Thermal infrared directs host-seeking behaviour in Aedes aegypti mosquitoes.

Mosquito-borne diseases affect hundreds of millions of people annually and disproportionately impact the developing world1,2. One mosquito species, Aedes aegypti, is a primary vector of viruses that cause dengue, yellow fever and Zika. The attraction of Ae. aegypti female mosquitos to humans requires integrating multiple cues, including CO2 from breath, organic odours from skin and visual cues, all sensed at mid and long ranges, and other cues sensed at very close range3-6. Here we identify a cue that Ae. aegypti use as part of their sensory arsenal to find humans. We demonstrate that Ae. aegypti sense the infrared (IR) radiation emanating from their targets and use this information in combination with other cues for highly effective mid-range navigation. Detection of thermal IR requires the heat-activated channel TRPA1, which is expressed in neurons at the tip of the antenna. Two opsins are co-expressed with TRPA1 in these neurons and promote the detection of lower IR intensities. We propose that radiant energy causes local heating at the end of the antenna, thereby activating temperature-sensitive receptors in thermosensory neurons. The realization that thermal IR radiation is an outstanding mid-range directional cue expands our understanding as to how mosquitoes are exquisitely effective in locating hosts.

BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon). BNT162b2 encodes the full-length transmembrane S glycoprotein, locked in its prefusion conformation by the substitution of two residues with proline (S(K986P/V987P); hereafter, S(P2) (also known as P2 S)). The flexibly tethered RBDs of the RBD-foldon bind to human ACE2 with high avidity. Approximately 20% of the S(P2) trimers are in the two-RBD 'down', one-RBD 'up' state. In mice, one intramuscular dose of either candidate vaccine elicits a dose-dependent antibody response with high virus-entry inhibition titres and strong T-helper-1 CD4+ and IFNγ+CD8+ T cell responses. Prime-boost vaccination of rhesus macaques (Macaca mulatta) with the BNT162b candidates elicits SARS-CoV-2-neutralizing geometric mean titres that are 8.2-18.2× that of a panel of SARS-CoV-2-convalescent human sera. The vaccine candidates protect macaques against challenge with SARS-CoV-2; in particular, BNT162b2 protects the lower respiratory tract against the presence of viral RNA and shows no evidence of disease enhancement. Both candidates are being evaluated in phase I trials in Germany and the USA1-3, and BNT162b2 is being evaluated in an ongoing global phase II/III trial (NCT04380701 and NCT04368728).

Predicting futility of upfront surgery in perihilar cholangiocarcinoma: Machine learning analytics model to optimize treatment allocation.

BACKGROUND: While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. METHODS: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome. RESULTS: A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. CONCLUSIONS: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.

Impact of stalling events on microcirculatory hemodynamics in the aged brain.

OBJECTIVE: The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied. METHODS: Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events. RESULTS: Using a non-linear plasma skimming model, it is observed that Ht increases in the penetrating arteries from the pial vessels as a function of cortical depth. The incidence of stalling on Ht distribution along the blood network vessels shows reduction of RBCs around the tissue near occlusion sites and decreased Ht concentration downstream from the blockage points. Moreover, upstream of the occlusion, there is a noticeable increase of the Ht, leading to larger flow resistance due to higher blood viscosity. We predicted marked changes in transit time behavior due to stalls which match trends observed in mice in vivo. CONCLUSIONS: These changes to blood cell quantity and quality may be implicated in the development of Alzheimer's disease and contribute to the course of the illness.

Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible.

BACKGROUND: A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA. METHODS: Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy-left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS). RESULTS: Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27-34) after left and 23 months (95% CI 20-25) after right liver resection (p < 0.001), and 33 months (95% CI 28-38), 27 months (95% CI 23-32), 25 months (95% CI 21-30), and 21 months (95% CI 18-24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities. CONCLUSIONS: A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

BACKGROUND: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver. METHODS: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival. Factors affecting survival were evaluated using univariable and multivariable Cox regression analyses. RESULTS: In total, 199 patients were included from 7 centres, of whom 39 underwent PVE/HVE and 160 PVE alone. Groups differed in median age (P = 0.008). As reported previously, PVE/HVE resulted in a significantly higher resection rate than PVE alone (92 versus 68%; P = 0.007). Three-year overall survival was significantly higher in the PVE/HVE group (median survival not reached after 36 months versus 20 months after PVE; P = 0.004). Univariable and multivariable analyses identified PVE/HVE as an independent predictor of survival (univariable HR 0.46, 95% c.i. 0.27 to 0.76; P = 0.003). CONCLUSION: Overall survival after PVE/HVE is substantially longer than that after PVE alone in patients with primary and secondary liver tumours.

Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma.

AIMS: The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions. METHODS AND RESULTS: All patients treated with surgically resected iCCA at Frankfurt University Hospital between December 2005 and March 2023 were retrospectively analysed. Histomorphological features of SD- and LD-iCCA were evaluated by an expert hepatobiliary pathologist. Tissue samples suspicious for subtype heterogeneity were further investigated. Immunohistochemistry for N-cadherin, S100P, MUC5AC, MUC6, TFF1 and AGR2 and mutational profiling with the Illumina TruSight Oncology 500 (TSO500) assay were performed separately for the SD- and LD-iCCA regions. Of 129 patients with surgically resected iCCA, features of either SD- or LD-iCCA were present in 67.4% (n = 87) and 24.8% of the patients (n = 32), respectively; 7.8% (n = 10) had histomorphological features of both SD- and LD-iCCA, seven patients (5.4%) of which had sufficient formalin-fixed, paraffin-embedded tissue for further analysis. Heterogeneity of both subtypes could be confirmed with immunohistochemistry. In five of seven (71.4%) patients, molecular profiling revealed intratumoural differences in genetic alterations between the SD- and LD-iCCA region. In one patient, a BRAF mutation (p.V600E) was found in the SD-iCCA but not in the LD-iCCA region of the tumour. CONCLUSIONS: A marked portion of patients with iCCA exhibits both SD- and LD-iCCA in different tumour regions. In case of the presence of histopathological heterogeneity, mutational profiling should be considered to avoid missing therapeutically relevant genetic alterations.

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

BACKGROUND AND PURPOSE: A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN. METHODS: This single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2. RESULTS: Eighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001). CONCLUSIONS: A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

Incidence and risk factors for developing chemotherapy-induced neuropathic pain in 500 cancer patients: A file-based observational study.

OBJECTIVE: To define the incidence and risk factors for developing chemotherapy-induced neuropathic pain (CINP). METHODS: Retrospective, file-based analysis on cancer patients who received any type of conventional chemotherapy and for whom neurological evaluation was asked to reveal the extent of chemotherapy-induced peripheral neurotoxicity (CIPN) with or without CINP. CINP was assessed by means of the PI-NRS and Douleur Neuropathique-4 questionnaire. The total neuropathy score-clinical version graded the severity of CIPN. RESULTS: The medical files of 500 chemotherapy-treated cancer patients were reviewed. Any grade chronic CIPN was disclosed in 343 (68.6%) patients and CINP in 127 (37%) of them, corresponding to an overall percentage of 25.4% among all 500 included patients. The logistic regression analysis identified as independent predictors for CINP development the presence of uncomplicated diabetes (OR: 2.17; p = .039) and grade 2-3 chronic CIPN (OR: 1.61; p < .001) as also the administration of combined paclitaxel plus cisplatin (reference variable), compared to oxaliplatin (OR: 0.18; p = .001) and taxanes (OR: 0.16; p < .001). The increased severity of acute OXAIPN was associated with CINP (OR: 4.51; p < .001). OXA-treated patients with persistent CINP presented a worst likelihood to improve after chemotherapy discontinuation, than patients receiving combined paclitaxel plus cisplatin (OR: 50; p < .001). CONCLUSION: The incidence of CINP in our cohort was comparable to previous reports, with severities fluctuating upwards during chemotherapy and declined post-chemotherapy. Uncomplicated diabetes, the combined paclitaxel plus cisplatin treatment and the increased severity of acute oxaliplatin neurotoxicity mostly increase the risk for developing CINP. OXA-treated patients present less possibilities to recover from CINP after chemotherapy discontinuation, than other chemotherapies.

Considerations for establishing and maintaining international research collaboration: the example of chemotherapy-induced peripheral neurotoxicity (CIPN)-a white paper.

