Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial and temporal variation in the community prevalence of antibiotic resistance in Bangladesh: an integrated surveillance study protocol

Introduction Increasing antibiotic resistance (ABR) in low-income and middle-income countries such as Bangladesh presents a major health threat. However, assessing the scale of the health risk is problematic in the absence of reliable data on the community prevalence of antibiotic-resistant bacteria. We describe the protocol for a small-scale integrated surveillance programme that aims to quantify the prevalence of colonisation with antibiotic-resistant bacteria and concentrations of antibiotic-resistant genes from a ‘One Health’ perspective. The holistic assessment of ABR in humans, animals and within the environment in urban and rural Bangladesh will generate comprehensive data to inform human health risk. Methods and analysis The study design focuses on three exposure-relevant sites where there is enhanced potential for transmission of ABR between humans, animals and the environment: (1) rural poultry-owning households, (2) commercial poultry farms and (3) urban live-bird markets. The comparison of ABR prevalence in human groups with high and low exposure to farming and poultry will enable us to test the hypothesis that ABR bacteria and genes from the environment and food-producing animals are potential sources of transmission to humans. Escherichia coli is used as an ABR indicator organism due to its widespread environmental presence and colonisation in both the human and animal gastrointestinal tract. Ethics and dissemination The study has been approved by the Institutional Review Board of the International Centre for Diarrhoeal Disease Research, Bangladesh, and Loughborough University Ethics Committee. Data for the project will be stored on the open access repository of the Centre for Ecology and Hydrology, Natural Environment Research Council. The results of this study will be published in peer-reviewed journals and presented at national and international conferences.
Application of ECMO in Multitrauma Patients With ARDS as Rescue Therapy

Abstract Background: Despite recent advances in critical care management, the mortality of acute respiratory distress syndrome (ARDS) remains high. The final rescue therapy for patients with severe hypoxia refractory to conventional therapy modalities is the extracorporeal gas exchange. Methods: We report the management of three polytraumatized patients with life‐threatening injuries, severe blunt thoracic trauma, and consecutive ARDS treating by extracorporeal membrane oxygenation (ECMO). Two patients suffered a car accident with severe lung contusion and parenychmal bleeding. Bronchial rupture and mediastinal emphysema was found in one of them. Another patient developed ARDS after attempted suicide with multiple fractures together with blunt abdominal and thoracic trauma. Results: All patients were placed on ECMO and could be rapidly stabilized. They were weaned from ECMO after a mean of 114 ± 27 hours of support without complications, respectively. Mean duration of ICU stay was 37 ± 23 days. Conclusions: Quick encouragement of ECMO for the temporary management of gas exchange may increase survival rates in trauma patients with ARDS.
Regular points of extremal subsets in Alexandrov spaces

We define regular points of an extremal subset in an Alexandrov space and study their basic properties. We show that a neighborhood of a regular point in an extremal subset is almost isometric to an open subset in the Euclidean space and that the set of regular points in an extremal subset has full measure and is dense. These results actually hold for strained points in an extremal subset.
Delirium induced by tigecycline treatment for Acinetobacter baumannii infection

Rationale: Tigecycline is a broad-spectrum antimicrobial agent structurally belong to tetracyclines and covers against many multidrug-resistant organisms. Arising clinical cases reporting its adverse drug reactions have emerged alongside with the increasing off label use globally. By literature review, delirium caused by tigecycline has not been reported yet. We present what we believe to be the first case of tigecycline-induced delirium. Patient concerns: A 77-year-old male patient with end-stage renal disease was hospitalized due to acute exacerbation of chronic obstructive pulmonary disease. Diagnosis: The patient developed delirium after infused with a loading dose of tigecycline for pulmonary infection. Interventions: All potential causes inducing delirium were evaluated and the symptoms improved soon after discontinuation of tigecycline. He experienced delirium once again after reusing tigecycline for the exacerbation of the pulmonary infection even without a loading dose. Tigecycline was discontinued and the symptoms quickly relieved. Outcomes: According to the Naranjo adverse drug reaction probability scale, tigecycline was the probable cause of his delirium. Lessons: Clinicians should be aware of this potential adverse effect of tigecycline. We recommend that clinicians monitor patients for signs and symptoms of delirium during treatment with tigecycline.
Development of an anatomically correct mouse phantom for dosimetry measurement in small animal radiotherapy research

