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“Coconut atrium” or complete dystrophic left atrial wall calcification is rare and occurs almost exclusively in the middle-aged and the elderly, often following chronic conditions such as rheumatic heart disease, end-stage renal disease and tuberculosis. Hyperparathyroidism, lipid storage disease and use of xenografts are known causes of incomplete intra-cardiac dystrophic calcification in older children. The present report describes a rare case of cardiac calcification demonstrated by Trans-thoracic 2-D Echocardiography in a two-year old Indian boy who presented at a private hospital in Hyderabad, India with breathlessness. Unfortunately, his parents declined further extensive investigations and treatment, but this case was instructive due to the rarity of complete dystrophic left atrial wall calcification, the exclusion of the common known aetiologies and the extremely young age of the patient.

Paleontological site monitoring in National Park Service units can deviate from the recommended cyclical protocol because of unique challenges each unit may face. These challenges include staffing limitations or turnover, difficulty accessing remote sites, and high work volume. Insufficient monitoring of fossil sites might result in the loss of knowledge or data due to degradation or loss of resources. New monitoring protocols were tested at the Copper Canyon ichnofossil locality in Death Valley National Park (DEVA) to address the highlighted management challenges. The monitoring protocol presented here was designed to be streamlined and simple, to be utilized by paleontologists and non-paleontologists alike, and to overcome challenges, thereby, improving undermanaged sites. The monitoring protocol included baseline evaluation and imaging of the 78 track localities within Copper Canyon. Each site was assigned a sensitivity status; identifying its recommended monitoring cyclicity of high, moderate, or low. It was determined that monitors could take as few as two field trips to Copper Canyon per year and monitor between five to ten sites each trip. This could be accomplished by DEVA’s resources management, interpretation, or law enforcement staff, or a volunteer. Monitors use a portable device, pre-loaded with site-specific paleontological data, to interactively record changes at a site and complete a short seven question form with their observations. Data are stored on the device and later transferred to a central paleontological database. Through this protocol, DEVA can utilize a community-based approach to better manage fossil resources, one which could be replicated by other National Park Service units that grapple with similar monitoring challenges.

Indonesian has become the official language of the UN. Many BIPA students want to learn Indonesian online. However, online learning creates obstacles such as time differences between teachers and BIPA students, internet connections, and providing less than optimal feedback. This research aims to develop m-learning with automatic feedback for BIPA level 2 learners. This research uses a 4D development model: define, design, develop and deploy. This study's instrument is a questionnaire distributed to 2 validators and 18 BIPA learners. The results of this study are m-learning products that minimize internet connections; once installed, students only need to be connected to the internet when working on questions. In addition, m-learning is also equipped with automatic feedback that appears immediately after students answer questions. The results of the product trial show that students can use m-learning to learn anytime and anywhere, including in areas with minimal internet access. Automatic feedback in m-learning also helps students learn independently because they do not need to wait for feedback from teachers. The automatic feedback in M-learning is only for listening and reading questions while speaking and writing questions are still in the form of answer keywords or assessment rubrics that the teacher must correct. Based on expert validation and product trials with an average score of 88.8, we conclude that the development of m-learning is suitable for BIPA level 2 students.

Abstract Aims Chronic kidney disease (CKD) is a well‐established risk factor for heart failure (HF); however, patients with an estimated glomerular filtration rate (eGFR) eGFR ≥ 30 and eGFR eGFR ≥ 30 and 72.2% for patients with eGFR eGFR ≥ 30 and eGFR 30 (4 year incidence of kidney outcome as the first event was 5.0% for eGFR ≥ 60, 4.8% for 60 > eGFR ≥ 30 and 20.1% for eGFR

Aim: To compare the Subfoveal Choroidal Thickness (SFCT) measured by Enhanced Depth Imaging (EDI) technique of Spectral Domain Optical Coherence Tomography (SD-OCT) in healthy pregnant and preeclamptic women. Methods: Our study was cross-sectional hospital-based study in which healthy pregnant women and women having preeclampsia were selected from Obstetrics and Gynecology department and enrolled in it. The guidelines of the American College of Obstetricians and Gynecologists were used to diagnose the cases of preeclampsia. The study included 100 women (200 eyes) which were grouped into 50 healthy pregnant women (group 1), i.e., n = 100 eyes and 50 preeclamptic women (group 2), i.e., n = 100 eyes. SFCT was measured using the EDI technique of SD-OCT and data were entered in a Microsoft Excel sheet. Statistical analysis was done using Epi Info. Software version 7.2.1.0 (Atlanta, Georgia, US) and the results of both the groups were compared. Results: The mean SFCT in both the eyes of the healthy pregnant group and the preeclamptic group was 318.12 ± 37.12 µm and 209.04 ± 26.73 µm, respectively, with a P-value 0.001 showing a statistically significant difference between both the groups. Conclusion: The SFCT is significantly decreased in preeclamptic pregnant women than in healthy pregnant women.

