bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of type 1 diabetes’ partial clinical remission after three years of heterologous adipose tissue derived stromal/stem cells transplantation associated with vitamin D supplementation
Authors: Leão Isabella Sued , Dantas Joana Rodrigues , Araújo Débora Baptista , Ramos Maria Eduarda Nascimento , Silva Karina Ribeiro , Batista Leandra S. , Pereira Maria de Fátima Carvalho , Luiz Ronir Raggio , da Silva César Cláudio , Maiolino Angelo , Rebelatto Carmen Lúcia Kuniyoshi , Daga Débora Regina , Senegaglia Alexandra Cristina , Brofman Paulo Roberto Slud , de Oliveira José Egídio Paulo , Zajdenverg Lenita , Rodacki Melanie
Published: May 2024

Background

Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group. Methods: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c. Results: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control. Conclusion: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control.

Trial Registration

37001514.0.0000.5257.
Exploring the roles of ribosomal peptides in prokaryote-phage interactions through deep learning-enabled metagenome mining
Authors: Gao Ying , Zhong Zheng , Zhang Dengwei , Zhang Jian , Li Yong-Xin
Published: May 2024

Background

Microbial secondary metabolites play a crucial role in the intricate interactions within the natural environment. Among these metabolites, ribosomally synthesized and post-translationally modified peptides (RiPPs) are becoming a promising source of therapeutic agents due to their structural diversity and functional versatility. However, their biosynthetic capacity and ecological functions remain largely underexplored.

Results

Here, we aim to explore the biosynthetic profile of RiPPs and their potential roles in the interactions between microbes and viruses in the ocean, which encompasses a vast diversity of unique biomes that are rich in interactions and remains chemically underexplored. We first developed TrRiPP to identify RiPPs from ocean metagenomes, a deep learning method that detects RiPP precursors in a hallmark gene-independent manner to overcome the limitations of classic methods in processing highly fragmented metagenomic data. Applying this method to metagenomes from the global ocean microbiome, we uncover a diverse array of previously uncharacterized putative RiPP families with great novelty and diversity. Through correlation analysis based on metatranscriptomic data, we observed a high prevalence of antiphage defense-related and phage-related protein families that were co-expressed with RiPP families. Based on this putative association between RiPPs and phage infection, we constructed an Ocean Virus Database (OVD) and established a RiPP-involving host-phage interaction network through host prediction and co-expression analysis, revealing complex connectivities linking RiPP-encoding prokaryotes, RiPP families, viral protein families, and phages. These findings highlight the potential of RiPP families involved in prokaryote-phage interactions and coevolution, providing insights into their ecological functions in the ocean microbiome.

Conclusions

This study provides a systematic investigation of the biosynthetic potential of RiPPs from the ocean microbiome at a global scale, shedding light on the essential insights into the ecological functions of RiPPs in prokaryote-phage interactions through the integration of deep learning approaches, metatranscriptomic data, and host-phage connectivity. This study serves as a valuable example of exploring the ecological functions of bacterial secondary metabolites, particularly their associations with unexplored microbial interactions.
Knowledge of fertility period among reproductive age women in Kenya: a multilevel analysis based on 2022 Kenyan demographic and health survey
Authors: Fente Bezawit Melak , Asgedom Yordanos Sisay , Asmare Zufan Alamrie , Kebede Tirusew Nigussie , Damtew Beyene Sisay , Workneh Tadesu Wondu , Beyene Muluken Adamu , Seifu Beminate Lemma
Published: May 2024

Background

Knowledge of the fertility period aids women in refraining and engaging in sexual intercourse to avoid and to get pregnant, respectively. The effect of community-level factors on knowledge of the fertility period was not yet known in Kenya. Therefore, we aimed to investigate the community- and individual-level determinants of knowledge of fertility period among women of childbearing age in Kenya.

Methods

The 2022 Kenyan Demography and Health Survey data was used for the current study. This study included 16,901 women of reproductive age. To account for the clustering effects of DHS data and the binary nature of the outcome variable, a multilevel binary logistic regression model was applied. An adjusted odds ratio with a 95% confidence interval was reported to declare the statistical significance. In addition, the model that had the lowest deviance was the one that best fit the data.

Results

The overall prevalence of knowledge of the fertility period among Kenyan women was 38.1% (95%CI = 37.3, 38.9). Women’s age, women’s education status, heard FP, contraceptive use, media exposure, and distance from health facility significant individual factors while place of residence, and community-level education, were all of factors were found to be strongly associated with knowledge of fertility period.

