Miracle-dz/UniFAR-FTUs huggingface dataset:
Human thymic epithelial cells maintain long‐term survival of clonogenic myeloid and erythroid progenitor cells in vitro

Precursor cells that migrate into the thymus are still multipotent. Therefore, thymic epithelial cells (TECs) may provide microenvironments not only for T‐cell development, but also for maintenance of multipotent precursor cells until they undergo T‐cell commitment. In the present study, we performed long‐term cultures of CD34+ bone‐marrow (BM) cells on TEC lines that were derived from cortical epithelial cells of post‐natal thymus, to investigate whether human TECs could maintain long‐term non‐lymphoid haematopoiesis. Haematopoietic cells maintained in direct contact with established TEC lines were able to generate clonogenic progeny to both myeloid and erythroid cells for periods in excess of 5 weeks. Their abilities to support colony‐forming units of granulocytes–macrophages (CFU‐GM) and burst‐forming units of erythroids (BFU‐E) were almost equal to those of BM stromal cells. We observed similar results by using cloned TEC lines derived by limiting dilution, as well as those by using parental TEC lines. Colony‐forming activities were maintained even when haematopoietic progenitor cells were physically separated from TEC lines and cultured on microporous membrane. These observations indicate that haematopoiesis maintained in TEC‐contact long‐term cultures may depend on soluble factors produced by TEC lines. Our results suggest that thymic cortical epithelial cells have the ability to support not only the differentiation of haematopoietic cells, but also long‐term survival of clonogenic myeloid/erythroid progenitor cells.
Giant Rashba‐Type Spin Splitting in Ferroelectric GeTe(111)

Photoelectron spectroscopy in combination with piezoforce microscopy reveals that the helicity of Rashba bands is coupled to the nonvolatile ferroelectric polarization of GeTe(111). A novel surface Rashba band is found and fingerprints of a bulk Rashba band are identified by comparison with density functional theory calculations.
Low expression of ZHX2, but not RCBTB2 or RAN, is associated with poor outcome in multiple myeloma

RAN, ZHX2 and RCBTB2 (CHC1L) expression was evaluated by quantitative real time reverse transcription polymerase chain reaction in plasma cells from 85 monoclonal gammopathies: 58 symptomatic multiple myeloma (MM) (52 untreated, six relapsed), eight smouldering MM, five monoclonal gammopathy of undetermined significance, four plasma cell leukaemias and 10 myeloid cell lines. ZHX2 was weakly expressed in high‐risk/proliferative disease compared to low‐risk or indolent disease. High ZHX2 expression was associated with better response and longer survival after high‐dose therapy. RCBTB2 expression was weaker in hyperdiploid versus non‐hyperdiploid cases while RAN was more expressed in symptomatic MM and cell lines.
An evaluation of the development, implementation and outcome of a pilot prescription monitoring program in Newfoundland and Labrador

Since the late 1980s, local medical professional associations, drug dependency groups, and the police had noted an apparent increase in the inappropriate clinical and illicit use of prescription medications in Newfoundland and Labrador. -- The Newfoundland Medical Board implemented a provincial government funded, province-wide, pilot Prescription Monitoring Program ("PMP") for narcotics and benzodiazepines in June 2000. Pharmacists electronically submitted batch prescription information to the Program. -- The purpose of this research was to analyze the policy process used to develop and implement the pilot PMP in comparison to a published guideline and to undertake a thorough clinical evaluation of this Program using a before/after study design. -- The Program did not impact the prescribing of program monitored drugs, identified substitutes, and the incidence of multiple doctoring as expected. However, increased break and enters at retail pharmacies after the Program was implemented suggested that these medications had become more difficult to access. Surveys of prescribing appropriateness indicated that the PMP might have positively impacted the prescribing of these drugs. However, various biases and a small sample size limited the ability to accurately determine the magnitude of the impact. Assessments of long-standing prescriptions that were abruptly discontinued suggested that the PMP did not adversely impact legitimate patient access to these medications. Most suspected drug-seeking patients reduced the number of physicians they visited. A small number increased their visits. A small number of physicians had prescribing volumes that exceeded ten times the mean. -- Numerous legal, budgetary, confidentiality and stakeholder participation problems hindered the Program's orderly implementation and its impact. Contrary to legislation, at least eleven pharmacies failed to report data. Some high prescribing physicians identified by the Province's drug subsidy program were located near these pharmacies. Professional regulatory groups appeared unable to accommodate the financial and legal risks necessary to address suspected inappropriate behavior among physicians, pharmacists and patients. -- Specifically targeted peer prescribing reports, academic detailing and regulatory sanctions were recommended to replace the PMP. A recommendation was made to forward the names of patients suspected of double doctoring to the police. The Province's drug subsidy and physician payment programs may suffice as a necessary future data source for specifically targeted interventions. Researchers concluded that the Program had a marginal positive impact.
A Stretchable and Highly Sensitive Graphene‐Based Fiber for Sensing Tensile Strain, Bending, and Torsion

