bluuebunny/crossref_metadata_2025 huggingface dataset:
IL-1R1 and IL-18 Signals Regulate Mesenchymal Stromal Cells in an Aged Murine Model of Myelodysplastic Syndromes
Authors: Kawano Yuko , Kawano Hiroki , LaMere Mark W. , LaMere Elizabeth A. , Byun Daniel K. , McGrath Kathleen , Palis James , Bajaj Jeevisha , Liesveld Jane L. , Katayama Yoshio , Yamazaki Satoshi , Kapur Reuben , Calvi Laura M. , Ho Tzu-Chieh , Becker Michael W
Published: January 2025

Myelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs). In the current study, BM samples from patients with MDS demonstrated upregulated levels of IL-1 family cytokines including IL-18. Utilizing highly purified primary BM-derived mesenchymal stromal cells (MSCs), both interleukin-1b (IL-1b) and IL-18 were found to exert direct effects on MSCs, thus influencing their ability to support HSPCs as well as erythroid progenitors. This confirms the significant involvement of both these IL-1 family cytokines in regulating the BM niche. Furthermore, targeting IL-1 receptor type I (IL-1R1) mitigated these aging phenotypes in elderly mice. We subsequently employed an age-appropriate murine model of MDS by transplanting NUP98-HOXD13 transgenic mice (NHD13Tg) cells into aged wild-type mice. Treatment with inhibitors targeting interleukin-1 receptor-associated kinase 4 (IRAK4) and NLR family pyrin domain containing 3 (NLRP3) reversed the proliferation of dysfunctional MSCs and enhanced their functionality. Additionally, IRAK4 inhibition selectively suppressed MDS clonal cells while sparing non-MDS cells in the BM. These findings suggest that targeting IL-1 signaling holds promise for MDS treatment by addressing the underlying myeloid malignancy and restoring the altered BMME via BM-MSCs.
Dual Biological Role and Clinical Impact of De Novo Chromatin Activation in Chronic Lymphocytic Leukemia
Authors: Chapaprieta Vicente , Maiques-Diaz Alba , Nadeu Ferran , Clot Guillem , Massoni-Badosa Ramon , Mozas Pablo , Mateos-Jaimez Judith , Vidal Crespo Anna , Charalampopoulou Stella , Duran-Ferrer Martí , Royo Romina , Russiñol Núria , Llaó Cid Laura , Piñeyroa Juan A. , Villamor Neus , Heyn Holger , Herbst Sophie A. , Lu Junyan , Bryant Dean J. , Strefford Jonathan C. C. , Dietrich Sascha , Zenz Thorsten , Delgado Julio , López-Guillermo Armando , Campo Elías , Martin-Subero Jose Ignacio
Published: January 2025

Previous studies have reported that chronic lymphocytic leukemia (CLL) shows a de novo chromatin activation pattern as compared to normal B cells. Here, we explored whether the level of chromatin activation is related to the clinical behavior of CLL. We identified that in some regulatory regions, increased de novo chromatin activation is linked to clinical progression whereas, in other regions, it is associated with an indolent course. We next developed two prognostic scores for progressive and indolent disease, respectively, calculated a single score representing the balance between them, and further generated surrogate scores based on gene and protein expression of the target genes. The balance score outperformed the clinical impact of the two individual scores, as it seemed to capture the prognostic information provided by each of them. Biologically, CLLs with higher balance score showed increased activation of TNF-α/NF-κB and mTOR signaling pathways. Regulatory programs related to progression were predominantly activated in the lymph node microenvironment, whereas those linked to indolent disease appeared to be microenvironment-independent. Finally, we thoroughly validated the balance score as a powerful and independent quantitative prognostic factor for time to first treatment across independent CLL cohorts and data modalities such as chromatin, transcriptome or proteome data. Our findings support the concept that de novo acquisition of chromatin changes in CLL cells plays a dual biological role, and that the balance between pro-progression and pro-indolence is a strong independent determinant of CLL prognosis.
Two-layered immune escape in AML is overcome by Fcγ receptor activation and inhibition of PGE2 signaling in NK cells
Authors: Rothfuß Charlotte , Baumann Tobias , Donakonda Sainitin , Brauchle Bettina , Marcinek Anetta , Urban Christian , Mergner Julia , Pedde Anna-Marie , Hirschberger Anna , Krupka Christina , Neumann Anne-Sophie , Hänel Gerulf , Merten Camilla , Öllinger Rupert , Hecker Judith S. , Bauer Tanja , Schmid Christian Rudolf , Götze Katharina S , Altomonte Jennifer , Bücklein Veit L. , Jacobs Roland , Rad Roland , Dawid Corinna , Simeoni Luca , Schraven Burkhart , Pichlmair Andreas , Subklewe Marion , Knolle Percy Alexander , Böttcher Jan P , Höchst Bastian
Published: January 2025

