bluuebunny/crossref_metadata_2025 huggingface dataset:
Queering algorithms: LGBTQ+ content creators’ non-conforming and non-confronting workarounds to digital normativity in China
Authors: Shi Jiannan
Published: November 2024

Popular social media platforms in China, such as Bilibili, Douyin, and Xiaohongshu (REDnote), use machine learning algorithms to curate personalized feeds and enforce content moderation. But the opacity of such algorithms introduces socially consequential and often problematic mechanisms of classification. Given the playful resistance of queer individuals against a normative social environment, the interaction between algorithms and content creators warrants close examination. This study investigates how LGBTQ+ content creators navigate these algorithm-driven platforms, focusing on their negotiation of digital normativity to share non-heterosexual content and foster queer sociality in China. Avoiding the oversimplification of viewing algorithms and those implementing them as monolithic entities, I explore how content creators creatively manage to produce and distribute their work within the constraints of these platforms, and even by playing with these constraints. I collected data from an ethnography on algorithms, interviews, and an open-source investigation into recommendation algorithms, through a scavenge approach. I argue that LGBTQ+ content creators engage with algorithms in ways that are simultaneously non-conforming and non-confrontational. They imagine algorithmic effects, appropriate outcomes, and play with the opacity of machine learning to navigate three aspects of digital normativity in China: heteronormativity, Internet civilization, and commercialization. Empirically, I identified three strategies used to create and expand queer sociality within these constraints: camouflaging, filtering, and verticalizing. Theoretically, I introduce ‘workarounds’ as a framework that transcends the binary perspectives of conformity and resistance in discussions of authoritarian governance, algorithmic control, and user-platform interaction.
Role of antibody drug conjugates in the treatment of patients with breast cancer brain metastases
Authors: Pan Stacey , Gadrey Jayant Y. , Sammons Sarah , Lin Nancy U. , Tolaney Sara M. , Tarantino Paolo , Schlam Ilana
Published: November 2024

Breast cancer remains a leading cause of brain metastases (BM), which carry a poor prognosis. The current approach to managing BMs in breast cancer patients involves a combination of local therapies (surgery, radiotherapy) and systemic treatments. Developing newer antibody–drug conjugates (ADCs) has sparked a revolution in metastatic breast cancer (MBC) care. ADCs such as ado-trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan have demonstrated significant improvement in patient outcomes and are standard of care in the treatment of MBC. Most of the ADC registration studies included patients with stable BMs but excluded individuals with active BM, making intracranial (IC) response assessment a challenge. Promising data has recently emerged, suggesting relevant IC activity for certain ADCs and ongoing studies in patients with active BM that will expand our knowledge. This review aims to summarize the effectiveness of approved ADCs as well as promising new ADCs in development for breast cancer with BM.
Single Center Experience With Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) in Kidney Transplant Recipients With Diabetes
Authors: Angjeli Albi , Montada-Atin Tess , Nisenbaum Rosane , Dacouris Niki , Nash Michelle , Prasad G.V. Ramesh , Zaltzman Jeffrey
Published: November 2024

Background:

Sodium-glucose co-tranporter-2 inhibitors have been shown to be safe and effective in patients with type 2 diabetes for improving glycemia. Furthermore large, randomized control trials have shown cardiovascular and renal benefits. However, limited safety and efficacy data is available in kidney transplant patients with diabetes.

Objective:

To investigate the safety and efficacy of SGLT2i use on stability of renal function in adult kidney transplant recipients (KTR) with type 2 diabetes mellitus (DM2) or New Onset Diabetes After Transplantation (NODAT).

Design:

We performed a single center, retrospective cohort study pre- and post-SGLT2i exposure.

Patients:

Adults with DM2 or NODAT who received a living or deceased kidney transplant (Tx) and started on an SGLT2i post-Tx were reviewed. Patients who had type 1 diabetes were excluded.

Measurements and Methods:

The baseline was the SGLT2i start date. We reviewed available data from 24 months (M) before and after SGLT2i initiation. The primary endpoints were the effects of SGLT2i use on stability of renal function using serum creatinine and eGFR, change in urine albumin excretion(uACR), and glycosylated hemoglobin (A1C). Secondary endpoints compared blood pressure, body mass index and adverse reactions at baseline and quarterly after SGLT2i initiation.

Results:

125 KTRs were included in cohort: NODAT (52, 42%), DM2 (73, 58%); female (33, 27%); mean age at Tx 55 years (25-75); LD (56, 45%), DD (69, 55%); mean duration of Tx (6.8 years, 0.1-42.5); study follow-up (1.8 years, 0.3-4.9). The mean eGFR remained stable pre-SGLT2i at 64.6 mL/min/1.73m2, vs post at 64.3 mL/min/1.73m2. There was no difference in mean A1C after SGLT2i initiation. The slope of uACR using natural log transformation pre-SGLT2i compared with post-SGLT2i slope reduced from +0.7 (0.03, 0.11) to -0.04 (-0.01, -0.35) mg/mmol/3mths ( P = .002). The risk of developing new genital mycotic infections among all patients was 4% (95% CI 1.3%-9.1%) While there was no significant difference in UTI before (13.6%) and after (12%) SGLT2i use ( P = .68), there was a higher risk of UTI seen in patients with a previous history of UTI (23.5%) vs no previous history (10.2%) post initiation. There was no significant increase in AKI pre 8%, post 10.4%, P = .51. There was a single DKA event pre- and post-SGLT2.

