bluuebunny/crossref_metadata_2025 huggingface dataset:
The Gaza Crisis and  the Indian Urdu Press
Authors: Quamar Md. Muddassir
Published: October 2024

Urdu is widely spoken in India, and due to historical, demographic, and political reasons, it is commonly associated with the Indian Muslim population. India has a vibrant Urdu press represented in both electronic and print media that caters largely to the Muslim population and reflects their views. Issues related to Israel, Zionism, and Jews, in addition to other Middle Eastern developments, are widely covered in the Indian Urdu press due to religious and historical factors. The coverage also reflects the ignorance, biases, and prejudices that are widely held among South Asian Muslims regarding Jews, Zionism, and Israel, which at times acquire extremist and anti-Semitic overtones. The Hamas attack of October 7, 2023, and the Israeli military response have been widely covered and commented upon in the Indian Urdu press, reinforcing the established ideas of the oppressive Israeli state and the perpetual Palestinian victimhood. However, one witnesses certain nuances and a diversity of opinion within the Urdu press. A systematic content analysis of the Indian Urdu press and its coverage of the Gaza crisis provides an understanding of views held among a large section of the Muslim population in India toward the Israel–Hamas conflict, in particular, and toward the Israeli–Palestinian conflict, in general.
Congenital insensitivity to pain with anhidrosis: a literature review and the advocacy for stem cell therapeutic interventions
Authors: Ikrama Muhammad , Usama Muhammad , Haider Muhammad Hassan , Israr Shifa , Humayon Maryam
Published: October 2024

Congenital Insensitivity to Pain with Anhidrosis (CIPA) is a rare genetic disorder affecting the autonomic nervous system, leading to an inability to feel pain, temperature, or sweat1. This condition is caused by mutations in the NTRK1 gene, which encodes a receptor for nerve growth factor (NGF). The lack of NGF signaling results in the improper development and function of sensory and sympathetic neurons. Patients with CIPA often suffer from repeated injuries, infections, and hyperthermia due to their inability to sense pain and regulate body temperature. Management focuses on preventing injuries, controlling infections, and providing supportive care, as there is no definitive cure for CIPA. We present several hypotheses for treating CIPA using stem cells and modern genetic techniques. One approach involves using induced pluripotent stem cells (iPSCs) to replace defective neurons. Another hypothesis suggests in vivo gene editing of neural progenitors to restore TrkA function. Additionally, mesenchymal stem cells (MSCs) genetically modified to overexpress NGF could provide trophic support. Other strategies include epigenetic modulation of NTRK1 expression and exosome-mediated gene therapy. These innovative approaches aim to address the underlying genetic defects and restore normal cellular functions in CIPA patients.
A stepwise guide for pangenome development in crop plants: an alfalfa (Medicago sativa) case study
Authors: Kaur Harpreet , Shannon Laura M. , Samac Deborah A.
Published: October 2024

Background

The concept of pangenomics and the importance of structural variants is gaining recognition within the plant genomics community. Due to advancements in sequencing and computational technology, it has become feasible to sequence the entire genome of numerous individuals of a single species at a reasonable cost. Pangenomes have been constructed for many major diploid crops, including rice, maize, soybean, sorghum, pearl millet, peas, sunflower, grapes, and mustards. However, pangenomes for polyploid species are relatively scarce and are available in only few crops including wheat, cotton, rapeseed, and potatoes.

Main body

In this review, we explore the various methods used in crop pangenome development, discussing the challenges and implications of these techniques based on insights from published pangenome studies. We offer a systematic guide and discuss the tools available for constructing a pangenome and conducting downstream analyses. Alfalfa, a highly heterozygous, cross pollinated and autotetraploid forage crop species, is used as an example to discuss the concerns and challenges offered by polyploid crop species. We conducted a comparative analysis using linear and graph-based methods by constructing an alfalfa graph pangenome using three publicly available genome assemblies. To illustrate the intricacies captured by pangenome graphs for a complex crop genome, we used five different gene sequences and aligned them against the three graph-based pangenomes. The comparison of the three graph pangenome methods reveals notable variations in the genomic variation captured by each pipeline.

Conclusion

Pangenome resources are proving invaluable by offering insights into core and dispensable genes, novel gene discovery, and genome-wide patterns of variation. Developing user-friendly online portals for linear pangenome visualization has made these resources accessible to the broader scientific and breeding community. However, challenges remain with graph-based pangenomes including compatibility with other tools, extraction of sequence for regions of interest, and visualization of genetic variation captured in pangenome graphs. These issues necessitate further refinement of tools and pipelines to effectively address the complexities of polyploid, highly heterozygous, and cross-pollinated species.
Comparison of two different suction curettage methods in cesarean scar pregnancy treatment
Authors: Elmas Burak , Ozturk Neslihan , Kizil Emine , Laleli Koc Bergen , Zorlu Ugurcan , Tugrul Ersak Duygu , Dikici Aktas Turkan , Erten Asuman , Erkaya Salim
Published: October 2024

Background

Cesarean scar pregnancy (CSP), the incidence of which is increasing, can lead to life-threatening consequences. In this study, it was aimed to compare the results of two different ultrasound-assisted suction curettage (SC) approaches that we applied to endogenous type CSPs in different time periods.

