Bis(bicyclo[1.1.1]pentyl)chlorophosphine as a Precursor for the Preparation of Bis(bicyclo[1.1.1]pentyl)phosphines.

Dialkylchlorophosphines are among the most versatile building blocks for tertiary phosphine ligands, but their synthesis relies on the nucleophilic substitution of PCl3, leaving substituents that require P-H precursors largely inaccessible. The primary phosphine reagent iPr2NPH2·BH3 can serve as a doubly protected PH2Cl proxy, enabling the synthesis of bis(bicyclo[1.1.1]pentyl)chlorophosphine (Bcp2PCl) for the first time. Bcp2PCl serves as a general reagent for the preparation of a family of bis(bicyclo[1.1.1]pentyl) alkyl- and arylphosphines, including new members of privileged phosphine ligand scaffolds.

Dialysis disequilibrium syndrome in neurosurgery: literature review and illustrative case example.

INTRODUCTION: The dialysis disequilibrium syndrome (DDS) is a complication in those undergoing dialysis for chronic kidney disease (CKD) or acute kidney injury (AKI), characterized by nonspecific symptoms that may progress to coma and death secondary to cerebral edema. This syndrome is associated with rapid change in electrolytes during dialysis with changes in intracranial pressure (ICP) and may have a higher incidence in the elderly neurosurgical patient population. METHODS: Literature review and illustrative case example. RESULTS: A 62-year-old female presented with acute mental status change during hemodialysis (HD), with a history of a nonsurgical acute subdural hematoma (SDH) 10 days prior. Imaging showed a conversion of the acute SDH to chronic SDH of 12.2 mm in size with a 14.1 midline shift, for which she underwent a hemicraniectomy with SDH evacuation, with a gradual return to baseline. The literature review identified 5 publications meeting the inclusion criteria. Major theories of DDS include a reverse urea effect, intracerebral acidosis, idiogenic osmoles, and local inflammation. This complication may occur more frequently in the elderly neurosurgical patient population, likely due to age-related comorbidities, preexisting neurological insult, and increased permeability of the blood-brain barrier (BBB), leading to cerebral edema. CONCLUSION: DDS is a rare and potentially fatal complication of HD that may have a higher incidence in the elderly neurosurgical patient population, yet remains to be fully understood. Further study is recommended to characterize the pathophysiological mechanism and incidence of DDS in neurosurgical patients.

An analysis of iris pattern as a risk factor for skin cancer development in immunosuppressed renal transplant recipients.

INTRODUCTION: Renal transplant recipients are at increased risk of keratinocyte skin cancers with a tendency to have multiple, aggressive and difficult to treat tumours. The eye and the skin share the same embryological ectoderm. Iris pattern has recently been reported as a predictive risk factor for skin cancer in non-immunosuppressed Southern European (Grigore et al., J Eur Acad Dermatol Venereol, 2018, 1662) and Irish populations (Ridge et al., J Eur Acad Dermatol Venereol, 2022, e542). AIMS: To analyse if an individual's iris pattern is an independent risk factor for the development of keratinocyte skin cancers in renal transplant recipients. METHODS: Iris patterns of 110 renal transplant recipients were evaluated using the Simionescu visual three-step technique (iris periphery, colarette and iris freckling [Simionescu et al., Ann Res Rev Biol, 2014, 2525]). Established risk factors for skin cancer in transplant patients were recorded as confounding factors. RESULTS: Observational cross-sectional study including 110 renal transplant population. Thirty-one participants had skin cancer. In the skin cancer group, iris periphery was blue/grey in 74.3% (p = 0.053, OR 2.5), the colarette was light brown in 57.1% (p < 0.0043) and iris freckles were present in 55%(p = 0.044). Dark brown and blue colarettes were observed in controls. Binary Logistic Regression analysis showed light brown colarette is a significant independent risk factor for skin cancer (OR 4.54, p < 0.02, CI 1.56-10.57). CONCLUSION: Within this renal transplant population a blue iris periphery, light brown colarette and presence of freckling confers an independent risk for keratinocyte skin cancer. Iris pattern is a useful tool for identification of transplant patients at risk of keratinocyte skin cancer and an easy-to-use technique for risk evaluation in this cohort. This is the first study looking at iris pattern and keratinocyte skin cancer risk in renal transplant population.

