Factors influencing imaging clinical decision-making in low back pain management. A scoping review.

BACKGROUND: The use of diagnostic imaging in low back pain (LBP) management is often inappropriate, despite recommendations from clinical practice guidelines. There is a limited understanding of factors that influence the imaging clinical decision-making (CDM) process. AIM: Explore the literature on factors influencing imaging CDM for people with LBP and consider how these findings could be used to reduce inappropriate use of imaging in LBP management. DESIGN: Scoping review. METHOD: This review followed the Preferred Reporting Items for Systematic Review extension for scoping reviews. A digital search was conducted in Medline, the Cumulative Index of Nursing and Allied Health Literature, Scopus, and the Cochrane Central Register of Controlled Trials for eligible studies published between January 2010-2023. Data reporting influences on imaging CDM were extracted. Data were then analysed through an inductive process to group the influencing factors into categories. RESULTS: After screening, 35 studies (5 qualitative and 30 quantitative) were included in the review, which reported factors influencing imaging CDM. Three categories were developed: clinical features (such as red flags, pain, and neurological deficit), non-modifiable factors (such as age, sex, and ethnicity) and modifiable factors (such as beliefs about consequences and clinical practice). Most studies reported non-modifiable factors. CONCLUSIONS: The results of this scoping review challenge the perception that imaging CDM is purely based on clinical history and objective findings. There is a complex interplay between clinical features, patient and clinician characteristics, beliefs, and environment. These findings should be considered when designing strategies to address inappropriate imaging behaviour.

Affimer reagents as tool molecules to modulate platelet GPVI-ligand interactions and specifically bind GPVI dimer.

Glycoprotein (GP)VI plays a key role in collagen-induced platelet aggregation. Affimers are engineered binding protein alternatives to antibodies. We screened and characterized GPVI-binding Affimers as novel tools to probe GPVI function. Among the positive clones, M17, D22 and D18 bound GPVI with the highest affinities (KD in the nM range). These Affimers inhibited GPVI-CRP-XL/collagen interactions, CRP-XL/collagen induced platelet aggregation and D22 also inhibited in vitro thrombus formation on a collagen surface under flow. D18 bound GPVI dimer but not monomer. GPVI binding was increased for D18 but not M17/D22 upon platelet activation by CRP-XL and ADP. D22 but not M17/D18 displaced nanobody2 (Nb2) binding to GPVI, indicating similar epitopes for D22 with Nb2 but not for M17/D18. Mapping of binding sites revealed that D22 binds a site that overlaps with Nb2 on the D1-domain, while M17 targets a site on the D2-domain, overlapping in part with the glenzocimab binding site, a humanized GPVI antibody Fab-fragment. D18 targets a new region on the D2-domain. We found that D18 is a stable non-covalent dimer and forms a stable complex with dimeric GPVI with 1:1 stoichiometry. Taken together, our data demonstrate that Affimers modulate GPVI-ligand interactions and bind different sites on GPVI D1/D2-domains. D18 is dimer-specific and could be used as a tool to detect GPVI dimerization or clustering in platelets. A dimeric epitope regulating ligand binding was identified on the GPVI D2-domain, which could be used for the development of novel bivalent antithrombotic agents selectively targeting GPVI dimer on platelets.

Intermittent theta burst stimulation and functional connectivity in people living with HIV/AIDS who smoke tobacco cigarettes: a preliminary pilot study.

Background: People living with HIV (PLWHA) smoke at three times the rate of the general population and respond poorly to cessation strategies. Previous studies examined repetitive transcranial magnetic stimulation (rTMS) over left dorsolateral prefrontal cortex (L. dlPFC) to reduce craving, but no studies have explored rTMS among PLWHA who smoke. The current pilot study compared the effects of active and sham intermittent theta-burst stimulation (iTBS) on resting state functional connectivity (rsFC), cigarette cue attentional bias, and cigarette craving in PLWHA who smoke. Methods: Eight PLWHA were recruited (single-blind, within-subject design) to receive one session of iTBS (n=8) over the L. dlPFC using neuronavigation and, four weeks later, sham iTBS (n=5). Cigarette craving and attentional bias assessments were completed before and after both iTBS and sham iTBS. rsFC was assessed before iTBS (baseline) and after iTBS and sham iTBS. Results: Compared to sham iTBS, iTBS enhanced rsFC between the L. dlPFC and bilateral medial prefrontal cortex and pons. iTBS also enhanced rsFC between the right insula and right occipital cortex compared to sham iTBS. iTBS also decreased cigarette craving and cigarette cue attentional bias. Conclusion: iTBS could potentially offer a therapeutic option for smoking cessation in PLWHA.

