Syndrome of inappropriate antidiuretic hormone release secondary to central nervous system coccidioidomycosis with vasculitis.

A man in his 60s presented to the clinic due to night sweats and weight loss following pneumonia. He was found to have hyponatraemia due to a syndrome of inappropriate antidiuretic hormone (SIADH). CT of the thorax was concerning for pulmonary nodules. He was ultimately diagnosed with pulmonary coccidioidomycosis (CM) and started on fluconazole 400 mg daily with improvement in symptoms. Due to the report of headaches, head MRI was conducted which suggested central nervous system (CNS) involvement. Cerebrospinal fluid analysis was consistent with CNS CM and head magnetic resonance angiography confirmed the presence of CNS vasculitis. Fluconazole dose was increased to 800 mg daily which the patient continued to tolerate and showed improvement. This report depicts a case of SIADH associated with CNS CM with vasculitis and demonstrates the importance of high clinical suspicion for SIADH secondary to CNS CM in the setting of hyponatraemia and headache.

Systematic Coarse Graining of Environments for the Nonperturbative Simulation of Open Quantum Systems.

Conducting precise electronic-vibrational dynamics simulations of molecular systems poses significant challenges when dealing with realistic environments composed of numerous vibrational modes. Here, we introduce a technique for the construction of effective phonon spectral densities that capture accurately open-system dynamics over a finite time interval of interest. When combined with existing nonperturbative simulation tools, our approach can reduce significantly the computational costs associated with many-body open-system dynamics.

To B(enign) or Not to B: functionalisation of variant in a mild form of argininosuccinate lyase deficiency identified through newborn screening.

Argininosuccinate lyase (ASL) deficiency is an autosomal recessive disorder of the urea cycle with a diverse spectrum of clinical presentation that is detectable in newborn screening. We report an 8-year-old girl with ASL deficiency who was detected through newborn screening and was confirmed using biochemical and functional assay. She is compound heterozygous for a likely pathogenic variant NM_000048.4(ASL):c.283C>T (p.Arg95Cys) and a likely benign variant NM_000048.4(ASL): c.1319T>C (p.Leu440Pro). Functional characterisation of the likely benign genetic variant in ASL was performed. Genomic sequencing was performed on the index patient presenting with non-specific symptoms of poor feeding and lethargy and shown to have increased serum and urine argininosuccinic acid. Functional assay using HEK293T cell model was performed. ASL enzymatic activity was reduced for Leu440Pro. This study highlights the role of functional testing of a variant that may appear benign in a patient with a phenotype consistent with ASL deficiency, and reclassifies NM_000048.4(ASL): c.1319T>C (p.Leu440Pro) variant as likely pathogenic.

Unusual Pheochromocytoma Presentation: From Dysuria to Catecholamine Crisis.

Pheochromocytomas are catecholamine-secreting tumors that can present as a surgical emergency, with a mortality rate as high as 15%. When these lesions present as a crisis, diagnosis and management can be very challenging, given the profound physiologic consequences, such as cardiovascular collapse or multiple organ failure, occurring over a rapid time frame. We describe an unusual case of a pheochromocytoma presenting with urinary frequency and subsequent shock and tumor hemorrhage following a urological procedure. Our patient was successfully managed with resuscitation and appropriate blood pressure control to stabilize hemodynamics prior to proceeding with open adrenalectomy. Furthermore, our patient presented initially with urinary symptoms, which has not been described as an initial presentation of pheochromocytoma. This case brings important learning points regarding unusually presenting pheochromocytomas and emergency management to improve patient survival.

Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.

Merkel Cell Carcinoma (MCC) is a highly aggressive neuroendocrine cutaneous malignancy arising from either ultraviolet-induced mutagenesis or Merkel cell polyomavirus (MCPyV) integration. It is the only known neuroendocrine tumor (NET) with a virus etiology. Despite extensive research, our understanding of the molecular mechanisms driving the transition from normal cells to MCC remains limited. To address this knowledge gap, we assessed the impact of inducible MCPyV T antigens into normal human fibroblasts by performing RNA sequencing. Our findings suggested that the WNT signaling pathway plays a critical role in the development of MCC. To test this model, we bioinformatically evaluated various perturbagens for their ability to reverse the MCC gene expression signature and identified pyrvinium pamoate, an FDA-approved anthelminthic drug known for its anti-tumor potential in multiple cancers. Leveraging transcriptomic, network, and molecular analyses, we found that pyrvinium effectively targets multiple MCC vulnerabilities. Specifically, pyrvinium not only reverses the neuroendocrine features of MCC by modulating canonical and non-canonical WNT signaling pathways but also inhibits cancer cell growth by activating the p53-mediated apoptosis pathway, disrupting mitochondrial function, and inducing endoplasmic reticulum (ER) stress. Pyrvinium also effectively inhibits tumor growth in an MCC mouse xenograft model. These findings offer new avenues for the development of therapeutic strategies for neuroendocrine cancer and highlight the utility of pyrvinium as a potential treatment for MCC.

