bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging in peripheral bronchoscopy
Authors: Shaller Brian D. , Sethi Sonali , Cicenia Joseph
Published: November 2023

Purpose of review

Historically the sampling of peripheral lung lesions via bronchoscopy has suffered from inferior diagnostic outcomes relative to transthoracic needle aspiration, and neither a successful bronchoscopic navigation nor a promising radial ultrasonographic image of one's target lesion guarantees a successful biopsy. Fortunately, many of peripheral bronchoscopy's shortcomings – including an inability to detect and compensate for computed tomography (CT)-body divergence, and the absence of tool-in-lesion confirmation – are potentially remediable through the use of improved intraprocedural imaging techniques.

Recent findings

Recent advances in intraprocedural imaging, including the integration of cone beam CT, digital tomosynthesis, and augmented fluoroscopy into bronchoscopic procedures have yielded promising results. These advanced imaging modalities may improve the outcomes of peripheral bronchoscopy through the detection and correction of navigational errors, CT-body divergence, and malpositioned biopsy instruments.

The incorporation of advanced imaging is an essential step in the improvement of peripheral bronchoscopic procedures.
Tobacco treatment in the setting of lung cancer screening
Authors: Verdone James E. , Marciniak Ellen T. , Deepak Janaki
Published: November 2023

Purpose of review

Lung cancer screening by low-dose CT is an increasingly implemented preventive medicine tool. Screening for lung cancer is incomplete without addressing problematic tobacco use, the greatest modifiable risk factor in the development of lung cancer. This review describes recent work related to lung cancer screening and treatment of tobacco use in that context.

Recent findings

Implementation of lung cancer screening demonstrates socioeconomic disparities in terms of adherence to screening as well as likelihood of successful tobacco dependence treatment. Active tobacco dependence is a common comorbidity for patients undergoing lung cancer screening. The optimal implementation of tobacco dependence treatment in the context of lung cancer screening is still an area of active investigation.

Treatment of tobacco dependence at time of lung cancer screening is a major opportunity for clinicians to intervene to reduce the major modifiable risk factor for lung cancer, tobacco use. Providing comprehensive tobacco dependence treatment is most effective using combination pharmacologic and behavioral interventions. Practices providing comprehensive treatment will benefit from accurate documentation for billing and coding and supplementing with external resources such as state Quit Lines.
Optimizing the prelung transplant candidate
Authors: Pagteilan John , Atay Scott
Published: November 2023

Purpose of review

Lung transplant outcomes are impacted by multiple modifiable risk factors. Candidate deterioration on the wait list remains problematic. Innovative technology and strategies to identify and impact pretransplant morbidity have improved short- and long-term outcomes. We focus our review on recent advances in pretransplant recipient assessment and optimization.

Recent findings

Advancements in recipient management have focused on risk factor identification for adverse outcomes and the development of a lung transplant specific frailty assessment. Early surgical correction of gastroesophageal reflux disease (GERD), including the use of partial fundoplication in the setting of esophageal dysmotility, leads to improvements in graft function/longevity. New evidence supports expanding criteria for extracorporeal life support as a bridge to transplant.

Candidate optimization requires early intervention to limit functional deterioration potentially contributing to adverse outcomes. Frailty can be identified with a transplant specific frailty assessment, and positively impacted with dedicated rehabilitation. Pretransplant frailty is reversible following transplant and should be considered in the context of overall fitness at the time of candidate selection. Invasive support modes including extracorporeal membrane oxygenation (ECMO) are appropriate to preserve strength and mobility, with awake, ambulatory ECMO preferred. The deleterious effect of GERD on graft function can be managed with early fundoplication over medical management alone.
Varicose vein embolization and portal vein stenting in a patient with sinistral portal hypertension-induced gastrointestinal hemorrhage: a case report
Authors: Li Xi , Li Wenbo , Wu Yu , Liu Yuan
Published: November 2023

Introduction and importance:

Massive gastrointestinal hemorrhage is a severe hemorrhage that occurs in the gastrointestinal tract and is a life-threatening condition. Sinistral portal hypertension is a common etiology for massive gastrointestinal hemorrhage, whose occurrence might be derived from pathological changes induced by obstruction and/or increased blood flow to the portal vein system. However, there is a rare study reporting pancreatic disease-induced sinistral portal hypertension.

Case presentation:

An 80-year-old female pancreatic cancer patient was admitted to our hospital on 22 January 2022 due to a massive gastrointestinal hemorrhage with shock after receiving radio-chemotherapy. Abdominal enhanced computerized tomography showed that the patient presented with pancreatic cancer-causing sinistral portal hypertension with massive collateral circulation, intrahepatic bile duct dilation, and the formation of massive ascites. Subsequent portography interventional procedure revealed the esophageal and gastric varix. Then, the varicose vein was embolized, and the stent was implanted at the lumen of the superior mesenteric vein accessing the portal vein. The patient recovered from pancreatic cancer-causing sinistral portal hypertension, and a normal direction of blood flow was observed in the superior mesenteric vein with a decreasing amount of ascites. In addition, a transfusion was also carried out, and the massive gastrointestinal hemorrhage was alleviated.