Estimating blue mussel (Mytilus edulis) connectivity and settlement capacity in mid-latitude fjord regions.

The mussel industry faces challenges such as low and inconsistent levels of larvae settlement and poor-quality spat, leading to variable production. However, mussel farming remains a vital sustainable and environmentally responsible method for producing protein, fostering ecological responsibility in the aquaculture sector. We investigate the population connectivity and larval dispersion of blue mussels (Mytilus edulis) in Scottish waters, as a case study, using a multidisciplinary approach that combined genetic data and particle modelling. This research allows us to develop a thorough understanding of blue mussel population dynamics in mid-latitude fjord regions, to infer gene-flow patterns, and to estimate population divergence. Our findings reveal a primary south-to-north particle transport direction and the presence of five genetic clusters. We discover a significant and continuous genetic material exchange among populations within the study area, with our biophysical model's outcomes aligning with our genetic observations. Additionally, our model reveals a robust connection between the southwest coast and the rest of the west coast. This study will guide the preservation of mussel farming regions, ensuring sustainable populations that contribute to marine ecosystem health and resilience.

Enabling Extreme Low-Temperature (≤ -100 °C) Battery Cycling with Niobium Tungsten Oxides Electrode and Tailored Electrolytes.

The degradation of current Li-ion batteries (LIBs) hinders their use in electronic devices, electric vehicles, and other applications at low temperatures, particularly in extreme environments like the polar regions and outer space. This study presents a pseudocapacitive-type niobium tungsten oxides (NbWO) electrode material combined with tailored electrolytes, enabling extreme low-temperature battery cycling for the first time. The synthesized NbWO material exhibits analogous structural properties to previous studies. Its homogenous atom distribution can further facilitate Li+ diffusion, while its pseudocapacitive Li+ storage mechanism enables faster Li+ reactions. Notably, the NbWO electrode material exhibits remarkable battery performance even at -60 and -100 °C, showcasing capacities of ≈90 and ≈75 mAh g-1 , respectively. The electrolytes, which have demonstrated favorable Li+ transport attributes at low temperatures in the earlier investigations, now enable extreme low-temperature battery operations, a feat not achievable with either NbWO or the electrolytes independently. Moreover, the outcomes extend to -120 °C and encompass a pouch-type cell configuration at -100 °C, albeit with reduced performance. This study highlights the potential of NbWO for developing batteries for their use in extremely frigid environments.

Assessment of Comorbid Obsessive-Compulsive Disorder and Posttraumatic Stress Disorder.

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) are commonly comorbid and share prominent features (e.g., intrusions, safety behaviors, and avoidance). Excellent self-report and clinician-administered assessments exist for OCD and PTSD individually, but few assess both disorders, and even fewer provide instruction on differential diagnosis or detection of comorbid OCD and PTSD. To address this gap in the literature, the current paper aims to (1) highlight diagnostic and functional similarities and differences between OCD and PTSD to inform differential diagnosis, (2) outline assessment recommendations for individuals with suspected comorbid OCD and PTSD, OCD with a significant trauma history or posttraumatic symptoms, or PTSD with significant obsessive-compulsive symptoms, and (3) explore future directions to evaluate and improve methods for assessing co-occurring OCD and PTSD.

SMRT-AgRenSeq-d in potato (Solanum tuberosum) as a method to identify candidates for the nematode resistance Gpa5.