PURPOSE: This white paper provides guidance regarding the process for establishing and maintaining international collaborations to conduct oncology/neurology-focused chemotherapy-induced peripheral neurotoxicity (CIPN) research. METHODS: An international multidisciplinary group of CIPN scientists, clinicians, research administrators, and legal experts have pooled their collective knowledge regarding recommendations for establishing and maintaining international collaboration to foster advancement of CIPN science. RESULTS: Experts provide recommendations in 10 categories: (1) preclinical and (2) clinical research collaboration; (3) collaborators and consortiums; (4) communication; (5) funding; (6) international regulatory standards; (7) staff training; (8) data management, quality control, and data sharing; (9) dissemination across disciplines and countries; and (10) additional recommendations about feasibility, policy, and mentorship. CONCLUSION: Recommendations to establish and maintain international CIPN research collaboration will promote the inclusion of more diverse research participants, increasing consideration of cultural and genetic factors that are essential to inform innovative precision medicine interventions and propel scientific discovery to benefit cancer survivors worldwide. RELEVANCE TO INFORM RESEARCH POLICY: Our suggested guidelines for establishing and maintaining international collaborations to conduct oncology/neurology-focused chemotherapy-induced peripheral neurotoxicity (CIPN) research set forth a challenge to multinational science, clinical, and policy leaders to (1) develop simple, streamlined research designs; (2) address logistical barriers; (3) simplify and standardize regulatory requirements across countries; (4) increase funding to support international collaboration; and (5) foster faculty mentorship.

Continuous infusion versus bolus injection of loop diuretics for acute heart failure.

BACKGROUND: Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload. OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults. SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence. MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics. AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.

Impact of the exposure of sublethal dose of mosquito coil on the development of insecticide resistance in Aedes aegypti (L.) (Diptera: Culicidae).

Mosquito coil is commonly used in many African households for protection against mosquito bites. The coil usually has semi-volatile pyrethroids as an active ingredient, which usually diffuse across open space, and the cloud either kills mosquitoes that are exposed, or mosquitoes can be exposed to sublethal doses of the insecticides. This study was conducted to assess the impact of sublethal doses of mosquito coil on the development of insecticide resistance in Aedes aegypti, a major vector for dengue fever and several other arboviral diseases. A laboratory colony of Ae. aegypti was exposed to sublethal doses of a meperfluthrin-based mosquito coil in a Peet-Grady chamber once per generation for 16 generations. The susceptibility of the exposed colony to a diagnostic dose of the mosquito coil as well as to three other insecticides was determined. Three different kdr mutations and five enzyme activities were evaluated in both the exposed and control colonies. After 16 generations of sublethal exposure to mosquito coils, the full diagnostic dose of the coil caused 68% mortality to the exposed colony compared to 100% mortality in the control colony. Mortality caused by deltamethrin (0.05%) was also significantly lower in the exposed colony. The frequency of 1016I kdr mutation as well as MFO and alpha esterase activities were higher in the exposed colony compared to the control colony. This study provides evidence of the development of pyrethroid resistance in an Ae. aegypti population due to sublethal exposure to mosquito coil for 16 generations. Given the large-scale use of mosquito coils in many African households, its role as a pyrethroid resistance selection source should be taken into consideration when designing resistance management strategies.

Influence of aberrant right hepatic artery on survival after pancreatic resection for ductal adenocarcinoma of the pancreatic head.

PURPOSE: The presence of an aberrant right hepatic artery (aRHA), arising from the superior mesenteric artery, is a common variant of the liver vascular anatomy. Considering that tumor spread occurs along vessels, the question arises, whether the presence of an aRHA influences the oncologic outcome after resection for cancer of the pancreatic head. METHODS: Patients with ductal adenocarcinoma of the pancreatic head, who underwent resection from 2011 to 2020 at the Frankfurt University Hospital, Germany, were analyzed retrospectively. Surgical records and computed tomography imaging were reviewed for the presence of aRHA. Overall and disease-free survival as well as hepatic recurrence were analyzed according to the presence of aRHA. RESULTS: aRHA was detected in 21 out of 145 patients (14.5%). The median overall survival was 26 months (95%CI 20.8-34.4), median disease-free survival was 12.1 months (95%CI 8.1-17.3). There was no significant difference in overall survival (26.1 versus 21.4 months, adjusted hazard ratio 1.31, 95%CI 0.7-2.46, p = 0.401) or disease-free survival (14.5 months versus 12 months, adjusted hazard ratio 0.98, 95%CI 0.57-1.71, p = 0.957) without and with aRHA. The hepatic recurrence rate was 24.4.% with conventional anatomy versus 30.8% with aRHA (adjusted odds ratio 1.36, 95%CI 0.3-5.38, p = 0.669). In the multivariable analysis, only lymphatic vessel invasion was an independent prognostic factor for hepatic recurrence. CONCLUSIONS: The presence of an aRHA does not seem to influence the long-term survival and hepatic recurrence after resection for ductal adenocarcinoma of the pancreatic head.