Clinical discussion and conclusion:

This study emphasizes the successful treatment of massive gastrointestinal hemorrhage induced by pancreatic cancer-causing sinistral portal hypertension by varicose vein embolization and portal vein stenting, which could be considered an alternative opinion for these patients.
Predictive factors for the development of capecitabine-induced hand-foot syndrome: a retrospective observational cohort study
Authors: Chantharakhit Chaichana , Sujaritvanichpong Nantapa
Published: November 2023

Background:

Capecitabine-induced hand-foot syndrome (HFS) is a common condition that significantly affects patients’ quality of life. The exact underlying mechanisms are currently not clearly understood. Therefore, the study of predictive factors for HFS is of critical importance.

Materials and methods:

This prognostic factor research used a retrospective observational cohort as the study design. Data collected from the medical records of 205 patients treated with capecitabine between January 2019 and June 2022 were subjected to univariable and multivariable regression analysis to determine the predictive factors for the development of grade 2 and grade 3 HFS.

Results:

The incidence of grade 2 and grade 3 HFS was 26.8%. The independent predictive factors, such as age over 60 years (OR 4.80, 95% CI: 2.16–10.68, P<0.001), capecitabine dose greater than 3000 mg/day (OR 2.47, 95% CI: 1.09–5.59, P=0.030), and the number of cycles five or more in the total capecitabine regimen (OR 2.94, 95% CI: 1.29–6.71, P=0.01), were significantly associated with the development of grade 2 and grade 3 HFS.

Conclusions:

Independent predictive factors for the development of grade 2 and grade 3 HFS in patients treated with capecitabine include age over 60, capecitabine dose greater than 3000 mg/day, and patients who plan to undergo five or more cycles in the total capecitabine regimen. This knowledge can be valuable for guiding clinical monitoring and follow-up of patients.
Alcoholic pellagrous encephalopathy: a case report on atypical presentation and diagnostic dilemma in alcohol-related disorders
Authors: Yogi Tek N. , B.C. Pooja , Bhusal Amrit , Limbu Suren , Kafle Rijan
Published: November 2023

Introduction:

Alcohol use disorder is a global health concern with various complications, including pellagra, often overlooked due to its rarity. This case explores the neurological presentation of pellagra in a long-term alcohol and substance abuser, emphasizing the diagnostic challenges in resource-constrained settings.

Case presentation:

A 36-year-old male with a history of substance abuse presented with multiple symptoms, including hallucinations and neurological deficits. His complex clinical history included alcohol dependence, seizures, and relapses. Physical and neurological examinations revealed characteristic signs of pellagrous encephalopathy. Laboratory findings confirmed anemia and a fatty liver.

Discussion:

Alcoholic pellagrous encephalopathy (APE) presents a diagnostic challenge due to its atypical symptoms, overlapping with other alcohol-related disorders. Niacin deficiency, central to its pathogenesis, affects neurotransmitter synthesis, contributing to neurological symptoms. Diagnosis relies on clinical presentation, but laboratory tests for niacin levels can aid in confirmation. Neuroimaging can exclude alternative causes. This case underscores the importance of considering pellagrous encephalopathy in alcohol-related disorders with neurological symptoms.

Conclusion:

This case underscores the importance of recognizing atypical presentations of APE in chronic alcohol-dependent individuals. Prompt diagnosis, nutritional correction, and addressing alcohol use are vital for successful management. Healthcare providers must be aware of the diagnostic complexities and socioeconomic barriers hindering timely intervention in APE.
Ultrasound-guided continuous erector spinae plane block vs continuous thoracic epidural analgesia for the management of acute and chronic postthoracotomy pain: a randomized, controlled,double-blind trial
Authors: Shaker Ehab Hanafy , Elshal Mamdouh Mahmoud , Gamal Reham Mohamed , Zayed Norma Osama Abdallah , Samy Samuel Fayez , Reyad Raafat M. , Shaaban Mohammed H. , Abd Alrahman Abd Alrahman M. , Abdelgalil Ahmed Salah
Published: November 2023

Introduction:

Postthoracotomy pain (PTP) is a severe pain complicating thoracic surgeries and its good management decreases the risk of PTP syndrome (PTPS).

Objectives:

This randomized controlled study evaluated the efficacy of ultrasound-guided continuous erector spinae plane block (ESPB) with or without dexmedetomidine compared with thoracic epidural analgesia (TEA) in managing acute postoperative pain and the possible emergence of PTPS.

Methods:

Ninety patients with chest malignancies planned for thoracotomy were randomly allocated into 3 equal groups. Group 1: TEA (20 mL of levobupivacaine 0.25% bolus, then 0.1 mL/kg/h of levobupivacaine 0.1%), group 2: ESPB (20 mL of levobupivacaine only 0.1% bolus every 6 hours), and group 3: ESPB (20 mL of levobupivacaine 0.25% and 0.5 μg/kg of dexmedetomidine Hcl bolus every 6 hours).

