bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking national primary care electronic health records to individual records from the U.S. Census Bureau’s American Community Survey: evaluating the likelihood of linkage based on patient health
Authors: Limburg Aubrey , Gladish Nicole , Rehkopf David H , Phillips Robert L , Udalova Victoria
Published: November 2024

Objectives

To evaluate the likelihood of linking electronic health records (EHRs) to restricted individual-level American Community Survey (ACS) data based on patient health condition.

Materials and Methods

Electronic health records (2019-2021) are derived from a primary care registry collected by the American Board of Family Medicine. These data were assigned anonymized person-level identifiers (Protected Identification Keys [PIKs]) at the U.S. Census Bureau. These records were then linked to restricted individual-level data from the ACS (2005-2022). We used logistic regressions to evaluate match rates for patients with health conditions across a range of severity: hypertension, diabetes, and chronic kidney disease.

Results

Among more than 2.8 million patients, 99.2% were assigned person-level identifiers (PIKs). There were some differences in the odds of receiving an identifier in adjusted models for patients with hypertension (OR = 1.70, 95% CI: 1.63, 1.77) and diabetes (OR = 1.17, 95% CI: 1.13, 1.22), relative to those without. There were only small differences in the odds of matching to ACS in adjusted models for patients with hypertension (OR = 1.03, 95% CI: 1.03, 1.04), diabetes (OR = 1.02, 95% CI: 1.01, 1.03), and chronic kidney disease (OR = 1.05, 95% CI: 1.03, 1.06), relative to those without.

Discussion and Conclusion

Our work supports evidence-building across government consistent with the Foundations for Evidence-Based Policymaking Act of 2018 and the goal of leveraging data as a strategic asset. Given the high PIK and ACS match rates, with small differences based on health condition, our findings suggest the feasibility of enhancing the utility of EHR data for research focused on health.
Rapid Dual-Gene Detection of Burkholderia gladioli and Subspecies Cocovenenans in Fresh Noodles and Tremella Using CRISPR-Cas12a/Cas13a
Authors: Yao Xurong , Luo Mansi , Huang Jianzhao , Zhou Langjun , Zhang Binbin , Liang Zhisen , Li Xiuying
Published: November 2024

Background

Burkholderia gladioli pv. cocovenenans is a notable foodborne pathogen that poses a significant risk to food safety. Contaminated food requires distinct classification and treatment procedures for non-pathogenic B. gladioli and its pathogenic subspecies cocovenenans. Hence, establishing a rapid and sensitive detection method to distinguish them is necessary.

Objective

In this study, we aimed to establish a method combining the CRISPR-Cas12a/Cas13a (Clustered regularly short palindromic repeats-CRISPR associated proteins 12a and 13a) dual system with recombinase-aided amplification for rapid, specific, and sensitive detection of non-pathogenic B. gladioli and pathogenic subspecies cocovenenans in food.

Methods

First, an RAA (Recombinase-aided amplification)-CRISPR-Cas12a/Cas13a method was developed, and its feasibility was assessed. Next, specificity was analyzed using 23 strains of B. gladioli and 5 non-target strains. Following this, sensitivity was evaluated by preparing gradient dilutions of B. gladioli pv. cocovenenans bacterial solutions. Finally, real food test samples, including fresh noodles and tremella artificially contaminated with B. gladioli pv. cocovenenans, were utilized for method validation and sensitivity comparison.

Results

The established RAA-CRISPR-Cas12a/Cas13a method exhibited high specificity and achieved 100% accuracy in detecting species B. gladioli and its subspecies cocovenenans. This rapid method could be finished within 45 min with a detection limit of 100 CFU/mL (Colony-forming units per millilter) for bacterial concentration. Additionally, it achieved detection limits of 102 CFU/g for fresh noodles and 103 CFU/g for tremella.

Conclusion

The rapid RAA-CRISPR-Cas12a/Cas13a method demonstrated high specificity and sensitivity in detecting and distinguishing species B. gladioli and subspecies cocovenenans in both food test samples and post-cultivation colonies.

Highlights

The RAA-CRISPR-Cas12a/Cas13a method presented in this study offers a novel molecular approach for the rapid, accurate, and sensitive detection of B. gladioli and its subspecies cocovenenans in foods.
Outcomes of single-incision-augmented core decompression using trochanteric autograft in osteonecrosis of femoral head—a mean 5-year follow-up study
Authors: Ansari Sajid , Gupta Kshitij , Bondarde Parshwanath , Madhusudan Ch Raja Bhaskar Venkatasai , Kalia R.B
Published: November 2024

