Spatial spillovers of violent conflict amplify the impacts of climate variability on malaria risk in sub-Saharan Africa.

Africa carries a disproportionately high share of the global malaria burden, accounting for 94% of malaria cases and deaths worldwide in 2019. It is also a politically unstable region and the most vulnerable continent to climate change in recent decades. Knowledge about the modifying impacts of violent conflict on climate-malaria relationships remains limited. Here, we quantify the associations between violent conflict, climate variability, and malaria risk in sub-Saharan Africa using health surveys from 128,326 individuals, historical climate data, and 17,429 recorded violent conflicts from 2006 to 2017. We observe that spatial spillovers of violent conflict (SSVCs) have spatially distant effects on malaria risk. Malaria risk induced by SSVCs within 50 to 100 km from the households gradually increases from 0.1% (not significant, P>0.05) to 6.5% (95% CI: 0 to 13.0%). SSVCs significantly promote malaria risk within the average 20.1 to 26.9 °C range. At the 12-mo mean temperature of 22.5 °C, conflict deaths have the largest impact on malaria risk, with an approximately 5.8% increase (95% CI: 1.0 to 11.0%). Additionally, a pronounced association between SSVCs and malaria risk exists in the regions with 9.2 wet days per month. The results reveal that SSVCs increase population exposure to harsh environments, amplifying the effect of warm temperature and persistent precipitation on malaria transmission. Violent conflict therefore poses a substantial barrier to mosquito control and malaria elimination efforts in sub-Saharan Africa. Our findings support effective targeting of treatment programs and vector control activities in conflict-affected regions with a high malaria risk.

Relationship of environmental exposure temperature and temperature extremes on sperm DNA fragmentation index in men with different BMI values and the indirect effect of DNA fragmentation index on semen parameters.

Prior studies have established a significant correlation between the DNA fragmentation index (DFI) and infertility. Additionally, certain investigations suggest that environmental exposure may serve as an etiological factor impacting semen quality. This study aimed to explore the impact of season, ambient temperature, and weather extremes on the DFI of sperm, along with other relevant parameters. Furthermore, it sought to assess how ambient temperature affects the DFI of sperm and other semen parameters in populations with varying BMI values. Additionally, the study analyzed the transient indirect effect of DFI on sperm parameters. This retrospective study analyzed semen samples from 11,877 men, selected based on female factor considerations, spanning from January 2016 to December 2021. Participants were grouped according to the season of semen collection. The results showed that samples collected in summer had a lower semen volume and sperm motility, while those collected in autumn had a lower DFI. We analyzed the exposure-response ratio between environmental exposure temperature and semen parameters using a generalized additive model. Results showed that the curve of the exposure-response relationship was U-shaped or inverted U-shaped; when the air temperature exposure was below the threshold, for each degree of temperature increase, the total sperm motility, sperm concentration, and progressive motility increased by 0.16 %, 0.29 × 10 (Levine, 1999)/ml and 0.14 %, respectively, while the DFI and inactivity rate decreased by 0.078 % and 0.15 %, respectively. When the air temperature exposure exceeded the threshold, for each degree of temperature increase, the sperm concentration, total sperm motility, semen volume and progressive motility decreased by 0.42 × 10 (Levine, 1999)/ml, 0.11 %, 0.0078 ml and 0.15 %, respectively, while the DFI and inactivity rate increased by 0.13 % and 0.12 %, respectively. Extremely cold weather during spermatogenesis was positively correlated with DFI, and extremely hot weather was negatively correlated with sperm motility. Subgroup analysis revealed that individuals classified as overweight / obese exhibited more pronounced changes in sperm parameters and the DFI in response to variations in environmental exposure temperature compared to those with a normal BMI. In the analysis of the relationship between DFI and sperm parameters, the results showed an inverted U-shape relationship between DFI and semen volume, and a negative correlation between DFI and sperm concentration and sperm motility. And we found that ambient temperature affects sperm parameters through DFI at low as well as average temperatures, whereas at high temperatures this indirect effect is no longer present.

Exactly solvable statistical physics models for large neuronal populations.

