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In 2010, a Cryptosporidium hominis outbreak resulted in 27,000 clinical cryptosporidiosis cases (45% of the population) in Östersund, Sweden. Long-term abdominal and joint symptoms are common following cryptosporidiosis in adults, and it can affect the development of children in low-income countries. We investigated the potential consequences for children in a high-income setting. In 2011, we prospectively surveyed 600 randomly selected children aged 0-5 years from Östersund. Cases were defined as respondents reporting new episodes of diarrhoea during the outbreak. After 10 years, respondents received a follow-up questionnaire about long-term symptoms (n = 423). We used X 2 and Mann-Whitney U tests to assess between-group differences in demographics and the mean number of symptoms. Logistic regressions adjusted for sex, age, and prior issues with loose stools were used to examine associations between case status and symptoms reported at follow-up. We retrieved data on healthcare visits from patient records. In total, 121 cases and 174 non-cases responded to the follow-up questionnaire (69.7%). Cases reported 1.74 (median 1.00, range 0-14) symptoms and non-cases 1.37 (median 0.00, range 0-11) symptoms (p = 0.029). Cases were more likely to report joint symptoms (aOR 4.0, CI 1.3-12.0) and fatigue (aOR 1.9, CI 1.1-3.4), but numbers were generally low. We found no between-group differences in abdominal symptoms, healthcare utilization, or disease diagnoses. Children aged 0-5 years from high-income countries may experience long-term symptoms after cryptosporidiosis, but may not be affected to the same extent as adults or their peers living in low-income countries., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the regional research ethics review board in Umeå, Sweden (2010/392–31, 2015/495-31Ö), the regional research ethics review board in Stockholm (2011/220–31/4, 2011/1289–32), and the Swedish Ethical Review Authority (2020–05554). Consent to participate: Respondents were informed about the purpose of the study via a written letter. Consent was given by answering the questionnaire. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To assess the role of occupational noise exposure on pregnancy complications in urban Nordic populations., Methods: A study population covering five metropolitan areas in Denmark, Finland, Norway and Sweden was generated using national birth registries linked with occupational and residential environmental exposures and sociodemographic variables. The data covered all pregnancies during 5-11 year periods in 2004‒2016, resulting in 373 184 pregnancies. Occupational noise exposure was based on a Swedish-developed job-exposure-matrix, containing measured A-weighted annual 8 hour noise levels (L Aeq8h ), and linked with person-specific job-history. Outcomes included diagnosed gestational diabetes, gestational hypertension, mild pre-eclampsia and severe pre-eclampsia. The data were analysed with logistic regression models separately in each country, adjusting for maternal (age, parity, birth year, education and marital status) and residential environmental factors (low neighbourhood income, NO 2 and green and blue space). The results were combined by meta-analysis., Results: Occupational noise exceeding 80 dB, compared with less than 70 dB, was associated with an increased odds of gestational diabetes in all countries, with a combined OR of 1.26 (95% CI 1.04 to 1.51), and mild pre-eclampsia in all countries except Finland, resulting in a combined OR of 1.22 (95% CI 0.99 to 1.51). Further adjustment by maternal body-mass index attenuated these associations. No association with gestational hypertension or severe pre-eclampsia was found., Conclusions: Register data from four nationalities show that gestational diabetes and, tentatively, mild pre-eclampsia was increased among pregnant workers working in occupations where noise levels exceed 80 dB L Aeq8h but not in occupations with lower noise levels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

The androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear. Here, we use a genome-wide approach to modulate canonical androgen response element (ARE) motifs-the classic DNA binding elements for AR-to delineate distinct AR transcriptional programs. We find that activating these AREs promotes differentiation and growth-suppressive transcription, potentially leading to AR + PCa cell death, while ARE repression is tolerated by PCa cells but deleterious to normal prostate cells. Gene signatures driven by ARE activity correlate with improved prognosis and luminal phenotypes in PCa patients. Canonical AREs maintain a normal, lineage-specific transcriptional program that can be reengaged in PCa cells, offering therapeutic potential and clinical relevance., Competing Interests: Competing interests: M.S. reports grants from the Swedish Research Council, the Swedish Society of Medicine, and the Prostate Cancer Foundation during the conduct of the study. A.H., Y.L., and E.D. are employees of Veracyte, Inc. M.A.A. and D.L. are currently employees of Loxo Oncology. C.E.B. is a co-inventor on a patent issued to Weill Medical College of Cornell University on SPOP mutations in prostate cancer. F.Y.F. reports fees from Janssen Oncology, Bayer, PFS Genomics, Myovant Sciences, Roivant Sciences, Astellas Pharma, Foundation Medicine, Varian, Bristol Myers Squibb (BMS), Exact Sciences, BlueStar Genomics, Novartis, and Tempus; other support from Serimmune and Artera outside the submitted work. The authors declare no other potential competing interests., (© 2024. The Author(s).)

Tumors escape immune detection and elimination through a variety of mechanisms. Here, we used prostate cancer as a model to examine how androgen-dependent tumors undergo immune evasion through downregulation of the major histocompatibility complex class I (MHCI). We report that response to immunotherapy in late-stage prostate cancer is associated with elevated MHC expression. To uncover the mechanism, we performed a whole genome CRISPRi screen and identified AR as a repressor of the MHCI pathway. Syngeneic mouse models of aggressive prostate cancer deficient in AR also demonstrated increased tumor immunogenicity and promoted T cell mediated tumor-control. Notably, the increase in MHCI expression upon androgen receptor blockade is transient and correlates with resistance to AR inhibition. Mechanistic studies identified androgen response elements upstream of MHCI transcription start sites which increased MHCI expression when deleted. Together, this body of work highlights another mechanism by which hormones can promote immune escape.

