bluuebunny/crossref_metadata_2025 huggingface dataset:
Smartphone Application Versus Standard Instruction for Colonoscopic Preparation
Authors: Patel Sunil V. , Yu David , Taylor Connie , McKay Jackie , Hookey Lawrence
Published: March 2024

Objective:

To compare smartphone application (Colonoscopic Preparation) instructions versus paper instructions for bowel preparation for colonoscopy.

Background:

Adhering to bowel preparation instructions is important to ensure a high-quality colonoscopy.

Patients and Methods:

This randomized controlled trial included individuals undergoing colonoscopy at a tertiary care hospital. Individuals were randomized (1:1) to receive instructions through a smartphone application or traditional paper instructions. The primary outcome was the quality of the bowel preparation as measured by the Boston Bowel Preparation Score. Secondary outcomes included cecal intubation and polyp detection. Patient satisfaction was assessed using a previously developed questionnaire.

Results:

A total of 238 individuals were randomized (n = 119 in each group), with 202 available for the intention-to-treat analysis (N = 97 in the app group and 105 in the paper group). The groups had similar demographics, indications for colonoscopy, and type of bowel preparation. The primary outcome (Boston Bowel Preparation Score) demonstrated no difference between groups (Colonoscopic Preparation app mean: 7.26 vs paper mean: 7.28, P = 0.91). There was no difference in cecal intubation (P = 0.37), at least one polyp detected (P = 0.43), or the mean number of polyps removed (P = 0.11). A higher proportion strongly agreed or agreed that they would use the smartphone app compared with paper instructions (89.4% vs 70.1%, P = 0.001).

Conclusions:

Smartphone instructions performed similarly to traditional paper instructions for those willing to use the application. Local patient preferences need to be considered before making changes in the method of delivery of medical instructions.
Gynura segetum induces hepatic sinusoidal obstruction syndrome in a child: A case report
Authors: Zheng Qian , Zhang Haiyang
Published: March 2024

Rationale:

Hepatic sinusoidal obstruction syndrome (HSOS), which includes hepatic stasis and portal hypertension, is a rare vascular disorder of the liver. It is often associated with hematopoietic stem cell transplantation. It is also possible to treat this disease using Chinese herbal medicines that contain pyrrolizidine alkaloids (PAs). This disease is extremely rare in children and poses a serious threat to their health. To our knowledge, this is the first case of HSOS in a child with PAs.

Patient concerns:

We report a 4-year-old boy suffering from abdominal pain, hepatomegaly, massive ascites, elevated liver enzyme level, and severe portal hypertension as a result of the consumption of Gynura segetum (also known as Tusanqi in Chinese, a traditional herbal medicine containing PAs).

Diagnoses:

The child was finally diagnosed with PA-HSOS based on pathological diagnosis and imaging examination.

Intervention:

With active symptomatic and supportive care and sequential anticoagulation therapy, the abdominal distension and liver function improved in the patient.

Outcomes:

The patient was eventually recovered. The levels of liver enzymes, hemoglobin, and bilirubin were normal, and the international normalized ratio fluctuated between 2.0 and 3.0 during 1-year follow-up after discharge.

Lessons:

This case report emphasizes the prevention of Chinese herb-induced liver injury in children and the importance of active long-term sequential anticoagulant therapy to reduce the progressive damage of PA-HSOS in the liver.
Impact of delayed diagnosis and treatment on tuberculosis infection within families: A case report
Authors: Liu Jian-Jun , Feng Yin-Ping , Liu Zhong-Da , Guo Jing
Published: March 2024

Background:

A 32-year-old male patient was diagnosed with a 30% left pneumothorax on November 5, 2020, during which chest imaging indicated abnormalities. Despite this, pulmonary tuberculosis (TB) was not diagnosed or treated at that time due to a negative result in the MGIT960 culture. The patient experienced symptoms of cough and expectoration on April 24, 2022. Upon repeating the chest imaging, the condition had worsened, confirming the presence of pulmonary TB, leading to the patient’s hospitalization. On September 1, 2022, the 11-year-old daughter of the patient was diagnosed with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy.

Methods:

The diagnosis of pulmonary tuberculosis was confirmed through sputum smears and Gene Xpert MTB/RIF testing, for the patient and his 11-year-old daughter in 2022. The patient underwent a 6-month combination therapy (2HRZE/4HR) comprising isoniazid, rifampicin, pyrazinamide, and ethambutol. His daughter with pulmonary tuberculosis accompanied by bronchial tuberculosis and tuberculous pleurisy underwent a 12-month combination therapy.

Results:

Late diagnosis and treatment delays contribute to tuberculosis infections within families. Fortunately, after more than 3 months of antituberculosis treatment, the patient experienced relief from cough and sputum secretion, and there was improvement observed in the chest CT scan. Six months later, the patient was successfully cured of TB. 12 months later, his daughter also was successfully cured of TB.

