Miracle-dz/UniFAR-FTUs huggingface dataset:
Classification of disease recurrence using transition likelihoods with expectation‐maximization algorithm

When an infectious disease recurs, it may be due to treatment failure or a new infection. Being able to distinguish and classify these two different outcomes is critical in effective disease control. A multi‐state model based on Markov processes is a typical approach to estimating the transition probability between the disease states. However, it can perform poorly when the disease state is unknown. This article aims to demonstrate that the transition likelihoods of baseline covariates can distinguish one cause from another with high accuracy in infectious diseases such as malaria. A more general model for disease progression can be constructed to allow for additional disease outcomes. We start from a multinomial logit model to estimate the disease transition probabilities and then utilize the baseline covariate's transition information to provide a more accurate classification result. We apply the expectation‐maximization (EM) algorithm to estimate unknown parameters, including the marginal probabilities of disease outcomes. A simulation study comparing our classifier to the existing two‐stage method shows that our classifier has better accuracy, especially when the sample size is small. The proposed method is applied to determining relapse vs reinfection outcomes in two Plasmodium vivax treatment studies from Cambodia that used different genotyping approaches to demonstrate its practical use.
The semantic basis of argument structure

1. Introduction 1.1 Argument structure and linking 1.2 Previous approaches to argument structure 1.3 Theoretical framework 1.4 Overview 2. Semantic constraints on argument structure 2.1 Notions 2.2 Cause and effect 2.3 The part rule 2.4 Conclusion 3. Oblique complements 3.1 Prepositions and co-predication 3.2 The restricted recipient NP 3.3 Valency and for-datives 3.4 Predictions of the account 3.5 Comparison with previous analysis 3.6 Restricted NP complements in Swedish and Dutch 3.7 Overview of the theory 4. Reformulations in the Hierarchical Lexicon 4.1 Preposition selection revisited 4.2 The semantics of argument structure revisited 4.3 Valence and subjects 4.4 Summary References.
A detailed redescription of the mesoderm/neural crest cell boundary in the murine orbitotemporal region integrates the mammalian cranium into a pan‐amniote cranial configuration

The morphology of the mammalian chondrocranium appears to differ significantly from those of other amniotes, since the former possesses uniquely developed brain and cranial sensory organs. In particular, a question has long remained unanswered as to the developmental and evolutionary origins of a cartilaginous nodule called the ala hypochiasmatica. In this study, we investigated the embryonic origin of skeletal elements in the murine orbitotemporal region by combining genetic cell lineage analysis with detailed morphological observation. Our results showed that the mesodermal embryonic environment including the ala hypochiasmatica, which appeared as an isolated mesodermal distribution in the neural crest‐derived prechordal region, is formed as a part of the mesoderm that continued from the chordal region during early chondrocranial development. The mesoderm/neural crest cell boundary in the head mesenchyme is modified through development, resulting in the secondary mesodermal expansion to invade into the prechordal region. We thus revealed that the ala hypochiasmatica develops as the frontier of the mesodermal sheet stretched along the cephalic flexure. These results suggest that the mammalian ala hypochiasmatica has evolved from a part of the mesodermal primary cranial wall in ancestral amniotes. In addition, the endoskeletal elements in the orbitotemporal region, such as the orbital cartilage, suprapterygoid articulation of the palatoquadrate, and trabecula, some of which were once believed to represent primitive traits of amniotes and to be lost in the mammalian lineage, have been confirmed to exist in the mammalian cranium. Consequently, the mammalian chondrocranium can now be explained in relation to the pan‐amniote cranial configuration.
Emergency Medical Services Clinicians’ Perspectives on Pediatric Non-Transport

