Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-Leg Squat Performance and Its Relationship to Extensor Mechanism Strength After Anterior Cruciate Ligament Reconstruction

Background: Performance in strength and functional testing is important when considering return to sport after anterior cruciate ligament (ACL) reconstruction. Both knee extensor strength and the single-leg squat (SLS) have been used in this context. Purpose: To evaluate the relationship between knee extensor strength and SLS performance after primary ACL reconstruction. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: A prospective cohort of 100 patients was assessed 6 and 12 months after primary ACL reconstruction with a hamstring tendon autograft. Knee extensor peak torque was measured. Three sequential SLSs were performed, and the maximum flexion angle identified from frame-by-frame video analysis was used as the measure of squat performance. A limb symmetry index (LSI) was calculated and satisfactory performance defined as ≥90%. Results: Extensor mechanism strength deficits were seen in 75% of patients at 6 months and 57% at 12 months postoperatively. Mean extensor mechanism strength showed a large improvement between 6 and 12 months (123.6 vs 147.8 N·m, respectively; P < .001; Cohen d = 1.10), and while there was also a statistically significant improvement in the mean maximum flexion angle, the change was small (66.1° vs 68.1°, respectively; P = .011; Cohen d = 0.26). There was a weak positive correlation between knee extensor strength and the SLS maximum flexion angle at 6 months (r = 0.342; P < .001) and 12 months (r = 0.245; P = .014). An SLS LSI <90% was 80% specific and 35% sensitive for extensor mechanism weakness at 6 months and 79% specific and 18% sensitive at 12 months. Conclusion: Extensor mechanism strength deficits are common after ACL reconstruction but reduce between 6 and 12 months. The SLS maximum flexion angle has a weak linear relationship to knee extensor strength. SLS performance has high specificity but low sensitivity in identifying extensor mechanism strength deficits. The SLS maximum flexion angle is therefore a suboptimal surrogate test to identify extensor mechanism strength deficits as diagnosed by isokinetic dynamometric testing. However, unsatisfactory SLS performance indicates a very high chance of underlying extensor mechanism weakness.
Psychiatric morbidity, quality of life and caregiver burden in patients undergoing hemodialysis

Background: Psychiatric illnesses such as, depression, adjustment disorders, delirium, and anxiety disorders are common in dialysis patients and are likely to reduce patient's quality of life (QOL). Presence of chronic medical and psychiatric illness in patients increases burden on caregivers. Aims: The aim was to assess sociodemographic profile and to estimate the prevalence and type of psychiatric morbidity, QOL in patients undergoing hemodialysis. Furthermore, the study aimed to assess perceived burden in caregivers of these patients. Materials and Methods: This was a cross-sectional observational study conducted at hemodialysis unit of an urban tertiary care hospital. Fifty consecutive patients undergoing hemodialysis were included. Sociodemographic profile was assessed through semi-structured proforma. Psychiatric morbidity was assessed using Diagnostic and Statistical Manual IV Text Revised Criteria and World Health Organization QOL Scale-BREF scale was used to measure patient's QOL. Perceived burden in caregiver was assessed using Zarit Burden Interview. Data obtained were tabulated and analyzed using the SPSS software version 17. Results: Majority of patients was males, in middle-age group, secondary educated, unemployed and married. Psychiatric diagnosis was observed in 64% of the patients. Most common psychiatric diagnoses were major depressive disorder, adjustment disorder with depressed mood. Overall QOL score in patients was significantly low in those with psychiatric morbidity. Caregiver's burden was significantly high in those caring for patients with co-morbid psychiatric illness. Conclusions: Psychiatric morbidity in hemodialysis patients is high and impairs their QOL. Perceived burden of care in their caregivers is high in the presence of psychiatric co-morbidity.
Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test

Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous, multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study was to establish a test that allows for an objective assessment of the pathological potential of NPC1 gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying distinct sequence variants. Filipin staining was used to test for complementation of the phenotype. The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and 24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met, and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance. Moreover, we present a system that can be utilized to screen for new drugs.
Evaluation of the host cytokine response in dogs with sepsis and noninfectious systemic inflammatory response syndrome.

