bluuebunny/crossref_metadata_2025_split huggingface dataset:
rTMS and TENS Relieve Neuropathic Pain in CCI Model Rats by Modulating Central Nervous System TRPV1 and Neuroinflammation
Authors: Xu Zhangyu , Zhong Quanzhen , Xing Fei , Zhu Yuanliang , Hu Yue , Huang Maomao , Zhou Mouwang , Wang Jianxiong 
Published: November 2024

Background: Repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) and transcutaneous electrical nerve stimulation (TENS) have both been demonstrated as effective at alleviating neuropathic pain (NP). However, the comparative efficacy of these two neuromodulation techniques and the specific neural mechanisms underlying their effects remain unclear.Objective: This study aims to compare the efficacy of rTMS in the PFC and TENS in mitigating peripheral NP and to investigate the impact of rTMS on neuroinflammation.Methods: Eighteen adult male Sprague–Dawley rats were randomly divided into three groups: NP (chronic constriction injury [CCI] group, n = 6), rTMS (n = 6), and TENS (n = 6). rTMS was applied to the PFC, while TENS was applied to the right hind limb of the rats 1 week postoperatively. This treatment regimen was administered once daily, 5 days a week, for 4 consecutive weeks. The paw withdrawal mechanical threshold (PWMT) was measured to assess the pain‐alleviating effects of rTMS and TENS. We further conducted enzyme‐linked immunosorbent assays (ELISAs) to measure the levels of interleukin (IL)‐1β, IL‐6, and tumor necrosis factor alpha (TNF‐α) in the PFC and L4–L6 spinal cord to evaluate their impact on neuroinflammation. Additionally, we examined transient receptor potential vanilloid type 1 (TRPV1) expression in the PFC and the L4‒L6 spinal cord using western blotting and real‐time quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) to explore the potential mechanisms involved. Hematoxylin and eosin (H&E) staining of the sciatic nerve was further performed to observe pathological changes.Results: Compared to the CCI group, both the rTMS and TENS groups exhibited a significant increase in PWMT, with the rTMS group demonstrating a notably greater PWMT than the TENS group. Furthermore, rTMS treatment triggered a significant decrease in IL‐1β, IL‐6, and TNF‐α levels in the PFC and spinal cord, while TENS only decreased IL‐1β expression in these regions. In both treatment groups, TRPV1 expression was significantly lower in the spinal cord, while H&E staining indicated improved pathological manifestations in the sciatic nerve.Conclusion: Both rTMS and TENS effectively ameliorated CCI‐induced NP, with rTMS of the PFC showing superior performance. Both treatments reduced TRPV1 expression and suppressed neuroinflammation in the spinal cord, indicating that this may be one of the mechanisms through which they exert their therapeutic effects.
S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models
Authors: Kehr Dorothea , Ritterhoff Julia , Glaser Manuel , Jarosch Lukas , Salazar Rafael E. , Spaich Kristin , Varadi Karl , Birkenstock Jennifer , Egger Michael , Gao Erhe , Koch Walter J. , Sauter Max , Freichel Marc , Katus Hugo A. , Frey Norbert , Jungmann Andreas , Busch Cornelius , Mather Paul J. , Ruhparwar Arjang , Busch Martin , Völkers Mirko , Wade Rebecca C. , Most Patrick 
Published: November 2024

BACKGROUND:

The EF-hand Ca
2+
sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca
2+
ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75–94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

METHODS:
We applied an integrative translational research pipeline ranging from in silico computational molecular modeling and in vitro biochemical molecular assays as well as isolated rodent and human cardiomyocyte performance assessments to in vivo safety and efficacy studies in small and large animal cardiac disease models.

RESULTS:

We characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardium in vitro and in vivo. This activity translates into improved contractile performance and survival in preclinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca
2+
cycling and prevents β-adrenergic receptor–triggered Ca
2+
imbalances by targeting SERCA2a and RyR2 activity. In line with the S100A1ct-mediated enhancement of SERCA2a activity, modeling suggests an interaction of the peptide with the transmembrane segments of the sarcoplasmic Ca
2+
pump. Incorporation of a cardiomyocyte-targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potency in vitro and in vivo.