Methods

Patients who were diagnosed with CSP and treated with SC in the early pregnancy service between January 2012 and March 2019 were included in the study. While classical SC was applied until December 2016, patients were treated with SC modified by us after this date. Demographic characteristics, preoperative clinical findings, intraoperative characteristics and postoperative short-term follow-up of these two groups of patients belonging to different time periods were compared.

Results

34 patients were treated with classic SC (Group 1) and 32 patients with modified SC (Group 2). The amount of decrease in Hemoglobin values measured at the sixth hour postoperatively compared to the preoperative period was found to be less in group 2 (1.01 ± 0.67 g/dl) than in group 1 (1.39 ± 0.85 g/dl) (p = 0.042). The treatment failure rate was found to be lower in group 2 (p = 0.028). According to the results of multiple logistic regression analysis of significant factors associated with treatment outcome, myometrial thickness measurement and the largest gestational diameter measurement were found to be significant independent factors.

Conclusion

In CSP cases, SC procedure with abdominal ultrasonography is an effective and reliable approach. At the beginning of this surgical procedure, if the gestational sac is removed from the uterine wall with the curettage cannula before suction, the success of the procedure will increase even more.
Discrimination based on gender identity and decision-making regarding HIV/STI-protected sex, a cross-sectional study among trans and non-binary people in Germany
Authors: Martín-Sánchez Mario , Pöge Kathleen , Hahne Alexander , Hamm Jonas , Bremer Viviane , Koppe Uwe ,   The TASG-study group, Appenroth Max , Wenzel Mine Pleasure Bouvar , Fink Né , Rentzsch Silvia , Garcia Manuel Ricardo , Schuler Christoph , Spurgat Chris , Voß Heinz-Jürgen
Published: October 2024

Background

Trans and non-binary people are often discriminated against. Discrimination has a negative impact on health and may affect sexual health and behavior. We explored the relationship between discrimination based on gender identity and the perceived ability to make decisions about their sex life to feel as protected as desired from HIV and sexually transmitted infections (STI) among trans and non-binary people in Germany. Secondarily, we assessed whether feeling unable of making HIV/STI-protected sex decisions was associated with behaviors related to increased HIV/STI risk.

Methods

We conducted a cross-sectional study using data from the Sexual Health and HIV/STI in Trans and Non-Binary Communities (TASG) survey conducted online between March-July 2022 among trans and/or non-binary people aged 18 years and older living in Germany. We described the prevalence of frequent discrimination based on gender identity. We calculated prevalence ratios (PR) with 95% confidence intervals (95% CI) for the associations between frequent experienced discrimination based on gender identity and feeling unable of making HIV/STI-protected sex decisions, and between feeling unable of making HIV/STI-protected sex decisions and behaviors related to increased HIV/STI risk.

Results

Among 3077 participants, 22% reported frequent discrimination based on gender identity. Participants experiencing such discrimination reported 1.4 times more often to feel unable to make HIV/STI-protected sex decisions (PR 1.4, 95% CI 1.1–1.8). This perceived inability was associated with increased prevalence of sex under drug influence (PR 2.9, 95% CI 2.3–3.7) and condomless penetrative sex with multiple partners without PrEP (PR 2.0, 95% CI 1.4–2.9).

Conclusion

Feeling unable to make decisions to feel protected from HIV/STI among trans and non-binary people was associated with both frequent discrimination and behaviors that increase the HIV/STI risk. Strategies for empowering trans and non-binary people to assert their sexual decision-making needs should be explored.
Timely empirical antibiotic therapy against sepsis in a rural Norwegian ambulance service: a prospective cohort study
Authors: Andersson Lars-Jøran , Simonsen Gunnar Skov , Solligård Erik , Fredriksen Knut
Published: October 2024

Background

Early diagnosis and antibiotic therapy in patients with sepsis reduce morbidity and mortality, thus pre-hospital management is likely to affect patient outcomes. Pre-hospital administration may increase the risk of unnecessary use of broad-spectrum antibiotics, but identification of an infectious focus enables more targeted antibiotic therapy. The aim of this study was to investigate how paramedics, with or without the assistance of general practitioners, can administer empiric intravenous antibiotic treatment against sepsis in a timely manner.

Methods

Cohort study of patients with suspected sepsis that received pre-hospital intravenous antibiotics and were transported to hospital. The setting was mainly rural with long average distance to hospital. Patients received targeted antibiotic treatment after an assessment based on clinical work-up supported by scoring systems. Patients were prospectively included from May 2018 to August 2022. Results are presented as median or absolute values, and chi-square tests were used to compare categorical data.

Results

We included 328 patients. Median age was 76 years (IQR 64, 83) and 48.5% of patients were female. 30-days all-cause mortality was 10.4%. In cases where a suspected infectious focus was determined, the hospital discharge papers confirmed the pre-hospital diagnosis focus in 195 cases (79.3%). The presence of a general practitioner during the pre-hospital assessment increased the rate of correctly identified infectious focus from 72.6% to 86.1% (p = 0.009). Concordance between pre-hospital identification of a tentative focus and discharge diagnosis was highest for lower respiratory tract (p = 0.02) and urinary tract infections (p = 0.03). Antibiotic treatment was initiated 44 min (median) after arrival of ambulance, and median transportation time to hospital was 69 min. Antibiotic therapy was started 76 min (median) before arrival at hospital.

