bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics and outcomes of patients with primary abdominopelvic aggressive angiomyxoma: a retrospective review of 12 consecutive cases from a sarcoma referral center
Authors: Li Wenjie , Chen Jun , Zhang Enlong , Chen Weida , Hu Yuru , Miao Chengli , Luo Chenghua 
Published: April 2023

Abstract
Background
Aggressive angiomyxoma (AAM) is a rare mesenchymal tumor that mostly arises from the pelvic and perineal soft tissues. Few studies reported its characteristics and outcomes previously due to its rarity and challenges of treatments. This study aimed to investigate the clinical characteristics as well as surgical and short-term survival outcomes of primary abdominopelvic AAM.

Methods
Medical records of patients who were admitted to surgery with pathological confirmation of primary abdominopelvic AAM at Peking University International Hospital from January 2016 through December 2021 were retrospectively retrieved from our retroperitoneal tumor database. Demographics, operative outcomes and pathological findings were collected. Patients received followed-up routinely after the surgery. Survival probabilities were calculated and determined through Kaplan–Meier analysis.

Results
A total of 12 consecutive patients (male/female 4:8) were included in this study. The median age was 45 years old. The clinical presentation varied among individuals, consisting of 2 abdominal discomforts, 4 constipations, 1 lumbago, 1 prolonged menstruation, and 1 buttock swelling. R0/R1 resection was achieved in 100% of patients. Postoperatively, 50% of patients developed various complications including 3 fistulas and 3 wound infections. No operative mortality was observed. Histopathology of all patients was suggestive of AAM. Immunohistochemistry was done with a 91.7% positive rate for estrogen and progesterone receptors. The median recurrence-free survival time was 38 months. There were no cases of deceased or presented with distal metastasis during a median of 42 months’ follow-up.

Conclusions
The clinical manifestations of abdominopelvic AAM are mostly atypical. Surgical resection with curative intents remains the mainstay treatment of this disease, which was strongly suggested in experienced sarcoma centers due to the high probability of severe postoperative complications. In addition, long-term follow-up is necessary due to the high rate of local recurrences.
Perceptions of the primary health care team about the implementation of integrated care of patients with type 2 diabetes and hypertension in Slovenia: qualitative study
Authors: Stojnić Nataša , Klemenc-Ketiš Zalika , Mori Lukančič Majda , Zavrnik Črt , Poplas Susič Antonija 
Published: April 2023

Abstract
Background
Integrated care involves good coordination, networking, and communication within health care services and externally between providers and patients or informal caregivers. It affects the quality of services, is more cost-effective, and contributes to greater satisfaction among individuals and providers of integrated care. In our study, we examined the implementation and understanding of integrated care from the perspective of providers - the health care team - and gained insights into the current situation.

Methods
Eight focus groups were conducted with health care teams, involving a total of 48 health care professionals, including family physicians, registered nurses, practice nurses, community nurses, and registered nurses working in a health education center. Prior to conducting the focus groups, a thematic guide was developed based on the literature and contextual knowledge with the main themes of the integrated care package. The analysis was conducted using the NVivo program.

Results
We identified 12 main themes with 49 subthemes. Health care professionals highlighted good accessibility and the method of diagnostic screening integrated with preventive examinations as positive aspects of the current system of integrated care in Slovenia. They mentioned the good cooperation within the team, with the involvement of registered nurses and community nurses being a particular advantage. Complaints were made about the high workload and the lack of workforce. They feel that patients do not take the disease seriously enough and that patients as teachers could be useful.