Conclusion subsections:

Early diagnosis and treatment of tuberculosis (TB) is vital to reduce transmission, morbidity, and mortality.
A randomized controlled study investigating the efficacy of electro-acupuncture and exercise-based swallowing rehabilitation for post-stroke dysphagia: Impacts on brainstem auditory evoked potentials and cerebral blood flow
Authors: Zhang Wen , Jin Hai-Tao , Wang Fei , Zhang Jing-Lan , Bao Yuan , Wang Song
Published: March 2024

Background:

Swallowing rehabilitation behavioral therapy and traditional Chinese acupuncture therapy are widely used in the treatment of post-stroke dysphagia (PSD). This study investigated the therapeutic effect of electro-acupuncture combined with exercise-based swallowing rehabilitation on PSD and its effect on brainstem auditory evoked potential (BAEP) and cerebral blood flow.

Methods:

The 120 PSD patients were divided into 2 groups (n = 60 each) by simple random grouping method, that is, an experimental and control group, receiving routine swallowing training, or additional intervention with electro-acupuncture at a frequency of 5 times/week. Data in swallowing function, BAEP, and cerebrovascular color Doppler ultrasound parameters were collected before treatment, as well as after treatment. An intergroup comparison was conducted using an independent sample t-test, and an intra-group comparison was conducted among different time points using a paired t-test. The data were analyzed using the SPSS Statistics 22.0 software; P < .05 was considered statistically significant.

Results:

The therapeutic effects were significantly better in the experimental group compared with the control group (P < .05). The standard swallowing function assessment scores were significantly lower in both groups after treatment (P < .05), and the score in the observation group was lower than in the control group (P < .05). The peak latency of BAEP waves III and IV, and the inter-peak latency between peaks III to V and I to V in the 2 groups changed significantly (P < .05). The peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV) were significantly increased in both groups after treatment (P < .05). The pulsatility index decreased significantly in both groups (P < .05), and the PSV, EDV, and MV were higher in the experimental group than in the control group (P < .05).

Conclusion:

Electro-acupuncture, combined with swallowing training in the treatment of Post-stroke Dysphagia, effectively improved cerebral microcirculation and conduction velocity, enhanced the motor function of swallowing muscles, and promoted the recovery of swallowing function.
A comparison of symptoms and quality of life between medial flap and coblation turbinator of inferior turbinate reduction in endoscopic septoturbinoplasty: an analysis of 108 cases
Authors: Nguyen Nguyen , Nguyen Ngoc Quang , Trinh Le Nam Phuong , Duong Thi My , Ton Nu Thi Nhu Quynh , Dang Thanh
Published: March 2024

Introduction:

The combination of septoplasty and turbinoplasty is a common surgical and accepted intervention to correct the nasal obstruction. The coblation submucosal reduction turbinator is a new surgical device, and it started to be used recently. On the other hand, the medial flap inferior turbinoplasty is not a conservative technique, but it provides a reliable and robust reduction.

Objective:

This study aims to compare the symptoms as well as health-related quality of life (HQOL) in 55 patients who underwent septoplasty with concomitent medial flap inferior turbinoplasty (group 1), 53 patients who patients underwent septoplasty with concomitent coblation turbinator (group 2).

Patients and methods:

The authors performed a prospective, randomized study of 108 patients who consulted the otorhinolaryngology department at the university hospital for surgery of septoturbinoplasty.

Results:

Preoperatively, the two patient groups had quite similar symptoms and health-related quality of life, and the anterior width of the inferior turbinate showed significant differences between the contralateral and deviated sides but not the posterior part. The significant difference (P<0.05) was noted for postoperatively improved symptom scores on visual analogue scale (VAS), nasal obstruction septoplasty effectiveness (NOSE) and better HQOL [Sino-Nasal Outcome Test-22 (SNOT-22)] in all patient groups. In addition, the NOSE and SNOT-22 scores in group 2 had significantly greater improvement than group 1 (P<0.05).

Conclusions:

Septoturbinoplasty treatment of septum deviation and inferior turbinate hypertrophy led to less symptoms as well as better HQOL for all two patient groups. Therefore, these techniques were an effective intervention for turbinate reduction, and they are equally efficient in the long term.
A case report of vaping-associated sudden cardiac arrest in a young healthy patient
Authors: Ahmed Hasaan , Ismayl Mahmoud , Palicherla Anirudh , May Joshua , Goldsweig Andrew M. , Thirumalareddy Joseph
Published: March 2024

Introduction and importance:

While vaping has increased significantly among young individuals, the effects of vape aerosol constituents on cardiac electrophysiological dynamics remain unknown.

Case presentation:

A 22-year-old female with a history of energy vaping presented with cardiac arrest. Found to have no pulse, CPR was started and an initial rhythm of ventricular tachycardia was obtained. Shock was administered with a follow-up rhythm of ventricular fibrillation. She was emergently defibrillated and entered atrial fibrillation with rapid ventricular response. Toxicology and troponins were all negative. Left heart catheterization and cardiac MRI were unremarkable. She was discharged with an external defibrillation vest and a tentative plan for outpatient electrophysiology study in the setting of negative work-up for cardiopulmonary arrest.

Clinical discussion:

Vaping-induced sudden cardiac arrest may be attributed to a reduction in cardiac repolarization reserve. Exposure to vegetable glycerin and propylene glycol, substances present in nearly all vape products, have been found to incite arrhythmias and disrupt cardiac conduction in animals. Acrolein, an aldehyde byproduct of glycerin, has also been found to induce arrhythmias due to autonomic dysfunction. Increased intracellular calcium concentration and free radical damage, which occur as a result of inhaling particulate matter generated from e-cigarettes, further propagates the risk of arrhythmia.