Limitations:

The limitations of this study include its retrospective nonrandomized nature.

Conclusion:

In this retrospective analysis, SGLT2i use in KTR appears to be safe and efficacious with stable renal function and glycemic control, alongside improvements in uACR. There was a low risk of new genital yeast infections after SGLT2i start. UTI occurrence was higher in patients with a previous history of UTI compared with those with no previous history.
CerviXpert: A multi-structural convolutional neural network for predicting cervix type and cervical cell abnormalities
Authors: Akash Rashik Shahriar , Islam Radiful , Badhon SM Saiful Islam , Hossain KSM Tozammel
Published: November 2024

Objectives

Cervical cancer, a leading cause of cancer-related deaths among women globally, has a significantly higher survival rate when diagnosed early. Traditional diagnostic methods like Pap smears and cervical biopsies rely heavily on the skills of cytologists, making the process prone to errors. This study aims to develop CerviXpert, a multi-structural convolutional neural network designed to classify cervix types and detect cervical cell abnormalities efficiently.

Methods

We introduced CerviXpert, a computationally efficient convolutional neural network model that classifies cervical cancer using images from the publicly available SiPaKMeD dataset. Our approach emphasizes simplicity, using a limited number of convolutional layers followed by max-pooling and dense layers, trained from scratch. We compared CerviXpert’s performance against other state-of-the-art convolutional neural network models, including ResNet50, VGG16, MobileNetV2, and InceptionV3, evaluating them on accuracy, computational efficiency, and robustness using five-fold cross-validation.

Results

CerviXpert achieved an accuracy of 98.04% in classifying cervical cell abnormalities into three classes (normal, abnormal, and benign) and 98.60% for five-class cervix type classification, outperforming MobileNetV2 and InceptionV3 in both accuracy and computational demands. It demonstrated comparable results to ResNet50 and VGG16, with significantly reduced computational complexity and resource usage.

Conclusion

CerviXpert offers a promising solution for efficient cervical cancer screening and diagnosis, striking a balance between accuracy and computational feasibility. Its streamlined architecture makes it suitable for deployment in resource-constrained environments, potentially improving early detection and management of cervical cancer.
Alienation That Continues: Changpas—A Borderland Community
Authors: Tripathi Dhananjay , Dogra Amit
Published: November 2024

The Ladakh region of India has been recently in the limelight due to border tension between India and China. The differing perception of borders and vague demarcation has led to contested claims in the Ladakh region. India and China have fought a war (1962) and are presently engaged in intermittent skirmishes in the Ladakh region. Following the conflict, the borderland of Ladakh witnessed increased troop presence in the area, which created problems for the Changpas, a semi-nomadic community of Ladakh that is primarily dependent on available natural resources for survival. The political tension between India and China leads to the militarisation of the region and restrictions on the movement of Changpas near the borders. These have unintended consequences for the borderland community. The areas with counter-territorial claims include pastures for grazing the herds, and due to the dispute, the Changpas cannot access them. As a result, Changpas suffer economically and socially. While there is much discussion on the India and China border dispute in the region and beyond, the Changpas hardly get required attention in the mainstream debate. Drawing from Border Studies, this article argues that Changpas are an alienated borderland community. Changpas, because of their semi-nomadic lifestyles, lack an agency to highlight their plight or to articulate demands. This article underlines the ordeals of Changpas to present how border communities in conflict zones are compelled to adopt a life forced by circumstances and controlled by external actors.
Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation
Authors: Czyzynska-Cichon Izabela , Kotlinowski Jerzy , Blacharczyk Oliwia , Giergiel Magdalena , Szymanowski Konrad , Metwally Sara , Wojnar-Lason Kamila , Dobosz Ewelina , Koziel Joanna , Lekka Malgorzata , Chlopicki Stefan , Zapotoczny Bartlomiej
Published: November 2024

Background

Liver sinusoidal endothelial cells (LSECs) have transcellular pores, called fenestrations, participating in the bidirectional transport between the vascular system and liver parenchyma. Fenestrated LSECs indicate a healthy phenotype of liver while loss of fenestrations (defenestration) in LSECs is associated with liver pathologies.

Methods

We introduce a unique model of systemic inflammation triggered by the deletion of Mcpip1 in myeloid leukocytes (Mcpip1fl/flLysMCre) characterised by progressive alterations in LSEC phenotype. We implement multiparametric characterisation of LSECs by using novel real-time atomic force microscopy supported with scanning electron microscopy and quantitative fluorescence microscopy. In addition, we provide genetic profiling, searching for characteristic genes encoding proteins that might be connected with the structure of fenestrations.

Results

We demonstrate that LSECs in Mcpip1fl/flLysMCre display two phases of defenestration: the early phase, with modest defenestration that was fully reversible using cytochalasin B and the late phase, with severe defenestration that is mostly irreversible. By thorough analysis of LSEC porosity, elastic modulus and actin abundance in Mcpip1fl/flLysMCre and in response to cytochalasin B, we demonstrate that proteins other than actin must be additionally responsible for inducing open fenestrations. We highlight several genes that were severely affected in the late but not in the early phase of LSEC defenestration shedding a light on complex structure of individual fenestrations.