Novel usage of everolimus-eluting coronary stent for intracranial atherosclerotic disease: a technical report and case series.

Objectives: This report describes the use of an Everolimus-eluting stent (Xience Skypoint stent) for the treatment of medically-refractory ICAD. Design: Retrospective, case-series. Setting: In-hospital patients. Participants: All patients in this report had a history of stroke secondary to ICAD. All patients failed aggressive medical treatments and had recurrence of symptoms despite anticoagulation or dual-antiplatelet therapy plus a statin. Diagnostic angiogram in each case showed severe vessel stenosis, therefore patients were recommended for intracranial artery stenting. Main outcome measures: Technical feasibility of deploying Xience Skypoint stent for treatmet of ICAD. Results: The Xience Skypoint stent was safely and effectively deployed in the vertebral artery (x1) and the internal carotid artery (x2) using trans-ulnar (x1), trans-radial (x1), and trans-femoral (x1) approaches without the use of an intermediate catheter. Conclusion: Second-generation EES such as Xience Skypoint may be utilized for treatment of medically-refractory ICAD. This technical report serves as a proof of concept for further studies analysing long-term safety and efficacy of such stents for treatment of ICAD.

Hydrogen-Atom-Transfer-Initiated Radical/Polar Crossover Annulation Cascade for Expedient Access to Complex Tetralins.

A radical/polar crossover annulation between allyl-substituted arenes and electron-deficient alkenes is described. Cobalt-catalyzed hydrogen atom transfer (HAT) facilitates tandem radical C-C bond formation that generates functionalized tetralin products in the face of potentially problematic hydrofluorination, hydroalkoxylation, hydrogenation, alkene isomerization, and radical polymerization reactions. The reactions proceed under mild conditions that tolerate many functional groups, leading to a broad substrate scope. This powerful ring-forming reaction very quickly assembles complex tetralins that are the formal products of the largely infeasible Diels-Alder cycloadditions of styrenes.

Tris(bicyclo[1.1.1]pentyl)phosphine: An Exceptionally Small Tri-tert-alkylphosphine and Its Bis-Ligated Pd(0) Complex.

Tris(bicyclo[1.1.1]pentyl)phosphine can be prepared by radical addition of PH3 to [1.1.1]propellane, giving the smallest tri-tert-alkylphosphine known. PBcp3 is substantially smaller than PCy3 and is comparable in electron-donating power to PEt3. It gives a bis-ligated Pd(0) complex Pd(PBcp3)2 that is exceptionally reactive toward alkyl halide oxidative addition and functions as a general ligand for palladium-catalyzed cross-coupling of sp3 electrophiles. Radical addition of [1.1.1]propellane to phenylphosphine gives the bis(bicyclo[1.1.1]pentyl)phosphine derivative PBcp2Ph, illustrating the generality of this approach to bicyclopentylphosphine synthesis.

A Synthesis of Alstonlarsine A via Alstolucines†B and F Demonstrates the Chemical Feasibility of a Proposed Biogenesis.

We offer a new biogenetic proposal for the origin of the complex alkaloid alstonlarsine A, through rearrangement of the Strychnos alkaloids alstolucines B and F. Further, we provide evidence of the chemical feasibility of this proposal in the facile conversion of synthetic alstolucines into alstonlarsine A through a short, efficient sequence of N-methylation, ß-elimination, and a cascade 1,7-hydride shift/Mannich cyclization. We believe that this is the first biogenetic proposal involving the "tert-amino effect", a hydride-shift-based internal redox trigger of a Mannich cyclization. A further interesting feature of the cascade is that its stereochemical outcome most likely originates in conformational preferences during the hydride shift.

Analysis of Circulating Tumor DNA to Predict Risk of Recurrence in Patients With Esophageal and Gastric Cancers.

