Miracle-dz/UniFAR-FTUs huggingface dataset:
Case Report: Late Onset of Myelodysplastic Syndrome From Donor Progenitor Cells After Allogeneic Stem Cell Transplantation. Which Lessons Can We Draw From the Reported Case?

Background Myelodysplastic syndromes and acute leukemias after allogeneic stem cell transplantation (allo-SCT) are mainly caused by recurrence of the primitive leukemic clones. More rarely, they originate from donor hematopoietic stem cells, developing the so-called donor cell leukemia (DCL) or myelodysplastic syndromes (DC-MDSs). DCL and DC-MDS can be considered as an in vivo model of leukemogenesis, and even if the pathogenetic mechanisms remain speculative, a genetic predisposition of donor progenitor cells, an altered host microenvironment, and the impairment of immune surveillance are considered the main causes. Case Presentation We report a case of DC-MDS diagnosed 5 years after an allo-SCT from a matched related donor (patient’s sister) in a patient with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). The sex-mismatch allowed us to identify the donor cell origin. At the onset, the DC-MDS was characterized by chromosome seven monosomy and NRAS, RUNX1, and BCOR mutations. Because of a familiar history of colorectal neoplasia and the variant allele frequency (VAF) of NRAS mutation at the onset, this mutation was searched on germline DNA in both the donor and the recipient, but the result was negative. Moreover, after transplant (+4 months), the patient developed severe and long-lasting chronic graft-versus-host disease (cGVHD), requiring multiple lines of treatments. Because of the severe immunosuppression, recurrent infections occurred and, lately, the patient died due to septic shock. Conclusion This case report highlights the need, whenever possible, to evaluate the donor origin of the posttransplant myelodysplasia and acute leukemias. The potential key role of the impaired immune surveillance and of long-lasting immunosuppression appears to be emerging in the development of this case of DC-MDS. Finally, this case reminds the importance to investigate the familiar genetic predisposition in donors with a familiar history of neoplasia.
Peroxisome Deficiency Impairs BDNF Signaling and Memory

Peroxisome is an intracellular organelle that functions in essential metabolic pathways including β-oxidation of very-long-chain fatty acids and biosynthesis of plasmalogens. Peroxisome biogenesis disorders (PBDs) manifest severe dysfunction in multiple organs including central nervous system (CNS), whilst the pathogenic mechanisms are largely unknown. We recently reported that peroxisome-deficient neural cells secrete an increased level of brain-derived neurotrophic factor (BDNF), resulting in the cerebellar malformation. Peroxisomal functions in adulthood brain have been little investigated. To induce the peroxisome deficiency in adulthood brain, we here established tamoxifen-inducible conditional Pex2-knockout mouse. Peroxisome deficiency in the conditional Pex2-knockout adult mouse brain induces the upregulated expression of BDNF and its inactive receptor TrkB-T1 in hippocampus, which notably results in memory disturbance. Our results suggest that peroxisome deficiency gives rise to the dysfunction of hippocampal circuit via the impaired BDNF signaling.
Mutational Pathways and Trade-Offs Between HisA and TrpF Functions: Implications for Evolution via Gene Duplication and Divergence

When a new activity evolves by changes in a pre-existing enzyme this is likely to reduce the original activity, generating a functional trade-off. The properties of this trade-off will affect the continued evolution of both functions. If the trade-off is strong, gene duplication and subsequent divergence would be favored whereas if the trade-off is weak a bi-functional enzyme could evolve that performs both functions. We previously showed that when a bi-functional HisA enzyme was evolved under selection for both HisA and TrpF functions, evolution mainly proceeded via duplication-divergence and specialization, implying that the trade-off is strong between these two functions. Here, we examined this hypothesis by identifying the mutational pathways (i.e., the mutational landscape) in the Salmonella enterica HisA enzyme that conferred a TrpF-like activity, and examining the trade-offs between the original and new activity. For the HisA enzyme there are many different paths toward the new TrpF function, each with its own unique trade-off. A total of 16 single mutations resulted in HisA enzyme variants that acquired TrpF activity and only three of them maintained HisA activity. Twelve mutants were evolved further toward increased TrpF activity and during evolution toward improved TrpF activity the original HisA activity was completely lost in all lineages. We propose that, aside from various relevant ecological factors, two main genetic factors influence whether evolution of a new function proceeds via duplication – divergence (specialization) or by evolution of a generalist: (i) the relative mutation supply of the two pathways and (ii) the shape of the trade-off curve between the native and new function.
Mechano-Regulation of Trabecular Bone Adaptation Is Controlled by the Local in vivo Environment and Logarithmically Dependent on Loading Frequency