Conclusion:

The effects of inhaling vape aerosols remain not fully understood. While there is a perceived notion that nicotine-free aerosols may be harmless, that remains unclear. Further studies are needed to evaluate proarrhythmogenic effects and autonomic dysfunction from the various chemical substances present in vape aerosols.
Incidental diagnosis of primary appendiceal signet-ring cell adenocarcinoma after appendectomy for acute appendicitis: a case report
Authors: Xie Miao , Li Fei
Published: March 2024

Introduction:

Appendiceal signet-ring cell adenocarcinoma (ASCA) is rare and more aggressive in malignant appendiceal neoplasms. The presentation can be appendicitis, which is lack of specific symptom and makes early diagnosis difficult. There is no effective surveillance. Prognosis largely relies on timely detection. We report a case of ASCA incidentally diagnosed through pathological examination after appendectomy for appendicitis.

Case presentation:

The patient presented to our department with a progressive right lower quadrant abdominal pain lasting for 3 days. Physical examination revealed rigidity, tenderness, and rebound tenderness on the right lower quadrant. A computed tomography scan showed a thickened, inflamed appendix with peri-appendiceal fat stranding without noticeable appendiceal mass at initial evaluation. The diagnosis was considered acute appendicitis, and an appendectomy was performed. The appendix was inflamed, gangrenous and perforated, and no mass was found during the surgery. Surgical specimen was sent for physiological examination, which incidentally detected signet-ring cell in H&E staining. And immunohistochemistry confirmed the diagnosis of ASCA with small amount of neuroendocrine neoplasms.

Conclusion:

Early diagnosis of ASCA can incidentally be made on pathological specimen following appendectomy for appendicitis. A routine pathological examination should be emphasized, and appendectomy may not be the endpoint of the treatment. Hemicolectomy and adjuvant therapy might ensue upon the diagnosis of appendiceal neoplasm. The poor prognosis of ASCA makes a timely diagnosis significant. Basic research is promising to unravel the molecular mechanisms of pathogenesis, finding typical tumor markers for screening and novel effective therapies for advanced cases.
Retrospective Cohort Study on the Impact of the COVID-19 Pandemic on Pregnancy Outcomes for Women Living With HIV in British Columbia
Authors: Fu Winnie , McClymont Elisabeth , Av-Gay Gal , Dorling Marisa , Atkinson Andrea , Azampanah Arezou , Elwood Chelsea , Sauvé Laura , van Schalkwyk Julie , Sotindjo Tatiana , Money Deborah
Published: March 2024

Background:

For pregnant women living with HIV (WLWH), engagement in care is crucial to maternal health and reducing the risk of perinatal transmission. To date, there have been no studies in Canada examining the impact of the COVID-19 pandemic on pregnant WLWH.

Methods:

This was a retrospective cohort study assessing the impact of the pandemic on perinatal outcomes for pregnant WLWH using data from the Perinatal HIV Surveillance Program in British Columbia, Canada. We compared maternal characteristics, pregnancy outcomes, and clinical indicators related to engagement with care between a prepandemic (January 2017–March 2020) and pandemic cohort (March 2020–December 2022). We investigated preterm birth rates with explanatory variables using logistic regression analysis.

Results:

The prepandemic cohort (n = 87) had a significantly (P < 0.05) lower gestational age at the first antenatal encounter (9.0 vs 11.8) and lower rates of preterm births compared with the pandemic cohort (n = 56; 15% vs 37%). Adjusted odds of preterm birth increased with the presence of substance use in pregnancy (aOR = 10.45, 95% confidence interval: 2.19 to 49.94) in WLWH. There were 2 cases of perinatal transmission of HIV in the pandemic cohort, whereas the prepandemic cohort had none.

Conclusions:

The pandemic had pronounced effects on pregnant WLWH and their infants in British Columbia including higher rates of preterm birth and higher gestational age at the first antenatal encounter. The nonstatistically significant increase in perinatal transmission rates is of high clinical importance.
Hand of the 42-armed Avalokiteśvara Holding A Skull Rod
Authors: Jung Sung Gyun , Hwang Kun , Hwang Young Joong
Published: March 2024

The skull most commonly symbolizes death, mortality, and the unachievable nature of immortality. However, in Korean Buddhist art, skulls are rarely found. The aim of this study was to explore the image and meaning of the skull in the Joseon dynasty (1392 to 1910) of Korea. The terms [Buddhist] and [painting] and [Korea] were used to search Google (www.google.com), and the Research Information Sharing Service of Korea (https://www-riss-kr-ssl.openlink), was also searched for [Buddhism] (佛敎) and [art] (美術) and [skull] (骸骨). This study focused on paintings or statues of Avalokiteśvara because Avalokiteśvara was often depicted holding various items in the hands, especially the multiarmed Avalokiteśvara. The corresponding Buddhist texts were searched on “Archives of Buddhist Culture” (http://kabc.dongguk.edu). In the paintings and statues of the 42-armed Sahasra-bhuja Avalokiteśvara, one of the hands was holding a skull rod. In the royal version of the “Five Great Dhārāṇis Collection (五大眞言集),” which was published in 1458, a skull was found in a rod held by a 42-armed Avalokiteśvara. This corresponds to one of the verses of the “42-Hand Mantras” (Om dhuna vajra ha). The purpose of the mantra was to communicate with and manipulate ghosts. The meaning in the original Susiddhikara Sutra is quite different from the 42-Hand Mantras in the Joseon dynasty of Korea. The reason for this difference is thought to be the merger of esoteric Buddhism with the folk religions of China and Korea.
Nunchaku-like Free Fibula Osteocutaneous Flap in Through-and-through Composite Oromandibular Defect Reconstruction
Authors: Lin Joyce Jui-An , Wang Tien-Hsiang , Chen Ching-En
Published: March 2024

