Miracle-dz/UniFAR-FTUs huggingface dataset:
Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes

ABSTRACT Hepatitis A virus (HAV) is an enterically transmitted virus that replicates predominantly in hepatocytes within the liver before excretion via bile through feces. Hepatocytes are polarized epithelial cells, and it has been assumed that the virus load in bile results from direct export of HAV via the apical domain of polarized hepatocytes. We have developed a subclone of hepatocyte-derived HepG2 cells (clone N6) that maintains functional characteristics of polarized hepatocytes but displays morphology typical of columnar epithelial cells, rather than the complex morphology that is typical of hepatocytes. N6 cells form microcolonies of polarized cells when grown on glass and confluent monolayers of polarized cells on semipermeable membranes. When N6 microcolonies were exposed to HAV, infection was restricted to peripheral cells of polarized colonies, whereas all cells could be infected in colonies of nonpolarized HepG2 cells (clone C11) or following disruption of tight junctions in N6 colonies with EGTA. This suggests that viral entry occurs predominantly via the basolateral plasma membrane, consistent with uptake of virus from the bloodstream after enteric exposure, as expected. Viral export was also found to be markedly vectorial in N6 but not C11 cells. However, rather than being exported from the apical domain as expected, more than 95% of HAV was exported via the basolateral domain of N6 cells, suggesting that virus is first excreted from infected hepatocytes into the bloodstream rather than to the biliary tree. Enteric excretion of HAV may therefore rely on reuptake and transcytosis of progeny HAV across hepatocytes into the bile. These studies provide the first example of the interactions between viruses and polarized hepatocytes.
Personalised lamellar keratoplasty and keratopigmentation in Asian corneal leucoma patients.

OBJECTIVE To describe a personalised lamellar keratoplasty (LK) associated with the keratopigmentation (KTP) technique for corneal leucoma among Asian patients. METHODS This report was a non-randomised, retrospective clinical study performed in 32 consecutive eyes of 32 patients to improve cosmetic appearance. Twenty-two patients underwent LK combined with KTP, either by intralamellar or superficial route. Ten patients underwent the single personalised keratopigmentation method. The subjective and objective cosmetic results, ocular irritation, colour fading, neovascularisation formation and incidence of immune rejection were evaluated until three years after surgery. RESULTS No complications occurred, and the corneal leucoma was successfully stained with India ink in all 32 patients. Most of the patients showed good cosmetic appearance. Pain, conjunctival congestion, corneal edema and foreign body sensation disappeared gradually within two to three weeks after surgery in all patients. Graft swelling, non-healing, or detaching was not observed during follow-up. However, two patients had slight opacity three years after LK. Colour fading was observed in one patient who underwent intralamellar corneal staining 10 months after surgery. Re-staining was performed. CONCLUSION KTP combined with personalised LK is an effective personalised technique that presents long-standing colour staining and good cosmetic efficacy.
Minimally invasive reposition of intraarticular calcaneal fractures: a case report.

BACKGROUND Calcaneal fracture is a most common bony injury of the hindfoot. In constitutes 60% of foot fractures and 1-2% of all fractures. According to current literature 75% of these fractures involve articular surfaces, which makes them especially difficult to treat. Intraarticular fractures often result in permanent disability impairing foot function and ambulation, sometimes due to inadequate treatment method. According to literature, in developed countries open reduction and internal plate fixation is standard treatment of intraarticular calcaneal fractures. This treatment poses a risk of impaired wound healing and is appropriate for selected group of patients without additional risk factors. Other patients are treated with minimally invasive methods. Proponents of minimally invasive techniques apply distraction, which makes most intraarticular calcaneal fractures amenable to this method. CASE REPORT This paper presents a minimally invasive treatment technique for intraarticular (depression type according to Essex-Lopresti, IIA accordind to Sanders) calcaneal fracture in 63-years old man. External fixator (Monotube) is used for intraoperative distraction. Posterior facet is reduced with additional maneuvers. RESULTS With this technique we were able to reduce posterior faced, correct varus alignment and restore Böhler's angle. With restoration of shape of calcaneal bone optimal functional result can be expected. At six moths follow-up very good result was observed.
Calbindin-D9k and parvalbumin are exclusively located along basolateral membranes in rat distal nephron.