Results:

Resting and dynamic visual analog scales were higher in group 2 compared with groups 1 and 3 at 6, 24, and 36 hours and at 8 and 12 weeks. Postthoracotomy pain syndrome incidence was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. The grading system for neuropathic pain score was higher in group 2 compared with groups 1 and 3 at 8 and 12 weeks, whereas it was indifferent between groups 1 and 3. Itching, pruritis, and urine retention were higher in group 1 than in ESPB groups.

Conclusion:

Ultrasound-guided ESPB with dexmedetomidine is as potent as TEA in relieving acute PTP and reducing the possible emergence of chronic PTPS. However, the 2 techniques were superior to ESPB without dexmedetomidine. Erector spinae plane block has fewer side effects compared with TEA.
Prosthetics and orthotics for persons with movement disabilities in India in the postpandemic milieu
Authors: Prajapati Arvind Kumar , Komath Manoj , N. N. Subhash
Published: November 2023

The SARS-CoV-2 disease had a severe impact on global socioeconomic growth, and its harmful effects continue with virus mutation. Over the past 3 years, the pandemic has caused isolation, mental trauma, stress, financial losses, and various health complications in individuals. Recent reports have stressed the sufferings of the physically abled population. However, we should not neglect the challenges faced by the disabled population, which were more severe in many ways due to their dependency on others at various levels. The strategies implemented to contain the virus have further aggravated their sufferings and made it even worse because health care priorities were skewed toward public-centered care. As a result, it is difficult to determine the extent of care the disabled population received during the pandemic. Moreover, a single-centered study reports that amputations in India increased by 54.1% compared with those during the prepandemic era. This indicates the need for special attention to the physically disabled community, especially persons with movement disabilities. These individuals are partially dependent and have the potential to make significant contributions to the gross domestic product if included in the human resources pool. The Indian government had launched various initiatives to improve their living status. But delays in policy implementation, reduction in budget allocation, and the ongoing pandemic have derailed the efforts. For these reasons, this article emphasizes several challenges in movement disability care. In addition, it makes recommendations for improving the quality of life of persons with movement disabilities. These include collaboration, creating start-up businesses, applying state-of-the-art logistics, establishing a technological ecosystem, raising public awareness, accessing high-quality care, and using contemporary medical devices.
Oral Manganese Chloride Tetrahydrate: A Novel Magnetic Resonance Liver Imaging Agent for Patients With Renal Impairment
Authors: Brismar Torkel B. , Geisel Dominik , Kartalis Nikolaos , Madrazo Beatrice L. , Persson Hedman Hanna , Norlin Andreas
Published: November 2023

Manganese-based contrast agents (MBCAs) show promise to complement gadolinium-based contrast agents (GBCAs) in magnetic resonance imaging (MRI) of the liver. Management of patients with focal liver lesions and severely impaired renal function uses unenhanced liver MRI or GBCA-enhanced MRI. However, unenhanced MRI risks reducing patient's survival.

Gadolinium-based contrast agents, which help to detect and visualize liver lesions, are associated with increased risk of nephrogenic systemic fibrosis in renally impaired patients, a severe adverse event (AE) with potentially fatal outcome. Therefore, use of GBCA in patients with impaired renal function requires careful consideration. Other concerns are related to tissue deposition in the brain and other organs due to lack of gadolinium clearance, which could lead to concerns also for other patient populations, for example, those exposed to multiple procedures with GBCA. Of particular concern are the linear chelates that remain available for liver MRI, where there is no replacement technology. This has highlighted the urgency for safer alternatives.

An alternative may be the drug candidate Ascelia-MBCA (ACE-MBCA, Orviglance), oral manganese chloride tetrahydrate. This candidate effectively visualizes and detects focal liver lesions, as demonstrated in 8 clinical studies on 201 adults (healthy or with known or suspected focal liver lesions). ACE-MBCA has a low and transient systemic exposure, which is likely the reason for its beneficial safety profile. The AEs were primarily mild and transient, and related to the gastrointestinal tract. This new, orally administered product may offer a simple imaging approach, allowing appropriate patient management in renally impaired patients when use of GBCA requires careful consideration.

In this review, we highlight the clinical development of ACE-MBCA—a novel, liver-specific contrast agent. We begin with a brief overview of manganese properties, addressing the need for MBCAs and describing their optimal properties. We then review key findings on the novel agent and how this allows high-quality MRIs that are comparable to GBCA and superior to unenhanced MRI. Lastly, we provide our view of future perspectives that could advance the field of liver imaging, addressing the medical needs of patients with focal liver lesions and severe renal impairment.