Abstract Rapidly waning immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires continued global access to affordable vaccines. Globally, inactivated SARS-CoV-2 vaccines have been widely used during the SARS-CoV-2 pandemic. In this proof-of-concept study we adapted an original-D614G SARS-CoV-2 virus to Vero cell culture as a strategy to enhance inactivated vaccine manufacturing productivity. A passage 60 (P60) virus showed enhanced fitness and 50-fold increased virus yield in a bioreactor compared to the original-D614G virus. It further remained susceptible to neutralization by plasma from SARS-CoV-2 vaccinated and convalescent individuals, suggesting exposure of relevant epitopes. Monovalent inactivated P60 and bivalent inactivated P60/omicron BA.1 vaccines induced neutralizing responses against original-D614G and BA.1 viruses in mice and hamsters, demonstrating that the P60 virus is a suitable vaccine antigen. Antibodies further cross-neutralized delta and BA.5 viruses. Importantly, the inactivated P60 vaccine protected hamsters against disease upon challenge with original-D614G or BA.1 virus, with minimal lung pathology and lower virus loads in the upper and lower airways. Antigenicity of the P60 virus was thus retained compared to the original virus despite the acquisition of cell culture adaptive mutations. Consequently, cell culture adaptation may be a useful approach to increase yields in inactivated vaccine antigen production.

Abstract Background Enamelin is an enamel matrix protein that plays an essential role in the formation of enamel, the most mineralized tissue in the human body. Previous studies using animal models and proteins from natural sources point to a key role of enamelin in promoting mineralization events during enamel formation. However, natural sources of enamelin are scarce and with the current study we therefore aimed to establish a simple microbial production method for recombinant human enamelin to support its use as a mineralization agent. Results In the study the 32 kDa fragment of human enamelin was successfully expressed in Escherichia coli and could be obtained using immobilized metal ion affinity chromatography purification (IMAC), dialysis, and lyophilization. This workflow resulted in a yield of approximately 10 mg enamelin per liter culture. Optimal conditions for IMAC purification were obtained using Ni2+ as the metal ion, and when including 30 mM imidazole during binding and washing steps. Furthermore, in vitro mineralization assays demonstrated that the recombinant enamelin could promote calcium phosphate mineralization at a concentration of 0.5 mg/ml. Conclusions These findings address the scarcity of enamelin by facilitating its accessibility for further investigations into the mechanism of enamel formation and open new avenues for developing enamel-inspired mineralized biomaterials.

OBJECTIVES: The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure–response relationship for asbestosis in a general working population setting. We examined the exposure–response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. METHODS: We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure–response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. RESULTS: The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15– -1.22]. The IRR was 1.94 (95% CI 1.53–2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. CONCLUSIONS: This study found exposure–response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.

