bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor dosimetry using 177Lu: influence of background activity, measurement method and reconstruction algorithm
Authors: Staanum Peter Frøhlich 
Published: June 2023

Abstract
Background
Image-based tumor dosimetry after radionuclide therapy, using the isotope 177Lu, finds application e.g., for tumor-to-organ dose comparison and for dose response evaluation. When the tumor extent is not much larger than the image resolution, and when 177Lu is found in nearby organs or other tumors, an accurate determination of tumor dose is particularly challenging. Here a quantitative evaluation of three different methods for determining the 177Lu activity concentration in a phantom is performed, and the dependence on a variety of parameters is described. The phantom (NEMA IEC body phantom) has spheres of different size in a background volume, and sphere-to-background 177Lu activity concentration ratios of infinity, 9.5, 5.0 and 2.7 are applied. The methods are simple to implement and well-known from the literature. They are based on (1) a large VOI encompassing the whole sphere, without background activity and with volume information from other sources, (2) a small VOI located in the sphere center, and (3) a VOI consisting of voxels with voxel value above a certain percentage of the maximum voxel value.

Results
The determined activity concentration varies significantly with sphere size, sphere-to-background ratio, SPECT reconstruction method and method for determining the concentration. Based on the phantom study, criteria are identified under which the activity concentration can be determined with a maximal error of 40% even in the presence of background activity.

Conclusions
Tumor dosimetry is feasible in the presence of background activity using the above-mentioned methods, provided appropriate SPECT reconstructions are applied and tumors are selected for dosimetry analysis according to the following criteria for the three methods: (1) solitary tumor with diameter > 15 mm, (2) tumor diameter > 30 mm and tumor-to-background ratio > 2, and (3) tumor diameter > 30 mm and tumor-to-background ratio > 3.
Enhancing biofeedback-driven self-guided virtual reality exposure therapy through arousal detection from multimodal data using machine learning
Authors: Rahman Muhammad Arifur , Brown David J. , Mahmud Mufti , Harris Matthew , Shopland Nicholas , Heym Nadja , Sumich Alexander , Turabee Zakia Batool , Standen Bradley , Downes David , Xing Yangang , Thomas Carolyn , Haddick Sean , Premkumar Preethi , Nastase Simona , Burton Andrew , Lewis James 
Published: June 2023

AbstractVirtual reality exposure therapy (VRET) is a novel intervention technique that allows individuals to experience anxiety-evoking stimuli in a safe environment, recognise specific triggers and gradually increase their exposure to perceived threats. Public-speaking anxiety (PSA) is a prevalent form of social anxiety, characterised by stressful arousal and anxiety generated when presenting to an audience. In self-guided VRET, participants can gradually increase their tolerance to exposure and reduce anxiety-induced arousal and PSA over time. However, creating such a VR environment and determining physiological indices of anxiety-induced arousal or distress is an open challenge. Environment modelling, character creation and animation, psychological state determination and the use of machine learning (ML) models for anxiety or stress detection are equally important, and multi-disciplinary expertise is required. In this work, we have explored a series of ML models with publicly available data sets (using electroencephalogram and heart rate variability) to predict arousal states. If we can detect anxiety-induced arousal, we can trigger calming activities to allow individuals to cope with and overcome distress. Here, we discuss the means of effective selection of ML models and parameters in arousal detection. We propose a pipeline to overcome the model selection problem with different parameter settings in the context of virtual reality exposure therapy. This pipeline can be extended to other domains of interest where arousal detection is crucial. Finally, we have implemented a biofeedback framework for VRET where we successfully provided feedback as a form of heart rate and brain laterality index from our acquired multimodal data for psychological intervention to overcome anxiety.
Single-dose trastuzumab monotherapy achieved pathological complete response (pCR) in a patient with HER2-positive breast cancer: a case report
Authors: Isogai Ayaka , Kotani Haruru , Sawaki Masataka , Hattori Masaya , Yoshimura Akiyo , Kataoka Ayumi , Nozawa Kazuki , Ozaki Yuri , Endo Yuka , Nakakami Akira , Komaki Rie , Iwata Hiroji 
Published: June 2023

Abstract
Background
With advances in breast cancer treatment, the importance of de-escalation therapy to reduce harm during the treatment of elderly patients has attracted attention in recent years. Certain patient populations are expected to have a superior response to anti-HER2 drugs, particularly those with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer. In this report, we describe our experience of dramatic anti-HER2 drug response in a patient who achieved pathological complete response (pCR) with a single dose of trastuzumab.