Loss of anticancer NK cell function in AML patients is associated with fatal disease progression and remains poorly understood. Here, we demonstrate that AML-blasts isolated from patients rapidly inhibit NK cell function and escape NK cell-mediated killing. Transcriptome analysis of NK cells exposed to AML-blasts revealed increased CREM expression and transcriptional activity, indicating enhanced cAMP signalling, confirmed by uniform production of the cAMP-inducing prostanoid PGE2 by all AML-blast isolates from patients. Phosphoproteome analysis disclosed that PGE2 induced a blockade of LCK-ERK signalling that is crucial for NK cell activation, indicating a two-layered escape of AML-blasts with low expression of NK cell-activating ligands and inhibition of NK cell signalling. To evaluate the therapeutic potential to target PGE2 inhibition, we combined Fcg-receptor-mediated activation with the prevention of inhibitory PGE2-signalling. This rescued NK cell function and restored the killing of AML-blasts. Thus, we identify the PGE2-LCK signalling axis as the key barrier for NK cell activation in two-layered immune escape of AML-blasts that can be targeted for immune therapy to reconstitute anti-cancer NK cell immunity in AML patients.
CpG island methylator phenotype classification improves risk assessment in pediatric T-cell Acute Lymphoblastic Leukemia
Authors: Schäfer Hackenhaar Fernanda , Refhagen Nina , Hagleitner Melanie M , van Leeuwen Frank N. , Marquart Hanne Vibeke , Madsen Hans Ole , Landfors Mattias , Osterman Pia , Schmiegelow Kjeld , Flaegstad Trond , Jonsson Olafur G , Kanerva Jukka , Abrahamsson Jonas , Heyman Mats , Noren-Nystrom Ulrika , Hultdin Magnus , Degerman Sofie
Published: January 2025

Current intensive treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has substantial side-effects, highlighting a need for novel biomarkers to improve risk stratification. Canonical biomarkers such as genetics and immunophenotype are largely not used in pediatric T-ALL stratification. This study aimed to validate the prognostic relevance of DNA methylation CpG island methylator phenotype (CIMP) risk stratification in two pediatric T-ALL patient cohorts: the Nordic NOPHO ALL2008 T-ALL study cohort (n=192) and the Dutch DCOG ALL-10/ALL-11 validation cohorts (n=156). Both cohorts showed that combining CIMP classification at diagnosis with measurable residual disease (MRD) at treatment day 29 or 33 significantly improved outcome prediction. The poor prognosis subgroup, characterized by CIMP low/D29 or D33 MRD≥0.1%, showed a cumulative incidence of relapse (pCIR5yr) of 29.0% and 23%, and overall survival (pOS5yr) of 59.7% and 65.4%, in NOPHO and DCOG, respectively. Conversely, a good prognosis subgroup was also identified representing CIMP high/D29 or D33 MRD<0.1% with pCIR5yr of 0% and 3.4%, and pOS5yr of 98.2% and 94.8%, in NOPHO and DCOG, respectively. For NOPHO, MRD was also evaluated on D15, and the relapse prediction accuracy of CIMP/D29 MRD (0.79) and CIMP/D15 MRD (0.75) classification was comparable, indicating potential for earlier stratification. The evaluation of the biology behind the CIMP subgroups revealed associations with transcriptome profiles, genomic aberrations, and mitotic history, suggesting distinct routes for leukemia development. In conclusion, integrating MRD assessment with the novel CIMP biomarker has the potential to improve risk stratification in pediatric T-ALL and guide future therapeutic decisions.
Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction in Newly Diagnosed Myeloma: Analysis of the MIDAS Trial
Authors: Perrot Aurore , Touzeau Cyrille , Lambert Jerome , Hulin Cyrille , Caillot Denis , Karlin Lionel , Arnulf Bertrand , Rey Philippe , Garderet Laurent , Macro Margaret , Escoffre-Barbe Martine , Gay Julie , Chalopin Thomas , Gounot Romain , Schiano de Colella Jean Marc , Tiab Mourad , Mohty Mohamad , Kuhnowski Frédérique , Fontan Jean , Manier Salomon , Orsini Piocelle Frederique , Vincent Laure , Rigaudeau Sophie , Leleu Xavier , Hébraud Benjamin , Flet Laurent , Malfuson Jean-Valère , Jacquet Caroline , Chaoui Driss , Meuleman Nathalie , Abarah Wajed , Montes Lydia , Benramdane Riad , Sonntag Cécile , Zerazhi Hacene , Danu Alina , Allangba Olivier , Dib Mamoun , Roussel Murielle , Cereja Sophie , Depaus Julien , Branche Nicolas , Demarquette Hélène , Richez Valentine , Bruiec Cherel , Frenzel Laurent , Vekemans Marie-Christiane MB , Bigot Noemie , Avet-Loiseau Hervé , Corre Jill , Moreau Philippe
Published: January 2025

In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD. Between December 2021 and July 2023, 791 patients were enrolled across 72 centers. The median age was 59 years; 13% had ISS-stage III, 5% had R-ISS-stage III, and 8% had high-risk cytogenetics (IFM Linear Predictor cytogenetic score >1). Overall, 96% (N=757) of patients completed induction. The median CD34+ cell yield was 7 × 106/Kg, with 94% of patients able to proceed with a potential tandem transplant. The best overall response rate was 95%. In the intent-to-treat population, 91% achieved a very good partial response or better after induction, with MRD-negativity rates of 63% at 10-5 and 47% at 10-6. MRD-negativity rates differed across ISS stages and cytogenetic subgroups. During induction, 7 patients experienced disease progression, and 5 died due to disease progression (N=1), cardiac events (N=2), or other causes (N=2). The most common grade 3/4 adverse events were neutropenia (25%), thrombocytopenia (5%), and infections (7%); only 13% of patients reported any grade peripheral neuropathy. IsaKRD induction yielded deep responses and high MRD-negativity rates while ensuring successful stem cell collection, with no new safety signals. Continued follow-up of this ongoing study is required to confirm these findings.
HSP-CAR30 WITH A HIGH PROPORTION OF LESS-DIFFERENTIATED T CELLS PROMOTES DURABLE RESPONSES IN REFRACTORY CD30+ LYMPHOMA
Authors: Caballero Gonzalez Ana Carolina , Ujaldón-Miró Cristina , Pujol-Fernández Paula , Montserrat-Torres Rosanna , Guardiola-Perello Maria , Escudero-López Eva , Garcia-Cadenas Irene , Esquirol Albert , Martino Rodrigo , Jara-Bustamante Paola , Ezquerra Condeminas Pol , Soria Jose Manuel , Iranzo Ribera Eva , Moreno-Martinez Maria-Estela , Riba Mireia , Sierra Jorge , Alvarez-Fernández Carmen , Escribà-Garcia Laura , Briones Javier
Published: January 2025

