bluuebunny/crossref_metadata_2025 huggingface dataset:
Consolidating Research Data Management Infrastructure: Towards Sustainable Digital Scholarship
Authors: Gooch Megan , Strange Damon
Published: October 2023

The sustainability of digital research outputs, particularly in the humanities where these frequently comprise archives of digital cultural heritage material, has always offered a challenge to the researchers and institutions who have responsibility for them. The amount of upfront care, effort, and funding that goes into developing a research project during the active (and funded) research phase is rarely replicated within the post-project maintenance and curation of the delivered digital assets or archives. What often defines the sustainability of a research project and its archive is a combination of research method and expected life span for the digital collection. Innovation in research data design is often at the expense of its longevity. But this does not need to be so. The tradeoff between longevity and functionality is a false dichotomy. Yet what is clear is that care and consideration in planning the research data storage or archive for a project can make a big difference. A data management plan that meets grant funder requirements is asked for for many research projects, but it is more than simply a funding document. Good research data management ensures that outputs are available online for years to come and available for future research and innovation. This article offers a practical insight to the methods being employed at the University of Oxford to support Digital Humanities scholars (and beyond) safeguard their digital legacy for future generations.
Ahdc1 is a potent regulator of obesity and energy metabolism
Authors: Li Linyi , Shao Shipeng , Wang Yu , Du Zhiyong , Yu Huahui , Li Fan , Qin Yanwen
Published: October 2023

In this first metabolic phenotype study of Ahdc1 deficiency, we generated a survivable Ahdc1-deficient mouse line. We found that Ahdc1 deficiency in both male and female mice resulted in adiposity from weaning and obesity characterized by reduced energy expenditure and respiratory quotient. Additionally, there was a progressive development of hyperleptinemia, insulin resistance, abnormal glycolipid metabolism, and fatty liver. These findings demonstrate that Ahdc1 is a novel key regulator of obesity and energy metabolism.
Slc12a2 loss in insulin-secreting β-cells links development of overweight and metabolic dysregulation to impaired satiation control of feeding
Authors: Rathod Yakshkumar Dilipbhai , Abdelgawad Rana , Hübner Christian A. , Di Fulvio Mauricio
Published: October 2023

Obesity, defined as excess fat accumulation, increases the absolute risk for metabolic diseases. Although obesity is usually attributed to increased food intake, we demonstrate that body weight gain can be hastened without consuming excess calories. In fact, impaired meal termination control, i.e., satiation, is detectable before the development of overweight in an animal model that develops a metabolic syndrome-like phenotype.
Voluntary muscle activation in people with multiple sclerosis is reduced across a wide range of forces following maximal effort-fatiguing contractions
Authors: Brotherton Emily J. , Sabapathy Surendran , Heshmat Saman , Kavanagh Justin J.
Published: October 2023

We use transcranial magnetic stimulation to demonstrate that people with relapsing-remitting multiple sclerosis (MS) have a reduced ability to activate muscles following maximal effort-fatiguing contractions. A reduced ability to activate the elbow flexor muscles after a fatiguing contraction was associated with disease duration and not self-reported levels of fatigue.
Kinematics Model Estimation of 4W Skid-Steering Mobile Robots Using Visual Terrain Classification
Authors: Chen Yang , Wu Yao , Zeng Wei , Du Shaoyi
Published: October 2023

Accurate real-time kinematics model is very important for the control of a skid-steering mobile robot. In this study, the kinematics model of the skid-steering mobile robots was first designed based on instantaneous rotation centers (ICRs). Then, the extended Kalman filter (EKF) technique was applied to obtain the parameters of ICRs under the same specific terrain online. To adapt to different terrain environments, the fractal dimension-based SFTA (segmentation-based fractal texture analysis) method was used to extract features of different terrains, and the k-nearest neighbor (KNN) method was used to classify the terrains. In the case of real-time terrain recognition, the filter parameters of the EKF for estimating the ICRs are adjusted adaptively. Experiments on a real skid-steering mobile robot show that this method can quickly estimate the kinematics model of the robot in the case of terrain changes, and can meet the needs of practical applications. The average error of odometer estimation based on visual terrain classification is 0.06 m, while the average error of odometer estimation without terrain classification is 0.14 m.
Dental Pulp Stem Cells for Bone Tissue Engineering: A Literature Review
Authors: Bai Xiaolei , Cao Ruijue , Wu Danni , Zhang Huicong , Yang Fan , Wang Linhong
Published: October 2023

Bone tissue engineering (BTE) is a promising approach for repairing and regenerating damaged bone tissue, using stem cells and scaffold structures. Among various stem cell sources, dental pulp stem cells (DPSCs) have emerged as a potential candidate due to their multipotential capabilities, ability to undergo osteogenic differentiation, low immunogenicity, and ease of isolation. This article reviews the biological characteristics of DPSCs, their potential for BTE, and the underlying transcription factors and signaling pathways involved in osteogenic differentiation; it also highlights the application of DPSCs in inducing scaffold tissues for bone regeneration and summarizes animal and clinical studies conducted in this field. This review demonstrates the potential of DPSC-based BTE for effective bone repair and regeneration, with implications for clinical translation.
Stagnation Point Flow of
CoF

e

2

O

4

/
Ti

O

2

-

H

2

O
-Casson Nanofluid past a Slippery Stretching/Shrinking Cylindrical Surface in a Darcy–Forchheimer Porous Medium
Authors: Duguma Kifle Adula , Makinde Oluwole Daniel , Enyadene Lemi Guta
Published: October 2023