Conclusions

Pre-hospital identification of infectious focus in suspected sepsis was feasible, and collaboration with primary care physicians increased level of diagnostic accuracy. This allowed initiation of intravenous focus-directed antibiotics more than one hour before arrival in hospital in a rural setting. The effect of pre-hospital therapy on timing was much stronger than in previous studies from more urban areas.
Use, perceptions, and effectiveness of e-cigarettes for smoking cessation among older adults in England: a population study, 2014–2024
Authors: Jackson Sarah E. , Brown Jamie , Shahab Lion , Cox Sharon
Published: October 2024

Background

This study aimed to characterise patterns of tobacco smoking and vaping among older adults (≥ 65 years) in England, to explore harm perceptions of e-cigarettes among those who smoke, and to estimate the real-world effectiveness of e-cigarettes for helping older adults to stop smoking.

Methods

Data were collected as part of a representative monthly cross-sectional household survey in England between April 2014 and April 2024 (n = 197,219). We analysed differences between older (≥ 65 years) and younger/middle-aged adults (18–64 years) in (a) time trends in tobacco smoking and vaping, (b) harm perceptions of e-cigarettes vs. cigarettes (adjusting for gender, socioeconomic position, and vaping status), and (c) the real-world effectiveness of e-cigarettes for smoking cessation (adjusting for gender, socioeconomic position, characteristics of the quit attempt, and use of other evidence-based cessation aids).

Results

Tobacco smoking prevalence remained relatively unchanged over time among older adults (at ~ 9%; 9.5% [8.5–10.6%] in April 2014 and 8.7% [7.7–9.8%] in April 2024) but vaping prevalence increased (from 2.1% [1.6–2.7%] to 3.7% [3.0–4.6%], respectively). These trends differed from those observed among younger/middle-aged adults, among whom there was a clear decline in smoking (from 21.8% [21.0–22.7%] to 18.2% [17.3–19.0%]) and a larger increase in vaping (from 5.6% [5.2–6.1%] to 16.2% [15.3–17.0%]). Older adults were consistently less likely than younger/middle-aged adults to use e-cigarettes to support attempts to quit smoking (26.8% [17.2–39.3%] vs. 43.7% [39.6–48.0%] in April 2024). Older smokers reported greater uncertainty about the harms of e-cigarettes compared with cigarettes (ORadj = 2.48 [2.28–2.69]). E-cigarettes appeared to be effective for helping older adults to stop smoking (ORadj = 1.50 [0.96–2.34]); whether effectiveness was lower than for younger/middle-aged adults was inconclusive.

Conclusions

Over the past decade, smoking prevalence has remained stable among older adults while decreasing among the rest of the adult population in England. Older adults are more unsure about the relative harms of e-cigarettes and less likely to use them to support attempts to quit smoking, despite evidence that they are effective for smoking cessation in this population.
Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B
Authors: Shokry Doha , Khan Mehwish W. , Powell Christine , Johnson Samantha , Rennels Brayden C. , Boyd Raya I. , Sun Zhengyang , Fazal Zeeshan , Freemantle Sarah J. , Parker Maryanna H. , Vieson Miranda D. , Samuelson Jonathan P. , Spinella Michael J. , Singh Ratnakar
Published: October 2024

Testicular germ cell tumors (TGCTs) can be treated with cisplatin-based therapy. However, a clinically significant number of cisplatin-resistant patients die from progressive disease as no effective alternatives exist. Curative cisplatin therapy results in acute and life-long toxicities in the young TGCT patient population providing a rationale to decrease cisplatin exposure. In contrast to genetic alterations, recent evidence suggests that epigenetics is a major driving factor for TGCT formation, progression, and response to chemotherapy. Hence, targeting epigenetic pathways with “epidrugs” is one potential relatively unexplored strategy to advance TGCT treatment beyond cisplatin. In this report, we demonstrate for the first time that targeting polycomb demethylases KDM6A and KDM6B with epidrug GSK-J4 can treat both cisplatin-sensitive and -resistant TGCTs. While GSK-J4 had minimal effects alone on TGCT tumor growth in vivo, it dramatically sensitized cisplatin-sensitive and -resistant TGCTs to cisplatin. We validated KDM6A/KDM6B as the target of GSK-J4 since KDM6A/KDM6B genetic depletion had a similar effect to GSK-J4 on cisplatin-mediated anti-tumor activity and transcriptome alterations. Pharmacologic and genetic targeting of KDM6A/KDM6B potentiated or primed the p53-dominant transcriptional response to cisplatin, with also evidence for basal activation of p53. Further, several chromatin modifier genes, including BRD4, lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development.
Hyperuricemia suppresses lumican, exacerbating adverse remodeling after myocardial infarction by promoting fibroblast phenotype transition
Authors: Zhuang Zehao , Liu Ao , Zhang Jinghong , Han Shuangjian , Tang Lu , Yu Tingting , Shi Yiping , Li Hui , Yang Heng , Bai Peiyuan , Tang Yanhua
Published: October 2024

Background

Hyperuricemia is independently associated with a poor prognosis in patients with myocardial infarction (MI). Furthermore, MI induces activation of the repair response in local fibroblasts, resulting in extracellular matrix accumulation that generates a stable fibrotic scar in the infarcted area. However, researchers have not determined whether hyperuricemia affects fibroblast activation and its involvement in postinfarction cardiac remodeling.

Objectives

We aimed to trigger hyperuricemia by administering potassium oxonate in a mouse model of MI to evaluate the role of hyperuricemia in MI pathogenesis.

