bluuebunny/crossref_metadata_2025 huggingface dataset:
Cone dysfunction in ARR3-mutation-associated early-onset high myopia: an electrophysiological study
Authors: Fehér Tamás , Széll Noémi , Nagy István , Maróti Zoltán , Kalmár Tibor , Sohajda Zoltán , Barboni Mirella T. S.
Published: October 2024

Background

Myopia-26, a Mendelian form of early-onset high-myopia (eoHM) caused by mutations in the X-chromosomal ARR3 gene and predominantly affecting females, curiously, may provide an alternative route of investigation to unveil retinal mechanisms underlying pathological eye growth. We conducted a case-control cross-sectional prospective electrophysiological study in genetically characterized Myopia-26 patients (ARR3 heterozygous symptomatic females) compared with high myopes harboring intact ARR3 alleles and one carrier hemizygous male.

Results

Participants were 26 volunteers: 10 healthy control females (E-CTRL, mean age = 31.5 ± 8.8 years), one healthy control male, one carrier male of the mutant ARR3 allele and 14 female eoHM patients (mean age = 27.0 ± 13.1 years) divided in two groups: seven without (M-CTRL) and seven with (MYP-26) genetic alteration in the ARR3 gene. The clinical evaluation included complete eye screening and full-field electroretinograms (ERGs) recorded from both eyes under mydriasis. Spherical equivalent was comparable (mean=-9.55 ± 2.46 and − 10.25 ± 3.22 for M-CTRL and MYP-26, respectively) and best corrected visual acuity (BCVA) was significantly different between M-CTRL and MYP-26 (1.0 vs. 0.406 ± 0.253, respectively). E-CTRL and M-CTRL showed similar light-adapted flash and flicker ERG amplitudes; however, the prior values were reduced by ~ 35% (a- and b-waves alike), the latter by ~ 55% in the MYP-26 group (F(2, 45) > 21.821, p < 0.00001). Dark-adapted a-wave amplitudes were slightly reduced (by ~ 20%) in all myopic patients compared to E-CTRL, irrespective of the ARR3 genotype (E-CTRL vs. eoHM, p = 0.038).

Conclusions

The cone dysfunction observed in Myopia-26 patients is specifically linked to the mutation of ARR3, and is not the consequence of eoHM, i.e. elongation of the eye. It may play a role in myopic refractive error development through a yet unconfirmed pathomechanism.
Targeting cancer-associated fibroblasts/tumor cells cross-talk inhibits intrahepatic cholangiocarcinoma progression via cell-cycle arrest
Authors: Mancarella Serena , Gigante Isabella , Pizzuto Elena , Serino Grazia , Terzi Alberta , Dituri Francesco , Maiorano Eugenio , Vincenti Leonardo , De Bellis Mario , Ardito Francesco , Calvisi Diego F. , Giannelli Gianluigi
Published: October 2024

Background

Cancer-associated fibroblasts (CAFs), mainly responsible for the desmoplastic reaction hallmark of intrahepatic Cholangiocarcinoma (iCCA), likely have a role in tumor aggressiveness and resistance to therapy, although the molecular mechanisms involved are unknown. Aim of the study is to investigate how targeting hCAF/iCCA cross-talk with a Notch1 inhibitor, namely Crenigacestat, may affect cancer progression.

Methods

We used different in vitro models in 2D and established new 3D hetero-spheroids with iCCA cells and human (h)CAFs. The results were confirmed in a xenograft model, and explanted tumoral tissues underwent transcriptomic and bioinformatic analysis.

Results

hCAFs/iCCA cross-talk sustains increased migration of both KKU-M213 and KKU-M156 cells, while Crenigacestat significantly inhibits only the cross-talk stimulated migration. Hetero-spheroids grew larger than homo-spheroids, formed by only iCCA cells. Crenigacestat significantly reduced the invasion and growth of hetero- but not of homo-spheroids. In xenograft models, hCAFs/KKU-M213 tumors grew significantly larger than KKU-M213 tumors, but were significantly reduced in volume by Crenigacestat treatment, which also significantly decreased the fibrotic reaction. Ingenuity pathway analysis revealed that genes of hCAFs/KKU-M213 but not of KKU-M213 tumors increased tumor lesions, and that Crenigacestat treatment inhibited the modulated canonical pathways. Cell cycle checkpoints were the most notably modulated pathway and Crenigacestat reduced CCNE2 gene expression, consequently inducing cell cycle arrest. In hetero-spheroids, the number of cells increased in the G2/M cell cycle phase, while Crenigacestat significantly decreased cell numbers in the G2/M phase in hetero but not in homo-spheroids.

Conclusions

The hCAFs/iCCA cross-talk is a new target for reducing cancer progression with drugs such as Crenigacestat.

