bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimuli-responsive hydrogels: smart state of-the-art platforms for cardiac tissue engineering
Authors: El-Husseiny Hussein M. , Mady Eman A. , El-Dakroury Walaa A. , Doghish Ahmed S. , Tanaka Ryou
Published: June 2023

Biomedicine and tissue regeneration have made significant advancements recently, positively affecting the whole healthcare spectrum. This opened the way for them to develop their applications for revitalizing damaged tissues. Thus, their functionality will be restored. Cardiac tissue engineering (CTE) using curative procedures that combine biomolecules, biomimetic scaffolds, and cells plays a critical part in this path. Stimuli-responsive hydrogels (SRHs) are excellent three-dimensional (3D) biomaterials for tissue engineering (TE) and various biomedical applications. They can mimic the intrinsic tissues’ physicochemical, mechanical, and biological characteristics in a variety of ways. They also provide for 3D setup, adequate aqueous conditions, and the mechanical consistency required for cell development. Furthermore, they function as competent delivery platforms for various biomolecules. Many natural and synthetic polymers were used to fabricate these intelligent platforms with innovative enhanced features and specialized capabilities that are appropriate for CTE applications. In the present review, different strategies employed for CTE were outlined. The light was shed on the limitations of the use of conventional hydrogels in CTE. Moreover, diverse types of SRHs, their characteristics, assembly and exploitation for CTE were discussed. To summarize, recent development in the construction of SRHs increases their potential to operate as intelligent, sophisticated systems in the reconstruction of degenerated cardiac tissues.
Weak noncovalent interactions in two positional isomers of acrylonitrile derivatives: inputs from PIXEL energy, Hirshfeld surface and QTAIM analyses
Authors: Percino M. Judith , Udayakumar Mani , Cerón Margarita , Pérez-Gutiérrez Enrique , Venkatesan Perumal , Thamotharan Subbiah
Published: June 2023

A single crystal X-ray diffraction analysis was performed on two positional isomers (m-tolyl and p-tolyl) of acrylonitrile derivatives, namely, (Z)-3-(4-(pyridin-2-yl) phenyl)-2-(m-tolyl) acrylonitrile (1) and (Z)-3-(4-(pyridin-2-yl)phenyl)-2-(p-tolyl) acrylonitrile (2). Compound 1 crystallized in the monoclinic P21/n space group with two crystallographically independent molecules. Compound 2 also possesses two crystallographically independent molecules and crystallized in the triclinic P-1 space group. The Hirshfeld surface analysis revealed that, in both isomers, intermolecular H⋅⋅⋅H/C/N contacts contribute significantly to the crystal packing. More than 40% of the contribution arises from intermolecular C–H⋅⋅⋅C(π) contacts. In both compounds, the relative contribution of these contacts is comparable, indicating that the positional isomeric effects are marginal. The structures in which these isomers are arranged in the solid state are very similar, and the lattice energies are also comparable between the isomers. The Coulomb-London-Pauli-PIXEL (CLP-PIXEL) energy analysis identified the energetically significant dimers. The strength of the intra- and intermolecular interactions was evaluated using the quantum theory of atoms in molecules approach. The UV-Vis absorbance in three different solvents (chloroform, ethanol, and ethyl acetate) for isomers 1 and 2 are very similar. This result is in good agreement with the time-dependent density-functional theory (TD-DFT) calculations.
Development of the first geldanamycin-based HSP90 degraders
Authors: Wurnig Silas , Vogt Melina , Hogenkamp Julian , Dienstbier Niklas , Borkhardt Arndt , Bhatia Sanil , Hansen Finn K.
Published: June 2023

Despite the early clinical promise, adverse events such as acquired resistance and dose-limiting toxicities have barred the widespread use of HSP90 inhibitors as anticancer drugs. A new approach involving proteolysis-targeting chimeras (PROTACs) to degrade the protein instead of inhibiting it may overcome these problems. In this work, we describe the design, synthesis, and evaluation of cereblon-recruiting geldanamycin-based HSP90 degraders based on the PROTAC technology. Our best degrader, 3a, effectively decreased HSP90α and HSP90β levels in cells utilizing the ubiquitin–proteasome pathway.
Case report: A case of ocular infection caused by Corynespora cassiicola
Authors: Wang Qin , Wang Lu , Lian Lisha , Pu Xiaofeng , Tang Lu , Li Yanmei , Liu Yuan
Published: June 2023

Objective

The aim of this study is to identify the pathogen causing ocular infection in a Chinese patient and to describe its morphological characteristics.

Methods

Samples from the patient’s intraoperative pus were collected for microscopic examination and culture. Morphology and drug sensitivities of the isolated fungus were analyzed. Ribosomal DNA (rDNA) sequencing was performed and blasted in GenBank.

