bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2—a study protocol for a randomized controlled trial
Authors: Thankachen Shani S. , Devasenapathy Niveditha , Bassi Abhinav , Ghosh Arpita , Arfin Sumaiya , Gummidi Balaji , Basheer Aneesh , Bangi Ashfak , Sahu Dibakar , Bhalla Ashish , Blesson Merlin , Jain Manish , Jha Vivekanand 
Published: June 2024

Abstract
Background
There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID.

Methods
This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared.

Discussion
Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice.

Trial registration
This clinical trial has been registered prospectively on www.clinicaltrials.gov with registration CTRI/2021/11/038234 dated November 24, 2021.
Generalized music therapy to reduce neuroactive drug needs in critically ill patients. Study protocol for a randomized trial
Authors: Mistraletti Giovanni , Solinas Anna , Del Negro Silvia , Moreschi Carlotta , Terzoni Stefano , Ferrara Paolo , Negri Katerina , Calabretta Davide , Formenti Paolo , Formenti Angelo , Umbrello Michele 
Published: June 2024

Abstract
Background
Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh intensive care unit (ICU) environment. However, this pharmacological therapy presents several side effects: guidelines suggest using a light sedation target, keeping critically ill patients calm, conscious, and cooperative. Personalized music therapy (MT) can reduce stress and anxiety, decreasing the need for drugs. The aim of the current investigation is to compare different approaches for MT in the ICU: a personalized approach, with music selected by patients/families and listened through headphones, or a generalized approach, with ambient music chosen by a music therapist and transmitted through speakers. Primary outcome: number of days “free from neuroactive drugs” in the first 28 days after ICU admission. Secondary outcomes: total amount of neuroactive drugs (midazolam, propofol, morphine, fentanyl, haloperidol), stress during ICU stay (sleep at night, anxiety and agitation, use of physical restraints, stressors evaluated at discharge), the feasibility of generalized MT (interruptions requested by staff members and patients/families).

Methods
Randomized, controlled trial with three groups of critically ill adults: a control group, without MT; a personalized MT group, with music for at least 2 h per day; a generalized MT group, with music for 12.5 h/day, subdivided into fifteen 50-min periods.

Discussion
One hundred fifty-three patients are expected to be enrolled. This publication presents the rationale and the study methods, particularly the strategies used to build the generalized MT playlist. From a preliminary analysis, generalized MT seems feasible in the ICU and is positively received by staff members, critically ill patients, and families.

Trial registration
ClinicalTrials.gov Identifier: NCT03280329. September 12, 2017.
Alterations of plasma circulating microRNAs in BALB/c mice with Toxocara canis visceral and cerebral larva migrans
Authors: Yang Yifan , Chen Yi , Zheng Zhiwan , Lin Lijun , Chen Xueqiu , Yang Chenyu , Zhong Die , Wu Haiyan , Xiong Zhiwei , Liu Sishi , Wang Tao , Yang Yi , Du Aifang , Ma Guangxu 
Published: June 2024

Abstract
Background
Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host–parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases.

Methods
Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host–parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice.

Results
This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice.

Conclusions
Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals.

Graphical Abstract
Ectopic adrenocortical adenoma characterized by hypogonadism: a case report and review of the literature
Authors: Wang Zhihua , Zhong Xueyu , Yu Jiayu , Li Huiqing , Zheng Juan 
Published: June 2024

Abstract
Background
Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas.

Case presentation
A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. Review: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization.

Conclusion
Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.
Cryo-EM structures reveal tau filaments from Down syndrome adopt Alzheimer’s disease fold
Authors: Ghosh Ujjayini , Tse Eric , Yang Hyunjun , Shi Marie , Caro Christoffer D. , Wang Feng , Merz Gregory E. , Prusiner Stanley B. , Southworth Daniel R. , Condello Carlo 
Published: June 2024