Case presentation
An 88-year-old woman presented with a 2-cm palpable mass in the left breast. Vacuum-assisted breast biopsy, ultrasonography, and positron emission tomography–computed tomography revealed estrogen receptor-negative and HER2-positive, T1N0M0, stage I breast cancer. Mastectomy was scheduled within 2 months of the initial visit; however, the patient was anxious about the length of the waiting period and requested medication in the interim. Therefore, prior to surgery, one cycle of trastuzumab monotherapy was administered at the discretion of the attending physician. Postoperative pathology showed no remnant of invasive carcinoma and pCR with only a 0.2-mm ductal carcinoma in situ remnant. The patient refused further medication after surgery because of severe diarrhea after trastuzumab administration. Postoperative treatment was limited to follow-up, and no recurrence was observed at 1 year and 6 months postoperatively.

Conclusion
This case suggests that trastuzumab monotherapy may be effective in certain patients with HER2-positive breast cancer. In the future, identifying patients who are more likely to respond to trastuzumab, as in this case, will allow for more options regarding de-escalation therapy without chemotherapy, particularly in elderly patients who are concerned about the side effects of chemotherapy.
ECMOLIFE intra-hospital transport in life-saving for pulmonary vein obstruction
Authors: Condello Ignazio , Nasso Giuseppe , Contegiacomo Gaetano , Solimando Carlo , Balducci Giuseppe , Scaringi Domenico , D’Alessandro Pasquale , Speziale Giuseppe 
Published: June 2023

Abstract
Background
Transport with extracorporeal membrane oxygenation (ECMO) in the hospital setting can become a challenge as well as in the out-of-hospital setting. In particular, the management of intra-hospital transport with ECMO support of the critically ill patient foresees his shift from the intensive care to the diagnostic areas, from the diagnostic areas to the interventional and surgical areas.

Case presentation
In this context, we present a life-saving transport case with the veno-venous (VV) configuration of the ECMOLIFE Eurosets system, for right heart and respiratory failure in a 54-year-old woman, due to thrombosed obstruction of the right superior pulmonary vein, following mitral valve repair surgery in minimally invasive approach in a patient already operated on for complex congenital heart disease. After stabilizing the vital parameters with Veno-venous ECMO for 19 h, the patient was transported to hemodynamics for angiography of the pulmonary vessels, where the diagnosis of obstruction of the pulmonary venous return was made. Subsequently, the patient was brought back to the operating room for a procedure of unblocking the right superior pulmonary vein using a minimally invasive approach, passing from the ECMO to the support in extracorporeal circulation.

Conclusions
The transportable ECMOLIFE Eurosets System was safe and effective during transport in maintaining the vital parameters of oxygenation and CO2 reuptake and systemic flow, allowing the patient to be mobilized for diagnostic tests instrumental to diagnosis. The patient was extubated 36 h after the surgical procedures and was discharged 10 days later from the hospital.
Seroprevalence of hepatitis E viral infection among apparently healthy personnels and patients with certain neurological disorders in Alexandria University Hospitals
Authors: Hanno Abd El-Fattah , Khouly Ehab El , Abdel-Rauof Mervat , Moghazy Ahmed , Dauod Shaimaa 
Published: June 2023

Abstract
Introduction
Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis. There are thought to be 20 million infections per year in poorer nations with inadequate sanitation. In Egypt, awareness about the possible hazards linked to HEV infection is limited due to low socioeconomic and educational levels. Only a small number of sequences have been characterized, making HEV study in Egypt constrained. Numerous factors may have contributed to this neglect. Various extra-hepatic symptoms of HEV infection include neurological problems are recognized. Many European nations have implemented regular HEV monitoring, or targeted screening of blood provided by patients at greater risk to stop the spread of HEV by transfusion.

Aim
Assess the prevalence of HEV infection in asymptomatic blood donors. Increasing awareness about HEV testing in patients with some unexplained neurological disorders.

Methods
Cross-sectional study involving 550 patients: 500 apparently healthy blood donors and 50 patients with some neurological disorders. All subjects were tested for serological markers (IgG and IgM) for HEV using ELISA technique in addition to HEV RNA PCR testing for seropositive patients.

