Identifying Putative Biomarkers of Foodborne Pathogens Using a Metabolomic Approach.

Metabolomics is the study of low molecular weight biochemical molecules (typically <1500 Da) in a defined biological organism or system. In case of food systems, the term "food metabolomics" is often used. Food metabolomics has been widely explored and applied in various fields including food analysis, food intake, food traceability, and food safety. Food safety applications focusing on the identification of pathogen-specific biomarkers have been promising. This chapter describes a nontargeted metabolite profiling workflow using gas chromatography coupled with mass spectrometry (GC-MS) for characterizing three globally important foodborne pathogens, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica, from selective enrichment liquid culture media. The workflow involves a detailed description of food spiking experiments followed by procedures for the extraction of polar metabolites from media, the analysis of the extracts using GC-MS, and finally chemometric data analysis using univariate and multivariate statistical tools to identify potential pathogen-specific biomarkers.

Diagnostic Performance of Multiparametric MRI for the Detection of suspected Prostate Cancer in Biopsy-Naive Patients: A Systematic Review and Meta-analysis.

RATIONALE AND OBJECTIVES: This meta-analysis aimed to assess the diagnostic accuracy of multiparametric MRI (mpMRI) in detecting suspected prostate cancer (PCa) in biopsy-naive men. MATERIALS AND METHODS: PubMed, Scopus, and the Cochrane Library databases were systematically searched for studies published from January 2013 to April 2024. Sixteen studies comprising 4973 patients met the inclusion criteria. Data were extracted to construct 2×2 contingency tables for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A random-effects model was used for pooled estimation, and subgroup analyses were conducted. Summary receiver operating characteristic (SROC) curves were generated to summarize overall diagnostic performance. RESULTS: The overall detection rate of PCa across studies was 57.3%. For detecting any PCa, mpMRI showed pooled sensitivity of 82% (95% CI, 80-83%) and specificity of 62% (95% CI, 60-64%), with positive likelihood ratio (LR) of 1.97 (95% CI, 1.71-2.26), negative LR of 0.28 (95% CI, 0.24-0.34), and diagnostic odds ratio (DOR) of 7.34 (95% CI, 5.60-9.63), and an area under the SROC curve of 0.81. For clinically significant PCa (csPCa), mpMRI had pooled sensitivity of 88% (95% CI, 87-90%) and specificity of 64% (95% CI, 63-66%), with positive LR of 2.49 (95% CI, 2.03-3.05), negative LR of 0.20 (95% CI, 0.16-0.25), DOR of 13.83 (95% CI, 9.14-20.9), and area under the curve of 0.90. CONCLUSION: This meta-analysis suggests that mpMRI is effective in detecting PCa in biopsy-naive patients, particularly for csPCa. It can help reduce unnecessary biopsies and lower the risk of missing clinically significant cases, thereby guiding informed biopsy decisions.

Update on Cytomegalovirus Infection Management in Allogeneic Hematopoietic Stem Cell Transplant Recipients. A Consensus Document of the Spanish Group for Hematopoietic Transplantation and Cell Therapy (GETH-TC).

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations. Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines. Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed. Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

Interpersonal Processes in the Duration of Sick Leave of Workers with Chronic Diseases: A Dyadic Analysis.

PURPOSE: Although there is increasing awareness that significant others' perceptions and behavior can affect health outcomes, the role of interpersonal processes between sick-listed workers and significant others in sick leave and return to work (RTW) has hardly been studied. This study aims to examine the associations between illness perceptions, RTW expectations, and behaviors of significant others (engagement, buffering and overprotection) with sick leave duration within dyads of sick-listed workers with chronic diseases and their significant others. METHODS: We used survey data linked with sick leave registry data of 90 dyads. Pearson correlations were used to study the interdependence within dyads. Multiple linear regression analyses were conducted to examine associations between survey data of both dyad members and sick leave duration. RESULTS: We found moderate to strong correlations between workers and significant others, indicating interdependence within dyads regarding illness perceptions, RTW expectations and perceived significant other behaviors. Dyad members' illness perceptions (R2 = .204, p = .001) and RTW expectations (R2 = .326, p = < .001) were associated with sick leave duration, explaining respectively 12.3% and 24.5% of the variance. We found no associations between sick leave duration and active engagement, protective buffering and overprotection. CONCLUSIONS: This study indicates that negative illness perceptions and RTW expectations of both workers and their significant others are associated with a longer sick leave duration. Considering the interdependence within dyads, involving significant others when intervening on maladaptive illness perceptions and RTW expectations may be more effective than solely focusing on the worker's perceptions and expectations.