AbstractDown syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and cardiovascular disabilities, individuals with DS have an increased risk of developing progressive dementia and early-onset Alzheimer’s disease (AD). This dementia is attributed to the increased gene dosage of the amyloid-β (Aβ) precursor protein gene, the formation of self-propagating Aβ and tau prion conformers, and the deposition of neurotoxic Aβ plaques and tau neurofibrillary tangles. Tau amyloid fibrils have previously been established to adopt many distinct conformations across different neurodegenerative conditions. Here, we report the characterization of brain samples from four DS cases spanning 36–63 years of age by spectral confocal imaging with conformation-specific dyes and cryo–electron microscopy (cryo-EM) to determine structures of isolated tau fibrils. High-resolution structures revealed paired helical filament (PHF) and straight filament (SF) conformations of tau that were identical to those determined from AD cases. The PHFs and SFs are made of two C-shaped protofilaments, each containing a cross-β/β-helix motif. Similar to filaments from AD cases, most filaments from the DS cases adopted the PHF form, while a minority (approximately 20%) formed SFs. Samples from the youngest individual with no documented dementia had sparse tau deposits. To isolate tau for cryo-EM from this challenging sample we used a novel affinity-grid method involving a graphene oxide surface derivatized with anti-tau antibodies. This method improved isolation and revealed that primarily tau PHFs and a minor population of chronic traumatic encephalopathy type II–like filaments were present in this youngest case. These findings expand the similarities between AD and DS to the molecular level, providing insight into their related pathologies and the potential for targeting common tau filament folds by small-molecule therapeutics and diagnostics.
Novel synthesis of some heterocycles and their molluscicidal activity against the destructive land snail, Theba pisana
Authors: Abeed Ahmed Abdou O. , El-Emary Talaat I. , Youssef Mohamed Salah K. , Hefzy Ibrahim , Ibrahim Hesham A. M. 
Published: June 2024

Abstract
Background
Terrestrial snails, specifically Theba pisana, represent significant agricultural pests in the Mediterranean region, particularly in Egypt. They are gastropods that cause substantial damage to a variety of vegetation, rendering them important agricultural pests that result in economic losses. In response, we have developed unique and non-toxic molluscicides. The study assessed nine novel heterocycles compared with methomyl as a reference compound, to study their molluscicidal effects on T. pisana. These heterocycles include 2-pyrazolines, 2-oxocyclohex-3-ene, and 3-cyano-2-ethoxypyridine.

Results
The obtained data revealed that the majority of the produced chemicals were remarkably effective against T. pisana snails, exhibiting different degrees of toxicity seven days post-treatment. Methomyl exhibited the highest toxicity, followed by prop-2-en-1-one and 1-thiocarbamoyl-2-pyrazoline derivatives, with LC50 values of 44.14, 59.54, and 72.00 ppm, respectively.

Conclusions
These findings will inform the potential of these synthetic compounds as one of the sources for molluscicide development and their integration into pest management strategies.

Graphical Abstract
Effect of nutrition assessment, counselling and support integration on mother-infant nutritional status, practices and health in Tororo and Butaleja districts, Uganda: A comparative non-equivalent quasi-experimental study
Authors: Namukose Samalie , Maina Gakenia Wamuyu , Kiwanuka Suzanne N , Makumbi Fredrick Edward 
Published: June 2024

Abstract
Background
Malnutrition remains a health challenge for women aged 15 to 49 years and their infants. While Nutrition Assessment Counselling and Support (NACS) is considered a promising strategy, evidence of its effectiveness remains scanty. This study assessed the effect of the comprehensive NACS package on the mother-infant practices, health and nutrition outcomes in two districts in Eastern Uganda.

Methods
A comparative non-equivalent quasi-experimental design was employed with two groups; Comprehensive NACS (Tororo) and Routine NACS (Butaleja). Pregnant mothers were enrolled spanning various trimesters and followed through the antenatal periods and post-delivery to monitor their health and nutrition status. Infants were followed for feeding practices, health and nutritional status at birth and weeks 6, 10, 14 and at months 6, 9 and 12 post-delivery. Propensity score matching ensured study group comparability. The NACS effect was estimated by nearest neighbour matching and the logistic regression methods. Statistical analysis utilised STATA version 15 and R version 4.1.1.

Results
A total of 666/784 (85%) with complete data were analysed (routine: 412, comprehensive: 254). Both groups were comparable by mothers’ age, Mid Upper Arm Circumference, prior antenatal visits, meal frequency, micronutrient supplementation and instances of maternal headache, depression and diarrhoea. However, differences existed in gestation age, income, family size, education and other living conditions. Comprehensive NACS infants exhibited higher infant birth weights, weight-for-age z-scores at the 3rd -6th visits (p < 0.001), length-for-age z scores at the 4th -7th visits (p < 0.001) and weight-for-length z-scores at the 3rd − 5th (p < = 0.001) visits. Despite fewer episodes of diarrhoea and fever, upper respiration infections were higher.