Summary: Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer (LARC) increases pathologic complete response (pCR) rate and reduces the risk of systemic recurrences over chemoradiotherapy (CRT) in randomised trials, e.g., the RAPIDO trial. A modified RAPIDO schedule was prospectively explored in Sweden to evaluate TNT in routine health care before the RAPIDO results were published. Methods: Between July 2016 and June 2020, 273 patients with high-risk LARC (clinical tumour stage cT4, clinical nodal stage cN2, extramural vascular invasion, involved mesorectal fascia or enlarged lateral lymph nodes) were treated in a prospective observational cohort study at 16 hospitals (LARCT-US). Another 189 patients at 18 (including the 16) hospitals were similarly treated (ad modum LARCT-US, AdmL) during the same period. Inclusion and exclusion criteria were identical to the RAPIDO trial. Patients received short-course radiotherapy (5 × 5 Gy for 5 days) followed by four cycles of CAPOX or six FOLFOX-6, followed by total mesorectal excision or, if clinical complete response (cCR), inclusion into a watch-and-wait (W&W) study. The primary endpoint was complete response (CR), i.e., the sum of pCR in specimens and cCR exceeding one year in W&W patients. Safety was assessed in all patients. Findings: Compared to the RAPIDO trial, patients were older, and tumours more advanced. Median follow-up was 4.8 years (IQR 4.2–5.2). In LARCT-US all patients received radiotherapy and 268 (98%) started chemotherapy whereas in AdmL all patients received radiotherapy and chemotherapy. In LARCT-US 34 patients had pCR and 31 sustained cCR resulting in a CR-rate of 24% (95% CI 20–28). In AdmL, results were similar (23%, 95% CI 17–30). Locoregional recurrences were 6% (95% CI 4–10) and 5% (95% CI 2–9), respectively, both at 3 years and at last follow-up. Neurotoxicity, recorded in LARCT-US, was lower than in RAPIDO (EORTC-QLQ-CIPN20 tingling toes or feet mean score 24 (SD 31) vs 43 (SD 37)). One treatment-associated death occurred. Interpretation: Despite older patients and more advanced tumours, results similar to the RAPIDO trial were obtained. Hence, two chemotherapy cycles less do not compromise the results maintaining a high CR-rate. This TNT schedule resulted in favourable outcomes in a nation-wide real-life situation. Funding: Swedish Cancer Society.

Additive manufacturing (AM) of ceramic bone implants from tricalcium phosphate (TCP) offers several benefits for bone regeneration and defect treatment. TCP scaffolds, e.g. featuring lattice or gyroid geometries, can effectively induce bone ingrowth and integration, showing a high potential in the treatment of large bone defects, e.g. as filler material for large bone defects. A major advantage of TCP is its osteoconductivity making it an effective choice for a broad range of orthopedic and dental applications. In addition, AM allows for the possibility to create precise, patient-specific implants with controllable mechanical properties. Those properties can be controlled by the implants' microstructure, e.g. in relation to bulk density and internal porosity. In this contribution, eleven resorbable bone implants were produced from β-tricalcium phosphate (β-TCP) in order to quantify the internal porosity in three dimensions using microcomputed tomography (μ CT). All components were manufactured using an extrusion-based process and scanned using an industrial μCT system at a voxel size of 10 μm. Two samples were physically prepared to allow a high-resolution μCT analysis at a voxel size of 1 μm. Results show that post-processed image data enables the non-destructive inspection of highly complex ceramic AM implants. Using μCT we were able to quantify internal porosity in β-TCP bone implant and quantify the geometry and distribution of wall thicknesses in the gyroid geometry. However, a detailed microstructural analysis is only possible using high-resolution μCT volume data, e.g. in relation to internal porosity. The findings emphasize that ceramic AM is able to produce complex components. However, NDT using μCT is crucial in the development of new materials and geometries. μCT provides high-resolution insights into the internal and external structure of ceramic AM components. It plays a critical role in detecting internal features, including small-scale porosity and delamination which are crucial for the integrity and functionality of medical implants. Moreover, μCT provides volumetric data that supports the design and manufacturing process at various stages, enabling an iterative approach of continuous improvement in mechanical performance and osseointegration.

Maternal vitamin D levels during pregnancy may be important for reproductive health in male offspring by regulating cell proliferation and differentiation during development. We conducted a follow-up study of 827 young men from the Fetal Programming of Semen Quality (FEPOS) cohort, nested in the Danish National Birth Cohort to investigate if maternal vitamin D levels were associated with measures of reproductive health in adult sons. These included semen characteristics, testes volume, and reproductive hormone levels and were analysed according to maternal vitamin D (25(OH)D3) levels during pregnancy. In addition, an instrumental variable analysis using seasonality in sun exposure as an instrument for maternal vitamin D levels was conducted. We found that sons of mothers with vitamin D levels  75 nmol/L. Continuous models, spline plots and an instrumental variable analysis supported these findings. Low maternal vitamin D levels were associated with lower testes volume and lower total sperm count with indications of dose-dependency. Maternal vitamin D level above 75 nmol/L during pregnancy may be beneficial for testes function in adult sons.

