Miracle-dz/UniFAR-FTUs huggingface dataset:
On the specificity of protein–protein interactions in the context of disorder

With the increased focus on intrinsically disordered proteins (IDPs) and their large interactomes, the question about their specificity — or more so on their multispecificity — arise. Here we recapitulate how specificity and multispecificity are quantified and address through examples if IDPs in this respect differ from globular proteins. The conclusion is that quantitatively, globular proteins and IDPs are similar when it comes to specificity. However, compared with globular proteins, IDPs have larger interactome sizes, a phenomenon that is further enabled by their flexibility, repetitive binding motifs and propensity to adapt to different binding partners. For IDPs, this adaptability, interactome size and a higher degree of multivalency opens for new interaction mechanisms such as facilitated exchange through trimer formation and ultra-sensitivity via threshold effects and ensemble redistribution. IDPs and their interactions, thus, do not compromise the definition of specificity. Instead, it is the sheer size of their interactomes that complicates its calculation. More importantly, it is this size that challenges how we conceptually envision, interpret and speak about their specificity.
Decreased Basal Ganglia Volume in Cerebral Amyloid Angiopathy

Background and Purpose Cerebral amyloid angiopathy (CAA) is a common pathology of the leptomeningeal and cortical small vessels associated with hemorrhagic and non-hemorrhagic brain injury. Given previous evidence for CAA-related loss of cortical thickness and white matter volume, we hypothesized that CAA might also cause tissue loss in the basal ganglia. Methods We compared basal ganglia volumes expressed as a percentage of total intracranial volume (pBGV) of non-demented patients with sporadic and hereditary CAA to age-matched healthy control (HC) and Alzheimer’s disease (AD) cohorts. Results Patients with sporadic CAA had lower pBGV (n=80, 1.16%±0.14%) compared to HC (n=80, 1.30%±0.13%, P<0.0001) and AD patients (n=80, 1.23%±0.11%, P=0.001). Similarly, patients with hereditary CAA demonstrated lower pBGV (n=25, 1.26%±0.17%) compared to their matched HC (n=25, 1.36%±0.15%, P=0.036). Using a measurement of normalized basal ganglia width developed for analysis of clinical-grade magnetic resonance images, we found smaller basal ganglia width in patients with CAA-related lobar intracerebral hemorrhage (ICH; n=93, 12.35±1.47) compared to age-matched patients with hypertension-related deep ICH (n=93, 13.46±1.51, P<0.0001) or HC (n=93, 15.45±1.22, P<0.0001). Within the sporadic CAA research cohort, decreased basal ganglia volume was independently correlated with greater cortical gray matter atrophy (r=0.45, P<0.0001), increased basal ganglia fractional anisotropy (r=–0.36, P=0.001), and worse performance on language processing (r=0.35, P=0.003), but not with cognitive tests of executive function or processing speed. Conclusions These findings suggest an independent effect of CAA on basal ganglia tissue loss, indicating a novel mechanism for CAA-related brain injury and neurologic dysfunction.
Association of AFF3 Gene Polymorphism rs10865035 with Rheumatoid Arthritis: A Population-Based Case-Control Study on a Pakistani Cohort

Rheumatoid arthritis (RA) is one of the complex diseases with the involvement of the genetic as well as environmental factors in its onset and severity. Different genome-wide association and candidate gene studies have shown the role of several genetic variants in multiple loci/genes with ethnical and geographical variations. This study was designed to detect the association of a single-nucleotide polymorphism (SNP) rs10865035 in the AFF3 gene with the genetic background of rheumatoid arthritis (RA) in the Pakistani cohort. A total of 703 individuals, including 409 RA patients and 294 healthy controls, were genotyped using TaqMan assay and Tri primer ARMS-PCR (amplification-refractory mutation system-polymerase chain reaction) methods. The association of rs10865035 with the RA was statistically determined using different models. Interestingly, besides the homozygous recessive model (G/G vs. A/G + A/A) (OR = 1.693(1.06–2.648); P = 0.025), all other models, which included the codominant (χ2 = 5.169; P = 0.075), homozygous dominant (A/A vs. G/G + A/G) (OR = 0.867 (0.636–1.187); P = 0.41), heterozygous (A/G vs. A/A + GG) (OR = 0.491 (0.667–1.215); P = 0.49), and additive model (OR = 0.826 (0.665–1.027); P = 0.08) showed insignificant distribution of the genotypes among the cases and controls. These findings suggest that the AFF3 gene (rs10865035) has no significant role in the onset of RA in the Pakistani population.
The Role of Virtual Physical Therapy in a Post Pandemic World - Pearls, Pitfalls, Challenges, and Adaptations.