Conclusion

As per the findings of our study, Knowledge of the fertility period among reproductive women was low in Kenya. In the era of increasing refusal of hormone-based family planning, fertility-awareness-based family planning methods may be an option. Promoting the correct fertility period through education and media outreach may be helpful strategies for enhancing fertility decision-making.
Effects of fluid saturation and viscosity on seismic dispersion characteristics in Berea sandstone
Authors: Wei Qianqian , Han De-Hua , Li Hui , Wang Jianhua , Wang Yang , Chen Jianjun
Published: May 2024

Despite additional availability of laboratory data from water-saturated sandstone at seismic frequencies, measurements of rock samples saturated with high viscous fluids, particularly at partial saturation, are still rare. To quantify the effects of fluid viscosity and saturation levels on seismic dispersion and attenuation characteristics, we conducted two comparative forced-oscillation measurements in partially saturated sandstone with varying fluid viscosity (e.g., water, glycerin) at seismic frequencies (2–400 Hz). The results demonstrate that fluid viscosity and saturation levels substantially influence the dispersion and attenuation characteristics at the measured frequencies. Significant dispersion and attenuation are observed in the presence of a relatively small amount of gas (approximately 6%–8%) for glycerin and water saturation cases but vary in their magnitudes and characteristic frequencies. Specifically, the maximum extensional attenuation (approximately 0.024) occurs at approximately 200 Hz for water-saturated rock at 94% saturation, whereas at approximately 30 Hz with a peak of 0.032 for glycerin-saturated rock at 92% saturation. Based on theoretical modeling analysis, we suggest that mesoscopic fluid flow might be a dominant mechanism accounting for the observed attenuation in partial water or glycerin saturation, while the microscopic (squirt) flow mechanism possibly dominates the fully saturated cases.
Use of Natural Language Processing to Infer Sites of Metastatic Disease From Radiology Reports at Scale
Authors: Tay See Boon , Low Guat Hwa , Wong Gillian Jing En , Tey Han Jieh , Leong Fun Loon , Li Constance , Chua Melvin Lee Kiang , Tan Daniel Shao Weng , Thng Choon Hua , Tan Iain Bee Huat , Tan Ryan Shea Ying Cong
Published: May 2024

PURPOSE

To evaluate natural language processing (NLP) methods to infer metastatic sites from radiology reports.

METHODS

A set of 4,522 computed tomography (CT) reports of 550 patients with 14 types of cancer was used to fine-tune four clinical large language models (LLMs) for multilabel classification of metastatic sites. We also developed an NLP information extraction (IE) system (on the basis of named entity recognition, assertion status detection, and relation extraction) for comparison. Model performances were measured by F1 scores on test and three external validation sets. The best model was used to facilitate analysis of metastatic frequencies in a cohort study of 6,555 patients with 53,838 CT reports.

RESULTS

The RadBERT, BioBERT, GatorTron-base, and GatorTron-medium LLMs achieved F1 scores of 0.84, 0.87, 0.89, and 0.91, respectively, on the test set. The IE system performed best, achieving an F1 score of 0.93. F1 scores of the IE system by individual cancer type ranged from 0.89 to 0.96. The IE system attained F1 scores of 0.89, 0.83, and 0.81, respectively, on external validation sets including additional cancer types, positron emission tomography-CT ,and magnetic resonance imaging scans, respectively. In our cohort study, we found that for colorectal cancer, liver-only metastases were higher in de novo stage IV versus recurrent patients (29.7% v 12.2%; P < .001). Conversely, lung-only metastases were more frequent in recurrent versus de novo stage IV patients (17.2% v 7.3%; P < .001).

CONCLUSION

We developed an IE system that accurately infers metastatic sites in multiple primary cancers from radiology reports. It has explainable methods and performs better than some clinical LLMs. The inferred metastatic phenotypes could enhance cancer research databases and clinical trial matching, and identify potential patients for oligometastatic interventions.
Safety and Efficacy of CT041 in Patients With Refractory Metastatic Pancreatic Cancer: A Pooled Analysis of Two Early-Phase Trials
Authors: Qi Changsong , Zhang Panpan , Liu Chang , Zhang Jun , Zhou Jun , Yuan Jiajia , Liu Dan , Zhang Miao , Gong Jifang , Wang Xicheng , Li Jian , Zhang Xiaotian , Li Ning , Peng Xiaohui , Liu Zhen , Yuan Daijing , Baffa Raffaele , Wang Yumeng , Shen Lin
Published: May 2024

PURPOSE

CT041 is a chimeric antigen receptor (CAR)–modified T-cell therapy that specifically targets claudin18.2 in solid tumors. Here, we report the pooled analysis results of two exploratory clinical trials to evaluate CT041 in patients with previously treated pancreatic cancer (PC).

PATIENTS AND METHODS

These two multicenter, open-label phase I/Ib trials (CT041-CG4006, CT041-ST-01) have a similar target population and evaluation schedule. The primary objective was to assess the safety and tolerability of CT041, whereas secondary objectives included efficacy, pharmacokinetics, and immunogenicity.

RESULTS

The combined cohort comprised 24 patients with advanced PC. Among them, five patients (20.8%) had previously received one line of therapy, whereas 19 (79.2%) received ≥2 lines of therapy. The most common treatment-emergent adverse events of grade 3 or more were preconditioning-related hematologic toxicities. Cytokine release syndrome (CRS) and GI disorders were most reported grade 1 or 2 adverse events. The overall response rate and disease control rate were 16.7% and 70.8%. The median progression-free survival (mPFS) after infusion was 3.3 months (95% CI, 1.8 to 6.2), and the median overall survival (mOS) was 10.0 months (95% CI, 5.5 to 17.6). The median duration of response (mDoR)was 9.5 months (95% CI, 2.6 to Not reached), with a DoR rate at 12 months of 50% (95% CI, 5.8 to 84.5). The mPFS (6.0 v 1.0 months, P < .001) and mOS (17.6 v 4.0 months, P < .001) were prolonged in patients achieving partial response/stable disease than the progressive disease group. CA19-9 levels had reduced by at least 30% in 17 (70.8%) patients.