It is well-established that cyclic, but not static, mechanical loading has anabolic effects on bone. However, the function describing the relationship between the loading frequency and the amount of bone adaptation remains unclear. Using a combined experimental and computational approach, this study aimed to investigate whether trabecular bone mechano-regulation is controlled by mechanical signals in the local in vivo environment and dependent on loading frequency. Specifically, by combining in vivo micro-computed tomography (micro-CT) imaging with micro-finite element (micro-FE) analysis, we monitored the changes in microstructural as well as the mechanical in vivo environment [strain energy density (SED) and SED gradient] of mouse caudal vertebrae over 4 weeks of either cyclic loading at varying frequencies of 2, 5, or 10 Hz, respectively, or static loading. Higher values of SED and SED gradient on the local tissue level led to an increased probability of trabecular bone formation and a decreased probability of trabecular bone resorption. In all loading groups, the SED gradient was superior in the determination of local bone formation and resorption events as compared to SED. Cyclic loading induced positive net (re)modeling rates when compared to sham and static loading, mainly due to an increase in mineralizing surface and a decrease in eroded surface. Consequently, bone volume fraction increased over time in 2, 5, and 10 Hz (+15%, +21% and +24%, p ≤ 0.0001), while static loading led to a decrease in bone volume fraction (−9%, p ≤ 0.001). Furthermore, regression analysis revealed a logarithmic relationship between loading frequency and the net change in bone volume fraction over the 4 week observation period (R2 = 0.74). In conclusion, these results suggest that trabecular bone adaptation is regulated by mechanical signals in the local in vivo environment and furthermore, that mechano-regulation is logarithmically dependent on loading frequency with frequencies below a certain threshold having catabolic effects, and those above anabolic effects. This study thereby provides valuable insights toward a better understanding of the mechanical signals influencing trabecular bone formation and resorption in the local in vivo environment.
Detection of Simulated Tactile Gratings by Electro-Static Friction Show a Dependency on Bar Width for Blind and Sighted Observers, and Preliminary Neural Correlates in Sighted Observers

The three-dimensional micro-structure of physical surfaces produces frictional forces that provide sensory cues about properties of felt surfaces such as roughness. This tactile information activates somatosensory cortices, and frontal and temporal brain regions. Recent advances in haptic-feedback technologies allow the simulation of surface micro-structures via electro-static friction to produce touch sensations on otherwise flat screens. These sensations may benefit those with visual impairment or blindness. The primary aim of the current study was to test blind and sighted participants’ perceptual sensitivity to simulated tactile gratings. A secondary aim was to explore which brain regions were involved in simulated touch to further understand the somatosensory brain network for touch. We used a haptic-feedback touchscreen which simulated tactile gratings using digitally manipulated electro-static friction. In Experiment 1, we compared blind and sighted participants’ ability to detect the gratings by touch alone as a function of their spatial frequency (bar width) and intensity. Both blind and sighted participants showed high sensitivity to detect simulated tactile gratings, and their tactile sensitivity functions showed both linear and quadratic dependency on spatial frequency. In Experiment 2, using functional magnetic resonance imaging, we conducted a preliminary investigation to explore whether brain activation to physical vibrations correlated with blindfolded (but sighted) participants’ performance with simulated tactile gratings outside the scanner. At the neural level, blindfolded (but sighted) participants’ detection performance correlated with brain activation in bi-lateral supplementary motor cortex, left frontal cortex and right occipital cortex. Taken together with previous studies, these results suggest that there are similar perceptual and neural mechanisms for real and simulated touch sensations.
Anxiety and Depression Symptoms in COVID-19 Isolated Patients and in Their Relatives

Background: While focusing on the management and care of COVID-19 patients, the mental health of these patients and their relatives is being overlooked. The aim of the current study was to measure anxiety and depression, and to assess their association with socio-demographic and pandemic-related stress factors in COVID-19 patients and their relatives during the initial stage of hospitalization. Methods: We assessed isolated hospitalized patients (N = 90) and their relatives (adults and children, N = 125) by phone, 25–72 h following patients' admission. The quantitative measures included the Anxiety and Depression modules of the Patient-Reported Outcomes Measurement Information System (PROMIS) and pandemic-related stress factors. Qualitative measures included questions exploring worries, sadness, and coping modes. Results: Both patients and relatives suffer from high levels of anxiety and related pandemic worries, with lower levels of depressive symptoms. Compared to adult relatives, child relatives reported significantly lower anxiety. The multivariable logistic regression analysis revealed an increased risk for anxiety among females and a decreased risk among ultra-orthodox participants. While increased anxiety among patients was associated with feelings of isolation, increased anxiety among relatives was associated with a feeling of not being protected by the hospital. Conclusions: Patients and relatives experience similar high anxiety levels which are more robust in women and lower in ultra-orthodox participants. Our findings indicate that anxiety symptoms of both patients and adult relatives should be addressed.
In utero exposure to di-(2-ethylhexyl) phthalate reveals the presence of an adrenal-testis axis regulating androgen formation

