Miracle-dz/UniFAR-FTUs huggingface dataset:
Revisiting the Interaction of Melittin with Phospholipid Bilayers: The Effects of Concentration and Ionic Strength

Melittin is an anti-microbial peptide (AMP) and one of the most studied membrane-disrupting peptides. There is, however, a lack of accurate measurements of the concentration-dependent kinetics and affinity of binding of melittin to phospholipid membranes. In this study, we used surface plasmon resonance spectroscopy to determine the concentration-dependent effect on the binding of melittin to 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) bilayers in vesicles. Three concentration ranges were considered, and when combined, covered two orders of magnitudes (0.04 µM to 8 µM), corresponding to concentrations relevant to the membrane-disrupting and anti-microbial activities of melittin. Binding kinetics data were analysed using a 1:1 Langmuir-binding model and a two-state reaction model. Using in-depth quantitative analysis, we characterised the effect of peptide concentration, the addition of NaCl at physiological ionic strength and the choice of kinetic binding model on the reliability of the calculated kinetics and affinity of binding parameters. The apparent binding affinity of melittin for POPC bilayers was observed to decrease with increasing peptide/lipid (P/L) ratio, primarily due to the marked decrease in the association rate. At all concentration ranges, the two-state reaction model provided a better fit to the data and, thus, a more reliable estimate of binding affinity. Addition of NaCl significantly reduced the signal response during the association phase; however, no substantial effect on the binding affinity of melittin to the POPC bilayers was observed. These findings based on POPC bilayers could have important implications for our understanding of the mechanism of action of melittin on more complex model cell membranes of higher physiological relevance.
Comparison of balance changes after inspiratory muscle or Otago exercise training

The inspiratory muscles contribute to balance via diaphragmatic contraction and by increasing intra-abdominal pressure. We have shown inspiratory muscle training (IMT) improves dynamic balance significantly with healthy community-dwellers. However, it is not known how the magnitude of balance improvements following IMT compares to that of an established balance program. This study compared the effects of 8-week of IMT for community-dwellers, to 8-week of the Otago exercise program (OEP) for care-residents, on balance and physical performance outcomes. Nineteen healthy community-dwellers (74 ± 4 years) were assigned to self-administered IMT. Eighteen, healthy care-residents (82 ± 4 years) were assigned to instructor-led OEP. The IMT involved 30 breaths twice-daily at ~50% of maximal inspiratory pressure (MIP). The OEP group undertook resistance and mobility exercises for ~60 minutes, twice-weekly. Balance and physical performance were assessed using the mini Balance Evaluation System Test (mini-BEST) and time up and go (TUG). After 8-week, both groups improved balance ability significantly (mini-BEST: IMT by 24 ± 34%; OEP by 34 ± 28%), with no between-group difference. Dynamic balance sub-tasks improved significantly more for the IMT group (P < 0.01), than the OEP group and vice versa for static balance sub-tasks (P = 0.01). The IMT group also improved MIP (by 66 ± 97%), peak inspiratory power (by 31 ± 12%) and TUG (by -11 ± 27%); whereas the OEP did not. IMT and OEP improved balance ability similarly, with IMT eliciting greater improvement in dynamic balance, whilst OEP improved static balance more than IMT. Unlike IMT, the OEP did not provide additional benefits in inspiratory muscle function and TUG performance. Our findings suggest that IMT offers a novel method of improving dynamic balance in older adults, which may be more relevant to function than static balance and potentially a useful adjunct to the OEP in frailty prevention.
Fluorene-Based Donor-Acceptor Copolymers Containing Functionalized Benzotriazole Units: Tunable Emission and their Electrical Properties

