Miracle-dz/UniFAR-FTUs huggingface dataset:
Dientamoeba fragilis in children: a systematic review on diagnostic considerations and efficacy of treatment

ABSTRACT Introduction: The presence of D. fragilis in feces is characterized by an asymptomatic carrier ship to a spectrum of gastrointestinal symptoms. However, a causal relationship remains to be elucidated. In this systematic review, we aimed to evaluate the relationship between the eradication of D. fragilis and symptoms to establish the strength of evidence that D. fragilis in symptomatic children warrants antibiotic treatment. Areas covered: This systematic review covers a challenge in daily clinical practice. Is it necessary to test for D. fragilis in children with gastrointestinal symptoms and does a positive fecal PCR test warrant treatment? Expert opinion: Testing for D. fragilis seems justified in a selection of children with persistent unexplained chronic abdominal pain and diarrhea. Treatment of D. fragilis should be withhold until other causes like celiac disease have been excluded. Both microscopic and Real Time-PCR methods (or a combination of the two) can be used for diagnosis. Paromomycin or clioquinol are antibiotics of choice based on their small spectrum of activity, fewer side effects, and better eradication rates than metronidazole. Future randomized studies, with strict inclusion criteria, appropriate diagnostic testing, and doses of antibiotics based on bodyweight are warranted.
The impact of leprosy, podoconiosis and lymphatic filariasis on family quality of life: A qualitative study in Northwest Ethiopia

Background Several studies have shown that leprosy, podoconiosis and lymphatic filariasis impact individual quality of life. In contrast, family quality of life has not received as much attention despite evidence that families are also affected. This is especially relevant given the crucial role of the family in most societies around the world. This study looks at the impact of leprosy, podoconiosis and lymphatic filariasis on family quality of life. Methodology The study used a cross-sectional design with a qualitative approach. Both semi-structured interviews and focus group discussions were conducted. Participants, persons affected and their family members, were selected by purposive sampling. Data were collected between August and November 2017 in Awi zone, Northwest Ethiopia and analysed by three independent researchers using open, inductive coding and content analysis. Results A total of 86 participants were included in this study: 56 participants in the in-depth interviews and 30 participants in the focus group discussions. We found that participation restrictions, reduced productivity and marginalisation were common. In addition, discrimination in the communities occurred often, often extending to family members of persons affected. Divorce and difficulties in finding a spouse were common for persons affected and their family members. Many persons affected reported mental health problems. While most people got social and physical support from their families, there were a few exceptions. In particular, persons with younger children seemed to lack social support. Having to provide for their affected family member sometimes caused stress, school dropouts and an additional workload. Financial problems and loss of livelihood were reported by almost all participants. Conclusion This study revealed that leprosy, lymphatic filariasis and podoconiosis have an effect on several dimensions of family quality of life. Many problems reported related to stigma and poverty.
Organic Spherical Nucleic Acids Facilitate NIR-II Emitting Dye to Cross Blood-Brain Barrier.

DNA nanotechnology plays an increasingly important role in the biomedical field; however, its application in the design of organic nanomaterials has still been underexplored. Herein, we innovatively exploit the DNA nanotechnology to aid a NIR-II emitting nanofluorophore to break through the limit of the brain-blood barrier (BBB) in non-invasive imaging of the brain tumor. Specifically, the DNA block copolymer, PS- b -DNA, is synthesized through a solid-phase "click" reaction. We demonstrate that its self-assembled structure shows exceptional cluster-effects, among which BBB-crossing is the most notable one. Therefore, for the first time, PS- b -DNA is utilized as an amphiphilic matrix to fabricate the NIR-II nanofluorephore and applied in in vivo bio-imaging. Accordingly, the DNA-based nanofluorophore shows a 3.8-fold enhancement in the NIR-II fluorescence signal of the glioblastoma imaging in comparison with the PEG-based counterpart. Undoubtedly, the notably increased imaging resolution will significantly benefit the further diagnosis and therapy of brain tumors.
Insights into origins and function of the unexplored majority of the reductive dehalogenase gene family as a result of genome assembly and ortholog group classification.

