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Association between chiropractic spinal manipulation for sciatica and opioid-related adverse events: A retrospective cohort study

Background Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM. Methods We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.) of more than 216 million patients, yielding data ranging from 2009 to 2024. We included patients aged ≥18 years with sciatica, excluding those post-spine surgery, prior anesthesia, serious pathology, high risk of ORADEs, and an ORADE ≤ 1-year prior. Patients were divided into two cohorts: (1) CSM and (2) usual medical care. We used propensity score matching to control for confounding variables associated with ORADEs. Comparative outcomes were analyzed by calculating risk ratios (RRs) and 95% confidence intervals (CIs) for the incidence of ORADEs and oral opioid prescription between cohorts. Results 372,471 patients per cohort remained after matching. The incidence of ORADEs over 1-year follow-up was less in the CSM cohort compared to the usual medical care cohort (CSM: 0.09%; usual medical care: 0.30%), yielding an RR of 0.29 (95% CI: 0.25–0.32; P < .00001). CSM patients had a lower risk of receiving an oral opioid prescription (RR of 0.68 [95% CI: 0.68–0.69; P < .00001]). Conclusions This study found that adults with sciatica who initially received CSM had a lower risk of an ORADE compared to matched controls not initially receiving CSM, likely explained by a lower probability of opioid prescription. These findings corroborate existing practice guidelines which recommend adding CSM to the management of sciatica when appropriately indicated.

An analytical model of label-free nanoscale chemical imaging reveals avenues toward improved spatial resolution and sensitivity

Atomic force microscopy–infrared spectroscopy (AFM-IR) is a photothermal scanning probe technique that combines nanoscale spatial resolution with the chemical analysis capability of mid-infrared spectroscopy. Using this hybrid technique, chemical identification down to the single molecule level has been demonstrated. However, the mechanism at the heart of AFM-IR, the transduction of local photothermal heating to cantilever deflection, is still not fully understood. Existing physical models only describe this process in few special cases but not in many of the types of sample geometries encountered in the practical use of AFM-IR. In this work, an analytical expression for modeling the temperature and photothermal expansion process is introduced, verified with finite element simulations, and validated with AFM-IR experiments. This method describes AFM-IR signal amplitudes in vertically and laterally heterogeneous samples and allows studying the effect of position and size of an absorber, pump laser repetition rate and pulse width on AFM-IR signal amplitudes and spatial resolution. The analytical model can be used to identify optimal AFM-IR experimental settings in conventional and advanced AFM-IR modes (e.g., tapping mode, surface-sensitive mode). The model also paves the way for signal inversion based superresolution AFM-IR.

Correction: Intersecting paths: Corporate and green innovation in Chinese firms—A penal cointegration analysis

Violence against women and girls research: Leveraging gains across disciplines

Violence against women and girls (VAWG) is a leading cause of mortality and morbidity worldwide, linked to numerous health, economic, and human rights outcomes. Target 5.2 of the Sustainable Development Goals calls for elimination of all forms of VAWG; however, progress toward achieving this goal has been inadequate. A lack of sufficient data and evidence has hindered global efforts to meet this target and hold governments accountable for action. While there have been substantial advancements in VAWG research methodology over the past three decades, researchers from diverse disciplines tend to work in silos, inhibiting progress in VAWG research. To address this challenge, we offer four key recommendations to support researchers in expanding transdisciplinary approaches: 1) leverage insights from a variety of VAWG data sources, 2) improve precision of VAWG definitions and outcomes, 3) create strategies to address underreporting, and 4) advance research ethics and equity. We conclude with a call to action for researchers, institutions, and donors to advance transdisciplinary research and foster collaboration, learning, and cross-fertilization across scientific fields to accelerate VAWG prevention efforts now and for future generations.