There is strong evidence that vitamin D-dependent Ca(2+)-binding proteins, i.e., calbindin-D9k and calbindin-D28k, facilitate diffusion of Ca2+ through the cytosolic compartment of renal and intestinal cells, which transport Ca2+ transcellularly. In the study presented here, parvalbumin, calbindin-D9k, and calbindin-D28k were localized precisely by immunocytochemistry in rat kidney. Antisera recognizing specifically the thick ascending loop of Henle, the connecting tubules and collecting ducts, and the intercalated cells of the collecting ducts were used to identify different cell types. In rat kidney cortex, parvalbumin and calbindin-D9k colocalized in the thick ascending loop of Henle, the distal convoluted tubule, the connecting tubule, and the intercalated cells of the collecting duct. Strikingly, in all responsive cells, parvalbumin and calbindin-D9k were exclusively present in a thin layer along the basolateral membrane. In contrast, calbindin-D28k was only present in the distal convoluted and connecting tubule, where it was evenly distributed through the cytosol. In conclusion, the exclusive localization of parvalbumin and calbindin-D9k at the basolateral membrane of immunopositive renal cells implies their involvement in the regulation of transport processes located in these membranes rather than a role as intracellular Ca2+ buffer and Ca2+ shuttle between the two opposing membranes.
The use of the early cannulation prosthetic graft (Acuseal™) for angioaccess for haemodialysis

Objectives Autogenous arteriovenous (AV) accesses are the preferred choice for the delivery of haemodialysis (HD). With an increase in the prevalence of end-stage renal disease and in the life expectancy of these patients, the quality and availability of superficial vessels can be limited and reduced with time. The use of prosthetic AV accesses may therefore become necessary for the delivery of HD. A new early cannulation vascular prosthesis (GORE® ACUSEAL Vascular Graft) has been introduced, developed to hinder suture line and cannulation needle bleeding. The authors report their experience with this new conduit at a London teaching hospital. Methods Between May 2011 and June 2013, 52 patients underwent 55 procedures where the ACUSEAL® prosthetic AV access was utilized to facilitate HD. The majority of procedures involved the placement of prosthetic brachio-axillary accesses or prosthetic axillo-axillary chest accesses. Results The 1-year primary and secondary patency was found to be 46% and 61%, respectively. Successful cannulation of the newly placed AV access was performed with 24 hours of surgery in 40 patients (73%). Tunnelled vascular catheters were required in only 10 (18%) patients. Six (11%) of the patients in the study suffered early complications, and 9 (16%) patients developed AV access infection. Conclusions These results show that, while providing patency results that compare favourably to those published for other types of regular prosthetic accesses, the conduits are amenable to very early cannulation with few cannulation-related complications. This leads to a dramatic reduction in the need for temporary or tunnelled catheters.
Ciliary Body/Iris Appositioning Producing Mechanical Pupillary Defects in Carotid-Cavernous Sinus Fistula: An Overlooked Pathophysiologic Mechanism

Background: Variable pupillary responses have been described with carotid-cavernous sinus fistulas. These often are associated with a decrease in visual acuity and attributed to retinal ischemia. We propose a novel pathophysiologic mechanism for changes in pupillary reactivity involving anatomic changes secondary to choroidal effusion. Methods: To demonstrate proof-of-concept, we investigated 2 consecutive patients with carotid-cavernous sinus fistulas and pupillary disturbances using repeated refractions and anterior segment ultrasound biomicroscopy. Results: Ultrasound biomicroscopy demonstrated choroidal thickening and ciliary body effusion with forward rotation of the lens–iris diaphragm altering refraction and mechanically limiting iris movements. Conclusions: Where there are acute elevations in orbital venous pressure causing ciliary body effusion, changes in visual acuity and pupillary abnormalities can be produced by mechanical effects.
Effects of dietary energy intake by gilts and heat stress from days 3 to 24 or 30 after mating on embryo survival and nitrogen and energy balance.