Conclusions

The presented model of LSEC derived from Mcpip1fl/flLysMCre provides a valuable reference for developing novel strategies for LSEC refenestration in the early and late phases of liver pathology.
Targeting splicing for hematological malignancies therapy
Authors: Szelest Monika , Giannopoulos Krzysztof
Published: November 2024

Alterations in splicing patterns of leukemic cells have a functional impact and influence most cellular processes since aberrantly spliced isoforms can provide a proliferative advantage, enable to evade apoptosis, induce metabolic reprogramming, change cell signaling and antitumor immune response, or develop drug resistance. In this Review, we first characterize the general mechanism of mRNA processing regulation with a focus on the role of splicing factors, which are commonly mutated in blood neoplasms. Next, we provide a comprehensive summary on the current understanding of alternative splicing events, which confer resistance to targeted treatment strategies and immunotherapy. We introduce the functional consequences of mis-spliced variants (CD19-∆ex2, CD22-∆ex2, CD22-∆ex5-6, CD33-∆ex2, PIK3CD-S, BCR-ABL35INS, BIM-γ, FPGS-8PR, dCK-∆ex2-3, and SLC29A1-∆ex13) production in leukemic cells. Of therapeutic relevance, we summarize novel strategies focused on pharmacological correction of aberrant splicing, including small-molecule splicing modulators and splice-switching oligonucleotides. We also include the findings of recent preclinical investigation of the antisense strategies based on modified oligonucleotides. Finally, we discuss the potential of emerging combination therapies for the treatment of hematological disorders with disrupted splicing.
Multi-omics approaches define novel aphid effector candidates associated with virulence and avirulence phenotypes
Authors: Thorpe Peter , Altmann Simone , Lopez-Cobollo Rosa , Douglas Nadine , Iqbal Javaid , Kanvil Sadia , Simon Jean-Christophe , Carolan James C. , Bos Jorunn , Turnbull Colin
Published: November 2024

Background

Compatibility between plant parasites and their hosts is genetically determined {Citation}both interacting organisms. For example, plants may carry resistance (R) genes or deploy chemical defences. Aphid saliva contains many proteins that are secreted into host tissues. Subsets of these proteins are predicted to act as effectors, either subverting or triggering host immunity. However, associating particular effectors with virulence or avirulence outcomes presents challenges due to the combinatorial complexity. Here we use defined aphid and host genetics to test for co-segregation of expressed aphid transcripts and proteins with virulent or avirulent phenotypes.

Results

We compared virulent and avirulent pea aphid parental genotypes, and their bulk segregant F1 progeny on Medicago truncatula genotypes carrying or lacking the RAP1 (Resistance to Acyrthosiphon pisum 1) resistance quantitative trait locus. Differential gene expression analysis of whole body and head samples, in combination with proteomics of saliva and salivary glands, enabled us to pinpoint proteins associated with virulence or avirulence phenotypes. There was relatively little impact of host genotype, whereas large numbers of transcripts and proteins were differentially expressed between parental aphids, likely a reflection of their classification as divergent biotypes within the pea aphid species complex. Many fewer transcripts intersected with the equivalent differential expression patterns in the bulked F1 progeny, providing an effective filter for removing genomic background effects. Overall, there were more upregulated genes detected in the F1 avirulent dataset compared with the virulent one. Some genes were differentially expressed both in the transcriptome and in the proteome datasets, with aminopeptidase N proteins being the most frequent differentially expressed family. In addition, a substantial proportion (27%) of salivary proteins lack annotations, suggesting that many novel functions remain to be discovered.

Conclusions

Especially when combined with tightly controlled genetics of both insect and host plant, multi-omics approaches are powerful tools for revealing and filtering candidate lists down to plausible genes for further functional analysis as putative aphid effectors.
COVID-19 inflammatory signature in a Mozambican cohort: unchanged red blood series and reduced levels of IL-6 and other proinflammatory cytokines
Authors: Maphossa Vânia , Guiliche Onélia , Babetine Teresa , Castiano Celso , Inlamea Osvaldo , Marengue Marino , Capitine Igor , Chambal Lúcia , Tivane Almiro , Sacarlal Jahit , Terra-Granado Eugênia , Chissumba Raquel Matavele
Published: November 2024

Background

Alterations in haematological, biochemical parameters and cytokine levels, were reported in patients with COVID-19, however, there is an underrepresentation of the African population, which could provide evidence for understanding SARS-CoV-2 pathogenesis and useful tools for clinical management of cases. In this study, we aimed to determine the haematological, biochemical and cytokine profile in Mozambican individuals with SARS-CoV-2.

Methods

A cohort of 85 Mozambican individuals with RT-PCR SARS-CoV-2 results, was stratified into negative, asymptomatic, mild, moderate, and severe categories. Haematological, biochemical and cytokines measurement were performed on samples from the study participants. Principal component analysis (PCA) was performed to identify similar patterns among the study cases. Comparisons between groups were performed using the Kruskal-Wallis test. Receiver operating characteristic (ROC) and area under the curve (AUC) analysis were conducted to evaluate the ability of these parameters to distinguish severe from non-severe cases of SARS-CoV-2 infection.