Mounting temperatures in electronic devices during operation may damage sensitive internal components if too much thermal energy accumulates inside the system. The advent of an innovative ultrahigh-performance thermal management technology known as nanofluid has provided a veritable platform to improve the system performance and reliability by removing the high heat flux generated in the engineering and industrial devices. This paper examines the combined effects of Darcy–Forchheimer porous medium-resistant heating and viscous dissipation on stagnation point flow of a Casson nanofluid (

CoF

e

2

O

4

-

H

2

O

and

Ti

O

2

-

H

2

O

) towards a convectively heated slippery stretching/shrinking cylindrical surface in a porous medium. The governing nonlinear model equations are obtained, analysed, and tackled numerically via the shooting technique with the Runge–Kutta–Fehlberg integration scheme. A unique solution is obtained when the surface is stretching. For shrinking cylindrical surface, the model exhibits nonunique dual solutions for a defined range of parameter values, and a temporal stability analysis is conducted to ascertain the stable and physically achievable solution. The effects of emerging thermophysical parameters on the overall flow structure and thermal management such as velocity and temperature profiles, skin friction, and Nusselt number are quantitatively discussed through graphs and in tabular form. It is found that the thermal performance heat transfer enhancement capability of

Ti

O

2

-

H

2

O

is higher than that of

CoF

e

2

O

4

-

H

2

O

. Moreover, the nanofluid thermal performance is enhanced with nanoparticles volume fraction, Casson nanofluid parameter, and Biot number but lessened with porous medium permeability.
Male Genital Mutilation in the Name of Ritual Circumcision: A Case Report and Literature Review
Authors: Dar Latif , Baarimah Alhareth , Alshehrani Saeed , Alasiri Alhassan , Alassiri Mohammad , Al-Ghamdi Saleh
Published: October 2023

Unlike female genital mutilation, the alteration of male genitals has not received much attention. Circumcision is the most common and oldest surgical procedure being performed. When performed by surgeons or well-trained personal the procedure is safe, but most of the times it is being performed by untrained people with no or little medical background. This has led to many complications. Total skin loss is an uncommon but serious complication. There is an ongoing debate regarding the management of this complication. Here, we present a case of total penile skin loss which had resulted from penile mutilation in the name of ritual circumcision.
Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells
Authors: Hirai Soichi , Yamada Tadaaki , Katayama Yuki , Ishida Masaki , Kawachi Hayato , Matsui Yohei , Nakamura Ryota , Morimoto Kenji , Horinaka Mano , Sakai Toshiyuki , Sekido Yoshitaka , Tokuda Shinsaku , Takayama Koichi
Published: October 2023

Few treatment options exist for pleural mesothelioma (PM), which is a progressive malignant tumor. However, the efficacy of molecular-targeted monotherapy is limited, and further therapeutic strategies are warranted to treat PM. Recently, the cancer cell-cycle checkpoint inhibitors have attracted attention because they disrupt cell-cycle regulation. Here, we aimed to establish a novel combinational therapeutic strategy to inhibit the cell-cycle checkpoint kinase, ATR in PM cells. The siRNA screening assay showed that anexelekto (AXL) knockdown enhanced cell growth inhibition when exposed to ATR inhibitors, demonstrating the synergistic effects of the ATR and AXL combination in some PM cells. The AXL and ATR inhibitor combination increased cell apoptosis via the Bim protein and suppressed cell migration when compared with each monotherapy. The combined therapeutic targeting of AXL and ATR significantly delayed regrowth compared with monotherapy. Thus, optimal AXL and ATR inhibition may potentially improve the PM outcome.
Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma
Authors: Secrier Maria , McGrath Lara , Ng Felicia , Gulati Sakshi , Raymond Amelia , Nuttall Barrett R. B. , Berthe Julie , Jones Emma V. , Sidders Ben S. , Galon Jérôme , Barrett J. Carl , Angell Helen K.
Published: October 2023

Head and neck squamous cell carcinoma (HNSCC) is a molecularly and spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, disease progression still occurs quickly after treatment in the majority of cases, suggesting the need to improve patient selection strategies. In the quest for biomarkers that may help inform response to checkpoint blockade, we characterized the tumor microenvironment (TME) of 162 HNSCC primary tumors of diverse etiologic and spatial origin, through gene expression and IHC profiling of relevant immune proteins, T-cell receptor (TCR) repertoire analysis, and whole-exome sequencing. We identified five HNSCC TME categories based on immune/stromal composition: (i) cytotoxic, (ii) plasma cell rich, (iii) dendritic cell rich, (iv) macrophage rich, and (v) immune-excluded. Remarkably, the cytotoxic and plasma cell rich subgroups exhibited a phenotype similar to tertiary lymphoid structures (TLS), which have been previously linked to immunotherapy response. We also found an increased richness of the TCR repertoire in these two subgroups and in never smokers. Mutational patterns evidencing APOBEC activity were enriched in the plasma cell high subgroup. Furthermore, specific signal propagation patterns within the Ras/ERK and PI3K/AKT pathways associated with distinct immune phenotypes. While traditionally CD8/CD3 T-cell infiltration and immune checkpoint expression (e.g., PD-L1) have been used in the patient selection process for checkpoint blockade treatment, we suggest that additional biomarkers, such as TCR productive clonality, smoking history, and TLS index, may have the ability to pull out potential responders to benefit from immunotherapeutic agents.

