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Abstract Image segmentation of the liver is an important step in treatment planning for liver cancer. However, manual segmentation at a large scale is not practical, leading to increasing reliance on deep learning models to automatically segment the liver. This manuscript develops a generalizable deep learning model to segment the liver on T1-weighted MR images. In particular, three distinct deep learning architectures (nnUNet, PocketNet, Swin UNETR) were considered using data gathered from six geographically different institutions. A total of 819 T1-weighted MR images were gathered from both public and internal sources. Our experiments compared each architecture’s testing performance when trained both intra-institutionally and inter-institutionally. Models trained using nnUNet and its PocketNet variant achieved mean Dice-Sorensen similarity coefficients>0.9 on both intra- and inter-institutional test set data. The performance of these models suggests that nnUNet and PocketNet liver segmentation models trained on a large and diverse collection of T1-weighted MR images would on average achieve good intra-institutional segmentation performance.

Abstract Background Evidence suggests that patients suffering from different mental disorders benefit from exercise programs combined with behavior change techniques. Based on this evidence, we have developed an exercise program (ImPuls) specifically designed to provide an additional treatment option in the outpatient mental health care system. The implementation of such complex programs into the outpatient context requires research that goes beyond the evaluation of effectiveness, and includes process evaluation. So far, process evaluation related to exercise interventions has rarely been conducted. As part of a current pragmatic randomized controlled trial evaluating ImPuls treatment effects, we are therefore carrying out comprehensive process evaluation according to the Medical Research Council (MRC) framework. The central aim of our process evaluation is to support the findings of the ongoing randomized controlled trial. Methods The process evaluation follows a mixed-methods approach. We collect quantitative data via online-questionnaires from patients, exercise therapists, referring healthcare professionals and managers of outpatient rehabilitative and medical care facilities before, during, and after the intervention. In addition, documentation data as well as data from the ImPuls smartphone application are collected. Quantitative data is complemented by qualitative interviews with exercise therapists as well as a focus-group interview with managers. Treatment fidelity will be assessed through the rating of video-recorded sessions. Quantitative data analysis includes descriptive as well as mediation and moderation analyses. Qualitative data will be analyzed via qualitative content analysis. Discussion The results of our process evaluation will complement the evaluation of effectiveness and cost-effectiveness and will, for example, provide important information about mechanisms of impact, structural prerequisites, or provider qualification that may support the decision-making process of health policy stakeholders. It might contribute to paving the way for exercise programs like ImPuls to be made successively available for patients with heterogeneous mental disorders in the German outpatient mental health care system. Trial registration The parent clinical study was registered in the German Clinical Trials Register (ID: DRKS00024152, registered 05/02/2021, https://drks.de/search/en/trial/DRKS00024152 ).

Introduction Degenerative changes in the otolithic organs have been theorized to be caused by the mechanical obstruction to endolymphatic flow, possibly resulting in endolymphatic hydrops (ELH). Otolin-1 is an otoconial matrix protein that crosses the blood labyrinth barrier and has been found in the serum of healthy and diseased patients.

Background: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. Methods: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. Results: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02–71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120–250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813–967). Overall survival was 100% (95% CI 100–100%) at both years one and two; 75% (95% CI 13–96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. Conclusions: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.

Abstract Background Mental disorders are prevalent and cause considerable burden of disease. Exercise has been shown to be efficacious to treat major depressive disorders, insomnia, panic disorder with and without agoraphobia and post traumatic stress disorder (PTSD). Methods This pragmatic, two arm, multi-site randomised controlled trial will evaluate the efficacy and cost-effectiveness of the manualized, group-based six-months exercise intervention “ImPuls”, among physically inactive patients with major depressive disorders, insomnia, panic disorder, agoraphobia and PTSD within a naturalistic outpatient context in Germany. A minimum of 375 eligible outpatients from 10 different study sites will be block-randomized to either ImPuls in addition to treatment as usual (TAU) or TAU only. ImPuls will be conducted by trained exercise therapists and delivered in groups of six patients. The program will combine (a) moderate to vigorous aerobic exercise carried out two-three times a week for at least 30 min with (b) behavior change techniques for sustained exercise behavior change. All outcomes will be assessed pre-treatment, post-treatment (six months after randomization) and at follow-up (12 months after randomization). Primary outcome will be self-reported global symptom severity assessed with the Brief Symptom Inventory (BSI-18). Secondary outcomes will be accelerometry-based moderate to vigorous physical activity, self-reported exercise, disorder-specific symptoms, quality-adjusted life years (QALY) and healthcare costs. Intention-to-treat analyses will be conducted using mixed models. Cost-effectiveness and cost-utility analysis will be conducted using incremental cost-effectiveness and cost-utility ratios. Discussion Despite its promising therapeutic effects, exercise programs are currently not provided within the outpatient mental health care system in Germany. This trial will inform service providers and policy makers about the efficacy and cost-effectiveness of the group-based exercise intervention ImPuls within a naturalistic outpatient health care setting. Group-based exercise interventions might provide an option to close the treatment gap within outpatient mental health care settings. Trial registration The study was registered in the German Clinical Trials Register (ID: DRKS00024152 , 05/02/2021).