CD30-directed CART cell therapy (CART30) has limited efficacy in relapsed or refractory patients with CD30+ lymphoma, with a low proportion of durable responses. We have developed an academic CART30 cell product (HSP-CAR30) by combining strategies to improve performance. HSP-CAR30 targets a proximal epitope within the non-soluble part of CD30, and the manufacturing process includes a modulation of ex vivo T cell activation, as well as the addition of interleukin-21 to IL-7 and IL-15 to promote stemness of T cells. We translated HSP-CAR30 to a phase 1 clinical trial of 10 patients with relapsed/refractory classical Hodgkin lymphoma (HL) or CD30+ T cell lymphoma (T-NHL). HSP-CAR30 was mainly composed of memory stem-like (TSCM-LIKE) and central memory (TCM) CAR30+ T cells (87.5%±5%). No dose-limiting toxicities were detected. Six patients had grade 1 cytokine release syndrome, and no patient developed neurotoxicity. The overall response rate was 100%, and 5 out of 8 patients with HL achieved complete remission (CR). An additional HL patient achieved CR after a second HSP-CAR30 infusion. Remarkably, 60% of patients have ongoing CR after a mean follow-up of 34 months. Of note, CAR30+ T cells at expansion peak had a predominance of TSCM and TCM cells, and CAR30+ T cells remained detectable in 3 of 5 evaluable patients at least 12 months after infusion. Our study shows that selection of the epitope targeting CD30 and ex vivo preservation of less-differentiated memory T cells may enhance the efficacy of CART30 in patients with refractory HL. This trial is registered at www.clinicaltrials.gov (NCT04653649).
Potential alternative and novel biomarkers for paediatric MAFLD: exploratory evidence from a Chinese cohort
Authors: Yang Fan , Hu Mengyuan , Xu Lulian , Zheng Xiaowei , Zhu Lihong , Zhang Le , Zhang Haoyang
Published: January 2025

Background

While the associations between pediatric non-obese metabolic dysfunction-associated fatty liver disease (MAFLD) and multiple diagnostic biomarkers are well-established, the role of a broader range of blood-based, urine-based, and body composition-based biomarkers for monitoring MAFLD are needed.

Methods

A pediatric cohort was established in Wuxi, China. We measured body composition biomarkers, blood-based and urine-based biomarkers, and liver stiffness in participants to diagnose MAFLD and identify alternative and novel potential biomarkers for MAFLD. Body mass index (BMI), high-density lipoprotein cholesterol (HDLC), triglycerides, glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist perimeter were used as MAFLD diagnostic biomarkers. To identify alternative biomarkers, we performed correlation analysis to determine biomarkers exhibited strong correlation (|r| > 0.8, p-value < 0.05) with diagnostic biomarkers. To identify novel potential biomarkers, we performed regression analysis to determine biomarkers associated with MAFLD (p-value < 0.05 in stepwise multivariate regression) among the remaining biomarkers that are not related to the diagnostic biomarkers.

Results

Out of 1,108 participants who completed all examinations (N biomarker = 91), 113 participants were diagnosed with MAFLD (prevalence: 14.99% in boys and 5.18% in girls). 27 biomarkers that were strongly correlated with diagnostic biomarkers were identified as alternative biomarkers. A multivariate logistic regression analysis identified 9 novel potential biomarkers including 5 blood-based biomarkers (plateletocrit, calcium, insulin, AST/ALT ratio, total bilirubin), urine pH, and body fat measurements in the arm, leg, and thigh.

Conclusions

This study illustrated the characteristics and potential alternative and novel biomarkers of MAFLD based on a Chinese paediatric cohort. These findings posed new paths in guiding the prevention and early diagnosis and prevention.

Trial registration

This trial was registered in the Chinese Clinical Trials Registry (ChiCTR2400080508). The date of first registration, 01/31/2024. Retrospectively registered.
Impact of COVID-19 pandemic measures on hospitalizations and epidemiological patterns of twelve respiratory pathogens in children with acute respiratory infections in southern China
Authors: Wang Wei , Luo Xiaojuan , Ren Zhenmin , Fu Xiaoying , Chen Yunsheng , Wang WenJian , Bao Yanmin , Zheng Yuejie , Cao Ke , Chen Jiehua
Published: January 2025

Objectives

To investigate the impact of COVID-19 pandemic measures on hospitalizations and the alterations and persistence of the epidemiological patterns of 12 common respiratory pathogens in children during the COVID-19 pandemic and after the cessation of the “zero-COVID-19” policy in southern China.