PURPOSE: Circulating tumor DNA (ctDNA) analyses allow for postoperative risk stratification in patients with curatively treated colon and breast cancers. Use of ctDNA in esophagogastric cancers (EGC) is less characterized and could identify high-risk patients who have been treated with curative intent. METHODS: In this retrospective analysis of real-world data, ctDNA levels were analyzed in the preoperative, postoperative, and surveillance settings in patients with EGC using a personalized multiplex polymerase chain reaction-based next-generation sequencing assay. Plasma samples (n = 943) from 295 patients at > 70 institutions were collected before surgery, postoperatively, and/or serially during routine clinical follow-up from September 19, 2019, to February 21, 2022. ctDNA detection was annotated to clinicopathologic features and recurrence-free survival. RESULTS: A total of 295 patients with EGC were analyzed, and 212 patients with stages I-III disease were further explored. Pretreatment ctDNA was detected in 96% (23/24) of patients with preoperative time points. Postoperative ctDNA was detected in 23.5% (16/68) of patients with stage I-III EGC within 16 weeks (molecular residual disease window) after surgery without receiving systemic therapy. ctDNA detection at any time point after surgery (hazard ratio [HR], 23.6; 95% CI, 10.2 to 66.0; P < .0001), within the molecular residual disease window (HR, 10.7; 95% CI, 4.3 to 29.3; P < .0001), and during the surveillance period (HR, 17.7; 95% CI, 7.3 to 50.7; P < .0001) was associated with shorter recurrence-free survival. In multivariable analysis, ctDNA status and clinical stage of disease were independently associated with outcomes. CONCLUSION: Using real-world data, we demonstrate that postoperative tumor-informed ctDNA detection in EGC is feasible and allows for enhanced patient risk stratification and prognostication during curative-intent therapy.

Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 (MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients.

Background: Renal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the Methylenetetrahydrofolate Reductase (MTHFR) gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs. Objective: We sought to find further genetic variation in MTHFR and overlap genes that may be associated with a diagnosis of KC in RTRs. Methods: Genotyping of a combined RTR population (n = 821) from two centres, Ireland (n = 546) and the USA (n = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the MTHFR gene and seven in the overlap gene MTHFR Chloride transport protein 6 (CLCN6) were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model. Results: Polymorphism at MTHFR CLCN6 (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17-1.91, p < 0.00061) and cSCC (HR 1.63, 95% CI 1.14-2.34, p = 0.007). A separate SNP, MTHFR C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05-1.63, p = 0.016), but not American RTRs. Conclusions: We report the association of a SNP in the MTHFR overlap gene, CLCN6 and KC in a combined RTR population. While the exact function of CLCN6 is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.

Update on intrathecal management of cerebral vasospasm: a systematic review and meta-analysis.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) accounts for a relatively small portion of strokes but has the potential to cause permanent neurological deficits. Vasospasm with delayed ischemic neurological deficit is thought to be responsible for much of the morbidity associated with aSAH. This has illuminated some treatment options that have the potential to target specific components of the vasospasm cascade. Intrathecal management via lumbar drain (LD) or external ventricular drain (EVD) offers unique advantages in this patient population. The aim of this review was to provide an update on intrathecal vasospasm treatments, emphasizing the need for larger-scale trials and updated protocols using data-driven evidence. METHODS: A search of PubMed, Ovid MEDLINE, and Cochrane databases included the search terms (subarachnoid hemorrhage) AND (vasospasm OR delayed cerebral ischemia) AND (intrathecal OR intraventricular OR lumbar drain OR lumbar catheter) for 2010 to the present. Next, a meta-analysis was performed of select therapeutic regimens. The primary endpoints of analysis were vasospasm, delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome. RESULTS: Twenty-nine studies were included in the analysis. There were 10 studies in which CSF drainage was the primary experimental group. Calcium channel antagonists were the focus of 7 studies. Fibrinolytics and other vasodilators were each examined in 6 studies. The meta-analysis included studies examining CSF drainage via LD (n = 4), tissue plasminogen activator in addition to EVD (n = 3), intraventricular nimodipine (n = 2), and cisternal magnesium (n = 2). Results showed that intraventricular nimodipine decreased vasospasm (OR 0.59, 95% CI 0.37-0.94; p = 0.03). Therapies that significantly reduced DCI were CSF drainage via LD (OR 0.47, 95% CI 0.25-0.88; p = 0.02) and cisternal magnesium (OR 0.27, 95% CI 0.07-1.02; p = 0.05). CSF drainage via LD was also found to significantly reduce the incidence of cerebral infarction (OR 0.35, 95% 0.24-0.51; p < 0.001). Lastly, functional outcome was significantly better in patients who received CSF drainage via LD (OR 2.42, 95% CI 1.39-4.21; p = 0.002). CONCLUSIONS: The authors' results showed that intrathecal therapy is a safe and feasible option following aSAH. It has been shown to attenuate cerebral vasospasm, reduce the incidence of DCI, and improve clinical outcome. The authors support the use of intrathecal management in the prevention and rescue management of cerebral vasospasm. More randomized controlled trials are warranted to determine the best combination of pharmaceutical agents and administration route in order to formulate a standardized treatment approach.

Fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography for staging of canine insulinoma: 3 cases (2019-2020).

OBJECTIVES: Canine insulinomas are uncommon malignant functional pancreatic neuroendocrine tumours with a high metastatic rate. Diagnostic imaging aids with staging and surgical planning of these tumours; however, identification is unpredictable across modalities. High-grade human pancreatic neuroendocrine tumours display increased avidity on 18 F-fluorodeoxyglucose positron emission tomography-CT. MATERIALS AND METHODS: Dogs with clinicopathologic findings consistent with pancreatic insulinoma were prospectively enrolled. Patients underwent 18 F-fluorodeoxyglucose positron emission tomography-CT and CT angiography, followed by exploratory laparotomy. RESULTS: Three patients met the inclusion criteria and had histologically confirmed insulinomas. Both metastatic lesions in patient 1 were mildly avid (SUVmax 2.79 and 3.01). In patient 2, the primary pancreatic insulinoma was minimally avid (SUVmax 2.16). The primary pancreatic lesion in patient 3 had similar avidity to normal pancreatic parenchyma (SUVmax 1.54) and was undetected on 18 F-fluorodeoxyglucose positron emission tomography-CT. Insulinomas demonstrated variable attenuation and contrast enhancement patterns on CT angiography and certain lesions were more conspicuous than on 18 F-fluorodeoxyglucose positron emission tomography-CT. Two metastatic lesions not visible on either imaging modality were discovered in patient 2 at surgery. CLINICAL SIGNIFICANCE: Canine insulinomas were inconsistently avid on 18 F-fluorodeoxyglucose positron emission tomography-CT. This finding is likely attributable to the confounding clinicopathological features and multifaceted transformation of these tumours, in addition to the influence of variable tumour size, composition and vascularity. Unpredictable tumoural avidity limits the value of 18 F-fluorodeoxyglucose positron emission tomography-CT for staging canine insulinomas.

Reported incidence and treatment modalities of giant cerebral aneurysms in the pediatric population: A systematic review and illustrative case report.

Giant intracranial aneurysms represent a complex pathology that pose challenges for management, especially in the pediatric population. With emerging endovascular techniques, combined endovascular and open surgical approaches may be a favorable alternative for complex cases. In this systematic review, we characterize the treatment modalities of giant aneurysms in the pediatric population and provide an update on the number of giant aneurysms reported in the literature by anatomic location. We conducted a literature search of PubMed, Embase, and Medline databases with the following terms: 'pediatric' AND 'giant' AND 'intracranial aneurysm.' Studies were included if data on treatment modality and aneurysm location were available for pediatric patients with giant intracranial aneurysms. The literature search yielded a total of 188 papers, with 82 pediatric patients from 33 articles ultimately meeting inclusion criteria. There were significantly more male than female patients (p = 0.011), with 52 and 29 respectively. Patients presenting with a ruptured aneurysm were significantly younger than patients presenting without rupture (p = 0.018), with a median age of 8.0 and 12.0 years, respectively. There were 45 giant aneurysms reported in the anterior circulation and 37 in the posterior circulation. Anterior aneurysms were most often treated with surgical approaches, while posterior aneurysms were typically treated with endovascular interventions (p = 0.002). Although combined surgical and endovascular approaches were the least frequently utilized, we suggest a combined approach may be particularly useful for patients with complex cases that require a management plan tailored to their needs.

Aquila_stLFR: diploid genome assembly based structural variant calling package for stLFR linked-reads.