Our review suggests that ACE-MBCA is a promising, effective, and well-tolerated new tool in the radiologist's toolbox.
Management of Greenstick Fracture at the Root of Adult Zygomatic Arch
Authors: Wu Benxing , Liu Mingwen , Lv Kun
Published: November 2023

Greenstick fractures mostly occur in children and rarely in adults. In adult zygomaticomaxillary complex fractures, the greenstick fracture at the root of the zygomatic arch is occasionally encountered. This makes it difficult to move the fracture segment. Therefore, achieving anatomic reduction is very difficult. Our preoperative 3D repaired model shows that if only the maxilla and zygomatic bones are restored, the patient’s face will still have depression and protrusion. The greenstick fracture segment at the root of the zygomatic arch needs to undergo osteotomy to achieve anatomic reduction and restore facial symmetry. The patient’s facial appearance was restored after the surgery. The postoperative computed tomography scan showed good alignment of the fracture. The authors believe that a fracture at the root of the zygomatic arch can serve as an indication for open reduction and fixation.
A Novel Approach to Reduce Lid Weight in the Upper Eyelid Blepharoplasty: Split-Thickness Excision of the Palpebral Part of Orbicularis Oculi Muscle
Authors: Demir Ahmet , Ünverdi Ömer Faruk , Orhan Abdullah Erkan
Published: November 2023

Objectives:

With the effect of advancing age and environmental factors, excess skin and muscle start to weigh on the eyelids and cause a tired facial expression. The prevailing opinion is that by partially excising muscle in surgical treatment, this load on the eyelid will be reduced, and more successful results will be obtained. Using a classic strip orbicularis oculi excision, the integrity of the muscle is disrupted, and morbidities such as lagophthalmos and edema increase. In this paper, we share our clinical experiences regarding the split excision of the palpebral part of the orbicularis oculi muscle and the subsequent process.

Methods:

Twenty-seven patients who applied to our clinic to undergo blepharoplasty were operated on under local anesthesia. The orbicularis oculi muscle was split-excised together with the skin from the marked areas.

Results:

The split excision of the orbicularis oculi muscle did not cause prolonged edema. The general appearance of the eyelid and face of the patients was observed to have significantly improved in the third month after surgery compared with the preoperative period. No complications such as wound healing, hypertrophic scar, asymmetry, or infection were observed during the follow-up period.

Conclusions:

The split excision of the orbicularis oculi muscle can be considered a new and effective method in cases in which a muscle excision is planned as part of blepharoplasty. Prolonged edema due to the strip muscle excision is not observed clinically. This technique can eliminate the negative effects of excess muscle tissue on the eyelid without disrupting the integrity of the muscle.

Level of Evidence:

Evidence Based Medicine Level V
Therapeutic effects of Naohuan Dan combined with idebenone in treating mild cognitive impairment with kidney deficiency and phlegm stasis: A retrospective study
Authors: Ye Jiaxi , Zhu Min , Fan Shengnuo , Huang Qihui
Published: November 2023

Background

Naohuan Dan is a prescription used to treat dementia. This study aims to assess the effectiveness and safety of Naohuan Dan combined with idebenone in treating mild cognitive impairment (MCI) with kidney deficiency and phlegm stasis.

Materials and methods

This retrospective, observational clinical trial enrolled 64 MCI patients treated in the Sun Yat-sen Memorial Hospital, Zhongshan University, from May 1, 2019, to April 30, 2022. The 32 patients in the treatment group received Naohuan Dan combined with idebenone, whereas the 32 patients in the control group were treated with idebenone alone. The observation lasted for 12 weeks. The primary outcomes were the Mini-Mental State Examination (MMSE) score and clinical efficacy, whereas secondary outcomes included the Montreal Cognitive Assessment (MCS) score, the activities of daily living (ADL) score, the Geriatric Depression Scale (GDS) score, the traditional Chinese medicine (TCM) syndrome score, and changes in serum markers. Neuron-specific enolase (NSE), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α) were taken as the serological indicators for evaluating cognitive function. Adverse events in both groups were recorded during the treatment period.

Results

The treatment group demonstrated higher MMSE scores and clinical efficacy than the control group, specifically in the scores of spatial orientation, attention and calculation, and language proficiency in the MMSE scale. The treatment group outperformed the control group in MCS, ADLs, GDS, and TCM syndrome scores. Furthermore, the treatment group was superior to the control group in recovering the levels of NSE, IL-8, and TNF-α. In addition, the treatment group had lower incidence of adverse reactions such as nausea and poor appetite than the control group.

Conclusions

The 12-week treatment with Naohuan Dan combined with idebenone significantly improved the cognitive function and daily life abilities, lowered the depression levels, and reduced the occurrence of adverse events among patients with MCI. These findings offer valuable insights into the efficacy of integrating TCM with Western medicine in the clinical management of MCI.

(ClinicalTrials.gov ID: NCT05931029; https://clinicaltrials.gov/study/NCT05931029?cond=Naohuan%20Dan&rank=1)
A Murine Polytrauma Model for the Study of Thromboinflammation
Authors: MacArthur Taleen A. , Goswami Julie , Navarro Sergio M. , Spears Grant M. , Bailey Kent R. , Thompson Riley , Dong Jing-Fei , Kozar Rosemary A. , Auton Matthew T. , Knight Jason , Park Myung S.
Published: November 2023

INTRODUCTION

Neutrophil Extracellular Traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine polytrauma model that induces thrombo-inflammatory response i.e., NETosis and accelerated thrombin generation.