Significant improvements in radiotherapy are likely to come from biological rather than technical optimization, for example increasing tumour radiosensitivity via combination with targeted therapies. Such paradigms must first be evaluated in preclinical models for efficacy, and recent advances in small animal radiotherapy research platforms allow advanced irradiation protocols, similar to those used clinically, to be carried out in orthotopic models. Dose assessment in such systems is complex however, and a lack of established tools and methodologies for traceable and accurate dosimetry is currently limiting the capabilities of such platforms and slowing the clinical uptake of new approaches. Here we report the creation of an anatomically correct phantom, fabricated from materials with tissue-equivalent electron density, into which dosimetry detectors can be incorporated for measurement as part of quality control (QC). The phantom also allows training in preclinical radiotherapy planning and cross-institution validation of dose delivery protocols for small animal radiotherapy platforms without the need to sacrifice animals, with high reproducibility. Mouse CT data was acquired and segmented into soft tissue, bone and lung. The skeleton was fabricated using 3D printing, whilst lung was created using computer numerical control (CNC) milling. Skeleton and lung were then set into a surface-rendered mould and soft tissue material added to create a whole-body phantom. Materials for fabrication were characterized for atomic composition and attenuation for x-ray energies typically found in small animal irradiators. Finally cores were CNC milled to allow intracranial incorporation of bespoke detectors (alanine pellets) for dosimetry measurement.
Effects of scleral collagen crosslinking with different carbohydrate on chemical bond and ultrastructure of rabbit sclera: Future treatment for myopia progression

Background Myopia is the most common ocular disorder and is mainly caused by axial elongation of the sclera. If the stiffness of sclera increased, it can inhibit myopia progression. The aim of this study is to compare the effect of the collagen crosslinking with different types and concentrations of carbohydrates on chemical bond and ultrastructural change of rabbit sclera. Methods Nine New Zealand white rabbits were treated with five, sequential sub-Tenon injections of 0.15 mL solutions of ribose, sucrose, and glycogen of 0.1, 0.2 and 0.4 M concentration at the right eye over 14 days. Ten weeks after the last injection, the rabbits were sacrificed and chemical bond and ultrastructural changes were compared with those of the untreated left sclera using Raman spectroscopy, atomic force microscopy (AFM), and histology. Results Raman spectroscopy of the control and cross-linked rabbit sclera tissue revealed different types of collagen interactions. Raman shift of 919 cm-1 (C-C stretching and vibration of the proline ring in collagen) was the highest in ribose, followed by sucrose and glycogen. Total energy intensity was also highest in ribose, followed by sucrose and glycogen, and showed a tendency to increase at higher concentrations. AFM revealed interlocking arrangements of collagen fibrils. The collagen fibril diameter was 105.6 ± 21.2 nm, 109.4 ± 28.8 nm, 113.1 ± 30.8 nm and 137.6 ± 25.3 nm for control group, 0.4 M glycogen, sucrose, and ribose, respectively. Histology indicated increased density of the collagen bundle and no increase in inflammatory cell recruitment compared to control at high concentrations of ribose. Conclusions Scleral crosslinking using glycation increased the scleral biomechanical rigidity and these results were particularly pronounced in ribose. Scleral crosslinking using glycation may be a promising method for inhibiting high myopia progression.
A Splice Variant of Estrogen Receptor β Missing Exon 3 Displays Altered Subnuclear Localization and Capacity for Transcriptional Activation.

