bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity
Authors: Villa-González Mario , Rubio Marina , Martín-López Gerardo , Mallavibarrena Paula R. , Vallés-Saiz Laura , Vivien Denis , Wandosell Francisco , Pérez-Álvarez Maria José 
Published: April 2024

AbstractIschemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes. In this context, deciphering the molecular mechanisms underlying such reactive microglial is essential to devise strategies to protect neurons and maintain certain brain functions affected by early neuroinflammation after ischemia. Here, we studied the role of mammalian target of rapamycin (mTOR) activity in the microglial response using a murine model of cerebral ischemia in the acute phase. We also determined the therapeutic relevance of the pharmacological administration of rapamycin, a mTOR inhibitor, before and after ischemic injury. Our data show that rapamycin, administered before or after brain ischemia induction, reduced the volume of brain damage and neuronal loss by attenuating the microglial response. Therefore, our findings indicate that the pharmacological inhibition of mTORC1 in the acute phase of ischemia may provide an alternative strategy to reduce neuronal damage through attenuation of the associated neuroinflammation.
A placebo-controlled, crossover trial to investigate the efficacy of tiotropium bromide or placebo added to usual care in stable symptomatic post-hematopoietic stem cell transplantation (HSCT) bronchiolitis obliterans syndrome (BOS)
Authors: Dini Naeemeh , Khoshbin Amin Pastaki , Aliannejad Rasoul , Bakhshandeh Hooman , Najafizadeh Katayoun , Mehdizadeh Mahshid , Amini Shahideh 
Published: April 2024

Abstract
Background
Despite the fundamental progress in hematopoietic stem cell transplant, this treatment is also associated with complications. Graft-versus-host disease is a possible complication of HSCT. Bronchiolitis obliterans syndrome (BOS) is the pulmonary form of this syndrome. Due to the high morbidity and mortality rate of BOS, various studies have been conducted in the field of drug therapy for this syndrome, although no standard treatment has yet been proposed. According to the hypotheses about the similarities between BOS and chronic obstructive pulmonary disease, the idea of using tiotropium bromide as a bronchodilator has been proposed.

Method/design
A randomized, double-blind, placebo-controlled, and crossover clinical trial is being conducted to evaluate the efficacy of tiotropium in patients with BOS. A total of 20 patients with BOS were randomly assigned (1:1) to receive a once-daily inhaled capsule of either tiotropium bromide (KP-Tiova Rotacaps 18 mcg, Cipla, India) or placebo for 1 month. Patients will receive tiotropium bromide or placebo Revolizer added to usual standard care. Measurements will include spirometry and a 6-min walking test.

Ethics/dissemination
This study was approved by the Research Ethics Committees of Imam Khomeini Hospital Complex, Tehran University of Medical Science. Recruitment started in September 2022, with 20 patients randomized. The treatment follow-up of participants with tiotropium is currently ongoing and is due to finish in April 2024. The authors will disseminate the findings in peer-reviewed publications, conferences, and seminar presentations.

Trial registration
Iranian Registry of Clinical Trial (IRCT) IRCT20200415047080N3. Registered on 2022–07-12, 1401/04/21.
Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial
Authors: Liebano Richard E. , Sluka Kathleen A. , Roy Joshua , Savinelli Meghan , Dailey Dana L. , Riley Sean P. 
Published: April 2024

Abstract
Background
Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP.

Methods/design
This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2–125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05.

Discussion
This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants.

Trial registration
ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.
Synthesis, anticancer evaluation, molecular docking and ADME study of novel pyrido[4ʹ,3ʹ:3,4]pyrazolo[1,5-a]pyrimidines as potential tropomyosin receptor kinase A (TrKA) inhibitors
Authors: Metwally Nadia Hanafy , Deeb Emad Abdullah , Hasani Ibrahim Walid 
Published: April 2024