CONCLUSIONS:
S100A1ct is a promising lead for the development of novel peptide-based therapeutics against heart failure with reduced ejection fraction.
MRI-Proven Incident Ischemia: A New Marker of Disease Progression in Small Vessel Diseases
Authors: Grosset Lina , Dimitrovic Ana , Guillonnet Antoine , Tamazyan Ruben , Benzakoun Joseph , Dusonchet Antoine , Chabriat Hugues , Oppenheim Catherine , Zuber Mathieu , Calvet David , Jouvent Eric 
Published: November 2024

BACKGROUND:
In ischemic cerebral small vessel diseases (cSVD), recurrent ischemic stroke is rare (2%–3% per year). Because acute ischemia may not always lead to stroke in cSVD due to the small size of lesions, acute stroke may not reliably reflect ischemic activity or the risk of further clinical worsening, as both incident lacunes and incidental diffusion-weighted imaging–positive lesions can occur without stroke symptoms. We aimed to evaluate the total ischemic activity by measuring the incidence of magnetic resonance imaging (MRI)–proven incident ischemia, independent of the presence of stroke symptoms in a large cohort of cSVD.

METHODS:
DHU-LAC is an ongoing French multicenter cohort study of MRI-proven ischemic stroke presumably due to cSVD. We report data on patients recruited between June 2018 and October 2023. In DHU-LAC, patients are enrolled within 15 days of stroke onset and are cared for according to current guidelines. During the first 6 months, patients are systematically reassessed clinically and by brain MRI: (1) at any time if stroke symptoms occur and (2) at the end of the period. We defined MRI-proven incident ischemia as either recurrent ischemic stroke or at least 1 incident lacune or incidental diffusion-weighted imaging–positive lesion on brain MRI at 6 months.

RESULTS:
Two hundred forty-nine patients were included, of whom 172 had available data at both inclusion and after 6 months. They were aged 63±6 years, 28% were women, and 65% had hypertension. Six (3%) had a recurrent ischemic stroke, but 25 more (15%) had at least 1 incident lacune or incidental diffusion-weighted imaging–positive lesion on brain MRI. MRI-proven ischemia occurs about 5× more frequently than ischemic stroke in cSVD.

CONCLUSIONS:
As data confirming the detrimental clinical effect of both incident lacunes and incidental diffusion-weighted imaging–positive lesions accumulate, MRI-proven incident ischemia may become a plausible outcome for future clinical trials in cSVD.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03552926.
Public Procurement and Child Labour in Ghana and Nigeria
Authors: Mbah-Amanze Miriam 
Published: November 2024

Abstract
Despite numerous domestic laws and treaties prohibiting child labour, the practice persists in many African countries, including in government supply chains. It is important to highlight the connection between public procurement and child labour in Africa because the continent hosts over 50% of the world’s child labourers. Furthermore, tackling child labour through public procurement processes has not attracted much academic and policy attention. In order to shift this narrative, this article examines the public procurement frameworks of Ghana and Nigeria to reveal how they address child labour throughout the process of planning, tendering, contract award and contract management. It finds that the selected countries’ legal frameworks are inadequate in addressing child labour and recommends measures to improve the identified limitations.
Obligations to Protect and Preserve Marine Environment from Land-Based Sources of Pollution: A Case of the Indian Ocean in Tanzania
Authors: Massawe Martin Patrice 
Published: November 2024

Abstract
The 1982 United Nations Convention on the Law of the Sea (UNCLOS) regulates marine pollution from land-based sources worldwide. It provides a comprehensive framework for the development of regional conventions and national laws addressing marine pollution from land-based sources. UNCLOS is closely tied to human rights treaties, since the environment and human rights are interconnected. This study examines Tanzania’s legal system and its adherence to international and regional commitments to protect the maritime environment. Based on a review of relevant documents, the study finds that Tanzania’s regulatory framework largely aligns with international and regional conventions on marine pollution from land-based sources. However, the study concludes that environmental pollution caused by land-based sources remains a significant concern in the Indian Ocean in Tanzania. This may be attributed to factors such as unplanned settlements, limited institutional capacity for waste management, inadequate fines for environmental offenses, insufficient enforcement of environmental regulations, and restricted locus standi. By addressing these shortcomings, Tanzania can better fulfill its obligations under international agreements to improve environmental protection and promote sustainable development.
Defects of English Rules of Contractual Interpretation and Their Challenges for African Businesses
Authors: Iheme Williams C. 
Published: November 2024