Graphical abstract
Recruitment of pregnant and breastfeeding women in pharmacokinetic studies: strategies, opportunities, barriers, and recommendations
Authors: Nakijoba Ritah , Kawuma Aida N. , Asiimwe Simon Peter , Turyahabwe Christine , Tabwenda Jovia Christine , Kyeyune Jacqueline , Magoola Johnson , Ojara Francis Williams , Waitt Catriona
Published: October 2024

Pregnant and breastfeeding women are often under-represented in clinical research, including pharmacokinetic studies, due to ethical and logistical challenges. This paper examines strategies to improve the recruitment and retention of this demographic in pharmacokinetic research, drawing on experiences from five studies conducted at the Infectious Diseases Institute, Makerere University, Uganda. Key strategies implemented include Community Advisory Board meetings, the involvement of Peer Mothers as Co-Investigators, established recruitment sites, the use of safety protocols, and the utilization of diverse communication platforms, including social media and stakeholder meetings. Despite these efforts, substantial barriers, such as scheduling conflicts and frequent staff turnover at recruitment sites, continue to threaten progress. The paper recommends flexible scheduling, strengthening public engagement, and transparent demonstration of adherence to ethical principles; justice, non-maleficence, respect, and beneficence to ensure the safety and inclusivity of pregnant and breastfeeding women. The inclusion of this population in pharmacokinetic studies is essential for providing evidence-based care that meets their unique health needs.
Performance evaluation of compansion-based clipped OFDM systems
Authors: Pfletschinger Stephan , Dietl Guido
Published: October 2024

The peak-to-average power ratio (PAPR), commonly used to describe the amplitude variations of an OFDM (orthogonal frequency-division multiplex) signal, does not accurately reflect its impact on the system performance. This paper applies the mutual information as a metric to assess the effects of nonlinear PAPR reduction schemes on the performance of OFDM systems. Evaluation of the achieved mutual information shows that a significant capacity loss from clipping occurs only at high SNR (signal-to-noise ratio) and a simple compression/expansion technique is proposed to achieve close to optimal performance in this regime. The effectiveness of this method is validated through WER (word error rate) simulations with several modulation and coding schemes.
Designing injectable dermal matrix hydrogel combined with silver nanoparticles for methicillin-resistant Staphylococcus aureus infected wounds healing
Authors: Chen Sunfang , Yao Jun , Huo Shicheng , Xu Chennan , Yang Ruting , Tao Danhua , Fang Bin , Ma Gaoxiang , Zhu Zaihua , Zhang Ye , Guo JingJing
Published: October 2024

Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds.

Graphical Abstract
Impulsivity and epilepsy: a bidirectional mendelian randomization study
Authors: Chen Tao , Liao Yuqi , Hong Peiwei
Published: October 2024

Background

Previous studies have found that patients with epilepsy are more likely to suffer impulsivity. However, the causal relationship between impulsivity and epilepsy is unknown. In this study, we conduct a bidirectional Mendelian randomization (MR) study to explore the causal relationship between impulsivity and epilepsy with recurrent seizure.

Methods

Data of the genome-wide association studies (GWAS) on 14 impulsivity traits and epilepsy were obtained from the GWAS catalog and UK Biobank. Inverse-variance weighted (IVW) and weighted median (WM) methods were utilized for MR estimates. IVW, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used to assess heterogeneity and pleiotropy.

Results

Single-nucleotide polymorphisms (SNPs) related to the lack of perseverance were associated with a decreased risk of epilepsy with recurrent seizures according to the results of IVW (odd ratio [OR] = 0.93, 95% confident interval [CI] = 0.90–0.97, P = 0.001) and WM (OR = 0.93, 95%CI = 0.87–0.98, P = 0.007). Meanwhile, heterogeneity was not observed with a Cochran Q-derived P value of 0.819 for MR egger and a P value of 0.808 for IVW. Pleiotropy was not found according to the MR-PRESSO (P = 0.273). The other 13 impulsivity traits had no causal effect on epilepsy with recurrent seizures. Meanwhile, SNPs related with epilepsy with recurrent seizures had no causal effect on the 14 impulsivity traits.

Conclusions

This MR study suggests that lack of perseverance may be a protective factor against epilepsy with recurrent seizures. However, epilepsy with recurrent seizures does not affect impulsivity.
Mean platelet volume (MPV) and red blood cell distribution width coefficient of variation (RDW_CV) as prognostic markers in community-acquired pneumonia in children: a cross-sectional study
Authors: Kiani Masoud , Shahnouri Hengameh , Mahmoodi Hasan , Pournasrollah Mohammad , Ahangar Hemmat Gholinia , Mohammadi Mohsen
Published: October 2024

Background

Community-acquired pneumonia (CAP) is a major global health threat for children, causing numerous hospitalizations and deaths. CAP is a leading cause of mortality in children under five and results in millions of hospital admissions each year. Identifying reliable prognostic markers is crucial. Mean platelet volume (MPV) and red blood cell distribution width coefficient of variation (RDW_CV) are accessible and cost-effective options for prognosis assessment. This study investigates MPV and RDW_CV as prognostic markers in children with CAP.