OBJECTIVE To quantify plasma cytokine concentrations in dogs with sepsis and noninfectious systemic inflammation and to evaluate the association between plasma cytokines and outcome in dogs with sepsis. DESIGN Prospective, observational cohort study. SETTING University teaching hospital. ANIMALS Forty-five dogs with sepsis, 10 dogs with noninfectious systemic inflammation (nSIRS), and 15 healthy controls were consecutively enrolled from June 2015 to February 2016 and followed to hospital discharge. Dogs with sepsis satisfied ≥2 SIRS criteria and had a documented or highly suspected bacterial infection. Dogs with nSIRS satisfied ≥2 SIRS criteria but had no evidence of infection. Dogs <3 kg and those with documented coagulopathy were excluded. INTERVENTIONS Measurement of inflammatory cytokines and high-mobility group box-1 (HMGB-1) was performed on each group. MEASUREMENTS AND MAIN RESULTS High-mobility group box-1 concentrations were analyzed by ELISA. Plasma concentrations of 13 cytokines were measured in singlet using multiplex magnetic bead assays. Kruskal-Wallis with Dunn's multiple comparison tests were used to compare biomarker concentrations between groups. Mann-Whitney U-tests were used to compare biomarker concentrations between survivors and nonsurvivors. Associations between biomarkers were evaluated using Spearman's correlation coefficients. Independent outcome predictors were identified using multivariable logistic regression. Alpha was set at 0.05. Concentrations of interleukin (IL)-6, C-X-C motif chemokine (CXCL)-8, keratinocyte-derived chemokine (KC)-like, C-C motif chemokine ligand 2 (CCL2), and HMGB-1 were significantly greater in dogs with sepsis versus healthy controls (all P ≤ 0.034). In dogs with sepsis, only CCL2 was independently associated with survival (odds ratio [OR] 0.996, 95% CI 0.993-0.999, P = 0.004). A cut-off of 385 pg/mL for CCL2 was 80% sensitive and 91.4% specific for nonsurvival (area under the ROC curve [AUROC] 0.866). CONCLUSIONS Dogs with sepsis have significantly increased concentrations of HMGB-1 and inflammatory cytokines, including IL-6, CXCL8, and KC-like. Increased CCL2 concentration is a negative prognostic indicator in dogs with sepsis. These findings should be confirmed using duplicate analyses in larger, distinct populations of dogs with sepsis before applying them to clinical patients.
Insomnia‐related interpretational bias is associated with pre‐sleep worry

Cognitive models of insomnia highlight the role of biased cognition in sleep‐related information, which is proposed to underlie pre‐sleep worry, which in turn results in both subjective and objective sleep deficits. To test this hypothesis, the current study investigated interpretational bias, which is a tendency to interpret ambiguous stimuli in a threat‐related (here: insomnia‐related) manner. We specifically hypothesized that interpretational bias would be associated with (a) pre‐sleep worry and (b) poor subjective and objective sleep. Interpretational bias was measured using the ambiguous scenario task, in which participants (n = 76, community sample) were presented with two types of scenarios (insomnia and anxiety related) that could be alternatively interpreted in a neutral manner. Participants additionally completed questionnaires to assess global sleep quality and pre‐sleep worry, which were followed by 1‐week sleep assessments (via diaries and actigraphy) to estimate specific, daily subjective and objective sleep parameters. The results showed that insomnia‐related (but not anxiety‐related) interpretational bias was positively associated with pre‐sleep worry as well as overall sleep quality. However, these associations could be explained by general trait anxiety. We also found no connection to specific subjective or objective parameters of daily sleep, such as sleep onset latency. These findings support the cognitive‐hyperarousal mechanism, where biased cognition (together with trait anxiety) underlies pre‐sleep worry. The association with overall sleep quality, but not with specific, daily subjective or objective sleep parameters, may suggest that interpretational bias is specifically relevant for how individuals judge and describe their sleep quality.
Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

ABSTRACT Epithelial cells are immune sensors and mediators that constitute the first line of defense against infections. Using the epididymis, a model for studying tubular organs, we uncovered a novel and unexpected role for professional proton-secreting ‘clear cells’ in sperm maturation and immune defense. The epididymal epithelium participates in the maturation of spermatozoa via the establishment of an acidic milieu and transfer of proteins to sperm cells, a poorly characterized process. We show that proton-secreting clear cells express mRNA transcripts and proteins that are acquired by maturing sperm, and that they establish close interactions with luminal spermatozoa via newly described ‘nanotubes’. Mechanistic studies show that injection of bacterial antigens in vivo induces chemokine expression in clear cells, followed by macrophage recruitment into the organ. Injection of an inflammatory intermediate mediator (IFN-γ) increased Cxcl10 expression in clear cells, revealing their participation as sensors and mediators of inflammation. The functional diversity adopted by clear cells might represent a generalized phenomenon by which similar epithelial cells decode signals, communicate with neighbors and mediate mucosal immunity, depending on their precise location within an organ. This article has an associated First Person interview with the first author of the paper. Summary: Proton-secreting cells lining the epididymal tubule can switch their function to become previously unrecognized regulators of immune responses, while establishing close interactions with spermatozoa.
Excitation of Diverse Classes of Cholecystokinin Interneurons in the Basal Amygdala Facilitates Fear Extinction