Intraosseous myofibroma mimicking an odontogenic lesion: case report, literature review, and differential diagnosis.

BACKGROUND: Intraosseous myofibroma of the jaw is a rare neoplasm of mesenchymal origin with limited comprehensive understanding. It typically affects patients in the first two decades of life with a male predilection. CASE PRESENTATION: This study presents a rare case of myofibroma mimicking an odontogenic lesion in a 2-year-old boy. The patient presented with an incidental finding of a painless swelling of the right mandibular ramus of unknown etiology. Imaging analysis revealed a solid, expansile lesion adjacent to the germinal zone of the right mandibular first molar. Histopathologic analysis and immunohistochemistry after incisional biopsy suggested a possible central odontogenic fibroma, and the patient underwent total enucleation, leading to the final diagnosis of intraosseous myofibroma. Follow-up examinations showed no evidence of recurrence. CONCLUSIONS: This report contributes to the understanding of myofibroma in pediatric patients and underscores the critical role of meticulous histopathologic examination for effective surgical planning and optimal patient outcomes.

Systematic evaluation of spatial resolution and gamma criteria for quality assurance with detector arrays in stereotactic radiosurgery.

PURPOSE: To characterize detector array spacing and gamma index for quality assurance (QA) of stereotactic radiosurgery (SRS) deliveries. Use the Nyquist theorem to determine the required detector spacing in SRS fields, and find optimal gamma indices to detect MLC errors using the SRS MapCHECK, ArcCHECK, and a portal imaging device (EPID). METHODS: The required detector spacing was determined via Fourier analysis of small radiation fields and profiles of typical SRS treatment plans. The clinical impact of MLC errors of 0.5, 1, and 2 mm was evaluated. Global gamma (low-dose threshold 10%) was evaluated for the three detector systems using various combinations of the distance to agreement and the dose difference. RESULTS: While MLC errors only slightly affected mean dose to PTV and a 2 mm thick surrounding structure (PTV_2 mm), significant PTV underdose incurred with increase in maximum dose to PTV_2 mm. Gamma indices with highest sensitivity to the introduced errors at 95% tolerance level for plans on target volumes of 3.2 cm3 (plan 3 cc) and 35.02 cm3 (plan 35 cc) were 2%/1 mm for the SRS MapCHECK and 2%/3 mm for the ArcCHECK, with 3%/1 mm (plan 3cc) and 2%/1 mm (plan 35cc) for the EPID. Drops in passing rates for a 2 mm MLC error were (46.2%, 41.6%) for the SRS MapCHECK and (12.2%, 4.2%) for the ArcCHECK for plan 3cc and plan 35cc, respectively. For Portal Dose, values were 4.5% (plan 3cc) and 7% (plan 35cc). The Nyquist frequency of two SRS dose distributions lie between 0.26  and 0.1 mm-1 , corresponding to detector spacings of 1.9 and 5 mm. Evaluation of SRS MapCHECK data with doubled detector density indicates that increased detector density may reduce the system's sensitivity to errors, necessitating a tighter gamma index. CONCLUSIONS: The present results give insight on the performance of detector arrays and gamma indices for the investigated detectors during SRS QA.

Is the collateral circulation pattern in the hard palate affected by cleft deformity?

OBJECTIVES: To evaluate the influence of collateral vascularization on surgical cleft palate closure and deformities. MATERIALS AND METHODS: Corrosion casting was performed using red-colored acrylic resin in twelve fresh adult cadavers with a normal hard palate. Additionally, white-colored barium sulfate was injected into a fetus with a unilateral complete cleft palate, and layer-by-layer tissue dissection was performed. Both substances were injected into the external carotid arteries. Corrosion casting involved dissolving the soft and hard tissues of the orofacial area utilizing an enzymatic solution. RESULTS: In normal palates, bilateral intraosseous infraorbital arteries formed a network in the premaxilla with the intraosseous nasopalatine- and greater palatine arteries (GPAs). The perforating GPAs anastomosed with the sphenopalatine artery sub-branches. Bilateral extraosseous GPA anastomoses penetrated the median palatine suture. Complex vascularization in the retrotuberal area was detected. In the cleft zone, anastomoses were omitted, whereas in the non-cleft zone, enlarged GPAs were distributed along the cleft edges and followed the anatomical course anteriorly to initiate the network with facial artery sub-branches. CONCLUSIONS: The anatomical subunits of the palate exhibited distinct anastomosis patterns. Despite omitted anastomoses with collateral circulation in the cleft zone, arteries maintained their anatomical pattern as seen in the normal specimen in the non-cleft zone. CLINICAL RELEVANCE: Based on the findings in normal- and cleft palates, surgeons may expect developed anastomosis patterns in the non-cleft zone. Due to the lack of microcirculation in the cleft zone, the existent anastomoses should be maintained as much as possible by the surgical technique. This applies anteriorly in the incisive canal territory, alveolar ridges, and posteriorly in the retrotuberal area.

