2-year Study Research Articles

Instant Futures: an experimental study of the imagination of alternative near futures thanks to science fiction.

Following Vygotsky's seminal work, sociocultural psychology has developed a powerful theory of imagination, considered as a process with mutual and transformative impacts with the social world. In this paper, we focus on the imagination of the future, which is an arena of special social and political contestation. We argue for integrating experimental methods into the scientific study of the re-composition, or synthesis process, in the imagination of the future. Provoking the imagination of the future in well-structured conditions allows for intra and interpersonal comparisons, as well as for comparisons through time. We introduce an experimental task, a "protokool", inspired by the work of a French group of science fiction writers, "le collectifZanzibar"; we also suggest a way to analyse the data collected through this "telescope into the imagination of the future" looking at a specific process of imagining the future in dystopian and utopian ways. Finally, we present some main findings from the analysis of a corpus of 186 narratives collected in a 4-year study with Bachelor students in psychology and education. We show that the process of imagining the future is asymetrical for dystopian and utopian futures. We also point at some major patterns in these imaginations of the future, and evolutions over the four years. The research has theoretical and methodological implications for the study of the imagination of the future in sociocultural psychology.

Predisposing conditions in patients with small intestinal adenocarcinomas in the Netherlands: A 20-year nationwide cohort study.

Small intestinal adenocarcinomas (SIAs) are associated with predisposing conditions, including inflammatory bowel disease (IBD) and celiac disease, but also genetic syndromes such as Lynch syndrome (LS) and familial adenomatous polyposis (FAP). This nationwide cohort study investigated the incidence of genetic and non-genetic predisposing conditions in SIA and their influence on tumor characteristics and clinical features. Data were obtained from the Netherlands Cancer Registry. The incidence, characteristics, and clinical features per predisposing condition were analyzed in 2697 SIA patients diagnosed from 1999 through 2019. Of all SIA patients, 5.6% were known to have a genetic predisposing syndrome, of whom 4.0% had LS and 1.6% had a polyposis syndrome. In addition, 6.8% of SIA patients had a non-genetic predisposing condition: 3.9% IBD and 2.9% celiac disease. SIAs of patients with such predisposing syndromes or conditions were diagnosed at a younger age and earlier stage and affected the duodenum less often as compared to sporadic SIA patients. Both genetic and non-genetic predisposing conditions were associated with significantly better overall survival (OS) compared to sporadic SIA: sporadic SIA (median OS: 13.0 months, 95% CI: 11.8-14.2), LS (213.1 months, 99.3-NA), polyposis syndromes (61.3 months, 19.7-NA), IBD (29.5 months, 20.3-69.8), and celiac disease (50.4 months, 24.6-124.7). This nationwide cohort study shows significant differences between SIA with and without predisposing conditions and highlights the need for research on underlying molecular mechanisms to improve outcomes of SIA patients.

Coil or Plug-Assisted Retrograde transvenous obliteration (CARTO/PARTO) for treating portal hypertensive variceal bleeding: A multi-center, real-world 10-year retrospective study

Background & Aims: CARTO and PARTO are well-accepted treatment for gastric variceal (GV) bleeding. However, long-term (>2 years) clinical outcomes have yet to be studied. In this study, we investigated long-term clinical outcomes, including overall survival (OS) in 10 years Methods: We performed a multi-national, multi-center, retrospective study of CARTO/PARTO in GV treatments between 05/2012 and 07/2024. The primary study outcomes were a long-term OS and prognostic factors of CARTO/PARTO. The secondary outcomes were long-term clinical/technical success, complications, clinical changes including portal hypertensive symptoms. Results: A total of 311 patients (41% female; 69% CARTO) from 13 centers in five countries were included. The cumulative 1-, 3-, 5-, 7-, and 10-year OS rates were 98, 80, 68, 52, and 33%, respectively, with a median OS of 99 months. Prophylactic CARTO/PARTO showed a better OS than CARTO/PARTO for active bleeding (p=0.00035). The independent prognostic factors of OS were having high pre-MELD, concurrent HCC, treating GOV2, history of esophageal variceal bleeding, high pre-TBili, and ammonia levels. Notably, a high pre-MELD score >27 had a significantly higher mortality rate (92.6%) than a lower pre-MELD score (p<0.001). The overall cumulative 1-, 3-, 5-, 7-, and 10-year recurrent GV bleeding rates were 0.9, 3.2, 4.0, 4.5, and 5.4%, respectively. The overall technical and clinical success rates were 96.5% and 95.3%, respectively, with a 4.5% major complication rate over 10 years. Conclusions: CARTO and PARTO have excellent long-term survival and clinical outcomes. However, these are negatively affected by high MELD scores, concomitant HCC, and coexisting esophageal varices.