Results

SARS-CoV-2 infection was associated with a significant (p < 0.05) decrease in peripheral blood absolute counts of total lymphocytes and eosinophils, below the reference values along with no abnormal change (p > 0.05) in red blood cell count, haemoglobin, platelets and other red series parameters. At the serum level, SARS-CoV-2 infection was associated with an increase in serum levels of C-reactive protein (C-RP) and glucose above the reference values and to a significant reduction a significant (p < 0.05) reduction in levels of interferon-gamma (INF-γ), Tumour Necrosis Factor alfa (TNF-α) and the interleukin 1 beta (IL-1β) and IL-6 in severe cases, when compared to negative cases. Haematological, biochemical and cytokine profiles segregate severe from non-severe cases of COVID-19 with an excellent performance of C-RP (AUC = 0.95; p < 0.001) and good performance of lymphocytes (AUC = 0.88; p < 0.001) and IL-15 (AUC = 0.86; p < 0.001).

Conclusion

The lack of variation in red and platelet series, coupled with a decrease in the levels of classical pro-inflammatory in severe cases, deviates from what has been reported in other contexts suggesting, that there may be peculiarities in COVID-19 manifestation within the context of this study population. Furthermore, these results identify parameters with potential for clinical management of COVID-19 and therefore good resource allocation, particularly for severe cases.
Second primary cancers in patients with a pharyngeal index tumour: a register-based cohort study
Authors: Nikkilä Rayan , Hirvonen Elli , Haapaniemi Aaro , Pitkäniemi Janne , Malila Nea , Mäkitie Antti
Published: November 2024

Background

While prior research on the SPC (second primary cancer) risk among pharyngeal carcinoma (PC) patients has been conducted in other regions, the European perspective is underrepresented. Our register-based cohort study aims to assess the subsite-specific risk of SPC among individuals initially diagnosed with a pharyngeal index tumour.

Methods

Standardized incidence ratios (SIR) of SPC were calculated relative to the general population for all patients diagnosed with a primary oropharyngeal, nasopharyngeal, and hypopharyngeal carcinoma (OPC, NPC, and HPC) in Finland during 1953–2021.

Results

A total of 4701 PC patients – 3320 men (71%) and 1381 women (29%) – were identified. The average and median follow-up times were 5.7 and 2.8 years, respectively. A SPC was diagnosed in 561 patients (11.9%): in 12.3% of men (n = 410) and 10.9% of women (n = 151). For male PC patients, the overall SIR for an SPC at any primary site was 1.83 (95% CI: 1.65–2.01). For female patients, the corresponding SIR was 1.89 (95% CI: 1.60–2.22). OPC and HPC showed increased risks for SPCs of the mouth/pharynx (SIR 4.41 and 6.91, respectively) and respiratory organs (SIR 3.51 and 4.80). OPC patients also had an increased risk in digestive organs (SIR 1.83). Male NPC patients exhibited increased risks for oral/pharyngeal, brain, and haematolymphoid SPCs (SIRs 5.14, 6.60, and 3.05, respectively).

Conclusion

PC patients face an 80% higher SPC risk, which persists decades after treatment. Healthcare professionals must be aware of this, providing counselling and encouraging a healthy lifestyle, including smoking cessation, while monitoring symptoms.
Motor outcomes in individuals born small for gestational age at term: a systematic review
Authors: Taiar Hoda , Benum Silje Dahl , Aakvik Kristina Anna Djupvik , Evensen Kari Anne I.
Published: November 2024

Background

Being born small for gestational age (SGA) is a risk factor for motor difficulties. Previous reviews exploring this topic are mostly focused on children born preterm. We aimed to review the literature to determine the association between being born SGA at term and motor outcomes.

Methods

PubMed and Embase were searched for relevant articles without any restrictions on publication year or participants’ age. Inclusion criteria were SGA exposure at term (≥ 37 weeks of gestation), cohort studies or randomized controlled trials with motor outcome assessed by standardized motor tests with results reported as continuous scores (mean/median) compared with a control group. Exclusion criteria were abstracts, editorials and commentaries, articles in non-English language or no full text available. Reviews were screened for relevant articles. Quality of included studies was assessed by the Newcastle-Ottawa Scale.

Results

In total, 674 records were identified by the literature search and screened by two independent authors. Thirteen original articles were eligible and included in a qualitative synthesis, and five (38%) of these were included in a meta-analysis. Nine (69%) studies were from high-income countries. Most studies were carried out in early childhood, and only one study in adulthood. Seven (54%) articles reported that individuals born SGA at term had poorer scores on standardized motor tests compared with controls, while no differences were reported in five (38%) articles. One article did not report p-values, although the differences were comparable to the other studies. Group differences were of small to moderate effect size (0.19 to 0.65 standard deviation units). The pooled effect size was -0.43 (95% confidence interval: -0.60 to -0.25). Adjustment for covariates were reported in seven (54%) articles and did not change the results. Proportions of motor difficulties, reported in five (38%) articles, ranged from 8.9 to 50% in individuals born SGA from infancy to adolescence.

Conclusions

This systematic review shows that being born SGA, also at term, may be a risk factor for poorer motor outcomes throughout childhood, confirmed by a meta-analysis in early childhood. Further research is needed to establish the risk of adult motor difficulties in individuals born SGA at term.
Engagement in a virtual group-based walking intervention for persons with schizophrenia: a qualitative study
Authors: Browne Julia , Battaglini Claudio , Imamoglu Aslihan , Stiles Bryan , Jarskog L. Fredrik , Sheeran Paschal , Abrantes Ana M. , Elliott Tonya , Gonzalez Oscar , Penn David L.
Published: November 2024

Background

Exercise is beneficial for persons with schizophrenia; however, high dropout rates limit the impact of interventions. Virtual exercise programs have the potential to improve engagement; however, few intervention studies of virtual programs have been conducted in this population.

