bluuebunny/crossref_metadata_2025_split huggingface dataset:
The long lost denture: a rare case of an acquired, non-malignant tracheo-oesophageal fistula
Authors: Jesani Hannah , Hundle Aaron , Nankivell Paul , Kalkat Maninder 
Published: November 2024

Abstract
Background
Ingested dental prosthesis are susceptible to impaction in the gastrointestinal tract due to their sharp edges, size and contour. Delays in presentation arise from the lack of clear history of ingestion and misdiagnosis occurs due to the radiolucency of denture material on plain radiography. An acquired, non-malignant tracheo-oesophageal fistula (TOF) may develop from a chronically impacted denture. Surgical management of a TOF secondary to denture is a challenging clinical problem that is rarely reported in the literature and no previous case reports have described the two-staged reconstruction approach that we present here.

Case presentation
We report a case of a male in his early 60s who presented to an acute general hospital with symptoms ongoing for over one year of dysphagia, recurrent chest infections and weight loss. Barium swallow and computed tomography identified an ingested dental prosthesis (denture) that had caused a TOF. He was transferred to our specialist thoracic surgery unit where an attempt to remove the foreign body endoscopically was abandoned due to firm impaction and risk of further injury. The subsequent multi-disciplinary management of this complex case required a two-staged reconstruction approach. The first procedure involved extracting the foreign body, repairing the underlying defects with tracheal resection and anastomosis, and creating an oesophageal diversion with cervical oesophagostomy. The second procedure achieved continuity of the gastrointestinal tract with gastric pull-up and pharyngo-gastric anastomosis. Following rehabilitation, the patient was discharged on oral intake alongside percutaneous jejunostomy feeding.

Conclusions
Early recognition and removal of impacted dental prosthesis is essential to prevent morbidity and mortality. Delayed diagnosis can lead to acquired TOF with associated consequences such as recurrent pulmonary infection, mediastinitis and nutritional deficit. Challenges we encountered, such as failed attempts at endoscopic retrieval and the difficult dissection of fibrotic tissue, were directly due to the delayed identification of the denture. We highlight the importance of holding a high index of clinical suspicion of foreign body ingestion in dental prosthesis wearers who present with recurrent chest infections and ongoing dysphagia. We also promote the need for a collaborative multi-disciplinary approach in the surgical management of complex cases.
Notch1 blockade by a novel, selective anti-Notch1 neutralizing antibody improves immunotherapy efficacy in melanoma by promoting an inflamed TME
Authors: de Freitas Juliano Tiburcio , Thakur Varsha , LaPorte Kathryn M. , Thakur Vijay S. , Flores Brian , Caicedo Valentina , Ajaegbu Chioma G. E. , Ingrasci Giuseppe , Lipman Zoe M. , Zhang Keman , Qiu Hong , Malek Thomas R. , Bedogni Barbara 
Published: November 2024

Abstract
Background
Immune checkpoint inhibitors (ICI) have dramatically improved the life expectancy of patients with metastatic melanoma. However, about half of the patient population still present resistance to these treatments. We have previously shown Notch1 contributes to a non-inflamed TME in melanoma that reduces the response to ICI. Here, we addressed the therapeutic effects of a novel anti-Notch1 neutralizing antibody we produced, alone and in combination with immune checkpoint inhibition in melanoma models.

Methods
Anti-Notch1 was designed to interfere with ligand binding. Mice were immunized with a peptide encompassing EGF-like repeats 11–15 of human Notch1, the minimal required region that allows ligand binding and Notch1 activation. Positive clones were expanded and tested for neutralizing capabilities. Anti-Notch1-NIC was used to determine whether anti-Notch1 was able to reduce Notch1 cleavage; while anti-SNAP23 and BCAT2 were used as downstream Notch1 and Notch2 targets, respectively. K457 human melanoma cells and the YUMM2.1 and 1.7 syngeneic mouse melanoma cells were used. Cell death after anti-Notch1 treatment was determined by trypan blue staining and compared to the effects of the gamma-secretase inhibitor DBZ. 10 mg/kg anti-Notch1 was used for in vivo tumor growth of YUMM2.1 and 1.7 cells. Tumors were measured and processed for flow cytometry using antibodies against major immune cell populations.

Results
Anti-Notch1 selectively inhibited Notch1 but not Notch2; caused significant melanoma cell death in vitro but did not affect normal melanocytes. In vivo, it delayed tumor growth without evident signs of gastro-intestinal toxicities; and importantly promoted an inflamed TME by increasing the cytotoxic CD8+ T cells while reducing the tolerogenic Tregs and MDSCs, resulting in enhanced efficacy of anti-PD-1.