Methods

This cross-sectional study included 150 children aged 1–15 years diagnosed with CAP upon initial examination and admitted to the hospital. CAP diagnosis was based on clinical symptoms, physical examination, and/or radiographic findings, with hospitalization criteria set for CAP in children. CAP severity was assessed using the Clinical Respiratory Score, categorizing patients into mild, moderate, and severe groups. MPV and RDW_CV were compared among these groups.

Results

Among the patients, 71 (47.3%) were girls, and 79 (52.7%) were boys. The average hospitalization duration was 6.24 ± 3.82 days, with a median of 5 days. Disease severity distribution was 58 (38.7%) mild, 54 (36.0%) moderate, and 38 (25.3%) severe. Both RDW_CV and MPV were higher in severe cases and in children hospitalized for more than 10 days (P < 0.001). A significant positive correlation was observed between RDW_CV and MPV (r = 0.636, P < 0.001). Mean RDW and MPV values were significantly elevated in children needing ICU admission and those with pleural effusion (P < 0.001). The RDW_CV cutoff was 13.75, with 97.4% sensitivity and 80.4% specificity. The MPV cutoff was 8.25, with 78.9% sensitivity and 69.6% specificity.

Conclusion

Elevated RDW_CV and MPV levels are associated with severe CAP in hospitalized children, providing valuable prognostic insights. RDW_CV is a more precise prognostic indicator than MPV, demonstrating superior predictive value in CAP management.
Studying of serum bile acids metabolomics as potential biomarkers for differentiation between hepatocellular carcinoma and cholangiocarcinoma
Authors: El Sheashaey Azza Mahmoud , Al Agha Marium Nagah Al Zafrany , shalaby Amr ragab Ibrahim , El Kousy Salah Mohammed , Elgedawy Gamalate Abd Ellatef
Published: October 2024

Background

Metabolomics is an emerging field that quantifies numerous metabolites systematically aiming to determine the metabolites corresponding to each biological phenotype and then provide an analysis of the mechanisms involved. Bile acids (as an organic metabolites) are synthesized in the liver from cholesterol and could be used as indicator of hepatobiliary impairment. However, the role of these bile acids in the pathogenesis of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) is still unclear. Therefore, the current study aimed to use serum bile acid profiles potential diagnostic biomarkers for early detection of cholangiocarcinoma and differentiating it from hepatocellular carcinoma.

Subjects and methods

Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/ MS) analytical method was used for the measurement of bile acids in the serum of patients with hepatocellular carcinoma (n = 35), cholangiocarcinoma (n = 35), and control group (n = 35) to determine role as markers for differentiation between hepatocellular carcinoma and cholangiocarcinoma.

Results

This study revealed that there was a significant increase in all 14 bile acids in both HCC and CCA compared to control. Also, there was significant increase in LCA, TCA, GDCA, and GCA in cholangiocarcinoma (CCA) compared to HCC with AUC 0.775, 0.825, 0.797, and 0.831 respectively with highest sensitivity and specificity for GCA (82% and 74%, respectively) for differentiation between the two types of cancers.

Conclusion

Determination of the serum bile acids pattern using UPLC/MS/MS may help to differentiate between hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) especially GCA which may be a good biomarker for differentiation between two types of liver cancers.
Exploring potential working mechanisms of accelerated HF-rTMS in refractory major depression with a focus on locus coeruleus connectivity
Authors: Wu Guo-Rong , Baeken Chris
Published: October 2024

Background

This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD).

Methods

We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain’s noradrenergic system and key to mood regulation and stress response.

Results

A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement. We observed such LC functional connectivity decreases with several brain regions, including the superior frontal gyrus, precentral gyrus, middle occipital gyrus, and cerebellum. Moreover, our exploratory analyses hint at a possible role for E-field modeling in forecasting clinical outcomes. Additional analyses suggest potential genetic and dopaminergic factors influencing changes in LC functional connectivity in relation to clinical response.