There are two separate estrogen receptors (ERs), ERalpha and ERbeta. The ERbeta gene is variably spliced, and in some cases variant expression is high. Besides the full-length ERbeta (equivalent to ERbeta1), splice variants can encode proteins bearing an insert within the ligand-binding domain (beta2), a deletion of exon 3 (ERbeta1delta3) disrupting the DNA-binding domain, or both (ERbeta2delta3). Here we examine the intracellular localization and transcriptional properties of each of the ERbeta splice variants heterologously expressed in cultured cells. In accordance with ERalpha, ERbeta1 and ERbeta2 are both distributed in a reticular pattern within the nucleus after exposure to ligand. In contrast, ERbeta1delta3 and ERbeta2delta3 localize to discrete spots within the nucleus in the presence of ER agonists. In the presence of ER antagonists, the delta3 variants are distributed diffusely within the nucleus. We also show that the spots are stable nuclear structures to which the delta3 variants localize in a ligand-dependent manner. Coactivator proteins of ER colocalize with delta3 variants in the spots in the presence of agonists. The delta3 variants of ERbeta can activate luciferase reporter constructs containing an activator protein complex-1 site, but not an estrogen response element (ERE). These data suggest that without an intact DNA-binding domain, ERbeta is functionally altered, allowing localization to discrete nuclear spots and activation from activator protein-1-containing reporter genes.
High-Throughput Dissolution/Permeation Screening—A 96-Well Two-Compartment Microplate Approach

Early formulation screening can alleviate development of advanced oral drug formulations, such as amorphous solid dispersions (ASDs). Traditionally, dissolution is used to predict ASD performance. Here, a high-throughput approach is described that simultaneously screens drug dissolution and permeation employing a two-compartment 96-well plate. Freeze-drying from hydro-alcoholic solutions was used to prepare amorphous formulations. The screening approach was tested on amorphous and crystalline tadalafil formulations with and without Soluplus®. The workflow consisted of: (1) dispersion of the formulations; (2) incubation within the two-compartment plate, where a dialysis membrane separated donor (dispersed formulation) and acceptor; (3) sampling (donor and acceptor), where donor samples were centrifuged to remove non-dissolved material; and (4) quantification by UHPLC-UV. To identify optimal screening conditions, the following parameters were varied: dispersion medium (buffer/biomimetic media), acceptor medium (buffer/surfactant solutions), and incubation time (1, 3, and 6 h). Surfactants (acceptor) increased tadalafil permeation. Biomimetic medium (donor) enhanced dissolution, but not permeation, except for freeze-dried tadalafil, for which the permeated amount increased. The predictiveness was evaluated by comparing dissolution-/permeation-results with in vivo bioavailability. In general, both dissolution and permeation reflected bioavailability, whereof the latter was a better predictor. High-throughput dissolution/permeation is regarded promising for formulation screening.
Evaluation of the Parameter "Mean Impedance" for Representing Eustachian tube Functions During Pressure Increase and Decrease in Pressure Chamber Measurements.

HYPOTHESIS The hypothesis of the study is that the mean impedance (MI) during compression and decompression provides additional information of the Eustachian tube (ET) function. BACKGROUND The continuous impedance measurement in a pressure chamber can provide valuable information about the opening function of the ET. METHODS Around 55 ear-healthy volunteers were examined in a pressure chamber. These were subjected to a decompression phase and a compression phase. The pressure change was constantly 20 kPa/min. Using evaluation software, the MI could be determined for both ears in each case for the phases of compression and decompression. RESULTS In 49 participants, we could interpret the data successfully. On average, an output value (without pressure changes) of the impedance of 0.58 ±0.11 Pa on the right side and 0.43 ± 0.1 Pa on the left side were measured. During decompression, 0.098 ± 0.05 Pa (right) and 0.087 ± 0.043 Pa (left) could be determined. For compression, values of 0.086 ± 0.044 Pa on the right and 0.079 ± 0.045 Pa on the left were detected. The retest reliability was higher with an intraclass correlation coefficient for the decompression MI of 0.833 than the 0.772 compression MI. CONCLUSIONS It is possible to measure MI in healthy subjects during compression and decompression. This value represents a good average in terms of the pressure tolerance of the middle ear. In future, studies will be required to determine whether MI will be a useful parameter in differentiating normal and abnormal ET function.
An atypical case of serotonin syndrome with normal dose of selective serotonin inhibitors