METHODS

Wild-type male mice (n = 10, age 8 – 12 weeks) underwent polytrauma (gastrocnemius crush, femur fracture, and laparotomy) and were compared to an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (Calibrated Automated Thrombogram), myeloperoxidase (MPO), and von Willebrand Factor (vWF) quantification. Immunohistochemistry of lung tissue was performed to assess for Citruillinated H3 (Cit H3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for Cit H3 at 400 X magnification (CitH3 cluster). Data presented either as mean (SD) or median [IQR] with p < 0.05 significant. Sham and trauma treated animals were compared by the 2-sample Wilcoxon ranksum test.

RESULTS

Animals subjected to polytrauma had accelerated thrombin generation compared to controls with greater peak height (nM) (61.3 [41.2, 73.2] vs. 28.4 [19.5, 37.5], p = 0.035) and shorter time to peak (min) (3.37 [2.81, 3.81] vs. 4.5 [4.08, 4.75], p = 0.046). Markers of neutrophil activation were greater following polytrauma than in controls (MPO (ng/ml) 961.1 [858.1, 1116.8] vs. 481.3 [438.0, 648.9], p = 0.004). NETosis, as evidenced by the above defined number of CitH3 clusters in the lung, was greater in polytrauma than in controls (mean 3 [2.9] vs. 0.2 [0.7], p = 0.009).

CONCLUSIONS

This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine polytrauma model, as early as three hours following injury.

STUDY TYPE

Animal study

LEVEL OF EVIDENCE

NA
Dimethyl malonate protects the lung in a murine model of acute respiratory distress syndrome
Authors: Taghavi Sharven , Campbell Alexandra , Engelhardt David , Duchesne Juan , Shaheen Farhana , Pociask Derek , Kolls Jay , Jackson-Weaver Olan
Published: November 2023

BACKGROUND

Succinate is a proinflammatory citric acid cycle metabolite that accumulates in tissues during pathophysiological states. Oxidation of succinate after ischemia-reperfusion leads to reversal of the electron transport chain and generation of reactive oxygen species. Dimethyl malonate (DMM) is a competitive inhibitor of succinate dehydrogenase, which has been shown to reduce succinate accumulation. We hypothesized that DMM would protect against inflammation in a murine model of ARDS.

METHODS

C57BL/6 mice were given ARDS via 67.7 μg of intratracheally administered lipopolysaccharide. Dimethyl malonate (50 mg/kg) was administered via tail vein injection 30 minutes after injury, then daily for 3 days. The animals were sacrificed on day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts were performed to examine cellular influx. Supernatant protein was quantified via Bradford protein assay. Animals receiving DMM (n = 8) were compared with those receiving sham injection (n = 8). Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify the endothelial glycocalyx (EGX).

RESULTS

Total cell counts in BAL was less for animals receiving DMM (6.93 × 106 vs. 2.46 × 106, p = 0.04). The DMM group had less BAL macrophages (168.6 vs. 85.1, p = 0.04) and lymphocytes (527.7 vs. 248.3; p = 0.04). Dimethyl malonate–treated animals had less protein leak in BAL than sham treated (1.48 vs. 1.15 μg/μl, p = 0.03). Treatment with DMM resulted in greater staining intensity of the EGX in the lung when compared with sham (12,016 vs. 15,186 arbitrary units, p = 0.03). Untreated animals had a greater degree of weight loss than treated animals (3.7% vs. 1.1%, p = 0.04). Dimethyl malonate prevented the upregulation of monocyte chemoattractant protein-1 (1.66 vs. 0.92 RE, p = 0.02) and ICAM-1 (1.40 vs. 1.01 RE, p = 0.05).

CONCLUSION

Dimethyl malonate reduces lung inflammation and capillary leak in ARDS. This may be mediated by protection of the EGX and inhibition of monocyte chemoattractant protein-1 and ICAM-1. Dimethyl malonate may be a novel therapeutic for ARDS.
Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation
Authors: Arain Amir M. , Mirro Emily A. , Brown Dan , Peters Angela , Newman Blake , Richards Sindhu , Rolston John D.
Published: November 2023

Purpose:

The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah.

Methods:

Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records.

Results:

Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes (>1 year), and 25 patients had enough recorded data (>6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG.

Conclusions:

Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.
Association of Scalp High-Frequency Oscillation Detection and Characteristics With Disease Activity in Pediatric Epilepsy
Authors: Maeda Keisuke , Hosoda Nami , Fukumoto Junichi , Kawai Shun , Hayafuji Mizuki , Tsuboi Himari , Fujita Shiho , Ichino Naohiro , Osakabe Keisuke , Sugimoto Keiko , Ishihara Naoko
Published: November 2023

Purpose:

High-frequency oscillation (HFO) in scalp electroencephalography is a promising new noninvasive prognostic epilepsy biomarker, but further data are needed to ascertain the utility of this parameter. The present work investigated the association between epileptic activity and scalp HFO in pediatric patients with various types of epilepsy, using multivariable regression models to correct for possible confounding factors.

