity in undirected graphs. The previous bound on the space complexity of undirected st-connectivity was log4/3(ṡ) obtained by Armoni, Ta-Shma, Wigderson and Zhou (JACM 2000). As undirected st-connectivity is complete for the class of problems solvable by symmetric, nondeterministic, log-space computations (the class SL), this algorithm implies that SL = L (where L is the class of problems solvable by deterministic log-space computations). Independent of our work (and using different techniques), Trifonov (STOC 2005) has presented an O(log n log log n)-space, deterministic algorithm for undirected st-connectivity. Our algorithm also implies a way to construct in log-space a fixed sequence of directions that guides a deterministic walk through all of the vertices of any connected graph. Specifically, we give log-space constructible universal-traversal sequences for graphs with restricted labeling and log-space constructible universal-exploration sequences for general graphs.
Readmissions of long-stay psychiatric patients to the acute services from hostels in the community

The asylum movement was developed in the 19th century to provide care and cure for people with mental disorders. In the 20th century the old vision of asylum was abandoned, but no new alternative vision of community mental health care has taken its place. A divide between acute psychiatric services and provision for the social aspects of care has been described by Murphy (1991).
Virtual Physiological Human research initiative: the future for rational HIV treatment design?

The clinical management of HIV-positive patients receiving existing drug regimens is performed largely as a clinician’s best guess, based on available viral and patient data. The development of new antiretroviral therapies for HIV is at an impasse. How can we progress beyond this? ViroLab, an example of a new ‘style’ of research project, is attempting to answer this question by stepping into the realm of prediction. A method is in development that can model and predict the efficacy of antiretroviral treatment and may enhance clinical decision support. If extended, this method can potentially target any other pathology where a ligand–substrate interaction is concerned. This type of research falls within the remit of a new initiative: the Virtual Physiological Human (VPH). The potential impact of VPH on current and future rational treatment design is discussed.
Age at Intervention for Permanent Hearing Loss and 5-Year Language Outcomes

The benefit of early age at intervention for language development of children with PCHL increases with the degree of hearing loss. OBJECTIVES: Universal newborn hearing screening has been implemented to detect permanent childhood hearing loss (PCHL) early, with the ultimate goal of improving outcomes through early treatment. However, there is disagreement between studies on the size of this benefit and in some cases whether it is significantly different from 0. There have been no studies of sufficient size in which researchers have determined reliably whether the effect varies with degree of PCHL. We aimed to explore how intervention timing influences 5-year language in children with PCHL. METHODS: Via a prospective study of 350 children, we used standard multiple regression analyses to investigate the effect of age at intervention or hearing screening on language outcomes after allowing for the effects of nonverbal IQ, degree of PCHL, sex, birth weight, maternal education, additional disabilities, and communication mode. RESULTS: The benefit of early intervention for language development increased as hearing loss increased. Children whose amplification started at age 24 months had poorer language than those whose amplification started at 3 months. The difference was larger for 70-dB HL (−11.8 score points; 95% confidence interval [95% CI]: −18.7 to −4.8) than for 50-dB HL (−6.8; 95% CI: −10.8 to −2.8). Children who received cochlear implants at 24 months had poorer language than those implanted at 6 months (−21.4; 95% CI: −33.8 to −9.0). There was no significant effect of screening on outcomes. CONCLUSIONS: Early intervention improves language outcomes, thereby lending support to streamlining clinical pathways to ensure early amplification and cochlear implantation after diagnosis.
A ONE-YEAR PRAGMATIC TRIAL OF NALTREXONE VS DISULFIRAM IN THE TREATMENT OF ALCOHOL DEPENDENCE

Aims: To compare the efficacy of naltrexone and disulfiram in preventing an alcoholic relapse in routine clinical practice in an Indian metropolis. Methods: Hundred alcohol-dependent men, for whom a family member would accompany the patient to follow-up appointments, were randomly allocated to a year of treatment with either naltrexone or disulfiram. Patients, the accompanying family member and the treating psychiatrist were aware of the nature of treatment given. Alcohol consumption, craving and adverse events were recorded weekly for the first three months, then fortnightly for the rest of the year, by the treating psychiatrist. Serum gamma-glutamyl transferase (GGT) was measured at the start and the end of the study. Results: At the end of the year, 97 patients were still in contact. Relapse, the consumption of >5 drinks (40 g of ethanol) in a 24 h period, occurred at a mean of 119 days with disulfiram and at 63 days with naltrexone (P = 0.020). Mean serum GGT, which had not differed between the two groups initially, was 117 U/l with naltrexone and 85 U/l with disulfiram (P = 0.038) at the end of the study. Eighty-six per cent of the patients remained abstinent throughout the study with disulfiram compared to 44% with naltrexone (P = 0.0009). However, patients allocated to naltrexone had significantly lower craving than those allocated to disulfiram. Conclusions: Disulfiram is superior to naltrexone in preventing a relapse among alcohol-dependent men with family support. Comparison between these treatments in other settings and in different types of alcoholics is warranted.
Continuity of Medication Management: Is Transition a Barrier?