Maximum entropy methods provide a principled path connecting measurements of neural activity directly to statistical physics models, and this approach has been successful for populations of N~100 neurons. As N increases in new experiments, we enter an undersampled regime where we have to choose which observables should be constrained in the maximum entropy construction. The best choice is the one that provides the greatest reduction in entropy, defining a "minimax entropy" principle. This principle becomes tractable if we restrict attention to correlations among pairs of neurons that link together into a tree; we can find the best tree efficiently, and the underlying statistical physics models are exactly solved. We use this approach to analyze experiments on N~1500 neurons in the mouse hippocampus, and show that the resulting model captures the distribution of synchronous activity in the network.

A nonequilibrium allosteric model for receptor-kinase complexes: The role of energy dissipation in chemotaxis signaling.

The Escherichia coli chemotaxis signaling pathway has served as a model system for the adaptive sensing of environmental signals by large protein complexes. The chemoreceptors control the kinase activity of CheA in response to the extracellular ligand concentration and adapt across a wide concentration range by undergoing methylation and demethylation. Methylation shifts the kinase response curve by orders of magnitude in ligand concentration while incurring a much smaller change in the ligand binding curve. Here, we show that the disproportionate shift in binding and kinase response is inconsistent with equilibrium allosteric models. To resolve this inconsistency, we present a nonequilibrium allosteric model that explicitly includes the dissipative reaction cycles driven by adenosine triphosphate (ATP) hydrolysis. The model successfully explains all existing joint measurements of ligand binding, receptor conformation, and kinase activity for both aspartate and serine receptors. Our results suggest that the receptor complex acts as an enzyme: Receptor methylation modulates the ON-state kinetics of the kinase (e.g., phosphorylation rate), while ligand binding controls the equilibrium balance between kinase ON/OFF states. Furthermore, sufficient energy dissipation is responsible for maintaining and enhancing the sensitivity range and amplitude of the kinase response. We demonstrate that the nonequilibrium allosteric model is broadly applicable to other sensor-kinase systems by successfully fitting previously unexplained data from the DosP bacterial oxygen-sensing system. Overall, this work provides a nonequilibrium physics perspective on cooperative sensing by large protein complexes and opens up research directions for understanding their microscopic mechanisms through simultaneous measurements and modeling of ligand binding and downstream responses.

Effects of Damage to the Integrity of the Left Dual-Stream Frontotemporal Network Mediated by the Arcuate Fasciculus and Uncinate Fasciculus on Acute/Subacute Post-Stroke Aphasia.

(1) Background: To investigate the correlation between the integrity of the left dual-stream frontotemporal network mediated by the arcuate fasciculus (AF) and uncinate fasciculus (UF), and acute/subacute post-stroke aphasia (PSA). (2) Methods: Thirty-six patients were recruited and received both a language assessment and a diffusion tensor imaging (DTI) scan. Correlations between diffusion indices in the bilateral LSAF/UF and language performance assessment were analyzed with correlation analyses. Multiple linear regression analysis was also implemented to investigate the effects of the integrity of the left LSAF/UF on language performance. (3) Results: Correlation analyses showed that the diffusion indices, including mean fractional anisotropy (FA) values and the fiber number of the left LSAF rather than the left UF was significantly positively associated with language domain scores (p < 0.05). Multiple linear regression analysis revealed an independent and positive association between the mean FA value of the left LSAF and the percentage score of language subsets. In addition, no interaction effect of the integrity of the left LSAF and UF on language performance was found (p > 0.05). (4) Conclusions: The integrity of the left LSAF, but not the UF, might play important roles in supporting residual language ability in individuals with acute/subacute PSA; simultaneous disruption of the dual-stream frontotemporal network mediated by the left LSAF and UF would not result in more severe aphasia than damage to either pathway alone.

Primary prostate Burkitt's lymphoma resected with holmium laser enucleation of the prostate: A rare case report.

BACKGROUND: Primary prostate Burkitt's lymphoma is a rare and aggressive condition with a poor prognosis. Its clinical presentation can be challenging to differentiate from benign prostatic hyperplasia. Given the rarity of primary prostate Burkitt's lymphoma, its diagnosis and treatment remain unclear. CASE SUMMARY: This report presents a case of a 57-year-old male with primary prostate Burkitt's lymphoma, initially misdiagnosed as prostatic hyperplasia. This case's operative process, intraoperative findings and postoperative management are discussed in detail. CONCLUSION: Primary prostate lymphoma is difficult to distinguish from other prostate diseases. Holmium laser enucleation of the prostate (HoLEP), a minimally invasive procedure, is crucial in diagnosing and treating this rare disease. Clinicians should remain vigilant and thoroughly combine physical examination, imaging and test results when encountering patients of younger age with small prostate size but a rapid progression of lower urinary tract symptoms. HoLEP is an essential diagnostic and therapeutic tool in managing primary prostate Burkitt's lymphoma.