Right hemicolectomy for colon cancer: does the anastomotic configuration affect short-term outcomes?

OBJECTIVES: Right hemicolectomy is a common colorectal operation for resection of cancers of the right colon. The ileocolic anastomosis may be created using a stapled end-to-side, stapled side-to-side or handsewn technique. Anastomotic leak and post-operative bleeding are uncommon but serious causes of morbidity and mortality, while post-operative ileus contributes to prolonged length of stay. The aim of this study was to evaluate differences in short-term outcomes between different anastomotic configurations following right hemicolectomy for colon cancer. METHODS: We conducted a retrospective study using data from the Bowel Cancer Outcomes Registry (BCOR), including 94 hospitals across Australia and New Zealand, of all patients who underwent right hemicolectomy or extended right hemicolectomy for colon cancer with formation of a primary anastomosis between 2007 and 2021. RESULTS: We included 8164 patients in the analysis. There was no significant difference in rates of anastomotic leak and anastomotic bleeding based on anastomotic technique. A stapled end-to-side anastomosis was associated with a lower rate of post-operative ileus than stapled side-to-side anastomosis (6.5% vs. 7.2%; P = 0.03). CONCLUSION: Both handsewn and stapled anastomosis techniques may be utilized for oncologic right hemicolectomy, with comparable rates of anastomotic leak and post-operative bleeding. Stapled end-to-side anastomosis resulted in lower rates of prolonged ileus compared to stapled side-to-side anastomoses.

Cardiovascular disease risk assessment using a deep-learning-based retinal biomarker: a comparison with existing risk scores.

Aims: This study aims to evaluate the ability of a deep-learning-based cardiovascular disease (CVD) retinal biomarker, Reti-CVD, to identify individuals with intermediate- and high-risk for CVD. Methods and results: We defined the intermediate- and high-risk groups according to Pooled Cohort Equation (PCE), QRISK3, and modified Framingham Risk Score (FRS). Reti-CVD's prediction was compared to the number of individuals identified as intermediate- and high-risk according to standard CVD risk assessment tools, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the results. In the UK Biobank, among 48 260 participants, 20 643 (42.8%) and 7192 (14.9%) were classified into the intermediate- and high-risk groups according to PCE, and QRISK3, respectively. In the Singapore Epidemiology of Eye Diseases study, among 6810 participants, 3799 (55.8%) were classified as intermediate- and high-risk group according to modified FRS. Reti-CVD identified PCE-based intermediate- and high-risk groups with a sensitivity, specificity, PPV, and NPV of 82.7%, 87.6%, 86.5%, and 84.0%, respectively. Reti-CVD identified QRISK3-based intermediate- and high-risk groups with a sensitivity, specificity, PPV, and NPV of 82.6%, 85.5%, 49.9%, and 96.6%, respectively. Reti-CVD identified intermediate- and high-risk groups according to the modified FRS with a sensitivity, specificity, PPV, and NPV of 82.1%, 80.6%, 76.4%, and 85.5%, respectively. Conclusion: The retinal photograph biomarker (Reti-CVD) was able to identify individuals with intermediate and high-risk for CVD, in accordance with existing risk assessment tools.

Surgical management of splenic flexure cancer: is there an optimal technique? A bi-national registry analysis.

BACKGROUND: Splenic flexure tumours (SFC) are uncommon and present at more advanced disease stages. The optimal surgical technique for SFC remains controversial. We sought to compare the short-term outcomes of a left hemicolectomy (LHC) versus an extended resection (subtotal colectomy, STC) for SFCs. METHODS: A retrospective analysis using the Binational Colorectal Cancer Audit (BCCA) registry was performed. All patients with SFC who underwent elective or emergency surgery for a SFC between 2010 and 2021 were included. Primary outcomes included short-term inpatient complications. Secondary outcomes included survival outcomes. RESULTS: Six hundred and ninety-nine patients underwent resections for SFCs. A LHC was more common, performed in 64.1%. Patients having a LHC were significantly older, with proportionally more LHCs done laparoscopically. Overall grade III/IV complications were similar between both operations. Prolonged ileus and return to theatre were significantly higher in patients undergoing a STC. On multivariate analysis, anastomotic leak and overall grade III/IV complications were not independently associated with the type of operation. There was no difference in medial survival based on type of operation. Higher tumour stage (Stage III/IV) were independently associated with worse survival. CONCLUSION: Segmental and extended resections are both oncologically sound procedures for SFCs. Segmental resections are associated with lower rates of prolonged ileus.

