Nevin Manimala

Mol Ecol. 2025 Jan 10:e17639. doi: 10.1111/mec.17639. Online ahead of print.

ABSTRACT

Invading species along with increased anthropogenization may lead to hybridization events between wild species and closely related domesticates. As a consequence, wild species may carry introgressed alleles from domestic species, which is generally assumed to yield adverse effects in wild populations. The opposite evolutionary consequence, adaptive introgression, where introgressed genes are positively selected in the wild species, is possible but has rarely been documented. Grey wolves (Canis lupus) are widely distributed across the Holarctic and frequently coexist with their close relative, the domestic dog (C. familiaris). Despite ample opportunity, hybridization rarely occurs in most populations. Here we studied the geographically isolated grey wolves of the Iberian Peninsula, who have coexisted with a large population of loosely controlled dogs for thousands of years in a human-modified landscape. We assessed the extent and impact of dog introgression on the current Iberian grey wolf population by analysing 150 whole genomes of Iberian and other Eurasian grey wolves as well as dogs originating from across Europe and western Siberia. We identified almost no recent introgression and a small (< 5%) overall ancient dog ancestry. Using a combination of single scan statistics and ancestry enrichment estimates, we identified positive selection on six genes (DAPP1, NSMCE4A, MPPED2, PCDH9, MBTPS1, and CDH13) for which wild Iberian wolves carry alleles introgressed from dogs. The genes with introgressed and positively selected alleles include functions in immune response and brain functions, which may explain some of the unique behavioural phenotypes in Iberian wolves such as their reduced dispersal compared to other wolf populations.

PMID:39791197 | DOI:10.1111/mec.17639

Eur J Pain. 2025 Feb;29(2):e4782. doi: 10.1002/ejp.4782.

ABSTRACT

BACKGROUND: The internet is increasingly used as a primary source of information for patients with musculoskeletal pain. Private physiotherapy practices provide informative content on low back pain (LBP) and neck pain (NP) on their websites, but the extent to which this information is biopsychosocial, guidelines-consistent, and fear-inducing is unknown. The aim of this study was to analyse the information on websites of private physiotherapy practices in the Netherlands about LBP and NP regarding consistency with the guidelines and the biopsychosocial model and to explore the use of fear-inducing language.

METHODS: The content of all existing Dutch private physiotherapy practice websites was examined in a cross sectional study design. Content analysis was based on predetermined criteria of the biopsychosocial model and evidence-based guidelines. Descriptive statistics were applied.

RESULTS: After removing duplicates and sites without information, 834 (10%) of 8707 websites remained. Information about LBP was found on 449 (54%) websites and 295 (35%) websites informed about NP. A majority of websites (LBP: n = 287, 64%; NP: n = 174, 59%) were biomedically oriented. Treatment advice was given 1855 times on n = 560 (67%) websites. Most of the recommended interventions were inconsistent with or not mentioned in the guidelines. Fear-inducing language was provided n = 1624 (69%) times.

CONCLUSIONS: The majority of the information on the Dutch private physiotherapy websites was biomedical and not in line with the current guidelines and fear-inducing.

SIGNIFICANCE: This study revealed that the majority of private physiotherapy practice websites that provide information on LBP and NP are inconsistent with the biopsychosocial model and current guidelines. This information has a negative impact on patients’ knowledge, attitudes, beliefs, and expectations, potentially affecting treatment outcomes. Consequently, most physiotherapy practice websites are unreliable sources of information on LBP and NP for patients. There is an urgent need to implement strategies to make websites reliable and helpful sources of information.

PMID:39791187 | DOI:10.1002/ejp.4782

J Law Med. 2024 Nov;31(3):515-522.

ABSTRACT

Risk assessment is an important component of judicial decision-making in many areas of the law. In Australia, those convicted of terrorist offences may be the subject of continued detention in prison or extended supervision in the community if there is an “unacceptable risk” of them committing future terrorism offences. Forensic psychologists and psychiatrists may provide evidence of risk through identifying and measuring risk factors with the aid of tools that use scales based on statistical or actuarial risk prediction. This column focuses on criticisms of the use of the second revision of the Violent Extremism Risk Assessment tool (VERA-2R) in determining the risk of future terrorist acts.

PMID:39789681

J Am Med Inform Assoc. 2025 Jan 10:ocae317. doi: 10.1093/jamia/ocae317. Online ahead of print.