Monomers 4,7-dibromo-2H-benzo[d]1,2,3-triazole (m1) and 4,7-(bis(4-bromophenyl)ethynyl)-2H-benzo[d]1,2,3-triazole (m2) have been synthesized in good yields using different procedures. Monomers m1 and m2 have been employed for building new copolymers of fluorene derivatives by a Suzuki reaction under microwave irradiation using the same conditions. In each case different chain lengths have been achieved, while m1 gives rise to polymers for m2 oligomers have been obtained (with a number of monomer units lower than 7). Special interest has been paid to their photophysical properties due to excited state properties of these D-A units alternates, which have been investigated by density functional theory (DFT) calculations using two methods: (i) An oligomer approach and (ii) by periodic boundary conditions (PBC). It is highly remarkable the tunability of the photophysical properties as a function of the different monomer functionalization derived from 2H-benzo[d]1,2,3-triazole units. In fact, a strong modulation of the absorption and emission properties have been found by functionalizing the nitrogen N-2 of the benzotriazole units or by elongation of the π-conjugated core with the introduction of alkynylphenyl groups. Furthermore, the charge transport properties of these newly synthesized macromolecules have been approached by their implementation in organic field-effect transistors (OFETs) in order to assess their potential as active materials in organic optoelectronics.
Role of a noncanonical disulfide bond in the stability, affinity, and flexibility of a VHH specific for the Listeria virulence factor InlB

A distinguishing feature of camel (Camelus dromedarius) VHH domains are noncanonical disulfide bonds between CDR1 and CDR3. The disulfide bond may provide an evolutionary advantage, as one of the cysteines in the bond is germline encoded. It has been hypothesized that this additional disulfide bond may play a role in binding affinity by reducing the entropic penalty associated with immobilization of a long CDR3 loop upon antigen binding. To examine the role of a noncanonical disulfide bond on antigen binding and the biophysical properties of a VHH domain, we have used the VHH R303, which binds the Listeria virulence factor InlB as a model. Using site directed mutagenesis, we produced a double mutant of R303 (C33A/C102A) to remove the extra disulfide bond of the VHH R303. Antigen binding was not affected by loss of the disulfide bond, however the mutant VHH displayed reduced thermal stability (Tm = 12°C lower than wild‐type), and a loss of the ability to fold reversibly due to heat induced aggregation. X‐ray structures of the mutant alone and in complex with InlB showed no major changes in the structure. B‐factor analysis of the structures suggested that the loss of the disulfide bond elicited no major change on the flexibility of the CDR loops, and revealed no evidence of loop immobilization upon antigen binding. These results suggest that the noncanonical disulfide bond found in camel VHH may have evolved to stabilize the biophysical properties of the domain, rather than playing a significant role in antigen binding.
Carbonic Anhydrase XII Expression Is Modulated during Epithelial Mesenchymal Transition and Regulated through Protein Kinase C Signaling

Members of the carbonic anhydrase family are functionally involved in the regulation of intracellular and extracellular pH in physiological and pathological conditions. Their expression is finely regulated to maintain a strict control on cellular homeostasis, and it is dependent on the activation of extracellular and intracellular signaling pathways. Combining RNA sequencing (RNA-seq), NanoString, and bioinformatics data, we demonstrated that the expression of carbonic anhydrase 12 (CAXII) is significantly different in luminal and triple negative breast cancer (BC) models and patients, and is associated with the activation of an epithelial mesenchymal transition (EMT) program. In BC models, the phorbol ester 12-myristate 13-acetate (PMA)-mediated activation of protein kinase C (PKC) induced a down-regulation of CAXII with a concomitant modulation of other members of the transport metabolon, including CAIX and the sodium bicarbonate cotransporter 3 (NBCn1). This is associated with a remodeling of tumor glycolytic metabolism induced after PKC activation. Overall, this analysis highlights the dynamic nature of transport metabolom and identifies signaling pathways finely regulating this plasticity.
Conversion to Everolimus was Beneficial and Safe for Fast and Slow Tacrolimus Metabolizers after Renal Transplantation