Composite Cold-Formed Steel Beams with Diagonal Rebars for Earthquake-Resistant Buildings.

The construction industry is on the lookout for cost-effective structural members that are also environmentally friendly. Built-up cold-formed steel (CFS) sections with minimal thickness can be used to make beams at a lower cost. Plate buckling in CFS beams with thin webs can be avoided by using thick webs, adding stiffeners, or strengthening the web with diagonal rebars. When CFS beams are designed to carry heavy loads, their depth logically increases, resulting in an increase in building floor height. The experimental and numerical investigation of CFS composite beams reinforced with diagonal web rebars is presented in this paper. A total of twelve built-up CFS beams were used for testing, with the first six designed without web encasement and the remaining six designed with web encasement. The first six were constructed with diagonal rebars in the shear and flexure zones, while the other two with diagonal rebars in the shear zone, and the last two without diagonal rebars. The next set of six beams was constructed in the same manner, but with a concrete encasement of the web, and all the beams were then tested. Fly ash, a pozzolanic waste byproduct of thermal power plants, was used as a 40% replacement for cement in making the test specimens. CFS beam failure characteristics, load-deflection behavior, ductility, load-strain relationship, moment-curvature relationship, and lateral stiffness were all investigated. The results of the experimental tests and the nonlinear finite element analysis performed in ANSYS software were found to be in good agreement. It was discovered that CFS beams with fly ash concrete encased webs have twice the moment resisting capacity of plain CFS beams, resulting in a reduction in building floor height. The results also confirmed that the composite CFS beams have high ductility, making them a reliable choice for earthquake-resistant structures.

Mechanical bowel preparation with pre-operative oral antibiotics in elective colorectal resections: an Australian single institution experience.

BACKGROUND: Anastomotic leaks (AL) and surgical site infections (SSI) are serious complications after colorectal resection. Studies have shown the benefits of pre-operative oral antibiotics (OAB) with mechanical bowel preparation (MBP) in reducing AL and SSI rates. We aim to investigate our experience with the short-term outcomes of AL and SSI following elective colorectal resections in patients receiving OAB with MBP versus MBP only. METHODS: A retrospective analysis was performed from our database for patients who underwent elective colorectal resection between January 2019 and November 2021. Prior to August 2020, OAB was not used as part of MBP. After 2020, Neomycin and Metronidazole were used in conjunction with MBP. We evaluated differences in AL and SSI between both groups. RESULTS: Five hundred and seventeen patients were included from our database with 247 having MBP while 270 had OAB and MBP. There was a significantly lower rate of AL in patients receiving MBP and OAB as compared to MBP alone (0.4% versus 3.0%, P-value = 0.03). The SSI rate at our institution was 4.4%. It was lower in patients with MBP and OAB as compared to MBP alone, but this was not clinically significant (3.3% versus 5.7%, P-value = 0.19). CONCLUSION: The association in the reduction of AL with the addition of OAB to the MBP protocol seen here reinforces the need for future randomized controlled trials in the Australasian context. We recommend colorectal institutions in Australian and New Zealand consider OAB with MBP as part of their elective colorectal resection protocol.

The Network Zoo: a multilingual package for the inference and analysis of gene regulatory networks.

Inference and analysis of gene regulatory networks (GRNs) require software that integrates multi-omic data from various sources. The Network Zoo (netZoo; netzoo.github.io) is a collection of open-source methods to infer GRNs, conduct differential network analyses, estimate community structure, and explore the transitions between biological states. The netZoo builds on our ongoing development of network methods, harmonizing the implementations in various computing languages and between methods to allow better integration of these tools into analytical pipelines. We demonstrate the utility using multi-omic data from the Cancer Cell Line Encyclopedia. We will continue to expand the netZoo to incorporate additional methods.

Rare dual surgical pathology at emergency laparotomy: a case report of concurrent small bowel obstruction and appendicitis.