Methods:

The authors analyzed 97 subjects who were divided into groups with active epilepsy (within 1 year of seizure), seizure-free epilepsy (>1 year without seizure), and nonepilepsy. Regarding the frequency of seizure occurrence as an indicator of epileptic activity, we categorized subjects into four groups (Daily/Weekly, Monthly, Yearly, and Rarely).

Results:

Multiple linear regression analysis showed that the scalp HFO detection rate was significantly higher in patients with active epilepsy than in those with nonepilepsy (β [95% confidence interval] = 2.77 [1.79–4.29]; P < 0.001). The association between scalp HFO detection rate and frequency of seizure occurrence was highest in the Daily/Weekly group (β [95% confidence interval] = 3.38 [1.57–7.27]; P = 0.002), followed by Monthly and Yearly groups (β [95% confidence interval] = 2.42 [1.02–5.73]; P = 0.046 and 0.36 [0.16–0.83]; P = 0.017). In addition, HFO duration, number of peaks, and number of channels detected were significantly higher in patients with active epilepsy.

Conclusions:

Pediatric patients with active epilepsy and high frequency of seizure occurrence exhibited a higher scalp HFO detection rate. These results may help to establish HFO detectable by noninvasive scalp electroencephalography as a biomarker of active epilepsy in pediatric patients.
Neurophysiological and Clinical Outcomes in Episodic Migraine Without Aura: A Cross-Sectional Study
Authors: Deodato Manuela , Granato Antonio , Martini Miriam , Buoite Stella Alex , Galmonte Alessandra , Murena Luigi , Manganotti Paolo
Published: November 2023

Purpose:

The aim of this study was to assess differences between people with episodic migraine and healthy controls in some neurophysiological and clinical outcomes, which, in turn, may highlight the differences in sensory processing, especially in cortical excitability, pain processing, and executive function.

Methods:

A cross-sectional study was performed, including the following outcomes: pressure pain thresholds with algometry; resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation with transcranial magnetic stimulation; and executive functions with the trail making test and the frontal assessment battery.

Results:

Thirty adults with migraine (36 ± 10 years) and 30 healthy controls (29 ± 14 years) were included in this study. Compared with the healthy controls, participants with migraine presented lower pressure pain thresholds values in all the assessed muscles (P < 0.001), lower resting motor threshold (−10.5% of the stimulator output, 95% CI: −16.8 to −4.2, P = 0.001, Cohen d = 0.869) and higher short-interval intracortical inhibition motor-evoked potential's amplitude at 3 ms (0.25, 95% CI: 0.05 to 0.46, P = 0.015, Cohen d = 0.662), and worse performances both in trail making test (7.1, 95% CI: 0.9 to 13.4, P = 0.027, Cohen d = 0.594) and frontal assessment battery (−1.1, 95% CI: −1.7 to −0.5, P = 0.001, Cohen d = 0.915).

Conclusions:

Participants with migraine presented significant differences in cortical excitability, executive functions, and pressure pain thresholds, compared with healthy controls.
Spliceosomal introns in the diplomonad parasite Giardia duodenalis revisited
Authors: Seabolt Matthew H. , Roellig Dawn M. , Konstantinidis Konstantinos T.
Published: November 2023

Complete reference genomes, including correct feature annotations, are a fundamental aspect of genomic biology. In the case of protozoan species such as Giardia duodenalis, a major human and animal parasite worldwide, accurate genome annotation can deepen our understanding of the evolution of parasitism and pathogenicity by identifying genes underlying key traits and clinically relevant cellular mechanisms, and by extension, the development of improved prevention strategies and treatments. This study used bioinformatics analyses of Giardia mRNA libraries to characterize known introns and identify new intron candidates, working towards completion of the G. duodenalis assemblage A strain ‘WB’ genome and further elucidating Giardia’s gene expression. By using a set of experimentally validated positive control loci to calibrate our intron detection pipeline, we were able to detect evidence of previously missed candidate splice junctions directly from expressed transcript data. These intron candidates were further studied in silico using NMDS (non-metric multidimensional scaling) clustering to determine shared characteristics and their relative importance such as secondary structure, splicing efficiency and motif conservation, and thus to refine intron models. Results from this study identified 34 new intron candidates, with several potential introns showing evidence that secondary structure of the mRNA molecule might play a more significant role in splicing than previously reported eukaryotic splicing activity mediated by a reduced spliceosome present in G. duodenalis.
Reduced ambiguity and improved interpretability of bacterial genome-wide associations using gene-cluster-centric k-mers
Authors: Sommer Hannes , Djamalova Dilfuza , Galardini Marco
Published: November 2023