Osteonecrosis of femoral head (ONFH) can be a debilitating disease, for which numerous salvage surgeries have been popularized to halt its progression. The aim of this study was to assess the clinical and radiological outcomes of a single-incision core decompression (CD) technique using trochanteric autograft in ONFH and to determine the prognostic factors of treatment success. Sixty-six hips (41 patients) of Association Research Circulation (ARCO) 1 and 2 ONFH undergoing CD were included in the study with a mean follow-up of 58 months. Treatment failure was taken as radiographic collapse and/or conversion to total hip arthroplasty (THA). The following clinical and radiological factors impacting outcomes were evaluated—symptom duration, etiology, age, sex and body mass index, ARCO grade, Japanese Investigation Committee grade, modified Kerboul angle, and bone marrow edema (BME) on magnetic resonance imaging. Twenty-one of the 66 hips (31.8%) had a radiological collapse by the last follow-up, and 6 hips (9%) required THA. Overall, significant improvement in Harris hip scores (60.18 versus 80.81, P-value = .012) and visual analog scale scores (7.3 versus 1.2, P-value = .025) were noted postoperatively with no surgical complications. Late presentation (>3 months) (P-value = .001) and presence of BME (P = 0.0002) were significantly correlated with poor outcomes. The 5-year collapse-free rate was 68.2%, and 91% hips were arthroplasty free. Our single-incision CD technique using a trochanteric autograft yielded favorable outcomes for precollapse stages of nontraumatic ONFH at 5-year follow-up. Delayed presentation and presence of BME are poor prognostic factors. Adequate patient selection is for achieving a good survivorship and improvement in patient-reported outcomes.
Twenty-five years of integrated pest management in Nepali agriculture: lessons, gaps, and the way forward in the context of climate change
Authors: Adhikari Subodh , Bastola Rabin , GC Yubak Dhoj , Achhami Buddhi
Published: November 2024

The Government of Nepal implemented a globally adopted integrated pest management (IPM) approach in the late 1990s to minimize the negative environmental effects of pesticides and keep pest damage below the economic injury level. Current farm management systems, land use patterns, heavy reliance on chemical pesticides, and climate change have exacerbated pest issues and negatively affected crop production, requiring a revisit and modification of IPM implementation for modern Nepali agriculture. In this paper, we aimed to critically assess the progress and gaps in implementing IPM over more than 25 years in Nepal. Our assessment shows that growers have been practicing a wide range of pest management tactics, such as adopting local cultivars, cultural control, biological control, behavioral and mechanical control, indigenous technology and knowledge, and mixed approaches. Despite these practices, dependencies on synthetic chemicals are continuously increasing, becoming a major tool of the current agricultural pest management toolbox. To reduce the dependence on synthetic chemicals and the subsequent negative effects of chemicals on the environment and nontarget organisms, we propose a multistep and ecosystem-centered IPM framework aiming to include multi-trophic interactions and abiotic factors in agroecosystems. To make Nepali agriculture pest-resilient and climate-smart, it is imperative to shift a paradigm in national agricultural policies and develop well-funded research and extension entities that coordinate federal, provincial, and local institutions across the country. The Government of Nepal should lead the effort in collaboration with universities and national and international researchers, private industries, and other stakeholders.
“What do you want to do?”: expertise tension and authority negotiation in emergency nurse–physician interactions
Authors: Woo DaJung , Miller Laura E , Lamsen Leonard N
Published: November 2024

Collaborative work represents a communicative context in which organizational actors navigate the blurring of knowledge and authority boundaries as they address complex problems. This article theorizes about expertise tension that arises when individuals with valuable insights lack corresponding authority to act, or vice versa. Using observations and interviews, we studied how physicians and nurses navigated this tension in problem-solving situations in a hospital emergency department. We found that nurses, who identified emergent problems, simultaneously asserted their situational authority and displayed a veneer of deference by asking physicians, “What do you want to do [in this situation]?” The question prompted one of three problem-solving activities (i.e., instruction by demand, reversed instruction, and collaborative improvisation) depending on the situation’s urgency and ambiguity. We discuss how nurses and physicians managed expertise tension without undermining their different claims to expertise and authority, highlighting the value of a communication-centered view in examining such dynamics.
Temporal summation of pain in sickle cell disease: comparison of adolescents and young adults with chronic vs. infrequent pain
Authors: Karlson Cynthia , Dickens Harrison , Williams-Kirkwood Wynette , Mascaro Megan , Jackson Erin , Carullo Veronica , McNaull Melissa , Morris Matthew C
Published: November 2024

Objective

This study examined the role of central sensitization in the experience of pain among adolescents and young adults with the most severe genotypes of sickle cell disease (SCD). We hypothesized that adolescents and young adults with chronic SCD pain would demonstrate a higher perceptual response to repeated stimulation of identical intensity (i.e., temporal summation of pain, TSP) compared to counterparts with infrequent pain. We also examined psychological risk factors that can impact pain sensitivity.

Methods

Patients ages 12–21 years, diagnosed with SCD type Hb SS or Hb S Beta0Thalasemia, who reported infrequent pain (≤2 pain days/month; n = 25) or met AAPT criteria for chronic SCD pain (n = 25) were enrolled. Patients were age- and sex-matched, with similar proportions receiving chronic blood transfusion and hydroxyurea. Patients completed static quantitative sensory testing (QST) and dynamic TSP testing to assess pain sensitivity. Patients and a caregiver completed demographic and psychological measures (depression, anxiety, pain interference, pain catastrophizing).

Results

Simple slope analysis revealed differentially elevated heat TSP among adolescents and young adults with chronic SCD pain (b = 3.14, p = .002) but not those with infrequent pain (b = 0.45, p = .61). Faster habituation was further observed for those with chronic compared to infrequent pain. Adolescents and young adults with chronic pain reported more frequent depression, anxiety, and pain interference symptoms; however, psychological symptoms and pain catastrophizing were not associated with QST or TSP (ps >.17).