Conclusion
Primary care teams described the importance of implementing integrated care for diabetes and hypertension patients at four levels: Patient, community, care providers, and state. Primary care teams also recognized the importance of including more professionals from different health care settings on their team.
Exploring the causal role of the immune response to varicella-zoster virus on multiple traits: a phenome-wide Mendelian randomization study
Authors: Yu Xinzhu , Lophatananon Artitaya , Mekli Krisztina , Muir Kenneth R. , Guo Hui 
Published: April 2023

AbstractBackgroundThe immune response to infections could be largely driven by the individual’s genes, especially in the major histocompatibility complex (MHC) region. Varicella-zoster virus (VZV) is a highly communicable pathogen. In addition to infection, the reactivations of VZV can be a potential causal factor for multiple traits. Identification of VZV immune response-related health conditions can therefore help elucidate the aetiology of certain diseases.MethodsA phenome-wide Mendelian randomization (MR) study of anti-VZV immunoglobulin G (IgG) levels with 1370 traits was conducted to explore the potential causal role of VZV-specific immune response on multiple traits using the UK Biobank cohort. For the robustness of the results, we performed MR analyses using five different methods. To investigate the impact of the MHC region on MR results, the analyses were conducted using instrumental variables (IVs) inside (IVmhc) and outside (IVno.mhc) the MHC region or all together (IVfull).ResultsForty-nine single nucleotide polymorphisms (IVfull) were associated with anti-VZV IgG levels, of which five (IVmhc) were located in the MHC region and 44 (IVno.mhc) were not. Statistical evidence (false discovery rate < 0.05 in at least three of the five MR methods) for a causal effect of anti-VZV IgG levels was found on 22 traits using IVmhc, while no evidence was found when using IVno.mhcor IVfull. The reactivations of VZV increased the risk of Dupuytren disease, mononeuropathies of the upper limb, sarcoidosis, coeliac disease, teeth problems and earlier onset of allergic rhinitis, which evidence was concordant with the literature. Suggestive causal evidence (P < 0.05 in at least three of five MR methods) using IVfull, IVmhcand IVno.mhcwas detected in 92, 194 and 56 traits, respectively. MR results from IVfullcorrelated with those from IVmhcor IVno.mhc. However, the results between IVmhcand IVno.mhcwere noticeably different, as evidenced by causal associations in opposite directions between anti-VZV IgG and ten traits.ConclusionsIn this exploratory study, anti-VZV IgG was causally associated with multiple traits. IVs in the MHC region might have a substantial impact on MR, and therefore, could be potentially considered in future MR studies.
Lean adipose tissue macrophage derived exosome confers immunoregulation to improve wound healing in diabetes
Authors: Xia Wenzheng , Liu Yunhan , Jiang Xingyu , Li Minxiong , zheng Shengwu , Zhang Zewei , Huang Xin , Luo Shenying , Khoong Yimin , Hou Meng , Zan Tao 
Published: April 2023

AbstractChronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.
Graphic Abstract
HIGD2A silencing impairs hepatocellular carcinoma growth via inhibiting mitochondrial function and the MAPK/ERK pathway
Authors: Huang Kuiyuan , Liu Ziying , Xie Zhanglian , Li Xiaoran , Zhang Haixing , Chen Yu , Wang Yiran , Lin Zimo , Li Chuanjiang , Liu Hongyan , Zhang Xiaoyong 
Published: April 2023

Abstract
Background
The Hypoxia inducible gene domain family member 2A (HIGD2A) protein is indispensable for the assembly of the mitochondrial respiratory supercomplex, which has been implicated in cell proliferation and cell survival under hypoxic conditions. Because the liver has a naturally low oxygen microenvironment, the role of HIGD2A in the development of hepatocellular carcinoma (HCC) remains largely unknown.

Methods
Gene expression data and clinical information were obtained from multiple public databases. A lentivirus-mediated gene knockdown approach was conducted to explore the function and mechanism of HIGD2A activity in HCC cells. In vivo and in vitro assays were performed to investigate the biological roles of HIGD2A.

Results
HIGD2A was overexpressed in HCC tissues and cell lines and was associated with a worse prognosis. Silencing HIGD2A expression significantly attenuated cell proliferation and migration, caused S-phase cell cycle arrest, and decreased tumor formation in nude mice. Mechanistically, HIGD2A depletion greatly decreased cellular ATP levels by disrupting mitochondrial ATP production. Moreover, HIGD2A knockdown cells displayed impaired mitochondrial function, such as mitochondrial fusion, increased expression of the mitochondrial stress response protein, and decreased oxygen consumption. Furthermore, knockdown of HIGD2A markedly attenuated the activation of the MAPK/ERK pathway.