Results

A strain of fungi was repeatedly isolated from pus samples in different types of medium. No conidia were shown when the isolate cultured on normal PDA medium, whereas pseudoseptate thick-walled conidia were shown when cultured on medium containing leaf leachate. The results of BLAST and phylogenetic trees based on internal transcribed spacer, beta-tubulin, translation elongation factor 1-alpha, and RNA polymerase II gene demonstrated that the isolated fungus was Corynespora cassiicola. Minimum inhibitory concentration results of this organism were as follows: anidulafungin, 0.06 μg/ml; amphotericin B, 0.12 μg/ml; micafungin, 0.06 μg/ml; caspofungin, 0.5 μg/ml; 5-fluorocytosine, >64 μg/ml; posaconazole, 2 μg/ml; voriconazole, 0.25 μg/ml; itraconazole, 0.5 μg/ml; fluconazole, 64 μg/ml.

Conclusion

The case was infected with Corynespora cassiicola and led to eye suppurative endophthalmitis and blindness. Combined applications of morphological and molecular biology techniques facilitate accurate diagnosis of fungal infections.
Acute limb ischemia caused by floating thrombus in the aorta: a case report and literature review
Authors: Guo Fuzheng , He Zhibin
Published: June 2023

This report presents a patient with rheumatoid arthritis and COVID-19 infection one month earlier who experienced embolic episodes resulting in acute lower-limb ischemia from an unusual source. The blood flow was successfully restored by femoropopliteal thromboembolectomy. In determining the source of the embolism, the patient underwent electrocardiogram, transthoracic echocardiogram, and aortic CTA. The latter revealed a large, pedunculated, and mobile thrombus arising from the aortic arch and the descending thoracic aorta. Considering the patient's general health condition, we performed anticoagulation of the floating thrombus in the aortic lumen. The mechanism of aortic floating thrombosis exhibits considerable complexity. There are no standardized treatment protocols or clinical guidelines, and its treatment mainly includes open surgery, aortic endoluminal stent -graft insertion and pharmacological anticoagulation. Treatment strategy should be based on the cause of the disease and the patient's physical condition.
Successes and challenges of artificial intelligence in cardiology
Authors: Vandenberk Bert , Chew Derek S. , Prasana Dinesh , Gupta Sunny , Exner Derek V.
Published: June 2023

In the past decades there has been a substantial evolution in data management and data processing techniques. New data architectures made analysis of big data feasible, healthcare is orienting towards personalized medicine with digital health initiatives, and artificial intelligence (AI) is becoming of increasing importance. Despite being a trendy research topic, only very few applications reach the stage where they are implemented in clinical practice. This review provides an overview of current methodologies and identifies clinical and organizational challenges for AI in healthcare.
Oxidative stress and mitochondrial dysfunction of granulosa cells in polycystic ovarian syndrome
Authors: Gao Yiyin , Zou Yinggang , Wu Guijie , Zheng Lianwen
Published: June 2023

Polycystic ovarian syndrome (PCOS) is one of the leading causes of anovulatory infertility in women, affecting 5%–15% of women of reproductive age worldwide. The clinical manifestations of patients include ovulation disorders, amenorrhea, hirsutism, and obesity. Life-threatening diseases, such as endometrial cancer, type 2 diabetes, hyperlipidaemia, hypertension, and cardiovascular disease, can be distant complications of PCOS. PCOS has diverse etiologies and oxidative stress (OS) plays an important role. Mitochondria, as the core organelles of energy production, are the main source of reactive oxygen species (ROS). The process of follicular growth and development is extremely complex, and the granulosa cells (GCs) are inextricably linked to follicular development. The abnormal function of GCs may directly affect follicular development and alter many symptoms of PCOS. Significantly higher levels of OS markers and abnormal mitochondrial function in GCs have been found in patients with PCOS compared to healthy subjects, suggesting that increased OS is associated with PCOS progression. Therefore, the aim of this review was to summarize and discuss the findings suggesting that OS and mitochondrial dysfunction in GCs impair ovarian function and induce PCOS.
Coffee consumption decreases the connectivity of the posterior Default Mode Network (DMN) at rest
Authors: Picó-Pérez Maria , Magalhães Ricardo , Esteves Madalena , Vieira Rita , Castanho Teresa C. , Amorim Liliana , Sousa Mafalda , Coelho Ana , Moreira Pedro S. , Cunha Rodrigo A. , Sousa Nuno
Published: June 2023

Habitual coffee consumers justify their life choices by arguing that they become more alert and increase motor and cognitive performance and efficiency; however, these subjective impressions still do not have a neurobiological correlation. Using functional connectivity approaches to study resting-state fMRI data in a group of habitual coffee drinkers, we herein show that coffee consumption decreased connectivity of the posterior default mode network (DMN) and between the somatosensory/motor networks and the prefrontal cortex, while the connectivity in nodes of the higher visual and the right executive control network (RECN) is increased after drinking coffee; data also show that caffeine intake only replicated the impact of coffee on the posterior DMN, thus disentangling the neurochemical effects of caffeine from the experience of having a coffee.
Distinctive properties of biological neural networks and recent advances in bottom-up approaches toward a better biologically plausible neural network
Authors: Jeon Ikhwan , Kim Taegon
Published: June 2023