Wearable sensors are increasingly finding their way into applications of kinesthetic sensing, personal health monitoring, and smart prosthetics/robotics. A graphene-based composite fiber sensor with a "compression spring" structure is fabricated, featuring the ability of detecting multiple kinds of deformation. This fiber sensor is integrated into wearable sensors for monitoring human activities and intricate movements of robotics successfully.
Specific impairment of proximal tubular cell proliferation by a monoclonal κ light chain responsible for Fanconi syndrome.

BACKGROUND Fanconi syndrome (FS) is a rare renal disorder featuring proximal tubule dysfunction that may occur following tubular reabsorption of a monoclonal light chain (LC), in patients with multiple myeloma. FS may precede the recognition of multiple myeloma by several years. In most cases, crystalline inclusions of monoclonal κ LCs are observed within the lysosomes of proximal tubular cells (PTCs) and probably participate in their functional alteration. METHODS To investigate the mechanism implicated in proximal tubule dysfunction, we compared the effects of κ LC-CHEB obtained from a patient with myeloma-associated FS to those of control κ LC-BON obtained from a patient without evidence of FS, on the viability and proliferation of two different PTC lines. RESULTS Our data suggest that the tubular atrophy in myeloma-associated FS does not result from increased apoptosis of PTCs, but from their impaired capacity to proliferate and renew. Indeed, in vitro incubation of cultured PTCs with physiological amounts of the nephrotoxic κ LC-CHEB was sufficient to cause a depression in DNA synthesis and in cell proliferation. This effect was observed neither with control κ LC-BON nor in the absence of κ LC. CONCLUSIONS The reduced turnover of PTCs may affect tubular repair and regeneration. In addition, the reduced proliferation of myeloma cells producing the same monoclonal κ LC might explain the frequent association of FS with smoldering multiple myeloma.
EXPLORING MI'KMAQ WOMEN'S EXPERIENCES WITH PAP SMEAR SCREENING IN NOVA SCOTIA

Mi’kmaq women in Nova Scotia are reported to have lower rates of Papanicolaou (Pap) smear screening and have higher rates of cervical cancer compared to non-Aboriginal women. Much of the cervical cancer literature reflects mainstream values and tends to essentialize Aboriginal women as one at-risk homogenous group lacking knowledge about cervical cancer prevention. The primary purpose of this qualitative participatory study was to explore Mi’kmaq women’s and primary healthcare providers’ experiences with Pap smear screening and to consider the broader historical, economic, and socio-political contexts that shape those healthcare experiences. Mi’kmaq women’s experiences accessing Pap screening services, their encounters with healthcare providers and the health care system, and women’s past experiences with Pap smear screening were also explored. This inquiry was grounded in postcolonial feminist perspectives and Indigenous principles in a two-eyed seeing approach. Community facilitators were identified to assist with recruitment and the research process. Women participated in talking circles to learn about and shape the study. Sixteen Mi’kmaq women and five healthcare providers participated in two semi-structured interviews. Five themes were identified from the women: a) Finding Our Way, b) Our Understanding and Perceptions about Pap Smear Screening, c) The Impact of History on Our Health and Healthcare Experiences, d) Healthcare Providers’ Encounters: “Making a Difference in Our Path to Paps,” and e) “The Healthcare System is Complicating Our Going for Paps. ” Two themes were identified from healthcare providers: a) Understanding the Realities of Aboriginal Women’s Lives and b) Fostering Aboriginal Women’s Access to Pap Smear Screening. This research contributes to an understanding of the continued impact of wider historical, political, and socioeconomic conditions that have resulted from colonialism, residential schools, and assimilation on Pap smear screening. It reinforces the importance of not essentializing women’s views or experiences and recognizing that some are accessing Pap smear screening regularly in spite of challenging circumstances. Mi’kmaq women have been underrepresented in the previous Pap smear screening literature. It is critical that healthcare providers understand how they can improve access to Pap smear screening and the screening process itself.
A mechanism for Ikaros regulation of human globin gene switching