The wide adoption of bacterial genome sequencing and encoding both core and accessory genome variation using k-mers has allowed bacterial genome-wide association studies (GWAS) to identify genetic variants associated with relevant phenotypes such as those linked to infection. Significant limitations still remain because of k-mers being duplicated across gene clusters and as far as the interpretation of association results is concerned, which affects the wider adoption of GWAS methods on microbial data sets. We have developed a simple computational method (panfeed) that explicitly links each k-mer to their gene cluster at base-resolution level, which allows us to avoid biases introduced by a global de Bruijn graph as well as more easily map and annotate associated variants. We tested panfeed on two independent data sets, correctly identifying previously characterized causal variants, which demonstrates the precision of the method, as well as its scalable performance. panfeed is a command line tool written in the python programming language and is available at https://github.com/microbial-pangenomes-lab/panfeed.
Publication, Funding, and Experimental Data in Support of Human Reference Atlas Construction and Usage
Authors: Kong Yongxin , Börner Katy
Published: November 2023

Experts from 18 consortia are collaborating on the Human Reference Atlas (HRA) which aims to map the 37 trillion cells in the healthy human body. Information relevant for HRA construction and usage is held by experts (clinicians, pathologists, anatomists, single-cell experts), published in scholarly papers, and captured in experimental data. However, these data sources use different metadata schemes and cannot be cross-searched efficiently. This paper documents the compilation of a dataset, called HRAlit, that links the 136 HRA v1.4 digital objects (31 organs with 2,689 anatomical structures, 590 cell types, 1,770 biomarkers) to 583,117 experts; 7,103,180 publications; 896,680 funded projects, and 1,816 experimental datasets. The resulting HRAlit represents 23 tables with 21,704,001 records including 7 junction tables with 13,042,188 relationships. We demonstrate how HRAlit can be mined to identify leading experts, major papers, funding trends, or alignment with existing ontologies in support of systematic HRA construction and usage. Data and code are athttps://github.com/cns-iu/hra-literature.
Microbial functional pathways based on metatranscriptomic profiling enable effective saliva-based health assessments for precision wellness
Authors: Patridge Eric , Gorakshakar Anmol , Molusky Matthew M. , Ogundijo Oyetunji , Janevski Angel , Julian Cristina , Hu Lan , Vuyisich Momchilo , Banavar Guruduth
Published: November 2023

It is increasingly recognized that an important step towards improving overall health is to accurately measure biomarkers of health from the molecular activities prevalent in the oral cavity. We present a general methodology for computationally quantifying the activity of microbial functional pathways using metatranscriptomic data. We describe their implementation as a collection of eight oral pathway scores using a large salivary sample dataset (n=9,350), and we evaluate score associations with oropharyngeal disease phenotypes within an unseen independent cohort (n=14,129). As clinical validation, we show that the relevant oral pathway scores are significantly worse in individuals with periodontal disease, acid reflux, and nicotine addiction, compared with controls. Given these associations, we make the case to use these oral pathway scores to provide molecular health insights from simple, non-invasive saliva samples, and as molecular endpoints for actionable interventions to address the associated conditions.

Highlights

Microbial functional pathways in the oral cavity are quantified as eight oral scores

Scores are significantly worse for individuals with oropharyngeal disease phenotypes

This methodology may be generalized to other pathways and other sample types

These scores provide longitudinal health insights in a precision wellness application

Graphical Abstract
The circulating immune cell landscape stratifies metastatic burden in breast cancer patients
Authors: Mangiola S , Brown R , Berthelet J , Guleria S , Liyanage C , Ostrouska S , Wilcox J , Merdas M , Larsen PF , Bell C , Schroder J , Mielke L , Mariadason J , Chang-Hao Tsao S , Chen Y , Yadav VK , Anderson RL , Vodala S , Merino D , Behren A , Yeo B , Papenfuss AT , Pal B
Published: November 2023

Advanced breast cancers show varying degrees of metastasis; however, reliable biomarkers of metastatic disease progression remain unknown. In circulation, immune cells are the first line of defence against tumour cells. Herein, using >109,591 peripheral blood mononuclear cells from healthy individuals and breast cancer patients, we tested whether molecular traits of the circulating immune cells, probed with single-cell transcriptomics, can be used to segregate metastatic profiles. Our analyses revealed significant compositional and transcriptional differences in PBMCs of patients with restricted or high metastatic burden versus healthy subjects. The abundance of T cell and monocyte subtypes segregated cancer patients from healthy individuals, while memory and unconventional T cells were enriched in low metastatic burden disease. The cell communication axes were also found to be tightly associated with the extent of metastatic burden. Additionally, we identified a PBMC-derived metastatic gene signature capable of discerning metastatic condition from a healthy state. Our study provides unique molecular insights into the peripheral immune system operating in metastatic breast cancer, revealing potential new biomarkers of the extent of the metastatic state. Tracking such immune traits associated with metastatic spread could complement existing diagnostic tools.
Long-term serial passaging of SARS-CoV-2 reveals signatures of convergent evolution
Authors: Foster Charles S.P. , Walker Gregory J. , Jean Tyra , Wong Maureen , Brassil Levent , Isaacs Sonia R. , Lyu Yonghui , Turville Stuart , Kelleher Anthony , Rawlinson William D.
Published: November 2023

