bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin-1 Blockade With RPH-104 (Goflikicept) in Patients With ST-Segment Elevation Myocardial Infarction: Secondary End Points From an International, Double-Blind, Randomized, Placebo-Controlled, Phase 2a Study
Authors: Abbate Antonio , Van Tassell Benjamin , Bogin Vlad , Markley Roshanak , Pevzner Dmitry V. , Cremer Paul C. , Meray Imad A. , Privalov Dmitry V. , Taylor Angela , Grishin Sergey A. , Egorova Alina N. , Ponomar Ekaterina G. , Lavrovsky Yan , Samsonov Mikhail Yu.
Published: October 2024

In a randomized double-blinded clinical trial of patients with ST segment elevation myocardial infarction (STEMI), goflikicept, an interleukin-1 blocker, significantly reduced systemic inflammation, measured as the area under the curve (AUC) for high-sensitivity C reactive protein at 14 days. We report secondary analyses of biomarkers at 28 days, and cardiac function and clinical end points at 1 year. Patients received a single administration of goflikicept 80 mg (n = 34), goflikicept 160 mg (n = 34), or placebo (n = 34). Both doses of goflikicept significantly reduced the AUC for high-sensitivity C reactive protein at 28 days compared with placebo, without statistically significant differences between the doses. There were no statistically significant differences between groups in the AUC for natriuretic peptides at 28 days. There were no significant differences between placebo, goflikicept 80 mg, and 160 mg groups in deaths (2.9%, 2.9%, and 0%), hospitalization for cardiovascular reasons (9.1%, 5.9%, and 0%), new-onset or progression of heart failure (9.1%, 5.9%, and 5.9%), and new or increased use of loop diuretics (24.2%, 14.7%, and 17.6%), nor in the number of patients with treatment emergent adverse events, with no treatment-related serious adverse events in any group. In conclusion, in patients with STEMI, interleukin-1 blockade with goflikicept 80 mg or 160 mg was well tolerated and associated with significant reduction of systemic inflammation. Further adequately powered studies are warranted to determine whether the reduction in systemic inflammation with goflikicept translates into a clinical benefit in patients with STEMI.
Use of Plasma Rich in Growth Factors for Ocular Surface Disorders: A Systematic Review
Authors: Gemae Mohamed R. , Patil Nikhil S. , Yu Caberry W. , Agarwal Manokamna , Slomovic Allan R. , Chan Clara C.
Published: October 2024

Purpose:

Ocular surface disorders (OSDs) can severely affect vision and quality of life. Autologous blood products, such as plasma rich in growth factors (PRGF), are recently available to treat OSDs refractory to traditional therapies. This review aims to summarize the efficacy and safety of PRGF in OSDs.

Methods:

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was established a priori and published on PROSPERO (CRD42024522119). MEDLINE, Embase, and Cochrane Library were searched for primary articles until February 6, 2024. Primary outcomes included slit-lamp examination findings and patient-reported outcomes. Secondary outcomes included visual outcomes and adverse events. Risk of bias was assessed using the Cochrane Risk of Bias and ROBINS-I tools.

Results:

Twenty-two studies involving 1158 eyes were included. PRGF showed notable improvement in objective and subjective outcomes in OSDs. Comparative studies did not show PRGF to be superior to a standard steroid taper for dry eye disease. However, the use of PRGF was also reported in persistent epithelial defects and corneal ulcerations. In these conditions, there were high rates of complete healing and reduced corneal staining. PRGF has also been reported to improve ocular surface healing and stability when used as an adjunct to refractive and pterygium surgeries. No serious adverse events were reported.

Conclusions:

PRGF has potential as an effective treatment of OSDs resistant to traditional therapies with minimal safety concerns. Large randomized controlled trials are needed to better evaluate the role of PRGF within the treatment armamentarium for corneal pathologies.
Care trajectories for musculoskeletal disorders following a new episode of low back pain
Authors: Dagenais Pierre , Courteau Mireille , Courteau Josiane , Martel Gilles , Vanasse Alain
Published: October 2024

This study explored diverse care trajectories (CTs) for low back pain (LBP) and other musculoskeletal disorders (MSDs), over a 5-year period following a first episode of LBP. Based on Quebec's administrative health data from 2007 to 2011, this longitudinal cohort study involved 12,608 adults seeking health care for LBP. Using a new multidimensional state sequence analysis, we identified 6 distinct types of CTs. The most prevalent types 1, 2, and 3 (comprising 79.2%, 18.0%, and 21.7% of the cohort, respectively) exhibit rapid recovery and similar patterns of healthcare use over 5 years but differing in initial diagnoses: nonspecific LBP in type 1, trauma-related LBP in type 2 (mostly younger men and highest initial emergency consultation), and specific LBP in type 3. Types 4 to 6, representing smaller groups, show high healthcare utilization with comparable mixed LBP diagnoses at entry but distinctive subsequent care use patterns. Patients in types 4 and 6 (mainly older age groups and women) sought care for other MSDs from general practitioners or specialists, while middle-aged patients in type 5 experienced persistent nonspecific LBP with frequent general practitioner consultations over 5 years. The CTs typology revealed several key areas for improvement in nonpharmacological interventions, including the need to address possible inappropriate medical imaging and invasive interventions for older women with MSDs and the lack of ambulatory care access for younger patients with trauma-related LBP. Finally, results clearly highlighted poor access to rehabilitation physicians and rehabilitation services for all patients suffering from LBP and MSDs.
Early life stress modulates neonatal somatosensation and the transcriptional profile of immature sensory neurons
Authors: Harbour Kyle , Eid Fady , Serafin Elizabeth , Hayes Madailein , Baccei Mark L.
Published: October 2024