Methods

Respiratory specimens were collected from hospitalized children with acute respiratory infections at Shenzhen Children’s Hospital from January 2020 to June 2024. Twelve common respiratory pathogens were detected using multiplex PCR. Data on demographic characteristics, pathogen detection rates, epidemiological patterns, co-infections, and ICU admission rates were compared between the ‘during COVID-19’ period (Phase 1: January 2020 to December 2022) and the ‘post COVID-19’ period (Phase 2: January 2023 to June 2024).

Results

In Phase 2, there was a significant increase in average annual cases, with a higher median age of affected children, higher pathogen detection rates, and increased co-infection rates compared to Phase 1. The epidemiological patterns of most pathogens were altered by the COVID-19 pandemic. Human Parainfluenza Virus, Human Metapneumovirus, Human Bocavirus (HBOV), and Human Coronavirus remained active during Phase 1, while Mycoplasma pneumoniae (Mp) and Adenovirus (ADV) were low, and Respiratory Syncytial Virus (RSV) lacked a seasonal peak in 2022. In Phase 2, Mp, ADV, and RSV experienced outbreaks, with Mp’s high prevalence continuing into 2024. RSV showed out-of-season epidemics for two consecutive years. Influenza A (H1N1), Influenza A (H3N2), and InfB lost their seasonal patterns during Phase 1 but reemerged and regained their seasonal characteristics in 2023–2024. ICU admission rates did not significantly differ between the two phases, except for HBOV, which had higher rates in Phase 2.

Conclusion

The epidemiological patterns of various respiratory pathogens were affected by the COVID-19 pandemic to varying degrees. Pathogens suppressed during the pandemic experienced outbreaks or out-of-season epidemics after the lifting of non-pharmaceutical interventions, with Mp and RSV continuing into the second year and HBOV associated ICU admission rates increasing in the post-pandemic era. Continuous monitoring of these patterns is essential to understand the duration of these effects and to inform effective response strategies.
Assessing public support for air pollution mitigation and control policies: health, socioeconomic, and ideological predictors in an overburdened and vulnerable region of the U.S.
Authors: Zarate-Gonzalez Gilda , Brown Paul , Cisneros Ricardo
Published: January 2025

Background

The San Joaquin Valley (SJV) in California is one of the most polluted regions in the U.S. This study examined favorability for air pollution mitigation policies, interventions, and identified predictors amongst region’s residents.

Methods

A cross-sectional online survey asked about health status and conditions, self-protective behaviors, attitudes toward air pollution recommendations, air quality information knowledge and mitigation behaviors, as well as whether their views were favorable or unfavorable towards policy and interventions. EuroQOL-5D-3L was utilized to estimate quality-of-life distribution equity and air pollution policy favorability.

Results

A total of 310 adults residing in the SJV participated in the survey. The mean age was 42.90 years, with 34% having asthma. People with asthma reported the lowest health-related quality of life (HRQoL) compared to other air pollution “sensitive” groups. Concerns included the costs, charge and attributes of adopting hybrid or electric vehicles. Residents supported air pollution control and public space preservation, with socioeconomic factors and health state being significant predictors. Left-wing ideologies favor policies charging polluters, controlling emissions, and preserving public spaces, whereas right-wing views negatively predict support for electric vehicle charges and local organization interventions.

Conclusions

Results may help air pollution control policymakers, public health agencies, environmental justice organizations, and the health equity research community understand the reasons for differential responses to air pollution interventions and mitigation efforts. This new knowledge could assist stakeholders in recommending sustainable and cost-effective interventions for improving air quality, elicit behavior change, and climate change adaptation in the region.
The impact of regular physical activity on vertebral fractures: Korean nationwide population-based cohort study
Authors: Han Sangsoo , Choi Sungwoo , Jang Hae-Dong , Park Jiwon , Han Kyungdo , Nah Sangun , Suh Dong Hun , Im Dong Sub , Hong Jae-Young
Published: January 2025

Background

Vertebral fractures are a common medical issue. Physical activity helps improve bone health and manage the risk of fractures. However, much controversy exists about the association between physical activity and vertebral fractures. Therefore, we aimed to investigate the association between changes in regular physical activity (RPA) and vertebral fractures.

Methods

This study was a nationwide, observational cohort study based on claim data from the Korean National Health Insurance Service. Physical activity level was obtained from self-reported questionnaires from 2009 to 2012. Participants were divided depending on their levels of physical activity and the occurrence of vertebral fractures from 2013 to 2016 was recorded.

Results

The group with sufficient RPA, compared to the Insufficient group (incidence rate showed a decrease of 1.93/1,000 PY; adjusted HR (aHR): 0.83; 95% CI: 0.81–0.84), had a reduced risk of vertebral fracture. From the perspective of RPA changes, the Continuous Sufficient group had an aHR of 0.74, 95% CI 0.72–0.76, and the Increased group had an aHR of 0.87, 95% CI 0.85–0.88. The Decreased group had an aHR of 0.94, 95% CI 0.92–0.95.

Conclusion

The degree of RPA could reduce the risk of vertebral fracture. Continuous sufficient RPA helped lower the risk of vertebral fracture.
Medical student training with next-generation handheld ultrasound devices – hands on examination of fetal biometry in obstetrics
Authors: Plöger Ruben , Matschl Julia , Walter Adeline , Gembruch Ulrich , Strizek Brigitte , Behning Charlotte , Wittek Agnes , Recker Florian
Published: January 2025

Introduction

The technical development of ultrasound devices based on silicon chips has revolutionized ultrasound examinations, leading to the implementation of these portable handheld devices (PUD) in different medical fields. However, training on these devices is necessary to assure appropriate use and ensure valid results. While training programs for the use of conventional standard ultrasound devices (SUD) have been described, no training program for these handheld devices has been developed thus far.

