Miracle-dz/UniFAR-FTUs huggingface dataset:
Atypical cells in fine needle aspiration biopsies of pancreas: Causes, work‐up, and recommendations for management

Endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is a sensitive and specific method for diagnosing cancer in solid pancreatic masses. However, some cases receive indeterminate atypical diagnoses, which creates management dilemmas. In the 2014 Papanicolaou Society of Cytopathology (PSC) standardized guidelines for pancreatobiliary cytology, specimens in the “Atypical” category show a spectrum of architectural and/or cellular changes beyond normal or reactive, but, quantitatively or qualitatively, insufficient for classification as neoplastic (benign/other), suspicious or positive for malignancy. Implementation of the PSC system decreased atypical diagnoses, particularly for cystic lesions, and redistributed many cases into benign and neoplastic categories. Because no set cytologic criteria exist for the “Atypical” category there is wide variability in its use, and its frequency ranges from 0%–16% (mean 6%). It consists of a heterogeneous mix of cases that occur because of preanalytic, lesion‐specific (low cellularity, necrosis, cystic, reactive and premalignant changes), to pathologist‐dependent factors (experience, expertise, training and institutional case volume). Outcomes of atypical diagnoses in solid pancreatic masses range from benign to premalignant and malignant and include reactive atypia in pancreatitis, well differentiated adenocarcinoma, and non‐ductal malignancies. The associated risk of malignancy (ROM) ranges from 28%–100%, with an overall intermediate ROM in large‐scale studies. Cytopathologists and institutions should monitor and keep their personal and/or laboratory's atypical rates low by judiciously using rapid onsite evaluation, ancillary studies, consensus or expert review, as well as correlation with clinical and radiologic findings. Early repeat EUS‐FNA is indicated for unresolved cases.
Lessons from studying roundworm and whipworm in the mouse: common themes and unique features

Abstract Abstract Ascaris lumbricoides, the roundworm, and Trichuris trichiura, the whipworm, are human intestinal nematode parasites; both are soil-transmitted helminths, are often placed together in an epidemiological context and both remain neglected despite high prevalence. Our understanding of parasitic disease continues to be enhanced through animal models. Despite the similarities between whipworm and roundworm, there are key differences between the two species and these have influenced the application of their respective animal models. In the case of T. trichiura, the fact that a murine equivalent, T. muris completes its life cycle in a mouse model has greatly enhanced our knowledge of whipworm biology, pathogenicity and immunology. In contrast, A. lumbricoides and its porcine equivalent, Ascaris suum, lack a rodent model in which the life cycle is completed. However, evidence continues to accumulate demonstrating that mice represent useful models of early Ascaris infection, a key stage of the life cycle. The use of mouse models for both Ascaris and Trichuris has a long history with early pioneers discovering fundamental aspects of each parasite's biology. Novel technologies and perspectives, as outlined in this special issue, demonstrate how through the prism of mouse models, we can continue to explore the similarities and differences between roundworms and whipworms.
Facile synthesis of Cu/Co-ZIF nanoarrays for non-enzymatic glucose detection

Cu/Co-ZIF nanoflake arrays on carbon cloth are fabricated by controlling the introducing of Cu2+ ions during the growth of Co-ZIF. The Cu/Co-ZIF-20 electrode prepared with 20 mM Cu2+ possesses large electrochemically active surface area and bimetallic active sites, which can be revealed by cyclic voltammetry tests. The amperometric i–t measurements demonstrate that the Cu/Co-ZIF-20 electrode displays a wide linear range from 0.05 mM to 6.0 mM, and a high sensitivity of 1.03 mA mM−1 cm−2. Good selectivity, repeatability and practical applicability indicate its promising application in enzyme-free glucose sensing.
Neuromarkers from Whole-Brain Functional Connectivity Reveal the Cognitive Recovery Scheme for Overt Hepatic Encephalopathy after Liver Transplantation