Significance:

Here we present our findings on the genomic and immune landscape of primary disease in a cohort of 162 patients with HNSCC, benefitting from detailed molecular and clinical characterization. By employing whole-exome sequencing and gene expression analysis of relevant immune markers, TCR profiling, and staining of relevant proteins involved in immune response, we highlight how distinct etiologies, cell intrinsic, and environmental factors combine to shape the landscape of HNSCC primary disease.
Leisure-Time Television Viewing and Computer Use, Family History, and Incidence of Dementia
Authors: Zhuang Zhenhuang , Zhao Yimin , Song Zimin , Wang Wenxiu , Huang Ninghao , Dong Xue , Xiao Wendi , Li Yueying , Jia Jinzhu , Liu Zhonghua , Qi Lu , Huang Tao
Published: October 2023

Introduction: Time spent on screen-based sedentary activities is significantly associated with dementia risk, however, whether the associations vary by family history (FHx) of dementia is currently unknown. We aimed to examine independent associations of two prevalent types of screen-based sedentary activities (television [TV] viewing and computer use) with dementia and assess the modifying effect of FHx. Methods: We included 415,048 individuals free of dementia from the UK Biobank. Associations of TV viewing, computer use, and FHx with dementia risk were determined using Cox regression models. We estimated both multiplicative- and additive-scale interactions between TV viewing and computer use and FHx. Results: During a median follow-up of 12.6 years, 5,549 participants developed dementia. After adjusting for potential confounding factors, we observed that moderate (2–3 h/day; hazard ratio [HR] 1.13, 95% confidence interval 0.03–1.23) and high (>3 h/day; 1.33, 1.21–1.46) TV viewing was associated with a higher dementia risk, compared with low (0–1 h/day) TV viewing. Using restricted cubic spline models, the relationship of TV viewing with dementia was nonlinear (relative to 0 h/day; p for nonlinear = 0.005). We found that >3 h/day of TV viewing was associated with a 42% (1.42, 1.18–1.71) higher dementia risk in participants with FHx while a 30% (1.30, 1.17–1.45) in those without FHx. For computer use, both low (0 h/day; 1.41, 1.33–1.50) and high (>2 h/day; 1.17, 1.05–1.29) computer use were associated with elevated dementia risk, compared with moderate (1–2 h/day) computer use. We observed a J-shaped relationship with dementia (relative to 2 h/day; p for nonlinear <0.001). Compared with 1–2 h/day of computer use, the HRs of dementia were 1.46 (1.29–1.65) and 1.10 (0.90–1.36) for 0 h/day and >2 h/day of computer use in participants with FHx, respectively, while the corresponding HRs were 1.40 (1.30–1.50) and 1.19 (1.06–1.33) in those without FHx. We observed a positive additive interaction (RERI 0.29, 0.06–0.53) between computer use and FHx, while little evidence of interaction between TV viewing and FHx. Conclusions: The time spent on TV viewing and computer use were independent risk factors for dementia, and the adverse effects of computer use and FHx were additive. Our findings point to new behavioral targets for intervention on preventing an early onset of dementia, especially for those with FHx.
Mentalizing in Adolescents and Young Adults with Attention Deficit Hyperactivity Disorder: Associations with Age and Attention Problems
Authors: Poznyak Elena , Samson Jessica Lee , Barrios Juan , Rafi Halima , Hasler Roland , Perroud Nader , Debbané Martin
Published: October 2023

Introduction: Growing, albeit heterogenous evidence questions whether attention deficit/hyperactivity disorder (ADHD) is associated with socio-cognitive impairments, especially beyond childhood. This study focuses on mentalizing – the socio-cognitive ability to attribute and reason in terms of mental states. We aimed to characterize mentalizing performance in terms of correct scores and types of errors in adolescents and young adults with ADHD. Methods: Forty-nine adolescents and adults with ADHD and 49 healthy controls matched for age and gender completed a computerized naturalistic mentalizing task, the Movie for Assessment of Social Cognition (MASC). Repeated measures analyses of variance examined the effects of age group and ADHD diagnosis on MASC performance. Additionally, associations between mentalizing scores, the severity of attention problems, and the presence of comorbidity were explored in the ADHD group. Results: Results showed an increased prevalence of hypomentalizing errors in adolescents with ADHD. Lower mentalizing scores in adolescents with ADHD were correlated with indices of inattentiveness, impulsivity, and vigilance problems. Hypomentalizing errors in adolescents showed to be particularly associated with inattentiveness, after controlling for age and comorbidity. In contrast, adults with ADHD performed similarly to controls and their scores on the mentalizing task were not correlated to attention problems. Conclusion: These findings highlight potential developmental differences in mentalizing abilities in ADHD youths and their association with attentional impairments.
Non-Surgical Site Pain in Women following Breast Cancer Surgery: A Systematic Review and Meta-Analysis
Authors: Burton George , Masannat Yazan A. , Forget Patrice
Published: October 2023