Correction: The moderating role of sociodemographic and work-related variables in burnout and mental health levels of Mexican medical residents

Molecular glue for phycobilisome attachment to photosystem II in <i>Synechococcus</i> sp. PCC 7002

Phycobilisomes (PBS) are the major photosynthetic light-harvesting complexes in cyanobacteria and red algae. While the structures of PBS have been determined in atomic resolutions, how PBS are attached to the reaction centers of photosystems remains less clear. Here, we report that a linker protein (LcpA) is required for the attachment of PBS to photosystem II (PSII) in the cyanobacterium Synechococcus sp. PCC 7002. We also report that the PB-loop of PBS, which is located within the α-APC domain of ApcE, is required for the attachment of PBS to PSII. Deletion of either PB-loop or the gene A0913 led to a decreased rate of photoautotrophic growth under illumination of green light, which is preferentially absorbed by PBS. A double mutant lacking the PB-loop and A0913 (ΔPBL-0913) showed a complete inhibition of O 2 evolution under the 590 nm light and could not grow under green light illumination. While assembled PBS could be isolated from ΔPBL-0913, the energy transfer from its PBS to PSII was blocked as measured by fluorescence induction. Photobleaching with intact cells showed that the PBS movement speed in ΔPBL-0913 was 2.5 times as fast as that of the wild type, suggesting that association of its PBS with thylakoids was weakened significantly. The pull-down and coimmunoprecipitation results showed that the LcpA interacts with the CP47 subunit of PSII through its N-terminal region and interacts with ApcB of PBS through its C-terminal α-helix motif. Our results provide insights into the molecular mechanism of PBS–PSII association and shed light on excitation energy transfer from PBS to PSII.

A novel approach for the router nodes placement in wireless mesh networks using phasing with approximation optimization algorithms

Optimal router node placement (RNP) is an effective method for improving the performance of wireless mesh networks (WMN). However, solving the RNP problem in WMN is difficult because it is NP-hard. As a result, this problem can only be solved using approximate optimization algorithms such as heuristics and meta-heuristics. In this study, we propose a new and effective method for solving the RNP problem. The idea behind this method is to solve the RNP problem in two stages using an optimal algorithm with fewer variables than the original RNP problem. In stage 1, we build an RNP sub problem using 15% to 20% of the number of routers, with the objective function of minimizing coverage overlap between routers to form a core network. Stage 2 is built into another RNP sub problem with the remaining number of routers, and the objective function is to maximize the network connectivity. Each sub problem was solved using an approximate optimal algorithm. The experimental results demonstrate that, in terms of client coverage and network connectivity, our proposed method outperforms widely used RNP problem-solving methods.

Complement C3 of tumor-derived extracellular vesicles promotes metastasis of RCC via recruitment of immunosuppressive myeloid cells

Heterogeneous roles of complement C3 have been implicated in tumor metastasis and are highly context dependent. However, the underlying mechanisms linking C3 to tumor metastasis remain elusive in renal cell carcinoma (RCC). Here, we demonstrate that C3 of RCC cell-derived extracellular vesicles (EVs) contributes to metastasis via polarizing tumor-associated macrophages (TAMs) into the immunosuppressive phenotype and recruiting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, EV C3 induces the secretion of CCL2 and CXCL1 by lung macrophages and subsequently enhances TAM polarization and PMN-MDSC recruitment. Notably, targeting the CCL2/CCR2 or CXCL1/CXCR2 axis with the inhibitors RS504393 or Navarixin, respectively, effectively suppresses lung metastasis induced by RCC-derived C3 in a mouse model. Clinically, RCC patients with high expression of C3 demonstrate poor prognosis. Collectively, our findings reveal that tumor-derived EV C3 induces an immunosuppressive tumor microenvironment via TAMs, and thus promoting RCC metastasis.

Separation effectiveness of ideal ion exchange membranes: Application of the Gibbs-Donnan theory