Resolving the binding-kinase discrepancy in bacterial chemotaxis: A nonequilibrium allosteric model and the role of energy dissipation.

The Escherichia coli chemotaxis signaling pathway has served as a model system for studying the adaptive sensing of environmental signals by large protein complexes. The chemoreceptors control the kinase activity of CheA in response to the extracellular ligand concentration and adapt across a wide concentration range by undergoing methylation and demethylation. Methylation shifts the kinase response curve by orders of magnitude in ligand concentration while incurring a much smaller change in the ligand binding curve. Here, we show that this asymmetric shift in binding and kinase response is inconsistent with equilibrium allosteric models regardless of parameter choices. To resolve this inconsistency, we present a nonequilibrium allosteric model that explicitly includes the dissipative reaction cycles driven by ATP hydrolysis. The model successfully explains all existing measurements for both aspartate and serine receptors. Our results suggest that while ligand binding controls the equilibrium balance between the ON and OFF states of the kinase, receptor methylation modulates the kinetic properties (e.g., the phosphorylation rate) of the ON state. Furthermore, sufficient energy dissipation is necessary for maintaining and enhancing the sensitivity range and amplitude of the kinase response. We demonstrate that the nonequilibrium allosteric model is broadly applicable to other sensor-kinase systems by successfully fitting previously unexplained data from the DosP bacterial oxygen-sensing system. Overall, this work provides a new perspective on cooperative sensing by large protein complexes and opens up new research directions for understanding their microscopic mechanisms through simultaneous measurements and modeling of ligand binding and downstream responses.

Time-reversal symmetry breaking in the chemosensory array: asymmetric switching and dissipation-enhanced sensing.

The Escherichia coli chemoreceptors form an extensive array that achieves cooperative and adaptive sensing of extracellular signals. The receptors control the activity of histidine kinase CheA, which drives a non-equilibrium phosphorylation-dephosphorylation reaction cycle for response regulator CheY. Recent single-cell FRET measurements revealed that kinase activity of the array spontaneously switches between active and inactive states, with asymmetric switching times that signify time-reversal symmetry breaking in the underlying dynamics. Here, we show that the asymmetric switching dynamics can be explained by a non-equilibrium lattice model, which considers both the dissipative reaction cycles of individual core units and the coupling between neighboring units. The model reveals that large dissipation and near-critical coupling are required to explain the observed switching dynamics. Microscopically, the switching time asymmetry originates from irreversible transition paths. The model shows that strong dissipation enables sensitive and rapid signaling response by relieving the speed-sensitivity trade-off, which can be tested by future single-cell experiments. Overall, our model provides a general framework for studying biological complexes composed of coupled subunits that are individually driven by dissipative cycles and the rich non-equilibrium physics within.

Poor Spontaneous Recovery of Aphemia Accompanied by Damage to the Anterior Segment of the Left Arcuate Fasciculus: A Case Report.

Aphemia is a rare and special type of speech disorder, and the mechanisms underlying the occurrence and recovery remain unclear. Here, we present a clinical case of poor spontaneous recovery of aphemia, with the anterior segment of the left arcuate fasciculus server damaged and the posterior segment intact, as detected by diffusion tensor imaging. Aphemia could be caused by the disruption of the cortical and subcortical language circuits. In particular, our data support the view that damage to the anterior segment of the left arcuate fasciculus may result in poor spontaneous recovery from speech production deficits and that an intact posterior segment seems to be crucial for supporting residual language comprehension ability in patients with post-stroke aphasia. Collectively, these data imply the importance of the left arcuate fasciculus during recovery from the language disorder in the subacute stage of stroke.

Integrity of the Left Arcuate Fasciculus Segments Significantly Affects Language Performance in Individuals with Acute/Subacute Post-Stroke Aphasia: A Cross-Sectional Diffusion Tensor Imaging Study.