Introduction: Dental education blends theoretical and practical training to prepare students for independent patient care. This study examines the confidence levels of dental students at Umeå University, Sweden regarding independent performance of general dentistry tasks, and whether this confidence changes after clinical training., Material and Methods: Surveys were conducted before and after a summer clinical internship, with students rating their comfort levels on a scale from 0 to 10 for various procedures., Results: Results from 64 initial surveys and 54 follow-up surveys showed no significant difference in confidence before and after the internship except for performing a tooth extraction (p = 0.010). However, confidence levels varied based on whether students had practiced specific tasks during the internship., Discussion: Students felt least confident in managing acute dental trauma (mean 6.1-6.2) and treating cavities in young children (mean 6.2-6.7), while they were most confident in tasks like obtaining radiographic surveys (mean 8.5-8.6) and debriding periodontally compromised dentition (mean 8.2-8.3). Tooth extraction and dental fillings were the most practiced procedures during the internship., Conclusions: The study concludes that the internship between the ninth and tenth semesters does not notably boost students' confidence in specific dental procedures except for dental extractions. This result can possibly be explained due to the short duration of the training. Further exploration, including input from clinical supervisors, is suggested to optimise clinical training in dental education., Competing Interests: Competing interests: The authors report no conflicts of interest. Ethics declaration: The study underwent ethical review by the Swedish Ethical Review Authority. Because no intervention or other action would be performed on a research subject and no personal data would be processed, the Ethical Review Authority concluded that the study is not subject to the Swedish Ethical Review Act and therefore does not require ethical approval (Reference number: 2022-01934-01). The study was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study., (© 2024. The Author(s).)

Purpose: To retrospectively evaluate long-term outcomes after temporomandibular joint (TMJ) discectomy., Methods: Included patients (n = 64) had undergone discectomy during 1989-1998 at Umeå University Hospital. A questionnaire was used to evaluate pre- and postoperative symptoms, postoperative complications, general pain, and subjective opinion about the outcome of the surgery., Results: The results are based on responses from 47 patients (40 women/7 men), including 36 (30 women/6 men) who completed the questionnaire and 11 (10 women/1 man) who were contacted by telephone and answered selected questions. Seventeen patients were excluded because of death, a move abroad, declining to participate, or no available patient information. Among the respondents, 41 (87%) were satisfied with the results, five (11%) were unsatisfied, and one (2%) patient did not answer the question. The results showed a significant long-term improvement in locking, clicking/crepitation, and pain when chewing or opening the jaw (p = 0.001). The prevalence of headaches had decreased significantly at follow-up (p = 0.001). Reported impaired jaw-opening capacity showed no significant improvement (p = 0.08). Of the 47 respondents, 19 (40%) had asked for additional treatment after the discectomy, and six of the 19 patients (13%) had undergone more surgery of the joint., Conclusion: The results of this retrospective long-term follow-up study indicate that TMJ discectomy has a high success rate, as most patients were satisfied with the postoperative results. Discectomy is thus an effective surgical intervention for patients with disabling TMJ pain and dysfunction when conservative interventions have been unsuccessful., (© 2024. The Author(s).)

Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates., Methods: An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT., Results: 429 (69%) patients' tumors had a high POLAR score and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of LRR: 20% (15%-26%) vs 5% (2%-11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT: 0.37 [0.23-0.60], p < .001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], p = .832). The test for interaction between RT and POLAR was statistically significant (p = .022)., Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required., (© The Author(s) 2024. Published by Oxford University Press.)

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types. In a clinical dataset of 3003 breast cancer samples treated with neoadjuvant chemotherapy, the TP53-loss phenocopy samples were 56% more likely to have a pathologic complete response (pCR), with a significant association between TP53-loss phenocopy and pCR in both ER positive and ER negative tumors. In an independent clinical validation in the I-SPY2 trial (N = 987), we confirmed the association with neoadjuvant chemotherapy pCR and found higher rates of chemoimmunotherapy response in TP53-loss phenocopy tumors compared to non-TP53-loss phenocopy tumors (64% vs. 28%). The TP53-loss phenocopy signature predicts chemotherapy response across cancer types in vitro, and in a proof-of-concept clinical validation is associated with neoadjuvant chemotherapy response across multiple clinical breast cancer cohorts., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Therapies against cell-surface targets (CSTs) represent an emerging treatment class in solid malignancies. However, high-throughput investigations of CST expression across cancer types have been reliant on data sets of mostly primary tumors, despite therapeutic use most commonly in metastatic disease. We identified a total of 818 clinical trials of CST therapies with 78 CSTs. We assembled a data set spanning RNA-seq and microarrays in 7,927 benign samples, 16,866 primary tumor samples, and 6,124 metastatic tumor samples. We also utilized single-cell RNA-seq data from 36 benign tissues and 558 primary and metastatic tumor samples, and matched RNA versus protein expression in 29 benign tissue samples, 1,075 tumor samples, and 942 cell lines. High RNA expression accurately predicted high protein expression across CST therapies in benign tissues, tumor samples, and cell lines. We compared metastatic versus primary tumor expression, identified potential opportunities for repositioning, and matched cell lines to tumor types based on CST and global RNA expression. We evaluated single-cell heterogeneity across tumors, and identified rare normal cell subpopulations that may contribute to toxicity. Finally, we identified combinations of CST therapies for which bispecific approaches could improve tumor specificity. This study helps better define the landscape of CST expression in metastatic and primary cancers.

Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease that resists therapy targeting androgen signaling, the primary driver of prostate cancer. mCRPC resists androgen receptor (AR) inhibitors by amplifying AR signaling or by evolving into therapy-resistant subtypes that do not depend on AR. Elucidation of the epigenetic underpinnings of these subtypes could provide important insights into the drivers of therapy resistance. In this study, we produced chromatin accessibility maps linked to the binding of lineage-specific transcription factors (TF) by performing assay for transposase-accessible chromatin sequencing on 70 mCRPC tissue biopsies integrated with transcriptome and whole-genome sequencing. mCRPC had a distinct global chromatin accessibility profile linked to AR function. Analysis of TF occupancy across accessible chromatin revealed 203 TFs associated with mCRPC subtypes. Notably, ZNF263 was identified as a putative prostate cancer TF with a significant impact on gene activity in the double-negative subtype (AR- neuroendocrine-), potentially activating MYC targets. Overall, this analysis of chromatin accessibility in mCRPC provides valuable insights into epigenetic changes that occur during progression to mCRPC. Significance: Integration of a large cohort of transcriptome, whole-genome, and ATAC sequencing characterizes the chromatin accessibility changes in advanced prostate cancer and identifies therapy-resistant prostate cancer subtype-specific transcription factors that modulate oncogenic programs., (©2024 American Association for Cancer Research.)