The free fibula osteocutaneous flap (FFOCF) has been used for oromandibular reconstruction over several decades. However, when facing through-and-through composite oromandibular defects (COMDs), significant challenges still arise. The complexity of COMD necessitates the reconstruction of bone, intraoral mucosa, and extraoral skin. Additional flaps are often needed, which extend surgical durations and heighten associated risks. This report presents a 62-year-old man with squamous cell carcinoma of the left lower gingiva. After ablative surgery, successful reconstruction of a through-and-through COMD was achieved with a single FFOCF through innovative design. The flap was osteotomized into 2 segments with attached skin islands while preserving the vascular pedicle. Rotation of 1 segment created 2 skin islands on opposing sides, simultaneously repairing intraoral and extraoral defects. Postoperative outcomes at the 1-month follow-up were encouraging. Although technically challenging, the “Nunchaku-like FFOCF” offers a safe and effective approach for the comprehensive reconstruction of through-and-through COMD.
Effect of zinc oxide nanoparticle types on the structural, mechanical and antibacterial properties of carrageenan-based composite films
Authors: Shin Ga Young , Kim Hyo-Lyn , Park So-Yoon , Park Mi So , Kim Chanhyeong , Her Jae-Young
Published: March 2024

In this study, zinc oxide nanoparticles (ZnONPs) were synthesized using three distinct zinc salts: zinc acetate, zinc chloride, and zinc nitrate. These ZnONPs were subsequently utilized in the fabrication of carrageenan-ZnONPs (Car-ZnONPs) composite films. The study assessed influence of the various ZnONPs on the morphological, water vapor barrier, color, optical, and antimicrobial properties of the Car-ZnONPs composite films. The surface morphology and UV-blocking attributes of the composite films were affected by the type of ZnONPs used, but their surface color, transparency, and chemical structure remained unaltered. The composite film's thickness and elongation at break (EB) significantly increased, while the tensile strength significantly decreased. In contrast, film’s elastic modulus (EM) and water vapor permeability coefficient (WVP) showed no significant difference. All the composite films with added ZnONPs demonstrated potent antibacterial activity against Escherichia coli O157:H7 and Listeria monocytogenes. Among the carrageenan-based composite films, Car-ZnONPsZC showed the highest antibacterial and UV-blocking properties, and its elongation at break was significantly higher than that of the pure carrageenan films. This suggests that ZnONPs composite films have the potential to be used as an active packaging film, preserve the safety of the packaged food and extend shelf life.
The effect of storage temperature on antioxidant capacity and
storability of paprika
Authors: Park Me-Hea , Eum Hyang Lan , Park Pue Hee , Baek Dong Ryeol , Malka Siva Kumar
Published: March 2024

Storage temperature profoundly influences the storability of paprika
(Capsicum annuum L.). However, the impact of storage
temperature on storability and its association with the antioxidant activity of
paprika are poorly understood. In this study, we evaluated the storage
attributes, activity, and gene expression levels of antioxidant enzymes in
paprika stored at 4, 10, and 20° for 14 d and then at 20° for an
additional 5 d (14+5 d; retail conditions). Storage at 10°C
effectively mitigated pitting, stalk browning, shriveling, and decay while
significantly enhancing the marketability of paprika. The fruits stored at
4°C were prone to pitting, whereas those stored at 20°C were
sensitive to stalk browning and decay. Moreover, paprika stored at 10°C
exhibited higher 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
activity and total phenolic content than those stored at 4 and 20°C,
indicating improved antioxidant activity. Additionally, storage at 10°C
upregulated the expression levels of the antioxidant genes,
catalase and peroxidase, suggesting the
mechanism underlying the quality enhancement of paprika. Our findings suggest
that paprika storage at 10°C alleviates chilling injuries, preserves the
quality and marketability, and enhances the antioxidant potential of paprika.
These findings provide insights into how temperature influences the quality and
minimizes post-harvest losses during the storage and distribution of
paprika.
Anti-obesity effects of lactic acid bacteria ferments cultured in industrial medium with ethanol extract of ramie leaf (Boehmeria nivea L.)
Authors: Oh Byung-Min , Oh Hyeon Hwa , Song Geun-Seoup
Published: March 2024