Assessment of Blood Prostaglandin E2 Metabolite Levels among Infants Born Preterm with Patent Ductus Arteriosus: A Prospective Study.

OBJECTIVE: To assess the role of prostaglandin E2 (PGE2) by measuring blood prostaglandin E2 metabolite (PGEM) concentrations in preterm infants with patent ductus arteriosus (PDA). STUDY DESIGN: A prospective observational study of preterm infants born before 32 weeks of gestational age (GA) was performed in a single tertiary hospital in Japan. Blood samples were collected to measure serum concentrations of PGEM, ibuprofen (IBU), and cytokines. Multiple regression analyses assessed associations between blood PGEM levels and perinatal factors, development of hemodynamically significant PDA (hsPDA), and IBU treatment response of hsPDA. RESULTS: Seventy-nine infants (median GA 28 weeks) were enrolled in this study. Forty-seven received IBU for hsPDA treatment 1 d after birth in median. PDA closure occurred in 25 infants after a single IBU treatment. Serum PGEM concentrations were associated with histological chorioamnionitis (p <0.01), but not with GA, respiratory distress syndrome, or serum IL-6 concentrations. Serum PGEM concentrations decreased after initial IBU treatment; however, they were not associated with hsPDA development (p = 0.39). IBU concentrations correlated with IBU treatment response (aOR 1.29, p <0.01). However, pre-IBU serum PGEM levels and PGEM reduction ratio did not (p = 0.13, 0.15, respectively). CONCLUSIONS: Serum PGEM concentrations in preterm infants were associated with maternal histological chorioamnionitis, but not hsPDA development. IBU treatment response was associated with higher blood IBU concentrations, but not PGEM concentrations.

Hopelessness for family members of individuals with borderline personality disorder.

Family members and loved ones of individuals with Borderline Personality Disorder (BPD) can experience high levels of distress. Types of distress reported by family members include burden, grief, depression, guilt, and powerlessness. Hopelessness is a construct that has received little attention despite its potential relevance for this group. This study sought to examine, and assess potential change in, hopelessness among individuals attending a 12-week Family Connections (FC) program. Participants were 75 family members, 29 men and 46 women. Most participants were parents (n = 43; 57%). Data were collected at four time-points and outcomes included hopelessness, burden, and grief. The majority of participants (82%) reported scores within the 'minimal' or 'mild' ranges of hopelessness before the FC program. A greater proportion of participants in the 60-70 year age group reported scores in the 'moderate/severe' category when compared with younger age groups. The mean hopelessness score for all participants before FC was 4.61 which is considered mild. There was no significant difference in hopelessness scores after program completion. Although mean scores increased at both 3-month and 12-month follow-ups, they continued to remain in the 'mild' category. Hopelessness scores in the current study are similar to those reported in previous studies, although no significant change was found after FC completion. Concepts of personal vs. situational hopelessness should be considered, as well as the relevance of assessing personal hopelessness for this participant group. Further research is needed to determine the relationship between family member hopelessness and index client wellbeing.

A concise proof of Benford's law.

This article presents a concise proof of the famous Benford's law when the distribution has a Riemann integrable probability density function and provides a criterion to judge whether a distribution obeys the law. The proof is intuitive and elegant, accessible to anyone with basic knowledge of calculus, revealing that the law originates from the basic property of human number system. The criterion can bring great convenience to the field of fraud detection.

Cognitive Targeted Prostate Biopsy Alone for Diagnosing Clinically Significant Prostate Cancer in Selected Biopsy-Naïve Patients: Results from a Retrospective Pilot Study.

(1) Background: To identify a particular setting of biopsy-naïve patients in which it would be reasonable to offer only cognitive targeted prostate biopsy (PBx) with a transrectal approach. (2) Methods: We designed an observational retrospective pilot study. Patients with a prostatic specific antigen (PSA) level > 10 ng/mL, either a normal or suspicious digital rectal examination (DRE), and a lesion with a PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone were included. All patients underwent a transrectal PBx, including both systematic and targeted samples. The detection rate of clinically significant prostate cancer (csPCa) (Gleason Score ≥ 7) was chosen as the primary outcome. We described the detection rate of csPCa in systematic PBx, targeted PBx, and overall PBx. (3) A total of 92 patients were included. Prostate cancer was detected in 84 patients (91.30%) with combined biopsies. A csPCa was diagnosed in all positive cases (100%) with combined biopsies. Systematic PBxs were positive in 80 patients (86.96%), while targeted PBxs were positive in 84 men (91.30%). Targeted PBx alone would have allowed the diagnosis of csPCa in all positive cases; systematic PBx alone would have missed the diagnosis of 8/84 (9.52%) csPCa cases (4 negative patients and 4 not csPCa) (p = 0.011). (4) Conclusions: Cognitive targeted PBx with a transrectal approach could be offered alone to diagnose csPCa in biopsy-naïve patients with PSA ≥ 10 ng/mL, either normal or suspicious DRE, and a lesion with PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone.