Conclusions
The comprehensive NACS demonstrated improved mother-infant nutritional and other health outcomes suggesting the need for integrated and holistic care for better maternal, infant and child health.
Longitudinally extensive transverse myelitis with trident sign and positive AQP4 antibody: a case report
Authors: Shojaei Maziar , Maghsudloo Faezeh , Ramezani Mahtab , Ahmadzadeh Arman , Monjazeb Somayeh , Rezaii Amir , Sahraian Mohammad Ali 
Published: June 2024

Abstract
Background
Longitudinally extensive transverse myelitis (LETM) is characterized by spinal cord lesions that affect at least three spinal cord segments. It can be associated with various inflammatory conditions. While imaging characteristics can aid in diagnosis, relying solely on them may lead to misinterpretation.

Case presentation
We describe a 35-year-old woman who presented with subacute myelitis. Her cervical MRI (magnetic resonance imaging) revealed an extensive lesion from the area postrema down to the second thoracic level, with a trident sign observed in axial T1-weighted post-gadolinium imaging. The presence of a trident sign in MRI of patients with myelopathy is more commonly associated with sarcoidosis than other conditions. But our patient had positive (rechecked) AQP4 antibody and negative FDG-PET (fluorodeoxyglucose positron emission tomography) scan that shows trident sign could be seen in other inflammatory disorders such as NMO (neuromyelitis optica).

Conclusion
Trident sign is not pathognomonic for sarcoidosis, additional investigations are necessary to identify the diagnoses related to the trident sign.
Unveiling the evolution of generative AI (GAI): a comprehensive and investigative analysis toward LLM models (2021–2024) and beyond
Authors: Akhtar Zarif Bin 
Published: June 2024

AbstractThis comprehensive exploration of recent breakthroughs in artificial intelligence (AI) traversed the realms of language models, computer vision, and generative models, unraveling the intricacies of cutting-edge technologies such as GPT-3.5, GPT-4, Pix2Seq, and multimodal models in terms of generative AI. In this multifaceted journey, the focus extended beyond technological prowess to ethical considerations, emphasizing responsible AI practices guided by Google's AI Principles. The nuanced discussions encapsulated the transformative impact of AI on user experiences across various Google products and toolsets, paving the way for a future where natural language interaction, creative content generation, and multimodal understanding redefine human–computer interactions. The research investigation showcased not only the advancements themselves but also the critical lens through which these innovations are approached, underscoring the importance of ethical and responsible AI in shaping the technological landscape.
TOP: A phase III, multicentre, randomized controlled study comparing osimertinib in combination with carboplatin and pemetrexed to osimertinib monotherapy for untreated patients with advanced non-squamous (Non-sq) non-small cell lung cancer (NSCLC) with concurrent EGFR and TP53 mutations.
Authors: Yang Yunpeng , Feng Weineng , Jiang Wei , Huang Lu , Zhao Yanqiu , Chen Lili , Fang Yong , Ji Mei , Zhang Tingting , Zhu Junfei , Zhang Li 
Published: June 2024