Bred gilts were used in two experiments (n = 140) to study the interaction and main effects of dietary energy intake and heat stress on embryo survival and nitrogen (N) and energy balance from d 3 to slaughter on d 30 (Exp. 1) or d 24 (Exp. 2) after mating. In both experiments, the ME treatments were 5.4 or 8.1 Mcal of ME/(gilt.d). Temperatures were either a constant thermoneutral of 23 +/- 1 degrees C or a heat stress regimen, making four treatments in a 2 x 2 factorial arrangement. Gilts were allotted directly to one of the treatments on d 3 after mating. In Exp. 1, the 24-h cyclic heat stress regimen consisted of an increase from 25 degrees C at 0800 to 34 degrees C at 1400, 34 degrees C from 1400 to 1700, then a decline to 25 degrees C at 2000, with 25 degrees C until 0800. In Exp. 2, heat stress was constant at 33 +/- 1 degrees C. No energy x temperature treatment interactions occurred (P > .2 to .8) for the variables measured in Exp. 1 and 2. Heat stress reduced (P < .05 or .01) diet and ME intake/day, ME retained/day, and ME/GE compared with the thermoneutral controls in Exp. 1 and 2. Heat stress reduced (P < .05) N digestibility in Exp. 1 and reduced (P < .01) N retained/day and N retention/N intake in Exp. 2. Rectal temperature and respiration rate were increased (P < .01) by heat stress in Exp. 1 and 2. (ABSTRACT TRUNCATED AT 250 WORDS)
Automated measurement of site‐specific N‐glycosylation occupancy with SWATH‐MS

Asparagine‐linked glycosylation is a common post‐translational modification of proteins catalyzed by oligosaccharyltransferase that is important in regulating many aspects of protein function. Analysis of protein glycosylation, including glycoproteomic measurement of the site‐specific extent of glycosylation, remains challenging. Here, we developed methods combining enzymatic deglycosylation and protease digestion with SWATH‐MS to enable automated measurement of site‐specific occupancy at many glycosylation sites. Deglycosylation with peptide‐endoglycosidase H, leaving a remnant N‐acetylglucosamine on asparagines previously carrying high‐mannose glycans, followed by trypsin digestion allowed robust automated measurement of occupancy at many sites. Combining deglycosylation with the more general peptide‐N‐glycosidase F enzyme with AspN protease digest allowed robust automated differentiation of nonglycosylated and deglycosylated forms of a given glycosylation site. Ratiometric analysis of deglycosylated peptides and the total intensities of all peptides from the corresponding proteins allowed relative quantification of site‐specific glycosylation occupancy between yeast strains with various isoforms of oligosaccharyltransferase. This approach also allowed robust measurement of glycosylation sites in human salivary glycoproteins. This method for automated relative quantification of site‐specific glycosylation occupancy will be a useful tool for research with model systems and clinical samples.
International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: IV. Therapeutic dose dependence and abuse liability of benzodiazepines in the long-term treatment of anxiety disorders.

