Miracle-dz/UniFAR-FTUs huggingface dataset:
Same-Day Tools, Including Xpert Ultra and IRISA-TB, for Rapid Diagnosis of Pleural Tuberculosis: a Prospective Observational Study

The diagnosis of pleural tuberculosis (TB) is problematic. The comparative performance of newer same-day tools for pleural TB, including Xpert MTB/RIF Ultra (ULTRA), has hitherto not been comprehensively studied. Adenosine deaminase (ADA), IRISA-TB (interferon gamma ultrasensitive rapid immunosuspension assay), Xpert MTB/RIF, and ULTRA performance outcomes were evaluated in pleural fluid samples from 149 patients with suspected pleural TB. ABSTRACT The diagnosis of pleural tuberculosis (TB) is problematic. The comparative performance of newer same-day tools for pleural TB, including Xpert MTB/RIF Ultra (ULTRA), has hitherto not been comprehensively studied. Adenosine deaminase (ADA), IRISA-TB (interferon gamma ultrasensitive rapid immunosuspension assay), Xpert MTB/RIF, and ULTRA performance outcomes were evaluated in pleural fluid samples from 149 patients with suspected pleural TB. The reference standard was culture positivity (fluid, biopsy specimen, or sputum) and/or pleural biopsy histopathology (termed definite TB). Those designated as having non-TB were negative by microbiological testing and were not initiated on anti-TB treatment. To determine the effect of sample concentration, 65 samples underwent pelleting by centrifugation, followed by conventional Xpert MTB/RIF and ULTRA. Of the 149 patients, 49 had definite TB, 16 had probable TB (not definite but treated for TB), and 84 had non-TB. ULTRA sensitivity and specificity (95% confidence intervals [CI]) were similar to those of Xpert MTB/RIF [sensitivity, 37.5% (25.3 to 51.2) versus 28.6% (15.9 to 41.2), respectively; specificity, 98.8% (96.5 to 100) versus 98.8% (96.5 to 100), respectively]. Centrifugation did not significantly improve ULTRA sensitivity (29.5% versus 31.3%, respectively). Adenosine deaminase and IRISA-TB sensitivity were 84.4% (73.9 to 95.0) and 89.8% (81.3 to 98.3), respectively. However, IRISA-TB demonstrated significantly better specificity (96.4% versus 87.5% [P = 0.034]), positive predictive value (93.6% versus 80.9 [P = 0.028]), and positive likelihood ratio (25.1 versus 6.8 [P = 0.032]) than ADA. In summary, Xpert ULTRA has poor sensitivity for the diagnosis of pleural TB. Alternative assays (ADA and IRISA-TB) are significantly more sensitive, with IRISA-TB demonstrating a higher specificity and rule-in value than ADA in this high-TB-burden setting where HIV is endemic.
Chronotype in bipolar disorder: an 18-month prospective study

Objective: Circadian dysregulation plays an important role in the etiology of mood disorders. Evening chronotype is frequent in these patients. However, prospective studies about the influence of chronotype on mood symptoms have reached unclear conclusions in patients with bipolar disorder (BD). The objective of this study was to investigate relationship between chronotype and prognostic factors for BD. Methods: At the baseline, 80 euthymic BD patients answered a demographic questionnaire and clinical scales to evaluate anxiety, functioning and chronotype. Circadian preference was measured using the Morningness-Eveningness Questionnaire, in which lower scores indicate eveningness. Mood episodes and hospitalizations were evaluated monthly for 18 months. Results: Among the BD patients, 14 (17.5%) were definitely morning type, 35 (43.8%), moderately morning, 27 (33.7%) intermediate (neither) and 4 (5%) moderately evening. Eveningness was associated with obesity or overweight (p = 0.03), greater anxiety (p = 0.002) and better functioning (p = 0.01), as well as with mood episodes (p = 0.04), but not with psychiatric hospitalizations (p = 0.82). This group tended toward depressive episodes (p = 0.06), but not (hypo)mania (p = 0.56). Conclusion: This study indicated that evening chronotype predicts a poor prognostic for BD. It reinforces the relevance of treating rhythm disruptions even during euthymia to improve patient quality of life and prevent mood episodes.
Skeletal Mineralization in Association with Type X Collagen Expression Is an Ancestral Feature for Jawed Vertebrates