Conclusions

The findings of this study underscore the pivotal role of the LC in orchestrating higher cognitive functions through its extensive connections with the prefrontal cortices, facilitating decision-making, influencing attention, and addressing depressive rumination. Additionally, the observed enhancement in LC-(posterior) cerebellar connectivity not only highlights the cerebellum’s role in moderating clinical outcomes through noradrenergic system modulation but also suggests its potential as a predictive marker for aHF-rTMS efficacy. These results reveal new insights into the neural mechanisms of refractory depression and suggest therapeutic targets for enhancing noradrenergic activity, thereby addressing both cognitive and psychomotor symptoms associated with the disorder.
Impact of the Affordable Care Act and Medicaid Expansion Among Patients With HIV-Associated Aggressive B-Cell Non-Hodgkin Lymphomas
Authors: Premnath Naveen , Liu Yulun , Reves Heather , Pandey Urvashi , Nair Rasmi G. , Anderson Julia , Afrough Aimaz , Anderson Larry D. , Chung Stephen S. , Kaur Gurbakhash , Khan Adeel M. , Kumar Kiran A. , Madanat Yazan F. , Wolfe Heather R. , Yilmaz Elif , Awan Farrukh T. , Sweetenham John , Ramakrishnan Geethakumari Praveen
Published: October 2024

PURPOSE

To study the influence of the Affordable Care Act (ACA) policy and its Medicaid expansion on insurance status and survival in patients with HIV with aggressive lymphoma.

METHODS

We used the National Cancer Database, a hospital-based national registry, to identify adults age 18-64 years with HIV-associated aggressive B-cell non-Hodgkin lymphomas (HIV-a-B-NHLs), diagnosed during 2007 to 2016. Survival analysis was performed on a subset of patients with HIV-a-B-NHL for whom location data were available who resided in Medicaid expansion–adopted and nonadopted states. Using a quasi-experimental difference-in-difference model, the difference in adjusted 2-year survival rates obtained with a flexible parametric Weibull model was compared for states that adopted the Medicaid expansion of ACA against those that did not adopt the expansion.

RESULTS

We identified 8,231 patients with HIV-a-B-NHL and 50,650 non-HIV patients with a-B-NHL. We found that a lower proportion of individuals were uninsured at diagnosis in the expansion states compared with nonexpansion states. We also found that the ACA policy adoption led to a reduction in the proportion of uninsured individuals with HIV-a-B-NHL in expansion states of 34.9%, compared with 15.9% in non–expansion-adopted states. There was a statistically significant improvement in the 2-year survival rate among patients with HIV-a-B-NHL in the expansion compared with nonexpansion states with the adoption of ACA (7.17%
v
1.58%,
P
= .02).

CONCLUSION

Using a novel quasi-experimental model, we found that the ACA policy corresponded with a greater survival improvement in patients with HIV-a-B-NHL within Medicaid expansion–adopted states compared with nonexpansion states. We believe that this evidence should be taken into consideration in future policy making.
The IGF System and Aging
Authors: Conover Cheryl A , Oxvig Claus
Published: October 2024

There is strong evidence that IGF signaling is involved in fundamental aspects of the aging process. However, the extracellular part of the IGF system is complex with various receptors, ligand effectors, high-affinity IGF-binding proteins, proteinases, and endogenous inhibitors that all, along with their biological context, must be considered. The IGF system components are evolutionarily conserved, underscoring the importance of understanding this system in physiology and pathophysiology. This review will briefly describe the different components of the IGF system and then discuss past and current literature regarding IGF and aging, with a focus on cellular senescence, model organisms of aging, centenarian genetics, and 3 age-related diseases—pulmonary fibrosis, Alzheimer disease, and macular degeneration—in appropriate murine models and in humans. Commonalities in mechanism suggest conditions where IGF system components may be disease drivers and potential targets in promoting healthy aging in humans.
Poor Things
Authors: Davis Lennard J.
Published: October 2024

For generations most of the canonical works that detail the lives of poor people have been created by rich or middle-class writers like Charles Dickens, John Steinbeck, or James Agee. This has resulted in overwhelming depictions of poor people as living abject, violent lives in filthy and degrading conditions. In Poor Things, Lennard J. Davis labels this genre “poornography”: distorted narratives of poverty written by and for the middle and upper classes. Davis shows how poornography creates harmful and dangerous stereotypes that build barriers to social justice and change. To remedy this, Davis argues, poor people should write realistic depictions of themselves, but because of representational inequality they cannot. Given the obstacles to the poor accessing the means of publication, Davis suggests that the work should, at least for now, be done by “transclass” writers who were once poor and who can accurately represent poverty without relying on stereotypes and clichés. Only then can the lived experience of poverty be more fully realized.
Immunometabolism and mitochondria in inflammatory bowel disease: a role for therapeutic intervention?
Authors: Adams Claire E. , Rutherford Duncan G. , Jones Gareth R. , Ho Gwo-tzer
Published: October 2024

Inflammatory bowel diseases (IBDs), incurable conditions characterised by recurrent episodes of immune-mediated gut inflammation and damage of unknown aetiology, are common. Current advanced therapies target key leukocyte-trafficking and cytokine-signalling hubs but are only effective in 50% of patients. With growing evidence of mitochondrial dysfunction in IBD and advances in our understanding of the role of metabolism in inflammation, we provide an overview of novel metabolic approaches to IBD therapy, challenging the current ‘therapeutic ceiling’, identifying critical pathways for intervention and re-imagining metabolic biomarkers for the 21st century.
Effect of patient factors and procedure on proximal tibia fracture recovery - A retrospective analysis
Authors: Ahmad Tashfeen , Abdul Muhammad Zehra , Zehra Fatima
Published: October 2024