BACKGROUNDAndrogen receptor signaling inhibitors (ARSIs) have improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), but their clinical benefit is limited by treatment resistance.METHODSTo investigate the mechanisms of ARSI resistance, we analyzed the whole-genome (n = 45) and transcriptome (n = 31) sequencing data generated from paired metastatic biopsies obtained before initiation of first-line ARSI therapy for mCRPC and after radiographic disease progression. We investigated the effects of genetic and pharmacologic modulation of SSTR1 in 22Rv1 cells, a representative mCRPC cell line.RESULTSWe confirmed the predominant role of tumor genetic alterations converging on augmenting androgen receptor (AR) signaling and the increased transcriptional heterogeneity and lineage plasticity during the emergence of ARSI resistance. We further identified amplifications involving a putative enhancer downstream of the AR and transcriptional downregulation of SSTR1, encoding somatostatin receptor 1, in ARSI-resistant tumors. We found that patients with SSTR1-low mCRPC tumors derived less benefit from subsequent ARSI therapy in a retrospective cohort. We showed that SSTR1 was antiproliferative in 22Rv1 cells and that the FDA-approved drug pasireotide suppressed 22Rv1 cell proliferation.CONCLUSIONOur findings expand the knowledge of ARSI resistance and point out actionable next steps, exemplified by potentially targeting SSTR1, to improve patient outcomes.FUNDINGNational Cancer Institute (NCI), NIH; Prostate Cancer Foundation; Conquer Cancer, American Society of Clinical Oncology Foundation; UCSF Benioff Initiative for Prostate Cancer Research; Netherlands Cancer Institute.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming that allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified zinc finger protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a ten-eleven translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR-targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity. Significance: This study reveals a bifurcated role of ZNF397, and a TET2-driven epigenetic mechanism regulating tumor lineage plasticity and therapy response in prostate cancer, enhances the understanding of drug resistance, and unveils a new therapeutic strategy for overcoming androgen receptor-targeted therapy resistance., (©2024 The Authors; Published by the American Association for Cancer Research.)

The impact of variations in the three-dimensional structure of the genome has been recognized, but solid cancer tissue studies are limited. Here, we performed integrated deep Hi-C sequencing with matched whole-genome sequencing, whole-genome bisulfite sequencing, 5-hydroxymethylcytosine (5hmC) sequencing and RNA sequencing across a cohort of 80 biopsy samples from patients with metastatic castration-resistant prostate cancer. Dramatic differences were present in gene expression, 5-methylcytosine/5hmC methylation and in structural variation versus mutation rate between A and B (open and closed) chromatin compartments. A subset of tumors exhibited depleted regional chromatin contacts at the AR locus, linked to extrachromosomal circular DNA (ecDNA) and worse response to AR signaling inhibitors. We also identified topological subtypes associated with stark differences in methylation structure, gene expression and prognosis. Our data suggested that DNA interactions may predispose to structural variant formation, exemplified by the recurrent TMPRSS2-ERG fusion. This comprehensive integrated sequencing effort represents a unique clinical tumor resource., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the effect of orthognathic surgery on quality of life among Swedish patients., Materials and Methods: Patients subjected to orthognathic surgery due to dentofacial deformity (DFD) and registered in the National Register of Orthognathic Surgery (NROK) in Sweden between 2017 and 2020 were eligible for inclusion in this study. The Swedish-validated Orthognathic Quality of Life Questionnaire (S-OQLQ) was used to evaluate patient quality of life before and after surgery. The S-OQLQ measured each patient's subjective experience regarding social aspects., Results: Eighty-four participants were included in this cohort study, including 45 men (mean age 24.7 years), 48 women (mean age 23.4 years), and eight patients who stated no gender. Women generally graded several aspects of the S-OQLQ higher than men, including facial aesthetics p = 0.029), oral function (p < 0.001), and awareness of facial deformity (p = 0.0054). For all domains of the questionnaire (social, facial aesthetics, function, and awareness), a significant improvement was seen 6-24 months after surgery (p < 0.001). Women rated improvement of function and awareness of facial deformity higher than men (p < 0.001 and p = 0.039, respectively)., Conclusion: Quality of life aspects of orthognathic surgery have a strong impact on the treatment outcome. Although functional impairment is often considered a major indication for surgery, the social and aesthetic influence of DFD is highly rated by patients, whereas pain is not an issue before or after treatment., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Background: Magnetic resonance imaging (MRI) of the brain is frequently performed on patients with neurofibromatosis type 1 (NF1), to detect and follow-up intracranial findings. In addition, NF1-related pathologies can appear in the jaws. This case study investigates if it is advantageous to assess the depicted parts of the jaws in the imaging of NF1 patients with intracranial findings, thereby detecting jaw pathologies in their initial stages., Case Presentation: We report on the 3-year management with clinical and radiological follow-ups of a central giant cell granuloma and a neurofibroma in the mandible of a patient with NF1 who underwent examinations with brain MRIs. A review of the mandible in the patient's MRIs disclosed lesions with clear differences in progression rates., Conclusion: NF1-related jaw pathologies may be detected in the early stages if the depicted parts of the jaws are included in the assessment of the imaging of NF1 patients with intracranial findings. This could impact the treatment of eventual pathologies before lesion progression and further damage to the vicinity., (© 2024. The Author(s).)