CONCLUSION

In patients with metastatic PC after progression on previous therapy, CT041 demonstrated a tolerable safety profile and encouraging anticancer efficacy signals. Response benefit observed here needs to be ascertained in the future.
Multicenter Analysis of Cardiometabolic-Related Diagnoses in Youth With Congenital Adrenal Hyperplasia: A PEDSnet Study
Authors: Chen Li-Min , Valentine Anna , Davis Shanlee M , Graber Evan , Fechner Patricia Y , Furniss Anna , Nahata Leena , Pyle Laura , Vyas Arpita K , Vogiatzi Maria G , Nokoff Natalie J
Published: May 2024

Context

Small cohorts of youth with congenital adrenal hyperplasia (CAH) demonstrate increased risk of obesity and poor cardiometabolic health.

Objective

To determine the odds of cardiometabolic-related diagnoses in youth with CAH compared with matched controls in a cross-sectional analysis in a large, multisite database (PEDSnet).

Methods

Electronic health record data (2009-2019) from 6 PEDSnet sites were used to determine odds of cardiometabolic-related outcomes based on diagnosis, anthropometric, and laboratory data using logistic regression among youth with CAH vs controls. Youth with CAH and ≥1 outpatient visit in PEDSnet (n = 1647) were propensity score–matched on 8 variables to controls (n = 6588). A subset of youth with classic CAH (n = 547, with glucocorticoid and mineralocorticoid prescriptions) were matched to controls (n = 2188). Odds of having cardiometabolic-related diagnoses among youth over 2 years with CAH were compared with matched controls.

Results

Outcomes were calculated for all individuals with CAH (median age at last visit 12.9 years [7.3, 17.6]) and a subset with classic CAH (median age at last visit 11.6 years [4.7, 17.5]) compared with their matched controls. All individuals with CAH had higher odds of overweight/obesity (odds ratio [95% CI] 3.63 [3.24,4.07]), hypertension (3.07 [2.60,3.64]), dysglycemia (1.95 [1.35,2.82], dyslipidemia (2.28 [1.79,2.91]), and liver dysfunction (2.30 [1.91,2.76]) than matched controls. Individuals with classic CAH had higher odds of overweight/obesity (3.21 [2.61,3.93]), hypertension (8.22 [6.71,10.08]), and liver dysfunction (2.11 [1.55,2.89]) than matched controls.

Conclusion

Overall, youth with CAH are at increased risk of diagnoses related to worse cardiometabolic health.
Investigating GABA Neuron–Specific Androgen Receptor Knockout in two Hyperandrogenic Models of PCOS
Authors: Sucquart Irene E , Coyle Chris , Rodriguez Paris Valentina , Prescott Melanie , Glendining Kelly A , Potapov Kyoko , Begg Denovan P , Gilchrist Robert B , Walters Kirsty A , Campbell Rebecca E
Published: May 2024

Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signaling in GABAergic neurons is critical in PCOS pathogenesis in 2 well-characterized hyperandrogenic mouse models of PCOS. Using cre-lox transgenics, GABA-specific androgen receptor knockout (GABARKO) mice were generated and exposed to either acute prenatal androgen excess (PNA) or chronic peripubertal androgen excess (PPA). Females were phenotyped for reproductive and metabolic features associated with each model and brains of PNA mice were assessed for elevated GABAergic input to gonadotropin-releasing hormone (GnRH) neurons. Reproductive and metabolic dysfunction induced by PPA, including acyclicity, absence of corpora lutea, obesity, adipocyte hypertrophy, and impaired glucose homeostasis, was not different between GABARKO and wild-type (WT) mice. In PNA mice, acyclicity remained in GABARKO mice while ovarian morphology and luteinizing hormone secretion was not significantly impacted by PNA or genotype. However, PNA predictably increased the density of putative GABAergic synapses to GnRH neurons in adult WT mice, and this PNA-induced plasticity was absent in GABARKO mice. Together, these findings suggest that while direct androgen signaling in GABA neurons is largely not required for the development of PCOS-like traits in androgenized models of PCOS, developmental programming of GnRH neuron innervation is dependent upon androgen signaling in GABA neurons.
Decadent Dinosaurs: Directed Evolution in British and North American Literature, 1890s–1970s
Authors: Fallon Richard
Published: May 2024

Despite paying concerted attention to evolutionary mechanisms, literary scholars have rarely focused on forms of “directed evolution” like orthogenesis (evolution along a linear track) and phylogeronty—the parallel between the lifespan of an animal group and the lifespan of an aging individual—analogical concepts reflecting a paleontological manifestation of a wider interest in human decadence. This essay analyzes how these concepts are explored in three areas: popular adventure fiction, social reform novels by Marie Stopes and H. G. Wells, and writings by paleontologists. Across these texts, the essay argues that directed evolution offered a recognizable trajectory with which to render the complexity and strangeness of prehistoric and modern life alike into a familiar linear shape by reading certain extinct animals as moral exemplars of evolutionary failure. While reformers hoped that humans could escape the orthogenetic grooves confining nonhuman animals to extinction, this optimism was shadowed both with fears that humans might inevitably face decadence and with a sense that survival meant mediocrity.
Youth Caregivers of Adults in the United States: Prevalence and the Association Between Caregiving and Education
Authors: Miller Katherine E. M. , Hart Joanna L. , Useche Rosania Mateo , Coe Norma B.
Published: May 2024