Conclusion

Current results demonstrate that a well-established, prognostic, QST risk marker (i.e., TSP) may distinguish chronic from infrequent pain subgroups of adolescents and young adults with SCD.
Transition to Enteral Triazole Antifungal Therapy for Pediatric Invasive Candidiasis: Secondary Analysis of a Multicenter Cohort Study Conducted by the Pediatric Fungal Network
Authors: Bucayu Robert F T , Boge Craig L K , Yildirim Inci , Avilés-Robles Martha , Vora Surabhi B , Berman David M , Sharma Tanvi S , Sung Lillian , Castagnola Elio , Palazzi Debra L , Danziger-Isakov Lara , Yin Dwight E , Roilides Emmanuel , Maron Gabriela , Tribble Alison C , Soler-Palacin Pere , López-Medina Eduardo , Romero José , Belani Kiran , Arrieta Antonio C , Carlesse Fabianne , Nolt Dawn , Halasa Natasha , Dulek Daniel , Rajan Sujatha , Muller William J , Ardura Monica I , Pong Alice , Gonzalez Blanca E , Salvatore Christine M , Huppler Anna R , Aftandilian Catherine , Abzug Mark J , Chakrabarti Arunaloke , Green Michael , Lutsar Irja , Knackstedt Elizabeth D , Johnson Sarah K , Steinbach William J , Fisher Brian T , Wattier Rachel L
Published: November 2024

Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy.
SNAP25 as a prognostic marker in transcriptome analysis of meningioma
Authors: Ge Yu , Zhang Tao
Published: November 2024

Background

Meningiomas are the most common intracranial tumors and their diagnosis relies mostly on neuroimaging and histology. However, the histology grades cannot predict the outcome exactly and some meningiomas tend to recur after resection of even benign tumors. Therefore, it is necessary to explore prognostic and diagnostic molecular targets.

Methods

Differential expression analysis between meningiomas and meninges was performed based on the merged data of GSE43290 and GSE84263. Next, we performed gene set enrichment analysis (GSEA), immune cell infiltration analysis, protein-protein interaction analysis, and survival analysis using public data. The expression level of Synaptosome-associated-protein-25kDa (SNAP25) was verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting in meningioma tissues.

Results

There were 263 upregulated and 592 downregulated genes identified in meningiomas by differential expression analysis. GSEA results revealed that meningiomas were negatively related to the pathway of soluble N-ethylmaleimide sensitive factor attachment protein receptor interactions in vascular transport and chemokine signaling. SNAP25 was characterized as a hub gene and downregulated in meningiomas. The Kaplan-Meier plot indicated that high expression of SNAP25 is a favorable factor.

Conclusion

SNAP25 was downregulated and identified as a potential prognostic marker in meningioma.
Microbial decomposer for crop residue management in rice–wheat cropping system
Authors: Lamba Shubham , Gill Ranvir Singh
Published: November 2024

Crop residue management is vital in the rice–wheat cropping system, influencing soil health and crop productivity. This study examined the effects of organic and inorganic fertilizers and microbial decomposers on rice growth and yield. We evaluated seven treatments: 100% recommended dose fertilizer (RDF); 50% residue + 50% RDF; 50% residue + 50% RDF + Pusa decomposer; 50% residue + 50% green manuring (GM)/green leaf manuring (GLM); 50% residue + 50% GM/GLM + Pusa decomposer; residue @ 2.5 tons per acre + Pusa decomposer; residue @ 2.5 tons per acre + no Pusa decomposer; and absolute control. Results indicate that integrating organic and inorganic fertilizers with microbial decomposers positively affects rice growth and yield parameters. While adding microbial decomposer to RDF did not consistently enhance rice yield, it improved soil enzymatic properties. This suggests that the effectiveness of microbial decomposers may vary based on specific soil and crop conditions. Therefore, microbial decomposers present a promising approach to boost soil health and fertility. Further research is needed to optimize conditions for their use and systematically assess their impact on crop yields
White dwarf–black hole binary progenitors of low-redshift gamma-ray bursts
Authors: Lloyd-Ronning Nicole M , Johnson Jarrett , Upton Sanderbeck Phoebe , Silva Makana , Cheng Roseanne M
Published: November 2024

Although there is strong evidence that many long gamma-ray bursts (LGRBs) are associated with the collapse of a massive star, tantalizing results in recent years have upended the direct association of all LGRBs with massive stars. In particular, kilonova signals in some LGRB light curves as well as a suggested uptick in the rate density of LGRBs at low redshifts (deviating significantly from the star formation rate) suggest that compact object mergers may be a non-negligible fraction of the LGRB population. Here, we investigate the contribution of white dwarf–black hole mergers to the LGRB population. We present evidence for the deviation of the LGRB rate density from the star formation rate at low redshifts, and provide analytic and numerical arguments for why a white dwarf–black hole merger system may be a viable progenitor to explain this deviation. We show the range of parameter space in which the durations, energetics, and rates of these systems can account for a significant subpopulation of low-redshift LGRBs.
Testing Bayesian inference of GRMHD model parameters from VLBI data
Authors: Yfantis A I , Zhao S , Gold R , Mościbrodzka M , Broderick A E
Published: November 2024