Conclusions
Anti-Notch1 safely exerts anti-melanoma effects and improves immune checkpoint inhibitor efficacy. Thus, anti-Notch1 could represent a novel addition to the immunotherapy repertoire for melanoma.
Nepali oral microbiomes reflect a gradient of lifestyles from traditional to industrialized
Authors: Ryu Erica P. , Gautam Yoshina , Proctor Diana M. , Bhandari Dinesh , Tandukar Sarmila , Gupta Meera , Gautam Guru Prasad , Relman David A. , Shibl Ahmed A. , Sherchand Jeevan Bahadur , Jha Aashish R. , Davenport Emily R. 
Published: November 2024

Abstract
Background
Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called “vanishing microbiomes” potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations.

Results
Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the USA within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain sources.

Conclusion
Our findings demonstrate that by studying populations within Nepal, we can isolate an important role of lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes.
Identification of powdery mildew resistance quantitative trait loci in melon and development of resistant near-isogenic lines through marker-assisted backcrossing
Authors: Wang Chun-San , Lin Ssu-Yu , Huang Jin-Hsing , Chang Hsin-Yi , Lew Di-Kuan , Wang Yu-Hua , Hwu Kae-Kang , Huang Yung-Fen 
Published: November 2024

Abstract
Background
Melon (Cucumis melo L.), an important cucurbit crop, faces production limitations due to powdery mildew (PM). Developing resistant varieties offers a sustainable, genetics-based alternative to chemical treatments. Therefore, identifying PM resistance quantitative trait loci (QTL) and creating trait-associated markers are essential for efficient melon PM resistance improvement through marker-assisted backcrossing (MABC).

Results
Three F2 populations, A6, B2, and C4, were generated for QTL mapping of PM resistance. Major QTL were identified on chromosome 2 in A6, chromosome 5 in B2, and chromosomes 5 and 12 in C4. A series of TaqMan® assays targeting regions on chromosomes 2, 5, and 12 were developed and validated for foreground and recombinant selection, complemented by the double digest restriction-site associated DNA genotyping system to evaluate the recurrent parent genome recovery. Three MABC programs using resistant donor parents from A6 and C4 crossed with elite susceptible recurrent parents with green and orange fruit flesh were implemented. After two to three cycles of MABC, individual QTL was successfully introgressed into elite genetic backgrounds, giving six PM resistance lines in each green- and orange-fleshed background. PM inoculation on the twelve near-isogenic lines confirmed their resistance to PM.

Conclusions
We have identified major PM resistance QTL for melon on chromosomes 2, 5, and 12 and have introgressed individual QTL to elite genetic backgrounds using MABC in three and a half years. This study demonstrates the power of combining high-throughput genotyping with breeding efforts and showcases the efficiency of molecular breeding.
Dysbiosis of oral bacteria in patients with chronic kidney disease
Authors: Yasuno Tetsuhiko , Tada Kazuhiro , Takahashi Koji , Watanabe Maho , Ito Kenji , Arima Hisatomi , Masutani Kosuke 
Published: November 2024

Abstract
Background
Oral bacteria are altered in patients with diabetes, cardiovascular diseases, and cancer. However, the oral microbiome of patients with chronic kidney disease (CKD), including those receiving renal replacement therapy, remains unclear. Here, we report changes in the oral microbiome of patients with CKD.

Methods
In total, 103 individuals were recruited for this study, including 46 with stages 3–5 and 22 with stage 5D CKD, including those receiving renal replacement therapy (CKD group), and 35 with CKD stages 1–2. The oral microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.

Results
At the genus level, the periodontal pathogens Tannerella, Fusobacterium, and Capnocytophaga were more abundant in the CKD group (stages 3–5) than in the control group (linear discriminant analysis score > 3). Streptococcus, which has been shown to be involved in dental plaque formation, and Capnocytophaga were abundant in the CKD group (stage 5D). The unweighted UniFrac distance revealed a separation trend among CKD stages 1–2, 3–5, and 5D groups (stages 1–2 versus 3–5: P = 0.137. ; stages 3–5 versus 5D: P = 0.002). As the CKD stage progressed, the number of bacteria with significant differences qualitative and quantitative changes were observed in the β-diversity assessment.