Methods

Microarray datasets and single-cell sequencing data from gout patients, heart failure patients, and model mice were used to identify the underlying mechanisms responsible for the effect of hyperuricemia on MI progression. A hyperuricemia-related MI mouse model was established. Cardiac function was assessed, followed by sample collection and a uric acid assay. We conducted an enzyme-linked immunosorbent assay, histological detection, immunofluorescence, sequencing data processing, single-cell RNA-seq, and functional enrichment analysis. We then isolated and cultured cardiac fibroblasts and performed Western blotting, quantitative real-time polymerase chain reaction, and shRNA-mediated lumican knockdown assays.

Results

Hyperuricemia decreased cardiac function, increased mortality, and aggravated adverse fibrosis remodeling in mice after MI. These outcomes were closely related to reduced levels of fibroblast-derived lumican. This reduction activated the TGF-β/SMAD signaling pathway to induce aberrant myofibroblast activation and extracellular matrix deposition in the infarcted area. Furthermore, lumican supplementation or uric acid-lowering therapy with allopurinol alleviated hyperuricemia-mediated abnormal cardiac remodeling.

Conclusion

Hyperuricemia aggravates postinfarction cardiac remodeling by reducing lumican expression and promoting fibroblast phenotype transition. We highlight the clinical importance of lowering uric acid levels in hyperuricemia-related MI to prevent adverse ventricular remodeling.
Operational and organizational variation in determinants of policy implementation success: the case of policies that earmark taxes for behavioral health services
Authors: Purtle Jonathan , Stadnick Nicole A. , Mauri Amanda I. , Walker Sarah C. , Bruns Eric J. , Aarons Gregory A.
Published: October 2024

Background

Research on determinants of health policy implementation is limited, and conceptualizations of evidence and implementation success are evolving in the field. This study aimed to identify determinants of perceived policy implementation success and assess whether these determinants vary according to: (1) how policy implementation success is operationally defined [i.e., broadly vs. narrowly related to evidence-based practice (EBP) reach] and (2) the role of a person’s organization in policy implementation. The study focuses on policies that earmark taxes for behavioral health services.

Methods

Web-based surveys of professionals involved with earmarked tax policy implementation were conducted between 2022 and 2023 (N = 272). The primary dependent variable was a 9-item score that broadly assessed perceptions of the tax policy positively impacting multiple dimensions of outcomes. The secondary dependent variable was a single item that narrowly assessed perceptions of the tax policy increasing EBP reach. Independent variables were scores mapped to determinants in the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Multiple linear regression estimated associations between measures of determinants and policy implementation success.

Results

Perceptions of tax attributes (innovation determinant), tax EBP implementation climate (inner-context determinant), and inter-agency collaboration in tax policy implementation (outer-context and bridging factor determinant) were significantly associated with perceptions of policy implementation success. However, the magnitude of associations varied according to how success was operationalized and by respondent organization type. For example, the magnitude of the association between tax attributes and implementation success was 42% smaller among respondents at direct service organizations than non-direct service organizations when implementation success was operationalized broadly in terms of generating positive impacts (β = 0.37 vs. β = 0.64), and 61% smaller when success was operationalized narrowly in terms of EBP reach (β = 0.23 vs. β = 0.59). Conversely, when success was operationalized narrowly as EBP reach, the magnitude of the association between EBP implementation climate and implementation success was large and significant among respondents at direct service organizations while it was not significant among respondents from non-direct service organizations (β = 0.48 vs. β=-0.06).

Conclusion

Determinants of perceived policy implementation success may vary according to how policy implementation success is defined and the role of a person’s organization in policy implementation. This has implications for implementation science and selecting policy implementation strategies.
Posterior tracheal diverticulum: a case report
Authors: Safarian Afsaneh , Karimi Mehdi , Deravi Niloofar , Naseri Reza , Agin Khosrow
Published: October 2024

Background

Tracheal diverticulum is a rare condition often linked to other malformations. This case study highlights the posterior tracheal diverticulum, covering its causes, symptoms, diagnosis, treatment, and prognosis. The report is significant due to the rarity of tracheal diverticulum and potential for misdiagnosis, which can result in complications such as respiratory infections. The case offers novel insights into the presentation and management of tracheal diverticulum, helping to guide future diagnosis and treatment.

Case presentation

A 73-year-old Iranian man with a history of cardiac surgery 15 years ago was admitted to the Loghman Hakim Hospital in Tehran, Iran, for retrosternal chest pain, shoulder radiation, and a persistent cough lasting 4 months. The patient underwent cardiac tests and a lung computed tomography scan, which showed a 16 × 18 mm air-filled outpouching connected to the trachea’s right posterolateral side, leading to a diagnosis of tracheal diverticulum. The patient was treated with bronchodilators and antibiotics.