Motivation: Identifying structural variants (SVs) is critical in health and disease, however, detecting them remains a challenge. Several linked-read sequencing technologies, including 10X Genomics, TELL-Seq and single tube long fragment read (stLFR), have been recently developed as cost-effective approaches to reconstruct multi-megabase haplotypes (phase blocks) from sequence data of a single sample. These technologies provide an optimal sequencing platform to characterize SVs, though few computational algorithms can utilize them. Thus, we developed Aquila_stLFR, an approach that resolves SVs through haplotype-based assembly of stLFR linked-reads. Results: Aquila_stLFR first partitions long fragment reads into two haplotype-specific blocks with the assistance of the high-quality reference genome, by taking advantage of the potential phasing ability of the linked-read itself. Each haplotype is then assembled independently, to achieve a complete diploid assembly to finally reconstruct the genome-wide SVs. We benchmarked Aquila_stLFR on a well-studied sample, NA24385, and showed Aquila_stLFR can detect medium to large size deletions (50 bp-10 kb) with high sensitivity and medium-size insertions (50 bp-1 kb) with high specificity. Availability and implementation: Source code and documentation are available on https://github.com/maiziex/Aquila_stLFR. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

A retrospective review of pregnancies on biologics for the treatment of dermatological conditions.

Psoriasis often first presents in young adulthood, with the average age of diagnosis in women being 28 years, thus in the prime reproductive years. In addition, approximately 50% of pregnancies worldwide are unplanned. Although biologic therapies have revolutionized the treatment of moderate-to-severe psoriasis, there are no controlled studies of biologics in pregnant women. The increasing use of these agents in women of childbearing age highlights the need to further assess their safety during pregnancy. Postmarketing experience regarding the safety of these drugs is accumulating and being published, with largely reassuring results. We present our real-world experience of 17 pregnancies occurring in women on treatment with biologic agents for dermatological conditions to further add to the body of knowledge.

A retrospective analysis of stereotactic body radiation therapy for canine heart base tumors: 26 cases.

INTRODUCTION: This study retrospectively evaluated outcomes and adverse radiation effects (AREs) associated with stereotactic body radiation therapy (SBRT) for canine heart base tumors (HBTs). A secondary aim was to identify any demographic or echocardiographic factors that might determine which dogs would most benefit from SBRT. ANIMALS: Twenty-six dogs that received SBRT for an imaging-based diagnosis of a HBT were evaluated. METHODS: Twenty-three dogs were treated with three fractions of 10 Gy delivered daily or every other day. The remaining 3 dogs received variable protocols of one to five fractions. Demographic, echocardiographic, and radiographic information, AREs, and treatment responses were collected. Correlations of these data with survival time were evaluated. RESULTS: The median overall survival time was 404 days (95% confidence interval: 239-554 days). The majority of dogs experienced a partial response (25%) or stable disease (60%) for a median duration of 333 days (95% confidence interval: 94-526 days). Three dogs had progressive disease within six months of SBRT. Radiographic pneumonitis was identified in 7 of 23 dogs, and clinical pneumonitis was identified in 4 dogs. No other AREs were noted. The rate of distant metastasis was 13%. On multivariate analysis, it was found that vena caval obstruction, supraventricular and ventricular arrhythmias, clinical signs, and enlarged locoregional lymph nodes at presentation were negatively associated with survival time. CONCLUSIONS: Stereotactic body radiation therapy was delivered with a low rate and degree of normal tissue complications. Asymptomatic dogs with confirmed, progressive growth of a HBT may most likely benefit from SBRT.

Embolization and Open Decompression of a Giant Aneurysm Involving the P2 Segment of the Posterior Cerebral Artery.

A 5-year-old girl was brought to the clinic because of chronic intermittent left-sided headaches. The patient underwent computed tomographic angiography, which demonstrated a giant aneurysm that involved the P2 segment of the left posterior cerebral artery. Before treatment proceeded, consent was obtained from the patient's legal guardian. A trapping-evacuation technique was used for proximal control and decompression so that a clip could be placed on the proximal inflow artery of the aneurysm. First, embolization was performed for aneurysm trapping and for sacrifice of the parent vessel. Two days later, the patient was taken to the operating room for open surgical decompression, clipping, and reconstruction. Heparin was administered during the embolization stage of the operation. The patient did well postoperatively and was discharged home. The 3-month follow-up evaluation demonstrated a right superior homonymous quadrantanopia and no other neurologic deficits. The patient's clinical course is summarized in Video 1.