Methods

This study examined qualitative data from 15 adults with schizophrenia who participated in a pilot randomized controlled trial of Virtual PACE-Life, a live, video-delivered group walking intervention guided by self-determination theory. Interviews elicited feedback on the intervention, barriers and facilitators to engagement, recommendations for intervention refinement, and preferences for exercise programming modality. Rapid qualitative analysis was used to explore similarities and differences between completers (i.e., those that attended ≥ 50% of virtual walking sessions; n = 9) and non-completers (i.e., those that attended < 50% of virtual walking sessions; n = 6).

Results

Both groups viewed Virtual PACE-Life positively but found the virtual exercise sessions challenging and inadequate for facilitating social interaction. Work obligations impacted completers’ attendance whereas technological issues and forgetting impacted non-completers’ attendance at virtual walking sessions. Completers preferred virtual exercise programs and non-completers preferred in-person exercise programs.

Conclusions

These findings suggest that future virtual group-based walking programs should prioritize enhancing the social aspect, offering scheduling choices, and regularly assessing the perceived difficulty of exercise sessions. These modifications not only have the potential to improve intervention engagement but they also may increase participant autonomy and relatedness, core components of self-determination theory.
Strategies to optimise the health equity impact of digital pain self-reporting tools: a series of multi-stakeholder focus groups
Authors: Ali Syed Mustafa , Gambin Amanda , Chadwick Helen , Dixon William G. , Crawford Allison , Van der Veer Sabine N.
Published: November 2024

Background

There are avoidable differences (i.e., inequities) in the prevalence and distribution of chronic pain across diverse populations, as well as in access to and outcomes of pain management services. Digital pain self-reporting tools have the potential to reduce or exacerbate these inequities. This study aimed to better understand how to optimise the health equity impact of digital pain self-reporting tools on people who are experiencing (or are at risk of) digital pain inequities.

Methods

This was a qualitative study, guided by the Health Equity Impact Assessment tool—digital health supplement (HEIA-DH). We conducted three scoping focus groups with multiple stakeholders to identify the potential impacts of digital pain self-reporting tools and strategies to manage these impacts. Each group focused on one priority group experiencing digital pain inequities, including older adults, ethnic minorities, and people living in socio-economically deprived areas. A fourth consensus focus group was organised to discuss and select impact management strategies. Focus groups were audio-recorded, transcribed verbatim, and analysed using a framework approach. We derived codes, grouped them under four pre-defined categories from the HEIA-DH, and illustrated them with participants’ quotes.

Results

A total of fifteen people living with musculoskeletal pain conditions and thirteen professionals took part. Participants described how digital pain self-reports can have a positive health equity impact by better capturing pain fluctuations and enriching patient-provider communication, which in turn can enhance clinical decisions and self-management practices. Conversely, participants identified that incorrect interpretation of pain reports, lack of knowledge of pain terminologies, and digital (e.g., no access to technology) and social (e.g., gender stereotyping) exclusions may negatively impact on people’s health equity. The participants identified 32 strategies, of which 20 were selected as being likely to mitigate these negative health equity impacts. Example strategies included, e.g., option to customise self-reporting tools in line with users’ personal preferences, or resources to better explain how self-reported pain data will be used to build trust.

Conclusion

Linked to people’s personal and social characteristics, there are equity-based considerations for developing accessible digital pain self-reporting tools, as well as resources and skills to enable the adoption and use of these tools among priority groups. Future research should focus on implementing these equity-based considerations or strategies identified by our study and monitoring their impact on the health equity of people living with chronic pain.
From gene to therapy: a review of deciphering the role of ABCD1 in combating X-Linked adrenoleukodystrophy
Authors: Zuo Xinxin , Chen Zeyu
Published: November 2024

X-linked adrenoleukodystrophy (X-ALD) is a severe genetic disorder caused by ABCD1 mutations, resulting in the buildup of very-long-chain fatty acids, leading to significant neurological decline and adrenal insufficiency. Despite advancements in understanding the mechanisms of X-ALD, its pathophysiology remains incompletely understood, complicating the development of effective treatments. This review provides a comprehensive overview of X-ALD, with a focus on the genetic and biochemical roles of ABCD1 and the impacts of its mutations. Current therapeutic approaches are evaluated, discussing their limitations, and emphasizing the need to fully elucidate the pathogenesis of X-ALD. Additionally, this review highlights the importance of international collaboration to enhance systematic data collection and advance biomarker discovery, ultimately improving patient outcomes with X-ALD.
Variability and repeatability of spinal manipulation force–time characteristics in thoracic spinal manipulation on a manikin
Authors: Nyirö Luana , Gorrell Lindsay M. , Cecchini Valentina , Menon Carlo , Elgendi Mohamed , Schweinhardt Petra
Published: November 2024

Background

As part of multimodal therapy, spinal manipulation (SM) is a recommended and effective treatment for musculoskeletal pain. However, the underlying physiological mechanisms for pain relief are largely unknown. SM thrusts can be described and quantified using force–time characteristics (e.g. preload force, peak force, thrust speed, thrust duration, and thrust impulse). If these biomechanical parameters of SM are important for clinical outcomes, a large variability in the delivery of SM could lead to inconsistent responses and could thereby potentially mask a significant clinical effect. Our goal was to determine variability, and repeatability of thoracic spinal manipulation (SM) force–time profiles in a sample of Swiss chiropractors.