BackgroundCholangiocarcinoma management is constantly being updated in view of existing evidence in order to establish practice guidelines and consensus statements. However, the available treatment guidelines to optimize outcomes for cholangiocarcinoma patients who require liver transplantation are still controversial. This study contributing to the cholangiocarcinoma care field by investigating a new promising neoadjuvant therapy that might be help to grant the liver transplant option to the patients with cholangiocarcinoma. Here, we evaluate and compare the potential efficacy of chemotherapy combination of Gemcitabine plus Cisplatin versus non- Gemcitabine and Cisplatin regimens as a neo-adjuvant treatment for cholangiocarcinoma patients prior to liver transplantation.MethodsIn this retrospective study, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with either the combination of neo-adjuvant Gemcitabine plus Cisplatin with no radiation or other standard options of neo-adjuvant treatment. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center in collaboration with the same institution’s transplant center according to an open-labeled, and centers-approved clinical management protocol. Patients were listed for liver transplantation if they had a minimum of six months of scans showing response or confirmation of disease stability. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. This report, which was censored on March 18, 2022.ResultsOut of a total of 707 liver transplant recipients were screened, 37 patients were confirmed with a diagnosis of cholangiocarcinoma and only 18 patients (11 males and 7 females) with a median age of 61.83 [interquartile range: 58.27-68.74] met inclusion criteria. Of the 18 patients enrolled, 10 received Gemcitabine/Cisplatin, while 8 patients received either Gemcitabine monotherapy or Capecitabine or FOLFIRI. Months for recurrence after transplantation was 20.1 (IRQ: 20.1-20.1) in the Gemcitabine/Cisplatin group and 9.5 (8.9-12.47) months in the non-Gemcitabine/Cisplatin group (p-value=0.18). Median months of follow-up in the Gemcitabine/Cisplatin group was 28.35 (27.1-32.23) months versus 40.12 (20.6-56.22) months in the non-Gemcitabine/Cisplatin group (p-value=0.33). In non-Gemcitabine/Cisplatin patients, overall survival was 75% (95% CI 31-93%) at both years 1 and 2; 63% (95% CI 23-86%) at years 3 to 5. In Gemcitabine/Cisplatin patients, overall survival was 100% (95% CI 100-100%) at both years 1 and 2; 75% (95% CI 13-96%) at years 3 to 5. Three non-Gemcitabine/Cisplatin patients died at 328 days, 340 days, and 896 days, respectively. One Gemcitabine/Cisplatin patient died at 885 days.ConclusionOur findings suggest improved overall survival outcomes with Gemcitabine plus Cisplatin as neo-adjuvant treatment with no concomitant radiation compared to non-Gemcitabine/Cisplatin regimens in patients with cholangiocarcinoma prior to liver transplantation.

Sudden sensorineural hearing loss (SSNHL) is an enigmatic entity, with obscure pathophysiology and debatable efficacy of the treatment agents used. An underlying cause is identified in only 10–15% of cases. The management of the remaining patients, classified as ‘idiopathic’, is empirical, and is conventionally with systemic steroids, vasodilator therapy, rheological agents, and antioxidants, to list a few amongst the host of the agents employed for the treatment. The availability of conflicting outcomes and lack of conclusive evidence has resulted in the propagation of consensus-based treatment protocols. In the present review, we discuss the various controversial issues and newer developments in the management of idiopathic SSNHL. The current review aims to present a narrative outlook of the updated evidence base available from PUBMED, augmented with relevant designated publications.