This study investigated the anti-obesity effects of lactic acid bacteria ferments cultured in industrial medium with ethanol extract of ramie leaf (Boehmeria nivea L.). On the 4th day of fermentation, the maximum live cell counts were 8.75-8.85 log CFU/mL, pH was 3.74-3.79, and total acidity was 2.07-2.19%. The fermentation of lactic acid bacteria on the fourth day resulted in the amount of lactic acid reaching 1,676.03-1,910.12 mg%. The lipase inhibitory activities of Lactiplantibacillus plantarum (L. plantarum) JBLAB0101 (FRLPLA) and Lactobacillus rhamnosus GG (LGG, (FRLLGG)) ferments were 30.10%, and 25.63%, respectively, at a concentration of 0.5 mg/mL. The lipid accumulation, leptin production, PPAR-γ and SREBP-1c mRNA levels were decreased to 37.54%, 54.64%, 24.18%, and 31.32%, respectively, at 200 μg/mL concentration of FRLPLA. These results suggest that anti-obesity effect could be increased by lactic acid bacteria in industrial medium with extract of ramie leaf.
Quality characteristics of plant-based whipped cream with ultrasonicated pea protein
Authors: Kim Insun , Moon Kwang-Deog
Published: March 2024

The rise in popularity of vegetarian and plant-based diets has led to extensive research into plant-based whipped creams. Whipped cream is an oil-in-water emulsion that creates foam through whipping, stabilizing the foam with proteins and fats. Pea protein is an excellent emulsifier and foaming agent among plant-based proteins, but its application in whipped cream is currently limited. The objective of this study was to investigate the quality characteristics of plant-based whipped cream made with ultrasonicated pea protein. The whipped creams were evaluated based on their quality characteristics. A commercially available dairy whipped cream (CON) was used as a control. Plant-based creams were evaluated using pea protein solution, cocoa butter, and canola oil to produce un-ultrasonicated pea protein whipped cream (PP) and ultrasonicated pea protein whipped cream (UPP) at 360 W for 6 min. UPP significantly reduced whipping time and foam drainage compared with CON and PP, resulting in significantly increased overrun, fat destabilization, and hardness. Optical microscopy showed that UPP had smaller fat globules and bubble size than PP. The fat globules of UPP and CON were mostly below 5 μm, whereas those of PP were distributed at 5-20 μm. Finally, ultrasonication significantly improved the overrun, foam drainage, fat destabilization, and hardness of UPP, which are significant quality characteristics of whipped creams. Therefore, ultrasonicated plant-based pea protein whipped cream is believed to be a viable alternative to dairy whipped cream.
Machine Learning in Acute Stroke Care: A Novel Model for Assessing the Need for Enteral Nutrition
Authors: Okamoto Kazuhiro , Irie Keisuke , Hoyano Kengo , Matsushita Isao
Published: March 2024

Aim

Early enteral nutrition is often recommended for patients with acute stroke who have difficulty with oral intake. This study aimed to develop a predictive model to assess the need for enteral nutrition in older patients with acute cerebrovascular disorders. The model employs a machine learning algorithm using observational parameters related to swallowing ability.

Methods

Ninety patients experiencing a cerebrovascular accident for the first time were included in this study. Swallowing function was assessed using the Food Intake LEVEL Scale. Nine specific variables were used to create a model for determining the need for enteral nutrition. Initially, variable selection was conducted through correlation analysis. Subsequently, the data were randomly divided into training and test groups. Five machine learning methods were applied to identify the most effective algorithm: logistic regression, decision tree, random forest, support vector machine, and XG Boost.

Results

Through correlation analysis, we identified the independent variables Functional Independence Measure, motor and cognitive scores and speech intelligibility. The logistic regression model demonstrated high performance (accuracy, 0.82; area under the curve, 0.82).

Conclusion

We demonstrated that a predictive model, employing machine learning and integrating Functional Independence Measure motor and cognitive scores and speech intelligibility, exhibits superior predictive efficacy and ascertains the necessity for enteral nutrition. This model can be expediently appraised even by individuals not specialized in dysphagia. Additionally, it is applicable to patients who are incapable of adhering to conventional swallowing assessment protocols owing to compromised consciousness or cognitive impairments, or those with an exceptionally elevated risk of aspiration.
Is delirium after stroke associated with dysregulation of Hypothalamic pituitary axis?
Authors: Barugh AJ , MacLullich AMJ , Shenkin SD , Allerhand M , Mead GE
Published: March 2024

Delirium after stroke is a serious condition associated with poorer longer term cognition. However the mechanism of delirium is poorly understood. The aberrant stress response has been postulated as a mechanism for delirium.

Aim

To explore the relationship between cortisol dysregulation and delirium over the first year after stroke in a prospective cohort study of patients admitted to an acute stroke unit.

Methods

Consecutive patients admitted to an acute stroke unit over a one year period were identified and recruited if they were aged 65 or over and not taking steroids. Patients with incapacity were included if proxy consent could be obtained. Baseline data included stroke severity, cognition, illness severity, and pre-stroke cognition. Patients were assessed at 1, 3, 5, 7, 14, 21, 28 days, 4 months and 12 months for delirium. Salivary samples were taken morning and evening for cortisol analysis.

Results

Of the 831 patients screened, 304 met inclusion criteria and of these 95 agreed to participant. Twenty-six (27%) had delirium at some point during the 12 months follow-up. Delirium was associated with increasing age (mean age 83.5 years vs 74 years, p<0.001), being female (62% vs 23%, p=0.013), not independent in pre-stroke activities of daily living (35% vs 33%), higher IQCODE score median 3.56 vs 3.19), worse stroke severity (median National Institute of Stroke Scale 5 vs 8.5) p=0.009) and having had a total anterior circulation stroke (p<0.001). Univariable analyses identified several associations between delirium and cortisol in the first 28 days but not at 4 or 12 months. However, on multivariable analyses there were no significant associations between delirium and cortisol at any time point e.g. odds ratio for median 9am cortisol 0.95 (95% CI 0.89 to 1.01, p=0.08).