Although it may appear infeasible and impractical, building artificial intelligence (AI) using a bottom-up approach based on the understanding of neuroscience is straightforward. The lack of a generalized governing principle for biological neural networks (BNNs) forces us to address this problem by converting piecemeal information on the diverse features of neurons, synapses, and neural circuits into AI. In this review, we described recent attempts to build a biologically plausible neural network by following neuroscientifically similar strategies of neural network optimization or by implanting the outcome of the optimization, such as the properties of single computational units and the characteristics of the network architecture. In addition, we proposed a formalism of the relationship between the set of objectives that neural networks attempt to achieve, and neural network classes categorized by how closely their architectural features resemble those of BNN. This formalism is expected to define the potential roles of top-down and bottom-up approaches for building a biologically plausible neural network and offer a map helping the navigation of the gap between neuroscience and AI engineering.
Surgical techniques for evacuation of chronic subdural hematoma: a mini-review
Authors: Rodriguez Benjamin , Morgan Isabella , Young Tirone , Vlastos Joseph , Williams Tyree , Hrabarchuk Eugene I. , Tepper Jaden , Baker Turner , Kellner Christopher P. , Bederson Joshua , Rapoport Benjamin I.
Published: June 2023

Chronic subdural hematoma is one of the most common neurosurgical pathologies with over 160,000 cases in the United States and Europe each year. The current standard of care involves surgically evacuating the hematoma through a cranial opening, however, varied patient risk profiles, a significant recurrence rate, and increasing financial burden have sparked innovation in the field. This mini-review provides a brief overview of currently used evacuation techniques, including emerging adjuncts such as endoscopic assistance and middle meningeal artery embolization. This review synthesizes the body of available evidence on efficacy and risk profiles for each critical aspect of surgical technique in cSDH evacuation and provides insight into trends in the field and promising new technologies.
Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis
Authors: Tao Jing-Wei , Fan Xiao , Zhou Jing-Ya , Huo Lu-Yao , Mo Yan-Jun , Bai Hui-Zhong , Zhao Yi , Ren Jing-Pei , Mu Xiao-Hong , Xu Lin
Published: June 2023

Background

Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury.

Objective

To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI.

Methods

We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria.

Results

Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35  days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92–2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9–T10 or T10 segment injury model and the T8–T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger’s test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy.

Conclusion

Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.

Systematic review registration: PROSPERO, identifier: CRD42023388315.
Impact of e-cigarette vaping aerosol exposure in pregnancy on mTOR signaling in rat fetal hippocampus
Authors: Lee Jehoon , Orzabal Marcus R. , Naik Vishal D. , Ramadoss Jayanth
Published: June 2023

Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and many view them as less harmful and may help quit or reduce combustible cigarettes. Implementing a state-of-the-art engineered vaping system, comprising an atomizer similar to those sold in vape shops, we aimed to utilize a translational e-cig inhalation delivery method to provide crucial information on the impact of prenatal e-cig aerosols on the developing brain hippocampal mTOR system in a rat model system. Gestational e-cig vaping significantly increased P-mTOR levels (p < 0.05) in the rat fetal hippocampi in the nicotine group (comprising of VG/PG + nicotine) compared to the control and the juice (comprising of VG/PG) groups. Total mTOR expression was not different among groups. Immunofluorescence imaging demonstrated P-mTOR was detected exclusively in the granule cells of the dentate gyrus of the fetal hippocampus. E-cig did not alter DEPTOR, but RAPTOR and RICTOR were higher (p < 0.05) in the Nicotine group. Gestational e-cig vaping with nicotine increased (p < 0.05) the activity and expression of 4EBP1, p70S6K, but decreased (p < 0.05) P-PKCα in the fetal hippocampi. In summary, dysregulation of mTORC1 and the related mTORC2, their activity, and downstream proteins together may play a critical role in e-cig-vaping-induced neurobiological phenotypes during development.
Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey
Authors: Ünal Çağlar , Özmen Tolga , Ordu Çetin , Pilanci Kezban Nur , İlgün Ahmet Serkan , Gökmen Erhan , Almuradova Elvina , Özdoğan Mustafa , Güler Nilüfer , Uras Cihan , Kara Halil , Demircan Orhan , Işık Selver , Alço Gül , Saip Pınar , Aydın Esra , Duymaz Tomris , Çelebi Filiz , Yararbaş Kanay , Soybir Gursel , Ozmen Vahit
Published: June 2023

Background

The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions.

Patients and methods

Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS.

Results

A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18.