AbstractThe starting compound 3-amino-1,7-dihydro-4H-pyrazolo[4,3-c]pyridine-4,6(5H)-dione (1) is reacted with each of diketone and β-ketoester, forming pyridopyrazolo[1,5-a]pyrimidines 4a,b and 14a,b, respectively. The compounds 4 and 14 reacted with each of aromatic aldehyde and arenediazonium salt to give the respective arylidenes and arylhydrazo derivatives, respectively. The structure of the new products was established using spectroscopic techniques. The cytotoxic activity of selected targets was tested in vitro against three cancer cell lines MCF7, HepG2 and HCT116. The data obtained from enzymatic assays of TrKA indicated that compounds 7b and 16c have the strongest inhibitory effects on TrKA with IC50 = 0.064 ± 0.0037 μg/ml and IC50 = 0.047 ± 0.0027 μg/ml, respectively, compared to the standard drug Larotrectinib with IC50 = 0.034 ± 0.0021 μg/ml for the HepG2 cancer cell line. In cell cycle analysis, compounds 7b, 15b, 16a and 16c caused the greatest arrest in cell cycle at the G2/M phase. In addition, compound 15b has a higher apoptosis-inducing effect (36.72%) than compounds 7b (34.70%), 16a (21.14) and 16c (26.54%). Compounds 7b, 16a and 16c were shown fit tightly into the active site of the TrKA kinase crystal structure (PDB: 5H3Q). Also, ADME study was performed on some selected potent anticancer compounds described in this study.
Polyvinyl chloride solvent cement poisoning: a case report
Authors: Marambahewa S. R. , Chandrasiri D. A. C. T , Wijesekara W. A. I. C. , Munasinghe B. M. 
Published: April 2024

Abstract
Background
S-lon® (S) is a locally produced polyvinyl chloride-based solvent cement. It is a clear, slightly viscous liquid. Other constituents include 1-cyclohexanone, 3-butanone, and 1-acetone. It is used ubiquitously for building construction in Sri Lanka. Although the clinical effects of the compound have not yet been ascertained, the constituents have been implicated in neurotoxicity, respiratory tract, eye and skin irritation, and delayed liver and renal injury.

Case description
A 42-year-old South Asian male presented following self-ingestion of S. His vital parameters were stable and initially managed symptomatically. A few hours later, he developed central nervous system depression and stridor requiring elective intubation. Examination of the upper airway revealed inflammation and edema. He was sedated and ventilated, and intravenous dexamethasone was administered. Attempts at removal of the nasogastric tube after extubation on day 3 failed. The patient had to be reintubated and sedated owing to extreme agitation not responding to routine doses of sedatives. The nasogastric tube had been amalgamated after reacting with S, forming a solid clump, later found after removal. The posterior pharynx and nasopharynx were packed and later removed before extubation. The patient made a full recovery and was transferred to the ward on day 5.

Conclusion
Ingestion of a sufficient quantity of S could result in gut absorption with central nervous system depression, coma, and even death. No antidote is available for toxicity, and management is largely supportive. As witnessed in our patient, chemical laryngitis and upper airway inflammation may lead to upper airway obstruction. Chemical reactions with medical equipment may lead to unforeseen outcomes.
In-vivo inhibition of neutral endopeptidase 1 results in higher absorbed tumor doses of [177Lu]Lu-PP-F11N in humans: the lumed phase 0b study
Authors: Rottenburger Christof , Hentschel Michael , Fürstner Markus , McDougall Lisa , Kottoros Danijela , Kaul Felix , Mansi Rosalba , Fani Melpomeni , Vija A. Hans , Schibli Roger , Geistlich Susanne , Behe Martin , Christ Emanuel R. , Wild Damian 
Published: April 2024

Abstract
Background
A new generation of radiolabeled minigastrin analogs delivers low radiation doses to kidneys and are considered relatively stable due to less enzymatic degradation. Nevertheless, relatively low tumor radiation doses in patients indicate limited stability in humans. We aimed at evaluating the effect of sacubitril, an inhibitor of the neutral endopeptidase 1, on the stability and absorbed doses to tumors and organs by the cholecystokinin-2 receptor agonist [177Lu]Lu-PP-F11N in patients. In this prospective phase 0 study eight consecutive patients with advanced medullary thyroid carcinoma and a current somatostatin receptor subtype 2 PET/CT scan were included. Patients received two short infusions of ~ 1 GBq [177Lu]Lu-PP-F11N in an interval of ~ 4 weeks with and without Entresto® pretreatment in an open-label, randomized cross-over order. Entresto® was given at a single oral dose, containing 48.6 mg sacubitril. Adverse events were graded and quantitative SPECT/CT and blood sampling were performed. Absorbed doses to tumors and relevant organs were calculated.