Abstract
The Law Society of England and Wales, as well as English politicians and judges, claim that English (contract) law is admirable, settled and predictable, and non-English legal systems are “laxer systems” whose judges are not as exceptionally knowledgeable as English judges. These claims of legal superiority attract foreign litigants such as African businesspeople to use English laws and forums to resolve their contractual disputes. This article aims to disprove these claims by rigorously assessing them from an Afrocentric lens, as well as from the prediction theory of law, English case law, and rules of contractual interpretation. It finds that English contract law and dispute resolution mechanisms are far from predictable and settled. Also, there is a staggering level of disagreement among English judges regarding their interpretation of commercial contracts. The article exposes the defects of English contract laws to enable foreign businesses to make informed decisions about their choice of laws and forums to resolve their contractual disputes.
Comparison of wide‐field/deconvolution and confocal microscopy in bioengineering. Interest of multi‐photon microscopy in the study of articular cartilage
Authors: Dumas D. , Grossin L. , Cauchois G. , Gentils M. , Santus R. , Stoltz J.F. 
Published: November 2024

The increase in lateral and spatial resolutions is one of the major targets of research and development in the field of optical microscopies applied to living tissue. The optical geometry of Confocal Laser Scanning Microscopy (CLSM) demonstrates its undeniable advantage on conventional fluorescence microscopy by segregating the planes outside the focussing plane. The methodological and technological advances of the last five years have been fast evolving, especially with regard to the optimisation of CLSM and deconvolution process. The limited analysis in thick tissue have given rise to the development of other techniques, multi‐photon excitation microscopy in particular. In this paper, we have applied these techniques on major biological applications in bioengineering (endothelial cell, chondrocyte in 3D‐culture, human cartilage) and discussed the technical limitations and perspectives.
The influence of exercise on bone morphogenic enzyme activity of immature equine subchondral bone
Authors: van de Lest Chris H.A. , Brama Pieter A.J. , van Weeren P.R. 
Published: November 2024

This study aimed at the determination of the influence of exercise on the levels of a number of bone morphogenic enzymes in subchondral bone and at the comparison of these data with other (subchondral) bone‐related parameters that have been investigated in the same experimental population. Forty‐three foals were reared until weaning at 5 months of age under similar conditions, except for the type and amount of exercise. Fifteen foals remained at pasture (Pasture group and also control group), 14 foals were kept in box stalls (Box group) and 14 foals were kept in the same box stalls but were subjected daily to an increasing number of gallop sprints (Training group). After weaning 8 foals from each group were euthanised. All remaining 19 animals were housed together in a loose box with access to a small paddock to study a possible reversibility of exercise‐induced effects. Post mortem subchondral bone samples were collected from the femoropatellar joint and analysed for the bone morphogenic enzymes alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP) and lysyl oxidase (LO). Data were compared to calcium content, numbers of collagen cross‐links, bone mineral density (BMD) and cross‐sectional area (CSA) collected in other bone‐related studies in the same group of experimental animals. At 5 months of age, ALP levels were significantly lower and TRAP levels higher in both the Box and the Training group, making the ALP : TRAP ratio reversed in relation to the Pasture group. LO levels were lower in the Box group only. The ALP and TRAP data corresponded with changes in CSA, but not with calcium and BMD, the levels of which were the same in the Training and Pasture groups. The LO levels corresponded nicely with hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross‐links. At 11 months of age ALP and TRAP levels had reached similar levels in most groups, normalising the ALP : TRAP ratio. TRAP levels in the former Training group lagged somewhat behind. LO levels were still significantly lower in the former Box rest group. It is concluded that the overall increase in bone mass (characterised by the change in CSA) is apparently related to continuous, evenly distributed exercise as in the Pasture group (natural situation). This process seems to be related with ALP and TRAP levels and their ratio. For normal cross‐link levels and BMD, short heavy bouts of exercise superimposed on a basic rest regimen seem sufficient. However, both data from this study and from earlier studies suggest that this latter exercise regimen might have a long‐term deleterious effect.
Assessing the Causal Impact of Culture on Socio-economic Variables in European Countries
Authors: Mažeikaite˙ Kristina 
Published: November 2024