Conclusion

This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.
Oncoplastic and reconstructive breast surgery
Authors: Wignarajah Primeera , Malata Charles M. , Benson John R.
Published: June 2023

This article provides an overview of the principles and techniques of oncoplastic and reconstructive breast surgery for patients with early-stage breast cancer. Oncoplastic breast surgery (OPBS) with partial breast reconstruction is a natural evolution in the application of breast conserving surgery and permits wide surgical resection of tumours that might otherwise mandate mastectomy and whole breast reconstruction. These reconstructive techniques must be optimally selected and integrated with ablative breast surgery together with non-surgical treatments such as radiotherapy and chemotherapy that may be variably sequenced with each other. A multidisciplinary approach with shared decision-making is essential to ensure optimal clinical and patient-reported outcomes that address oncological, aesthetic, functional and psychosocial domains. Future practice of OPBS must incorporate routine audit and comprehensive evaluation of outcomes.
Clinical features and surgical outcomes of high grade pleomorphic xanthoastrocytomas: a single-center experience with a systematic review
Authors: Zuo Pengcheng , Li Tian , Sun Tao , Wu Wenhao , Wang Yujin , Zhang Mingxin , Wu Zhen , Zhang Junting , Zhang Liwei
Published: June 2023

Purpose

High grade pleomorphic xanthoastrocytomas (HGPXAs) are very rare and their management and prognostic outcomes remain unclear. To better understand the disease, we aimed to evaluate the risk factors for progression-free survival (PFS) and overall survival (OS), and propose a treatment protocol based on cases from our institute and cases from the literature.

Methods

The authors reviewed the clinical data of 26 patients with HGPXAs who underwent surgical treatment in Department of Neurosurgery of Beijing Tiantan Hospital between August 2014 and September 2021. We also searched the PubMed database using the keywords “anaplastic” combined with “pleomorphic xanthoastrocytoma(s)” between January 1997 and October 2022. Risk factors for PFS and OS were evaluated in the pooled cases.

Results

The authors’ cohort included 11 males and 15 females with a mean age of 36.7 ± 20.3 years (range: 5.5-71 years). Gross-total resection (GTR) and non-GTR were achieved in 17 (65.4%) and 9 (34.6%) patients, respectively. Radiotherapy and chemotherapy were administered to 22 and 20 patients, respectively. After a mean follow-up of 20.5 ± 21.2 months (range: 0.5-78.1 months), 7 patients suffered tumor recurrence and 6 patients died with a mean OS time of 19.4 ± 10.8 months (range: 8-36 months). In the literature between January 1997 and October 2022, 56 cases of HGPXAs were identified in 29 males and 27 females with a mean age of 29.6 ± 19.6 years (range; 4-74 years). Among them, 24 (44.4%) patients achieved GTR. Radiotherapy and chemotherapy was administered to 31 (62%) patients and 23 (46%) patients, respectively. After a median follow-up of 31.4 ± 35.3 months (range: 0.75-144 months), the mortality and recurrence rates were 32.5% (13/40) and 70% (28/40), respectively. Multivariate Cox regression model demonstrated that non-GTR (HR 0.380, 95% CI 0.174-0.831, p=0.015), age≥30 (HR 2.620, 95% CI 1.183-5.804, p=0.018), no RT (HR 0.334,95% CI 0.150-0.744, p=0.007) and no CT (HR 0.422, 95% CI 0.184-0.967, p=0.042) were negative prognostic factors for PFS. Non-GTR (HR 0.126, 95% CI 0.037-0.422, p=0.001), secondary HGPXAs (HR 7.567, 95% CI 2.221-25.781, p=0.001), age≥30 (HR 3.568, 95% CI 1.190-10.694, p=0.023) and no RT (HR 0.223,95% CI 0.073-0.681, p=0.008) were risk factors for OS.

Conclusion:

High grade pleomorphic xanthoastrocytomas are very rare brain tumors. Children and younger adults have better clinical outcome than elderly patients. Secondary HGPXAs had worse OS than primary HGPXAs. Complete surgical excision plus RT and CT is recommended for this entity. The frequency of BRAF mutations in HGPXAs is 47.5% (19/40) in this study, however, we do not find the connections between BRAF mutations and clinical outcomes. Future studies with larger cohorts are necessary to verify our findings.
Cost-effectiveness and budget impact of pembrolizumab+axitinib versus sunitinib in patients with advanced clear-cell renal cell carcinoma in the Netherlands
Authors: Xander Nicolas S. H. , Fiets W. Edward , Uyl-de Groot Carin A.
Published: June 2023

Background

The phase 3 clinical trial KEYNOTE-426 suggested a higher efficacy regarding overall survival (OS) and progression-free survival (PFS) of pembrolizumab+axitinib compared to sunitinib as a first-line treatment for patients with advanced renal cell carcinoma. In this analysis, the potential cost-effectiveness of this combination treatment versus sunitinib for patients with advanced clear-cell renal cell carcinoma (accRCC) was examined from the societal perspective in the Netherlands.