Haptic experience to significantly motivate anatomy learning in medical students.

BACKGROUND: Currently, multiple tools exist to teach and learn anatomy, but finding an adequate activity is challenging. However, it can be achieved through haptic experiences, where motivation is the means of a significant learning process. This study aimed to evaluate a haptic experience to determine if a tactile and painting with color marker interactive experience, established a better learning process in comparison to the traditional 2D workshop on printed paper with photographs. METHODS: Plaster bone models of the scapulae, humerus and clavicle were elaborated from a computerized scan tomography. Second year undergraduate medical students were invited to participate, where subjects were randomly assigned to the traditional 2D method or the 3D plaster bone model. A third group decided not to join any workshop. Following, all three groups were evaluated on bone landmarks and view, laterality, muscle insertions and functions. 2D and 3D workshop students were asked their opinion in a focus group and answered a survey regarding the overall perception and learning experience. Evaluation grades are presented as mean ± standard deviation, and answers from the survey are presented as percentages. RESULTS: The survey demonstrated the students in the 3D model graded the experience as outstanding, and in five out of the six questions, answers were very good or excellent. In contrast, for students participating in the 2D workshop the most common answers were fair or good. The exception was the answer regarding the quiz, where both groups considered it good, despite the average among all groups not being a passing grade. CONCLUSIONS: To learn the anatomy of the shoulder, the conventional methodology was compared with a haptic experience, where plaster bone models were used, enabling students to touch and paint on them. Based on the focus group and survey this study revealed the 3D workshop was an interactive experience where, the sense of touch and painting greatly contributed to their learning process. Even though this activity was useful in terms of learning bone landmarks, view muscle insertions, and establish relations, further activities must be developed to increase their understanding regarding their function, and its relevance in a clinical setting.

[Transrectal ultrasonography of intravesical prostatic protrusion and the detection rate of clinically significant prostate cancer].

OBJECTIVE: To investigate the value of transrectal ultrasonography (TRUS) in the detection of clinically significant prostate cancer (CsPCa) in patients with intravesical prostatic protrusion (IPP). METHODS: We retrospectively analyzed the data on 128 patients undergoing TRUS-guided prostate biopsy in the General Hospital of Eastern Theater Command and Jiangsu Province Hospital from January 2019 to December 2022. We measured the size of and graded IPP, compared the clinicopathological and ultrasonographic features of the patients in the CsPCa group (Gleason score ≥7) and those in the control group (Gleason score <7), and analyzed the correlation of the IPP grades with the detection rate of CsPCa by multivariate logistic regression analysis. RESULTS: The prostate volume was significantly higher in the CsPCa group than in the control (ï¼»51.3±12.1ï¼½ vs ï¼»43.5±11.3ï¼½ ml, P< 0.05), while the PSA density (PSAD) remarkably lower in the former than in the latter (ï¼»0.45±1.92ï¼½ vs ï¼»0.59±2.14ï¼½ ng/ml, P< 0.05) and so was the detection rate of CsPCa in the patients with IPP grade 3 than in those with IPP grades 0, 1 and 2 (56.0% vs 85.4%, 87.1% and 80.6%, P< 0.05). Spearman correlation analysis showed that the Gleason score was correlated positively with the prostate volume (r = 0.612) but negatively with PSAD (r = －0.735) and the IPP grade (r = －0.619) (P< 0.05). Logistic regression analysis indicated that IPP grade 3 (OR: 0.690, 95% CI: 0.380－0.995, P = 0.032) was an independent protective factor for CsPCa. CONCLUSION: CsPCa is significantly correlated with the IPP grade, and the detection rate of CsPCa by TRUS-guided biopsy is lower in patients with IPP grade 3 than in those with IPP grades 0－2. Therefore, special attention should be paid to false negative probability in case of high-grade IPP.