Objective: Tibia plateau fractures account for 1-2% of all fractures and might adversely affect the knee joint. The current research aimed to evaluate the effect of surgical procedures, age, and gender on proximal tibia fracture functional outcomes.
Methods: The present data for the retrospective analysis was obtained from an observational longitudinal cohort trauma registry study, initiated at a tertiary care hospital in June 2015. A total of 51 isolated tibia plateau fracture patients were routinely treated with open reduction internal fixation or external fixator and assessed for functional outcomes till twelve months by the Rasmussen scoring scale. Patients were divided into five age groups. The functional outcome association to gender, age groups, and surgical procedures was assessed by the Fisher Exact test and logistic regression analysis.
Results: The mean age of the total 51 patients was 40±11 years. Patients operated with Open Reduction and Internal Fixation (74.5%) or with an external fixator (25.5%). Road traffic accidents were the common mechanism of injury. There were non-significantly different functional outcomes observed among age groups or between surgical procedures at all follow-ups but significantly different between genders at three-month follow-ups. Males recovered better than females (p=0.02).
Conclusion: Tibia Plateau fracture patients respond almost equally to both external fixation and Open Reduction Internal Fixation procedures. Age does not influence the outcome. However, males had better functional outcomes at three months post-surgery indicating that gender could affect the outcomes. Further exploration might assist in planning gender-based proximal tibia fracture treatment strategies for optimum outcomes.
doi: https://doi.org/10.12669/pjms.40.10.9154
How to cite this: Ahmad T, Muhammad ZA, Zehra F. Effect of patient factors and procedure on proximal tibia fracture recovery - A retrospective analysis. Pak J Med Sci. 2024;40(10):2281-2286. doi: https://doi.org/10.12669/pjms.40.10.9154
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Psychological distress, General health and Life satisfaction among children with Thalassemia and children undergoing Haemodialysis
Authors: Ramzan Aansah , Ahmad Saima
Published: October 2024

Objective: To compare and find out the relationship between psychological distress, general health and life satisfaction among children with thalassemia and children undergoing dialysis.
Method: The current study utilized cross sectional research design. A representative group of children with Thalassemia (n=60) and children undergoing dialysis (n=60) with ages ranging from 6-14 years were included in the sample. The sample was drawn from Children’s Hospital and Sundas Foundation from February 2023 to August 2023 through a purposive sampling technique.
Results: Psychological distress significantly correlates negatively with general health (-.34**) and life satisfaction (-.44**) in Children with Thalassemia. A significant negative relationship is also observed between psychological distress and general health (-.43**) and life satisfaction (-.54**) in Children undergoing Hemodialysis. Children undergoing hemodialysis experience more psychological distress whereas children with thalassemia have better general health. However, no significant difference was found in life satisfaction. The findings of the present study will be helpful for healthcare professionals and clinical psychologists to develop strategies and training programs which can increase resilience among patients. Training the patients and caregivers regarding how to fight chronic illnesses will lead to an improvement in their quality of life.
Conclusion: Psychological distress is higher in children undergoing hemodialysis and general health is also not good but the level of satisfaction is almost equal between the two groups. This is justified that chronic illnesses do not preclude children from leading happy and satisfying lives.
doi: https://doi.org/10.12669/pjms.40.10.9412
How to cite this: Ramzan A, Ahmad S. Psychological distress, General health and Life satisfaction among children with Thalassemia and children undergoing Haemodialysis. Pak J Med Sci. 2024;40(10):2309-2312. doi: https://doi.org/10.12669/pjms.40.10.9412
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A streamlined workflow for long-read DNA methylation analysis with NanoMethViz and Bioconductor
Authors: Su Shian , Xiao Lucinda , Lancaster James , Cameron Tamara , Breslin Kelsey , Hickey Peter F. , Blewitt Marnie E. , Gouil Quentin , Ritchie Matthew E.
Published: October 2024

