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Abstract The hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signaling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients revealed an active JAK-STAT1 signaling signature along with upregulation of antigen presentation and downregulation of key components of the EGFR pathway. Our findings offer molecular insights and highlight a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.

Abstract Apnoeic oxygenation has experienced a resurgence in interest in critical care and perioperative medicine. However, its effect on cerebral oxygenation and factors influencing it, have not yet been investigated in detail. By using near-infrared spectroscopy, we intended to provide further evidence for the safety of apnoeic oxygenation and to increase our understanding of the association between cerebral perfusion, haemodynamic, respiratory and demographic factors. In this secondary analysis of a prospective randomized controlled noninferiority trial, we recruited 125 patients, who underwent surgery under general anaesthesia with neuromuscular blockade. Arterial blood samples were taken every 2 min for a total of 15 min under apnoeic oxygenation with 100% oxygen. Near-infrared spectroscopy and cardiac output were continuously measured. Statistical analysis was performed using uni- and multivariable statistics. Ninety-one complete data sets were analysed. In six patients the SpO2 fell below 92% (predefined study termination criterion). The significant average increase of cerebral oxygenation was 0.5%/min and 2.1 mmHg/min for the arterial pressure of carbon dioxide (paCO2). The median cardiac output increased significantly from 5.0 l/min (IQR 4.5–6.0) to 6.5 l/min (IQR 5.7–7.5). The most significant effect on cerebral oxygenation was exhibited by the variable paCO2 and non-specific patient factors, followed by cardiac output and paO2. Apnoeic oxygenation proves to have a high safety profile while significantly increasing cerebral oxygenation, paCO2 and cardiac output. In reverse, NIRS might act as a reliable clinical surrogate of paCO2 and cardiac output during stable arterial oxygenation.

OBJECTIVES: While the overall incidence and prevalence of diaphragmatic paralysis are unknown due to a wide variety of underlying causes, symptomatic patients experience a marked decline in their quality of life. The goal of this study was to measure the impact of diaphragm plication surgery on the quality of life in patients who were diagnosed with diaphragmatic paralysis. METHODS: A retrospective review of the medical records of 46 patients who underwent diaphragmatic plication surgery was performed. The review included patients who experienced unilateral and bilateral diaphragmatic paralysis. Patients who underwent repeat diaphragm plication surgery were also included in the study. Patients from the retrospective cohort were then contacted by telephone to answer the Dyspnea-12 (D-12) questionnaire. Patients were asked to recall the severity of their symptoms and quality of life preplication, 1-month postplication, and 6-month postplication. Severity of symptoms was ranked as either none, mild, moderate, or severe. Values were then assigned to each rank as follows: none = 0, mild = 1, moderate = 2, and severe = 3. Relative change and statistical significance were calculated with preplication measurements used as the baseline. Scores between preplication versus 1-month postplication and 6-month postplication were then compared by Student's paired t-test. All tests were two-sided and statistical significance was set at P < 0.05. RESULTS: Forty-six patients were included in the study, from which 21 answered the D-12 questionnaire. Average scores from each component of the D-12 questionnaire showed improvement in the severity of symptoms from preplication to 1-month postplication. The latter period was then followed by continued improvement in all areas when symptoms 6-month postplication were assessed. CONCLUSION: In patients with diaphragmatic paralysis, diaphragm plication was effective in reducing patients' symptoms while improving overall quality of life.