[Causes of missed diagnosis of clinically significant prostate cancer by targeted biopsy].

OBJECTIVE: To retrospectively analyze the causes of missed diagnosis of clinically significant PCa (csPCa) by targeted biopsy (TB). METHODS: This retrospective study included 652 males aged (71.32 ± 16.53) years with elevated PSA and abnormal MRI signals detected in our hospital from June 2018 to December 2020. We further examined the patients by transperineal prostatic TB and systematic biopsy (SB), analyzed the detection rates of PCa and csPCa by TB and SB, and investigated the causes of missed diagnosis of csPCa in TB using the fishbone diagram. RESULTS: The total detection rate of PCa and csPCa by TB combined with SB was 45.7% (298/652), and that of csPCa was 37.4% (244/652), with 38 cases of csPCa missed in TB, including 23 cases of negative TB and 15 cases of low ISUP grade. The causes of missed diagnosis of csPCa by TB included low MRI image quality, PSA density ≤0.15 ng/ml/cm3, target area <10 mm, and PI-RADS 2 score ≤3. The detection rate of csPCa by TB alone was 31.6%, which was increased by 5.8% (P = 0.027) when TB combined with SB. CONCLUSION: TB combined with SB yields a higher detection rate of csPCa than either used alone. Missed diagnosis of csPCa by TB is closely related to the characteristics of tumor and MR image of the target area.

Bone Mineral Density Monitoring in Contiguous versus Non-Contiguous Lumbar Vertebrae: The Manitoba BMD Registry.

INTRODUCTION: Only change in bone mineral density (BMD) on repeat DXA that exceeds the 95% least significant change (LSC) should be considered clinically meaningful. Frequently lumbar spine DXA must be reported after omitting vertebrae with localized structural artifact, which reduces measurement precision. Previous reports have raised concerns of higher least significant change (LSC) when spine BMD is based on non-contiguous rather than contiguous vertebrae. The current study was performed to compare lumbar spine LSC and BMD response to intervening anti-osteoporosis medication use from non-contiguous versus contiguous vertebrae. METHODOLOGY: LSCs for lumbar spine DXA based on L1-L4 and all combinations of non-contiguous and contiguous vertebrae were calculated using 879 scan-pairs from the Manitoba BMD Program. We compared BMD change from these regions, overall and in relation to intervening anti-osteoporosis medication use, in 11,722 patients who had 2 DXA examinations. RESULTS: LSCs were slightly greater when calculated from combinations of fewer than 4 vertebrae, but there was no meaningful difference between contiguous versus non-contiguous vertebrae. There were consistently high correlations between lumbar spine BMD change from L1-L4 and all combinations of continuous and non-contiguous vertebrae (all Pearson r≥ 0.9, p<0.001). Percentage changes in spine BMD and the fraction with treatment-concordant change exceeding the LSC were similar using contiguous or non-contiguous vertebrae. CONCLUSIONS: Lumbar spine BMD change can be assessed from 2 or 3 non-contiguous vertebrae when clinically necessary, and precision in such cases is similar to using contiguous vertebrae. Non-contiguous vertebrae can detect treatment-concordant changes similar in spine BMD to contiguous vertebrae.

IVDCheckR - simplifying documentation for laboratory developed tests according to IVDR requirements by introducing a new digital tool.

OBJECTIVES: A recent challenge for clinical laboratories is the lack of clear guidelines for handling significant modifications of CE-marked assays. The modifications may involve, for example, extending measurement intervals, changing dilution procedures or using non-validated sample materials. The challenge arises due to the amended Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), which is now poised for implementation, despite the extended transition periods. The IVDR application imposes challenges not only for diagnostic companies but also for clinical laboratories when using laboratory developed tests (LDTs), often referred to as in-house assays. In this context, a coherent and meticulously structured LDT documentation is highly beneficial. While laboratories are obliged to meet the IVDR requirements, the absence of a streamlined framework or guideline hampers the ability to gain a comprehensive overview on the requirements and possible options for their fulfilment. METHODS: To address this issue, we introduce a web based digital tool powered by an R Shiny web application. This tool facilitates a seamless implementation of IVDR requirements for LDTs across diverse laboratory environments in terms of their transparency and validity. Our approach focuses on adequate handling of significant modifications of CE-marked in vitro diagnostic medical devices (IVD). RESULTS: IVDRCheckR is an open-source tool that is easily accessible and free from system dependencies. The tool promotes a seamless process and a guide to enhance transparency, reliability, and validity of laboratory examination results based on LDTs. Additionally, the tool further provides modules for evaluating quality control data and quantitative method comparison data. CONCLUSIONS: Our Shiny web application-based platform is a digitised, user-friendly tool that simplifies the documentation for LDTs according to IVDR requirements with special emphasis on solutions for handling modifications to CE-marked assays.