Dans notre souci de faire prévaloir l’importance du capital humain dans la sauvegarde des acquis d’une banque, la présente recherche se voudrait d’être une réponse par rapport aux préalables qu’il importe de retenir pour quiconque tiendrait à assurer la stabilité des banques de dépôts au plan interne. N’est-ce pas qu’il existe une interdépendance et une forte corrélation entre les dispositifs préventifs internes des risques bancaires, qui se manifestent souvent sous l’effet boule de neige et qui prend racines à partir des erreurs que commettent les agents préposés ? Ce qui ne peut manquer de susciter d’autres risques de porter atteinte, notamment au remboursement de crédits, à la liquidité, à la solvabilité, à la réputation,… De là tout l’intérêt d’endiguer voire de résorber tout hasard dangereux susceptible d’être le catalyseur des autres risques.

L’article que voici est destiné à faire montre de l’importance de la fiscalité efficace dans la mobilisation des moyens dont ont besoin les pouvoirs publics pour leur fonctionnement à travers la décentralisation par ordre de prérogatives d’entités et des administrations commises aux différents prélèvements fiscaux et non-fiscaux. Pour y parvenir, il est exposé la nécessité de la mise en œuvre de certains préalables notamment l’innovation des méthodes dont la radiation tous azimuts des cas éventuels de fraude et évasion fiscales, l’instauration d’un système autonome digitalisé partant de l’assiette, du recouvrement jusqu’au traitement des cas litigieux d’impôts en tenant compte des réalités et du contexte congolais.

OBJECTIVES: This study aimed to estimate the validity of self-reported information on ever-night shift work among women with and without breast cancer and illustrate the consequences for breast cancer risk estimates. METHODS: During 2015–2016, 225 women diagnosed with breast cancer and 1800 matched controls without breast cancer employed within the Danish hospital regions during 2007–2016 participated in a questionnaire-based survey. Their reported night shift work status was linked with objective payroll register day-by-day working hour data from the Danish Working Hour Database and the Danish Cancer Registry. For the breast cancer patients and their matched controls, we estimated sensitivity and specificity for ever-working night shifts using the payroll data as the gold standard. We also used quantitative bias analysis to estimate the impact on relative risk estimates for a hypothetical population. RESULTS: For breast cancer patients, we observed a sensitivity of ever-night shifts of 86.2% and a specificity of never-night shifts of 82.6%. For controls, the sensitivity was 80.6% and the specificity 83.7%. Odds ratio for breast cancer in a hypothetical population decreased from 1.12 [95% confidence interval (CI) 1.03–1.21] to 1.05 (95% CI 0.95–1.16) when corrected by the sensitivity and specificity estimates. CONCLUSION: This study shows that female breast cancer patients had slightly better recall of previous night shift work than controls. Additionally, both breast cancer patients and controls recalled previous never-night shift work with low specificity. The net effect of this misclassification is a small over-estimation of the relative breast cancer risk due to night shift work.

Abstract Background The caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons’ semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality. Methods This study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs). Results Among included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): − 7.5% (− 14.1% to − 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally. Conclusions This large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.

BackgroundAcute Kidney Injury (AKI) incidence has continued to rise and is recognized as a major risk factor for kidney disease progression and cardiovascular complications. Early recognition of factors associated with post-AKI complications is fundamental to stratifying patients that could benefit from closer follow-up and management after an episode of AKI. Recent studies have shown that proteinuria is a prevalent sequela after AKI and a strong predictor of complications post-AKI. This study aims to evaluate the frequency and timing of the development of de-novo proteinuria after an AKI episode in patients with known kidney function and no prior history of proteinuria.MethodsWe retrospectively analyzed data from adult AKI patients with pre- and post-kidney function information between Jan 2014 and March 2019. The presence of proteinuria determined before and after index AKI encounter was based on ICD-10 code and/or urine dipstick and UPCR during the follow-up period.ResultsOf 9697 admissions with AKI diagnoses between Jan 2014 and March 2019, 2120 eligible patients with at least one assessment of Scr and proteinuria before AKI index admission were included in the analysis. The median age was 64 (IQR 54-75) years, and 57% were male. 58% (n-1712) patients had stage 1 AKI, 19% (n = 567) stage 2 AKI, and 22% (n = 650) developed stage 3 AKI. De novo proteinúria was found in 62% (n = 472) of patients and was already present by 90 days post-AKI in 59% (209/354). After adjusting for age and comorbidities, severe AKI (stage 2/3 AKI) and diabetes, were independently associated with increased risk for De novo proteinuria.ConclusionSevere AKI is an independent risk factor for subsequent de novo proteinuria post-hospitalization. Further prospective studies are needed to determine whether strategies to detect AKI patients at risk of proteinuria and early therapeutics to modify proteinuria can delay the progression of kidney disease.