Development of HIV Drug-Resistance Mutations and Antiretroviral Efficacy Among Vietnamese Patients After Failure of 5-Year First-Line Therapy.

The emergence of drug-resistant mutations in human immunodeficiency virus (HIV) over time presents a challenge to treatment. We describe the development of drug-resistance mutations and ART efficacy reduction in Vietnamese patients with failure of first-line ART during a 5-year period. This is a 5-year observational cohort study with HIV viral loads of patients evaluated annually for 5 years (2017-2022) at the hospitals in Vietnam. Patients with a viral load ≥ 1000 copies/mL were subjected to identifying mutations in reverse transcriptase, protease, and integrase to evaluate HIV resistance and the efficacy of ART. After 5 years of monitoring the HIV load of 2932 patients on ART, 75 (2.56%) patients had concurrent virological failure at all 5 years. In 2017, only 2/75 HIV strains possessed Protease Inhibitor (PI) resistance mutations, while 75/75 HIV strains had both Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) resistance mutations. Only four PI resistance variants were found, while 40 and 32 mutations were resistant to NRTIs and NNRTIs. After 5 years, the number of HIV PI resistance mutations had increased to 14, with 13 new mutations emerging. There were six novel mutations associated with resistance to NRTIs, NNRTIs, and the proportion of preexisting mutations increased from 1.3% to 13.3%. Furthermore, HIV sensitivity to ART decreased from 2.7% to 18.6%. After 5 years, HIV had increased resistance mutations to PIs, NRTIs, and NNRTIs, with PI resistance mutations increasing the most rapidly, and the decrease in HIV sensitivity to PIs was higher than that to NRTIs and NNRTIs.

Single-Center 5-Year Observational Study of Thrice-Weekly Single-Strength Sulfamethoxazole–Trimethoprim as Adequate Prophylaxis for Pneumocystis jirovecii Pneumonia in Patients with Heart Transplants

Background/Objectives: Pneumocystis jirovecii pneumonia is a significant contributor to morbidity and mortality in patients with solid organ transplants. Sulfamethoxazole–trimethoprim prophylaxis has greatly reduced the incidence of this deadly fungal infection. Traditional prophylactic dosing includes single strength (400–80 mg) daily or double strength (800–160 mg) thrice weekly, but is limited by side effects. This study evaluates the efficacy and tolerability of a sulfamethoxazole–trimethoprim single-strength thrice-weekly prophylactic dosing strategy. Methods: This was a single-center, retrospective chart review of 421 patients with 423 total heart transplants at Cedars Sinai Medical Center between July 2016 and June 2020.A total of 361 patients (363 heart transplants) were started on single-strength sulfamethoxazole–trimethoprim thrice weekly for 1 year, based on institutional guidelines. Results: Patients were followed for a median of 3.86 years (range 0.17 to 6.57). Sulfamethoxazole–trimethoprim was started at a median of 7 days (range 0 to 132) for median duration of 11.5 months (range 0.25 to 22). There were no documented Pneumocystis jirovecii pneumonia cases during the study period. At 1 year, 36% of patients had discontinued sulfamethoxazole–trimethoprim. The most common causes for discontinuation were leucopenia (30.8%) and hyperkalemia (2.2%). Conclusions: In our experience, single-strength sulfamethoxazole–trimethoprim thrice weekly for 1 year effectively prevents Pneumocystis jirovecii pneumonia after heart transplant. Further multicenter studies with other patient populations will need to be performed to explore this well-tolerated strategy.

Long-Term Outcomes on Pallidal Neurostimulation for Dystonia: A Controlled, Prospective 10-Year Follow-Up.

