Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-Reactivity, Epitope Mapping, and Potency of Monoclonal Antibodies to Class 5 Fimbrial Tip Adhesins of Enterotoxigenic Escherichia coli

Enterotoxigenic Escherichia coli (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed to be a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of the class 5 fimbrial family being the best characterized. The eight related members of the ETEC class 5 fimbrial family are subdivided into three subclasses (5a, 5b, and 5c) that share similar structural arrangements, including a fimbrial tip adhesin. ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is a leading diarrheagenic bacterial pathogen among travelers and children in resource-limited regions. Adherence to host intestinal cells mediated by ETEC fimbriae is believed to be a critical first step in ETEC pathogenesis. These fimbriae are categorized into related classes based on sequence similarity, with members of the class 5 fimbrial family being the best characterized. The eight related members of the ETEC class 5 fimbrial family are subdivided into three subclasses (5a, 5b, and 5c) that share similar structural arrangements, including a fimbrial tip adhesin. However, sequence variability among the class 5 adhesins may hinder the generation of cross-protective antibodies. To better understand functional epitopes of the class 5 adhesins and their ability to induce intraclass antibody responses, we produced 28 antiadhesin monoclonal antibodies (MAbs) to representative adhesins CfaE, CsbD, and CotD, respectively. We determined the MAb cross-reactivities, localized the epitopes, and measured functional activities as potency in inhibition of hemagglutination induced by class 5 fimbria-bearing ETEC. The MAbs’ reactivities to a panel of class 5 adhesins in enzyme-linked immunosorbent assays (ELISAs) revealed several reactivity patterns, including individual adhesin specificity, intrasubclass specificity, intersubclass specificity, and class-wide cross-reactivity, suggesting that some conserved epitopes, including two conserved arginines, are shared by the class 5 adhesins. However, the cross-reactive MAbs had functional activities limited to strains expressing colonization factor antigen I (CFA/I), coli surface antigen 17 (CS17), or CS1, suggesting that the breadth of functional activities of the MAbs was more restricted than the repertoire of cross-reactivities measured by ELISA. The results imply that multivalent adhesin-based ETEC vaccines or prophylactics need more than one active component to reach broad protection.
Structural Alterations in Deep Brain Structures in Type 1 Diabetes

Even though well known in type 2 diabetes, the existence of brain changes in type 1 diabetes (T1D) and both their neuroanatomical and clinical features are less well characterized. To fill the void in the current understanding of this disease, we sought to determine the possible neural correlate in long-duration T1D at several levels, including macrostructural, microstructural cerebral damage, and blood flow alterations. In this cross-sectional study, we compared a cohort of 61 patients with T1D with an average disease duration of 21 years with 54 well-matched control subjects without diabetes in a multimodal MRI protocol providing macrostructural metrics (cortical thickness and structural volumes), microstructural measures (T1-weighted/T2-weighted [T1w/T2w] ratio as a marker of myelin content, inflammation, and edema), and cerebral blood flow. Patients with T1D had higher T1w/T2w ratios in the right parahippocampal gyrus, the executive part of both putamina, both thalami, and the cerebellum. These alterations were reflected in lower putaminal and thalamic volume bilaterally. No cerebral blood flow differences between groups were found in any of these structures, suggesting nonvascular etiologies of these changes. Our findings implicate a marked nonvascular disruption in T1D of several essential neural nodes engaged in both cognitive and motor processing.
The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model

Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken embryo tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from embryo tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in embryo tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV.
Genetic variation in the MacAB-TolC efflux pump influences pathogenesis of invasive Salmonella isolates from Africa

The various sub-species of Salmonella enterica cause a range of disease in human hosts. The human-adapted Salmonella enterica serovar Typhi enters the gastrointestinal tract and invades systemic sites to cause enteric (typhoid) fever. In contrast, most non-typhoidal serovars of Salmonella are primarily restricted to gut tissues. Across Africa, invasive non-typhoidal Salmonella (iNTS) have emerged with an ability to spread beyond the gastrointestinal tract and cause systemic bloodstream infections with increased morbidity and mortality. To investigate this evolution in pathogenesis, we compared the genomes of African iNTS isolates with other Salmonella enterica serovar Typhimurium and identified several macA and macB gene variants unique to African iNTS. MacAB forms a tripartite efflux pump with TolC and is implicated in Salmonella pathogenesis. We show that macAB transcription is upregulated during macrophage infection and after antimicrobial peptide exposure, with macAB transcription being supported by the PhoP/Q two-component system. Constitutive expression of macAB improves survival of Salmonella in the presence of the antimicrobial peptide C18G. Furthermore, these macAB variants affect replication in macrophages and influence fitness during colonization of the murine gastrointestinal tract. Importantly, the infection outcome resulting from these macAB variants depends upon both the Salmonella Typhimurium genetic background and the host gene Nramp1, an important determinant of innate resistance to intracellular bacterial infection. The variations we have identified in the MacAB-TolC efflux pump in African iNTS may reflect evolution within human host populations that are compromised in their ability to clear intracellular Salmonella infections.
Transposable Element Evolution in the Allotetraploid Capsella bursa-pastoris