Despite the growing attention to the impact of culture on socio-economic indicators, there is a lack of causality evidence. Scholars have noted that cultural values or norms, as well as, a vibrant cultural environment can have a positive impact on GDP growth, labour productivity, the attraction of human capital and the improvement of human well-being. However, the issue of endogeneity is not thoroughly debated. Not only can culture impact economic development, but socio-economic environment also affects the cultural indicators. Therefore, it is essential to identify the causal effects of culture. This article aims to assess whether culture has a causal impact on socio-economic variables. The Granger procedure is utilised to evaluate causal relationships, describing the cultural environment with a comprehensive set of 45 cultural indicators across 30 European countries. This enables the comparison of the relationship between culture and socio-economic variables using the same method across different countries. Additionally, cultural indices are constructed. The research is extended by employing a panel vector autoregression (VAR) model. The key finding of this article demonstrates a causal impact of culture on socio-economic indicators, confirmed by both the Granger procedure and panel VAR estimations. JEL Code: Z1
Impact of WHO's Surgical Safety Checklist-Based Program on Cleft-lip and Palate Repair Outcomes in LMICs—The CLEAN CLEFT Program
Authors: Alamnie Getaw , Timo Manuella , Arimino Sedera , Eshete Mekonen , Gebreegziabher Abraham , Abate Fikre , Kebede Hillena , Mehendale Felicity , Ehua-Koua Manuela , Moulot Olivier , Bankole Roumanatou , Starr Nichole , Mammo Tihitena Negussie 
Published: November 2024

Background “Clean Cleft” (CC) is an adaptation of the Lifebox Clean Cut program, designed to reduce surgical site infections (SSIs) in cleft lip and palate repairs. It focuses on 6 key processes: hand and site decontamination, surgical linen integrity, instrument sterility, timely antibiotic use, gauze counting, and WHO Surgical Safety Checklist compliance. The study explores CC's effectiveness in reducing infections, other complications, and enhancing early recovery. Methods CC was piloted in 2 Ethiopian hospitals and 1 in Côte d'Ivoire, the primary public cleft care centers in each country. Baseline data were collected through direct observation in the operating room, with patients monitored postoperatively for infections and complications through daily ward visits and follow-up calls or clinic visits at 30 days. Post-intervention data were collected for 5 months. Data was captured in DHIS2 software and analyzed using SPSS version 26. Results The program enrolled 275 patients, with 156 during baseline and 119 post-implementation. Complications significantly dropped from 21.7% to 8.7% ( P = .008), a 60% decrease. SSI rates fell from 18.1% to 8.0% ( P = .03), while palatal fistulas decreased from 13.0% to 6.1% ( P = .1) and wound dehiscence from 18.0% to 8.0% ( P = .03). Adherence to perioperative standards improved, except for hand and skin preparation while pain management remained effective throughout the program. Conclusion CC improved perioperative practices, significantly reducing infections, palatal fistulas, and wound dehiscence, supporting the broader program expansion to any subspecialty.
Expanding the PD-L1 Paradigm: A Comprehensive Systematic Review and Meta-Analysis of Scoring Systems and Additional Biomarkers Influencing Immune Checkpoint Inhibitor Outcomes in Breast Cancer
Authors: Mo Shuangwei , Wang Yuxian , Wang Yaoling , Chen Xinhai , Zhu Hongyi , Zou Zhengrong , Xiao Weikai 
Published: November 2024