Including significant others in psychological therapy with people with intellectual disabilities: A national survey of the practice of UK psychologists.

BACKGROUND: Talking therapy for people with intellectual disabilities is often specifically adapted. One adaptation is the involvement of significant others in therapy, however, there is no systematic description of the use of this adaptation in routine clinical practice. METHOD: An online survey of UK psychologists regarding the inclusion of significant others in individual therapy with people with intellectual disabilities. Data were analysed using qualitative content analysis. RESULTS: Ninety-five psychologists who work with people with intellectual disabilities provided responses to questions regarding the decision to include significant others in therapy, factors that make including significant others more or less likely and how the role of significant others is explained to them. CONCLUSIONS: Psychologists consider a range of factors in deciding the involvement of significant others. We discuss implications for training of therapists working with people with intellectual disabilities, issues of consent and how the roles of significant others are understood.

The Association of Preoperative Hip Pain Duration With Delayed Achievement of Clinically Significant Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement Syndrome.

BACKGROUND: Patients with hip pain ≥2 years before hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) have been shown to achieve inferior short-term and midterm outcomes compared with patients with a shorter pain duration, although there is limited literature that has evaluated the time to achieve clinically significant outcomes (CSOs) in this population. PURPOSE: To compare the time to achieve CSOs after hip arthroscopic surgery for FAIS in patients with and without prolonged hip pain and to identify independent predictors of the delayed achievement of CSOs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients who underwent primary hip arthroscopic surgery for FAIS between January 2012 and July 2019 with 6-month, 1-year, and 2-year Hip Outcome Score-Activities of Daily Living (HOS-ADL) and Hip Outcome Score-Sports Subscale (HOS-SS) scores were identified. Patients with prolonged hip pain (preoperative duration ≥2 years) were propensity score matched to a control group (preoperative duration <2 years), controlling for age, sex, and body mass index (BMI). The times to achieve the minimal clinically important difference and Patient Acceptable Symptom State were compared between groups using Kaplan-Meier survival analysis. Multivariate Cox regression considering age, sex, BMI, pain duration, activity level, and chondral status was used to identify independent predictors of the delayed achievement of CSOs. RESULTS: A total of 179 patients with prolonged hip pain were matched to 179 control patients (mean pain duration, 60.5 ± 51.2 vs 9.7 ± 5.1 months, respectively; P < .001) of a similar age, sex, and BMI (P≥ .488) with similar baseline HOS-ADL and HOS-SS scores (P≥ .971). The prolonged hip pain group showed delayed achievement of the minimal clinically important difference and Patient Acceptable Symptom State for both the HOS-ADL and HOS-SS on Kaplan-Meier analysis (P≤ .020). On multivariate Cox regression, hip pain duration ≥2 years was shown to be an independent predictor of the delayed achievement of CSOs, with hazard ratios ranging from 1.32 to 1.65 (P≤ .029). Additional independent predictors of the delayed achievement of CSOs included increasing age, increasing BMI, female sex, self-endorsed weekly participation in physical activity, and high-grade chondral defects (hazard ratio range, 1.01-4.89; P≤ .045). CONCLUSION: Findings from this study demonstrate that preoperative hip pain duration ≥2 years was an independent predictor of the delayed achievement of CSOs after primary hip arthroscopic surgery for FAIS.

Navigating the trauma-The experiences of significant others supporting patients with severe burn injury: A narrative inquiry.