Methods

For this analysis, a partitioned survival model was constructed. Clinical data were obtained from the published KEYNOTE-426 trial reports; data on costs and (dis-)utilities were derived from published literature. Costs outside of the healthcare sector included treatment-related travel, informal care and productivity loss. Next to a probabilistic scenario analysis, various scenario analyses were performed that aimed at survival extrapolation, different utility values, treatment duration and drug pricing, as well as restricting the cohort to patients with an intermediate or poor prognosis. Further, a budget impact analysis over three years was conducted, in which a sensitivity analysis concerning ranges in costs and the number of patients was applied. Moreover, a scenario concerning increasing market penetration of pembrolizumab+axitinib up to a market share of 80% in the third year was analyzed.

Results

The incremental cost-effectiveness ratio (ICER) of pembrolizumab+axitinib was estimated at €368,396/quality-adjusted life year (QALY) gained, with an incremental QALY gain of 0.55 over sunitinib. The probability of cost-effectiveness at a willingness-to-pay threshold of €80,000/QALY was estimated at 0%, a 50% probability was estimated at €340,000/QALY. Cost-effectiveness was not achieved in any of the applied scenarios. The budget impact over three years amounted to €417.3 million upon instantaneous and full replacement of sunitinib, and to €214.9 million with increasing market penetration.

Conclusion

Pembrolizumab+axitinib was not estimated to be cost-effective compared to sunitinib as a first-line treatment for patients with accRCC in the Netherlands from a societal perspective. In none of the analyzed scenarios, cost-effectiveness was achieved. However, price reductions and shorter treatment durations might lead to a more favorable ICER.
People's experiences living with peripheral neuropathy: a qualitative study
Authors: Alkandari Maryam , Hollywood Amelia
Published: June 2023

Introduction

Peripheral neuropathy is a neurological disorder characterised by pain, numbness, or tingling due to nerve damage. Peripheral neuropathy is one of the main health issues in Kuwait and is a rising concern which affects a large proportion of the population, therefore the lived experience needs to be explored to identify areas for improvement in care. This qualitative study explored the experiences of people living with peripheral neuropathy in Kuwait.

Methods

Semi-structured interviews were conducted with 25 participants recruited from the Neurology Outpatient Clinic of the Ibn Sina Hospital in Kuwait. The interview questions explored their experiences and understanding of pain along with the impact on their daily life. The interviews were audio recorded, transcribed and translated into English then coded using NVivo 12. Thematic analysis was conducted to identify patterns and themes in the data.

Results

Three major themes were identified including treatment beliefs (perceived effectiveness of treatment and seeking alternative treatments), the barriers to pain management (medication side effects, relationships with healthcare professionals and lack of information and access to healthcare), and the impact on quality of life (impact on work and social, physical, and psychological consequences). Self-efficacy was a key construct and over-arching theme that was discussed in all aspects, which finds reflection in the protection motivation theory.

Discussion

This paper presents the experiences of people living with peripheral neuropathy and highlights there is scope for improvement of current treatments in Kuwait. Self-management strategies are recommended alongside prescribed medication and healthcare professionals are encouraged to use a patient-centered approach. More importantly, information and support on the condition to promote coping strategies and self-efficacy should be adopted to improve quality of life. These findings can be implemented locally and globally to improve the quality of care provided to people living with peripheral neuropathy.
Dalbavancin as suppressive antibiotic therapy in patients with prosthetic infections: efficacy and safety
Authors: Ruiz-Sancho Andrés , Núñez-Núñez María , Castelo-Corral Laura , Martínez-Marcos Francisco Javier , Lois-Martínez Nagore , Abdul-Aziz Mohd Hafiz , Vinuesa-García David
Published: June 2023

Suppressive antibiotic therapy (SAT) is a strategy to alleviate symptoms and/or to reduce the progression of an infection when other treatment options cannot be used. Dalbavancin, due to its prolonged half-life, enables (bi) weekly dosing. Here, we report our multicenter real-life clinical experience with dalbavancin used as SAT in patients with prosthetic joint or vascular infections. Medical records of all adult patients with documented vascular or orthopedic chronic prosthetic infections, who received dalbavancin as SAT between 2016 and 2018 from four Spanish hospitals were reviewed for inclusion. Descriptive analysis of demographic characteristics, Charlson Comorbidity index, Barthel index, isolated pathogens and indication, concomitant antibiotic use, adverse events, and clinical outcome of SAT were performed. Eight patients were eligible for inclusion, where six patients had prosthetic vascular infections (aortic valve) and two patients had knee prosthetic joint infections. The most common pathogens were methicillin-susceptible Staphylococcus aureus and Enterococcus faecium. All patients had a history of prior antibiotic treatment for the prosthetic infection [median duration of antibiotic days 125 days (IQR, 28–203 days)]. The median number of dalbavancin doses was 29 (IQR, 9–61) and concomitant antibiotic use (n = 5, 62.5%). Clinical success was reported in 75% (n = 6) of patients. Adverse events were reported in two patients (mild renal and hepatic impairment). The median estimated cost savings due to the avoided hospital days was €60185 (IQR, 19,916–94984) per patient. Despite the limitations of our study, this preliminary data provides valuable insight to support further evaluation of dalbavancin for SAT in patients with prosthetic infections in the outpatient setting when alternative treatments are not feasible.
The optimal method for improving postural balance in healthy young and older people: specific training for postural tasks encountered in personal physical practice
Authors: Paillard Thierry
Published: June 2023