Long-read sequencing technologies have transformed the field of epigenetics by enabling direct, single-base resolution detection of DNA modifications, such as methylation. This produces novel opportunities for studying the role of DNA methylation in gene regulation, imprinting, and disease. However, the unique characteristics of long-read data, including the modBAM format and extended read lengths, necessitate the development of specialised software tools for effective analysis. The NanoMethViz package provides a suite of tools for loading in long-read methylation data, visualising data at various data resolutions. It can convert the data for use with other Bioconductor software such as bsseq, DSS, dmrseq and edgeR to discover differentially methylated regions (DMRs). In this workflow article, we demonstrate the process of converting modBAM files into formats suitable for comprehensive downstream analysis. We leverage NanoMethViz to conduct an exploratory analysis, visually summarizing differences between samples, examining aggregate methylation profiles across gene and CpG islands, and investigating methylation patterns within specific regions at the single-read level. Additionally, we illustrate the use of dmrseq for identifying DMRs and show how to integrate these findings into gene-level visualization plots. Our analysis is applied to a triplicate dataset of haplotyped long-read methylation data from mouse neural stem cells, allowing us to visualize and compare the characteristics of the parental alleles on chromosome 7. By applying DMR analysis, we recover DMRs associated with known imprinted genes and visualise the methylation patterns of these genes summarised at single-read resolution. Through DMR analysis, we identify DMRs associated with known imprinted genes and visualize their methylation patterns at single-read resolution. This streamlined workflow is adaptable to common experimental designs and offers flexibility in the choice of upstream data sources and downstream statistical analysis tools.
Natural sea water and artificial sea water are not equivalent in plastic leachate contamination studies
Authors: Ullmann Clemens Vinzenz , Arnone Maria Ina , Jimenez-Guri Eva
Published: October 2024

Background Plastic contamination is one of the concerns of our age. With more than 150 million tons of plastic floating in the oceans, and a further 8 million tons arriving to the water each year, in recent times the scientific community has been studying the effects these plastics have on sea life both in the field and with experimental approaches. Laboratory based studies have been using both natural sea water and artificial sea water for testing various aspects of plastic contamination, including the study of chemicals leached from the plastic particles to the water. We set out to test this equivalence, looking at the leaching of heavy metals form plastic particles. Methods We obtained leachates of polyvinyl chloride plastic pre-production nurdles both in natural and artificial sea water and determined the elements in excess from untreated water by Inductively coupled plasma – optical emission spectrometry. We then used these different leachates to assess developmental success in the tunicate Ciona intestinalis by treating fertilised eggs through their development to hatched larvae. Results Here we report that chemical analysis of polyvinyl chloride plastic pre-production pellet leachates shows a different composition in natural and artificial sea water. We find that the zinc leaching from the plastic particles is up to five times higher in natural seawater than in artificial seawater, and this can have an effect in the toxicological studies derived. Indeed, we observe different effects in the development of C. intestinalis when using leachates in natural or artificial sea water. We also observe that not all artificial sea waters are suitable for studying the development of the tunicate C. intestinalis. Conclusions Our results show that, at least in this case, both types of water are not equivalent to produce plastic leachaetes and suggest that precaution should be taken when conclusions are derived from results obtained in artificial sea water.
Network for forest by-products charcoal, resin, tar, potash (COST Action EU-PoTaRCh)
Authors: Zborowska Magdalena , Brózdowski Jakub , Starlander Jakob , Woitsch Jiri , Ribechini Erika , Ion Rodica-Mariana , Nelle Oliver , Deforce Koen , Varga Anna , Szabó Péter , Badea Elena , Tintiner-Olifiers Johannes , Tikka Katja , Lucejko Jeannette Jacqueline
Published: October 2024

The COST EU-PoTaRCh Action establishes a network focused on the past, present, and future significance, production, and use of major forest by-products in Europe and beyond. The Action centers around forest by-products—primarily potash, tar, resin, and charcoal (PoTaRCh), along with plant extracts—which have been produced and utilized for over 100,000 years due to their unique chemical, biological, and therapeutic properties. The primary goal of the Action is to demonstrate the importance of these products for the socio-economic development of European countries and beyond, as well as their impact on biodiversity and the natural environment. The Action's objectives are organized into five Working Groups (WGs), each aligned with specific areas of interest: heritage, chemical characterization, archaeology, environmental history, and future perspectives of PoTaRCh materials. A key aspect of the Action is its support for stakeholders outside the scientific community who possess knowledge of PoTaRCh products through their use in industries such as production, education, and the promotion of forests' natural and cultural heritage. In doing so, the Action brings together stakeholders with diverse activity profiles, including museums, state forests, the forestry industry, associations dedicated to preserving traditions, and the tourism sector. The EU-PoTaRCh Action adheres to the three key principles of COST’s inclusiveness policy: participation of inclusiveness target countries, gender balance, and the involvement of young researchers, including in leadership positions.
Using single-dose liposomal amphotericin B for cryptococcal meningitis induction therapy: nurse pearls and practical perspectives
Authors: Ndyetukira Jane Frances , Kwizera Richard , Ahimbisibwe Cynthia , Namujju Carol , Meya David B.
Published: October 2024