Abstract There is growing evidence that interneurons (INs) orchestrate neural activity and plasticity in corticoamygdala circuits to regulate fear behaviors. However, defining the precise role of cholecystokinin-expressing INs (CCK INs) remains elusive due to the technical challenge of parsing this population from CCK-expressing principal neurons (CCK PNs). Here, we used an intersectional genetic strategy in CCK-Cre;Dlx5/6-Flpe double-transgenic mice to study the anatomical, molecular and electrophysiological properties of CCK INs in the basal amygdala (BA) and optogenetically manipulate these cells during fear extinction. Electrophysiological recordings confirmed that this strategy targeted GABAergic cells and that a significant proportion expressed functional cannabinoid CB1 receptors; a defining characteristic of CCK-expressing basket cells. However, immunostaining showed that subsets of the genetically-targeted cells expressed either neuropeptide Y (NPY; 29%) or parvalbumin (PV; 17%), but not somatostatin (SOM) or Ca2+/calmodulin-dependent protein kinase II (CaMKII)-α. Further morphological and electrophysiological analyses showed that four IN types could be identified among the EYFP-expressing cells: CCK/cannabinoid receptor type 1 (CB1R)-expressing basket cells, neurogliaform cells, PV+ basket cells, and PV+ axo-axonic cells. At the behavioral level, in vivo optogenetic photostimulation of the targeted population during extinction acquisition led to reduced freezing on a light-free extinction retrieval test, indicating extinction memory facilitation; whereas photosilencing was without effect. Conversely, non-selective (i.e., inclusive of INs and PNs) photostimulation or photosilencing of CCK-targeted cells, using CCK-Cre single-transgenic mice, impaired extinction. These data reveal an unexpectedly high degree of phenotypic complexity in a unique population of extinction-modulating BA INs.
Predictability and Uncertainty in the Pleasure of Music: A Reward for Learning?

Music ranks among the greatest human pleasures. It consistently engages the reward system, and converging evidence implies it exploits predictions to do so. Both prediction confirmations and errors are essential for understanding one's environment, and music offers many of each as it manipulates interacting patterns across multiple timescales. Learning models suggest that a balance of these outcomes (i.e., intermediate complexity) optimizes the reduction of uncertainty to rewarding and pleasurable effect. Yet evidence of a similar pattern in music is mixed, hampered by arbitrary measures of complexity. In the present studies, we applied a well-validated information-theoretic model of auditory expectation to systematically measure two key aspects of musical complexity: predictability (operationalized as information content [IC]), and uncertainty (entropy). In Study 1, we evaluated how these properties affect musical preferences in 43 male and female participants; in Study 2, we replicated Study 1 in an independent sample of 27 people and assessed the contribution of veridical predictability by presenting the same stimuli seven times. Both studies revealed significant quadratic effects of IC and entropy on liking that outperformed linear effects, indicating reliable preferences for music of intermediate complexity. An interaction between IC and entropy further suggested preferences for more predictability during more uncertain contexts, which would facilitate uncertainty reduction. Repeating stimuli decreased liking ratings but did not disrupt the preference for intermediate complexity. Together, these findings support long-hypothesized optimal zones of predictability and uncertainty in musical pleasure with formal modeling, relating the pleasure of music listening to the intrinsic reward of learning. SIGNIFICANCE STATEMENT Abstract pleasures, such as music, claim much of our time, energy, and money despite lacking any clear adaptive benefits like food or shelter. Yet as music manipulates patterns of melody, rhythm, and more, it proficiently exploits our expectations. Given the importance of anticipating and adapting to our ever-changing environments, making and evaluating uncertain predictions can have strong emotional effects. Accordingly, we present evidence that listeners consistently prefer music of intermediate predictive complexity, and that preferences shift toward expected musical outcomes in more uncertain contexts. These results are consistent with theories that emphasize the intrinsic reward of learning, both by updating inaccurate predictions and validating accurate ones, which is optimal in environments that present manageable predictive challenges (i.e., reducible uncertainty).
THP-1 and Dictyostelium Infection Models for Screening and Characterization of Anti-Mycobacterium abscessus Hit Compounds

NCR1! presents a great challenge to antimycobacterial therapy due to its innate resistance against most antibiotics. M. abscessus is able to grow intracellularly in human macrophages, suggesting that intracellular models can facilitate drug discovery. Thus, we have developed two host cell models: human macrophages for use in a new high-content screening method for M. abscessus growth and a Dictyostelium discoideum infection model with the potential to simplify downstream genetic analysis of host cell factors. ABSTRACT ! NCR1! presents a great challenge to antimycobacterial therapy due to its innate resistance against most antibiotics. M. abscessus is able to grow intracellularly in human macrophages, suggesting that intracellular models can facilitate drug discovery. Thus, we have developed two host cell models: human macrophages for use in a new high-content screening method for M. abscessus growth and a Dictyostelium discoideum infection model with the potential to simplify downstream genetic analysis of host cell factors. A screen of 568 antibiotics for activity against intracellular M. abscessus led to the identification of two hit compounds with distinct growth inhibition. A collection of 317 human kinase inhibitors was analyzed, with the results yielding three compounds with an inhibitory effect on mycobacterial growth, strengthening the notion that host-directed therapy can be applied for M. abscessus.
PREVENTIVE ROLE OF VITAMIN D SUPPLEMENTATION FOR ACUTE PHASE REACTION AFTER BISPHOSPHONATE INFUSION IN PAGET'S DISEASE.