Phthalates are endocrine disruptors with shortand longterm antiadrogenic properties. In the adult, in utero exposure to di-(2-ethylhexyl) phthalate (DEHP) results in decreased testosterone levels despite normal serum levels of LH, proteins and enzymes involved in cholesterol transport and biosynthesis, suggesting that the effects of DEHP are independent of the classic steroidogenic pathway. The purpose of this body of work is to identify the mechanism mediating this antiandrogenic effect of DEHP. The mineralocorticoid receptor (NR3C2; MR) mediates testosterone production and we show that in utero exposure to DEHP decreases MRexpression in Leydig cells. The reduced MR expression was accompanied by a decrease in circulating levels of aldosterone biosynthesized in the adrenal gland and was similar in magnitude to the decrease seen in testosterone. In search of the mechanism underlying the reduced aldosterone formation, we observed that DEHP decreases the expression of angiotensin II (ATII) receptors despite normal serum levels of the main aldosterone stimulants, ATII and potassium. The ATII receptor decrease did not have an impact on the proteins and enzymes involved in aldosterone biosynthesis. Paradoxically, the pathways for extracellular cholesterol and de novo
Alocação de biomassa e ajuste de equações para estimativa de biomassa em compartimentos aéreos de Eucalyptus benthamii

This paper presents the results of the adjustment of equations for estimating biomass of aerial compartments of Eucalyptus benthamii trees. The percentile allocation of biomass, in the compartments wood, bark, leaves and branches is also presented. The trees of Eucalyptus benthamii were sampled from stands of 12, 24, 36 and 48 months of age, planted at the spacing 3 m x 2 m, in the region of Guarapuava-PR. For the compartments considered, the generalized logarithmic model gave better indices of adjustment for branches and, together with logarithmic combined variable, the minor error for bark variable. Leaves and wood had minor error with model lnY=b0 +b1*lnDBH and logarithmic combined variable, respectively. The allocation of biomass in the different compartments was differentiated for each age. In the age of 12 months the greater percentile of biomass was in the leaves. However in the age of 48 months, wood had the greater percentage of biomass. The biomass allocation had the following ratios, respectively, for wood, bark, branches and leaves, 33, 3, 29 and 35% for the age of 24 months, 51, 5, 25 and 19% for the age of 24 months, 63, 5, 18 and 14% for the age of 36 months and 71, 7, 15 and 7% for the age of 48 months.
Equivariant Normalizing Flows for Point Processes and Sets

A point process describes how random sets of exchangeable points are generated. The points usually influence the positions of each other via attractive and repulsive forces. To model this behavior, it is enough to transform the samples from the uniform process with a sufficiently complex equivariant function. However, learning the parameters of the resulting process is challenging since the likelihood is hard to estimate and often intractable. This leads us to our proposed model - CONFET. Based on continuous normalizing flows, it allows arbitrary interactions between points while having tractable likelihood. Experiments on various real and synthetic datasets show the improved performance of our new scalable approach.
Method for Studying Microbial Biofilms in Flowing-Water Systems

A method for the study of microbial biofilms in flowing-water systems was developed with special reference to the flow conditions in electrochemical concentration cells. Seawater was circulated in a semiclosed flow system through biofilm reactors (3 cm s−1) with microscope cover slips arranged in lamellar piles parallel with the flow. At fixed time intervals cover slips with their biofilm were removed from the pile, stained with crystal violet, and mounted on microscope slides. The absorbances of the slides were measured at 590 nm and plotted against time to give microbial biofilm development. From calibration experiments a staining time of 1 min and a rinse time of 10 min in a tap water flow (3 cm s−1) were considered sufficient. When an analysis of variance was performed on biofilm development data, 78% of the total variance was found to be due to random natural effects; the rest could be explained by experimental effects. The absorbance values correlated well with protein N, dry weight, and organic weight in two biofilm experiments, one with a biofilm with a high (75%) and one with a low (∼25%, normal) inorganic content. Comparisons of regression lines revealed that the absorbance of the stained biofilms was an estimate closely related to biofilm dry weight.
Bronchopulmonary dysplasia-associated pulmonary hypertension