Abstract Objectives Emergency medical services clinicians do not transport one-third of all children assessed, even without official pediatric non-transport protocols. Little is known about how EMS clinicians and caregivers decide not to transport a child. Our objectives were to describe how EMS clinicians currently decide whether or not to transport a child and identify barriers to and enablers of successfully implementing an EMS clinician-initiated pediatric non-transport protocol. Methods We conducted six virtual focus groups with EMS clinicians from the mid-Atlantic. A PhD trained facilitator moderated all groups using a semi-structured moderator guide. Multiple investigators independently coded a deidentified sample transcript. One team member then completed axial coding of the remaining transcripts. Thematic saturation was achieved. Clusters of similar codes were grouped into themes by consensus. Results We recruited 50 participants, of whom 70% were paramedics and 28% emergency medical technicians. There was agreement that caregivers often use 9-1-1 for low acuity complaints. Participants stated that non-transport usually occurs after shared decision-making between EMS clinicians and caregivers; EMS clinicians advise whether transport is necessary, but caregivers are responsible for making the final decision and signing refusal documentation. Subthemes for how non-transport decisions were made included the presence of agency protocols, caregiver preferences, absence of a guardian on the scene, EMS clinician variability, and distance to the nearest ED. Participants identified the following features that would enable successful implementation of an EMS clinician-initiated non-transport process: a user-friendly interface, clear protocol endpoints, the inclusion of vital sign parameters, resources to leave with caregivers, and optional direct medical oversight. Conclusions EMS clinicians in our study agreed that non-transport is currently a caregiver decision, but noted a collaborative process of shared decision-making where EMS clinicians advise caregivers whether transport is indicated. Further research is needed to understand the safety of this practice. This study suggests there may be a need for EMS-initiated alternative disposition/non-transport protocols.
Invariant natural killer T cells minimally influence gut microbiota composition in mice

ABSTRACT Invariant Natural Killer T (iNKT) cells are unconventional T cells that respond to glycolipid antigens found in microbes in a CD1d-dependent manner. iNKT cells exert innate-like functions and produce copious amounts of cytokines, chemokines and cytotoxic molecules within only minutes of activation. As such, iNKT cells can fuel or dampen inflammation in a context-dependent manner. In addition, iNKT cells provide potent immunity against bacteria, viruses, parasites and fungi. Although microbiota-iNKT cell interactions are not well-characterized, mounting evidence suggests that microbiota colonization early in life impacts iNKT cell homeostasis and functions in disease. In this study, we showed that CD1d−/− and Vα14 Tg mice, which lack and have increased numbers of iNKT cells, respectively, had no significant alterations in gut microbiota composition compared to their littermate controls. Furthermore, specific iNKT cell activation by glycolipid antigens only resulted in a transient and minimal shift in microbiota composition when compared to the natural drift found in our colony. Our findings demonstrate that iNKT cells have little to no influence in regulating commensal bacteria at steady state. Abbreviations: iNKT: invariant Natural Killer T cell; αGC: α-galactosylceramide
Introducing the QACP: development and preliminary validation of an instrument to measure psychotherapist’s core competencies

The movement towards the conceptualization, description and evaluation of psychotherapists’ competencies has been widely developed in the last years and has relevant implications for psychotherapy, training, and continuous education. In Italy, this movement has been supported by the Committee for Psychotherapists’ Competencies established in 2010 by FIAP (Italian Federation of Psychotherapy’s Associations) and CNSP (National Association of Psychotherapy’s Training Institutes) and has involved more than 1000 psychotherapists from different approaches, by means of conferences, expert meetings, workshops, and focus groups. One of the outcomes of this process has been the development of a new self-assessment tool for core competencies (i.e., those that are shared by therapists from all modalities): the QACP (Questionario per l’Autovalutazione delle Competenze dello Psicoterapeuta). The present study aims to present the process of development and the preliminary proofs of the validity of this tool. Construct and knowngroup validity of the questionnaire were examined, and reliability was estimated by computing the internal consistency reliability coefficients for both the overall and the subscale scores. Overall, the instrument showed satisfactory psychometric characteristics. The limitations of the study and the results are discussed and directions for further research are proposed.
Early CD49d downmodulation in chronic lymphocytic leukemia patients treated front-line with ibrutinib plus rituximab predicts long-term response