Methods

A training program for obstetric ultrasound examination was modified through the addition of an extra module focusing on the use of these PUDs. After the module the students had to attend an OSCE in which their skills of using the PUD and the SUD were tested and analyzed by applying the agreement rate, the intraclass correlation coefficient (ICC) and Bland–Altman plots. Furthermore, the students’ ultrasound results were compared with those of trained physicians by employing the one-sample Student's t-test. After the OSCE, the students answered a survey regarding their experience and their expected use of these devices.

Result

An agreement of one hundred percent was reached for basic parameters such as fetal position, placental position, fetal heartbeat and for the classification of the amniotic fluid. The ICC showed a good to moderate agreement between the results of fetal biometry achieved by SUD and PUD. The T-test results confirmed a high reliability between the physicians’ results and the students’ results, independent of the used device. The students remarked a good handling of the ultrasound devices and supported the use in their future specialties.

Discussion

The reliability between the examinations using the SUD and PUD were high but lower than the results observed for trained physicians. Therefore, the implementation of an additional module for portable ultrasound teaches the students to reliably examine basic obstetric parameters and provides a solid basis for further training and improvement of ultrasound skills in use of PUD.
Physiology-informed use of Cupriavidus necator in biomanufacturing: a review of advances and challenges
Authors: Weldon Michael , Euler Christian
Published: January 2025

Biomanufacturing offers a potentially sustainable alternative to deriving chemicals from fossil fuels. However, traditional biomanufacturing, which uses sugars as feedstocks, competes with food production and yields unfavourable land use changes, so more sustainable options are necessary. Cupriavidus necator is a chemolithoautotrophic bacterium capable of consuming carbon dioxide and hydrogen as sole carbon and energy sources, or formate as the source of both. This autotrophic metabolism potentially makes chemical production using C. necator sustainable and attractive for biomanufacturing. Additionally, C. necator natively fixes carbon in the form of poly-3-hydroxybutyrate, which can be processed to make biodegradable plastic. Recent progress in development of modelling and synthetic biology tools have made C. necator much more usable as a biomanufacturing chassis. However, these tools and applications are often limited by a lack of consideration for the unique physiology and metabolic features of C. necator. As such, further work is required to better understand the intricate mechanisms that allow it to prioritise generalization over specialization. In this review, progress toward physiology-informed engineering of C. necator across several dimensions is critically discussed, and recommendations for moving toward a physiological approach are presented. Arguments for metabolic specialization, more focus on autotrophic fermentation, C. necator-specific synthetic biology tools, and modelling that goes beyond constraints are presented based on analysis of existing literature.
Sprengel deformity: What is the functional outcome of conservative treatment versus surgical correction?
Authors: Antfang C. , Frommer A. , Gosheger G. , Toporowski G. , Laufer A. , Rölfing J. D. , Roedl R. , Vogt B.
Published: January 2025

Background

Sprengel deformity is a rare congenital malformation of the scapula defined by malposition during embryonic development. Affected individuals have limited range of motion of the shoulder and torticollis. Surgical reconstruction is an option to treat patients with severe deformity and functional impairment. This retrospective single centre study evaluated 19 patients with 21 Sprengel deformities treated from 2016 to 2023. 11/19 patients had mild ROM limitations of the affected shoulder with a median abduction of 130° (interquartile range (IQR) 100–150) and were treated conservatively. 8/19 patients with severe Sprengel deformity and functional impairment underwent surgery (median age 6 years (IQR 4–6)). Surgery was conducted in a modified technique according to Green. The Cavendish and Rigault scores were employed to analyse function, cosmesis and the radiographic location of the scapula. Patient reported outcome measurements (EQ-5D-Y and the quick Disabilities of the Arm, Shoulder and Hand Questionnaire) were both administered at the latest follow-up.

Results

Patients treated conservatively had a median abduction of the affected arm of 130° (IQR 100–150) and a median Cavendish and Rigault score of both 2 (IQR 2–3 and 1.3-2, respectively). In the surgery group the median abduction improved by 45° (IQR 28–53) from 90° (IQR 90–90) preoperatively to 135° (IQR 120–140) 3 months postoperatively and was 110° (IQR 108–128) at latest follow-up. The median Cavendish score improved from 4 (IQR 2–4) to 1 (IQR 1–2). The median Rigault score was lowered from 3 (IQR 3–3) to 1 (IQR 1–2). The median time to return to daily life was 3 months (IQR 2.2–3.5). The median quickDASH score was 11.4 (IQR 7–31) in the surgical cohort and 9.1 (IQR 5–22) in the conservative cohort at median maximum follow-up of 62 months (IQR 22–118). The median EQ-VAS (Visual Analogue Scale) score was 81/100 (IQR 79–85/100) in the surgical cohort and 80/100 (IQR 59–95/100) in the non-surgical cohort. 4/8 patients treated surgically had fully reversible complications.