Rationale: As increasing frequency of serotonergic drug use, SS (serotonin syndrome) occurred more than ever. But clinicians have not enough knowledge and experience about SS as a potentially life-threatening condition. SS is usually caused by the increased serotonin activity in the central nervous system which may due to a serotonergic agent overdose or the concomitant use of 2 or more serotonergic antidepressants. We report a case of SS due to a normal dose of selective serotonin inhibitors (SSRIs) thus to remind clinicians to pay attention to such patients and make an early diagnosis and initiation of therapy in the clinical practice. Patient concerns: We report here a 49-year-old man presented with lethargic, less communicative, and insomnia for 20 days while a diagnosis of depression was considered and he was treated with SSRIs. Diagnosis: The patient in our case fulfilled the 3 criteria existed now for diagnosing SS, including the Sternbach criteria, Radomski revised diagnostic criteria, and the Hunter serotonin toxicity criteria. Interventions: All the antidepressants were stopped and cyproheptadine with an initial dose of 12 mg a day was started along with supportive care. The patient was also admitted to emergency intensive care unit for further treatment. He was sedated and paralyzed by intravenous Midazolam and Clonazepam along with physical cooling and supportive care. Outcomes: All of the patient's symptoms abated gradually and he soon could get off the bed and be communicative. Finally, the patient made a full recovery and he was discharged from the hospital. Lessons: Our case suggests an atypical clinical course while the medicine the patient takes was not in so much dose. We assumed that there may have been some variation in metabolism of these agents, resulting in increased possibility that led to the subsequent syndrome. Thus, it is essential for clinicians to keep in mind when patients taking serotonergic agents who demonstrate acute change in their mental status. Besides, clinicians should be aware of such patients who seem to be sensitive to SSRIs, who may require a genetic testing before the initiation of SSRI therapy.
Heritability estimates for psychotic disorders: the Maudsley twin psychosis series.

BACKGROUND Previous twin studies have supported a genetic contribution to the major categories of psychotic disorders, but few of these have employed operational diagnostic criteria, and no such study has been based on a sample that included the full range of functional psychotic disorders. METHODS A total of 224 twin probands (106 monozygotic, 118 dizygotic) with a same-sex co-twin and a lifetime history of psychosis was ascertained from the service-based Maudsley Twin Register in London, England. Research Diagnostic Criteria psychotic diagnoses were made on a lifetime-ever basis. Main-lifetime diagnoses of DSM-III-R and International Statistical Classification of Diseases, 10th Revision schizophrenia were also made. Probandwise concordance rates and correlations in liability were calculated, and biometrical model fitting applied. RESULTS A substantial genetic contribution to variance in liability was confirmed for the major diagnostic categories except Research Diagnostic Criteria depressive psychosis and unspecified functional psychosis, where familial transmission was confirmed, but the relative contribution of genetic and common environmental factors was unclear. Heritability estimates for Research Diagnostic Criteria schizophrenia, schizoaffective disorder, mania, DSM-III-R schizophrenia, and International Statistical Classification of Diseases, 10th Revision schizophrenia were all between 82% and 85%. None of the estimates differed significantly from any other. CONCLUSIONS Heritability estimates for schizophrenia, schizoaffective disorder, and mania were substantial and similar. Population morbid risk estimates were inferred rather than directly measured, but the results were very similar to those from studies where morbid risks were directly estimated.
Coded Distributed Tracking

We consider the problem of tracking the state of a process that evolves over time in a distributed setting, with multiple observers each observing parts of the state, which is a fundamental information processing problem with a wide range of applications. We propose a cloud-assisted scheme where the tracking is performed over the cloud. In particular, to provide timely and accurate updates, and alleviate the straggler problem of cloud computing, we propose a coded distributed computing approach where coded observations are distributed over multiple workers. The proposed scheme is based on a coded version of the Kalman filter that operates on data encoded with an erasure correcting code, such that the state can be estimated from partial updates computed by a subset of the workers. We apply the proposed scheme to the problem of tracking multiple vehicles. We show that replication achieves significantly higher accuracy than the corresponding uncoded scheme. The use of maximum distance separable (MDS) codes further improves accuracy for larger update intervals. In both cases, the proposed scheme approaches the accuracy of an ideal centralized scheme when the update interval is large enough. Finally, we observe a trade-off between age-of- information and estimation accuracy for MDS codes.
Genetics of FTLD: overview and what else we can expect from genetic studies