The utilization of the Solar Salt (60 wt%NaNO3/40 wt%KNO3) mixture as a Thermal Energy Storage (TES) medium is gaining importance due to its scalability and cost-effectiveness. However, the corrosion of metallic components presents a significant challenge. This study explores the intricate interplay between salt chemistry and its corrosivity, particularly at elevated temperatures exceeding the state-of-the-art bulk temperature 565 °C. The study manipulates salt decomposition by adjusting the oxygen partial pressure in the purge gas over Solar Salt and investigates the evolution of salt chemistry with and without the presence of steel. It analyzes the corrosion behavior of two types of stainless steel, AISI 316L and AISI 310, under different gas purging atmospheres. Furthermore, it employs a gold particle tracing technique to identify and monitor the formation and growth of the corrosion layer on the steel surface. The results reveal that nitrogen gas purging significantly enhances salt decomposition and its corrosivity over time. The presence of steel also influences salt decomposition depending on the purged gas atmosphere. In a nitrogen atmosphere, the presence of steel can increase the nitrite levels, while an air atmosphere results in an elevated concentration of oxide ions. In air, the AISI 310 alloy shows slightly better performance than AISI 316L. Both alloys experience substantial mass loss in the nitrogen-purged atmosphere. Interestingly, the presence of gold particles within the middle of the corrosion layer in the air purged atmosphere visually illustrates a counter diffusion involving various cations and anions across the corrosion layer.

Among the variety of energy storage techniques thermal energy storage (TES), based on molten salts, is already in use for the storage of heat in a gigawatt hour scale. At the time of writing virtually all TES in CSP utilize Solar Salt (60 wt-% NaNO3 and 40 wt-% KNO3) due to its competitively low price, low vapor pressure and non-toxicity. On the downside, the operating temperature is limited to 560 °C based on its thermal stability. However, increasing the operating temperature while maintaining thermal stability of the salt using techniques that are realizable in industrial scale remains one of the main challenges. Up to now this could only be achieved in a small scale by flushing with synthetic purge gas or sealing and pressurizing the system, maintaining the necessary gas atmosphere and shifting the chemical equilibrium to the nitrate side. Both methods are hardly realizable in an industrial scale. In this work we show a new strategy to stabilize Solar Salt at 620 °C by combining the gas-purged configuration and sealed system with maximum pressure of few tens of millibars in a 100 kg scale. The formed gas phase was within the expected range in terms of oxygen and nitrous gases. Additionally, the concentration of the nitrate and nitrite ions aligned well with salt systems with gas-purged atmosphere at 620 °C. We demonstrate the first experiments on long-term thermal stabilization (4000 h) of Solar Salt at 620 °C in a 100 kg technical-scale. These findings represent an important step in the development of modern storage systems.

ABSTRACT Cutibacterium avidum is an emerging causative agent of orthopedic device-related infections (ODRIs). There are no guidelines for the antimicrobial treatment of C. avidum ODRI, but oral rifampin is frequently used in combination with a fluoroquinolone following intravenous antibiotics. We describe the in vivo emergence of combined resistance to rifampin and levofloxacin in a C. avidum strain isolated from a patient with early-onset ODRI treated with debridement, antibiotic treatment, and implant retention (DAIR) using rifampin combined with levofloxacin as the oral treatment. Whole-genome sequencing of C. avidum isolates before and after antibiotic exposure confirmed strain identity and identified new mutations in rpoB and gyrA, leading to amino acid substitutions previously reported to be associated with resistance to rifampin (S446P) and fluoroquinolones (S101L), respectively, in other microbial agents, in the posttherapy isolate. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing a DAIR procedure for C. avidum ODRI and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens. IMPORTANCE In this study, we report for the first time the in vivo emergence of dual resistance to levofloxacin and rifampin in C. avidum isolated from a patient who received both antibiotics orally in the setting of a salvage debridement and implant retention of an ODRI. Aside from the molecular insights reported here, this study highlights potential limitations of the combination of oral rifampin and levofloxacin in patients undergoing these surgical procedures and the potential need to evaluate specific optimal therapy for emerging ODRI pathogens.