It is well known that regular exercise or physical activity (training) improves postural balance in healthy young and older subjects, but the optimal exercise or physical activity (i.e., likely to induce the greatest postural improvements) and the context in which it is carried out remain to be explored and determined for each population. The most beneficial adaptations would depend, in particular, on gestural conditions (body position, movement and gesture practiced) and material conditions (nature of the ground surface, sports equipment used, type of environment - stable or changing). In fact, the global postural adaptations induced by training do not result from the transfer between different trained and untrained postural tasks, but are the sum of the adaptations related to each trained postural task in healthy young and older subjects. Based on current knowledge, optimal training programs should include the full range of postural tasks encountered in personal physical practice for each population. To date, the method of implementing progressive postural balance tasks with different degrees of difficulty and instability has been used as the effective method to improve postural balance, but it should not be considered as the reference method. Instead, it should be considered as a complementary method to the one based on specific postural tasks. An intervention strategy is proposed for young and older adults consisting of three different steps (general, oriented and specific/ecologic training). However, some parameters still need to be explored and possibly reconsidered in future studies to improve postural balance in an optimal way.
An open-label, acute clinical trial in adults to assess ketone levels, gastrointestinal tolerability, and sleepiness following consumption of (R)-1,3-butanediol (Avela™)
Authors: Lowder James , Fallah Shafagh , Venditti Carolina , Musa-Veloso Kathy , Kotlov Vassili
Published: June 2023

Introduction: A study was undertaken to determine the acute effects of a beverage made with Avela™ (R)-1,3-butanediol, on blood beta-hydroxybutyrate (BHB) levels (using the Keto-Mojo monitor), gastrointestinal (GI) tolerability (using the modified visual analogue scale GI Symptoms Tool), and sleepiness (using the Stanford Sleepiness Scale).

Methods: Following a 12-h overnight fast, 26 healthy adults consumed one beverage containing 11.5 g of (R)-1,3-butanediol at each of 0, 30, and 60 min, culminating in a total intake of 34.5 g of (R)-1,3-butanediol. Blood BHB levels, GI tolerability, and sleepiness were assessed at baseline (0 min), and at 30, 60, 90, 120, 180, 240, and 300 min. At 240 min, a protein bar was consumed.

Results: The mean (±SD) BHB fasting baseline level, maximal concentration, time at maximal concentration, and incremental area under the curve over 300 min were 0.23 ± 0.21 mmol/L, 2.10 ± 0.97 mmol/L, 133.85 ± 57.07 min, and 376.73 ± 156.76 mmol/L*min, respectively. BHB levels at each time point were significantly increased relative to baseline. In females, BHB Tmax was significantly greater (p = 0.046), and BHB iAUC0–300 min nearly significantly greater (p = 0.06) than in males.

Discussion: The beverage formulated with Avela™ had no impact on sleepiness and was generally well-tolerated, with no or mild GI symptoms reported in most participants. Mild headaches were reported as an adverse event by five participants and judged possibly related to the study product in two of the participants.
The origin and early evolution of cytokinin signaling
Authors: Powell Anahid E. , Heyl Alexander
Published: June 2023

Angiosperms, especiallyArabidopsisand rice, have long been at the center of plant research. However, technological advances in sequencing have led to a dramatic increase in genome and transcriptome data availability across land plants and, more recently, among green algae. These data allowed for an in-depth study of the evolution of different protein families – including those involved in the metabolism and signaling of phytohormones. While most early studies on phytohormone evolution were phylogenetic, those studies have started to be complemented by genetic and biochemical studies in recent years. Examples of such functional analyses focused on ethylene, jasmonic acid, abscisic acid, and auxin. These data have been summarized recently. In this review, we will focus on the progress in our understanding of cytokinin biology. We will use these data to synthesize key points about the evolution of cytokinin metabolism and signaling, which might apply to the evolution of other phytohormones as well.
L1 variation and L2 acquisition: L1 German /eː/-/ɛː/ overlap and its effect on the acquisition of L2 English /ɛ/-/æ/
Authors: Schlechtweg Marcel , Peters Jörg , Frank Marina
Published: June 2023