Conclusions

Surgical treatment of severe Sprengel deformity improves abduction of the affected shoulder and reduces disability in daily life. Patients with mild Sprengel deformity can have very good function of the shoulder and should not be considered for surgery.
Associations of maternal night shift work during pregnancy with DNA methylation in offspring: a meta-analysis in the PACE consortium
Authors: Marques Irene F. , Domènech-Panicello Carola , Geurtsen Madelon L. , Hoang Thanh T. , Richmond Rebecca , Polinski Kristen , Sirignano Lea , Page Christian M. , Binter Anne-Claire , Everson Todd , Burt Amber , Deuschle Michael , Gilles Maria , Streit Fabian , Mumford Sunni L. , Magnus Per , Reiss Irwin K. M. , Vermeulen Marijn J. , Witt Stephanie H. , Chaves Inês , Yeung Edwina , London Stephanie J. , Guxens Mònica , Felix Janine F.
Published: January 2025

Background

Night shift work during pregnancy has been associated with differential DNA methylation in placental tissue, but no studies have explored this association in cord blood. We aimed to examine associations of maternal night shift work with cord blood DNA methylation.

Methods

A total of 4487 mother–newborn pairs from 7 studies were included. Maternal night shift work during pregnancy was ascertained via questionnaires and harmonized into “any” versus “no”. DNA methylation was measured in cord blood using the Illumina Infinium Methylation arrays. Robust linear regression models adjusted for relevant confounders were run in the individual cohorts, and results were meta-analyzed.

Results

Maternal night shift work during pregnancy ranged from 3.4% to 26.3%. Three CpGs were differentially methylated in relation to maternal night shift work during pregnancy at a false discovery rate adjusted P < 0.05: cg10945885 (estimate (β) 0.38%, standard error (SE) 0.07), cg00773359 (β 0.25%, SE 0.05), and cg21836426 (β − 0.29%, SE 0.05). Associations of the identified CpGs were found in previous literature for gestational age and childhood and adolescent BMI. In a mouse model of prenatal jet lag exposure, information on offspring DNA methylation of ten homologous genes annotated to the 16 CpGs with P < 1 × 10−5 in our analysis was available, of which eight were associated (enrichment P: 1.62 × 10−11).

Conclusion

Maternal night shift work during pregnancy was associated with newborn DNA methylation at 3 CpGs. Top findings overlapped with those in a mouse model of gestational jet lag. This work strengthens evidence that DNA methylation could be a marker or mediator of impacts of circadian rhythm disturbances.
Empirical case study of a digitally enabled energy community with prosumers and P2P trading
Authors: Staudt Philipp , Richter Bent
Published: January 2025

Background

An ’energy community’ can add socioeconomic components to microgrids and has recently been solidified as the regulatory concept of a ’Citizen Energy Community’ by the European Union. Such energy communities can further be supplemented with digital capabilities. This paper provides insights from a 13-month case study on a digitally enabled energy community with prosumers with limited ability to provide manual demand response, who were enabled to engage in peer-to-peer trading of local energy generation.

Results

Long-term willingness to pay for local sustainable electricity in the market environment was lower than expected. Overall willingness and ability to provide manual demand response might be low. Participants’ use of the provided digital tools were at least partly driven by their desire to control energy costs.

Conclusions

Repeat interaction with the energy community’s market and its inherent complexities might limit the ability of energy communities to provide technical and economic benefits. This diminishes the appeal of corresponding business models. One direction to make energy communities more attractive to regulators and utilities is the conceptualization, design, and empirical evaluation of systems that lead to low perceived complexity for participants while enabling high levels of external automated control.
Cognitive impairment, depressive and anxiety disorders among post-COVID-19 survivors: a follow-up study
Authors: Aziz Ayman A. , Latif Ahmed A. , Elseesy Sandra W.
Published: January 2025

Background

Psychiatric signs may be induced by the cytokine storm that is implicated in the immune response to coronavirus through neuro-inflammation. Survivors disclosed symptoms of obsessive–compulsive disorder, melancholy, anxiety, panic disorder, and post-traumatic stress disorder. For the first year following the SARS disease, they generally suffer from suicide and psychosis.

Aim

To evaluate the presence of cognitive impairment, anxiety disorders, and depression in adult survivors of COVID-19, 1 month and 3 months post-recovery.

Method

It is an observational longitudinal study. Forty-four COVID-19 survivor patients, with no past psychiatric history were evaluated at 3 months and 1 month after recovery. The Montreal Cognitive Impairment Basic (MoCA-B) was employed to evaluate cognitive impairment. However, anxiety and depressive disorders were identified via structured clinical interview for DSM IV, axis I (SCID-I) and their severity was examined by the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) consecutively.

Results

Regarding cognitive impairment, MoCA-B results showed a mean score of 25.95 ± 1.98 in the 1st interview and 27.7 ± 1.05 in the 2nd interview, with a marked change, P-value = 0.001. SCID-I showed that 43.2% of our sample was diagnosed with both anxiety and depression at 1 month post-recovery, with the improvement of some cases at 3 months to affect only 18.2%, showing a statistically significant difference, P-value = 0.036. The percentage of patients who suffered from sleep difficulties was 59.1% at 1st interview and 27.3% at 2nd interview. While 61.4% of patients suffered from fatigue and low concentration at 1st interview and went down to 31.8% at 2nd interview, showing a statistically significant difference, P-value < 0.001. The severity of depression and anxiety in those diagnosed also declined from the 1st interview to the 2nd, BDI mean score in 1st interview was 12.30 ± 10.46, and in the 2nd interview was 7.09 ± 9.24 with marked variation P-value < 0.001, while BAI means score at the 1st interview was 18.18 ± 16.85 and at the 2nd interview was 11.32 ± 16.12 with statistically significant difference P = 0.001.