Dual surgical pathology at emergency laparotomy is an uncommon finding outside of trauma scenarios. There is a scarcity of case reports of concomitant small bowel obstruction and appendicitis at laparotomy, likely in part because of advancements in investigative tools, diagnostic processes and the ready availability of medical care, which is demonstrated by harrowing statistics from developing nations where these factors are lacking. However, despite these advancements, initial diagnosis of dual pathology can be difficult. We report a case of concurrent small bowel obstruction and occult appendicitis discovered at emergency laparotomy in a previously well female with a virgin abdomen.

Structural and functional integration of human forebrain organoids with the injured adult rat visual system.

Brain organoids created from human pluripotent stem cells represent a promising approach for brain repair. They acquire many structural features of the brain and raise the possibility of patient-matched repair. Whether these entities can integrate with host brain networks in the context of the injured adult mammalian brain is not well established. Here, we provide structural and functional evidence that human brain organoids successfully integrate with the adult rat visual system after transplantation into large injury cavities in the visual cortex. Virus-based trans-synaptic tracing reveals a polysynaptic pathway between organoid neurons and the host retina and reciprocal connectivity between the graft and other regions of the visual system. Visual stimulation of host animals elicits responses in organoid neurons, including orientation selectivity. These results demonstrate the ability of human brain organoids to adopt sophisticated function after insertion into large injury cavities, suggesting a translational strategy to restore function after cortical damage.

Spin-Dependent Momentum Conservation of Electron-Phonon Scattering in Chirality-Induced Spin Selectivity.

The elucidation of the mechanisms underpinning chirality-induced spin selectivity remains an outstanding scientific challenge. Here we consider the role of delocalized phonon modes in electron transport in chiral structures and demonstrate that spin selectivity can originate from spin-dependent energy and momentum conservation in electron-phonon scattering events. While this mechanism is robust to the specific nature of the vibrational modes, the degree of spin polarization depends on environmental factors, such as the specific temperature and phonon relaxation rates, as well as the presence of external driving fields. This parametric dependence is used to present experimentally testable predictions of our model.

Does intra-operative humidification with warmed CO2 reduce surgical site infection in open colorectal surgery? A randomized control trial.

BACKGROUNDS: Surgical site infections (SSI) are a significant cause of postoperative morbidity and mortality, contributing to a considerable financial burden on the healthcare system. Insufflation of the open surgical wound with warm, humidified carbon dioxide (CO2 ) is a novel measure aimed to reduce SSI. The local atmosphere of warm, humidified CO2 within the open surgical wound is proposed to decrease airborne contamination, bacterial growth, desiccation, and heat loss while improving tissue oxygenation and perfusion. This randomized controlled trial evaluates the impact of the HumiGard™ surgical humidification system on the incidence of SSI in patients undergoing open colorectal surgery. METHODS: We conducted a multi-site single-blinded randomized control trial on patients undergoing elective or emergency laparotomy at a single tertiary Colorectal Surgery service. The primary outcome measure was the incidence of SSI, with secondary outcomes including ICU length of stay (LOS), total LOS and mean core temperature. RESULTS: Patients who received HumiGard™ had a lower incidence of SSI, although this did not reach statistical significance (4.5% for treatment group versus 13.0% for control group; P = 0.092). There was no significant difference in ICU LOS or total LOS between cohorts. The HumiGard™ group had a higher mean core temperature than the control at the end of surgery (P < 0.001). CONCLUSION: The present study could not confirm that utilization of warm, humidified CO2 with HumiGard™ reduces SSI in open colorectal surgery. Further research is indicated to validate and extend these findings.

Examining Miliary Disease Etiology in a Coccidioides-Endemic Center: A Retrospective Cohort Study.