Conclusions
HIGD2A promoted liver cancer cell growth by fueling mitochondrial ATP synthesis and activating the MAPK/ERK pathway, suggested that targeting HIGD2A may represent a new strategy for HCC therapy.
Update of cellular responses to the efferocytosis of necroptosis and pyroptosis
Authors: Purnama Chandra Agung , Meiliana Anna , Barliana Melisa Intan , Lestari Keri 
Published: April 2023

AbstractCell death is a basic physiological process that occurs in all living organisms. A few key players in these mechanisms, as well as various forms of cell death programming, have been identified. Apoptotic cell phagocytosis, also known as apoptotic cell clearance, is a well-established process regulated by a number of molecular components, including ‘find-me’, ‘eat-me’ and engulfment signals. Efferocytosis, or the rapid phagocytic clearance of cell death, is a critical mechanism for tissue homeostasis. Despite having similar mechanism to phagocytic clearance of infections, efferocytosis differs from phagocytosis in that it induces a tissue-healing response and is immunologically inert. However, as field of cell death has rapid expanded, much attention has recently been drawn to the efferocytosis of additional necrotic-like cell types, such as necroptosis and pyroptosis. Unlike apoptosis, this method of cell suicide allows the release of immunogenic cellular material and causes inflammation. Regardless of the cause of cell death, the clearance of dead cells is a necessary function to avoid uncontrolled synthesis of pro-inflammatory molecules and inflammatory disorder. We compare and contrast apoptosis, necroptosis and pyroptosis, as well as the various molecular mechanisms of efferocytosis in each type of cell death, and investigate how these may have functional effects on different intracellular organelles and signalling networks. Understanding how efferocytic cells react to necroptotic and pyroptotic cell uptake can help us understand how to modulate these cell death processes for therapeutic purposes.
Cooled radiofrequency ablation versus cryoneurolysis of the genicular nerves for the symptomatic pain management in knee osteoarthritis: a study protocol of a prospective, randomized, single-blinded clinical trial
Authors: Panagopoulos A. , Tsiplakos P. , Katsanos K. , Antzoulas P. , Lakoumentas J. 
Published: April 2023

Abstract
Background
Cooled radiofrequency ablation (CRFA) and cryoneurolysis (CRYO) are two novel methods of genicular neurolysis to relief pain in symptomatic knee osteoarthritis (KOA). In this study, the two methods will be compared, giving us the opportunity to investigate their efficacy, safety and complications.

Methods
In this prospective randomized trial 70 patients with KOA will be recruited using a diagnostic block of four genicular nerves. Two groups will be created through software randomization: a CRFA group (35 patients) and a CRYO group (35 patients). The target of the interventions will be four genicular nerves; the superior medial, superior lateral, inferior medial, as well as the medial (retinacular) genicular branch from vastus intermedius. The primary outcome of this clinical trial will be the efficacy of CRFA or CRYO at 2-, 4-, 12-and 24-weeks post-intervention using the Numerical Rating Pain Scale (NRPS). The secondary outcomes are the safety of the two techniques, as well as the clinical evaluation using the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Oxford Knee Score (OKS), and the 7-point scale of Patient Global Impression of Change (PGIC).

Discussion
These two novel techniques can block pain transmission through genicular nerves in different ways. In contrast to cryoneurolysis, the CRFA method has been well documented in the past. This is the first clinical trial to compare CRFA vs CRYO and draw conclusions about their safety and efficacy.

Trial registration

ISRCTN87455770 [https://doi.org/10.1186/ISRCTN87455770]. Registered 29/3/2022, first patient recruited 31/8/2022.
The quantification of 3D-trabecular architecture of the fourth cervical vertebra using CT osteoabsorptiometry and micro-CT
Authors: Poilliot Amélie , Gay-Dujak Max Hans-Peter , Müller-Gerbl Magdalena 
Published: April 2023

Abstract
Background
Bone functional adaptation rationalises the inhomogeneous morphology found in bone. By means of computed tomography osteoabsorptiometry and micro-computed tomography, the mineralisation of the subchondral endplates and trabecular microstructure of vertebral bodies can be assessed to visualise the chronic loading conditions bone endures over time. In this study, we determined cancellous and compartment-specific trabecular architecture in the cervical vertebra to aid with successful integration of orthopaedic implants.