CONTEXT Intravenous amino-bisphosphonates (N-BPs) can induce an acute phase reaction (APR) in up to 40-70% of first infusions, causing discomfort and often requiring intervention with analgesics or antipyretics. OBJECTIVE Our aim was to explore the risk factors of APR in a large sample of patients with Paget's disease of bone (PDB) and to assess the possible preventive effects of vitamin D administration. METHODS An observational analysis was performed in 330 PDB cases at the time of N-BP infusion. Then, an interventional study was performed in 66 patients with active, untreated PDB to evaluate if vitamin D administration (oral cholecalciferol 50000 IU/weekly for 8 weeks before infusion) may prevent APR. RESULTS In retrospective study APR occurred in 47.6% and 18.3% of naive or previously treated patients, respectively. Its prevalence progressively increased in relation to the severity of vitamin D deficiency, reaching 80.0% in patients with 25OHD levels below 10 ng/ml (RR=3.7; 95%CIs 2.8-4.7, p<0.0001), even in cases previously treated with N-BPs. Moreover, APR occurred more frequently in patients who experienced a previous APR (RR=2.8; 95%CIs 1.5-5.2; p<0.001) or in carriers of SQSTM1 mutation (RR=2.3; 95%CIs 1.3-4.2; p=0.005). In the interventional study, vitamin D supplementation prevented APR in most cases, equivalent to a RR of 0.31 (95%CIs 0.14-0.67; p<0.005) with respect to prevalence rates of the observational cohort. A similar trend was observed concerning the occurrence of hypocalcaemia. CONCLUSIONS The achievement of adequate 25OHD levels is recommended before N-BP infusion in order to minimize the risk of APR or hypocalcaemia in PDB.
Emotional and personality predictors that influence the appearance of somatic complaints in children and adults.

BACKGROUND Personality and emotional factors may be contributing to the emergence of somatic complaints. The purpose of this study was to analyse the combined contribution of emotional awareness, moods and personality to somatic complaints in children and adults. METHOD Participants were 1,476 children (M= 9.90 years, SD= 1.27, 52.10% girls) and 940 adults (M= 32.30 years, SD= 11.62, 64% women) who were administered self-reports. Analysis was performed using fuzzy qualitative comparative analysis (fsQCA), an analytical technique that enables in-depth analysis of how a series of causal conditions contribute to a given outcome. RESULTS Emotional awareness, moods and personality account for 59% of high levels of somatic complaints in children and 69% in adults. In both samples, interaction between low levels of emotional awareness, high levels of negative moods and low levels of positive mood, high levels of neuroticism and low levels of the other personality factors appear to lead to high levels of somatic complaints (children: raw coverage = .18, consistency = .95; adults: raw coverage = .15, consistency = .97). CONCLUSION A similar contribution of emotional and personality components was found to explain somatic complaints in children and adults.
Seroprevalence and trend of hepatitides among blood donors in a district hospital in Ghana: a nine-year retrospective, descriptive cross-sectional study

ABSTRACT Hepatitis infections are among the greatest threats to human existence and survival and hence poses a serious public health challenge in blood donation. This study aimed to determine the prevalence and trend of hepatitis infections among voluntary blood donors at Nkenkaasu District Hospital. A retrospective study of voluntary blood donors’ records from January 2010 to December 2018 was conducted. Data on the donors’ age, sex and serum HBsAg and Hepatitis C virus results were retrieved from the Laboratory’s register and analyzed with SPSS version 16.0. Out of the 3306 total donors, the seroprevalence of hepatitis C infection was 11.7% and hepatitis B infection was 10.3%. Only 1.4% of the donors were co-infected with both pathogens and 82.7% had no infection. Rhesus blood group had a significant association with Hepatitis B (P = 0.005). As at 2010, both hepatitis infections had the same prevalence (73), from 2011 to 2018 both showed inconsistent trends. The relatively high seroprevalence of hepatitis infections identified from the study poses a greater threat to blood safety. Extensive screening of blood donors using standard techniques is highly recommended to ensure that recipients receive safe blood.