The human β globin locus consists of an upstream LCR and functional genes arranged sequentially in the order of their expression during development: 5′‐HBE1, HBG2, HBG1, HBD, HBB‐3′. Haemoglobin switching entails the successive recruitment of these genes into an active chromatin hub (ACH). Here we show that the transcription factor Ikaros plays a major role in the formation of the β‐globin ACH, and in haemoglobin switching. In Plastic mice, where the DNA‐binding region of Ikaros is disrupted by a point mutation, there is concomitant marked down‐regulation of HBB, and up‐regulation of HBG expression. We show for the first time Ikaros and its family member Eos, bind to critical cis elements implicated in haemoglobin switching and deletional hereditary persistence of fetal haemoglobin (HPFH). Chromatin conformation capture (3C) data demonstrated that Ikaros facilitates long‐distance DNA looping between the LCR and a region upstream of HBD. This study provides new insights into the mechanism of stage‐specific assembly of the β‐globin ACH, and HPFH.
A Bioinspired Multifunctional Heterogeneous Membrane with Ultrahigh Ionic Rectification and Highly Efficient Selective Ionic Gating

A bioinspired multifunctional heterogeneous membrane composed of a block copolymer (PS-b-P4VP) membrane and a porous anodic alumina membrane is fabricated. The ionic rectification is so strong that the maximum ratio is ≈489, and the chemical actuation of the anion or cation gate from the "OFF" to the "ON" state promotes a 98.5% increase in the channel conductance.
Rab GAP cascade regulates dynamics of Ypt6 in the Golgi traffic

Significance The Golgi apparatus functions as the central station of membrane traffic in cells. A series of Rab GTPases, which control various steps in membrane traffic, act consecutively during the course of Golgi maturation. Here, we report that Ypt6, a Rab6 homologue in yeast, resides temporarily at the Golgi and dissociates into the cytosol upon arrival of Ypt32, another Rab GTPase functioning in the late Golgi. We have found that Gyp6, a putative GTPase-activating protein for Ypt6, specifically interacts with Ypt32 as an effector. Taken together with the previously proposed Rab cascade within the Golgi, we propose that multiple Rab cascades interact at the intersection of secretory and endosomal pathways and play significant roles in traffic within and around the Golgi apparatus. The Golgi apparatus functions as the central station of membrane traffic in cells, where newly synthesized proteins moving along the secretory pathway merge with proteins recycled from subsequent membrane organelles such as endosomes. A series of Rab GTPases act consecutively and in concert with the maturation of cis- to-trans cisternae of the Golgi apparatus. Rab GTPases control various steps in intracellular membrane traffic by recruiting downstream effector proteins. Here, we report the dynamics of Ypt6, a yeast member of the Rab GTPase family, which mediates the fusion of vesicles from endosomes at the Golgi apparatus. Ypt6 resides temporarily at the Golgi and dissociates into the cytosol upon arrival of Ypt32, another Rab GTPase functioning in the late Golgi. We found that Gyp6, a putative GTPase-activating protein (GAP) for Ypt6, specifically interacts with Ypt32, most likely as an effector. Disruption of GYP6 or introduction of a Rab–GAP activity-deficient mutation in GYP6 resulted in continual residence of Ypt6 at the Golgi. We propose that Ypt32 acts to terminate endosome-to-Golgi traffic through a Rab–GAP cascade as it does for cis-to-trans intra-Golgi traffic. Simultaneous disruption of GAP for early-acting Rab proteins in the Golgi showed appreciable defects in post-Golgi trafficking, but did not significantly affect cell growth.
Priming by the variability of visual information

