bluuebunny/crossref_metadata_2025 huggingface dataset:
Second opinions for spinal surgery: a scoping review
Authors: Ferreira Giovanni E. , Zadro Joshua , Liu Chang , Harris Ian A. , Maher Chris G.
Published: March 2022

Background

Second opinions have the goal of clarifying uncertainties around diagnosis or management, particularly when healthcare decisions are complex, unpleasant, and carry considerable risks. Second opinions might be particularly useful for people recommended surgery for their back pain as surgery has at best a limited role in the management of back pain.

Methods

We conducted a scoping review. Two independent researchers screened PubMed, EMBASE, Cochrane CENTRAL and CINAHL from inception to May 6th, 2021. Studies of any design published in any language were eligible provided they described a second opinion intervention for people with spinal pain (low back or neck pain with or without radicular pain) either considering surgery or to whom surgery had been recommended. We assessed the methodological quality with the Downs & Black scale. Outcomes were: i) characteristics of second opinion services for people considering or who have been recommended spinal surgery, ii) agreement between first and second opinions in terms of diagnoses, need for surgery and type of surgery, iii) whether they reduce surgery and improve patient outcomes; and iv) the costs and healthcare use associated with these services. Outcomes were presented descriptively.

Results

We screened 6341 records, read 27 full-texts, and included 12 studies (all observational; 11 had poor methodological quality; one had fair). Studies described patient, doctor, and insurance-initiated second opinion services. Diagnostic agreement between first and second opinions varied from 53 to 96%. Agreement for need for surgery between first and second opinions ranged from 0 to 83%. Second opinion services may reduce surgery rates in the short-term, but it is unclear whether these reductions are sustained in the long-term or if patients only delay surgery. Second opinion services may reduce costs and healthcare use (e.g. imaging), but might increase others (e.g. injections).

Conclusions

Second opinion services typically recommend less surgical treatments compared to first opinions and may reduce surgery rates in the short-term, but it is unclear whether these reductions are sustained in the long-term or if patients only delay surgery. There is a need for high-quality randomised trials to determine the value of second opinion services for reducing spinal surgery.
High pericoronary adipose tissue attenuation on computed tomography angiography predicts cardiovascular events in patients with type 2 diabetes mellitus: post-hoc analysis from a prospective cohort study
Authors: Ichikawa Keishi , Miyoshi Toru , Osawa Kazuhiro , Nakashima Mitsutaka , Miki Takashi , Nishihara Takahiro , Toda Hironobu , Yoshida Masatoki , Ito Hiroshi
Published: March 2022

Background

Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a non-invasive biomarker for pericoronary inflammation. We aimed to investigate the prognostic value of PCAT attenuation in patients with type 2 diabetes mellitus (T2DM).

Methods

We included 333 T2DM patients (mean age, 66 years; male patients, 211; mean body mass index, 25 kg/m2) who underwent clinically indicated coronary CTA and examined their CT findings, coronary artery calcium score, pericardial fat volume, stenosis (> 50% luminal narrowing), high-risk plaque features of low-attenuation plaque and/or positive remodelling and/or spotty calcification, and PCAT attenuation. We assessed PCAT attenuation in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery (RCA). Cardiovascular events were defined as cardiac death, hospitalisation for acute coronary syndrome, late coronary revascularisation, and hospitalisation for heart failure.

Results

During a median follow-up of 4.0 years, we observed 31 cardiovascular events. LAD-PCAT attenuation was significantly higher in patients with cardiovascular events than in those without (− 68.5 ± 6.5 HU vs − 70.8 ± 6.1 HU, p = 0.045), whereas RCA-PCAT attenuation was not (p = 0.089). High LAD-PCAT attenuation (> − 70.7 HU; median value) was significantly associated with cardiovascular events in a model that included adverse CTA findings, such as significant stenosis and/or high-risk plaque (hazard ratio; 2.69, 95% confidence interval; 1.17–0.20, p = 0.020). After adding LAD-PCAT attenuation to the adverse CTA findings, the C-statistic and global chi-square values increased significantly from 0.65 to 0.70 (p = 0.037) and 10.9–15.0 (p = 0.043), respectively.