Transcription factor (TF) proteins regulate gene activity by binding to regulatory regions, most importantly at gene promoters. Many genes have alternative promoters (APs) bound by distinct TFs. The role of differential TF activity at APs during tumour development is poorly understood. Here we show, using deep RNA sequencing in 274 biopsies of benign prostate tissue, localized prostate tumours and metastatic castration-resistant prostate cancer, that AP usage increases as tumours progress and APs are responsible for a disproportionate amount of tumour transcriptional activity. Expression of the androgen receptor (AR), the key driver of prostate tumour activity, is correlated with elevated AP usage. We identified AR, FOXA1 and MYC as potential drivers of AP activation. DNA methylation is a likely mechanism for AP activation during tumour progression and lineage plasticity. Our data suggest that prostate tumours activate APs to magnify the transcriptional impact of tumour drivers, including AR and MYC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Prostate cancer is a heterogenous disease, but once it becomes metastatic it eventually becomes treatment resistant. One mechanism of resistance to AR-targeting therapy is lineage plasticity, where the tumor undergoes a transformation to an AR-indifferent phenotype, most studied in the context of neuroendocrine prostate cancer (NEPC). However, activation of additional de- or trans-differentiation programs, including a gastrointestinal (GI) gene expression program, has been suggested as an alternative method of resistance. In this study, we explored the previously identified GI prostate cancer phenotype (PCa-GI) in a large cohort of metastatic castration-resistant prostate cancer (mCRPC) patient biopsy samples., Methods: We analyzed a dataset of 634 mCRPC samples with batch effect corrected gene expression data from the West Coast Dream Team (WCDT), the East Coast Dream Team (ECDT), the Fred Hutchinson Cancer Research Center (FHCRC) and the Weill Cornell Medical center (WCM). Survival data was available from the WCDT and ECDT cohorts. We calculated a gene expression GI score using the sum of z-scores of genes from a published set of PCa-GI-defining genes (N=38). Survival analysis was performed using the Kaplan-Meier method and Cox proportional hazards regression with endpoint overall survival from time of biopsy to death of any cause., Results: We found that the PCa-GI score had a bimodal distribution, identifying a distinct set of tumors with an activated GI expression pattern. Approximately 35% of samples were classified as PCa-GI high, which was concordant with prior reports. Liver metastases had the highest median score but after excluding liver samples, 29% of the remaining samples were still classified as PCa-GI high, suggesting a distinct phenotype not exclusive to liver metastases. No correlation was observed between GI score and proliferation, AR signaling, or NEPC scores. Furthermore, the PCa-GI score was not associated with genomic alterations in AR, FOXA1, RB1, TP53 or PTEN. However, tumors with MYC amplifications showed significantly higher GI scores (p=0.0001). Patients with PCa-GI tumors had a shorter survival (HR=1.5 [1.1-2.1], p=0.02), but this result was not significant after adjusting for the liver as metastatic site (HR=1.2 [0.82-1.7], p=0.35). Patients with PCa-GI low samples had a better outcome after androgen receptor signaling inhibitors (ASI, abiraterone or enzalutamide) than other therapies (HR=0.37 [0.22-0.61], p=0.0001) while the benefit of ASI was smaller and non-significant for PCa-GI high samples (HR=0.55 [0.29-1.1], p=0.07). A differential pathway analysis identified FOXA2 signaling to be upregulated PCa-GI high tumors (FDR = 3.7 × 10 -13 )., Conclusions: The PCa-GI phenotype is prevalent in clinical mCRPC samples and may represent a distinct biological entity. PCa-GI tumors may respond less to ASI and could offer a strategy to study novel therapeutic targets.

Purpose: The aim was to assess skeletal stability after maxillary advancement using either distraction osteogenesis (DO) or conventional Le Fort I osteotomy (CO) in patients with cleft lip and palate (CLP) or cleft palate (CP) utilising a new superimposition-based cephalometric method., Method: This retrospective study included patients who were treated with DO (N = 12) or CO (N = 9). Sagittal and vertical changes after surgery, and skeletal stability at 18 months post-operatively were assessed with superimposition-based cephalometry, comparing lateral cephalograms performed pre-operatively (T0), post-operatively after CO or immediately after completed distraction in DO (T1), and at 18 months of follow-up (T2)., Results: The mean sagittal movements from T0 to T2 in the DO and CO groups were 5.9 mm and 2.2 mm, respectively, with a skeletal relapse rate of 16% in the DO group and 15% in the CO group between T1 and T2. The vertical mean movement from T0 to T2 in the DO and CO groups was 2.8 mm and 2.0 mm, respectively, and the skeletal relapse rate between T1 and T2 was 36% in the DO group and 32% in the CO group., Conclusion: Sagittal advancement of the maxilla was stable, in contrast to the vertical downward movement, which showed more-extensive relapse in both groups. Despite more-extensive maxillary advancement in the DO group, the rates of skeletal relapse were similar., (© 2024. The Author(s).)

Purpose: App-based treatment of urgency (UUI) and mixed (MUI) urinary incontinence has proved to be effective. To further improve treatment, it will be beneficial to analyze baseline and treatment-related factors that are associated with satisfaction., Methods: A secondary analysis was conducted of data from a randomized controlled trial (RCT) assessing an app for UUI or MUI treatment, encompassing 98 women for whom there was long-term treatment satisfaction data. All participants completed a short-term (15 weeks) and a long-term (15 months) follow-up questionnaire after being given access to treatment. The outcome was a 3-item question on current treatment satisfaction at the long-term follow-up. Factors potentially associated with the outcome were analyzed using the chi-square test, Student's t test or logistic regression., Results: At the long-term follow-up, 58% of the women were satisfied with the treatment. The most important baseline variable associated with satisfaction was incontinence-related quality of life (International Consultation on Incontinence Questionnaire (ICIQ) - Lower Urinary Tract Symptoms Quality of Life Module) (OR 0.91, 95% CI 0.58-0.97). Short-term follow-up variables associated with long-term treatment satisfaction were improvement in the ability to endure urgency (OR 4.33, 95% CI 1.43-13.12), and confidence in pelvic floor contraction ability (OR 2.67, 95% CI 1.04-6.82)., Conclusion: App-based treatment for UUI and MUI may be an alternative first-line treatment that is satisfactory to many women over the long-term. Furthermore, short-term treatment that focuses on improving the ability to endure urgency, and confidence in pelvic floor contraction ability, can also be recommended for long-term satisfaction., (© 2023. The Author(s).)