Results
Five hundred asymptomatic blood donors (370 males and 130 females), ages ranging from 20 to 50 years (median 33), 22.6% of them tested positive for HEV (IgG and IgM) of which 2 subjects only had positive HEV RNA PCR testing. In the second group 50 patients (26 males and 24 females) with various unexplained neurological disorders. Liver functions were within normal or showed only a mild increase. Forty-four percent of the patients had positive serology for HEV, with 6 patients testing positive for HEV RNA on PCR.

Conclusion
No need for mass screening for HEV serology among blood donors. HEV infection needs to be considered in patients with unexplained neurological disorders even if the liver functions are not markedly elevated.
Lower body positive pressure treadmill gait training for neurological patients: a systematic review
Authors: Almutairi Sattam M. 
Published: June 2023

Abstract
Background
Among various body weight-supported locomotor training methods for neurological patients, some studies have recognized the lower body positive pressure (LBPP) treadmill as superior for gait training in neurological patients. The aim of this study is to explore the clinical use and efficacy of LBPP treadmill gait training in neurological patients.

Methods
A systematic review was performed following PRISMA guidelines. The inclusion criteria were studies published in English using LBPP with neurological patients were included from the database's inception to March 2023 to avoid misinterpretation of translation. The search was conducted in multiple databases, including Google Scholar, PubMed, Scopus, PEDro, and the Cochrane Database. To improve accuracy and comprehensiveness, studies mentioned in the main articles were also evaluated.

Results
The search identified 16 articles that use LBPP with neurological patients. Only a few randomized control studies on the use of LBPP after stroke have been reported. For neurological rehabilitation, LBPP treadmill gait training is safe and feasible. Current research suggests that using the LBPP treadmill in conjunction with traditional rehabilitation treatment has a successively beneficial impact on motor function, particularly in patients with subacute to chronic stroke and Parkinson’s disease. There are no studies that compare the LBPP to the body weight supported treadmill (BWST). Furthermore, to the best of our knowledge, the LBPP treadmill has not yet been evaluated on for its effectiveness in treating traumatic brain injury (TBI) or spinal cord injury (SCI).

Conclusion
There was insufficient evidence to support the claim that LBPP is effective and superior to other gait training methods. Larger randomized control studies with sufficient sample sizes are needed to better understand the potential effects of the LBPP treadmill intervention on the functional performance of people with neurological disorders.
Tobacco-free campuses – a pipe dream? A survey of current smoking cessation practice in mental health units in Ireland
Authors: Harrington Colm , Walsh Elaine 
Published: June 2023

Aims and methodSmoking and vaping are prohibited on Ireland's Health Service Executive (HSE) campuses. The HSE states that there is no evidence to suggest vaping is less damaging than cigarettes. Recent meta-analyses have shown that e-cigarettes are in fact less dangerous and can help smokers quit. Our study analyses the current smoking policies in place in mental health ‘approved centres’ in Ireland, what is being done to help smokers quit while in-patients and the level of support among staff for the introduction of e-cigarettes as a harm reduction tool. Clinical nurse managers from each mental health approved centre were surveyed to assess adherence to smoking policies.ResultsOnly 5% of surveyed units enforce the HSE's Tobacco Free Campus Policy; 55% of units supported the idea of using e-cigarettes to help patients quit cigarettes.Clinical implicationsIreland's hospital campuses are not tobacco free. Changes need to be made to our smoking policies and their enforcement.
Severe Hepatopathy in National Wilms Tumor Studies 3-5: Prevalence, Clinical Features, and Outcomes After Reintroduction of Chemotherapy
Authors: Oosterom Natanja , Gooskens Saskia L.M. , Renfro Lindsay A. , Perlman Elizabeth J. , van den Heuvel-Eibrink Marry M. , Hamilton Thomas E. , Green Daniel M. , Grundy Paul E. , Daw Najat C. , Geller James I. , Dome Jeffrey S. , Fernandez Conrad V. , Mullen Elizabeth A. 
Published: June 2023