Background: Chronic pain after breast cancer surgery affects up to 60% of patients. Evidence supports the fact that pain outwith the surgical site is a significant issue. This systematic review and meta-analysis sought to evaluate the prevalence of non-surgical site pain (NSSP) in women after breast cancer surgery at 6 months post-operatively. Methods: Adult women with a confirmed breast cancer diagnosis who had undergone breast cancer surgery were identified. The outcome pursued was pain outwith the surgical site measured on either NRS/VRS or VAS rating scale. CENTRAL, Embase, PubMed, MEDLINE, CINAHL, PsycInfo, Web of Science, and Scopus were searched to identify studies that examined NSSP after breast cancer surgery at 6 months. Data were gathered via pre-piloted Excel forms and analysed both quantitively and qualitatively. Meta-analysis was carried out using a random-effects model to assess risk difference with 95% confidence interval (CI). Results: A total of sixteen studies were identified for inclusion. Eleven studies failed to provide sufficient data and consequently were analysed qualitatively. Five studies were adequate for quantitative analysis, including a total of 995 patients. Meta-analysis identified a risk difference of 18% (95% CI: 5–31%) between patients who had breast cancer surgery and a reference, however, this is low-quality evidence. Conclusion: This review has highlighted that breast cancer surgery increases the risk of pain outwith the surgical site postoperatively. It was additionally identified that NSSP data are often gathered in research yet rarely presented in results or highlighted as a primary outcome. As the quality of evidence was low, research specifying NSSP as a primary outcome is required to provide more certainty.
Variations in Determining Actual Orientations of Segmented Deep Brain Stimulation Leads Using the DiODe Algorithm: A Retrospective Study Across Different Lead Designs and Medical Institutions
Authors: Henry Kaylee R. , Miulli Milina Michelle , Nuzov Noa B. , Nolt Mark J. , Rosenow Joshua M. , Elahi Behzad , Pilitsis Julie , Golestanirad Laleh
Published: October 2023

Introduction: Directional deep brain stimulation (DBS) leads have become widely used in the past decade. Understanding the asymmetric stimulation provided by directional leads requires precise knowledge of the exact orientation of the lead in respect to its anatomical target. Recently, the DiODe algorithm was developed to automatically determine the orientation angle of leads from the artifact on postoperative computed tomography (CT) images. However, manual DiODe results are user-dependent. This study analyzed the extent of lead rotation as well as the user agreement of DiODe calculations across the two most common DBS systems, namely, Boston Scientific’s Vercise and Abbott’s Infinity, and two independent medical institutions. Methods: Data from 104 patients who underwent an anterior-facing unilateral/bilateral directional DBS implantation at either Northwestern Memorial Hospital (NMH) or Albany Medical Center (AMC) were retrospectively analyzed. Actual orientations of the implanted leads were independently calculated by three individual users using the DiODe algorithm in Lead-DBS and patients’ postoperative CT images. The deviation from the intended orientation and user agreement were assessed. Results: All leads significantly deviated from the intended 0° orientation (p < 0.001), regardless of DBS lead design (p < 0.05) or institution (p < 0.05). However, the Boston Scientific leads showed an implantation bias toward the left at both institutions (p = 0.014 at NMH, p = 0.029 at AMC). A difference of 10° between at least two users occurred in 28% (NMH) and 39% (AMC) of all Boston Scientific and 76% (NMH) and 53% (AMC) of all Abbott leads. Conclusion: Our results show that there is a significant lead rotation from the intended surgical orientation across both DBS systems and both medical institutions; however, a bias toward a single direction was only seen in the Boston Scientific leads. Additionally, these results raise questions into the user error that occurs when manually refining the orientation angles calculated with DiODe.
Targeting Breast Cancer Signaling via Phytomedicine and Nanomedicine
Authors: Ansari Jeba Ajgar , Malik Jonaid Ahmad , Ahmed Sakeel , Bhat Faisal Ashraf , Khanam Afreen , Mir Suhail Ahmad , Abouzied Amr S. , Ahemad Nafees , Anwar Sirajudheen
Published: October 2023

Background: The development of breast cancer (BC) and how it responds to treatment have both been linked to the involvement of inflammation. Chronic inflammation is critical in carcinogenesis, leading to elevated DNA damage, impaired DNA repair machinery, cell growth, apoptosis, angiogenesis, and invasion. Studies have found several targets that selectively modulate inflammation in cancer, limit BC’s growth, and boost treatment effectiveness. Drug resistance and the absence of efficient therapeutics for metastatic and triple-negative BC contribute to the poor outlook of BC patients. Summary: To treat BC, small-molecule inhibitors, phytomedicines, and nanoparticles are conjugated to attenuate BC signaling pathways. Due to their numerous target mechanisms and strong safety records, phytomedicines and nanomedicines have received much attention in studies examining their prospects as anti-BC agents by such unfulfilled demands. Key Messages: The processes involved in the affiliation across the progression of tumors and the spread of inflammation are highlighted in this review. Furthermore, we included many drugs now undergoing clinical trials that target cancer-mediated inflammatory pathways, cutting-edge nanotechnology-derived delivery systems, and a variety of phytomedicines that presently address BC.
Determination of Surgical Nurses’ Compliance with Isolation Precautions
Authors: Gökce Işıklı Ayşe , Yıldız Fındık Ümmü
Published: October 2023

Introduction: Patients are impacted by healthcare-associated infections. The aim of the study is to determine the compliance status of surgical nurses to isolation precautions. Methods: This research is a descriptive and cross-sectional research. The research was carried out between July and September 2022 in two training and research hospitals, with the participation of 215 surgical nurses. Face-to-face interviews were used to collect the research data using the Nurse Information Form and the scale. Results: The mean score of the Scale of Compliance with Isolation Precautions was determined as 53.38 ± 4.45 over 18–90 points. Upon comparing the total mean scores of surgical nurses on the scale by gender, the compliance of female surgical nurses with isolation precautions was found to be higher compared to male surgical nurses (p < 0.05). Conclusion: The compliance of the surgical nurses participating in the study with isolation precautions was determined to be moderate. The compliance of surgical nurses with isolation precautions should be increased.
Krukenberg Tumor of Gastric Origin in Pregnant Women with Preeclampsia
Authors: Zhang Yongke , Du Hui , Li Taili , Li Huan , Deng Yuqing , Wu Ruifang
Published: October 2023