Abstract In order to characterize the molecular bases of mineralizing cell evolution, we targeted type X collagen, a nonfibrillar network forming collagen encoded by the Col10a1 gene. It is involved in the process of endochondral ossification in ray-finned fishes and tetrapods (Osteichthyes), but until now unknown in cartilaginous fishes (Chondrichthyes). We show that holocephalans and elasmobranchs have respectively five and six tandemly duplicated Col10a1 gene copies that display conserved genomic synteny with osteichthyan Col10a1 genes. All Col10a1 genes in the catshark Scyliorhinus canicula are expressed in ameloblasts and/or odontoblasts of teeth and scales, during the stages of extracellular matrix protein secretion and mineralization. Only one duplicate is expressed in the endoskeletal (vertebral) mineralizing tissues. We also show that the expression of type X collagen is present in teeth of two osteichthyans, the zebrafish Danio rerio and the western clawed frog Xenopus tropicalis, indicating an ancestral jawed vertebrate involvement of type X collagen in odontode formation. Our findings push the origin of Col10a1 gene prior to the divergence of osteichthyans and chondrichthyans, and demonstrate its ancestral association with mineralization of both the odontode skeleton and the endoskeleton.
Emerging trends in the treatment of rectal cancer

Abstract The conventional treatment for cT3-T4 or node-positive clinically resectable rectal cancer is long course preoperative chemoradiation followed by surgery and postoperative adjuvant chemotherapy. Disadvantages of this approach include possible overtreatment of patients, 6 weeks of daily radiation treatment, and undetected metastatic disease. There are a number of emerging trends which are changing this approach to treatment. Selected topics included in this manuscript include the selective use of pelvic radiation, the role of radiation for a positive radial margin, the interval between radiation and surgery, non-operative management, new chemoradiation regimens, short vs. long course radiation, and the role of postoperative adjuvant chemotherapy.
Influence of synthesis parameters on properties and characteristics of poly (urea-formaldehyde) microcapsules for self-healing applications

Abstract Poly(urea-formaldehyde) (PUF) microcapsules filled with dicyclopentadiene (DCPD) were prepared by in situ polymerisation and the effect of synthesis parameters, such as pH of the solution and agitation rate, on microcapsules size and shell thickness was evaluated. Scanning electron microscopy (SEM) and Fourier transform infra-red spectroscopy (FTIR) were performed. Adjusted pH conditions (pH = 3.5) and agitation rate (1350 RPM) were found using a design of experiments (DOE). SEM results indicated that microcapsule size was directly affected by agitation rate, whereas shell thickness was mostly affected by pH. After obtaining adjusted synthesis conditions, microcapsules presenting mean size of 60 µm and mean shell thickness of 4 µm were embedded in an epoxy matrix for evaluating the self-healing effect. FTIR and SEM analyses in damaged samples suggested that a healing agent was delivered to the crack location.
Altered Synaptic Drive onto Birthdated Dentate Granule Cells in Experimental Temporal Lobe Epilepsy

Dysregulated adult hippocampal neurogenesis occurs in many temporal lobe epilepsy (TLE) models. Most dentate granule cells (DGCs) generated in response to an epileptic insult develop features that promote increased excitability, including ectopic location, persistent hilar basal dendrites (HBDs), and mossy fiber sprouting. However, some appear to integrate normally and even exhibit reduced excitability compared to other DGCs. To examine the relationship between DGC birthdate, morphology, and network integration in a model of TLE, we retrovirally birthdated either early-born [EB; postnatal day (P)7] or adult-born (AB; P60) DGCs. Male rats underwent pilocarpine-induced status epilepticus (SE) or sham treatment at P56. Three to six months after SE or sham treatment, we used whole-cell patch-clamp and fluorescence microscopy to record spontaneous excitatory and inhibitory currents from birthdated DGCs. We found that both AB and EB populations of DGCs recorded from epileptic rats received increased excitatory input compared with age-matched controls. Interestingly, when AB populations were separated into normally integrated (normotopic) and aberrant (ectopic or HBD-containing) subpopulations, only the aberrant populations exhibited a relative increase in excitatory input (amplitude, frequency, and charge transfer). The ratio of excitatory-to-inhibitory input was most dramatically upregulated for ectopically localized DGCs. These data provide definitive physiological evidence that aberrant integration of post-SE, AB DGCs contributes to increased synaptic drive and support the idea that ectopic DGCs serve as putative hub cells to promote seizures. SIGNIFICANCE STATEMENT Adult dentate granule cell (DGC) neurogenesis is altered in rodent models of temporal lobe epilepsy (TLE). Some of the new neurons show abnormal morphology and integration, but whether adult-generated DGCs contribute to the development of epilepsy is controversial. We examined the synaptic inputs of age-defined populations of DGCs using electrophysiological recordings and fluorescent retroviral reporter birthdating. DGCs generated neonatally were compared with those generated in adulthood, and adult-born (AB) neurons with normal versus aberrant morphology or integration were examined. We found that AB, ectopically located DGCs exhibit the most pro-excitatory physiological changes, implicating this population in seizure generation or progression.
Reduced Active Muscle Stiffness after Intermittent Submaximal Isometric Contractions.