Organohalide respiring bacteria (OHRB) express reductive dehalogenases for energy conservation and growth. Some of these enzymes catalyze the reductive dehalogenation of chlorinated and brominated pollutants in anaerobic subsurface environments, providing a valuable ecosystem service. Dehalococcoides mccartyi strains have been most extensively studied owing to their ability to dechlorinate all chlorinated ethenes - most notably carcinogenic vinyl chloride - to ethene. The genomes of OHRB, particularly obligate OHRB, often harbour multiple putative reductive dehalogenase genes (rdhA), most of which have yet to be characterized. We recently sequenced and closed the genomes of eight new strains, increasing the number of available D. mccartyi genomes in NCBI from 16 to 24. From all available OHRB genomes, we classified predicted translations of reductive dehalogenase genes using a previously established 90% amino acid pairwise identity cut-off to identify Ortholog Groups (OGs). Interestingly, the majority of D. mccartyi dehalogenase gene sequences, once classified into OGs, exhibited a remarkable degree of synteny (gene order) in all genomes sequenced to date. This organization was not apparent without the classification. A high degree of synteny indicates that differences arose from rdhA gene loss rather than recombination. Phylogenetic analysis suggests that most rdhA genes have a long evolutionary history in the Dehalococcoidia with origin prior to speciation of Dehalococcoides and Dehalogenimonas. We also looked for evidence of synteny in the genomes of other species of OHRB. Unfortunately, there are too few closed Dehalogenimonas genomes to compare at this time. There is some partial evidence for synteny in the Dehalobacter restrictus genomes, but here too more closed genomes are needed for confirmation. Interestingly, we found that the rdhA genes that encode enzymes that catalyze dehalogenation of industrial pollutants are the only rdhA genes with strong evidence of recent lateral transfer - at least in the genomes examined herein. Given the utility of the RdhA sequence classification to comparative analyses, we are building a public web server (http://RDaseDB.biozone.utoronto.ca) for the community to use, which allows users to add and classify new sequences, and download the entire curated database of reductive dehalogenases.
Pressure-Sensitive Insoles for Real-Time Gait-Related Applications

Wearable robotic devices require sensors and algorithms that can recognize the user state in real-time, in order to provide synergistic action with the body. For devices intended for locomotion-related applications, shoe-embedded sensors are a common and convenient choice, potentially advantageous for performing gait assessment in real-world environments. In this work, we present the development of a pair of pressure-sensitive insoles based on optoelectronic sensors for the real-time estimation of temporal gait parameters. The new design makes use of a simplified sensor configuration that preserves the time accuracy of gait event detection relative to previous prototypes. The system has been assessed relatively to a commercial force plate recording the vertical component of the ground reaction force (vGRF) and the coordinate of the center of pressure along the so-called progression or antero-posterior plane (CoPAP) in ten healthy participants during ground-level walking at two speeds. The insoles showed overall median absolute errors (MAE) of 0.06 (0.02) s and 0.04 (0.02) s for heel-strike and toe-off recognition, respectively. Moreover, they enabled reasonably accurate estimations of the stance phase duration (2.02 (2.03) % error) and CoPAP profiles (Pearson correlation coefficient with force platform ρCoP = 0.96 (0.02)), whereas the correlation with vGRF measured by the force plate was lower than that obtained with the previous prototype (ρvGRF = 0.47 (0.20)). These results confirm the suitability of the insoles for online sensing purposes such as timely gait phase estimation and discrete event recognition.
Metabolic Stability Assessment of New PARP Inhibitor Talazoparib Using Validated LC–MS/MS Methodology: In silico Metabolic Vulnerability and Toxicity Studies