Krukenberg tumor refers to a malignancy in the ovary that metastasizes from a primary site, classically the gastrointestinal tract. Pregnancy complicated with a Krukenberg tumor is very rare. In this report, we present two unusual cases of pregnant women with Krukenberg tumors of gastric origin. One case was a full-term pregnant woman with preeclampsia (PE) who underwent a caesarean section when bilateral enlarged ovaries were incidentally identified. Histopathology of the wedge resection biopsy showed single-ring cell carcinoma; this was followed by gastroscopy, which indicated a gastric origin. The woman received chemotherapy but died 6 months later. Another case was a pregnant woman at 30 gestational weeks with abdominal pain complicated with early-onset PE. Ultrasonography and magnetic resonance imaging showed bilateral enlarged ovaries and elevated tumor markers. Gastroscopy indicated linitis plastica. After an emergency caesarean section, adnexectomy was performed, and postoperative histopathology confirmed a Krukenberg tumor. The woman died 2 months after delivery. Gastrointestinal symptoms during pregnancy may indicate a malignancy of rare gastrointestinal origin. PE complicated with Krukenberg tumors in pregnancy should be considered in future studies.
Validation of a Parvovirus B19 NAT Assay for Screening of Umbilical Cord Blood for Allogenic Hematopoietic Stem Cell Donation
Authors: Steininger Philipp , Korn Klaus , Hackstein Holger , Strasser Erwin F.
Published: October 2023

Introduction: Parvovirus B19 transmitted by umbilical cord blood (UCB) products may cause severe disease in allogenic hematopoietic stem cell transplant recipients. Thus, commercially available nucleic acid test (NAT) assays for highly sensitive detection of parvovirus B19 DNA validated for the specimen cord blood plasma (CBP) are required to avoid parvovirus B19 transmission by umbilical hematopoietic stem cell preparations. Methods: The multiplex cobas DPX NAT assay was validated for detection of parvovirus B19 DNA in CBP derived from citrate anticoagulated UCB units which have been processed by the Rubinstein method. In total, 363 retained CBP samples pretested negative for parvovirus B19 DNA were prepared for analyzing sensitivity, specificity, and interference of that NAT assay. The 3rd WHO International Standard for parvovirus B19 DNA was used for determining the 95% limit of detection (LOD95) by probit analysis. Results: The validation of the parvovirus B19 NAT assay for CBP demonstrated high sensitivity, specificity, intra- and inter-assay precision. Dilution series and replicate analyses showed a high linearity of the assay with a coefficient of determination above 0.99 and revealed a LOD95 of 17 International Units (IU)/mL (95% confidence interval, 14–44 IU/mL) for parvovirus B19 DNA in CBP samples. Conclusion: The validation of a commercially available parvovirus B19 NAT assay for the specimen CBP demonstrated a high assay performance fulfilling German guidelines and international regulations.
Botulinum Toxin-A for the Treatment of Neuropathic Pain after Decompressive Craniotomy in Stroke: Two Cases
Authors: Teuschl Yvonne , Bancher Christian , Dachenhausen Alexandra , Matz Karl , Pinter Michaela M.
Published: October 2023

Botulinum toxin-A (BoNT-A) is recommended as third-line off-label treatment for the management of neuropathic pain. BoNT-A has been reported as treatment for different neuropathic pain conditions; however, not for neuropathic pain after decompressive craniotomy for stroke. The aim of this retrospective case series is to provide information on safety, the effect, and the application method of BoNT-A in clinical practice for the treatment of neuropathic pain after trepanation. This case series describes 2 patients treated in 2021 at a BoNT outpatient clinic for chronic neuropathic pain at the incisional site after decompressive craniotomy for stroke who were resistant to pain medication. Cases were a 48-year-old woman and a 63-year-old man suffering from chronic neuropathic pain since 3 and 6 years, respectively. They were treated regularly with BoNT-A with a total dose of 100 mouse units of incobotulinumtoxin-A injected into peri-incisional sites of the scalp. Both patients reported subjective decrease in pain frequency (40% and 60%), in pain intensity (60% and 90%), and an increase of quality of life (80%). BoNT-A should be further investigated as treatment for neuropathic pain – especially in underreported conditions such as neuropathic pain after craniotomy in stroke.
ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway
Authors: Yin Xiaohong , Xia Keshun , Peng Song , Tan Bo , Huang Yaohui , Wang Mao , He Mingfang
Published: October 2023

