bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexistence of craniopharyngioma and cranial fibrous dysplasia: a case series of clinicopathological study
Authors: Fan Yang-Hua , Li Zhi 
Published: March 2022

Abstract
Background
Craniopharyngioma (CP) and cranial fibrous dysplasia (CFD) are rare embryonic benign cranial diseases that most commonly present during childhood or adolescence. The coexistence of CP and CFD is extremely rare and has not yet been reported.

Methods
We retrospectively reviewed the data of five patients with concomitant CP and CFD treated at Beijing Tiantan Hospital from January 2003 to January 2021 and summarized their clinicopathological features, treatment modalities, and outcomes. We also performed a comprehensive literature review, tested the patients for characteristic GNAS gene mutations related to CFD, and tested the CP specimens for corresponding Gsα protein to explore the potential connection leading to the coexistence of CP and CFD.

Results
The cohort comprised four men and one woman (median age, 39 years). The symptoms mainly included headache, dizziness, fatigue, polyuria/polydipsia, hypogonadism, and blurred vision. CFD most commonly involved the sphenoid bone (n = 4). Four patients underwent surgery to remove the CP (one trans-sphenoidal and three transcranial resections); complete and subtotal resection were achieved in two patients, respectively. The tumor subtype was adamantinomatous in three patients and unknown in one. The common postoperative complications were panhypopituitarism, diabetes insipidus, and hypothyroidism. The mean follow-up duration was 57.2 months. Two patients required postoperative hormone replacement therapy. Three patients underwent genetic study of the tumor specimens; GNAS mutations were not detected, but these patients were positive for Gsα protein.

Conclusions
Although a definite causative relationship has not been proved, the coexistence of CP and CFD means that potential interplay or an atypical fibrous dysplasia course as uncommon manifestations of CP cannot be excluded. It is more challenging to initiate prompt diagnosis and appropriate treatment for concomitant CP and CFD than for solitary CP because of skull base deformations. Current management strategies are aimed at surgical treating the CP and regularly monitoring the CFD.
The role of inflammation in neurodegeneration: novel insights into the role of the immune system in C9orf72 HRE-mediated ALS/FTD
Authors: Masrori Pegah , Beckers Jimmy , Gossye Helena , Van Damme Philip 
Published: March 2022

AbstractNeuroinflammation is an important hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). An inflammatory reaction to neuronal injury is deemed vital for neuronal health and homeostasis. However, a continued activation of the inflammatory response can be detrimental to remaining neurons and aggravate the disease process. Apart from a disease modifying role, some evidence suggests that neuroinflammation may also contribute to the upstream cause of the disease. In this review, we will first focus on the role of neuroinflammation in the pathogenesis of chromosome 9 open reading frame 72 gene (C9orf72) hexanucleotide repeat expansions (HRE)-mediated ALS/FTD (C9-ALS/FTD). Additionally, we will discuss evidence from ex vivo and in vivo studies and finally, we briefly summarize the trials and progress of anti-inflammatory therapies.
In situ antigen modification-based target-redirected universal chimeric antigen receptor T (TRUE CAR-T) cell therapy in solid tumors
Authors: Sun Zhichen , Li Rutian , Shen Yun , Tan Siyi , Ding Naiqing , Xu Ruihan , Wang Xinyue , Wei Jia , Liu Baorui , Meng Fanyan 
Published: March 2022