OBJECTIVE To keep patients healthy and safe during the pandemic, payers and the Federal Government temporarily relaxed restrictions, expanded the eligible provider list for providing telehealth services, and developed a reimbursement structure. Physical therapists were uniquely challenged during the pandemic, requiring a reassessment of techniques and strategies in order to best support patients. The purpose of this case report is to describe a musculoskeletal institution's experience with implementing telehealth physical therapy. METHODS (CASE DESCRIPTION) Previous telehealth experience enabled the infrastructure of a wide-scale adoption across institutions response to the Covid-19 pandemic. However, to fill in training gaps for HSS outpatient physical therapists, HSS Rehabilitation developed a robust education and implementation program. This training was influenced by clinician and patient surveys as well as the development of a published HSS Rehabilitation telehealth guide. Prior to performing telehealth physical therapist visits, clinicians were required to complete all training material to ensure comfortability and confidence. RESULTS The adoption of telehealth among clinicians was born out of necessaity, however the speed in which HSS rehabilitation pivoted was critical to avoid lapses in care. In a four week period after the NYC shelter in-place orders, 173 therapists were trained and performing virtual visits. HSS rehabilitation determined telehealth physical therapy had quicker access to care, similar patient satisifaction, and increase geographical outreach when compared to in-person care. CONCLUSIONS The tranisition to telehealth physical therapy included a multi-step process that provided clinician training, establishment of protocols and guidelines, and obtaining a better understanding of the patient experience. Telehealth physical therapy has shown early benefits such as improving patient access to care, and better continuity of care for patients traveling. Even after the current public health emergency, there is a place for high value telehealth physical therapy in caring for patients with musculoskeletal conditions.
Cognitive Functions in Adult‐Onset Phenotypes of X‐Linked Adrenoleukodystrophy

X‐linked adrenoleukodystrophy (X‐ALD) is a rare genetic disorder characterized by progressive demyelination ranging from mild myelopathic forms (adrenomyeloneuropathy [AMN]) to severe cerebral variants (adult cerebral adrenoleukodystrophy [ACALD]). The aim of this study was to compare cognitive function in adult‐onset X‐ALD phenotypes.
Effect of low and high concentrate supplementation on health and welfare indicators in different breeds in small-scale mountain dairy farms

Abstract We investigated and compared the effects of low and high concentrate supplementation in terms of animal welfare, health and reproductive performance in two different dairy cow breeds on small-scale mountain farms. 64 South Tyrolean dairy farms were evaluated using an on-farm assessment for animal-based and resource-based welfare indicators, data from test day records, and a questionnaire for the farmer. Farms were divided into four groups: low input Tyrolean Grey (L-TG), low input Brown Swiss (L-BS), high input Tyrolean Grey (H-TG) and high input Brown Swiss (H-BS). Effects of intensity level, breed and their interaction were calculated and analyzed statistically. The predominant husbandry system across all groups was tie-stall. The average energy-corrected milk yield increased with increasing concentrate level, with L-TG showing the lowest and H-BS showing the highest milk yield. Age at first calving was lowest in H-BS when compared to all other systems, while numbers of lactations were higher in L-TG compared to H-BS. Feed efficiency (percentage of milk out of roughage) was significantly higher in L-TG and L-BS when compared to H-TG and H-BS. L-BS showed the poorest results for most of the welfare indicators such as lean cows, lesions and percentage of dirty animals. In conclusion, a higher concentrate level in diets does not lead automatically to lower animal welfare for dairy cows in alpine regions. Indeed, keeping high yielding breeds in extensive systems seems to be challenging. The dual-purpose breed TG showed some clear advantages in that calving interval was lower and the number of lactations greater.
International nurse education leaders’ experiences of responding to the COVID‐19 pandemic: A qualitative study