Background In Uganda where the burden of HIV-associated cryptococcal meningitis is high, conventional amphotericin B deoxycholate has been standard to manage patients with cryptococcal meningitis in research settings. However, liposomal amphotericin B (AmBisome) is now available via the efforts of UNITAID. We sought to describe our nursing experience using AmBisome within a clinical trial for cryptococcal meningitis. Methods We describe the experience of using single-dose 10mg/kg liposomal amphotericin B from the perspective of a research nurse in Uganda. Second, we described the process of preparing and administering amphotericin. Third, we assessed the nursing time required for the administration of daily amphotericin B versus single-dose liposomal amphotericin. Fourth, we discuss the major challenges faced while using liposomal amphotericin B. Results We provide estimates for the nursing time required for reconstituting, filtering, diluting and administering liposomal amphotericin B and a visual aid for nursing tasks. Based on five trained nurses, the process of reconstitution and filtration lasts an average of 52 minutes (Range: 40 to 60 minutes), to reconstitute a mean of 11 (range: 8 to 15) 50mg vials (median weight 55kg). Overall, less nursing time was required for single-dose administration than for daily amphotericin B dosing. From a nursing perspective, liposomal amphotericin B was preferable to amphotericin B deoxycholate due to its reduced infusion reactions and other toxicities. Conclusions Single-dose liposomal amphotericin B is a better alternative to daily amphotericin B. In addition to less toxicity, nosocomial infections, reduced hospital stay, and the potential for lower hospitalisation costs, the nursing implications should not be discounted. Quality nursing care is a finite resource in low- and middle-income countries, and single-dose amphotericin B reduced the nursing time required for the care of patients with cryptococcal meningitis.
The genome sequence of the willow leaf beetle, Lochmaea capreae Linnaeus, 1758
Authors: Barclay Maxwell V. L. , Vassiliades Danaë , Bayfield-Farrell Will , Cristóvão Joana , Matsumoto Keita , Geiser Michael ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2024

We present a genome assembly from an individual female Lochmaea capreae (the willow leaf beetle; Arthropoda; Insecta; Coleoptera; Chrysomelidae). The genome sequence is 534.7 megabases in span. Most of the assembly is scaffolded into 17 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.85 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,254 protein coding genes.
A nationwide longitudinal investigation on the role of prenatal exposure to infectious diseases on the onset of chronic conditions in children and adolescents in Brazil
Authors: Paixao Enny S. , Cerqueira-Silva Thiago , Florentino Pilar T.V. , Carroll Orlagh , Sanchez Clemente Nuria , Lawlor Deborah A. , Ribeiro Silva Rita de Cássia , Rodrigues Laura Cunha , Smeeth Liam , Barreto Mauricio L.
Published: October 2024

Background In utero exposure to infections might set the stage for a chain of events leading to a wide spectrum of long-term health outcomes observed in children and adolescents. This proposal aims to investigate whether syphilis, zika, dengue and chikungunya during pregnancy can increase the risk of the offspring developing a non-infectious chronic condition during childhood and adolescence. Objectives 1) Estimate the risk of non-infectious chronic conditions associated to syphilis, zika, dengue and chikungunya during pregnancy and when appropriate, explore if the risk varies by timing during pregnancy when the infection is acquired (first, second or third trimester) and severity (such as severe or mild dengue); 2) Investigate whether in uterus exposure to maternal infection affects the growth pattern of children and adolescents; 3) Examine the extent to which the relationship between maternal infection and non-infectious chronic outcomes are mediated by intrauterine growth restriction and preterm birth. Methods We will compare health outcomes and growth trajectories of children and adolescents born to mothers with and without specific infections during pregnancy using conventional multivariable regression in the whole study population, in a within sibship design, using the subgroup of offspring with at least one sibling who is not exposed to the infection, and negative control outcome. Then we will decompose the direct and mediated effects (by preterm birth and small for gestational age) of maternal infection on chronic disorders. Results and Conclusions The results from this study will advance our understanding of the relationship between infections during pregnancy and chronic disorders, with widespread implications enabling targeting of critical points along the path from in utero exposure to outcomes to avoid or mitigate illness and disability over the life course.
Data note on the Avian Contact Study: a questionnaire resource for avian influenza public health planning
Authors: Thomas Amy C. , Gokool Suzanne , Clapp Genevieve , Whitlow Harry , McGrath Carmel , Moore Peter , Helwegen Maud , Logunleko Mariam , Bueno Irene , Bailey Mick , Masterton Sarah , Taylor-Egbeyemi Jo , Brown Ian , Puleston Richard , Pae Riinu , Smith Louise E , Lambton Sarah , Brooks-Pollock Ellen
Published: October 2024

The Avian Contact Study is a cross-sectional questionnaire of poultry workers and other individuals who have contact with domestic and/or wild birds in the UK. The questionnaire was launched online in May 2024 and in-person responses were gathered at the British Pig and Poultry Fair in Birmingham on 15 and 16 May 2024. This Data Note documents questionnaire development, content and delivery methods. Data collected include information on demographics, seasonal influenza vaccination, avian influenza exposure, contact with birds and people, and awareness of avian influenza. This Data Note provides insights into the first data release collected up to 31 July 2024 for 225 respondents. Data have been released as a University of Bristol held dataset available upon request. The Avian Contact Study provides a pilot resource for research into avian influenza from a zoonotic perspective.
The genome sequence of the planthopper, Conomelus anceps (Germar, 1821)
Authors: Moran Stephen , Griffiths Andy , Crowley Liam M. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2024