Frontotemporal lobar degeneration (FTLD) comprises a highly heterogeneous group of disorders clinically associated with behavioral and personality changes, language impairment, and deficits in executive functioning, and pathologically associated with degeneration of frontal and temporal lobes. Some patients present with motor symptoms including amyotrophic lateral sclerosis. Genetic research over the past two decades in FTLD families led to the identification of three common FTLD genes (microtubule‐associated protein tau, progranulin, and chromosome 9 open reading frame 72) and a small number of rare FTLD genes, explaining the disease in almost all autosomal dominant FTLD families but only a minority of apparently sporadic patients or patients in whom the family history is less clear. Identification of additional FTLD (risk) genes is therefore highly anticipated, especially with the emerging use of next‐generation sequencing. Common variants in the transmembrane protein 106 B were identified as a genetic risk factor of FTLD and disease modifier in patients with known mutations. This review summarizes for each FTLD gene what we know about the type and frequency of mutations, their associated clinical and pathological features, and potential disease mechanisms. We also provide an overview of emerging disease pathways encompassing multiple FTLD genes. We further discuss how FTLD specific issues, such as disease heterogeneity, the presence of an unclear family history and the possible role of an oligogenic basis of FTLD, can pose challenges for future FTLD gene identification and risk assessment of specific variants. Finally, we highlight emerging clinical, genetic, and translational research opportunities that lie ahead.
Dissemination of the CTX-M-25 family beta-lactamases among Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae and identification of the novel enzyme CTX-M-41 in Proteus mirabilis in Israel.

OBJECTIVES The CTX-M-25 family of beta-lactamases is a closely related family of enzymes found rarely in the world. We aimed to describe the occurrence and to understand the dissemination of this extended-spectrum beta-lactamase family among Enterobacteriaceae strains in our hospital. METHODS Fifty-four CTX-M-producing Enterobacteriaceae strains collected from 2000 to 2005 were screened for bla(CTX-M-25) genes by PCR and sequencing. Genetic relatedness was analysed by PFGE. Antibiotic susceptibilities were determined by VITEK-2. Plasmids encoding bla(CTX-M-25)-type genes were isolated, transformed and analysed by Southern blot using a bla(CTX-M-25) probe. Chromosomal location of bla(CTX-M-25)-type was studied by I-CeuI restriction analysis. The bla(CTX-M-25) genetic environment was characterized by PCR mapping and partial sequencing. RESULTS Ten out of 54 CTX-M-producing isolates (18.5%) carried bla(CTX-M-25) genes, including Klebsiella pneumoniae (n = 4), Escherichia coli (n = 3), Enterobacter cloacae (n = 1) and Proteus mirabilis (n = 2). Isolates were genetically unrelated. Four beta-lactamases were found: CTX-M-25, CTX-M-26, CTX-M-39 and CTX-M-41, a new member of the family (accession no. DQ023162) that differed from CTX-M-25 in three amino acids, Ala80Val, Val106Ile and Ile126Ser. bla(CTX-M-25)-type genes were plasmid-mediated in all genera but P. mirabilis, organized in a class I integron and located downstream of an ISEcp1 element. The genes were encoded on different plasmids with varying degree of similarities. Several antibiotic-resistant determinants conferring resistance to trimethoprim and aminoglycosides existed on the same integron. CONCLUSIONS bla(CTX-M-25) exists in Israel in different enteric species. Spread of these enzymes within and between species is due to transfer of plasmids with common regions and by dissemination of determinants encoding these genes. CTX-M-41, a novel member of this family, was identified in the chromosome of P. mirabilis.