Introduction: Optimal sound transmission across the ossicular chain is dependent on the appropriate alignment of the middle ear ossicles. Incudostapedial joint (ISJ) is conventionally considered to be at right angle. Objective: We intended to study the ISJ anatomy and the impact of temporal bone pneumatization on the same. Methods: In a cadaveric study comprising of 47 human temporal bones, canal wall down mastoidectomy was carried out under microscopic guidance keeping the ossicular chain intact. The morphology of ISJ was recorded and analysed with respect to the pneumatization status of the temporal bone. The data analysis was performed using statistical software Stata version 12.0. Results: The mean ISJ angle for the 47 bones was 90.50 (SD-150; range:540-1220). The mean angle in well pneumatized bones was 93.70 (SD-16.5; Range:54°-1220) and in sclerotic mastoids was 88.70 (SD-14; Range:68°-1180). The difference in the ISJ angle in these two conditions was not statistically significant (p = 0.27). The mean angle was found to be significantly more obtuse in the cases with partially eroded ISJ (111.40 {SD-8.8; range:100.30-121.90}; p = 0.0001) and in the cases with an ‘adherent/tilted morphology’ of the stapes suprastructure with the promontory (mean-95.80{SD-13.8; range:70.70- 120.40); p-

The past decade has witnessed a change in landscape of cancer management with the advent of precision oncology. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have played an important role in improving patient survival. While the patients are living longer, treatment with ICIs are sometimes associated with adverse effects, some of which could be fatal. Radiologists can play a crucial role by early identification of some of these adverse effects during restaging scans. Our paper focuses on the imaging features of commonly occurring ICI toxicities based on organ system.

Introduction Successful cochlear implantation requires an appropriate insertion depth of the electrode, which depends on cochlear duct length CDL). The CDL can vary due to ethnic factors. Objective The objective of the current study was to determine the CDL in an Indian adult cadaveric population. Methods The present was a cadaveric study using the temporal bones obtained after permission of the Institutional Review Board. The temporal bones were subjected to high-resolution computed tomography (HRCT), and the double oblique reformatted CT images were reconstructed through the basal turn of the cochlea. The reformatted images were then viewed in the minimum-intensity projection (minIP) mode, and the ‘A’ value (the diameter of the basal turn of the cochlea) was calculated. The CDL was then measured using the formula CDL = 4.16A - 4 (Alexiades et al). The data analysis was performed using the Microsoft Excel software, version 2016. Results A total of 51 temporal bones were included for imaging analysis. The CDL varied from 27.6 mm to 33.4 mm, with a mean length of 30.7 mm. There was no statistically significant difference between the two sides. Conclusion The CDL can be calculated with preoperative high-resolution CT, and can provide a roadmap for effective cochlear implant electrode insertion. The population-based anatomical variability needs to be taken into account to offer the most efficient and least traumatic insertion of the electrode.

Belugas (Delphinapterus leucas) from the Eastern Beaufort Sea (EBS) population are harvested annually in the Inuvialuit Settlement Region (ISR) during their seasonal migration past coastal communities and harvest camps. The beluga harvest monitoring program is a flagship program of the ISR’s Fish and Marine Mammal Community Monitoring Program, and it has provided critical information about beluga health and observed changes in the EBS population. This study aimed to develop a suite of local indicators of beluga health that bridged traditional ecological knowledge (TEK) about beluga condition, illness, and disease, with western science through the co-production of knowledge. Community members from Inuvik, Paulatuk, and Tuktoyaktuk with beluga harvesting and preparation experience were engaged to characterize beluga health from an Inuvialuit perspective. Inuvialuit knowledge about the environment and beluga health, values about hunting beluga, and Inuvialuit cosmology — the foundation of the knowledge system — were documented through semi-structured questionnaires (n = 66), semi-structured interviews (n = 78), and focus group meetings (n = 3). This research furthers our understanding of how Inuvialuit view beluga health from the physical and behavioural characteristics of belugas, values, and appropriate behaviours by harvesters and how observations made about beluga can be explained. To support the co-production of knowledge, a suite of local indicators was developed that bridged TEK about beluga condition, illness, and disease with western science.