Conclusions

In T2DM patients undergoing clinically indicated coronary CTA, high LAD-PCAT attenuation could significantly predict cardiovascular events. This suggests that assessing LAD-PCAT attenuation can help physicians identify high-risk T2DM patients.
Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing
Authors: Dimitri Alexander , Herbst Friederike , Fraietta Joseph A.
Published: March 2022

Chimeric Antigen Receptor (CAR) T-cells represent a breakthrough in personalized cancer therapy. In this strategy, synthetic receptors comprised of antigen recognition, signaling, and costimulatory domains are used to reprogram T-cells to target tumor cells for destruction. Despite the success of this approach in refractory B-cell malignancies, optimal potency of CAR T-cell therapy for many other cancers, particularly solid tumors, has not been achieved. Factors such as T-cell exhaustion, lack of CAR T-cell persistence, cytokine-related toxicities, and bottlenecks in the manufacturing of autologous products have hampered the safety, effectiveness, and availability of this approach. With the ease and accessibility of CRISPR-Cas9-based gene editing, it is possible to address many of these limitations. Accordingly, current research efforts focus on precision engineering of CAR T-cells with conventional CRISPR-Cas9 systems or novel editors that can install desired genetic changes with or without introduction of a double-stranded break (DSB) into the genome. These tools and strategies can be directly applied to targeting negative regulators of T-cell function, directing therapeutic transgenes to specific genomic loci, and generating reproducibly safe and potent allogeneic universal CAR T-cell products for on-demand cancer immunotherapy. This review evaluates several of the ongoing and future directions of combining next-generation CRISPR-Cas9 gene editing with synthetic biology to optimize CAR T-cell therapy for future clinical trials toward the establishment of a new cancer treatment paradigm.
Using experience to create evidence: a mixed methods process evaluation of the new free family planning policy in Burkina Faso
Authors: Browne Lalique , Cooper Sarah , Tiendrebeogo Cheick , Bicaba Frank , Bila Alice , Bicaba Abel , Druetz Thomas
Published: March 2022

Background

In 2019, Burkina Faso was one of the first countries in Sub-Saharan Africa to introduce a free family planning (FP) policy. This process evaluation aims to identify obstacles and facilitators to its implementation, examine its coverage in the targeted population after six months, and investigate its influence on the perceived quality of FP services.

Methods

This process evaluation was conducted from November 2019 through March 2020 in the two regions of Burkina Faso where the new policy was introduced as a pilot. Mixed methods were used with a convergent design. Semi-directed interviews were conducted with the Ministry of Health (n = 3), healthcare workers (n = 10), and women aged 15–49 years (n = 10). Surveys were also administered to the female members of 696 households randomly selected from four health districts (n = 901).

Results

Implementation obstacles include insufficient communication, shortages of consumables and contraceptives, and delays in reimbursement from the government. The main facilitators were previous experience with free healthcare policies, good acceptability in the population, and support from local associations. Six months after its introduction, only 50% of the surveyed participants knew about the free FP policy. Higher education level, being sexually active or in a relationship, having recently seen a healthcare professional, and possession of a radio significantly increased the odds of knowing. Of the participants, 39% continued paying for FP services despite the new policy, mainly because of stock shortages forcing them to buy their contraceptive products elsewhere. Increased waiting time and shorter consultations were also reported.

Conclusion

Six months after its introduction, the free FP policy still has gaps in its implementation, as women continue to spend money for FP services and have little knowledge of the policy, particularly in the Cascades region. While its use is reportedly increasing, addressing implementation issues could further improve women’s access to contraception.
Molecular characterization of enterovirus detected in cerebrospinal fluid and wastewater samples in Monastir, Tunisia, 2014–2017
Authors: Rmadi Yosra , Elargoubi Aida , González-Sanz Rubén , Mastouri Maha , Cabrerizo Maria , Aouni Mahjoub
Published: March 2022

Background

Enteroviruses (EVs) are considered the main causative agents responsible for aseptic meningitis worldwide. This study was conducted in the Monastir region of Tunisia in order to know the prevalence of EV infections in children with meningitis symptoms. Detected EV types were compared to those identified in wastewater samples.

Methods

Two hundred CSF samples collected from hospitalized patients suspected of having aseptic meningitis for an EV infection between May 2014 and May 2017 and 80 wastewater samples collected in the same time-period were analyzed. EV detection and genotyping were performed using PCR methods followed by sequencing. Phylogenetic analyses in the 3′-VP1 region were also carried-out.