Conclusion

There was no independent association between delirium and cortisol dysregulation after stroke. If an association does exist, it is likely to be small.
Molecular insights into mitoepigenetic stress response signaling in age-associated cardiovascular disease risk
Authors: Soni Nikita , Kaur Prasan , Gurjar Vikas , Bhargava Arpit , Tiwari Rajnarayan , Raghuwanshi Vinay Singh , Srivastava Rupesh K. , Mishra Pradyumna Kumar
Published: March 2024

Cardiovascular diseases (CVD) represent a major challenge for the elderly population and continue to be among the leading causes of mortality worldwide. The integrity of mitochondria in peripheral lymphocytes can indicate age-related degenerative disorders, revealing the balance between bioenergetics, inflammation, and senescence. The present study aims to investigate the impact of aging on mitochondrial-mediated epigenetic stress response mechanisms in both young and elderly individuals. Mitochondrial oxidative DNA damage, repair response, copy number, methylation, fusion, fission genes, electron transport chain enzyme complex activities, pro-inflammatory cytokine levels, and associated epigenetic mechanisms were studied. The results demonstrate that the elderly group experienced more significant disruption in the expression of mitochondrial genes, leading to impaired mitochondrial DNA (mtDNA) integrity intricately linked to mitochondrial-nuclear crosstalk, increasing their susceptibility to CVD. The findings highlight mitochondria’s crucial role in cellular dynamics, influencing stress responses and epigenetic mechanisms through fusion and fission cycles. Overall, these insights provide valuable information about the complex molecular processes linking mitochondrial dysfunction to age-related cardiovascular risks, paving the way for further exploration and potential interventions in aging-related health outcomes.

Graphical Abstract

Figure showing the molecular mechanisms underlying the mitoepigenetic stress response signaling pathways in age-associated cardiovascular diseases.
Understanding monogenic Parkinson's disease at a global scale
Authors: Junker Johanna , Lange Lara M. , Vollstedt Eva-Juliane , Roopnarain Karisha , Doquenia Maria Leila M. , Ahmad-Annuar Azlina , Avenali Micol , Bardien Soraya , Bahr Natascha , Ellis Melina , Galandra Caterina , Gasser Thomas , Heutink Peter , Illarionova Anastasia , Kanana Yuliia , Keller Sarmiento Ignacio J. , Kumar Kishore R. , Lim Shen-Yang , Madoev Harutyun , Mata Ignacio , Mencacci Niccolo E. , Nalls Mike A. , Padmanabhan Shalini , Shambetova Cholpon , Solle J , Tan Ai-Huey , Trinh Joanne , Valente Enza Maria , Singleton Andrew , Blauwendraat Cornelis , Lohmann Katja , Fang Zih-Hua , Klein Christine ,   the Global Parkinson's Genetics Program (GP2)
Published: March 2024

Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at global scale. The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD (MJFF GMPD) Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's (GP2) Monogenic Network took a different approach by targeting PD centers not yet represented in the medical literature. Here, we describe combining both efforts in a "merger project" resulting in a global monogenic PD cohort with build-up of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expression of monogenic PD. This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results.
An Analysis of Controlled Human Infection Studies Registered on ClinicalTrials.gov
Authors: Toomey Danny , Adams-Phipps Jupiter , Wilkinson James , Pietro John , Kamenicek Steffen , Kaufman Daniel , Jamrozik Euzebiusz , Osowicki Joshua , Roestenberg Meta , Saldanha Ian
Published: March 2024

OBJECTIVES: Controlled human infection studies (CHIS) involve intentional exposure of human volunteers to infectious agents. Given the small size of CHIS, aggregating data across studies is critical to the field. The objectives of the current analysis were to (1) evaluate the use of ClinicalTrials.gov for CHIS data reporting and (2) compare CHIS clinical trial participant flow and AE reporting in ClinicalTrials.gov with the same data in corresponding published articles. DESIGN: ClinicalTrials.gov records that described a CHIS were included and data were accessed using the AACT API. These data were compared with results extracted from publications associated with included records NCT identifiers and compared in groups stratified by sponsor type, cohort size, and risk of bias in selection of the reported result as determined by Domain 5 of the Cochrane Risk of Bias 2.0 tool. RESULTS: We screened 5,131 ClinicalTrials.gov records for inclusion, reviewed 410 records in full, and included 344 records. The overall prevalence of any discrepancy was 40%. Compared with their respective groups, significant discrepancies were observed in publicly funded trials, trials in the 3rd quartile of study size, and trials with a high risk of bias in selection of the reported result. Five studies reported a total of five SAEs in ClinicalTrials.gov records but not in any associated publications. CONCLUSION: We identified an overall prevalence of discrepancy of 40% in CHIS, which is comparable to the prevalence observed in other types of clinical trials. In general, medium-sized, publicly funded trials tended to have more discrepancies in reporting, which may reflect the resources typically available to large, privately funded trials or the relative ease of reporting in smaller trials with fewer overall AEs. These results highlight the need to facilitate clear and consistent reporting in CHIS.
Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France
Authors: Lee Amy , Davido Benjamin , Beck Ekkehard , Demont Clarisse , Joshi Keya , Kohli Michele , Maschio Michael , Uhart Mathieu , El Mouaddin Nadia
Published: March 2024