Conclusions

Tracheal diverticulum is typically asymptomatic but can present with respiratory difficulties, dysphagia, and hoarseness. Diagnosis relies on imaging, and treatment ranges from conservative management to surgical intervention, particularly in symptomatic cases or those with complications. Recognizing tracheal diverticulum in surgical and anesthesia planning is crucial to prevent severe risks such as airway obstruction or trauma. This case report highlights the importance of early detection and personalized management, potentially improving patient outcomes and guiding clinical decision-making in similar cases.
Preregistered test of whether a virtual nose reduces cybersickness
Authors: Yip Sai Ho , Ng Adrian K. T. , Lau Henry Y. K. , Saunders Jeffrey A.
Published: October 2024

Recent findings suggest that adding a visual depiction of a nose to virtual reality displays (virtual nose) can reduce motion sickness. If so, this would be a simple intervention that could improve the experience of a variety of VR applications. However, only one peer-reviewed study has reported a benefit from a virtual nose, and the effect was observed in a single low-powered experiment. To further test the effectiveness of a virtual nose for mitigating motion sickness in VR, we performed a preregistered experiment with higher power and better control. Subjects were presented with simulated movement in a virtual environment using a head-mounted display, and the resulting motion sickness was measured using the Fast Motion Sickness Scale (FMS) and the Simulator Sickness Questionnaire (SSQ). Conditions with and without a virtual nose were tested in separate sessions on different days, and the mean habituation effects were removed analytically. Awareness of the manipulation was assessed with a funnel debriefing procedure. The sample size (n = 32) was chosen to have over 90% power to detect the estimated effect size based on previous data (dz = 0.6). We found no significant difference between motion sickness in conditions with and without the virtual nose. The estimated effect size was close to zero, dz = − 0.02, with a 95% credible interval [− 0.37, 0.33]. Results from a Bayesian analysis imply that any benefit from a virtual nose is unlikely to be more than a 26% reduction in FMS scores, and any cost is unlikely to be more than a 23% increase. Our results do not support the hypothesis that a virtual nose is a general and effective way to relieve motion sickness in virtual reality.
Diagnostic and prognostic value of heparin-binding protein in pediatric community-acquired pneumonia
Authors: Mohamed Samah Abdelghany , Elmeazawy Rehab , Sharaby Radwa El , Razik Ahmed Abdel
Published: October 2024

Background

Community-acquired pneumonia (CAP) and its associated complications pose a noteworthy public health apprehension in the pediatric population, leading to considerable morbidity and mortality. The objective of this study was to assess the diagnostic and prognostic value of heparin-binding protein (HBP) as a promising biomarker in children hospitalized with CAP.

Methods

This prospective, single-center study included 50 children admitted to the Pediatric Pulmonology Unit between April 2023 and January 2024 with a diagnosis of CAP, as well as age-matched 50 healthy children as a control group. Demographic, clinical, and laboratory data were recorded. The measurement of serum HBP was conducted upon admission utilizing the enzyme-linked immunosorbent assay technique.

Results

Serum HBP was elevated in the CAP group in comparison to the control group (p < 0.001). Out of 50 patients, 27 (54.0%) had non-complicated pneumonia, and 23 (46.0%) had complicated pneumonia. The levels of HBP were significantly elevated in patients compared to the healthy control group and even higher in patients with complicated CAP compared to those with non-complicated CAP (p < 0.001). Analysis of the ROC curve revealed that the HBP level of ≥ 34.97 ng/ml was linked to a significantly higher AUC of 0.837 (95% CI 0.722–0.951, P < 0.001).

Conclusion

The level of HBP was observed to be notably elevated in patients as compared to the healthy control, thereby indicating its potential applicability in the early detection of CAP. Moreover, elevated HBP was an independent prognostic factor for complicated CAP in children.
Breast cancer risk among women with schizophrenia and association with duration of antipsychotic use: population-based cohort study in South Korea
Authors: Yang Ji Su , Kang Sunghyuk , Kim Kwanghyun , Tsai Alexander C. , Cho Chul-Hyun , Jung Sun Jae
Published: October 2024

Background

Breast cancer is a major global health issue, especially among women. Previous research has indicated a possible association between psychiatric conditions, particularly schizophrenia, and an increased risk of breast cancer. However, the specific risk of breast cancer in women with schizophrenia, compared with those with other psychiatric disorders and the general population, remains controversial and needs further clarification.

Aims

To estimate the risk of breast cancer among people with schizophrenia compared with people with other psychiatric disorders and people in the general population.

Method

We utilised medical claims data of women aged 18 to 80 years in the Korean National Health Information Database from 2007 to 2018. Individuals with schizophrenia were defined as women with ICD-10 codes F20 or F25 (n = 224 612). The control groups were defined as women with other psychiatric disorders (n = 224 612) and women in the general Korean population (n = 449 224). Cases and controls were matched by index date and age, in a 1:1:2 ratio. We estimated the hazard of breast cancer using the Cox proportional hazards model, adjusting for insurance premiums and medical comorbidities. Among the people with schizophrenia, we used the landmark method to estimate the association between duration of antipsychotic medication use and the incidence of breast cancer.

Results

In multivariable Cox regression models, the hazard rate of breast cancer was 1.26 times higher in the people with schizophrenia than in the general population (95% CI: 1.20–1.32). In comparison with the psychiatric patient group, the hazard ratio was 1.17 (95% CI: 1.11–1.28). Among women with schizophrenia, the hazard of breast cancer was greater among those who took antipsychotic medications for 1 year or more compared with those who took antipsychotics for less than 6 months.