Abstract Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with overt hepatic encephalopathy (OHE). Liver transplantation (LT) can restore liver function, but how it reverses the impaired brain function is still unclear. MRI of resting-state functional connectivity can help reveal the underlying mechanisms that lead to these cognitive deficits and cognitive recovery. In this study, 64 patients with cirrhosis (28 with OHE; 36 without OHE) and 32 healthy control subjects were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated presurgical and postsurgical neurocognitive performance in cirrhosis patients using psychomotor tests. Network-based statistics found significant disrupted connectivity in both groups of cirrhotic patients, with OHE and without OHE, compared with control subjects. However, the presurgical connectivity disruption in patients with OHE affected a greater number of connections than those without OHE. The decrease in functional connectivity for both OHE and non-OHE patient groups was reversed after LT to the level of control subjects. An additional hyperconnected network (i.e., higher connected than control subjects) was observed in OHE patients after LT. Regarding the neural–behavior relationship, the functional network that predicted cognitive performance in healthy individuals showed no correlation in presurgical cirrhotic patients. The impaired neural–behavior relationship was re-established after LT for non-OHE patients, but not for OHE patients. OHE patients displayed abnormal hyperconnectivity and a persistently impaired neural–behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery compared with those without, which needs further clarification in future studies.
Designing Self-Inhibitory fusion peptide analogous to viral spike protein against novel severe acute respiratory syndrome (SARS-CoV-2)

Abstract COVID-19 is a highly contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is declared pandemic by the World Health Organization (WHO). The spike protein of SARS-CoV-2 is a key component playing a pivotal role in facilitating viral fusion as well as release of genome into the host cell. Till date there is no clinically approved vaccine or drug available against Covid-19. We designed four hydrophobic inhibitory peptides (ITPs) based on WWIHS (Wimley and White interfacial hydrophobicity scale) score, targeting the HR1 domain of spike protein. Two inhibitory peptides out of four have a strong affinity to the hydrophobic surface of HR1 domain in pre-fusion spike protein. The MD simulation result showed the strong accommodation of ITPs with HR1 domain surface. These self-inhibitory peptides mimic the function of HR2 by binding to HR1 domain, thus inhibiting the formation of HR1-HR2 post-fusion complex, which is a key structure for virus-host tropism. Communicated by Ramaswamy H. Sarma Proposed mechanism of inhibitory peptides against Covid-19.
Health Service- and Provider-Level Factors Influencing Engagement in HIV Pre-Exposure Prophylaxis Care Among Male Sex Workers.

Multilevel barriers to pre-exposure prophylaxis (PrEP) care among male sex workers (MSW) include aspects of interactions with health services and providers. We examined relationships between health service- and provider-level factors and PrEP care among MSW. Between 2017 and 2019, we enrolled 111 MSW in the Northeast United States who were not on PrEP, but expressed interest in potentially using PrEP, in a behavioral intervention to promote PrEP uptake and adherence. Using baseline data, we examined whether having a primary care provider, past year frequency of medical visits, comfort discussing sexual practices with providers, and transportation difficulties to accessing general health care were associated with PrEP use self-efficacy, anticipated barriers to PrEP uptake, adherence, and retention (linear regression), and intention to initiate PrEP (logistic regression). Models adjusted for age, race/ethnicity, sexual identity, education, and income. Participants' mean age was 34.2 [standard deviation (SD) = 8.5], and 47% were non-White. Three-quarters (76%) intended to initiate PrEP within the next month. Comfort discussing sexual practices with providers was associated with PrEP use self-efficacy (b = 0.41, p = 0.008). Comfort discussing sexual practices with providers was negatively associated with anticipated barriers to PrEP uptake (b = -0.29, p = 0.006). Transportation difficulties to accessing general health care were associated with barriers to PrEP uptake (b = 0.30, p = 0.007) and barriers to PrEP adherence and retention (b = 0.57, p < 0.001). No health service- and provider-level characteristics were associated with intention to initiate PrEP. PrEP programs targeting MSW may benefit from interventions to foster communication between MSW and providers about sexual practices and should consider structural barriers to accessing care, including lack of access to transportation.
Expression of genes associated with nutrient uptake in intestines of chickens with different growth potentials show temporal changes but are not correlated with growth