Objectives The study aimed to conduct an in-depth analysis of the influence of PD-L1 status and expression levels and other variables on the effectiveness of immune checkpoint inhibitors (ICIs) in treating breast cancer. Methods A total of 19 articles, involving 16 trials and 7899 patients, were included in the analysis. The outcomes of interest were odds-ratio (OR) for pathological complete response (pCR) in early breast cancer, and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) in advanced breast cancer. Results In early breast cancer, individuals with PD-L1-positive tumors were more likely to benefit from ICIs than those with PD-L1-negative tumors. Furthermore, patients with PD-L1 positivity in immune cells (IC) had superior outcomes compared to those scoring positively on combined positive score (CPS), with ORs for ICIs benefit being 2.28 for IC-positive patients vs 1.78 for CPS-positive patients. Regarding the impact of breast cancer subtypes on the efficacy of ICIs, our findings indicated that triple-negative breast cancer (TNBC) exhibits the greatest therapeutic response with OR of 1.93, followed by the hormone receptor-positive (HoR+) / human epidermal growth factor receptor 2-negative (HER2−), while the HER2+ was the worst. Additionally, age was identified as a key predictive factor in responding to ICIs. In advanced breast cancer, there was an upward trend in CPS values associated with enhanced ICIs responsiveness, with the predictive value increasing from 12% at a CPS threshold of 10 to 13.6% at 20. Conclusion The study concluded that the PD-L1 expression scoring system effectively discriminates between patients with breast cancer in terms of the degree of benefit they may attain from ICIs. Patients with little or no PD-L1 expression experienced a diminished therapeutic benefit from ICIs.
Spontaneous globe rupture from an intraocular melanotic schwannoma
Authors: Yoo Hannah , Ueberroth Jordan , Anderson Collin , Shah Khushali , Iacob Codrin E , Carruth Bryant 
Published: November 2024

Introduction Melanotic schwannoma (MS) is a rare neoplasm composed of Schwann cells with melanosomes in various maturation stages. While MS is typically observed in spinal nerve roots or peripheral nerves, their involvement in intraocular structures is uncommon. Here, we present a case of spontaneous globe rupture as the presenting feature of intraocular extension of a MS. Methods Enucleation was performed to remove the lesion. Confirmatory light microscopy and immunohistochemistry were used to properly diagnose and differentiate from conventional schwannoma and uveal malignant melanoma. Results The ocular tumor in our patient showed melanin pigmentation with positive melanocytic markers. The tumor revealed spindle and epithelioid cells proliferating in fascicles, which has previously been described for MS. No choroidal invasion, moderate nuclear pleomorphism, and a low mitotic rate were observed supporting a diagnosis of MS in our patient. Conclusion With reports of MS with high recurrence and metastatic spread rates, there have been some suggestions that MS should be considered an aggressive malignancy. This case highlights a dramatic presentation of a rare ocular malignancy with some features of aggressiveness. Our case report endorses the importance of close monitoring for local recurrence or metastasis to prevent a poor outcome.
Effects of Hawthorn Fruit Extract Drink in Chinese Patients With Mild Hypertension and/or Hyperlipidaemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study
Authors: Zeng Weiwei , Chu Tanya T. W. , Fok Benny S. P. , Ho Walter K. K. , Chan Juliana C. N. , Tomlinson Brian 
Published: November 2024

Objectives: The purpose of this study was to examine the effect of hawthorn extract drink in mildly hypertensive and/or hyperlipidaemic Chinese patients. Methods: We performed a randomized double-blind placebo-controlled crossover study. Subjects who were randomly divided into 2 groups and asked to consume either hawthorn fruit extract drink or placebo with the same sugar content for 8-weeks with crossover to the alternative drink separated by a 4-weeks washout period. Adverse effects, lipid profile, fasting plasma glucose and blood pressure were recorded. Results: In 61 participants, body weight increased by mean (95% CI) 0.42 kg (−0.85, 1.69 kg) with the hawthorn drink and 0.94 kg (0.52, 1.36 kg) with placebo ( P > .05). Systolic blood pressure and plasma total cholesterol increased significantly with both treatments and cholesterol sub-fractions showed no significant changes. Significant increases were seen in fasting plasma glucose with placebo. The increase in plasma glucose was reversed during the 4-week washout period. Conclusions: Although our results didn’t show significant effects of hawthorn drink compared to placebo, there was a trend toward fewer adverse metabolic effects. A longer study with hawthorn fruit extract without additional calories would be useful to determine if beneficial effects occur in patients with mild hyperlipidaemia or hypertension.