ABSTRACT

OBJECTIVE: Propose a framework to empirically evaluate and report validity of findings from observational studies using pre-specified objective diagnostics, increasing trust in real-world evidence (RWE).

MATERIALS AND METHODS: The framework employs objective diagnostic measures to assess the appropriateness of study designs, analytic assumptions, and threats to validity in generating reliable evidence addressing causal questions. Diagnostic evaluations should be interpreted before the unblinding of study results or, alternatively, only unblind results from analyses that pass pre-specified thresholds. We provide a conceptual overview of objective diagnostic measures and demonstrate their impact on the validity of RWE from a large-scale comparative new-user study of various antihypertensive medications. We evaluated expected absolute systematic error (EASE) before and after applying diagnostic thresholds, using a large set of negative control outcomes.

RESULTS: Applying objective diagnostics reduces bias and improves evidence reliability in observational studies. Among 11 716 analyses (EASE = 0.38), 13.9% met pre-specified diagnostic thresholds which reduced EASE to zero. Objective diagnostics provide a comprehensive and empirical set of tests that increase confidence when passed and raise doubts when failed.

DISCUSSION: The increasing use of real-world data presents a scientific opportunity; however, the complexity of the evidence generation process poses challenges for understanding study validity and trusting RWE. Deploying objective diagnostics is crucial to reducing bias and improving reliability in RWE generation. Under ideal conditions, multiple study designs pass diagnostics and generate consistent results, deepening understanding of causal relationships. Open-source, standardized programs can facilitate implementation of diagnostic analyses.

CONCLUSION: Objective diagnostics are a valuable addition to the RWE generation process.

PMID:39789670 | DOI:10.1093/jamia/ocae317

Hereditas. 2025 Jan 9;162(1):4. doi: 10.1186/s41065-024-00363-7.

ABSTRACT

BACKGROUND: Cervical cancer (CC) is a prevalent gynecological malignancy, contributing to a substantial number of fatalities among women. MicroRNAs (miRNAs) have emerged as promising biomarkers with significant potential for the early detection and prognosis of CC.

OBJECTIVE: This study aimed to explore the clinical significance and biological role of miR-615-5p in CC, with the goal of identifying novel biomarkers for this disease.

MATERIALS AND METHODS: The levels of miR-615-5p and TMIGD2 mRNA in tissue samples and cells were quantified through quantitative reverse transcription real-time PCR, followed by statistical analyses to investigate the correlation between miR-615-5p and clinical data. The effects of miR-615-5p on the proliferation and metastasis of CC cells were evaluated using the Cell Counting Kit-8 and Transwell assays. The potential mechanism of miR-615-5p was elucidated by bioinformatics analyses and Dual-luciferase reporter assay. Western blotting was employed to measure the protein levels of TMIGD2.

RESULTS: In CC, the downregulation of miR-615-5p was related to poor prognosis and emerged as an independent prognostic factor. The levels of miR-615-5p were reduced in CC cells. miR-615-5p overexpression restrained the proliferation and metastasis of CC cells. Furthermore, TMIGD2 was identified as a target gene regulated by miR-615-5p, and its expression was notably elevated in CC. The influence of miR-615-5p on the biological behaviors of CC cells was mediated through the modulation of TMIGD2.

CONCLUSIONS: Downregulation of miR-615-5p was a prognostic indicator of poor prognosis in CC. miR-615-5p exerted its tumor-suppressive effects by inhibiting cell growth and metastasis through the regulation of TMIGD2.

PMID:39789663 | DOI:10.1186/s41065-024-00363-7

Porcine Health Manag. 2025 Jan 9;11(1):5. doi: 10.1186/s40813-024-00417-2.

ABSTRACT

BACKGROUND: Digestive disorders are one of the main health problems in suckling piglets. The correct visual identification of feces in suckling piglets is an important tool for the diagnosis of enteric diseases. The aim of the present observational study was to analyze different physicochemical parameters of the feces of suckling piglets aged 0 to 21 days: visual appearance (color and consistency), fecal dry matter (FDM) content and pH. A total of 482 fecal samples were collected and visually classified into six categories: meconium, colostrum stage feces and 4 further scores according to the degree of consistency: 0 = form; 1 = pasty; 2 = liquid; and 3 = watery feces. The percentage of FDM was estimated by two drying methods, oven and microwave, doing duplicates in each one to evaluate methods, and both were compared.