Background: Prostate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited., Objective: To explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival., Design, Setting, and Participants: This was a retrospective cohort study including 165 men with grade group 2-4 prostate cancer who underwent RP at a single academic institution (2016-2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR., Outcomes Measurements and Statistical Analysis: Prompted by heterogeneity within pattern 4 subtypes identified via exploratory analyses, we investigated transcriptomic consensus clusters using partitioning around medoids and hallmark gene set scores. The primary clinical outcome was BCR, defined as two consecutive prostate-specific antigen measurements >0.2 ng/ml at least 8 wk after RP, or any additional treatment. Multivariable Cox proportional-hazards models were used to determine factors associated with BCR-free survival., Results and Limitations: In this cohort, 99/165 patients (60%) had EC and 67 experienced BCR. Exploratory analyses and clustering demonstrated transcriptomic heterogeneity within each Gleason pattern 4 subtype. In the multivariable model controlled for pattern 4 subtype, margin status, Cancer of the Prostate Risk Assessment Post-Surgical score, and Decipher score, a newly identified steroid hormone-driven cluster (hazard ratio 2.35 95% confidence interval 1.01-5.47) was associated with worse BCR-free survival. The study is limited by intermediate follow-up, no validation cohort, and lack of accounting for intratumoral and intraprostatic heterogeneity., Conclusions: Transcriptomic heterogeneity was present within and across each Gleason pattern 4 subtype, demonstrating there is additional biologic diversity not captured by histologic subtypes. This heterogeneity can be used to develop novel signatures and to classify transcriptomic subtypes, which may help in refining risk stratification following RP to further guide decision-making on adjuvant and salvage treatments., Patient Summary: We studied prostatectomy specimens and found that tumors with similar microscopic appearance can have genetic differences that may help to predict outcomes after prostatectomy for prostate cancer. Our results demonstrate that further gene expression analysis of prostate cancer subtypes may improve risk stratification after prostatectomy. Future studies are needed to develop novel gene expression signatures and validate these findings in independent sets of patients., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to create a quantitative job-exposure matrix (JEM) for noise including a large set of measurements for the Swedish workforce, a detailed exposure-level assessment, spanning over an extensive time period from 1970 to 2014., Methods: The JEM was developed by 2 teams, each with an experienced occupational hygienist and an occupational safety engineer. Each pair assessed the exposure using measurements performed and reported by occupational hygienists, occupational safety engineers, or similar, from 1970 to 2014. The measurements included either the original LAeq(8h) measurements or an LAeq(8h) levels calculated from partial measurements of the working day, provided that the measurement targeted a regular task usually performed during a full workday. The collection of measurement reports was done in 2008 and 2012 by contacting clinics working in the area of occupational health or occupational safety engineers and their submitted reports were added to our own material. Noise exposure assessments were inserted at the appropriate time period for the relevant job family. The final matrix was developed in a consensus procedure and the validity was investigated by comparison of the 2 team's individual results., Results: The noise JEM contains 321 job families with information regarding occupational noise from 1970 to 2014. The time-period label has a 5-yr scale starting in 1970. The estimated average 8 h (TWA) noise level in decibels [dB(A)] for every job family and 5-yr period was coded as 1: <70 dB(A), 2: 70 to 74 dB(A), 3: 75 to 79 dB(A), 4: 80 to 84 dB(A) or 5: 85(+) dB(A). The validation showed no systematic difference in relative position and very high agreement in the ordering of paired ordinal classifications. The JEM has also successfully been applied in several epidemiological studies., Conclusions: We present a JEM for occupational noise using Swedish data from 1970 to 2014 with a higher degree of sensitivity in assessed noise exposure compared with the previously existing version. Repeated application of the JEM, in epidemiological studies, has shown consistent results and contributed to yielding important findings., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

This review describes the role of modern preprosthetic surgery. The atrophic edentulous jaw can cause severe functional impairment for patients, leading to inadequate denture retention, reduced quality of life, and significant health problems. The aim of preprosthetic surgery is to restore function and form due to tooth loss arising from congenital deformity, trauma, or ablative surgery. Alveolar bone loss is due to disuse atrophy following tooth loss. The advent of dental implants and their ability to preserve bone heralded the modern version of preprosthetic surgery. Their ability to mimic natural teeth has overcome the age-old problem of edentulism and consequent jaw atrophy. Controversies with preprosthetic surgery are discussed: soft tissue versus hard tissue augmentation in the aesthetic zone, bone regeneration versus prosthetic tissue replacement in the anterior maxilla, sinus floor augmentation versus short implants in the posterior maxilla-interpositional bone grafting versus onlay grafts for vertical bone augmentation. Best results for rehabilitation are achieved by the team approach of surgeons, maxillofacial prosthodontists/general dentists, and importantly, informing patients about the available preprosthetic surgical options.

Background: Complications of orthognathic surgery are quite rare, but they cause suffering in affected individuals. The range of complications is broad and includes both hard and soft tissue., Case Presentation: We here present a case of a fully healthy woman without signs of impaired healing capacity. The patient underwent bimaxillary orthognathic surgery and experienced multiple complications both peri- and post-operatively. During the post operative period, the patient also suffered from soft tissue complications after an orthopaedic injury. Therefore, we referred the patient to her general practitioner for further medical investigation. We also present the result after restorative surgery and endodontic and prosthodontic treatment resulting in a successful rehabilitation., Conclusion: This case report clearly shows the need for a good collaboration between different odontological and medical fields to achieve a good and predictable result. In situations where normal healing processes do not occur, in-depth analysis must be carried out., Highlights: Orthognathic surgery affects soft and hard tissue which can result in adverse healing and complications. It is of great importance to follow up performed surgery to see late complications. Be restrictive with early re-operations when there are signs of necrosis. Always use a multidisciplinary approach when handling complications after surgery., (© 2023. The Author(s).)

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide co-activator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that TET2 inhibitor can eliminate the AR targeted therapies resistance in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate and breast cancers acquire lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity., Statement of Significance: This study reveals a novel epigenetic mechanism regulating tumor lineage plasticity and therapy response, enhances understanding of drug resistance and unveils a new therapeutic strategy for prostate cancer and other malignancies. Our findings also illuminate TET2's oncogenic role and mechanistically connect TET2-driven epigenetic rewiring to lineage plasticity and therapy resistance.

Introduction: The present article aimed to investigate 1) if mental health problems (depression and burnout including the dimensions; emotional exhaustion, mental distance and cognitive and emotional impairment) differed between nurses and physicians in Sweden, 2) if any differences were explained by differences in sex compositions, and 3) if any sex differences were larger within either of the two professions., Method: Data were derived from a representative sample of nurses (n = 2903) and physicians (n = 2712) in 2022. Two scales were used to assess burnout (KEDS and BAT) and one to assess depression (SCL-6). The BAT scale has four sub-dimensions. Descriptive statistics and logistic regression were used to analyse each scale and dimension separately., Results: Results showed that 16-28 % of nurses and physicians reported moderate to severe symptoms of burnout. The prevalence differed between occupations across the scales and dimensions used. Nurses reported higher scores on KEDS while physicians reported higher scores on BAT including the four dimensions. Also, 7 % of nurses' and 6 % of physicians' scores were above the cut-off for major depression. The inclusion of sex in the models changed the odds ratios of differences between doctors and nurses in all mental health dimensions except mental distance and cognitive impairment., Limitations: This study was based on cross-sectional survey data which has some limitations., Conclusion: Our study suggests that the prevalence of mental health problems is prominent among nurses and physicians in Sweden. Sex plays an important role in the difference in the prevalence of mental health problems between the two professions., Competing Interests: Declaration of competing interest Authors have no conflicting interest to report., (Copyright © 2023. Published by Elsevier B.V.)