An economic evaluation was conducted to predict the economic and clinical burden of vaccinating immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines in Fall 2023 and Spring 2024 versus BNT162b2 variant-adapted vaccines in France. The number of symptomatic COVID-19 infections, hospitalizations, deaths, and long COVID cases, costs and quality-adjusted life years (QALYs) was estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from prior versions, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were tested in sensitivity analyses. The mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs saved. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.
Seroprevalence and risk factors for SARS-CoV-2 infection in middle-sized cities of Burkina Faso: a descriptive cross-sectional study
Authors: Sana Adama , Djemaï Elodie , Vreyer Philippe De , Thivillon Thomas , Badolo Hermann , Berthé Abdramane , Kania Dramane
Published: March 2024

Background

Since March 2020, COVID-19 has evolved from a localized outbreak to a global pandemic. We assessed the seroprevalence of COVID-19 in three towns in the Centre Sud region of Burkina Faso.

Methods

A population-based cross-sectional survey was conducted in three medium-sized towns in Burkina Faso’s Centre Sud region, from June to July 2021. Subjects aged 16 or over at the time of the survey were considered for this seroprevalence study. The Biosynex COVID-19 BSS rapid test was used to detect immunoglobulin G (IgG) and immunoglobulin M (IgM) against SARS-CoV-2. A standardized questionnaire was also administered to collect additional information.

Results

A total of 2449 eligible participants (age ≥ 16 years) were identified. Serological tests for COVID-19 were performed in 2155 individuals. Finally, 2143 valid tests were retained and analyzed. Out of the entire sample, 246 positive tests were observed, corresponding to a prevalence of 11.48%. Prevalence was 9.35% (58 cases) in Kombissiri, 12.86% (80 cases) in Manga and 11.99% (108 cases) in Pô. By gender, 13.37% of women (164 cases) tested positive, and 8.95% of men (82 cases). Women accounted for 66.67% of all positive test subjects. The results show a significantly higher seroprevalence in women (P = 0.007), people over 55 years old (P = 0.004), overweight or obese people (P =0.026) and those with drinking water sources at home (0.013).

Conclusions

The results of this study show that the COVID-19 virus also circulates in the population of medium-sized towns in Burkina Faso, far more than is officially reported in the country. The study also highlighted the greater vulnerability of women to the epidemic, and the challenge of access to water in the face of diseases such as COVID-19. The preventive measures put in place to fight the pandemic must take these different factors into account.
High throughput screening of nuclear receptors identifies NR4A1, a novel tumor suppressor with potential as a therapeutic target in gallbladder cancer
Authors: Sarkar Sajib Kumar , Minocha Rashmi , Das Prasenjit , Dash Nihar Ranjan , Dhar Ruby , Kumar Deepak , Kapoor Vinay Kumar , Shukla Ratnakar , Karmakar Subhradip
Published: March 2024

Introduction

Gallbladder cancer (GBC) is one of the most common cancer of the hepato-biliary tract, with a strikingly variable incidence and prevalence across different regions of the world. The Indo-Gangetic belt in Northern India is reported to have one of the highest incidences of about 21/100,000. GBC usually goes unnoticed due to the lack of any early symptoms with two third of GBC cases present late at inoperable stages and have very limited treatment options. Nuclear receptors, a family of 48 members are ligand dependent transcription factors. They are of particular interest in cancer research because of their established role in cancer pathogenesis and their excellent druggability that makes them a suitable therapeutic target.

Methodology

mRNA expression 48 nuclear receptors were assessed in GBC tissue samples (n=13) and chronic cholecystitis tissue samples by Nanostring nCounter. The screening identified orphan receptor NR4A1 to be significantly downregulated in GBC. Western blot were performed to further validate the same. We next interrogated the above findings in 2 different gallbladder cancer cell lines, the highly invasive NOZ and the non-invasive TGBC24TKB. In order to investigate the role of NR4A1 in GBC pathogenesis, NOZ cells were treated with cytosporone B (10µM for 24hours) an agonist of NR4A1. On the other hand NR4A1 was knocked down in TGBC24TKB by siRNA. Expression of different markers of proliferation, invasion and epithelial mesenchymal transition was assessed by qPCR. Cell cycle analysis was done using flow cytometry.

Results

NR4A1 was one of the top differentially expressed (down regulated) nuclear receptors in GBC both in RNA and protein level. Similar finding was observed in highly invasive cell line NOZ in comparison to TGBC24TKB. Cytosporone B treatment led to upregulation of NR4A1, which resulted in reduction of cell migration as evident by delayed wound healing, reduction in invasion with an increase in G0/G1 populations implying a growth arrest. NR4A1 knockdown in TGBC24TKB lead to reduction in G0/G1 fraction and also increase in proliferation markers like mki67.