Early life stress (ELS) is associated with an increased risk of experiencing chronic pain during adulthood, but surprisingly little is known about the short-term influence of ELS on nociceptive processing in the immature nervous system and the concomitant effects on somatosensation in the neonate. Here, we investigate how ELS modulates pain in neonatal mice and the transcriptional and electrophysiological signatures of immature dorsal root ganglia (DRG). Shortly after the administration of a neonatal limiting bedding (NLB) paradigm from postnatal days (P)2 to P9, both male and female pups exhibited robust hypersensitivity in response to tactile, pressure, and noxious cold stimuli compared with a control group housed under standard conditions, with no change in their sensitivity to noxious heat. Bulk RNA-seq analysis of L3-L5 DRGs at P9 revealed significant alterations in the transcription of pain- and itch-related genes following ELS, highlighted by a marked downregulation in Sst, Nppb, Chrna6, Trpa1, and Il31ra. Nonetheless, ex vivo whole-cell patch-clamp recordings from putative A- and C-fiber sensory neurons in the neonatal DRG found no significant changes in their intrinsic membrane excitability following NLB. Overall, these findings suggest that ELS triggers hyperalgesia in neonates across multiple pain modalities that is accompanied by transcriptional plasticity within developing sensory neurons. A better understanding of the mechanisms governing the interactions between chronic stress and pain during the neonatal period could inform the future development of novel interventional strategies to relieve pain in infants and children who have experienced trauma.
Analysis of treatment benefits and prognostic factors for posttransplant HCC recurrence in a large Euro-American-Asian cohort
Authors: Li Zhihao , Chen Itsuko Chih-Yi , Centonze Leonardo , Magyar Christian T.J. , Choi Woo Jin , Shah Sachin , O’Kane Grainne M. , Vogel Arndt , De Carlis Luciano , Lerut Jan , Lai Quirino , Mehta Neil , Chen Chao-Long , Sapisochin Gonzalo
Published: October 2024

Posttransplant HCC recurrence significantly impacts survival, yet its management is challenging due to limited evidence. With recent advancements in HCC treatment, updated data on managing recurrent diseases are needed. In this retrospective study across 6 centers (2000–2022), we employed Cox proportional-hazards regression and log-rank tests to assess survival differences. A prognostic score model was developed to categorize patient survival. The efficacy of tyrosine kinase inhibitors was evaluated through propensity score matching. In our study, 431 of 3349 (14%) patients with HCC who underwent transplantation developed recurrence within a median interval of 18 (IQR: 9–32) months. One hundred forty-seven (34%) underwent curative-intent treatments, 207 (48%) received palliative treatments, and 77 (18%) were given best-supportive care. Patients undergoing curative-intent treatments had better survival from the time of recurrence with a median survival of 45 (95% CI: 36–63) months and 1/3/5-year survival of 90%/56%/43% compared to those receiving noncurative treatments (median: 11 [95% CI: 10–13] mo, 1/3/5-y survival of 46%/10%/7%, log-rank p < 0.001). Patients with recurrence diagnosed in the era 2018–2022 showed improved survival over the previous era (HR 0.64 [95% CI: 0.47–0.86]). Multivariable analysis identified 5 prognostic factors: ineligibility for curative-intent treatment (HR: 3.5 [95% CI: 2.7–4.6]), recurrence within 1 year (HR: 1.7 [95% CI: 1.3–2.1]), poor tumor differentiation (HR: 1.5 [95% CI: 1.1–1.9]), RETREAT score ≥3 (HR: 1.4 [95% CI: 1.1–1.8]), and alpha-fetoprotein at recurrence ≥400 ng/mL (HR: 1.4 [95% CI: 1.1–1.9]). These factors contributed to a prognostic scoring system (0–9) that stratified patients into 3 prognosis groups. Both propensity score-matched analysis and multivariable regression indicated that lenvatinib was not statistically superior to sorafenib in terms of efficacy. Curative-intent treatments should be advocated for patients with posttransplant recurrence whenever possible. Prognostic factors linked to aggressive tumor biology significantly influence survival. Advancements in HCC management have improved survival outcomes over the past 5 years.
Marked variation in disease acuity and outcomes on the liver transplant waiting list by sociodemographic characteristics
Authors: Jackson Whitney E. , Lopez Rocio , Forman Lisa M. , Arrigain Susana , Schold Jesse D.
Published: October 2024