A person’s first language (L1) affects the way they acquire speech in a second language (L2). However, we know relatively little about the role different varieties of the L1 play in the acquisition of L2 speech. This study focuses on German (L1) learners of English (L2) and asks whether the degree to which German speakers distinguish between the two vowels /eː/ and /ɛː/ in their L1 has an impact on how well these individuals identify /æ/ and discriminate between the two English vowels /ɛ/ and /æ/. These two English vowels differ in both vowel quality and duration (/æ/ is longer than /ɛ/). We report on an identification and a discrimination experiment. In the first study, participants heard a sound file and were asked to indicate whether they heard “pen” or “pan” (or “pedal” or “paddle”). The stimuli differed from each other in terms of both vowel quality (11 steps on a spectral continuum from an extreme /æ/ to an extreme /ɛ/) and duration (short, middle, long). In the second study, participants had to signal whether two sound files they were exposed to differed from each other. We modeled the percentage of /æ/ (“pan,” “paddle”) selection (identification task only, binomial logistic regression), accuracy (discrimination task only, binomial logistic regression), and reaction time (identification and discrimination tasks, linear mixed effects models) by implementing the German Pillai score as a measure of vowel overlap in our analysis. Each participant has an individual Pillai score, which ranges from 0 (= merger of L1 German /eː/ and /ɛː/) to 1 (=maintenance of the contrast between L1 German /eː/ and /ɛː/) and had been established, prior to the perception experiments reported here, in a production study. Although the findings from the discrimination study remain inconclusive, the results from the identification test support the hypothesis that maintaining the vowel contrast in the L1 German leads to a more native-like identification of /æ/ in L2 English. We conclude that sociolinguistic variation in someone’s L1 can affect L2 acquisition.
The impact of basketball on the social adjustment of Chinese middle school students: the chain mediating role of interpersonal relationships and self-identity
Authors: Haoran Sui , Tianci Lu , Hanwen Chen , Baole Tao , Yiran Chen , Yan Jun
Published: June 2023

Background

This study examines the effects of 12 weeks of basketball on interpersonal relationships, self-identity and social adjustment of middle school students, as well as exploring the mediating role of interpersonal relationships and self-identity in basketball’s influence on social adjustment.

Methods

A total of 87 students from a middle school in Jiangsu Province, China, were selected to participate in this study. A 12-week basketball intervention experiment was conducted, and questionnaires were administered to measure the study variables. Common method bias test, normality test, ANOVA and Pearson correlation analysis were used to analyze the study variables. The theoretical model of this study was also validated using the Process plug-in developed by Hayes, setting p < 0.05 (two-tail) as statistically significant.

Results

After a 12-week basketball intervention experiment, the interpersonal relationships, self-identity and social adjustment of the middle school students in the experimental and control groups showed improvement, with the experimental group showing significantly more significant improvement than the control group. A 12-week basketball intervention can positively impact the social adjustment of middle school students, with interpersonal relationships and self-identity acting as a chain mediator in the impact process.
Stretch marks: a visible expression of connective’s involvement in autism spectrum disorders
Authors: Veronese Sheila , Zoccante Leonardo , Smania Nicola , Sbarbati Andrea
Published: June 2023

In autism spectrum disorders (ASDs) in the pediatric population, skin manifestations are generally attributable to the concomitance of allergic forms or to accidental, self-inflicted or abusive lesions. However, clinical evidence has highlighted the presence of an increasing number of abdominal stretch marks, probably caused by the increase in the number of obesity cases in the pediatric population, in general, and therefore also among children with ASD. Stretch marks are often attributed to obesity, as they have an incidence of more than 50% in obese individuals. In the first part of this article we hypothesized that in addition to obesity there are other factors, such as a structural alteration on the skin in people with ASD, which can contribute/aggravate the phenomenon of stretch marks. Despite the high frequency with which stretch marks are found in children with ASD, this aspect has never been studied, the structure of the skin of children with ASD is not known. Furthermore, it is not known whether this structure is different from that of subjects without ASD. In the second part of the article, we hypothesized the mechanisms of the negative impact of simple abdominal stretch marks on the symptomatic picture of children with ASD. The presence of stretch marks, altered tactile perception, altered sensitivity to clothing fabrics can be a combination that influences development and determines negative consequences in the neurological picture of a child with ASD, as it is already known that the altered sensory perception in children with ASD contributes to the deterioration of social behavior. Furthermore, the presence of stretch marks may play a role in the postural and motor defects of children with ASD.
Is a combination of individual consultations, text message reminders and interaction with a Facebook page more effective than educational sessions for encouraging university students to increase their physical activity levels?
Authors: Alsaleh Eman
Published: June 2023

Background

Physical activity (PA) has been consistently reported as a crucial component of disease prevention and improvement of people’s health. Nevertheless, data has evidenced a decline in physical activity levels among adults in Jordan. Although previous behavioral change interventions have documented efficacy in increasing physical activity among adults, the PA levels is low among adults. A new motivational intervention that focuses on changing behavior toward performing the recommended level of physical activity is on need.

Objective

This two-arm single-center randomized controlled trial aimed to measure the efficacy of a multi-component behavioral intervention (including goal setting, self-monitoring, and feed-back) for increasing physical activity levels and self-efficacy for exercise and decreasing body mass index and blood pressure among students at a Jordanian University.

Setting

Philadelphia University in Jordan.

Methods

A behavioral intervention based on individualized consultations, text messages reminders and interaction with a Facebook page was compared with educational sessions in terms of efficacy for increasing physical activity levels among students at Philadelphia University.