Fast tacrolimus (TAC) metabolism (concentration/dose (C/D) ratio <1.05 ng/mL/mg) is a risk factor for inferior outcomes after renal transplantation (RTx) as it fosters, e.g., TAC-related nephrotoxicity. TAC minimization or conversion to calcineurin-inhibitor free immunosuppression are strategies to improve graft function. Hence, we hypothesized that especially patients with a low C/D ratio profit from a switch to everolimus (EVR). We analyzed data of 34 RTx recipients (17 patients with a C/D ratio <1.05 ng/mL/mg vs. 17 patients with a C/D ratio ≥1.05 ng/mL/mg) who were converted to EVR within 24 months after RTx. The initial immunosuppression consisted of TAC, mycophenolate, prednisolone, and basiliximab induction. During an observation time of 36 months after changing immunosuppression from TAC to EVR, renal function, laboratory values, and adverse effects were compared between the groups. Fast TAC metabolizers were switched to EVR 4.6 (1.5–21.9) months and slow metabolizers 3.3 (1.8–23.0) months after RTx (p = 0.838). Estimated glomerular filtration rate (eGFR) did not differ between the groups at the time of conversion (baseline). Thereafter, the eGFR in all patients increased noticeably (fast metabolizers eGFR 36 months: + 11.0 ± 11.7 (p = 0.005); and slow metabolizers eGFR 36 months: + 9.4 ± 15.9 mL/min/1.73 m2 (p = 0.049)) vs. baseline. Adverse events were not different between the groups. After the switch, eGFR values of all patients increased statistically noticeably with a tendency towards a higher increase in fast TAC metabolizers. Since conversion to EVR was safe in a three-year follow-up for slow and fast TAC metabolizers, this could be an option to protect fast metabolizers from TAC-related issues.
Non-mycosis fungoides cutaneous lymphomas in a referral center in Taiwan: A retrospective case series and literature review

Background While mycosis fungoides (MF) and Sézary syndrome (SS) are the most common cutaneous lymphomas (CLs), there is limited data about non-MF/SS CLs. Objective We aimed to evaluate clinical characteristics of non-MF/SS CLs. Methods A retrospective analysis evaluated patients with non-MF/SS CLs covering a period of 17 years. The records of 59 patients with non-MF/SS CLs were reviewed for demographic profiles, clinical features, and survival outcomes. Results Our series consisted of 38 non-MF/SS cutaneous T-cell lymphomas (CTCLs) and 21 cutaneous B-cell lymphomas (CBCLs). In the group of non-MF/SS CTCLs including 33 primary and five secondary cases, there were cases of anaplastic large cell lymphoma (15.3% of non-MF/SS CLs), extranodal natural killer/ T-cell lymphoma (13.5%), peripheral T-cell lymphoma, not otherwise specified (13,5%), adult T-cell leukemia/lymphoma (8.5%), subcutaneous panniculitis-like T-cell lymphoma (6.8%) and angioimmunoblastic T-cell lymphoma (6.8%). In the group of CBCLs including nine primary and 12 secondary cases, there were cases of diffuse large B-cell lymphoma (22.0%), mantle cell lymphoma (5.1%), extranodal marginal lymphoma of mucosa associated lymphoid tissue (3.4%), follicle center lymphoma (3.4%) and intravascular large B-cell lymphoma (1.7%). The overall survivals were 57 months for non-MF/SS CTCLs and 41.5 months for CBCLs. Elevated serum lactate dehydrogenase level, thrombocytopenia, multiple anatomical sites of skin involvement and lower albumin level may be associated with poor prognosis in non-MF/SS CTCLs, but the latter two were not in CBCLs. Conclusion With this series, we hope to provide indigenous data and outcome of non-MF/SS CLs. The overall survival of non-MF/SS CTCLs was better than CBCLs.
Cultural Connectedness as a Determinant of Physical Activity Among Indigenous Adults in Saskatchewan.