Methods

All interventions were performed on a human analogue manikin. Participating chiropractors received three case scenarios with the following scenarios: 50-year-old male patient, 30-year-old male athlete, and a 70-year-old female patient, each presenting with uncomplicated musculoskeletal thoracic pain. Clinicians were asked to perform three consecutive thoracic SM thrusts for each of the scenarios and repeated the same interventions after 24–48 h.

Results

Eighty-one chiropractors participated in the study, including 32 females (39.5%) with a mean age of 45.22 ± 12.96 years. The variability in SM force–time characteristics between clinicians was substantial, with preload forces ranging from 4.50 to 450.25 N and peak forces ranging from 146.08 to 1285.17 N. Significant differences between case scenarios were observed for peak force (p < 0.0001), maximum thrust speed (p = 0.0002), and thrust impulse (p = 0.0004). Except for thrust duration, repeatability within and between sessions was fair to excellent (ICCs between 0.578 and 0.957).

Conclusion

Substantial variability in application of SM was evident across clinicians and between case scenarios. Despite substantial clinician-dependent variability, the high repeatability of thoracic SM thrusts suggests a level of standardization in SM delivery, indicating that chiropractors might have ‘their’ individual force–time profile that they are capable to reproduce. Further research based on these findings should explore how to enhance the consistency, effectiveness, and safety of thoracic SM delivered clinically to humans.
Electroacupuncture alleviates neuropathic pain in a rat model of CCD via suppressing P2X3 expression in dorsal root ganglia
Authors: Zheng Yu , Jiang Minjian , Wei Zhouyuan , Chi Hengyu , Kang Yurong , Li Siyi , Zheng Yinmu , He Xiaofen , Shao Xiaomei , Fang Jianqiao , Jiang Yongliang
Published: November 2024

Background

Sciatica and low back pain are prevalent clinical types of neuropathic pain that significantly impair patients' quality of life. Conventional therapies often lack effectiveness, making these conditions challenging to treat. Electroacupuncture (EA) is an effective physiotherapy for pain relief. Prior research has demonstrated a relationship between the frequency of neuropathic pain and the analgesic impact of EA stimulation. This work aimed to assess the analgesic effects of EA in a rat model of chronic compression of the dorsal root ganglion (CCD) and to understand the underlying processes.

Methods

We established a rat CCD model to simulate sciatica and low back pain. EA was applied to rats with CCD at various frequencies (2 Hz, 100 Hz, and 2/100 Hz). The paw withdrawal threshold (PWT) was measured to assess analgesic effects. Additionally, protein levels of the purinergic receptor P2X3 (P2X3) and the expression of nociceptive neuronal markers were analyzed using immunohistochemistry and western blot (WB) techniques. The study also measured levels of proinflammatory cytokines TNF-α and IL-1β in the dorsal root ganglion (DRG). The involvement of P2X3 receptors was further investigated using the P2X3 agonist, α,β-methylene ATP (α,β-meATP).

Results

CCD rats developed pronounced mechanical allodynia. EA stimulation at all tested frequencies produced analgesic effects, with 2/100 Hz showing superior efficacy compared to 2 Hz and 100 Hz. The expression of P2X3 was increased in ipsilateral DRG of CCD model rats. P2X3 were co-labeled with isolectin B4 (IB4) and transient receptor potential vanilloid (TRPV1), indicating their role in nociception. 2/100 Hz EA treatment significantly reduced mechanical allodynia and inhibited the overexpression of P2X3, TRPV1, substance P (SP), and calcitonin gene-related peptide (CGRP) in the ipsilateral DRG of CCD model rats. Additionally, EA reduced the levels of proinflammatory cytokines TNF-α and IL-1β in the ipsilateral DRG, indicating an anti-inflammatory effect. The P2X3 agonist α,β-me ATP attenuated the analgesic effect of 2/100 Hz EA in CCD rats. The WB and immunofluorescence results consistently demonstrated P2X3 inhibition contributed to the analgesic effects of 2/100 Hz EA on CCD-induced neuropathic pain.

Conclusions

Our findings suggest that 2/100 Hz EA alleviates neuropathic pain in rats by inhibiting the upregulation of P2X3 receptors in the ipsilateral DRG. This study backs up EA as a viable treatment option for sciatica and low back pain in clinical settings.
Detailed statistical analysis plan for a guided self-determination intervention versus an attention control for outpatients with type 2 diabetes in the randomised OVERCOME trial
Authors: Mathiesen Anne Sophie , Zoffmann Vibeke , Lindschou Jane , Jakobsen Janus Christian , Gluud Christian , Olsen Markus Harboe , Rasmussen Bodil , Marqvorsen Emilie Haarslev Schröder , Rothmann Mette Juel
Published: November 2024

Background

Autonomy-supporting interventions may be a prerequisite to achieve better long-term management of type 2 diabetes. Evidence suggests that the guided self-determination (GSD) method might improve haemoglobin A1c and diabetes distress in people with type 1 diabetes. The evidence of an effect of a GSD intervention compared with an attention control group in adults with type 2 diabetes is unknown.