Pallidal neurostimulation is an effective treatment for severe isolated dystonia, but long-term data from clinical trials are lacking. To evaluate long-term efficacy and safety of pallidal neurostimulation in patients with isolated generalized or segmental dystonia. Extension study of the prospective multicenter trial (n = 40; July 2002 to May 2004), all patients received effective stimulation and underwent regular follow-up. The 10-year follow-up (n = 31) included Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability score, Beck Depression Inventory, Beck Anxiety Inventory, and Mattis Dementia Rating Scale. Primary and secondary endpoints compared motor symptoms, disability scores, mood, and cognition changes. Thirty-one patients (12 female), aged 23-72 years, completed the 10-year study extension. Per protocol analysis showed sustained significant improvement in BFMDRS motor scores at 10 years compared with baseline, without significant change from the 6-month or 5-year follow-up. On average, motor scores decreased by 25.3 ± 5.2 points at 10 years (P < 0.0001; 56% improvement). Individual outcomes varied, with 27 responders (≥25% improvement; mean improvement 65.2 ± 21.4%) and 13 non-responders compared with baseline. Sustained improvements were seen in disability, mood, and anxiety scores. Cognition remained stable. This study presents the longest prospective, multicenter follow-up of pallidal neurostimulation in generalized and segmental dystonia. Two-thirds of patients showed strong and stable long-term improvements of dystonia, confirming sustained efficacy and safety over 10 years in treatment-refractory dystonic patients. However, one-third experienced primary (3/40) or secondary (10/40) treatment failure. Diagnostic advances, including genetic testing, and technological progress in pallidal neurostimulation may help to reduce the non-responder rates in the future. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Role of cognitive impairment in predicting the long-term risk of all-cause mortality: a 20-year prospective cohort study in China.

There is limited evidence of the relationship between cognitive changes and all-cause mortality. And it has no report of population-attributable fraction (PAF) of mortality due to cognitive impairment in Chinese elderly. In light of this, we comprehensively examined the relationship between cognitive impairment and all-cause mortality after 20-year follow-up among the elderly Chinese. This is an epidemiological survey with a 20-year prospective cohort study design. A total of 9093 participants came from the Chinese Longitudinal Healthy Longevity Survey 1998-2018 waves. Cox proportional hazards regressions were performed to analyze the relationship between baseline cognitive impairment status, the rate of change in the MMSE scores over two years and subsequent all-cause mortality. We observed a dose-response relationship between cognition and mortality. Compared to those with no impairment, elderly with mild (AHR = 1.11, 95% CI 1.05-1.18), moderate (AHR = 1.22, 95% CI 1.13-1.33) and severe (AHR = 1.30, 95% CI 1.19-1.42) cognitive impairment showed increased mortality risk. Elderly with rapid cognitive decline had 24% higher mortality risk than those with stable cognitive (AHR = 1.24, 95%CI 1.10-1.39). The PAF of mortality due to severe cognitive impairment was 3.69% (95%CI:2.36-5.25%). Impairment in the subdomain of naming foods (AHR = 1.12, 95% CI 1.04-1.21), registration (AHR = 1.18, 95% CI 1.11-1.26), attention and calculation (AHR = 1.13, 95% CI 1.07-1.21), copy figure (AHR = 1.13, 95% CI 1.06-1.20), delayed recall (AHR = 1.14, 95% CI 1.07-1.20) and language (AHR = 1.14, 95% CI 1.05-1.24) were independently associated with increased mortality risk among participants. Baseline cognitive impairment was inversely associated with longevity among the elderly Chinese. The rapid cognitive decline increased all-cause mortality, and this risk would continue for 20 years. These findings underscore the crucial role of early detection and management of cognitive impairment in the elderly.

Left atrial strain predicts paroxysmal atrial fibrillation recurrence after catheter ablation: a 1-year study using three-dimensional speckle-tracking echocardiography.