Summary: Introduction: This study aims to analyze whether autologous breast reconstruction as compared to expander/implant reconstruction has a higher risk of postoperative wound healing problems (WHPs) and thus potentially delays chemotherapy start. Methods: Between January 2012 and December 2019, a total of 64 women with NSME/SSME and autologous (Group1, n = 33) or expander/implant reconstruction (Group2, n = 31) and adjuvant chemotherapy were enrolled in this study conducted at Innsbruck Medical University Hospital. Immediate postoperative WHPs in each group were compared, and the time from operation to initiation of chemotherapy was analyzed. If the start of chemotherapy was postponed for more than six weeks postoperatively due to WHP, it was defined as delayed. Statistical analysis was performed with SPSS and Fisher's exact test. Results: More postoperative WHP occurred in Group 1 than in Group 2 (51.6% vs. 9.7%, p

The transverse myocutaneous gracilis (TMG) and the profunda artery perforator (PAP) flap are both safe choices for autologous breast reconstruction originating from the same donor region in the upper thigh. We aimed to compare the post-operative outcome regarding donor-site morbidity and quality of life. We included 18 patients who had undergone autologous breast reconstruction with a PAP flap (n = 27 flaps). Prospective evaluation of donor-site morbidity was performed by applying the same questionnaire that had already been established in a previous study evaluating TMG flap (n = 25 flaps) outcome, and results were compared. Comparison of the two patient groups showed equivalent results concerning patient-reported visibility of the donor-site scar and thigh symmetry. Still, the TMG group was significantly more satisfied with the scar (p = 0.015) and its position (p = 0.001). No difference was found regarding the ability to sit for prolonged periods. Donor-site wound complications were seen more frequently in the PAP group (29.6%) than in the TMG group (4.0%). Both groups expressed rather high satisfaction with their quality of life. Both flaps show minimal functional donor-site morbidity and high patient satisfaction. To minimize wound healing problems in PAP patients, thorough planning of the skin paddle is necessary.

Objective: The study objective was to determine the relationship between lung resection and the development of postoperative hiatal hernia. Methods: Preoperative and postoperative computed tomography imaging from 373 patients from the International Early Lung Cancer Action Program and the Initiative for Early Lung Cancer Research on Treatment were compared at a median of 31.1 months of follow-up after resection of clinical early-stage non–small cell lung cancer. Incidence of new hiatal hernia or changes to preexisting hernias were recorded and evaluated by patient demographics, surgical approach, extent of resection, and resection site. Results: New hiatal hernias were seen in 9.6% of patients after lung resection (5.6% after wedge or segmentectomy and 12.4% after lobectomy; P = .047). The median size of new hernias was 21 mm, and the most commonly associated resection site was the left lower lobe (24.2%; P = .04). In patients with preexisting hernias, 53.5% demonstrated a small but significant increase in size from 21 to 22 mm (P

Thermal energy storage (TES) based on molten salts has been identified as a key player in the transition from fossil fuels to renewable energy sources. Solar Salt, a mixture of NaNO3 (60 wt%) and KNO3 (40 wt%), is currently the most advanced heat transfer and storage material used in concentrating solar power (CSP) plants. Here, it is utilized to produce electricity via a Rankine cycle, with steam temperatures reaching 550 °C. The goal of this study is to increase the operating temperature of solar salt to over 600 °C, allowing it to be adapted for use in high-temperature Rankine cycles with steam temperatures greater than 600 °C. Yet, this goal is impaired by the lack of available thermodynamic data given the salt’s complex high-temperature decomposition and corrosion chemistry. The study explores the thermodynamics of the decomposition reactions in solar salt, with a focus on suppressing decomposition into corrosive oxide ions up to a temperature of 620 °C. The results provide a new understanding of the stabilization of solar salt at previously unexplored temperatures with effective utilization of gas management techniques.