Nadia Peragine, Maria Stefania De Propris, Stefania Intoppa, Maria Laura Milani, Francesca Romana Mauro , Antonio Cuneo, Gian Matteo Rigolin, Ilaria Del Giudice , Robin Fo a and Anna Guarini Hematology, Department of Translational and Precision Medicine, Sapienza University, Rome, Italy; Hematology, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; Department of Molecular Medicine, Sapienza University, Rome, Italy
Elevated c-di-GMP Levels and Expression of the Type III Secretion System Promote Corneal Infection by Pseudomonas aeruginosa

Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a plac-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. ABSTRACT Pseudomonas aeruginosa is generally believed to establish biofilm-associated infections under the regulation of the secondary messenger c-di-GMP. To evaluate P. aeruginosa biofilm physiology during ocular infections, comparative transcriptomic analysis was performed on wild-type P. aeruginosa PAO1, a ΔwspF mutant strain (high c-di-GMP levels), and a plac-yhjH-containing strain (low c-di-GMP levels) from mouse corneal infection, as well as in vitro biofilm and planktonic cultures. The c-di-GMP content in P. aeruginosa during corneal infection was monitored using a fluorescent c-di-GMP reporter strain. Biofilm-related genes were induced in in vivo PAO1 compared to in vitro planktonic bacteria. Several diguanylate cyclases and phosphodiesterases were commonly regulated in in vivo PAO1 and in vitro biofilm compared to in vitro planktonic bacteria. Several exopolysaccharide genes and motility genes were induced and downregulated, respectively, in in vivo PAO1 and the in vivo ΔwspF mutant compared to the in vivo plac-yhjH-containing strain. Elevation of c-di-GMP levels in P. aeruginosa began as early as 2 h postinfection. The ΔwspF mutant was less susceptible to host clearance than the plac-yhjH-containing strain and could suppress host immune responses. The type III secretion system (T3SS) was induced in in vivo PAO1 compared to in vitro biofilm bacteria. A ΔwspF mutant with a defective T3SS was more susceptible to host clearance than a ΔwspF mutant with a functional T3SS. Our study suggests that elevated intracellular c-di-GMP levels and T3SS activity in P. aeruginosa are necessary for establishment of infection and modulation of host immune responses in mouse cornea.
Diagnostic significance of lactate dehydrogenase in measles virus reinfection cases

Lactate dehydrogenase (LDH) levels in measles virus (MeV) reinfection cases for the diagnosis of measles have not been extensively studied. Thus, we evaluated the significance of serum LDH in the immune response of patients with MeV reinfection in comparison with those of patients with primary infection. Among 70 patients who tested positive for MeV‐RNA, 42 with high MeV–specific IgG avidity (HA) were suspected as cases of reinfection and 28 with low MeV–specific IgG (LA) were suspected as cases of primary infection. The viral loads in the HA group were also lower than those in the LA group (P < 0.001). The titers of MeV‐specific IgM and IgG in the HA group were significantly lower and higher, respectively, than those in the LA group (P < 0.001). The total LDH and LDH isozyme levels were elevated in the LA group compared with those in the HA group (P < 0.001). Through receiver operating characteristic curve analyses, we determined that the area under the curve of total LDH level was 0.87 (95% CI 0.74–1.00) and that the discriminatory accuracy was high for total LDH and all isozymes. By stepwise binary logistic regression analysis considering MeV‐specific IgG avidity, we developed a model using IgG, IgM, and total LDH as explanatory variables, which was optimal for distinguishing the LA and HA groups (adjusted R2 = 0.773, P < 0.001). Thus, the serum LDH level in addition to IgM and IgG may be useful parameters for differentiating MeV reinfection from primary infection.
High dietary Ca and microbial phytase reduce the expression of Ca transporters while enhancing claudins involved in paracellular Ca absorption in the porcine jejunum and colon