Conclusions

Women with schizophrenia have an elevated risk of breast cancer, and long-term use of antipsychotics is associated with an increased risk of breast cancer.
Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice
Authors: Leong Ivone U.S. , Cabrera Claudia P. , Cipriani Valentina , Ross Paul J. , Turner Richard M. , Stuckey Alex , Sanghvi Sonali , Pasko Dorota , Moutsianas Loukas , Odhams Christopher A. , Elgar Greg S. , Chan Georgia , Giess Adam , Walker Susan , Foulger Rebecca E. , Williams Eleanor M. , Daugherty Louise C. , Rueda-Martin Antonio , Rhodes Daniel J. , Niblock Olivia , Pickard Alexandra , Marks Lauren , Leigh Sarah E.A. , Welland Matthew J. , Bleda Marta , Snow Catherine , Deans Zandra , Murugaesu Nirupa , Scott Richard H. , Barnes Michael R. , Brown Matthew A. , Rendon Augusto , Hill Sue , Sosinsky Alona , Caulfield Mark J. , McDonagh Ellen M.
Published: October 2024

PURPOSE

As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.

METHODS

Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (
DPYD
,
NUDT15
,
TPMT
,
UGT1A1
) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants. In a subset of 7,081 patients with cancer,
DPYD
variants were reported back to clinicians and outcomes were collected.

RESULTS

We identified clinically relevant PGx variants across the four genes in 62.7% of participants in our cohort. Extending this to annual prescription numbers in England for the drugs affected by these PGx variants, approximately 14,540 patients per year could potentially benefit from a reduced dose or alternative drug to reduce the risk of ADRs. Validating PGx associations in a real-world data set, we found a significant association between PGx variants in
DPYD
and toxicity-related phenotypes in patients treated with capecitabine or fluorouracil. Reported
DPYD
variants were deemed informative for clinical decision making in a majority of cases.

CONCLUSION

Reporting PGx variants from germline WGS relevant to patients with cancer alongside primary findings related to their cancer can be clinically informative, informing prescribing to reduce the risk of ADRs. Extending the range of actionable variants to those found in patients of non-European ancestry is important and will extend the potential clinical impact.
Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos
Authors: Zadmajid Vahid , Shahriar Shayan , Gorelick Daniel A.
Published: October 2024

Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants exhibited a significant reduction in cardiac edema after testosterone exposure. Additionally, co-treatment of wild-type embryos with testosterone and GPRC6A antagonists significantly suppressed the cardiac edema phenotype. Using RNA-seq and RNA rescue approaches, we found that testosterone and GPRC6A cause cardiac phenotypes by reducing Pak1 signaling. Our results indicate that testosterone induces cardiac edema in zebrafish embryos through GPRC6A, independent of nuclear androgen receptors, highlighting a previously unappreciated non-genomic androgen signaling pathway in embryonic development.
An image-based RNAi screen identifies the EGFR signaling pathway as a regulator of Imp RNP granules
Authors: Graeve Fabienne De , Debreuve Eric , Pushpalatha Kavya Vinayan , Zhang Xuchun , Rahmoun Somia , Kozlowski Djampa , Cedilnik Nicolas , Vijayakumar Jeshlee , Cassini Paul , Schaub Sebastien , Descombes Xavier , Besse Florence
Published: October 2024

Biomolecular condensates have recently retained much attention given that they provide a fundamental mechanism of cellular organization. Among those, cytoplasmic ribonucleoprotein (RNP) granules selectively and reversibly concentrate RNA molecules and regulatory proteins, thus contributing to the spatiotemporal regulation of associated RNAs. Extensive in vitro work has unraveled the molecular and chemical bases of RNP granule assembly. The signaling pathways controlling this process in a cellular context are, however, still largely unknown. Here, we aimed at identifying regulators of cytoplasmic RNP granules characterized by the presence of the evolutionarily conserved Imp RNA-binding protein (a homolog of IGF2BP proteins). We performed a high-content image-based RNAi screen targeting all Drosophila genes encoding RNA-binding proteins, phosphatases and kinases. This led to the identification of dozens of genes regulating the number of Imp-positive RNP granules in S2R+ cells, among which were components of the MAPK pathway. Combining functional approaches, phospho-mapping and generation of phospho-variants, we further showed that EGFR signaling inhibits Imp-positive RNP granule assembly through activation of the MAPK-ERK pathway and downstream phosphorylation of Imp at the S15 residue. This work illustrates how signaling pathways can regulate cellular condensate assembly by post-translational modifications of specific components.
A Novel Low-Impact Resistance Exercise Program Increases Strength and Balance in Females Irrespective of Menopause Status
Authors: SVENSEN ERIKA , KOSCIEN CHRISTOPHER P. , ALAMDARI NIMA , WALL BENJAMIN T. , STEPHENS FRANCIS B.
Published: October 2024

Introduction

The reduction in sex hormone production across the menopause transition is thought to accelerate age-related decline in muscle mass, strength, and stability, increasing the risk of falls and fractures. We aimed to investigate whether a novel low-impact resistance exercise program could improve strength, balance, and body composition and whether any improvement was affected by menopause status.

Methods

Seventy healthy, moderately active pre- (PRE; 46.7 ± (SD) 3.2 yr), peri- (PERI; 52.3 ± 2.2 yr), or post- (POST; 57.0 ± 2.5 yr) menopausal females, not taking hormone replacement therapy (HRT), were randomized to continue habitual physical activity (CON; n = 25) or complete a supervised resistance exercise program 4 d·wk−1 for 12 wk (EXC; n = 45). Strength at the hip and shoulder (isokinetic dynamometer), dynamic balance (Y-balance), flexibility (sit-and-reach and back-scratch), muscle thickness (rectus femoris, vastus intermedius (VI), and medial deltoid), and lean and % body fat (dual-energy x-ray absorptiometry) were measured before and after training.