Conclusion

NR4A1 in our study acts as a tumor suppressor, loss of which seems to provide a growth and survival advantage to GBC cells. NR4A1 activation by agonist reduced cell proliferation and invasion. We therefore propose NR4A1 as a novel biomarker in GBC with its loss associated with overall poor outcome. Hence its agonists may emerge as a potential candidate for neo-adjuvant therapy for advanced gallbladder cancer.
Investigating low birthweight and preterm birth as potential mediators in the relationship between prenatal infections and early child development: A linked administrative health data analysis
Authors: Hardie Iain , Murray Aja , King Josiah , Hall Hildigunnur Anna , Okelo Kenneth , Luedecke Emily , Marryat Louise , Thompson Lucy , Minnis Helen , Lombardo Michael , Wilson Philip , Auyeung Bonnie
Published: March 2024

Background

Prenatal infections are associated with childhood developmental outcomes such as reduced cognitive abilities, emotional problems and other developmental vulnerabilities. However, there is currently a lack of research examining whether this arises due to potential intermediary variables like low birthweight or preterm birth, or due to some other mechanisms of maternal immune activation arising from prenatal infections.

Methods

Administrative data from the National Health Service (NHS) health board of Greater Glasgow & Clyde, Scotland, was used, linking birth records to hospital records and universal child health review records for 55,534 children born from 2011-2015, and their mothers. Causal mediation analysis was conducted to examine the extent to which low birthweight and preterm birth mediate the relationship between hospital-diagnosed prenatal infections and having developmental concern(s) identified by a health visitor during 6-8 week or 27-30 month child health reviews.

Results

Model estimates suggest that 5.18% [95% CI: 3.77-7.65%] of the positive association observed between hospital diagnosed prenatal infections and developmental concern(s) was mediated by low birthweight, whilst 7.37% [95% CI: 5.36-10.88%] was mediated by preterm birth.

Conclusion

Low birthweight and preterm birth appear to mediate the relationship between prenatal infections and childhood development, but only to a small extent. Maternal immune activation mechanisms unrelated to low birthweight and preterm birth remain the most likely explanation for associations observed between prenatal infections and child developmental outcomes, although other factors (e.g. genetic factors) may also be involved.
Physical basis for the interaction betweenDrosophilaROS1 and the GPCR BOSS
Authors: Zhang Jianan , Tsutsui Yuko , Li Hengyi , Li Tongqing , Wang Yueyue , Klein Daryl E.
Published: March 2024

Abstract/Summary

DrosophilaROS1 (dROS1, Sevenless) is a receptor tyrosine kinase (RTK) essential for the differentiation ofDrosophilaR7 photoreceptor cells1, 2. Activation of dROS1 is mediated by binding to the extracellular region (ECR) of the GPCR (G protein coupled receptor) BOSS (Bride Of Sevenless) on adjacent cells1, 3, 4. Genetic evidence together within vitroactivity assays confirmed the activation of dROS1 by BOSS and identified subsequent downstream signaling pathways including SOS (Son of Sevenless)1, 5. However, the physical basis for how dROS1 interacts with the GPCR BOSS has long remained unknown. Here we provide the first structure, using Cryo-Electron Microscopy (CryoEM), of dROS1’s extracellular region, which mediates ligand binding. We show that the N-terminal region of dROS1 adopts a folded-over conformation harboring a novel structural domain. We further narrowed down the interacting binding epitopes on both dROS1 and BOSS. This includes a beta-strand in dROS1’s third Fibronectin type III (FNIII) domain and the C-terminal portion of BOSS’ ECR. Our mutagenesis studies, coupled with AlphaFold complex predictions, support a binding interaction mediated by a hydrophobic interaction and beta-strand augmentation between these regions. Our findings provide a fundamental understanding of the regulatory function of dROS1 and further provide mechanistic insight into the human ortholog and oncogene ROS1.
Whole protein sequencing and quantification without proteolysis, terminal residue cleavage, or purification: A computational model
Authors: Sampath G.
Published: March 2024

Sequencing and quantification of whole proteins in a sample without separation, terminal residue cleavage, or proteolysis are modeled computationally. Similar to recent work on DNA sequencing (PNAS113, 5233–5238, 2016), a high-volume conjugate is attached to every instance of amino acid (AA) type AAi, 1 ≤ i ≤ 20, in an unfolded whole protein, which is then translocated through a nanopore. From the volume excluded by 2L residues in a pore of length L nm (a proxy for the blockade current), a partial sequence containing AAiis obtained. Translocation is assumed to be unidirectional, with residues exiting the pore at a roughly constant rate of ∼1/μs (Nature Biotechnology41, 1130–1139, 2023). The blockade signal is sampled at intervals of 1 μs and digitized with a step precision of 70 nm3; the positions of the AAis are obtained from the positions of well-defined quantum jumps in the signal. This procedure is applied to all 20 standard AA types, the resulting 20 partial sequences are merged to obtain the whole protein sequence. The complexity of subsequence computation is O(N) for a protein with N residues. The method is illustrated with a sample protein from the human proteome (Uniprot id UP000005640_9606). A mixture of M’ protein molecules (including multiple copies) can be sequenced by constructing an M’ × 20 array of partial sequences from which proteins occurring multiple times are first isolated and their sequences obtained separately. The remaining M singly-occurring molecules are detected from M disjoint paths through the 20 columns of the reduced M × 20 array. Detection complexity is O(M20), which is nominally in polynomial time but practical only for small M; to use this method a sample may be subdivided into subsamples down to this level. Quantification of proteins can be done by sorting their computed sequences on the sequence strings and counting the number of duplicates. The possibility of translating this procedure into practice and related implementation issues are discussed.