Background Talazoparib (BMN673) is a new poly(ADP-ribose) polymerase inhibitor that has been FDA approved for patients suffering from metastatic breast cancer with germline BRCA mutations. Method and Results In the current study, an accurate and efficient liquid chromatography-tandem mass spectrometry (LC–MS/MS) analytical methodology was developed for TZB estimation in addition to its metabolic stability assessment. TZB and lapatinib (LAP) (which is chosen as an internal standard; IS) were separated using reversed phase elution system (Hypersil C18 column) with an isocratic mobile phase. The linearity range of the established method was 5–500 ng/mL (r2 ≥ 0.999) in the human liver microsomes (HLMs) matrix. Different parameters were calculated to confirm the method sensitivity (limit of quantification was 2.0 ng/mL), and reproducibility (intra- and inter-day precision and accuracy were below 3.1%) of our methodology. For evaluation of TZB metabolic stability in HLM matrix, intrinsic clearance (9.59 µL/min/mg) and in vitro half-life (72.7 mins) were calculated. TZB treatment discontinuations were reported due to adverse events and dose accumulation, so in silico metabolic vulnerability (experimental and in silico) and toxicity assessment (in silico) of TZB were performed utilizing P450 Metabolism and DEREK modules of StarDrop software. Conclusion TZB is slowly metabolized by the liver. TZB was reported to be minimally metabolized by the liver that approved our outcomes. We do recommend that plasma levels be monitored in cases when talazoparib is used for a long period of time, since it is possible for TZB to bioaccumulate after multiple doses to toxic levels. According to our knowledge, the current method is considered the first LC-MS/MS methodology for evaluating TZB metabolic stability. Further drug discovery studies can be done depending on this concept allowing the designing of new series of compounds with more safety profile through reducing side effects and improving metabolic behavior.
The Nocebo Effect and Informed Consent—Taking Autonomy Seriously

Abstract The nocebo effect, a phenomenon whereby learning about the possible side effects of a medical treatment increases the likelihood that one will suffer these side effects, continues to challenge physicians and ethicists. If a physician fully informs her patient as to the potential side effects of a medicine that may produce nocebogenic effects, which is usually conceived of as being a requirement associated with the duty to respect autonomy, she risks increasing the likelihood that her patient will experience these side effects and therefore suffer (unnecessary) harm, a violation of the duty of nonmaleficence. If, on the other hand, she intentionally withholds side effect information in an effort to protect her patient from suffering unnecessary harm from side effects, which is consistent with the duty of nonmaleficence, she violates the duty to respect patient autonomy. In this paper, the author discusses several previous attempts to deal with the nocebo effect and explains their weaknesses. He then proposes a means of managing the nocebo effect and argues that it does not share the weaknesses found in previous approaches. He concludes with a discussion of a simple, yet practical tool that might help clinicians manage the tension resulting from the nocebo effect.
Evaluation of p16/Ki-67 Dual-Stained Cytology in Triaging HPV-Positive Women during Cervical Cancer Screening

Background: We aimed to evaluate the utility of p16/Ki-67 dual-stained cytology for triaging human papillomavirus (HPV)-positive women. Methods: HPV-positive women ages ≥ 21 years were recruited in a multicenter prospective observational study between May 2016 and May 2017. The clinical performance of dual-stained cytology, with or without HPV16/18 genotyping, was evaluated for all HPV-positive women to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Results: 846 HPV-positive women ages ≥ 21 years with valid cervical biopsies were enrolled for this study. For CIN2+ detection, dual-stained cytology showed statistically higher specificity (85.28%) than Pap cytology (80.00%, P < 0.001) and HPV16/18 genotyping (72.36%, P < 0.001), while the sensitivity of dual-stained cytology (63.49%) remained comparable with that of Pap cytology (61.90%, P = 0.832) and HPV16/18 genotyping (61.90%, P = 0.897). HPV16/18 genotyping in combination with dual-stained cytology was more specific (62.50% vs. 58.06%, P < 0.001), while it showed similar sensitivity (86.51% vs. 85.71%, P = 1.000), as compared with HPV16/18 genotyping in combination with Pap cytology. Similar patterns were also observed for CIN3+. Conclusions: p16/Ki-67 dual-stained cytology, either alone or in combination with HPV16/18 genotyping, showed a good stratification with high specificity and comparable sensitivity for HPV-positive women. Impact: This is one of the few studies that has evaluated the performance of dual-stained cytology for triaging HPV-positive women in China. The higher specificity and comparable sensitivity of dual-stained cytology in comparison with Pap cytology in the detection of CIN2+ or CIN3+ is of vital importance to developing countries, where Pap cytology faces many challenges.
Preliminary investigation on a new natural based poly(gamma-glutamic acid)/Chitosan bioink.