Significance Sensory systems in the mammalian brain adapt to the context provided by the local environment. The high-level statistics of visual information, such as the central tendency (mean) or heterogeneity (variance) of features or objects, provide important contextual cues for perception. Here, we show that participants categorize a “target” array faster when it occurs in the context of a preceding “prime” array with similar levels feature variance, even when prime and target features are drawn from different categories. This finding suggests that humans rapidly extract and adapt to the variance of visual information. Adaptation to variance may facilitate gain control in heterogeneous or cluttered environments, and contribute to ecologically important behaviors, such as detection in camouflage. According to recent theories, perception relies on summary representations that encode statistical information about the sensory environment. Here, we used perceptual priming to characterize the representations that mediate categorization of a complex visual array. Observers judged the average shape or color of a target visual array that was preceded by an irrelevant prime array. Manipulating the variability of task-relevant and task-irrelevant feature information in the prime and target orthogonally, we found that observers were faster to respond when the variability of feature information in the prime and target arrays matched. Critically, this effect occurred irrespective of whether the element-by-element features in the prime and target array overlapped or not, and was even present when prime and target features were drawn from opposing categories. This “priming by variance” phenomenon occurred with prime–target intervals as short as 100 ms. Further experiments showed that this effect did not depend on resource allocation, and occurred even when prime and target did not share the same spatial location. These results suggest that human observers adapt to the variability of visual information, and provide evidence for the existence of a low-level mechanism by which the range or dispersion of visual information is rapidly extracted. This information may in turn help to set the gain of neuronal processing during perceptual choice.
Reexpression of pyruvate kinase M2 in type 1 myofibers correlates with altered glucose metabolism in myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is caused by expansion of CTG repeats in the 3′ UTR of the DMPK gene. Expression of CUG expansion (CUGexp) RNA produces a toxic gain of function by disrupting the functions of RNA splicing factors, such as MBNL1 and CELF1, leading to splicing changes associated with clinical abnormalities. Progressive skeletal muscle weakness and wasting is one of the most prominent clinical features in DM1; however, the underlying mechanisms remain unclear. Here we report that the embryonic M2 isoform of pyruvate kinase (PKM2), a key enzyme contributing to the Warburg effect in cancer, is significantly induced in DM1 tissue and mouse models owing to aberrant splicing. Expression of PKM2 in DM1 skeletal muscle is restricted to the type 1 fibers, which are particularly susceptible to wasting in DM1. Using antisense oligonucleotides to shift PKM splicing toward increased PKM2 expression, we observed increased glucose consumption with reduced oxidative metabolism in cell culture and increased respiratory exchange ratio in mice, suggesting defects in energy metabolism conferred by PKM2 expression. We propose that PKM2 expression induces changes in type 1 fibers associated with muscle atrophy and muscle weakness in DM1.
Prevalence of musculoskeletal symptoms among Hong Kong nurses

This study aims to investigate how different prevalence selection criteria affect the prevalence rates of musculoskeletal symptoms in single and multiple body regions among female nurses working in a hospital setting in the Hong Kong area. Results showed that the 12-month prevalence rate for each body region was consistently higher than the 1-month prevalence rate. The 1-month prevalence rate for lower back was 59%, and 30-39% for lower extremity, upper back and neck, and the corresponding values for 12-month prevalence rates were 98% for lower back, and 89-91% for lower extremity, upper back, and neck. A similar trend was recorded for the 12-month prevalence of musculoskeletal disorder cases (MSD) (a case was defined as a reported symptom by the study participant, which is characterized by high frequency and/or intensity symptom) in the lower back (42%), knees/lower legs (30%), upper back (23%), hips - thigh (21%), and shoulders (21%). The 12-month MSD prevalence rates for lower back and one other body region ranged from 6% to 17%. The prevalence of MSD in the lower back - knees - and hips or ankles ranged from 11% to 12%. In addition, MSD cases in the lower back regions were significantly associated with those in the upper back, hip, knee, and hand regions. It is concluded that musculoskeletal symptoms are prevalent in single and multiple body regions, and symptoms originating from one body region may be associated with those in other body regions. A holistic approach in the evaluation and prevention of musculoskeletal problems for high-risk occupations is needed.
Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: results from the Turkish OL-HDF Study.