Frontal sinus Cerebrospinal Fluid (CSF) leak is relatively uncommon. Surgical treatment is indicated when conservative management fails. Here we present a case report of 19-year-old male who presented with delayed CSF rhinorrhea after trauma with one episode of meningitis. On evaluation, frontal sinus posterior vault leak was seen. The repair was done by osteoplastic flap raising approach. Follow-up clinico-radiological assessment showed no evidence of leak or defect. Although endoscopic approach is used most commonly now-a-days, defect in posterior vault may not be adequately dealt especially if defect is laterally or superiorly located as seen in this case. This case is reported to highlight the indication of open approach in endoscopic era.

Abstract Introduction Sigmoid sinus (SS) variations have been classified variously in the literature. These classifications suffer from some form of shortcoming from a clinical point of view for their application. Objective We propose a clinically relevant classification of the SS in relation to the posterior semicircular canal (PSCC) and to the exposure of the presigmoid dural plate. The positioning of the SS was analyzed with reference to the volume of the mastoid and to the level of mastoid pneumatization. Methods A total of 94 formalin-preserved human cadaveric temporal bones were microdissected to carry out a complete mastoidectomy. The SS, the presigmoid dural plate, and the PSCC were exposed, and the position of the former was analyzed in relation to the latter two in order to classify the position of the SS into three grades. Results Grade I had the best exposure of the presigmoid dura and of the PSCC, while grade III had the poorest exposure of the presigmoid dura and of the PSCC. Grade I SS was associated with good pneumatization and higher mastoid volumes compared with grades II and III. Conclusions The SS exhibits considerable anatomic variability. A favorable positioning of the SS is associated with a large mastoid volume and pneumatization. A careful preoperative study of the imaging may help in understanding the positioning of the SS and the safety of various transmastoid approaches.

ABSTRACT Purpose To study the intraoperative findings in case of early and delayed decompression of facial nerve paralysis and compare their results. Methods Retrospective data analysis of 23 cases of longitudinal temporal bone fracture with House-Brackmann grade V and VI facial nerve paralysis. All cases were thoroughly evaluated and underwent facial nerve decompression through the transmastoid approach. All cases were under regular follow-up till the date of manuscript submission. Results Clinical improvement of the facial nerve function was observed for early vs. delayed facial nerve decompression. In the early decompression group, facial nerve function improved to grade II in eight cases (80%) and grade III in two cases (20%), whereas in the delayed decompression group it improved to grade II in one case (7.70%), grade III in four cases (30.76%), grade IV in seven cases (53.84%), and grade V in one case (7.70%). Conclusions Early decompression of facial nerve provides better results than delayed decompression because it enables early expansion of the nerve.

Greenhouse gas emissions from fossil fuel combustion and land use are changing the radiative budget of the Earth and changing its climate. The negative impacts of this climate change on natural and human systems are already emergent. The solution is to eliminate greenhouse gas emissions altogether as soon as possible, but the rate at which these emissions can decrease is limited by human reliance on fossil fuels for energy and the infrastructural, socio-economic, and behavioral inertia of current systems around the world. In this chapter, we discuss the physical impacts as well as the many challenges and obstacles to ‘bending the curve’, and provide a framework of possible solutions.

Abstract Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC.

How is the brain engaged when people are thinking about their hopes, dreams, and obligations? Regulatory focus theory postulates two classes of personal goals and motivational systems for pursuing them. Ideal goals, such as hopes and aspirations, are pursued via the promotion system through making good things happen. Ought goals, such as obligations or responsibilities, are pursued via the prevention system through keeping bad things from happening. This study investigated the neural correlates of ideal and ought goal priming using an event-related fMRI design with rapid masked stimulus presentations. We exposed participants to their self-identified ideal and ought goals, yoked control words and nonwords. We also examined correlations between goal-related activation and measures of regulatory focus, behavioral activation/inhibition, and negative affect. Ideal priming led to activation in frontal and occipital regions as well as caudate and thalamus, whereas prevention goal priming was associated with activation in precuneus and posterior cingulate cortex. Individual differences in dysphoric/anxious affect and regulatory focus, but not differences in BAS/BIS strength, were predictive of differential activation in response to goal priming. The regions activated in response to ideal and ought goal priming broadly map onto the cortical midline network that has been shown to index processing of self-referential stimuli. Individual differences in regulatory focus and negative affect impact this network and appeared to influence the strength and accessibility of the promotion and prevention systems. The results support a fundamental distinction between promotion and prevention and extend our understanding of how personal goals influence behavior.