Understanding the association of social determinants of health with liver transplant listing and waitlist outcomes can inform health care policy and interventions aimed at improving access to care. We analyzed the Scientific Registry of Transplant Recipients database merged with the Social Deprivation Index (SDI) to evaluate if the area of residence is associated with the Model for End-Stage Liver Disease incorporating sodium (MELD-Na) at the time of waitlist placement and outcomes following waitlisting, and if this varied based on sociodemographic variables. Compared to candidates residing in areas of low SDI, those residing in areas of high SDI (most socioeconomic disadvantage) had 11% higher adjusted likelihood (aOR [95% CI] = 1.11 [CI 1.05,1.17]) of being listed for transplant with a MELD-Na score ≥30; this was not statistically significant when also adjusted for race/ethnicity (aOR = 1.02 [0.97,1.08]). When stratified by race/ethnicity, residing in an area of high SDI was associated with a MELD-Na score ≥30 at the time of waitlisting among Hispanic White candidates (aOR = 1.24, 95% CI: 1.04, 1.49). Candidates residing in areas of high SDI had an 8% lower chance (adjusted hazard ratio [aHR] = 0.92 [0.88,0.96]) of undergoing a liver transplant, a 6% higher risk of death (aHR = 1.06 [1.002,1.13]), and a 20% higher risk (aHR = 1.20 [1.13,1.28]) of removal on the waitlist independent of race, ethnicity, insurance status, or sex. In the United States, residence in areas of high socioeconomic disadvantage is significantly associated with higher MELD-Na at the time of waitlisting among Hispanic White candidates. In addition, residence in areas of high socioeconomic disadvantage was associated with a higher risk of death or removal from the waitlist and lower chances of receiving a liver transplant after waitlist placement, particularly among Non-Hispanic White candidates and older candidates.
Evaluation of brain metabolism using F18-FDG PET/CT imaging in patients diagnosed with lung cancer
Authors: Şen Ahmet E. , Kaya Buğra , Bozcuk Hakan Ş. , Şahin Özlem , Uyar Mehmet , Artaç Mehmet , Erol Mustafa
Published: October 2024

Objectives

Brain imaging of regional metabolic changes in cancer patients can provide insights into cancer biology. We aimed to detect regional metabolic changes in the brains of untreated lung cancer patients without brain metastases using 2-deoxy-2-[18F]fluoroglucose PET/computed tomography.

Methods

The study included 44 lung cancer patients and 17 non-cancer patients as controls. Standardized uptake value (SUV) mean values of 68 different brain regions were recorded, and their ratios to whole brain and brainstem SUVmean were calculated.

Results

Comparisons between the groups showed significant reductions in the frontal lobe, inferior temporal gyrus, and right cingulate and paracingulate gyrus ratios in the patient group. Conversely, the right nucleus caudatus and right pallidum ratios were elevated. Correlation analysis with total lesion glycolysis (TLG) revealed positive correlations in the basal ganglia, right insula, amygdala, and right hippocampus ratios. Negative correlations were observed in the left frontal lobe and some temporal and parietal regions.

Conclusions

While most brain regions showed reduced metabolism, potentially due to tumor-brain glucose competition, others were preserved or positively correlated with TLG, suggesting a link to poor prognosis. The reduced metabolism in the frontal lobe might be associated with depression and cognitive decline in cancer patients.
Spontaneous transomental hernia: a case report of a rare internal hernia with a challenging diagnosis
Authors: Ben Khalifa Mohamed , Ghannouchi Mossaab , Sarraj Achref , Aouadi Sabri , Maatouk Mohamed , Boudokhane Moez
Published: October 2024

Introduction and Importance:

Transomental hernia (TOH) is an extremely rare clinical condition that represents 1–4% of all internal hernias. Spontaneous TOH occurs in patients with no history of surgery or previous abdominal trauma. It happens after protrusion of the abdominal viscera, commonly the small bowel loops through a defect on the great omentum.

Presentation of the case:

We present a case of occlusion due to TOH in a 66-year-old man who underwent a laparotomy, and operative exploration showed 10 cm of small bowel incarcerated through a defect in the right side of the greater omentum of 4 cm in diameter.

Discussion:

The diagnosis is usually delayed because symptoms are nonspecific. Postoperative morbidity and mortality are important because patients present most frequently with gangrenous bowel, making morbidity and mortality higher. Therefore, it constitutes a critical surgical emergency and must be quickly recognized and managed. Computed tomography (CT) scan plays a prominent role in diagnosis. Midline laparotomy is the main emergency approach for patients with unknown bowel obstruction. Some authors suggest a laparoscopic approach, but it requires a surgeon’s experience and propitious patient’s conditions.

Conclusion:

TOH is the rarest type of internal hernia with extremely difficult preoperative diagnosis due to nonspecific semiology. This type of hernia has the highest morbidity and mortality rates of all internal hernias. Thus, it must be suspected whenever there is bowel obstruction of unknown origin and quickly managed.
Pharmacological Dissociation in Hemicrania Continua With Persistent Visual Aura Evolved From Episodic Migraine
Authors: Grosberg Brian M. , Friedman Deborah I. , Robbins Matthew S. , Verhaak Allison M.S.
Published: October 2024

Objective:

To report a case of hemicrania continua (HC) and persistent visual aura without infarction in a patient with previous episodic migraine with visual aura, whose persistent aura symptoms improved only after treatment with divalproex sodium.

Background:

Once regarded as highly specific for migraine, visual aura has been associated with trigeminal autonomic cephalalgias, including HC. In previous descriptions of HC and episodes of typical visual aura, the aura occurred exclusively with severe headache exacerbations and, like the pain, resolved with indomethacin.

Methods:

Case report and literature review.

Results:

A 54-year-old man with a history of episodic migraine with visual aura reported a gradual onset of HC with persistent visual aura of 15 months duration. General medical and neurological examinations were normal, including imaging studies. HC's headache responded to indomethacin, while the visual aura was recalcitrant, only improving with oral divalproex sodium treatment.