PURPOSE The safety of reintroducing chemotherapy in the pediatric renal tumor setting after severe hepatopathy (SH), including sinusoidal obstruction syndrome (SOS), is uncertain. We describe the incidence, severity, outcomes, and impact on subsequent treatment for patients with SH from National Wilms Tumor Study (NWTS) protocols 3-5. PATIENTS AND METHODS Archived charts for patients enrolled on NWTS 3-5 who met study inclusion criteria for SH by using established hepatopathy grading scales and clinical criteria were reviewed for demographics, tumor characteristics, radio- and chemotherapy details, SH-related dose modifications, and oncologic outcomes. Genomic analysis for candidate polymorphisms associated with SH was performed in 14 patients. RESULTS Seventy-one of 8,862 patients (0.8%) met study inclusion criteria. The median time from therapy initiation to SH was 51 days (range, 2-293 days). Sixty percent received radiotherapy, and 56% had right-sided tumors. Grade 1-4 thrombocytopenia was noted in 70% at initial occurrence of SH (median 22,000/microliter). Among 69 of 71 children with SH occurring before the end of therapy (EOT) and post-SH treatment information available, chemotherapy was delayed posthepatopathy for 65% (69% of these at a reduced dose), continued without delay for 20% (57% of these at reduced dose), and stopped completely for 15% (4 of 10 of whom died of SH). Overall, 42% of patients with dose reductions achieved full dose by EOT. The five-year post-SH event-free survival for patients who continued therapy was 89% (95% CI, 81 to 98), with no significant differences by whether delay or dose reduction occurred. We identified no SH-associated pharmacogenomic polymorphism. CONCLUSION The incidence of SH on NWTS 3-5 was low; many had associated severe thrombocytopenia. Careful reintroduction of chemotherapy appeared to be feasible for the majority of patients who developed severe chemotherapy- and/or radiotherapy-induced liver toxicity.
Highly Sensitive Circulating Tumor DNA Assay Aids Clinical Management of Radiographically Occult Isolated Peritoneal Metastases in Patients With GI Cancer
Authors: Singh Harshabad , Klempner Samuel J. , Melnitchouk Nelya , Chander Deepak P. , Negrea Ovidiu George , Patel Anuj K. , Schlechter Benjamin L. , Rubinson Douglas A. , Huffman Brandon M. , Nambiar Chetan , Remland Joshua , Andrews Elizabeth , Leahy Megan E. , Brais Lauren K. , Enzinger Peter C. , Mamon Harvey J. , Giannakis Marios , Meyerhardt Jeffrey A. , Ng Kimmie , Perez Kimberly J. , Aguirre Andrew J. , Clark Jeffrey W. , Cleary James M. , Wolpin Brian M. 
Published: June 2023

PURPOSE GI cancers commonly spread to the peritoneal cavity, particularly from primary adenocarcinomas of the stomach and appendix. Peritoneal metastases are difficult to visualize on cross-sectional imaging and cause substantial morbidity and mortality. The purpose of this study was to determine whether serial highly sensitive tumor-informed circulating tumor DNA (ctDNA) measurements could longitudinally track changes in disease burden and inform clinical care. METHODS This was a retrospective case series of patients with gastric or appendiceal adenocarcinoma and isolated peritoneal disease that was radiographically occult. Patients underwent quantitative tumor-informed ctDNA testing (Signatera) as part of routine clinical care. No interventions were prespecified based on ctDNA results. RESULTS Of 13 patients studied, the median age was 65 (range, 45-75) years, with 7 (54%) women, 5 (38%) patients with gastric, and 8 (62%) patients with appendiceal adenocarcinoma. Eight (62%) patients had detectable ctDNA at baseline measurement, with median value 0.13 MTM/mL (range, 0.06-11.68), and assay was technically unsuccessful in two cases with appendiceal cancer because of limited tumor tissue. Five (100%) patients with gastric cancer and 3 (50%) patients with appendiceal cancer had detectable ctDNA at baseline. Although baseline levels of ctDNA were low, longitudinal assessment tracked with changes in disease burden among patients undergoing chemotherapy for metastatic disease. In two patients undergoing surveillance after definitive surgical management of gastric adenocarcinoma, detection of ctDNA prompted diagnosis of isolated peritoneal disease. CONCLUSION Quantitative tumor-informed serial ctDNA testing aids clinical management of patients with isolated peritoneal disease. Low levels of baseline ctDNA suggest a role for highly sensitive ctDNA approaches over panel-based testing. Further exploration of this approach should be considered in patients with isolated peritoneal malignant disease.
Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data
Authors: Bergagnini-Kolev Mackenzie , Kane Katie , Templeton Ian E. , Curran Aidan K. 
Published: June 2023