Conclusions
Our findings highlight that periodontal disease bacteria increased in the CKD (stages 3–5 and 5D) group, including those receiving renal replacement therapy.
Poloxamer®s anchored with TAT enhance blood–brain barrier penetration of carbamazepine for the treatment of epilepsy: an in vivo study
Authors: Sotoudegan Farnaz , Amini Mohsen , Sharifzadeh Mohammad , Samadi Nasrin , Sotoudegan Farzaneh 
Published: November 2024

AbstractCarbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier.Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed.The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity.
Graphical Abstract
Trends and inequalities in the use of deworming medication during pregnancy in Sierra Leone, 2008–2019
Authors: Osborne Augustus , Bai-Sesay Alpha Umaru , Tommy Alieu , Bangura Camilla , Ahinkorah Bright Opoku 
Published: November 2024

Abstract
Background
Intestinal worm infections are a significant public health concern for pregnant women in low- and middle-income countries. These infections can lead to anaemia, malnutrition, and adverse pregnancy outcomes, including premature birth and low birth weight. Deworming medication during pregnancy is a safe and effective strategy to prevent these complications and improve maternal and child health. This study aims to investigate the trends and inequalities in the use of deworming medication during pregnancy among women in Sierra Leone between 2008 and 2019.

Methods
The study utilised data from the Sierra Leone Demographic Health Surveys conducted in 2008, 2013, and 2019. We used the Health Equity Assessment Toolkit developed by the World Health Organisation to calculate various measures of inequality, including difference, ratio, population attributable risk, and population attributable fraction. An inequality assessment was conducted for five stratifiers: age, economic status, level of education, place of residence, and sub-national province.

Results
The prevalence of deworming medication during pregnancy was 43.8% in 2008, 72.4% in 2013, and 83.5% in 2019 in Sierra Leone. There was a decrease in age-related inequality from a difference of 3.7% in 2008 to −0.8% in 2019. Economic-related inequality increased from a difference of −8.5% in 2008 to −8.2% in 2019. Both population attributable fraction and population attributable risk were zero in all survey years for economic status, indicating no improvement in the setting average without economic-related inequality. Inequality in education increased from a difference of -8.9% in 2008 to −8.4% in 2019 and decreased from a difference of −2.6% in 2008 to –5.5% in 2019 for place of residence. Provincial inequality decreased from a difference of 29.5% in 2008 to 11.8% in 2019. The population attributable risk for province reveals that the setting average could have been 10.5 percentage points lower in 2008, 8.2 percentage points lower in 2013, and 5.9 percentage points lower in 2019 without provincial inequality.

Conclusion
The prevalence of deworming medication use during pregnancy substantially increased from 2008 to 2019 (43.8% to 83.5%) in Sierra Leone. This suggests a positive public health trend in maternal healthcare access and education. Inequalities related to economic status and education increased slightly while age-related, place of residence and provincial inequalities decreased. This indicates an inequitable distribution of this essential healthcare intervention across these stratifiers. The government and policymakers should continue efforts to raise awareness and promote the use of deworming medication during pregnancy.
Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures
Authors: Ekong Moses B. , Bassey Okokon O. , Ebeh Deborah I. , Usukuma Godslove D. , Samuel Darlington C. , Bassey Rosemary B. , Peter Aniekan I. , Mbadugha Christopher C. , Okokon Jude E. , Akpanabiatu Monday I. 
Published: November 2024

Abstract
Background
Rauvolfia vomitoria (R. vomitoria) is a plant of economic importance due to its diverse ethnomedicinal properties, including the anticonvulsant effect. In this study, we studied the antiseizure and neuroprotective potentials of R. vomitoria extracts against pentylenetetrazol (PTZ)-induced kindling.

Methods
Twenty-five adult Swiss mice (25–30 g) were assigned to five groups (n = 5): control group, PTZ treatment group, and PTZ treatment after receiving oral R. vomitoria crude extract (100 mg/kg), R. vomitoria phenol extract (50 mg/kg) or sodium valproate (15 mg/kg) every 48 h for 28 days. Seizure scores, cognitive behavioral tests including novel object test, Y-maze test, and the elevated plus maze test, as well as brain neurochemicals and histomorphology studies, were performed.

Results
Compared with the control group, the PTZ group showed comparable body weight and durations in closed and open arms (P > 0.05), but preference for familiar objects, significant (P < 0.05) spontaneous alternation, increased monoamine oxidase activity and nitric oxide level, and Nissl chromatolysis in the temporal lobe structures including the cortex, hippocampus, and amygdala. R. vomitoria phenol extract pretreatment significantly (P < 0.05) reduced seizures, prevented adverse cognitive behaviors, decreased the nitric oxide level, and reduced the temporal lobe Nissl chromatolysis compared with the R. vomitoria crude extract pretreatment group and the sodium valproate pretreatment groups.