Conclusion:

As our patient experienced HC, which evolved from episodic migraine, we hypothesize that migraine and HC may share a common pathophysiology. However, the persistence of the visual aura, despite the abolition of pain and autonomic features with a therapeutic dose of indomethacin, and the subsequent successful treatment of the aura with divalproex sodium, suggest that aura and HC headache arise from distinct and dissociable mechanisms.
West Nile Virus Neuroinvasive Disease
Authors: Taga Arens , Filippatou Angeliki , Divakaruni Sai Sachin , Pardo Carlos , Green Kemar
Published: October 2024

Background and Objective:

West Nile neuroinvasive disease (WNND) displays a wide range of clinical manifestations due to its involvement of various structures within the central nervous system and peripheral nervous system, often including prolonged unresponsiveness as the presenting symptom.

Methods and Results:

We describe 2 patients presenting with coma and bilateral thalamic lesions on brain magnetic resonance imaging, found to have WNND after extensive workup. These cases illustrate some of the challenges associated with evaluating coma in general and specifically in diagnosing WNND.

Conclusion:

The clinical diagnosis of WNND requires a high index of suspicion, particularly in immunocompromised and elderly patients. Brain and spine magnetic resonance imaging findings can help narrow down the differential diagnosis, although other diseases may manifest similarly. Serological studies on the cerebrospinal fluid are essential to confirm the diagnosis but have inherent limitations. Given these challenges, WNND should be considered in all patients living in endemic areas who present with unexplained altered mental status during the late summer and early fall seasons.
Concurrent Intracranial and Spinal Dural Metastases Demonstrated by 68Ga-DOTATATE PET/CT With Negative 123I-MIBG SPECT/CT in a Pediatric Neuroblastoma Patient
Authors: Qiao Haizhou , Li Siqi , Xu Yanfeng , Wang Wei , Yang Jigang
Published: October 2024

Contrast enhancement MRI of the brain and spine showed abnormal enhancement in intracranial and spinal dural lesions in a 6-year-old boy with high-risk neuroblastoma, suggesting the possibility of dural metastases. 123I-MIBG SPECT/CT did not show any abnormal MIBG accumulation in these lesions. However, 68Ga-DOTATATE PET/CT showed obvious DOTATATE uptake in these metastatic lesions. Surgical pathology confirmed the diagnosis of intracranial dural metastasis. Concurrent intracranial and spinal dural metastases from neuroblastoma demonstrated by 68Ga-DOTATATE PET/CT with negative 123I-MIBG SPECT/CT have not been reported previously.
Detection and Response Evaluation of Extramedullary and Medullary Blast Crisis in Chronic Myeloid Leukemia on 18F-FDG PET/CT
Authors: Behera Abhishek , Prabhu Meghana , Khanna Gaurav , Sawhney Shikhar , Mishra Pravas Chandra
Published: October 2024

FDG PET/CT imaging is usually not routinely undertaken in patients of chronic myeloid leukemia (CML). We present a case of CML on tyrosine kinase inhibitor treatment with disease control indicated by BCR-ABL1 quantitative reverse transcription–polymerase chain reaction, who underwent PET/CT for evaluation of recent onset vision deterioration with subretinal exudates on ophthalmological examination. PET CT detected FDG-avid sinonasal thickening and bilateral marrow lesions. These lesions on histopathological sampling, examination revealed extramedullary and intramedullary CML blast crisis. Patient was then treated with steroids and change of tyrosine kinase inhibitor for the CML blast crisis. FDG PET/CT done subsequently was able to demonstrate morphological and metabolic response in the lesions.
Positive 68Ga-FAPI-04 PET/MRI and Negative 18F-FDG PET/CT Imaging in Incidental Appendiceal Goblet Cell Adenocarcinoma
Authors: Sun Yu , Wang Haiyan , Chen Xing , Wang Weilun , Zhao Jun
Published: October 2024

A 70-year-old woman presented with left ovarian mass and thickened peritoneum. 18F-FDG PET/CT showed no significant FDG-avid in the whole body. 68Ga-FAPI-04 demonstrated abnormally high FAPI uptake in the ileocecal region, left ovarian lesion, and thickened peritoneum. The postoperative pathology confirmed the appendiceal goblet cell adenocarcinoma. This case highlights the superior and innovative diagnostic role of 68Ga-FAPI-04 in appendiceal goblet cell adenocarcinoma and its metastases.
Value of 68Ga-DOTATATE PET/CT in Follow-up of Renal Cell Carcinoma With Multiple Atypical Metastatic Sites
Authors: Filizoglu Nuh , Ozguven Salih , Ones Tunc , Turoglu Halil Turgut , Erdil Tanju Yusuf
Published: October 2024

The development of late metastatic recurrence after nephrectomy is a well-known characteristic of renal cell carcinoma (RCC). Correct diagnosis is often challenging due to the long time between primary tumor excision and the development of metastases. 68Ga-DOTATATE PET/CT has the potential to be employed in the follow-up of RCC, because RCC expresses somatostatin receptors. However, limited cases have been reported demonstrating 68Ga-DOTATATE uptake in the metastases of RCC. Herein, we describe a unique case of RCC with multiple atypical metastatic sites, emphasizing the usefulness of 68Ga-DOTATATE PET/CT in the evaluation and follow-up of patients with RCC.
Lateral Sacral Artery Perforator Flap as a New Option in Myelomeningocele Reconstruction
Authors: Bas Soysal , Goker Burcu
Published: October 2024

Background

This study aims to present lateral sacral artery perforator (LSAP) flaps as a new option for myelomeningocele reconstruction and to discuss their advantages and disadvantages.