Recent observations by the Event Horizon Telescope (EHT) of supermassive black holes M87* and Sgr A* offer valuable insights into their space–time properties and astrophysical conditions. Utilizing a library of model images ($\sim 2$ million for Sgr A*) generated from general-relativistic magnetohydrodynamic (GRMHD) simulations, limited and coarse insights on key parameters such as black hole spin, magnetic flux, inclination angle, and electron temperature were gained. The image orientation and black hole mass estimates were obtained via a scoring and an approximate rescaling procedure. Lifting such approximations, probing the space of parameters continuously, and extending the parameter space of theoretical models is both desirable and computationally prohibitive with existing methods. To address this, we introduce a new Bayesian scheme that adaptively explores the parameter space of ray-traced, GRMHD models. The general relativistic radiative transfer code IPOLE is integrated with the EHT parameter estimation tool THEMIS. The pipeline produces a ray-traced model image from GRMHD data, computes predictions for very long baseline interferometric (VLBI) observables from the image for a specific VLBI array configuration and compares to data, thereby sampling the likelihood surface via a Markov chain Monte Carlo scheme. At this stage we focus on four parameters: accretion rate, electron thermodynamics, inclination, and source position angle. Our scheme faithfully recovers parameters from simulated VLBI data and accommodates time-variability via an inflated error budget. We highlight the impact of intrinsic variability on model fitting approaches. This work facilitates more informed inferences from GRMHD simulations and enables expansion of the model parameter space in a statistically robust and computationally efficient manner.
On the possible core shift break in relativistic jets
Authors: Nokhrina E E
Published: November 2024

Measurement of a jet geometry transition region is an important instrument of assessing the jet ambient medium properties, plasma bulk motion acceleration, parameters of a black hole, and location of a jet-launching radius. In this work, we explore the possibility of a presence of a core shift break, associated with the geometry and jet physical properties transition. We obtain the relations on the core shift offset jump due to a change in a core shift exponent. The condition of a proper frame magnetic field continuity and the core shift break can be used as an instrument to refine the magnetic field estimates upstream the break. This method is applied to the jet in NGC 315. We also argue that a local change in the plasma properties in the jet, for example due to the occurrence of a standing shock or a magnetic field reconnection, will also affect the dependence of the core shift on frequency. The properties of such a jump will be different than in the previous case. We propose to use the multifrequency core shift measurements to increase the number of sources with a detected jet shape break and to boost the accuracy of assessing the properties of a jet geometry transition region.
The Bayesian Phylogenetic Bootstrap and its Application to Short Trees and Branches
Authors: Lemoine Frédéric , Gascuel Olivier
Published: November 2024

Felsenstein's bootstrap is the most commonly used method to measure branch support in phylogenetics. Current sequencing technologies can result in massive sampling of taxa (e.g. SARS-CoV-2). In this case, the sequences are very similar, the trees are short, and the branches correspond to a small number of mutations (possibly 0). Nevertheless, these trees contain a strong signal, with unresolved parts but a low rate of false branches. With such data, Felsenstein's bootstrap is not satisfactory. Due to the frequentist nature of bootstrap sampling, the expected support of a branch corresponding to a single mutation is ∼63%, even though it is highly likely to be correct. Here, we propose a Bayesian version of the phylogenetic bootstrap in which sites are assigned uninformative prior probabilities. The branch support can then be interpreted as a posterior probability. We do not view the alignment as a small subsample of a large sample of sites, but rather as containing all available information (e.g. as with complete viral genomes, which are becoming routine). We give formulas for expected supports under the assumption of perfect phylogeny, in both the frequentist and Bayesian frameworks, where a branch corresponding to a single mutation now has an expected support of ∼90%. Simulations show that these theoretical results are robust to realistic data. Analyses on low-homoplasy viral and nonviral datasets show that Bayesian bootstrap support is easier to interpret, with high supports for branches very likely to be correct. As homoplasy increases, the two supports become closer and strongly correlated.
Cellular targets of cytotoxic copper phenanthroline complexes: a multimodal imaging quantitative approach in single PC3 cells
Authors: Pinheiro Teresa , Alves Luís C , Matos António P , Correia Isabel , Costa Pessoa João , Marques Fernanda
Published: November 2024

Metal complexes are emerging as promising alternatives to traditional platinum-based cancer treatments, offering reduced side effects. However, understanding their cellular uptake and distribution and quantifying their presence at the single cell level remains challenging. Advanced imaging techniques, including transmission electron microscopy, synchrotron radiation X-ray fluorescence, and energetic ion beam-based nuclear microscopy (scanning transmission ion microscopy, particle-induced X-ray emission, elastic backscattering spectrometry), allow detailed high-resolution visualization of structure and morphology, high sensitivity for elemental detection with quantification within single cells, and the construction of 3D models of metal distribution, positioning them as powerful tools for assessing the cellular uptake and compartmentalization of complexes. Three Cu(II) complexes [Cu(phen)2(H2O)](NO3)2 (1), [Cu(Me2phen)2(NO3)]NO3 (2) and [Cu(amphen)2(H2O)](NO3)2 (3), (phen = 1,10-phenanthroline, Me2phen = 4,7-dimethyl-1,10-phen, amphen = 5-amino-phen) were investigated for Cu uptake and distribution in PC3 prostate cancer cells. All complexes show significant Cu uptake regardless of media concentration. Cu concentrations in the cytoplasm and nucleus are similar between treatments. Complexes 1 and 3 concentrate Cu in the nuclear region and show a vesicle-like pattern around the nucleus, while 2 shows a dispersed cytoplasmic pattern with large vesicles. The 3D models confirm that Cu is not retained at the plasma membrane, with complex 1 targeting the nucleus and 2 remaining in the cytoplasm. These results highlight the importance of quantifying metal distribution and correlating it with structural changes to understand the relevance of the ligand in the mechanisms of cellular uptake and targeting, crucial for the development of effective metal-based cancer therapies.
Characteristics, treatment and disease burden among stage 3–4 chronic kidney disease patients with and without type 2 diabetes in Finland during 2016–2022
Authors: Metsärinne Kaj , Bodegård Johan , Toppila Iiro , Uusi-Rauva Kristiina , Frederiksen Line Elmerdahl , Brinkmann Satu
Published: November 2024

Background

Real-world evidence on the management of chronic kidney disease (CKD) with and without type 2 diabetes (T2D) is limited. This study described the characteristics, treatment and disease burden in patients with stage 3–4 CKD with and without T2D in Finland.