Cultural connectedness has been associated with increased self-esteem and mental health among Indigenous peoples. Physical activity is an important contributor to health, though the importance of culture as a determinant of physical activity for Indigenous peoples in Canada is unclear. The purpose of this study is to evaluate differences in cultural connectedness between Indigenous adults in Canada achieving high and low physical activity levels. Questionnaires evaluated cultural connectedness and physical activity. Indigenous adults were classified into high and low physical activity groups at the specific group mean and as meeting or not meeting musculoskeletal activity guidelines of twice per week. First Nations and specifically Cree/Nehiyaw First Nations adults who were more physically active reported greater identity, spirituality, traditions, exploration, commitment, affirmation/belonging and overall cultural connectedness. Cultural connectedness elements of commitment, exploration, identity, affirmation/belonging, traditions, spirituality and overall cultural connectedness were not different between high and low physical activity Métis adults. Musculoskeletal activity was not associated with any elements of cultural connectedness among any Indigenous identity. Cultural connectedness is a protective factor for physical activity among First Nations and Cree/Nehiyaw First Nations, but not among Métis adults in Canada. Novelty Bullets: • Musculoskeletal activity was not associated with cultural connectedness • Cultural connectedness is a protective factor of physical activity for First Nations • Moving away from one's home community was associated with lower cultural connectedness for Indigenous peoples.
Prognostic Value of 18F-FDG PET/CT-Metabolic Parameters at Baseline and Interim Assessment in Pediatric Anaplastic Large Cell Lymphoma.

INTRODUCTION The event-free survival in pediatric anaplastic large cell lymphoma (ALCL) remains at 70% irrespective of the diverse chemotherapy regimens used. There is lack of valid prognostic factors identifying high-risk patients. We investigated the prognostic value of baseline metabolic parameters and interim response on F-FDG PET/CT in pediatric ALCL patients. METHODS We retrospectively reviewed 40 pediatric ALCL patients with paired F-FDG PET/CT and treated uniformly on vinblastine-based institution protocol. The SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis of the lymphomatous lesion were measured. Continuous PET parameters were stratified by their median values. Deauville scoring system was used to assess response to chemotherapy in the interim scan. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. RESULTS At median follow-up of 52 months, 13 patients died and 13 had recurrence. On univariate analysis, higher whole-body MTV (WBMTV) and partial response on interim scan were statistically associated with OS. High-risk features, WBMTV, and partial response were statistically associated with DFS. On multivariate analysis combining baseline characteristics and interim response, interim response (hazard ratio, 3.56; P = 0.034) was statistically significant for OS. Multivariate analysis for DFS using only baseline characteristics revealed WBMTV as statistically significant (hazard ratio, 4.08; P = 0.035), but none of the parameters was statistically significant when baseline characteristics and interim response were evaluated together. CONCLUSIONS Whole-body tumor burden assessment with MTV and interim response may help to identify high-risk patients who might get benefitted from intensive therapy.
Radiographic Fusion Rates Following a Stand-alone Interbody Cage versus an Anterior Plate Construct for Adjacent Segment Disease after Anterior Cervical Discectomy and Fusion.

STUDY DESIGN Case-Control. OBJECTIVE To evaluate fusion rates and compare a stand-alone cage construct with an anterior-plate construct in the setting revision ACDF for adjacent segment disease. SUMMARY OF BACKGROUND DATA Anterior cervical discectomy and fusion is considered the gold standard of surgical treatment for cervical myelopathy and radiculopathy. One common consequence is adjacent segment disease. Treatment of adjacent segment disease is complicated by the prior surgical implants which may make application of an additional anterior cervical plate difficult. Stand-alone cage constructs obviate the need for removal or revision of prior implants in the setting of adjacent segment disease. METHODS All patients undergoing surgery for adjacent segment disease in a 2 year period were identified and separated into groups based on implant construct. A control group of patients undergoing primary, single level ACDF were selected from during the same 2 year period. Demographic variables, fusion rate and reoperation rate were compared between groups. Continuous variables were compared using Student's t-test, fusion and revision rates were compared using Pearson chi-square test. RESULTS Patients undergoing primary ACDF had lower age and ASA score as well as shorter operative time. Fusion rate was higher for primary ACDF compared to all patients who underwent ACDF for adjacent segment disease (95% vs 74%). When compared to primary ACDF, patients with a stand-alone cage construct had significantly lower fusion rate and (69% vs 95%) and higher re-operation rate (14% vs 0%). There were no significant differences in anterior plate construct versus stand-alone cage construct in terms of fusion and re-operation. CONCLUSIONS Symptomatic adjacent segment disease can be managed surgically with either revision anterior plating or a stand-alone cage constructs, although our results raise questions regarding a difference in fusion rates that requires further investigation. LEVEL OF EVIDENCE 3.
Systematic Review and Meta-Analyses: Motor Skill Interventions to Improve Fine Motor Development in Children Aged Birth to 6 Years.