Methods

Eleven patients were included in the study, and reconstruction was performed with 22 LSAP flaps. Patients were evaluated in age, gender, birth weight, kyphosis status, defect localization and size, flap size, operation time, amount of bleeding, and postoperative complications.

Results

Sixteen flaps were raised from the first and 6 from the second LSA. The average time for soft tissue reconstruction was 57 minutes. The mean blood loss was 11.1 mL/kg. No cerebrospinal fluid leakage was detected in any patient. In 1 of the 22 flaps, venous congestion did not completely resolved and resulted in partial necrosis secondary to venous insufficiency. In 2 patients, minimal wound dehiscence was detected in the distal part of the flap. No wound infections, hematomas, donor site complications, or seromas were observed in any patient.

Conclusions

Considering that myelomeningoceles are often located in the lumbar region, we think that LSAP flaps will be a new option among other flaps. Additionally, if other flaps are used in the neonatal period, it may be a good alternative for pressure sore reconstruction in the kyphotic area.
Effectiveness of Colonoscopy in Reducing Incidence of Late-stage Colorectal Cancer Within an Opportunistic Screening Program
Authors: Casas Maria A. , Pereyra Lisandro , Angeramo Cristian A. , Monrabal Lezama Manuela , Schlottmann Francisco , Rotholtz Nicolás A.
Published: October 2024

Background:

The effectiveness of colonoscopy in preventing colorectal cancer (CRC) within opportunistic screening programs has not been clearly established. The aim of this study was to analyze the effectiveness of colonoscopy within an opportunistic screening program using nested case-control study.

Methods:

Subjects who received a diagnosis of CRC (CG) between the ages of 50 and 90 years were included and matched by age and gender in a 1:5 ratio with patients without CRC diagnosis (COG) during the period 2015 to 2023. Using conditional regression analyses, we tested the association between screening colonoscopy and CRC. Subgroup analyses were then performed for CRC location, endoscopist specialty, and colonoscopy quality.

Results:

Of the 134 patients in CG, 19 (14.18%) had a colonoscopy in the preceding 5 years compared with 258 out of 670 (38.51%) in COG (AOR, 0.24; 95% CI: 0.14-0.41). Any colonoscopy was strongly associated with decreased odds for left-sided CRC (AOR, 0.09; 95% CI: 0.04-0.24) but not for right-sided CRC (AOR, 0.58; 95% CI: 0.29-1.17). Only complete colonoscopy (AOR, 0.41; 95% CI: 0.19-0.89) and colonoscopy with satisfactory bowel preparation (AOR, 0.38; 95% CI: 0.15-0.98) were associated with decreased odds for right-sided CRC. No significant differences in colonoscopy outcomes were found when stratifying by endoscopist specialty.

Conclusions:

In the setting of an opportunistic screening program, exposure to any colonoscopy significantly reduced left-sided CRC incidence; however, only high-quality colonoscopy was associated with a lower incidence of right-sided CRC. Therefore, every possible effort should be made to optimize the quality and cost-effectiveness of colonoscopy within an opportunistic screening program.
Is Intraoperative Muscle Motor Evoked Potential Variability due to Fluctuating Lower Motor Neuron Background Excitability?
Authors: Segura Martín J. , Talarico María E. , Piantoni Lucas , Noel Mariano A. , MacDonald David B.
Published: October 2024

Purpose:

This pilot study tests the contribution of fluctuating lower motor neuron excitability to motor evoked potential (MEP) variability.

Methods:

In six pediatric patients with idiopathic scoliosis and normal neurologic examination, cascades of 30 intraoperative H-reflexes (HRs) and MEPs were evoked in the soleus muscle using constant-current stimulators and recorded through surface electrodes with a 20-second interstimulus interval. First, HRs were obtained with an intensity capable of evoking the maximum response. Subsequently, MEPs were obtained with double trains and an intensity of 700 to 900 mA. Coefficients of variation (CVs) of amplitude and area under the curve from HRs and MEPs were compared using a paired two-tailed Student t test. Coefficients of correlation between the mean CVs of HR and MEP parameters were also assessed.

Results:

Pooling the results from the six patients, the mean CV of amplitude from the MEP (24.6 ± 3) was significantly higher than that from the HR (3.5 ± 4.4) (P = 0.000091). The mean CV of the MEP area under the curve (21.8 ± 4.8) was also statistically significantly higher than that from the HR area under the curve (3.4 ± 4.5) (P = 0.00091). The coefficients of correlation of the mean CV of the HR amplitude and area under the curve compared with the corresponding values of the MEP were low (r = 0.29) and very low (r = 0.03), respectively.

Conclusions:

Our results suggest that fluctuations in lower motor neuron excitability may be less important than previously thought to explain the magnitude of MEP variability. The efficacy of corticospinal volleys to recruit a larger and more stable lower motor neuron population would be critical to obtain reproducible MEPs.
Chronobiological Spatial Clusters of Cortical Regions in the Human Brain
Authors: Arya Ravindra , Petito Gabrielle T. , Housekeeper Jeremy , Buroker Jason , Scholle Craig , Ervin Brian , Frink Clayton , Horn Paul S. , Liu Wei , Ruben Marc , Smith David F. , Skoch Jesse , Mangano Francesco T. , Greiner Hansel M. , Holland Katherine D.
Published: October 2024

Purpose:

We demonstrate that different regions of the cerebral cortex have different diurnal rhythms of spontaneously occurring high-frequency oscillations (HFOs).