Premise of the study Shifts in ploidy affect the evolutionary dynamics of genomes in a myriad of ways. Population genetic theory predicts that transposable element (TE) proliferation may follow because the genome wide efficacy of selection should be reduced and the increase in gene copies may mask the deleterious effects of TE insertions. Moreover, in allopolyploids TEs may further accumulate because of hybrid breakdown of TE silencing. However, to date the evidence of TE proliferation following an increase in ploidy is mixed, and the relative importance of relaxed selection vs. silencing breakdown remains unclear. Methods We used high-coverage whole genome sequence data to evaluate the abundance, genomic distribution, and population frequencies of TEs in the self-fertilizing recent allotetraploid Capsella bursa-pastoris (Brassicaceae). We then compared the C. bursa-pastoris TE profile with that of its two parental diploid species, outcrossing C. grandiflora and self-fertilizing C. orientalis. Key results We found no evidence that C. bursa-pastoris has experienced a large genome wide proliferation of TEs relative to its parental species. However, when centromeric regions are excluded, we find evidence of significantly higher abundance of retrotransposons in C. bursa-pastoris along the gene-rich chromosome arms, compared to C.grandiflora and C. orientalis. Conclusions The lack of a genome-wide effect of allopolyploidy on TE abundance, combined with the increases TE abundance in gene-rich regions suggest that relaxed selection rather than hybrid breakdown of host silencing explains the TE accumulation in C. bursa-pastoris
Gaps in Training: Misunderstandings of Airway Management in Medical Students and Internal Medicine Residents

Objectives (1) Evaluate baseline airway knowledge of medical students (MSs) and internal medicine (IM) residents. (2) Improve MS and IM resident understanding of airway anatomy, general tracheostomy and laryngectomy care, and management of airway emergencies. Methods A before-and-after survey study was carried out over a single academic year. MS and IM resident knowledge was evaluated before and after an educational, grand rounds–style lecture reviewing airway anatomy, tracheostomy tube components, tracheostomy and laryngectomy care, and clinical vignettes. The primary outcome measure was change in pre- and postlecture survey scores. Results Prelecture surveys were completed by 90 participants, and 83 completed a postlecture assessment. Postlecture scores were statistically improved for all questions on the assessment (P < .001). Level of training did not confer an improved pre- or postlecture survey score. Discussion While the majority of participants in our study had previously cared for patients with a tracheostomy or laryngectomy, less than half were able to correctly address basic airway emergencies. Senior IM residents were no more proficient than MSs in addressing airway emergencies. The lack of formal airway training places patients at risk with routine care and in emergencies, demonstrating the need for formal airway education for early medical trainees. Implications for Practice Our data demonstrate a serious gap in MS and IM resident knowledge with respect to emergent airway care in patients with tracheostomies and laryngectomies. An interdepartmental collaborative curriculum offers a realistic and potentially life-saving solution for medical trainees.
Testing the low dose mixtures hypothesis from the Halifax project

Abstract In 2013, 60 scientists, representing a larger group of 174 scientists from 26 nations, met in Halifax, Nova Scotia to consider whether – using published research – it was logical to anticipate that a mixture of chemicals, each thought to be non-carcinogenic, might act together in that mixture as a virtual carcinogen. The group identified 89 such chemicals, each one affecting one or more Hallmark(s) – collectively covering all Hallmarks of Cancer – confirming the possibility that a chemical mixture could induce all the Hallmarks and function as a virtual carcinogen, thereby supporting the concern that chemical safety research that does not evaluate mixtures, is incomplete. Based on these observations, the Halifax Project developed the Low-Dose Carcinogenesis Hypothesis which posits “…that low-dose exposures to [mixtures of] disruptive chemicals that are not individually carcinogenic may be capable of instigating and/or enabling carcinogenesis. ” Although testing all possible combinations of over 80,000 chemicals of commerce would be impractical, prudence requires designing a methodology to test whether low-dose chemical mixtures might be carcinogenic. As an initial step toward testing this hypothesis, we conducted a mini review of published empirical observations of biological exposures to chemical mixtures to assess what empirical data exists on which to base future research. We reviewed studies on chemical mixtures with the criteria that the studies reported both different concentrations of chemicals and mixtures composed of different chemicals. We found a paucity of research on this important question. The majority of studies reported hormone related processes and used chemical concentrations selected to facilitate studying how mixtures behave in experiments that were often removed from clinical relevance, i.e., chemicals were not studied at human-relevant concentrations. New research programs must be envisioned to enable study of how mixtures of small doses of chemicals affect human health, starting, when at all possible, from non-malignant specimens when studies are done in vitro. This research should use human relevant concentrations of chemicals, expand research beyond the historic focus on endocrine endpoints and endocrine related cancers, and specifically seek effects that arise uniquely from exposure to chemical mixtures at human-relevant concentrations.
Oxygen as a Controlling Factor in the Regeneration of Tubularia