Methods
We examined the micro-computed tomography scans of seven prospectively healthy C4 vertebrae, evaluated their microstructure parameters (bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number per volume (Tb.N), connectivity density (Conn.D), structure model index (SMI), and degree of anisotropy (DA), and compared the trabecular architecture in twelve predefined volumes of interest: the cranial and caudal 0–10%, 10–15%, and 25–50% in both the ventral and dorsal half. Using computed tomography osteoabsorptiometry, the subchondral bone mineralisation of the subchondral endplates of nine C4 vertebrae was also evaluated.

Results
Highest mineralisation is located dorsally at the endplates. Tb.Sp and Tb.N were the only two parameters that displayed significant differences in averaged values of VOI. Nonetheless, distinct, consistent ventral–dorsal modulations were seen in matched sample ventral–dorsal comparison in the BV/TV, BS/BV, and SMI overall levels, as well as in Tb.Th in the three caudal levels. To simplify, the vertebra was split into ventral–cranial, dorsal–cranial, ventral–caudal, and dorsal–caudal equal quarters. The ventral quarters display lower BV/TV, respectively, higher BS/BV and SMI than their sample paired dorsal quarters. The ventral–cranial quarter shows the lowest BV/TV and the highest BS/BV and SMI, describing spacious cancellous bone with rod-like trabeculae. In contrast, the dorsal–caudal quarter exhibits the highest BV/TV and Tb.Th and the lowest BS/BV and SMI, illustrating thicker, denser, and more plate-like trabeculae. The dorsal–cranial and ventral–caudal quarters are comparable and represent intermediate characteristics.

Conclusions
CT-OAM and µCT demonstrate the interdependence of compact and trabecular bone in response to long-term loading conditions. Results show highest mineralisation in the dorso-caudal part of the C4 vertebra. Recommended placement of orthopaedic implants should be positioned dorsally with screws anchored in the dorsal–caudal region.
Internet-delivered cognitive behavioral therapy for tinnitus compared to Internet-delivered mindfulness for tinnitus: a study protocol of a randomized controlled trial
Authors: Eimontas Jonas , Gegieckaitė Goda , Asačiova Irena , Stičinskaitė Nikol , Arcimavičiūtė Livija , Savickaitė Dovilė , Vaitiekūnaitė-Zubriakovienė Donata , Polianskis Marius , Gans Jennifer , Beukes Eldre , Manchaiah Vinaya , Andersson Gerhard , Lesinskas Eugenijus 
Published: April 2023

Abstract
Background
Tinnitus affects around 15% of the population and can be a debilitating condition for a sizeable part of them. However, effective evidence-based treatments are scarce. One recommended treatment for tinnitus is cognitive behavioral therapy which has been found to be effective when delivered online. However, more treatments including mindfulness-based interventions have been studied recently in an attempt to facilitate the availability of effective treatments. There are promising findings showing great effects in reducing tinnitus-induced distress and some evidence about the efficacy of such intervention delivered online. However, there is a lack of evidence on how these two treatments compare against one another. Therefore, the aim of this study will be to compare Internet-delivered cognitive behavioral therapy for tinnitus against an Internet-delivered mindfulness-based tinnitus stress reduction intervention in a three-armed randomized controlled trial with a waiting list control condition.

Methods
This study will be a randomized controlled trial seeking to recruit Lithuanian-speaking individuals suffering from chronic tinnitus. The self-report measure Tinnitus Handicap Inventory will be used. Self-referred participants will be randomized into one of three study arms: Internet-delivered cognitive behavioral therapy, Internet-delivered mindfulness-based tinnitus stress reduction intervention, or a waiting-list control group. Post-treatment measures will be taken at the end of the 8-week-long intervention (or waiting). Long-term efficacy will be measured 3 and 12 months post-treatment.