AbstractBackgroundChimeric antigen receptor (CAR)-T cell therapy has demonstrated remarkable success in the treatment of hematologic malignancies, while the success has not yet been replicated in solid tumors. To some extent, the disappointing results can be attributed to the paucity and heterogeneity of target antigens in solid tumors since adequate antigens are the cornerstone for CAR-T cells to recognize and attack tumor cells.MethodsWe established a target-redirected universal CAR-T (TRUE CAR-T) cell therapeutic modality, in which exogenous antigens are loaded onto fusogenic nanoparticles to achieve in situ modification of cell membrane in solid tumors, providing targets for subsequent CAR-T cell therapy. The modification effect was evaluated by flow cytometry and confocal microscopic imaging. The in vivo metabolism and biodistribution of fusogenic antigen loaded nanoparticles (F-AgNPs) was explored using near infrared living imaging. Then F-AgNPs mediated in situ antigen modification were cooperated with corresponding CAR-T cell therapy, and its antitumor efficacy was evaluated using immune function experiments and further investigated in different tumor models.ResultsUsing F-AgNPs, exogenous antigens were selectively modified onto tumor cell membranes through membrane fusion, spread deeper into tumor tissues through intercellular lipid transfer, further activating corresponding CAR-T cells and mediating antitumor immune responses towards multiple types of tumor cells, despite of their inherent antigen profiles. The cooperative treatment of F-AgNPs and CAR-T cell therapy successfully suppressed tumor proliferation and prolonged survival in both subcutaneous and peritoneally disseminated tumor models.ConclusionThe fusogenic nanoparticle-based in situ antigen modification overcome the limitation of target antigens paucity and heterogeneity in solid tumors, improving the efficacy and broadening the applications of CAR-T cells, thus establishing a novel TRUE CAR-T cell therapeutic modality with universal application and translational potential in immunotherapies for solid tumors.
Altered pathways and targeted therapy in double hit lymphoma
Authors: Zhuang Yuxin , Che Jinxin , Wu Meijuan , Guo Yu , Xu Yongjin , Dong Xiaowu , Yang Haiyan 
Published: March 2022

AbstractHigh-grade B-cell lymphoma with translocations involvingMYCandBCL2orBCL6, usually referred to as double hit lymphoma (DHL), is an aggressive hematological malignance with distinct genetic features and poor clinical prognosis. Current standard chemoimmunotherapy fails to confer satisfying outcomes and few targeted therapeutics are available for the treatment against DHL. Recently, the delineating of the genetic landscape in tumors has provided insight into both biology and targeted therapies. Therefore, it is essential to understand the altered signaling pathways of DHL to develop treatment strategies with better clinical benefits. Herein, we summarized the genetic alterations in the two DHL subtypes (DHL-BCL2 and DHL-BCL6). We further elucidate their implications on cellular processes, including anti-apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.
Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP)—a single center, open-label, three-arm, randomized, controlled intervention trial
Authors: Sekandarzad Asieb , Weber Enya , Prager Eric Peter , Graf Erika , Bettinger Dominik , Wengenmayer Tobias , Supady Alexander 
Published: March 2022

Abstract
Background
Liver cirrhosis is a major healthcare problem and the mortality rate is high. During recent years, systemic inflammation has been recognized as a major driver of hepatic decompensation and progression of liver cirrhosis to acute-on-chronic liver failure (ACLF). The aim of the CYTOHEP study is to assess the impact of extracorporeal hemoadsorption with the CytoSorb adsorber on serum bilirubin concentrations, humoral inflammation parameters, liver function parameters, and patient survival in patients with ACLF and acute kidney injury (AKI).

Methods
The CYTOHEP study is a prospective, single-center, open-label, three-arm, randomized, controlled intervention trial. Patients with ACLF and AKI stage 3 according to Kidney Disease: Improving Global Outcome (KDIGO) criteria will be randomized into three groups to be treated with (1) continuous renal replacement therapy (CRRT) and CytoSorb, (2) CRRT without CytoSorb, and (3) without both, CRRT and CytoSorb. In the hemoadsorption group, CytoSorb will be used for 72 h. The other groups receive standard of care with early or late initiation of CRRT, respectively. Primary endpoint of the study is serum bilirubin concentration after 72 h, important secondary endpoints are 30-day survival and a panel of inflammatory parameters.

Discussion
The CYTOHEP study is designed to evaluate the benefit of extracorporeal hemoadsorption in patients with ACLF. The results of this study will help to better understand the potential role of hemoadsorption for the treatment of ACLF and its impact on bilirubin levels, inflammatory parameters, and survival.