Methods

This cohort study used data from primary and hospital care in five municipalities in Finland to identify adults with stage 3–4 CKD, defined as having either one estimated glomerular filtration rate (eGFR) measurement of 15–59 mL/min/1.73 m2 followed by a second measurement taken ≥90 days later, or a registered CKD diagnosis. Prevalence was determined on 31 December 2022, and a cohort of incident stage 3–4 CKD patients was followed from the first date fulfilling eligibility criteria since 1 January 2016 (index) until death or 31 December 2022, and analyzed by T2D status.

Results

The prevalence of stage 3–4 CKD was 6.3%. Among the 12 474 incident stage 3–4 CKD patients, the majority were non-T2D (73%). The median age was similar for non-T2D and T2D CKD patients, respectively. Baseline albuminuria screening was 9% among non-T2D and 53% among T2D. The use of kidney-protective treatments at index was also lower in non-T2D patients (47%), compared with T2D patients (69%). The use of kidney-protective treatments remained unchanged during 12 months after index. Healthcare resource utilization was high, and CKD or heart failure contributed considerably more to the all-cause healthcare costs than atherosclerotic diseases, regardless of T2D status. In both CKD subgroups, 10% had died within 1 year.

Conclusions

In Finland, CKD is highly prevalent and associated with high risks and low use of albuminuria testing and kidney-protective medications. Most CKD patients were non-T2D, which showed lower use of preventive management and similar risks compared with T2D patients. These findings call for an urgent need for improved awareness and risk management, especially in non-T2D CKD patients.
Glioma–astrocyte connexin43 confers temozolomide resistance through activation of the E2F1/ERCC1 axis
Authors: Gui Yanping , Qin Hongkun , Zhang Xinyu , Chen Qianqian , Ye Fangyu , Tian Geng , Yang Shihe , Ye Yuting , Pan Di , Zhou Jieying , Fan Xiangshan , Wang Yajing , Zhao Li
Published: November 2024

Background

Glioma is the most prevalent and lethal tumor of the central nervous system. Routine treatment with temozolomide (TMZ) would unfortunately result in inevitable recurrence and therapy resistance, severely limiting therapeutic efficacy. Tumor-associated astrocytes (TAAs) are key components of the tumor microenvironment and increasing evidence has demonstrated that aberrant expression of connexin43 (Cx43) was closely associated with glioma progression and TMZ resistance. However, the specific role of Cx43 in mediating TMZ resistance through glioma and astrocyte interactions has not been fully explored.

Methods

The expression and prognostic value of Cx43 were evaluated in tumor samples and clinical databases. ShRNA-medicated knockdown and Gfap-Cre Cx43flox/flox gene mouse were used to assess the role and functional significance of Cx43 in vitro and in vivo. Moreover, we performed mass spectrometry analysis, chromatin immunoprecipitation, and other biochemical assays to define the molecular mechanisms by which Cx43 promotes TMZ resistance.

Results

We confirmed that the upregulation of Cx43 expression between TAAs and glioma cells contributed to TMZ resistance and tumor recurrence. Genetic knockdown or pharmacological inhibition of Cx43 enhanced TMZ-induced cytotoxicity. Mechanistically, elevated Cx43 expression induced β-catenin accumulation at the cell surface of glioma cells, suppressing T-cell factor/lymphoid enhancer-binding factor transcription. This led to impaired miR-205-5p expression and subsequent activation of the E2F1/ERCC1 axis, which eventually led to chemoresistance.

Conclusions

Our study reveals a novel regulatory mechanism in which the Cx43/miR-205-5p/E2F1/ERCC1 axis contributes to TMZ resistance in glioma. These findings further highlight the potential of targeting Cx43 as a therapeutic strategy in glioma.
Pediatric spinal high-grade glioma in the pediatric precision oncology registry INFORM: Identification of potential therapeutic targets
Authors: Pfaff Elke , Schramm Kathrin , Blattner-Johnson Mirjam , Jones Barbara C , Stark Sebastian , Balasubramanian Gnana Prakash , Previti Christopher , Autry Robert J , Fiesel Petra , Sahm Felix , Reuss David , von Deimling Andreas , van Tilburg Cornelis M , Pajtler Kristian W , Milde Till , Dirksen Uta , Kramm Christof M , von Bueren André O , Munthe-Kaas Monica C , Øra Ingrid , Pfister Stefan M , Witt Olaf , Jones David T W
Published: November 2024

Background

High-grade glioma (HGG) of the spinal cord constitutes rare tumors in the pediatric population. Knowledge of the molecular profile of this pediatric HGG (pedHGG) subgroup is limited and the clinical outcome is poor. Therefore, the aim of this study is to provide more profound investigations of molecular characteristics and clinical features of these tumors.