OBJECTIVE: To investigate the correlation between the left arcuate fasciculus (AF) segments and acute/subacute post-stroke aphasia (PSA). METHODS: Twenty-six patients underwent language assessment and MRI scanning. The integrity of the AF based on a three-segment model was evaluated using diffusion tensor imaging. All patients were classified into three groups according to the reconstruction of the left AF: completely reconstructed (group A, 8 cases), non-reconstructed (group B, 6 cases), and partially reconstructed (group C, 12 cases). The correlations and intergroup differences in language performance and diffusion indices were comprehensively estimated. RESULTS: A correlation analyses showed that the lesion load of the language areas and diffusion indices on the left AF posterior and long segments was significantly related to some language subsets, respectively. When controlled lesion load was variable, significant correlations between diffusion indices on the posterior and long segments and comprehension, repetition, naming, and aphasia quotient were retained. Multiple comparison tests revealed intergroup differences in diffusion indices on the left AF posterior and long segments, as well as these language subsets. No significant correlation was found between the anterior segment and language performance. CONCLUSIONS: The integrity of the left AF segments, particularly the posterior segment, is crucial for the residual comprehension and repetition abilities in individuals with acute/subacute PSA, and lesion load in cortical language areas is an important factor that should be taken into account when illustrating the contributions of damage to special fiber tracts to language impairments.

Geographic and gender disparities in global education achievement during the COVID-19 pandemic.

School closures induced by the COVID-19 pandemic have negatively impacted on 1.7 billion children, resulting in losses of learning time and a decline of learning scores. However, the learning losses of students exposed to the COVID-19 pandemic at the country level have been quantitatively unaddressed. Here we model the global learning losses of students due to the COVID-19 in 2020. Our results reveal a global average Harmonized Test Scores (HTS) loss of 2.26 points. Learning continuity measures reduce the global average HTS loss by 1.64 points. South Asia and Sub-Saharan Africa have high HTS losses (5.82 and 2.94 points), while Europe & Central Asia and North America have low HTS losses (0.85 and 0.93 points). Compared with South Asia and Sub-Saharan Africa, North America and Europe & Central Asia implement more effective learning continuity measures. HTS losses in low-income and lower-middle-income countries are higher (3.35 and 3.13 points) than those in high-income and upper-middle-income countries (0.99 and 2.31 points). Learning losses of global female students are higher than their male counterparts, and there is significant heterogeneity across national regions. Our results reveal both global learning losses and gender inequality in learning scores due to the COVID-19 pandemic. Global disparities highlight the importance of the need to mitigate education inequality.

State-space renormalization group theory of nonequilibrium reaction networks: Exact solutions for hypercubic lattices in arbitrary dimensions.

Nonequilibrium reaction networks (NRNs) underlie most biological functions. Despite their diverse dynamic properties, NRNs share the signature characteristics of persistent probability fluxes and continuous energy dissipation even in the steady state. Dynamics of NRNs can be described at different coarse-grained levels. Our previous work showed that the apparent energy dissipation rate at a coarse-grained level follows an inverse power-law dependence on the scale of coarse-graining. The scaling exponent is determined by the network structure and correlation of stationary probability fluxes. However, it remains unclear whether and how the (renormalized) flux correlation varies with coarse-graining. Following Kadanoff's real space renormalization group (RG) approach for critical phenomena, we address this question by developing a state-space renormalization group theory for NRNs, which leads to an iterative RG equation for the flux correlation function. In square and hypercubic lattices, we solve the RG equation exactly and find two types of fixed point solutions. There is a family of nontrivial fixed points where the correlation exhibits power-law decay, characterized by a power exponent that can take any value within a continuous range. There is also a trivial fixed point where the correlation vanishes beyond the nearest neighbors. The power-law fixed point is stable if and only if the power exponent is less than the lattice dimension n. Consequently, the correlation function converges to the power-law fixed point only when the correlation in the fine-grained network decays slower than r^{-n} and to the trivial fixed point otherwise. If the flux correlation in the fine-grained network contains multiple stable solutions with different exponents, the RG iteration dynamics select the fixed point solution with the smallest exponent. The analytical results are supported by numerical simulations. We also discuss a possible connection between the RG flows of flux correlation with those of the Kosterlitz-Thouless transition.