MgCl2–KCl–NaCl is a promising thermal energy storage (TES) material and heat transfer fluid (HTF) with high operating temperatures of >700°C for next-generation concentrating solar power (CSP) plants. One major challenge for future implementation of the molten chloride TES/HTF technology arises from the presence of some corrosive impurities, especially MgOHCl, a hydrolysis product of hydrated MgCl2. Even extremely low-concentration MgOHCl (tens of ppm O in weight) can cause unneglectable corrosion of commercial Fe–Cr–Ni alloys, which limits their service time as the structural materials in the molten chloride TES/HTF system. Thus, the chemical analysis and monitoring techniques of MgOHCl at the tens of ppm O level are vital for corrosion control. In this work, a chemical analysis technique based on direct titration and a high-precision automatic titrator was developed for an exact measurement of MgOHCl at the tens of ppm O level. It shows a standard deviation below 5 ppm O and an average error below 7 ppm O when the concentration of MgOHCl is 36 ppm O. Moreover, compared to other methods available in some literature reports, it can exclude the influence of co-existing MgO on the MgOHCl concentration measurement. This chemical analysis technique was used to calibrate the previously developed electrochemical method based on cyclic voltammetry (CV) to achieve reliable in situ monitoring of MgOHCl in the MgCl2–KCl–NaCl molten salt at a concentration as low as the tens of ppm O level. The in situ monitoring technique shows a monitoring limitation of

Molten chloride mixtures such as MgCl2–KCl–NaCl are potential thermal energy storage (TES) materials and heat transfer fluids (HTFs) for next-generation concentrating solar power (CSP) systems due to their high operation temperatures (>700°C) and low costs. This ternary MgCl2–KCl–NaCl salt mixture with a low material cost (

Digital federated platforms and data cooperatives for secure, trusted and sovereign data exchange will play a central role in the construction industry of the future. With the help of platforms, cooperatives and their novel value creation, the digital transformation and the degree of organization of the construction value chain can be taken to a new level of collaboration. The goal of this research project was to develop an experimental prototype for a federated innovation data platform along with a suitable exemplary use case. The prototype is to serve the construction industry as a demonstrator for further developments and form the basis for an innovation platform. It exemplifies how an overall concept is concretely implemented along one or more use cases that address high-priority industry pain points. This concept will create a blueprint and a framework for further developments, which will then be further established in the market. The research project illuminates the perspective of various governance innovations to increase industry collaboration, productivity and capital project performance and transparency as well as the overall potential of possible platform business models. However, a comprehensive expert survey revealed that there are considerable obstacles to trust-based data exchange between the key stakeholders in the industry value network. The obstacles to cooperation are predominantly not of a technical nature but rather of a competitive, predominantly trust-related nature. To overcome these obstacles and create a pre-competitive space of trust, the authors therefore propose the governance structure of a data cooperative model, which is discussed in detail in this paper.

Abstract Purpose The aim of this study was to translate, adapt and validate in French the Ankle Ligament Reconstruction ‐ Return to Sport after Injury (ALR‐RSI), a 12‐item English language scale assessing the psychological impact of returning to sports after ACL reconstruction. Our hypothesis was that the French version of the ALR‐RSI scale would be valid and adaptable to the French population. Methods The procedure followed the guidelines for the intercultural adaptation of the self‐administered questionnaires. A version of the ALR‐RSI‐Fr questionnaire was validated according to the international guidelines of COSMIN (COnsensus‐based Standards for the selection of health status Measurement INstruments). A prospective study was conducted between March 2020 and June 2021. The study included two population groups, the first one being that of adult athletes of all levels who underwent arthroscopic ankle ligament reconstruction and the second being that of adult athletes who did not suffer from any ankle problems. After consent, patients completed three questionnaires, the ALR‐RSI‐Fr, the AOFAS and the Karlsson score. Results The study included 30 patients and 30 controls who were all athletes. The mean age of the patients was 34.6 with 60% male and 40% female. The average time for patients to return to sport was 5.6 months. Twenty‐nine patients (96.6%) underwent arthroscopic ankle reconstruction while only one was eligible for ligament reinsertion. The control group with demographic data matched to the patient group was included in this study. Correlations between ALRSI, the total Karlsson score and its different sub items and the AOFAS were estimated using Spearman coefficients. Discriminant validity was tested between the “patient” and “control” groups and sub‐groups using the Wilcoxon tests. Reliability was evaluated on the ρ intraclass correlation coefficient (ICCC). A strong correlation was noted between the ALR‐RSI‐Fr, Karlsson and AOFAS with a Spearman score of 0.90 [0.76‐0.96].A highly significant difference was found between the “patient” and “control” groups. The internal consistency of the questionnaire was excellent with a Cronbach's alfa of 0.94. Reproducibility was “excellent” with an interclass correlation coefficient of q = 0.97 [0.94‐0.99]. Conclusion This study showed that the cross‐cultural adaptation of the English version of the ALR‐RSI was successful and validated for the French‐speaking population. The discriminant capacity of the scale between patients who underwent reconstruction and healthy subjects was also confirmed. This questionnaire will allow surgeons to better evaluate the psychological impact of returning to sports after ankle ligament reconstruction in French speaking patients Level of evidence LEVEL II: Prospective cohort study (patients enrolled at different points in their disease) Control arm of randomized trial.