Conclusion

Impairment of cognitive functions; especially delayed recall; was one of the important COVID-19 psychiatric sequelae, In addition to anxiety and depressive signs in the form of depressed/anxious mood, fatigue, decreased concentration, and sleep disturbances. The severity of symptoms declined over the 3 months period of the study.
Microcredit as a catalyst for microbusiness growth: a myth or reality; a case of Asante-Akim Central Municipality, Ghana
Authors: Musah Ibrahim
Published: January 2025

This study investigates the effect of microcredit on the growth of microenterprises in the Asante-Akim Central Municipal Area of Ghana. The analysis reveals that while larger loan amounts positively influence business growth, high interest rates and rigid repayment terms impede these benefits. Entrepreneurs with higher education levels report better growth outcomes, emphasizing the significance of financial literacy and management skills. However, the evidence indicates that microcredit alone is insufficient to consistently drive sustainable growth for microenterprises, as structural challenges persist. Practical implications suggest that microfinance institutions (MFIs) should revise loan structures to include lower interest rates, extended grace periods, and flexible repayment options. Additionally, integrating financial literacy programs into microfinance services could enhance loan utilization and business outcomes. These findings challenge the universal applicability of microcredit as a growth catalyst, advocating for tailored approaches to better align financial products with the needs of microenterprises in emerging markets.
Identifying and evaluating causes of waste effect in green building projects
Authors: Issa Usama Hamed , AbdelHaffez Ahmed Gamal , Abdel-Hafez Alaa Atif , Assaf Kamal Abbas
Published: January 2025

Green building (GB) projects in the Middle East face several causes of waste that occur during design and construction stages. These causes affect the objectives of GB projects (economic, environmental, and social). Therefore, this research aims to define causes of waste in GB projects and evaluate the effect of these causes on the objectives of GB projects. Forty-five causes of waste are determined and classified into five main groups as follows: (G01) green materials, (G02) green building design, (G03) sustainable site, (G04) green building technologies, and (G05) green building stakeholders. Through field surveys, including semi-structured interviews and brainstorming sessions, the probability of occurrence for each cause of waste and impact on the economic, environmental, and social objectives are evaluated, as well as the waste severity is determined based on a combined effect of probability and impacts. The correlations among the waste indices are assessed, and the highest correlation is observed between probability and economic followed by economic and social objective. The results show that the most significant cause of waste that has the highest value for economic, environmental, and social objectives is “Poor assessment of site conditions before design, such as topography, hydrology, climate, vegetation, and soil.” Group 05 has the maximum number of critical causes of waste, which is considered the most significant group, due to its high values related to all objectives. Results indicate that the economic objective is classified as the most affected one by the causes of waste, followed by the environmental objective.
Geophysical characterization of dissolution features and deformation in bedded salt formations in NE Delaware Basin
Authors: Schuba Nur , Moscardelli Lorena , Dooley Tim P. , Peel Frank J. , Martinez-Doñate Ander , Lawton Tim , Apps Gillian , Schuba Jonathan P.
Published: January 2025

Salt formations have resource potential for energy storage, nuclear waste repositories, brine production; but their mineralogical heterogeneity and complex structures present significant challenges for characterization. This geophysical analysis uses 3-D seismic reflection and petrophysical data to explore the intricate characteristics of the Lopingian bedded salt formations in the Delaware Basin located within the Greater Permian Basin Area in the United States. The study focuses on the Castile and Salado formations and reveals an area of deformed strata linked to an intrasalt fold-thrust belt in the southwestern portion of the 215 mi2 (557 km2) seismic volume within the bedded salt interval. The proposed mechanism for the deformation involves gravitational gliding initiated during the Lopingian, influenced by a northeasternward tilt of the décollement towards the shelf. Adjacent to the fold-thrust belt, there is a geophysically distinct area we term the buffer zone. The Castile Formation within the buffer zone differs from its expected cyclical anhydrite-halite members and is only composed of anhydrite. The buffer zone’s unique composition prompts a reevaluation of halite absence, suggesting gypsum deposition, followed by conversion to anhydrite, instead of a dissolutional mechanism, as previously postulated. The overlying Salado Formation exhibits heterogeneity and karst features (i.e. sags, suffusion, and collapse features), indicating potential complications and geohazards. The findings underscore the importance of multidisciplinary approaches and extensive data sets for accurate mapping, geohazard assessments, strategic placement of salt caverns in underground storage, and for assessment of evaporitic sequences as effective seals for underlying petroleum systems and water resources.
Child mental health problems and poverty
Authors: Graham Philip , Maughan Barbara
Published: January 2025

Waiting lists for children and young people with mental health problems are at an all-time high. Almost the only policies proposed to deal with this situation involve increasing the number of mental health professionals. Little attention is given to dealing with the underlying causative stresses, of which poverty is easily the most pervasive. It is suggested that unless levels of poverty are reduced, the rates of psychiatric disorders will not change. As psychiatrists, we need to become much more active in pressing for action over child poverty.
‘If one doesn't happen, the other will’: forensic mental health service patients’ experiences of co-occurring self-harm and aggression
Authors: Shafti Matina , Taylor Peter , Forrester Andrew , Robinson Louise , Mathews Sandeep , Pratt Daniel
Published: January 2025

Background

Co-occurring self-harm and aggression (dual harm) is particularly prevalent among forensic mental health service (FMHS) patients. There is limited understanding of why this population engages in dual harm.