Abstract Aims To explore the experiences of strategic leads for nurse education as they sought to respond to the COVID‐19 pandemic. Design We utilised a qualitative interpretative approach to explore education leaders’ experiences of leading during the early months of the pandemic. Methods Nineteen leaders with significant strategic responsibility for nurse education in Australia, Canada, New Zealand, Singapore and the United Kingdom were identified via purposive sampling and agreed to participate. Interviews were held between May and July 2020. Results Four overarching themes arose from the analysis: (1) Crisis driven adaptability & flexibility; (2) Responsive, complex and changing communication; (3) Making decisions for student and staff safety; (4) Looking to the future; stronger partnerships. Conclusion Internationally, while nursing education leaders faced different problems, they shared a common goal amidst the crisis to remain student‐centred. They demonstrated they were able to face major challenges, respond to large scale logistical problems and make decisions under significant and ongoing pressure. Impact In responding to the pandemic, nurse leaders shared knowledge and offered mutual support. This bodes well for future collaboration. The move to online learning accelerated an existing trend and it seems likely that this will continue. Given the pressures they experienced over an extended period, the sector may wish to consider how it prepares and supports existing and future leaders.
Supplementation of rice husk activated charcoal in feed and its effects on growth and histology of the stomach and intestines from giant trevally, Caranx ignobilis

Background: Research on supplementing feed with rice husk activated charcoal was carried out to determine the effect of variations in the concentration of rice husk activated charcoal on the growth and histological features of the giant trevally Caranx ignobilis intestine. Methods: This study used an experimental method with a completely randomized design consisting of six treatments and four replications, including adding activated charcoal to feed at concentrations of 0%, 1%, 1.5%, 2%, 2.5%, and 3% for 42 days. The measured parameters included daily growth rate (DGR), specific growth rate (SGR), absolute growth rate (AGR), feed conversion ratio (FCR), feed efficiency (FE), survival rate (SR), length of foveola gastrica, width of foveola gastrica, length of intestinal villi, and width of intestinal villi. Data were analyzed statistically using one-way analysis of variance and Duncan’s test. Results: The results showed that supplementing fish feed with rice husk activated charcoal at different concentrations significantly affected the values of DGR, AGR, FCR, FE, SR, length of the foveola gastrica, length of the villous intestine, and width of the villous intestine, but did not significantly affect SGR or foveola gastrica width. Conclusion: The 2% rice husk activated charcoal treatment showed the best results for all parameters.
Kidney-Targeted Delivery of Prolyl Hydroxylase Domain Protein 2 Small Interfering RNA with Nanoparticles Alleviated Renal Ischemia/Reperfusion Injury

Inhibition of hypoxia-inducible factor–prolyl hydroxylase (PHD) has been shown to protect against various kidney diseases. However, there are controversial reports on the effect of PHD inhibition in renoprotection. The present study determined whether delivery of PHD2 small interfering RNA (siRNA) using an siRNA carrier, folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA), would mainly target kidneys and protect against renal ischemia/reperfusion injury (I/R). The renal I/R was generated by clipping the renal pedicle for 30 minutes in uninephrectomized mice. Mice were sacrificed 48 hours after I/R. Normal saline or G5-FA complexed with control or PHD2 siRNA was injected via tail vein 24 hours before ischemia. After the injection of near-infrared fluorescent dye–labeled G5-FA, the fluorescence was mainly detected in kidneys but not in other organs. The reduction of PHD2 mRNA and protein was only observed in kidneys but not in other organs after injection of PHD2-siRNA-G5-FA complex. The injection of PHD2-siRNA-G5-FA significantly alleviated renal I/R injury, as shown by the inhibition of increases in serum creatinine and blood urea nitrogen, the blockade of increases in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and the improvement of histologic damage compared with mice treated with control siRNA. PHD2 siRNA can be delivered specifically into kidneys using G5-FA, and that local knockdown of PHD2 gene expression within the kidney alleviates renal I/R injury. Therefore, G5-FA is an efficient siRNA carrier to deliver siRNA into the kidney, and that local inhibition of PHD2 within the kidney may be a potential strategy for the management of acute I/R injury. SIGNIFICANCE STATEMENT Folic acid (FA)-decorated polyamidoamine dendrimer generation 5 (G5-FA) was demonstrated to be an effective carrier to deliver small interfering RNA (siRNA) into kidneys. Delivery of prolyl hydroxylase domain protein 2 siRNA with G5-FA effectively protected the kidneys against the acute renal ischemia/reperfusion injury.
Gait asymmetries are exacerbated at faster walking speeds in individuals with acute anterior cruciate ligament reconstruction