Conclusions
Thus, R. vomitoria phenol extract showed promising results against seizures and potential for general brain protection, suggesting that the anticonvulsant property of R. vomitoria may be attributed to its phenol constituent. More studies are needed to delineate the mechanisms of its action.
Simplified magnetic resonance index of activity score versus simple endoscopic score in Crohn's disease: prospective study
Authors: Hassan Nada Saad Mohamed Saad , Moghazy Khaled Mohamed Mourad , Salem Osama Ebada , Afifi Ahmed Hafez , Emara Doaa Mohamed , Mohamed Mohamed Masoud Radwan 
Published: November 2024

Abstract
Background
To evaluate the correlation between simplified MR index of activity (sMaRIA) score and simple endoscopic score (SES-CD) in Crohn's disease activity assessment. A prospective study was done on established Crohn's disease patients referred to our institution. Magnetic resonance enterography and colonoscopy were performed as an activity assessment protocol searching for activity signs through calculation of sMaRIA score and SES-CD score and correlation between them. One hundred patients were enrolled in the study in period from July 2021 to July 2022. Patients with isolated upper gastrointestinal Crohn's disease (n = 4) or performed surgery before completion of activity assessment protocol (n = 9) or dropout (n = 18) were excluded. Patients with any age group, with ileal or colonic or ileo-colonic Crohn's disease and completed the protocol were eligible for the study (n = 69).

Results
Sixty-nine patients with 345 bowel segments (five segments for each patient: ileum, right colon, transverse colon, left colon/sigmoid and rectum) were completely evaluated: 33 males and 36 females with mean age 29.16 ± 11.37 years. sMaRIA and SES-CD scores were calculated for each patient (global), and each bowel segment showed 97.50% sensitivity and 79.31% specificity at the level of global scores as well as significant positive correlation between the two scores at patient level/overall segments (rs = 0.816, p < 0.001), at ileal segments (rs = 0.704, p < 0.001) and colonic segments (right colon rs = 0.661, p ≤ 0.001, transverse colon rs = 0.586, p ≤ 0.001, left colon rs = 0.731, p < 0.001 and rectum rs = 0.786, p < 0.001). There were good inter-rater agreement between the two radiologists for the three parameters (wall thickness > 3 mm, mural edema and fat stranding) and moderate for mucosal ulcer detection with k value 0.666, 0.712, 0.712 and 0.565, respectively.

Conclusions
sMaRIA score is considered to be a reliable tool for Crohn's disease activity evaluation as compared to SES-CD.
Comparative study between effect of preoperative multimodal analgesia and pregabalin as unimodal analgesia in reduction of postoperative opioids consumption and postoperative pain in laparoscopic cholecystectomy
Authors: Kamal Yassmin M. , Wahsh Engy A. , Abdelwahab Hisham A. , ElBaz Walied A. , Hussein Hazem A. , Rabea Hoda M. 
Published: November 2024

Abstract
Background
Laparoscopic cholecystectomy is a popular abdominal surgery and the most common problem for patients undergoing laparoscopic cholecystectomy is the postoperative pain, and associated side effects due to opioids use for pain management and multimodal analgesia is suggested to reduce postoperative pain and need for postoperative opioids. This controlled clinical trial compares the effects of multimodal analgesia and pregabalin as unimodal analgesia on postoperative pain management, postoperative opioids consumption, and reduction of opioids accompanied adverse effects in patients undergoing laparoscopic cholecystectomy where large multicenter studies evaluating specific analgesic combinations are lacking.

Method
This comparison randomized controlled trial between multimodal analgesia approach and pregabalin as unimodal analgesia included 95 laparoscopic cholecystectomy patients that were randomly allocated to three groups using a simple randomization method where multimodal and pregabalin groups included 30 patients in each and the drugs was administered orally one hour before the incision and control group included 35 patients that did not receive any preoperative analgesia. Multimodal analgesic therapy included acetaminophen 1 g, pregabalin 150 mg and celecoxib 400 mg while pregabalin group received pregabalin 150 mg only.

Results
Multimodal group showed a significantly lower need for total opioid analgesics mean ± SD (1.33 ± 1.918) as compared to the control group mean ± SD (3.31 ± 2.784) with p-value 0.014. Pregabalin and multimodal groups showed significantly lower postoperative visual analogue scale used for pain assessment mean ± SD (3.50 ± 2.543) and mean ± SD (3.70 ± 2.231), respectively, compared to the control group mean ± SD (5.89 ± 2.857) with p-value 0.001.

Conclusion
Multimodal analgesia reduced postoperative opioids consumption more than pregabalin alone when used preoperatively in laparoscopic cholecystectomy and consequently reduced opioids associated adverse effects, but they have the same efficacy in reducing postoperative pain, so pregabalin can be used alone preoperatively in patients with contraindications for using some analgesics included in multimodal analgesia protocol. The study was registered retrospectively in clinical trials; Trial registration ID: NCT05547659.