Methods

Between January 2015 and October 2023, 17 spinal tumors with HGG histology were analyzed by the Individualized Therapy For Relapsed Malignancies in Childhood (INFORM) precision oncology registry. Comprehensive molecular profiling (including next-generation sequencing approaches and DNA methylation analysis) was performed. Clinical data provided by the treating centers were evaluated regarding treatment approaches and outcomes.

Results

Subgroup classification based on DNA methylation analysis revealed molecular HGG subgroups in 12/17 cases, while 2/17 were classified as molecular low-grade glioma (LGG) and 3/17 were not unequivocally classifiable. Typical genetic alterations described in pedHGG usually presenting at other localizations were also present in the counterparts located in the spinal cohort. Alterations that might serve as a promising target for personalized therapy approaches were identified in a subset of tumors.

Conclusion

With this cohort of 12 molecularly confirmed spinal pedHGG cases, we provide a compilation of genomic as well as clinical features of this rare subgroup, contributing to a better understanding and eventually to future treatment approaches.
Perceptions and Barriers to Outpatient Antiviral Therapy for COVID-19 and Influenza as Observed by Infectious Disease Specialists in North America: Results of an Emerging Infections Network (EIN) Survey, February 2024
Authors: Singleton Jordan B , Wang Dennis , Louis Souci , Smith Dallas J , Lambrou Anastasia S , Beekmann Susan E , Midgley Claire M , Polgreen Philip , Garg Shikha , Ricaldi Jessica N , Uyeki Timothy M , Santibañez Scott , Patel Pragna
Published: November 2024

Antiviral therapy is underutilized for outpatients at increased risk for severe COVID-19 or influenza. Results from this survey offer insights into treatment barriers from the infectious disease specialist perspective. Further education is needed about the benefits of early antiviral therapy.
Q-band line survey observations toward a carbon-chain-rich clump in the Serpens South region
Authors: Taniguchi Kotomi , Nakamura Fumitaka , Liu Sheng-Yuan , Shimoikura Tomomi , Chiong Chau-Ching , Dobashi Kazuhito , Hirano Naomi , Yonekura Yoshinori , Nomura Hideko , Nishimura Atsushi , Ogawa Hideo , Chien Chen , Ho Chin-Ting , Hwang Yuh-Jing , Yeh You-Ting , Lai Shih-Ping , Fujii Yasunori , Yamasaki Yasumasa , Nguyen-Luong Quang , Kawabe Ryohei
Published: November 2024

We have conducted Q-band (30–50 GHz) line survey observations toward a carbon-chain emission peak in the Serpens South cluster-forming region with the extended Q-band (eQ) receiver installed on the Nobeyama 45 m radio telescope. Approximately 180 lines have been detected, including tentative detection, and these lines are attributed to 52 molecules including isotopologues. It has been found that this position is rich in carbon-chain species as much as Cyanopolyyne Peak in the Taurus Molecular Cloud-1 (TMC-1 CP), suggesting chemical youth. Not only carbon-chain species, but also several complex organic molecules (CH$_3$OH, CH$_3$CHO, HCCCHO, CH$_3$CN, and tentatively C$_2$H$_3$CN) have also been detected, which is similar to the chemical complexity found in evolved prestellar cores. The HDCS$/$H$_2$CS ratio has been derived to be $11.3\% \pm 0.5\%$, and this value is similar to the prestellar core L1544. The chemically young features that are similar to the less-dense starless core TMC-1 CP ($10^4$–$10^5\:$cm$^{-3}$) and chemically evolved characters which resemble the dense prestellar core L1544 (${\sim}10^6\:$cm$^{-3}$) mean that the clump including the observed position is a pre-cluster clump without any current star formation activity.
Do mindfulness interventions cause harm? Findings from the Learning to Apply Mindfulness to Pain (LAMP) Pragmatic Clinical Trial
Authors: Burgess Diana J , Calvert Collin , Bangerter Ann , Branson Mariah , Cross Lee J S , Evans Roni , Ferguson John E , Friedman Jessica K , Hagel Campbell Emily M , Haley Alexander C , Hennessy Sierra , Kraft Colleen , Mahaffey Mallory , Matthias Marianne S , Meis Laura A , Serpa J Greg , Taylor Stephanie L , Taylor Brent C
Published: November 2024

Background

Although mindfulness-based interventions (MBIs) are widely used in clinical and nonclinical settings, there has been little systematic study of their potential risks. To address this gap, we examined differences in psychological and physical worsening among participants in the usual care and intervention conditions of a 3-group, randomized pragmatic trial (Learning to Apply Mindfulness to Pain [LAMP]) that tested the effectiveness of 2 approaches to delivering MBIs to patients with chronic pain.

Methods

The sample consisted of 374 male and 334 female patients with chronic pain enrolled in the LAMP trial who completed a 10-week follow-up survey, 61% of whom had a mental health diagnosis. Psychological and physical worsening was assessed by a checklist asking whether participants experienced specific symptoms since beginning the study. We used multivariable logistic regression models with imputed data to determine whether predicted probabilities of increased symptoms differed between usual care and the 2 MBIs.