Previous research suggests more biomechanically demanding tasks (e.g., stair descent, hopping) magnify biomechanical asymmetries compared with walking after anterior cruciate ligament (ACL) reconstruction. However, it is unclear if modifying task‐specific constraints, like walking speed also elicits greater biomechanical asymmetries in this population. We examined the effects of manipulating walking speed on ground reaction force (GRF) asymmetries in individuals with ACL reconstruction and uninjured controls. Thirty individuals with ACL reconstruction (age = 20.6 ± 5.4 years, body mass index [BMI] = 23.9 ± 3.3 kg/m2) and 15 controls (age = 23.1 ± 4.5 years, BMI = 23.6 ± 2.7 kg/m2) were tested on an instrumented treadmill at three speeds (100%, 120%, and 80% self‐selected speed). Bilateral vertical and posterior‐anterior GRFs were recorded at each speed. GRF asymmetries were calculated by subtracting the uninjured from the injured limb at each percent of stance. Statistical parametric mapping was used to evaluate the effects of speed on GRF asymmetries across stance. We found vertical and posterior GRF asymmetries were exacerbated at faster speeds and reduced at slower speeds in ACL individuals but not controls (p < .05). No differences in anterior GRF asymmetries were observed between speeds in either group (p > .05). Our results suggest increasing walking speed magnifies GRF asymmetries in individuals with ACL reconstruction. Statement of Clinical Significance: Evaluating both preferred and fast walking speeds may aid in characterizing biomechanical asymmetries in individuals with ACL reconstruction which may be valuable in earlier rehabilitative time points when more difficult tasks like hopping and running are not feasible.
Color Preference for Host-Seeking Activity of Aedes albopictus and Culex pipiens (Diptera: Culicidae)

Abstract A cue for long-range vision allows mosquitoes to identify hosts and differentiate the ecological niches (e.g., habitats). However, the visual factors involved in attracting mosquitoes to a host are complex and have not been fully understood. Therefore, we assessed color preference to Aedes albopictus (Skuse) and Culex pipiens (Conquillett) as diurnal and nocturnal species, respectively, using seven fundamental colors including black, white, red, yellow, green, blue, and purple with each trap at 100 lux in a laboratory. We used a binary behavioral assay using the Mosquito Preference Index (MPI) as a preference ratio with a range of 0–1. Our analyses showed that Ae. albopictus had a greater response to black (MPIs, 0.7), followed closely by red, blue, and purple (MPIs, 0.6). We also found that red, blue, and purple were significantly higher (P < 0.05) than those of green (MPI, 0.5), white (MPI, 0.3), and yellow (MPI, 0.2). Similarly, the MPIs for Cx. pipiens were significantly higher at black and red (MPIs, 0.7; P < 0.05) compare to those of white and yellow (MPIs, 0.3; P < 0.05). The color preference of Ae. albopictus showed significant correlation to luminous intensities (L-value) (r = –0.640; P = 0.000) and blue intensities (b-value) (r = –0.372; P = 0.000) for all seven colors. In addition, Cx. pipiens negatively correlated (r = –0.703; P = 0.000) between color preference and L-value. Our analyses provide a greater understanding of how color plays a role in visual sensory stimuli, and how that could potentially affect mosquito host-seeking behavior.
Coping as a Mediator of the Relationship between Stress and Anxiety in Caregivers of Patients with Acute Stroke

According to Lazarus and Folkman’s theory, stress and coping affect an individual’s anxiety, which is an adaptive outcome. This study examined the mediation effects of stress-coping strategies on the relationship between stress and anxiety in caregivers of patients with acute stroke. A cross-sectional descriptive design was used to analyze a total of 131 caregivers caring for patients with acute stroke at a university hospital. The Caregivers Stress Scale, Ways of Coping Questionnaire, and Korean Beck Anxiety Inventory were used to quantify the participants’ responses. Our results revealed that emotion-focused coping (β = .56, p < .001) partially mediated the relationship between stress and anxiety (Z = 3.30, p < .001), suggesting its ability to exacerbate anxiety in the short term by acting as a mediator between stress and anxiety. Developing appropriate coping strategies for caregivers of patients with acute stroke is therefore critical for reducing their anxiety.
PURIFICATION AND CHARACTERISATION OF A NOVEL THERMAL STABLE LACCASE FROM PYCNOPORUS SP. SYBC-L3 AND ITS USE IN DYE DECOLORISATION