We present a genome assembly from an individual male Conomelus anceps (planthopper; Arthropoda; Insecta; Hemiptera; Delphacidae). The genome sequence has a total length of 957.80 megabases. Most of the assembly is scaffolded into 12 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 21.98 kilobases in length.
The genome sequence of black elder, Sambucus nigra Linnaeus, 1753 (Adoxaceae)
Authors: Christenhusz Maarten J. M. , Leitch Ilia J. ,   Royal Botanic Gardens Kew Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Plant Genome Sizing collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2024

We present a genome assembly from an individual Sambucus nigra (the European elder; Streptophyta; Magnoliopsida; Dipsacales; Adoxaceae). The genome sequence has a total length of 11,813.70 megabases. Most of the assembly is scaffolded into 18 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies have lengths of 724.11 kilobases and 158.06 kilobases, respectively.
latest treatment of colorectal cancer - a review paper
Authors: Wojtkiewicz Anna , Piekarska Magda , Kudas Zuzanna , Szerej Krzysztof , Górka Mateusz , Stec Weronika
Published: October 2024

The review article discusses the latest therapeutic approaches in the treatment of colorectal cancer (CRC), with a particular focus on metastatic disease. Despite advancements in standard treatments such as surgery, chemotherapy, and targeted therapies, the prognosis for patients with metastatic CRC remains poor, with five-year survival rates still low. The article examines the potential of immunotherapy, including PD-1 inhibitors like dostarlimab, which have shown promising results in treating selected patient groups. Additionally, the role of the ketogenic diet and probiotics as supportive strategies in CRC treatment is discussed, highlighting their potential to influence cancer metabolism and improve therapeutic outcomes. The article also addresses the development of nanotechnology-based therapies, such as PEGylated PLGA nanoparticles and sphingomyelin nanosystems, which may enhance drug delivery precision, thereby improving treatment efficacy and minimizing side effects. The conclusion emphasizes the need for further research into these innovative therapies and their integration with existing treatment protocols to improve survival and quality of life for CRC patients.
Unlocking Better Sleep and Stress Relief: The Power of Ashwagandha (Withania somnifera) Supplementation – A Literature Review
Authors: Grabowski Wojciech Krzysztof , Karoń Karolina Anna , Karoń Łukasz Mikołaj , Zygmunt Anna Ewa , Drapała Grzegorz , Pedrycz Emilia , Pedrycz Daria Katarzyna
Published: October 2024

Ashwagandha (Withania somnifera) is known for its adaptogenic properties, helping the body manage stress from various sources. This review, based on 23 studies, evaluates Ashwagandha's effectiveness in enhancing sleep quality and reducing stress. The herb's bioactive compounds modulate stress responses and neurotransmitter systems, contributing to improved mental and physical resilience. The studies consistently show that Ashwagandha supplementation (250 to 600 mg daily for 4 to 12 weeks) significantly improves sleep quality, latency, and efficiency. These effects are largely due to the modulation of the hypothalamic-pituitary-adrenal (HPA) axis, cortisol reduction, and enhancement of GABAergic and serotonergic pathways. Ashwagandha also extends total sleep time in various populations, including healthy adults and the elderly. In addition to enhancing sleep, Ashwagandha reduces stress by lowering cortisol levels and modulating neurotransmitter systems. Numerous studies highlight its role in alleviating anxiety and improving mental well-being. However, some studies report gastrointestinal issues and potential interactions with medications, necessitating caution and consultation with healthcare providers. This review synthesizes current research, identifies trends, and highlights gaps in the literature, contributing to a better understanding of Ashwagandha's role in modern health practices. Given the challenges of sleep disorders and stress-related conditions, Ashwagandha shows promise as a natural remedy, particularly for those with anxiety or chronic stress. Future research should focus on understanding the underlying mechanisms, ensuring long-term safety, and standardizing supplement quality to strengthen its therapeutic applications.
Coexistence of asthma and obstructive sleep apnea
Authors: Andrzejak Alicja , Olszewski Hubert , Walter Marcin , Stolarek Kacper , Szarek Mateusz
Published: October 2024

Obstructive sleep apnea (OSA) and asthma are common respiratory diseases that can coexist in the same patient. Epidemiological and pathophysiological data suggest an independent association between the two diseases. Over the past few decades, a wealth of data has emerged on the prevalence of asthma and OSA. The prevalence ranges from 38% to as high as 70%.