PURPOSE Whether muscle stiffness is influenced by fatigue remains unclear. Classical methods used to assess muscle stiffness provide a global measure at the joint level. As fatigue may selectively affect specific muscles, a joint-level approach may not be sensitive enough to detect potential changes in muscle stiffness. Taking advantage of ultrasound shear wave elastography, this study aimed to determine the influence of a fatiguing protocol involving intermittent submaximal isometric contractions on muscle shear modulus (an index of stiffness). METHODS Shear modulus was measured on either the vastus lateralis (VL; n=9) or the abductor digiti minimi (ADM; n=10) before and after 15-mins of intermittent submaximal isometric contractions at 60% of maximal voluntary contraction (MVC; 4 s ON, 4 s OFF). An index of active muscle stiffness was estimated PRE and POST-fatigue as the slope of the linear regression established between shear modulus and absolute joint force up to 60% MVC. RESULTS After the fatiguing exercise, MVC was significantly decreased by 22 ± 7 % and 32 ± 15 % for knee extension and little finger abduction, respectively (p<0.001). When compared to PRE-fatigue, the index of active muscle stiffness was 12 ± 15 % lower for the VL (p < 0.031) and 44 ± 19 % lower for the ADM (p < 0.001) POST-fatigue. CONCLUSION Although the present results cannot clearly determine the involved mechanisms, they demonstrate a decreased active muscle stiffness after a fatiguing task involving intermittent submaximal isometric contractions. Further studies should now determine whether this change in stiffness affects performance and risk of injury.
Electronic Patient-Reported Outcome Collection Systems in Orthopaedic Clinical Practice.

» The recent emphasis on the electronic collection of patient health information has catalyzed the development of numerous platforms for capturing electronic patient-reported outcome measures (EPROMs). » There are several important considerations for selecting the most appropriate PROM for each orthopaedic practice. » In this article, we evaluate various aspects of PROMs, examine the challenges and obstacles that are associated with routine collection, and review 6 commonly used electronic collection systems for orthopaedic clinical practice. T raditionally, clinical outcome measures in medicine primarily have been rooted in objective data, such as read-mission rate, complications, and mortality. However, as medicine continues to
Preeclampsia: The Relationship between Uterine Artery Blood Flow and Trophoblast Function

Maternal uterine artery blood flow is critical to maintaining the intrauterine environment, permitting normal placental function, and supporting fetal growth. It has long been believed that inadequate transformation of the maternal uterine vasculature is a consequence of primary defective trophoblast invasion and leads to the development of preeclampsia. That early pregnancy maternal uterine artery perfusion is strongly associated with placental cellular function and behaviour has always been interpreted in this context. Consistently observed changes in pre-conceptual maternal and uterine artery blood flow, abdominal pregnancy implantation, and late pregnancy have been challenging this concept, and suggest that abnormal placental perfusion may result in trophoblast impairment, rather than the other way round. This review focuses on evidence that maternal cardiovascular function plays a significant role in the pathophysiology of preeclampsia.
Predicting dry matter intake using conceptual models for cattle kept under tropical and subtropical conditions.

Using empirical models to predict voluntary dry matter intake (VDMI) of cattle across production systems in the (Sub-)Tropics often yields VDMI estimates with low adequacy (i.e. accuracy and precision). Thus, we investigated whether semi-mechanistic conceptual mathematical models (CMM) developed for cattle in temperate areas could be adopted and adjusted to adequately predict VDMI of stall-fed cattle in the (Sub-)Tropics. The CMM of Conrad et al. (1964) (C1) and Mertens (1987) (M1) were identified and adopted for their simplicity in reflecting physico-physiological VDMI regulation. Both CMM use two equations that estimate the physiologically and physically regulated VDMI and retain the lower VDMI prediction as actual VDMI. Furthermore, C1 was modified by increasing the daily average faecal dry matter output from 0.0107 to 0.0116 kg/kg body-weight, yielding the modified model C2. For M1, the daily neutral detergent fibre intake capacity was increased from 0.012 to 0.0135 kg/kg body-weight and the daily metabolizable energy requirements for maintenance from 0.419 to 0.631 MJ/kg0.75 body-weight, whereas the metabolizable energy requirements for gain was reduced from 32.5 to 24.3 MJ/kg body-weight gain, yielding the modified model M2. Lastly, also the mean of the physically and physiologically regulated VDMI rather than the lower of both estimates was retained as actual VDMI to generate the models C3 (from C1), C4 (from C2), M3 (from M1), and M4 (from M2). The eight CMM were then evaluated using a dataset summarizing results from 52 studies conducted under (sub-)tropical conditions. The mean bias, root mean square error of prediction (RMSEP), relative prediction error (RPE), and concordance correlation coefficient (CCC) were used to evaluate adequacy and robustness of all CMM. The M4, C2, and C1 were the most adequate CMM (i.e. lowest mean biases [0.07, -0.22, and 0.14 kg/animal and day, respectively], RMSEP [1.62, 1.93, and 2.0 kg/animal and day, respectively], and CCC [0.91, 0.86, and 0.85, respectively]) and robust of the eight CMM. Hence, CMM can adequately predict VDMI across diverse stall-fed cattle systems in the (Sub-)Tropics. Adjusting CMM to reflect the differences in feed quality and animal physiology under typical husbandry conditions in the (Sub-)Tropics and those in temperate areas improves adequacy of their VDMI predictions.
Influence of bovine follicular fluid on thawed bovine spermatozoa - assessment by CASA system and flow cytometry.