Glioblastoma (GBM) is the most prevalent and fatal form of brain tumor, which is associated with a poor prognosis. ATP-binding cassette subfamily F member 1 (ABCF1) is an E2 ubiquitin-conjugating enzyme, which is implicated in regulating immune responses and tumorigenesis. Aberrant E3 ubiquitylation has been evidenced in GBM. However, the role of ABCF1 in GBM needs to be further explored. The expression of ABCF1, CXC chemokine ligand 12 (CXCL12), and CXC chemokine receptor 4 (CXCR4) in GBM tissues was examined by the GEPIA tool, real-time PCR and Western blotting. HMC3, U251MG, and LN-229 cells were cultured and transfected with shRNA targeting ABCF1 and ABCF1 plasmids. The proliferative, migrative, and invasive ability of cells was detected. Western blotting was used to detect the levels of phosphorylated phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (AKT). We observed that GBM tissues had higher ABCF1, CXCL12, and CXCR4 expression levels. The expression levels of CXCL12 and CXCR4 were enhanced by ABCF1 overexpression, which were significantly reversed by silence of ABCF1 in GBM cells. Silencing ABCF1 or CXCR4 inhibition weakened the capacity of GBM cell growth, migration, and invasion, while ectopic ABCF1 expression or CXCL12 treatment enhanced the cellular function of GBM cells. Furthermore, p-PI3K and p-AKT protein levels were downregulated by ABCF1 knockdown or CXCR4 blockade, which were prompted by ABCF1 overexpression or CXCL12 supplement. The ABCF1-CXCL12-CXCR4 axis was identified as a key player in GBM cell survival and metastasis by activating the PI3K/AKT signaling pathway in GBM cells.
Efficacy and Safety of Mechanical Thrombectomy in Elderly and Non-Elderly Patients with Large Vessel Occlusion Stroke: Systematic Review and Meta-Analysis
Authors: Ali Aisha , Testai Fernando D. , Trifan Gabriela
Published: October 2023

Introduction: Mechanical thrombectomy (MT) is recommended for large vessel occlusion (LVO) stroke. However, most of the studies that investigated the superiority of MT over best medical management (BMM) alone included preponderantly non-elderly patients. Thus, there is uncertainty in relation to the efficacy of MT in the elderly. We aim to compare the effect of BMM to BMM plus MT among elderly and non-elderly patients with LVO. Methods: We performed a systematic search of medical databases from inception to April 2023 to identify randomized studies that reported the functional outcome at 90 days by age for patients with LVO treated with MT versus BMM. Patients were divided into elderly (>70 or >80 years, depending on the cutoff used in each study) and non-elderly. Outcomes were defined as excellent (modified Rankin Scale [mRS] ≤1), good (mRS ≤3), poor (mRS ≥5), or death. Effect sizes were calculated by using random effects meta-analyses. Results were represented by odds ratio (OR) and their 95% confidence intervals (95% CIs). Results: A total of 2,195 patients were included in the analysis (≥70 years, 7 trials, n = 696; ≥80 years, 2 trials, n = 139). Non-elderly patients treated with MT had higher odds of excellent outcome (OR: 3.05; 95% CI: 2.23–4.18) and good outcome (OR: 2.70; 95% CI: 1.94–3.74), and lower odds of poor outcome (OR: 0.54; 95% CI: 0.40–0.72) and death (OR: 0.63; 95% CI: 0.41–0.96). Similarly, elderly patients treated with MT had higher odds of excellent (OR: 2.39; 95% CI: 1.05–5.45) and good outcomes (OR: 2.18; 95% CI: 1.43–3.33) and lower odds of poor outcome (OR: 0.48; 95% CI: 0.33–0.70) and mortality (OR: 0.50; 0.26–0.95). When outcomes were analyzed by age subgroups, MT was associated with higher odds of good outcome in patients ≥70 years (OR: 1.95, 95% CI: 1.26–3.03) and ≥80 years (OR: 4.43, 95% CI: 1.02–19.23). Conclusion: MT increases the likelihood of achieving a good outcome in elderly and non-elderly patients without increasing the risk of severe disability or death. MT, when otherwise clinically indicated, should be considered over BMM alone in both age groups.
Increased Responsiveness of Stored Platelets after Short-Term Refrigeration
Authors: Zeller-Hahn Julia , Kobsar Anna , Bittl Marius , Koessler Angela , Weber Katja , Boeck Markus , Koessler Juergen
Published: October 2023

Introduction: Refrigeration of platelets is considered to provide advantages in therapy of acute hemorrhage due to increased platelet responsiveness. The alleviation of inhibitory signaling caused by cold temperature (CT) has been identified as an important mechanism contributing to enhanced platelet reactivity, detectable in freshly prepared platelets within 1 h of cold storage. The aim of this study was to confirm the effects of short-term refrigeration in platelets from apheresis-derived platelet concentrates (APC). Methods: APC were stored under standardized conditions for 1 day or for 2 days at room temperature and then refrigerated for 1 h, followed by sampling of platelets for analysis. Platelet reactivity was measured by aggregation studies using threshold concentrations of different agonists and by detection of fibrinogen binding using flow cytometry. The exploration of inhibitory signaling comprised the detection of VASP phosphorylation using flow cytometry or Western blot and the measurement of cyclic nucleotide levels. Results: Aggregation responses induced with ADP, collagen, or thrombin receptor-activating peptide-6 (TRAP-6) were increased in APC after cold storage for 1 h, associated with elevated TRAP-6-induced fibrinogen binding. VASP phosphorylation levels were decreased after cold exposition, detectable in 1-day- and 2-day-stored APC with flow cytometry, and in 2-day-stored APC with Western blot technique. Induced cGMP levels were lower after storage at CT in APC on day 1 and on day 2, whereas cAMP levels were reduced on 2-day-stored APC. Conclusion: Short-term refrigeration for 1 h is sufficient to induce an attenuation of inhibitory signaling, accompanied with increased aggregation responses in APC stored for up to 2 days. The “on demand” refrigeration of PC may be a reasonable approach for the preparation of platelets with enhanced responsiveness to treat patients with hemorrhage more effectively, which should be further addressed in consecutive studies.
Pulmonary Embolism Associated with Major Liposuction: A Case Report
Authors: Elgohary Doaa , Nadeem Rashid
Published: October 2023