Results
Pretreatment with Entresto® showed no additional toxicity and increased the stability of [177Lu]Lu-PP-FF11N in blood significantly (p < 0.001). Median tumor-absorbed doses were 2.6-fold higher after Entresto® pretreatment (0.74 vs. 0.28 Gy/GBq, P = 0.03). At the same time, an increase of absorbed doses to stomach, kidneys and bone marrow was observed, resulting in a tumor-to-organ absorbed dose ratio not significantly different with and without Entresto®.

Conclusions
Premedication with Entresto® results in a relevant stabilization of [177Lu]Lu-PP-FF11N and consecutively increases radiation doses in tumors and organs.
Trial registration clinicaltrails.gov, NCT03647657. Registered 20 August 2018.
Tools for assessing the methodological limitations of a QES—a short note
Authors: Nøkleby Heid , Ames Heather Melanie R. , Langøien Lars Jørun , Hestevik Christine Hillestad 
Published: April 2024

AbstractThe increasing prevalence and application of qualitative evidence syntheses (QES) in decision-making processes underscore the need for robust tools to assess the methodological limitations of a completed QES. This commentary discusses the limitations of three existing tools and presents the authors’ efforts to address this gap. Through a simple comparative analysis, the three tools are examined in terms of their coverage of essential topic areas. The examination finds that existing assessment tools lack comprehensive coverage, clarity, and grounding in qualitative research principles. The authors advocate for the development of a new collaboratively developed evidence-based tool rooted in qualitative methodology and best practice methods. The conclusion emphasizes the necessity of a tool that can provide a comprehensive judgement on the methodological limitations of a QES, addressing the needs of end-users, and ultimately enhancing the trustworthiness of QES findings in decision-making processes.
Predicting UPDRS in Parkinson’s disease using ensembles of self-organizing map and neuro-fuzzy
Authors: Zhao Siren , Zhang Jilun , Zhang Jianbin 
Published: April 2024

AbstractParkinson's Disease (PD) is a complex, degenerative disease that affects nerve cells that are responsible for body movement. Artificial Intelligence (AI) algorithms are widely used to diagnose and track the progression of this disease, which causes symptoms of Parkinson's disease in its early stages, by predicting the results of the Unified Parkinson's Disease Rating Scale (UPDRS). In this study, we aim to develop a method based on the integration of two methods, one complementary to the other, Ensembles of Self-Organizing Map and Neuro-Fuzzy, and an unsupervised learning algorithm. The proposed method relied on the higher effect of the variables resulting from the analysis of the initial readings to obtain a correct and accurate preliminary prediction. We evaluate the developed approach on a PD dataset including speech cues. The process was evaluated with root mean square error (RMSE) and modified R square (modified R2). Our findings reveal that the proposed method is effective in predicting UPDRS outcomes by a combination of speech signals (measures of hoarseness). As the preliminary results during the evaluation showed numbers that proved the worth of the proposed method, such as UPDRS = 0.955 and RMSE approximately 0.2769 during the prediction process.
Endotoxin-induced alterations of adipose tissue function: a pathway to bovine metabolic stress
Authors: Chirivi Miguel , Contreras G. Andres 
Published: April 2024

AbstractDuring the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues (AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte’s insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins’ impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows’ disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.
Social media addiction and academic engagement as serial mediators between social anxiety and academic performance among college students
Authors: Mou Qiaoxing , Zhuang Jie , Wu Qunhong , Zhong Yaqin , Dai Qianqian , Cao Xin , Gao Yuexia , Lu Qingyun , Zhao Miaomiao 
Published: April 2024

Abstract
Background
Social anxiety has been shown to affect college students’ academic performance. However, the role of social media addiction and academic engagement in this association is unclear.