AIM The aim of this study was to analyze the effect of bovine follicular fluid on the survival, morphology and kinetic parameters of bovine thawed spermatozoa under laboratory conditions. MATERIALS AND METHODS The semen from 5 bulls of proven fertility was incubated in follicular and physiological fluid for 8 hours. During this time assessment using the CASA system was performed. At the beginning and the end of incubation process evaluation by flow cytometry was conducted. RESULTS The results of the sperm motility assessment showed a significant decrease in the analyzed parameters both in the follicular and physiological fluid. A significant reduction in all parameters characterizing movement properties in the semen incubated in the follicular fluid was found. In the physiological fluid, a similar trend was demonstrated only for the following properties: VAP, VSL, VCL, ALH, BCF. A significant difference was found for both fluids in: VCL (p=0.026), ALH (p=0.038) and LIN (p⟨0.001) at the beginning of incubation. The results of the plasma membrane integrity assessment showed a statistically significant increase in the percentage of dying sperm at the 8th hour of the incubation in the follicular fluid. In the case of semen incubation in physiological fluid, a statistically significant decrease in the percentage of live non-damaged cells was found with a simultaneous increase in the subpopulation of undamaged dead cells. CONCLUSIONS Follicular fluid rapidly accelerates the capacitation process. The results of flow cytometry support the hypothesis concerning the ability of follicular fluid to prolong sperm survival.
Late correction of tetralogy of Fallot in children.

AIM OF STUDY To report our experience of late correction after infancy in patients with tetralogy of Fallot (ToF). METHODS Observational single-centre retrospective analysis of the surgical techniques and perioperative development of patients from developing countries undergoing total surgical correction of ToF after infancy, between 1 November 2011 and 30 November 2016. Variables are presented as numbers with percentages or as mean ± standard deviation. Due to the setting of the humanitarian programme, clinical and echocardiographic follow-up procedures could be conducted for only one month postoperatively. RESULTS Twenty-five children (mean age: 70.8 ± 42 months, range 23-163; 44% female) underwent total surgical correction of ToF. Two patients (0.8%) initially received a Blalock-Taussig shunt and underwent subsequent correction 24 and 108 months later, respectively. Preoperative mean right ventricular/pulmonary artery (RV/PA) gradient was 84 ± 32 mm Hg, with a Nakata index of 164 ± 71 mm2/m2. Major aortopulmonary collateral arteries (MAPCAs) were observed in eight children (32%), six (26%) of whom underwent transcatheter closure before surgery. 24 children (96%) underwent a valve-sparing pulmonary valve repair and one patient received a transannular patch (TAP). There were no cases which saw major adverse cardiac and cerebrovascular events (MACCE). Mean duration of mechanical ventilation was 28 ± 19.6 hours (range 7-76). Pre-discharge echocardiography demonstrated a mean RV/PA gradient of 25 ± 5.7 mm Hg, with left ventricular ejection fraction >60% in all cases. Overall length of hospital stay was 11.7 ± 4.5 days. There were no in-hospital mortality cases. CONCLUSIONS Late surgical correction of ToF can be safely performed and produce highly satisfying early postoperative results comparable to those of classical “timely” correction. A valve-sparing technique can be applied in the majority of children.
High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity

Objective A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC. Design Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence. Results We discovered that a previously unappreciated innate lymphocyte population (Lin–CD7+CD127–CD56+CD45RO+) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103+CD69+) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DR+CD38+PD-1+) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes. Conclusion This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.
Inter-observer variability in target delineation increases during adaptive treatment of head-and-neck and lung cancer

Abstract Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample (p-value range .063–.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.