The energy cost and optimal design of networks for biological discrimination.

Many biological processes discriminate between correct and incorrect substrates through the kinetic proofreading mechanism that enables lower error at the cost of higher energy dissipation. Elucidating physico-chemical constraints for global minimization of dissipation and error is important for understanding enzyme evolution. Here, we identify theoretically a fundamental error-cost bound that tightly constrains the performance of proofreading networks under any parameter variations preserving the rate discrimination between substrates. The bound is kinetically controlled, i.e. completely determined by the difference between the transition state energies on the underlying free energy landscape. The importance of the bound is analysed for three biological processes. DNA replication by T7 DNA polymerase is shown to be nearly optimized, i.e. its kinetic parameters place it in the immediate proximity of the error-cost bound. The isoleucyl-tRNA synthetase (IleRS) of E. coli also operates close to the bound, but further optimization is prevented by the need for reaction speed. In contrast, E. coli ribosome operates in a high-dissipation regime, potentially in order to speed up protein production. Together, these findings establish a fundamental error-dissipation relation in biological proofreading networks and provide a theoretical framework for studying error-dissipation trade-off in other systems with biological discrimination.

Energy Cost for Flocking of Active Spins: The Cusped Dissipation Maximum at the Flocking Transition.

We study the energy cost of flocking in the active Ising model (AIM) and show that, besides the energy cost for self-propelled motion, an additional energy dissipation is required to power the alignment of spins. We find that this additional alignment dissipation reaches its maximum at the flocking transition point in the form of a cusp with a discontinuous first derivative with respect to the control parameter. To understand this singular behavior, we analytically solve the two- and three-site AIM models and obtain the exact dependence of the alignment dissipation on the flocking order parameter and control parameter, which explains the cusped dissipation maximum at the flocking transition. Our results reveal a trade-off between the energy cost of the system and its performance measured by the flocking speed and sensitivity to external perturbations. This trade-off relationship provides a new perspective for understanding the dynamics of natural flocks and designing optimal artificial flocking systems.

Rare coexistence of multiple manifestations secondary to thalamic hemorrhage: A case report.

BACKGROUND: A growing body of literature indicates that the occurrence of thalamic lesions could lead to various dysfunctions, such as somatosensory disturbances, hemiparesis, language deficits, and movement disorders. However, clinical cases describing the coexistence of these types of manifestations have not been reported. Herein, we report a patient who exhibited these rare complications secondary to thalamic hemorrhage. CASE SUMMARY: A 53-year-old right-handed man experienced sudden left hemiparesis, numbness of the left side of body, and language alterations due to an acute hemorrhage located in the right basal ganglia and thalamus 18 mo ago. Approximately 17 mo after the onset of stroke, he exhibited rare complications including dysphasia, kinetic tremor confined to the left calf, and mirror movement of the left arm which are unique and interesting, and a follow-up computed tomography scan revealed an old hemorrhagic lesion in the right thalamus and posterior limb of the internal capsule. CONCLUSION: Hypophonia may be a recognizable clinical sign of thalamus lesions; thalamus injury could cause tremor confined to the lower extremity and mimicking extremity movements.

Relationship between Air Pollutant Exposure and Gynecologic Cancer Risk.

Exposure to air pollution has been suggested to be associated with an increased risk of women's health disorders. However, it remains unknown to what extent changes in ambient air pollution affect gynecological cancer. In our case-control study, the logistic regression model was combined with the restricted cubic spline to examine the association of short-term exposure to air pollution with gynecological cancer events using the clinical data of 35,989 women in Beijing from December 2008 to December 2017. We assessed the women's exposure to air pollutants using the monitor located nearest to each woman's residence and working places, adjusting for age, occupation, ambient temperature, and ambient humidity. The adjusted odds ratios (ORs) were examined to evaluate gynecologic cancer risk in six time windows (Phase 1-Phase 6) of women's exposure to air pollutants (PM2.5, CO, O3, and SO2) and the highest ORs were found in Phase 4 (240 days). Then, the higher adjusted ORs were found associated with the increased concentrations of each pollutant (PM2.5, CO, O3, and SO2) in Phase 4. For instance, the adjusted OR of gynecological cancer risk for a 1.0-mg m-3 increase in CO exposures was 1.010 (95% CI: 0.881-1.139) below 0.8 mg m-3, 1.032 (95% CI: 0.871-1.194) at 0.8-1.0 mg m-3, 1.059 (95% CI: 0.973-1.145) at 1.0-1.4 mg m-3, and 1.120 (95% CI: 0.993-1.246) above 1.4 mg m-3. The ORs calculated in different air pollution levels accessed us to identify the nonlinear association between women's exposure to air pollutants (PM2.5, CO, O3, and SO2) and the gynecological cancer risk. This study supports that the gynecologic risks associated with air pollution should be considered in improved public health preventive measures and policymaking to minimize the dangerous effects of air pollution.