Potato is the third most important food crop in the world. Diverse pathogens threaten sustainable crop production but can be controlled, in many cases, through the deployment of disease resistance genes belonging to the family of nucleotide-binding, leucine-rich-repeat (NLR) genes. To identify effective disease resistance genes in established varieties, we have successfully established SMRT-AgRenSeq in tetraploid potatoes and have further enhanced the methodology by including dRenSeq in an approach that we term SMR-AgRenSeq-d. The inclusion of dRenSeq enables the filtering of candidates after the association analysis by establishing a presence/absence matrix across resistant and susceptible varieties that is translated into an F1 score. Using a SMRT-RenSeq-based sequence representation of the NLRome from the cultivar Innovator, SMRT-AgRenSeq-d analyses reliably identified the late blight resistance benchmark genes Rpi-R1, Rpi-R2-like, Rpi-R3a, and Rpi-R3b in a panel of 117 varieties with variable phenotype penetrations. All benchmark genes were identified with an F1 score of 1, which indicates absolute linkage in the panel. This method also identified nine strong candidates for Gpa5 that controls the potato cyst nematode (PCN) species Globodera pallida (pathotypes Pa2/3). Assuming that NLRs are involved in controlling many types of resistances, SMRT-AgRenSeq-d can readily be applied to diverse crops and pathogen systems.

Obsessive-Compulsive Symptoms and Daily Experiences of Posttraumatic Stress and Mental Contamination Following Sexual Trauma.

Although cross-sectional research highlights similarities between symptoms of obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) among individuals exposed to sexual trauma, little is known about how these disorders relate over time. The goal of the present study was to examine whether 1) OCD symptoms prospectively predicted daily symptoms of PTSD, and 2) OCD and PTSD symptoms prospectively predicted daily experiences of sexual trauma-related mental contamination (i.e., dirtiness in the absence of a physical pollutant). Forty-one women with a sexual trauma history completed baseline measures of OCD and PTSD, as well as twice-daily assessments of PTSD symptoms and mental contamination over a two-week period. Total OCD symptoms and the unacceptable thoughts dimension significantly predicted daily PTSD symptoms after accounting for other OCD dimensions. Only total OCD symptoms significantly predicted daily mental contamination when examined together with total PTSD symptoms. No individual PTSD or OCD clusters/dimensions significantly predicted daily mental contamination when examined simultaneously. Findings from this study highlight the nuanced associations among OCD symptoms, PTSD symptoms, and experiences of mental contamination. Future research is needed to further understand the development of PTSD, OCD, and mental contamination over time to inform targets for intervention.

Fear of sin and fear of God: Scrupulosity predicts women's daily experiences of mental contamination following sexual trauma.

Mental contamination refers to feelings of dirtiness in response to thoughts, images, or memories. Mental contamination is frequently reported after sexual trauma and is associated with symptoms of posttraumatic stress disorder (PTSD). Differences in individuals' views about morality and purity may influence the severity of mental contamination, though this has been studied primarily outside of samples assessed for trauma and/or PTSD. The present study addressed this gap by investigating scrupulosity as a prospective predictor of daily sexual trauma-related mental contamination and PTSD symptoms. Participants included 40 adult women with a history of sexual trauma and current sexual trauma-related mental contamination who completed baseline diagnostic interviews and questionnaires followed by two assessments every day for 2 weeks. The results indicate that scrupulosity was positively correlated with PTSD symptom severity and sexual trauma-related mental contamination at baseline. Scrupulosity was also a prospective predictor of increased daily sexual trauma-related mental contamination, B = 0.19, SE = 0.07, p = .010, but not daily PTSD symptoms, B = -0.10, SE = .08, p = .198. The findings indicate that scrupulosity may be an important factor in understanding recovery from sexual assault.

AMTASTM and user-operated smartphone research application audiometry-An evaluation study.

OBJECTIVE: To evaluate two user-operated audiometry methods, the AMTASTM PC-based audiometry and a low-cost smartphone audiometry research application (R-App). DESIGN: A repeated-measures within-subject study design was used to compare both user-operated methods to traditional manual audiometry and to evaluate test-retest reliability of each method. STUDY SAMPLE: 58 subjects were recruited in the study of which 83 ears had normal hearing thresholds and 33 ears had hearing loss (pure-tone average > 25 dB HL). Average age of participants was 44.8 years, with an age range of 11-85. RESULTS: Standard deviation of absolute differences ranged between 3.9-6.9 dB on AMTASTM and 4.5-6.8 dB on the R-App. The highest variability was found at the 8000 Hz frequency (R-App and AMTASTM test) and 3000 Hz frequency (AMTASTM retest). Evaluation of test-retest reliability of AMTASTM and R-App showed SD of absolute differences ranging between 3.5-5.8 dB and 3.1-5.0 dB, respectively. The mean threshold difference between test and retest was within ±1.5 dB on AMTASTM and ±1 dB on the R-App. CONCLUSION: Accuracy of AMTASTM and the R-App was within acceptable limits for audiometry and comparable to traditional manual audiometry on all tested frequencies (250-8000 Hz). Evaluation of test-retest reliability showed acceptable variation on both AMTASTM and R-App. Both user-operated methods could be reliably performed in a quiet non-soundproofed environment.