Abstract Expression levels of genes (RT-qPCR) related to Ca and P homeostasis (transporters and claudins (CLDN)) were determined in porcine jejunal and colonic mucosa. Forty growing pigs (BW 30·4 (sem 1·3) kg) received a low and high Ca content (2·0 and 9·6 g/kg, respectively) diet with or without microbial phytase (500 FTU/kg) for 21 d. Dietary Ca intake enhanced serum Ca and alkaline phosphatase concentration and reduced P, 1,25(OH)2D3, and parathyroid hormone concentration. Jejunal transient receptor potential vanilloid 5 (TRPV5) mRNA expression was decreased (32%) with phytase inclusion only, while colonic TRPV5 mRNA was reduced by dietary Ca (34%) and phytase (44%). Both jejunal and colonic TRPV6 mRNA expression was reduced (30%) with microbial phytase. Calbindin-D9k mRNA expression was lower in colonic but not jejunal mucosa with high dietary Ca (59%) and microbial phytase (37%). None of the mRNAs encoding the Na–P cotransporters (NaPi-IIc, PiT-1, PiT-2) were affected. Jejunal, but not colonic expression of the phosphate transporter XPR1, was slightly downregulated with dietary Ca. Dietary Ca downregulated colonic CLDN-4 (20%) and CLDN-10 (40%) expression while CLDN-7 was reduced by phytase inclusion in pigs fed low dietary Ca. Expression of colonic CLDN-12 tended to be increased by phytase. In jejunal mucosa, dietary Ca increased CLDN-2 expression (48%) and decreased CLDN-10 (49%) expression, while phytase slightly upregulated CLDN-12 expression. In conclusion, compared with a Ca-deficient phytase-free diet, high dietary Ca and phytase intake in pigs downregulate jejunal and colonic genes related to transcellular Ca absorption and upregulate Ca pore-forming claudins.
Characteristics of colorectal cancer and use of colonoscopy before colorectal cancer diagnosis among individuals with inflammatory bowel disease: A population-based study

Introduction There are limited recent data on the characteristics of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) and the use of colonoscopy prior to CRC diagnosis among persons with IBD. We analyzed IBD-CRC characteristics, survival after IBD-CRC diagnosis and the use of colonoscopy prior to IBD-CRC diagnosis over time. Methods We identified individuals with and without IBD from the University of Manitoba IBD Epidemiology Database and CRC from linkage to the Manitoba Cancer Registry. We compared characteristics of IBD-CRC and sporadic-CRC using logistic regression and survival after CRC diagnosis using Cox regression analysis. We assessed rate and predictors of colonoscopy use 5 years to 6 months prior to IBD-CRC. Results 1,262 individuals with CRC were included (212 IBD-CRC). IBD was associated with an increased risk of death after CRC diagnosis in 2004–2011 (HR 1.89; 95% CI 1.25–2.88) but not in 2012–2017 (HR = 1.002; CI 0.50–2.03). In the 5 years to 6 months prior to IBD-CRC (1989–2018), 51% underwent colonoscopy, which was very similar to IBD without CRC and contrasted to 9% among sporadic CRCs. Exposure to colonoscopy pre IBD-CRC remained stable through the study period (1989–2002 OR = 1.25; CI 0.77–2.01; 2003–2011 OR = 1.21; CI 0.56–1.70; reference 2012–2018). Exposure to colonoscopy pre-IBD-CRC was not associated with improved post-CRC survival. Conclusion The risk of death following CRC diagnosis is not impacted by a diagnosis of IBD in recent years. There is a very high proportion of post colonoscopy CRC among IBD-CRC, which has not changed over the years and needs detailed root-cause analysis and interventions.
Multilocus Genotyping Identiﬁes Infections by Multiple Strains of Trichophyton tonsurans (cid:1)