ABSTRACT 1. The study was designed to compare the expression of genes that encode proteins located at either the brush border (BB) or basolateral (BL) of the gut epithelium among fast and slow-growing broilers. 2. Six broiler breeds with different growth capacities were used: Ross 708, Hubbard H1 (HH1), Cobb 500, Longenecker’s Heritage (LHR), Red-Bro, and the Athens Canadian Randombred Control (ACRB). Birds were sampled between embryonic day (ED) 19 and day 35 post-hatch (PH). 3. Performance parameters indicated that Ross 708, HH1, and Cobb 500 had the highest body weights (BW) while ACRBs had the lowest. 4. Quantitative RT-PCR was performed on 13 genes encoding proteins associated with nutrient processing and uptake. Statistical analysis was carried out (ANOVA) for eight BB genes: Aminopeptidase N (APN), four amino acid transporters, (ATBo,+, BoAT, bo,+AT, EAAT3) a di- and tri-peptide transporter (PepT1), and two sugar transporters (GLUT5 and SGLT1). Analysis of four amino acid transporters (CAT1, CAT2, LAT1, and γ+LAT1), and a single sugar transporter (GLUT2) associated with BL was carried out. 5. Four BB associated genes (APN, EAAT3, BoAT, and b0,+AT) in the small intestine were negatively correlated with growth. 6. In most cases, genes encoding BB proteins increased in expression over time (P < 0.05) in the small intestine, while, in the caeca, the expression decreased (P < 0.05). The mRNA of BL-associated proteins showed decreased (P < 0.05) expression over time in all gut segments, with exception of GLUT2, which increased in expression in the small intestine. 7. The temporal changes in gene expression were consistent among bird lines and BB associated genes tended to increase over time, while BL associated genes tended to decrease over time. Correlation analysis indicated that mRNA expression of nutrient transporter genes may not be a good predictor of growth potential.
Dimensional personality impairment is associated with disruptions in intrinsic intralimbic functional connectivity

Abstract Background Recently proposed alternative dimensional models of personality disorder (PD) place the severity of impairments in self and interpersonal functioning at the core of personality pathology. However, associations of these impairments with disturbances in social, cognitive, and affective brain networks remain uninvestigated. Methods The present study examined patterns of resting-state functional connectivity (rsFC) in a sample of 74 age- and sex-matched participants (45 inpatients with PD and 29 healthy controls). At a minimum, PD patients carried a diagnosis of borderline PD, although the majority of the sample had one or more additional PDs. rsFC patterns in the following networks were compared between groups and in association with dimensional personality impairments: default mode network (DMN)/core mentalization, frontolimbic, salience, and central executive. Further, the extent to which variation in rsFC was explained by levels of personality impairment as compared to typology-specific borderline PD symptom severity was explored. Results Relative to controls, the PD group showed disruptions in rsFC within the DMN/core mentalization and frontolimbic networks. Among PD patients, greater severity of dimensional self-interpersonal impairment was associated with stronger intralimbic rsFC. In contrast, severity of borderline PD-specific typology was not associated with any rsFC patterns. Conclusions Disruptions in core mentalization and affective networks are present in PD. Higher intralimbic functional connectivity may underlie self-interpersonal personality impairment in PD regardless of diagnostic typology-specific PD symptoms, providing initial neurobiological evidence supporting alternative dimensional conceptualizations of personality pathology.
NKTR-255, a polymer-conjugated IL-15 with unique mechanisms of action on T and natural killer cells.

NKTR-255 is a novel polyethylene glycol (PEG)-conjugate of recombinant human IL-15 (rhIL-15) being examined as a potential cancer immunotherapeutic. Since IL-15 responses can be mediated by trans- or cis-presentation via IL-15Rα or soluble IL-15/IL-15Rα complexes, we investigated the role of IL-15Rα in driving NKTR-255 responses using defined naïve and memory ovalbumin-specific CD8 T cells (OT-I) CD8 T and NK cells in mice. NKTR-255 induced a 2.5 and 2.0-fold expansion of CD8 T and NK cells, respectively in WT mice. In adoptive transfer studies, proliferation of naïve and memory Wt OT-I T cells in response to NKTR-255 was not impaired in IL-15Rα-/- mice, suggesting trans-presentation was not utilized by NKTR-255. Interestingly, naïve IL-15Rα-/- OT-I cells had deficient responses to NKTR-255 while memory IL-15Rα-/- OT-I cell responses were partially impaired, suggesting that naive CD8 T cells are more dependent on cis-presentation of NKTR-255 than memory CD8 T cells. In bone marrow chimeras studies, IL-15Rα-/- and WT NK cells present in WT recipients had similar responses to NKTR-255, suggesting that cis-presentation is not utilized by NK cells. NKTR-255 could form soluble complexes with IL-15Rα; binding to murine IL-15Rα generated superagonists that preferentially stimulated NK cells showing that conversion to IL-15Rβ agonist biases the response towards NK cells. These findings highlight the ability of NKTR-255 to utilize IL-15Rα for cis-presentation and act as an IL-15Rαβ agonist on CD8 T cells.
Distal Aortic Remodeling after Type A Dissection Repair: An Ongoing Mirage