Systemic targeted therapy in prostate cancer is primarily focused on ablating androgen signaling. Androgen deprivation therapy and second-generation androgen receptor (AR)-targeted therapy selectively favor the development of treatment-resistant subtypes of metastatic castration-resistant prostate cancer (mCRPC), defined by AR and neuroendocrine (NE) markers. Molecular drivers of double-negative (AR-/NE-) mCRPC are poorly defined. In this study, we comprehensively characterized treatment-emergent mCRPC by integrating matched RNA sequencing, whole-genome sequencing, and whole-genome bisulfite sequencing from 210 tumors. AR-/NE- tumors were clinically and molecularly distinct from other mCRPC subtypes, with the shortest survival, amplification of the chromatin remodeler CHD7, and PTEN loss. Methylation changes in CHD7 candidate enhancers were linked to elevated CHD7 expression in AR-/NE+ tumors. Genome-wide methylation analysis nominated Krüppel-like factor 5 (KLF5) as a driver of the AR-/NE- phenotype, and KLF5 activity was linked to RB1 loss. These observations reveal the aggressiveness of AR-/NE- mCRPC and could facilitate the identification of therapeutic targets in this highly aggressive disease., Significance: Comprehensive characterization of the five subtypes of metastatic castration-resistant prostate cancer identified transcription factors that drive each subtype and showed that the double-negative subtype has the worst prognosis., (©2023 The Authors; Published by the American Association for Cancer Research.)

Introduction: The study aimed to investigate in which way performance-based reimbursement (PBR) systems in Swedish healthcare services (1) subjectively impacted physicians' work and patient care and (2) were associated with the occurrence of stress-induced exhaustion disorders among physicians., Method: The study applied a mixed-method design. Data were collected from a representative sample of Swedish physicians. In the questionnaire, respondents were asked to answer an open-ended question regarding their reflections on PBR. The answers to the open-ended question were analysed using thematic analysis. Respondents were also asked to rate the impact of PBR on their work. The association between PBR and self-rated stress-induced exhaustion disease was analysed with logistic regressions. Stress-induced exhaustion disorder was measured using the Burnout Assessment Scale., Results: Thematic analysis resulted in four themes: (1) Money talks, (2) Patients are affected, (3) Medical morals are challenged, and (4) PBR increase the quantity of illegitimate tasks. Logistic regressions showed that physicians who experienced PBR had an impact on their work and had a two-fold higher risk of stress-induced exhaustion disorder., Discussion: Our findings suggest that current reimbursement systems in Sweden play an essential role in Swedish healthcare and negatively influence physicians' work and health. Also, current PBR impact patients negatively. No previous study has explored the potentially harmful impact of PBR on how physicians perceive work, health and patient care. Results indicate that policymakers should be encouraged to deeply review PBR systems and focus on ways that they can limit the negative impact on physicians' work and health while meeting future challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brulin, Ekberg, Landstad, Lidwall, Sjöström and Wilczek.)

Developing radiation tumor biomarkers that can guide personalized radiotherapy clinical decision making is a critical goal in the effort towards precision cancer medicine. High-throughput molecular assays paired with modern computational techniques have the potential to identify individual tumor-specific signatures and create tools that can help understand heterogenous patient outcomes in response to radiotherapy, allowing clinicians to fully benefit from the technological advances in molecular profiling and computational biology including machine learning. However, the increasingly complex nature of the data generated from high-throughput and "omics" assays require careful selection of analytical strategies. Furthermore, the power of modern machine learning techniques to detect subtle data patterns comes with special considerations to ensure that the results are generalizable. Herein, we review the computational framework of tumor biomarker development and describe commonly used machine learning approaches and how they are applied for radiation biomarker development using molecular data, as well as challenges and emerging research trends., (Published by Elsevier Inc.)

In late 2010, an outbreak of Cryptosporidium hominis affected 27,000 inhabitants (45%) of Östersund, Sweden. Previous research shows that abdomen and joint symptoms commonly persist up to 5 years post-infection. It is unknown whether Cryptosporidium is associated with sequelae for a longer duration, how persisting symptoms present over time, and whether sequelae are associated with prolonged infection. In this prospective cohort study, a randomly selected cohort in Östersund was surveyed about cryptosporidiosis symptoms in 2011 (response rate 69.2%). A case was defined as a respondent reporting new diarrhoea episodes during the outbreak. Follow-up questionnaires were sent after 5 and 10 years. Logistic regressions were used to examine associations between case status and symptoms reported after 10 years, with results presented as adjusted odds ratios (aOR) with 95% confidence intervals. Consistency of symptoms and associations with case status and number of days with symptoms during outbreak were analysed using X 2 and Mann-Whitney U tests. The response rate after 10 years was 74% (n = 538). Case status was associated with reporting symptoms, with aOR of ~3 for abdominal symptoms and ~2 for joint symptoms. Cases were more likely to report consistent symptoms. Cases with consistent abdominal symptoms at follow-up reported 9.2 days with symptoms during the outbreak (SD 8.1), compared to 6.6 days (SD 6.1) for cases reporting varying or no symptoms (p = 0.003). We conclude that cryptosporidiosis was associated with an up to threefold risk for reporting symptoms 10 years post-infection. Consistent symptoms were associated with prolonged infection., (© 2023. The Author(s).)

In modern applications such as robotics, autonomous vehicles, and speaker localization, the computational power for sound source localization applications can be limited when other functionalities get more complex. In such application fields, there is a need to maintain high localization accuracy for several sound sources while reducing computational complexity. The array manifold interpolation (AMI) method applied with the Multiple Signal Classification (MUSIC) algorithm enables sound source localization of multiple sources with high accuracy. However, the computational complexity has so far been relatively high. This paper presents a modified AMI for uniform circular array (UCA) that offers reduced computational complexity compared to the original AMI. The complexity reduction is based on the proposed UCA-specific focusing matrix which eliminates the calculation of the Bessel function. The simulation comparison is done with the existing methods of iMUSIC, the Weighted Squared Test of Orthogonality of Projected Subspaces (WS-TOPS), and the original AMI. The experiment result under different scenarios shows that the proposed algorithm outperforms the original AMI method in terms of estimation accuracy and up to a 30% reduction in computation time. An advantage offered by this proposed method is the ability to implement wideband array processing on low-end microprocessors.