Discussion
Internet-delivered interventions offer a range of benefits for delivering evidence-based treatments. This is the first randomized controlled trial to directly compare Internet-delivered CBT and MBTSR for tinnitus in a non-inferiority trial.

Trial registration
ClinicalTrials.gov NCT05705323. Registered on January 30, 2023.
Thermotolerance improvement of engineered Saccharomyces cerevisiae ERG5 Delta ERG4 Delta ERG3 Delta, molecular mechanism, and its application in corn ethanol production
Authors: Yang Peizhou , Wu Wenjing , Chen Jianchao , Jiang Suwei , Zheng Zhi , Deng Yanhong , Lu Jiuling , Wang Hu , Zhou Yong , Geng Yuyou , Wang Kanglin 
Published: April 2023

Abstract
Background
The thermotolerant yeast is beneficial in terms of efficiency improvement of processes and reduction of costs, while Saccharomyces cerevisiae does not efficiently grow and ferment at high-temperature conditions. The sterol composition alteration from ergosterol to fecosterol in the cell membrane of S. cerevisiae affects the thermotolerant capability.

Results
In this study, S. cerevisiae ERG5, ERG4, and ERG3 were knocked out using the CRISPR–Cas9 approach to impact the gene expression involved in ergosterol synthesis. The highest thermotolerant strain was S. cerevisiae ERG5ΔERG4ΔERG3Δ, which produced 22.1 g/L ethanol at 37 °C using the initial glucose concentration of 50 g/L with an increase by 9.4% compared with the wild type (20.2 g/L). The ethanol concentration of 9.4 g/L was produced at 42 ℃, which was 2.85-fold of the wild-type strain (3.3 g/L). The molecular mechanism of engineered S. cerevisiae at the RNA level was analyzed using the transcriptomics method. The simultaneous deletion of S. cerevisiae ERG5, ERG4, and ERG3 caused 278 up-regulated genes and 1892 down-regulated genes in comparison with the wild-type strain. KEGG pathway analysis indicated that the up-regulated genes relevant to ergosterol metabolism were ERG1, ERG11, and ERG5, while the down-regulated genes were ERG9 and ERG26. S. cerevisiae ERG5ΔERG4ΔERG3Δ produced 41.6 g/L of ethanol at 37 °C with 107.7 g/L of corn liquefied glucose as carbon source.

Conclusion
Simultaneous deletion of ERG5, ERG4, and ERG3 resulted in the thermotolerance improvement of S. cerevisiae ERG5ΔERG4ΔERG3Δ with cell viability improvement by 1.19-fold at 42 °C via modification of steroid metabolic pathway. S. cerevisiae ERG5ΔERG4ΔERG3Δ could effectively produce ethanol at 37 °C using corn liquefied glucose as carbon source. Therefore, S. cerevisiae ERG5ΔERG4ΔERG3Δ had potential in ethanol production at a large scale under supra-optimal temperature.
Transverse colon volvulus presenting as bowel obstruction, atelectasis, and displacement of the right lobe of the liver into the left upper abdominal quadrant: a case report
Authors: Kayiira Mubaraka , Muwanguzi Eria , Kasozi Derrick , Waitt Peter , Ayebare Rogers , Musinguzi Edwin , Orimunsi Innocent , Okeny Paul , Mbide Peter , Serumaga Timothy Arthur , Tamale Nicholas 
Published: April 2023

Abstract
Background
Transverse colon volvulus is an uncommon cause of intestinal obstruction. It is a surgical emergency that can lead to bowel infarction, peritonitis, and death.

Case presentation
We report a case of transverse colon volvulus in a 35-year-old Congolese immigrant man who had a rare presentation with features of intestinal obstruction associated with right lung collapse and left mediastinal shift.

Conclusion
This case is unusual because it presented with respiratory features that mimicked a pneumothorax in addition to features of intestinal obstruction. The use of point-of-care lung ultrasound was helpful in ruling out a pneumothorax, and this could help avoid situations such as unintentional chest drain insertions by other professionals who may encounter a similar case. Because transverse colon volvulus is rare, a high level of suspicion and awareness is required to make an accurate diagnosis.