Results

Participants in usual care were more likely to report experiencing increased psychological and physical worsening than were those in the MBIs, including an increase in disturbing memories; sadness, anxiousness, and fatigue; isolation and loneliness; and feeling more upset than usual when something reminded them of the past.

Conclusions

MBIs do not appear to cause harm, in terms of increased symptoms, for this population of patients with chronic pain and high levels of mental health comorbidities.

Clinical trial registration

Preregistration with an analysis plan at www.ClinicalTrials.gov: NCT04526158. Patient enrollment began December 4, 2020.
How initial perceptions of the effectiveness of mind and body complementary and integrative health therapies influence long-term adherence in a pragmatic trial
Authors: Zeliadt Steven B , Coggeshall Scott , Zhang Xiaoyi , Rosser Ethan W , Reed II David E , Elwy A Rani , Bokhour Barbara G , Toyama Joy A , Taylor Stephanie L
Published: November 2024

Objective

Beliefs and perceptions about pain intervention effectiveness when initiating a therapy may influence long-term engagement. This study examines how early perceived effectiveness of complementary and integrative health therapies impacts long-term engagement in a pragmatic trial context.

Participants

Veterans with chronic musculoskeletal pain participating in a pragmatic trial of provider-delivered complementary and integrative health therapies (acupuncture, chiropractic care, or massage therapy) used alone compared to combining those therapies with self-care therapies (yoga, Tai Chi/Qigong, or meditation). This analysis focuses on 1713 participants using self-care therapies at baseline.

Setting

18 Veterans Healthcare Administration Medical Facilities.

Design

Prospective cohort study.

Methods

Predictors of total self-care complementary and integrative health therapy sessions over a 6-month assessment period were assessed using linear regression to determine how strongly perceptions of initial therapy effectiveness was associated with total utilization. Perception of initial therapy effectiveness was assessed at study entry across four domains (pain, mental health, fatigue, and general well-being).

Results

In total, 56% (1032/1713) of Veterans reported a positive perceived effectiveness of their recent complementary and integrative health therapy use at study initiation. Older individuals and those using meditation were more likely to report early positive perceptions. Mean number of therapy sessions over the 6-month study was 11 (range 1 to 168). Early positive perceptions had a small effect on overall use, increasing mean sessions by 2.5 (1.3 to 3.6). Other factors such as recent physical therapy use and distance to primary care explained more variation in total utilization.

Conclusions

Pragmatic pain trials should examine factors associated with engagement across assigned treatment protocols, especially if any of the treatment protocols being tested are sensitive to long-term engagement.
Adapting to change: experiences and recommendations from the Pain Management Collaboratory on modifying statistical analysis plans
Authors: Yu Qilu , George Steven Z , Kyriakides Tassos C , Rhon Daniel I , Morasco Benjamin J , Dziura James , Fritz Julie M , Geda Mary , Peduzzi Peter , Long Cynthia R
Published: November 2024

Background

Best practices for clinical trials stipulate that statistical analysis plans (SAPs) need to be finalized before initiation of any analysis. However, there is limited guidance about when changes to SAPs are acceptable and how these changes should be incorporated into the research plan with appropriate documentation.

Methods

We conducted a survey of 12 pragmatic clinical trials (PCTs) in the Pain Management Collaboratory that evaluated nonpharmacological interventions for pain to assess the following SAP information: (1) location of statistical analysis details, (2) types of statistical analyses planned, (3) sponsor requirements, (4) templates used for development, (5) publication plan, (6) changes since trial launch, (7) process of documenting changes, and (8) process of updating the trial registry.

Results

All 12 PCTs provided details of their SAPs for the primary outcomes in the institutional review board–approved trial protocol; 8 included plans for secondary outcomes, and 6 included plans for tertiary/exploratory outcomes. Most PCTs made SAP changes after trial initiation, many as a result of COVID-19–related issues. Eleven of the PCTs were actively recruiting participants. Changes were made to sample size, study design, study arms, and analytical methods, all before the data lock/unblinding. In all cases, justification for the changes was documented in the trial protocol or SAP, signed off by the trial biostatistician and principal investigator, and reviewed/approved by an institutional review board, data and safety monitoring board, or sponsor.

Conclusions

We recommend that SAP changes can be acceptable up to the time of data lock/unblinding. To maintain full transparency and necessary rigor, clear documentation of such changes should include details, rationale, date(s) such changes were implemented, and evidence of approval by relevant oversight bodies.
Utility of the PICOTS framework to assess clinical trial disruptions: monitoring the impact of COVID-19 in the Pain Management Collaboratory
Authors: Peduzzi Peter , Brandt Cynthia , Dearth Christopher L , Dziura James , Farrokhi Shawn , George Steven Z , Kyriakides Tassos C , Long Cynthia R , Mascha Edward J , Patterson Charity G , Rhon Daniel I , Kerns Robert D
Published: November 2024

Objective

Despite careful design of clinical trials, unforeseen disruptions can arise. The PICOTS (Patient population, Intervention, Comparator, Outcomes, Timepoints, Setting) framework was used to assess disruptions in pain management research imposed by coronavirus disease 2019 (COVID-19) within the Pain Management Collaboratory.