Remodeling is a commonly encountered term in the field of cardiothoracic surgery that is often used to describe various pathophysiological changes in the dimension, structure, and function of various cardiac chambers, including the aorta. Stanford type A or DeBakey type 1 aortic dissection (TAAD) is a perplexing pathologic condition that can present surgical teams with the need to navigate a maze of complex decision-making. Ascending or hemi-arch replacement leaves behind a significant amount of distal diseased aortic tissue, which might have a persistent false lumen or primary or secondary intimal tears (or communications between lumina), which can lead to dilatation of the aortic arch. Unfavorable aortic remodeling is a major cause of distal aortic deterioration after the index surgery. Cardiac surgeons are aware of post-surgical cardiac chamber remodeling, but the concept of distal aortic remodeling is still idealized. The contemporary literature from established aortic centers supports aggressive management of the residual aortic pathology during the index surgery, and with continuing technical advancements, endovascular stenting options are readily available for patients with TAAD or for complicated type B aortic dissection cases. This review discusses the pathophysiology and treatment options for favorable distal aortic remodeling, as well as its impact on mid- to long-term outcomes following TAAD repair.
Differences in health outcomes for high‐need high‐cost patients across high‐income countries

Abstract Objective This study explores variations in outcomes of care for two types of patient personas—an older frail person recovering from a hip fracture and a multimorbid older patient with congestive heart failure (CHF) and diabetes. Data Sources We used individual‐level patient data from 11 health systems. Study Design We compared inpatient mortality, mortality, and readmission rates at 30, 90, and 365 days. For the hip fracture persona, we also calculated time to surgery. Outcomes were standardized by age and sex. Data Collection/Extraction Methods Data was compiled by the International Collaborative on Costs, Outcomes and Needs in Care across 11 countries for the years 2016–2017 (or nearest): Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States. Principal Findings The hip sample across ranged from 1859 patients in Aragon, Spain, to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia, and the majority of hip patients across countries were female. The congestive heart failure (CHF) sample ranged from 742 patients in England to 21,803 in the United States. Mean age ranged from 77.2 in the United States to 80.3 in Sweden, and the majority of CHF patients were males. Average in‐hospital mortality across countries was 4.1%. for the hip persona and 6.3% for the CHF persona. At the year mark, the mean mortality across all countries was 25.3% for the hip persona and 32.7% for CHF persona. Across both patient types, England reported the highest mortality at 1 year followed by the United States. Readmission rates for all periods were higher for the CHF persona than the hip persona. At 30 days, the average readmission rate for the hip persona was 13.8% and 27.6% for the CHF persona. Conclusion Across 11 countries, there are meaningful differences in health system outcomes for two types of patients.
Primary care practice-based care management for chronically ill patients (PraCMan) in German healthcare: Outcome of a propensity-score matched cohort study