Trial registration
ClinicalTrials.gov NCT05019352. Registered on August 24, 2021. Deutsches Register Klinischer Studien (DRKS) DRKS00026082.
Postpartum haemorrhage in anaemic women: assessing outcome measures for clinical trials
Authors: Brenner Amy , Roberts Ian , Balogun Eni , Bello Folasade Adenike , Chaudhri Rizwana , Fleming Charlotte , Javaid Kiran , Kayani Aasia , Lubeya Mwansa Ketty , Mansukhani Raoul , Olayemi Oladapo , Prowse Danielle , Vwalika Bellington , Shakur-Still Haleema 
Published: March 2022

Abstract
Background
Postpartum haemorrhage (PPH) is a leading cause of maternal mortality worldwide. Maternal anaemia greatly increases the risk of PPH, and over a third of all pregnant women are anaemic. Because anaemia reduces the oxygen-carrying capacity of the blood, anaemic women cannot tolerate the same volume of blood loss as healthy women. Yet the same blood loss threshold is used to define PPH in all women. The lack of an established PPH definition in anaemic women means the most appropriate outcome measures for use in clinical trials are open to question. We used data from the WOMAN-2 trial to examine different definitions of PPH in anaemic women and consider their appropriateness as clinical trial outcome measures.

Main body
The WOMAN-2 trial is assessing tranexamic acid (TXA) for PPH prevention in women with moderate or severe anaemia at baseline. To obtain an accurate, precise estimate of the treatment effect, outcome measures should be highly specific and reasonably sensitive. Some outcome misclassification is inevitable. Low sensitivity reduces precision, but low specificity biases the effect estimate towards the null. Outcomes should also be related to how patients feel, function, or survive. The primary outcome in the WOMAN-2 trial, a ‘clinical diagnosis of PPH’, is defined as estimated blood loss > 500 ml or any blood loss within 24 h sufficient to compromise haemodynamic stability. To explore the utility of several PPH outcome measures, we analysed blinded data from 4521 participants. For each outcome, we assessed its: (1) frequency, (2) specificity for significant bleeding defined as shock index ≥1.0 and (3) association with fatigue (modified fatigue symptom inventory [MFSI]), physical endurance (six-minute walk test) and breathlessness. A clinical diagnosis of PPH was sufficiently frequent (7%), highly specific for clinical signs of early shock (95% specificity for shock index ≥1) and associated with worse maternal functioning after childbirth.

Conclusion
Outcome measures in clinical trials of interventions for PPH prevention should facilitate valid and precise estimation of the treatment effect and be important to women. A clinical diagnosis of PPH appears to meet these criteria, making it an appropriate primary outcome for the WOMAN-2 trial.

Trial registration
ClinicalTrials.gov NCT03475342, registered on 23 March 2018; ISRCTN62396133, registered on 7 December 2017; Pan African Clinical Trial Registry PACTR201909735842379, registered on 18 September 2019.
The influence of TIVA or inhalation anesthesia with or without intravenous lidocaine on postoperative outcome in colorectal cancer surgery: a study protocol for a prospective clinical study
Authors: Alexa Alexandru L. , Tat Tiberiu F. , Ionescu Daniela 
Published: March 2022

Abstract
Background
Anesthetic agents are mandatory in colorectal cancer patients undergoing surgery. Studies published so far have shown that anesthetic drugs and intervention may have different impacts on patient’s outcome. Among these drugs, propofol and, more recently, local anesthetics have been mostly targeted.

Methods/design
This study will be a prospective randomized control trial aiming to include 400 patients scheduled for curative colorectal surgery. Patients will be randomized to have general anesthesia with propofol or with sevoflurane. Each study group will be further divided into 2 subgroups of patients, of which one will receive intravenous lidocaine perioperatively. The primary outcome is to compare the incidence of cancer recurrence and survival after propofol versus sevoflurane anesthesia added or not intravenous lidocaine. Secondary outcomes will include the severity of postoperative pain, resumption of bowel function, morphine consumption, length of hospital stay, postoperative chronic pain, and rate of postoperative complications.

Discussion
To our knowledge, this is the first randomized control trial registered on ClinicalTrials.gov designed to compare the effects of two different anesthetic techniques added perioperative intravenous lidocaine infusion on long-term outcomes exclusively in colorectal cancer patients undergoing surgery. The study will bring more accurate data on the effect of propofol-TIVA and perioperative iv lidocaine on the incidence of recurrences after intended curative colorectal surgery.