TPS8662 Background: Osimertinib is the current standard first-line treatment for advanced non-sq NSCLC with sensitive EGFR mutations. However, previous studies demonstrated that patients with concurrent EGFR and TP53 mutations had suboptimal clinical benefit with EGFR-TKI monotherapy. FLAURA2 study showed that osimertinib plus pemetrexed and platinum-based chemotherapy significantly improved progression-free survival (PFS) compared with osimertinib monotherapy for EGFR-mutated advanced NSCLC patients. Further study is needed to better understand the benefits of the FLAURA2 model for patients with concurrent mutations. The objective of this study is to determine whether osimertinib plus chemotherapy could improve efficacy compared with osimertinib monotherapy in patients with concurrent EGFR and TP53 Mutations. Methods: This is a phase III, randomized, open-label trial in patients with advanced Non-sq NSCLC harboring EGFR mutations (exon 19 deletion or L858R) and TP53 mutations, with a performance status of 0 to 1, and planned to receive first-line therapy. Eligible patients will be randomized 1:1 to osimertinib monotherapy arm (osimertinib 80 mg orally per day) or combination therapy arm (osimertinib 80 mg orally per day plus pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed and osimertinib). Randomization will be stratified by PS score (0 vs. 1), brain metastases status (yes vs. no) and mutation type (exon 19 deletion vs. L858R). The primary end point is PFS per RECIST 1.1 assessed by investigator. Secondary end points include overall survival, objective response rate, duration of response, adverse events and quality of life. Exploratory endpoint is correlation between concurrent mutations other than TP53 and efficacy, and the resistance mechanisms to combination therapy revealed by dynamic ctDNA profiling. Approximately 170 PFS events will be required to detect hazard ratio of 0.65 with 80% power at a two-sided significance level of 0.05. 292 patients will be enrolled. Until February 1, 2024, 204 patients have been enrolled, the last patient is expected to be enrolled in June 2024. Clinical trial information: NCT04695925 .
A randomized, controlled, multicenter, phase 3 study of vusolimogene oderparepvec (VO) combined with nivolumab vs treatment of physician’s choice in patients with advanced melanoma that has progressed on anti–PD-1 and anti–CTLA-4 therapy (IGNYTE-3).
Authors: Luke Jason J. , Kong George , Gullo Giuseppe , Robert Caroline 
Published: June 2024

TPS9604 Background: Melanoma is the 5th most common cancer type, with ~100,000 new cases and ~8,000 deaths estimated in the US for 2024. First-line systemic treatment with immune checkpoint inhibitors improved the objective response rate (ORR) and extended progression-free survival (PFS) and overall survival (OS) for patients with advanced disease. The combination of anti–PD-1 nivolumab (nivo) + anti–CTLA-4 ipilimumab (ipi) therapy is associated with the highest ORR and best PFS and OS in this setting. However, only about half of patients respond, and there is no standard of care for patients who progress after anti–PD-1–based therapy. VO (also referred to as RP1) is a selectively replication-competent HSV-1 oncolytic virus that expresses human GM-CSF and a fusogenic glycoprotein (GALV-GP-R–). Preliminary data from the phase 1/2 study (IGNYTE) showed that intratumoral (IT) VO plus intravenous (IV) nivolumab (nivo) was well tolerated and had meaningful antitumor activity (ORR, 31.4%) with durable responses in patients with advanced melanoma who progressed on prior anti–PD-1 therapy. This phase 3 study will evaluate the overall survival and clinical benefit as well as the safety of VO plus nivo for patients with advanced melanoma whose disease has progressed after receiving anti–PD-1 and anti–CTLA-4 therapy (or who are not eligible for anti–CTLA-4 therapy in addition to anti–PD-1) versus physician’s choice. Methods: This is a randomized, controlled, multicenter, phase 3 clinical trial comparing VO in combination with nivo vs physician’s choice of treatment in patients with unresectable or metastatic melanoma. Key eligibility criteria include age ≥12 years, stage IIIb–IV/M1a–M1d cutaneous melanoma, confirmed disease progression on an anti–PD–1 and anti–CTLA-4 treatment (administered in combination or in sequence with anti–PD-1 last), at least 1 measurable tumor (≥1 cm), and adequate hematologic, hepatic, and renal function. Patients who are not candidates for anti–CTLA-4 therapy may enroll if they have confirmed progression on anti–PD-1 therapy. Patients with BRAF V600 mutant melanoma must have received an anti-BRAF + anti-MEK targeted therapy prior to enrollment. Patients (N = ~400) will be randomized 1:1 to receive VO plus nivo or physician’s choice (nivo + relatlimab, anti–PD–1 monotherapy rechallenge [nivo or pembrolizumab], or single-agent chemotherapy [dacarbazine, temozolomide, or paclitaxel/albumin-bound paclitaxel]). VO is given IT Q2W; nivo is administered IV at 240 mg Q2W or 480 mg Q4W starting with the 2nd dose of VO. The primary endpoint of the study is OS; the key secondary endpoints are PFS and ORR. Additional endpoints include complete response rate, duration of response, disease control rate, and safety. Clinical trial information: NCT06264180 .