Understanding viral evolutionary dynamics is crucial to pandemic responses, informing prediction of virus adaptation over time, virus adaptation to antiviral and immune pressures, design of effective therapies, and virus surveillance for public health strategies. Whole-genome sequencing (WGS) of SARS-CoV-2 has enabled fine-grained studies of virus evolution in the human population. Serial passagingin vitrooffers a complementary controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage. In this study, nine virus lineages, including four "variants of concern" and three former "variants under investigation", were sampled over ≥33 serial passages (range 33-100) in Vero E6 cells. WGS was used to examine virus evolutionary dynamics and identify key mutations with implications for fitness and/or transmissibility. Mutations accumulated regularly during serial passaging. Many low-frequency variants were lost but others became fixed, suggesting eitherin vitrobenefits, or at least a lack of deleterious effect. Mutations arose convergently both across passage lines and compared with contemporaneous SARS-CoV-2 clinical sequences, including some hypothesised to drive lineage success through host immune evasion (e.g. S:A67V, S:H655Y). The appearance of these mutationsin vitrosuggested key mutations can arise convergently even in the absence of a multicellular host immune response through mechanisms other than immune-driven mutation. Such mutations may provide other benefits to the virusesin vitro, or arise stochastically. Our quantitative investigation into SARS-CoV-2 evolutionary dynamics spans the greatest number of serial passages to date, and will inform measures to reduce the effects of SARS-CoV-2 infection on the human population.

Importance

The ongoing evolution of SARS-CoV-2 has challenged public health efforts to minimise the health impacts of the virus during the COVID-19 pandemic. Carrying out whole-genome sequencing of outbreak cases has enabled global contact tracing efforts and the identification of mutations of concern within the virus’ genome. Here, we use a complementary approach of charting the evolution of the virus within a controlled cell culture environment, focusing on nine different virus lineages. Our approach demonstrates how SARS-CoV-2 continues to evolve readily in vitro, with many changes mirroring those seen in outbreak cases globally. Findings of the study are important for investigating how important mutations arise, and considering the future evolutionary trajectory of SARS-CoV-2.
Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2
Authors: Hoffmann Markus , Willruth Lina-Liv , Dietrich Alexander , Lee Hye Kyung , Knabl Ludwig , Trummer Nico , Baumbach Jan , Furth Priscilla A. , Hennighausen Lothar , List Markus
Published: November 2023

Bulk RNA sequencing (RNA-seq) of blood is typically used for gene expression analysis in biomedical research but is still rarely used in clinical practice. In this study, we argue that RNA-seq should be considered a routine diagnostic tool, as it offers not only insights into aberrant gene expression and splicing but also delivers additional readouts on immune cell type composition as well as B-cell and T-cell receptor (BCR/TCR) repertoires. We demonstrate that RNA-seq offers vital insights into a patient’s immune status via integrative analysis of RNA-seq data from patients infected with various SARS-CoV-2 variants (in total 240 samples with up to 200 million reads sequencing depth). We compare the results of computational cell-type deconvolution methods (e.g., MCP-counter, xCell, EPIC, quanTIseq) to complete blood count data, the current gold standard in clinical practice. We observe varying levels of lymphocyte depletion and significant differences in neutrophil levels between SARS-CoV-2 variants. Additionally, we identify B and T cell receptor (BCR/TCR) sequences using the tools MiXCR and TRUST4 to show that - combined with sequence alignments and pBLAST - they could be used to classify a patient’s disease. Finally, we investigated the sequencing depth required for such analyses and concluded that 10 million reads per sample is sufficient. In conclusion, our study reveals that computational cell-type deconvolution and BCR/TCR methods using bulk RNA-seq analyses can supplement missing CBC data and offer insights into immune responses, disease severity, and pathogen-specific immunity, all achievable with a sequencing depth of 10 million reads per sample.

Key Points

Computational deconvolution of transcriptomes can estimate immune cell abundances in SARS-CoV-2 patients, supplementing missing CBC data.

10 million RNA sequencing reads per sample suffice for analyzing immune responses and disease severity, including BCR/TCR identification.
Cross-phenotype associations between Alzheimer’s Disease and its comorbidities may provide clues to progression
Authors: Moore Anni , Ritchie Marylyn D.
Published: November 2023

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide, with one in nine people over the age of 65 living with the disease in 2023. In this study, we used a phenome wide association study (PheWAS) approach to identify cross-phenotype associations between previously identified genetic AD and for electronic health record (EHR) diagnoses from the UK Biobank (UKBB) (n=361,194 of European ancestry) and the eMERGE Network (n=105,108 of diverse ancestry). Based on 497 previously identified AD-associated variants from the Alzheimer’s Disease Variant Portal (ADVP), we found significant associations primarily in immune and cardiac related diseases in our PheWAS. Replicating variants have widespread impacts on immune genes in diverse tissue types. This study demonstrates the potential of using the PheWAS strategy to improve our understanding of AD progression as well as identify potential drug repurposing opportunities for new treatment and disease prevention strategies.