Association between cathepsins and benign prostate diseases: a bidirectional two-sample Mendelian randomization study

ObjectivesThe relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs). This study investigated the potential genetic link between cathepsins and BPDs through the utilization of Mendelian randomization (MR) analysis to determine if a causal relationship exists.MethodsPublicly accessible summary statistics on BPDs were obtained from FinnGen Biobank. The data comprised 149,363 individuals, with 30,066 cases and 119,297 controls for BPH, and 123,057 individuals, with 3,760 cases and 119,297 controls for prostatitis. The IEU OpenGWAS provided the Genome-wide association data on ten cathepsins. To evaluate the causal relationship between BPDs and cathepsins, five distinct MR analyses were employed, with the primary method being the inverse variance weighted (IVW) approach. Additionally, sensitivity analyses were conducted to examine the horizontal pleiotropy and heterogeneity of the findings.ResultsThe examination of IVW MR findings showed that cathepsin O had a beneficial effect on BPH (IVW OR=0.94, 95% CI 0.89–0.98, P=0.0055), while cathepsin X posed a threat to prostatitis (IVW OR=1.08, 95% CI 1.00–1.16, P=0.047). Through reverse MR analysis, it was revealed that prostatitis had an adverse impact on cathepsin V (IVW OR=0.89, 95% CI 0.80–0.99, P=0.035), while no favorable association was observed between BPH and cathepsins. The results obtained from MR-Egger, weighted median, simple mode, and weighted mode methods were consistent with the findings of the IVW approach. Based on sensitivity analyses, heterogeneity, and horizontal pleiotropy are unlikely to distort the results.ConclusionThis study offers the initial evidence of a genetic causal link between cathepsins and BPDs. Our findings revealed that cathepsin O was beneficial in preventing BPH, whereas cathepsin X posed a potential threat to prostatitis. Additionally, prostatitis negatively affected cathepsin V level. These three cathepsins could be targets of diagnosis and treatment for BPDs, which need further research

Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score

Objective To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. Methods A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1–4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). Results A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1–4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552–8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). Conclusion The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value

Novel mass spectrometric methodologies for in situ detection of hazardous chemical and biological agents

Mass spectrometry, widely recognized for its high speed, specificity and sensitivity as well as applicability in the analysis of a broad range of samples, is playing an even-increasingly important role in a broad range of applications. The objectives of the projects described in this thesis research are to develop novel mass spectrometric methodologies for in situ detection of hazardous chemical and biological agents. The first project described is the development and characterization of novel linear ion trap mass analyzers based on the rectilinear geometry. Such mass analyzers consist of either four or six planar electrode and employ pure RF voltages (or with supplementary DC voltages) for two dimensional ion trapping. The structure simplicity makes these devices particularly significant for the development of miniaturized ion trap mass spectrometers. The second project described is the discovery of new ion/molecule reactions and the associated implementation via ambient ionization techniques desorption atmospheric pressure chemical ionization (DAPCI) and desorption electrospray ionization (DESI), for the specificity enhancement in in situ detection of nitroaromatic explosives and organophosphonates. Such additional specificity is especially valuable for in situ chemical hazard detection since complex mixtures are necessarily examined. The third project described is the application of DESI to profile fresh intact microorganisms. This study demonstrates the possibility of performing in situ identification, including sub-species differentiation of microbiological agents by using DESI-MS. The lack of sample treatment and the known sensitivity of the DESI experiment represent progress toward rapid in situ mass spectrometric identification of biological threats. Future directions should include integration of ambient ionizations to miniaturized mass spectrometers, to produce a versatile portable device for in situ detection of chemical and biological threats

Hydrodynamic Limit of Bak-Sneppen Branching Diffusions

We study a hydrodynamic limit for a system of N diffusions moving in an open domain D ⊆ Rd undergoing branching when one particle reaches a certain subset of the boundary. The particle at the boundary and another random neighbor are eliminated and replaced with two new particles created instantaneously at a random point with distribution γ(dx) in D. This thesis proves the d = 1 case with D = (0,1), γ(dx) = δc(dx), c ∈ (0,1) while the general case is done in an upcoming paper. The mechanism represents a hybrid between the Fleming- Viot branching and a mean-field version of the Bak-Sneppen fitness model where the absorbing boundary represents the not viable, or minimal configuration. The limiting profile is the normalization of the solution of a heat equation with mass creation, which is studied using its representation via an auxiliary measure valued supercritical process. Self-criticality is manifested by the presence of the quasi- stationary distributions emerging as profiles under equilibrium.</p

Hydrodynamic Limit for the Bak-Sneppen Branching Diffusions

We prove a hydrodynamic limit for a system of N particles moving in an open domain D subset of R-d according to a diffusion and undergoing branching when one particle reaches the boundary. The particle at the boundary and another random particle are eliminated and replaced with two new particles created instantaneously at a random point with distribution gamma (dx) in D. The mechanism represents a hybrid between the Fleming-Viot branching and a mean-field version of the Bak-Sneppen fitness model where the absorbing boundary represents the minimal configuration, seen as biologically not viable. The limiting profile is the normalization of the solution of a heat equation with mass creation, a PDE with non-standard boundary conditions which was studied independently by one of the authors. Under stronger conditions, the limit solves a semi-linear parabolic equation of reaction-diffusion type with a reaction term depending directly on the flux balance that determines the mass creation. An outline of the tagged particle limit is included

Resilience of Wengding, the Phoenix Wa traditional village

The village of Wengding, ancestral home of the Wa ethnic group, considered as China’s last primitive tribe, suffered near-complete extinction due to a fire incident in 2021. Historical records indicate that stilt-style buildings, also in Wengding, are highly susceptible to fire. Nevertheless, this has not hindered the long-term existence of these distinctive architectural forms. This study analyses the reasons for the sustained existence of the traditional building forms in Wengding, from the perspective of resilience. The findings indicate that the requirements of the traditional nomadic civilization for rapid construction of dwellings, the communal consciousness toward disaster resistance, and the implementation of spatially oriented fire protection measures collectively account for the swift recovery and reconstruction observed in Wengding village after the disaster. These aspects are tangible manifestations of the capacity of the village for resilience. Overall, resilience is essential for the sustainability of such traditional villages in the long term

The correlation between migraine and patent foramen ovale

Background: Migraine is a widespread neurological disorder. The patent foramen ovale (PFO) is a remnant of the fetal circulation. Multiple studies suggest that migraine is more prevalent in subjects with PFO and vice versa. It is unclear if there is a causal relationship or simply a co-existence of these two conditions. Furthermore, the treatment of migraine with percutaneous closure PFO remains controversial. Methods: We reviewed studies pertaining to the relationship between PFO and migraine as well as the effects of treatments on migraine attacks. Results: We briefly summarized potential pathophysiological mechanisms of migraine, and elaborated on migraine type, frequency, and clinical symptoms of migraine with PFO and the clinical features of PFO with migraine. We also addressed the effects of PFO closure on migraine attacks. Conclusion: The evidence supports a "dose-response" relationship between migraine and PFO although more work needs to be done in terms of patient selection as well as the inclusion of an antiplatelet control group for PFO closure interventions to uncover possible beneficial results in clinical trials.Published versio