Chronic respiratory sequelae are a major health problem in surviving premature infants. Despite immense improvement in the care of premature infants, the rate of bronchopulmonary dysplasia (BPD) and pulmonary morbidities have remained the same or even slightly increased over the past decades. BPD results from the impairment of lung development following premature birth, and the resultant dysregulated pulmonary vasculature leads to chronic pulmonary hypertension (PH). It is seen more commonly in the setting of moderate to severe BPD. A high index of suspicion is necessary to diagnose PH in BPD. Diagnosis is most commonly done by echocardiogram, but cardiac catheterization may be required to delineate the cardiac structure, cardio-pulmonary vasculature and myocardial function. Once the diagnosis is made, a multidisciplinary approach for management of these patients is suggested, aiming to optimize management of BPD and use of various pulmonary vasodilators. The various therapeutic agents available help reduce pulmonary vascular resistance by acting on the nitric oxide (NO), prostacyclin and/or endothelin pathways. Serial echocardiograms and measurement of biomarkers are used to evaluate the response to therapy. Currently there is not much evidence to support optimal management approaches, but the recent guidelines published by the Pediatric Pulmonary Hypertension Network (PPHNet) provide practical recommendations for screening and management of these infants.
Serious cardiovascular adverse events with fluoroquinolones versus other antibiotics: A self‐controlled case series analysis

The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all‐cause mortality vs other commonly used antibiotics. We conducted a self‐controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014‐FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole‐trimethoprim), adjusted for time‐varying covariates. Using a 30‐day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all‐cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.
A 2-year longitudinal follow-up of performance characteristics in Chinese male elite youth athletes from swimming and racket sports

Training in elite sport aims at the optimization of the athletic performance, and to control the athletes`progress in physiological, anthropometrical and motor performance prerequisites. However, in most sports, the value of longitudinal testing is unclear. This study evaluates the longitudinal development and the influence of intense training over 2-years on specific physiological performance prerequisites, as well as certain body dimensions and motor abilities in elite youth athletes. Recruited between 11–13 years of age at Shanghai Elite Sport school, the sample of student-athletes (N = 21) was categorized as the swimming group (10 athletes), and the racket sports group (11 players: 7 table tennis and 4 badminton players). The performance monitoring took place over two years between September 2016 and September 2018 and included 5 test waves. In all the test waves, the athletes were assessed by means of three physiological measurements (vital capacity, hemoglobin concentration, heart rate at rest), three anthropometric parameters (body height, body weight, chest girth), and two motor tests (back strength, complex reaction speed). Seven out of eight diagnostic methods exhibit medium to high validity to discriminate between the different levels of performance development in the two sports groups. The investigated development of the performance characteristics is attributed partly to the inherited athletic disposition as well as to the different sport-specific training regimens of the two sports groups.
MEDIA RICHNESS ON INSTAGRAM INFLUENCES TOWARDS CONSUMER PURCHASE INTENTION: EXPLORING THE MODERATING EFFECT OF BRAND EQUITY

Social media has become a widely-adopted technology since it being introduced to the world, affecting businesses in myriad ways. Majority of companies nowadays started to invest on social media marketing in regards to the ability of this marketing initiative lead to better profitability. However, only few studies have looked at the empirical link between media richness from social media i.e. Instagram and purchase intention among consumers. This paper discusses the influences of media richness on Instagram towards consumers’ intention to purchase mediated by brand equity. This study was conducted utilising survey research method, aiming to create better understanding of consumer intention to purchase as being influenced by social media richness. A total of 537 undergraduate students in Kuala Lumpur, Malaysia age 19 to 24 years old took part in this study as respondents. The respondents are exposed to Instagram postings on similar products for sale. Partial least square structural equation modelling (PLS-SEM) applied to fit the data in the hypothesised model. The outcome of study is useful to both researchers and business practitioners to understand the importance of social media richness specifically utilising Instagram as business platform. Future study should consider on discovering different perspective of media richness involving other types of social media.
Consumer Perceived Risk by Online Purchasing: The Experiences in Hungary

Abstract The aim of this paper is to identify and categorize the perceived risks that Hungarian consumers connect with online purchasing. The research is based on empirical data collected via a questionnaire and analysed with statistical software. The applied exploratory factor analysis identified five risk categories connected to online purchasing: perceived after-sale risk, perceived data security risk, perceived delivery risk, and perceived product risk. The fifth risk factor seems the most characteristic to Hungarian customers, who are wary of the possibility of online vendors selling fake products on the Internet. The results offer valuable information to companies engaged in online vending concerning the risk factors Hungarian consumers associate with online shopping. One limitation of this study is that it does not evaluate risk-reducing strategies.