Methods

Rapid qualitative methods were employed to identify trial disruptions due to COVID-19 in 11 pragmatic clinical trials of nonpharmacological approaches for pain management. The PICOTS framework was applied by investigators of 4 Collaboratory trials selected to cover 4 types of trial designs (individually randomized, stepped-wedge, cluster, sequential multiple assignment randomized trial—SMART). Interviews with the lead investigators of these trials were completed, and findings were presented/discussed on video calls over a 6-month period (March-August 2021) from which themes/lessons learned were identified and consensus reached.

Results

Investigators indicated that patient populations remained generally stable. A major COVID-19 trial disruption was moving from in-person to virtual care affecting delivery of interventions/comparators and outcome assessments. The resultant mixed-mode of care delivery created issues with intervention fidelity posing analytic challenges. COVID-19 also induced ongoing/intermittent delays and other barriers to accessing primary and specialty care at some facilities, creating research capacity issues affecting delivery of experimental interventions requiring sustained, reliable participation of clinical partners. Study designs most affected by COVID-19 were stepped-wedge (intervention/comparator changing over time), cluster (increased site variability inflating intracluster correlation), and SMART (second-stage randomizations disrupted); stratified individually-randomized trials were less vulnerable because of individual-level randomization.

Conclusions

PICOTS provides a framework for assessing the impact of trial disruptions in a structured manner. Given the COVID-19 experience, it is important for researchers to consider the potential impact of future trial disruptions during study planning.
Energy metabolism dysregulation, cerebrovascular aging, and time-restricted eating: Current evidence and proof-of-concept findings
Authors: da C Pinaffi-Langley Ana Clara , Pinto Camila B , Mukli Peter , Peterfi Anna , Kaposzta Zalan , Owens Cameron D , Szarvas Zsofia , Muranyi Mihaly , Adams Cheryl , Shahriari Ali , Balasubramanian Priya , Ungvari Zoltan , Csiszar Anna , Conley Shannon , Hord Norman G , Anderson Leah , Tarantini Stefano , Yabluchanskiy Andriy
Published: November 2024

Dysregulated energy metabolism is a hallmark of aging, including brain aging; thus, strategies to restore normal metabolic regulation are at the forefront of aging research. Intermittent fasting, particularly time-restricted eating (TRE), is one of these strategies. Despite its well-established effectiveness in improving metabolic outcomes in older adults, the effect of TRE on preserving or improving cerebrovascular health during aging remains underexplored. We explored how aging itself affects energy metabolism and contextualized these age-related changes to cerebrovascular health. We also conducted a literature search on PubMed and Scopus to identify and summarize current studies on TRE in older adults. Finally, we provided preliminary data from our proof-of-concept pilot trial on the effect of 6-month TRE on cerebrovascular health in older adults. Current evidence shows the potential of TRE to improve energy metabolism and physiological outcomes in older adults. TRE may improve cerebrovascular function indirectly due to its effect on glucose homeostasis. However, to date, direct evidence of the effect of TRE on cerebrovascular parameters is lacking. TRE is a well-tolerated and promising dietary intervention for promoting and maintaining cerebrovascular health in older adults. Further studies on TRE in older adults must be better controlled for energy balance to elucidate its independent effects from those of caloric restriction.
Policing, Technology, and Public Values: A Public Administration Research Agenda
Authors: Feeney Mary K , Mughan Sian
Published: November 2024

There is a great deal of research investigating how technologies produce efficiencies for police departments. Criminal justice research often focuses on a single technology and from a single perspective—the police—noting how technologies increase efficiency and efficacy for police departments. Researchers in science and technology studies also investigate how police departments adopt and use technology, but typically focus on the tensions between technologies and society, including potential threats to individual and community privacy and rights. Public administration scholars tend to center their policing research on the tensions between police missions and behavior and the advancement of citizen rights, including privacy, social equity, and fairness, with little to no focus on theories of technology adoption and use. We bring together these three literatures on technology, policing, and public values to investigate how three key stakeholders—the administrative state, the police, and citizens—use technology in the context of policing to achieve public values. We argue public values shape technology adoption and use, and stakeholders use technologies to achieve specific public values. This interactive process is key to understanding technology in policing and variation in the achievement of public value outcomes. We develop a framework for assessing how technology is used in policing to advance public values from the perspectives of multiple stakeholders, applying it to the cases of body-worn cameras and predictive policing.
Mother–child closeness and adolescent structural neural networks: a prospective longitudinal study of low-income families
Authors: Hong Sunghyun H , Hardi Felicia A , Tillem Scott , Goetschius Leigh G , Brooks-Gunn Jeanne , McLoyd Vonnie , Lopez-Duran Nestor L , Mitchell Colter , Hyde Luke W , Monk Christopher S
Published: November 2024

Mother–child closeness, a mutually trusting and affectionate bond, is an important factor in shaping positive youth development. However, little is known about the neural pathways through which mother–child closeness is related to brain organization. Utilizing a longitudinal sample primarily from low-income families (N = 181; 76% African American youth and 54% female), this study investigated the associations between mother–child closeness at ages 9 and 15 years and structural connectivity organization (network integration, robustness, and segregation) at age 15 years. The assessment of mother–child closeness included perspectives from both mother and child. The results revealed that greater mother–child closeness is linked with increased global efficiency and transitivity, but not with modularity. Specifically, both the mother’s and child’s reports of closeness at age 15 years predicted network metrics, but report at age 9 years did not. Our findings suggest that mother–child closeness is associated with neural white matter organization, as adolescents who experienced greater mother–child closeness displayed topological properties indicative of more integrated and robust structural networks.