Abstract Over the last 10 years, the spawning population of invasive pink salmon (Oncorhynchus gorbuscha) has increased in the river systems in northern Norway to a level that is causing concern about their impact on endemic fauna and ecosystem processes. The scale of transfer of pink salmon carcasses into the terrestrial ecosystem is likely to be a key determinant of terrestrial impact. Bears (Ursus sp.) are responsible for most such transfers in North America but are rare in Norway. The white‐tailed eagle (Haliaeetus albicilla) is common however, and a candidate to be a main cause of such transfers. To evaluate this hypothesis, data on the abundance of white‐tailed eagles and pink salmon were collected along the river Skallelv in northern Norway in 2021, a year the pink salmon spawned in the river, and in 2022, a year no pink salmon spawned in the river. The abundance of white‐tailed eagles along the river was much higher the year pink salmon spawned in the river. Furthermore, white‐tailed eagles were observed aggregating and catching pink salmon where and when pink salmon were present at the spawning and post‐spawning stages. Based on our observations, we suggest that the white‐tailed eagle is the main species involved in the transport of pink salmon from the river into the riparian zone in northern Norway and that other scavengers, in particular the red fox (Vulpes vulpes) and common raven (Corvus corax), play an important role in transporting pink salmon carcasses from the riparian zone to the wider terrestrial ecosystem.

Perkembangan fasilitas teknologi mempermudah manusia untuk memanfaatkan berbagai sarana platform digital yang ada termasuk platform User Generated Conten (UCG). Namun, disamping berbagai dampak positif yang ada ternyata juga membawa dampak negatif berupa maraknya pelanggaran hak cipta karya seni musik dan lagu. Tidak adanya pengaturan hukum yang jelas dan tegas bagi perlindungan karya seni dan lagu yang dimanfaatkan melalui sarana platform digital berbasis UGC ini, hal ini tentu bisa menimbulkan kerumitan dalam penegakan hukum bagi pihak-pihak yang tidak bertanggung jawab atas pemanfaatan karya seni dan lagu. Adapun fokus permasalahan yang dikaji dalam penelitian ini adalah “bagaimana pengaturan perlindungan hak cipta karya musik dan lagu di dalam digital services platform berdasarkan Undang-Undang Hak Cipta (UUHC) dan bagaimana perlindungan hak cipta karya seni musik dan lagu di dalam digital services platform berbasis UGC berdasarkan UUHC”. Metode penelitian yang digunakan adalah yuridis normatif yang sumber datanya berbasis pada data sekunder berupa bahan hukum primer dan sekunder. Hasil penelitian menunjukkan bahwa di dalam UUHC masih terdapat kokosongan norma yang mengatur mengenai perlindungan atas pemanfaatan layanan digital platform yang berbasis UGC termasuk pasal-pasal yang mengatur mengenai penegakan hukumnya. Oleh karena itu, penting bagi pemerintah untuk dapat melakukan revisi dan evaluasi terhadap beberap pasal yang relevan di dalam UUHC khususnya terhadap pasal 10 dan pasal 114. Hal ini penting guna memberikan perlindungan hukum dan kepastian hukum terhadap hak ekslusif pencipta dan pemegang hak cipta.

Abstract Brown seaweeds have a rich bioactive content known to modulate biological processes, including the mucosal immune response and microbiota function, and may therefore have the potential to control enteric pathogens. Here, we tested if dietary seaweed (Saccharina latissima) supplementation could modulate pig gut health with a specific focus on parasitic helminth burdens, gut microbiota composition, and host immune response during a five week feeding period in pigs co-infected with the helminths Ascaris suum and Oesophagostomum dentatum. We found that inclusion of fermented S. latissima (Fer-SL) at 8% of the diet increased gut microbiota α-diversity with higher relative abundances of Firmicutes, Tenericutes, Verrucomicrobia, Spirochaetes and Elusimicrobia, and lower abundance of Prevotella copri. In the absence of helminth infection, transcription of immune-related genes in the intestine was only moderately influenced by dietary seaweed. However, Fer-SL modulated the transcriptional response to infection in a site-specific manner in the gut, with an attenuation of infection-induced gene expression in the jejunum and an amplification of gene expression in the colon. Effects on systemic immune parameters (e.g. blood lymphocyte populations) were limited, indicating the effects of Fer-SL were mainly localized to the intestinal tissues. Despite previously documented in vitro anti-parasitic activity against pig helminths, Fer-SL inclusion did not significantly affect parasite egg excretion or worm establishment. Collectively, our results show that although Fer-SL inclusion did not reduce parasite burdens, it may modify the gut environment during enteric parasite infection, which encourages continued investigations into the use of seaweeds or related products as novel tools to improve gut health.