Aims

This work aims to explore FMHS patients’ experiences of dual harm and how they make sense of this behaviour, with a focus on the role of emotions.

Method

Participants were identified from their participation in a previous study. Sixteen FMHS patients with a lifetime history of dual harm were recruited from two hospitals. Individuals participated in one-to-one, semi-structured interviews where they reflected on past and/or current self-harm and aggression. Interview transcripts were analysed using reflexive thematic analysis.

Results

Six themes were generated: self-harm and aggression as emotional regulation strategies, the consequences of witnessing harmful behaviours, relationships with others and the self, trapped within the criminal justice system, the convergence and divergence of self-harm and aggression, and moving forward as an FMHS patient. Themes highlighted shared risk factors of dual harm across participants, including emotional dysregulation, perceived lack of social support and witnessing harmful behaviours. Participants underlined the duality of their self-harm and aggression, primarily utilising both to regulate negative emotions. These behaviours also fulfilled distinct purposes at times (e.g. self-harm as punishment, aggression as defence). The impact of contextual factors within FMHSs, including restrictive practices and institutionalisation, were emphasised.

Conclusions

Findings provide recommendations that can help address dual harm within forensic settings, including (a) transdiagnostic, individualised approaches that consider the duality of self-harm and aggression; and (b) cultural and organisational focus on recovery-centred practice.
Ekata Work
Authors: Bigelow Anna
Published: January 2025

For decades, the Muslim-majority town of Malerkotla, Punjab, has been emblematic of communal harmony—the place where everyone gets along, a so-called island of peace. As the author has argued previously, this reputation is the result of hard work and constant vigilance to realize it on the ground, even imperfectly. It also persists despite enormous pressure. The last decade has proven challenging for Malerkotla citizens, but their work continues. From the protests in Shaheen Bagh, Delhi, against the Citizenship Amendment Act, to the farmers’ protests at the Delhi borders, to current political concerns after Malerkotla became a newly minted electoral district, Malerkotlans continue to strive for belonging in an India where divisive nationalisms are ascendant. This article addresses the past and present of citizen strategies to build intersectional solidarities, to affirm and reaffirm a long-standing collective identity built on communal harmony, and to imagine a future India that is diverse, inclusive, and just.
Rethinking “Brahmanization” and Caste Politics in Late Ancient South Asia
Authors: Witkowski Nicholas
Published: January 2025

This article contributes to the body of scholarship that is critical of overreliance on what Johannes Bronkhorst has called the “Brahmanization” model of historical transformation in late ancient South Asia (ca. 200 BCE–ca. 600 CE). By Brahmanization, the author refers to the process by which Brahmin communities of late ancient South Asia became managers of a socioeconomic order defined by the purity politics of caste. In particular, this article proposes to rethink the preponderant conceptions of power relations during the early first millennium CE by focusing on textual descriptions of outcaste groups that late ancient hegemonic forces collectively referred to as Caṇḍālas. This article will demonstrate that the Buddhist monastic governmentality was a critical institutional battleground upon which the combat between Brahmanizing forces across South Asia and those subaltern communities resistant to caste-based hegemony played out in the early centuries of the common era. This article argues that the Caṇḍāla communities that joined these Buddhist monasteries successfully carved out within these institutions spaces of relative social autonomy from Brahmanical power structures.
Exploring Perspectives and Challenges in Religious Property Administration
Authors: Papastathis Konstantinos
Published: January 2025

This article examines the issue of property administration within the Orthodox Patriarchate of Jerusalem from the late Ottoman period to the present, focusing on the acquisition and management of extensive land estates known as vakf that hold immense significance, especially given the ongoing land dispute between Israel and the Palestinians. In this context, the article provides a concise historical overview of the development of the church's immovable property portfolio and discusses the question of who should be its administrator and under which conditions the state authorities should be involved. To this end, it analyzes the charter of the patriarchate, established as law 27/1958 by the Kingdom of Jordan, highlighting its advantages as well as its implementation in practice. It argues that the legal status of Jerusalem is intricately linked to this matter, as the Israeli judiciary recognizes only the patriarch's authority in validating contracts, marginalizing the laity and the Brotherhood of the Holy Sepulchre. By shedding light on these challenges and the complex dynamics at play, the article provides insights into the current state of property administration within the Orthodox Church of Jerusalem and highlights the need for addressing these issues in the future.
GLOBAL TRENDS IN RUSSIAN BUSINESS AND THE PURPOSE OF THE PERSONNEL TRAINING AND DEVELOPMENT FUNCTION
Authors: Abolmasov Alexey , Dolzhenko Ruslan
Published: January 2025

The paper presents an analysis and synthesis of key trends in business development in the world and the Russian Federation, as well as their impact on the functions of human resources management (HR) and training and development (T&D). It is shown that constant changes and their abrupt nature have led to the accumulation of contradictions and the formation of a systemic crisis, including in the field of working with people and their training. The solution to this crisis may lie in a systemic reassembly of the role and function of training and development, and most importantly, its reorientation from solving problems on the part of the HR function to meeting business requests for changes, primarily through proactive training of employees to solve strategic and operational problems. The T&D function is finding new purpose in driving ongoing business change while maintaining the operational function.