Background: The implementation of immunological biomarkers for radiotherapy (RT) individualization in breast cancer requires consideration of tumor-intrinsic factors. This study aimed to investigate whether the integration of histological grade, tumor-infiltrating lymphocytes (TILs), programmed cell death protein-1 (PD-1), and programmed death ligand-1 (PD-L1) can identify tumors with aggressive characteristics that can be downgraded regarding the need for RT., Methods: The SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median time of 15.2 years. Immunohistochemical analyses of TILs, PD-1, and PD-L1 were performed. An activated immune response was defined as stromal TILs ≥10% and PD-1 and/or PD-L1 expression in ≥1% of lymphocytes. Tumors were categorized as high-risk or low-risk using assessments of histological grade and proliferation as measured by gene expression. The risk of ipsilateral breast tumor recurrence (IBTR) and benefit of RT were then analyzed with 10 years follow-up based on the integration of immune activation and tumor-intrinsic risk group., Results: Among high-risk tumors, an activated immune infiltrate was associated with a reduced risk of IBTR (HR 0.34, 95% CI 0.16 to 0.73, p=0.006). The incidence of IBTR in this group was 12.1% (5.6-25.0) without RT and 4.4% (1.1-16.3) with RT. In contrast, the incidence of IBTR in the high-risk group without an activated immune infiltrate was 29.6% (21.4-40.2) without RT and 12.8% (6.6-23.9) with RT. Among low-risk tumors, no evidence of a favorable prognostic effect of an activated immune infiltrate was seen (HR 2.0, 95% CI 0.87 to 4.6, p=0.100)., Conclusions: Integrating histological grade and immunological biomarkers can identify tumors with aggressive characteristics but a low risk of IBTR despite a lack of RT boost and systemic therapy. Among high-risk tumors, the risk reduction of IBTR conferred by an activated immune infiltrate is comparable to treatment with RT. These findings may apply to cohorts dominated by estrogen receptor-positive tumors., Competing Interests: Competing interests: PK: Consulting or advisory role for AstraZeneca. Contract with PFS Genomics/Exact Sciences regarding genomic profiling. Co-inventor on patent applications. Contract with Prelude Dx. EH: Contract with PFS Genomics/Exact Sciences regarding genomic profiling. Co-inventor on patent applications. Contract with Prelude Dx. AST: Co-inventor on patent applications. Contract with Prelude Dx., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The local immune infiltrate's influence on tumor progression may be closely linked to tumor-intrinsic factors. The study aimed to investigate whether integrating immunologic and tumor-intrinsic factors can identify patients from a low-risk cohort who may be candidates for radiotherapy (RT) de-escalation., Experimental Design: The SweBCG91RT trial included 1,178 patients with stage I to IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median of 15.2 years. We trained two models designed to capture immunologic activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could further stratify tumors, allowing for identifying a subgroup where RT de-escalation is feasible, despite clinical indicators of a high risk of ipsilateral breast tumor recurrence (IBTR)., Results: The prognostic effect of the immunologic model could be predicted by the tumor-intrinsic model (Pinteraction = 0.01). By integrating measurements of the immunologic- and tumor-intrinsic models, patients who benefited from an active immune infiltrate could be identified. These patients benefited from standard RT (HR, 0.28; 95% CI, 0.09-0.85; P = 0.025) and had a 5.4% 10-year incidence of IBTR after irradiation despite high-risk genomic indicators and a low frequency of systemic therapy. In contrast, high-risk tumors without an immune infiltrate had a high 10-year incidence of IBTR despite RT treatment (19.5%; 95% CI, 12.2-30.3)., Conclusions: Integrating tumor-intrinsic and immunologic factors may identify immunogenic tumors in early-stage breast cancer populations dominated by ER-positive tumors. Patients who benefit from an activated immune infiltrate may be candidates for RT de-escalation., (©2023 The Authors; Published by the American Association for Cancer Research.)

Response to androgen receptor signaling inhibitors (ARSI) varies widely in metastatic castration resistant prostate cancer (mCRPC). To improve treatment guidance, biomarkers are needed. We use whole-genomics (WGS; n = 155) with matching whole-transcriptomics (WTS; n = 113) from biopsies of ARSI-treated mCRPC patients for unbiased discovery of biomarkers and development of machine learning-based prediction models. Tumor mutational burden (q < 0.001), structural variants (q < 0.05), tandem duplications (q < 0.05) and deletions (q < 0.05) are enriched in poor responders, coupled with distinct transcriptomic expression profiles. Validating various classification models predicting treatment duration with ARSI on our internal and external mCRPC cohort reveals two best-performing models, based on the combination of prior treatment information with either the four combined enriched genomic markers or with overall transcriptomic profiles. In conclusion, predictive models combining genomic, transcriptomic, and clinical data can predict response to ARSI in mCRPC patients and, with additional optimization and prospective validation, could improve treatment guidance., (© 2023. The Author(s).)

Purpose: Adjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach., Methods: We analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132)., Results: Patients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P = .81, and HR, 1.5 [0.14 to 16], P = .74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P = .0055, and HR, 0.25 [0.07 to 0.92], P = .038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed ( P = .066)., Conclusion: The novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.

Purpose: In patients who underwent virtual planning and guided flapless implant surgery for teeth missing in the anterior maxilla, we compared buccal bone loss between those treated with and without autogenous bone augmentation., Methods: Of 22 patients with teeth missing because of trauma or aplasia, 10 (18 implant sites) were reconstructed with buccally placed bone graft harvested from the mandibular ramus, and 12 were non-reconstructed (16 sites). Baseline cone-beam computed tomography allowed for implant planning using the NobelClinician® software and was performed again at 1 year after functional loading. The marginal bone level was assessed radiographically at post-implant baseline and at follow-up., Results: At follow-up, buccal bone loss differed significantly between groups at the central level of the implant (p = 0.0005) but not at the coronal level (p = 0.329). The mean marginal bone level change was 0.6 mm, with no significant between-group difference (p = 0.876). The actual implant position often deviated in the vertical or sagittal plane by an average of 0.3-0.6 mm from the planned position., Conclusion: Compared with non-reconstructed patients, reconstructed patients experienced significantly more buccal bone loss at the central level of implants. The groups did not differ at the coronal level or in marginal bone loss, possibly because of the more augmented bone at the central level among reconstructed patients. Differences between planned versus actual implant positions should be considered in situations of limited bone volume at the planned implant site., (© 2022. The Author(s).)