Despite decades of relevant basic and clinical research, active debate continues about the appropriate extent and duration of benzodiazepine use in the treatment of anxiety and related disorders. The primary basis of the controversy seems to be concern among clinicians, regulators, and the public about the dependence potential and the abuse liability of benzodiazepines. This article reports systematically elicited judgments on these issues by a representative panel of 73 internationally recognized experts in the pharmacotherapy of anxiety and depressive disorders, a panel which was constituted by a multistage process of peer nomination. The criterion for inclusion at each stage was the nomination by at least two peers as one of the "professionally most respected physicians of the world with extensive experience and knowledge in the pharmacotherapy of anxiety and depressive disorders. " Sixty-six respondents (90%) completed a comprehensive questionnaire covering a wide range of topics relevant to the therapeutic use of benzodiazepines and other medications that might be used for the same purposes. Overall, the expert panel judged that benzodiazepines pose a higher risk of dependence and abuse than most potential substitutes but a lower risk than older sedatives and recognized drugs of abuse. There was little consensus about the relative risk of dependence and abuse among the benzodiazepines. Differences between benzodiazepines with shorter and longer half-lives in inducing withdrawal symptoms are much less clear during tapered than during abrupt discontinuation. There was little agreement about the most important factors contributing to withdrawal symptoms and failure to discontinue benzodiazepines. The pharmacologic properties of the medication may be the most important contributors to withdrawal symptoms. In contrast, the clinical characteristics of the patient may be the most important contributors to failure to discontinue medication. The experts' judgment seems to support the widespread use of benzodiazepines for the treatment of bona fide anxiety disorders, even over long periods. The experts generally viewed dependence and abuse liability as clinical issues amenable to appropriate management, as for other adverse events related to therapy. However, more definitive clinical research on the remaining controversial issues is urgently needed to promote optimal patient care.
Production and characterization of transgenic pigs expressing porcine CTLA4‐Ig

Phelps CJ, Ball SF, Vaught TD, Vance AM, Mendicino M, Monahan JA, Walters AH, Wells KD, Dandro AS, Ramsoondar JJ, Cooper DKC, Ayares DL. Production and characterization of transgenic pigs expressing porcine CTLA4‐Ig. Xenotransplantation 2009; 16: 477–485. © 2009 John Wiley & Sons A/S.
The Impact of Weather Condition on Radio-Based Distance Estimation: A Case Study in GSM Networks With Mobile Measurements

Distance estimation based on the received signal strength (RSS) of wireless radio has been extensively studied; however, the estimation accuracy is susceptible to radio propagation conditions, particularly during periods of precipitation. This study performed experiments on the 1.8-GHz band of Global System for Mobile Communications (GSM) networks at Yuan Ze University, Taoyuan, Taiwan, sensing actual radio power signals using mobile phones and recording transmission conditions during various weather events. The aim was to compare RSS performance under dry and wet weather conditions and study the dynamics of distance estimation from theoretical and empirical perspectives. Traditional rain attenuation models have largely discounted the impact of precipitation on GSM signals due to the relatively low frequency band; however, on-site experimental results demonstrated that dynamic weather significantly degrades accuracy in distance estimation. This study employed a typical rain attenuation model and a radio propagation model to evaluate errors in distance estimation under various rain conditions, i.e., heavy rain, extremely heavy rain, torrential rain, and extremely torrential rain, in accordance with the standards set out by the Central Weather Bureau, Taiwan. This study also investigated the RSS attenuation under various wind speeds. The Cramer-Rao lower bound (CRLB) was used as a benchmark for comparison.
Peptidic Termini Play a Significant Role in TCR Recognition1

TCR recognition of class I MHC is dependent on the composition of the antigenic peptide and the MHC. Single amino acid substitutions in either the MHC or the peptide may dramatically alter recognition. While the major interactions between TCR and the peptide/MHC complex appear to be focused on the complementarity-determining region (CDR)3, it is also clear from the cocrystal structure of class I MHC and TCR that the amino and carboxyl ends of the peptide may play a role through interactions with the CDR1. In this work we show that gp33 variants substituted at the peptidic termini at the putative CDR1 contact regions show improved recognition in B6 mice. The rank order of recognition is different using the P14 transgenic T cells, suggesting that one reason for improved recognition is a change in the TCR repertoire that recognizes the peptide. However, the affinity of the TCR by some of the peptide/MHC complex with increased recognition is improved, as shown by increased tetramer binding to P14 T cells. These substitutions at the termini of the peptide-binding cleft cause localized conformational changes as seen by changes in mAb binding and crystallographic structures. The different peptide structures also show different conformations in the center of the peptide, but these are shown to be energetically similar and thus most likely have no significance with respect to TCR recognition. Therefore, small conformational changes, localized to the CDR1 contact regions, may play a significant role in TCR recognition.
Involvement of the adherens junction – actin filament system in acantholytic dyskeratosis of Hailey‐Hailey disease