Results

EVs were detected in 12% (24/200) CSF and in 35% (28/80) wastewater samples. EV genotyping was reached in 50% (12/24) CSF-positive samples and in 64% (18/28) sewage. Most frequent types detected in CSF were CVB3, E-30 and E-9 (25% each). In wastewater samples, the same EVs were identified, but also other types non-detected in CSF samples, such as E-17,CVA9 and CVB1 from EV species B, and EV-A71 and CVA8 from EV-A, suggesting their likely lower pathogenicity. Phylogenetic analysis showed that within the same type, different strains circulate in Tunisia. For some of the EV types such as E-9, E-11 or CVB3, the same strains were detected in CSF and wastewater samples.

Conclusions

Epidemiological studies are important for the surveillance of the EV infections and to better understand the emergence of certain types and variants.
Human papillomavirus prevalence and genotype distribution landscapes in Shannan City, Tibet Tibetan Autonomous Region, China
Authors: Feng Dilu , Wei Sitian , Chen Jun , Yu Zhicheng , Lhamo Yeshe , Wang Hongbo , Zhu Xiaowu
Published: March 2022

Background

Data regarding human papillomavirus (HPV) prevalence and genotype distribution are limited in Shannan City, Tibet Tibetan Autonomous Region, China. The purpose of this study is to provide reliable data for guiding women in Shannan City in cervical cancer screening and HPV vaccine innoculation.

Methods

HPV testing was performed on women aged 16–109 years (mean age 44.03 ± 9.25 years) from Shannan City in 2019 and 2020, which was implemented technically by gynecological examination, vaginal discharge smear microscopy, cytology, and HPV detection. The overall prevalence, age-specific prevalence, and genotype distribution were analyzed.

Results

A total of 48,126 women received HPV testing, of which 3929 were detected human papillomavirus. The HPV-positive rate was 8.16% (3929/48,126), and the highest prevalence was in the ≤ 25-year-old age group (12.68%). After the age of 25, the prevalence rate decreased rapidly, and then slowly increased from 7.49% in the 46–55 age group to 9.82% in the ≥ 66 age group, showing a “U-shaped” pattern. The positive prevalence of HPV 16 or 18-only was 1.43%, that of other HPV genotypes except HPV 16 or 18 was 6.39%, and mixed HPV infections including HPV 16 or 18 was 0.34%.

Conclusions

The HPV infection rate in Shannan city is rather low, and the age-specific prevalence of HPV infection presents a “U” curve, suggesting the importance of screening among younger women and the necessity of detection among older women.
Traditional knowledge of edible plants used as flavoring for fish-grilling in Southeast Guizhou, China
Authors: He Jianwu , Peng Liping , Li Wei , Luo Jin , Li Qiang , Zeng Hanyong , Ali Maroof , Long Chunlin
Published: March 2022

Background

The local Dong people in Qiandongnan Prefecture, Guizhou Province, China, with rich biocultural diversity, have developed the traditional rice-duckweed-fish-duck agroecosystem (RDFDA) to support biodiversity conservation and to meet food and cultural needs. However, there is still not much research on traditional ecological knowledge (TEK) in this area. In particular, there is a lack of traditional knowledge of edible plants used by the Dong people as flavoring to grill fish (Cyprinus carpio) collected from RDFDA, which is extremely valuable in their traditional culture. The study focused on documenting plant species used in grilling fish and analyzing the status of its TEK.

Methods

Twenty-one sampling points of three Dong minority villages in Qiandongnan were selected for the research. The local TEK associated with plant resources for fish-grilling was recorded through free listing and semi-structured interviews. Fidelity level (FL) and ethnoecological importance value (EIV) indicators were designed to determine the socioeconomic influence of TEK. The non-metric multidimensional scaling (NMDS) method was used to evaluate the differentiation of edible plant species distribution in dissimilar accessibility types.

Results

A total of 430 people were interviewed about grilled fish, of whom 75% were men and 85% were farmers. Thirty-four edible plants were documented for fish-grilling in three Dong villages. They belong to 16 plant families, such as Apiaceae, and Asteraceae. The life forms included herbaceous (76%), shrubs (18%) and trees (6%). Leaves are the most commonly used part of for grilling fish, followed by aerial parts, and whole plants. Among these edible plants, Allium hookeri, A. macrostemon and Houttuynia cordata with the highest fidelity level (100%) were cited as edible plants for grilling fish by all informants. The NMDS showed different accessibility types of collection sites, with different importance values. Paddy rice field edge (2.03) has the highest value, followed by forest-farming ecotone (1.74), streamsides (1.71) and woodland (0.48).