A growing proportion of individuals adopt family caregiving roles. Family caregivers are the primary providers of long-term care in the United States yet limited federal policy supports exist, despite the known negative impacts of caregiving. There is also limited information about the prevalence of youth/young adult caregivers and the impacts of caregiving at formative ages in the United States. Our objective is to estimate the prevalence of youth caregivers and examine the association of caregiving with educational investments. We use the American Time Use Survey (2013–2019) to identify and describe youth caregivers (aged 15–18) and young adult caregivers (aged 19–22) and compare them with non-caregiving peers. We estimate that there are approximately 1,623,000 youth caregivers and 1,986,000 young adult caregivers, corresponding to 9.2% and 12.7% of these age groups, respectively. However, there is a wide range in the estimated prevalence per year, from approximately 364,000 to 2.8 million youth caregivers and from 353,000 to 2.2 million young adult caregivers, depending on caregiver definition. Unlike adult caregivers, we find that young men and women were nearly equally likely to provide care. We also find that non-White individuals are disproportionately represented as youth caregivers. Compared with non-caregiving peers, both youth and young adult caregivers are less likely to be enrolled in school and, among those enrolled in school, spend significantly less time on educational activities. Considering the association of caregiving among youth/young adults and education, policies supporting youth and young adult caregivers are critical.
Anti-Blackness and Other Fears of Black Consciousness
Authors: Gordon Lewis R.
Published: May 2024

This response essay addresses anti-Blackness and other fears of Black consciousness through discussing analyses and critiques of the author’s Fear of Black Consciousness (2022) offered by Nathalie Etoke, Terrence L. Johnson, and André Brock. Concepts under discussion include bad faith, b/Black consciousness, the blues and hip-hop, bridging the aesthetic and the ethical, colonization, decolonization, double-consciousness, embodied consciousness, epistemic closure, freedom, historical erasure, joy, language, liberalism, Negritude, neoliberalism, oppression, political life, and power.
Multiple intersecting pathways are involved in CPEB1 phosphorylation and regulation of translation during mouse oocyte meiosis
Authors: Kunitomi Chisato , Romero Mayra , Daldello Enrico Maria , Schindler Karen , Conti Marco
Published: May 2024

The RNA-binding protein cytoplasmic polyadenylation element binding 1 (CPEB1) plays a fundamental role in regulating mRNA translation in oocytes. However, the specifics of how and which protein kinase cascades modulate CPEB1 activity are still controversial. Using genetic and pharmacological tools, and detailed time courses, we have re-evaluated the relationship between CPEB1 phosphorylation and translation activation during mouse oocyte maturation. We show that both the CDK1/MAPK and AURKA/PLK1 pathways converge on CPEB1 phosphorylation during prometaphase of meiosis I. Only inactivation of the CDK1/MAPK pathway disrupts translation, whereas inactivation of either pathway alone leads to CPEB1 stabilization. However, CPEB1 stabilization induced by inactivation of the AURKA/PLK1 pathway does not affect translation, indicating that destabilization and/or degradation is not linked to translational activation. The accumulation of endogenous CCNB1 protein closely recapitulates the translation data that use an exogenous template. These findings support the overarching hypothesis that the activation of translation during prometaphase in mouse oocytes relies on a CDK1/MAPK-dependent CPEB1 phosphorylation, and that translational activation precedes CPEB1 destabilization.
KRAP regulates mitochondrial Ca2+ uptake by licensing IP3 receptor activity and stabilizing ER–mitochondrial junctions
Authors: Atakpa-Adaji Peace , Ivanova Adelina , Kujawa Karolina , Taylor Colin W.
Published: May 2024

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are high-conductance channels that allow the regulated redistribution of Ca2+ from the endoplasmic reticulum (ER) to the cytosol and, at specialized membrane contact sites (MCSs), to other organelles. Only a subset of IP3Rs release Ca2+ to the cytosol in response to IP3. These ‘licensed’ IP3Rs are associated with Kras-induced actin-interacting protein (KRAP, also known as ITPRID2) beneath the plasma membrane. It is unclear whether KRAP regulates IP3Rs at MCSs. We show, using simultaneous measurements of Ca2+ concentration in the cytosol and mitochondrial matrix, that KRAP also licenses IP3Rs to release Ca2+ to mitochondria. Loss of KRAP abolishes cytosolic and mitochondrial Ca2+ signals evoked by stimulation of IP3Rs via endogenous receptors. KRAP is located at ER–mitochondrial membrane contact sites (ERMCSs) populated by IP3R clusters. Using a proximity ligation assay between IP3R and voltage-dependent anion channel 1 (VDAC1), we show that loss of KRAP reduces the number of ERMCSs. We conclude that KRAP regulates Ca2+ transfer from IP3Rs to mitochondria by both licensing IP3R activity and stabilizing ERMCSs.
Bresser-Pereira: a reconstrução política do Brasil à luz das teses centrais do novo-desenvolvimentismo
Authors: Nassif André
Published: May 2024