AIM: To explore the experiences of significant others of adult patients with severe burn injury in the Intensive Care Unit. Specifically, this study explored the strategies implemented by significant others and obstacles faced that served to protect or placed them at risk of psychological sequelae during their experience of trauma. DESIGN: A qualitative study using a Narrative Inquiry approach was undertaken. METHODS: Individual semi-structured interviews were conducted with 17 participants during 2021-2022, who were a significant other of an adult patient in ICU with severe burn injury. These participants were recruited from the two major severe burns receiving hospitals in New South Wales, Australia. Participants' stories were analysed using a narrative analysis approach informed by Polkinghorne. The COREQ guideline was used in reporting. RESULTS: As each participant navigated the traumatic experience of supporting a loved one with a severe burn injury, they faced unique obstacles to maintaining their own mental health and well-being. They employed strategies that were likely to protect them on this journey. Psychologically protective factors included taking back control, coexisting in the trauma with the patient and forging a trauma bond. These strategies effectively contained the trauma and protected others (such as children, extended family and friends). While this allowed significant others an element of control, it also effectively isolated them from the support of family and friends. CONCLUSION: This study shows that significant others may also experience personal trauma and may not recognize this as they focus all their attention on supporting the patient with the burn injury. IMPLICATIONS FOR PRACTICE: With increased awareness of both protective and risk factors, support can be directed towards enhancing protective factors and addressing risk factors, thereby decreasing their impact and improving support for significant others. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Phylogenetic climatic niche evolution and diversification of the Neurergus species (Salamandridae) in the Irano-Anatolian biodiversity hotspot.

This study explores how climate variables influenced the evolution and diversification of Neurergus newts within the Irano-Anatolian biodiversity hotspot. We use a dated phylogenetic tree and climatic niche models to analyze their evolutionary history and ecological preferences. Using genetic data from nuclear (KIAA) and mitochondrial (16s and 12s) genes, we estimate divergence times and identify four major Neurergus clades. The initial speciation event occurred approximately 11.3 million years ago, coinciding with the uplift of the Zagros and Anatolian mountains. This geological transformation isolated newt populations, likely triggering the first speciation event. By integrating potential geographic distribution with climate variables, we reconstruct ancestral niche occupancy profiles. This highlights the critical roles of temperature and precipitation in shaping Neurergus habitat preferences and distribution. We observe both phylogenetic niche conservatism and divergence, with niche divergence playing a dominant role in diversification. This research emphasizes the complex interplay of geography, climate, and ecology in speciation and the vulnerability of isolated mountain newt populations to environmental changes.

Clinically significant prostate cancer detection rate in biopsy-naïve patients with mpMRI and microultrasound topographically discordant lesions: A single-center retrospective analysis.

INTRODUCTION AND OBJECTIVES: Multiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer (csPCa), and microultrasound (micro-US) shows promise in enhancing detection rates. We compared mpMRI-guided targeted biopsy (MTBx) and micro-US-guided targeted biopsy (micro-US-TBx) in biopsy-naïve patients with discordant lesions at micro-US and mpMRI to detect csPCa (grade group ≥2) and clinically insignificant PCa (ciPCa; grade group 1) and assessed the role of nontargeted systematic biopsy (SBx). MATERIAL AND METHODS: We analyzed 178 biopsy-naive men with suspected PCa and discordant lesions at mpMRI and micro-US. All patients underwent mpMRI followed by micro-US, the latter being performed immediately before the biopsy. Imaging findings were interpreted blindly, followed by targeted and SBx. Median age was 63 years (IQR, 57-70), median prostate-specific antigen level was 7 ng/mL (IQR, 5-9 ng/mL), and median prostate volume was 49 cm^3 (IQR, 35-64 cm^3). Overall, 86/178 (48%) patients were diagnosed with PCa, 51/178 (29%) with csPCa. RESULTS: Micro-USTBx detected csPCa in 36/178 men (20%; 95% CI: 26-46), and MTBx detected csPCa in 28/178 men (16%; 95% CI: 36-50), resulting in a -8% difference (95% CI: -10, 4; P = 0.022) and a relative detection rate of 0.043. Micro-USTBx detected ciPCa in 9/178 men (5%; 95% CI: 3, 15), while MTBx detected ciPCa in 12/178 men (7%; 95% CI: 5, 20), resulting in a -3% difference (95% CI: -2 to 4; P = 0.2) and a relative detection rate of 0.1. SBx detected ciPCa in 29 (16%) men. mpMRI plus micro-US detected csPCa in 51/178 men, with no additional cases with the addition of SBx. Similarly, MTBx plus micro-USTBx plus SBx detected ciPCa in 35/178 men (20%; 95% CI: 18, 37) compared to 9 (5%) in the micro-US pathway (P = 0.002) and 14/178 (8%; 95% CI: 6, 26) in the mpMRI plus micro-US pathway (P = 0.004). CONCLUSIONS: In conclusion, a combined micro-US/mpMRI approach could characterize primary disease in biopsy-naïve patients with discordant lesions, potentially avoiding SBx. Further studies are needed to validate our findings and assess micro-US's role in reducing unnecessary biopsies.