Hailey‐Hailey disease is a blistering genodermatosis that shows acantholytic dyskeratosis throughout the epidermis. The aim of our study was to investigate the involvement of adherens structures and cytofilaments in this particular type of acantholysis. Both lesional and non‐lesional skin from 18 patients was studied histologically and ultrastructurally. Additionally, the samples were stained for desmosomes, adherens junctions, keratin filaments, actin filaments, and actin‐associated proteins, and finally investigated with an electron and a confocal laser scanning microscope (CLSM), respectively. Acantholytic dyskeratosis was not only confined to lesions, but was also focally detectable in clinically unaffected skin. Despite disruption and internalization of the desmosomes, keratinocytes remained linked together by well‐preserved adherens junctions. Staining for actin filaments with fluorochrome‐labeled phalloidin showed a remarkable formation of actin stress fibers in these keratinocytes. Thus, incomplete acantholysis, as demonstrable in both lesional and non‐lesional skin of Hailey‐Hailey patients, may be due to a cohesive function of the adherens junction‐actin system succeeding the dissolution of desmosomes. Most remarkably, none of the adnexal epithelia expressed the intrinsic defect of cell adhesion. This finding offers an explanation for the successful treatment of Hailey‐Hailey disease by dermabrasion, which after complete removal of the involved epidermis results in reepithelialization from skin appendages.
STREPTOCOCCAL ENDOCARDITIS IN A CAPTIVE SOUTHERN WHITE RHINOCEROS (CERATOTHERIUM SIMUM SIMUM)

Abstract: Postmortem examination of a 43-yr-old male southern white rhinoceros (Ceratotherium simum simum) revealed gross lesions and histopathologic findings consistent with endocarditis. The animal was born in Umfolozi National Park, South Africa, and then it was moved at 2 yr of age to two successive European zoologic collections. For several weeks prior to death, the animal was increasingly recumbent or assuming a dog-sitting position. Postmortem examination revealed cutaneous pressure sores and multiple rough nodular structures on the mitral valve and left ventricular endocardium. Histopathologic examination revealed vegetative endocarditis, myocardial and hepatocellular degeneration, hepatic fibrosis, and chronic nephritis. Bacterial culture from the oral cavity, trachea, lung, skin, and heart isolated beta hemolytic Streptococcus dysgalactiae subsp. equisimilis and Streptococcus ovis. The cause of death was acute cardiopulmonary failure due mainly to endocarditis and moderate myocardial degeneration. Streptococcal infections are not uncommon causes of morbidity and mortality in rhinoceros. This is the first detailed report of streptococcal endocarditis in a rhinoceros.
Effect of Gonadotropin Types and Indications on Homologous Intrauterine Insemination Success: A Study from 1251 Cycles and a Review of the Literature

Objective To evaluate the IUI success factors relative to controlled ovarian stimulation (COS) and infertility type, this retrospective cohort study included 1251 couples undergoing homologous IUI. Results We achieved 13% clinical pregnancies and 11% live births. COS and infertility type do not have significant effect on IUI clinical outcomes with unstable intervention of various couples' parameters, including the female age, the IUI attempt rank, and the sperm quality. Conclusion Further, the COS used seemed a weak predictor for IUI success; therefore, the indications need more discussion, especially in unexplained infertility cases involving various factors. Indeed, the fourth IUI attempt, the female age over 40 years, and the total motile sperm count <5 × 106 were critical in decreasing the positive clinical outcomes of IUI. Those parameter cut-offs necessitate a larger analysis to give infertile couples more chances through IUI before carrying out other ART techniques.