Abstract:A lacease (lac-L) was purified from the culture supernatant of Pycnoporus sp. SYBC-L3 in submerged fermentation and its partial properties were characterised. A purification of about 4.67-fold was achieved with an overall yield of 28% using ammonium sulphate precipitation, Sephadex G-25 and Q-Sepharose Fast Flow. The molecular mass of lac-L was estimated as 58kDa by sodium dodecyl sulphate—polyacrylamide gel electrophoresis with the N-terminal amino acid sequence of AIGPVADLTLTNAAV. Lac-L showed high temperature optima (55-75 °C) and acidic pH optima (3.5-4.5) to oxidise four different substrates. The best substrate for lac-L was found to be 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (Km = 0.1mM, Vmax = 1484U mg⁻¹) followed by 2,6-dimethoxyphenol (Km = 0.5mM, Vmax = 500 U mg⁻¹), Gua (Km = 1.38mM, Vmax = 125U mg⁻¹) and syringaldazine (Km = 8.16mM, Vmax = 2.58U mg⁻¹). The half-life of lac-L was 5h and 3h at 60 °C and 70 °C, respectively, which was longer than many other Pycnoporus laceases. The lac-L retained 80% of initial activity after 24h of incubation in the 6.0-9.0 pH range. The lac-L was tolerant towards most metal ions except Fe³⁺, Fe²⁺ and Ag⁺. Lac-L can effectively decolorise Remazol Brilliant Blue R, Mordant Red 5G, Weak Acid Blue 25, and Acid Blue 129 without any mediators.
Role of Blood Lipid Levels and Lipid-Lowering Therapy in Stroke Patients with Different Levels of Cerebral Artery Diseases: Reconsidering Recent Stroke Guidelines

Hyperlipidemia is an important risk factor for ischemic stroke; the Stroke Prevention by Aggressive Reduction in Cholesterol Level and Treat Stroke to Target studies have shown that statins are beneficial for patients with stroke and that a low target for low-density lipoprotein cholesterol (LDL-C) concentration may maximize this benefit. Based on these results, recent guidelines have emphasized the application of “high-intensity statins” and “low LDL-C target” strategies in patients with stroke. However, it should be kept in mind that the role of blood lipids as a risk factor and benefit of lipid-lowering therapy are different among patients with different levels of cerebral arterial diseases. Studies have suggested that hypolipidemia, but not hyperlipidemia, is a risk factor for small vessel diseases (SVDs) such as intracerebral hemorrhages, microbleeds, white matter hyperintensities, and perhaps, lacunar infarction. Although lipid-lowering agents might benefit certain patients with SVD, high-intensity statin and low LDL-C target strategies cannot be applied. In contrast, these strategies are important in patients with extracranial atherosclerosis, such as internal carotid disease, considering ample evidence of the benefits of lipid-lowering agents. Imaging studies have shown that statins stabilize vulnerable plaques in these patients. Although lipid-lowering agents are likely to benefit patients with intracranial atherosclerosis, the degree of their benefit and appropriate target LDL-C level for these patients remain unclear. More studies are needed to elucidate the appropriate lipid-modifying strategies in patients with stroke with different levels of cerebral artery disease.
Magnetic field-temperature phase diagram, exchange constants and specific heat exponents of the antiferromagnet MnNb2O6

This work presents the magnetic field-temperature (H–T) phase diagram, exchange constants, specific heat (C P) exponents and magnetic ground state of the antiferromagnetic MnNb2O6 polycrystals. Temperature dependence of the magnetic susceptibility χ (=M/H) yields the Néel temperature T N = 4.33 K determined from the peak in the computed ∂(χT)/∂T vs T plot in agreement with the transition in the C P vs T data at T N = 4.36 K. The experimental data of C P vs T near T N is fitted to C P = A|T − T N|−α yielding the critical exponent α = 0.12 (0.15) for T > T N (T < T N). The best fit of χ vs T data for T > 50 K to χ = χ 0 + C/(T − θ) with χ 0 = −1.85 × 10−4 emu mol−1 Oe−1 yields θ = −17 K, and C = 4.385 emu K mol−1 Oe−1, the latter giving magnetic moment μ = 5. 920μ B per Mn2+ ion. This confirms the effective spin S = 5/2 and g = 2.001 for Mn2+ and the dominant exchange interaction being antiferromagnetic in nature. Using the magnitudes of θ and T N and molecular field theory (MFT), the exchange constants J 0/k B = −1.08 K for Mn2+ ions along the chain c-axis and J ⊥/k B = −0.61 K as the interchain coupling perpendicular to c-axis are determined. These exchange constants are consistent with the expected χ vs T variation for the Heisenberg linear chain. The H–T phase diagram, mapped using the M–H isotherms and M–T data at different H combined with the reported data of Nielsen et al, yields a triple-point T TP (H, T) = (18 kOe, 4.06 K). The spin–flopped state above T TP and the forced ferromagnetism for H > 192 kOe are used to estimate the anisotropy energy H A ≈ 0.8 kOe.