Background: Retention after orthodontic treatment is still a challenge and more evidence about post-treatment stability and patients' perceptions of different retention strategies is needed., Objectives: This trial compares removable vacuum-formed retainers (VFR) with bonded cuspid-to-cuspid retainers (CTC) after 5 years of retention., Trial Design: A single centre two-arm parallel-group randomized controlled trial., Methods: This trial included 104 adolescent patients, randomized into two groups (computer-generated), using sequentially numbered, opaque, and sealed envelopes. All patients were treated with fixed appliances in both jaws with and without tooth extractions. Patients in the intervention group received a VFR in the mandible (n = 52), and patients in the active comparator group received a CTC (n = 52). Both groups had a VFR in the maxilla. Dental casts at debond (T1), after 6 months (T2), after 18 months (T3), and after 5 years (T4) were digitized and analysed regarding Little's Irregularity Index (LII), overbite, overjet, arch length, and intercanine and intermolar width. The patients completed questionnaires at T1, T2, T3, and T4., Results: Post-treatment changes between T1 and T4 in both jaws were overall small. In the maxilla, LII increased significantly (median difference: 0.3 mm), equally in both groups. In the mandible, LII increased significantly in the group VFR/VFR (median difference: 0.6 mm) compared to group VFR/CTC (median difference: 0.1 mm). In both groups, overjet was stable, overbite increased, and arch lengths decreased continuously. Intercanine widths and intermolar width in the mandible remained stable, but intermolar width in the maxilla decreased significantly. No differences were found between groups. Regardless of retention strategy, patients were very satisfied with the treatment outcome and their retention appliances after 5 years., Limitations: It was not possible to perform blinded assessments of digital models at follow-up., Conclusions: Post-treatment changes in both jaws were small. Anterior alignment in the mandible was more stable with a bonded CTC retainer compared to a removable VFR after 5 years of retention. Patients were equally satisfied with fixed and removable retention appliances., Trial Registration: ClinicalTrials.gov (NCT03070444)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Orthodontic Society.)

Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution. Our analyses revealed a relationship between hormonal receptors status and proliferation levels resulting in the gain of somatic mutations and copy number. This in turn re-programmed the transcriptome and proteome towards a highly replicating and genomically unstable IBTRs, possibly enhanced by APOBEC3B. In order to investigate the origins of IBTRs, a second analysis that included primaries with no recurrence pinpointed proliferation and immune infiltration as predictive of IBTR. In conclusion, our study shows that breast tumors evolve into different IBTRs depending on hormonal status and proliferation and that immune cell infiltration and Ki-67 are significantly elevated in primary tumors that develop IBTR. These results can serve as a starting point to explore markers to predict IBTR formation and stratify patients for adjuvant therapy., (© 2023. The Author(s).)

One of the current main public health problems is the prevalence of obesity in children. Unhealthy lifestyle behaviors such as poor dietary habits, high sedentary screen time (SST), and low levels of physical activity (PA) have a strong tendency to track from childhood into adulthood. The aim of this manuscript is to assess the association between meeting or not meeting the PA and SST recommendations and the consumption of different food groups., Data were obtained from a sample of European adolescents from the multicenter cross-sectional HELENA study. In all, 1448 adolescents from 8 cities were included. PA was objectively measured by accelerometry and dietary intake by 24-hour dietary records. Adolescents were grouped according to PA and SST recommendations., In both sexes, intake of savory snacks was higher in those groups who did not meet any of the recommendations ( p  < 0.05). For males, those who met both recommendations were more likely to drink/eat milk, yogurt, and water ( p  < 0.05). Those not meeting recommendations were more likely to drink sugar-sweetened beverages ( p  < 0.05). For females, those not meeting recommendations were less likely to eat fruits and vegetables and more likely to have a higher intake of fats and oils ( p  < 0.05)., Those adolescents meeting PA and SST recommendations had a higher intake of healthy foods, like fruit and vegetables and dairy products. However, the negative relationship unhealthier food and SST is stronger in males independently of PA. More studies assessing the combined effect of both PA and SST regarding dietary habits in children and adolescents are needed.

Background: Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden., Aims: Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival., Material and Methods: We used data from the Swedish Head and Neck Cancer Register between 2008-2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions., Results: Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p  = .012), whereas overall survival did not differ (HR = 0.95, p  = .782)., Conclusions and Significance: Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.

Purpose: Although numerous biology-driven subtypes have been described previously in metastatic castration-resistant prostate cancer (mCRPC), unsupervised molecular subtyping based on gene expression has been less studied, especially using large cohorts. Thus, we sought to identify the intrinsic molecular subtypes of mCRPC and assess molecular and clinical correlates in the largest combined cohort of mCRPC samples with gene expression data available to date., Experimental Design: We combined and batch-effect corrected gene expression data from four mCRPC cohorts from the Fred Hutchinson Cancer Research Center (N = 157), a small-cell neuroendocrine (NE) prostate cancer (SCNC)-enriched cohort from Weill Cornell Medicine (N = 49), and cohorts from the Stand Up 2 Cancer/Prostate Cancer Foundation East Coast Dream Team (N = 266) and the West Coast Dream Team (N = 162)., Results: Hierarchical clustering of RNA-sequencing data from these 634 mCRPC samples identified two distinct adenocarcinoma subtypes, one of which (adeno-immune) was characterized by higher gene expression of immune pathways, higher CIBERSORTx immune scores, diminished ASI benefit, and non-lymph node metastasis tropism compared with an adeno-classic subtype. We also identified two distinct subtypes with enrichment for an NE phenotype, including an NE-liver subgroup characterized by liver metastasis tropism, PTEN loss, and APC and SPOP mutations compared with an NE-classic subgroup., Conclusions: Our results emphasize the heterogeneity of mCRPC beyond currently accepted molecular phenotypes, and suggest that future studies should consider incorporating transcriptome-wide profiling to better understand how these differences impact treatment responses and outcomes., (©2022 American Association for Cancer Research.)