Results

The intervention and control groups were comparable at baseline. At 6 months a significant increase was seen in the moderate physical activity and walking levels of the intervention group compared with the control group. The mean change (SD) in total METs of moderate physical activity and walking was 503 (325.20) METs/week in the intervention group and 6 (271.20) METs/week in the control group. The mean change (SD) in steps/day was 3,000 (1,217) steps/day in the intervention group and 876 (1120.23) steps/day in the control group. The difference between mean change of the two groups was very significant at 2,124 (−820 to −563). Self-efficacy for exercise scale significantly increased among the intervention group compared with the control group. In addition, body mass index (BMI) declined from the baseline (Mean: 28.23, SD: 4.82) to 6 months (Mean: 25.36, SD: 5.23) for the intervention group.

Conclusion

Behavioral intervention through multicomponent strategies, alongside the implementation of an advanced communication strategy via phone and social media, is effective for motivating adult students to increase their physical activity levels.

Clinical trial registration

ISRCTN54100536.
Clonal hematopoiesis as a novel risk factor for type 2 diabetes mellitus in patients with hypercholesterolemia
Authors: Kim Min Joo , Song Han , Koh Youngil , Lee Heesun , Park Hyo Eun , Choi Sung Hee , Yoon Ji Won , Choi Su-Yeon
Published: June 2023

Introduction

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with atherosclerosis and cardiovascular disease. It has been suggested that CHIP may be related to diabetes, so we investigated the association between CHIP and new-onset type 2 diabetes.

Methods

This study included 4,047 subjects aged >=40 years without diabetes. To detect CHIP, targeted gene sequencing of genomic DNA from peripheral blood cells was performed. The incidence of new-onset type 2 diabetes during the follow-up period was evaluated.

Results

Of the total subjects, 635 (15.7%) had CHIP. During the median follow-up of 5.1 years, the incidence of new-onset diabetes was significantly higher in CHIP carriers than in subjects without CHIP (11.8% vs. 9.1%, p = 0.039). In a univariate analysis, CHIP significantly increased the risk of new-onset diabetes (HR 1.32, 95% CI 1.02–1.70, p = 0.034), but in a multivariate analysis, it was not significant. The CHIP-related risk of new onset diabetes differed according to LDL cholesterol level. In the hyper-LDL cholesterolemia group, CHIP significantly increased the risk of diabetes (HR 1.64, 95% CI 1.09–2.47, p = 0.018), but it did not increase the risk in the non-hyper-LDL cholesterolemia group. The subjects with CHIP and hyper-LDL-cholesterolemia had approximately twice the risk of diabetes than subjects without CHIP and with low LDL cholesterol (HR 2.05, 95% CI 1.40–3.00, p < 0.001).

Conclusion

The presence of CHIP was a significant risk factor for new-onset type 2 diabetes, especially in subjects with high LDL cholesterol. These results show the synergism between CHIP and high LDL cholesterol as a high-risk factor for diabetes.
Burden of falls attributable to low bone mineral density among people aged 60 years and over in China from 1990 to 2019
Authors: Fu Yali , Ba Lei , Lü Nianqing , Yang Huafeng , Hong Xin , Zhou Jinyi , Sun Zhiming
Published: June 2023

Objective

Falls in older people have become a major public health, economic and societal problem. Osteoporosis predisposes older adults to high risk of falls, which were the most common outcome attributable to low bone mineral density (LBMD). In this study, we analyze the long-term trends in falls burden attributable to LBMD among people aged 60 years and over from 1990 to 2019, using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019).

Methods

Data from GBD 2019 were used to assess the long-term trends in mortality and disability-adjusted life-year (DALY) rates by Joinpoint regression. The age-period-cohort (APC) model was used to evaluate the effects of age, period and cohort on mortality rate of falls attributable to LBMD.

Results

The mortality and DALYs rates of falls attributable to LBMD among people aged 60 years and over increased from 1990 to 2019, with average annual percentage changes (AAPCs) of 1.74% (95% CI: −1.47 to 2.01%) and 0.99% (95% CI: 0.80–1.19%), respectively. APC analysis revealed that the mortality rate due to LBMD significantly increased among the older people over the age of 75 years. The risk of falls mortality due to LBMD during the period of 1990–2019 initially declined but later elevated. An overall increasing risk for falls death attributable to LBMD was presented across birth cohorts, but in cohorts born after 1930, the upward trend has slowed down. The overall net drift per year attributable to LBMD was above 0. The corresponding results showed that the negative impact of period and cohort effects among males was more pronounced than those among females.

Conclusions

Falls attributable to LBMD remain an ongoing health burden in the older people in China, and the mortality has been on the rise from 1990 to 2019, especially among the older people aged 80+ years group. The prevention and treatment of LBMD should be emphasized, especially among males and oldest-old people. Furthermore, there is an urgent need to strengthen the implementation of system-wide, integrated and effective public health policies and other health interventions in China.