Pulmonary embolism (PE) is probably the leading cause of death associated with liposuction. It occurs most frequently with general anesthesia or heavy intravenous sedation. Thrombosis is a manifestation of a complex series of events leading to vascular inflammation. A relationship may exist between the risk of thromboembolism and surgical or anesthetic techniques. New information may permit the liposuction surgeon to identify more easily and thus avoid patients at increased risk. In addition to massive liposuction and other co factors, was also COVID positive, several studies have documented an association between the COVID-19 pathogenesis and a pro-coagulant pattern that may lead to higher risk of thrombosis. Incidence of acute PE among patients hospitalized with COVID-19 ranged between 1.6 and 62.5%.
Antidepressants and Social Functioning in Patients with Major Depressive Disorder: Systematic Review and Meta-Analysis of Double-Blind, Placebo-Controlled RCTs
Authors: Kremer Stefanie , Wiesinger Teresa , Bschor Tom , Baethge Christopher
Published: October 2023

Introduction: Social functioning (SF) is the ability to fulfil one’s social obligations and a key outcome in treatment. Objective: The aim of the study was to estimate the effects of antidepressants on SF in patients with major depressive disorder (MDD). Methods: This meta-analysis and its reporting are based on Cochrane Collaboration’s Handbook of Systematic Reviews and Meta-Analyses and PRISMA guidelines (protocol registration at OSF). We systematically searched CENTRAL, Medline, PubMed Central, and PsycINFO for double-blind RCTs comparing antidepressants with placebo and reporting on SF. We computed standardized mean differences (SMDs) with 95% CIs and prediction intervals. Results: We selected 40 RCTs out of 1,188 records screened, including 16,586 patients (mean age 46.8 years, 64.2% women). In 27 studies investigating patients with MDD (primary depression), antidepressants resulted in a SMD of 0.25 compared to placebo ([95% CI: 0.21; 0.30] I2: 39%). In 13 trials with patients suffering from MDD comorbid with physical conditions or disorders, the summary estimate was 0.24 ([0.10; 0.37] I2: 75%). In comorbid depression, studies with high/uncertain risk of bias had higher SMDs than low-risk studies: 0.29 [0.13; 0.44] versus 0.04 [−0.16; 0.24]; no such effect was evident in primary depression. There was no indication of sizeable reporting bias. SF efficacy correlated with efficacy on depression scores, Spearman’s rho 0.67 (p < 0.001), and QoL, 0.63 (p < 0.001). Conclusions: The effect of antidepressants on SF is small, similar to its effect on depressive symptoms in primary MDD, and doubtful in comorbid depression. Strong correlations with both antidepressive and QoL effects suggest overlap among domains.
Effects of Elevated Intraocular Pressure on Retinal Ganglion Cell Density and Expression and Interaction of Retinal Aquaporin 9 and Monocarboxylate Transporters
Authors: Murai Yusuke , Mori Sotaro , Okuda Mina , Kusuhara Sentaro , Kurimoto Takuji , Nakamura Makoto
Published: October 2023

Introduction: Astrocyte-to-neuron lactate shuttle (ANLS) plays an important role in the energy metabolism of neurons, including retinal ganglion cells (RGCs). Aquaporin 9 (AQP9), which is an aquaglyceroporin that can transport lactate, may be involved in ANLS together with monocarboxylate transporters (MCTs) to maintain RGC function and survival. This study aimed to investigate the impact of elevated intraocular pressure (IOP) on AQP9-MCT interaction and RGC survival. Methods: IOP was elevated in Aqp9 knock-out (KO) mice and wild-type (WT) littermates by anterior chamber microbead injection. RGC density was measured by TUBB3 immunostaining on retinal flat mounts. Immunolabeling, immunoblot, and immunoprecipitation were conducted to identify and quantitate expressions of AQP9, MCT1, MCT2, and MCT4 in whole retinas and ganglion cell layer (GCL). Results: Aqp9 KO and WT mice had similar RGC density at baseline. Microbead injection increased cumulative IOP by approximately 32% up to 4 weeks, resulting in RGC density loss of 42% and 34% in WT and Aqp9 KO mice, respectively, with no statistical difference. In the retina of WT mice, elevated IOP decreased the amount of AQP9, MCT1, and MCT2 protein and changed the AQP9 immunoreactivity and reduced MCT1 and MCT2 immunoreactivities in GCL. Meanwhile, it decreased MCT1 and increased MCT2 that interact with AQP9, without affecting MCT4 expression. Aqp9 gene deletion increased baseline MCT2 expression in the GCL and counteracted IOP elevation regarding MCT1 and MCT2 expressions. Conclusion: The compensatory upregulation of MCT1 and MCT2 with Aqp9 gene deletion and ocular hypertension may reflect the need to maintain lactate transport in the retina for RGC survival.
Transcription Factor Sox9 Exacerbates Kidney Injury through Inhibition of MicroRNA-96-5p and Activation of the Trib3/IL-6 Axis
Authors: Wang Xiao , Chen Guang , Du Yongqiang , Yang Jiajia , Wang Wei
Published: October 2023