Methods:

High-frequency oscillations were assessed with standard-of-care stereotactic electroencephalography in patients with drug-resistant epilepsy. To ensure generalizability of our findings beyond patients with drug-resistant epilepsy, we excluded stereotactic electroencephalography electrode contacts lying within seizure-onset zones, epileptogenic lesions, having frequent epileptiform activity, and excessive artifact. For each patient, we evaluated twenty-four 5-minute stereotactic electroencephalography epochs, sampled hourly throughout the day, and obtained the HFO rate (number of HFOs/minute) in every stereotactic electroencephalography channel. We analyzed diurnal rhythms of the HFO rates with the cosinor model and clustered neuroanatomic parcels in a standard brain space based on similarity of their cosinor parameters. Finally, we compared overlap among resting-state networks, described in the neuroimaging literature, and chronobiological spatial clusters discovered by us.

Results:

We found five clusters that localized predominantly or exclusively to the left perisylvian, left perirolandic and left temporal, right perisylvian and right parietal, right frontal, and right insular-opercular cortices, respectively. These clusters were characterized by similarity of the HFO rates according to the time of the day. Also, these chronobiological spatial clusters preferentially overlapped with specific resting-state networks, particularly default mode network (clusters 1 and 3), frontoparietal network (cluster 1), visual network (cluster 1), and mesial temporal network (cluster 2).

Conclusions:

This is probably the first human study to report clusters of cortical regions with similar diurnal rhythms of electrographic activity. Overlap with resting-state networks attests to their functional significance and has implications for understanding cognitive functions and epilepsy-related mortality.
A Prototype Machine Learning Pipeline for Assessing and Tracking Keloid Scars
Authors: Abdolahnejad Mahla , Zandi Armita , Wong Jordan , Chan Hannah O. , Lin Victoria , Jeong Hyerin , Joshi Rakesh , Wong Joshua N. , Hong Colin
Published: October 2024

Dysregulated wound healing, marked by excessive collagen deposition, is the hallmark to keloid scar formation. Current methods for assessing keloids in clinical settings rely heavily on subjective measures, which are prone to interrater variability. This study introduces a machine learning (ML) pipeline prototype, designed to automate the detection, measurement, and colour analysis of keloid scars. Using a convolutional neural network (CNN), the pipeline segments keloid lesions from 2D images, applies fiducial markers for accurate size measurement, and utilizes K-Means clustering for colorimetry analysis. The CNN achieved a classification accuracy of 98% on a small test dataset. Segmentation was further refined using binary masks and contour-based detection.

Colorimetry analysis revealed heterogeneity in pigmentation across keloid lesions, was varied by patient skin type, and tracked changes over time. The pipeline was validated on patients over a 5–6-month period, accurately detecting changes in keloid size and colour. While the algorithm was highly effective in most cases, challenges were noted in patients with nascent keloid or those with dark skin tones where the contrast between keloid and skin was insufficient for accurate segmentation. Additionally, early-stage keloid detection showed inconsistencies in defining lesion boundaries, particularly when keloids expanded rapidly. Despite these limitations, the ML pipeline presents a promising tool for objective keloid assessment, offering a practical, accessible, and accurate alternative to current clinical practices.
A Method For Mimicking Tumour Tissue In Brain Ex-Vivo Ultrasound For Research Application And Clinical Training
Authors: Weld Alistair , Dixon Luke , Anichini Giulio , Faoro Giovanni , Menciassi Arianna , Camp Sophie , Giannarou Stamatia
Published: October 2024

Background

Intraoperative ultrasound is becoming a common tool in neurosurgery. However, effective simulation methods are limited. Current, commercial, and homemade phantoms lack replication of anatomical correctness and texture complexity of brain and tumour tissue in ultrasound images.

Methods

We utilise ex-vivo brain tissue, as opposed to synthetic materials, to achieve realistic echogenic complexity and anatomical correctness. Agar, at 10-20% concentrate, is injected into brain tissue to simulate the tumour mass. A commercially available phantom was purchased for benchmarking.

Results

Qualitative analysis is performed by experienced professionals, measuring the impact of the addition of agar and comparing it to the commercial phantom. Overall, the use of ex vivo tissue was deemed more accurate and representative, compared to the synthetic materials-based phantom, as it provided good visualisation of real brain anatomy and good contrast within tissue. The agar tumour correctly produced a region of higher echogenicity with slight diffusion along the margin and expected interaction with the neighbouring anatomy.

Conclusion

The proposed method for creating tumour-mimicking tissue in brain tissue is inexpensive, accurate, and simple. Beneficial for both the trainee clinician and the researcher. A total of 576 annotated images are made publicly available upon request.
Risk of Incident Cytopenia in Clonal Hematopoiesis
Authors: Brogan James , Kishtagari Ashwin , Corty Robert W. , Pershad Yash , Vlasschaert Caitlyn , Sharber Brian , Heimlich J. Brett , Luo Leo , Xu Yaomin , Bick Alexander G.
Published: October 2024

Clonal hematopoiesis of indeterminate potential (CHIP) is an asymptomatic condition associated with elevated risk for myeloid neoplasms (MN). Patients with CHIP and cytopenia are at greater risk of MN. Quantifying the incidence of cytopenia and identifying risk factors among CHIP patients is critical for improving clinical management. We analyzed sequencing data from 805,249 participants in the NIH All of Us Research Program (AoU), Vanderbilt’s BioVU repository, and UK Biobank (UKB). Genetic mutations, laboratory values, and MN diagnoses were included in survival analyses to determine predictors of cytopenia in individuals with CHIP and matched controls. The cohort contained 9,374 CHIP cases and 24,749 controls. Cytopenia occurred in 13.5% of cases and 11.6% of controls (HR = 1.17, 95% confidence interval:

1.10 – 1.25, P=2.5 × 10−6). Cytopenia risk factors included smoking, male sex, variant allele frequency ≥ 0.20, age ≥ 65, mean corpuscular volume ≥ 100 femtoliters, red cell distribution width ≥ 15%, mutations in high-risk CHIP genes, and ≥ 2 CHIP mutations. In BioVU, 45% of participants with ≥ 4 risk factors progressed to cytopenia within two years. Individuals with CHIP and cytopenia progressed to MN at a rate of ~2% per year, compared to <0.1% per year for those without cytopenia. Longitudinal analysis across three cohorts demonstrated an increased risk of cytopenia in CHIP patients and identified those at highest risk. These findings suggest that cytopenia is a critical step in progression from CHIP to MN, underscoring its utility as an endpoint in cancer prevention trials for CHIP patients.
Multiomics identifies unique modulators of calf muscle pathophysiology in peripheral artery disease and chronic kidney disease
Authors: Kim Kyoungrae , Thome Trace , Pass Caroline , Stone Lauren , Vugman Nicholas , Palzkill Victoria , Yang Qingping , O’Malley Kerri A. , Anderson Erik M. , Fazzone Brian , Yue Feng , Berceli Scott A. , Scali Salvatore T. , Ryan Terence E.
Published: October 2024

BACKGROUND

Chronic kidney disease (CKD) has emerged as a significant risk factor that accelerates atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the modulators underlying this exacerbated pathobiology are ill-defined. Recent work has demonstrated that uremic toxins are associated with limb amputation in PAD and have pathological effects in both the limb muscle and vasculature. Herein, we utilize multiomics to identify novel modulators of disease pathobiology in patients with PAD and CKD.

METHODS

A cross-sectional study enrolled four groups of participants: controls without PAD or CKD (n=28), patients with PAD only (n=46), patients with CKD only (n=31), and patients with both PAD and CKD (n=18). Both targeted (uremic toxins) and non-targeted metabolomics in plasma were performed using mass spectrometry. Calf muscle biopsies were used to measure histopathology, perform bulk and single-nucleus RNA sequencing (snRNAseq), and assess mitochondrial function. Differential gene and metabolite analyses, as well as pathway and gene set enrichment analyses were performed.

RESULTS

Patients with both PAD and CKD exhibited significantly lower calf muscle strength and smaller muscle fiber areas compared to controls and those with only PAD. Compared to controls, mitochondrial function was impaired in CKD patients, with or without PAD, but not in PAD patients without CKD. Plasma metabolomics revealed substantial alterations in the metabolome of patients with CKD, with significant correlations observed between uremic toxins (e.g., kynurenine, indoxyl sulfate) and both muscle strength and mitochondrial function. RNA sequencing analyses identified downregulation of mitochondrial genes and pathways associated with protein translation in patients with both PAD and CKD. Single nucleus RNA sequencing further highlighted a mitochondrial deficiency in muscle fibers along with unique remodeling of fibro-adipogenic progenitor cells in patients with both PAD and CKD, with an increase in adipogenic cell populations.

CONCLUSIONS

CKD significantly exacerbates ischemic muscle pathology in PAD, as evidenced by diminished muscle strength, reduced mitochondrial function, and altered transcriptome profiles. The correlation between uremic toxins and muscle dysfunction suggests that targeting these metabolites may offer therapeutic potential for improving muscle health in PAD patients with CKD.
Persistently high TB prevalence in Nairobi County neighbourhoods, 2015-2022
Authors: Ong’ang’o Jane R. , Ross Jennifer , Kiplimo Richard , Kerama Cheryl , Tram Khai Hoan , Zifodya Jerry S. , Mukiri Nellie , Nyadimo Erick , Njoroge Martha , Ronoh Aiban , Kathure Immaculate , Kirathe Dickson , Hawn Thomas R. , Nduba Videlis , Horne David J.
Published: October 2024

National and sub-national population-based surveys, when performed at intervals, may assess important changes in TB prevalence. In 2022 we re-surveyed nine Nairobi County neighbourhoods that were previously surveyed in 2015. We aimed to determine pulmonary TB prevalence, compare prevalence to 2015 estimates, and evaluate changes in risk groups. Participants who reported cough of any duration and/or whose chest x-ray suggested TB submitted sputum for smear microscopy, Xpert Ultra, and liquid culture. We defined prevalent TB asMycobacterium tuberculosisdetection by sputum Xpert or culture, excepting individuals who were only trace positive. Our methods differed from 2015, which used solid media, Xpert MTB/RIF, and cough duration >2 weeks. We calculated TB prevalence using random-effects logistic regression models with missing value imputations and inverse probability weighting. In 2022 among 6369 participants, 1582 submitted >1 sputum sample, among whom 42 (2·7%) had TB, a weighted TB prevalence of 806/100,000 (95% confidence interval (CI), 518-1096). An additional 31 (2·0%) participants tested Ultra trace-positive/culture-negative. For comparison to 2015, we excluded 2022 participants (n=2) whose only criterion for sputum was cough <2 weeks. There was no evidence for a decline in overall TB prevalence from 2015 to 2022. TB prevalence among men was high (1368/100,000) but unchanged compared to 2015 (p-value = 0·50). The age group with the highest estimated prevalence remained people ages 45–54 years. Among people with prevalent TB who reported cough, 76% had not sought health care. Dissimilar from other serial surveys that showed declines in TB prevalence, we found persistently high TB prevalence over a 7-year period in Nairobi County. Limitations of this study include changes in methodology between the two surveys and complex effects of the COVID-19 pandemic.
Dual Specificity Phosphatase 3 knockdown drives myeloid leukemia cells to differentiate into macrophages and polarize
Authors: Farias Jessica O. , Pacheco Diana R.D.C.G. , Magalhaes Yuli T. , Russo Lilian C. , Boell Viktor K. , Hilares Donna J.F. , Forti Fabio L.
Published: October 2024