Ion exchange membranes (IEMs) are permselective membranes that, in principle, only allow the flow of ions with a specific charge sign, opposite to that of the fixed membrane ionic groups (counter-ions). This charge-based selectivity, like the size-based selectivity of classic semipermeable membranes, leads to an uneven distribution of permeating ions on the two sides of the membrane, which allows for ion separation or recovery in various processes in industry or environmental protection. Here, we apply the principles of mass balance, charge neutrality, and equality of electrochemical potentials in the state of thermodynamic equilibrium to provide a simple method for estimating the Gibbs-Donnan factors and the equilibrium concentrations of permeating ions in two compartments separated by an ideal IEM, i.e. an IEM that is not permeable to co-ions. We present the method for the case when the equilibrium concentrations are known in one compartment and need to be estimated in the other compartment as well as for the case when the total masses of ions in both compartments are known and their equilibrium concentrations need to be predicted. For both cases, the presented nonlinear algebraic equations require in general the use of numerical methods to approximate their mathematical solutions, although we present as well some closed solutions for simple cases with ideal ionic mixtures. Based on the extended Debye–Hückel theory, we also provide analogous equations (general and for specific cases) for systems with non-ideal ionic mixtures. The presented method can provide the expected ideal separation effectiveness of an IEM, which can then be used to assess the relative separation effectiveness of a real membrane.

Molecular mechanism of ligand recognition and activation of lysophosphatidic acid receptor LPAR6

Lysophosphatidic acid (LPA) exerts its physiological roles through the endothelialdifferentiation gene (EDG) family LPA receptors (LPAR1-3) or the non-EDG family LPA receptors (LPAR4-6). LPAR6 plays crucial roles in hair loss and cancer progression, yet its structural information is very limited. Here, we report the cryoelectron microscopy structure of LPA-bound human LPAR6 in complex with a mini G 13 or G q protein. These structures reveal a distinct ligand binding and recognition mode that differs significantly from that of LPAR1. Specifically, LPA uses its charged head to form an extensive polar interaction network with key polar residues on the extracellular side of transmembrane helix 5-6 and the extracellular loop 2. Structural comparisons and homology analysis suggest that the EDG and non-EDG families use two distinct modes for LPA binding. The structural observations are validated through functional mutagenesis studies. We further uncover the mechanisms of LPAR6 activation and principles of G-protein coupling. The structural information revealed by our study lays the groundwork for understanding LPAR6 signaling and provides a rational basis for designing compounds targeting LPAR6.

Pre-treatment subjective sleep quality as a predictive biomarker of tDCS effects in preclinical Alzheimer’s disease patients: Secondary analysis of a randomised clinical trial

Background Despite transcranial direct current stimulation (tDCS) has demonstrated encouraging potential for modulating the circadian rhythm, little is known about how well and sustainably tDCS might improve the subjective sleep quality in older adults. This study sought to determine how tDCS affected sleep quality and cognition, as well as how well pre-treatment sleep quality predicted tDCS effects on domain-specific cognitive functions in patients with mild neurocognitive disorder due to Alzheimer’s disease (NCD-AD). Methods This clinical trial aimed to compare the effectiveness of tDCS and cognitive training in mild NCD-AD patients (n =  201). Over the course of four weeks, patients were randomized to receive either tDCS plus working memory training, or sham tDCS plus working memory training, or tDCS plus controlled cognitive training. The Pittsburgh Sleep Quality Index (PSQI) was used to measured subjective sleep quality. The Alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog) was used to evaluate domain-specific cognitive functions. Results Recurrent tDCS treatments enhanced subjective sleep quality and cognition considerably. The poor sleepers (i.e., PSQI &gt;  5) who received tDCS treatment had more cognitive benefits (p =  0.031, Cohen’s d =  0.605) and sleep improvements (p &lt;  0.001, Cohen’s d =  1.209) in comparison to cognitive training. Pre-treatment subjective sleep quality was linked to tDCS-induced improvement in memory function. Conclusion During the course of two months, repeated tDCS could considerably enhance subjective sleep quality. For the cognitive benefits of the treatments, the status of pre-treatment subjective sleep quality is crucial. More thorough research is necessary to explore an efficient approach to managing comorbidities for preclinical AD patients.