Neste ensaio, sintetizo as proposições do novo-desenvolvimentismo, corrente de pensamento econômico da qual o economista brasileiro Luiz Carlos Bresser-Pereira se destaca como o principal formulador. O argumento central do novo-desenvolvimentismo é que, nos países em desenvolvimento,  trajetórias bem-sucedidas de alcance de renda per capita e de padrões de bem-estar para níveis médios prevalecentes nos países desenvolvidos (ou seja, a efetivação do catching-up) dependem da harmonização das políticas públicas (particularmente, as políticas industrial e tecnológica lato sensu e o regime macroeconômico), destinadas a sustentar o crescimento econômico e a promover a diversificação da estrutura produtiva e da pauta exportadora. Arranjos inadequados de política econômica podem fazer com que a rota inicialmente exitosa de catching up nos países em desenvolvimento seja desviada para longos períodos de estagnação, como tem sido o caso do Brasil e de diversos outros países em desenvolvimento nas últimas décadas. O artigo mostra que o principal avanço do novo-desenvolvimentismo em relação ao desenvolvimentismo clássico e cepalino é o esforço de integrar a macroeconomia à teoria do desenvolvimento econômico. Neste estudo, analiso as teses principais do novo-desenvolvimentismo, especialmente sua crítica à estratégia de crescimento com poupança externa e à não-neutralização da doença holandesa, “políticas habituais” observadas no Brasil e em outros países em desenvolvimento que, ao sobrevalorizar a moeda doméstica em relação às moedas dos parceiros comerciais, leva à desindustrialização e à estagnação econômica. No final, os comentários críticos a pontos que, a meu juízo, merecem aprimoramento na teoria novo-desenvolvimentista em nada afetam a validade e robustez de suas principais teses analisadas neste ensaio.
Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes
Authors: Riaz Maira , Akram Maryam , Ibrahim Mohsina Noor , Khoso Zubair Ahmed
Published: May 2024

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic β-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM.
Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma.
Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects.
Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children.
doi: https://doi.org/10.12669/pjms.40.6.7794
How to cite this: Riaz M, Akram M, Ibrahim MN, Khoso ZA. Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes. Pak J Med Sci. 2024;40(6):1083-1086. doi: https://doi.org/10.12669/pjms.40.6.7794
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.
Unraveling the Role of BRCA1 variants in Dysregulation of Transcriptional and Post-Transcriptional Mechanisms in Breast Cancer
Authors: Majeed Ayesha , Zinan Sawdah , Faryal Rani
Published: May 2024

Objective: To screen BRCA1 gene variants and predict potential role of the identified variants in breast cancer.
Method: This case-control study included two hundred and fifty breast cancer patients and equal healthy individuals from the Federal Breast Cancer Screening Centre, Pakistan Institute of Medical Sciences, Islamabad from March 2021- January 2023. Demographic data was collected through questionnaires and clinical data was assessed using mammograms, ultrasound, histopathology and immunohistochemistry reports. Polymerase chain reaction and Sanger sequencing approach were used to detect variants in BRCA1 gene. In-silico analyses were carried out to predict mutation effect, miRNA binding site alterations and change in mRNA structure and stability.
Results: Invasive ductal carcinoma was the most prevalent type of breast cancer. Old age [OR: 2.8149 (1.5995 to 4.9538) p value = 0.0003] and family history [OR: 4.3186 (1.7336 to 10.7581) p value = 0.001] were significant breast cancer risk. Six variants were identified. Two novel missense variants, Chr17:43082553A>T and Chr17:43093710A>T were predicted deleterious as these disrupted interaction with PALB2 and importin alpha’s NLS2 site, respectively. In silico analysis predicted the loss of hsa-miR-1179 binding site due to variant Chr17:43093220T>C. Moreover, four variants were predicted to affect the mRNA structure and stability.
Conclusion: Two novel variants were predicted to be pathogenic. In-silico analysis predicted the loss of miRNA binding site along with change in mRNA secondary structure plus stability, possible mechanisms for oncogenesis. Further, expressional studies are required to confirm BRCA1 gene dysregulation in breast cancer due to these variants.
doi: https://doi.org/10.12669/pjms.40.6.8761
How to cite this: Majeed AI, Zinan S, Faryal R. Unraveling the Role of BRCA1 variants in Dysregulation of Transcriptional and Post-Transcriptional Mechanisms in Breast Cancer. Pak J Med Sci. 2024;40(6):1093-1098. doi: https://doi.org/10.12669/pjms.40.6.8761
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.
Machine-learning based road crash risk assessment fusing infrastructure, traffic and driver behaviour data
Authors: Νικολάου Δημήτριος
Published: May 2024