Background and purpose: Soft tissue defects after total knee arthroplasties (TKA) represent a major orthopedic challenge with amputation as a feared outcome. Microvascular free flap coverage (FFC) can increase limb salvage rates, but complications related to the procedure are yet to be explored further. We aimed to review a single-center experience with FFC for soft tissue defects related to revision total knee arthroplasty. Methods: Through a retrospective chart review from 2006 to 2021, we identified all patients who had FFC of a knee with an existing TKA. Typically, patients underwent 2-stage revision arthroplasty. To identify areas of intervention, we divided the entire regimen into 2 phases divided by the free flap surgery (pre- and post-free flap). Results: We identified 18 patients with a median age at free flap surgery of 69 years (range 39–85), who were followed for a median of 5.1 years (range 2 months to 10.6 years). The median duration from primary TKA to their final operation was 17.5 months (range 19 days to 7 years). Patients underwent a mean of 7.6 surgical procedures on their knee with 3.6 orthopedic revisions prior to the FFC and 0.6 after. Soft tissue coverage was achieved in all patients and no patients underwent amputation. One-third of patients experienced early complications at recipient site after free flap surgery. There were no donor site complications. Conclusion: Microvascular FFC of complex soft tissue defects after revision total knee arthroplasty proved achievable in all patients with successful limb salvage in all patients.

Introduction The incidence of type 2 diabetes is increasing globally. Recent research suggests that loneliness could be a potential risk factor for the development of type 2 diabetes. We aimed to investigate the association between loneliness and type 2 diabetes and the modifying effect of mental disorders.Research design and methods We conducted a prospective study including 465 290 adults (aged ≥16 years) who participated in either the Danish Health and Morbidity Survey or the Danish National Health Survey between 2000 and 2017. Loneliness was based on self-report, while type 2 diabetes was measured using an algorithm combining several health registers including type 2 diabetes patients treated both within the hospital sector and general practice. Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs).Results During a mean follow-up time of 6.3 years, 13 771 individuals (3%) developed type 2 diabetes. Feeling lonely once in a while was associated with a 14% increased risk of type 2 diabetes (95% CI 1.09 to 1.20), while feeling lonely often was associated with a 24% increased risk (95% CI 1.14 to 1.34), independent of sociodemographic factors and body mass index. The association was stronger among individuals without a mental disorder (HR 1.21, 95% CI 1.10 to 1.34 among those feeling lonely often) compared with those with a mental disorder (HR 1.07, 95% CI 0.93 to 1.23).Conclusions Loneliness independently increased the risk of type 2 diabetes. The effect was more pronounced in individuals without a mental disorder, as having a mental disorder itself likely increases the risk of type 2 diabetes. These findings emphasize the importance of addressing loneliness as a modifiable risk factor in preventing type 2 diabetes.