OBJECTIVE The objective of this study was to systematically review the evidence of motor skill intervention programs on typically developing children's fine motor development aged birth to 6 years. METHODS Six electronic databases were searched with no date restrictions. Inclusion criteria were any school-, community-, or home-based intervention targeting the development of fine motor skills of children aged birth to 6 years; randomized controlled trials using quasiexperimental, experimental, or single group prepost designs with a minimum sample size of 15 participants per group; and statistical analyses of fine motor skill development at both preintervention and postintervention or addressing the intervention effects on fine motor skill development. Data were extracted on design, participants, intervention components, methodological quality, and efficacy. RESULTS Twenty-five of the total 31 studies reported positive intervention effects on fine motor skills. The meta-analyses included 19 studies and revealed moderate effect sizes of motor skill programs on fine motor, visual motor, and manual dexterity outcomes. There were substantial differences between intervention settings, facilitators, length, and content with most studies implemented in school settings and facilitated by teachers. CONCLUSION Fine motor skill development in the early years is an extensive upcoming field of interest for many international researchers. This review study presents evidence on the positive effects of intervention programs that aim to enhance fine motor skills for young children. The findings are promising but need to be interpreted with caution because of the high risk of bias in many of the studies.
PCR for the detection of pathogens in neonatal early onset sepsis

Background A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. Methods Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. Results Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. Conclusion Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis.
Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants.

There is increasing evidence that long-term outcomes for infants born prematurely are adversely affected by repeated exposure to noxious procedures. These interventions vary widely, for example, in the extent of damage caused and duration. NICU (neonatal intensive care unit) procedures are therefore likely to each contribute differently to the overall pain burden of individual neonates, ultimately having a different impact on their development. In order for researchers to quantify the procedural pain burden experienced by infants on NICU, we aimed to estimate the pain severity of common NICU procedures using published pain scores. We extracted pain scores over the first minute (pain reactivity) from the literature, using 59 randomized controlled trials for 15 different procedures. Hierarchical cluster analysis of average pain scores resulted in five discrete severity groups; mild (n=1), mild to moderate (n=3), moderate (n=7), severe (n=3) and very severe (n=1). The estimate of the severity of individual procedures provided new insight into infant pain reactivity which is not always directly related to the invasiveness and duration of a procedure; thus both heel lance and skin tape removal are moderately painful procedures. This estimate of procedural pain severity, based on pain reactivity scores, provides a novel platform for retrospective quantification of an individual neonate's pain burden due to NICU procedures. The addition of measures that reflect the recovery from each procedure, such as brain activity and behavioural regulation, would further improve estimates of the pain burden of neonatal intensive care.
Use of solution-processed zinc oxide to prevent the breakdown in silver nanowire networks

The electrical breakdown is a bottleneck preventing AgNW networks from being used in high-current electronics such as transparent heaters or similar applications. The process of failure confirms that Joule-heating plays a key role in the formation of cracks perpendicular to the voltage direction. To improve the transfer of Joule heating, solution-processed ZnO nanoparticles were deposited on a gravure printed AgNW random network with good transparency. The AgNW-ZnO nanocomposites show better heating uniformity at higher temperatures because of their improved thermal conductivity. A 57.7% higher power density was obtained without failure, as well as the improved maximum average temperature rise from 72.2 °C to 97.9 °C, after the AgNW was composited with ZnO. This work opens up a new method to study AgNW failures for applications in high-current electronics.