Even a single night of total sleep-deprivation (SD) can have dramatic effects on economic decision making. Here we tested the novel hypothesis that SD influences economic decisions by altering the valuation process. Using functional magnetic resonance imaging (fMRI) we identified value signals related to the anticipation and the experience of monetary and social rewards (attractive female faces). We then derived decision value signals that were predictive of each participant’s willingness to exchange money for brief views of attractive faces in an independent market task. Strikingly, SD altered decision value signals in ventromedial prefrontal cortex (VMPFC) in proportion to the corresponding change in economic preferences. These changes in preference were independent of the effects of SD on attention and vigilance. Our results provide novel evidence that signals in VMPFC track the current state of the individual, and thus reflect not static but constructed preferences.

To dissociate a choice from its antecedent neural states, motivation associated with the expected outcome must be captured in the absence of choice. Yet, the neural mechanisms that mediate behavioral idiosyncrasies in motivation, particularly with regard to complex economic preferences, are rarely examined in situations without overt decisions. We employed functional magnetic resonance imaging (fMRI) in a large sample of participants while they anticipated earning rewards from two different modalities: monetary and candy rewards. An index for relative motivation toward different reward types was constructed using reaction times to the target for earning rewards. Activation in the nucleus accumbens (NAcc) and anterior insula (aINS) predicted individual variation in relative motivation between our reward modalities. NAcc activation, however, mediated the effects of aINS, indicating the NAcc is the likely source of this relative weighting. These results demonstrate that neural idiosyncrasies in reward efficacy exist even in the absence of explicit choices, and extend the role of NAcc as a critical brain region for such choice-free motivation.

Abstract Background The domestic cat has offered enormous genomic potential in the veterinary description of over 250 hereditary disease models as well as the occurrence of several deadly feline viruses (feline leukemia virus -- FeLV, feline coronavirus -- FECV, feline immunodeficiency virus - FIV) that are homologues to human scourges (cancer, SARS, and AIDS respectively). However, to realize this bio-medical potential, a high density single nucleotide polymorphism (SNP) map is required in order to accomplish disease and phenotype association discovery. Description To remedy this, we generated 3,178,297 paired fosmid-end Sanger sequence reads from seven cats, and combined these data with the publicly available 2X cat whole genome sequence. All sequence reads were assembled together to form a 3X whole genome assembly allowing the discovery of over three million SNPs. To reduce potential false positive SNPs due to the low coverage assembly, a low upper-limit was placed on sequence coverage and a high lower-limit on the quality of the discrepant bases at a potential variant site. In all domestic cats of different breeds: female Abyssinian, female American shorthair, male Cornish Rex, female European Burmese, female Persian, female Siamese, a male Ragdoll and a female African wildcat were sequenced lightly. We report a total of 964 k common SNPs suitable for a domestic cat SNP genotyping array and an additional 900 k SNPs detected between African wildcat and domestic cats breeds. An empirical sampling of 94 discovered SNPs were tested in the sequenced cats resulting in a SNP validation rate of 99%. Conclusions These data provide a large collection of mapped feline SNPs across the cat genome that will allow for the development of SNP genotyping platforms for mapping feline diseases.

Dengue virus (DENV) causes millions of infections each year, and there are currently no approved antivirals. Essential oils could serve as potential candidates for developing plant-based dengue treatments. Lippia alba (Mill.) N.E. Brown essential oil (LAEO) was selected to investigate the mode of antiviral action and its effect on activated platelets. Binding affinities of 20 LAEO compounds and platelet proteins were investigated through docking analyses. LAEO showed a potent virucidal effect (IC50, 2.1 to 5.1 μg/mL) against all DENV serotypes. LAEO reduced P-selectin (from 61% to 18%) and increased survival (from 71% to 97%) in DENV-2- and DENV NS1-stimulated human platelets. Sesquiterpene hydrocarbons showed the highest binding affinities (from −7.3 to −8.0 kcal/mol) with platelet innate immune receptors such as TLR2/1, TLR4/MD-2 and αIIbβ3 integrin. The data provide a first step towards defining the potential of LAEO as a candidate for developing phytotherapeutics for dengue. [ABSTRACT FROM AUTHOR]