ABSTRACTThis study assessed the accuracy of high-risk human papillomavirus testing of BD Onclarity HPV (Onclarity) assay on vaginal self-collected FLOQSwab versus cervical samples to ensure similar accuracy to detect cervical intraepithelial neoplasia. Testing was performed on two automated platforms, BD Viper LT and BD COR, to evaluate the effect of machine and using two vaginal self-samples to analyze the influence of collection, transport, and freezing-unfreezing on the results. A cervical sample and two self-samples were collected from 300 women. The first collected vaginal and the cervical sample were tested on BD Viper LT, and the second swab was frozen and subsequently tested on both automated systems. Test results on vaginal and cervical specimens were considered the index and comparator, respectively; colposcopy and histology were reference standards. Relative sensitivity for ≥CIN2 on vaginal samples analyzed versus the cervical sample was 1.01 (0.97–1.06), 1.01 (0.97–1.06), and 1.00 (0.95–1.05), for the first, second self-collected sample tested on BD VIPER LT, and second self-collected sample tested on BD COR, respectively. Relative specificity was 0.83 (0.73–0.94), 0.76 (0.67–0.87), and 0.82 (0.73–0.92) using the three different workflows. Cut-off optimization for human papillomavirus (HPV) positivity defined at Ct ≤38.3 for HPV16, ≤ 34.2 for HPV18, and ≤31.5 for all other types showed an increased relative specificity with similar sensitivity. No significant difference was observed between self-samples tested with the two platforms and between first- and second-collected swabs. Onclarity assay on FLOQSwab using both platforms showed similar sensitivity but lower specificity to detect ≥CIN2 compared to cervical samples. By cut-off optimization, non-inferior specificity could be reached.IMPORTANCEHuman papillomavirus (HPV) testing on self-collected vaginal samples has been shown to improve women’s participation to cervical cancer screening programs, particularly in regions with limited access to health care. Nevertheless, the introduction of self-sampling in cervical cancer screening programs requires prior clinical validation of the HPV assay in combination with a self-sample collection device, including also the laboratory workflow and automation required for high-throughput testing in screening. In this study, the performance of BD Onclarity HPV on FLOQSwab-collected vaginal self-samples has been compared to clinician-taken liquid-based cytology samples, to detect high-grade cervical intraepithelial neoplasia using two high-throughput platforms, BD Viper LT and BD COR. The study findings have shown a similar performance of BD Onclarity on testing self-collected samples, confirming the validation of the proposed pre-analytical and analytical protocols for their use in cervical cancer screening programs based on self-collected vaginal samples.

Abstract The biogas produced through anaerobic digestion (AD) of renewable feedstocks is one of the promising alternatives to replace fossil-derived energy. Even though lignocellulosic biomass is the most abundant biomass on earth, only a small fraction is being used towards resources recovery, leaving a great potential unexploited. In this study, the combination of state-of-art genomic techniques and engineered systems were used to further advance the knowledge on biogas production from lignocellulosic-rich residues and the microbiome involved in the anaerobic digestion hereof. A long-term adapted anaerobic microbiome capable of degrading wheat straw as the sole substrate was investigated using protein stable isotope probing (protein-SIP). The results indicated that a diverse microbial community, primarily composed of Firmicutes and Methanogens, played crucial roles in cellulose degradation and methane production. Notably, Defluviitoga tunisiensis, Syntrophothermus lipocalidus, and Pelobacter carbinolicus were identified as direct metabolizers of cellulose, while Dehalobacterium assimilated labelled carbon through cross-feeding. This study provides direct evidence of primary cellulose degraders and sheds light on their genomic composition. By harnessing the potential of lignocellulosic biomass and understanding the microbial communities involved, we can promote sustainable biogas production, contributing to energy security and environmental preservation.

Abstract Background Vaginal CO2 laser therapy is a new treatment option for genitourinary syndrome of menopause. Its potential is particularly interesting in breast cancer survivors, where existing treatment options often are insufficient as hormonal treatment is problematic in these women. The objective of this study is to investigate the effectiveness of vaginal laser treatment for alleviation of genitourinary syndrome of menopause in breast cancer survivors treated with adjuvant endocrine therapy. The secondary objective is to explore the importance of repeated vaginal laser treatment and the long-term effects in this patient population. Methods VagLaser consist of three sub-studies; a dose response study, a randomized, participant blinded, placebo-controlled study and a follow-up study. All studies include breast cancer survivors in adjuvant endocrine therapy, and are conducted at the Department of Obstetrics and Gynecology, Randers Regional Hospital, Denmark. The first participant was recruited on 16th of February 2023. Primary outcome is vaginal dryness. Secondary subjective outcomes are vaginal pain, itching, soreness, urinary symptoms and sexual function. Secondary objective outcomes are change in vaginal histology (punch biopsy), change in vaginal and urine microbiota, and change in vaginal pH. Discussion More randomized controlled trials, with longer follow-up to explore the optimal treatment regimen and the number of repeat vaginal laser treatments for alleviation the symptoms of genitourinary syndrome of menopause in breast cancer survivors treated with endocrine adjuvant therapy, are needed. This study will be the first to investigate change in vaginal and urine microbiota during vaginal laser therapy in breast cancer survivors. Trial registration ClinicalTrials.gov: NCT06007027 (registered 22 August, 2023). Protocol version: Version 1, Date 13.11.2023.

Abstract Background Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models—each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types. Methods We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies. Results We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92–96) for orthotopic and 95% (93–96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33–72) and heterotopic 82% (73–89)] and finally GEM revealed a TTR of 34% (26–43). Conclusion This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages). Systematic review registration: PROSPERO-ID CRD42022308833.