BACKGROUND Online haemodiafiltration (OL-HDF) is considered to confer clinical benefits over haemodialysis (HD) in terms of solute removal in patients undergoing maintenance HD. The aim of this study was to compare postdilution OL-HDF and high-flux HD in terms of morbidity and mortality. METHODS In this prospective, randomized, controlled trial, we enrolled 782 patients undergoing thrice-weekly HD and randomly assigned them in a 1:1 ratio to either postdilution OL-HDF or high-flux HD. The mean age of patients was 56.5 ± 13.9 years, time on HD 57.9 ± 44.6 months with a diabetes incidence of 34.7%. The follow-up period was 2 years, with the mean follow-up of 22.7 ± 10.9 months. The primary outcome was a composite of death from any cause and nonfatal cardiovascular events. The major secondary outcomes were cardiovascular and overall mortality, intradialytic complications, hospitalization rate, changes in several laboratory parameters and medications used. RESULTS The filtration volume in OL-HDF was 17.2 ± 1.3 L. Primary outcome was not different between the groups (event-free survival of 77.6% in OL-HDF versus 74.8% in the high-flux group, P = 0.28), as well as cardiovascular and overall survival, hospitalization rate and number of hypotensive episodes. In a post hoc analysis, the subgroup of OL-HDF patients treated with a median substitution volume >17.4 L per session (high-efficiency OL-HDF, n = 195) had better cardiovascular (P = 0.002) and overall survival (P = 0.03) compared with the high-flux HD group. In adjusted Cox-regression analysis, treatment with high-efficiency OL-HDF was associated with a 46% risk reduction for overall mortality {RR = 0.54 [95% confidence interval (95% CI) 0.31-0.93], P = 0.02} and a 71% risk reduction for cardiovascular mortality [RR = 0.29 (95% CI 0.12-0.65), P = 0.003] compared with high-flux HD. CONCLUSIONS The composite of all-cause mortality and nonfatal cardiovascular event rate was not different in the OL-HDF and in the high-flux HD groups. In a post hoc analysis, OL-HDF treatment with substitution volumes over 17.4 L was associated with better cardiovascular and overall survival.
Are low levels of 25-hydroxyvitamin D a risk factor for cardiovascular diseases or malignancies in renal transplantation?

BACKGROUND Observational studies in healthy people suggest an inverse relationship between 25-hydroxy-vitamin D (25(OH)D levels) and cardiovascular diseases and malignancies. We performed an observational prospective study in renal transplant recipients to investigate the effects of vitamin D deficiency on cardiovascular and malignancy risks. METHODS From 389 renal transplant recipients, 331 with a functioning graft at 12 months were included in the study. Mineral metabolism parameters were measured at 1, 3, 4 and 12 months. Information regarding the cardiovascular events and malignancies were collected from an electronic database. RESULTS According to the 1-year mean of 25(OH)D levels, 75 recipients (22.7%) had a normal vitamin D status, 161 (48.6%) had insufficiency and 95 (28.7%) had deficiency in vitamin D levels. During the follow-up, 80 recipients presented at least one cardiovascular event. The total cardiovascular diseases included: 27 patients with coronary diseases, 25 with cardiac failure, 18 with arrhythmia, 11 with acute cerebrovascular events and 19 with peripheral vascular disease. Cardiovascular events were not associated with 25(OH)D levels or vitamin D status, and the 10-year cumulative incidence was 29.3% for normal vitamin D status and 31.6% for insufficiency and 51.9% for deficiency (P = 0.216). Furthermore, Cox univariate analysis showed no association between cardiovascular events and vitamin D levels or vitamin D status. In addition, 53 recipients presented at least one malignancy: 33 non-melanoma skin malignancies and 20 non-skin malignancies (5 prostate, 3 kidney and urinary tract, 2 colon, 2 lung, 2 lymphoma, 2 breast and 4 from other locations). The cumulative incidence of malignancies was 21.3% for normal vitamin D status, 22.7% for insufficiency and 16.7% for deficiency (P = 0.818). CONCLUSIONS Our data suggested that low vitamin D levels were not associated with an increased risk of cardiovascular diseases or malignancies. However, due to the small number of patients and events, the results should not be considered as definitive. Additional studies with a higher number of patients are required to elucidate the true impact of vitamin D status on cardiovascular and malignancy risks.