Microfluidic purification of genomic DNA

We describe a microfluidic device to extract DNA from a cell lysate, without the need for centrifuges, magnetic beads, or gels. Instead, separation is driven by transverse migration of DNA, which occurs when a polyelectrolyte solution flowing through a microfluidic channel is subjected to an electric field. The coupling of the weak shearing with the axial electric field is highly selective for long, flexible, charged molecules, of which DNA is the sole example in a typical cell lysate. As a result of migration to the walls, DNA is held near the channel inlet by electrophoresis (there is no flow near the channel walls), while the remaining components are eluted by the much larger (at least 10-fold) convective flow. We have demonstrated the feasibility of the device by recovering up to 40 ng of purified DNA in less than 30 min from 10 μ L of Escherichia coli lysate. Gel electrophoresis indicates minimal additional fragmentation during purification, up to the maximum length recorded by the gel (60 kbp). Electropherograms were also obtained for purified mammalian DNA, using a Femto Pulse system (fragment lengths up to 165 kbp). Extracted samples show strong amplification by PCR, while the original lysate does not. Mixtures of λ -DNA and BSA were used to determine the extent of the separation of DNA from a physiological concentration of proteins (30 mg/mL). The protein concentration in the extract (0.3 to 0.5 ng/µL) was reduced by five orders of magnitude from the initial mixture.

Correction: The shadow of the family: Historical roots of social trust in Europe

Metabolic activity controls the emergence of coherent flows in microbial suspensions

Photosynthetic microbes have evolved and successfully adapted to the ever-changing environmental conditions in complex microhabitats throughout almost all ecosystems on Earth. In the absence of light, they can sustain their biological functionalities through aerobic respiration, and even in anoxic conditions through anaerobic metabolic activity. For a suspension of photosynthetic microbes in an anaerobic environment, individual cellular motility is directly controlled by its photosynthetic activity, i.e. the intensity of the incident light absorbed by chlorophyll. The effects of the metabolic activity on the collective motility on the population level, however, remain elusive so far. Here, we demonstrate that at high light intensities, a suspension of photosynthetically active microbes exhibits a stable reverse sedimentation profile of the cell density due to the microbes’ natural bias to move against gravity. With decreasing photosynthetic activity, and therefore suppressed individual motility, the living suspension becomes unstable giving rise to coherent bioconvective flows. The collective motility is fully reversible and manifests as regular, three-dimensional plume structures, in which flow rates and cell distributions are directly controlled via the light intensity. The coherent flows emerge in the highly unfavorable condition of lacking both light and oxygen and, thus, might help the microbial collective to expand the exploration of their natural habitat in search for better survival conditions.

Mental health challenges and perceptions of stigma among youth living with HIV in Tanzania

Youth living with HIV (YLWH) face psychosocial challenges and HIV-related stigma, which impact adherence to antiretroviral therapy (ART). This study was designed to understand better the change in mental health symptoms and experiences with stigma among YLWH in Tanzania who completed the original pilot Sauti ya Vijana (SYV), a mental health and life skills group intervention. YLWH who completed SYV and demonstrated a change of ≥2 points in either direction on their Patient Health Questionnaire PHQ-9 (depression screener) from baseline to 18 months were purposively sampled. HIV Stigma was measured using 10-questions from the Berger HIV Stigma Scale, and findings ranged from 4–16 for internal stigma and 6–24 for external stigma. In-depth interviews (IDI) were conducted in Kiswahili and included topics such as history of mental health challenges, perceptions of stigma, and experiences with the SYV intervention. Interviews were transcribed, translated to English, and analyzed for emergent themes. Ten youth, 18–25 years of age, were interviewed; 70% were male. Mean (SD) PHQ-9 scores were 7.3 (SD = 3.5) at baseline and 5.6 (SD = 5.0) at 18 months. All participants reported experiencing intermittent episodes of mental health challenges due to difficult interpersonal relationships and fear of stigma. Youth relied on peer support and skills from the SYV intervention to cope with mental health challenges and stigma. Participants reported fear of being stigmatized by others, which led to behaviors such as skipping medication or avoiding situations for worry about unintentional disclosure. All participants endorsed experiencing external stigma on the HIV stigma scale; however, only 3 of 10 participants reported experiencing enacted stigma when directly asked to describe an experience during in-depth interviews. Participants described how SYV helped them have “more confidence”, accept themselves, and incorporate positive coping skills such as relaxation (deep breathing) when they felt stressed. The findings suggest SYV helped YLWH accept themselves, develop positive coping methods, and identify and form peer social support; but stigma remains common. Descriptions of stigma were not recognized as such; experiences of enacted stigma were acknowledged by some participants. More research is needed to understand and measure mental distress and wellness as well as stigma in this population so that interventions may more accurately detect change in key outcomes.