Results

Hip abduction and flexion peak torque (19% ± 48% and 20% ± 17%, respectively; P < 0.05), posterolateral and posteromedial balance (12% ± 15% and 13% ± 15%, respectively; P < 0.001), flexibility (21% ± 36%, P < 0.001), VI thickness (12% ± 19%, P = 0.032), and lean mass (2% ± 2%, P = 0.007) all increased over 12 wk in EXC, but not CON, with no difference in response between PRE, PERI, and POST. The changes in shoulder strength and body mass over 12 wk were not different between CON and EXC.

Conclusions

This is the first study to demonstrate that the decline in sex hormones and an increase in age across the menopause transition do not affect the ability of lower limb (hip) strength and balance to adapt to a low-impact resistance exercise training program in females not taking HRT.
Real-Time Pricing and the Cost of Clean Power
Authors: Imelda  , Fripp Matthias , Roberts Michael J.
Published: October 2024

Solar and wind power are now cheaper than fossil fuels but are intermittent. The extra supply-side variability implies growing benefits of using real-time retail pricing (RTP). We evaluate the potential gains of RTP using a model that jointly solves investment, supply, storage, and demand to obtain a chronologically detailed dynamic equilibrium for the island of Oahu, Hawai‘i. We find that, holding demand assumptions fixed, RTP reduces costs in high-renewable systems by roughly 6 to 12 times as much as in fossil systems, markedly lowering the cost of clean energy integration. (JEL G31, L94, L98, Q42, Q48)
Achieving Air Pollution Control Targets with Technology‑Aided Monitoring: Better Enforcement or Localized Efforts?
Authors: Yang Lin , Lin Yatang , Wang Jin , Peng Fangyuan
Published: October 2024

Weak enforcement of environmental regulations remains a global issue due to inadequate monitoring and misaligned incentives. This paper examines the effects of automated monitoring on achieving air pollution control targets amidst China’s war on pollution. Utilizing the staggered rollout process and remote-sensing data, we find local governments respond to the advanced monitoring system by strategically targeting areas near monitors, resulting in a 3.2 percent decrease in pollution adjacent to automated monitors compared to areas farther away. Furthermore, we observe heterogeneity in response across cities with varying degrees of preexisting data manipulation and among officials facing different incentives and public pressure. (JEL O13, O18, P25, P28, Q53, Q55, R11)
Education and Geographical Mobility: The Role of the Job Surplus
Authors: Amior Michael
Published: October 2024

Better educated workers accept many more long-distance job offers, and relocate quicker following local shocks. I attribute this to a fundamental feature of their labor market experience, unrelated to geography: large returns to job match quality. If a good offer happens to originate from far away, the match surplus is then more likely to justify the cost of moving. This “lubricates” labor markets spatially. Using wage transition data (and a jobs ladder model), I show this can explain the bulk of mobility differentials. These differentials can be closed by subsidizing long-distance matches, and I quantify the cost of doing so. (JEL I26, J24, J41, J61, R23)
Leprosy-related disability in children and adolescents under 15 years old in Brazil: evaluation of macro-regional disparities from 2001 to 2022
Authors: Barbosa-Lima Ricardo , Vivian Geissiane Felizardo , Pinto Murilo Correzola , Santana Davi Moreira , Garcia Silas Zambaldi , De Gois Kaisa Silva Nascimento , Silva Glebson Moura
Published: October 2024

Objectives: to investigate macro-regional disparities in the incidence of leprosy in children and adolescents under 15 years old in Brazil from 2001 to 2022, with a focus on leprosy-related disabilities. Methods: an ecological study was carried out with data from the Brazilian Notifiable Diseases Information System (SINAN). The annual number of leprosy cases was normalized to every 100,000 residents in each macro-region (incidence), stratified by leprosy-related disability (grade 0, 1 and 2). The significance level was set at 5%, and Poisson regression adjusted for a robust dispersion was used to estimate the incidence ratio. Results: approximately 14% (7,694) of all leprosy cases in this age group were notified with grade 1 (78.9%) or 2 (21.1%) disability. Moreover, in grade 1 and 2, the incidence of leprosy was significantly higher in the North, Northeast and Central-West macro-regions when compared to the national estimate, as well as significantly lower in the Southeast and South (p-value <0.05). Conclusion: macro-regional disparities were observed in the incidence of leprosy in children and adolescents under 15 years old with grade 1 or 2 disability in Brazil from 2001 to 2022.
Novos biomarcadores séricos para o diagnóstico de pacientes com colite ulcerativa
Authors: De Andrade Tenorio Cavalcanti Camilla , Cardoso Campos de Assunção Beatriz , Beatriz de Andrade Moerbeck Emiliana , Vitória Gomes Diniz Larissa , Pimentel Duarte Letícia , Lucas Silva Pinheiro João , Henrique Marques Rodrigues Lucas , Oliveira Silva Damasceno Renan , De Albuquerque Nogueira Romildo , Silveira Duarte Filipe
Published: October 2024