RESULTS: The most frequent colors of each feces category were dark green or dark brown for meconium; orange for colostrum; formed feces were mostly ocher and for the rest of the feces, the colors varied predominantly cream and ocher. Regarding FDM, liquid and watery categories had no statistically significant differences between them; meconium and colostrum feces FDM were not statistically different from pasty feces. The correlation coefficient between the FDM values of the duplicate analyses of the samples by both methods (oven and microwave) was very high (> 0.988). Importantly, no differences were found while comparing the results between both methods (p = 0.078), and the correlation coefficient between all samples analyzed with both methods was very high (> 0.98). Meconium was the only one that differed significantly from the rest in terms of pH.

CONCLUSION: The physicochemical study of the feces of suckling piglets including color, FDM and pH allowed the establishment of an objective fecal score to characterize the stools in this age group.

PMID:39789643 | DOI:10.1186/s40813-024-00417-2

Breast Cancer Res. 2025 Jan 9;27(1):5. doi: 10.1186/s13058-024-01940-4.

ABSTRACT

BACKGROUND: Alcohol intake is associated with a higher risk of estrogen receptor-positive (ER+) breast cancer (BC), presumably through its confirmed ability to increase sex hormone levels. Whether consuming alcohol within the recommended limit of one serving per day increases sex hormone levels among postmenopausal women taking aromatase inhibitors (AI) to inhibit estrogen production remains unknown. Therefore, we compared sex hormone levels following white wine to levels following white grape juice among ER + BC survivors taking AIs.

METHODS: In this 10-week randomized controlled two-period crossover trial conducted from September 2022 to July 2023 among 20 postmenopausal women on AIs, we examined within-person changes in sex hormone levels following 3 weeks of 5 ounces of white wine daily versus 3 weeks of 6 ounces of white grape juice daily, with each drinking period preceded by two-week washouts and drinking period sequence allocated by randomization.

RESULTS: All 20 participants completed the trial. Compared to daily grape juice, daily wine led to decreases in total estradiol (11.1%, 95%confidence interval[CI] -49.8%,57.2%), free estradiol index (0.7%, 95%CI -2%,0.7%), and free estradiol concentration (7.7%, 95%CI -48%, 63.9%) but increases in estrone (13.8%, 95%CI -9.5%,43.1%), dehydroepiandrosterone sulfate (DHEAS; 11.4%, 95%CI -3.3%,28.4%), and testosterone (12.6%, 95%CI -0.8%,27.7%) and decreased sex hormone-binding globulin (SHBG; -2.7%, 95%CI -21.9%,21.2%).

CONCLUSIONS: Five ounces of white wine daily did not lead to statistically significant increases in estradiol, but it led to changes in other sex hormones suggesting higher BC risk. Whether this level of alcohol intake diminishes AI effectiveness warrants further investigation.

TRIALS REGISTRATION: Clinicaltrials.gov NCT05423730 registered June 14, 2022.

PMID:39789640 | DOI:10.1186/s13058-024-01940-4

Int J Retina Vitreous. 2025 Jan 9;11(1):3. doi: 10.1186/s40942-025-00629-w.

ABSTRACT

BACKGROUND: This study evaluates the efficacy of intravitreal Faricimab in reducing pigment epithelium detachment (PED) and fluid volumes in both treatment-naïve eyes and eyes unresponsive to anti-VEGF mono-therapies, all diagnosed with type 1 macular neovascularization (T1 MNV) over a period of 12-month.

METHODS: A retrospective, single-center cohort study was conducted at the Jules Gonin Eye Hospital, Lausanne, Switzerland. Clinical records of treatment-naïve and non-responder switch patients presenting T1 MNV secondary to neovascular age-related macular degeneration (nAMD) from September 2022 to March 2023 were reviewed. Patients received a loading dose of three monthly Faricimab injections followed by a treat-and-extend (T&E) regimen. Multimodal imaging, including structural OCT and AI-assisted analysis, was used to quantify PED volumes and related fluid biomarkers at baseline, 3-month, 6-month, and 12-month follow-up. Statistical analyses included linear mixed models to evaluate differences and trends in intraretinal (IRF), subretinal fluid (SRF) and PED volumes.

RESULTS: 65 eyes of 65 patients were enrolled (female: 70.7%; mean age = 80.7yrs, SD = 6.9yrs). 80% had received anti-VEGF treatment (Switch group) and 20% were treatment-Naïve at baseline. At 12 months, intravitreal treatments were more frequent in the Switch group (mean number = 8.3 vs. 6.0; p = 0.009). BCVA improved at the 12-month follow-up in Naïve eyes (+ 6.9 ETDRS letters from baseline, p = 0.053) and was maintained in Switch eyes. No cases of intraocular inflammation were observed. Significant reduction in SRF and IRF volumes were noted in both groups. A significant reduction in PED volume was observed over the follow-up period in both groups (mean slope = -206 nL, 95%CL = -273/-138; p-value < 0.001).