Acquisition of multiple genetic strains of a single dermatophyte species should not be unexpected in areas of high endemicity, and yet multistrain infections are infrequently reported. This communication details mixed Trichophyton tonsurans infections and highlights the need to conﬁrm the presence of multiple strains in a clinical single isolate by use of a multilocus approach. Clinical and epidemiological investigations, along with pop-ulation-based evolutionary studies, all beneﬁt from the ability to distinguish pathogen strains. Without the ability to reliably discriminate variants within a species one cannot adequately determine the extent of genetic variation within and between populations, the origins of phenetic di-versity within a species, insight into the relationship the G, restriction digestion with BstYI two fragments of 858 and 290 bp. When an A present, BstYI cut the PCR product three times, resulting in a pattern comprised of 570-bp, 290-bp, and 288-bp bands. One of two sequence variations present in exon 3 of MEP5 included in the typing scheme. The transition C (cid:3) T was detected after ampliﬁcation of a 283-bp fragment from genomic DNA by use of primers 5 (cid:2) -CAC GGC CAG GGT GGT AAA GGC and 5 (cid:2) -GGT TGG CTA GAT ATG ATG AGG. Re- striction digestion of the PCR product with AciI yielded fragments of 207 and 76 bp in the presence of C, while the amplicon remained uncut in the presence of T. Owing to the nature of this digest, a “reverse” assay was designed to conﬁrm the sequence variation. In the presence of a T, BstBI cut a 251-bp product generated with primers 5 (cid:2) -CTT GCC ATC AGG AGG GGT TTC G and 5 (cid:2) -TCA AAT TTG AGT CTT ATG CTC C into fragments that were 229 bp and 22 bp in length whereas the product remained uncut by BstBI in the presence of C. Each of the PCRs detailed above was performed in a total volume of 8 (cid:4) l with RedJumpStart Taq polymerase (Sigma-Aldrich) and 3.75% dimethyl sulfoxide according to the manufacturer’s recommendations. Annealing 58°C the CarbY- PCR 56°C for the MEP5 PCR Extension 2 min, length
RAPID DETECTION OF DRUG RESISTANT TUBERCULOSIS BY DIRECT NITRATE REDUCTASE ASSAY IN RESOURCE POOR SETTINGS

change in the culture medium after done on the samples turnaround to obtain the results of and DST of [5] The present study aimed for rapid drug susceptibility testing of by NRA directly on positive sputum samples in a tertiary care hospital The sputum by modified Petroff’s method. [6] The ABSTRACT Background: The most common method for detection of drug resistant tuberculosis is conventional proportion method requiring three months to yield the results. Delay in the proper diagnosis may hinder the effective treatment and increase the transmission of the drug resistant tuberculosis. Hence, this study was conducted to evaluate nitrate reductase assay (NRA) as a simple and rapid alternative method for detecting drug resistance tuberculosis in resource limited settings. Methods: A total of fifty eight new smear positive sputum samples were processed as per the standard guidelines. After decontamination, sputum samples were inoculated on NRA medium for rapid drug susceptibility testing and conventional culture medium. Results: NRA detected 13.2% isoniazid resistance, 11.3% rifampicin resistance and 5.7% multidrug resistant strains of Mycobacterium tuberculosis . A total of 44 samples yielded results within 21 days and 19 samples yielded results in 14 days. The mean duration for detection and drug susceptibility testing of Mycobacterium tuberculosis by NRA was 19.2 days. Conclusions: The present study concludes that NRA is a simple and rapid alternative method for detection of drug resistance to isoniazid and rifampicin in resource strain settings.
Earth and Planetary Science Letters A new perspective on West African hydroclimate during the last deglaciation

Widespread drought characterized the Heinrich 1 and Younger Dryas cold periods of the last deglaciation throughout much of Africa, causing large increases in dust emissions from the Sahara and Sahel. At the same time, increases in wind strength may have also contributed to dust ﬂux, making it diﬃcult to interpret dust records alone as reﬂecting changes in rainfall over the region. The Niger River has the third largest drainage basin in Africa and drains most of the Sahara and Sahel and thus preserves and propagates climatic signals. Here, we present new reconstructions of Niger Delta sea surface salinity and Niger River discharge for the last 20,000 years in order to more accurately reconstruct the onset of the Western African Monsoon system. Based on calculated δ 18 O SEAWATER ( δ 18 O SW ) and measured Ba/Ca ratios in planktonic foraminifera, these new records reﬂect changes in sub-Saharan precipitation across the Niger River Basin in West Africa and reveal that the West African Monsoon system began to intensify several thousand years after the equatorial Monsoon system in Central Africa. We also present new records of primary productivity in the Niger Delta that are related to wind-driven upwelling and show that productivity is decoupled from changes in Niger River discharge. Our results suggest that wind strength, rather than changes in monsoon moisture, was the primary driver of dust emissions from the Sahara and Sahel across the last deglaciation.