Well-implemented and functioning land administration systems are able to improve the wellbeing of rural households and support the achievement of the UN Sustainable Development Goals. As cadastral data are an essential part of a modern land administration system for documenting and securing the boundaries of parcels, Ethiopia recently embarked on one of the largest land surveying programs for rural land registration in Africa. Cadastral and land registration data provided by the land administration office of the woreda were analyzed using a Geographical Information System to investigate whether parcels of female-headed households were disadvantaged compared to parcels of male-headed households with regard to parcel size, parcel features, and access to infrastructure. In addition, the situation of female-headed households after the land registration process was analyzed in more detail. To this aim, quantitative and qualitative data were collected in the Ethiopian Machakel woreda through a household survey, in-depth interviews, focus group discussions, and key informant interviews. The results document no significant gender discrepancies in parcel features and access to infrastructures. In general, women confirmed an improvement in the wellbeing of female-headed households after the land registration and certification process.

Abstract Background Metastatic prostate cancer is a highly heterogeneous and dynamic disease and practicable tools for patient stratification and resistance monitoring are urgently needed. Liquid biopsy analysis of circulating tumor cells (CTCs) and circulating tumor DNA are promising, however, comprehensive testing is essential due to diverse mechanisms of resistance. Previously, we demonstrated the utility of mRNA-based in situ padlock probe hybridization for characterizing CTCs. Methods We have developed a novel combinatorial dual-color (CoDuCo) assay for in situ mRNA detection, with enhanced multiplexing capacity, enabling the simultaneous analysis of up to 15 distinct markers. This approach was applied to CTCs, corresponding tumor tissue, cancer cell lines, and peripheral blood mononuclear cells for single-cell and spatial gene expression analysis. Using supervised machine learning, we trained a random forest classifier to identify CTCs. Image analysis and visualization of results was performed using open-source Python libraries, CellProfiler, and TissUUmaps. Results Our study presents data from multiple prostate cancer patients, demonstrating the CoDuCo assay’s ability to visualize diverse resistance mechanisms, such as neuroendocrine differentiation markers (SYP, CHGA, NCAM1) and AR-V7 expression. In addition, druggable targets and predictive markers (PSMA, DLL3, SLFN11) were detected in CTCs and formalin-fixed, paraffin-embedded tissue. The machine learning-based CTC classification achieved high performance, with a recall of 0.76 and a specificity of 0.99. Conclusions The combination of high multiplex capacity and microscopy-based single-cell analysis is a unique and powerful feature of the CoDuCo in situ assay. This synergy enables the simultaneous identification and characterization of CTCs with epithelial, epithelial-mesenchymal, and neuroendocrine phenotypes, the detection of CTC clusters, the visualization of CTC heterogeneity, as well as the spatial investigation of tumor tissue. This assay holds significant potential as a tool for monitoring dynamic molecular changes associated with drug response and resistance in prostate cancer.