Conclusion

The purpose of this study was to investigate the traditional knowledge of edible plant materials used by the Dong people for grilling fish. The results demonstrate the strong connection between local people, the bio-environment and agroecosystem services. The survey and comparative analysis revealed that plant species with high FL values may be potential sources of natural flavors.
A cationic lipid mediated CRISPR/Cas9 technique for the production of stable genome edited citrus plants
Authors: Mahmoud Lamiaa M. , Kaur Prabhjot , Stanton Daniel , Grosser Jude W. , Dutt Manjul
Published: March 2022

Background

The genetic engineering of crops has enhanced productivity in the face of climate change and a growing global population by conferring desirable genetic traits, including the enhancement of biotic and abiotic stress tolerance, to improve agriculture. The clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) system has been found to be a promising technology for genomic editing. Protoplasts are often utilized for the development of genetically modified plants through in vitro integration of a recombinant DNA fragment into the plant genome. We targeted the citrus Nonexpressor of Pathogenesis-Related 3 (CsNPR3) gene, a negative regulator of systemic acquired resistance (SAR) that governs the proteasome-mediated degradation of NPR1 and developed a genome editing technique targeting citrus protoplast DNA to produce stable genome-edited citrus plants.

Results

Here, we determined the best cationic lipid nanoparticles to deliver donor DNA and described a protocol using Lipofectamine™ LTX Reagent with PLUS Reagent to mediate DNA delivery into citrus protoplasts. A Cas9 construct containing a gRNA targeting the CsNPR3 gene was transfected into citrus protoplasts using the cationic lipid transfection agent Lipofectamine with or without polyethylene glycol (PEG, MW 6000). The optimal transfection efficiency for the encapsulation was 30% in Lipofectamine, 51% in Lipofectamine with PEG, and 2% with PEG only. Additionally, plasmid encapsulation in Lipofectamine resulted in the highest cell viability percentage (45%) compared with PEG. Nine edited plants were obtained and identified based on the T7EI assay and Sanger sequencing. The developed edited lines exhibited downregulation of CsNPR3 expression and upregulation of CsPR1.

Conclusions

Our results demonstrate that utilization of the cationic lipid-based transfection agent Lipofectamine is a viable option for the successful delivery of donor DNA and subsequent successful genome editing in citrus.
Navigating intersecting public health crises: a qualitative study of people with opioid use disorders' experiences during the COVID-19 pandemic
Authors: Watson Dennis P. , Staton Monte D. , Grella Christine E. , Scott Christy K. , Dennis Michael L.
Published: March 2022

Background

The decades-long opioid epidemic and the more recent COVID-19 pandemic are two interacting events with significant public health impacts for people with opioid use disorder (OUD). Most published studies regarding the intersection of these two public health crises have focused on community, state, or national trends using pre-existing data. There is a need for complementary qualitative research aimed at identifying how people with opioid use disorder (OUD) are understanding, experiencing, and navigating this unprecedented time. The current study examines understandings and experiences of people with OUD while they have navigated these crises.

Methods

The study was guided by a pragmatic lens. We conducted brief semi-structured qualitative interviews with 25 individuals in Chicago, the majority of which had received methadone treatment during the pandemic. Thematic inductive analysis was guided by primary interview questions.

Results

The sample represents a high-risk group, being composed mostly of older non-Hispanic African American males and having considerable socioeconomic barriers. Themes demonstrate how individuals are keeping safe despite limited knowledge of COVID-19, how the pandemic has increased treatment motivation for some, how adaptations impacted treatment and recovery supports, how the availability social support had been reduced, and difficulties individuals had keeping or obtaining financial support.