Trial registration
Clinical Trial Registration NCT02786329. Registered on 1 June 2016
Efficacy of a new membrane obturator prosthesis in terms of speech, swallowing, and the quality of life of patients with acquired soft palate defects: study protocol of the VELOMEMBRANE randomized crossover trial
Authors: Naveau Adrien , Kret Marion , Plaire Valérie , Delorme Olivier , Marchi Sébastien , de Bataille Caroline , Destruhaut Florent , Arrive Elise , Bou Christophe 
Published: March 2022

Abstract
Background
Soft palate defects created during oral cancer surgery may prevent complete palatal closure and trigger palatopharyngeal insufficiency. One current treatment employs a rigid obturator prosthesis; an extension of acrylic resin at the level of the hard palate ensures surface contact with the remaining musculature. Unfortunately, airflow escape often causes hypernasality, compromises speech intelligibility, and creates swallowing problems (including leakage of food and fluid into the nasal airway). We plan to test a new removable denture featuring a thick dental dam that serves as a membrane obturator. The principal objective of the clinical trial is a comparison of speech handicap levels after 1 month in patients with acquired velar insufficiencies who wear either the new device or a conventional, rigid obturator. The secondary objectives are between-device comparisons of the swallowing handicaps and the health-related qualities of life.

Methods
The VELOMEMBRANE trial is a superiority, open-labeled, two-way, random crossover clinical trial. Adult patients exhibiting velar or palatovelar substance loss after tumor excision and who are indicated for rigid obturator-mediated prosthetic rehabilitation will be recruited in two teaching hospitals in France. Fourteen participants will be randomly allocated to wear both prostheses for 1-month periods in either order. The new membrane obturator is a removable resin prosthesis incorporating a rigid extension that holds a dental dam to restore the soft palate. The primary outcome will be the extent of phonation-related disability (the overall score on the Voice Handicap Index [VHI]). The secondary outcomes will be the Deglutition Handicap Index and health-related quality of life scores of the European Organization for Research and Treatment of Cancer (EORTC).

Discussion
High-quality evidence will be provided to document the utility of a new medical device that may greatly improve the management and quality of life of patients with acquired velar insufficiency.

Trial registration
ClinicalTrials.govNCT04009811. Registered on 4 July 2019
Aedes albopictus abundance and phenology along an altitudinal gradient in Lazio region (central Italy)
Authors: Romiti Federico , Casini Riccardo , Magliano Adele , Ermenegildi Arianna , De Liberato Claudio 
Published: March 2022

AbstractBackgroundThe Asian tiger mosquitoAedes albopictus(Skuse 1894), which is native to Southeast Asia, is among the top 100 invasive species worldwide and one of the most troubling vector species. It has become established in more than 20 European countries. Since its arrival in Italy in the 1990s, the species has colonized all the regions of the country, up to an altitude of 600 m. Nevertheless, no thorough investigation has ever been performed to confirm or extend its elevation limit (EL) in Italy.MethodsTo define the EL ofAe. albopictusand analyse its phenology along an altitudinal gradient, we carried out an investigation by means of ovitraps placed in Lazio region, central Italy. Sampling was performed on a weekly basis in 13 villages within five 200-m altitudinal ranges [0–1000 m above sea level (asl)], with the addition of higher localities to the species range whenever the species was recorded in the highest range.ResultsAedes albopictushas colonized sites well beyond its known EL, with established populations at 900 m asl and positive ovitraps recorded at 1193 m asl. The relationship between egg abundance and elevation was described by an exponential decay regression, which predicted an EL for oviposition at 1015 m asl. In the active season, egg-laying started earlier at low altitude and ended earlier within the highest altitudinal range.Aedes albopictusabundance and activity period (number of days active) decreased, respectively, by 95% and 34% from the lowest to the highest altitudinal range.ConclusionsUsing data from the present study, the altitudinal limit ofAe. albopictusin central Italy was updated from 600 to 900 m asl. In addition, established populations were predicted to exist up to 1015 m asl. Considering that up to 99.5% of Lazio region’s inhabitants could potentially be affected byAedes-borne virus outbreaks, the surveillance area forAe. albopictusshould be expanded accordingly. However, our results also indicate thatAe. albopictussurveillance programs need to be revised in order to harmonize the resources earmarked for these with the altitudinal changes in the phenology of this species.Graphical abstract
Management of anterior thigh injuries in soccer players: practical guide
Authors: Lempainen Lasse , Mechó Sandra , Valle Xavier , Mazzoni Stefano , Villalon Jose , Freschi Marco , Stefanini Luca , García-Romero-Pérez Alvaro , Burova Maria , Pleshkov Pavel , Pruna Ricard , Pasta Giulio , Kosola Jussi 
Published: March 2022