I T WAS suggested by Morgan (1903) that the inhibition of regeneration when the cut end of Tubularia was placed in sand was due to lack of oxygen. Child (1927, 1928) has shown that small pieces of Corymorpha in contact with the bottom of a dish develop hydranths from the free surface and stolons from the surface in contact with the glass. He suggests that the differential exposure of the surfaces of the fragment results in a difference in respiratory exchange which may determine the new polarity. There has been no attempt to study quantitatively the relation between oxygen tension and regeneration in Tubularia or Corymorpha. This paper will discuss, first, some qualitative observations on regeneration of ends of stems of Tubularia under conditions of reduced oxygen supply, and, second, a quantitative study of the size of the hydranth, time for regeneration, and rate of regeneration at various oxygen tensions. The experiments were carried out with the very able assistance of Mr. John Moore, who determined the oxygen tensions. The work was supported by a grant from the Rockefeller Foundation.
Sensory experience during early sensitive periods shapes cross-modal temporal biases

Typical human perception features stable biases such as perceiving visual events as later than synchronous auditory events. The origin of such perceptual biases is unknown. To investigate the role of early sensory experience, we tested whether a congenital, transient loss of pattern vision, caused by bilateral dense cataracts, has sustained effects on audio-visual and tactile-visual temporal biases and resolution. Participants judged the temporal order of successively presented, spatially separated events within and across modalities. Individuals with reversed congenital cataracts showed a bias towards perceiving visual stimuli as occurring earlier than auditory (Expt. 1) and tactile (Expt. 2) stimuli. This finding stood in stark contrast to normally sighted controls and sight-recovery individuals who had developed cataracts later in childhood: both groups exhibited the typical bias of perceiving vision as delayed compared to audition. These findings provide strong evidence that cross-modal temporal biases depend on sensory experience during an early sensitive period.
Rehabilitation of patients post-COVID-19 infection: a literature review

Rehabilitation is important for patients with coronavirus disease 2019 (COVID-19) infection. Given the lack of guidelines in English on the rehabilitation of these patients, we conducted a review of the most recent reports. We performed this literature review using the principal research databases and included randomized trials, recommendations, quasi-randomized or prospective controlled clinical trials, reports, guidelines, field updates, and letters to the editor. We identified 107 studies in the database search, among which 85 were excluded after screening the full text or abstract. In total, 22 studies were finally included. The complexity of the clinical setting and the speed of spread of the severe acute respiratory syndrome coronavirus 2, which leads to rapid occupation of beds in the intensive care unit, make it necessary to discharge patients with COVID-19 who have mild symptoms as soon as possible. For these reasons, it is necessary to formulate rehabilitation programs for these patients, to help them restore physical and respiratory function and to reduce anxiety and depression, particularly patients with comorbidities and those who live alone or in rural settings, to restore a good quality of life.
The role of the working alliance in psychological treatment of substance use disorder outpatients

Abstract Objective: The main objective of this study was to explore the relationship between alliance and treatment outcome of substance use disorder (SUD) outpatients in routine care. Attachment, type of substance use, and treatment orientation were analyzed as potential moderators of this relationship. Method: Ninety-nine SUD outpatients rated their psychological distress before every session. Patients and therapists rated the alliance after every session. At treatment start and end, the patient completed the Alcohol Use Disorders Identification Test (AUDIT), the Drug Use Disorders Identification Test (DUDIT), and the Experiences in Close Relationships (ECR-S). Data were analyzed using multilevel growth curve modeling and Dynamic Structural Equation Modeling (DSEM). Results: The associations between alliance and outcome on psychological distress and substance use were, on average, weak. Within-patient associations between patient-rated alliance and outcome were moderated by self-rated attachment. Type of abuse moderated associations between therapist-rated alliance and psychological distress. No moderating effect was found for treatment orientation. Conclusions: Patients’ attachment style and type of abuse may have influenced the association between alliance and problem reduction. A larger sample size is needed to confirm these findings.
Recent Developments on Modeling for a 3-DOF Micro-Hand Based on AI Methods