The functional role of oscillatory dynamics in neocortical circuits: A computational perspective

The dynamics of neuronal systems are characterized by hallmark features such as oscillations and synchrony. However, it has remained unclear whether these characteristics are epiphenomena or are exploited for computation. Due to the challenge of selectively interfering with oscillatory network dynamics in neuronal systems, we simulated recurrent networks of damped harmonic oscillators in which oscillatory activity is enforced in each node, a choice well supported by experimental findings. When trained on standard pattern recognition tasks, these harmonic oscillator recurrent networks (HORNs) outperformed nonoscillatory architectures with respect to learning speed, noise tolerance, and parameter efficiency. HORNs also reproduced a many characteristic features of neuronal systems, such as the cerebral cortex and the hippocampus. In trained HORNs, stimulus-induced interference patterns holistically represent the result of comparing sensory evidence with priors stored in recurrent connection weights, and learning-induced weight changes are compatible with Hebbian principles. Implementing additional features characteristic of natural networks, such as heterogeneous oscillation frequencies, inhomogeneous conduction delays, and network modularity, further enhanced HORN performance without requiring additional parameters. Taken together, our model allows us to give plausible a posteriori explanations for features of natural networks whose computational role has remained elusive. We conclude that neuronal systems are likely to exploit the unique dynamics of recurrent oscillator networks whose computational superiority critically depends on the oscillatory patterning of their nodal dynamics. Implementing the proposed computational principles in analog hardware is expected to enable the design of highly energy-efficient and self-adapting devices that could ideally complement existing digital technologies.

Improving paraffin precipitate inhibition using glycine and Palm-based Methyl Ester Sulfonate (MES) eco-friendly inhibitors

Oil fields located in cold environments and deep-sea locations often face challenges with paraffin wax buildup in pipelines during long-distance crude oil transportation. Various strategies have been employed to address this issue, with chemical methods being the most effective and economical. However, traditional chemical inhibitors present problems due to their high toxicity and low biodegradability, leading to increased operational costs and environmental concerns. This study focuses on developing an eco-friendly paraffin inhibitor system using three different concentrations of Glycine and Palm-based Methyl Ester Sulfonate (MES). Experiments were conducted on crude oil samples from the Dulang Oilfield. The experimental measurements include wax appearance temperature (WAT), pour point temperature (PPT), and rheological tests in the absence and presence of the proposed inhibitors. The results revealed that both Glycine and MES can effectively reduce WAT, viscosity, and yield point. Specifically, 10% Glycine was the best inhibitor, reducing WAT by 23.3%. However, MES (1%, 5%, and 10%) demonstrated greater overall effectiveness, with an average WAT reduction of 13.76% compared to Glycine’s 10.85%. MES also shows a better performance in reducing viscosity and yield stress. While PPT results were insignificant, MES is recommended as a flow improver rather than a pour point depressant. The successful development of these newly formulated chemical inhibitors promises an environmentally sustainable and economically efficient approach to maximizing oil production from mature fields while mitigating paraffin precipitation.

The LIM-domain-only protein LMO2 and its binding partner LDB1 are differentially required for class switch recombination

The LIM-domain-only protein LMO2 interacts with LDB1 in context-dependent multiprotein complexes and plays key roles in erythropoiesis and T cell leukemogenesis, but whether they have any roles in B cells is unclear. Through a CRISPR/Cas9-based loss-of-function screening, we identified LMO2 and LDB1 as factors for class switch recombination (CSR) in murine B cells. LMO2 contributes to CSR at least in part by promoting end joining of DNA double-strand breaks (DSBs) and inhibiting end resection. Although LDB1 stabilizes LMO2 proteins, it is not required for end joining but functions as a positive regulator of AID transcription independent of LMO2, and this function of LDB1 requires its dimerization domain. Moreover, LDB1 directly binds to and promotes the looping of the AID promoter to upstream enhancers through dimerization. Our study revealed the mechanistically separated roles of LMO2 and LDB1 in different steps of CSR for antibody diversification.