Radiofrequency catheter ablation (RFCA) is a widely employed method for restoring sinus rhythm(SR) in patients with drug-refractory paroxysmal atrial fibrillation (PAF). Three-dimensional speckle tracking echocardiography (3DSTE) is a precise and practical imaging technique for clinically assessing myocardial function in the left atrium. The objective of this study was to assess alterations in three-dimensional strains and predict recurrence in patients with PAF following RFCA. A total of 109 patients diagnosed with drug-refractory PAF and scheduled for RFCA were included in this study between September 2019 and June 2022. Conventional echocardiography and 3DSTE were performed prior to and one year(median period of 12.2 months) after RFCA. Global three-dimensional left atrial (LA) strain parameters, along with those of the left ventricle, were measured and analyzed statistically. The primary study endpoint was the recurrence of atrial fibrillation (AF). Among the 109 patients, 78 maintained a stable SR during the one-year follow-up after RFCA, while 31 experienced a recurrence of AF. Notably, patients who sustained SR demonstrated significant improvements in various LA strain parameters, including reservoir, pump, and conduit functions, compared to both their preoperative levels and those of patients who experienced recurrence(p < 0.05). Additionally, patients with sustained SR exhibited a significant reduction in LA volume compared to those with recurrence(p = 0.003). Furthermore, left ventricular global longitudinal strain (LVGLS) and left ventricular global area strain (LVGAS) of the left ventricle showed improvement while maintaining a preserved left ventricular ejection fraction (LVEF) after RFCA(p < 0.05). Our multivariate regression analysis revealed that left atrial reservoir strain (LASr) independently predicted the recurrence of AF [odds ratio (OR), 1.19, 95% confidence interval (CI), 1.05-1.35, p = 0.005]. Receiver operating characteristic(ROC) curve showed that the area under the curve(AUC) for LASr in assessing the risk of recurrence after RFCA in patients with PAF was 0.70 ( 95% CI, 0.60-0.81, P = 0.001). The calculated cutoff value was 16.5%. RFCA plays a pivotal role in preserving SR and restoring LA function in patients with PAF. 3D-STE is highly effective for post-RFCA prognostic assessment. LASr, a predictive marker for the recurrence of PAF assists in the stratification of risk and contributes to informed treatment decisions, offering valuable points of reference.

Hearing Loss Secondary to TECTA Gene Mutations.

To assess the prevalence and clinical characterization of variants in the TECTA gene among individuals with bilateral sensorineural hearing loss of unknown etiology in northern Spain. A 6-year (2018-2024) observational, prospective, and descriptive study was conducted on patients with bilateral sensorineural hearing loss at a tertiary hospital. Next generation sequencing using a gene panel for sensorineural hearing loss was performed to detect pathogenic, likely pathogenic, or variants of unknown significance in the TECTA gene. Among 326 patients, pathogenic or likely pathogenic TECTA variants were found in 7 patients (2.14%), including c.3107G>A (n = 6) and c.5383+6T>A (n = 1). Variants of unknown significance were found in 8 patients (2.45%). About 14 of 15 probands had a family history of hearing loss with autosomal dominant inheritance. Eight relatives with confirmed pathogenic variants were also included, totalling 23 cases. Six patients with pathogenic variants and 3 with variants of unknown significance had moderate mid-frequency hearing loss, while others had severe high-frequency loss. Hearing loss was typically progressive, ranging from congenital onset to the fifth decade. Most were treated with hearing aids; none required cochlear implants. TECTA gene variants are relatively common in this population, with c.3107G>A being the most frequent. The typical phenotype is slowly progressive, mid-to-high frequency sensorineural hearing loss, often starting in childhood and usually requiring hearing aids fitting with good results in improving speech intelligibility.

Temporal trends of the utilization patterns of sedative-hypnotic medications in children, adolescents and young adults: a 21-year population-based study with joinpoint regression analysis.

There is limited research on real-world utilization patterns of benzodiazepines and Z-drugs (collectively-termed benzodiazepine-receptor agonists [BZRAs]) in children and adolescents, particularly in non-western countries. We aimed to examine temporal trends of BZRA prescribing-practice among children, adolescents and young adults in Hong Kong over a 21-year period. This population-based study identified 60,660 individuals aged 4-24 years who had redeemed ≥ 1 BZRA prescription within 2000-2020, using data from medical-record database of Hong Kong public-healthcare-services. We calculated annual prescription prevalence (per 1,000 persons per year) for any BZRA, BZRA-subtypes (short- and long-acting benzodiazepines, Z-drugs) and individual BZRAs. Joinpoint-regression analyses were performed to assess temporal BZRA prescription trends, quantified by average annual-percent-change (AAPC), with 95% confidence-intervals (CIs). Overall BZRA prescription prevalence significantly increased (AAPC: 5.70% [95%CI: 5.31-6.54%]), from 1.88 in 2000 to 5.69 in 2020, uniformly across both sexes. Young adults (18-24 years-old) displayed the highest prescription prevalence, followed by adolescents (12-17 years-old) and children (4-11 years-old). Young adults and adolescents exhibited more pronounced increased BZRA use than children. Use of all BZRA subtypes consistently increased over time for all age-groups, except decline in Z-drug prescriptions in children. Lorazepam and diazepam represented the two most frequently-prescribed individual BZRAs, whereas alprazolam use showed the steepest increase. Anxiety and depression emerged as the most commonly-assigned diagnoses for BZRA-users. This first Asian population-based study indicates a significant rising trend of BZRA prescriptions, especially among adolescents and young adults. Judicious prescribing-practices and further investigation clarifying factors contributing to increased BZRA use are warranted.