Abstract Background Growing prevalence of chronic diseases is a rising challenge for healthcare systems. The Primary Care Practice-Based Care Management (PraCMan) programme is a comprehensive disease management intervention in primary care in Germany aiming to improve medical care and to reduce potentially avoidable hospitalisations for chronically ill patients. Objectives This study aimed to assess the effect of PraCMan on hospitalisation rate and related costs. Methods A retrospective propensity-score matched cohort study was performed. Reimbursement data related to patients treated in general practices between 1st July 2013 and 31st December 2017 were supplied by a statutory health insurance company (AOK Baden-Wuerttemberg, Germany) to compare hospitalisation rate and direct healthcare costs between patients participating in the PraCMan intervention and propensity-score matched controls following usual care. Outcomes were determined for the one-year-periods before and 12 months after beginning of participation in the intervention. Results In total, 6148 patients participated in the PraCMan intervention during the observation period and were compared to a propensity-score matched control group of 6148 patients from a pool of 63,446 eligible patients. In the one-year period after the intervention, the per-patient hospitalisation rate was 8.3% lower in the intervention group compared to control (p = 0.0004). Per-patient hospitalisation costs were 9.4% lower in favour of the intervention group (p = 0.0002). Conclusion This study showed that the PraCMan intervention may be associated with a lower rate of hospital admissions and hospitalisation costs than usual care. Further studies may assess long-term effects of PraCMan and its efficacy in preventing known complications of chronic diseases.
Diabetes and cardiovascular diseases are associated with the worsening of intermittent hypoxaemia

Intermittent hypoxaemia is a risk factor for numerous diseases. However, the reverse pathway remains unclear. Therefore, we investigated whether pre‐existing hypertension, diabetes or cardiovascular diseases are associated with the worsening of intermittent hypoxaemia. Among the included 2,535 Sleep Heart Health Study participants, hypertension (n = 1,164), diabetes (n = 170) and cardiovascular diseases (n = 265) were frequently present at baseline. All participants had undergone two polysomnographic recordings approximately 5.2 years apart. Covariate‐adjusted linear regression analyses were utilized to investigate the difference in the severity of intermittent hypoxaemia at baseline between each comorbidity group and the group of participants free from all comorbidities (n = 1,264). Similarly, we investigated whether the pre‐existing comorbidities are associated with the progression of intermittent hypoxaemia. Significantly higher oxygen desaturation index (β = 1.77 [95% confidence interval: 0.41–3.13], p = 0.011), desaturation severity (β = 0.07 [95% confidence interval: 0.00–0.14], p = 0.048) and desaturation duration (β = 1.50 [95% confidence interval: 0.31–2.69], p = 0.013) were observed in participants with pre‐existing cardiovascular diseases at baseline. Furthermore, the increase in oxygen desaturation index (β = 3.59 [95% confidence interval: 1.78–5.39], p < 0.001), desaturation severity (β = 0.08 [95% confidence interval: 0.02–0.14], p = 0.015) and desaturation duration (β = 2.60 [95% confidence interval: 1.22–3.98], p < 0.001) during the follow‐up were higher among participants with diabetes. Similarly, the increase in oxygen desaturation index (β = 2.73 [95% confidence interval: 1.15–4.32], p = 0.001) and desaturation duration (β = 1.85 [95% confidence interval: 0.62–3.08], p = 0.003) were higher among participants with cardiovascular diseases. These results suggest that patients with pre‐existing diabetes or cardiovascular diseases are at increased risk for an expedited worsening of intermittent hypoxaemia. As intermittent hypoxaemia is an essential feature of sleep apnea, these patients could benefit from the screening and follow‐up monitoring of sleep apnea.
Risk of proximal femoral nail antirotation (PFNA) implant failure upon different lateral femoral wall thickness in intertrochanteric fracture: a finite element analysis

Abstract Proximal Femoral Nail Antirotation (PFNA) has been commonly used to treat intertrochanteric fractures, despite the risk of implant failure. The integrity of the femur could influence the risk of implant failure. This study evaluated the influence of lateral femoral wall thickness on the potential of implant failure. A finite element model of the hip was reconstructed from the Computed Tomography of a female patient. Five intertrochanteric fracture models at different lateral femoral wall thickness (T1 = 27.6 mm, T2 = 25.4 mm, T3 = 23.4 mm, T4 = 21.4 mm, and T5 = 19.3 mm) were then created and fixed with PFNA. We simulated a critical loading condition by a high loading case during walking. Elastoplastic material models with yield stress and failure strain were applied to the bone and implant in which breakage can be simulated using the element deletion function. In addition, the stress and displacement of the implant and femur were analysed. Implant breakage occurred at the sides of the proximal nail canal in cases of T4 and T5 which was further supported by the higher maximum von Mises stress and nail displacement. The increased stress and displacement of the implant may implicate a reduction of stability and risk of implant failure. We suggested that precaution shall be taken when the wall thickness was less than 21.4 mm.