Methods/design

The trial is designed as a pragmatic, investigator-initiated, dual-centre, randomised, parallel-group, assessor-blinded, superiority clinical trial of persons with type 2 diabetes. A nurse will administer GSD intervention versus an attention control. The primary outcome is diabetes distress, and secondary outcomes are quality of life, depressive symptoms, and non-serious adverse events. Exploratory outcomes are haemoglobin A1c, motivation, and serious adverse events. Participants are assessed at baseline, 5-, and 12-month follow-up. Here, we present a detailed, comprehensive plan of all statistical analyses, including methods to handle missing data, and assessments of the underlying statistical assumptions. The statistical analyses will be conducted independently by two statisticians following the present plan.

Discussion

To mitigate the risk of analysis bias and increase the validity of the OVEROME trial, this statistical analysis plan was developed prior to unblinding of the trial results in concordance with the Declaration of Helsinki and the Conference on Harmonization of Good Clinical Practice Guidelines.

Trial registration

ClinicalTrials.gov NCT 04601311. Registered on October 2020.
Performance of Bt cotton evaluated in relation to mulching and weed control measures in northwest India
Authors: Priyanka Devi , Karmal Singh , Meena Sewhag , Sushil Kumar
Published: November 2024

Background

Weed infestation in cotton has been reported to offer severe competition and cause yield reduction to a large extent. Weeding via cultural practices is time consuming, tedious, and expensive due to long duration of cotton crop and regular monsoon rains during cotton production in India. Chemical weed control has been successfully utilized in cotton in the recent past. However, continuous use of similar herbicides leads to resistance in weeds against herbicides. And when sprayed to the field, herbicides not only suppress weeds but leave undesirable residues in the soil that are hazardous to the environment. Therefore, a study was performed at cotton research area at Chaudhary Charan Singh Haryana Agricultural University, Hisar, Haryana during two consecutive kharif seasons (2020 and 2021) to determine the most suitable and sustainable weed management strategy through the integration of chemical and cultural methods.

Results

Mulching with rice straw of 7.5 t ha−1 resulted in significantly higher cotton seed yield (3 189 and 3 084 kg ha−1) and better weed control in comparison to no mulch treatments (2 990 and 2904 kg ha−1) in 2020 and 2021, respectively. Among various weed management levels, the significantly lowest cotton seed yield was recorded in untreated control (1 841 and 1 757 kg·ha−1 during 2020 and 2021, respectively) in comparison to other treatments while all other treatments were statistically at par with each other during both years of crop experimentation.

Conclusion

Mulching with rice straw of 7.5 t·ha−1 along with a pre-emergence application of pendimethalin (active ingredient) at 1.5 kg·ha−1fb (followed by) one hoeings at 45 days after sowing (DAS) and fb glyphosate 2 kg·ha−1 (Shielded spray) at 90 DAS is a viable option for effective control of grassy and broadleaved weeds in Bt cotton in north-west India.
Load frequency and virtual inertia control for power system using fuzzy self-tuned PID controller with high penetration of renewable energy
Authors: Abdelghany Mohamed. A. , Syam Fathy A. , Aly Abouelmaaty M. , Abido Mohamed. A. , Ibrahim Shorouk Ossama
Published: November 2024

Reliance on renewable energy is increasing, and generating units are being added to the network. Since renewable power fluctuates greatly, the frequency deviation of the grid becomes a crucial problem with access to renewable power generation. The fluctuation of the renewable power output of the system puts forward a higher demand for load frequency control of the power grid to increase the penetration of renewable power in the system. PID controller has proven its effectiveness for the LFC due to its simple structure and clear concept. In this article, the virtual synchronous generator is introduced and a fuzzy self-tuned PID controller is proposed for inertia control. The proposed controller is implemented in light of the significant integration of renewable energy and virtual inertia. The efficacy of the suggested controller is evaluated against the traditional PID controller for the Egyptian Power System as a case study under various load disturbance scenarios. The control technique is employed for variable loads with photovoltaic and wind turbine generation systems. Three instances of load changes are studied and the controller design is performed based on grey wolf optimizer in each case. The overshot and integral time absolute error are considered as comparison measures. The new contribution is applied to the proposed controller for the grid and virtual inertia. In the case of many load variations imposed, the disturbances of residential and industrial loads varied from 0.05, 0.01, 0.15, and 0.02 pu. The maximum overshoot is 0.005 for the proposed controller and 0.0078 for the classic PID controller. The integral time absolute error is 0.06429 for the proposed controller and 0.11481 for the classic PID controller. The results demonstrate the efficacy of the proposed controller for inertia control with high penetration of renewable energy. The results show that the proposed fuzzy self-tuned PID controller has an overshot less than the classical PID controller by 25% and integral time absolute error by 45%. These results show that the use of the proposed fuzzy self-tune controller for the grid and inertia gave a better performance in terms of the overshot value and the integral time absolute error.
Effectiveness of auditory measures in the diagnosis of cochlear synaptopathy and noise-induced hidden hearing loss: a case–control study
Authors: Mekki Soha , Guindi Sherif , Elakkad Mona , Al-Aziz Maii Kamal Abd , El-Shafei Reham Rafei
Published: November 2024

Background

Cochlear synaptopathy is a disorder where auditory perceptual impairments, such as speech perception in noise and tinnitus, may not be accurately reflected by audiometric thresholds, even if the audiogram appears normal. It is proposed that the connections between hair cells and the auditory nerve are more susceptible to sound and aging damage than the cochlea’s hair cells. Cochlear synaptopathy can be present in ears with normal audiograms and undamaged hair cells, leading to hidden hearing loss. This study aims to construct electrophysiological and behavioral auditory parameters associated with persons exposed to loudness and having normal audiograms and auditory complaints to identify hidden hearing loss.