Recently, soft actuators have been expected to have many applications in various fields. Most of the actuators are composed of flexible materials and driven by air pressure. The 3-DOF micro-hand, which is a kind of soft actuator, can realize a three degrees of freedom motion by changing the applied air pressure pattern. However, the input–output relation is nonlinear and complicated. In previous research, a model of the micro-hand was proposed, but an error between the model and the experimental results was large. In this paper, modeling for the micro-hand is proposed by using multi-output support vector regression (MSVR) and ant colony optimization (ACO), which is one of the artificial intelligence (AI) methods. MSVR estimates the input–output relation of the micro-hand. ACO optimizes the parameters of the MSVR model.
Investigation of ecological behavior of two Coccinellidae beetle adults for biological control

INVESTIGATION OF ECOLOGICAL BEHAVIOR OF TWO COCCINELLIDAE BEETLE ADULTS FOR BIOLOGICAL CONTROL Folukemi Ebunoluwa Adedipe Biological control is the use of natural enemies, which is an effective strategy to control and suppress pest populations in a given agroecosystem; however farmers are not motivated to adopt this method because of the high cost and temporal unavailability of natural enemies. This thesis is based on reports on findings of a series of laboratory experiments carried out to investigate ecological behavioral of two major natural enemies (i.e. Harmonia axyridis Pallas (Coleoptera: Coccinellidae) and Cryptolaemus montrouzieri Mulsant (Coleoptera: Coccinellidae). Firstly, study was conducted to determine if H. axyridis could be attracted into cropping areas using companion plants with different olfactory and visual cues. Ten potential plants that can attract and provide H. axyridis with nectar and pollen were selected for a preference test. The result of the olfactory preference test showed that there was significant difference in the plant preference by H. axyridis; sunflower was the most preferred attractant plants. In a visual preference test, H. axyridis preferred yellow to other colors. Secondly, study was conducted to investigate within-plant distribution of long-tailed mealybug, Pseudococcus longispinus (Targioni-Tozzetti) (Hemiptera: Pseudococcidae) to quantify the searching and handling time of C. montrouzieri on three different plants heights and to determine preference of C. montrouzieri to the size of P. longispinus. P. longispinus were found more on the upper parts of the plants regardless of the height. The time C. montrouzieri spent to find the first P. longispinus was significantly (P < 0.05) different among the three different plant heights at two different releasing points. However, there were no significant differences in handling time and cleaning time. C. montrouzieri preferred smaller size of P. longispinus to medium and larger size. The finding of results in this thesis suggested that H. axyridis and C. montrouzieri can potentially be used as economical and sustainable biological control agents.
Recurrent Acute Pancreatitis in a Patient with COVID-19 Infection

Patient: Male, 38-year-old Final Diagnosis: Recurrent idiopathic acute pancreatitis with COVID-19 Symptoms: Nausea • severe abdominal pain • fever • vomiting Medication:— Clinical Procedure: — Specialty: Gastroenterology and Hepatology • Infectious Diseases • General and Internal Medicine Objective: Unusual clinical course Background: The novel COVID-19 disease has infected more than 2 million people worldwide, causing more than 120 000 deaths. While the disease is known to primarily affect the respiratory system, gastrointestinal manifestations can also occur. However, little is known about the development of acute pancreatitis in COVID-19. The present report highlights a patient with no precipitating risk factors for pancreatitis who presented with recurring acute pancreatitis following the diagnosis of SARS-CoV-2 infection. Case Report: An otherwise healthy 38-year-old man presented to the Emergency Department (ED) with fever and epigastric pain. Laboratory testing revealed a lipase level of 10 255 ukat/L. An abdominal ultrasound showed no gallstones. After ruling out the possible causes of acute pancreatitis, a diagnosis of idiopathic acute pancreatitis was made. He received conservative management and was discharged home after being medically stabilized. Of note, the patient tested positive for SARS-CoV-2 infection at a local testing center 1 week prior to presenting to the ED. One week following the discharge, the patient returned with recurrent severe epigastric pain. Laboratory testing showed a lipase level of 20 320 ukat/L. An abdominal CT revealed acute pancreatitis. Further workups, including abdominal ultrasound, hepatitis serology, and immunoglobulin G for autoimmune pancreatitis, were unrevealing. Repeated SARS-CoV-2 testing produced positive results. Conclusions: The temporal relationship between clinical presentation of acute pancreatitis and SARS-CoV-2 infection in this patient with no precipitating risk factors for pancreatitis suggests COVID-19-associated acute pancreatitis. Our review of the literature found a handful of reported cases of acute pancreatitis in patients with coexisting SARS-CoV-2 infection, and this report presents the first presumptive case of COVID-19-associated recurring acute pancreatitis.