OBJECTIVES: This study investigates the associations between the Danish version of a job exposure matrix for COVID-19 (COVID-19-JEM) and Danish register-based SARS-CoV-2 infection information across three waves of the pandemic. The COVID-19-JEM consists of four dimensions on transmission: two on mitigation measures, and two on precarious work characteristics. METHODS: The study comprised 2 021 309 persons from the Danish working population between 26 February 2020 and 15 December 2021. Logistic regression models were applied to assess the associations between the JEM dimensions and overall score and SARS-CoV-2 infection across three infection waves, with peaks in March–April 2020, December–January 2021, and February–March 2022. Sex, age, household income, country of birth, wave, residential region and during wave 3 vaccination status were accounted for. RESULTS: Higher risk scores within the transmission and mitigation dimensions and the overall JEM score resulted in higher odds ratios (OR) of a SARS-CoV-2 infection. OR attenuated across the three waves with ranges of 1.08–5.09 in wave 1, 1.06–1.60 in wave 2, and 1.05–1.45 in those not (fully) vaccinated in wave 3. In wave 3, no associations were found for those fully vaccinated. In all waves, the two precarious work dimensions showed weaker or inversed associations. CONCLUSIONS: The COVID-19-JEM is a promising tool for assessing occupational exposure to SARS-CoV-2 and other airborne infectious agents that mainly spread between people who are in close contact with each other. However, its usefulness depends on applied restrictions and the vaccination status in the population of interest.

Abstract The risks of post trauma complications are regulated by the injury, comorbidities, and the clinical trajectories, yet prediction models are often limited to single time-point data. We hypothesize that deep learning prediction models can be used for risk prediction using additive data after trauma using a sliding windows approach. Using the American College of Surgeons Trauma Quality Improvement Program (ACS TQIP) database, we developed three deep neural network models, for sliding-windows risk prediction. Output variables included early- and late mortality and any of 17 complications. As patients moved through the treatment trajectories, performance metrics increased. Models predicted early- and late mortality with ROC AUCs ranging from 0.980 to 0.994 and 0.910 to 0.972, respectively. For the remaining 17 complications, the mean performance ranged from 0.829 to 0.912. In summary, the deep neural networks achieved excellent performance in the sliding windows risk stratification of trauma patients.

IntroductionAccurately predicting patient outcomes is crucial for improving healthcare delivery, but large-scale risk prediction models are often developed and tested on specific datasets where clinical parameters and outcomes may not fully reflect local clinical settings. Where this is the case, whether to opt for de-novo training of prediction models on local datasets, direct porting of externally trained models, or a transfer learning approach is not well studied, and constitutes the focus of this study. Using the clinical challenge of predicting mortality and hospital length of stay on a Danish trauma dataset, we hypothesized that a transfer learning approach of models trained on large external datasets would provide optimal prediction results compared to de-novo training on sparse but local datasets or directly porting externally trained models.MethodsUsing an external dataset of trauma patients from the US Trauma Quality Improvement Program (TQIP) and a local dataset aggregated from the Danish Trauma Database (DTD) enriched with Electronic Health Record data, we tested a range of model-level approaches focused on predicting trauma mortality and hospital length of stay on DTD data. Modeling approaches included de-novo training of models on DTD data, direct porting of models trained on TQIP data to the DTD, and a transfer learning approach by training a model on TQIP data with subsequent transfer and retraining on DTD data. Furthermore, data-level approaches, including mixed dataset training and methods countering imbalanced outcomes (e.g., low mortality rates), were also tested.ResultsUsing a neural network trained on a mixed dataset consisting of a subset of TQIP and DTD, with class weighting and transfer learning (retraining on DTD), we achieved excellent results in predicting mortality, with a ROC-AUC of 0.988 and an F2-score of 0.866. The best-performing models for predicting long-term hospitalization were trained only on local data, achieving an ROC-AUC of 0.890 and an F1-score of 0.897, although only marginally better than alternative approaches.ConclusionOur results suggest that when assessing the optimal modeling approach, it is important to have domain knowledge of how incidence rates and workflows compare between hospital systems and datasets where models are trained. Including data from other health-care systems is particularly beneficial when outcomes are suffering from class imbalance and low incidence. Scenarios where outcomes are not directly comparable are best addressed through either de-novo local training or a transfer learning approach.