Copyright: © 2012 Athuraliya N. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. What is continuity of care in a health care system? It could be defined as ensuring continuum of care during transition from different care settings in a health system. There is an abundance of literature to indicate that transition is a potential threat to continuum of health care. Health related issues during patient movement from one health setting to another present multiple challenges for patients, care givers and health care providers. In an era where health care is heavily dependent on pharmaceuticals, more often than not the health issues during transition health issues are related to discrepancies in medications. The most vulnerable patients to ‘care transition related health problems’ are those with chronic diseases on multiple complex drug regimes [1]. Discrepancies in medication lists of these patients are attributed to; errors in medication documentation [2-4], poor communication between health care providers [5,6] and medication non adherence by patients [7].
Epidemiology of congenital heart disease in Merseyside—1979 to 1988

Abstract All infants and children born alive with documented congenital heart disease (excluding those weighing less than 2500 g at birth with a diagnosis of patent arterial duct) within the county of Merseyside between 1979 and 1988 were identified from the combined records of the Liverpool Congenital Malformations Registry and the Cardiac Unit, Royal Liverpool Children‘s Hospital Alder Hey, Liverpool. In total, 1543 cases were disclosed from a live-birth population of 203,880 providing a prevalence rate at birth of 7.57 (95% confidence interval: 7.20–7.96) cases per 1000 livebirths. The overall crude death rate was 18.5% (95% confidence interval: 16.4–20.3). An additional 240 (15.6% [95% confidence interval: 13.8–17.5%]) cases of heart disease not identified by the registry were disclosed from the records of the cardiac unit, demonstrating the unreliability of rates published by monitoring bodies. The annual prevalence rate at birth varied from 6.3 to 9.0 per 1000 livebirths, and seemed to be associated with the impact of new imaging technology. Regional variation was marked (5.3 to 8.9 per 1000 livebirths) and unaccountable in terms of potential morphogenetic mechanism, suggesting inconsistencies in referral of cases. Exclusion of regions of poor ascertainment in the calculation of a revised figure for the prevalence rate at birth suggests that as many as 89 in every 10,000 infants born alive may have structural cardiac anomalies. In conclusion, annual and regional variation of ascertainment in registry studies remains the enemy of an accurate description of the true prevalence rate at birth for congenital heart disease.
Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

BACKGROUND: Human papillomavirus types 16 (HPV-16) and 18 (HPV-18) cause approximately 70% of cervical cancers worldwide. A phase 3 trial was conducted to evaluate a quadrivalent vaccine against HPV types 6, 11, 16, and 18 (HPV-6/11/16/18) for the prevention of high-grade cervical lesions associated with HPV-16 and HPV-18. METHODS: In this randomized, double-blind trial, we assigned 12,167 women between the ages of 15 and 26 years to receive three doses of either HPV-6/11/16/18 vaccine or placebo, administered at day 1, month 2, and month 6. The primary analysis was performed for a per-protocol susceptible population that included 5305 women in the vaccine group and 5260 in the placebo group who had no virologic evidence of infection with HPV-16 or HPV-18 through 1 month after the third dose (month 7). The primary composite end point was cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer related to HPV-16 or HPV-18. RESULTS: Subjects were followed for an average of 3 years after receiving the first dose of vaccine or placebo. Vaccine efficacy for the prevention of the primary composite end point was 98% (95.89% confidence interval [CI], 86 to 100) in the per-protocol susceptible population and 44% (95% CI, 26 to 58) in an intention-to-treat population of all women who had undergone randomization (those with or without previous infection). The estimated vaccine efficacy against all high-grade cervical lesions, regardless of causal HPV type, in this intention-to-treat population was 17% (95% CI, 1 to 31). CONCLUSIONS: In young women who had not been previously infected with HPV-16 or HPV-18, those in the vaccine group had a significantly lower occurrence of high-grade cervical intraepithelial neoplasia related to HPV-16 or HPV-18 than did those in the placebo group.