Conclusions

The findings can be useful for informing future public health response to ensure appropriate treatment access and supports are available. In particular are the need for treatment providers to ensure people with OUD receive appropriate and understandable health crisis-related information and ensuring funds are appropriately allocated to address mental health impacts of social isolation. Finally, there is a need for appropriate financial and infrastructure supports to ensure health and treatment access disparities are not exacerbated for those in greatest need.
Impairment characteristics of static balance and plantar load distribution of patients undergoing tibial cortex transverse distraction for diabetic foot ulcers
Authors: Fan Zhi-Qiang , Liu De-Wu
Published: March 2022

Objective

Tibial cortex transverse distraction (TCTD) has been recently reported for the treatment of diabetic foot ulcers. Herein, we explored the characteristics of the impairments in static balance and plantar load distribution in patients.

Methods

We performed a retrospective study of 21 patients with diabetic foot ulcers who underwent TCTD, who were regularly followed up for > 1 year after surgery, and 20 healthy individuals (control group). A pressure platform was used to assess the standing balance functions of the lower extremities and the plantar load distribution.

Results

One patient underwent amputation because of severe infection. In patient group, center of pressure (COP) ellipse sway area, COP path length and angleθwere all larger, compared with those of control group (250.15 ± 98.36 mm2vs. 135.67 ± 53.21 mm2, 145.15 ± 67.43 mm vs. 78.47 ± 34.15 mm, 39.75 ± 17.61° vs. 22.17 ± 14.15°), with statistically significant differences (P < 0.01). The average plantar load and backfoot load of the unaffected side was significantly larger than that of the affected side (58.4 ± 5.5% vs. 41.6 ± 5.5%, 45.3 ± 6.4% vs. 36.5 ± 5.6%), but they were similar for the two feet of members of the control group.

Conclusions

Although TCTD may represent an appropriate method for the treatment of diabetic foot ulcers, postoperative impairments in static balance and plantar load distribution remain in the long term. These potential long-term problems should be taken into account in further rehabilitation planning.

Type of study/level of evidence: Therapeutic III.
Risk factors for lymph node metastasis of soft tissue sarcomas of the head, neck, and extremities, and the clinical significance of negative lymph node dissection
Authors: Liu Qi-Kun , Yu Xiao-Jun , Wang Ying-Guang , Lu Rui , Wang Shan-Xi , Xu Hao-Ran , Kang Hao
Published: March 2022

Background

This study sought to define the risk factors for lymph node metastasis (LNM) of soft tissue sarcomas (STS) of the head, neck, and extremities, and the clinical significance of negative lymph node dissection (NLND).

Methods

STS patient data in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2015 were extracted and pooled. Logistics regression analysis was used to identify risk factors for LNM, Cox proportional hazards and Fine–Grey’s models were used for survival analysis, and Propensity score matching analysis (PSM) was used to assess the impact of NLND on patient prognosis.

Results

A total of 3276 patients were enrolled in the study, of whom 283 (8.6%) developed LNM. Rhabdomyosarcoma had the highest rate of LNM (25.3%), followed by clear cell sarcoma (16.8%) and epithelioid sarcoma (12.4%), while leiomyosarcoma had the lowest rate of LNM (1.3%). Sex, tumor size, grade, histology, and site were significantly associated with LNM. For specific histologic subtypes of STS, NLND significantly improves overall survival (HR: 0.718, 95%CI 0.535–0.962; P = 0.026) and cancer-specific survival (HR: 0.699, 95%CI 0.506–0.967; P = 0.031) and reduces cancer-specific mortality (Gray’s test, P = 0.017). However, NLND did not improve overall survival (P = 0.46) or reduce cancer-specific mortality (Gray’s test, P = 0.772) of patients with leiomyosarcoma.

Conclusions

Histology is an independent risk factor for LNM in STS of the head, neck, and extremities. Prophylactic NLND treatment was necessary and had a clinical benefit for patients with STS who were at high risk for LNM but had no significant impact on the prognosis of patients with leiomyosarcoma.
Coexistence of craniopharyngioma and cranial fibrous dysplasia: a case series of clinicopathological study
Authors: Fan Yang-Hua , Li Zhi
Published: March 2022

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

Neuroinflammation 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

Background

Chimeric 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.

Methods

We 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.

Results

Using 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.

Conclusion

The 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

High-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

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

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

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

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

Background

The 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.

Methods

To 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.

Results

Aedes 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.

Conclusions

Using 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

Most 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

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

Background

Neuroblastoma (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.

Results

In 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.

Conclusion

GNE987 destroyed the abnormal transcriptional regulation of oncogenes in NB by downregulating BRD4, which could be a potential therapeutic candidate for NB.