Ο στόχος της παρούσας διδακτορικής διατριβής είναι η αξιολόγηση του κινδύνου οδικού ατυχήματος συνδυάζοντας δεδομένα υποδομής, κυκλοφορίας και συμπεριφοράς οδηγού. Για τον σκοπό αυτό, αναπτύχθηκαν δύο βάσεις δεδομένων. Η πρώτη αφορούσε τμήματα αυτοκινητοδρόμου και περιλάμβανε δεδομένα οδικών ατυχημάτων, κυκλοφορίας, γεωμετρίας και συμπεριφοράς των οδηγών, ενώ η δεύτερη αφορούσε τμήματα αστικών και υπεραστικών οδών μιας ευρύτερης περιοχής, για τα οποία δεν υπήρχαν διαθέσιμα δεδομένα ατυχημάτων και κυκλοφορίας. Τα αποτελέσματα του μοντέλου αρνητικής διωνυμικής παλινδρόμησης για τα τμήματα του αυτοκινητοδρόμου έδειξαν θετική και στατιστικά σημαντική συσχέτιση μεταξύ της συχνότητας οδικών ατυχημάτων και των συμβάντων απότομης συμπεριφοράς του οδηγού. Ακολούθως, λαμβάνοντας υπόψη τον αριθμό τον ατυχημάτων ανά μήκος τμήματος και τον κυκλοφοριακό φόρτο, διαμορφώθηκαν τέσσερα επίπεδα επικινδυνότητας των τμημάτων του αυτοκινητοδρόμου με χρήση της ιεραρχικής ομαδοποίησης. Τα τέσσερα επίπεδα επικινδυνότητας χρησιμοποιήθηκαν ως μεταβλητή απόκρισης σε πέντε ταξινομητές μηχανικής μάθησης που περιλάμβαναν προγνωστικούς παράγοντες σχετικά με τη γεωμετρία της οδού και επικίνδυνες συμπεριφορές οδήγησης. Μεταξύ των πέντε ταξινομητών που αναπτύχθηκαν, το μοντέλο Τυχαίων Δασών επέδειξε ανώτερες επιδόσεις ταξινόμησης σε όλες τις κατηγορίες επικινδυνότητας. Με βάση τις τιμές SHAP, προέκυψε ότι οι απότομες επιβραδύνσεις χρησιμεύουν ως καταλληλότερος Έμμεσος Δείκτης Ασφαλείας από τις απότομες επιταχύνσεις για την πρόβλεψη της επικινδυνότητας. Για τον λόγο αυτό, οι απότομες επιβραδύνσεις αποτέλεσαν την εξαρτημένη μεταβλητή των αναλύσεων για τα αστικά και υπεραστικά τμήματα του ευρύτερου οδικού δικτύου. Πέραν της ανάπτυξης μη χωρικών μοντέλων, ο εντοπισμός χωρικής αυτοσυσχέτισης οδήγησε στην ανάπτυξη χωρικών τεχνικών μοντελοποίησης, ώστε να ληφθούν υπόψη οι χωρικές εξαρτήσεις. Προέκυψε ότι ο αριθμός των διαδρομών ανά τμήμα, το μήκος και η γραμμικότητα του τμήματος, η υπέρβαση των ορίων ταχύτητας και η απόσπαση προσοχής συσχετίζονται θετικά με τις απότομες επιβραδύνσεις. Αντιθέτως, οι αυτοκινητόδρομοι παρουσίασαν λιγότερες απότομες επιβραδύνσεις συγκριτικά με άλλους τύπους οδού. Επιπλέον, προέκυψε ότι ο αριθμός των διαδρομών ανά τμήμα είναι ο πιο σημαντικός παράγοντας πρόβλεψης, αναδεικνύοντας την σημασία του ως υποκατάστατο μέτρο έκθεσης στον κίνδυνο. Όσον αφορά την επίδοση των μοντέλων, το Χωρικό Μοντέλο Υστέρησης ξεπέρασε τόσο το λογαριθμογραμμικό μοντέλο όσο και το Χωρικό Μοντέλο διόρθωσης του Σφάλματος. Καλύτερη προσαρμογή παρατηρήθηκε και για το χωρικό μοντέλο Μηδενικά Διογκωμένης Αρνητικής Διωνυμικής Παλινδρόμησης, συγκριτικά με το αντίστοιχο μη χωρικό μοντέλο. Τέλος, το Χωρικό μοντέλο Τυχαίων Δασών μείωσε τις απόλυτες τιμές της χωρικής αυτοσυσχέτισης στα κατάλοιπα και παρουσίασε καλύτερη προσαρμογή στα παρατηρούμενα δεδομένα συγκριτικά με το συμβατικό μοντέλο Τυχαίων Δασών.
Midwifery mentorship in Aotearoa New Zealand: The mentors’ perspective
Authors: Daellenbach Shanti , Dixon Lesley , Kensington Mary , Griffiths Christine , Pihema Nicole , Te Huia Jean , Otukolo Dinah , Gray Elaine
Published: May 2024

Background: In Aotearoa New Zealand, midwifery mentoring aims to develop professional confidence and is formalised in a number of programmes to support sustainable midwifery practice in different settings. Mentoring is shown to be beneficial for mentee midwives, but little is known about the impact on the person who is doing the mentoring. Aim: To explore the key attributes that underpin midwifery mentoring in Aotearoa New Zealand from the mentors’ perspective; how these are applied by mentors within the mentoring relationship; and what impact this has on them professionally. Method: This qualitative research used focus groups with mentor midwives identified from the Find Your Mentor database. A semi-structured topic guide used seven simple open-ended questions to stimulate discussion. Discussions were transcribed and analysed using the 6 steps of Braun and Clarke’s (2006) inductive thematic analysis. Findings: Four main themes were identified. The mentors described Creating an empowered, safe space in which power was balanced with trust and respect, and confidentiality built so that experiences could be shared and reflections supported. The second theme identified the mentors’ role in Building a support infrastructure which focused firstly on the mentees’ development, ensuring professional knowledge and professional responsibilities were met, and secondly on building a network of professional relationships to enable safe practice. The third theme Supporting professional cohesion described how the mentors and the profession benefit from the understanding and acceptance of different ways of practising midwifery and different midwifery roles as seen through the mentees’ lens. The final theme Sustaining midwifery practice described how mentoring keeps mentors up to date and that, by supporting the work-life balance of the mentees, they also reflect on their own work-life balance and holistic wellbeing. The enthusiasm of the mentored midwives affirmed and fed the mentors’ own passion for their roles as both a midwife and a mentor, and reflected positively for the health of the profession. Conclusion: Midwifery mentoring relationships benefit both mentees and mentors, and support cohesion and sustainability within the profession.
Legalidad difusa en el acceso a la administración de justicia en los casos de violencia intrafamiliar
Authors: Hernández Martínez Laura Carolina , Pabón Bolaños Karen Antonella , Salazar Mora Nicolás Esteban
Published: May 2024

En el marco del X Concurso Nacional de Semilleros de Investigación concerniente a los problemas de la justicia en Colombia, la presente ponencia propone un análisis fruto de un trabajo de investigación de tipología mixta respecto de las barreras existentes para el ejercicio efectivo del derecho de acceso a la justicia de las víctimas de violencia intrafamiliar en el marco de las comisarías de familia. La investigación realizada se basa en un estudio jurisprudencial de los conceptos de violencia intrafamiliar, derecho de acceso a la justicia y tutela judicial efectiva, así como en un estudio normativo de la legislación colombiana que deja en evidencia la falta de definición legal del concepto de conflicto familiar. Este estudio se contrasta con el trabajo de campo realizado al interior de la Clínica Jurídica contra la Violencia Intrafamiliar y de Género (vig) de la Universidad del Rosario, el cual muestra la aplicación discrecional y sin soporte jurídico de las comisarías de familia de Bogotá del concepto de conflicto familiar para negar medidas de protección a víctimas de violencia intrafamiliar. Esta investigación permite concluir la falta de estructura legislativa e institucional que rige a las comisarías de familia, la cual resulta en vulneración de derechos fundamentales.
Gender Promotion Gaps and Career Aspirations
Authors: Azmat Ghazala , Cuñat Vicente , Henry Emeric
Published: May 2024

Using a representative survey of U.S. lawyers, we document a sizeable gender gap in early partnership aspirations, which explains half of the later gender promotion gap. We further document that the correlation between aspirations and effort provides a “mechanical link” between aspirations and promotion. Early workplace experiences, such as harassment and demeaning comments, are linked to promotion aspirations. Moreover, early aspirations provide insight into eventual promotion outcomes that goes beyond what can be drawn only from expectations. Our study highlights that measuring aspirations and adapting the corporate culture that shapes them are key components for firms to improve workplace environments.

This paper was accepted by Joshua Gans, business strategy.

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.00715 .
Torus fractures – diagnosis and management
Authors: Tahir Abdullah , Naji Omar , Khawar Haseeb , Iqbal Mohammad Jawaid
Published: May 2024

Torus fractures are a common paediatric injury involving the distal radius. Patients typically present following a fall onto the outstretched hand, with wrist pain as their primary complaint. The principal investigation of choice is a plain radiograph of the wrist joint. These fractures should be managed with a soft-bandage and immediate discharge approach and do not require specialist follow-up. Clinicians have historically had differing views regarding optimal management of torus fractures. It is therefore important for hospital clinicians to uniformly understand the most up-to-date management of this condition. This review provides an overview of the epidemiology, anatomy, diagnosis and management, with an aim to improve outcomes.
Listeria monocytogenes: a rare cause of rhomboencephalitis in an immunocompetent patient
Authors: Heard Francesca , Sehgal Apurv
Published: May 2024

We present an unusual case of Listeria monocytogenes rhomboencephalitis in a young, healthy patient. Although L. monocytogenes meningitis is usually associated with immunodeficiency, rhomboencephalitis is more commonly seen in immunocompetent patients. The wide differential for rhomboencephalitis can create a diagnostic challenge. Without prompt pathogen identification and appropriate antibiotic regimen, L. monocytogenes central nervous system infections can be fatal. Cerebro-Spinal Fluid (CSF) Polymerase Chain Reaction (PCR) aided a prompt diagnosis and adjustment of therapy to achieve a good patient outcome.
Studies on the Rhagophthalmidae (Coleoptera) from China, part I. A new species of Menghuoius Kawashima, 2000 from Hunan, Central China
Authors: WANG CHENG-BIN
Published: May 2024

A new rhagophthalmid species, Menghuoius wukong Wang sp. nov., is described from Hunan, China. The species is similar to its congeners in general appearance, but can be separated based on a combination of the following characters: body more robust, pedicel relatively shorter, sternite IX distinctly curved ventrally in anterior part, median lobe much stouter with lateral margins oblique above lateral protuberances. As a result, including the new species, a total of four species of the genus Menghuoius are recorded from the Oriental Realm.
Selective nonoperative versus operative management of liver gunshot injuries: a retrospective cohort study
Authors: Dalcin RR , Petrillo YTM , Alves LAC , Fonseca MK , Almeida AS , Corso CO
Published: May 2024

Introduction

Experience accumulated over the last decades suggests nonoperative management (NOM) of civilian gunshot liver injuries can be safely applied in selected cases. This study aims to compare the outcomes of selective NOM versus operative management (OM) of patients sustaining gunshot wounds (GSW) to the liver.

Methods

A registry-based retrospective cohort analysis was performed for the period of 2008 to 2016 in a Brazilian trauma referral. Patients aged 16–80 years sustaining civilian GSW to right-sided abdominal quadrants and liver injury were included. Baseline data, vital signs, grade of liver injury, associated injuries, injury severity scores, blood transfusion requirements, liver- and non-liver-related complications, length-of-stay (LOS), and mortality were retrieved from individual registries.

Results

A total of 54 patients were eligible for analysis, of which 37 underwent NOM and 17 underwent OM. The median age was 25 years and all were male. No statistically significant differences were observed between groups regarding patients’ demographics, injury scores, grade of liver injury and associated lesions. NOM patients tended to sustain higher-grade injuries (86.5% vs 64.7%; p = 0.08), and failure of conservative management was recorded in two (5.4%) cases. The rate of complications was 48% with no between-group statistically significant difference. Blood transfusion requirements were significantly higher in the OM group (58.8% vs 21.6%; p = 0.012). The median LOS was seven days. No deaths were recorded.

Conclusion

Patients with liver GSW who are haemodynamically stable and without peritonitis are candidates for NOM. In this study, NOM was safe and effective even in high-grade injuries.
Impact of untreated preoperative asymptomatic bacteriuria in patients undergoing holmium laser enucleation of prostate
Authors: Bheenick D , Conroy M , Bondad J , Dawam D , Young T , Acher P
Published: May 2024

Introduction

Treatment of preoperative asymptomatic bacteriuria (ASB) before endoscopic surgery is recommended by European Association of Urology (EAU) guidelines. United Kingdom (UK) practice varies, however, owing to the historical nature of the evidence behind the guidelines, risk of increased antimicrobial resistance, the paradoxical view that treatment of ASB leads to increased infection and inefficiencies in rescheduling. We do not routinely treat ASB in our practice before holmium enucleation of the prostate (HoLEP). To determine the safety of this, we examined our experience focusing on the infective complications.

Methods

Retrospective data collection was performed on consecutive patients undergoing HoLEP between 2015 and 2020. Indication, preoperative urine cultures and infective complications were recorded. No patients were pretreated with oral antibiotics. All patients received intravenous antibiotics on induction and routine postoperative oral antibiotics at the surgeon's discretion.

Results

Some 443 patients were studied. No urosepsis occurred in the 125 patients with ASB compared with 2 of 318 patients (0.6%) with no growth on preoperative urine culture. Twenty-nine (7%) patients were treated with oral antibiotics for symptomatic postoperative complications (urinary tract infection without fever, epididymitis and haematuria). ASB did not predict for infective complications (urosepsis odds ratio [OR]: 0.50 p=0.66; oral antibiotics OR: 0.97 p=0.93).

Conclusion

Not treating ASB before a HoLEP procedure is safe. This supports the judicious use of antimicrobials preoperatively. Other modalities of endoscopic surgery should be similarly assessed.
Trainee as trainer in paediatric laparoscopic appendicectomy
Authors: Henderson L , Patwardhan N , Dagash H
Published: May 2024

Background

Intraoperative teaching is an essential surgical skill, but there is little literature regarding trainees acting as trainers; we characterised these cases in paediatric laparoscopic appendicectomy.

Methods

This is a retrospective review of casenotes over two years (2015–2017) in a single tertiary paediatric surgical centre in the UK. Operating were: paediatric surgery Core Trainees (CT) (postgraduate year (PGY)3–4), Junior Registrars (JR) (PGY5–6) and Senior Registrars (SR) (PGY7+); collectively described as trainees.

Results

A total of 53 (20.7%) of 256 appendicectomies were trainee as trainer (TT) cases; 22 cases (41.5%) were performed by a CT supervised by a Registrar, and 31 (58.4%) by a JR supervised by a SR. Among the cases, 17 (32.1%) were complex, 47 (88.7%) were in working hours (8am–5pm), and 50 (94.3%) took place Monday to Friday. Median (interquartile range) duration of surgery was 65 (52–77) minutes. In the first year, 60 (47%) appendicectomies were performed by JRs. JR 1 was TT in three cases (8.8%) and JR 2 in five cases (19.2%); in all cases, the learner was a CT. Overall, there were 26 (10.6%) negative appendicectomies, 8 (3%) conversions, 19 (7%) readmissions within 30 days of discharge and 3 (1.1%) required reoperation; there was no statistically significant difference in complications between TT and non-TT cases.

Conclusion

Laparoscopic appendicectomy is an excellent model for trainees to act as trainer; case selection included simple cases during daylight hours. Our outcomes are comparable with published literature, suggesting that this teaching method is safe for patients.