Results

A case–control study was done with forty participants with a documented history of exposure to loud sounds and various auditory complaints, compared to a control group of forty persons who had all been confirmed to have normal audiograms. The chosen behavioral core tests comprised the speech intelligibility in noise test (SPIN), gaps detection in noise (GIN test), and pitch pattern sequence test (PPS). The electrophysiological measures utilized in the study were the auditory brainstem response test (ABR) and electrocochleography (ECochG). The SPIN, PPS, and GIN test results demonstrated statistically significant disparities between the control and case groups. The amplitude ratio of wave I to wave V in ABR and the ratio of EcochG AP to SP demonstrated a statistically significant variance between the two groups. The SPIN test exhibited the highest AUC, signifying its superior diagnostic capability in identifying hidden hearing loss.

Conclusion

The present study has shown that the SPIN, as a behavioral test, and the EcochG AP amplitude measure, as an electrophysiological test, provide the greatest auditory diagnostic capability for identifying cochlear synaptopathy. Wave I amplitude in the auditory brainstem response (ABR) and the SP/AP ratio in electrocochleography (EcochG) are promising non-behavioral measures of cochlear synaptopathy or hidden hearing loss.
Mitigation of aflatoxin contamination of maize, groundnut, and sorghum by commercial biocontrol products in farmers’ fields across Burkina Faso, Mali, Niger, and Togo
Authors: Bonkoungou Saïdou , Dagno Karim , Basso Adamou , Ekanao Tedihou , Atehnkeng Joseph , Agbetiameh Daniel , Neya Adama , Toure Mahama , Tiendrebeogo Assiata , Konate Mamadou , Outani Bibata , Konlambigue Matieyedou , Callicott Kenneth A. , Cotty Peter J. , Dieng Ibnou , Falade Titilayo D. O. , Bandyopadhyay Ranajit , Ortega-Beltran Alejandro
Published: November 2024

Background

Aflatoxin contamination by
Aspergillus
section Flavi fungi poses a significant threat to food security and public health in sub-Saharan Africa (SSA). Maize, groundnut, and sorghum are staple crops frequently contaminated with aflatoxins, sometimes at dangerous levels. Despite its detrimental effects, many farmers in SSA lack access to effective tools for mitigating aflatoxin contamination. Biocontrol based on atoxigenic isolates of
A. flavus
is an effective tool to limit aflatoxin contamination.

Methods

The development, testing, registration, and commercial use of the aflatoxin biocontrol product Aflasafe BF01 for use in Burkina Faso is described. In addition, the deployment of the biocontrol technology across Mali, Niger, and Togo is documented, and for the first time, the use of aflatoxin biocontrol in sorghum is reported.

Results

In all four countries, treated crops had significantly (
P
 < 0.05) less aflatoxins than crops from untreated fields. Most treated crops met the stringent tolerance threshold for human consumption, 4 ppb total aflatoxin. Using native atoxigenic isolates of
A. flavus
and employing a multi-disciplinary approach, aflatoxin biocontrol products have demonstrated significant success in reducing aflatoxin levels in treated crops compared to untreated ones.

Conclusions

This multi-year, multi-funded source study underscores the effectiveness of biocontrol strategies in mitigating aflatoxin contamination at scale, offering a regional approach for sustainable management in West Africa and potentially unlocking significant health and economic benefits for the region.
Prophylactic and therapeutic vaccine development: advancements and challenges
Authors: Weerarathna Induni Nayodhara , Doelakeh Elijah Skarlus , Kiwanuka Lydia , Kumar Praveen , Arora Sanvi
Published: November 2024

Biomedical research is fundamental in developing preventive and therapeutic vaccines, serving as a cornerstone of global public health. This review explores the key concepts, methodologies, tools, and challenges in the vaccine development landscape, focusing on transitioning from basic biomedical sciences to clinical applications. Foundational disciplines such as virology, immunology, and molecular biology lay the groundwork for vaccine creation, while recent innovations like messenger RNA (mRNA) technology and reverse vaccinology have transformed the field. Additionally, it highlights the role of pharmaceutical advancements in translating lab discoveries into clinical solutions. Techniques like CRISPR-Cas9, genome sequencing, monoclonal antibodies, and computational modeling have significantly enhanced vaccine precision and efficacy, expediting the development of vaccines against infectious diseases. The review also discusses challenges that continue to hinder progress, including stringent regulatory pathways, vaccine hesitancy, and the rapid emergence of new pathogens. These obstacles underscore the need for interdisciplinary collaboration and the adoption of innovative strategies. Integrating personalized medicine, nanotechnology, and artificial intelligence is expected to revolutionize vaccine science further. By embracing these advancements, biomedical research has the potential to overcome existing challenges and usher in a new era of therapeutic and prophylactic vaccines, ultimately improving global health outcomes. This review emphasizes the critical role of vaccines in combating current and future health threats, advocating for continued investment in biomedical science and technology.