Inverse Power Law Scaling of Energy Dissipation Rate in Nonequilibrium Reaction Networks.

The energy dissipation rate in a nonequilibrium reaction system can be determined by the reaction rates in the underlying reaction network. By developing a coarse-graining process in state space and a corresponding renormalization procedure for reaction rates, we find that energy dissipation rate has an inverse power-law dependence on the number of microscopic states in a coarse-grained state. The dissipation scaling law requires self-similarity of the underlying network, and the scaling exponent depends on the network structure and the probability flux correlation. Existence of the inverse dissipation scaling law is shown in realistic biochemical systems such as biochemical oscillators and microtubule-kinesin active flow systems.

Morbidity and All-Cause Mortality Following Radical Prostatectomy Compared with Observation for Localized Prostate Cancer in Chinese Men: A Non-Randomized Retrospective Study.

BACKGROUND The Chinese 2018 guidelines and the current 2014 Chinese Urological Association guidelines for prostate cancer recommend radical prostatectomy for Chinese men with localized prostate cancer as the first choice, but it has treatment-related adverse effects. This study aimed to study morbidity and all-cause mortality following radical prostatectomy compared with observation for localized prostate cancer in Chinese men from a single center. MATERIAL AND METHODS Men diagnosed (histologically) as stage T1-T2N×M0 prostate cancer of any grade with 1-year history were included in the analysis. A total of 201 men underwent radical prostatectomy (RP cohort) and 209 men did not undergo radical prostatectomy (OS cohort). RESULTS During follow-up (17-24 years), 135 (67%) men died in the RP cohort and 156 (75%) men died in the OS cohort (P=0.103). All-cause mortality was lower for men with prostate-specific antigen level >10 ng/mL (P<0.0001), Gleason score ≥7 (P=0.004), and high D'Amico tumor risk scores (P=0.007) if they underwent radical prostatectomy. Age ≥65 years (P=0.041), Gleason score ≥7 (P=0.049), and tumor stage ≥2c (P=0.045) were associated with all-cause mortality. CONCLUSIONS The findings from this study showed that radical prostatectomy has no significant beneficial effects when compared with observation for Chinese men with localized prostate cancer, unless they had a prostate-specific antigen level >10 ng/mL, Gleason score ≥7, and high D'Amico tumor risk scores.

miR-30c-5p Alleviated Pyroptosis During Sepsis-Induced Acute Kidney Injury via Targeting TXNIP.

Sepsis-induced acute kidney injury (SAKI) is a common complication of hospitalized patients, often leading to unacceptable mortality. Limited effective treatment or diagnosis biomarkers are available and the underlying mechanism remains unclear. The miR-30c-5p is considered as a critical mediator of kidney diseases and aberrantly decreased in patients with SAKI, while the mechanism is still unclear. For this purpose, the role of miR-30c-5p in SAKI has been investigated in this study. Here, we first confirmed that miR-30c-5p expression decreased in our septic models and was associated with the activation of NLRP3/caspase-1-mediated pyroptosis. Overexpression of miR-30c-5p alleviated the kidney injury via suppressing HK-2 cell pyroptosis. Furthermore, we identified that TXNIP was a direct target of miR-30c-5p. Upregulation of miR-30c-5p repressed the expression of TXNIP, which inhibited NLRP3, ASC, and caspase-1 expression, as well as secretion of inflammatory cytokines. In conclusion, our data suggested that miR-30c-5p negatively controlled the NLRP3 signal pathway-related pyroptosis and sepsis-induced injury via TXNIP, indicating that this axis might be a positive therapeutic target for the patient with SAKI.