Tissue Doppler echocardiography predicts long-term cardiovascular mortality: the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) legacy 20-year follow-up study

BackgroundLeft ventricular diastolic function as assessed by tissue Doppler echocardiography predicts cardiovascular event rates at 4 years of follow-up in patients with hypertension. Our aim was to evaluate whether this...

ASO Visual Abstract: One- Or Two-Step Total Thyroidectomy for Cancer Indications: A 20-Year Retrospective Study from a Referral Center.

ASO Visual Abstract: One- Or Two-Step Total Thyroidectomy for Cancer Indications: A 20-Year Retrospective Study from a Referral Center.

Secular trends in cytomegalovirus (CMV) risk and outcomes: results from a 10-year longitudinal cohort study in adult kidney transplant recipients.

The goal of this study was to determine the secular trends in the incidence of CMV sero-mismatch (D+/R -) and if these trends meaningfully impact clinical outcomes. This was a single-center longitudinal cohort study in adult kidney recipients transplanted between Jan 2012 and June 2021 with follow-up through June 2022. Baseline and follow-up data were collected. Univariate and multivariate statistics were used to analyze the data. 2,392 kidney transplants were performed during the study period; 132 patients did not meet inclusion criteria. The mean age was 52years, 41% were female, 57% were black, and 19% were CMV D + /R -. The odds of being CMV high-risk increased by 6% each year (OR 1.06, 1.02-1.10 p = 0.003); 48% of the variability associated with CMV serostatus was explained by transplant year (R2 = 0.478, p = 0.002). Sequential modeling demonstrated that CMV D + /R - serostatus was a substantial risk factor for CMV infection (HR 5.7, 4.5-7.3), CMV disease (HR 8.4, 3.9-18.0), CMV resistance (HR 17.9, 3.8-84.2), CMV refractory infection (HR 35, 4-280), late CMV infection (HR 12.0, 8.3-17.1), acute rejection, and hospitalization for opportunistic infections. Secular trend analysis demonstrated that CMV infections, CMV resistance, and late CMV increased in incidence since 2012. The risks of CMV resistance and late infection was significantly influenced by D + /R - serostatus and transplant year, indicating that this risk is worsening over time. The CMV D + /R - serostatus remains the single most important risk factor for CMV infection, disease, resistance, refractory infection, and late CMV, which appears to be increasing in magnitude.

Exploring and detecting predictors associated with survival and mortality of cervical cancer patients: a 10-year retrospective study

Abstract Background Cervical cancer is the 4th most prevalent cancer among females globally. In India, approximately 123,907 women are diagnosed with cervical cancer every year, leading to 77,348 deaths annually. However, Indian healthcare system lacks the sufficient information regarding the factors influencing survival and mortality among cervical cancer patients at regional levels. Thus, we aimed to identify the predictors associated with survival outcomes and mortality rates among cervical cancer. Methods A retrospective cohort study was conducted over 8 months at a tertiary care hospital where 10-year (January 2013–December 2022) data of cervical cancer patients were analyzed from medical record department (MRD). Telephonic interviews were carried out with patients or patient parties to know the survival status of patients. The data was analyzed using descriptive statistics, Kaplan–Meier curve, log-rank test and Cox regression. Results Out of 330 cervical cancer patients, majority (64.24%) were &gt; 50 years of age followed by 35.76% were &lt; 50 years. Most of the patients had abnormal body mass index (BMI) (46.96%), postmenopausal stage (75.76%), stage II cancer (43.03%), histologically poorly differentiated grade (47.88%) and squamous cell carcinoma (87.88%), with radiation plus chemotherapy being popular treatment choice (48.79%) and with the overall mean age of 56 years. Age, BMI, menopause, stage of cancer, histological grades and types of treatment were found to be significant predictors (p &lt; 0.05) of survival among cervical cancer patients. Using cox regression analysis, advanced age (age &gt; 50 years: hazard ratio (HR): 1.82), underweight (BMI &lt; 18.5: HR:1), postmenopause (HR:1), advanced stage of cervical cancer (Stage I, Stage II, Stage III, Stage IV: HR:1, HR:2.78, HR:10.08, HR:20.81), poorly differentiated cervical cancer (HR:1.70), radiation therapy (HR:4.86), chemotherapy (HR:6.55) or chemoradiation therapy (HR:3.31) and surgery plus chemotherapy (HR: 4.55) were identified to be significant predictors of mortality among cervical cancer patients. Conclusion We conclude that the 5- and 10-year survival rates for cervical cancer patients were found to be 51.2% and 42.9%, respectively. Advanced age, underweight, postmenopausal status, advanced cancer stage, poor cancer cell differentiation and chemotherapy-based treatment were significant predictor of mortality and vice-versa for survival which might guide clinicians and policymakers in making informed clinical decisions to combat cervical cancer.