The study aims to investigate a novel bioink made from Chitosan (Cs)/ poly(gamma-glutamic acid) (Gamma-PGA) hydrogel that takes advantage of the two biodegradable and biocompatible polymers meeting most of the requirements for biomedical applications. The bioink could be an alternative to other materials commonly used in 3D-bioprinting such as gelatin or alginate. Cs/ Gamma-PGA hydrogel was prepared by double extrusion of Gamma-PGA and Cs solutions, where 2 × 105 human adult fibroblasts per ml Cs solution had been loaded, through Cellink 3D-Bioprinter at 37°C. A computer aided design model was used to get 3D-bioprinting of a four layers grid hydrogel construct with 70% infill. Hydrogel characterization involved rheology, FTIR analysis, stability study (mass loss [ML], fluid uptake [FU]), and cell retaining ability into hydrogel. 3D-bioprinted hydrogel gelation time resulted to be <60 s, hydrogel structure was maintained up to 36.79 Pa shear stress, FTIR analysis demonstrated Gamma-PGA/Cs interpolyelectrolyte complex formation. The 3D-bioprinted hydrogel was stable for 35 days (35% ML) in cell culture medium, with increasing FU. Cell loaded 3D-bioprinted Cs 6% hydrogel was able to retain 70% of cells which survived to printing process and cell viability was maintained during 14 days incubation.
Utility of Human Papillomavirus Testing for Cervical Cancer Screening in Korea

(1) Background: Cervical cancer is one of the most common cancers in Korean women. This study was performed to discover the utility of HPV (Human Papillomavirus) testing in screening of cervical lesions and to provide the prevalence of HPV and the genotype distribution in a single center of Korea. (2) Methods: A total of 15,141 women who underwent both HPV testing and cervical cytology were enrolled in this retrospective medical record review study. (3) Results: HPV testing showed higher sensitivity than cytology for the detection of histological high-grade squamous lesions. Furthermore, the sensitivity and specificity of HPV testing varied depending on the method used. The BD Onclarity™ HPV assay had higher sensitivity (90%) than the MyHPV CHIP™ kit (all types of HPV: 82%; high-risk HPV: 76%) for high-grade squamous lesions. A combination of MyHPV CHIP™ and cytology detected 90.9% (30/33) of histological high-grade squamous lesions. A combination of BD Onclarity™ HPV assay and cytology detected 96.55% (84/87) of histological high-grade squamous lesions. In addition, HPV prevalence and genotype distribution were different depending on the HPV testing method used. (4) Conclusion: HPV testing showed higher sensitivity than cytology, but the sensitivity and specificity of HPV testing had variation depending on the method used.
Analysis of the Bioactive Metabolites of the Endangered Mexican Lost Fungi Campanophyllum – A Report from India

Abstract Meghalaya, (in India), in the region of the mega-biodiversity hotspots, is home to a plethora of wild mushrooms. The present study concerns the exploration of the order Agaricales, which includes rare gilled mushrooms considered endangered under IUCN A4c criteria, due to the declining habitat. Electron microscopy of the gill sections revealed an abundance of clamp connections, hyphal cell walls, cystidia, and basidia. This rare species which belongs to the family Cyphellaceae, exhibits morphological and molecular differences from the Cyphella spp. Phylogenetic analysis revealed that it formed a clade under the genus Campanophyllum of the order Agaricales, confirmed by both Neighbor Joining (NJ) and Bayesian phylogenetic analysis. Being nutritionally potent along with its efficient antioxidant value, the fungal extract shows significant rise of two-fold in the antimicrobial activity along with the commercial antibiotics. The compound, Phenol, 2, 4-bis (1, 1-Dimethylethyl) (2, 4-DTBP) showed in ample range in the fungal extract along with aliphatic hydrocarbons, terpene, alcohol and volatile organic compounds on further characterization in GCMS. The present study indicates the endangered Campanophyllum proboscideum could be a rich source of natural antioxidants and an effective pharmaceutical agent.
High-throughput, combinatorial synthesis of multimetallic nanoclusters