Background: A miliary pattern on chest imaging is often attributed to tuberculosis (TB) infection. However, a myriad of conditions can cause a miliary pattern, many of which are imminently life-threatening. Research Question: The primary aim of our study is to elucidate the potential causes of miliary chest imaging patterns to improve workup and empiric therapy selection. The secondary aims are to discern the predictors of miliary disease etiology and to determine whether appropriate empiric antimicrobial therapies were given. Study Design and Methods: In this retrospective cohort study, we searched a radiology database for patients with chest imaging studies described by the word "miliary". Subjects were excluded if they were under 18 years of age and if there were insufficient objective data to support a miliary disease etiology. A radiologist independently reviewed all imaging studies, and studies that did not appear to have a true miliary pattern were excluded. The collected data include patient demographics, immunocompromising risk factors, conditions associated with miliary disease, ß-D-glucan levels, serum eosinophil count, and empiric therapies received. Results: From our 41-patient cohort, 22 patients (53.7%) were clinically diagnosed with coccidioidomycosis, 8 (19.5%) with TB, 7 (17.1%) with metastatic solid cancer, 1 (2.4%) with lymphoma, 1 (2.4%) with other (Mycobacterium simiae), and 3 (7.3%) with unknown diseases (the sum equals 42 patients because one individual was diagnosed with both coccidioidomycosis and TB). All six patients with greater than 500 eosinophils/µL were diagnosed with coccidioidomycosis. Of the 22 patients diagnosed with coccidioidomycosis, 20 (90.91%) were empirically treated with an antifungal regimen. Of the eight patients with TB, six were empirically treated for TB. Interpretation: Based on our data from a Coccidioides-endemic region with close proximity to tuberculosis-endemic areas, the leading cause of miliary disease is coccidioidomycosis, although TB and cancer are also common etiologies. Serum eosinophilia and elevated ß-D-glucan levels were strongly predictive of coccidioidomycosis in our patient cohort with a miliary chest imaging pattern.

A State of the Art Review of Fillet Welded Joints.

Fillet welded joints are commonly used in steel structures for various engineering applications such as buildings, bridges, railways, ships, and marine structures. Fillet welded joints are generally subjected to static and fatigue loading, resulting in failures of such welded joints. A number of experimental and numerical investigations on the strength and failure behaviour of fillet welded joints have been published. This paper presents a comprehensive review of research results on the static strength, fatigue life, and thermal performance of fillet welded joints. The review covers the various influential factors, such as loading direction, weld geometry, grades of steel, filler materials, welding process, weld penetration, strength mismatch of weld metal, and post-welded treatment. In total, 100 papers were critically reviewed, which were published from 1970 till date. The key findings and research developments on fillet welded joints are summarised. It was found that the transverse fillet welded joints have a higher static strength than the longitudinal fillet welded joints. Filler materials, post-welded treatment, and penetration of weld metal can offer significant strength enhancements in terms of their static and fatigue strength. Lastly, research gaps have been found in the existing body of knowledge, which will help guide future research.

Fingerprint and Universal Markovian Closure of Structured Bosonic Environments.

We exploit the properties of chain mapping transformations of bosonic environments to identify a finite collection of modes able to capture the characteristic features, or fingerprint, of the environment. Moreover we show that the countable infinity of residual bath modes can be replaced by a universal Markovian closure, namely, a small collection of damped modes undergoing a Lindblad-type dynamics whose parametrization is independent of the spectral density under consideration. We show that the Markovian closure provides a quadratic speedup with respect to standard chain mapping techniques and makes the memory requirement independent of the simulation time, while preserving all the information on the fingerprint modes. We illustrate the application of the Markovian closure to the computation of linear spectra but also to nonlinear spectral response, a relevant experimentally accessible many body coherence witness for which efficient numerically exact calculations in realistic environments are currently lacking.

Smart-Home Concept for Remote Monitoring of Instrumental Activities of Daily Living (IADL) in Older Adults with Cognitive Impairment: A Proof of Concept and Feasibility Study.

Assessment of instrumental activities of daily living (IADL) is essential for the diagnosis and staging of dementia. However, current IADL assessments are subjective and cannot be administered remotely. We proposed a smart-home design, called IADLSys, for remote monitoring of IADL. IADLSys consists of three major components: (1) wireless physical tags (pTAG) attached to objects of interest, (2) a pendant-sensor to monitor physical activities and detect interaction with pTAGs, and (3) an interactive tablet as a gateway to transfer data to a secured cloud. Four studies, including an exploratory clinical study with five older adults with clinically confirmed cognitive impairment, who used IADLSys for 24 h/7 days, were performed to confirm IADLSys feasibility, acceptability, adherence, and validity of detecting IADLs of interest and physical activity. Exploratory tests in two cases with severe and mild cognitive impairment, respectively, revealed that a case with severe cognitive impairment either overestimated or underestimated the frequency of performed IADLs, whereas self-reporting and objective IADL were comparable for the case with mild cognitive impairment. This feasibility and acceptability study may pave the way to implement the smart-home concept to remotely monitor IADL, which in turn may assist in providing personalized support to people with cognitive impairment, while tracking the decline in both physical and cognitive function.