Abstract
Itraconazole is a potent inhibitor of cytochrome P450 3A4 (CYP3A4), associated with numerous drug-drug interactions (DDI). PUR1900, a dry powder formulation of itraconazole for oral inhalation, results in high lung and low systemic exposure. This project used physiologically based pharmacokinetic (PBPK) modeling to assess the DDI potential of inhaled PUR1900, using midazolam as a “victim drug.” The basic and mechanistic static models evaluated the DDI potential of PUR1900, assuming 5 mg of midazolam coadministration at steady-state itraconazole exposure. Subsequently, Simcyp® PBPK simulation software and pharmacokinetic data from a Phase 1 clinical trial with PUR1900 (NCT03479411) were used to optimize an existing itraconazole PBPK model. The model was applied to investigate the potential for CYP3A4 DDI when 5 mg of midazolam is co-administered with inhaled PUR1900 at a steady state in a virtual healthy population at PUR1900 doses up to 40 mg per day. The basic static and mechanistic static models suggested a strong likelihood for DDI with inhaled PUR1900. The PBPK model was consistent with PUR1900 Phase 1 trial data. The geometric mean Cmax and AUC ratios of midazolam at a maximum dose of 40 mg PUR1900 were 1.14 and 1.26, respectively, indicating a minimal likelihood of DDI with inhaled PUR1900. The low systemic exposure of itraconazole when administered as PUR1900 results in minimal to no CYP3A4 inhibition, reducing the concern of drug-drug interactions. As the risk of CYP3A4 DDI is predicted to be significantly lower when itraconazole is administered via oral inhalation as PUR1900, it is likely that PUR1900 can be safely used for the treatment of pulmonary fungal infections in patients taking pharmaceuticals currently contraindicated with oral itraconazole.
Graphical Abstract
Substance Use and the Nervous System
Authors: Stitt Derek 
Published: June 2023

ABSTRACT

OBJECTIVE
This article informs and updates the practicing neurologist on the current landscape of known neurologic injuries linked to the use of illicit drugs, focusing on emerging agents.

LATEST DEVELOPMENTS
Synthetic opioids such as fentanyl and similar derivatives have exploded in prevalence, becoming the leading cause of overdose fatalities. The higher potency of synthetic opioids compared with semisynthetic and nonsynthetic opiates poses an increased risk for unintentional overdose when found as an adulterant in other illicit drug supplies such as heroin. Conversely, misinformation about the risk of symptomatic exposure to fentanyl through casual contact with the skin and ambient air has led to misdirected fear and stigma that threatens to impede valid harm-reduction measures for fentanyl users at risk of actual overdose. Finally, during the COVID-19 pandemic, overdose rates and deaths continued to climb, especially among those who use opioids and methamphetamine.

ESSENTIAL POINTS
A variety of potential neurologic effects and injuries can occur with illicit drug use owing to the diverse properties and mechanisms of action of the various classes. Many high-risk agents are not detected on standard drug screens, including so-called designer drugs, and the practicing neurologist is best served by recognizing the clinical features of the traditional toxidrome and other potential idiosyncratic effects of various illicit agents.
Neurologic Complications of Cancer Treatment
Authors: Porter Alyx B. 
Published: June 2023

ABSTRACT

Objective
Advances in cancer treatment have led to extended survival and increased risk of neurologic complications in an aging population. This review summarizes potential neurologic complications in patients who have undergone treatment for neurologic and systemic malignancies.

Latest Developments
Radiation and cytotoxic chemotherapy along with other targeted therapies continue to be the mainstay of cancer treatment. These advances in cancer care have led to improved outcomes and increased the need to understand the spectrum of neurologic complications that may arise from treatment. While radiation and older therapies including cytotoxic chemotherapies have side effect profiles that are widely known and well understood, this article serves as a review of the more commonly associated neurologic complications of both traditional and newer treatments being offered to this patient population.

Essential Points
Neurotoxicity is a common complication of cancer-directed treatment. In general, neurologic complications of radiation therapy are more common in central nervous system malignancies, and neurologic complications of chemotherapy are more common in non-neurologic malignancies. Attempts at prevention, early detection, and intervention remain paramount in the reduction of neurologic morbidity.