"I Can't Just Pull a Woman Out of a Hat": A Mixed-Methods Study on Journalistic Drivers of Women's Representation in Political News.

While the persisting issue of women's underrepresentation in political news partly arises from biases in the social reality, journalism plays a crucial role in mediating these biases. This study proposes a multilayered framework of gendered influences in journalistic news production to understand how journalistic factors exacerbate or mitigate women's media representation. Drawing from a mixed-methods design (content analysis, survey, interviews), journalists' own gender emerges as the strongest predictor of gendered representations. Women's underrepresentation is also influenced by professional roles but not by organizations' gender guidelines. We explore how journalists perceive these influences and discuss conceptual and practical implications.

Assessment of liver function by gadoxetic acid avidity in MRI in a model of rapid liver regeneration in rats.

BACKGROUND: This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). METHODS: Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver functionFLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensityFLR/DPL multiplied by the volumeFLR/DPL. RESULTS: In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volumeFLR and functionFLR increased proportionally, except on POD 1. Thereafter, functionFLR exceeded volumeFLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. DISCUSSION: This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI.

Pan-European survey on current treatment strategies in patients with upfront resectable colorectal liver metastases.

BACKGROUND: There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe. METHODS: A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM. RESULTS: The survey was completed by 87 surgeons from 24 countries. The resectability of CRLM is mostly based on the volume of the future liver remnant, while considering tumor biology. Thermal ablation was considered as an acceptable adjunct to resection in parenchymal-sparing CRLM surgery by 77 % of the respondents. A total of 40.2 % of the respondents preferred standard perioperative systemic therapy and 24.1 % preferred standard upfront local treatment. CONCLUSION: Among the participating European hepato-pancreato-biliary surgeons, there is a high degree of consensus on the definition of CRLM resectability. However, there is much variety in the use of adjunctive thermal ablation. Major variations persist in the use of perioperative systemic therapy in cases of upfront resectable CRLM, stressing the need for further evidence and a consensus.

Coronary microvascular function in male physicians with burnout and job stress: an observational study.

BACKGROUND: As a professional group, physicians are at increased risk of burnout and job stress, both of which are associated with an increased risk of coronary heart disease that is at least as high as that of other professionals. This study aimed to examine the association of burnout and job stress with coronary microvascular function, a predictor of major adverse cardiovascular events. METHODS: Thirty male physicians with clinical burnout and 30 controls without burnout were included. Burnout was assessed with the Maslach Burnout Inventory and job stress with the effort-reward imbalance and overcommitment questionnaire. All participants underwent myocardial perfusion positron emission tomography to quantify endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular function. Burnout and job stress were regressed on coronary flow reserve (primary outcome) and two additional measures of coronary microvascular function in the same model while adjusting for age and body mass index. RESULTS: Burnout and job stress were significantly and independently associated with endothelium-dependent microvascular function. Burnout was positively associated with coronary flow reserve, myocardial blood flow response, and hyperemic myocardial blood flow (r partial = 0.28 to 0.35; p-value = 0.008 to 0.035). Effort-reward ratio (r partial = - 0.32 to - 0.38; p-value = 0.004 to 0.015) and overcommitment (r partial = - 0.30 to - 0.37; p-value = 0.005 to 0.022) showed inverse associations with these measures. CONCLUSIONS: In male physicians, burnout and high job stress showed opposite associations with coronary microvascular endothelial function. Longitudinal studies are needed to show potential clinical implications and temporal relationships between work-related variables and coronary microvascular function. Future studies should include burnout and job stress for a more nuanced understanding of their potential role in cardiovascular health.