Association of preoperative body mass index with postoperative complications and survival for patients with gastric cancer: A systematic review and meta-analysis

Objective The relationship among body mass index (BMI), postoperative complications, and clinical outcomes in patients undergoing gastrectomy for gastric cancer remains unclear. This study aimed to evaluate this association using a meta-analysis. Method We conducted a systematic search of the PubMed, Embase, and Cochrane Library databases up to February 25, 2024. Patients were classified into underweight (&lt;18.5 kg/m2), normal weight (18.5–25.0 kg/m2), and overweight (≥25.0 kg/m2) groups based on BMI categories. Meta-analysis was performed using a random-effects model. Additionally, exploratory sensitivity and subgroup analyses were performed. Results Twenty-two studies involving 41,144 patients with gastric cancer were included for quantitative analysis. Preoperative underweight (odds ratio [OR]: 1.26; 95% confidence interval [CI]: 1.03–1.55; P = 0.024) and overweight (OR: 1.19; 95%CI: 1.09–1.30; P &lt;0.001) were associated with an increased risk of postoperative complications. Furthermore, preoperative underweight was associated with poorer overall survival (hazard ratio [HR]: 1.40; 95%CI: 1.28–1.53; P &lt;0.001), whereas preoperative overweight was associated with better over-survival (HR: 0.82; 95%CI: 0.73–0.91; P &lt;0.001). Furthermore, preoperative underweight was not associated with disease-free survival (HR: 1.48; 95%CI: 0.97–2.26; P = 0.069), whereas preoperative overweight was associated with longer disease-free survival (HR: 0.80; 95%CI: 0.70–0.91; P = 0.001). In terms of specific postoperative complications, preoperative underweight was associated with an increased risk of septic shock (OR: 3.40; 95%CI: 1.26–9.17; P = 0.015) and a reduced risk of fever (OR: 0.39; 95%CI: 0.18–0.83; P = 0.014). Preoperative overweight was associated with an increased risk of wound infections (OR: 1.78; 95%CI: 1.08–2.93; P = 0.023), intestinal fistula (OR: 5.23; 95%CI: 1.93–14.21; P = 0.001), arrhythmia (OR: 6.38; 95%CI: 1.70–24.01; P = 0.006), and pancreatic fistula (OR: 3.37; 95%CI: 1.14–9.96; P = 0.028). Conclusion This study revealed that both preoperative underweight and overweight status were associated with an increased risk of postoperative complications. Moreover, the postoperative survival outcomes were significantly better in overweight compared to that of underweight patients. Trial registration Registration: INPLASY202480004.

Coding relationship links RNA G-quadruplexes and protein RGG motifs in RNA-binding protein autoregulation

RNA G-quadruplexes (rG4s), the four-stranded structures formed by guanine-rich RNA sequences, are recognized by regions in RNA-binding proteins (RBPs) that are enriched in arginine-glycine repeats (RGG motifs). Importantly, arginine and glycine are encoded by guanine-rich codons, suggesting that some RGG motifs may both be encoded by and interact with rG4s in autogenous messenger RNAs (mRNAs). By analyzing transcriptome-wide rG4 datasets, we show that hundreds of RGG motifs in humans are at least partly encoded by rG4s, with an increased incidence for longer RGG motifs (~10 or more residues). Using randomized genetic codes, we demonstrate that the rG4/RGG coding relationship derives from the universal genetic code’s structure. Moreover, we show that proteins, which contain RGG motifs encoded by experimentally detected rG4s, are significantly enriched in RNA binding relative to all RGG-containing proteins. Finally, using enhanced crosslinking and immunoprecipitation (eCLIP) data, we identify several prominent RBPs, including FUS, FMRP, and G3BP1, which interact with autogenous mRNAs in regions where RGG motifs are encoded by rG4s. Our results define a physically realistic mechanism behind autogenous mRNA/protein interactions that is hardwired in the genetic code structure and may contribute to the establishment of autoregulatory feedback loops in the cell.