CONCLUSIONS: Intravitreal Faricimab significantly reduced PED volumes in both treatment-Naïve and non-responder Switch patients over 12 months. The study highlights Faricimab’s potential as an effective treatment option for T1 MNV in nAMD, offering significant improvements in PED volume and related fluid biomarkers.

PMID:39789631 | DOI:10.1186/s40942-025-00629-w

BMC Musculoskelet Disord. 2025 Jan 9;26(1):33. doi: 10.1186/s12891-024-08238-8.

ABSTRACT

BACKGROUND: Osteoarthritis (OA) often leads to pain and functional limitations, impacting work and daily life. Physical activity (PA) is an important part of the treatment. Wearable activity trackers (WATs) offer a novel approach to promote PA but could also aid in finding a sustainable PA level over time. The aim of this secondary analysis was to examine the effects of self-monitoring PA with a WAT on perceived joint function and health-related quality of life in people with hip and knee OA.

METHOD: A two-armed cluster-randomized controlled trial (C-RCT) was conducted in southern Sweden including 160 individuals with hip or knee OA. The participants were cluster-randomized to a Supported Osteoarthritis Self-management Program (SOASP) with the addition of self-monitoring PA using a commercial WAT for 12 weeks (n = 86), or only the SOASP (n = 74). The outcomes include perceived joint function measured with HOOS/KOOS and health-related quality of Life (HRQoL) measured with EQ-5D-3L index and EQ VAS. Participants responded to the questionnaires at baseline and at follow-up after 3, 6 and 12 months. Statistical analyses involved linear mixed models, ANCOVA and paired t-test.

RESULTS: Participants with data from baseline and at least one follow-up were included in the analyses (n = 124). The analyses showed no statistically significant differences in changes between the groups in perceived joint function or HRQoL throughout the study period. Both groups improved in pain and symptoms, but the changes were small.

CONCLUSION: The addition of WAT-use did not have any effect on perceived joint function or HRQoL. The participants’ relatively high baseline scores might have influenced the outcomes of this study. We suggest that future WAT-interventions target inactive people with OA and use devices that also captures other activities such as cycling or aquatic exercise.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03354091. Registered 15/11/2017.

PMID:39789623 | DOI:10.1186/s12891-024-08238-8

Porcine Health Manag. 2025 Jan 9;11(1):4. doi: 10.1186/s40813-024-00411-8.

ABSTRACT

BACKGROUND: Umbilical outpouchings (UOs) in pigs are a multifactorial disease and little is known about effective prevention strategies and risk factors for UO development. UOs are common in Danish pigs and legislation complicates and increases the cost of keeping and raising pigs with UO. Recommendations for preventive measures exist but the scientific evidence behind the recommendations is often lacking. This study´s purpose was to investigate veterinarians’ perspectives on UO pigs´ fitness for transport, the welfare of UO pigs, the significance of UO, risk factors for the development of UO, and the management of pigs with UO. This study´s purpose was to investigate veterinarians’ perspectives on UO pigs´ fitness for transport, the welfare of UO pigs, the significance of UO, risk factors for the development of UO, and the management of pigs with UO.

RESULTS: The survey received 93 complete responses from veterinarians working within porcine health management. Because of the large proportion of replies from Danish veterinarians, all reporting of results was divided among Danish and non-Danish veterinarians. There were no statistically significant differences between the two groups in the assessment of fitness for transport. Both groups mainly agreed to a series of statements regarding the significance of UO and risk factors for UO development. The management of UO was also similar across the groups except for the use of neonatal antibiotics which was used considerably more in Danish herds.

CONCLUSIONS: Umbilical outpouchings seem to be perceived as a challenge across pork production; affecting the welfare of the individual pig as well as the management of the entire production. There were no significant differences between Danish and non-Danish veterinarians’ assessments of fitness for transport, and almost all the veterinarians agreed that some UO pigs might need special attention and care. Most would also recommend preventive measures. Despite most respondents in this survey working under the laws of the European Union, some were unaware of legislation regarding UO pigs.

PMID:39789622 | DOI:10.1186/s40813-024-00411-8