Utilisation of Radiation Oncology Services by Patients with Head and Neck Malignancies in a Nigerian Tertiary Care Hospital: A 5-Year Retrospective Study

Abstract Background: Radiation oncology services are luxuries in resource-challenged settings that should not be underutilised; however, no studies are available on their utilisation. Objectives: To determine the rate and pattern of utilisation of radiation oncology services in a Nigerian teaching hospital. Materials and Methods: All cases of head and neck cancers diagnosed and referred to the Department of Radiation Oncology, of a Nigerian Tertiary Care Hospital, from January 2018 to December 2023 were retrospectively analysed. Data were extracted from the case notes of the patients. Those patients with incomplete information were excluded. Demographic and clinical data were collected. Demographic data included were age, sex, religion, and place of residence, while the clinical data were regional location of cancer, nature of the tumour, origin of tumour, histological type and grade of tumour, and referring department. Both descriptive and inferential statistics were determined. Data were analysed using IBM SPSS Statistics for Windows, version 23.0 software (IBM, Armonk, New York). A value of P &lt; 0.05 was considered significant. Results: A total of 13,690 patients presented for the radiation oncology treatment, of which 1777 patients were treated for head and neck cancer, giving a prevalence of 0.56%. The age 18 range was 20–78 years with a mean age of 49.4 ± 13.7 years. More than half (77%) of the patients were older than 60 years. Two-thirds (74%) of the patients were males. Most (46.8%) of the lesions were on the oral region, which was followed by the nasal region (25%), while the least (6.5%) were observed on the cervical region. More than two-thirds (87%) originated from epithelial cells. In the same vein, the majority (88.3%) were non-odontogenic in origin. More than half (51.9%) were squamous cell carcinomas. Most (51.9%) of the patients were referred from the Department Of Oral and Maxillofacial Surgery. Ethnicity significantly affected the nature of the tumour (P &lt; 0.05), as did the histological types (P &lt; 0.05) of head and neck cancers. Religion was associated with the type of referring departments (P &lt; 0.05). Conclusion: The utilisation of radio-oncological services was high. There was significant distribution of referrals, histological types and types of tumours according to religion and ethnicity.

Determining Spatial Responses of Fishers (Pekania Pennanti) to Mechanical Treatments of Forest Stands for Fuel Reduction

Historical forestry practices (e.g., fire suppression, heavy timber logging) have contributed to a discernable change in stand composition of western forests in the U.S., which now comprise a tinderbox mixture of increased surface and ladder fuels, dense stands, and fire-intolerant species. Forest managers are mitigating this concern by implementing silviculture practices (e.g., selective logging, thinning, prescribed burning) to reduce fuel loads and improve stand resiliency. Concern for habitat specialists, such as the fisher (Pekania pennanti), have arisen as they may be negatively influenced in the short-term by modifications to their environment that are needed to ensure long-term habitat persistence. To address this issue, we initiated an 8-year study in 2010 in Ashland, Oregon, to determine the behavioral response of fishers to fuel reduction treatments applied in forested stands. We measured the distance of each location from eight GPS-collared fishers to all treatments before and after they were treated within each home range, and performed three statistical tests for robustness, including a multi-response permutation procedure, chi-squared test of independence, and a Kolmogorov–Smirnov assessment. We found high variation among individuals to the tolerance of habitat manipulation. Using effect size to interpret the magnitude of fisher response to pre- and post-treatment effects, 1 fisher showed a moderate negative relationship to fuel reduction treatments, 5 exhibited a weak negative response, and 2 had a weak positive association with treatments. We used analysis of variance on the three fishers exhibiting the largest effect sizes to treatment disturbance, and used treatment, temporal, and habitat covariates to explore whether these factors influenced behavioral differences. Treatment season and vegetation class were important factors influencing response distance in the pre-treatment period. Post-treatment variables eliciting a negative treatment response were treatment season and treatment size, and results were slightly different when parsing out individual effects compared to a pooled sample set. Our findings suggested that seasonal timing and the location of management activities could influence fisher movement throughout their home range, but it was largely context-dependent based on the perceived risks or benefits to individuals.

Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study

Background and objectivesCladribine tablets (CladT) represent an effective immune reconstitution therapy, administered in short treatment courses over two consecutive years. To better understand the amplitude of immune changes, we performed a comprehensive analysis during the 2-year study period for the entire MAGNIFY-MS population (N=270). In addition to lymphocyte kinetics, we studied intracellular cytokines serum proteins, and their associations with clinical outcomes. To put these changes into perspective, we analyzed transcriptional changes in T and B cells and associated biological pathways before and after each treatment course with CladT.MethodsImmunophenotyping and transcriptomics were performed at regular visits with major differences reported between baseline (BL) and after each yearly treatment course. Assessments included: lymphocyte dynamics, RNA sequencing (B and T cells), intracellular cytokines, serum proteins (immunoglobulins [IgG and IgM], and serum neurofilament light chain [sNfL]). Clinical measures included: MRI activity, annualized relapse rate (ARR), 6-month confirmed disability progression (6mCDP), timed 25-foot walk (T25FW), and 9-hole peg test (9HPT).ResultsAll B, T and NK cells were reduced at month (M)3 after CladT administration, except regulatory B cells which increased above BL from M3 to M24. Naïve and transitional B cells recovered at M6; all other B and T cell subsets remained below BL levels. Reductions in all NK cell subtypes were observed at M3, CD16lowCD56bright and NKp46 cells reconstituted at M6 and M12 respectively. Changes in genes and pathways associated with innate and adaptive immune response were observed after CladT treatment, along with reductions in pro-inflammatory cytokine-producing B and T cells and increases in anti-inflammatory cytokine-producing T cells. IgG and IgM levels remained above the lower limits of normal in most participants. sNfL levels decreased, remaining reduced by M24. Significant reductions in the annualized combined unique active lesion count occurred from M2 onwards. ARR was 0.11 (95% confidence interval: 0.09,0.15), with 83% participants free of qualifying relapses. Over 90% of participants were free of 6mCDP, around 87% had no confirmed progression on T25FW and 9HPT. No significant correlations were seen between clinical parameters and lymphocyte dynamics to M6. The safety profile was consistent with previous reports.DiscussionDeep longitudinal immunophenotyping, analysis of transcriptional changes, reduction in cells expressing pro-inflammatory cytokines, along with the marker of neuroaxonal damage provide novel and innovative evidence of CladT rebalancing the immune system towards a more homeostatic and less pathogenic state.Clinical Trial Registrationhttps://clinicaltrials.gov/study/, identifier NCT03364036.

Long-term outcomes and re-intervention rates in women undergoing mri-guided focused ultrasound (mrgfus) for uterine fibroids: a 7-year follow-up study.

To assess the long-term outcomes of MR-guided focused ultrasound (MRgFUS) for treating uterine fibroids, focusing on re-intervention rates, pregnancy outcomes, and the onset of menopause over a 7-year follow-up period. We conducted a historical cohort study of 99 women with symptomatic uterine fibroids who underwent MRgFUS between 2013 and 2020 at a single tertiary medical center. Data collection included patient demographics, treatment details, and follow-up interviews. Re-intervention rates were evaluated using Kaplan-Meier curves and Cox regression analysis to identify predictors of further treatments, with a specific focus on age-related differences. Over a median follow-up of 6.1years, 33.1% of women required re-intervention for persistent fibroid symptoms. The median patient's age was 43years old. Women aged ≤ 43years had significantly higher re-intervention rates than those aged 44 + years (47.5% vs. 16.7%, p = 0.005). Multivariable Cox regression identified age as the sole significant predictor of re-intervention (HR44+vs. <43 0.303 95% CI 0.128-0.714, p = 0.006). Sixteen women conceived after MRgFUS, resulting in 21 pregnancies, with 72.2% live births and a spontaneous miscarriage rate of 22.2%. The mean age of menopause was 51.4years, similar to global averages. MRgFUS is a practical, noninvasive option for treating symptomatic uterine fibroids. Older women show lower re-intervention rates. Pregnancies post-MRgFUS are possible, and the procedure does not appear to affect the onset of menopause. Age remains a crucial predictor for further re-intervention.