Frontopolar multifocal transcranial direct current stimulation reduces conditioned fear reactivity during extinction training: A pilot randomized controlled trial.

Exposure-based therapies for anxiety and related disorders are believed to depend on fear extinction learning and corresponding changes in extinction circuitry. Frontopolar multifocal transcranial direct current stimulation (tDCS) has been shown to improve therapeutic safety learning during in vivo exposure and may modulate functional connectivity of networks implicated in fear processing and inhibition. A pilot randomized controlled trial was completed to determine the effects of frontopolar tDCS on extinction learning and memory. Community volunteers (n = 35) completed a 3-day fear extinction paradigm with measurement of electrodermal activity. Participants were randomized (single-blind) to 20-min of sham (n = 17, 30 s. ramp in/out) or active (n = 18) frontopolar (anode over Fpz, 10-10 EEG) multifocal tDCS (20-min, 1.5 mA) prior to extinction training. Mixed ANOVAs revealed a significant group*trial effect on skin conductance response (SCR) to the conditioned stimulus (CS + ) during extinction training (p = 0.007, Cohen's d = 0.55). The effects of frontopolar tDCS were greatest during the first two extinction trials, suggesting that tDCS may have promoted fear inhibition prior to safety learning. Return of fear to the CS + during tests were comparable across conditions (ps > 0.50). These findings suggest that frontopolar tDCS may modulate the processing of threat cues and associated circuitry or promote the inhibition of fear. This has clear implications for the treatment of anxiety and related disorders with therapeutic exposure.

Affimer-mediated locking of p21-activated kinase 5 in an intermediate activation state results in kinase inhibition.

Kinases are important therapeutic targets, and their inhibitors are classified according to their mechanism of action, which range from blocking ATP binding to covalent inhibition. Here, a mechanism of inhibition is highlighted by capturing p21-activated kinase 5 (PAK5) in an intermediate state of activation using an Affimer reagent that binds in the P+1 pocket. PAK5 was identified from a non-hypothesis-driven high-content imaging RNAi screen in urothelial cancer cells. Silencing of PAK5 resulted in reduced cell number, G1/S arrest, and enlargement of cells, suggesting it to be important in urothelial cancer cell line survival and proliferation. Affimer reagents were isolated to identify mechanisms of inhibition. The Affimer PAK5-Af17 recapitulated the phenotype seen with siRNA. Co-crystallization revealed that PAK5-Af17 bound in the P+1 pocket of PAK5, locking the kinase into a partial activation state. This mechanism of inhibition indicates that another class of kinase inhibitors is possible.

Neurofeedback for obsessive compulsive disorder: A randomized, double-blind trial.

We aim to develop fMRI neurofeedback as a treatment for obsessive compulsive disorder (OCD). In prior work, we found that providing neurofeedback of activity in the anterior prefrontal cortex (aPFC) improved control over contamination anxiety in a subclinical population. Here, we present the results of a randomized, double-blind clinical trial (NCT02206945) testing this intervention in patients with OCD. We recruited patients with primary symptoms in the fear-of-harm/checking or contamination/washing domains. During neurofeedback, they viewed symptom provocative images and attempted to up- and down-regulate the aPFC during different blocks of time. The active group received two sessions of neurofeedback and the control group received yoked sham feedback. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Symptom scale. The secondary outcome was control over aPFC. Thirty-six participants completed feedback training (18 active, 18 control). The active group had a slightly but significantly greater reduction of obsessive-compulsive symptoms after neurofeedback compared to the control group (p<.05) but no significant differences in control over the aPFC. These data demonstrate that neurofeedback targeting the aPFC can reduce symptoms in OCD. Future investigations should seek to optimize the training protocol to yield larger effects and to clarify the mechanism of action.