Significance Multielement nanomaterials hold great promise for various applications due to their widely tunable surface chemistry, yet it remains challenging to efficiently study this multidimensional space. Conventional approaches are typically slow and depend on serendipity, while a robust and general synthesis is still lacking among increasingly complex compositions. We report a high-throughput technique for combinatorial compositional design (formulation in solution phases) and rapid synthesis (within seconds) of ultrafine multimetallic nanoclusters with a homogeneous alloy structure. We synthesized and screened the PtPdRhRuIrFeCoNi compositional space using scanning droplet cell electrochemistry, with two promising catalysts quickly identified and further verified in a rotating disk setup. The reported high-throughput approach establishes a facile and reliable pipeline to significantly accelerate material discovery in multimetallic nanomaterials. Multimetallic nanoclusters (MMNCs) offer unique and tailorable surface chemistries that hold great potential for numerous catalytic applications. The efficient exploration of this vast chemical space necessitates an accelerated discovery pipeline that supersedes traditional “trial-and-error” experimentation while guaranteeing uniform microstructures despite compositional complexity. Herein, we report the high-throughput synthesis of an extensive series of ultrafine and homogeneous alloy MMNCs, achieved by 1) a flexible compositional design by formulation in the precursor solution phase and 2) the ultrafast synthesis of alloy MMNCs using thermal shock heating (i.e., ∼1,650 K, ∼500 ms). This approach is remarkably facile and easily accessible compared to conventional vapor-phase deposition, and the particle size and structural uniformity enable comparative studies across compositionally different MMNCs. Rapid electrochemical screening is demonstrated by using a scanning droplet cell, enabling us to discover two promising electrocatalysts, which we subsequently validated using a rotating disk setup. This demonstrated high-throughput material discovery pipeline presents a paradigm for facile and accelerated exploration of MMNCs for a broad range of applications.
Coupling Structural and Adsorption Properties of Metal-Organic Frameworks: From Pore Size Distribution to Pore Type Distribution.

Metal-organic frameworks (MOFs) attract a rapidly growing attention across the disciplines due to their multifarious pore structures and unique ability to selectively adsorb, store, and release various guest molecules. Pore structure characterization and coupling of adsorption and structural properties is imperative for rational design of advanced MOF materials and their applications. The pore structure of MOFs represents a three-dimensional network comprised of several types of pore compartments: interconnected cages and channels distinguished by their size, shape, and chemistry. Here, we propose a novel methodology for pore structure characterization of MOF materials based on matching the experimental adsorption isotherms to in-silico generated fingerprint isotherms of adsorption in individual pore compartments of the ideal crystal. The proposed approach couples structural and adsorption properties, determines the contributions of different types of pores into the total adsorption and estimates to what extent the pore structure of the sample under investigation is different from the ideal crystal. The MOF pore structure is characterized by the pore type distribution (PTD), which is more informative than the traditional pore size distribution that is based on oversimplistic pore models. The method is illustrated on the example of Ar adsorption at 87 K on hydrated and dehydrated structures of Cu-BTC, one of the most well-known MOF materials. The PTD determined from the experimental isotherm provides an estimate of the crystal fraction in the sample, and accessibility and degree of hydration of different types of pore compartments. In addition, the PTD determined from the experimental adsorption isotherm is used to predict the isosteric heat of adsorption that provides important information on the specifics of adsorption interactions. The results are found in excellent agreement with experimental data. Such detailed information about the pore structure and adsorption properties of practical MOF samples cannot be obtained with currently available methods of adsorption characterization.
Carbohydrates designed with different digestion rates modulate gastric emptying response in rats

Abstract We sought to determine whether design of carbohydrate-based microspheres to have different digestion rates, while retaining the same material properties, could modulate gastric emptying through the ileal brake. Microspheres made to have three slow digestion rates and a rapidly digested starch analogue (maltodextrin) were administrated to rats by gavage and starch contents in the stomach, proximal and distal small intestine, and caecum were measured 2 h post-gavage. A stepwise increase in the amount of starch retained in the stomach was found for microspheres with incrementally slower rates of digestion. Postprandial glycaemic and insulinaemic responses were incrementally lower for the different microspheres than for the rapidly digestible control. A second-meal effect was observed for slowly digestible starch (SDS) microspheres compared to glucose. Thus, dietary slowly digestible carbohydrates were designed to elicit incremental significant changes in gastric emptying, glycaemic and insulinaemic responses, and they may be a means to trigger the ileal brake.