Introduction: Our study investigated the possible mechanisms of the role of the transcription factor Sox9 in the development and progression of kidney injury through regulation of the miR-96-5p/Trib3/IL-6 axis. Methods: Bioinformatics analysis was performed to identify differentially expressed genes in kidney injury and normal tissues. An in vivo animal model of kidney injury and an in vitro cellular model of kidney injury were constructed using LPS induction in 8-week-old female C57BL/6 mice and human normal renal tubular epithelial cells HK-2 for studying the possible roles of Sox9, miR-96-5p, Trib3, and IL-6 in kidney injury. Results: Sox9 was highly expressed in both mouse and cellular models of kidney injury. Sox9 was significantly enriched in the promoter region of miR-96-5p and repressed miR-96-5p expression. Trib3 was highly expressed in both mouse and cellular models of kidney injury and promoted inflammatory responses and kidney injury. In addition, Trib3 promoted IL-6 expression, which was highly expressed in kidney injury, and promoted the inflammatory response and extent of injury in kidney tissue. In vivo and in vitro experiments confirmed that the knockdown of Sox9 improved the inflammatory response and fibrosis of mouse kidney tissues and HK-2 cells, while the ameliorative effect of silencing Sox9 was inhibited by overexpression of IL-6. Conclusion: Collectively, Sox9 up-regulates miR-96-5p-mediated Trib3 and activates the IL-6 signaling pathway to exacerbate the inflammatory response, ultimately promoting the development and progression of kidney injury.
Hydatid Disease of the Liver
Authors: Bhalla Virandera Pal , Paul Souvik , Klar Ernst
Published: October 2023

Background: Echinococcosis also known as hydatid disease is a zoonotic parasitic disease caused by a tapeworm. It has a worldwide distribution. For long, it was thought to be a problem of the poorly sanitized “third world” and not given the importance it deserved. However, its occurrence in countries like Australia and New Zealand and recently in countries in Central Europe has meant that it is included in a WHO list of neglected diseases, has recently been the subject of extensive epidemiological studies, and has been the recipient of increased research funding. Summary: The diagnosis is still based on clinical presentation in an endemic area corroborated with typical findings on imaging which routinely include ultrasound and CT scan. Serological tests have been used in some centers to support the diagnosis. Treatment depends on the site of involvement and can vary from wait and watch to extensive radical surgical procedures. The common element of all treatments is the addition of albendazole which forms an essential cornerstone of all treatment protocols. Inspite having been used for a fairly long time, there is still no consensus on the dose, duration, and timing of therapy with albendazole. Key Message: Hydatid disease continues to be a significant global health problem inspite of a good understanding of its life cycle and rising standards of public sanitation. Though diagnosis is straightforward and not expensive, treatment can sometimes be complicated. The addition of albendazole to all treatment protocols is an important advance, but firm guidelines on duration of its use are still awaited.
Two Distinct Characteristics of Immune Microenvironment in Human Hepatocellular Carcinoma with Wnt/β-Catenin Mutations
Authors: Aoki Tomoko , Nishida Naoshi , Kurebayashi Yutaka , Sakai Kazuko , Morita Masahiro , Chishina Hirokazu , Takita Masahiro , Hagiwara Satoru , Ida Hiroshi , Ueshima Kazuomi , Minami Yasunori , Tsurusaki Masakatsu , Nakai Takuya , Sakamoto Michiie , Nishio Kazuto , Kudo Masatoshi
Published: October 2023

Introduction: Immunotherapy is becoming a promising approach for unresectable-hepatocellular carcinoma (HCC); the anti-tumor response is affected by the tumor microenvironment (TME). Although Wnt/β-catenin mutations are reported to cause non-inflamed phenotype, their role on TME remains controversial. We aimed to clarify the heterogeneity of immunophenotype in HCC with Wnt/β-catenin mutations. Methods: This study includes 152 resected HCCs; mutations in the catenin beta-1, adenomatous polyposis coli, or AXIN1, or AXIN2 genes were defined as Wnt/β-catenin mutations. With hierarchical cluster analyses, TME was classified into inflamed or non-inflamed classes based on the gene expressions associated with T-cell activation. Expression profiles of molecules related to cell differentiation and biliary-stem cell markers were compared between the TME classes to investigate whether differences in tumor traits were associated with TME. Results: Forty of 152 (26.3%) HCCs carried the Wnt/β-catenin mutations. Of these, 33 were classified as non-inflamed (33/40, 82.5%) and 7 as inflamed (7/40, 17.5%). Non-inflamed class was characterized by low number of CD3+, CD4+, and CD8+ cells on immunostaining, and high mRNA expressions of AXIN2 and GLUL, which are involved in the canonical Wnt/β-catenin signaling and hepatocyte differentiation, respectively. Non-inflamed tumors showed higher enhancement on the hepatobiliary-phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) compared to inflamed tumors. HCCs classified as inflamed class are revealed to have high numbers of CD3+, CD4+, and CD8+ tumor infiltrating lymphocytes on immunostaining. This class is associated with increased expression of anti-epithelial cell adhesion molecule and FOXM1 accompanied by upregulation of genes related to interferon-gamma signaling, dendritic cell migration, regulatory T cells, and myeloid-derived suppressor cell activation and recognized as low enhancement nodule on Gd-EOB-DTPA-enhanced MRI. Conclusion: Heterogeneity of tumor traits and TME was observed in HCC with Wnt/β-catenin mutation. The potential was indicated that tumor traits and TME are determined not only by the activation of the HNF4A but also by FOXM1, both of which are downstream transcription factor of the Wnt/β-catenin signaling pathway.