Resumption of Employment after Cervical Cancer Surgery: a 3-Year Follow-Up Study of Long-term Outcomes

INTRODUCTION. Despite advancements in cervical cancer (CC) diagnosis and treatment, surgical intervention remains the cornerstone of radical treatment. However, surgical procedures can result in complications such as lymphedema, sexual dysfunction, and other physical and psychosocial disorders, significantly affecting patients' quality of life (QoL) and ability to return to work. This emphasizes the need for effective strategies to support patients in resuming their occupational activities post-treatment. AIM. To investigate the relationship between different rehabilitation programmes following cervical cancer surgery and return to work MATERIALS AND METHODS. The study included patients aged 18 and older with stage 1A–1B cervical cancer. Patients were randomized into two groups: those receiving an active comprehensive rehabilitation program (СС-1, 51 patients) and those receiving passive rehabilitation (СС-2, 52 patients). The active rehabilitation program included a personalized, year-long regimen encompassing physical therapy, psychotherapeutic support, and lifestyle modifications, among other interventions. In contrast, the passive rehabilitation group received standard post-operative care information and general recommendations based on local clinical guidelines. The primary outcome was the proportion of patients who returned to work at various time points up to 36 months post-surgery. RESULTS. Patients in the СС-1 group demonstrated significantly higher rates of return to work compared to the CC-2 group from the third month post-surgery onwards. At 36 months, all patients in the CC-1 group had returned to work, whereas only 66.7 % of patients in the CC-2 group had resumed their professional activities. In the CC-1 group the chance of returning to work within 3 years after surgery was 2.14 times higher compared to those in the CC-2 group (OR = 0.467, 95 % CI 0.309–0.706, p 0.001). CONCLUSION. The study highlights the significant impact of personalized comprehensive active rehabilitation programs on improving the likelihood of return to work following surgical treatment for early-stage cervical cancer. These findings suggest that such rehabilitation approaches may be crucial in enhancing the long-term recovery and social reintegration of cervical cancer patients, ultimately contributing to better overall outcomes. Further research is needed to identify the most effective components of these rehabilitation programs and optimize their implementation.

Delving into biomarkers and predictive modeling for CVD mortality: a 20-year cohort study

Accurate prediction of cardiovascular disease (CVD) mortality is essential for effective treatment decisions and risk management. Current models often lack comprehensive integration of key biomarkers, limiting their predictive power. This study aims to develop a predictive model for CVD-related mortality using a machine learning-based feature selection algorithm and assess its performance compared to existing models. We analyzed data from a cohort of 4,882 adults recruited between 1999 and 2004, followed for up to 20 years. After applying the Boruta algorithm for feature selection, key biomarkers including NT-proBNP, cardiac troponins, and homocysteine were identified as significant predictors of CVD mortality. Predictive models were built using these biomarkers alongside demographic and clinical variables. Model performance was evaluated using the concordance index (C-index), sensitivity, specificity, and accuracy, with internal validation conducted through bootstrap sampling. Additionally, decision curve analysis (DCA) was performed to assess clinical benefit. The combined model, incorporating both biomarkers and demographic variables, demonstrated superior predictive performance with a C-index of 0.9205 (95% CI: 0.9129–0.9319), outperforming models with demographic variables alone (C-index: 0.9030 (95% CI: 0.8938–0.9147)) or biomarkers alone (C-index: 0.8659 (95% CI: 0.8519–0.8826)). Cox regression analysis further identified key predictors of CVD mortality, including elevated AST/ALT, TyG, BUN, and systolic blood pressure, with protective factors such as higher chloride and iron levels. Nomogram construction and DCA confirmed that the combined model provided substantial net benefit across various time points. The integration of cardiac biomarkers, lipid profiles, and inflammatory markers significantly improves the accuracy of predictive models for CVD-related mortality. This novel approach offers enhanced prognostication, with potential for further optimization through the inclusion of additional clinical and lifestyle data.