Methods
A total 2661 college students completed a self-report questionnaire including Liebowitz Social Anxiety Scale, the Bergen Social Media Addiction Scale, the Utrecht Student Work Engagement Scale for Students, and the grade point average. Hayes’ PROCESS macro for SPSS was employed to test the serial mediation effect.

Results
Results indicated that social anxiety was negatively related to academic performance, only academic engagement played a single mediating role in the relationship between social anxiety and academic performance, meanwhile social media addiction and academic engagement acted as serial mediators between social anxiety on academic performance.

Conclusions
Social media addiction and academic engagement can explain the potential mechanisms of the association between social anxiety and academic performance, which have implications for devising intervention strategies to enhance the mental health and academic outcomes of college students.
The longitudinal relations between mental state talk and theory of mind
Authors: Sehlstedt Isac , Hansson Isabelle , Hjelmquist Erland 
Published: April 2024

Abstract
Background
Previous investigations of associations between children’s Theory of Mind (ToM) and parents’ use of words relating to mental states (or mental state talk; MST) have predominantly been performed using cross-sectional designs and false belief tasks as indicators of ToM.

Methods
We here report a longitudinal study of 3–5 year-olds (n = 80) investigating ToM development using the ToM scale and three different parental MST types: the absolute frequency of words, the proportions of words, and the vocabulary size.

Results
Our results revealed significant relations between all parental MST types and later child ToM. Proportions of parental MST were most often related to the children’s ToM at 4 years of age. However, the rate at which the children developed ToM from 3 to 5 years of age was associated with the other two parental MST type measures, namely, absolute frequency and vocabulary size. Additionally, our analyses revealed that parents’ use of cognitive MST words (e.g., think, or know) were most frequently associated with children’s ToM at 4 years of age compared to emotion and desire-related MST words.

Conclusions
We conclude that the parental ability to capture the thoughts, beliefs, and knowledge present in different scenarios is associated with children’s ability to understand other minds. Moreover, parents’ way of talking about the mental states of others is associated with their children’s ability to understand and further develop ToM.
Gamma camera imaging characteristics of 166Ho and 99mTc used in Selective Internal Radiation Therapy
Authors: Kästner David , Braune Anja , Brogsitter Claudia , Freudenberg Robert , Kotzerke Jörg , Michler Enrico 
Published: April 2024

Abstract
Background
The administration of a 166Ho scout dose is available as an alternative to 99mTc particles for pre-treatment imaging in Selective Internal Radiation Therapy (SIRT). It has been reported that the 166Ho scout dose may be more accurate for the prediction of microsphere distribution and the associated therapy planning. The aim of the current study is to compare the scintigraphic imaging characteristics of both isotopes, considering the objectives of the pre-treatment imaging using clinically geared phantoms.

Methods
Planar and SPECT/CT images were obtained using a NEMA image quality phantom in different phantom setups and another body-shaped phantom with several inserts. The influence of collimator type, count statistics, dead time effects, isotope properties and patient obesity on spatial resolution, contrast recovery and the detectability of small activity accumulations was investigated. Furthermore, the effects of the imaging characteristics on personalized dosimetry are discussed.

Results
The images with 99mTc showed up to 3 mm better spatial resolution, up to two times higher contrast recovery and significantly lower image noise than those with 166Ho. The contrast-to-noise ratio was up to five times higher for 99mTc than for 166Ho. Only when using 99mTc all activity-filled spheres could be distinguished from the activity-filled background. The measurements mimicking an obese patient resulted in a degraded image quality for both isotopes.

Conclusions
Our measurements demonstrate better scintigraphic imaging properties for 99mTc compared to 166Ho in terms of spatial resolution, contrast recovery, image noise, and lesion detectability. While the 166Ho scout dose promises better prediction of the microsphere distribution, it is important to consider the inferior imaging characteristics of 166Ho, which may affect individualized treatment planning in SIRT.