Objetivo: realizar uma revisão da literatura sobre possíveis marcadores séricos em pacientes com RU com o objetivo de identificar potenciais biomarcadores. Métodos: os descritores “Colitis Ulcerative”, “Biomarkers” e “Diagnosis” foram utilizados para a busca nas bases de dados PUBMED, LILACS, SciELO e SCOPUS. Após a aplicação dos critérios de inclusão e exclusão nas bases de dados, os 32 artigos foram classificados como amostras. Resultados: a pesquisa indica que os biomarcadores podem desempenhar papéis distintos na avaliação da atividade e no diagnóstico da RU. Por exemplo, o peptídeo nesfatin-1 apresentou níveis séricos elevados durante os períodos ativos da doença, enquanto o peptídeo trefoil factor 3 mostrou-se promissor na predição da atividade da RU. Vale destacar que a proteína C-reativa (PCR) é um marcador comumente utilizado, no qual valores elevados são observados em pacientes durante a fase ativa da doença; no entanto, estudos sugerem a necessidade de redefinir os valores de corte da PCR para melhor predizer a remissão endoscópica. Outras abordagens, como a análise de proteínas, ácidos graxos específicos e proteínas relacionadas à matriz extracelular, também têm sido exploradas, destacando seu potencial como biomarcadores. Conclusão: em resumo, há uma diversidade de possíveis biomarcadores de importância clínica que desempenham diferentes papéis na avaliação e diagnóstico da CU. No entanto, é essencial conduzir mais pesquisas para validar esses biomarcadores para obter maior confiabilidade.
Νέες μορφές αστικής διακυβέρνησης
Authors: Χατζηβασιλείου Διαμάντω
Published: October 2024

Τα τελευταία χρόνια, το Κεντρικό Κράτος αποχωρεί όλο και περισσότερο από βασικές ρυθμιστικές πολιτικές προς όφελος των τοπικών διοικήσεων, με αποτέλεσμα να αναδύονται νέες οπτικές και ζητήματα αναφορικά με τον ρόλο του πολίτη. Σε συνδυασμό με την ανάπτυξη της τεχνολογίας και την επέκταση της τριτογενοποίησης της οικονομίας, δημιουργούνται νέα αναδυόμενα τοπία της μεταμοντέρνας πόλης και εισάγονται νέες μορφές αστικής διακυβέρνησης μεταλλάσσοντας παράλληλα και τη συμμετοχική αντίληψη για την πόλη και τον δημόσιο χώρο, τόσο σε ατομικό όσο και σε συλλογικό επίπεδο. Σε επίπεδο Τοπικής Αυτοδιοίκησης, με το Πρόγραμμα «Καλλικράτης», εισάγεται μια νέα αντίληψη που αντιμετωπίζει τον πολίτη ως «πελάτη – καταναλωτή» των δημοσίων υπηρεσιών στα πλαίσια ενός επιχειρηματικού προτύπου διοίκησης, ενσωματώνοντας παράλληλα νέες αρχές δημοκρατικής διακυβέρνησης που οδηγούν – ή επιχειρούν να οδηγήσουν - στην αναβαθμισμένη συμμετοχή του πολίτη στα κοινά. Η συνύπαρξη του επιχειρηματικού προτύπου και των διαδικασιών άμεσης δημοκρατίας με στόχο μια περισσότερο δημοκρατική διοίκηση μέσω της ενίσχυσης της ουσιαστικής και ενεργούς συμμετοχής των πολιτών σε τοπικό επίπεδο, αλλά και το πώς κυρίως οι πολίτες αντιλαμβάνονται τη θέση τους, εντός αυτού του νέου, σχετικά για τη χώρα, προτύπου διοίκησης αποτελεί το βασικό προς διερεύνηση αντικείμενο της διατριβής. H διδακτορική διατριβή βασίστηκε σε θεωρητική και εμπειρική έρευνα. Η θεωρητική προσέγγιση αφορά στη μελέτη πρωτογενών και δευτερογενών πηγών πληροφόρησης αλλά και στην επιτόπια καταγραφή και συλλογή δεδομένων και πληροφοριών από το δήμο Ηλιούπολης (μελέτη περίπτωσης). Η εμπειρική έρευνα έγινε με δομημένα ερωτηματολόγια σε 3 ομάδες στόχους: πολίτες, εργαζόμενους και αιρετούς, εξετάζοντας μεταβλητές όπως: 1. Ποιότητα υπηρεσιών- Ικανοποίηση (έλεγχος με μοντέλο SERVQUAL), 2. Αντίληψη ρόλου εντός επιχειρηματικού πλαισίου διοίκησης 3. Συμμετοχή των πολιτών στις τοπικές διαδικασίες. Δυστυχώς, η εισαγωγή της νέας πολιτικής φιλοσοφίας που διέπει τη μεταρρύθμιση του «Καλλικράτη» όσον αφορά την ενίσχυση της δημοκρατικής συμμετοχής και την ενεργοποίηση του πολίτη, δεν φαίνεται να αποδίδει τα αναμενόμενα ως προς την αξιοποίηση πραγματικών ευκαιριών προκειμένου να ασκηθεί ουσιαστική πολιτική επιρροή, ενώ τα χρόνια προβλήματα και οι παθογένειες στο χώρο της Τοπικής Αυτοδιοίκησης, παρά την εισαγωγή στους Οργανισμούς Τοπικής Αυτοδιοίκησης του επιχειρηματικού προτύπου διακυβέρνησης, εξακολουθούν να υφίστανται. Το συγκεκριμένο ερωτηματολόγιο θα μπορούσε να αποτελέσει ένα χρήσιμο εργαλείο ελέγχου της σύνδεσης ποιότητας - ως την κατεξοχήν μεταβλητή του επιχειρηματικού προτύπου διοίκησης – ικανοποίησης του πολίτη και βαθμού συμμετοχής στην Τ.Α.