The dual-specificity phosphatase 3 (DUSP3) has been implicated in the maintenance of genomic stability, cell cycle, proliferation, and differentiation. Recently we reported an important role of the interaction between DUSP3 and nucleophosmin (NPM) proteins on the regulation of the p53 actions to maintain genomic stability. Since both p53 and NPM often have mutations related to a diverse set of leukemia, this work aimed to evaluate the roles of DUSP3 in the differentiation of two acute myeloid leukemia cell lines not expressing the p53 protein, and the potential correlations with NPM expression. The results demonstrated higher levels of DUSP3 in THP-1 cells compared to HL-60 cells under basal conditions. After PMA-induced differentiation into macrophages, only HL-60 cells presented a dramatic decrease in DUSP3 and NPM proteins expression. The permanent DUSP3 knockdown in THP-1 and HL-60 cells contributed to their differentiation and non-classical polarization after PMA exposure, since the CD14, MHCII, and CD163 markers were decreased whereas the CD11b and CD206 markers were increased. Bioinformatics analyses identified that the negative regulation of thenpm1anddusp3genes correlates with the reduced survival of patients with acute myeloid leukemia (AML) and the strong positive correlation existing between the expression of these two genes is progressively lost according to the degree of maturation of the myeloid cells. These results suggest DUSP3 plays regulatory roles of differentiation and polarization of myeloid cells, and its association with NPM expression levels may allow a better understanding of mechanisms involved in leukemia and treatment resistance.

HIGHLIGHTS

DUSP3 knockdown drives myeloid leukemia cells to differentiation

DUSP3 silencing drives myeloid leukemia cells to macrophage polarization

DUSP3 and NPM association are potential targets for leukemia treatment and resistance
Isobaric labeling update in MaxQuant
Authors: Ferretti Daniela , Kyriakidou Pelagia , Xiao Jinqiu , Urazbakhtin Shamil , Nart Carlo De , Cox Jürgen
Published: October 2024

We present an update of the MaxQuant software for isobaric labeling data and evaluate its performance on benchmark datasets. Impurity correction factors can be applied to labels mixing C- and N-type reporter ions, such as TMT Pro. Application to a single-cell multi-species mixture benchmark shows high accuracy of the impurity-corrected results. TMT data recorded with FAIMS separation can be analyzed directly in MaxQuant without splitting the raw data into separate files per FAIMS voltage. Weighted median normalization, is applied to several datasets, including large-scale human body atlas data. In the benchmark datasets the weighted median normalization either removes or strongly reduces the batch effects between different TMT plexes and results in clustering by biology. In datasets including reference channels, we find that weighted median normalization performs as well or better when the reference channels are ignored and only the sample channel intensities are used, suggesting that the measurement of reference channels is unnecessary when using weighted median normalization in MaxQuant. We demonstrate that MaxQuant including the weighted median normalization performs well on multi-notch MS3 data, as well as on phosphorylation data. MaxQuant is freely available for any purpose and can be downloaded fromhttps://www.maxquant.org/.
Ectonucleotidases and Purinergic Receptors in Mouse Prostate Gland
Authors: Yu Jovian , Sharkey Christina , Olumi Aria , Wang Zongwei
Published: October 2024

Extracellular ATP/ADP and its metabolite adenosine are important signaling molecules that regulate cellular function by binding to P2 and P1/adenosine receptors. The kinetics of these signaling molecules are critically modulated by ectonucleotidases, enzymes that convert ATP/ADP to adenosine. Although the expression and function of these enzymes and relevant purinergic receptors in the prostate gland are not well understood, recent reports indicate impaired ATP hydrolysis activity in the aging prostate. Purinergic signaling is known for its role in inflammation, muscle contraction, pain sensation, and cell proliferation in many systems, suggesting its potential importance in normal prostate function and pathological conditions such as benign prostatic hyperplasia and prostatitis. To better understand purine-converting enzymes and purinergic receptors in the prostate, we isolated mouse prostate glands for immunofluorescent staining and microscopy imaging using specific antibodies. Our study identified a differential expression profile of purinergic enzymes and receptors in the prostate: ENTPD1 and P2×1 receptors predominantly in prostate smooth muscle cells, ENTPD2 and NT5E in prostate interstitial cells, and ALPL in prostate epithelial cells. Functionally, in addition to the P2×1-mediated prostate smooth muscle contraction induced by agonist α,β-meATP, we observed an ATPγS-induced contraction force after P2×1 desensitization. This led to the identification of multiple P2Y receptors in mouse prostate smooth muscle, including P2Y1, P2Y2, and P2Y11 receptors, which potentially mediate the ATPγS-induced contraction force. These discoveries lay the foundation for further mechanistic understanding of how purinergic signaling regulates prostate function and dysfunction in both rodents and potentially humans.