HISS: Snakemake-based workflows for performing SMRT-RenSeq assembly, AgRenSeq and dRenSeq for the discovery of novel plant disease resistance genes.

BACKGROUND: In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of a k-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise. RESULTS: Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license. CONCLUSIONS: HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses.

Luminal-Type Invasive Carcinoma in Association With Microglandular Adenosis/Atypical Microglandular Adenosis: A Case Report and Molecular Comparison.

Microglandular adenosis (MGA) is a proliferative breast lesion composed of small, uniform glands lacking a myoepithelial cell layer while still invested by the basement membrane. The glands percolate haphazardly through the breast parenchyma rather than maintaining a lobular architecture, typical of other forms of adenosis.MGA is a benign lesion though atypical forms have been well described, often in close association with carcinoma. MGA, atypical MGA (AMGA), and the vast majority of MGA-associated carcinomas (MGACA) are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) by immunohistochemistry. In light of these findings and early molecular studies, MGA is hypothesized to represent a clonal process and nonobligate precursor of basal-type breast carcinomas. We present the case of a 58-year-old woman and the first published molecular comparison of a luminal-type invasive ductal carcinoma with its associated MGA/AMGA. Analysis of small nucleotide variants (SNVs) revealed that 63% of the SNVs identified in the MGA were present in the AMGA while only 10% of them were present in the MGACA, suggesting a direct relationship between MGA and AMGA but not MGA and MGACA.

Case report of a pan-cytokeratin negative NUT midline carcinoma of pulmonary origin, a BRD3-NUT variant: Challenges in cytomorphologic presentation.

NUT carcinoma is an aggressive malignancy defined genetically by a balanced translocation of the NUT gene on chromosome 15q14, most commonly associated with the bromodomain-containing protein 4 (BRD4) gene on 19p13.1 but less frequently with variant genes, including BRD3 and NSD-3. We present a case report of a metastatic pulmonary NUT carcinoma found to have a BRD3-NUT fusion and to have only focal pan-cytokeratin staining. Biopsy of the pulmonary mass revealed dyscohesive cells with enlarged nuclei, prominent nucleoli and high nuclear to cytoplasmic ratio without areas of squamous differentiation. Initial immunohistochemical stains were positive for NUT, p63 and retained SMARCA4, while negative for Lu-5 (pan-cytokeratin), TTF-1, p40, S100 protein, OCT-4, HMB-45, SMA, and PAX-8. Tempus ×T assay revealed a BRD3-NUTM1 fusion gene. Post-mortem analysis revealed an ill-defined mass abutting the trachea and superior vena cava, as well as a perirenal mass.

Interactive association of posttraumatic stress disorder, apolipoprotein ε4 genotype, and age on cognitive functioning.

BACKGROUND: The ε4 allele of the apolipoprotein (APOE) gene and posttraumatic stress disorder (PTSD) are associated with cognitive deficits. Both associations may vary depending on age. No previous study has examined a possible three-way interaction between APOE ε4, PTSD, and age on cognitive functioning. METHODS: Data were analyzed from 1244 European-American U.S. military veterans who participated in the 2011 National Health and Resilience in Veterans Study (NHRVS). Analyses of covariance were used to examine the main effects and interactions of APOE ε4, PTSD, and age on learning/working memory (LWM) and attention/psychomotor (APM) performance. RESULTS: A significant three-way interaction between APOE ε4, PTSD, and age on the LWM composite (ηp 2  = 0.011) was observed such that the main effect of APOE ε4 on LWM was only significant for older participants with PTSD. A significant two-way interaction between PTSD and age on the APM composite (ηp 2  = 0.011) was observed such that the main effect of PTSD on APM was only significant in older participants. CONCLUSION: Older APOE ε4 carriers with probable PTSD showed poorer LWM performance relative to other groups. Aging-related associations on APM performance were most pronounced in veterans with PTSD. These data are preliminary evidence that identification and treatment of PTSD may be beneficial for individuals at risk for age-related cognitive impairment.