AbstractMost of the anterior thigh injuries are contusions or strains, however, some of these injuries can be career ending. Early diagnosis and correct treatment are key to successful outcome. Analyzing injury mechanism and adding both clinical and imaging findings, clinicians can make the right treatment decisions already often in the acute phase of the injury. Low grade contusions and muscle strains are treated well with planned rehabilitation, but complete tendon injuries or avulsions can require operative treatment. Also, neglected minor injuries could lead to chronic disabilities and time lost from play. Typical clinical presentation of anterior thigh injury is swelling and pain during hip flexion or knee extension. In more severe cases a clear gap can be palpated. Imaging methods used are ultrasound and magnetic resonance imaging (MRI) which are helpful for clinicians to determine more exact the extent of injury. MRI can identify possible tendon retractions which may need surgery. Clinicians should also be aware of other traumatic lesions affecting anterior thigh area such as myositis ossificans formation. Optimal treatment should be coordinated including acute phase treatment with rest, ice, and compression together with designed return-to-play protocol. The anatomical structure involved lines the treatment pathway. This narrative review describes these more common reasons for outpatient clinical visits for anterior thigh pain and injuries among soccer players.
Breast carcinoma metastasis to the cheek: a case report
Authors: Miyazaki Ryo , Kimoto Natsuko , Okamoto Satsuki , Tsuji Asami , Nishigushi Yusuke , Miyahara Tomoya , Takahashi Nozomu , Omata Tetsuji 
Published: March 2022

Abstract
Background
Breast carcinoma is a common tumor in women, but it rarely metastasizes to the oral region. Furthermore, metastases to the oral region occur mainly to the maxillary and mandibular bone and rarely to soft tissue.

Case presentation
We describe a case of breast cancer metastasis to the buccal area. Examination of the right buccal mass of a 66-year-old Japanese woman was suggestive of breast cancer metastasis, and a breast lump was detected. Since receiving hormone-based treatment, the patient has survived more than 5 years and is now in remission.

Conclusions
An oral metastatic lesion may be the first sign of breast carcinoma; oral surgeons should be aware of this possibility.
BRD4 inhibitor GNE987 exerts anti-cancer effects by targeting super-enhancers in neuroblastoma
Authors: Chen Yan-Ling , Li Xiao-Lu , Li Gen , Tao Yan-Fang , Zhuo Ran , Cao Hai-Bo , Jiao Wan-yan , Li Zhi-Heng , Zhu Zhen-Hong , Fang Fang , Xie Yi , Liao Xin-Mei , Wu Di , Wang Hai-Rong , Yu Juan-Juan , Jia Si-Qi , Yang Yang , Feng Chen-Xi , Yang Peng-Cheng , Fei Xiao-Dong , Wang Jian-Wei , Xu Yun-Yun , Qian Guang-Hui , Zhang Zi-Mu , Pan Jian 
Published: March 2022

AbstractBackgroundNeuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play a critical role in the tumorigenesis and development of NB via regulating a wide range of oncogenes Thus, the synthesis and identification of chemical inhibitors specifically targeting SEs are of great urgency for the clinical therapy of NB. This study aimed to characterize the activity of the SEs inhibitor GNE987, which targets BRD4, in NB.ResultsIn this study, we found that nanomolar concentrations of GNE987 markedly diminished NB cell proliferation and survival via degrading BRD4. Meanwhile, GNE987 significantly induced NB cell apoptosis and cell cycle arrest. Consistent with in vitro results, GNE987 administration (0.25 mg/kg) markedly decreased the tumor size in the xenograft model, with less toxicity, and induced similar BRD4 protein degradation to that observed in vitro. Mechanically, GNE987 led to significant downregulation of hallmark genes associated withMYCand the global disruption of the SEs landscape in NB cells. Moreover, a novel candidate oncogenic transcript,FAM163A, was identified through analysis of the RNA-seq and ChIP-seq data.FAM163Ais abnormally transcribed by SEs, playing an important role in NB occurrence and development.ConclusionGNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB.